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Article: Evaluating optical coherence tomography (OCT) findings as potential biomarkers in central nervous system (CNS) lymphoma with or without ocular involvement.

Hassan, Muhammad / Halim, Muhammad Sohail / Afridi, Rubbia / Nguyen, Nam V / Nguyen, Quan Dong / Sepah, Yasir J

International journal of retina and vitreous

2021 Volume 7, Issue 1, Page(s) 70

Abstract: Background: To evaluate spectral domain optical coherence tomography (SD-OCT) findings as biomarkers in primary central nervous system lymphoma (PCNSL) with or without ocular involvement.: Methods: This study was a cross-sectional study and patients ... ...

Abstract	Background: To evaluate spectral domain optical coherence tomography (SD-OCT) findings as biomarkers in primary central nervous system lymphoma (PCNSL) with or without ocular involvement. Methods: 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. Results: 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). Conclusions: 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.
Language	English
Publishing date	2021-11-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2836254-8
ISSN	2056-9920
ISSN	2056-9920
DOI	10.1186/s40942-021-00345-1
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Article ; Online: Two Phase 3 Studies on Ophthalmologic Effects of Roxadustat Versus Darbepoetin.

Sepah, Yasir J / Nguyen, Quan Dong / Yamaguchi, Yusuke / Otsuka, Tetsuro / Majikawa, Yoshikatsu / Reusch, Michael / Akizawa, Tadao

Kidney international reports

2022 Volume 7, Issue 4, Page(s) 763–775

Abstract: 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 ( ...

Abstract	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, Conclusion: In these studies, roxadustat, compared with DA, was not associated with an increased risk of adverse ophthalmologic events in these cohorts.
Language	English
Publishing date	2022-01-19
Publishing country	United States
Document type	Journal Article
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2022.01.1045
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Article ; Online: Macular Sensitivity Endpoints in Geographic Atrophy: Exploratory Analysis of Chroma and Spectri Clinical Trials.

Chang, Dolly S / Callaway, Natalia F / Steffen, Verena / Csaky, Karl / Guymer, Robyn H / Birch, David G / Patel, Praveen J / Ip, Michael / Gao, Simon S / Briggs, Jayla / Honigberg, Lee / Lai, Phillip / Ferrara, Daniela / Sepah, Yasir J

Ophthalmology science

2023 Volume 4, Issue 1, Page(s) 100351

Abstract: Purpose: 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).: Design: Patients were included from 2 ... ...

Abstract	Purpose: 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). Design: Patients were included from 2 identically designed, phase III, double-masked, randomized controlled clinical trials, Chroma (NCT02247479) and Spectri (NCT02247531). Participants: Patients enrolled were aged ≥ 50 years with bilateral GA and no evidence of previous or active neovascular AMD. Methods: 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. Main outcome measures: 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). Results: 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 mm Conclusions: 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. Financial disclosures: Proprietary or commercial disclosure may be found after the references.
Language	English
Publishing date	2023-06-12
Publishing country	Netherlands
Document type	Journal Article
ISSN	2666-9145
ISSN (online)	2666-9145
DOI	10.1016/j.xops.2023.100351
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Article ; Online: ASSOCIATION OF ORAL MONTELUKAST WITH REDUCED ODDS OF DEVELOPING EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

Matsumiya, Wataru / Karaca, Irmak / Pham, Brandon Huy / Akhavanrezayat, Amir / Uludag, Gunay / Yasar, Cigdem / Ghoraba, Hashem / Mobasserian, Azadeh / Regenold, Jonathan / Halim, Muhammad Sohail / Sepah, Yasir J / Do, Diana V / Chong, Victor / Nguyen, Quan Dong

Retina (Philadelphia, Pa.)

2023 Volume 43, Issue 11, Page(s) 1914–1921

Abstract: Purpose: 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.: Methods: This case- ... ...

Abstract	Purpose: 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. Methods: 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. Subanalysis among 1913 exAMD and 324 nonexudative AMD was also conducted. Results: A total of 47 (2.5%) exAMD cases were identified to have a history of oral montelukast use before exAMD diagnosis, compared with 84 (4.4%) controls. Montelukast usage was significantly associated with reduced odds of exAMD in the multivariable analysis (adjusted odds ratio [OR]: 0.50, 95% confidence interval: 0.31-0.80) and nonsteroidal anti-inflammatory drug usage (adjusted OR: 0.69). Caucasian race, history of smoking, and nonexudative macular degeneration in either eye were also found to have a significant relationship with increased odds of exAMD. In the subanalysis, montelukast usage showed significant association with reduced odds of developing exAMD from nonexudative AMD (adjusted OR: 0.53, 95% confidence interval: 0.29-0.97) and the presence of atopic disease (adjusted OR: 0.60). Conclusion: The study results suggested that oral montelukast is linked to reduced odds of exAMD development.
MeSH term(s)	Humans ; Case-Control Studies ; Smoking ; Macular Degeneration/diagnosis
Chemical Substances	montelukast (MHM278SD3E)
Language	English
Publishing date	2023-06-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	603192-4
ISSN	1539-2864 ; 0275-004X
ISSN (online)	1539-2864
ISSN	0275-004X
DOI	10.1097/IAE.0000000000003870
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Article: Current concepts in the diagnosis and management of antiphospholipid syndrome and ocular manifestations.

Uludag, Gunay / Onghanseng, Neil / Tran, Anh N T / Hassan, Muhammad / Halim, Muhammad Sohail / Sepah, Yasir J / Do, Diana V / Nguyen, Quan Dong

Journal of ophthalmic inflammation and infection

2021 Volume 11, Issue 1, Page(s) 11

Abstract: Antiphospholipid syndrome (APS) is an autoimmune disorder associated with obstetrical complications, thrombotic complications involving both arteries and veins, and non-thrombotic manifestations affecting multiple other systems presenting in various ... ...

Abstract	Antiphospholipid syndrome (APS) is an autoimmune disorder associated with obstetrical complications, thrombotic complications involving both arteries and veins, and non-thrombotic manifestations affecting multiple other systems presenting in various clinical forms. Diagnosis requires the presence of antiphospholipid antibodies. The exact pathogenesis of APS is not fully known. However, it has recently been shown that activation of different types of cells by antiphospholipid antibodies plays an important role in thrombosis formation. Ocular involvement is one of the important clinical manifestations of APS and can vary in presentations. Therefore, as an ophthalmologist, it is crucial to be familiar with the ocular findings of APS to prevent further complications that can develop. Furthermore, the ongoing identification of new and specific factors contributing to the pathogenesis of APS may provide new therapeutic options in the management of the disease in the future.
Language	English
Publishing date	2021-04-09
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2592309-2
ISSN	1869-5760
ISSN	1869-5760
DOI	10.1186/s12348-021-00240-8
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Article ; Online: Distinct Patterns of Choroidal Lesions in Punctate Inner Choroidopathy and Multifocal Choroiditis Determined by Heatmap Analysis.

Park, Jong G / Halim, Muhammad Sohail / Uludag, Gunay / Onghanseng, Neil / Sredar, Nripun / Sepah, Yasir J / Nguyen, Quan Dong

Ocular immunology and inflammation

2021 Volume 30, Issue 2, Page(s) 276–281

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Choroidal Neovascularization ; Choroiditis/diagnosis ; Fluorescein Angiography ; Humans ; Multifocal Choroiditis ; Retrospective Studies ; Tomography, Optical Coherence ; Visual Acuity ; White Dot Syndromes
Language	English
Publishing date	2021-07-06
Publishing country	England
Document type	Journal Article
ZDB-ID	1193873-0
ISSN	1744-5078 ; 0927-3948
ISSN (online)	1744-5078
ISSN	0927-3948
DOI	10.1080/09273948.2021.1939391
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Article ; Online: Proteomic analysis of autoimmune retinopathy implicates NrCAM as a potential biomarker.

Al-Moujahed, Ahmad / Velez, Gabriel / Vu, Jennifer T / Lima de Carvalho, Jose R / Levi, Sarah R / Bassuk, Alexander G / Sepah, Yasir J / Tsang, Stephen H / Mahajan, Vinit B

Ophthalmology science

2022 Volume 2, Issue 2

Abstract: Purpose: To identify vitreous molecular biomarkers associated with autoimmune retinopathy (AIR).: Design: Case-control study.: Participants: We analyzed six eyes from four patients diagnosed with AIR and eight comparative controls diagnosed with ... ...

Abstract	Purpose: To identify vitreous molecular biomarkers associated with autoimmune retinopathy (AIR). Design: Case-control study. Participants: We analyzed six eyes from four patients diagnosed with AIR and eight comparative controls diagnosed with idiopathic macular holes and epiretinal membranes. Methods: Vitreous biopsies were collected from the participants and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) or multiplex ELISA. Outcome measures: Protein expression changes were evaluated by 1-way ANOVA (significant p-value <0.05), hierarchical clustering, and pathway analysis to identify candidate protein biomarkers. Results: 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. Conclusion: Protein biomarkers such as NrCAM in the vitreous may eventually help diagnose AIR.
Language	English
Publishing date	2022-02-24
Publishing country	Netherlands
Document type	Journal Article
ISSN	2666-9145
ISSN (online)	2666-9145
DOI	10.1016/j.xops.2022.100131
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Article ; Online: Efficacy and Safety of Tocilizumab in the Management of Non-Infectious Uveitis Failed with Conventional Immunomodulatory and Anti-TNFα Therapies.

Uludag, Gunay / Karaca, Irmak / Akhavanrezayat, Amir / Yasar, Cigdem / Matsumiya, Wataru / Pham, Brandon Huy / Halim, Muhammad Sohail / Trong Tuong Than, Ngoc / Sepah, Yasir J / Do, Diana V / Nguyen, Quan Dong

Ocular immunology and inflammation

2022 , Page(s) 1–7

Abstract: Purpose: To determine the outcomes of intravenous (IV) tocilizumab (TCZ) in patients with non-infectious uveitis who failed with conventional immunomodulatory and anti-TNFα therapies.: Methods: Records of seven patients with non-infectious uveitis ... ...

Abstract	Purpose: To determine the outcomes of intravenous (IV) tocilizumab (TCZ) in patients with non-infectious uveitis who failed with conventional immunomodulatory and anti-TNFα therapies. Methods: 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. Results: 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. Conclusion: IV TCZ is a potentially effective and safe therapeutic option for the management of refractory non-infectious uveitis.
Language	English
Publishing date	2022-12-21
Publishing country	England
Document type	Journal Article
ZDB-ID	1193873-0
ISSN	1744-5078 ; 0927-3948
ISSN (online)	1744-5078
ISSN	0927-3948
DOI	10.1080/09273948.2022.2126374
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Article ; Online: Longitudinal Comparative Analysis of Semi-Automated Aqueous Flare Measurements with Clinical Grading and Visual Outcomes in Uveitic Eyes.

Hasanreisoglu, Murat / Halim, Muhammad Sohail / Kesim, Cem / Doan, Hien Luong / Tran, Anh N T / Nguyen, Will / Besalti, Zelal / Lajevardi, Sherin / Hassan, Muhammad / Akhavanrezayat, Amir / Ahmed, Mohamed Ibrahim / Do, Diana V / Sepah, Yasir J / Nguyen, Quan Dong

Ocular immunology and inflammation

2022 Volume 31, Issue 9, Page(s) 1819–1824

Abstract: Purpose: 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 ... ...

Abstract	Purpose: 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. Methods: 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. Results: Mean change in LFP was correlated to those in BCVA ( Conclusions: LFP measurement is beneficial in monitoring inflammatory activity. Cases of identical clinical flare scores with different clinical prognosis may be predicted by LFP.
MeSH term(s)	Humans ; Aqueous Humor ; Uveitis, Anterior ; Uveitis/diagnosis ; Photometry ; Lasers
Language	English
Publishing date	2022-09-28
Publishing country	England
Document type	Journal Article
ZDB-ID	1193873-0
ISSN	1744-5078 ; 0927-3948
ISSN (online)	1744-5078
ISSN	0927-3948
DOI	10.1080/09273948.2022.2123365
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Article: Posterior segment inflammatory outcomes assessed using fluorescein angiography in the STOP-UVEITIS study.

Sadiq, Mohammad Ali / Hassan, Muhammad / Afridi, Rubbia / Halim, Muhammad Sohail / Do, Diana V / Sepah, Yasir J / Nguyen, Quan Dong

International journal of retina and vitreous

2020 Volume 6, Page(s) 47

Abstract: Background: 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. ... ...

Abstract	Background: 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. Methods: 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. Results: 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). Conclusions: IV infusions of tocilizumab (both 4 and 8 mg/kg) are effective in improving posterior segment inflammation in eyes with NIU. A semi-quantitative FA scoring system may be used as a reliable outcome measure for assessment of posterior segment inflammation.ClinicalTrials.gov Identifier: NCT01717170.
Language	English
Publishing date	2020-10-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2836254-8
ISSN	2056-9920
ISSN	2056-9920
DOI	10.1186/s40942-020-00245-w
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