Long-Term Clinical Course and Treatment Outcomes in Occult and Overt Acute Zonal Outer Retinopathy.

PURPOSE: To report the longitudinal outcomes for AZOOR patients including treatment response, imaging evolution, and overlap with multiple evanescent white dot syndrome (MEWDS). METHODS: Visual acuity (VA) and visual field (VF) outcomes of occult and overt AZOOR patients were retrospectively compared between the first and final visits as well as between the two AZOOR subtypes. For treated patients, rates of VA change and fundus lesion area were compared before and after treatment. Analyses were performed using STATA 17. RESULTS: Seventeen eyes from 11 occult AZOOR patients and 45 eyes from 29 overt AZOOR patients were included. In a composite VA/VF primary outcome, clinical improvement was noted in five occult AZOOR and three overt AZOOR patients. The decline of logarithm of the Minimal Angle of Resolution (logMAR) VA was minimal in both groups: 0.00016 units/month in occult AZOOR patients and 0.009 units/month in overt AZOOR patients (p = 0.94). Occult AZOOR patients were more likely to have improved or stable VF than overt AZOOR patients (p = 0.04). One occult AZOOR and two overt AZOOR patients developed MEWDS at subsequent visits. Treatment with steroids or immunomodulatory therapy (IMT) was initiated in one occult AZOOR patient and nine overt AZOOR patients. Treated patients had overall VA stability. Fundus lesion area in treated patients changed by a mean of 0.2831 mm2/month, with 40% of patients showing decreased lesion area. CONCLUSION: AZOOR patients generally maintained their VA. Overt AZOOR patients were more likely to receive steroids or IMT; treatment was associated with stabilization of VA.

Rare genetic variation in VE-PTP is associated with central serous chorioretinopathy, venous dysfunction and glaucoma.

Central serous chorioretinopathy (CSC) is a fluid maculopathy whose etiology is not well understood. Abnormal choroidal veins in CSC patients have been shown to have similarities with varicose veins. To identify potential mechanisms, we analyzed genotype data from 1,477 CSC patients and 455,449 controls in FinnGen. We identified an association for a low-frequency (AF=0.5%) missense variant (rs113791087) in the gene encoding vascular endothelial protein tyrosine phosphatase (VE-PTP) (OR=2.85, P=4.5×10-9). This was confirmed in a meta-analysis of 2,452 CSC patients and 865,767 controls from 4 studies (OR=3.06, P=7.4×10-15). Rs113791087 was associated with a 56% higher prevalence of retinal abnormalities (35.3% vs 22.6%, P=8.0×10-4) in 708 UK Biobank participants and, surprisingly, with varicose veins (OR=1.31, P=2.3×10-11) and glaucoma (OR=0.82, P=6.9×10-9). Predicted loss-of-function variants in VEPTP, though rare in number, were associated with CSC in All of Us (OR=17.10, P=0.018). These findings highlight the significance of VE-PTP in diverse ocular and systemic vascular diseases.

Circular Perivascular Autofluorescence Pattern in Patients With Autoimmune Retinopathy.

Purpose: To report the characteristics and prevalence of a previously undescribed circular perivascular fundus autofluorescence (FAF) pattern in paraneoplastic and nonparaneoplastic autoimmune retinopathy. Methods: This retrospective case series used clinical and imaging data extracted from charts of patients with autoimmune retinopathy in whom FAF imaging was performed from the initial presentation to the last visit. Results: Six of 25 patients with autoimmune retinopathy and FAF imaging developed circular perivascular FAF changes. Three patients had paraneoplastic autoimmune retinopathy, and 3 had nonparaneoplastic autoimmune retinopathy. The lesions appeared a mean of 25 months after symptom onset; however, the timing varied from months to years and did not correlate with the overall disease course. The lesions were initially typically hyperautofluorescent and varied in progression, distribution, and quality. Optical coherence tomography showed hyperreflective subretinal deposits in the corresponding areas in most patients. Conclusions: To our knowledge, these are the first reported cases with this circular perivascular FAF pattern in nonparaneoplastic autoimmune retinopathy. This finding could also be a useful diagnostic imaging marker in some patients with autoimmune retinopathy.

Malignancy Risk Associated With the Use of Systemic Immunomodulatory Therapy in the Management of Noninfectious Uveitis.

PURPOSE: Patients with noninfectious uveitis (NIU) can require treatment with systemic immunomodulatory therapy (IMT), but it is unclear whether IMT drug categories increase the risk of malignancy in NIU patients. The purpose of this study is to determine if the use of systemic IMT in patients with NIU is associated with an increased risk of malignancy. DESIGN: Clinical cohort study. METHODS: Patients were identified from a US administrative medical claims database including some Medicare Advantage and commercial plans, from 2000 to 2022. About 318,498 NIU patients were identified. Enrollees were included in the analysis if they met the following criteria: continuous enrollment in the plan for at least 1 year, and at least 2 consecutive visit diagnoses of any type of NIU, after initiation of systemic IMT. We compared the rates of incident malignancy in NIU patients treated with IMT versus the rates among NIU patients not treated with IMT. Multivariable Cox regression models were used to predict the hazard of developing incident cancer. RESULTS: Of the 318,498 patients with NIU identified over a 15-year period, 318,006 did not develop malignancy, and 492 did develop malignancy. Of the patients that developed a malignancy, 280 (57%) were treated with systemic corticosteroids; 204 (41%) were treated with antimetabolites; 44 (9%) were treated with T cell inhibitors; 108 (22%) were treated with TNF alpha inhibitors; 2 (0.004%) were treated with interleukin-6 (IL-6) inhibitors; and 1 was treated with CD-20 antibodies. There were no malignancies reported in the group treated with alkylating agents. There was no association between any of the drug classes and incidence of malignancy. CONCLUSIONS: This study suggests that there is no increased risk of malignancy associated with the use of systemic IMT for patients with NIU.

En Face Depth Resolved OCTA Monitoring of Macular Outer Retinal Deposits in a Case of Multifocal Choroiditis Mimicking Syphilitic Uveitis.

PURPOSE: Multifocal choroiditis (MFC) is a rare inflammatory condition characterized by retinal and choroidal lesions that may present similarly to ocular pathology of various etiologies. Here we present a case of MFC mimicking syphilitic uveitis with unique en face optical coherence tomography angiography (OCTA) imaging characteristics. METHODS: Case report. RESULTS: A 61-year-old woman presented with blurry vision, floaters and multiple whitish subretinal deposits on en face swept-source OCTA in the left eye. Fluorescent treponemal antibody test absorption was positive which led to the initial diagnosis of syphilitic uveitis and subsequent treatment with intravenous penicillin. During follow-up, OCTA of the left eye revealed the development of new choroidal neovascular membrane and new punched-out lesions in the posterior pole. The patient was eventually diagnosed with MFC and treated with aflibercept injections. CONCLUSIONS: Immune-mediated uveitis can simulate infectious and neoplastic uveitis. En face OCTA is unique imaging modality that allowed for the complete characterization and monitoring of the sub-macular deposits. This expands the clinical spectrum of multifocal choroiditis.

A practical model for effective eye care delivery in Southeast Asian rural communities: A proposal built based on experts' recommendations.

PURPOSE: To evaluate rural community-based eye care models from the perspective of community ophthalmology experts and suggest sustainable technological solutions for enhancing rural eye care delivery. METHODS: A semi-structured descriptive survey, using close-ended and open-ended questions, was administered to the experts in community ophthalmology sourced through purposive sampling. The survey was self-administered and was facilitated through online platforms or in-person meetings. Uniform questions were presented to all participants, irrespective of their roles. RESULTS: Surveyed participants (n = 22 with 15 from India and 7 from Nepal) in high-volume tertiary eye hospitals faced challenges with resources and rural outreach. Participants had mixed satisfaction with pre-operative screening and theatre resources. Delayed presentations and inexperienced surgeons contributed to the surgery complications. Barriers to rural eye care included resource scarcity, funding disparities, and limited infrastructure. In rural/peri-urban areas 87% of participants agreed with providing primary eye care services, with more than 60% of the experts not in agreement with the makeshift center model of eye care delivery. Key components for an effective eye care model are sustainability, accessibility, affordability, and quality. These can be bolstered through a healthcare management platform and a human-chain supply distribution system. CONCLUSION: Tailored interventions are crucial for rural eye care, emphasizing the need for stronger human resources, optimized funding, and community awareness. Addressing challenges pertinent to delayed presentation and surgical training is vital to minimizing complications, especially with advanced cataracts. Enhancements in rural eye care demand a comprehensive approach prioritizing accessibility, affordability, and consistent quality.

Fellow Eyes Conversion Rates in Patients With Unilateral Exudative Age-Related Macular Degeneration: An Academy IRIS® Registry Analysis.

BACKGROUND AND OBJECTIVE: This study aimed to examine conversion rates from non-exudative to exudative age-related macular degeneration (AMD) in the fellow eye of patients with unilateral exudative AMD using the Academy IRIS® Registry. PATIENTS AND METHODS: This study was a retrospective, cohort analysis from 2016 to 2019. Patient and disease characteristics including initial AMD stage were collected. Cox proportional-hazard (PH) and logistic regression modeling were performed. RESULTS: The risk of conversion was lower for men relative to women and for Asians and Blacks relative to Whites. Compared to never-smokers, active smokers were at increased risk of conversion, and compared to initially early non-exudative AMD eyes, intermediate and advanced non-exudative AMD eyes had higher rates of conversion. Compared to active choroidal neovascularization eyes, eyes with inactive choroidal neovascularization and inactive scars had lower rates of fellow eye conversion. CONCLUSIONS: In this cohort analysis of unilateral exudative AMD patients, women, Whites, and active smokers had higher rates of non-exudative to exudative AMD conversion in the fellow eye. [Ophthalmic Surg Lasers Imaging Retina 2024;55:220-226.].

Improving Access to Eye Care in Rural Communities: PocDoc's Web-Based Visual Acuity Screening Tool.

Objective: Visual acuity (VA) testing is crucial for early intervention in cases of visual impairment, especially in rural health care. This study aimed to determine the potential of a web-based VA test (PocDoc) in addressing the unique health care needs of rural areas through the comparison in its effectiveness against the conventional VA test in identifying visual impairment among an Indian rural population. Methods: Prospective comparative study conducted in December 2022 at a tertiary referral eye care center in central India. We evaluated all patients with the PocDoc VA tests using three device types, and the conventional VA test. Bland-Altman plot (BAP) compared PocDoc and conventional VA tests. Fisher's exact tests evaluated associations between categorical parameters. Kruskal-Wallis tests followed by post hoc Dunn's tests identified association between categorical parameters and numerical parameters. Results: We evaluated 428 patients (792 measurements of VA) with mean age 36.7 (±23.3) years. PocDoc resulted in slightly worse VA scores (mean logMAR: 0.345) than conventional (mean logMAR: 0.315). Correlation coefficient between the conventional and PocDoc logMAR VA values was rho = 0.845 and rho2 = 0.7133 (p = 6.617 × 10-215; adjusted p = 2.205 × 10-214). Most data points fell within the interchangeable range of ±0.32 on BAP. Difference between the two methods increased with higher logMAR values, indicating poorer agreement for worse VA scores. Conclusions: Identifying and addressing the unique health care needs of rural populations is critical, including access to appropriate and effective VA testing methods. Validating and improving VA testing methods can ensure early intervention and improve the quality of life for individuals with visual impairment.

The Epidemiology and Risk Factors for the Progression of Sympathetic Ophthalmia in the United States: An IRIS Registry Analysis.

PURPOSE: To investigate the demographic and clinical characteristics of patients with sympathetic ophthalmia (SO) and define the risk factors for its incidence following trauma and ophthalmic procedures. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients in the American Academy of Ophthalmology's (Academy) IRIS Registry (Intelligent Research in Sight) who were (n=1523) or were not diagnosed with SO following a documented procedure or trauma between January 1, 2013, and December 31, 2019. METHODS: Multiple demographic and clinical factors were collected, descriptive statistics and prevalence were calculated, and multivariate linear regression models were fit to the data. MAIN OUTCOME MEASURES: Prevalence of SO, demographic and clinical characteristics, and beta coefficient (ß) estimates of demographic and clinical characteristics impacting time to SO onset after procedure (Procedure Only cohort) or trauma (Trauma cohort). RESULTS: Of 65,348,409 distinct IRIS Registry patients, 1523 (0.0023%) were diagnosed with SO between 2013 and 2019, and also had a documented preceding trauma or procedure. Of these, 927 (60.87%) were female, 1336 (87.72%) belonged to the Procedure Only cohort, and 187 (12.28%) belonged to the Trauma cohort. The prevalence of SO after trauma was 0.0207%, whereas after procedures it was 0.0124%. The highest risk of procedure-related SO was seen in patients with history of "other anterior segment" (0.122%) followed by glaucoma (0.066%) procedures, whereas the lowest prevalence was noted with cataract surgeries (0.011%). The average time to onset of SO across both cohorts combined was 527.44 (±715.60) days, with statistically significant differences between the 2 cohorts (P < .001). On average, the time to onset from inciting event to SO was shorter with increasing age, by 9.02 (95% CI: -11.96, -6.08) days for every 1-year increase. CONCLUSIONS: SO following trauma and ophthalmic procedure is potentially rarer than previously reported, as measured in this large ophthalmic medical record database. Female sex may be a risk factor for SO. Older age may be a risk factor for quicker onset. These findings can guide clinical decision-making and management.

Knowledge and Current Practices in Monogenic Uveitis: An International Survey by IUSG and AIDA Network.

INTRODUCTION: This study aims to explore awareness, knowledge, and diagnostic/therapeutic practices in monogenic uveitis (mU) among uveitis experts. METHODS: This is an explorative, cross-sectional survey study. An anonymous, semi-structured, electronic survey was delivered to uveitis experts from the Autoinflammatory Diseases Alliance (AIDA) Network and International Uveitis Study Group (IUSG). We included respondents answering ≥ 50% of the survey. RESULTS: Seventy-seven participants rated their knowledge of mU as proficient (3.9%), adequate (15.6%), sufficient (16.9%), or poor (63.6%). When asked about the first mU gene they thought of, 60.4% mentioned NOD2, 3.9% mentioned NLRP3 or MEFV, and 49.4% provided incorrect or no answers. Success rates in clinical scenarios varied from 15.6% to 55.8% and were higher for ophthalmologists working in multidisciplinary teams (p < 0.01). Genetic testing was ordered for suspected mU by 41.6% of physicians. The availability of molecular techniques did not significantly differ based on geography (p > 0.05). The public healthcare system ensured a higher percentage of tests prescribed were obtained by patients compared to private insurances (p < 0.00). In terms of disease-modifying anti-rheumatic drugs (DMARDs), tumor necrosis factor-α inhibitors were the most familiar to uveitis experts. The difficulties with off-label therapy procedures were the primary barrier to DMARDs prescription for patients with mU and correlated inversely with the obtained/prescribed drug ratio for interleukin-1 (p < 0.01) and interleukin-6 (p < 0.01) inhibitors. CONCLUSIONS: This survey identifies proficiency areas, gaps, and opportunities for targeted improvements in patients care. The comprehensive outputs may inform evidence-based guidelines, empowering clinicians with standardized approaches, and drive an AIDA Network-IUSG unified effort to advance scientific knowledge and clinical practice.

Development of Portable Electronic Health Record Based Algorithms to Identify Individuals with Diabetic Retinopathy.

Objectives: To develop, validate and implement algorithms to identify diabetic retinopathy (DR) cases and controls from electronic health care records (EHR)s. Methods : We developed and validated EHR-based algorithms to identify DR cases and individuals with type I or II diabetes without DR (controls) in three independent EHR systems: Vanderbilt University Medical Center Synthetic Derivative (VUMC), the VA Northeast Ohio Healthcare System (VANEOHS), and Massachusetts General Brigham (MGB). Cases were required to meet one of three criteria: 1) two or more dates with any DR ICD-9/10 code documented in the EHR, or 2) at least one affirmative health-factor or EPIC code for DR along with an ICD9/10 code for DR on a different day, or 3) at least one ICD-9/10 code for any DR occurring within 24 hours of an ophthalmology exam. Criteria for controls included affirmative evidence for diabetes as well as an ophthalmology exam. Results: The algorithms, developed and evaluated in VUMC through manual chart review, resulted in a positive predictive value (PPV) of 0.93 for cases and negative predictive value (NPV) of 0.97 for controls. Implementation of algorithms yielded similar metrics in VANEOHS (PPV=0.94; NPV=0.86) and lower in MGB (PPV=0.84; NPV=0.76). In comparison, use of DR definition as implemented in Phenome-wide association study (PheWAS) in VUMC, yielded similar PPV (0.92) but substantially reduced NPV (0.48). Implementation of the algorithms to the Million Veteran Program identified over 62,000 DR cases with genetic data including 14,549 African Americans and 6,209 Hispanics with DR. Conclusions/Discussion: We demonstrate the robustness of the algorithms at three separate health-care centers, with a minimum PPV of 0.84 and substantially improved NPV than existing high-throughput methods. We strongly encourage independent validation and incorporation of features unique to each EHR to enhance algorithm performance for DR cases and controls.

Vitamin D deficiency and non-infectious uveitis: A systematic review and Meta-analysis.

BACKGROUND: Vitamin D plays a critical role in immunomodulation, and its deficiency is implicated in the pathogenesis of several autoimmune diseases. Nevertheless, its relationship with non-infectious uveitis (NIU), an inflammatory ocular disorder, remains inconclusive. METHODS: A systematic search was conducted in three databases from database inception until May 8, 2023, to investigate the potential relationship between vitamin D deficiency and NIU. We included observational studies reporting the measurement of vitamin D levels in patients with NIU and healthy controls without restriction of language or date of publication. Three pairs of authors independently screened the title and abstracts for potential eligibility and then in full text. A third author resolved disagreements. Three pairs of independent reviewers abstracted the data from the fully reviewed records and evaluated the risk of bias. We followed The MOOSE and PRISMA guidelines. Random effects meta-analyses were used for primary analysis. Studies not included in the meta-analysis were summarized descriptively. This review was registered in PROSPERO: CRD42022308105. FINDINGS: Of 933 records screened, 11 studies were included, and five were meta-analyzed, encompassing 354 cases and 5728 controls (mean participant age ranging from 7.1 to 58.9 years). Patients with vitamin D deficiency exhibited an Odds Ratio of 2.04 (95% CI = 1.55-2.68, P < 0.00001) for developing NIU compared to controls. Overall, potential sources of bias were low across most studies. INTERPRETATION: Our findings suggest that vitamin D may play an essential role in the pathophysiology of NIU. While the included studies demonstrated generally low potential bias, additional rigorous prospective studies are necessary to confirm these findings and further elucidate the underlying mechanisms involved. Vitamin D supplementation could represent a possible therapeutic strategy for preventing or managing NIU if substantiated. Clinicians should consider screening for and addressing vitamin D deficiency in patients with or at risk for NIU.

Chatbots Vs. Human Experts: Evaluating Diagnostic Performance of Chatbots in Uveitis and the Perspectives on AI Adoption in Ophthalmology.

PURPOSE: To assess the diagnostic performance of two chatbots, ChatGPT and Glass, in uveitis diagnosis compared to renowned uveitis specialists, and evaluate clinicians' perception about utilizing artificial intelligence (AI) in ophthalmology practice. METHODS: Six cases were presented to uveitis experts, ChatGPT (version 3.5 and 4.0) and Glass 1.0, and diagnostic accuracy was analyzed. Additionally, a survey about the emotions, confidence in utilizing AI-based tools, and the likelihood of incorporating such tools in clinical practice was done. RESULTS: Uveitis experts accurately diagnosed all cases (100%), while ChatGPT achieved a diagnostic success rate of 66% and Glass 1.0 achieved 33%. Most attendees felt excited or optimistic about utilizing AI in ophthalmology practice. Older age and high level of education were positively correlated with increased inclination to adopt AI-based tools. CONCLUSIONS: ChatGPT demonstrated promising diagnostic capabilities in uveitis cases and ophthalmologist showed enthusiasm for the integration of AI into clinical practice.

Psychosocial Well-Being and Quality of Life in Uveitis: A Review.

PURPOSE: As a potentially sight-threatening disease with ocular, systemic, and treatment-related complications, uveitis diminishes quality of life (QOL) and affects psychosocial well-being. This review summarizes the existing tools for evaluating psychosocial well-being and/or QOL in patients with uveitis, explores the biological and non-biological factors affecting psychosocial well-being and/or QOL, and proposes future directions for incorporating these tools into clinical practice. METHODS: A systematic search of the MEDLINE, Embase, and Cochrane databases from inception to June 8, 2022 was conducted, screening for articles focused on psychosocial well-being and/or QOL in patients with uveitis. Both quantitative and qualitative analyses were performed. RESULTS: In uveitis research, the most frequently studied patient-reported outcome measures were vision-related QOL (e.g. Visual Function Questionnaire [VFQ-25]) and health-related QOL (e.g. Short Form Survey [SF-36]), followed by mental health indicators including depression and anxiety. Instruments have also been developed specific to the pediatric population (e.g. Effects of Youngsters' Eyesight on Quality of Life [EYE-Q]). Generally, studies report worse psychosocial outcomes and QOL in patients with uveitis compared to the general population. Contributory factors include both clinical (e.g. visual impairment, ocular comorbidities) and patient-related (e.g. older age, female sex) factors. CONCLUSION: Given the heterogeneity of instruments used, it is worth considering standardization across large uveitis studies and trials. Beyond research, given the biopsychosocial effects on patients with uveitis, there are benefits to incorporating QOL and psychosocial assessments into clinical practice. Simplification of questionnaires into abridged forms, focusing on the most clinically relevant aspects of patient care, may be considered.

Evaluating the Diagnostic Accuracy and Management Recommendations of ChatGPT in Uveitis.

INTRODUCTION: Accurate diagnosis and timely management are vital for favorable uveitis outcomes. Artificial Intelligence (AI) holds promise in medical decision-making, particularly in ophthalmology. Yet, the diagnostic precision and management advice from AI-based uveitis chatbots lack assessment. METHODS: We appraised diagnostic accuracy and management suggestions of an AI-based chatbot, ChatGPT, versus five uveitis-trained ophthalmologists, using 25 standard cases aligned with new Uveitis Nomenclature guidelines. Participants predicted likely diagnoses, two differentials, and next management steps. Comparative success rates were computed. RESULTS: Ophthalmologists excelled (60-92%) in likely diagnosis, exceeding AI (60%). Considering fully and partially accurate diagnoses, ophthalmologists achieved 76-100% success; AI attained 72%. Despite an 8% AI improvement, its overall performance lagged. Ophthalmologists and AI agreed on diagnosis in 48% cases, with 91.6% exhibiting concurrence in management plans. CONCLUSIONS: The study underscores AI chatbots' potential in uveitis diagnosis and management, indicating their value in reducing diagnostic errors. Further research is essential to enhance AI chatbot precision in diagnosis and recommendations.

ENDOGENOUS ENDOPHTHALMITIS DUE TO STREPTOCOCCUS ANGINOSUS IN A HEALTHY, YOUNG WOMAN.

PURPOSE: The purpose of this study was to present a case of indolent endogenous endophthalmitis in a young, seemingly healthy woman. METHODS: This study is a retrospective case report. RESULTS: A 25-year-old woman with no significant medical history presented with vision loss in the left eye over the course of 1 month. Examination showed vitritis and a white-yellow lesion overlying the macula and optic nerve in the left eye. Initial laboratory testing for infectious and inflammatory causes was unrevealing. A diagnostic vitrectomy was performed, and the patient was found to have presumed endogenous endophthalmitis due to Streptococcus anginosus, an extremely uncommon bacterium. Subsequent workup did not reveal evidence of bacteremia, endocarditis, or orbital infection. This case is unique because, unlike the three previously reported cases of S. anginosus endophthalmitis, this patient was seemingly healthy, never had an elevated white blood cell count, never had documented bacteremia, had a normal echocardiogram, and had normal orbital findings on magnetic resonance imaging and computed tomography scans. Further questioning revealed a remote history of facial cellulitis and possible sinusitis treated with oral antibiotics, which are the presumed etiology. CONCLUSION: Streptococcus anginosus endophthalmitis can occur in young, seemingly healthy patients. Endogenous endophthalmitis should be considered in the differential diagnosis even without systemic comorbidities or other risk factors. Detailed questioning about medical history and thorough review of systems, including nonocular symptoms, are essential.