Diana Do, MD

All Publications

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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. 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

• 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., 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

• 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