Purpose:To develop and validate an interpretable deep learning model that classifies optical coherence tomography (OCT) scans as vitreoretinal lymphoma (VRL) or non-infectious uveitis (NIU)-intermediate, posterior, or panuveitis-and visualizes differentiating pathological OCT features. Methods:This cross-sectional study included 45 patients with VRL and 52 with NIU who underwent SPECTRALIS OCT imaging. OCT B-scans were analyzed with a custom-designed deep convolutional neural network classification model combined with gradient-weighted class activation mapping (Grad-CAM). Interpretability was assessed using Grad-CAM heat maps that visualize disease-specific OCT features. We evaluated diagnostic performance at the eye level using the area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), accuracy, F1 score, precision, sensitivity, specificity, and kappa. Results:The model differentiated VRL from NIU at the eye level, with mean ± SD scores of 76.0 ± 8.0 for AUROC, 79.4 ± 10.4 for AUPRC, 75.4 ± 13.3 for accuracy, 74.9 ± 13.7 for F1 score, 73.9 ± 19.3 for precision, 77.7 ± 13.6 for sensitivity, 73.4 ± 20.7 for specificity, and 51.0 ± 26.6 for kappa. Grad-CAM features of VRL included preretinal deposits and changes in the retinal pigment epithelium. In contrast, NIU features included denser vitreous cells and opacities, epiretinal membrane, intraretinal cells, and choroidal and scleral abnormalities consistent with NIU pathophysiology. Conclusions:A deep learning model with interpretability can reliably differentiate VRL from NIU, highlighting disease-relevant OCT features. Translational Relevance:The proposed deep learning method may serve as a non-invasive triage tool by identifying patients who need confirmatory pars plana vitrectomy.

Objective To evaluate the associations of demographic and socioeconomic factors—including race and ethnicity, sex, insurance type, age, and geographic region—with visual outcomes, ocular complications, and the need for ocular surgery in children with non-infectious uveitis Design Retrospective cohort study using the American Academy of Ophthalmology IRIS® (Intelligent Research in Sight) Registry, a national ophthalmic disease registry Participants Pediatric patients with non-infectious uveitis Methods Patients with non-infectious uveitis diagnosed and treated at age ≤18 with ≥1 year follow-up with complete demographic information identified in the IRIS® Registry between January 1, 2013 and December 31, 2019. Insurance type was used as a proxy for socioeconomic status, and analyses accounting for the inclusion of both eyes of the same patient were performed using generalized estimating equations. Multivariable logistic or linear regression were performed to assess whether age, sex, race, region and insurance type were associated with higher risk of poor visual acuity outcomes, complications of uveitis and requirement for ocular surgery. Results Data from 3611 unique patients (5723 eyes) were included. Compared to White children, Black children were more likely to have a final visual acuity of 20/200 or worse and develop glaucoma and cystoid macular edema (OR for White vs Black children for 20/200 or worse vision 0.59, 95% CI 0.42–0.82; P < 0.05). Compared to children with private insurance, those with Medicaid were more likely to have a final visual acuity of 20/200 or worse, as well as suffer from amblyopia, posterior synechiae, and band keratopathy (OR for private vs Medicaid for 20/200 or worse vision 0.50, 95% CI 0.37–0.67; P < 0.05 for all). Children with age ≤12 years were more likely to develop band keratopathy and amblyopia compared to those 13–18 years old (amblyopia OR 4.99, 95% CI 3.00–8.31; band keratopathy OR 2.62, 95% CI 1.89–3.63; P < 0.001 for both). Conclusion Socioeconomic and demographic factors associated with poorer clinical outcomes in pediatric non-infectious uveitis include younger age at presentation, Black

Purpose of review Corticosteroid-sparing immunosuppression is standard for chronic noninfectious uveitis, yet its long-term safety remains a dominant clinical concern. We synthesize the contemporary evidence on long-term safety, common adverse effects that drive treatment discontinuation, and how those effects are managed across various medication classes. Recent findings The largest cohort data show no statistically significant excess in overall or cancer mortality for antimetabolites, calcineurin inhibitors, or antitumor necrosis factor agents, whereas alkylating agents remain the principal malignancy concern. Discontinuation for toxicity is modest across classes and is usually driven by reversible, organ-specific effects: most often gastrointestinal intolerance for antimetabolites, nephrotoxicity for calcineurin inhibitors, and cytopenia for alkylating agents. Long-term data led by a 7-year adalimumab extension showed no new safety signals, with infection and tuberculosis reactivation as the main risks of tumor necrosis factor blockade. Summary Steroid-sparing agents appear to have excellent long-term safety when the agent is matched to disease severity and patients are screened and monitored proactively. The safest agent is the one whose specific toxicity is anticipated and managed.

PURPOSE:To describe the prevalence, characteristics, and treatment patterns of pediatric noninfectious uveitis in the United States. DESIGN:Retrospective database study. SUBJECTS:Patients with noninfectious uveitis diagnosed and treated at age ≤18 years with ≥1 year follow-up identified in the IRIS® (Intelligent Research in Sight) Registry between January 1, 2013, and December 31, 2019. METHODS:Mean annual prevalence of pediatric noninfectious uveitis was estimated overall and by anatomic location. Demographic information such as age, sex, race, ethnicity, and insurance status, along with types of anti-inflammatory medications, was evaluated. The Wilcoxon signed-rank test was used to compare distributions of visual acuity at baseline, 1 year, and final visits. Rates of ocular complications and surgeries among eyes with different anatomic locations of uveitis were compared using the chi-square test. MAIN OUTCOME MEASURES:Annual prevalence, demographic characteristics, ocular complications, need for ocular surgery, type of anti-inflammatory medications, and difference in visual acuity (VA, logarithm of the minimum angle of resolution) at presentation, 1 year, and final visit (≥15 months). RESULTS:A total of 5722 pediatric patients (9073 eyes) were identified, representing 2.1% of all patients with noninfectious uveitis in the IRIS Registry. Annual prevalence was 11.9 cases per 100 000 patients. The mean (standard deviation) age at diagnosis was 12.5 (4.0) years, 51.3% were female, 56.3% were White, 46.2% had private insurance, and 28.6% had Medicaid. Anatomical subtypes of uveitis included anterior (68.7%), intermediate (13.4%), posterior (6.1%), and panuveitis (10.2%). Mean VA ± standard deviation was 0.26 ± 0.37 at diagnosis, 0.18 ± 0.31 at 1 year (P < 0.001), and 0.21 ± 0.36 (P < 0.001) at final visit with a mean (standard deviation) follow-up of 1216 (579) days. Eight hundred forty-four (9.3%) eyes had severe vision loss (VA ≥1.00) during follow-up. Complications occurred in 1875 (20.7%) eyes, mostly as cataract (10.6%) and macular edema (5.4%), and 479 (5.3%) required ocular surgery. The highest rate of complications and ocular surgeries was seen in patients with panuveitis and posterior uveitis, respectively. Local corticosteroids were used in 5231 (91.4%), and 2467 (43.1%) were started on steroid-sparing agents after diagnosis, most commonly methotrexate (30.9%). CONCLUSION:Annual prevalence of pediatric noninfectious uveitis in the United States per the IRIS Registry is 11.9 cases per 100 000 patients. It represents 2.1% of all noninfectious uveitis. Most patients are White and have anterior uveitis. Unlike adults with uveitis, there is no strong sex predilection. Mean VA improved significantly 1 year after diagnosis, but 9.3% of eyes had severe vision loss. The anatomic subtype of uveitis significantly affected visual outcomes, complications, and the need for ocular surgery. Methotrexate was the most commonly used steroid-sparing immunosuppressive agent. Although complications occurred, patients rarely underwent ocular surgery. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Introduction:Female representation in ophthalmic oncology and pathology is unknown. We evaluated gender-based trends in authorship and leadership in these fields, focusing on intraocular tumors. Methods:Articles containing "uveal melanoma" (UM), "retinoblastoma" (Rb), "primary intraocular lymphoma" (PIOL), "choroidal metastasis" (CM), and articles in Ocular Oncology and Pathology (OOP) were searched on PubMed and author names obtained. Leadership/awards from 4 international ophthalmic oncology and pathology societies were recorded. GenderAPI was used to predict gender. Results:Among 4,245 UM, 9,660 Rb, 141 PIOL, 353 CM, and 568 OOP authors, more males were first (range, 52-67%) and last authors (range, 69-76%). Analysis of the 4 keywords showed overall female authorship increased from 2011 to 2016 to 2017-2022 (35%-40%, p < 0.001), with an increase in both first (45%-47%, p = 0.03) and last authorship (26%-33%, p < 0.001). Female first authors were more likely to publish with female last authors (Rb OR 1.72, p < 0.001; OOP OR 2.04, p = 0.01). Males held more leadership roles/awards in societies. Conclusion:Female representation in ophthalmic oncology and pathology has grown but gender disparities remain. Female first authors were more likely to publish with female last authors. Most society leaders and awardees were male. Cultivating mentorship through professional organizations may help achieve gender parity.

PURPOSE:To report the use of Gamma Knife stereotactic radiosurgery in the treatment of refractory uveal effusion in the setting of choroidal metastasis and checkpoint inhibitor therapy. METHODS:Review of a case of metastatic bronchial neuroendocrine carcinoma to the choroid that developed refractory unilateral uveal effusion after checkpoint inhibitor therapy initiation. RESULTS:A 47-year-old Caucasian female with stage T1bN3M1 bronchial neuroendocrine carcinoma metastatic to the brain and stage 1A, grade 1 endometrial carcinoma status post hysterectomy was referred to the retina service for evaluation of a choroidal mass identified in brain MRI. Two weeks after starting atezolizumab, vision declined to 20/200 with new serous uveal effusion solely in the left eye. Systemic therapy was continued as it was life-prolonging, but the uveal effusion was refractory to topical and periocular corticosteroids. Gamma Knife stereotactic radiosurgery was delivered to the left choroidal metastasis, with resolution of the uveal effusions within 2 weeks. The patient completed her last cycle of atezolizumab, vision remained stable, and no new effusions were noted 1 month after radiotherapy. CONCLUSION:Checkpoint inhibitor-associated uveal effusion can occur in eyes with intraocular metastases, presumably due to a crosstalk between the tumor microenvironment and the immune system. Gamma Knife radiotherapy to solitary choroidal metastases may aid in rapid resolution of refractory uveal effusions, especially in patients who cannot stop the life-prolonging treatment.

IntroductionPhosphoribosyl pyrophosphate synthetase 1 (PRPS1) is an X-linked gene critical for nucleotide metabolism. Pathogenic PRPS1 variants cause three overlapping phenotypes: Arts syndrome (severe neurological disease), Charcot-Marie-Tooth type 5 [CMTX5] (peripheral neuropathy), and non-syndromic sensorineural hearing loss (SNHL). Each may be associated with retinal dystrophy. Multicenter phenotypic studies are limited.MethodsA multicenter retrospective clinical case series of 15 patients from 12 pedigrees with PRPS1-associated retinal degeneration is presented.ResultsOf 15 patients, 11 (73.3%) were female. Mean age of ocular disease onset was 8.5 years (range, 0.5-35 years). Many were diagnosed with Leber congenital amaurosis prior to genetic testing (n = 5). Five patients had clinical diagnoses of CMTX5 and Arts syndrome, two had isolated ocular disease, and one was asymptomatic. Mean initial VA (LogMAR) was 0.74, 0.74, 0.83, and 0.85 for isolated ocular disease, CMTX5, Arts, and SNHL, respectively. Ten patients were hyperopic and eight had asymmetric VA. Macular atrophy (n = 13), optic atrophy (n = 13), bone spicules (n = 10), and parafoveal outer retinal atrophy (n = 12) were common findings. Electroretinogram showed delayed and attenuated photopic and scotopic responses (n = 10). Median follow-up of 2.9 years (range, 1.5-11.6 years) in six patients showed retinal disease progression in two patients.DiscussionPRPS1-associated retinal degeneration predominantly manifests as a bilateral asymmetric cone and rod dystrophy, commonly associated with hyperopia and optic atrophy.

MYCN-amplified RB1 wild-type (MYCNampRB1+/+) retinoblastoma is a rare and aggressive subtype, often resistant to standard therapies. Identifying unique MRI features is crucial for diagnosing this subtype, as biopsy is not recommended. This study aimed to differentiate MYCNampRB1+/+ from the most prevalent RB1-/- retinoblastoma using pretreatment MRI and radiomics. Ninety-eight unilateral retinoblastoma patients (19 MYCN cases and 79 matched controls) were included. Tumors on T2-weighted MR images were manually delineated and validated by experienced radiologists. Radiomics analysis extracted 120 features per tumor. Several combinations of feature selection methods, oversampling techniques and machine learning (ML) classifiers were evaluated in a repeated fivefold cross-validation machine learning pipeline to yield the best-performing prediction model for MYCN. The best model used univariate feature selection, data oversampling (duplicating MYCN cases), and logistic regression classifier, achieving a mean AUC of 0.78 (SD 0.12). SHAP analysis highlighted lower sphericity, higher flatness, and greater gray-level heterogeneity as predictive for MYCNampRB1+/+ status, yielding an AUC of 0.81 (SD 0.11). This study shows the potential of MRI-based radiomics to distinguish MYCNampRB1+/+ and RB1-/- retinoblastoma subtypes.

ImportanceBest recruitment practices for increasing diversity are well established, but the adoption and impact of these practices in ophthalmology residency recruitment are unknown.ObjectiveTo describe the adoption of bias reduction practices in groups underrepresented in ophthalmology (URiO) residency recruitment and determine which practices are effective for increasing URiO residents.Design, Setting, and ParticipantsThis cross-sectional survey study used an 18-item questionnaire included in the online survey of the Association of University Professors in Ophthalmology (AUPO) Residency Program Directors. Data collection occurred from July 2022 to December 2022. The data were initially analyzed on January 16, 2023. Participants included residency program directors (PDs) in the AUPO PD listserv database.Main Outcomes and MeasuresDescriptive analysis of resident selection committee approaches, evaluation of applicant traits, and use of bias reduction tools. Primary outcome was diversity assessed by presence of at least 1 resident in the last 5 classes who identified as URiO, including those underrepresented in medicine (URiM), lesbian, gay, bisexual, transgender, queer, intersex, and asexual plus, or another disadvantaged background (eg, low socioeconomic status). Multivariate analyses of recruitment practices were conducted to determine which practices were associated with increased URiO and URiM.ResultsAmong 106 PDs, 65 completed the survey (61.3%). Thirty-nine PDs used an interview rubric (60.0%), 28 used interview standardization (43.0%), 56 provided at least 1 bias reduction tool to their selection committee (86.2%), and 44 used postinterview metrics to assess diversity, equity, and inclusion efforts (67.7%). Application filters, interview standardization, and postinterview metrics were not associated with increased URiO. Multivariate logistic regression analysis showed larger residency class (odds ratio [OR], 1.34; 95% CI, 1.09-1.65; P = .01) and use of multiple selection committee bias reduction tools (OR, 1.47; 95% CI, 1.13-1.92; P = .01) were positively associated with increased URiO, whereas use of interview rubrics (OR, 0.72; 95% CI, 0.59-0.87; P = .001) and placing higher importance of applicant interest in a program (OR, 0.83; 95% CI, 0.75-0.92; P = .02) were negatively associated. URiM analyses showed similar associations.Conclusions and RelevanceOphthalmology residency interviews are variably standardized. In this study, providing multiple bias reduction tools to selection committees was associated with increased URiO and URiM residents. Prioritizing applicant interest in a program may reduce resident diversity. Interview rubrics, while intended to reduce bias, may inadvertently increase inequity.

Purpose: We describe a case of metastatic conjunctival squamous cell carcinoma (SCC) presenting as an infectious sclerokeratouveitis in a patient with autoimmune disease. Observations: A 63-year-old Caucasian female presented to the cornea service with a raised perilimbal scleral infiltrate, hypopyon, and corneal perforation concerning for infectious necrotizing sclerokeratoveitis. She had an ocular history of a recurrent “pyogenic granuloma” and her medical history was notable for well-controlled systemic lupus erythematosus and rheumatoid arthritis. Scleral debridement and repair with a corneal patch graft was performed. Bacterial cultures grew 4+ Proteus mirabilis sensitive to tobramycin. One month later, she developed bulky painless scleral lesions with leukoplakic features. A scleral biopsy revealed squamous cell carcinoma. Imaging suggested ciliary body and medial rectus infiltration without perineural invasion. Right anterior exenteration was performed as immunotherapy was felt to be unlikely to achieve success in light of her autoimmune conditions. Six months later, she developed a palpable right parotid mass with biopsy confirming metastatic squamous cell carcinoma. She underwent a right parotidectomy and is now undergoing consolidative radiotherapy. Conclusions and Importance: Ocular surface neoplasia can present as a necrotizing sclerokeratouveitis, contributed by both the tumor and an atypical infectious process. Malignancy with superinfection should be in the differential diagnosis of recurrent ocular surface inflammation.

Background and Objective: The impact of anti-sepsis-anesthesia sequence in intravitreal injection (IVI)-associated endophthalmitis is unknown. We compared outcomes of patients who had 10% topical povidone-iodine before or after 2% topical lidocaine gel during IVIs. Patients and Methods: A retrospective study of IVIs in nine clinical sites was undertaken. Group 1 had lidocaine gel applied first. This protocol was changed on March 1, 2020, with Group 2 having povidone-iodine applied first. Visual and micro-biological outcomes were compared. Results: Among 72 cases (0.07%) from 102,908 IVIs, Group 1 had 59 cases from 65,307 IVI (0.09%) and Group 2 had 13 cases from 37,601 IVI (0.03%; P = 0.001). There was no significant difference in the best-corrected visual acuity between groups. Highly virulent bacteria were predominantly isolated in Group 1, but proportions of gram-positive bacterial growth were similar. Conclusions: Application of povidone-iodine before lidocaine gel, compared to after, significantly decreased rate of IVI endophthalmitis, with no significant changes in visual and microbiological outcomes. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:520–525.]

Purpose: The aim of this study was to describe a case of corneal involvement as an early manifestation of ocular disease in the 2022 human mpox (monkeypox) virus outbreak. Methods: This is a single case report with longitudinal care. Results: A 47-year-old immunocompetent man presented with viral conjunctivitis before development of skin lesions or systemic symptoms. Subsequently, he developed membranous keratoconjunctivitis and a corneal epithelial defect. Orthopoxvirus-positive polymerase chain reaction test from his ocular surface was positive. The epithelial defect did not heal with conservative treatment but was successfully treated with amniotic membrane transplantation over 8 days. Reduced corneal sensation was noted after epithelial healing, and polymerase chain reaction from the ocular surface remained positive at 17 days from symptom onset, with slowly recovering conjunctivitis at 21 days. Continued membrane formation required repeated removal but significantly improved with topical corticosteroid treatment after epithelial healing by 29 days of symptom onset. Corneal sensation normalized by 87 days from symptom onset at which time symblepharon were noted but PCR testing from the ocular surface was negative. Conclusions: Early corneal involvement of human monkeypox virus is possible. Transient corneal hypoesthesia may be due to acute inflammation. Chronic inflammatory changes can result in symblepharon. These findings have potential implications in patient care and corneal donation.

To validate associations between MRI features and gene expression profiles in retinoblastoma, thereby evaluating the repeatability of radiogenomics in retinoblastoma. In this retrospective multicenter cohort study, retinoblastoma patients with gene expression data and MRI were included. MRI features (scored blinded for clinical data) and matched genome-wide gene expression data were used to perform radiogenomic analysis. Expression data from each center were first separately processed and analyzed. The end product normalized expression values from different sites were subsequently merged by their Z-score to permit cross-sites validation analysis. The MRI features were non-parametrically correlated with expression of photoreceptorness (radiogenomic analysis), a gene expression signature informing on disease progression. Outcomes were compared to outcomes in a previous described cohort. Thirty-six retinoblastoma patients were included, 15 were female (42 • Since retinoblastoma is increasingly treated using eye-sparing methods, MRI features informing on molecular subtypes that do not rely on histopathology material are important. • A part of the associations between retinoblastoma MRI features and gene expression profiles (radiogenomics) were validated. • Radiogenomics could be a non-invasive technique providing information on the molecular make-up of retinoblastoma.

Background MYCN-amplified RB1 wild-type (MYCNARB1+/+) retinoblastoma is a rare but clinically important subtype of retinoblastoma due to its aggressive character and relative resistance to typical therapeutic approaches. Because biopsy is not indicated in retinoblastoma, specific MRI features might be valuable to identify children with this genetic subtype. Purpose To define the MRI phenotype of MYCNARB1+/+ retinoblastoma and evaluate the ability of qualitative MRI features to help identify this specific genetic subtype. Materials and Methods In this retrospective, multicenter, case-control study, MRI scans in children with MYCNARB1+/+ retinoblastoma and age-matched children with RB1-/- subtype retinoblastoma were included (case-control ratio, 1:4; scans acquired from June 2001 to February 2021; scans collected from May 2018 to October 2021). Patients with histopathologically confirmed unilateral retinoblastoma, genetic testing (RB1/MYCN status), and MRI scans were included. Associations between radiologist-scored imaging features and diagnosis were assessed with the Fisher exact test or Fisher-Freeman-Halton test, and Bonferroni-corrected P values were calculated. Results A total of 110 patients from 10 retinoblastoma referral centers were included: 22 children with MYCNARB1+/+ retinoblastoma and 88 control children with RB1-/- retinoblastoma. Children in the MYCNARB1+/+ group had a median age of 7.0 months (IQR, 5.0-9.0 months) (13 boys), while children in the RB1-/- group had a median age of 9.0 months (IQR, 4.6-13.4 months) (46 boys). MYCNARB1+/+ retinoblastomas were typically peripherally located (in 10 of 17 children; specificity, 97%; P < .001) and exhibited plaque or pleomorphic shape (in 20 of 22 children; specificity, 51%; P = .011) with irregular margins (in 16 of 22 children; specificity, 70%; P = .008) and extensive retina folding with vitreous enclosure (specificity, 94%; P < .001). MYCNARB1+/+ retinoblastomas showed peritumoral hemorrhage (in 17 of 21 children; specificity, 88%; P < .001), subretinal hemorrhage with a fluid-fluid level (in eight of 22 children; specificity, 95%; P = .005), and strong anterior chamber enhancement (in 13 of 21 children; specificity, 80%; P = .008). Conclusion MYCNARB1+/+ retinoblastomas show distinct MRI features that could enable early identification of these tumors. This may improve patient selection for tailored treatment in the future. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Rollins in this issue.