Diana Do, MD

All Publications

• Risk factors for development of anti-adalimumab antibodies in non-infectious uveitis. Heliyon Bromeo, A. J., Karaca, I., Ghoraba, H. H., Lyu, X., Than, N. T., Ongpalakorn, P., Shin, Y. U., Uludag, G., Tran, A. N., Thng, Z. X., Do, D. V., Or, C. M., Nguyen, Q. D. 2024; 10 (9): e29313

  Abstract

  Purpose: To evaluate risk factors associated with development of anti-adalimumab antibodies (AAA) in patients with non-infectious uveitis treated with adalimumab.Methods: A retrospective, cross-sectional, case-control study was done evaluating patients with non-infectious uveitis treated with adalimumab for at least 12 months and have undergone testing for AAA levels. Demographics, clinical characteristics, grading of ocular inflammation, and previous and concomitant immunomodulatory therapy were assessed. Univariate and multivariate analysis were done to estimate odds ratio (OR) with 95% confidence intervals for the various risk factors.Results: A total of 31 patients were included in the analysis, in which 12 patients who tested positive (Group 1) were matched with 19 patients who tested negative for AAA (Group 2). The groups differed significantly in terms of sex (female) (91.7% vs 52.6%, p=0.046), presence of systemic disease (91.7% vs 42.1%, p=0.008), and presence of anterior chamber inflammation at baseline (100% vs 63.2%, p=0.026). A history of interruption in anti-TNF therapy prior to starting or restarting adalimumab was found to have an increased odds for development of AAA (OR 16.89 [2.92, 107.11], p=0.008), as well as flare-ups (reactivation of disease) during adalimumab therapy (OR 6.77 [1.80, 61.80], p=0.027). Weekly dosing of adalimumab was shown to decrease odds of AAA development (OR 0.34 [0.02, 0.70], p=0.040), while concomitant anti-metabolite therapy was not shown to be a statistically significant protective factor (OR 2.22 [0.50, 9.96], p=0.148).Conclusions: History of interruption in anti-TNF therapy and flare during adalimumab were associated with development of AAA, while weekly dosing of adalimumab was protective against AAA. Identification of those with higher risk of developing AAA may guide in clinical decision making to optimize management for these patients.

  View details for DOI 10.1016/j.heliyon.2024.e29313

  View details for PubMedID 38694084

• Importance of Baseline Fluorescein Angiography for Patients Presenting to Tertiary Uveitis Clinic. American journal of ophthalmology Karaca, I., Bromeo, A., Ghoraba, H., Lyu, X., Thng, Z. X., Yasar, C., Akhavanrezayat, A., Yavari, N., Kirimli, G. U., Than, N. T., Shin, Y., Gupta, A. S., Khatri, A., Mohammadi, S. S., Hung, J. H., Or, C., Do, D. V., Nguyen, Q. D. 2024

  Abstract

  To ascertain whether the use of ultra-wide-field fluorescein angiography (UWFFA) at baseline visit alters the assessment of disease activity and localization, as well as the management of patients presenting to a tertiary uveitis clinic.Retrospective comparison of diagnostic approaches.Baseline visits of 158 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were evaluated by three uveitis-trained ophthalmologists (I.K., A.B., and H.G.). Each eye had undergone clinical examination along with ultra-wide-field fundus photography (UWFFP) (Optos Plc, Dunfermline, Scotland, UK), spectral-domain optical coherence tomography (SD-OCT, Spectralis Heidelberg, Heidelberg Engineering, Heidelberg, Germany) and UWFFA (Optos Plc, Dunfermline, Scotland, UK) at the baseline visit. Investigators were asked to successively determine disease activity, localization of disease (anterior, posterior or both), and management decisions based on clinical examination and UWFFP and SD-OCT (Set 1) and Set 1 plus UWFFA (Set 2). The primary outcome was the percentage of eyes whose management changed based on the availability of UWFFA, compared with Set 1.The mean age of the patients was 46.9±22.4 (range, 7-96) and 91 (57.6%) were female. With Set 1 alone, 138 (55.2%) eyes were found to have active disease; localization was anterior in 58 (42.0%) eyes, posterior in 53 (38.4%) eyes and anterior + posterior in 27 (19.6%) eyes. With Set 2, 169 eyes of 107 patients had active anterior, posterior or pan-uveitis. In comparison with Set 1, assessment with Set 2 identified additional 31 (18.3%) eyes with active disease (p=0.006), and additional 31 (18.3%) eyes having disease in both anterior + posterior segments (p<0.001). Regarding the primary outcome, management was changed in 68 (27.4%) eyes in Set 2, compared to Set 1.Baseline UWFFA may alter assessment of disease activity, localization, and management decisions compared to clinical examination with only UWFFP and SD-OCT for eyes with uveitis. Thus, UWFFA may be considered as an essential tool in the evaluation of uveitis patients at the baseline visit.

  View details for DOI 10.1016/j.ajo.2024.04.016

  View details for PubMedID 38701875

• Aqueous humour interleukin-6 and vision outcomes with anti-vascular endothelial growth factor therapy. Eye (London, England) Sepah, Y. J., Do, D. V., Mesquida, M., Day, B. M., Blotner, S., Afridi, R., Halim, M. S., Hong, K., Wakshull, E., Fauser, S., Stoilov, I., Dong Nguyen, Q. 2024

  Abstract

  This analysis evaluated aqueous humour (AH) interleukin (IL)-6 concentrations and the association between AH IL-6 and visual outcomes in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular oedema (DMO) receiving anti-vascular endothelial growth factor (VEGF) monotherapy.Post hoc analysis of the multicentre, double-masked, randomised HARBOR (NCT00891735) and READ-3 (NCT01077401) trials. HARBOR enrolled treatment-naïve nAMD patients. READ-3 enrolled treatment-naïve/previously treated DMO patients. HARBOR patients received ranibizumab 0.5 or 2.0 mg monthly or as needed; AH samples were collected at month 2, after two previous intravitreal injections. READ-3 patients received ranibizumab 0.5 or 2.0 mg as needed; AH samples were collected at baseline and months 3, 6, 9, and 12.association between AH IL-6 concentrations and month 24 best-corrected visual acuity (BCVA).In both trials (HARBOR, N = 36; READ-3, N = 137), patients with higher AH IL-6 concentrations had worse visual outcomes. HARBOR patients with low AH IL-6 concentrations at month 2 had a mean (95% CI) BCVA change at month 24 of +2.9 (-2.6, 8.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of -9.0 (-22.7, 4.7) letters. READ-3 patients with low AH concentrations at baseline had a mean (95% CI) BCVA change at month 12 of +9.3 (7.4, 11.3) letters, whereas patients with high AH concentrations had a mean (95% CI) BCVA change of +5.6 (2.2, 9.1) letters.Higher IL-6 AH concentrations may predict suboptimal visual responses to anti-VEGF monotherapy in patients with nAMD/DMO.

  View details for DOI 10.1038/s41433-024-03015-2

  View details for PubMedID 38622330

  View details for PubMedCentralID 4176007

• Ocular and Systemic Risk Factors for Disease Worsening Among Patients with NPDR Post Hoc Analysis of the PANORAMA Trial OPHTHALMOLOGY RETINA Wykoff, C. C., Do, D., Goldberg, R. A., Dhoot, D. S., Lim, J. I., Du, W., Silva, F. Q., Desai, R., Moini, H., Reed, K., Berliner, A. J., Vitti, R., Clark, W. 2024; 8 (4): 399-408

  View details for DOI 10.1016/j.oret.2023.10.016

  View details for Web of Science ID 001222744300001

• Dr. Google vs. Dr. ChatGPT: Exploring the Use of Artificial Intelligence in Ophthalmology by Comparing the Accuracy, Safety, and Readability of Responses to Frequently Asked Patient Questions Regarding Cataracts and Cataract Surgery. Seminars in ophthalmology Cohen, S. A., Brant, A., Fisher, A. C., Pershing, S., Do, D., Pan, C. 2024: 1-8

  Abstract

  Patients are using online search modalities to learn about their eye health. While Google remains the most popular search engine, the use of large language models (LLMs) like ChatGPT has increased. Cataract surgery is the most common surgical procedure in the US, and there is limited data on the quality of online information that populates after searches related to cataract surgery on search engines such as Google and LLM platforms such as ChatGPT. We identified the most common patient frequently asked questions (FAQs) about cataracts and cataract surgery and evaluated the accuracy, safety, and readability of the answers to these questions provided by both Google and ChatGPT. We demonstrated the utility of ChatGPT in writing notes and creating patient education materials.The top 20 FAQs related to cataracts and cataract surgery were recorded from Google. Responses to the questions provided by Google and ChatGPT were evaluated by a panel of ophthalmologists for accuracy and safety. Evaluators were also asked to distinguish between Google and LLM chatbot answers. Five validated readability indices were used to assess the readability of responses. ChatGPT was instructed to generate operative notes, post-operative instructions, and customizable patient education materials according to specific readability criteria.Responses to 20 patient FAQs generated by ChatGPT were significantly longer and written at a higher reading level than responses provided by Google (p < .001), with an average grade level of 14.8 (college level). Expert reviewers were correctly able to distinguish between a human-reviewed and chatbot generated response an average of 31% of the time. Google answers contained incorrect or inappropriate material 27% of the time, compared with 6% of LLM generated answers (p < .001). When expert reviewers were asked to compare the responses directly, chatbot responses were favored (66%).When comparing the responses to patients' cataract FAQs provided by ChatGPT and Google, practicing ophthalmologists overwhelming preferred ChatGPT responses. LLM chatbot responses were less likely to contain inaccurate information. ChatGPT represents a viable information source for eye health for patients with higher health literacy. ChatGPT may also be used by ophthalmologists to create customizable patient education materials for patients with varying health literacy.

  View details for DOI 10.1080/08820538.2024.2326058

  View details for PubMedID 38516983

• Biosimilars of anti-vascular endothelial growth factor for ophthalmic diseases: A review. Survey of ophthalmology Bressler, N. M., Kaiser, P. K., Do, D. V., Nguyen, Q. D., Park, K. H., Woo, S. J., Sagong, M., Bradvica, M., Kim, M. Y., Kim, S., Sadda, S. R. 2024

  Abstract

  The development of intravitreally injected biologic medicines (biologics) acting against vascular endothelial growth factor (VEGF) substantially improved the clinical outcomes of patients with common VEGF-driven retinal diseases. The relatively high cost of branded agents, however, represents a financial burden for most healthcare systems and patients, likely resulting in impaired access to treatment and poorer clinical outcomes for some patients. Biosimilar medicines (biosimilars) are clinically equivalent, potentially economic alternatives to reference products. Biosimilars approved by leading health authorities have been demonstrated to be similar to the reference product in a comprehensive comparability exercise, generating the totality of evidence necessary to support analytical, pre-clinical, and clinical biosimilarity. Anti-VEGF biosimilars have been entering the field of ophthalmology in the US since 2022. We review regulatory and scientific concepts of biosimilars, the biosimilar development landscape in ophthalmology, with a specific focus on anti-VEGF biosimilars, and discuss opportunities and challenges facing the uptake of biosimilars.

  View details for DOI 10.1016/j.survophthal.2024.03.009

  View details for PubMedID 38521423

• Intravenous cyclophosphamide therapy for patients with severe ocular inflammatory diseases who failed other immunomodulatory therapies. Journal of ophthalmic inflammation and infection Karaca, I., Tran, E. M., Park, S., Bromeo, A., Khojasteh, H., Tran, A. N., Yavari, N., Akhavanrezayat, A., Yasar, C., Uludag Kirimli, G., Than, N. T., Hassan, M., Or, C., Ghoraba, H., Do, D. V., Nguyen, Q. D. 2024; 14 (1): 12

  Abstract

  Ocular inflammatory diseases, including scleritis and uveitis, have been widely treated with immunomodulatory therapies (IMTs) as a steroid-sparing approach. Such strategy includes conventional therapies (antimetabolites, alkylating agents, and calcineurin inhibitors) as well as biologic agents like adalimumab, infliximab, rituximab, and tocilizumab. Cyclophosphamide (CP) is an alkylating agent and mainly inhibits the functioning of both T and B cells. Though known to have potential adverse events, including bone marrow suppression, hemorrhagic cystitis, and sterility, CP has been shown to be efficacious, especially in recalcitrant cases and when used intravenous (IV) for a limited period.We conducted a retrospective case-series to assess the safety and efficacy of CP therapy for patients with severe ocular inflammatory diseases who failed other IMTs. Medical records of 1295 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were reviewed. Seven patients (10 eyes) who received CP therapy for ocular inflammatory diseases with at least one year of follow-up were included. The mean age of the patients (4 males, 3 females) was 61.6 ± 14.9 (43.0-89.0) years. Clinical diagnoses included necrotizing scleritis (5 eyes), peripheral ulcerative keratitis (2 eyes), orbital pseudotumor (1 eye), HLA-B27 associated panuveitis and retinal vasculitis (2 eyes). Ocular disease was idiopathic in 3 patients, and was associated with rheumatoid arthritis, IgG-4 sclerosing disease, dermatomyositis, and ankylosing spondylitis in 1 patient each. All the patients had history of previous IMT use including methotrexate (5), mycophenolate mofetil (3), azathioprine (1), tacrolimus (1), adalimumab (2), infliximab (4), and rituximab (1). The mean follow-up time was 34.4 ± 11.0 (13-45) months, and mean duration of CP therapy was 11.9 ± 8.8 (5-28) months. Remission was achieved in 5 patients (71.4%). Four patients (57.1%) experienced transient leukopenia (white blood cell count < 4000/mL).CP therapy can be considered a potentially effective and relatively safe therapeutic option for patients with severe ocular inflammatory diseases who failed other IMTs including biologics (TNFa and CD20 inhibitors).

  View details for DOI 10.1186/s12348-023-00372-z

  View details for PubMedID 38466527

  View details for PubMedCentralID PMC10928035

• Intravitreal aflibercept 8 mg in diabetic macular oedema (PHOTON): 48-week results from a randomised, double-masked, non-inferiority, phase 2/3 trial. Lancet (London, England) Brown, D. M., Boyer, D. S., Do, D. V., Wykoff, C. C., Sakamoto, T., Win, P., Joshi, S., Salehi-Had, H., Seres, A., Berliner, A. J., Leal, S., Vitti, R., Chu, K. W., Reed, K., Rao, R., Cheng, Y., Sun, W., Voronca, D., Bhore, R., Schmidt-Ott, U., Schmelter, T., Schulze, A., Zhang, X., Hirshberg, B., Yancopoulos, G. D., Sivaprasad, S. 2024

  Abstract

  A high-dose formulation of intravitreal aflibercept (8 mg) could improve treatment outcomes in diabetic macular oedema (DMO) by requiring fewer injections than the standard comparator, aflibercept 2 mg. We report efficacy and safety results of aflibercept 8 mg versus 2 mg in patients with DMO.PHOTON was a randomised, double-masked, non-inferiority, phase 2/3 trial performed at 138 hospitals and specialty retina clinics in seven countries. Eligible patients were adults aged 18 years or older with type 1 or 2 diabetes and centre-involved DMO. Patients were randomly assigned (1:2:1) to intravitreal aflibercept 2 mg every 8 weeks (2q8), aflibercept 8 mg every 12 weeks (8q12), or aflibercept 8 mg every 16 weeks (8q16), following initial monthly dosing. From week 16, dosing intervals for the aflibercept 8 mg groups were shortened if patients met prespecified dose regimen modification criteria denoting disease activity. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48 (non-inferiority margin of 4 letters). Efficacy and safety analyses included all randomly assigned patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov (NCT04429503).Between June 29, 2020, and June 28, 2021, 970 patients were screened for eligibility. After exclusions, 660 patients were enrolled and randomly assigned to receive aflibercept 8q12 (n=329), 8q16 (n=164), or 2q8 (n=167); two patients were randomly assigned in error and did not receive treatment. 658 (99·7%) patients were treated and included in the full analysis set and safety analysis set (8q12 n=328, 8q16 n=163, and 2q8 n=167). Mean patient age was 62·3 years (SD 10·4). 401 (61%) patients were male. 471 (72%) patients were White. Aflibercept 8q12 and 8q16 demonstrated non-inferior BCVA gains to aflibercept 2q8 (BCVA mean change from baseline 8·8 letters [SD 9·0] in the 8q12 group, 7·9 letters [8·4] in the 8q16 group, and 9·2 letters [9·0] in the 2q8 group). The difference in least squares means was -0·57 letters (95% CI -2·26 to 1·13, p value for non-inferiority <0·0001) between 8q12 and 2q8 and -1·44 letters (-3·27 to 0·39, p value for non-inferiority 0·0031) between aflibercept 8q16 and 2q8. Proportions of patients with ocular adverse events in the study eye were similar across groups (8q12 n=104 [32%], 8q16 n=48 [29%], and 2q8 n=46 [28%]).Aflibercept 8 mg demonstrated efficacy and safety with extended dosing intervals and could decrease treatment burden in patients with DMO.Regeneron Pharmaceuticals and Bayer.

  View details for DOI 10.1016/S0140-6736(23)02577-1

  View details for PubMedID 38461843

• LIGHTSITE III: 13-Month Efficacy and Safety Evaluation of Multiwavelength Photobiomodulation in Nonexudative (Dry) Age-Related Macular Degeneration Using the LumiThera Valeda Light Delivery System. Retina (Philadelphia, Pa.) Boyer, D., Hu, A., Warrow, D., Xavier, S., Gonzalez, V., Lad, E., Rosen, R. B., Do, D., Schneiderman, T., Hu, A., Munk, M. R., Jaffe, G., Tedford, S. E., Croissant, C. L., Walker, M., Rückert, R., Tedford, C. E. 2023

  Abstract

  The LIGHTSITE III study evaluated multiwavelength photobiomodulation (PBM) therapy in nonexudative (dry) AMD using the LumiThera Valeda® Light Delivery System.LIGHTSITE III is a randomized, controlled trial to assess the safety and effectiveness of PBM in dry AMD. Subjects were treated with multiwavelength PBM (590, 660 and 850 nm) or Sham treatment delivered 9 treatments over 3-5 weeks every four months over 24 months. Subjects were assessed for efficacy and safety outcomes. Data from the 13-month analysis are presented in this report.A total of 100 subjects (148 eyes) with dry AMD were randomized. LIGHTSITE III met the primary efficacy BCVA endpoint with a significant difference between PBM (n = 91 eyes) and Sham (n = 54 eyes) groups (Between group difference: 2.4 letters (SE 1.15), CI: -4.7 - -0.1, p = 0.02)(PBM alone: 5.4 letters (SE 0.96), CI: 3.5 - 7.3, p < 0.0001; Sham alone: 3.0 letters (SE 1.13), CI: 0.7 - 5.2, p < 0.0001). The PBM group showed a significant decrease in new onset GA (p = 0.024, Fisher exact test, odds ratio 9.4). A favorable safety profile was observed.LIGHTSITE III provides a prospective, randomized controlled trial showing improved clinical and anatomical outcomes in intermediate dry AMD following PBM.

  View details for DOI 10.1097/IAE.0000000000003980

  View details for PubMedID 37972955

• Structural and Functional Changes in Non-Paraneoplastic Autoimmune Retinopathy. Diagnostics (Basel, Switzerland) Akhavanrezayat, A., Khatri, A., Onghanseng, N. G., Halim, M. S., Or, C., Sredar, N., Razeen, M., Hasanreisoglu, M., Regenold, J., Thng, Z. X., Mohammadi, S. S., Jain, T., Yavari, N., Bazojoo, V., Gupta, A. S., Mobasserian, A., Yasar, C., Than, N. T., Uludag Kirimli, G., Karaca, I., Shin, Y., Yoo, W., Ghoraba, H., Do, D. V., Dubra, A., Nguyen, Q. D. 2023; 13 (21)

  Abstract

  BACKGROUND: To describe longitudinal changes in patients with non-paraneoplastic autoimmune retinopathy (npAIR) by utilizing different diagnostic modalities/tests.METHODS: The index study is a retrospective longitudinal review of sixteen eyes of eight patients from a tertiary care eye hospital diagnosed with npAIR. Multiple diagnostic modalities such as wide-angle fundus photography (WAFP), WA fundus autofluorescence (WAFAF), spectral-domain optical coherence tomography (SD-OCT), Goldmann visual field (GVF) perimetry, microperimetry (MP), electrophysiologic testing, and adaptive optics scanning laser ophthalmoscopy (AOSLO) were reviewed and analyzed.RESULTS: At the baseline visits, anomalies were detected by multimodal diagnostic tests on all patients. Subjects were followed up for a median duration of 11.5 [3.0-18.7] months. Structural changes at the baseline were detected in 14 of 16 (87.5%) eyes on WAFP and WAFAF and 13 of 16 (81.2%) eyes on SD-OCT. Eight of the ten (80%) eyes that underwent AOSLO imaging depicted structural changes. Functional changes were detected in 14 of 16 (87.5%) eyes on GVF, 15 of 16 (93.7%) eyes on MP, and 11 of 16 (68.7%) eyes on full-field electroretinogram (ff-ERG). Multifocal electroretinogram (mf-ERG) and visual evoked potential (VEP) tests were performed in 14 eyes, of which 12 (85.7%) and 14 (100%) of the eyes demonstrated functional abnormalities, respectively, at baseline. Compared to all the other structural diagnostic tools, AOSLO had a better ability to demonstrate deterioration in retinal microstructures occurring at follow-ups. Functional deterioration at follow-up was detected on GVF in 8 of 10 (80%) eyes, mf-ERG in 4 of 8 (50%) eyes, and MP in 7 of 16 (43.7%) eyes. The ff-ERG and VEP were stable in the majority of cases at follow-up.CONCLUSIONS: The utilization of multimodal imaging/tests in the diagnosing and monitoring of npAIR patients can aid in identifying anomalous changes over time. Analysis of both the anatomical and functional aspects by these devices can be supportive of detecting the changes early in such patients. AOSLO shows promise as it enables the capture of high-resolution images demonstrating quantifiable changes to retinal microstructure.

  View details for DOI 10.3390/diagnostics13213376

  View details for PubMedID 37958272

• Association of oral montelukast with reduced odds of developing exudative age-related macular degeneration. Retina (Philadelphia, Pa.) Matsumiya, W., Karaca, I., Pham, B. H., Akhavanrezayat, A., Uludag, G., Yasar, C., Ghoraba, H., Mobasserian, A., Regenold, J., Halim, M. S., Sepah, Y. J., Do, D. V., Chong, V., Nguyen, Q. D. 2023

  Abstract

  This study was conducted to evaluate the association of oral montelukast, selective antagonism for cysteinyl leukotriene receptor 1, with reduced odds of exudative age-related macular degeneration (exAMD) development.This case-control study was conducted using Institutional Cohort Finder tool, and included 1913 patients with exAMD (ICD: H35.32 and 362.52) and 1913 age- and gender-matched control subjects without exAMD. Sub-analysis among 1913 exAMD and 324 non-exudative AMD was also conducted.A total of 47 (2.5%) exAMD cases were identified to have a history of oral montelukast use prior to exAMD diagnosis, compared to 84 (4.4%) controls. Montelukast usage was significantly associated with reduced odds of exAMD in the multivariable analysis (adjusted OR: 0.50, 95% CI: 0.31 - 0.80) as well as NSAID usage (adjusted OR: 0.69). Caucasian race, history of smoking, non-exudative macular degeneration in either eye were also found to have significant relationship with increased odds of exAMD. In the sub-analysis, montelukast usage showed significant association with reduced odds of developing exAMD from non-exudative AMD (adjusted OR: 0.53 95% CI: 0.29 - 0.97) as well as the presence of atopic disease (adjusted OR: 0.60).The study results suggested that oral montelukast is linked to reduced odds of exAMD development.

  View details for DOI 10.1097/IAE.0000000000003870

  View details for PubMedID 37339446

• Assessment of the relationship between presence of active retinal vasculitis and aqueous flare values using laser flare meter Tran, A., Akhavanrezayat, A., Karaca, I., Khojasteh, H., Halim, M., Uludag, G., Shin, Y., Ghoraba, H., Or, C., Hassan, M., Bromeo, A., Ongpalakorn, P., Yasar, C., Bazojoo, V., Do, D., Nguyen, Q. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053795602037

• Intravenous cyclophosphamide therapy for patients with severe ocular inflammatory diseases who failed other immunomodulatory therapies Karaca, I., Tran, E., Park, S., Khojasteh, H., Tran, A., Bromeo, A., Akhavanrezayat, A., Yavari, N., Yasar, C., Uludag, G., Shin, Y., Jison, L., Or, C., Ghoraba, H., Do, D., Nguyen, Q. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053795602200

• LIGHTSITE III 24-Month Analysis: Evaluation of Multiwavelength Photobiomodulation in Dry Age-Related Macular Degeneration Using the LumiThera Valeda Light Delivery System Munk, M., Gonzalez, V., Boyer, D., Rosen, R., Xavier, S., Hu, A., Warrow, D., Lad, E., Do, D., Schneiderman, T., Ho, A., Jaffe, G., Tedford, S., Croissant, C., Ruckert, R., Tedford, C. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023

  View details for Web of Science ID 001053795606192

• Birdshot chorioretinopathy in an HLA-A29 positive Asian patient. American journal of ophthalmology case reports Regenold, J., Ghoraba, H., Akhavanrezayat, A., Ongpalakorn, P., Bazojoo, V., Do, D. V., Nguyen, Q. D., Or, C. 2023; 29: 101802

  Abstract

  Purpose: To present a case of birdshot chorioretinopathy (BCR) in a Chinese patient with HLA-A29 positivity.Observations: A 45-year-old Chinese female presented at a tertiary Ophthalmology Clinic with complaints of frequent headaches as well as blurred vision, photophobia, and pressure in the left eye (OS). The patient had a significant ocular history of left orbital cavernous hemangioma status post lateral orbitotomy and resection. Uncorrected visual acuity was 20/20 in the right eye (OD) and 20/40 in OS (pinhole 20/30). Funduscopic examination demonstrated optic disc edema, left eye worse than right eye, and vascular tortuosity in both eyes (OU). Late phase fluorescein angiography (FA) showed extensive perivascular and optic disc leakage and peripheral capillary leakage in OU. Laboratory evaluations were positive for human leukocyte antigen-A29 (HLA-A29). The patient was started on 40 mg prednisone daily; mycophenolate mofetil 500 mg twice daily was subsequently added.At the 3-month consultation visit to the Uveitis Clinic, dilated funduscopic examination revealed 1+ vitreous cells and improved optic disc edema in OU. FA showed improved vascular and optic disc leakage in OS but worsened leakage in OD. At this point, indocyanine green angiography (ICGA) was ordered which revealed hypocyanescent lesions throughout the choroid that were centered on the optic disc, supporting and confirming the diagnosis of BCR.Conclusions and Importance: The index patient is the first reported case of BCR in an HLA-A29 positive Asian patient.

  View details for DOI 10.1016/j.ajoc.2023.101802

  View details for PubMedID 36741421

• The Patient Experience with Diabetic Retinopathy: Qualitative Analysis of Patients with Proliferative Diabetic Retinopathy. Ophthalmology and therapy Sherman, S. A., Rofail, D., Levine, A., Hartford, C. R., Baldasaro, J., Marquis, P., Rao, R., Do, D. V. 2022

  Abstract

  INTRODUCTION: Few qualitative studies have explored the patient experience of daily life with proliferative diabetic retinopathy (PDR) and associated treatments. Herein, a conceptual model was developed to comprehensively examine symptoms, functional impacts, and treatment experiences in PDR.METHODS: A qualitative, mixed-methods study comprising a literature search and semi-structured interviews with clinicians and patients was conducted. Published literature and online patient resources were searched to identify concepts relevant to patients, including symptoms, functional impacts, and treatment experiences of PDR. Semi-structured interviews with experienced clinicians were conducted to identify symptoms and impacts reported by patients with PDR and to receive feedback regarding concepts identified from the literature search. A preliminary conceptual model was then developed based on findings from the literature search and clinician interviews. Patients with PDR participated in two rounds of semi-structured interviews to identify additional concepts relevant to the patient experience in PDR and associated treatments, which informed revisions to the conceptual model. Saturation of patient interviews was assessed.RESULTS: Findings from the literature search and clinician interviews yielded 109 concepts that were included in a preliminary conceptual model with three overarching domains: symptoms, impacts, and managing the disease. Clinicians confirmed concepts identified from the literature search. During interviews, patients reported a broad spectrum of symptoms (e.g., red vision); functional impacts relating to activities of daily living (e.g., reading), emotional functioning (e.g., loss of independence), and social functioning (e.g., problems recognizing faces); and treatment experiences (e.g., improves eye problems, no change) associated with PDR. Additional concepts elicited in patient interviews informed revisions to the conceptual model. Saturation was achieved in the patient sample.CONCLUSIONS: A wide variety of symptoms, functional impacts, and treatment experiences that significantly affect health-related quality of life were identified in patients with PDR. These insights are critical for understanding PDR symptomology and assessing treatment response.

  View details for DOI 10.1007/s40123-022-00614-8

  View details for PubMedID 36460939

• Cataract Surgery in Patients With Retinitis Pigmentosa: A Systematic Review. Journal of cataract and refractive surgery Khojasteh, H., Riazi-Esfahani, H., Mirghorbani, M., Pour, E. K., Mahmoudi, A., Mahdizad, Z., Akhavanrezayat, A., Ghoraba, H., Do, D. V., Nguyen, Q. D. 2022

  Abstract

  ABSTRACT: Retinitis pigmentosa (RP) is an inherited, bilateral retinal degenerative disease with an incidence of 1 in 4000 people. RP affects more than one million individuals worldwide. Even though night blindness and restricted visual field are the most typical symptoms of these individuals, generalized vision loss due to cataracts can be expected in the latter stages of the disease. It has been demonstrated that posterior subcapsular cataract is the most prevalent cataract in younger individuals with RP, as opposed to age-related cataracts. Even though most ophthalmologists may have a negative view of cataract surgery in RP patients, it appears that it can play an important role in the visual restoration of RP patients. However, there are concerns about performing cataract surgery for RP patients. Herein, we present a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) on databases of MEDLINE and SCOPUS.

  View details for DOI 10.1097/j.jcrs.0000000000001101

  View details for PubMedID 36730350

• Wide-Field Swept-Source Optical Coherence Tomography of Optic Disc Pit Maculopathy Demonstrates Connection Between Vitreous and Subretinal Fluid OPHTHALMIC SURGERY LASERS & IMAGING RETINA Li, A. S., Korot, E., Mishra, K., Perlroth, A., Do, D. V. 2022; 53 (10): 579-581

  Abstract

  The source of subretinal or intraretinal fluid in patients with optic disc pit maculopathy (ODP-M) remains unclear and is often thought to be either vitreous or cerebrospinal fluid.1 Here, we present the case of a 40-year-old man who developed ODP-M. Further imaging with wide-field swept-source optical coherence tomography demonstrated that the macular fluid was tracking from a nasal optic disc pit with superonasal communication to the vitreous. This suggests that swept-source optical coherence tomography can be a useful tool for determining the origin of macular fluid in patients with ODP-M. [Ophthalmic Surg Lasers Imaging Retina 2022;53:579-581.].

  View details for DOI 10.3928/23258160-20220819-01

  View details for Web of Science ID 000875398000008

  View details for PubMedID 36239681

• Longitudinal Comparative Analysis of Semi-Automated Aqueous Flare Measurements with Clinical Grading and Visual Outcomes in Uveitic Eyes. Ocular immunology and inflammation Hasanreisoglu, M., Halim, M. S., Kesim, C., Doan, H. L., Tran, A. N., Nguyen, W., Besalti, Z., Lajevardi, S., Hassan, M., Akhavanrezayat, A., Ahmed, M. I., Do, D. V., Sepah, Y. J., Nguyen, Q. D. 2022: 1-6

  Abstract

  To evaluate the correlation between longitudinal changes in aqueous flare measured by laser flare photometer (LFP), best-corrected visual acuity (BCVA), and clinical grade using both Standardization of Uveitis Nomenclature (SUN) and modified SUN (MSUN) scales uveitis patients.Patients were classified according to both SUN and MSUN grading scales. LFP measurements were acquired (Kowa FM-700) at each visit. Mean change in LFP was assessed longitudinally, comparing with those in visual acuity, SUN, and MSUN grading scales.Mean change in LFP was correlated to those in BCVA (p = .018), SUN scale (p < .001), and MSUN scale (p = .008). Cases within same initial SUN (0 and 1+) and MSUN (0.5+ and 1+) grades and different longitudinal flare prognosis (decreased/unchanged/increased) had significantly different initial LFP values (all p < .05).LFP measurement is beneficial in monitoring inflammatory activity. Cases of identical clinical flare scores with different clinical prognosis may be predicted by LFP.

  View details for DOI 10.1080/09273948.2022.2123365

  View details for PubMedID 36170559

• Trends in Leadership and Award Recognition Among Women in the American Society of Retina Specialists JOURNAL OF VITREORETINAL DISEASES Reeves, M. R., Pasricha, M., Ludwig, C. A., Chandramohan, A., Azad, A. D., Li, A. S., Rosenblatt, T. R., Sears, C., Kossler, A. L., Do, D., Pan, C. K. 2022; 6 (5): 374-380

  View details for DOI 10.1177/24741264211021019

  View details for Web of Science ID 000904830400006

• Frequency and timing of antivascular endothelial growth factor treatment for eyes with centre-involved diabetic macular oedema and good vision: Protocol V results in context BMJ OPEN OPHTHALMOLOGY Do, D., Moini, H., Wykoff, C. C. 2022; 7 (1)

  View details for DOI 10.1136/bmjophth-2022-000983

  View details for Web of Science ID 000836254600001

• Port Delivery System With Ranibizumab: As Always - Risks Versus Benefits for the Recipients OPHTHALMIC SURGERY LASERS & IMAGING RETINA Ghoraba, H. H., Do, D., Quan Dong Nguyen 2022; 53 (8): 416-417

  View details for DOI 10.3928/23258160-20220713-01

  View details for Web of Science ID 000863293200001

  View details for PubMedID 35951716

• Frequency and timing of antivascular endothelial growth factor treatment for eyes with centre-involved diabetic macular oedema and good vision: Protocol V results in context. BMJ open ophthalmology Do, D. V., Moini, H., Wykoff, C. C. 2022; 7 (1)

  View details for DOI 10.1136/bmjophth-2022-000983

  View details for PubMedID 36161828

• Predicting Systemic Health Features from Retinal Fundus Images Using Transfer-Learning-Based Artificial Intelligence Models. Diagnostics (Basel, Switzerland) Khan, N. C., Perera, C., Dow, E. R., Chen, K. M., Mahajan, V. B., Mruthyunjaya, P., Do, D. V., Leng, T., Myung, D. 2022; 12 (7)

  Abstract

  While color fundus photos are used in routine clinical practice to diagnose ophthalmic conditions, evidence suggests that ocular imaging contains valuable information regarding the systemic health features of patients. These features can be identified through computer vision techniques including deep learning (DL) artificial intelligence (AI) models. We aim to construct a DL model that can predict systemic features from fundus images and to determine the optimal method of model construction for this task. Data were collected from a cohort of patients undergoing diabetic retinopathy screening between March 2020 and March 2021. Two models were created for each of 12 systemic health features based on the DenseNet201 architecture: one utilizing transfer learning with images from ImageNet and another from 35,126 fundus images. Here, 1277 fundus images were used to train the AI models. Area under the receiver operating characteristics curve (AUROC) scores were used to compare the model performance. Models utilizing the ImageNet transfer learning data were superior to those using retinal images for transfer learning (mean AUROC 0.78 vs. 0.65, p-value < 0.001). Models using ImageNet pretraining were able to predict systemic features including ethnicity (AUROC 0.93), age > 70 (AUROC 0.90), gender (AUROC 0.85), ACE inhibitor (AUROC 0.82), and ARB medication use (AUROC 0.78). We conclude that fundus images contain valuable information about the systemic characteristics of a patient. To optimize DL model performance, we recommend that even domain specific models consider using transfer learning from more generalized image sets to improve accuracy.

  View details for DOI 10.3390/diagnostics12071714

  View details for PubMedID 35885619

• Efficacy and safety of intravitreal anti-VEGF therapy in diabetic retinopathy: what we have learned and what should we learn further? Expert opinion on biological therapy Uludag, G., Hassan, M., Matsumiya, W., Pham, B. H., Chea, S., Trong Tuong Than, N., Doan, H. L., Akhavanrezayat, A., Halim, M. S., Do, D. V., Nguyen, Q. D. 2022

  Abstract

  INTRODUCTION: Diabetic retinopathy (DR) is one of the most frequent microvascular complications of diabetes that can lead to blindness. Laser treatment has been the gold standard treatment for diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR) for many years. Recently, the role of vascular endothelial growth factor (VEGF) has been established in the pathogenesis of DR, and the use of intravitreal anti-VEGF therapy has gained popularity for the management of DR.AREAS COVERED: This review includes a brief overview of the efficacy and safety of currently available (bevacizumab, ranibizumab and aflibercept) and potential future (brolucizumab, faricimab, and KSI-301) anti-VEGF agents in patients with DR based mainly on publicly available data from phase 1, 2 and 3 clinical trials.EXPERT OPINION: Clinical trials investigating the efficacy of intravitreal bevacizumab, ranibizumab, and aflibercept injections demonstrated favorable functional and anatomical outcomes in patients with DME. Moreover, the use of these anti-VEGF agents showed a significant improvement in the severity of DR in patients with non-proliferative diabetic retinopathy (NPDR) and PDR. Recent clinical research for future anti-VEGF molecules aims to provide higher target-protein binding affinity and prolonged therapeutic effect. Brolucizumab, faricimab, and KSI-301 are three novel anti-VEGF agents that demonstrate promising data for the management of DME and potentially DR.

  View details for DOI 10.1080/14712598.2022.2100694

  View details for PubMedID 35818801

• Trends in Leadership and Award Recognition Among Women in the American Society of Retina Specialists. Journal of vitreoretinal diseases Reeves, M. R., Pasricha, M. V., Ludwig, C. A., Chandramohan, A., Azad, A. D., Li, A. S., Rosenblatt, T. R., Sears, C. M., Kossler, A. L., Do, D. V., Pan, C. K. 2022; 6 (5): 374-380

  Abstract

  This work evaluates trends in achievement of women in the retina field, through an analysis of gender representation in the American Society of Retina Specialists (ASRS).This retrospective, longitudinal study spans 1983 to 2020. Historical data classified by male or female gender were collected from ASRS's overall membership, board of directors and officers, and recipients of the 4 society awards. The proportion of each benchmark held by women was compared with prior decades since the founding of ASRS using the Fisher's exact test.Women's representation increased from 11% of ASRS members in 2007 to 19.7% in 2020. From 2010 to 2019, women received a higher proportion of society awards (21.1%) compared with membership prior to the start of that decade. In 2020, women were proportionally well represented in board of director positions (21.9%) and held a significantly higher proportion of board positions than in the period 1983 to 1989 (P = .02). From 1983 to 2020, women held 4.3% (1 of 23) of presidencies.Although the number of women in retina is increasing, women remain underrepresented in the leadership of ASRS. Interventions to increase exposure to female mentorship and improve childcare benefits are warranted to engage female ophthalmology trainees in retina and ultimately society leadership.

  View details for DOI 10.1177/24741264211021019

  View details for PubMedID 37006904

  View details for PubMedCentralID PMC9954927

• Quality, Readability, and Accessibility of Online Content From a Google Search of "Macular Degeneration": Critical Analysis. Journal of vitreoretinal diseases Hua, H. U., Rayess, N., Li, A. S., Do, D., Rahimy, E. 2022; 6 (6): 437-442

  Abstract

  This work aims to assess the quality, accountability, readability, accessibility, and presence of Spanish translation in online material through a Google search of "macular degeneration".In this retrospective cross-sectional analysis of website results from a Google search of "macular degeneration", the quality and accountability for each website were assessed using the DISCERN criteria and the Health on the Net Foundation Code of Conduct (HONcode) principles. All 31 sites were independently graded by 2 ophthalmologists. Readability was evaluated using an online tool. The presence of accessibility features on the website and Spanish translation was recorded. The primary outcome measure was the DISCERN and HONcode quality and accountability scores of each website. Secondary outcome measures included the readability, accessibility, and presence of Spanish translation.The mean ± SD of each criterion across all 15 DISCERN questions was 2.761 ± 0.666 (out of 5). The mean HONcode score for all websites was 7.355 ± 3.123. The mean consensus reading grade level was 10.258 ± 2.49. There were no statistically significant differences in any score between the top 5 websites and the bottom 26 websites evaluated. Accessibility was available on 10 of 31 websites. Spanish translation was available on 10 of 31 websites.The top 5 websites that appeared on a Google search did not have better quality or readability of online content. Improving quality, accountability, and readability can help improve patients' health literacy regarding macular degeneration.

  View details for DOI 10.1177/24741264221094683

  View details for PubMedID 37009540

  View details for PubMedCentralID PMC9954772

• Proliferative Diabetic Retinopathy Events in Patients With Diabetic Macular Edema: Post Hoc Analysis of VISTA and VIVID Trials. Journal of vitreoretinal diseases Do, D. V., Gordon, C., Suñer, I. J., Reed, K., Moini, H., Gibson, A., Du, W., Shah, C. P. 2022; 6 (4): 295-301

  Abstract

  This work aimed to assess the incidence of proliferative diabetic retinopathy (PDR) events and improvement to mild non-PDR (NPDR) or better after intravitreal aflibercept injection (IAI) or laser treatment (control) in diabetic macular edema (DME).PDR events in the VISTA (NCT01363440) and VIVID (NCT01331681) phase 3 clinical trials were evaluated in a combined IAI-treated group (IAI 2 mg every 4 weeks or 2 mg every 8 weeks after 5 initial monthly doses; n = 475) and a macular laser control group (n = 235) through week 100 in eyes without PDR at baseline (Diabetic Retinopathy Severity Scale [DRSS] score ≤ 53). Improvement in the DRSS score to 35 or better was evaluated in those with a baseline DRSS score of 43 or greater.A lower proportion of eyes in the IAI group than in the laser group developed a PDR event through week 100 (4.4% vs 11.1%; adjusted difference, -6.7%; 97.5% CI, -11.7 to -1.6; nominal P = .0008). All PDR events occurred in eyes with a baseline DRSS score of 43, 47, or 53 and not in those with a score of 35 or less. A greater proportion of eyes in the IAI group than in the control group achieved a DRSS score of 35 or less (20.0% vs 3.8%; nominal P < .0001).Fewer eyes with NPDR and DME treated with IAI than eyes treated with a laser had a PDR event. More eyes treated with IAI improved to mild NPDR or better (DRSS score ≤ 35) through 100 weeks.

  View details for DOI 10.1177/24741264221093914

  View details for PubMedID 37007930

  View details for PubMedCentralID PMC9976032

• Integration of Artificial Intelligence into a Telemedicine-Based Diabetic Retinopathy Screening Program Chen, K., Dow, E. R., Khan, N. C., Levine, M., Perera, C., Phadke, A., Dang, J., Weng, K., Do, D. V., Mahajan, V. B., Mruthyunjaya, P., Mishra, K., Leng, T., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401304101

• Efficacy, durability and safety of KSI-301 antibody biopolymer conjugate in wet AMD - Year 1 primary endpoint results from the pivotal DAZZLE study Regillo, C., Ehrlich, J. S., Janer, D., Do, D. V., Velazquez-Martin, P., Zawadzki, R., Perlroth, V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844437002173

• Novel retinopathy in pediatric retinal vasculitis: long term follow up Yasar, C., Ghoraba, H., Regenold, J., Or, C., Halim, M., Uludag, G., Hwang, J., Karaca, I., Mobasserian, A., Akhavanrezayat, A., Yasar, M., Khojasteh, H., Sepah, Y. J., Do, D. V., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844437001051

• Efficacy of infliximab and tocilizumab in non-infectious retinal vasculitis: 12-month outcomes Karaca, I., Ghoraba, H., Hwang, J., Or, C., Matsumiya, W., Uludag, G., Zaidi, M., Regenold, J., Khojasteh, H., Mobasserian, A., Park, S., Than, N., Yavari, N., Bazojoo, V., Do, D. V., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844437002245

• Correlation between Diopsys (R) NOVA fixed-luminance flicker phase and Diagnosys (R) flicker implicit time Regenold, J., Ghoraba, H., Hien Luong Doan, Zaidi, M., Hwang, J., Or, C., Karaca, I., Akhavanrezayat, A., Ngoc Than, Yasar, C., Yavari, N., Park, S., Khan, Y., Mobasserian, A., Do, D. V., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401302077

• Flicker ERG findings in posterior uveitis Than, N., Doan, H., Pham, B., Hwang, J., Regenold, J., Zaidi, M., Khan, Y., Matsumiya, W., Park, S., Ghoraba, H., Or, C., Uludag, G., Mobasserian, A., Akhavanrezayat, A., Do, D. V., Nguyen, Q. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401301053

• Visual Outcomes post-PPV for Tractional Retinal Detachment or Vitreous Hemorrhage in the Intelligent Research in Sight (IRIS) Registry Perlroth, A., Brant, A., Pershing, S., Mishra, K., Bair, H., Xu, C., Do, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401301248

• Trends for Proliferative Diabetic Retinopathy Vitrectomy Treatments in the IRIS (R) Registry (Intelligent Research in Sight) Xu, C. L., Brant, A., Pershing, S., Mishra, K., Perlroth, A., Bair, H., Do, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401306238

• Newly Diagnosed Central Serous Chorioretinopathy: Demographics and Epidemiology from the IRIS (R) Registry (Intelligent Research in Sight) Mishra, K., Brant, A., Pershing, S., Perlroth, A., Bair, H., Xu, C., Do, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844437000229

• Progression and Regression of Diabetic Retinopathy in the IRIS (R) Registry (Intelligent Research in Sight) Brant, A., Mishra, K., Perlroth, A., Bair, H., Xu, C., Pershing, S., Do, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401306218

• Predicting systemic health features from retinal fundus images using transfer-learning based AI models Khan, N. C., Perera, C., Dow, E. R., Leng, T., Mahajan, V. B., Mruthyunjaya, P., Do, D. V., Myung, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844437002058

• Trends of PRP and Anti-VEGF for NPDR in the IRIS (R) Registry (Intelligent Research in Sight), 2016-2018 Bair, H., Brant, A., Pershing, S., Mishra, K., Perlroth, A., Xu, C., Do, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401306239

• Representation of Women in Ophthalmology Subspecialty Societies over 20 OPHTHALMOLOGY Azad, A. D., Chandramohan, A., Li, A. S., Rosenblatt, T. R., Reeves, M. R., Veerappan-Pasricha, M., Ludwig, C. A., Nguyen, A., Winges, K. M., Wang, S. Y., Pan, C. K., Moss, H. E., Do, D. V., Fountain, T. R., Kossler, A. L. 2022; 129 (5): 587-590

  View details for Web of Science ID 000791327000022

• Utilisation of composite endpoint outcome to assess efficacy of tocilizumab for non-infectious uveitis in the STOP-Uveitis Study. The British journal of ophthalmology Hassan, M., Sadiq, M. A., Ormaechea, M. S., Uludag, G., Halim, M. S., Afridi, R., Do, D. V., Sepah, Y. J., Nguyen, Q. D. 2022

  Abstract

  BACKGROUND/AIMS: To use a composite endpoint scoring system in assessing efficacy of two doses of intravenous tocilizumab (TCZ), in eyes with non-infectious uveitis.METHODS: Data from STOP-Uveitis Study (a phase 2 multicentre, randomised, interventional clinical trial), where monthly intravenous infusions of 4 mg/kg (Group 1) or 8 mg/kg (Group 2) TCZ until month 6 (M6) were administered, were used. Efficacy was ascertained by a composite endpoint scoring system consisting of: (1) visual acuity; (2) intraocular inflammation; (3) central retinal thickness; (4) posterior segment inflammation on fluorescein angiographic and (5) steroid taper. Each component of grading system was graded as ((+1) improvement, (-1) worsening or (0) no change) based on specific criteria. The clinical response was classified as positive (improvement in at least one parameter and worsening in none), negative (worsening of any parameter) or stable (neither improvement nor worsening of any parameter). The percentage achieving various clinical responses was compared between groups.RESULTS: Thirty-seven patients were analysed. At M6, 31 (83.8%) subjects demonstrated a positive clinical response (Group 1=14 (77.8%) and Group 2=17 (89.5%)). Three (8.1%) subjects (all Group 1) met the criteria for treatment failure, whereas three (8.1%) subjects showed a stable clinical response (Group 1=1and Group 2=2). The difference in clinical responses between study groups was not significant (p>0.05).CONCLUSIONS: Both doses of intravenous TCZ were effective in either improving or maintaining stability in patients using the composite endpoint scoring system. A composite scoring system as used in this study may be a better measure to assess efficacy outcomes as compared with only vitreous haze or other single outcome measures.

  View details for DOI 10.1136/bjophthalmol-2021-320604

  View details for PubMedID 35379598

• Correlation of Clinical Aqueous Flare Grading to Semi-Automated Flare Measurements Using Laser Flare Photometry. Ocular immunology and inflammation Halim, M. S., Hasanreisoglu, M., Onghanseng, N., Tran, A. N., Hassan, M., Yilmaz, M., Segawa, A., Gurelik, G., Afridi, R., Ormaechea, M. S., Uludag, G., Kesim, C., Nguyen, N. V., Bae, J. H., Park, J. H., Do, D. V., Ibrahim, M. A., Sepah, Y. J., Nguyen, Q. D. 1800: 1-7

  Abstract

  PURPOSE: To compare laser flare photometry (LFP) measurements of aqueous flare with Standardization of Uveitis Nomenclature (SUN) and modified SUN grading.METHODS: In this prospective study with multicenter design, uveitis patients were classified according to SUN and modified SUN grading scales. LFP was performed with Kowa FM-700 flaremeter. Mean LFP values were compared with SUN and MSUN scores.RESULTS: The study included 475 LFP measurements, of which 216, 48, 150, 31, 28 and 2 had 0, 0.5+, 1+, 1.5+, 2+and 3+flare, respectively. LFP values were significantly different between each two consecutive steps for both clinical gradings (all P <.05). Cut-off values for modified SUN grading steps were defined as 5.7, 9.7, 15.7 and 43.2 for 0/0.5+, 0.5+/ 1+, 1+/1.5+and 1.5/2+borders of clinical flare, respectively.CONCLUSIONS: LFP proves to be an objective measurement in analyzing aqueous flare comparable to both SUN and MSUN clinical grading systems.

  View details for DOI 10.1080/09273948.2021.1971723

  View details for PubMedID 35081012

• Safety of Intravenous Methylprednisolone in Refractory and Severe Pediatric Uveitis. Clinical ophthalmology (Auckland, N.Z.) Ghoraba, H. H., Matsumiya, W., Khojasteh, H., Akhavanrezayat, A., Karaca, I., Or, C., Yavari, N., Lajevardi, S., Hwang, J., Yasar, C., Do, D., Nguyen, Q. D. 2022; 16: 1697-1706

  Abstract

  Purpose: To evaluate the safety of intravenous high-dose pulse methylprednisolone succinate (IVHDM) in the management of severe or refractory non-infectious pediatric uveitis.Methods: We reviewed all uveitis patients who were ≤16 years of age and who received IVHDM with a dose of ≥500 mg per day (1-3 days a month) for at least 3 months during their management at a tertiary care eye hospital.Results: Twenty pediatric patients with severe or refractory uveitis who received IVHDM were identified. Six patients received IVHDM either once, as a preoperative medication, or at a lower dose than 500 mg, and were excluded. The remaining 14 patients received IVHDM for at least 4 months. Age (mean±SD) was 11.9±2.4 years and 50% were female. Duration of treatment was 14.2±7.5 months. Thirteen patients received IVHDM in combination with other immunomodulatory therapy (IMT). Except for two outliers, IVHDM was given at a dose of 8-25 mg/kg per infusion. Three major adverse events (AEs) occurred in two patients: a single episode of bradycardia, compression fracture following minor trauma and adrenal insufficiency. The number of AEs (major and minor) strongly correlated with duration of treatment (p=0.004) and moderately correlated with the cumulative dose/weight (p=0.051). Weight gain was associated with the use of concomitant oral steroids and not with duration of treatment or cumulative dose.Conclusion: IVHDM may be a valid therapeutic option for aggressive/refractory pediatric uveitis. The reported AEs in this series can also be attributed to the concurrent IMT or the underlying disease itself.

  View details for DOI 10.2147/OPTH.S366370

  View details for PubMedID 35673349

• Effect of Pupil Size on Fixed-Luminance Flicker Full-Field Electroretinogram Magnitude. Clinical ophthalmology (Auckland, N.Z.) Mobasserian, A., Zaidi, M., Halim, S., Hwang, J. J., Regenold, J., Akhavanrezayat, A., Karaca, I., Khojasteh Jafari, H., Yavari, N., Matsumiya, W., Yasar, C., Than, N. T., Uludag, G., Do, D., Ghoraba, H., Nguyen, Q. D. 2022; 16: 3733-3740

  Abstract

  Purpose: Diopsys NOVA fixed-luminance flicker full-field electroretinogram (ffERG) device is a potential adjunct to conventional flicker ffERG testing for assessing cone cell function. Magnitude of measured electrical response is known to vary with pupil size in conventional ffERG testing. The index study characterizes the relationship between magnitude of measured electrical activity and pupil size, both pupil diameter and pupil area, for this device.Methods: Seventeen patients (34 eyes) with no known ocular diseases were enrolled in the study. Electrophysiologic function of cone cells was evaluated using fixed-luminance flicker ffERG before and after dilation. Linear regression models, with inter-eye correlations controlled as fixed-effects, were used to characterize the effect of pupil dilation on the magnitude of the measured responses.Results: Mean age of study patients was 33.5 (standard deviation 7.4 years), and 35.3% of the subjects were female. Mean value of electrical response magnitude was 10.07±2.79V before dilation and 15.30±4.08V after dilation. The correlations of ERG magnitude with pupil diameter and with pupil area were not significant for either dilated or undilated eyes considered separately but were highly significant (p<0.001) for dilated and undilated eyes considered in aggregate. ERG magnitude tended to increase by 1.08 V for every 1 mm increase in pupillary diameter.Conclusion: An increase in pupil size, both pupil diameter and pupil area, is significantly associated with an increase in flicker ffERG magnitude recorded by the Diopsys device, suggesting that pupil size should be measured and considered when making clinical judgments based on the flicker ffERGs recorded by the device, and that pupil size-specific reference ranges could improve the clinical utility of the device.

  View details for DOI 10.2147/OPTH.S382207

  View details for PubMedID 36389637

• Ocular Gene Therapy: A Literature Review with Special Focus on Immune and Inflammatory Responses. Clinical ophthalmology (Auckland, N.Z.) Ghoraba, H. H., Akhavanrezayat, A., Karaca, I., Yavari, N., Lajevardi, S., Hwang, J., Regenold, J., Matsumiya, W., Pham, B., Zaidi, M., Mobasserian, A., DongChau, A. T., Or, C., Yasar, C., Mishra, K., Do, D., Nguyen, Q. D. 2022; 16: 1753-1771

  Abstract

  Gene therapy has emerged as a research topic of choice in recent years. The eye in particular is one of few organs of the body for which gene therapy has received Food and Drug Administration approval, and it remains a field of great interest for gene therapy development. However, its associated immune and inflammatory reactions may render the treatment ineffective or harmful, which are of particular concern for the eyes due to their susceptibility to inflammation. The severity of immune and inflammatory reactions depends on the choice of vector and its route of administration. Furthermore, most preclinical and clinical studies have shown that the dose of vectors is correlated with the degree of humoral response and ocular inflammation. The route of administration directly impacts the degree of immune and inflammatory reaction. Subretinal delivery produces a weaker humoral response than the intravitreal route. However, some studies have demonstrated that the subretinal delivery induces a stronger inflammatory reaction. On the other hand, several instances of vision loss due to severe late onset intraocular inflammation were reported in a clinical trial involving intravitreal delivery of viral vectors. When compared with the intravitreal route, suprachoroidal gene delivery has been shown to produce weaker humoral response. However, unlike the subretinal space, the suprachoroidal space is not known to have immune privilege status. Inflammatory reactions following ocular gene therapy are typically mild and most clinical and preclinical studies have shown that they can be controlled with topical, local or systemic steroids. However, severe inflammatory responses may occur and require aggressive management to avoid permanent vision loss. Further investigations are required to elucidate and expand our knowledge of inflammatory reactions, and their optimal management, following ocular gene therapy.

  View details for DOI 10.2147/OPTH.S364200

  View details for PubMedID 35685379

• Representation of Women in Ophthalmology Subspecialty Societies over 20 Years. Ophthalmology Azad, A. D., Chandramohan, A., Li, A. S., Rosenblatt, T. R., Reeves, M. R., Pasricha, M. V., Ludwig, C. A., Nguyen, A., Winges, K. M., Wang, S. Y., Pan, C. K., Moss, H. E., Do, D. V., Fountain, T. R., Kossler, A. L. 1800

  Abstract

  The representation of women has increased over the last 20 years among ophthalmology subspecialty society new membership, award winners, and executive committee membership; however, proportional representation is still lacking at most benchmarks.

  View details for DOI 10.1016/j.ophtha.2021.12.011

  View details for PubMedID 34958831

• Serous retinal detachment as a presenting sign of acute lymphoblastic leukemia: A case report and literature review. American journal of ophthalmology case reports Veerappan Pasricha, M., Callaway, N. F., Nguyen, Q. D., Do, D. V. 2021; 23: 101142

  Abstract

  Purpose: To describe a unique case of unilateral serous retinal detachment as the presenting sign of B-cell acute lymphoblastic leukemia (ALL).Observations: A 74 year old woman presented with right eye blurry vision and was found to have an underlying serous retinal detachment, along with cotton wool spots, inner retinal hemorrhages, and retinal pigment epithelial changes throughout her bilateral fundi. Fluorescein angiography demonstrated bilateral vasculitis and ultrasonography revealed asymmetric thickening and enhancement of the affected eyes' choroid. This prompted a systemic lab workup and results were suspicious for an underlying hematologic malignancy. The patient was admitted to the hospital for bone marrow biopsy confirming B-cell ALL, underwent intensive intravenous and intrathecal chemotherapy, and was discharged one month later. Follow up appointment in the ophthalmology clinic demonstrated functional and anatomic improvement in the serous retinal detachment and choroidal thickening suggestive of infiltration in her right eye.Conclusions: SRDs are an uncommon ocular manifestation of leukemia, and even less common as a presenting sign of the disease. A comprehensive literature review demonstrated 11 other cases reported worldwide. We present the first such case with additional findings of leukemic retinopathy, optic nerve and choroidal infiltration, and vasculitis, as well as a complete library of ophthalmic imaging from the patient's initial presentation.Importance: A new diagnosis of serous retinal detachment(s) without any obvious cause should raise suspicion for leukemia and prompt further workup. Early recognition of this hematologic malignancy is crucial for prompt initiation of life-saving therapy.

  View details for DOI 10.1016/j.ajoc.2021.101142

  View details for PubMedID 34222714

• Altered patient demography and increased complexity of ICD coding in uveitis over 10 years Hwang, J., Halim, M., Uludag, G., Yasar, C., Ghoraba, H., Pham, B., Lajevardi, S., Lam, B., Regenold, J., Bazojoo, V., Karaca, I., Mobasserian, A., Do, D. V., Sepah, Y. J., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690761100498

• Effect of pupil size on fixed-luminance flicker full-field electroretinogram magnitude Mobasserian, A., Halim, M., Hwang, J., Regenold, J., Akhavanrezayat, A., Ghoraba, H., Matsumiya, W., Yavari, N., Karaca, I., Yasar, C., Lajevardi, S., Pham, B., Do, D., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690760500607

• The Impact of the COVID-19 Pandemic on Intravitreal Bevacizumab Use Perlroth, A., Mishra, K., Do, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690760500301

• Evaluation of correlation between Diopsys (R) NOVA fixed-luminance flicker electroretinography and Diagnosys (R) full-fi eldelectroretinography Regenold, J., Hien Luong Doan, Akhavanrezayat, A., Halim, M., Mobasserian, A., Hwang, J., Yavari, N., Bazojoo, V., Matsumiya, W., Karaca, I., Pham, B., Lam, B., Khojasteh, H., Lajevardi, S., Do, D., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690760500611

• Correlation between photoreceptor density in adaptive optics imaging with retinal structure and sensitivity in autoimmune retinopathy Matsumiya, W., Akhavanrezayat, A., Uludag, G., Yasar, C., Ghoraba, H., Mobasserian, A., Karaca, I., Lam, B., Pham, B., Hwang, J., Afridi, R., Halim, M., Do, D., Sepah, Y., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690760500009

• Association of oral montelukast with reduced odds of developing neovascular age-related macular degeneration Karaca, I., Matsumiya, W., Akhavanrezayat, A., Uludag, G., Yasar, C., Mobasserian, A., Hwang, J., Lajevardi, S., Lam, B., Afridi, R., Do, D., Sepah, Y., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690760500276

• Efficacy and safety of tocilizumab in the management of non-infectious retinal vasculitis Uludag, G., Halim, M., Akhavanrezayat, A., Matsumiya, W., Yasar, C., Pham, B., Hwang, J., Lajevardi, S., Lam, B., Karaca, I., Mobasserian, A., Regenold, J., Do, D. V., Sepah, Y. J., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690761100503

• Structural and functional changes in non-paraneoplastic autoimmune retinopathy Akhavanrezayat, A., Onghanseng, N. L., Halim, M., Uludag, G., Ghoraba, H., Matsumiya, W., Pham, B., Mobasserian, A., Regenold, J., Yasar, C., Karaca, I., Bazojoo, V., Lajevardi, S., Do, D. V., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690761100493

• Safety of intravenous high-dose pulse methylprednisolone succinate in the management of pediatric uveitis Ghoraba, H., Akhavanrezayat, A., Matsumiya, W., Pham, B., Yasar, C., Karaca, I., Mobasserian, A., Regenold, J., Lam, B., Hwang, J., Lajevardi, S., Yavari, N., Halim, M., Sepah, Y. J., Do, D. V., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690761100497

• The Impact of the COVID-19 Pandemic on Aflibercept and Ranibizumab Anti-VEGF Injections Mishra, K., Al Moujahed, A., Sanislo, S., Do, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690761400135

• Retinal Fluid and Thickness as Measures of Disease Activity in Neovascular Age-Related Macular Degeneration. Retina (Philadelphia, Pa.) Kaiser, P. K., Wykoff, C. C., Singh, R. P., Khanani, A. M., Do, D. V., Patel, H., Patel, N. 2021

  Abstract

  PURPOSE: Retinal fluid and thickness are important anatomical features of disease activity in neovascular age-related macular degeneration (nAMD), as evidenced by clinical trials that have used these features for inclusion criteria, re-treatment criteria, and outcome measures of the efficacy of intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents. Methods: A literature review of anatomical measures of disease activity was conducted.RESULTS: Treatment goals for nAMD include improving/maintaining vision by drying the retina, and several analyses have evaluated the relationship between visual function and anatomy. Change in retinal thickness has been found to correlate with change in visual acuity, and variation in retinal thickness may predict visual acuity outcomes. In addition, specific fluid compartments may have different prognostic values. For example, the presence of intraretinal fluid has been associated with poorer visual acuity while the presence of subretinal fluid has been associated with better visual acuity. Retinal fluid and thickness are important for selecting dosing interval durations in clinical trials and clinical practice.CONCLUSIONS: Retinal thickness and retinal fluid are common anatomical measures of disease activity in nAMD. Further research is required to fully elucidate the relationship between anatomical features and visual outcomes in nAMD.

  View details for DOI 10.1097/IAE.0000000000003194

  View details for PubMedID 33949342

• Current concepts in the diagnosis and management of antiphospholipid syndrome and ocular manifestations. Journal of ophthalmic inflammation and infection Uludag, G., Onghanseng, N., Tran, A. N., Hassan, M., Halim, M. S., Sepah, Y. J., Do, D. V., Nguyen, Q. D. 2021; 11 (1): 11

  Abstract

  Antiphospholipid syndrome (APS) is an autoimmune disorder associated with obstetrical complications, thrombotic complications involving both arteries and veins, and non-thrombotic manifestations affecting multiple other systems presenting in various clinical forms. Diagnosis requires the presence of antiphospholipid antibodies. The exact pathogenesis of APS is not fully known. However, it has recently been shown that activation of different types of cells by antiphospholipid antibodies plays an important role in thrombosis formation. Ocular involvement is one of the important clinical manifestations of APS and can vary in presentations. Therefore, as an ophthalmologist, it is crucial to be familiar with the ocular findings of APS to prevent further complications that can develop. Furthermore, the ongoing identification of new and specific factors contributing to the pathogenesis of APS may provide new therapeutic options in the management of the disease in the future.

  View details for DOI 10.1186/s12348-021-00240-8

  View details for PubMedID 33834305

• Racial Differences in Anti-VEGF Intravitreal Injections Among Commercially Insured Beneficiaries OPHTHALMIC SURGERY LASERS & IMAGING RETINA Al-Moujahed, A., Vail, D., Do, D. 2021; 52 (4): 208-+

  View details for DOI 10.3928/23258160-20210330-05

  View details for Web of Science ID 000641744800005

• Differences in the characteristics of subjects achieving complete, partial, or no resolution of macular edema in the READ-3 study. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie Halim, M. S., Afridi, R., Hasanreisoglu, M., Hassan, M., Ibrahim-Ahmed, M., Do, D. V., Sepah, Y. J., READ-3 Investigators 2021

  Abstract

  PURPOSE: To identify baseline characteristics of subjects enrolled in the READ-3 study that would predict the response of macular edema to ranibizumab (RBZ) therapy at year 1.METHODS: In this post hoc analysis of the READ-3 randomized, multicenter phase 2 clinical trial, subjects with diabetic macular edema (DME) were randomized to receive monthly intravitreal injections of RBZ (0.5 or 2.0 mg) for 6 consecutive injections followed by as-needed treatments based on pre-defined retreatment criteria. In this sub-study, subjects were divided into three groups (persistent, rebound, and resolved) based on edema status at month 12 (M12). Multi-logistic regression was utilized to assess the probability of edema outcomes M12, based on the baseline characteristics.RESULTS: One hundred twenty-three out of 152 subjects were analyzed for this sub-study. A significant difference was observed in the baseline (BL) central subfield thickness (CST) among the study groups (p < 0.05). BL CST was a significant predictor for edema outcome at M12 with > 80% probability of the subject having persistent edema if BL CST was > 570 mum (p < 0.05). This association persisted when controlled for the dose of RBZ (relative risk (RR), 1.007; p < 0.05). BL CST was also a significant predictor for having persistent edema at M12 in subjects without vitreomacular adhesion (VMA) (> 80% probability of edema persistence at CST > 570 mum [RR, 1.006; p < 0.05]). However, in the presence of VMA, BL CST was no longer a significant predictor of having persistent edema at month 12 (RR, 1.005; p > 0.05).CONCLUSIONS: Subjects with high CST (> 570 mum) at baseline may not benefit from repeated intravitreal injections of anti-VEGF for resolution of edema.

  View details for DOI 10.1007/s00417-021-05148-6

  View details for PubMedID 33792788

• Successful interventions to improve efficiency and reduce patient visit duration in a retina practice. Retina (Philadelphia, Pa.) Lin, C. C., Li, A. S., Ma, H., Lin, X., Olivares, M. Z., Haubrich, A., Sanislo, S., Do, D. V. 2021

  Abstract

  PURPOSE: To reduce the total clinic visit duration among retina providers in an academic ophthalmology department.METHODS: All patient encounters across all providers in the department were analyzed to determine baseline clinic visit duration time, defined as the elapsed time between appointment time and checkout. To increase photography capacity, a major bottleneck identified through root cause analysis, four interventions were implemented: training ophthalmic technicians to perform fundus photography in addition to OCTs, relocating photography equipment to be adjacent to exam rooms, procuring three additional Optos widefield retinal photography units, and shifting staff schedules to better align with that of the providers. These interventions were implemented in the clinics of two retina providers.RESULTS: The average baseline visit duration for all patients across all providers was 87 minutes (19550 patient visits). The prior the average visit duration was 80 minutes for provider 1 (557 patient visits) and 81 minutes for provider 2 (1246 patient visits). In the four weeks after interventions were implemented, the average visit duration decreased to 60 minutes for provider 1 and 57 minutes for provider 2.CONCLUSIONS: A systematic approach and a multi-disciplinary team resulted in targeted, cost-effective interventions that reduced total visit durations.

  View details for DOI 10.1097/IAE.0000000000003169

  View details for PubMedID 33758134

• Comparison of short-pulse subthreshold (532nm) and infrared micropulse (810nm) macular laser for diabetic macular edema. Scientific reports Al-Barki, A., Al-Hijji, L., High, R., Schatz, P., Do, D., Nguyen, Q. D., Luttrull, J. K., Kozak, I. 2021; 11 (1): 14

  Abstract

  The purpose of the study was to assess both anatomic and functional outcomes between short-pulse continuous wavelength and infrared micropulse lasers in the treatment of DME. This was a prospective interventional study from tertiary care eye hospital-King Khaled Eye Specialist Hospital (Riyadh, Saudi Arabia). Patients with center-involving diabetic macular edema were treated with subthreshold laser therapy. Patients in the micropulse group were treated with the 810-nm diode micropulse scanning laser TxCell (IRIDEX Corporation, Mountain View, CA, USA) (subthreshold micropulse-STMP group). Laser was applied according to recommendations for MicroPulse (125 microns spot size, 300ms pulse duration and power adjustment following barely visible testing burn) in a confluent mode (low intensity/high density) to the entire area of the macular edema. Patients in the short-pulse group were treated with grid pattern laser with 20ms pulse PASCAL laser 532nm (TopCon Medical Laser Systems, Tokyo, Japan) with EndPoint algorithm, which was either 30% or 50% of testing burn (EndPoint 30% and EndPoint 50% groups, respectively). Main outcome measures included best-corrected visual acuity (BCVA in logMAR) and foveal thickness at baseline and the last follow-up visit at 6months. There were 44 eyes in the micropulse group, 54 eyes in the EndPoint 50% group and 18 eyes in the EndPoint 30% group. BCVA for the whole cohort (logMAR) was 0.451 (Snellen equivalent 20/56) at baseline, 0.495 (Snellen equivalent 20/62) (p=0.053) at 3months, and 0.494 (Snellen equivalent 20/62) at the last follow-up (p=0.052). Foveal thickness for the whole cohort was 378.2±51.7 microns at baseline, 347.2±61.3 microns (p=0.002) at 3months, and 346.0±24.6 microns at the final follow-up (p=0.027). As such the short-pulse system yields more temporary reduction in edema. Comparison of BCVA between baseline and 6months for EndPoint 30%, EndPoint 50% and STMP groups was p=0.88, p=0.76 and p=0.003, respectively. Comparison of foveal thickness between baseline and 6months for EndPoint 30%, EndPoint 50% and STMP groups was p=0.38, p=0.22 and p=0.14, respectively. We conclude that the infrared micropulse system seems to improve functional outcomes. When applied according to previously published reports, short-pulse system may yield more temporary reduction in edema while infrared micropulse system may yield slightly better functional outcomes.

  View details for DOI 10.1038/s41598-020-79699-9

  View details for PubMedID 33420100

• Retraction Note to: Pharmacological agents in development for diabetic macular edema. International journal of retina and vitreous Sadiq, M. A., Halim, M. S., Hassan, M. M., Onghanseng, N., Karaca, I., Agarwal, A., Afridi, R., Sepah, Y. J., Do, D. V., Nguyen, Q. D. 2020; 6 (1): 65

  View details for DOI 10.1186/s40942-020-00271-8

  View details for PubMedID 33372631

• Drs. Carter and Do reply. The Journal of rheumatology Carter, K. L., Do, D. V. 2020

  Abstract

  We thank Dr. Martin-Iglesias, et al for their comments1 on our recent case report published in The Journal 2 We reported on a case of hydroxychloroquine (HCQ) retinopathy, and showcased the characteristic optical coherence tomography (OCT) and fundus autofluorescence imaging findings in a patient who had been taking approximately 13.6 mg/kg/day for 8 years, almost triple the recommended dose.

  View details for DOI 10.3899/jrheum.200913

  View details for PubMedID 33262299

• Effect of Fundus Fluorescein Angiography on Semiautomated Aqueous Flare Measurements. Ocular immunology and inflammation Halim, M. S., Onghanseng, N., Park, J. H., Yilmaz, M., Segawa, A., Ertop, M., Hassan, M., Tran, A. N., Aktas, Z., Ozdek, S., Gurelik, G., Do, D. V., Sepah, Y. J., Nguyen, Q. D., Hasanreisoglu, M. 2020: 1–4

  Abstract

  PURPOSE: To evaluate the effects of fluorescein fundus angiography (FFA) on semiautomated aqueous flare measurements.METHODS: Laser flare photometer (LFP) measurements was performed at baseline, 30min, and 4h after the intravenous administration of sodium fluorescein dye. FFA was performed immediately after the baseline LFP measurement. LFP values at 30min and 4h after FFA were compared to baseline values. Mean change in LFP measurements at 30min and 4hafter baseline was compared between FFA arm and controls.RESULTS: The mean flare measurement in the FFA and control arm dropped 6% (p value=0.002) and 9% (p value=0.04), respectively. Mean change in LFP measurement at 30min and 4h after baseline was not significant between FFA arm and controls.CONCLUSIONS: Administration of fluorescein dye does not increase LFP values. The decrease in the LFP measurement following FFA may be attributed to dilation drops.

  View details for DOI 10.1080/09273948.2020.1799036

  View details for PubMedID 32966150

• Anti-VEGF agents in the management of diabetic macular edema EXPERT REVIEW OF OPHTHALMOLOGY Li, A. S., Veerappan, M., Mittal, V., Do, D. 2020; 15 (5): 285–95

  View details for DOI 10.1080/17469899.2020.1806713

  View details for Web of Science ID 000576527200005

• Yet another case of ocular sarcoidosis. American journal of ophthalmology case reports Hien, D. L., Onghanseng, N., Ngoc, T. T., Hwang, J. J., Pham, B. H., Doan, H. L., Nguyen, H. V., Halim, M. S., Uludag, G., Sepah, Y. J., Do, D. V., Nguyen, Q. D. 2020; 19: 100825

  Abstract

  Purpose: To report a case of bilateral pan-uveitis resembling fungal and viral endophthalmitis in a patient who was ultimately diagnosed with sarcoidosis.Observation: A 64-year-old female presented with a four-day history of painless vision loss in the right eye. She presented with multiple concurrent systemic complaints, including a history of oral and genital sores, patches of hypopigmented skin on her forearms, and occasional shortness of breath. Upon further examination, she was noted to have bilateral pan-uveitis, which was more severe in the right than left eye. Posterior pole examination of the right eye revealed dense vitritis with multiple large whitish round balls that seemed suggestive of fungal or viral endophthalmitis. Initial therapies included intravitreal (IVT) foscarnet and intravenous (IV) acyclovir, followed by IV amphotericin B and oral voriconazole, which did not improve ocular signs and symptoms. Further evaluations ruled out infectious etiologies and lymphoma. Chest computerized tomography (CT) scan revealed findings suggestive of sarcoidosis, which was confirmed with lung biopsy. Anti-viral and -fungal treatments were discontinued, and the patient was started on IV methylprednisolone followed by oral prednisone and mycophenolate mofetil. Ocular symptoms improved, and the patient remained stable after treatment.Conclusion and Importance: The index report illustrates a case of ocular sarcoidosis that imitated the presentation of infectious endophthalmitis. Though ocular sarcoidosis is known to masquerade as a range of disorders and constitutes part of the differential diagnosis for infectious endophthalmitis, sarcoidosis has not been reported in recent literature to imitate the presentation of fungal endophthalmitis. The index case suggests that ocular sarcoidosis should be considered in the differential diagnoses of fungal endophthalmitis.

  View details for DOI 10.1016/j.ajoc.2020.100825

  View details for PubMedID 32715157

• Pharmacological agents in development for diabetic macular edema. International journal of retina and vitreous Sadiq, M. A., Halim, M. S., Hassan, M., Onghanseng, N., Karaca, I., Agarwal, A., Afridi, R., Sepah, Y. J., Do, D. V., Nguyen, Q. D. 2020; 6 (1): 29

  View details for DOI 10.1186/s40942-020-00234-z

  View details for PubMedID 33384024

• Longitudinal assessment of patients with anterior scleritis using scleral area vessel density Akhavanrezayat, A., Halim, M., Onghanseng, N. L., Hassan, M., Mahajan, S., Uludag, G., Ormaechea, M., Tran, A., Chea, S., Doan, H., Park, J., Do, D. V., Sepah, Y., Nguyen, Q. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020

  View details for Web of Science ID 000554528304121

• Difference in Treatment Effect Between Intravitreal Aflibercept Injection and Sham by Baseline Factors in Moderately Severe-to-Severe Nonproliferative Diabetic Retinopathy Do, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020

  View details for Web of Science ID 000554495703329

• Comparative efficacy of anti-vascular endothelial growth factor (VEGF) treatment regimens for neovascular age-related macular degeneration (nAMD): A network meta-analysis Garmo, V., Stoilov, I., Solon, C., Ali, F. S., Uyei, J., Bilir, P., Karabis, A., Singh, R., Jiang, Y., Do, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020

  View details for Web of Science ID 000554528303025

• Correction of perceived visual distortions using a software application and correlation to age-related macular degeneration THERAPEUTIC ADVANCES IN OPHTHALMOLOGY Hassan, M., Chakravarthy, A. D., Subramaniam, M., Chundi, P., Sadiq, M., Halim, M., Afridi, R., Tran, A. N. T., Sepah, Y. J., Do, D., Quan Dong Nguyen 2020; 12: 2515841420917783

  Abstract

  To investigate the use of software-generated corrections in neutralizing perceived distortions in age-related macular degeneration.A tablet-based application was utilized to elicit distortions. Five subjects (seven eyes: neovascular age-related macular degeneration and three eyes: non-neovascular age-related macular degeneration) traced the reference lines, and their distortion traces were recorded. To counter distortion, a software-generated trace was re-traced by subjects to produce a corrected trace. Final traces were superimposed on optical coherence tomography images and following distances calculated: (a) dDT: distance between distortion trace and reference line; (b) dGT: distance between software-generated trace and corrected trace; (c) dCT: distance between corrected trace and reference line. Mean percent improvement in distortion was reported. Mean effectiveness of correction was also reported by utilizing t test to compare dDT and dCT. The number of distortion traces with underlying lesions on optical coherence tomography was also analyzed.Mean age of the subjects was 76.6 (±9.5) years. Each patient traced six reference lines and each was considered a separate case. Out of 30 cases, 17 (56.6%) elicited distortion. Mean percent improvement in distortion was 71.3 ± 23% (p < 0.05). Twelve cases (70.6%) had an underlying lesion (eight cases: disrupted photoreceptor layer and four cases: normal photoreceptor layer). Mean percent improvement in cases with normal photoreceptor layer (90.8 ± 5.45%) was higher than with abnormal photoreceptor layer (58.5 ± 7.17%) (p < 0.05). Five cases with distortion had no associated underlying lesion. Mean percent improvement in these subjects was significantly higher than those with photoreceptor layer disruption.Software-generated corrections can potentially correct for perceived distortions in patients with age-related macular degeneration, especially in cases with preserved photoreceptor layer.

  View details for DOI 10.1177/2515841420917783

  View details for Web of Science ID 000537030800001

  View details for PubMedID 32524073

  View details for PubMedCentralID PMC7235661

• Hydroxychloroquine-induced Retinal Toxicity. The Journal of rheumatology Carter, K. L., DO, D. V. 2020; 47 (4): 632

  View details for DOI 10.3899/jrheum.190538

  View details for PubMedID 32238544

• Prior muscle activation affects the compound muscle action potential Reply MUSCLE & NERVE Peterson, G. W., Tsao, B. E., Nist, L. D., Brandstater, M. E. 2020; 61 (2): E13

  View details for DOI 10.1002/mus.26754

  View details for Web of Science ID 000507472000002

  View details for PubMedID 31725907

• Assessment of Online Sites Reliability, Accountability, Readability, Accessibility and Translation for Intravitreal Injections. Ophthalmology. Retina Rayess, N. n., Li, A. S., Do, D. V., Rahimy, E. n. 2020

  Abstract

  Patients increasingly use the internet to access health-related information to further understand their treatments and conditions. This study compares the quality, accountability, readability, accessibility and presence of translation between private and academic online source material available to the public regarding intravitreal injections.Cross-sectional analysis PARTICIPANTS: Top 20 websites on a Google search for the terms 'eye injections', 'intravitreal injections' and 'anti-VEGF injections'.Websites were classified as private or academic. Quality and accountability were assessed using the internationally recognized DISCERN criteria and the Health on the Net (HONcode). All 20 sites were independently graded by 2 retinal physicians and differences were adjudicated by a third experienced retinal physician. Readability was evaluated using an online tool that provides a consensus readability grade level. The presence of and languages available for translation were recorded. The top 5 ranked websites' content quality, accountability and readability was also compared with the other 15 websites.Primary outcome measure is comparing the DISCERN and HONcode quality and accountability scores between academic and private websites. Secondary outcome measures include evaluating readability, accessibility and presence of translation (in particular, Spanish).Eleven academic and 9 private websites were included. The overall mean score using DISCERN criteria for the academic websites (3.11±0.46) was significantly higher than that of private websites (2.23±0.61; p<0.007). Similarly, out of a possible total 14 points for the HONcode, the average quality score for academic websites (10.91±2.66) was higher compared to private websites (6.44±3.36; p<0.009). The mean consensus reading grade level was similar between academic (11.73±1.68) and private websites (11.78±1.48; p=0.94). Spanish translation was offered by only 7 of the 20 websites (5 academic and 2 private websites).The overall quality and accountability of online content for academic sites was significantly higher compared to private websites. Translation was rarely provided and the readability grade level was significantly higher for both groups than recommended. Improving the quality, accountability, readability, accessibility and incorporating translation in websites can help improve patients' health literacy regarding intravitreal injections, potentially leading to increased adherence to therapy plans and improved treatment outcomes.

  View details for DOI 10.1016/j.oret.2020.05.019

  View details for PubMedID 32497854

• Retinal arterial occlusive vasculitis following intravitreal brolucizumab administration. American journal of ophthalmology case reports Haug, S. J., Hien, D. L., Uludag, G. n., Ngoc, T. T., Lajevardi, S. n., Halim, M. S., Sepah, Y. J., Do, D. V., Khanani, A. M. 2020; 18: 100680

  Abstract

  To describe retinal arterial occlusion and vasculitis following intravitreal brolucizumab administration in a patient with neovascular age-related macular degeneration (nAMD).An 88-year-old Caucasian woman with neovascular age-related macular degeneration (nAMD) complained of painless loss of vision with light sensitivity in both eyes (OU) four weeks after bilateral intravitreal brolucizumab. Upon examination, her visual acuity decreased to 20/40 in the right eye (OD) and 20/50 in the left eye (OS). Examination revealed 0.5+ and 1+ anterior chamber cells in OD and OS, respectively. The patient was treated with 1% prednisolone acetate eyedrops in both eyes, and after several weeks, the anterior chamber cells resolved. However, the patient still reported a decline in visual acuity (VA). Fluorescein angiography (FA) revealed retinal arterial occlusion, vasculitis, and optic nerve inflammation in the left eye. Retinal intra-arterial grayish materials were also detected. Laboratory evaluations were performed for common infectious and inflammatory causes and were normal or negative. A delayed inflammatory reaction to brolucizumab was suspected as the cause of the ocular inflammation and retinal vasculitis. An intravitreal dexamethasone implant was inserted into the left eye to treat the inflammation. One week after the dexamethasone implant, VA improved to 20/40 in OU; FA showed improvement, but residual peri-vascular leakage remained.Medication-associated uveitis is a rare adverse effect that can lead to vision loss. The index report illustrates a case of intraocular inflammation, retinal arterial vaso-occlusion and vasculitis associated with intravitreal brolucizumab. The delay in developing uveitis suggests that the inflammation is due to a delayed hypersensitivity reaction which can occur several days or weeks after administration of the inciting agent. Recently, several cases of uveitis and vasculitis associated with brolucizumab have been presented and those cases have similar features compared to the index case (1). Therapy with steroids (either intraocular or systemic), after infectious etiologies have been excluded, may be beneficial in halting inflammation and preventing further vision loss.

  View details for DOI 10.1016/j.ajoc.2020.100680

  View details for PubMedID 32258827

  View details for PubMedCentralID PMC7125319

• Acute lymphocytic leukemia masquerading as acute retinal necrosis. American journal of ophthalmology case reports Carter, K. L., Hassan, M. n., Do, D. V., Nguyen, Q. D. 2020; 18: 100629

  Abstract

  To report a case of B-cell acute lymphocytic leukemia (ALL) relapse presenting as acute retinal necrosis.An 11-year old boy with history of B-cell ALL undergoing maintenance therapy presented with a three-month history of intermittent blurry vision and pain in the right eye when a routine lumbar puncture indicated an elevated lymphoblast-predominant white blood cell count. Bone marrow biopsy revealed 42% lymphoblasts, confirming ALL relapse. Ophthalmic imaging demonstrated a hyperemic optic disc, retinal whitening, perivascular sheathing, retinal hemorrhages, and retinal detachment in the right eye. Vitreous fluid biopsy revealed presence of rare atypical lymphoblasts. Chemotherapy, orbital radiation, and systemic prednisone resulted in improvement of visual acuity and retinal hemorrhages, and resolution of retinal detachment.We have described the clinical features, treatment, and response in a case of B-cell ALL relapse with presenting signs of acute retinal necrosis. The uncommon finding in B-cell ALL highlights the possibility of intraocular involvement and the importance of routine ophthalmologic evaluation in leukemia remission.

  View details for DOI 10.1016/j.ajoc.2020.100629

  View details for PubMedID 32258824

  View details for PubMedCentralID PMC7125310

• Serous Macular Detachment in Probable Vogt-Koyanagi-Harada Syndrome. JAMA ophthalmology Li, A. S., Tang, P. H., Do, D. V. 2020; 138 (5): e191981

  View details for DOI 10.1001/jamaophthalmol.2019.1981

  View details for PubMedID 32407448

• The Tie2 signaling pathway in retinal vascular diseases: a novel therapeutic target in the eye. International journal of retina and vitreous Nguyen, Q. D., Heier, J. S., Do, D. V., Mirando, A. C., Pandey, N. B., Sheng, H., Heah, T. 2020; 6: 48

  Abstract

  Background: Retinal vascular diseases such as neovascular age-related macular degeneration, diabetic retinopathy and/or diabetic macular edema, and retinal vein occlusion with macular edema-share several key pathophysiologic aspects including neovascularization, vascular permeability, and inflammation. The role of vascular endothelial growth factor (VEGF) in these processes, and the therapeutic benefits of VEGF inhibition, have been well characterized. Anti-VEGF therapy is highly effective for many patients but is not uniformly effective in all patients and imposes a significant treatment burden. More recently, the role of the Tie2 signaling pathway in the pathophysiology of retinal vascular diseases has been investigated, and the Tie2 pathway represents a novel therapeutic target for these conditions.Areas covered: The index review describes the Tie2 pathway and its complementary role to the VEGF pathway in the angiogenesis cascade and will summarize studies of molecules in development to therapeutically modulate the Tie2 pathway in retinal vascular diseases.Conclusions: Activation of the Tie2 pathway leads to downstream signaling that promotes vascular health and stability and decreases vascular permeability and inflammation. AXT107 is a collagen IV-derived synthetic peptide with a dual mechanism of action that involves suppression of VEGF signaling and activation of the Tie2 pathway; these actions are accomplished by AXT107 binding to and disrupting different integrin, leading to blockade of the VEGF receptor and rearrangement of cellular Tie2 rendering it susceptible to Ang2 agonism. Other Tie2 agonist compounds are also in development, including faricimab and razuprotafib. Tie2 activation only modestly impacts angiogenesis on its own but significantly potentiates VEGF suppression. Co-regulation of the VEGF and Tie2 signaling pathways has the potential to improve functional and structural outcomes in eyes with retinal vascular diseases.

  View details for DOI 10.1186/s40942-020-00250-z

  View details for PubMedID 33072401

• Posterior segment inflammatory outcomes assessed using fluorescein angiography in the STOP-UVEITIS study. International journal of retina and vitreous Sadiq, M. A., Hassan, M. n., Afridi, R. n., Halim, M. S., Do, D. V., Sepah, Y. J., Nguyen, Q. D. 2020; 6: 47

  Abstract

  Although fluorescein angiography (FA) is a frequently used imaging modality in patients with non-infectious uveitis (NIU), it has not been reliably used for objective assessment of posterior segment inflammatory outcomes in these patients. In this index study we report the posterior segment inflammatory outcomes of two different doses of intravenous (IV) infusions of tocilizumab (TCZ), an IL-6 inhibitor, in eyes with NIU using a semi-quantitative FA scoring system.STOP-Uveitis is a randomized, multi-center clinical trial conducted at 5 clinical centers across the United States. The study evaluated the role of TCZ in patients with NIU. Thirty-seven (37) patients with NIU were randomized into one of two treatment groups in a ratio of 1:1. Group 1 received IV infusions of 4 mg/kg TCZ and group 2 received IV infusions of 8 mg/kg TCZ. Infusions were given every 4 weeks in both groups until month 6 (primary endpoint). Posterior segment inflammatory outcomes were assessed by evaluating FA at baseline and month 6 by graders at a central reading center. A previously reported, semi-quantitative, scoring system for FA was used to assess signs that represent ongoing inflammatory processes in the posterior segment. These signs included optic disc hyperfluorescence, macular edema, retinal vascular staining and/or leakage, capillary leakage, retinal capillary nonperfusion, neovascularization of the optic disc, neovascularization elsewhere, pinpoint leaks, and retinal staining and/or subretinal pooling. Statistical significance was set at p < 0.05. Main outcome measures included change in posterior segment inflammation as assessed using FA at month 6.37 eyes (37 patients) were randomized in the STOP-Uveitis study. 30 eyes were found to be eligible for this sub-study based on study criteria. Seven eyes had ungradable images at either baseline or month 6 and were therefore excluded from the analysis. The reduction in FA inflammatory scores at month 6 were statistically significant in both groups (p < 0.05). The difference between the two groups was not significant (p = 0.351).IV infusions of tocilizumab (both 4 and 8 mg/kg) are effective in improving posterior segment inflammation in eyes with NIU. A semi-quantitative FA scoring system may be used as a reliable outcome measure for assessment of posterior segment inflammation.ClinicalTrials.gov Identifier: NCT01717170.

  View details for DOI 10.1186/s40942-020-00245-w

  View details for PubMedID 33042579

  View details for PubMedCentralID PMC7539516

• Pharmacological agents in development for diabetic macular edema. International journal of retina and vitreous Sadiq, M. A., Halim, M. S., Hassan, M. n., Onghanseng, N. n., Karaca, I. n., Agarwal, A. n., Afridi, R. n., Sepah, Y. J., Do, D. V., Nguyen, Q. D. 2020; 6: 29

  Abstract

  Diabetic macular edema (DME) is the leading cause of visual loss in patients with diabetic retinopathy. There has been a paradigm shift in the treatment of DME since the advent of anti-vascular endothelial growth factor (anti-VEGF) therapy. The safety and efficacy of anti-VEGF therapy has been well established. Although efficacious, currently approved anti-VEGF agents are associated with certain limitations, which include, among others: frequent need for injections, high treatment cost and variable response to treatment. These challenges have led to an active search for more novel agents that may be able to overcome these limitations.The index review focuses on novel treatment agents that target various pathways in patients with DME. These agents are used either as monotherapy or in combination with other agents in the management of DME. Drugs discussed include novel anti-VEGF inhibitors, TIE-2 receptor modulators, integrin peptide inhibitors, rho kinase inhibitors, and future therapies such as neuroprotection and gene therapy.The future of investigational pharmacological therapy appears promising for patients with DME. Results from early clinical trials indicate that newer agents highlighted in the study may be safe and efficacious treatment options for patients with DME. However, data from large multicenter clinical trials need to be analyzed before these agents can be incorporated into clinical practice.

  View details for DOI 10.1186/s40942-020-00234-z

  View details for PubMedID 32670612

  View details for PubMedCentralID PMC7341631

• Severe vision loss secondary to retinal arteriolar occlusions after multiple intravitreal brolucizumab administrations. American journal of ophthalmology case reports Jain, A. n., Chea, S. n., Matsumiya, W. n., Halim, M. S., Yaşar, Ç. n., Kuang, G. n., Sepah, Y. J., Khanani, A. M., Do, D. V., Nguyen, Q. D. 2020; 18: 100687

  Abstract

  To describe a case of unilateral retinal arteriolar occlusion following multiple intravitreal brolucizumab injections for neovascular age-related macular degeneration (nAMD).A 92-year-old Caucasian woman presented with blurry vision in her left eye (OS) after receiving the third dose of intravitreal brolucizumab. At the time of presentation, visual acuity (VA) was 20/40 in her right eye (OD) and had decreased from 20/150 to count finger (CF) at 1-foot OS. On examination, there was no evidence of active inflammation in the anterior chamber OU. Dilated fundus examination showed no vitritis in OD and 1+ vitreous cells OS, flame-shaped hemorrhage at the superior optic disc margin, and retinal whitening surrounding the proximal portion of the supero-temporal branch of the central retinal artery. There were drusen in OS and retinal pigment epithelial (RPE) changes in the maculae of OU. Intra-arteriolar greyish deposits were seen OS. Fluorescein angiography (FA) showed hyper-fluorescence in the maculae corresponding to fibrovascular pigment epithelial detachments (PED) OU. No peri-vascular leakage was noted OU. Delayed filling of multiple arterioles in early and late phases OS was observed on FA. The patient was diagnosed with retinal arteriolar occlusion associated with repeated intravitreal brolucizumab administrations.Retinal arteriolar occlusion with severe vision loss, possibly secondary to inflammatory responses, can occur after subsequent intravitreal brolucizumab injections, even if no inflammation occurred after initial administrations. Vaso-occlusive disease should be considered as a potential ocular complication, with acute as well as delayed onset, following intravitreal brolucizumab therapy.

  View details for DOI 10.1016/j.ajoc.2020.100687

  View details for PubMedID 32280811

  View details for PubMedCentralID PMC7139151

• Migration of a Fluocinolone Acetonide Intravitreal Implant Into the Anterior Chamber. JAMA ophthalmology Li, A. S., Nguyen, H. V., Do, D. V. 2020; 138 (10): e201388

  View details for DOI 10.1001/jamaophthalmol.2020.1388

  View details for PubMedID 33030543

• Brolucizumab: Evolution through Preclinical and Clinical Studies and the Implications for the Management of Neovascular Age-Related Macular Degeneration. Ophthalmology Nguyen, Q. D., Das, A. n., Do, D. V., Dugel, P. n., Gomes, A. n., Holz, F. G., Koh, A. n., Pan, C. n., Sepah, Y. J., Patel, N. n., MacLeod, H. n., Maurer, P. n. 2020

  Abstract

  Improving or maintaining visual acuity is the main goal for the treatment of neovascular age-related macular degeneration (nAMD). Current nAMD standard of care dictates frequent intravitreal (IVT) anti-vascular endothelial growth factor (VEGF) injections, which places a substantial burden on patients, caregivers, and physicians. Brolucizumab, a newly developed anti-VEGF molecule for nAMD treatment, has demonstrated longer durability and improvement in visual and anatomic outcomes in clinical studies in a q12-week regimen, indicating its potential to reduce treatment burden as an important therapeutic tool in nAMD management. This review focuses on the development of brolucizumab and the preclinical and clinical studies evaluating its efficacy, tolerability, and safety. Brolucizumab (also known as "RTH258" and "ESBA1008") is a humanized, single-chain variable fragment (scFv) antibody with a molecular mass of approximately 26 kDa that inhibits VEGF-A. Preclinical studies show that brolucizumab readily penetrates the retina to reach the retinal pigment epithelium (RPE)/choroid with minimal subsequent systemic exposure. The safety, tolerability, and efficacy of a single IVT brolucizumab administration in patients with treatment-naïve nAMD were first demonstrated in the SEE Phase 1/2 study. The OSPREY Phase 2 study showed brolucizumab to be as efficacious as aflibercept in a q8-week regimen with regard to best-corrected visual acuity (BCVA) and brolucizumab achieving greater fluid resolution. Brolucizumab-treated patients in the OSPREY study were subsequently challenged with a q12-week dosing interval, and the outcomes provided key information for the study design and end points of the Phase 3 studies. In the HAWK and HARRIER Phase 3 studies, after 3 monthly loading injections, brolucizumab treatment regimen (q12-week or q8-week) was guided by individual disease activity assessment using functional and anatomic parameters (central subfield thickness [CST], intraretinal fluid [IRF], or subretinal fluid [SRF]) versus aflibercept (q8-week). Fewer brolucizumab 6-mg treated eyes had disease activity versus aflibercept, and anatomic outcome results at weeks 16 and 48 demonstrate brolucizumab as a potent drying agent. Moreover, of patients treated with 6 mg brolucizumab, 55.6% and 51.0% maintained a q12-week dosing interval immediately after the loading phase until week 48 in HAWK and HARRIER, respectively. These Phase 3 studies demonstrated that the brolucizumab q12-week regimen maintains efficacy and safety while reducing treatment burden associated with regular IVT injections for patients with nAMD.

  View details for DOI 10.1016/j.ophtha.2019.12.031

  View details for PubMedID 32107066

• Reply. Retina (Philadelphia, Pa.) Do, D. V., Rhoades, W., Nguyen, Q. D. 2019

  View details for DOI 10.1097/IAE.0000000000002711

  View details for PubMedID 31876890

• Safety of systemic therapy for noninfectious uveitis. Expert opinion on drug safety Ormaechea, M. S., Hassan, M., Onghanseng, N., Park, J. H., Mahajan, S., Al-Kirwi, K. Y., Uludag, G., Halim, M. S., Schlaen, A., Sepah, Y. J., Do, D. V., Nguyen, Q. D. 2019; 18 (12): 1219–35

  Abstract

  Introduction: The treatment strategies for noninfectious uveitis (NIU) aim to achieve disease remission, prevention of recurrences, and preserving vision, while minimizing the side effects associated with the therapies used.Areas covered: The index review aims to provide a detailed overview of the adverse events and safety parameters associated with the systemic therapies for the management of the NIU.Expert opinion: Despite being the cornerstone of management of acute cases of NIU, long-term corticosteroid use is associated with multi-system side effects, requiring the use of steroid-sparing agents. Adalimumab was recently approved by the FDA for the management of NIU based on the results of VISUAL studies. Similarly, newer drugs targeting various aspects of the inflammatory cascade are being developed. However, until we completely understand the molecular pathways of the inflammatory diseases, the therapeutic profile of these newer agents needs to be broad enough to suppress inflammatory cascade and narrow enough to spare normal cellular processes. Another strategy that has shown some potential in decreasing the systemic side effects is to provide local drug delivery. Therefore, the future of management of NIU is very bright with many novel therapeutic agents and strategies of drug delivery on the horizon.

  View details for DOI 10.1080/14740338.2019.1692810

  View details for PubMedID 31801415

• Progression characteristics of ellipsoid zone loss in macular telangiectasia type 2 ACTA OPHTHALMOLOGICA Pauleikhoff, D., Bonelli, R., Dubis, A. M., Gunnemann, F., Rothaus, K., Charbel Issa, P., Heeren, T. F. C., Peto, T., Clemons, T. E., Chew, E. Y., Bird, A. C., Sallo, F. B., Bakri, S., Bernstein, P. S., Blodi, B., Brucker, A., Bucher, F., Issa, P., Chung, M., Comer, G., Constable, I., Cooney, M., Do, D., Duncan, J., Egan, C., Elman, M. J., Fawzi, A., Friedlander, M., Gaudric, A., Gillies, M. C., Goldberg, R., Googe, J. M., Guymer, R., Higgins, P., Holz, F., Houghton, O., Hoyng, C. B., Hubschman, J., Jhaveri, C., Khanani, A., Lally, D., Lee, C., Lee, M., Miller, J. W., Miller, D., Moisseiev, J., Murphy, R., Narayanan, R., Pauleikhoff, D., Randhawa, S., Raphaelian, P. V., Rich, R., Rosen, R., Rosenfeld, P., Ruys, J., Sahel, J., Schwartz, S., Singerman, L., Sneed, S., Soubrane, G., Vingerling, J. R., Warrow, D., Weinberg, D., Wolf, S., Wykoff, C., Yan, J., Yannuzzi, L. A., Zhuk, S. A., MacTel Study Grp 2019; 97 (7): E998–E1005

  Abstract

  To investigate the progression characteristics of ellipsoid zone (EZ) loss in eyes with macular telangiectasia type 2 (MacTel) as reflected by area and linear measurements, and their relevance for visual acuity.Participants were selected from the MacTel Study cohort. Linear and area measurements of EZ loss were performed in Spectral-Domain Optical Coherence Tomograph (SD-OCT) volume scans. Progression characteristics and correlations between linear and area measurements were analysed using linear mixed effects models.A total of 134 eyes of 70 patients were included (85 eyes with follow-up, mean 4.7 years, range: 1.4-8 years). Ellipsoid zone (EZ) loss significantly progressed at a mean annual increment of 0.057 mm2 (p = 0.005). The progression rate was non-linear and interacted significantly with initial EZ lesion size indicating an exponential growth before reaching a plateau. There was a strong heterogeneity in area sizes between fellow eyes. EZ break length had a significant linear effect on EZ break area (b = 1.06, p < 0.001) and could predict it. The location of the EZ break had a significant impact on visual acuity.Ellipsoid zone (EZ) loss in MacTel has a non-linear progression characteristic, and its rate depends on area size at baseline, which must be taken into account at sample selection in clinical trials. Our results show a good correlation of linear and area measures of EZ loss and a segregation of best-corrected visual acuity by EZ location, which may help routine clinical practice.

  View details for DOI 10.1111/aos.14110

  View details for Web of Science ID 000491011100022

  View details for PubMedID 30968592

  View details for PubMedCentralID PMC6785352

• ISOPT Clinical Hot Topic Panel Discussion on Medical Treatment of Retinal Diseases. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics Kuppermann, B. D., Bernstein, P., Mones, J., Do, D. V., Neumann, R., Rosenfeld, P. J. 2019; 35 (8): 424–32

  Abstract

  Topics change as time flows. This is especially true in retinal therapeutics that merely 25 years ago was mainly a surgical field and in two decades has been transformed into a classic pharmacologic medical field. That said, the classic questions of pharmacology such as pharmacokinetics, pharmacodynamics, dosing and delivery systems currently engage most retina specialists. It was therefore easy for us to focus the 2018 ISOPT Clinical retinal discussions on delivery systems, drug efficacy and classic questions such as: have we reached the unbreakable glass ceiling of efficacy in wet age-related macular degeneration (AMD)? Can we aim our target to achieve an even higher effect? Can it be reached by new chemical/biological entities or would delivery system allow us to reach higher points of efficacy? The discussion also addressed the issue of dry AMD and the glorious parade of failures so far, and how do we measure success and failure via relevant endpoints.

  View details for DOI 10.1089/jop.2019.0073

  View details for PubMedID 31596664

• Higher-Order Assessment of OCT in Diabetic Macular Edema from the VISTA Study: Ellipsoid Zone Dynamics and the Retinal Fluid Index. Ophthalmology. Retina Ehlers, J. P., Uchida, A., Hu, M., Figueiredo, N., Kaiser, P. K., Heier, J. S., Brown, D. M., Boyer, D. S., Do, D. V., Gibson, A., Saroj, N., Srivastava, S. K. 2019

  Abstract

  PURPOSE: To investigate retinal fluid features and ellipsoid zone (EZ) integrity dynamics on spectral-domain OCT (SD-OCT) in eyes with diabetic macular edema (DME) treated with intravitreal aflibercept injection (IAI) in the VISTA-DME study.DESIGN: A post hoc subanalysis of a phase III, prospective clinical trial.PARTICIPANTS: Eyes received either IAI 2 mg every 4 weeks (2q4) or every 8 weeks after 5 initial monthly doses (2q8).METHODS: All eyes from the VISTA Phase III study in the IAI groups imaged with the Cirrus HD-OCT system (Zeiss, Oberkochen, Germany) were included. The OCT macular cube datasets were evaluated using a novel software platform to generate retinal layer and fluid boundary lines that were manually corrected for assessment of change in EZ parameters and volumetric fluid parameters from baseline. The retinal fluid index (i.e., proportion of the retinal volume consisting of cystic fluid) was also calculated at each time point.MAIN OUTCOME MEASURES: The feasibility of volumetric assessment of higher-order OCT-based retinal parameters and its correlation with best-corrected visual acuity (BCVA).RESULTS: Overall, 106 eyes of 106 patients were included. Specifically, 52 eyes of 52 patients were included in the IAI 2q4 arm, and 54 eyes of 54 patients were included in the IAI 2q8 arm. Ellipsoid zone integrity metrics significantly improved from baseline to week 100, including central macular mean EZ to retinal pigment epithelium (RPE) thickness (2q4: 26.6 mum to 31.6 mum, P < 0.001; 2q8: 25.2 mum to 31.4 mum, P < 0.001). At week 100, central macular intraretinal fluid volume was reduced by >65% (P < 0.001) and central macular subretinal fluid volume was reduced by >99% in both arms (P < 0.001). Central macular retinal fluid index (RFI) significantly improved in both arms (2q4: 17.9% to 7.2%, P < 0.001; 2q8: 19.8% to 4.2%, P < 0.001). Central macular mean EZ-RPE thickness (i.e., a surrogate for photoreceptor outer segment length) and central RFI were independently correlated with BCVA at multiple follow-up visits.CONCLUSIONS: Intravitreal aflibercept injection resulted in significant improvement in EZ integrity and quantitative fluid metrics in both 2q4 and 2q8 arms and correlated with visual function.

  View details for DOI 10.1016/j.oret.2019.06.010

  View details for PubMedID 31473172

• Assessing Scleral Area Vessel Density in Subjects with Anterior Scleritis using Optical Coherence Tomography Angiography Mahajan, S., Halim, M., Hassan, M., Ormaechea, M., Uludag, G., Anh Ngoc Tram Tran, Bae, J., Afridi, R., Karkhur, S., Hasanreisoglu, M., Pham, A., Al-Kirwi, K., Do, D. V., Quan Dong Nguyen, Sepah, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488628107209

• Role of Circumferential Full Thickness Scleral Debridement in Fulminant Infective Ring Scleritis Karkhur, S., Sen, A., Shenoy, P., Hassan, M., Halim, M., Hasanreisoglu, M., Afridi, R., Sepah, Y., Do, D. V., Quan Dong Nguyen, Gupta, V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488628102051

• Phase 1 first-in-human study of KSI-301: a novel anti-VEGF antibody biopolymer conjugate with extended durability Patel, S. S., Naor, J., Qudrat, A., Do, D. V., Buetelspacher, D., Liang, H., Perlroth, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488800700237

• Phase I/IIa Clinical Trial of Human Embryonic Stem Cell (hESC)-Derived Retinal Pigmented Epithelium (RPE, OpRegen) Transplantation in Advanced Dry Form Age-Related Macular Degeneration (AMD): Interim Results Banin, E., Barak, A., Boyer, D. S., Do, D. V., Ehrlich, R., Jaouni, T., McDonald, R., Tealander, D. G., Gurevich, M., Cohen, O., Razag, G., Hogge, G. S., Reubinoff, B. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488800707128

• Correlation of Clinical Aqueous Flare Grade to Semi-automated Flare Assessment using Laser Flare Meter Anh Ngoc Tram Tran, Halim, M., Hassan, M., Hasanreisoglu, M., Afridi, R., Ormaechea, M., Uludag, G., Nguyen, N. V., Mahajan, S., Bae, J., Al-Kirwi, K., Do, D. V., Ibrahim, M. A., Sepah, Y., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488800707204

• Trend in the Utilization of Fluorescein Angiography and Optical Coherence Tomography Li, A., Huang, L. C., Do, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488628103338

• Relationship Between Adult Body Height and Age-Related Macular Degeneration: A Korean Nationwide Population-Based Survey Bae, J., Hwang, I., Hassan, M., Halim, M., Ormaechea, M., Uludag, G., Tran, A. N. T., Mahajan, S., Al-Kirwi, K., Afridi, R., Sepah, Y., Do, D. V., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488628100050

• Regression of diabetic retinopathy with anti-VEGF treatment: what is learned from a meta-analysis of four pivotal clinical trials Do, D. V., Quan Dong Nguyen, Day, B., Ecoiffier, T., Stoilov, I. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488628104113

• Traumatic chorioretinitis sclopetaria: Risk factors, management, and prognosis. American journal of ophthalmology case reports Ludwig, C. A., Shields, R. A., Do, D. V., Moshfeghi, D. M., Mahajan, V. B. 2019; 14: 39–46

  Abstract

  Purpose: To describe new cases of sclopetaria and evaluate the risk factors, management, and visual prognosis of all reported cases in the literature.Observations: We performed a retrospective, observational case series. This study included six cases (median age 23, interquartile range 33) of sclopetaria. Additionally, literature searches were conducted in the PubMed and Cochrane Library databases to uncover risk factors associated with all published cases of sclopetaria. Main outcome measure was best corrected visual acuity (BCVA) worse than 20/20. Sixty-seven cases (71 eyes) of sclopetaria have been reported, of which 59 cases (61 eyes) met inclusion criteria in this study. Most were young (median age 19.5 years) men (51/59, 88.1%). Thirty-seven eyes were observed while 24 underwent immediate surgery including six pars plana vitrectomies and three scleral buckles. Compared to initial presentation, BCVA improved in 31/48 (64.6%) eyes, remained stable in 12/48 eyes (25.0%), and worsened in 5/48 eyes (10.4%). Ten patients (16.4%) achieved a final BCVA of 20/20 with median follow up time of seven months. In a multivariate model, location of sclopetaria in the macula, temporal retina, or immediate orbital foreign body removal predicted poor final BCVA with an area under receiver operating characteristic curve of 0.767.Conclusions and importance: Traumatic chorioretinitis sclopetaria is rare, but reports have increased dramatically over the past two decades. While pars plana vitrectomy may be required for the management of retinal detachments and non-clearing vitreous hemorrhage, close observation is appropriate in most cases. Visual prognosis is poor with most patients attaining 20/200 vision or worse.

  View details for PubMedID 30834355

• Alendronate induced chorioretinitis: The importance of meticulous assessments. American journal of ophthalmology case reports Hassan, M., Maleki, A., Ying, Q., Nguyen, N., Halim, M. S., Sepah, Y. J., Do, D. V., Nguyen, Q. D. 2019; 14: 21–25

  Abstract

  Purpose: To report a case of presumed bilateral chorioretinitis secondary to alendronate therapy.Observations: A 71-year-old female presented to the clinic in July 2017 with six months history of difficulty in reading along with floaters in both eyes which were more severe in the right eye. Past medical and surgical history revealed a history of hypertension, gout, hyperthyroidism, osteoporosis, and humerus fracture. She was started on alendronate three months before developing ocular symptoms. On ocular examination, best corrected visual acuity was 20/30 in the right and 20/25 in the left eye. Slit-lamp examination demonstrated normal anterior chamber examination in both eyes. Dilated fundus examination revealed geographic chorioretinal lesions around the optic nerve head in both eyes, more extensively in the right eye; and superior and temporal to the macula in the right eye. Past ocular records in February 2015 did not reveal any such findings. Fundus autofluorescence demonstrated hyper-autofluorescence in the peripapillary lesions in both eyes. The lesion adjacent to the macula in right eye displayed mixed hyper and hypo-autofluorescence. Fluorescein angiography showed combined hyper- and hypo-fluorescence compatible with window defect, staining and blockage. However, no leakage was appreciated in the macula, peripapillary, and peripheral lesions in both eyes. Optical coherence tomography scan showed septate hyporeflective intraretinal spaces in the right eye.Conclusion and importance: The index report underscore the importance of considering alendronate as an etiologic cause of chorioretinitis, especially in subjects with atypical lesions developing after alendronate therapy. We, therefore, recommend discontinuation of this medication in subjects who develop chorioretinitis after employing this medication.

  View details for PubMedID 30809598

• PHARMACOKINETIC STUDY OF INTRAVITREAL AFLIBERCEPT IN HUMANS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION. Retina (Philadelphia, Pa.) Do, D. V., Rhoades, W., Nguyen, Q. D. 2019

  Abstract

  PURPOSE: To investigate the half-life of aflibercept in aqueous humor after a single intravitreal injection in patients with neovascular age-related macular degeneration.METHODS: Prospective, noncomparative, interventional case series of five eyes with neovascular age-related macular degeneration naive to anti-vascular endothelial growth factor therapy were enrolled and treated with intravitreal aflibercept. At baseline, best-corrected visual acuity, optical coherence tomography imaging, and aqueous humor (treatment eye) and blood/plasma samples were taken. Patients underwent best-corrected visual acuity, optical coherence tomography imaging, and sampling of aqueous humor from the eye and blood/plasma at six additional post-treatment time points of 4 hours and Days 1, 3, 7, 14, and 28. Concentrations of aflibercept were quantified using an enzyme-linked immunosorbent assay.RESULTS: Median peak concentration (Cmax) of free aflibercept in the aqueous was 122 mg/L. The median half-life of free aflibercept was 11 days in the eye. In plasma, the concentrations of free aflibercept were low and transient, reaching undetectable levels during the first week after injection, and undetectable in all patients at time points beyond 7 days.CONCLUSION: The pharmacokinetic profile in the aqueous humor described here together with the previously reported affinity of aflibercept for vascular endothelial growth factor is consistent with and adds to our understanding for the duration of its clinical efficacy.

  View details for DOI 10.1097/IAE.0000000000002566

  View details for PubMedID 31145389

• Microperimetry for geographic atrophy secondary to age-related macular degeneration SURVEY OF OPHTHALMOLOGY Csaky, K. G., Patel, P. J., Sepah, Y. J., Birch, D. G., Do, D., Ip, M. S., Guymer, R. H., Luu, C. D., Gune, S., Lin, H., Ferrara, D. 2019; 64 (3): 353–64

  View details for DOI 10.1016/j.survophthal.2019.01.014

  View details for Web of Science ID 000471740900007

• New therapies in development for the management of non-infectious uveitis: a review. Clinical & experimental ophthalmology Hassan, M., Karkhur, S., Bae, J., Halim, M. S., Ormaechea, M. S., Nguyen, N. V., Afridi, R., Sepah, Y. J., Do, D. V., Nguyen, Q. D. 2019

  Abstract

  Uveitis is a spectrum of inflammatory disorders characterised by ocular inflammation and is one of the leading causes of preventable visual loss. The main aim of the treatment of uveitis is to control the inflammation, prevent recurrences of the disease, and preserve vision while minimizing the adverse effects associated with the therapeutic agents. Initial management of uveitis relies heavily on the use of corticosteroids. However, monotherapy with hi-dose corticosteroids is associated with side effects and cannot be maintained long term. Therefore, steroid-sparing agents are needed to decrease the burden of steroid therapy. Currently, the therapeutic approach for non-infectious uveitis (NIU) consists of a step-ladder strategy with the first line option being corticosteroids in various formulations followed by the use of first, second, and third line agents in cases with suboptimal steroid response. Unfortunately, the agents currently at our disposal have limitations such as having a narrow therapeutic window along with their own individual potential side-effect profiles. Therefore, research has been targeted to identify newer drugs as well as new uses for older drugs that target specific pathways in the inflammatory response. Such efforts are made in order to provide targeted and safer therapy with reduced side effects and greater efficacy. Several specially designed molecular antibodies are currently in various phases of investigations that can potentially halt the inflammation in patients with NIU. In the review, we have provided a comprehensive overview of the current and upcoming therapeutic options for patients with NIU.

  View details for PubMedID 30938012

• New therapies in development for the management of non-infectious uveitis: A review CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY Hassan, M., Karkhur, S., Bae, J. H., Halim, M. S., Ormaechea, M. S., Onghanseng, N., Nguyen, N. V., Afridi, R., Sepah, Y. J., Do, D. V., Nguyen, Q. D. 2019; 47 (3): 396–417

  View details for DOI 10.1111/ceo.13511

  View details for Web of Science ID 000466807900009

• ENDOGENOUS KLEBSIELLA PNEUMONIAE ENDOPHTHALMITIS IN NORTHERN CALIFORNIA. Retina (Philadelphia, Pa.) Shields, R. A., Smith, S. J., Pan, C. K., Do, D. V. 2019; 39 (3): 614–20

  Abstract

  PURPOSE: To report the clinical features, treatment modalities, and visual outcomes in 12 eyes with endogenous Klebsiella pneumoniae endophthalmitis (EKPE).METHODS: The medical records of all patients diagnosed with EKPE at Stanford Hospital (Palo Alto, CA) and Santa Clara Valley County Hospital (Santa Clara, CA) from January 2000 to March 2017 were retrospectively reviewed.RESULTS: A total of 10 patients (12 eyes) were diagnosed with EKPE. The median age at presentation was 56, 80% were male, and 30% were non-Asian. Presenting visual acuities ranged from 20/20 to no light perception. Of the 12 eyes 10 received a tap and injection (range, 1-33 injections per eye), 2 eyes underwent primary enucleation or evisceration, and 1 patient underwent pars plana vitrectomy after tap and injection. Final visual acuities ranged from no light perception (six eyes) to 20/300 or better (five eyes). Five patients eventually underwent evisceration or enucleation. All cases were associated with positive blood and/or vitreous cultures and had concurrent systemic infection.CONCLUSION: Endogenous Klebsiella pneumoniae endophthalmitis is a rare, but devastating, ocular infection. Most cases in this series resulted in light perception vision or worse, and almost half required enucleation or evisceration. In light of the virulence of EKPE, early diagnosis and treatment should be initiated in all suspected cases.

  View details for PubMedID 29232335

• ENDOGENOUS KLEBSIELLA PNEUMONIAE ENDOPHTHALMITIS IN NORTHERN CALIFORNIA RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Shields, R. A., Smith, S. J., Pan, C. K., Do, D. V. 2019; 39 (3): 614–20

  View details for DOI 10.1097/IAE.0000000000001994

  View details for Web of Science ID 000480740100022

• Microperimetry for Geographic Atrophy Secondary to Age-Related Macular Degeneration. Survey of ophthalmology Csaky, K. G., Patel, P. J., Sepah, Y. J., Birch, D. G., Do, D. V., Ip, M. S., Guymer, R. H., Luu, C. D., Gune, S., Lin, H., Ferrara, D. 2019

  Abstract

  Geographic atrophy (GA) is a progressive, advanced form of age-related macular degeneration leading to visual function impairment and irreversible vision loss. Standard clinical tests to evaluate visual function in patients with GA provide poor anatomic-functional correlation, while fundus imaging does not assess the visual function deficit. Microperimetry is a psychophysical visual function test that spatially maps retinal sensitivity and allows for correlation of anatomic features with visual function. In this review, we present an overview of mesopic microperimetry for GA, including: commercially available microperimetry devices, strategies to capture a mesopic microperimetry test, and strategies to assess and interpret microperimetry data in patients with GA. We demonstrate the importance of microperimetry data for assessing GA progression and for evaluating visual function loss through anatomic-functional correlations. Although valuable, current microperimetry tests require an extensive time commitment from patient and examiner, and the development of faster, more reproducible, and accessible methods is important to enable broader use of microperimetry in both clinical and research settings.

  View details for PubMedID 30703401

• Comparison of montage with conventional stereoscopic seven-field photographs for assessment of ETDRS diabetic retinopathy severity. International journal of retina and vitreous Nguyen, N. V., Vigil, E. M., Hassan, M. n., Halim, M. S., Baluyot, S. C., Guzman, H. A., Afridi, R. n., Do, D. V., Sepah, Y. J. 2019; 5: 51

  Abstract

  The ETDRS stereoscopic seven-field (7F) has been a standard imaging and grading protocol for assessment of diabetic retinopathy (DR) severity score in many clinical trials. To the best of our knowledge, the comparison between montage and stereoscopic 7F has not been reported in the literature. Therefore, the main purpose of this study is to compare agreement between montage and stereoscopic seven-field (7F) photographs in the assessment of DR severity.Stereoscopic 7F photographs were captured from subjects with DR. Montages of monoscopic 7F images were created using Adobe Photoshop CS6 Extended©. The best quality image of each stereo pair was selected and placed on a 150 × 125-inch canvas field according to the standard location from field 1 to 7. All the fields were aligned following the vessels and overlaid using the built-in blending tool. The resulting montage was utilized for grading and compared with grading on stereoscopic 7F photographs. Three independent graders were asked to assess DR severity on stereoscopic 7F photographs and montage. Severity level agreement between stereo 7F and montage was cross-tabulated and the agreement of DR severity levels between stereoscopic 7-field images and montage was analyzed using κ intergrader agreement; statistical significance was set at p < 0.05.A total of 50 eyes were included in the study. There was a substantial agreement between stereoscopic 7F and montage (κ = 0.745, κweighted = 0.867) in assessment of DR severity. Of 50 eyes, 80% of the cases showed complete agreement, and 100% of the cases had agreement within one-step. There was a moderate agreement among graders, and κ-value ranged from 0.4705 to 0.5803.In this study, we found a substantial agreement in assessing DR severity score employing non-stereoscopic montage and stereoscopic 7F photographs.

  View details for DOI 10.1186/s40942-019-0201-z

  View details for PubMedID 31890280

  View details for PubMedCentralID PMC6909536

• Choosing Core Outcomes for Use in Clinical Trials in Ophthalmology: Perspectives from Three Ophthalmology Outcomes Working Groups OPHTHALMOLOGY Saldanha, I. J., Le, J. T., Solomon, S. D., Repka, M. X., Akpek, E. K., Li, T., Afshari, N., Ambrus, A., Asbell, P., Baudoin, C., Bunya, V., Chew, E., Chuck, R., Do, D., Eydelman, M., Gregory, D., Grzybowski, A., Haller, J., Hamrah, P., Holmes, J., Khurana, R., Jabs, D., Jampel, H., Jones, L., Loewenstein, A., Lum, F., Maguire, M., Maskin, S., Medow, N., Messmer, E., Perez, V., Perry, H., Petris, R., Pulido, J., Schmid-Erfurth, U., Starr, C., Tsubota, K., Vitale, S., Wenick, A., Ophthalmology Outcomes Working Grp 2019; 126 (1): 6–9

  View details for DOI 10.1016/j.ophtha.2018.09.008

  View details for Web of Science ID 000453531300011

  View details for PubMedID 30577918

• Interleukin-6 inhibition in the management of non-infectious uveitis and beyond. Journal of ophthalmic inflammation and infection Karkhur, S. n., Hasanreisoglu, M. n., Vigil, E. n., Halim, M. S., Hassan, M. n., Plaza, C. n., Nguyen, N. V., Afridi, R. n., Tran, A. T., Do, D. V., Sepah, Y. J., Nguyen, Q. D. 2019; 9 (1): 17

  Abstract

  Uveitis consists of a spectrum of inflammatory disorders characterized by ocular inflammation. The underlying pathophysiology consists of a complex interplay of various inflammatory pathways. Interleukin 6 is an important mediator of inflammation in uveitis and constitutes focus of research toward development of newer biological therapies in the management of non-infectious uveitis.Pan-blockade of the inflammatory pathways with steroids is generally the first step in the management of acute non-infectious uveitis. However, long-term therapy with steroids is associated with systemic and ocular side effects, thereby necessitating the need for development of steroid sparing agents. IL-6 is a cytokine produced by various immune cells, in response to molecular patterns and affects multiple inflammatory cells. In particular, IL-6 is involved in differentiation of CD-4 cells into Th-17 cells that have been shown to play a significant role in various immune-mediated diseases such as uveitis. This broad-spectrum immunomodulatory activity makes IL-6 an excellent target for immunomodulatory therapy. Tocilizumab was the first IL-6 inhibitor to demonstrate efficacy in humans. It inhibits IL-6 from binding to both membrane-bound and soluble receptor and can be administered via intravenous (IV) and subcutaneous (SC) routes. It has been FDA approved for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). Following the approval in systemic diseases, its efficacy was demonstrated in various uveitis studies including a phase 2 clinical trial (STOP-Uveitis). Overall, tocilizumab has shown a good safety profile with the risk of malignancy consistent with that expected in patients with rheumatoid arthritis. However, tocilizumab therapy has been shown to increase the risk for gastrointestinal perforation and dose-dependent neutropenia. Following the success of tocilizumab, several other agents targeting the IL-6 pathway are in the pipeline. These include sirukumab, siltuximab, olokizumab, clazakizumab, and EBI-031 which target IL-6; Sarilumab and ALX-0061 act on the IL-6 receptor.Studies have shown that IL-6 inhibitors can be effective in the management of NIU. In addition, the levels of IL-6 are elevated in other ocular vascular diseases such as retinal vein occlusion and diabetic macular edema. The roles of IL-6 inhibition may be broadened in the future to include the management of retinal vascular diseases and non-uveitic macular edema.

  View details for DOI 10.1186/s12348-019-0182-y

  View details for PubMedID 31523783

• Primary outcomes of the VIDI study: phase 2, double-masked, randomized, active-controlled study of ASP8232 for diabetic macular edema. International journal of retina and vitreous Nguyen, Q. D., Sepah, Y. J., Berger, B., Brown, D., Do, D. V., Garcia-Hernandez, A., Patel, S., Rahhal, F. M., Shildkrot, Y., Renfurm, R. W., VIDI Research Group 2019; 5: 28

  Abstract

  Background: ASP8232 is a potent and specific small molecule vascular adhesion protein-1 (VAP-1) inhibitor. This study evaluated the effect of ASP8232 on excess retinal thickness when given alone or in combination with ranibizumab in patients with center-involved diabetic macular edema (CI-DME).Methods: This was a phase 2a, placebo and sham-injection controlled, double-masked, randomized, parallel-group clinical trial. Participants were patients with CI-DME and central subfield thickness (CST)≥375m in the study eye as assessed by spectral domain optical coherence tomography. Eligible patients were randomized to (1) daily oral ASP8232 40mg monotherapy; (2) combination therapy of daily oral ASP8232 40mg and monthly intravitreal ranibizumab 0.3mg; or (3) monthly intravitreal ranibizumab 0.3mg monotherapy. The treatment period was 12weeks. CST and best corrected visual acuity (BCVA) were assessed at baseline and at Weeks 2, 4, 8, 12, 16 and 24. The primary outcome was the mean percent change from baseline in excess CST at Week 12. Secondary outcomes were BCVA, safety and tolerability, and pharmacokinetic and pharmacodynamic characteristics of ASP8232.Results: After 12weeks, the mean (95% confidence interval) percent change in excess CST was 11.4% (-15.0%, 37.8%) in the ASP8232 group, -61.7% (-86.1%, -37.2%) in the ASP8232/ranibizumab group, and -75.3% (-94.8%, -55.8%) in the ranibizumab group. The change from baseline in the two ranibizumab arms was statistically significant (P<0.001) as was the difference between the ranibizumab groups and the ASP8232 group (P<0.001). Mean (SD) increase in BCVA score from baseline was 3.1 (7.3) in the ASP8232 group, 5.2 (7.1) in the ASP8232/ranibizumab group, and 8.2 (9.5) in the ranibizumab group. The increase from baseline in BCVA score was statistically and clinically significant in the ranibizumab group compared with the ASP8232 group (P=0.015). ASP8232 resulted in near complete inhibition of plasma VAP-1 activity whilst ranibizumab had no effect.Conclusions: Near complete inhibition of plasma VAP-1 activity with ASP8232 had no effect on CST in patients with CI-DME. Furthermore, combination therapy did not provide additional benefit to treatment with ranibizumab alone, which significantly reduced CST and improved BCVA.Trial registration clinicaltrials.gov; NCT02302079. Registered on November 26, 2014.

  View details for DOI 10.1186/s40942-019-0178-7

  View details for PubMedID 31388454

• Effect of vitreomacular adhesion on the treatment outcomes in the STOP-Uveitis clinical trial for non-infectious uveitis. Journal of ophthalmic inflammation and infection Hassan, M. n., Nguyen, N. V., Halim, M. S., Afridi, R. n., Sadiq, M. A., Karkhur, S. n., Vigil, E. n., Karabekirogullari, S. n., Nguyen, Q. D., Do, D. V., Sepah, Y. J. 2019; 9 (1): 12

  Abstract

  To evaluate the role of vitreomacular adhesion (VMA) in visual and anatomic outcomes in patients with non-infectious uveitis.Phase 2 clinical trial PARTICIPANTS: Data from the Safety, Tolerability, and Efficacy of Tocilizumab in Patients with Non-infectious Uveitis (STOP-Uveitis) study was analyzed.In the STOP-Uveitis study, patients with non-infectious uveitis (NIU) received monthly intravenous infusions of either 4 or 8 mg/kg tocilizumab until month 6 (M6). Spectral domain optical coherence tomography (SD-OCT) images of patients that completed M6 of the study were analyzed at baseline to stratify the patients by the presence (VMA+) or absence (VMA-) of VMA. Patients with vitreomacular traction (VMT) or epiretinal membrane causing structural abnormalities within center 1 mm were excluded. All images were graded by two independent graders.Mean change in best-corrected visual acuity (BCVA), central retinal thickness (CRT), and vitreous haze (VH) at M6.Out of 37 patients randomized in the STOP-Uveitis study, 48 eyes (27 patients) were eligible based on the study criteria. At baseline, 19 eyes were classified as VMA+, and 32 eyes were classified as VMA-. The distribution of two doses of TCZ (4 mg/kg and 8 mg/kg) were similar between the two groups. At M6, the mean improvement in BCVA was 2.00 ± 5.3 and 6.50 ± 7.98 letters in the VMA+ and VMA- groups, respectively (p = 0.02). The mean improvement in CRT was 34.85 ± 72.36 and 80.37 ± 157.21 μm in the VMA+ and VMA- groups, respectively (p = 0.18). Similarly, the mean change in VH was - 0.65 ± 0.47 and - 0.76 ± 0.71 in the VMA+ and VMA- groups, respectively (p = 0.32). Out of 16 eyes with VMA at baseline, 3 eyes developed posterior vitreous detachment (PVD) at M6. The mean change in BCVA was significantly higher (p = 0.02), while CRT and VH score were similar (p > 0.05) in eyes with PVD compared to eyes with persistent VMA.The absence of VMA or development of PVD in eyes with VMA seems to have a beneficial effect on the vision of subjects receiving treatment for uveitis. Therefore, patients with uveitis should be assessed using SD-OCT for the presence of vitreomacular interface abnormalities.

  View details for DOI 10.1186/s12348-019-0179-6

  View details for PubMedID 31325001

• Intravitreal Sirolimus for the Treatment of Noninfectious Uveitis: Evolution through Preclinical and Clinical Studies. Ophthalmology Nguyen, Q. D., Merrill, P. T., Sepah, Y. J., Ibrahim, M. A., Banker, A., Leonardi, A., Chernock, M., Mudumba, S., Do, D. V. 2018

  Abstract

  In recent decades, the treatment paradigm for noninfectious intermediate uveitis, posterior uveitis, and panuveitis, a group of intraocular inflammatory diseases, has included systemic and local (periocular or intraocular) corticosteroids, biologics, and other steroid-sparing immunomodulatory therapy agents. Recently, an intravitreal formulation of sirolimus, an immunosuppressant that inhibits the mammalian target of rapamycin, a key regulator of cell growth in the immune system, was developed. On the basis of this mechanism and the local method of delivery, it was hypothesized that intravitreal sirolimus can improve ocular inflammation in patients with noninfectious intermediate uveitis, posterior uveitis, and panuveitis, with minimal systemic exposure and systemic adverse events (AEs). This review summarizes the pharmacokinetics, efficacy, and safety results of intravitreal sirolimus from 3 preclinical studies and 4 phase 1-3 clinical studies. Preclinical studies in rabbits showed that 22 to 220 mug intravitreal sirolimus results in sustained release of sirolimus in the vitreous for 2 months or more, with systemic concentrations below the threshold for systemic immunosuppression (approximately 8 ng/ml). Subsequently, 2 phase 1 studies (n= 50 and n= 30) established that intravitreal sirolimus improves ocular inflammation in humans. Further investigation in phase 2 and 3 studies (n= 24 and n= 347, respectively) suggested that 440 mug has the best benefit-to-risk profile. In the phase 3 study, the proportion of patients who showed complete resolution of ocular inflammation at month 5 was significantly higher in the 440-mug group than in the 44-mug group (22.8% vs. 10.3%; P= 0.025, Fisher exact test). In addition, 47 of 69 patients (68.1%) who were treated with systemic corticosteroids at baseline discontinued corticosteroid use at month 5. No sirolimus-related systemic AEs were reported in phase 1-3 studies. Collectively, these preclinical and clinical study data of intravitreal sirolimus support the therapeutic rationale of treating noninfectious uveitis with a local mammalian target of rapamycin inhibitor and suggest that 440 mug intravitreal sirolimus has the potential to be an effective and well-tolerated anti-inflammatory and corticosteroid-sparing treatment for noninfectious intermediate uveitis, posterior uveitis, and panuveitis.

  View details for PubMedID 30060978

• Trend in Utilizing Wide-Field Fundus Photography in Ophthalmology Huang, L. C., Do, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442912501296

• Posterior Segment Inflammatory Outcomes (Month-6) in the STOP-Uveitis Study: Evaluating the Safety, Tolerability, and Efficacy of Tocilizumab in Patients with Non-Infectious Uveitis Sadiq, M., Hassan, M., Halim, M., Afridi, R., Do, D. V., Quan Dong Nguyen, Sepah, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442932807084

• Low Luminance Deficits in Retinal Disease Bodnar, Z., Shields, R., Dobrota, S., Do, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442932800292

• Baseline characteristics associated with good visual acuity outcomes in myopic choroidal neovascularization: results from the RADIANCE trial Pan, C., Do, D. V., Hill, L., Ecoiffier, T., Stoilov, I. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442912502066

• RPGR-associated retinitis pigmentosa display unique outer retinal and choroidal vascular changes on optical coherence tomography angiography Tang, P., Tsang, S., Bassuk, A., Do, D. V., Mahajan, V. B. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442912508143

• Rethinking Management Strategies for Proliferative Diabetic Retinopathy OPHTHALMIC SURGERY LASERS & IMAGING RETINA Tang, P. H., Hariprasad, S. M., Do, D. V. 2018; 49 (4): 224-+

  View details for DOI 10.3928/23258160-20180329-01

  View details for Web of Science ID 000430534800001

  View details for PubMedID 29664976

• Epidemiology and clinical features of inflammatory retinal vascular occlusions: pooled data from two tertiary-referral institutions CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY Agarwal, A., Karkhur, S., Aggarwal, K., Invernizzi, A., Singh, R., Dogra, M. R., Gupta, V., Gupta, A., Do, D. V., Nguyen, Q. D. 2018; 46 (1): 62–74

  Abstract

  In a subset of patients with retinal vasculitis, there is occlusion of blood flow through the retinal vessels. These eyes are at high risk of sight-threatening complications.To characterize epidemiology, clinical course, treatment and outcomes of occlusive retinal vasculitis (ORV).Retrospective study PARTICIPANTS: Seventy-seven uveitis patients with ORV at two large tertiary-care institutions (the USA and India).Out of 2438 patients screened, 346 patients were diagnosed with retinal vasculitis of which 77 patients (96 eyes) were diagnosed with ORV. Patients with ORV (capillary, arteriolar and/or venular) were further analysed. Diagnostic criteria for occlusive vasculitis included (i) absence of blood flow in vessels (arterioles, venules and/or capillaries), (ii) capillary non-perfusion areas and/or arteriolar-venous anastomosis and (iii) intraretinal haemorrhages, cotton-wool spots or vitreous haemorrhage.Best-corrected visual acuity, treatment and complications.The mean age was 32.09 ± 13.51 years. Most common aetiologies were tuberculosis and Adamantiades-Behçet's disease in India and systemic lupus erythematosus in the USA. Best-corrected visual acuity improved from 0.38 ± 0.30 logMAR (20/48 Snellen equivalent) (baseline) to 0.25 ± 0.30 (20/35 Snellen equivalent) at final visit (P < 0.0001). Vitreous haemorrhage was seen in 31.08% eyes. Pars plana vitrectomy was performed in 12.16% eyes. Therapy with systemic steroids was required in 78.48% patients. In addition, 46.75% patients required immunomodulators and/or biologics.Occlusive retinal vasculitis is caused by heterogeneous group of uveitides depending upon the geographic location. It is imperative to identify eyes with ORV as they are predisposed to complications requiring aggressive therapy.

  View details for PubMedID 28557287

• Evaluating the Impact of Intravitreal Aflibercept on Diabetic Retinopathy Progression in the VIVID-DME and VISTA-DME Studies. Ophthalmology. Retina Mitchell, P. n., McAllister, I. n., Larsen, M. n., Staurenghi, G. n., Korobelnik, J. F., Boyer, D. S., Do, D. V., Brown, D. M., Katz, T. A., Berliner, A. n., Vitti, R. n., Zeitz, O. n., Metzig, C. n., Lu, C. n., Holz, F. G. 2018; 2 (10): 988–96

  Abstract

  To evaluate the impact of intravitreal aflibercept (EYLEA, Regeneron Pharmaceuticals, Tarrytown, NY) versus laser on progression of diabetic retinopathy (DR) severity in Intravitreal Aflibercept Injection in Vision Impairment due to DME (VIVID-DME) and Study of Intravitreal Aflibercept Injection in Patients with Diabetic Macular Edema (VISTA-DME).Secondary and exploratory analyses of 2 phase 3, randomized, controlled studies.All patients with a baseline Diabetic Retinopathy Severity Scale (DRSS) score based on fundus photograph (full analysis), patients who progressed to proliferative DR (PDR) (safety analysis) in VIVID-DME (n = 403) and VISTA-DME (n = 459), or both.We randomized patients with diabetic macular edema (DME) to intravitreal aflibercept 2 mg every 4 weeks (2q4), intravitreal aflibercept 2 mg every 8 weeks after 5 initial monthly doses (2q8), or macular laser photocoagulation at baseline and sham injections at every visit.Proportions of patients with 2-step or more and 3-step or more improvements from baseline in DRSS score, who progressed to PDR, and who underwent panretinal photocoagulation (PRP).Among patients with an assessable baseline DRSS score, most showed moderately severe or severe nonproliferative DR. The proportions of patients treated with 2q4, 2q8, and laser with a 2-step or more improvement in DRSS score at week 100 were 29.3%, 32.6%, and 8.2%, respectively, in VIVID-DME and 37.0%, 37.1%, and 15.6%, respectively, in VISTA-DME; the proportions with a 3-step or more improvement in DRSS score were 7.3%, 2.3%, and 0%, respectively, and 22.7%, 19.9%, and 5.2%, respectively. Fewer patients in the 2q4 and 2q8 groups versus the laser group progressed to PDR at week 100 in VISTA-DME (1.5% and 2.2% vs. 5.3%) and VIVID-DME (3.2% and 2.0% vs. 12.3%). The proportions of patients who underwent PRP were 2.9%, 0.7%, and 4.5%, respectively, in VIVID-DME and 1.9%, 0.7%, and 5.2%, respectively, in VISTA-DME. The most frequent serious ocular adverse event at week 100 was cataract (pooled intravitreal aflibercept, 1.7% of patients; laser, 3.5% of patients).These analyses demonstrate the benefit of intravitreal aflibercept over laser with respect to DR progression, suggesting a benefit on DME, and on underlying DR.

  View details for PubMedID 31047501

• Surgery for postvitrectomy cataract. The Cochrane database of systematic reviews Do, D. V., Gichuhi, S., Vedula, S. S., Hawkins, B. S. 2018; 1: CD006366

  Abstract

  BACKGROUND: Cataract formation or acceleration can occur after intraocular surgery, especially following vitrectomy, a surgical technique for removing the vitreous that is used in the treatment of many disorders that affect the posterior segment of the eye. The underlying problem that led to vitrectomy may limit the benefit from removal of the cataractous lens.OBJECTIVES: To evaluate the effectiveness and safety of surgery versus no surgery for postvitrectomy cataract with respect to visual acuity, quality of life, and other outcomes.SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 5), MEDLINE Ovid (1946 to 17 May 2017), Embase.com (1947 to 17 May 2017), PubMed (1946 to 17 May 2017), Latin American and Caribbean Health Sciences Literature database (LILACS) (January 1982 to 17 May 2017), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com); last searched May 2013, ClinicalTrials.gov (www.clinicaltrials.gov); searched 17 May 2017, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 17 May 2017. We did not use any date or language restrictions in the electronic searches for trials.SELECTION CRITERIA: We planned to include randomized controlled trials (RCTs) and quasi-RCTs that had compared surgery versus no surgery to remove the lens from eyes of adults in which cataracts had developed following vitrectomy.DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results according to the standard methodological procedures expected by Cochrane.MAIN RESULTS: We found no RCTs or quasi-RCTs that had compared surgery versus no surgery to remove the lens from eyes of adults in which cataracts had developed following vitrectomy.AUTHORS' CONCLUSIONS: There is no evidence from RCTs or quasi-RCTs on which to base clinical recommendations for surgery for postvitrectomy cataract. There is a clear need for RCTs to address this evidence gap. Such trials should stratify participants by their age, the retinal disorder leading to vitrectomy, and the status of the underlying disease process in the contralateral eye. Outcomes assessed in such trials may include changes (both gains and losses) of visual acuity, quality of life, and adverse events such as posterior capsular rupture and retinal detachment. Both short-term (six-month) and long-term (one- or two-year) outcomes should be examined.

  View details for PubMedID 29364503

• SUPRACHOROIDAL INJECTION OF TRIAMCINOLONE ACETONIDE, CLS-TA, FOR MACULAR EDEMA DUE TO NONINFECTIOUS UVEITIS: A Randomized, Phase 2 Study (DOGWOOD). Retina (Philadelphia, Pa.) Yeh, S. n., Kurup, S. K., Wang, R. C., Foster, C. S., Noronha, G. n., Nguyen, Q. D., Do, D. V. 2018

  Abstract

  Evaluate a single suprachoroidal injection of a proprietary triamcinolone acetonide suspension, CLS-TA, in subjects with macular edema due to noninfectious uveitis.Randomized, controlled, masked Phase 2 study. Safety and efficacy of a single suprachoroidal injection of CLS-TA (4.0 and 0.8 mg in a 4:1 ratio) were assessed at 1 and 2 months after injection. The primary efficacy endpoint was change in central subfield thickness from baseline to Month 2, assessed by spectral domain optical coherence tomography.Twenty-two adults were enrolled. The primary endpoint was met in subjects who received suprachoroidal injection of CLS-TA 4.0 mg, mean central subfield thickness significantly decreased from baseline by 135 µm and 164 µm at Month 1 (P = 0.0056) and Month 2 (P = 0.0017), respectively. At Month 2, 69% of subjects who received 4.0 mg experienced ≥20% reduction in central subfield thickness, and 65% had improvement of best-corrected visual acuity of ≥5 Early Treatment Diabetic Retinopathy Study letters, with a mean improvement of 9.2 letters (P = 0.0004). Safety analyses supported acceptable safety/tolerability, with no corticosteroid-related increases in intraocular pressure.A single suprachoroidal injection of CLS-TA (4.0 mg; 0.1 mL) in subjects with macular edema due to noninfectious uveitis was well-tolerated, significantly reduced central subfield thickness from baseline at 2 months, and significantly improved visual acuity.

  View details for PubMedID 30113933

• Diurnal variation of choriocapillaris vessel flow density in normal subjects measured using optical coherence tomography angiography. International journal of retina and vitreous Sarwar, S., Hassan, M., Soliman, M. K., Halim, M. S., Sadiq, M. A., Afridi, R., Agarwal, A., Do, D. V., Nguyen, Q. D., Sepah, Y. J. 2018; 4: 37

  Abstract

  Background: Vessel flow density (VFD) may provide important information regarding perfusion status. Diurnal variation in VFD of choriocapillaris has not been reported in literature. In the index study, optical coherence tomography angiography (OCTA) was used to assess the diurnal variation of the VFD in the choriocapillaris of subjects with no known ocular disease.Methods: Fifty eyes with no known ocular disease (25 subjects) were included. OCTA images were acquired using AngioVue (Optovue, Fremont, CA, USA) at two different time points on a single day: 9:00 AM and 6:00 PM. Macular cube scan protocol (3*3mm) centered on the fovea was used. Automatic segmentation of the retinal layers and choriocapillaris was performed using ReVue software, which was also used to measure the choriocapillaris VFD. Horizontal line scan passing through fovea was obtained by the device at both time points to measure the subfoveal choroidal thickness (CT). Linear measurement tool of software was used to measure subfoveal CT according to a standardized reproducible method. Wilcoxon signed-rank test was used to assess the differences in choriocapillaris VFD and subfoveal CT at the two time points. Correlation between change in choriocapillaris VFD and subfoveal CT at the two time points was assessed using the Pearson correlation coefficient (r).Results: The mean age of the subjects was 31.96±11.23years. Choriocapillaris VFD was significantly higher at 9:00 AM compared to 6:00 PM (P<0.0001) with mean choriocapillaris VFD of 68.74±4.80% at 9:00 AM and 67.57±5.41% at 6:00 PM, with a mean diurnal amplitude of 1.17%. Mean subfoveal CT was 287.74±61.51m at 9:00 AM and 270.06±60.73m at 6:00 PM. Subfoveal CT was also significantly higher at 9:00 AM compared to 6:00 PM (P<0.0001) with a mean diurnal amplitude of 17.68m. Change in choriocapillaris VFD correlated with change in subfoveal CT (r=0.87, P<0.001).Conclusion: OCTA demonstrated significant diurnal change in choriocapillaris VFD in subjects without any ocular disease with VFD being higher in the morning and lower in the evening. Decrease in choriocapillaris VFD in the evening correlated with a reduction in subfoveal CT.

  View details for PubMedID 30338130

• Primary (Month-6) Outcomes of the STOP-Uveitis Study: Evaluating the Safety, Tolerability, and Efficacy of Tocilizumab in Patients With Noninfectious Uveitis AMERICAN JOURNAL OF OPHTHALMOLOGY Sepah, Y., Sadiq, M., Chu, D. S., Dacey, M., Gallemore, R., Dayani, P., Hanout, M., Hassan, M., Afridi, R., Agarwal, A., Halim, M., Do, D. V., Quan Dong Nguyen 2017; 183: 71–80

  Abstract

  To report the primary endpoint analyses of the safety and efficacy of 2 different doses of intravenous (IV) infusions of tocilizumab (TCZ), an IL-6 inhibitor, in eyes with noninfectious intermediate uveitis, posterior uveitis, or panuveitis.Randomized, controlled, multicenter clinical trial.STOP-Uveitis is a randomized, open-label safety, efficacy, and bioactivity clinical trial conducted at 5 clinical centers across the United States. The study evaluated the role of TCZ in patients with noninfectious uveitis (NIU). Thirty-seven patients with NIU were randomized into one of 2 treatment groups in a ratio of 1:1. Group 1 received IV infusions of 4 mg/kg TCZ and group 2 received IV infusions of 8 mg/kg TCZ. Infusions were given every 4 weeks in both groups until month 6 (primary endpoint). Primary outcome measure was incidence and severity of systemic and ocular adverse events through month 6. Secondary outcome measures included mean change in visual acuity (VA), vitreous haze (VH), and central macular thickness (CMT) at month 6.A total of 37 patients were randomized in the study. At month 6, 43.5% of patients who had the potential for a 2-step decrease in VH demonstrated a 2-step decrease (40% in Group 1 and 46.1% in Group 2). Mean change in CMT was -83.88 ± 136.1 μm at month 6 (-131.5 ± 41.56 μm in Group 1 and -38.92 ± 13.7 μm in Group 2). Mean change in VA was +8.22 ± 11.83 ETDRS letters at month 6 (10.9 ± 14.6 in Group 1 and 5.5 ± 7.8 in Group 2). Repeated infusions of TCZ were well tolerated.Repeated IV administrations of TCZ are well tolerated. TCZ (both 4 and 8 mg/kg) is effective in improving VA and reducing VH and CMT in eyes with noninfectious intermediate uveitis, posterior uveitis, and panuveitis.

  View details for PubMedID 28887113

• Comparison of Clinical Trial and Systematic Review Outcomes for the 4 Most Prevalent Eye Diseases JAMA OPHTHALMOLOGY Saldanha, I. J., Lindsley, K., Do, D. V., Chuck, R. S., Meyerle, C., Jones, L. S., Coleman, A. L., Jampel, H. D., Dickersin, K., Virgili, G. 2017; 135 (9): 933–40

  Abstract

  Suboptimal overlap in outcomes reported in clinical trials and systematic reviews compromises efforts to compare and summarize results across these studies.To examine the most frequent outcomes used in trials and reviews of the 4 most prevalent eye diseases (age-related macular degeneration [AMD], cataract, diabetic retinopathy [DR], and glaucoma) and the overlap between outcomes in the reviews and the trials included in the reviews.This cross-sectional study examined all Cochrane reviews that addressed AMD, cataract, DR, and glaucoma; were published as of July 20, 2016; and included at least 1 trial and the trials included in the reviews. For each disease, a pair of clinical experts independently classified all outcomes and resolved discrepancies. Outcomes (outcome domains) were then compared separately for each disease.Proportion of review outcomes also reported in trials and vice versa.This study included 56 reviews that comprised 414 trials. Although the median number of outcomes per trial and per review was the same (n = 5) for each disease, the trials included a greater number of outcomes overall than did the reviews, ranging from 2.9 times greater (89 vs 30 outcomes for glaucoma) to 4.9 times greater (107 vs 22 outcomes for AMD). Most review outcomes, ranging from 14 of 19 outcomes (73.7%) (for DR) to 27 of 29 outcomes (93.1%) (for cataract), were also reported in the trials. For trial outcomes, however, the proportion also named in reviews was low, ranging from 19 of 107 outcomes (17.8%) (for AMD) to 24 of 89 outcomes (27.0%) (for glaucoma). Only 1 outcome (visual acuity) was consistently reported in greater than half the trials and greater than half the reviews.Although most review outcomes were reported in the trials, most trial outcomes were not reported in the reviews. The current analysis focused on outcome domains, which might underestimate the problem of inconsistent outcomes. Other important elements of an outcome (ie, specific measurement, specific metric, method of aggregation, and time points) might have differed even though the domains overlapped. Inconsistency in trial outcomes may impede research synthesis and indicates the need for disease-specific core outcome sets in ophthalmology.

  View details for PubMedID 28772305

  View details for PubMedCentralID PMC5625342

• Evaluation of macular and peripapillary vessel flow density in eyes with no known pathology using optical coherence tomography angiography. International journal of retina and vitreous Hassan, M. n., Sadiq, M. A., Halim, M. S., Afridi, R. n., Soliman, M. K., Sarwar, S. n., Agarwal, A. n., Do, D. V., Nguyen, Q. D., Sepah, Y. J. 2017; 3: 27

  Abstract

  To assess normal vessel flow density (VFD) in macular and peripapillary regions of eyes with no known ocular pathology using optical coherence tomography angiography (OCTA).AngioVue (Optovue, Fremont, CA, USA) was used to capture OCTA images. A 3 × 3 mm grid and a 4.5 × 4.5 mm grid was used to scan parafoveal and peripapillary regions, respectively. ReVue software was utilized to measure VFD in five sectors within the inner two circles of ETDRS grid in macular region and correlated to retinal thickness of same sectors. At optic disc, VFD was calculated in six sectors based on Garway-Heath map. Area and morphology of foveal avascular zone (FAZ) was correlated with VFD in central 1 mm. The influence of myopia on mean VFD was also assessed.Twenty-four eyes (mean age: 30 years) were analyzed. Mean VFD in macular sectors was 43.5 (±4.5) and 45.8 (±5.0) % in superficial and deep retinal plexuses, respectively. Mean VFD was significantly higher in deep retinal plexus compared to superficial retinal plexus in all sectors except central 1 mm (p < 0.05). Mean VFD in central 1 mm increases with an increase in central retinal thickness in both superficial and deep retinal plexuses (p < 0.001). Mean parafoveal VFD at level of both superficial and deep retinal plexuses decrease with an increase in spherical equivalent in myopics (p < 0.05). Mean VFD in myopics was found to be significantly lower in parafoveal region of deep retinal plexus (p < 0.05). Mean area of FAZ was 0.33 (±0.15) and 0.47 mm2 (±0.15) in superficial and deep retinal plexuses, respectively. Area of FAZ decreases with an increase in central 1 mm thickness and foveal VFD (p < 0.001).OCTA may be used to measure VFD in macular and peripapillary regions. Vessels in the parafoveal region are more densely packed in the deep retinal plexus leading to higher VFD compared to superficial plexus. Thicker retina in fovea translates into higher foveal VFD due to more compact arrangement of retinal layers and continuity of inner nuclear layer (INL). Myopia is associated with lower VFD in parafoveal region at level of deep retinal plexuses which may explain thinning of INL in myopics.

  View details for PubMedID 28781889

  View details for PubMedCentralID PMC5535290

• Effects of Two Different Doses of Ranibizumab on Diabetic Retinopathy Severity Ophthalmology Retina Sadiq, M. A., Hassan, M., Soliman, M. K., Afridi, R., Do, D. V., Nguyen, Q. D., Sepah, Y. J. 2017; 1 (6): 566-567

  View details for DOI 10.1016/j.oret.2017.03.002

• Recent advances in the management and understanding of diabetic retinopathy. F1000Research Powers, M. n., Greven, M. n., Kleinman, R. n., Nguyen, Q. D., Do, D. n. 2017; 6: 2063

  Abstract

  Despite recent advances in the diagnosis and treatment of diabetic retinopathy, this complication remains a steadfast challenge to patients and physicians. This review summarizes recent progress in the diagnosis and management of diabetic retinopathy, including automated screening, optical coherence tomography, control of systemic risk factors, surgical techniques, laser treatment, and pharmaceutical treatment, including vascular endothelial growth factor inhibitors. Recent advances in pharmaceutical treatments, in particular, hold strong promise of halting and sometimes reversing the disease process. Clinicians nevertheless must remain vigilant in their efforts to diagnose and treat this disease early in its course.

  View details for PubMedID 29225791

  View details for PubMedCentralID PMC5710306

• Effects of Two Different Doses of Ranibizumab on Diabetic Retinopathy Severity. Ophthalmology. Retina Sadiq, M. A., Hassan, M. n., Soliman, M. K., Afridi, R. n., Do, D. V., Nguyen, Q. D., Sepah, Y. J. 2017; 1 (6): 566–67

  View details for PubMedID 31047459

• Multimodal Imaging in Retinal Vasculitis. Ocular immunology and inflammation Agarwal, A. n., Afridi, R. n., Agrawal, R. n., Do, D. V., Gupta, V. n., Nguyen, Q. D. 2017; 25 (3): 424–33

  Abstract

  Retinal vasculitis presents with inflammation involving the retinal vasculature as an isolated disease or in combination with other ocular or systemic conditions. This entity may be associated with a wide variety of clinical manifestations such as vascular sheathing, cotton-wool spots, retinal ischemia, and neovascularization. Often, retinal vasculitis and its complications lead to diagnostic challenges in identifying the exact etiology of the inflammation. Ancillary investigations such as fundus photography, fluorescein angiography, and more recently, adaptive optics imaging and optical coherence tomography angiography, may provide valuable information that help in establishing the exact diagnosis and initiation of appropriate therapy. In the index review, multimodal imaging features of retinal vasculitis are described. In addition, detection of vascular inflammation using novel noncontact imaging techniques has been highlighted.

  View details for PubMedID 28696172

• Management of macular edema due to central retinal vein occlusion - The role of aflibercept. Taiwan journal of ophthalmology Rhoades, W. n., Dickson, D. n., Nguyen, Q. D., Do, D. V. ; 7 (2): 70–76

  Abstract

  Central retinal vein occlusion (CRVO) can cause vision loss. The pathogenesis of CRVO involves a thrombus formation leading to increased retinal capillary pressure, increased vascular permeability, and possibly retinal neovascularization. Vision loss due to CRVO is commonly caused by macular edema. Multiple treatment modalities have been used to treat macular edema. Currently, the most common therapy used is intravitreal inhibition of vascular endothelial growth factor (VEGF). The three most widely used agents are aflibercept, bevacizumab, and ranibizumab and they are effective at blocking VEGF. In addition, intraocular steroids can be used to treat macular edema. This review will briefly cover the treatment options and discuss in greater detail the efficacy and safety of aflibercept.

  View details for PubMedID 29018760

  View details for PubMedCentralID PMC5602151