Publications by authors named "Lucia Sobrin"

145 Publications

Inflammatory Complications of Intravitreal Anti-VEGF Injections.

J Clin Med 2021 Mar 2;10(5). Epub 2021 Mar 2.

Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA 02114, USA.

Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents is a commonly used therapy for numerous retinal diseases. The most commonly used of these medications are bevacizumab, ranibizumab, aflibercept, and brolucizumab. However, intravitreal administration of these agents is also associated with several inflammatory and non-inflammatory adverse events. The three inflammatory adverse events are sterile intraocular inflammation, brolucizumab-associated retinal vasculitis, and post-injection endophthalmitis. This narrative review summarizes the current literature regarding these conditions, including their epidemiology, presentation, management, outcomes, and pathogenesis. The inflammatory adverse events also share a number of overlapping features, which can make them difficult to discern from one another in a clinical context. This review discusses certain distinguishing features of these conditions that may aid providers in discerning between them and establishing the correct diagnosis.
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http://dx.doi.org/10.3390/jcm10050981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957879PMC
March 2021

Risk of Non-infectious Uveitis with Metformin Therapy in a Large Healthcare Claims Database.

Ocul Immunol Inflamm 2021 Mar 8:1-7. Epub 2021 Mar 8.

Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Purpose: To determine if metformin is associated with noninfectious uveitis (NIU).

Methods: Patients in an insurance claims database who initiated metformin (n = 359,139) or other oral anti-diabetic medications (n = 162,847) were followed for NIU development. Both cohort and case-control analyses were performed to assess differing exposure lengths using Cox and conditional logistic regression, respectively.

Results: The hazard ratio (HR) for incident NIU was not significantly different between the metformin and non-metformin cohorts [HR = 1.19, 95% Confidence Interval (CI): 0.92-1.54, = .19]. The case control analysis similarly showed no association between any metformin use 2 years before the outcome date and NIU [odds ratio (OR) = 0.64, 95% CI: 0.39-1.04, = .07]. However, there was a protective 20 association between cumulative metformin duration [(445-729 days) adjusted OR (aOR) = 0.49, 95% CI: 0.27-0.90, = .02] and dosage (>390,000 mg aOR = 0.44, 95% CI: 0.25-0.78, = .001) compared with no metformin use.

Conclusions: Our results suggest metformin use for longer durations may be protective of NIU onset.
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http://dx.doi.org/10.1080/09273948.2021.1872650DOI Listing
March 2021

Management of Central Retinal Artery Occlusion: A Scientific Statement From the American Heart Association.

Stroke 2021 Mar 8:STR0000000000000366. Epub 2021 Mar 8.

Purpose: Central retinal artery occlusion (CRAO) is a form of acute ischemic stroke that causes severe visual loss and is a harbinger of further cerebrovascular and cardiovascular events. There is a paucity of scientific information on the appropriate management of CRAO, with most strategies based on observational literature and expert opinion. In this scientific statement, we critically appraise the literature on CRAO and provide a framework within which to consider acute treatment and secondary prevention.

Methods: We performed a literature review of randomized controlled clinical trials, prospective and retrospective cohort studies, case-control studies, case reports, clinical guidelines, review articles, basic science articles, and editorials concerning the management of CRAO. We assembled a panel comprising experts in the fields of vascular neurology, neuro-ophthalmology, vitreo-retinal surgery, immunology, endovascular neurosurgery, and cardiology, and document sections were divided among the writing group members. Each member received an assignment to perform a literature review, synthesize the data, and offer considerations for practice. Multiple drafts were circulated among the group until consensus was achieved.

Results: Acute CRAO is a medical emergency. Systems of care should evolve to prioritize early recognition and triage of CRAO to emergency medical attention. There is considerable variability in management patterns among practitioners, institutions, and subspecialty groups. The current literature suggests that treatment with intravenous tissue plasminogen activator may be effective. Patients should undergo urgent screening and treatment of vascular risk factors. There is a need for high-quality, randomized clinical trials in this field.
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http://dx.doi.org/10.1161/STR.0000000000000366DOI Listing
March 2021

Single-cell RNA sequencing: An overview for the ophthalmologist.

Semin Ophthalmol 2021 Feb 26:1-7. Epub 2021 Feb 26.

Massachusetts Eye and Ear, Harvard Medical School Department of Ophthalmology, Boston, MA, USA.

Understanding the molecular composition of pathogenic tissues is a critical step in understanding the pathophysiology of disease and designing therapeutics. First described in 2009, single cell RNA sequencing (scRNAseq) is a methodology whereby thousands of cells are simultaneously isolated into individual micro-environments that can be altered experimentally and the genome-wide RNA expression of each cell is captured. It has undergone significant technological improvement over the last decade and gained tremendous popularity. scRNAseq is an improvement over prior pooled RNA analyses which cannot identify the cellular composition and heterogeneity of a tissue of interest. This new approach offers new opportunity for new discovery, as tissue samples can now be sub-categorized into groups of cell types based on genome-wide gene expression in an unbiased fashion. As ophthalmologists, we are uniquely positioned to obtain pathologic samples from the eye for further study. ScRNAseq has already been applied in ophthalmology to characterize retinal tissue, and it may offer the key to understanding various pathological processes in the future.
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http://dx.doi.org/10.1080/08820538.2021.1889615DOI Listing
February 2021

Angiotensin Converting Enzyme-Inhibitors and Incidence of Non-infectious Uveitis in a Large Healthcare Claims Database.

Ophthalmic Epidemiol 2021 Feb 23:1-6. Epub 2021 Feb 23.

Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

: To determine if angiotensin converting enzyme-inhibitors (ACE-I) alter the incidence of non-infectious uveitis (NIU). Patients in a large healthcare claims database who initiated ACE-I (n = 695,557) were compared to patients who initiated angiotensin receptor blockers (ARB, n = 354,295). A second comparison was also made between patients who initiated ACE-I (n = 505,958) and those who initiated beta-blockers (BB, n = 538,109). The primary outcome was incident NIU defined as a first diagnosis code for NIU followed by a second instance of a NIU code within 120 days. For the secondary outcome, a corticosteroid prescription or code for an ocular corticosteroid injection within 120 days of the NIU diagnosis code was used instead of the second NIU diagnosis code. Data were analyzed using Cox regression modeling with inverse probability of treatment weighting (IPTW). Sub-analyses were performed by anatomic subtype. When comparing ACE-I to ARB initiators, the hazard ratio (HR) for incident NIU was not significantly different for the primary outcome [HR = 0.95, 95% Confidence Interval (CI): 0.85-1.07, = .41] or secondary outcome [HR = 0.96, 95% CI: 0.86-1.07, = .44]. Similarly, in the ACE-I and BB initiators comparison, the HR for incident NIU was not significantly different comparing ACE-I and BB initiators for either outcome definition or any of the NIU anatomical subtypes. Our results suggest there is no evidence that ACE-I have a protective effect on NIU.
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http://dx.doi.org/10.1080/09286586.2021.1887284DOI Listing
February 2021

Genome-Wide Association Studies Identify Two Novel Loci Conferring Susceptibility to Diabetic Retinopathy in Japanese Patients with Type 2 Diabetes.

Hum Mol Genet 2021 Feb 19. Epub 2021 Feb 19.

Department of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.

Several reports have suggested that genetic susceptibility contributes to the development and progression of diabetic retinopathy. We aimed to identify genetic loci that confer susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes. We analysed 5 790 508 single nucleotide polymorphisms (SNPs) in 8880 Japanese patients with type 2 diabetes, 4839 retinopathy cases and 4041 controls, as well as 2217 independent Japanese patients with type 2 diabetes, 693 retinopathy cases, and 1524 controls. The results of these two genome-wide association studies (GWAS) were combined with an inverse variance meta-analysis (Stage-1), followed by de novo genotyping for the candidate SNP loci (p < 1.0 × 10-4) in an independent case-control study (Stage-2, 2260 cases and 723 controls). After combining the association data (Stage-1 and -2) using meta-analysis, the associations of two loci reached a genome-wide significance level: rs12630354 near STT3B on chromosome 3, p = 1.62 × 10-9, odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.11-1.23, and rs140508424 within PALM2 on chromosome 9, p = 4.19 × 10-8, OR = 1.61, 95% CI 1.36-1.91. However, the association of these two loci were not replicated in Korean, European, or African American populations. Gene-based analysis using Stage-1 GWAS data identified a gene-level association of EHD3 with susceptibility to diabetic retinopathy (p = 2.17 × 10-6). In conclusion, we identified two novel SNP loci, STT3B and PALM2, and a novel gene, EHD3, that confers susceptibility to diabetic retinopathy; however, further replication studies are required to validate these associations.
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http://dx.doi.org/10.1093/hmg/ddab044DOI Listing
February 2021

Nationwide incidence and treatment pattern of retinopathy of prematurity in South Korea using the 2007-2018 national health insurance claims data.

Sci Rep 2021 Jan 14;11(1):1451. Epub 2021 Jan 14.

Department of Ophthalmology, Hanyang University College of Medicine, Seoul, Korea.

The aim of this study is to investigate the nationwide incidence and treatment pattern of retinopathy of prematurity (ROP) in South Korea. Using the population-based National Health Insurance database (2007-2018), the nationwide incidence of ROP among premature infants with a gestational age (GA) < 37 weeks (GA < 28 weeks, GA28; 28 weeks ≤ GA < 37 weeks; GA28-37) and the percentage of ROP infants who underwent treatment [surgery (vitrectomy, encircling/buckling); retinal ablation (laser photocoagulation, cryotherapy)] were evaluated. We identified 141,964 premature infants, 42,300 of whom had ROP, with a nationwide incidence of 29.8%. The incidence of ROP in GA28 group was 4.3 times higher than in GA28-37 group (63.6% [2240/3522] vs 28.9% [40,060/138,442], p < 0.001). As for the 12-year trends, the incidence of ROP decreased from 39.5% (3308/8366) in 2007 to 23.5% (2943/12,539) in 2018. 3.0% of ROP infants underwent treatment (25.0% in GA28; 1.7% in GA28-37); 0.2% (84/42,300) and 2.9% (1214/42,300) underwent surgery and retinal ablation, respectively. The overall percentage of ROP infants who underwent treatment has decreased from 4.7% in 2007 to 1.8% in 2018. This first Korean nationwide epidemiological study of ROP revealed a decreased incidence of ROP and a decreased percentage of ROP infants undergoing conventional treatment during a 12-year period.
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http://dx.doi.org/10.1038/s41598-021-80989-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809441PMC
January 2021

Application of Metagenomic Sequencing in the Diagnosis of Infectious Uveitis.

Semin Ophthalmol 2020 Aug 18;35(5-6):276-279. Epub 2020 Oct 18.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School , Boston, MA, USA.

: to summarize the origin and very recent history of the use of metagenomic sequencing for the diagnosis of infectious uveitis, convey the technique as described by one of the primary institutions experimenting with the technology, and present recent successful applications of the technology as well as potential advantages and pitfalls compared to other current diagnostic tools.: review of peer-reviewed literature concerning metagenomic sequencing for the diagnosis of infectious uveitis.: compared to existing diagnostic methods, metagenomic deep sequencing is a sensitive, unbiased, and comprehensive technique with great potential for diagnosing the causative pathogens of cases of infectious uveitis. However, many issues remain to be addressed in the process of developing this technology, including but not limited to the potentially overwhelming amount of information generated, definition of diagnostic thresholds, demonstration of validity, contamination, and cost.
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http://dx.doi.org/10.1080/08820538.2020.1818795DOI Listing
August 2020

Correlation of Immunological Markers with Disease and Clinical Outcome Measures in Patients with Autoimmune Retinopathy.

Transl Vis Sci Technol 2020 06 16;9(7):15. Epub 2020 Jun 16.

Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.

Purpose: To determine if immunological markers (1) are significantly different between autoimmune retinopathy (AIR) patients and controls and (2) correlate with disease progression in AIR patients.

Methods: We enrolled patients with a possible AIR diagnosis, as well as control participants without eye disease, autoimmunity, or cancer. Immunological markers were tested in all participants. In addition, AIR patients had up to three blood draws for testing over their disease course. For AIR patients, clinical measures, including visual acuity (VA) and Goldmann visual field (GVF) area, were recorded at each draw. We used the Mann-Whitney test to compare the immunological markers between AIR patients and controls. We used multilevel mixed-effect regression to investigate the correlation between markers and clinical parameters over time in AIR patients.

Results: Seventeen patients with AIR and 14 controls were included. AIR patients had a higher percent of monocytes ( = 3.076, = 0.002). An increase in immunoglobulin G against recoverin was correlated with a VA decrease (β = 0.0044, < 0.0001). An increase in monocyte proportion was correlated with a decrease in GVF area (β = -7.27, = 0.0021). Several markers of B-cell depletion were correlated with GVF improvement.

Conclusions: Monocytes may play a role in AIR pathophysiology and be a disease activity marker. B-cell depletion markers correlated with clinical parameter improvement, particularly GVF.

Translational Relevance: This work elucidates immunologic markers that may improve the accuracy of diagnosis and treatment of AIR.
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http://dx.doi.org/10.1167/tvst.9.7.15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7414616PMC
June 2020

Widefield Swept-Source OCTA in Vogt-Koyanagi-Harada Disease.

Ophthalmic Surg Lasers Imaging Retina 2020 07;51(7):407-412

Herein, the authors describe an initial case report of widefield swept-source optical coherence tomography angiography (SS-OCTA) in Vogt-Koyanagi-Harada (VKH) disease. When compared to fluorescent angiography, indocyanine green angiography, and enhanced-depth OCT - upon which the revised criteria for VHK are based - widefield SS-OCTA enables detection of vitreous inflammation, noninvasive identification of characteristic areas of flow void at the level of choriocapillaris in the acute phase and may be a novel valuable tool not only for noninvasive diagnosis and monitoring of disease progression, persistence, resolution, and recurrence to guide therapy in VKH disease in the future. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:407-412.].
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http://dx.doi.org/10.3928/23258160-20200702-06DOI Listing
July 2020

Risk of Noninfectious Uveitis with Female Hormonal Therapy in a Large Healthcare Claims Database.

Ophthalmology 2020 11 27;127(11):1558-1566. Epub 2020 Apr 27.

Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania.

Purpose: To determine if female hormonal therapy (FHT) increases the incidence of noninfectious uveitis.

Design: Retrospective cohort study.

Participants: Women exposed to FHT and matched women unexposed to FHT enrolled in a national insurance plan.

Methods: Estimation of noninfectious uveitis incidence used multivariable Cox proportional hazards regression. To account for differences between the exposed and unexposed cohorts, a propensity score for being prescribed FHT was created using logistic regression, and inverse probability of treatment weighting was performed.

Main Outcome Measures: Incidence of noninfectious uveitis. For the primary outcome, incident noninfectious uveitis was defined as a new diagnosis code for noninfectious uveitis followed by a second instance of a noninfectious uveitis code within 120 days. For the alternative outcome definition, a corticosteroid prescription or code for an ocular corticosteroid injection within 120 days of the uveitis diagnosis code was used instead of the second uveitis diagnosis code.

Results: There were 217 653 women exposed to FHT and 928 408 women not unexposed to FHT. For the primary outcome, the hazard ratio (HR) for incident noninfectious uveitis was not significantly different between the FHT and unexposed cohorts (HR, 0.99; 95% confidence interval [CI], 0.83-1.17; P = 0.87). With the alternative outcome definition, the FHT cohort was more likely to develop uveitis (HR, 1.21; 95% CI, 1.04-1.41; P = 0.01). When examined by anatomic subtype, for anterior uveitis there was a greater likelihood of incident uveitis in the exposed cohort (HR, 1.23; 95% CI, 1.05-1.45; P = 0.01) for the alternative outcome definition but not for the primary outcome. With age stratification, women exposed to FHT aged ≥45 years at the time of FHT prescription were more likely to develop uveitis (HR, 1.23; 95% CI, 1.03-1.47; P = 0.03) for the alternative outcome definition. A similar HR (1.22) was seen for women aged ≤44 years at the time of prescription, but this association did not meet statistical significance (P = 0.20).

Conclusions: Exposure to FHT increases the rate of incident noninfectious uveitis when uveitis is defined on the basis of both diagnostic codes and documentation of corticosteroid treatment. However, the risk is modest and FHT is likely safe with regard to noninfectious uveitis risk in the majority of patients exposed to these drugs.
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http://dx.doi.org/10.1016/j.ophtha.2020.04.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606220PMC
November 2020

Uveitis Therapy: The Corticosteroid Options.

Drugs 2020 Jun;80(8):765-773

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA, 02114, USA.

Uveitis is characterized by intraocular inflammation involving the uveal tract; its etiologies generally fall into two broad categories: autoimmune/inflammatory or infectious. Corticosteroids  are a powerful and important class of medications ubiquitous in the treatment of uveitis. They may be given systemically or locally, in the form of topical drops, periocular injection, intravitreal suspension, or intravitreal implant. This review describes each of the currently available corticosteroid treatment options for uveitis, including favorable and unfavorable characteristics of each as well as applicable clinical trials. The main advantage of corticosteroids as a whole is their ability to quickly and effectively control inflammation early on in the course of uveitis. However, they can have serious side effects, whether localized to the eye (such as cataract and elevated intraocular pressure) or systemic (such as osteonecrosis and adrenal insufficiency) and in the majority of cases of uveitis are not an appropriate option for long-term therapy.
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http://dx.doi.org/10.1007/s40265-020-01314-yDOI Listing
June 2020

Case 14-2020: A 37-Year-Old Man with Joint Pain and Eye Redness.

N Engl J Med 2020 04;382(18):1750-1758

From the Department of Ophthalmology, Massachusetts Eye and Ear (L.S.), the Departments of Medicine (J.H.S.), Radiology (A.J.H.), and Pathology (J.L.N., R.M.N.), Massachusetts General Hospital, and the Departments of Ophthalmology (L.S.), Medicine (J.H.S.), Radiology (A.J.H.), and Pathology (J.L.N., R.M.N.), Harvard Medical School - all in Boston.

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http://dx.doi.org/10.1056/NEJMcpc1909623DOI Listing
April 2020

Vitamin D and Ocular Inflammation.

Ocul Immunol Inflamm 2020 04;28(3):337-340

Centre for Ophthalmology, University Tuebingen, Tuebingen, Germany.

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http://dx.doi.org/10.1080/09273948.2020.1734421DOI Listing
April 2020

BEST1-One Gene, Many Diseases.

JAMA Ophthalmol 2020 05;138(5):552

Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Department of Ophthalmology, Boston.

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http://dx.doi.org/10.1001/jamaophthalmol.2020.0683DOI Listing
May 2020

MULTIMODAL IMAGING IN ACUTE RETINAL NECROSIS PRESENTING WITH MACULAR INVOLVEMENT.

Retin Cases Brief Rep 2020 Feb 6. Epub 2020 Feb 6.

Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.

Purpose: To report an unusual case of early macular necrosis in acute retinal necrosis and its features on multimodal imaging.

Methods: Findings on fundus examination, laboratory workup, fluorescein angiography, autofluorescence, optical coherence tomography, and optical coherence tomography angiography.

Results: A 31-year-old healthy woman presented with 1 week of photophobia and central scotoma of the right eye. Initial examination revealed vitritis, hyperemia of the optic disc, and a yellow-white macular lesion without any peripheral findings. Peripheral involvement was first noted only 4 days later. The patient was diagnosed with acute retinal necrosis secondary to varicella zoster virus and was successfully treated with intravitreal and oral antiviral medications. Optical coherence tomography imaging of the macular lesion showed involvement of both the inner and outer retina. Optical coherence tomography angiography revealed a large flow void in the choriocapillaris, which has not been previously demonstrated.

Conclusion: Multimodal imaging offers valuable information in the evaluation of patients with acute retinal necrosis.
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http://dx.doi.org/10.1097/ICB.0000000000000978DOI Listing
February 2020

Shedding (Sun)light on Risk Factors for Noninfectious Uveitis.

Authors:
Lucia Sobrin

Ophthalmology 2020 02;127(2):238-239

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http://dx.doi.org/10.1016/j.ophtha.2019.09.011DOI Listing
February 2020

Factors Predictive of Remission of Chronic Anterior Uveitis.

Ophthalmology 2020 06 28;127(6):826-834. Epub 2019 Nov 28.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts; MCM Eye Unit, MyungSung Christian Medical Center and MyungSung Medical School, Addis Ababa, Ethiopia.

Purpose: To estimate the incidence of medication-free remission of chronic anterior uveitis and identify predictors thereof.

Design: Retrospective cohort study.

Participants: Patients diagnosed with anterior uveitis of longer than 3 months' duration followed up at United States tertiary uveitis care facilities.

Methods: Estimation of remission incidence and identification of associated predictors used survival analysis.

Main Outcome Measures: Incidence of medication-free remission. For the primary analysis, remission was defined as inactive uveitis while off treatment at all visits spanning an interval of at least 90 days or-for patients who did not return for follow-up after 90 days-remaining inactive without receiving suppressive medications at all of the last visits. Association of factors potentially predictive of medication-free remission was also studied.

Results: Two thousand seven hundred ninety-five eyes of 1634 patients with chronic anterior uveitis were followed up over 7936 eye-years (4676 person-years). The cumulative medication-free, person-year remission incidence within 5 years was 32.7% (95% confidence interval [CI], 30.4%-35.2%). Baseline clinical factors predictive of reduced remission incidence included longer duration of uveitis at presentation (for 2 to 5 years vs. less than 6 months: adjusted hazard ratio [aHR], 0.61; 95% CI, 0.44-0.83), bilateral uveitis (aHR, 0.75; 95% CI, 0.59-0.96), prior cataract surgery (aHR, 0.70; 95% CI 0.56-0.88), and glaucoma surgery (aHR, 0.63; 95% CI, 0.45-0.90). Two time-updated characteristics were also predictive of reduced remission incidence: keratic precipitates (aHR, 0.36; 95% CI, 0.21-0.60) and synechiae (aHR, 0.62; 95% CI, 0.41-0.93). Systemic diagnosis with juvenile idiopathic arthritis and spondyloarthropathy were also associated with reduced remission incidence. Older age at presentation was associated with higher incidence of remission (for age ≥40 years vs. <40 years: aHR, 1.29; 95% CI, 1.02-1.63).

Conclusions: Approximately one third of patients with chronic anterior uveitis remit within 5 years. Longer duration of uveitis, younger age, bilateral uveitis, prior cataract surgery, glaucoma surgery, presence of keratic precipitates and synechiae, and systemic diagnoses of juvenile idiopathic arthritis and spondyloarthropathy predict reduced remission incidence; patients with these factors should be managed taking into account the higher probability of a longer disease course.
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http://dx.doi.org/10.1016/j.ophtha.2019.11.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246152PMC
June 2020

Comparison of Modified Posterior Sub-Tenon's vs. Trans-Septal Triamcinolone Injection for Non-infectious Uveitis.

Ocul Immunol Inflamm 2020 Jan 4:1-8. Epub 2020 Jan 4.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA.

: To compare the safety and efficacy of trans-septal vs. modified posterior sub-Tenon's (PST) corticosteroid injections for noninfectious uveitis.: Retrospective comparison of periocular triamcinolone injection by modified PST (n = 36) vs. traditional trans-septal (n = 79) techniques. Safety and efficacy outcomes were analyzed with regression models.: There was no significant difference in visual acuity improvement between the groups at 6 months. There were higher rates of vitritis resolution in the modified PST group but this was not statistically significant (85.7% vs 62.9%, = .07). Intraocular pressure (IOP) elevation rate trended higher with the modified PST injection (21.9% vs 9.0%, = .06), with no instances of glaucoma surgery in either group. Two modified PST injection patients with refractory IOP rises had IOP normalization after corticosteroid depot removal. One year cataract surgery rates were similar.: Modified PST injection offers clinical efficacy but with possibly higher IOP response rate which could be managed with corticosteroid removal.
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http://dx.doi.org/10.1080/09273948.2019.1698748DOI Listing
January 2020

Lack of Correlation between Number of Antiretinal Antibodies and Clinical Outcome Measures in Autoimmune Retinopathy Patients.

Ophthalmol Retina 2019 11 18;3(11):1007-1009. Epub 2019 Jun 18.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts. Electronic address:

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http://dx.doi.org/10.1016/j.oret.2019.06.007DOI Listing
November 2019

Atypical herpes simplex virus type 2 acute retinal necrosis presentation with large subretinal lesion.

Am J Ophthalmol Case Rep 2019 Sep 20;15:100501. Epub 2019 Jun 20.

Department of Ophthalmology, The University of Chicago, 5841 S. Maryland Avenue, Chicago, IL, USA.

Purpose: To report the unique clinical findings of a case of Herpes Simplex Virus Type 2 herpetic retinitis manifesting as a large elevated subretinal lesion.

Observations: A 26-year-old Hispanic male with no significant past medical history presented with a one-week history of right eye pain and endorsement of worsening vision. Ophthalmic examination of the right eye identified a markedly elevated white subretinal lesion with associated findings of vitritis and hypotony. Ultrasound biomicroscopy demonstrated a diffusely thickened choroid and confirmed the observed subretinal mass. Examination of the fellow left eye was largely unremarkable with the exception of lesions suggestive of inactive chorioretinal scars. Diagnostic vitrectomy and vitreous PCR (polymerase chain reaction) was positive only for HSV-2 (herpes simplex virus type 2) and verified by two independent laboratories. The observed subretinal lesion of right eye improved on intravenous acyclovir and intravitreal foscarnet treatment.

Conclusions And Importance: Presented here is an unusual, novel clinical presentation of HSV-2 acute retinal necrosis manifesting as an elevated subretinal lesion along with findings of panuveitis. This case suggests that consideration should be given to the diagnosis of HSV ARN (acute retinal necrosis) when a subretinal elevation is concomitantly appreciated in the setting of vitritis and chorioretinal lesions.
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http://dx.doi.org/10.1016/j.ajoc.2019.100501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599871PMC
September 2019

Predictive value of genetic testing for inherited retinal diseases in patients with suspected atypical autoimmune retinopathy.

Am J Ophthalmol Case Rep 2019 Sep 10;15:100461. Epub 2019 May 10.

Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, 243 Charles Street, Boston, MA, USA.

Purpose: The clinical features of autoimmune retinopathy (AIR) can resemble and be difficult to differentiate from inherited retinal degenerations (IRDs). Misdiagnosis of an IRD as AIR causes unnecessary treatment with immunosuppressive agents. The purpose of this study is to calculate the predictive value of genetic testing for IRDs in patients with suspected AIR and provide clinical examples where genetic testing has been useful.

Methods: We identified patients seen at MEEI between April 2013 and January 2017 for whom the differentiation of AIR vs. IRDs was difficult based on clinical assessment alone. All patients had some atypical features for AIR, but tested positive for anti-retinal antibodies. Within this group, we identified six patients who had genetic testing for IRDs with the Genetic Eye Disease panel for retinal genes (GEDi-R). We calculated the positive predictive value (PPV) and negative predictive value (NPV) of genetic testing in a population with approximately equal numbers of IRD and AIR patients.

Results: Six patients had clinical features that made distinguishing between IRDs and AIR on a clinical basis difficult and were sent for genetic testing: four women and two men with a mean age of 59.5 years. In two of these six patients, genetic diagnoses were made based upon the identification of known pathogenic variants in the common IRD genes and . Two patients had variants of unknown significance within genes associated with IRDs, and the other two had no relevant genetic findings. Given the 60% sensitivity and 3% false positive rate for GEDi-R testing and assuming a 50% pre-test probability of having an IRD, the PPV for GEDi-R for detecting IRD is 95.2% and the NPV is 70.8%.

Conclusions And Importance: In patients for whom the differential diagnosis of AIR and IRDs is unclear based on clinical information, genetic testing can be a valuable tool when it identifies an IRD, sparing the patient unnecessary immunosuppressive treatment. However, the test has a low NPV so a negative genetic testing result does not confidently exclude IRD as the true diagnosis.
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http://dx.doi.org/10.1016/j.ajoc.2019.100461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6523031PMC
September 2019

Real-Time Multiplex PCR Analysis in Infectious Uveitis.

Semin Ophthalmol 2019 9;34(4):252-255. Epub 2019 Jun 9.

a Massachusetts Eye and Ear Infirmary/Harvard Medical School , Boston , MA , USA.

: Infectious uveitis is a serious inflammatory condition that often causes grave ocular morbidity including permanent vision loss and damage to the structures of the eye. The most common causes of infectious uveitis include herpesviruses and . Traditionally, these infections have been identified and differentiated based on characteristic clinical examination findings; however, there is often overlap between these presentations and the unique cause of a given patient's infection is not always clear. Therefore, a reliable and fast method for definitively diagnosing infectious uveitis would be helpful and potentially sight-saving. Several groups have recently found experimental success with real-time multiplex polymerase chain reaction (PCR) techniques. : A comprehensive review of the literature was undertaken to further understand the current state of real-time multiplex PCR and its clinical use. Search terms including "real time multiplex PCR", "infectious uveitis", and "uveitis diagnosis" were used. Appropriate English-language articles were included in this review. : Publications from four main groups (two from the United States, one from Japan, and one from India) citing success with real-time multiplex PCR were compared and contrasted. All four groups used the same technique to develop a highly sensitive and specific multiplex PCR analysis and found that their tests maintained high sensitivity and specificity during validation testing. These tests confirmed clinical suspicions in the majority of cases of infectious uveitis, but there were also cases of clinical misdiagnosis that were corrected based on molecular pathogen detection. These patients were then initiated on appropriate antimicrobial therapy with subsequent clinical improvement. : Real-time multiplex PCR is a highly sensitive and specific laboratory assay that allows for rapid and reliable molecular diagnosis of causative agents in infectious uveitis. This in turn facilitates swift initiation of effective therapy and prevents long-term ocular damage and vision loss.
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http://dx.doi.org/10.1080/08820538.2019.1620803DOI Listing
July 2019

Ocular Adverse Events following Use of Immune Checkpoint Inhibitors for Metastatic Malignancies.

Ocul Immunol Inflamm 2020 Aug 23;28(6):854-859. Epub 2019 Apr 23.

Department of Ophthalmology, National Eye Institute , Bethesda, USA.

Purpose: To report the clinical features, severity, and management of ocular immune-related adverse events (irAEs) in the setting of immune checkpoint inhibitor therapy for metastatic malignancies.

Methods: Retrospective chart review at three tertiary ophthalmology clinics. Electronic medical records were reviewed between 2000 and 2017 for patients with new ocular symptoms while undergoing checkpoint inhibition therapy.

Results: Eleven patients were identified. Ocular irAEs ranged from keratoconjunctivitis sicca to Vogt-Koyanagi-Harada-like findings. Average timing of irAEs from starting checkpoint inhibitor therapy was 15.7 weeks. Ocular inflammation was successfully controlled with corticosteroids in most cases, however three patients discontinue treatment as a result of ocular inflammation with decreased visual acuity, two discontinued due to progression of metastatic disease, and one discontinued due to severe systemic irAEs.

Conclusion: We found a wide spectrum of ocular irAEs associated with immune checkpoint inhibitors. In most cases, ocular AEs did not limit ongoing cancer treatment.
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http://dx.doi.org/10.1080/09273948.2019.1583347DOI Listing
August 2020

The Genetic Influence on Corticosteroid-Induced Ocular Hypertension: A Field Positioned for Discovery.

Am J Ophthalmol 2019 06 11;202:1-5. Epub 2019 Feb 11.

Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA. Electronic address:

Purpose: To provide evidence that corticosteroid-induced ocular hypertension has a genetic component.

Design: Evidence-based perspective.

Methods: We conducted a comprehensive literature search for studies exploring genetic influences on intraocular pressure responses to corticosteroid treatment.

Results: Studies demonstrating increased risk of corticosteroid-induced ocular hypertension among first-degree relatives of affected individuals support a genetic contribution to the disease. Family and personal history of primary open-angle glaucoma also increases the risk of corticosteroid-induced intraocular pressure elevation, suggesting common genetic etiologies. A number of studies have attempted to identify predisposing genetic factors; however, reproducible findings have not yet been reported. The recent availability of large data sets with clinical and genetic data for patients affected by corticosteroid-induced ocular hypertension and glaucoma provides new opportunities to study the genetic underpinnings of this important condition.

Conclusions: There is substantial evidence suggesting a genetic component to corticosteroid-related ocular hypertension and glaucoma, but specific genetic risk factors have yet to be identified. The current confluence of large genetic data sets and affordable genetic sequencing technologies has great potential for discovering the genes that increase risk for this blinding complication of corticosteroid therapy.
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http://dx.doi.org/10.1016/j.ajo.2019.02.001DOI Listing
June 2019

Comparison of choroidal neovascularization secondary to white dot syndromes and age-related macular degeneration by using optical coherence tomography angiography.

Clin Ophthalmol 2019 31;13:95-105. Epub 2018 Dec 31.

Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02114, USA,

Purpose: To characterize and compare choroidal neovascularization (CNV) secondary to white dot syndromes (WDS) and age-related macular degeneration (AMD) using optical coherence tomography angiography (OCT-A).

Methods: This is a cross-sectional study in which we imaged patients with CNV secondary to WDS and AMD with either the Zeiss Angioplex OCT-A or Optovue AngioVue OCT-A. Relevant demographic and clinical characteristics were collected and analyzed. CNV area and vessel density (VD) were measured by three independent graders, and linear regression analysis was subsequently performed.

Results: Three patients with multifocal choroiditis and panuveitis, one patient each with birdshot chorioretinopathy, presumed ocular histoplasmosis syndrome, and persistent placoid maculopathy, and eleven patients with AMD with sufficient image quality were included. CNV associated with WDS was significantly smaller than that secondary to AMD (0.56±0.32 vs 2.79±1.80 mm, =-2.22, =0.01), while no difference in VD was detected (0.46±0.09 vs 0.44±0.09, =0.02, =0.71).

Conclusion: CNV networks secondary to WDS appear to be smaller than those secondary to AMD but have similar VD. OCT-A is a powerful tool to investigate properties of CNV from various etiologies. Larger studies are needed for further characterization and understanding of CNV pathogenesis in inflammatory conditions.
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http://dx.doi.org/10.2147/OPTH.S185468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318713PMC
December 2018

Visualization of Choriocapillaris and Choroidal Vasculature in Healthy Eyes With En Face Swept-Source Optical Coherence Tomography Versus Angiography.

Transl Vis Sci Technol 2018 Nov 20;7(6):25. Epub 2018 Dec 20.

Retina Service, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA, USA.

Purpose: To compare the visualization of the choriocapillaris and deeper choroidal vessels in healthy eyes in en face swept-source optical coherence tomography (SS-OCT) versus SS-OCT angiography (SS-OCTA).

Methods: This is a cross-sectional study of consecutive eyes without chorioretinal disease. En face SS-OCT and SS-OCTA images of the choriocapillaris and choroid were assessed for visualization of the vasculature. Choroidal vessel densities (CVD) of the choriocapillaris, inner choroid, midchoroid, and outer choroid were calculated from binarized en face SS-OCT and SS-OCTA images. Paired -tests and linear regression were used for statistical analysis.

Results: Twenty-seven eyes of 27 patients were included. There was no statistically significant difference between the CVDs of the midchoroid assessed with en face SS-OCT versus SS-OCTA ( = 0.21). However, there were statistically significant differences between the CVDs for the choriocapillaris ( < 0.001), inner choroid ( < 0.001), and outer choroid ( = 0.006). Qualitative analysis revealed incomplete visualization of vessels in the inner choroid and exaggeration of vessel lumens in the outer choroid with SS-OCTA.

Conclusions: Visualization of the choriocapillaris is superior with SS-OCTA, but it has numerous limitations that make visualization of deeper choroidal vessels less reliable when compared with en face SS-OCT. It is important to understand such limitations when using these technologies to study the choroidal vasculature in chorioretinal disease.

Translational Relevance: The presented study of optimal imaging techniques for the choroidal vessels of healthy eyes provides an important foundation for future investigations into the role of the choroidal vasculature in chorioretinal diseases.
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http://dx.doi.org/10.1167/tvst.7.6.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6306077PMC
November 2018

Choroidal Infiltrate of Unknown Cause.

JAMA Ophthalmol 2019 Feb;137(2):222-223

Retina Service, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston.

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http://dx.doi.org/10.1001/jamaophthalmol.2018.4488DOI Listing
February 2019

Techniques for improving ophthalmic studies performed on administrative databases.

Ophthalmic Epidemiol 2019 06 6;26(3):147-149. Epub 2018 Dec 6.

e Department of Ophthalmology , Scheie Eye Institute, University of Pennsylvania , Philadelphia , Pennsylvania , USA.

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http://dx.doi.org/10.1080/09286586.2018.1554160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529239PMC
June 2019