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  • 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. 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

  • Correlation between Subfoveal Choroidal Thickness and Anterior Segment Inflammation in Patients with Chronic Stage of Vogt-Koyanagi-Harada Disease. Ocular immunology and inflammation Ormaechea, M. S., Hassan, M., Mahajan, S., Nguyen, Q. D., Couto, C., Schlaen, A. 2020: 1–6

    Abstract

    To correlate changes in subfoveal choroidal thickness (SCT) with the degree of anterior inflammatory activity in chronic Vogt-Koyanagi-Harada (VKH) disease.Anterior segment inflammation was assessed using SUN anterior chamber cell grading criteria, and SCT was measured using EDI-OCT in patients with VKH at multiple visits. ANOVA was used to compare the mean SCT for each anterior chamber cell grade. Regression analysis was used to correlate the anterior segment cell grade and the SCT.14 patients were included in the study. A total of 432 data points consisting of SCT and anterior segment cell values were analyzed. ANOVA demonstrated significant difference between the mean SCT for different anterior chamber cell grades (p < .0001). Regression analysis demonstrated significant correlation between SCT and grade of anterior chamber cells (R2 = 0.37, p < .001).Chronic VKH is characterized by a dynamic change in SCT that correlates with anterior segment inflammatory activity.

    View details for DOI 10.1080/09273948.2020.1826533

    View details for PubMedID 33021859

  • Acute syphilitic posterior placoid chorioretinopathy: An infectious or autoimmune disease? American journal of ophthalmology case reports Ormaechea, M. S., Hassan, M., Nguyen, Q. D., Schlaen, A. 2019; 14: 70–73

    Abstract

    Purpose: To report a case of acute syphilitic posterior placoid chorioretinopathy (ASPPC) that demonstrated partial resolution with immunosuppressive therapy secondary to a misdiagnosis as Behcet's disease followed by a relapse which was successfully treated with the appropriate treatment.Observations: A 34-year-old female patient presented to our service with complaints of decreased vision in the left eye (OS). She initially developed similar symptoms seven months prior to presentation and was diagnosed as Behcet's disease based on the clinical picture of papillitis, vasculitis and placoid chorioretinitis in the posterior pole of OS. She was started on daily oral prednisone 60 mg and weekly methotrexate 10mg by her rheumatologist. The patient's ocular symptoms improved one month prior to presentation with resolution of the placoid lesion but persistence of vasculitis and papillitis. At that time, the dose of the prednisone was decreased to 30 mg which resulted in a relapse of the placoid chorioretinal lesions and worsened visual acuity at the time of presentation to us. Extensive laboratory workup demonstrated positive serology for syphilis. A diagnosis of syphilitic placoid chorioretinitis was made and the patient was treated with intravenous penicillin G for 2 weeks. The vitritis, papillitis, and placoid chorioretinitis resolved along with improvement in vision following the treatment.Conclusions and importance: Ocular findings in syphilis are heterogeneous and may mimic variety of ocular diseases. ASPPC is a rare ocular manifestation of syphilis and its natural course and underlying pathophysiology is not well understood. However, irrespective of the underlying mechanism of the disease, all patients with ASPPC should receive treatment to prevent recurrence and long-term functional damage.

    View details for PubMedID 30923777

  • Cyclodialysis cleft repair with scleral band-buckle encirclage without cryopexy in the management of traumatic hypotony maculopathy. American journal of ophthalmology case reports Karkhur, S., Vigil, E., Shenoy, P., Soni, D., Plaza-Laguardia, C., Hassan, M., Sharma, B., Nguyen, Q. D. 2020; 20: 100946

    Abstract

    Purpose: To describe the technique of traumatic cyclodialysis cleft repair in the management of hypotony maculopathy using anterior placement of encircling scleral band-buckle.Observations: A 51-year-old male who had sustained blunt trauma in the left eye two months prior to presentation in the clinics, presented with visual acuity of 20/200, a persistent cyclodialysis cleft with hypotony maculopathy and intraocular pressure (IOP) of 6mm Hg. A silicone band-buckle was passed 360°; with its anterior edge hugging the insertion of rectus muscles along the 'spiral of Tillaux'. Post-operative course showed closure of the cleft with an IOP of 20mm Hg at day 4. Patient underwent cataract extraction with intraocular lens implantation at two months and improved to 20/40 at the last follow up visit with a normal IOP.Conclusion and Importance: We successfully managed a case of hypotony maculopathy due to persistent cyclodialysis cleft using a circumferential band buckle. We avoided the use of cryopexy to avoid the potential risk of inflammation - further worsening choroidal effusion and rare occurrence of suprachoroidal hemorrhage.

    View details for DOI 10.1016/j.ajoc.2020.100946

    View details for PubMedID 33089010

  • 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

  • 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
  • Significance of External Limiting Membrane Integrity as an OCT Biomarker on Functional Outcomes in Eyes with Macular Edema Huy Vu Nguyen, Hassan, M., Yusuf, K., Ormaechea, M., Uludag, G., Halim, M., Afridi, R., Nam Nguyen, Vigil, E., Sepah, Y., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020
  • Ocular Toxoplasmosis Lesion Detection on Fundus Photograph using a Deep Learning Model Hasanreisoglu, M., Halim, M., Chakravarthy, A., Soledad Ormaechea, M., Uludag, G., Hassan, M., Ozdemir, H., Ozdal, P., Colombero, D., Rudzinski, M. N., Ariel Schlaen, B., Sepah, Y., Chundi, P., Subramaniam, M., Nguyen, Q. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020
  • 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: 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

  • Acute lymphocytic leukemia masquerading as acute retinal necrosis. American journal of ophthalmology case reports Carter, K. L., Hassan, M., 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

  • Posterior segment inflammatory outcomes assessed using fluorescein angiography in the STOP-UVEITIS study. International journal of retina and vitreous Sadiq, M. A., Hassan, M., Afridi, R., 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

  • Topographic correlation between multifocal electroretinography, microperimetry, and spectral-domain optical coherence tomography of the macula in patients with birdshot chorioretinopathy. Journal of ophthalmic inflammation and infection Afridi, R., Agarwal, A., Nguyen, N. V., Hassan, M., Sadiq, M. A., Nguyen, Q. D., Sepah, Y. J. 2019; 9 (1): 24

    Abstract

    PURPOSE: To correlate the findings of retinal function with multifocal electroretinogram (mfERG), microperimetry (MP), and structural assessments with spectral-domain optical coherence tomography (SD-OCT) in topographically corresponding areas of the macula of patients with birdshot chorioretinopathy (BSCR).METHODS: Patients diagnosed with BSCR by clinical and imaging findings were included in the study. The mfERG was performed using 61 hexagon stimulus patterns grouped into 5 rings (Diagnosys Inc., USA). Individual responses [N1-P1 amplitudes in nanovolt (NV)/degree2 and P1 implicit time in milliseconds (msec)] for each hexagon in the central 3 rings (R1, 0°-2.3°; R2,2.3°-7.7°; and R3, 7.7°-12°) were obtained (19 hexagons). MP examination consisted of Polar 3-12° test with 28 points in 3 concentric rings with diameters of approximately 2.3°, 6.6°, and 11.1° from the foveal center. SD-OCT was performed using macular scans of 20° * 20°. The retinal sensitivity values on MP and thickness values of retinal layers were correlated with the responses on the mfERG for each topographically correlated hexagon.RESULTS: Sixteen eyes of eight patients were included in the study (mean age, 59.87 ± 10.01 years; range, 41-73 years). The amplitudes and the implicit times on mfERG and retinal sensitivities on MP were decreased for each of the 19 hexagons. Considering retinotopically matched points, there was correlation between the retinal sensitivities and mfERG implicit times and response amplitudes in all three rings. The thickness of the retinal pigment epithelium showed modest correlation with the mfERG parameters (rho = 0.29; p = 0.04). The structural changes on SD-OCT, such as IS-OS disruption, were associated with changes in the mfERG trace arrays.CONCLUSIONS: The structural and functional assessments in retinae of eyes with BSCR suggest that each imaging tool may be capturing unique aspects of retinal dysfunction. Multimodal imaging may allow detailed analyses of retinal damage at various corresponding loci. These findings are important when considering the use of these techniques in BSCR.

    View details for DOI 10.1186/s12348-019-0188-5

    View details for PubMedID 31884521

  • 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

  • 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. T., Mahajan, S., Al-Kirwi, K., Afridi, R., Sepah, Y., Do, D. V., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • 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
  • Evaluating the Short-Term Effects on Semi-automated Aqueous Flare Assessment After Fundus Fluorescein Angiography Imaging Nguyen, N. V., Halim, M., Hassan, M., Segawa, A., Ertop, M., Aktas, Z., Ozdek, S., Gurelik, G., Anh Ngoc Tram Tran, Mahajan, S., Afridi, R., Ibrahim, M. A., Sepah, Y., Quan Dong Nguyen, Hasanreisoglu, M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • 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
  • Adaptive Optics Findings in Vogt-Koyanagi-Harada Disease Pham, A., Halim, M., Razeen, M. M., Hassan, M., Ormaechea, M., Razeen, E., Uludag, G., Anh Ngoc Tram Tran, Al-Kirwi, K., Mahajan, S., Afridi, R., Dubra, A., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • Evolving demographics, risk factors, and treatment strategies for uveitis at a tertiary care hospital over a decade: 2008-2018 Park, J., Halim, M., Ormaechea, M., Hassan, M., Anh Ngoc Tram Tran, Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • 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
  • 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

  • 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

  • Blue light versus green light fundus autofluorescence in normal subjects and in patients with retinochoroidopathy secondary to retinal and uveitic diseases. Journal of ophthalmic inflammation and infection Bittencourt, M. G., Hassan, M., Halim, M. S., Afridi, R., Nguyen, N. V., Plaza, C., Tran, A. N., Ahmed, M. I., Nguyen, Q. D., Sepah, Y. J. 2019; 9 (1): 1

    Abstract

    PURPOSE: The aim of this study is to evaluate the differences in the fundus autofluorescence (FAF) signal between the blue light autofluorescence (BAF) from Spectralis (Heidelberg, CA) and green light autofluorescence (GAF) 200TxTM (OPTOS, UK, in normal subjects and in patients with retinochoroidopathies (RC).METHODS: In this prospective study, FAF was performed using BL (lambda=488nm) and GL (lambda=532nm) on normal subjects and patients with RC. The corresponding pairs of BAF and GAF images from both groups were analyzed using Photoshop. The strength of the FAF signal was measured on a gray scale, where optic disc was a standard to indicate absence of AF. In addition, gray values obtained from three identical points (foveal center, and points of hypo and hyper autofluorescence) in the corresponding BAF and GAF images of normal and RC subjects were divided by the optic disc value to calculate autofluorescence signal ratio (R). The R values at fovea (R1), hypoautofluorescent point (R2), and hyperautofluorescent point (R3) were compared between BAF and GAF modalities, in normal and in RC subjects separately.RESULTS: One hundred six pairs (106 eyes) of FAF images analyzed (37 pairs: normal and 69 pairs: RC subjects). In normal subjects, the mean R1, R2, and R3 values for BAF were (1.5±0.88, 1.23±0.58, and 4.73±2.85, respectively) and for GAF were (0.78±0.20, 0.78±0.20, and 1.62±0.39, respectively). Similarly, in subjects with RC, the mean R1, R2, and R3 values for BAF were (1.68±1.02, 1.66±1.15, and 7.75±6.82, respectively) and for GAF were (0.95±0.59, 0.79±0.45, and 2.50±1.65, respectively). The mean difference in the R1, R2, and R3 ratios between BAF and GAF in normal and in RC subjects was statistically significant (p<0.001). The strength of the correlation (r) between ratios for BAF and GAF was weak or not statistically significant in both normal and RC subjects (p>0.05).CONCLUSION: The distribution and intensity of the AF signal differ in BAF and GAF and cannot be used interchangeably. In BAF, optic disc signal is always weaker than in other areas, which was not true for GAF where optic disc signal was stronger than fovea and hypoautofluorescent point in both groups.

    View details for PubMedID 30617430

  • Blue light versus green light fundus autofluorescence in normal subjects and in patients with retinochoroidopathy secondary to retinal and uveitic diseases JOURNAL OF OPHTHALMIC INFLAMMATION AND INFECTION Bittencourt, M., Hassan, M., Halim, M., Afridi, R., Nguyen, N. V., Plaza, C., Tran, A. T., Ahmed, M., Quan Dong Nguyen, Sepah, Y. 2019; 9
  • 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., Halim, M. S., Baluyot, S. C., Guzman, H. A., Afridi, R., 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

  • Fungal Endogenous Endophthalmitis during Pregnancy as a Complication of In-Vitro Fertilization. Ocular immunology and inflammation Hasanreisoglu, M., Mahajan, S., Ozdemir, H. B., Ozdal, P. C., Halim, M. S., Hassan, M., Nguyen, Q. D. 2019: 1–4

    Abstract

    Purpose: To report a Candida endogenous endophthalmitis in a pregnant woman with a prior history of in-vitro fertilization (IVF).Methods: Case report.Results: 21-year-old healthy woman within the first trimester of her pregnancy of a successful IVF developed a focal retinitis and panuveitis. Ocular findings suggested fungal endophthalmitis. The patient was treated with pars plana vitrectomy and repeated intravitreal antifungal injections. No systemic therapy was given. Cultures showed Candida albicans. IVF procedure was the only identifiable risk factor for endogenous endophthalmitis.Conclusions: In-vitro fertilization appeared as a possible risk factor for endogenous endophthalmitis during pregnancy. In the absence of systemic fungal infection, local intravitreal antifungal injections seem to be effective options to treat endogenous candida endophthalmitis, especially in the first trimester.

    View details for DOI 10.1080/09273948.2019.1677917

    View details for PubMedID 31664877

  • Interleukin-6 inhibition in the management of non-infectious uveitis and beyond. Journal of ophthalmic inflammation and infection Karkhur, S., Hasanreisoglu, M., Vigil, E., Halim, M. S., Hassan, M., Plaza, C., Nguyen, N. V., Afridi, R., 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

  • 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., Nguyen, N. V., Halim, M. S., Afridi, R., Sadiq, M. A., Karkhur, S., Vigil, E., Karabekirogullari, S., 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

  • Effects of Vitreomacular Adhesion on Treatment Outcomes in the Study of Safety and Bioactivity of TOcilizumab in Patients with Non-Infectious UVEITIS: The STOP-UVEITIS Study Nguyen, N. V., Hassan, M., Halim, M., Afridi, R., Baluyot, S., Sepah, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • 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
  • Scleral Vessel Density Using Novel Optical Coherence Tomography Angiography Methodology Halim, M., Hassan, M., Afridi, R., Nguyen, N. V., Maleki, A., Baluyot, S., Sepah, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Can Fundus Photograph Montage Replace the Standard 7-Field Stereo Images for Diabetic Retinopathy Severity Scale Assessments? Baluyot, S., Hassan, M., Halim, M., Afridi, R., Nguyen, N. V., Sepah, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • 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

  • Short-Term Effects of Ranibizumab on Diabetic Retinopathy Severity and Progression. Ophthalmology. Retina Hassan, M., Sadiq, M. A., Halim, M. S., Afridi, R., Nguyen, N. V., Sepah, Y. J. 2018; 2 (7): 749–51

    View details for PubMedID 31047386

  • Fundus Autofluorescence Imaging in Posterior Uveitis Multimodal Imaging in Uveitis Afridi, R., Agarwal, A., Sadiq, M. A., Hassan, M., Do, D. V., Nguyen, Q. D. Springer International Publishing. 2018: 69–85
  • Multifocal Choroiditis The Uveitis Atlas Hassan, M., Nguyen, N., Sepah, Y. J., Nguyen, Q. D. Springer, New Delhi. 2018
  • 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

  • Effect of Myopia on the Macular Vessel Flow Density in Eyes Using Optical Coherence Tomography Angiography Sepah, Y., Hassan, M., Halim, M., Sadiq, M., Afridi, R., Do, D. V., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2017
  • Correction of Perceived Visual Distortions Using a Software Application and Correlation to Age-Related Macular Degeneration. Hassan, M., Chakarvarthy, A., Subramaniam, M., Chundi, P., Jawed, M., Halim, M., Sadiq, M., Afridi, R., Sepah, Y., Quan Dong Nguyen, Do, D. V., Margalit, E. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2017
  • Effect of Vitreomacular Adhesion on Treatment Outcomes in the Ranibizumab for Edema of the mAcula in Diabetes-3 (READ-3) Study -Month 24 Results Sadiq, M., Hassan, M., Afridi, R., Halim, M., Do, D. V., Quan Dong Nguyen, Sepah, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2017
  • Differences in the characteristics of subjects achieving complete or partial resolution of diabetic macular edema in the READ-3 Study Halim, M., Afridi, R., Hassan, M., Sadiq, M., Do, D. V., Quan Dong Nguyen, Sepah, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2017
  • Can the levels of inflammatory cytokines in the anterior chamber of eyes with diabetic macular edema predict response to therapy? Afridi, R., Halim, M., Sadiq, M., Hassan, M., Agarwal, A., Do, D. V., Quan Dong Nguyen, Sepah, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2017
  • Assessment of Changes in Quality of Life Among Subjects in the STOP-Uveitis Study Greer, L. C., Jawed, M., Caldwell, K., Wilson, R., Halim, M., Hassan, M., Sadiq, M., Afridi, R., Do, D. V., Sepah, Y., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2017
  • Towards Automated Distortion and Health Correlation for Age-Related Macular Degeneration Chakravarthy, A. D., Subramaniam, M., Chundi, P., Hassan, M., Nguyen, Q., IEEE IEEE. 2017: 486–91
  • 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): 566–67

    View details for PubMedID 31047459

  • 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
  • The Role of Sirolimus in the Management of Uveitis Evolution of intravitreal sirolimus through clinical trials Retinal Physician Hassan, M., Halim, M. S., Afridi, R., Sadiq, M. A., Sepah, Y. J., Dong Nguyen Quan 2017; 14 (September): 40-44
  • 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., Sadiq, M. A., Halim, M. S., Afridi, R., Soliman, M. K., Sarwar, S., Agarwal, A., 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

  • Twenty-four-Month Outcomes of the Ranibizumab for Edema of the Macula in Diabetes - Protocol 3 with High Dose (READ-3) Study OPHTHALMOLOGY Sepah, Y. J., Sadiq, M., Boyer, D., Callanan, D., Gallemore, R., Bennett, M., Marcus, D., Halperin, L., Hassan, M., Campochiaro, P. A., Nguyen, Q., Do, D. V. 2016; 123 (12): 2581–87

    Abstract

    To compare 2.0 mg ranibizumab (RBZ) injections with 0.5 mg RBZ for eyes with center-involved diabetic macular edema (DME).Randomized, controlled, double-masked (to the dose), interventional, multicenter clinical trial.A total of 152 patients (152 eyes) with DME.Eligible eyes were randomized in a 1:1 ratio to 0.5 mg (n = 77) or 2.0 mg (n = 75) RBZ. Study eyes received 6 monthly mandatory injections followed by as-needed injections until month 24.The primary efficacy end point of the study was mean change in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) at month 6. Secondary outcomes included the mean change in BCVA and CFT at month 24, and incidence and severity of systemic and ocular adverse events through month 24.A total of 152 eyes were randomized in the study. At month 24, the mean improvement from baseline BCVA was +11.06 letters in the 0.5 mg RBZ group (n = 59) and +6.78 letters in the 2.0 mg RBZ group (n = 54) (P = 0.02). The mean numbers of RBZ injections through month 24 were 18.4 and 17.3 in the 0.5 mg and 2.0 mg RBZ groups, respectively (P = 0.08). The mean change in CFT was -192.53 μm in the 0.5 mg RBZ group and -170.64 μm in the 2.0 mg RBZ group (P = 0.41). By month 24, 3 deaths had occurred in the 0.5 mg RBZ group and 3 deaths had occurred in the 2.0 mg RBZ group; 5 of these 6 deaths occurred secondary to cardiovascular causes, and 1 death occurred as the result of severe pneumonia. All 5 patients with a cardiovascular cause of death had a history of coronary heart disease.At month 24, there were significant visual and anatomic improvements in both groups, with subjects in the 0.5 mg RBZ group gaining more vision. Visual and anatomic gains achieved at month 6 were largely maintained through month 24. No new safety events were identified. In this study population, 2.0 mg RBZ does not appear to provide additional benefit over 0.5 mg RBZ.

    View details for PubMedID 27707550

  • The Role of Optical Coherence Tomography Angiography in the Management of Uveitis. International ophthalmology clinics Hassan, M., Agarwal, A., Afridi, R., daSilva, M. J., Karaca, I., Sadiq, M. A., Nguyen, Q. D., Do, D. V. 2016; 56 (4): 1-24

    View details for DOI 10.1097/IIO.0000000000000130

    View details for PubMedID 27575755

  • Assessment of vitreous haze using ultra-wide field retinal imaging JOURNAL OF OPHTHALMIC INFLAMMATION AND INFECTION Dickson, D., Agarwal, A., Sadiq, M., Hassan, M., High, R., Quan Dong Nguyen, Sepah, Y. J. 2016; 6: 35

    Abstract

    Conventional fundus imaging has been used to assess vitreous haze (VH) in patients with uveitis. Ultra-wide field (UWF) retinal imaging that uses scanning laser technology has not been evaluated for the detection of VH. This pilot study evaluates the ability of UWF imaging in detecting VH. Patients with intermediate, posterior, or panuveitis were examined to assess the level of VH using slit-lamp biomicroscopy. Colored fundus images were acquired using a Carl Zeiss FF450 camera. The same photographer obtained fundus images of the same eyes during the same visit by Optos UWF P200Tx retinal camera. Two graders independently analyzed UWF fundus images for presence or absence of VH, without quantifying the degree of VH using any scale. The images were analyzed using the composite red plus red-free wavelengths utilized by the Optos UWF camera and by using each wavelength exclusively. These findings were compared to clinical detection of VH and detection of VH using conventional fundus photography.Ninety-two eyes were included in the study. For composite UWF images, sensitivity was 0.27, specificity was 0.88, PPV was 0.31, NPV was 0.86, positive LR was 2.25, and negative LR was 0.83. For the conventional Zeiss images, sensitivity was 0.5, specificity was 0.84, PPV was 0.33, NPV was 0.91, positive LR was 3.13, and negative LR was 0.6. Agreement between the composite UWF and Zeiss techniques was substantial with k = 0.64. Inter-observer agreement for composite UWF images was also substantial with k = 0.65. Inter-observer agreement for Zeiss images was moderate with k = 0.471. Intra-observer agreement for both imaging modalities was substantial with a composite UWF k = 0.76 and Zeiss k = 0.7.UWF fundus imaging using scanning laser technique may be used to assess VH and employed in the management of intermediate, posterior, and panuveitis.

    View details for DOI 10.1186/s12348-016-0105-0

    View details for Web of Science ID 000387947000001

    View details for PubMedID 27687961

    View details for PubMedCentralID PMC5042918

  • Evaluation of Macular and Peripapillary Vessel Flow Density in Eyes with no known Pathology Using Optical Coherence Tomography Angiography. Hassan, M., Sadiq, M., Agarwal, A., Soliman, M., Afridi, R., Sarwar, S., Jawed, M., Do, D. V., Quan Dong Nguyen, Sepah, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2016
  • Effects of Two Different Doses of Ranibizumab on Diabetic Retinopathy Severity and Progression in the Ranibizumab for Edema of the Macula in Diabetes (READ-3) Study Sadiq, M., Hassan, M., Soliman, M., Sarwar, S., Afridi, R., Agarwal, A., Do, D. V., Quan Dong Nguyen, Sepah, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2016
  • The role of Aflibercept in the management of age-related macular degeneration EXPERT OPINION ON BIOLOGICAL THERAPY Hassan, M., Afridi, R., Sadiq, M., Soliman, M., Agarwal, A., Sepah, Y., Do, D. V., Quan Dong Nguyen 2016; 16 (5): 699–709

    Abstract

    During the past decade, significant advances have occurred in the management of neovascular age-related macular degeneration (NV-AMD). The advent of anti-vascular endothelial growth factor (anti-VEGF) therapy has shifted the treatment goal of NV-AMD from merely salvaging vision to improving visual acuity and maintaining a good quality of life. Aflibercept (AFL) is a significant addition to the arsenal of anti-VEGF therapies against the NV-AMD. In the index review, pharmacology and efficacy of AFL has been reviewed.An extensive literature search was performed to identify preclinical and clinical studies performed to illustrate the role of AFL in NV-AMD. Randomized clinical trials evaluating other anti-VEGF agents were also included for comparison. Additionally, studies where AFL was employed to treat anti-VEGF-resistant cases agents have been reviewed.AFL is an effective agent in the management of NV-AMD and its efficacy has been found to be comparable to ranibizumab (RBZ). Additionally, AFL is a good alternative agent in patients with NV-AMD resistant to RBZ and bevacizumab (BVZ), and can potentially lessen the treatment burden. As more research is conducted, the role of AFL in varying dosing regimens, as monotherapy and in combination with other agents, will become further defined.

    View details for DOI 10.1517/14712598.2016.1167182

    View details for Web of Science ID 000374600700010

    View details for PubMedID 26982640

  • High-Resolution Imaging of Parafoveal Cones in Different Stages of Diabetic Retinopathy Using Adaptive Optics Fundus Camera PLOS ONE Soliman, M., Sadiq, M., Agarwal, A., Sarwar, S., Hassan, M., Hanout, M., Graf, F., High, R., Do, D. V., Quan Dong Nguyen, Sepah, Y. J. 2016; 11 (4): e0152788

    Abstract

    To assess cone density as a marker of early signs of retinopathy in patients with type II diabetes mellitus.An adaptive optics (AO) retinal camera (rtx1™; Imagine Eyes, Orsay, France) was used to acquire images of parafoveal cones from patients with type II diabetes mellitus with or without retinopathy and from healthy controls with no known systemic or ocular disease. Cone mosaic was captured at 0° and 2°eccentricities along the horizontal and vertical meridians. The density of the parafoveal cones was calculated within 100×100-μm squares located at 500-μm from the foveal center along the orthogonal meridians. Manual corrections of the automated counting were then performed by 2 masked graders. Cone density measurements were evaluated with ANOVA that consisted of one between-subjects factor, stage of retinopathy and the within-subject factors. The ANOVA model included a complex covariance structure to account for correlations between the levels of the within-subject factors.Ten healthy participants (20 eyes) and 25 patients (29 eyes) with type II diabetes mellitus were recruited in the study. The mean (± standard deviation [SD]) age of the healthy participants (Control group), patients with diabetes without retinopathy (No DR group), and patients with diabetic retinopathy (DR group) was 55 ± 8, 53 ± 8, and 52 ± 9 years, respectively. The cone density was significantly lower in the moderate nonproliferative diabetic retinopathy (NPDR) and severe NPDR/proliferative DR groups compared to the Control, No DR, and mild NPDR groups (P < 0.05). No correlation was found between cone density and the level of hemoglobin A1c (HbA1c) or the duration of diabetes.The extent of photoreceptor loss on AO imaging may correlate positively with severity of DR in patients with type II diabetes mellitus. Photoreceptor loss may be more pronounced among patients with advanced stages of DR due to higher risk of macular edema and its sequelae.

    View details for DOI 10.1371/journal.pone.0152788

    View details for Web of Science ID 000373604800011

    View details for PubMedID 27057752

    View details for PubMedCentralID PMC4825992

  • Subcutaneous repository corticotropin gel for non-infectious panuveitis: Reappraisal of an old pharmacologic agent. American journal of ophthalmology case reports Agarwal, A., Hassan, M., Sepah, Y. J., Do, D. V., Nguyen, Q. D. 2016; 4: 78–82

    Abstract

    To describe the clinical course of a patient with non-infectious idiopathic unilateral panuveitis and retinal vasculitis treated with subcutaneous repository adrenocorticotropic hormone (ACTH) gel.A 33-year-old male presented with blurry vision and floaters in the left eye (OS). The best-corrected visual acuity was 20/20 in the right eye (OD) and 20/50 in OS at the time of initial presentation. Slit-lamp examination revealed mild anterior segment inflammation in OS. There were 1 + vitreous haze and 2 + cells noted in OS. Clinical examination and ancillary imaging assessment including fluorescein angiography revealed retinal vasculitis and optic nerve head inflammation. After infectious etiologies were ruled out, the patient was started on oral corticosteroids and enrolled in a clinical trial employing intravenous tocilizumab therapy. Six months after completion of the tocilizumab trial, the patient demonstrated recurrence of disease. Twice weekly subcutaneous ACTH gel was initiated and the patient demonstrated improvement of retinal vascular inflammation.Repository subcutaneous ACTH gel formulation may be a safe and viable therapeutic option for patients with non-infectious uveitis and retinal vasculitis. Clinical trials using this formulation in a larger patient cohort with longer monitoring are indicated to evaluate its tolerability and bioactivity.

    View details for DOI 10.1016/j.ajoc.2016.09.004

    View details for PubMedID 29503933

    View details for PubMedCentralID PMC5757479

  • Sirolimus for Retinal and Uveitic Diseases RETINAL PHARMACOTHERAPEUTICS Agarwal, A., Rajagopalan, N., Hassan, M., Sadiq, M., Soliman, M. K., Afridi, R., Sepah, Y., Quan Dong Nguyen, Nguyen, Q. D., Rodrigues, E. B., Farah, M. E., Mieler, W. F., Do, D. V. 2016; 55: 276–81

    Abstract

    Chronic inflammation plays an important role in the pathogenesis of ocular diseases such as diabetic retinopathy, uveitis and age-related macular degeneration. Activation and proliferation of naïve T cells may result in pathological changes responsible for significant visual morbidity. Sirolimus (earlier termed rapamycin) is a novel drug that inhibits cellular kinases and, thereby, inhibits T-cell proliferation. Preclinical studies in experimental models have shown promising results with the use of this pharmacological agent in various ocular conditions. Subsequently, early phase I/II studies have provided encouraging safety and efficacy data. This chapter focuses on the mechanisms of action, preclinical study results and data from human clinical trials of sirolimus in human eye diseases. Key highlights from ongoing phase III clinical trials are also provided. Sirolimus, thus, appears to be an important addition to the armamentarium of steroid-sparing therapeutic agents that act on various steps in the inflammatory pathway.

    View details for DOI 10.1159/000438951

    View details for Web of Science ID 000413475300031

    View details for PubMedID 26501229

  • Platelet-Derived Growth Factor Inhibitors: A Potential Therapeutic Approach for Ocular Neovascularization RETINAL PHARMACOTHERAPEUTICS Sadiq, M., Hanout, M., Sarwar, S., Hassan, M., Agarwal, A., Sepah, Y., Do, D. V., Quan Dong Nguyen, Nguyen, Q. D., Rodrigues, E. B., Farah, M. E., Mieler, W. F., Do, D. V. 2016; 55: 310–16

    Abstract

    Retinochoroidal vascular diseases are the leading causes of blindness in the developed world. They include diabetic retinopathy, retinal vein occlusion, retinopathy of prematurity, age-related macular degeneration (AMD), and pathological myopia, among many others. Several different therapies are currently under consideration for the aforementioned disorders. In the following section, agents targeting platelet-derived growth factors (PDGF) are discussed as a potential therapeutic option for retinochoroidal vascular diseases. PDGF play an important role in the angiogenesis cascade that is activated in retinochoroidal vascular diseases. The mechanism of action, side effects, efficacy, and the potential synergistic role of these agents in combination with other treatment options is discussed. The future of treatment of retinochoroidal vascular diseases, particularly neovascular AMD, has become more exciting due to agents like PDGF antagonists.

    View details for DOI 10.1159/000438953

    View details for Web of Science ID 000413475300035

    View details for PubMedID 26501397

  • Endogenous endophthalmitis: diagnosis, management, and prognosis JOURNAL OF OPHTHALMIC INFLAMMATION AND INFECTION Sadiq, M., Hassan, M., Agarwal, A., Sarwar, S., Toufeeq, S., Soliman, M. K., Hanout, M., Sepah, Y., Do, D. V., Quan Dong Nguyen 2015; 5: 32

    Abstract

    Endogenous endophthalmitis is an ophthalmic emergency that can have severe sight-threatening complications. It is often a diagnostic challenge because it can manifest at any age and is associated with a number of underlying predisposing factors. Microorganisms associated with this condition vary along a broad spectrum. Depending upon the severity of the disease, both medical and surgical interventions may be employed. Due to rarity of the disease, there are no guidelines in literature for optimal management of these patients. In this review, treatment guidelines based on clinical data and microorganism profile have been proposed.

    View details for DOI 10.1186/s12348-015-0063-y

    View details for Web of Science ID 000379234900001

    View details for PubMedID 26525563

    View details for PubMedCentralID PMC4630262

  • Platelet derived growth factor inhibitors: A potential therapeutic approach for ocular neovascularization SAUDI JOURNAL OF OPHTHALMOLOGY Sadiq, M., Hanout, M., Sarwar, S., Hassan, M., Do, D. V., Quan Dong Nguyen, Sepah, Y. 2015; 29 (4): 287–91

    Abstract

    Retinochoroidal vascular diseases are the leading causes of blindness in the developed world. They include diabetic retinopathy (DR), retinal vein occlusion, retinopathy of prematurity, age-related macular degeneration (AMD), and pathological myopia, among many others. Several different therapies are currently under consideration for the aforementioned disorders. In the following section, agents targeting platelet-derived growth factor (PDGF) are discussed as a potential therapeutic option for retinochoroidal vascular diseases. PDGF plays an important role in the angiogenesis cascade that is activated in retinochoroidal vascular diseases. The mechanism of action, side effects, efficacy, and the potential synergistic role of these agents in combination with other treatment options is discussed. The future of treatment of retinochoroidal vascular diseases, particularly AMD, has become more exciting due to agents such as PDGF antagonists.

    View details for DOI 10.1016/j.sjopt.2015.05.005

    View details for Web of Science ID 000217146700009

    View details for PubMedID 26586980

    View details for PubMedCentralID PMC4625223

  • Novel Therapies in Development for Diabetic Macular Edema CURRENT DIABETES REPORTS Agarwal, A., Afridi, R., Hassan, M., Sadiq, M., Sepah, Y. J., Do, D. V., Nguyen, Q. 2015; 15 (10): 75

    Abstract

    Diabetic macular edema (DME) secondary to diabetic retinopathy (DR) is a major cause for functional visual loss in the developed world. Laser photocoagulation has been used for decades in the treatment of DME. However, the advent of anti-vascular endothelial growth factor (anti-VEGF) has revolutionized the treatment of DME. Three important anti-VEGF agents whose efficacy has been well established via phase III clinical trials include ranibizumab, bevacizumab, and aflibercept. However, even in the era of anti-VEGF therapies, there are some challenges that retina specialists have to confront in managing patients with DME. These include the need for frequent treatment and an unpredictable response to therapy. There is evidence to suggest that pathways other than the VEGF pathway may be playing a role in the development of DME. Thus, extensive research is focused on development of novel agents that target these pathways. This review focuses on novel therapeutic agents in development, which may be used as a monotherapy or in combination with anti-VEGF agents, for the management of DME in the future.

    View details for DOI 10.1007/s11892-015-0652-z

    View details for Web of Science ID 000361488100009

    View details for PubMedID 26294336

  • Assessment of Vitreous Haze using Ultra-Wide Field Retinal Imaging Dickson, D., Agarwal, A., Sadiq, M., High, R., Quan Dong Nguyen, Sepah, Y., Ocular Imaging Reading Res Ctr ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2015
  • Taxi drivers' attitudes toward road safety in Pakistan PUBLIC HEALTH Rehman, A., Imran, S., Hassan, M., Akhlaq, A., Iqbal, S., Beg, F., Zahid, G., Khalid, H., Qadir, F. S., Murad, H. F., Baloch, N. A., Awais, M., Saleem, S. 2015; 129 (6): 818–21

    View details for DOI 10.1016/j.puhe.2015.03.022

    View details for Web of Science ID 000356368100027

    View details for PubMedID 25936972

  • High Resolution Imaging of Parafoveal Cones in Different Stages of Diabetic Retinopathy using Adaptive Optics Fundus Camera Soliman, M., Sadiq, M., Agarwal, A., Sarwar, S., Hanout, M., Graf, F. E., High, R., Do, D. V., Quan Dong Nguyen, Sepah, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2015
  • Therapies in Development for Non-Infectious Uveitis CURRENT MOLECULAR MEDICINE Sadiq, M. A., Agarwal, A., Hassan, M., Afridi, R., Sarwar, S., Soliman, M. K., Do, D. V., Nguyen, Q. D. 2015; 15 (6): 565–77

    Abstract

    Uveitis represents a spectrum of diseases characterized by ocular inflammation that leads to significant visual loss if left untreated. Adequate, long-term control of inflammation with minimal systemic and local adverse effects is the preferred strategy for treating patients with uveitis. Pharmacotherapy for uveitis consists mainly of corticosteroids in various formulations such as topical, local, intraocular and systemic. However, monotherapy with corticosteroids is often unacceptable due to serious adverse effects on various organ systems. There exist limitations with the use of steroid-sparing systemic immunosuppressive agents, as these medications may have significant adverse events and a narrow therapeutic window. Thus, newer molecular targets that act on various steps of the inflammatory pathway appear to be promising emerging strategies for treating uveitis. Specially designed monoclonal antibodies in development can potentially halt the inflammatory processes resulting in remission of the disease. In the index review, novel molecular agents and biological therapies that have shown promising efficacy and safety data in preclinical and clinical studies have been summarized. In addition, new drug delivery systems that may ensure high intraocular therapeutic levels of pharmacologic agents have been highlighted.

    View details for DOI 10.2174/1566524015666150731103847

    View details for Web of Science ID 000359986900009

    View details for PubMedID 26238367

  • Assessment of Retinal Structural and Functional Characteristics in Eyes with Autoimmune Retinopathy CURRENT MOLECULAR MEDICINE Sepah, Y. J., Sadiq, M. A., Hassan, M., Hanout, M., Soliman, M., Agarwal, A., Afridi, R., Coupland, S. G., Nguyen, Q. D. 2015; 15 (6): 578–86

    Abstract

    To evaluate the thicknesses of individual retinal layers, and the correlation between structural changes and functional loss using spectral domain optical coherence tomography (SD-OCT) scans and electroretinograms (ERG), in eyes with autoimmune retinopathy (AIR).SD-OCT raster scans of 12 eyes from 6 patients serologically diagnosed with AIR were evaluated. Retinal layers were segmented along a 5 mm horizontal scan passing through the fovea. Retinal layers analyzed include full retinal thickness (FRT), retinal pigment epithelium and Bruch's membrane complex (RPE+BM complex), photoreceptor layer (PRL), inner nuclear layer (INL), combined ganglion cell and inner plexiform layers (GCL+), nerve fiber layer (NFL), and combined GCL+ and NFL layers (GCL+/NFL). Changes in the thicknesses of the layers were assessed in 0.5 mm increments along the B-scan in the central, nasal, and temporal regions. These recorded values were compared to corresponding values of 51 eyes from 51 subjects with no known ocular pathology. Full-field ERGs were obtained at corresponding visits and were interpreted by a grader masked to the diagnoses and OCT findings.The mean age of the patients was 59.5 years (range, 33-83), with 4 males (66.6%). Within the control population of 51 subjects, mean age was 51.5 years (range, 40-75), with 25 males (49%). Eyes with AIR showed a loss of retinal tissue compared to eyes with no known ocular pathology at the fovea. Specifically, the FRT, RPE+BM complex, and PRL exhibited thinning of statistically significance. ERG findings demonstrated a functional deficit which showed a good correlation with structural loss. Fifty (50) percent of eyes experienced central photoreceptor (rod and cone) dysfunction and 75% of eyes displayed peripheral photoreceptor (rod and cone) dysfunction.Eyes with AIR show a loss of retinal tissue compared to eyes with no known ocular pathology. The greatest loss appears to occur in the RPE and PRL. ERG findings correlate strongly with the loss of tissue seen in these layers. Thus, therapeutic options may be targeted to preserve these regions of the retina.

    View details for DOI 10.2174/1566524015666150731104626

    View details for Web of Science ID 000359986900010

    View details for PubMedID 26238366