Yasir J Sepah is an Assistant Professor at the Byers Eye Institute with a decade of experience in drug repositioning, development of biomarkers and multicenter clinical trials. He completed his medical education at The Aga Khan Medical College, Karachi, Pakistan. He completed his postdoctoral studies in ophthalmic imaging and clinical trials at the Wilmer Eye Institute, Johns Hopkins University, and a BioDesign fellowship at the Stanford Center for Biodesign.

Yasir Sepah is internationally known for his innovative approaches to low-cost, investigator sponsored, first in-human clinical trials that has put several molecules on track for regulatory approval. He also develops biomarkers and methods to identify early disease and objectively assess response to therapy and has recently developed an imaging method (image guided microperimetery) that can potentially allow a paradigm shift in how we assess disease progression in age related macular degeneration, inherited retinal degenerations and diabetic macular ischemia .

Academic Appointments

  • Assistant Professor (Research), Ophthalmology

Administrative Appointments

  • Co-Founder, Crest Trials (2022 - Present)
  • Co-Founder, Ocular Imaging Research & Reading Center (2016 - Present)

Boards, Advisory Committees, Professional Organizations

  • Associate Member, American Academy of Ophthalmology (2012 - Present)
  • Associate Member, Association for Research in Vision and Ophthalmology (2010 - Present)
  • Executive Board Member, Foster Ocular Immunology Society (2014 - Present)

Current Research and Scholarly Interests

Yasir's primary focus is on early identification of ocular diseases and objective assessment of response to therapy via biomarker (imaging and molecular) discovery and endpoints development for clinical trials. His lab is also developing and implementing protocols and methods to make decentralized clinical trials in ophthalmology viable.

Yasir is also engaged in developing low-tech, low cost and less intelligent solutions in order to improve patient's access to care.

All Publications

  • Macular Sensitivity Endpoints in Geographic Atrophy: Exploratory Analysis of Chroma and Spectri Clinical Trials. Ophthalmology science Chang, D. S., Callaway, N. F., Steffen, V., Csaky, K., Guymer, R. H., Birch, D. G., Patel, P. J., Ip, M., Gao, S. S., Briggs, J., Honigberg, L., Lai, P., Ferrara, D., Sepah, Y. J. 2024; 4 (1): 100351


    To assess different microperimetry (MP) macular sensitivity outcome measures capturing functional deterioration in eyes with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).Patients were included from 2 identically designed, phase III, double-masked, randomized controlled clinical trials, Chroma (NCT02247479) and Spectri (NCT02247531).Patients enrolled were aged ≥ 50 years with bilateral GA and no evidence of previous or active neovascular AMD.Patients were randomized 2:1:2:1 to receive through 96 weeks intravitreal lampalizumab 10 mg every 4 weeks (LQ4W), every 6 weeks (LQ6W), or corresponding sham procedures. For this study, mesopic macular sensitivity of the central 20° was assessed using MP-1 microperimeter at selected sites.Two exploratory endpoints were developed, namely perilesional sensitivity (average of points adjacent to absolute scotomatous points) and responding sensitivity (average of all nonscotomatous points; > 0 dB at baseline) by using customized masks for each patient. These were compared with conventional MP endpoints (mean macular sensitivity and number of absolute scotomatous points).Of 1881 Chroma and Spectri participants, 277 agreed to participate in the present study. Of these, 197 (LQ4W, n = 63; LQ6W, n = 68; pooled sham, n = 66) had reliable MP results. Enlargement of GA lesion area by approximately 2 mm2/year across treatment groups was accompanied by deterioration in all MP parameters. There was no difference in worsening of macular sensitivity or absolute scotomatous points among treatment groups. Perilesional and responding sensitivities showed greater decline over time than mean macular sensitivity. Change in GA lesion area at week 48 showed better correlation with perilesional sensitivity (r = -0.17) and responding sensitivity (r = -0.20) than mean macular sensitivity (r = -0.03), while the correlation was highest with the number of absolute scotomatous points (r = 0.37).Perilesional or responding macular sensitivity measured by MP should be considered more sensitive endpoints than mean macular sensitivity for monitoring functional decline over time in GA. Although perilesional, responding, and mean macular sensitivity had weak correlation with GA lesion area, the number of absolute scotomatous points may provide additional information on the anatomic/functional correlation.Proprietary or commercial disclosure may be found after the references.

    View details for DOI 10.1016/j.xops.2023.100351

    View details for PubMedID 37869030

    View details for PubMedCentralID PMC10587617

  • Optical coherence tomography angiography in diabetic retinopathy. Progress in retinal and eye research Waheed, N., Rosen, R. B., Jia, Y., Munk, M. R., Huang, D., Fawzi, A., Chong, V., Nguyen, Q. D., Sepah, Y., Pearce, E. 2023: 101206


    There remain many unanswered questions on how to assess and treat the pathology and complications that arise from diabetic retinopathy (DR). Optical coherence tomography angiography (OCTA) is a novel and non-invasive three-dimensional imaging method that can visualize capillaries in all retinal layers. Numerous studies have confirmed that OCTA can identify early evidence of microvascular changes and provide quantitative assessment of the extent of diseases such as DR and its complications. A number of informative OCTA metrics could be used to assess DR in clinical trials, including measurements of the foveal avascular zone (FAZ; area, acircularity, 3D para-FAZ vessel density), vessel density, extrafoveal avascular zones, and neovascularization. Assessing patients with DR using a full-retinal slab OCTA image can limit segmentation errors and confounding factors such as those related to center-involved diabetic macular edema. Given emerging data suggesting the importance of the peripheral retinal vasculature in assessing and predicting DR progression, wide-field OCTA imaging should also be used. Finally, the use of automated methods and algorithms for OCTA image analysis, such as those that can distinguish between areas of true and false signals, reconstruct images, and produce quantitative metrics, such as FAZ area, will greatly improve the efficiency and standardization of results between studies. Most importantly, clinical trial protocols should account for the relatively high frequency of poor-quality data related to sub-optimal imaging conditions in DR and should incorporate time for assessing OCTA image quality and re-imaging patients where necessary.

    View details for DOI 10.1016/j.preteyeres.2023.101206

    View details for PubMedID 37499857

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


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

    View details for DOI 10.1097/IAE.0000000000003870

    View details for PubMedID 37339446

  • Efficacy and Safety of Tocilizumab in the Management of Non-Infectious Uveitis Failed with Conventional Immunomodulatory and Anti-TNFα Therapies. Ocular immunology and inflammation Uludag, G., Karaca, I., Akhavanrezayat, A., Yasar, C., Matsumiya, W., Pham, B. H., Halim, M. S., Trong Tuong Than, N., Sepah, Y. J., Do, D. V., Nguyen, Q. D. 2022: 1-7


    To determine the outcomes of intravenous (IV) tocilizumab (TCZ) in patients with non-infectious uveitis who failed with conventional immunomodulatory and anti-TNFα therapies.Records of seven patients with non-infectious uveitis treated with monthly IV TCZ (4-10 mg/kg) or biweekly IV TCZ (8 mg/kg) were reviewed. Outcome measures were changes in visual acuity, anterior chamber cell and flare grade, vitreous haze, central subfield thickness (CST), and fluorescein angiography (FA) score.Ten eyes of seven patients received TCZ therapy. Median age of patients was 14 (range, 7-24) years. Median duration of TCZ therapy was 15 (range, 5-32) months. Mean CST reduced from 373 ± 101.0 μm to 298.2 ± 40.3 μm. Mean FA score reduced from 12.5 ± 4.3 to 3.6 ± 2.6. One patient developed elevated liver transaminases.IV TCZ is a potentially effective and safe therapeutic option for the management of refractory non-infectious uveitis.

    View details for DOI 10.1080/09273948.2022.2126374

    View details for PubMedID 36542775

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


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

    View details for DOI 10.1080/09273948.2022.2123365

    View details for PubMedID 36170559

  • HORNBILL: a phase I/IIa trial examining the safety, tolerability and early response of BI 764524 in patients with diabetic retinopathy and diabetic macular ischaemia-rationale, study design and protocol. Trials Chong, V., Nguyen, Q. D., Sepah, Y., Giani, A., Pearce, E. 2022; 23 (1): 669


    BACKGROUND: Diabetic macular ischaemia (DMI) is a complication of diabetic retinopathy that leads to irreversible vision loss. DMI is characterised by reduced retinal vessel density and enlargement of the foveal avascular zone (FAZ). Despite its clinical burden, there is no formal consensus on the definition of DMI, and no approved treatment. Semaphorin 3A (Sema3A) is an axonal guidance molecule that blocks revascularisation of the ischaemic retina. Sema3A modulation is therefore a promising mechanism of action for the treatment of ischaemic eye diseases. BI 764524 is an intravitreal anti-Sema3A ischaemia modulator agent.METHODS: HORNBILL (NCT04424290) is a phase I/IIa trial comprising a non-randomised, open-label, single rising dose (SRD) part and a randomised, masked, sham-controlled multiple dose (MD) part to investigate the safety, tolerability and early biological response of ischaemia modulator BI 764524 in adults (≥18 years) with DMI. DMI will be defined using optical coherence tomography angiography (OCTA) as either any degree of disruption in the retinal vascularity (SRD) or a FAZ of ≥0.5 mm2 (MD). Subjects in the SRD part will receive 0.5, 1.0 or 2.5 mg of BI 764524; the maximum tolerated dose will then be used in the MD part. A minimum of 12 subjects will be enrolled into the SRD part; planned enrollment is 30 for the MD part. The primary endpoint of the SRD part is the number of subjects with dose-limiting adverse events (AEs) until day 8. The primary endpoint of the MD part is the number of subjects with drug-related AEs from baseline to end of study, and secondary endpoints include change from baseline in the size of the FAZ, best-corrected visual acuity and central retinal thickness.DISCUSSION: DMI is a poorly defined condition with no treatment options. HORNBILL is the first clinical trial to assess a treatment for DMI and to use OCTA as a means to define and examine DMI. The OCTA data generated in this trial could form the basis of formal diagnostic criteria for DMI. Furthermore, the novel mechanism of action (Sema3A modulation) explored in this trial has the potential to revolutionise the treatment landscape for patients with DMI.TRIAL REGISTRATION: NCT04424290 ; EudraCT 2019-004432-28. Registered on 9 June 2020.

    View details for DOI 10.1186/s13063-022-06527-y

    View details for PubMedID 35978329

  • Corrigendum to Phase 1b Randomized Controlled Study of Short Course Topical Recombinant Human Nerve Growth Factor (rhNGF) for Neuroenhancement in Glaucoma: Safety, Tolerability, and Efficacy Measure Outcomes. Am J Ophthalmol 2022;234:223-234. American journal of ophthalmology Beykin, G., Stell, L., Halim, M. S., Nunez, M., Popova, L., Nguyen, B. T., Groth, S. L., Dennis, A., Li, Z., Atkins, M., Khavari, T., Wang, S. Y., Chang, R., Fisher, A. C., Sepah, Y. J., Goldberg, J. L. 2022

    View details for DOI 10.1016/j.ajo.2022.07.018

    View details for PubMedID 35977854

  • Multifocal electroretinographic findings in eyes with posterior uveitis and angiographic macular leakage Hwang, J., Karaca, I., Lajevardi, S., Or, C., Zaidi, M., Regenold, J., Halim, M., Uludag, G., Yasar, C., Bazojoo, V., Than, N., Mobasserian, A., Sepah, Y. J., Khojasteh, H., Nguyen, Q., Ghoraba, H. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • Proteomic analysis of autoimmune retinopathy implicates NrCAM as a potential biomarker. Ophthalmology science Al-Moujahed, A., Velez, G., Vu, J. T., Lima de Carvalho, J. R., Levi, S. R., Bassuk, A. G., Sepah, Y. J., Tsang, S. H., Mahajan, V. B. 2022; 2 (2)


    To identify vitreous molecular biomarkers associated with autoimmune retinopathy (AIR).Case-control study.We analyzed six eyes from four patients diagnosed with AIR and eight comparative controls diagnosed with idiopathic macular holes and epiretinal membranes.Vitreous biopsies were collected from the participants and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) or multiplex ELISA.Protein expression changes were evaluated by 1-way ANOVA (significant p-value <0.05), hierarchical clustering, and pathway analysis to identify candidate protein biomarkers.There were 16 significantly upregulated and 17 significantly downregulated proteins in the vitreous of three AIR patients compared to controls. The most significantly upregulated proteins included lysozyme C (LYSC), zinc-alpha-2-glycoprotein (ZA2G), complement factor D (CFAD), transforming growth factor-beta induced protein (BGH3), beta-crystallin B2, and alpha-crystallin A chain. The most significantly downregulated proteins included disco-interacting protein 2 homolog (DIP2C), retbindin (RTBDN), and amyloid beta precursor like protein 2 (APLP2). Pathway analysis revealed that vascular endothelial growth factor (VEGF) signaling was a top represented pathway in the vitreous of AIR patients compared to controls. In comparison to a different cohort of three AIR patients analyzed by multiplex ELISA, a commonly differentially expressed protein was neuronal cell adhesion molecule (NrCAM) with p-values of 0.027 in the LC-MS/MS dataset and 0.035 in the ELISA dataset.Protein biomarkers such as NrCAM in the vitreous may eventually help diagnose AIR.

    View details for DOI 10.1016/j.xops.2022.100131

    View details for PubMedID 35529077

    View details for PubMedCentralID PMC9075676

  • Novel retinopathy in pediatric retinal vasculitis: long term follow up Yasar, C., Ghoraba, H., Regenold, J., Or, C., Halim, M., Uludag, G., Hwang, J., Karaca, I., Mobasserian, A., Akhavanrezayat, A., Yasar, M., Khojasteh, H., Sepah, Y. J., Do, D. V., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • Utilisation of composite endpoint outcome to assess efficacy of tocilizumab for non-infectious uveitis in the STOP-Uveitis Study. The British journal of ophthalmology Hassan, M., Sadiq, M. A., Ormaechea, M. S., Uludag, G., Halim, M. S., Afridi, R., Do, D. V., Sepah, Y. J., Nguyen, Q. D. 2022


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

    View details for DOI 10.1136/bjophthalmol-2021-320604

    View details for PubMedID 35379598

  • Two Phase 3 Studies on Ophthalmologic Effects of Roxadustat Versus Darbepoetin. Kidney international reports Sepah, Y. J., Nguyen, Q. D., Yamaguchi, Y., Otsuka, T., Majikawa, Y., Reusch, M., Akizawa, T. 2022; 7 (4): 763-775


    Introduction: Roxadustat is an orally administered hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that represents a novel therapeutic option for patients with anemia of chronic kidney disease (CKD).Methods: Conducted in Japan, CL-0307 (NCT02952092) and CL-310 (NCT02988973) were phase 3, darbepoetin alfa (DA)-controlled studies conducted in dialysis-dependent (DD) and non-DD (NDD) patients with CKD, respectively, where patients were randomized to receive roxadustat or DA. Ophthalmic imaging and assessments of visual acuity were performed up to week 24 or at study discontinuation. Ophthalmic imaging was centrally evaluated by independent readers masked to the study treatment.Results: In CL-0307, 302 patients (roxadustat, n= 150; DA, n= 152) received≥1 dose of the study drug and were included in this analysis. In CL-0310, 262 patients (roxadustat, n= 131; DA, n= 131) received≥1 dose of the study drug and were included in this analysis. Proportions of DD patients with new or worsening retinal hemorrhages (RHs) in the roxadustat group and DA group were 32.4% (46 of 142) and 36.6% (53 of 145), respectively. Proportions of NDD patients with CKD with new or worsening RH in the roxadustat and DA groups were 31.4% (38 of 121) and 39.8% (51 of 128), respectively. Similar trends were apparent in subgroup analyses: patients with/without RH at baseline and with/without diabetes mellitus at baseline. In both studies, there were no differences in retinal thickness, visual acuity, presence of hard exudates or cotton wool spots, or presence of intra- and subretinal fluid between groups, at any given time point.Conclusion: In these studies, roxadustat, compared with DA, was not associated with an increased risk of adverse ophthalmologic events in these cohorts.

    View details for DOI 10.1016/j.ekir.2022.01.1045

    View details for PubMedID 35497806

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


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

    View details for DOI 10.1080/09273948.2021.1971723

    View details for PubMedID 35081012

  • Evaluating optical coherence tomography (OCT) findings as potential biomarkers in central nervous system (CNS) lymphoma with or without ocular involvement INTERNATIONAL JOURNAL OF RETINA AND VITREOUS Hassan, M., Halim, M., Afridi, R., Nguyen, N. V., Nguyen, Q., Sepah, Y. J. 2021; 7 (1): 70


    To evaluate spectral domain optical coherence tomography (SD-OCT) findings as biomarkers in primary central nervous system lymphoma (PCNSL) with or without ocular involvement.This study was a cross-sectional study and patients with a confirmed diagnosis of PCNSL with or without ocular involvement were included. Patient cohort finder tool was used to identify patients with lymphoma using ICD-10 codes (C82-C88), from January 2004 to October 2017. A total of 14,820 patients were identified. Procedure code (92134) for optical coherence tomography (OCT) was then applied to identify patients who had underdone OCT imaging at ophthalmology clinic. Clinic charts of 460 patients with lymphoma and available OCT were reviewed to identify patients with confirmed diagnosis of PCNSL and divided into two groups (Group 1: with and Group 2: without ocular involvement). OCT scans of patients in both study groups were analyzed for the presence of (1) Hyperreflective deposits in choroid, retinal pigment epithelium (RPE), outer and inner retina; (2) RPE thickening; (3) Vitreous debris; (4) Intraretinal fluid; (5) Ellipsoid zone disruption by masked graders. Chi-square was used to analyze the difference between the groups.Twenty-two eyes (11 patients) with PCNSL were included this study (Group 1: 6 eyes and Group 2: 16 eyes). Mean age of subjects was 65 years. Five patients (45.45%) were female. There was no statistically significant difference between the groups for the presence of hyperreflective deposits in choroid, RPE, outer and inner retina, and presence of RPE thickening, intraretinal fluid, and ellipsoid zone disruption. Vitreous debris was found more commonly in group 1 subjects (83%) than group 2 (31.25%) (p = 0.029). All subjects in both groups showed hyperreflective deposits in the RPE demonstrating RPE infiltration. However, RPE thickening was noted only in 3 patients (Group1: 1 and Group2: 2).OCT finding of hyperreflective deposits present in eyes with lymphoma secondary to PCNSL are also observed in eyes with PCNSL without ocular disease. However, the vitreous deposits are more commonly found in eyes with ocular disease. These hyperreflective deposits can serve as biomarkers for early detection of ocular involvement by PCNSL.

    View details for DOI 10.1186/s40942-021-00345-1

    View details for Web of Science ID 000722191900001

    View details for PubMedID 34819169

  • Effect of light backscattering from anterior segment structures on automated flare meter measurements. European journal of ophthalmology Hasanreisoglu, M., Kesim, C., Yalinbas, D., Yilmaz, M., Uzunay, N. S., Aktas, Z., Halim, M. S., Sepah, Y. J., Nguyen, Q. D., Sahin, A. 2021: 11206721211039350


    BACKGROUND: To evaluate effect of maximal anterior cortical lens density, iris scatter and anterior chamber depth on laser flare photometry.METHODS: Patients diagnosed with clinical uveitis were enrolled in the study. Clinical flare gradings were recorded upon the Standardization of Uveitis Nomenclature. Aqueous flare was measured with an automated device (Kowa FM-700). Back-scattering from anterior cortical lens and anterior iris surface was calculated from Scheimpflug images. A curvilinear regression model was used to calculate estimated values for each clinical grade. These values were used to split cases in Group I (laser flare photometry lower than estimated) and Group II (laser flare photometry higher than estimated). Mean anterior chamber depth, pupil aperture, maximal anterior cortical lens density and iris scatter values were compared between two groups. A stepwise multiple regression analysis was performed to determine the effect of clinical flare gradings and ocular parameters on aqueous flare measurements.RESULTS: The study included 228 eyes of 114 cases. Scheimpflug images were obtained from 105 eyes. Estimated aqueous flare measurements (in photons/milliseconds) were 4.87, 8.50, 14.81, 25.83, 45.04 and 136.93 for 0, 0.5+, 1+, 1.5+, 2+ and 3+ clinical flare respectively. Group II had higher maximal anterior cortical lens density than Group I (96.6±37.1 vs 77.9±17.1 pixel unit, p=0.001). The measured aqueous flare was significantly related to clinical flare, maximal anterior cortical lens density and pupil aperture (adjusted R2: 0.480, p<0.001).CONCLUSION: The back-scattered light from anterior cortical lens could affect laser flare photometry measurements. This effect might be quantified by Scheimpflug imaging.

    View details for DOI 10.1177/11206721211039350

    View details for PubMedID 34382443

  • Distinct Patterns of Choroidal Lesions in Punctate Inner Choroidopathy and Multifocal Choroiditis Determined by Heatmap Analysis. Ocular immunology and inflammation Park, J. G., Halim, M. S., Uludag, G., Onghanseng, N., Sredar, N., Sepah, Y. J., Nguyen, Q. D. 2021: 1-6


    Purpose: A heatmap analysis of choroidal lesions in patients with punctate inner choroidopathy (PIC) or multifocal choroiditis (MFC) with or without uveitis was performed to determine if there were any distinguishing features among these uveitic entities.Methods: Retrospective review of medical records was conducted at the Byers Eye Institute, Stanford. Fundus photographs were masked and placed on a standardized template. Lesions were identified and heatmaps were generated in a standardized fashion.Results: 30 eyes were identified with PIC or MFC. Heatmap analysis revealed three distinct patterns of fundus lesions: posterior, peripheral, and combined. All patients with PIC had the posterior pattern. Patients with MFC had the peripheral or combined pattern, and all patients with MFC with uveitis had the combined pattern.Conclusion: Three patterns of fundus lesions were identified in patients with PIC and MFC. PIC and MFC may represent two separate disease entities with distinct phenotypes of choroidal lesions.

    View details for DOI 10.1080/09273948.2021.1939391

    View details for PubMedID 34228580

  • Safety of intravenous high-dose pulse methylprednisolone succinate in the management of pediatric uveitis Ghoraba, H., Akhavanrezayat, A., Matsumiya, W., Pham, B., Yasar, C., Karaca, I., Mobasserian, A., Regenold, J., Lam, B., Hwang, J., Lajevardi, S., Yavari, N., Halim, M., Sepah, Y. J., Do, D. V., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
  • Correlation between photoreceptor density in adaptive optics imaging with retinal structure and sensitivity in autoimmune retinopathy Matsumiya, W., Akhavanrezayat, A., Uludag, G., Yasar, C., Ghoraba, H., Mobasserian, A., Karaca, I., Lam, B., Pham, B., Hwang, J., Afridi, R., Halim, M., Do, D., Sepah, Y., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
  • Association of oral montelukast with reduced odds of developing neovascular age-related macular degeneration Karaca, I., Matsumiya, W., Akhavanrezayat, A., Uludag, G., Yasar, C., Mobasserian, A., Hwang, J., Lajevardi, S., Lam, B., Afridi, R., Do, D., Sepah, Y., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
  • Measuring Anterior Chamber Flare using Novel Slit-Lamp Imaging Technique Halim, M., Chakravarthy, A., Onghanseng, N., Hassan, M., Ormaechea, M., Hasanreisoglu, M., Matsumiya, W., Uludag, G., Tran, A., Sepah, Y., Subramaniam, M., Nguyen, Q. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
  • Novel retinopathy identified in pediatric retinal vasculitis Yasar, C., Matsumiya, W., Akhavanrezayat, A., Ghoraba, H., Halim, M., Uludag, G., Pham, B., Hwang, J., Karaca, I., Lajevardi, S., Lam, B., Regenold, J., Sepah, Y. J., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
  • Altered patient demography and increased complexity of ICD coding in uveitis over 10 years Hwang, J., Halim, M., Uludag, G., Yasar, C., Ghoraba, H., Pham, B., Lajevardi, S., Lam, B., Regenold, J., Bazojoo, V., Karaca, I., Mobasserian, A., Do, D. V., Sepah, Y. J., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
  • Efficacy and safety of tocilizumab in the management of non-infectious retinal vasculitis Uludag, G., Halim, M., Akhavanrezayat, A., Matsumiya, W., Yasar, C., Pham, B., Hwang, J., Lajevardi, S., Lam, B., Karaca, I., Mobasserian, A., Regenold, J., Do, D. V., Sepah, Y. J., Quan Dong Nguyen ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021
  • Current concepts in the diagnosis and management of antiphospholipid syndrome and ocular manifestations. Journal of ophthalmic inflammation and infection Uludag, G., Onghanseng, N., Tran, A. N., Hassan, M., Halim, M. S., Sepah, Y. J., Do, D. V., Nguyen, Q. D. 2021; 11 (1): 11


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

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

    View details for PubMedID 33834305

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


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

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

    View details for PubMedID 33792788

  • Eye trauma in falls presenting to the emergency department from 2006 through 2015 BRITISH JOURNAL OF OPHTHALMOLOGY Usmani, B., Latif, A., Iftikhar, M., Sepah, Y. J., Parker, C., Fliss, J. A., Dansingani, K. K., Shah, S. 2021; 105 (2): 198-204


    To characterise the epidemiology of eye trauma in the event of falls presenting to the emergency departments (ED) in the USA.Retrospective cohort study. Nationwide Emergency Department Sample was used to analyse fall encounters presenting to the ED with eye trauma from 2006 to 2015. National estimates of the leading diagnoses were determined, and multivariable regression was used to determine the relationship between factors involved in fall encounters presenting with eye trauma.From 2006 to 2015, an estimated 87 991 036 fall encounters presented to the ED, of which 952 781 encounters had eye trauma as either a primary or secondary diagnosis. The overall incidence of fall encounters with eye trauma per 100 000 US population increased from 30.7 encounters in 2006 to 33.8 encounters per 100 000 population in 2014 with a decrease seen in 2015. Eye trauma, including vision-threatening type, was highest in females (n=500 520, 52.5%), elderly (n=400 209, 42%) and children (n=2 06 741, 21.7%). Elderly were more likely to have eye trauma in the setting of falls (adjusted OR (aOR) 2.06, 95% CI 2.02 to 2.11) and be admitted (aOR 1.89, 95% CI 1.86 to 1.91) than adults (reference). The leading types of eye trauma were contusion of orbital tissues (n=174 292, 18.3%), laceration of eyelid and periocular area (n=172 361, 18.1%) and orbital fractures (n=151 013, 15.8%).Falls are preventable, yet the incidence of falls and resulting eye trauma are increasing despite our best efforts. As ophthalmologists, we should not only develop guidelines to recognise and counsel at-risk groups under our care but also strategies for prevention of eye trauma secondary to falls.

    View details for DOI 10.1136/bjophthalmol-2019-314669

    View details for Web of Science ID 000614238600010

    View details for PubMedID 32327415

  • Phase 1b randomized controlled study of short course topical recombinant human nerve growth factor (rhNGF) for neuroenhancement in glaucoma: safety, tolerability and efficacy measure outcomes. American journal of ophthalmology Gala, B., Laurel, S., Sohail, H. M., Mariana, N., Lilia, P., Bac T, N., Sylvia L, G., Amy, D., Zhongqiu, L., Melissa, A., Tom, K., Sophia Y, W., Robert, C., Ann C, F., Yasir J, S., Jeffrey L, G. 2021


    No approved therapies directly target retinal ganglion cells (RGCs) for neuroprotection or neuroenhancement in glaucoma. Recombinant human nerve growth factor (rhNGF) has been shown to promote RGC survival and function in animal models of optic neuropathy. Here we evaluate safety, tolerability, and efficacy of short-term, high-dose rhNGF eye drops versus placebo in a cohort of glaucoma patients.This study is a single-center, randomized, double-masked, vehicle-controlled, parallel group study designed to assess safety and tolerability as well as short-term neuroenhancement of structure and function ( NCT02855450). Sixty open-angle glaucoma patients were randomized 40:20 to receive either 180 μg/ml rhNGF or vehicle control eye drops in both eyes, three times daily for 8 weeks, with a 24-week post-treatment follow-up. One eye was officially selected as the study eye, although both eyes were studied and dosed. Primary endpoints were safety, as assessed through adverse events, and tolerability, as assessed through patient reported outcomes. Secondary outcome measures included best corrected visual acuity (BCVA), Humphrey visual field (HVF), electroretinogram (ERG), and optical coherence tomography (OCT) of retinal nerve fiber layer (RNFL) thickness at baseline, after 8 weeks of treatment, and at 4 and 24 weeks after treatment (12- and 32-weeks total).Of the 60 randomized subjects, 23 were female (38%) and the average age was 66.1 years. Through week 32, there were no treatment-related serious adverse events, including no unexpectedly severe progression of optic neuropathy, no adverse events affecting ocular function or pressure, and no drug-related systemic toxicity. Topical high-dose rhNGF was tolerated well, with low level of symptom burden mainly eliciting periocular ache (in 52% of treated, 5% of placebo) and only 3 patients (7.5%) discontinuing treatment due to discomfort, out of whom 1 patient (2.5%) prematurely withdrawing from the study. There were no statistically significant differences in global indices of HVF, and no meaningful differences in total, quadrant, or clock-hour mean RNFL thickness between the groups, although both of these function and structure measures showed non-significant trends towards significance in favor of rhNGF. Real-world participant data was used to generate an estimate of cohort size needed to power subsequent studies.rhNGF is safe and tolerable in a topical 180 μg/ml formulation. Although no statistically significant short-term neuroenhancement was detected in this trial, given the strong effects of NGF in preclinical models and trends detected in this study, analysis for efficacy in a neuroprotection trial is warranted.

    View details for DOI 10.1016/j.ajo.2021.11.002

    View details for PubMedID 34780798

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

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

    View details for PubMedID 33372631

  • 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


    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

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


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

    View details for DOI 10.1016/j.ajoc.2020.100825

    View details for PubMedID 32715157

  • 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
  • Eye-Related Emergency Department Visits and the Opioid Epidemic: A 10-year Analysis Shah, S., Usmani, B., Latif, A., Amarasekera, S., Mukhtar, S., Iftikhar, M., Kherani, S. A., Sepah, Y., Raghavan, D., Smith, W., Jhanji, V., Dansingani, K. K. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2020
  • A Distinct Pattern of Choroidal Lesions in Multifocal Choroiditis and Pan-uveitis Determined by Heatmap Analysis Park, J., Halim, M., Uludag, G., Onghanseng, N. L., Sredar, N., Sepah, Y., Quan Dong Nguyen 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
  • 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


    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

  • Eye-Related Emergency Department Visits and The Opioid Epidemic: a 10-Year Analysis OPHTHALMIC EPIDEMIOLOGY Usmani, B., Latif, A., Amarasekera, S., Mukhtar, S., Iftikhar, M., Kherani, S., Sepah, Y. J., Raghavan, D., Smith, W. D., Jhanji, V., Dansingani, K. K., Shah, S. A. 2020: 300–309


    To describe the epidemiology of Emergency Department (ED) visits related to opioid abuse with primary ophthalmic diagnoses in the United States (US).This retrospective cross-sectional study used National ED Sample (NEDS) (2006-2015), a representative sample of all US EDs, to analyze and compare the epidemiology of primary ophthalmic diagnoses in opioid abusers and a control group of non-opioid users. National incidence and descriptive statistics were calculated for demographics and prevalent diagnoses. Multivariable logistic regression was used to compare outcomes between primary ophthalmic diagnoses in opioid and non-opioid abusers.An estimated 10,617 visits had a primary ophthalmic diagnosis and an accompanying opioid abuse diagnosis, and the incidence increased from 0.2 in 2006 to 0.6 per 100,000 US population in 2015. Opioid abuse group had more adults (6,747:63.5%) and middle-aged (3,361:31.7%) patients, while in controls adults (7,905,003:40.4%) and children (4,068,534:20.8%) were affected more. Leading etiologies were similar: traumatic and infectious etiologies were most common; however, opioid abuse patients had more severe ophthalmic diagnoses such as orbital fractures (8.4%), orbital cellulitis (7.4%), globe injury (3.4%) and endophthalmitis (3.2%) compared to controls. Patients in the opioid abuse group were also more likely to be admitted (adjusted Odds Ratio [aOR], 28.38 [95% CI, 24.50-32.87]).In the era of opioid crisis, an increase in ED visits with ophthalmic complaints is seen, with increasing direct and indirect costs on the healthcare system. More research is needed to establish causality and devise strategies to lower this burden.

    View details for DOI 10.1080/09286586.2020.1744165

    View details for Web of Science ID 000523735300001

    View details for PubMedID 32223491

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


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

    View details for DOI 10.1016/j.ophtha.2019.12.031

    View details for PubMedID 32107066

  • Proteomic analysis of intermediate uveitis suggests myeloid cell recruitment and implicates IL-23 as a therapeutic target. American journal of ophthalmology case reports Sepah, Y. J., Velez, G. n., Tang, P. H., Yang, J. n., Chemudupati, T. n., Li, A. S., Nguyen, Q. D., Bassuk, A. G., Mahajan, V. B. 2020; 18: 100646


    To profile vitreous protein expression of intermediate uveitis (IU) patients.We identified a mean of 363 ± 41 unique proteins (mean ± SD) in IU vitreous and 393 ± 69 unique proteins in control samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of liquid vitreous biopsies collected during pars plana vitrectomy. A total of 233 proteins were differentially expressed among control and IU samples, suggesting a protein signature that could distinguish the two groups. Pathway analysis identified 22 inflammatory mediators of the interleukin-12 (IL-12) signaling pathway in IU vitreous. Upstream regulator analysis identified downstream mediators of IL-23 and myeloid differentiation primary response protein (MYD88), both of which are involved in the recruitment and differentiation of myeloid cells. Taken together, our results suggest the recruitment of myeloid cells as an upstream pathway in the pathogenesis of IU.This study provides insights into proteins that will serve as biomarkers and therapeutic targets for IU. These biomarkers will help design future clinical trials using rational molecular therapeutics.

    View details for DOI 10.1016/j.ajoc.2020.100646

    View details for PubMedID 32274442

    View details for PubMedCentralID PMC7132169

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


    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 Identifier: NCT01717170.

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

    View details for PubMedID 33042579

    View details for PubMedCentralID PMC7539516

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


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

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

    View details for PubMedID 32670612

    View details for PubMedCentralID PMC7341631

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


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

    View details for DOI 10.1016/j.ajoc.2020.100687

    View details for PubMedID 32280811

    View details for PubMedCentralID PMC7139151

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


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

    View details for DOI 10.1016/j.ajoc.2020.100680

    View details for PubMedID 32258827

    View details for PubMedCentralID PMC7125319

  • 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


    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


    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

  • 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
  • Macular sensitivity endpoints in geographic atrophy secondary to age-related macular degeneration - exploratory analysis of two parallel randomized phase 3 trials Chang, D., Steffen, V., Gao, S. S., Briggs, J., Rabe, C., Honigberg, L., Sepah, Y., Ferrara, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • 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
  • 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


    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

  • 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
  • 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


    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

  • 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


    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

  • 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


    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
  • 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


    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

  • Comparison of Retinal Layer Thickness in Eyes with Resolved Diabetic Macular Edema Receiving Ranibizumab with Normal Eyes. Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde Rentiya, Z. S., Kherani, S. n., Usmani, B. n., Qazi, M. A., Sadiq, M. A., Iftikhar, M. n., Nguyen, Q. D., Shah, S. M., Sepah, Y. J. 2019: 1–10


    To evaluate the thickness of individual retinal layers in eyes with resolved diabetic macular edema (DME) after treatment with ranibizumab (RBZ).Spectral-domain optical coherence tomography (OCT) scans of 25 eyes (25 patients) with DME that had been treated with RBZ (and shown resolution of edema as evident by the absence of fluid in a high-resolution grid placed on the fovea) were acquired using Spectralis HRA + OCTTM. Thickness measurements of individual layers were calculated using papillomacular bundle (PMB), central subfield, and inner- and outer-ring Early Treatment Diabetic Retinopathy Study (ETDRS) grids. Measurements were compared to 45 normal eyes with no known retinal disease. A post-hoc analysis was done correlating visual acuity (VA) with individual retinal layer thickness.Full retinal thickness (FRT) was thinner than normal individuals across all 4 grids. There were similarities and differences among the 4 grids; however, PMB and inner-ring ETDRS grids displayed the most resemblance. The VA significantly correlated with the FRT measured in PMB (p = 0.004), central subfield (p = 0.02), and inner-ring (p = 0.006) ETDRS.Segmentation of OCT scans revealed significant differences in the overall thickness of the retina and of individual retinal layers in patients with resolved DME. PMB grid showed a stronger correlation between affected retinal layers and VA compared to ETDRS. PMB also showed significance with VA in layers that were shown to be not significant in ETDRS grid.

    View details for DOI 10.1159/000503326

    View details for PubMedID 31747663

  • An Approach Towards Automatic Detection of Toxoplasmosis using Fundus Images Chakravarthy, A. D., Abeyrathna, D., Subramaniam, M., Chundi, P., Halim, M., Hasanreisoglu, M., Sepah, Y. J., Quan Dong Nguyen, IEEE IEEE. 2019: 710-717
  • Comparison of montage with conventional stereoscopic seven-field photographs for assessment of ETDRS diabetic retinopathy severity. International journal of retina and vitreous Nguyen, N. V., Vigil, E. M., Hassan, M. n., Halim, M. S., Baluyot, S. C., Guzman, H. A., Afridi, R. n., Do, D. V., Sepah, Y. J. 2019; 5: 51


    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

  • 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


    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


    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; 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 Quan Dong Nguyen, Merrill, P. T., Sepah, Y. J., Ibrahim, M. A., Banker, A., Leonardi, A., Chernock, M., Mudumba, S., Do, D. V. 2018; 125 (12): 1984–93
  • 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


    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

  • 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
  • Short-Term Effects of Ranibizumab on Diabetic Retinopathy Severity and Progression OPHTHALMOLOGY RETINA Hassan, M., Sadiq, M. A., Halim, M., Afridi, R., Nguyen, N. V., Sepah, Y. J. 2018; 2 (7): 749-751
  • 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


    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. n., Sadiq, M. A., Halim, M. S., Afridi, R. n., Nguyen, N. V., Sepah, Y. J. 2018; 2 (7): 749–51

    View details for PubMedID 31047386

  • 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


    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
  • 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


    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

  • Corticosteroids as adjuvant therapy for ocular toxoplasmosis COCHRANE DATABASE OF SYSTEMATIC REVIEWS Jasper, S., Vedula, S. S., John, S. S., Horo, S., Sepah, Y. J., Quan Dong Nguyen 2017: CD007417


    Ocular infection caused by Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea, and consequently lead to complications such as glaucoma, cataract, and posterior synechiae.The objective of this systematic review was to assess the effects of adjunctive use of corticosteroids to anti-parasitic therapy versus anti-parasitic therapy alone for ocular toxoplasmosis.We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register (2016; Issue 11)), MEDLINE Ovid, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, MEDLINE Ovid Daily (January 1946 to December 2016), Embase (January 1980 to December 2016), Latin American and Caribbean Literature on Health Sciences (LILACS (January 1982 to December 2016)), the ISRCTN registry (, (, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 7 December 2016.We had planned to include randomized and quasi-randomized controlled trials. Eligible trials would have enrolled participants of any age who were immunocompetent and were diagnosed with acute ocular toxoplasmosis. Included trials would have compared anti-parasitic therapy plus corticosteroids versus anti-parasitic therapy alone, different doses or times of initiation of corticosteroids.Two authors independently screened titles and abstracts retrieved through the electronic searches. We retrieved full-text reports of studies categorized as 'unsure' or 'include' after we reviewed the abstracts. Two authors independently reviewed each full-text report for eligibility. Discrepancies were resolved through discussion.We identified no completed or ongoing trial that was eligible for this Cochrane review.Although research has identified a wide variation in practice regarding the use of corticosteroids, our review did not identify any evidence from randomized controlled trials for or against the role of corticosteroids in the management of ocular toxoplasmosis. Several questions remain unanswered by well-conducted randomized trials in this context, including whether the use of corticosteroids as an adjunctive agent is more effective than the use of anti-parasitic therapy alone; if so, when corticosteroids should be initiated in the treatment regimen (early versus late course of treatment), and what would be the best dose and duration of steroid use.

    View details for PubMedID 28125765

    View details for PubMedCentralID PMC5369355

  • 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
  • Aspiration in injections: should we continue or abandon the practice? F1000Research Sepah, Y., Samad, L., Altaf, A., Halim, M. S., Rajagopalan, N., Javed Khan, A. 2014; 3: 157-?


    Aspiration during any kind of injection is meant to ensure that the needle tip is at the desired location during this blind procedure. While aspiration appears to be a simple procedure, it has generated a lot of controversy concerning the perceived benefits and indications. Advocates and opponents of aspiration both make logically sound claims. However, due to scarcity of available data, there is no evidence that this procedure is truly beneficial or unwarranted. Keeping in view the huge number of injections given worldwide, it is important that we draw attention to key questions regarding aspiration that, up till now, remain unanswered. In this review, we have attempted to gather and present literature on aspiration both from published and non-published sources in order to provide not only an exhaustive review of the subject, but also a starting point for further studies on more specific areas requiring clarification. A literature review was conducted using the US National Institute of Health's PubMed service (including Medline), Google Scholar and Scopus. Guidelines provided by the World Health Organization, Safe Injection Global Network, International Council of Nursing, Center for Disease Control, US Federal Drug Agency, UK National Health Services, British Medical Association, Europe Nursing and Midwifery Council, Public Health Agency Canada, Pakistan Medical Association and International Organization of Standardization recommendations 7886 parts 1-4 for sterile hypodermics were reviewed for relevant information. In addition, curricula of several medical/nursing schools from India, Nigeria and Pakistan, the US pharmacopeia Data from the WHO Program for International Drug Monitoring network in regard to adverse events as a result of not aspirating prior to injection delivery were reviewed. Curricula of selected major medical/nursing schools in India, Nigeria and Pakistan, national therapeutic formularies, product inserts of most commonly used drugs and other possible sources of information regarding aspiration and injections were consulted as well.

    View details for DOI 10.12688/f1000research.1113.3

    View details for PubMedID 28344770