Background: Applicants to ophthalmology residency programs have increasingly expressed interest in international surgical rotations. As such, ophthalmology residency program directors (PDs) have expanded international offerings to meet this desire but the true number of residency programs with international offerings is unknown. Methods: In February 2023, the official residency websites of all 125 accredited US-based ophthalmology residency programs were analyzed for any mention of international rotations. Websites were identified using a Google™ search by entering the program name and “ophthalmology residency.” All websites were surveyed for information regarding international rotations including the presence/absence of an international rotation and any additional information on the rotation provided including elective length, location, program year, and any other relevant information available. Results: Of the 125 accredited ophthalmology residency programs in the US, only 35% (n=44) mentioned an international rotation on their website. Of those, the majority sent residents abroad during later years of residency (postgraduate year three or four). Rotation length was variable with an average of two weeks (range one to eight weeks). The geographic location of international rotations included sites in Central and South America, Africa, Asia, and Europe. The most frequently listed country was India where 30% (n=13/44) of programs had an international rotation including several with connections to the Aravind Eye Care System. Conclusions: The majority of US-based, ACGME accredited ophthalmology residency programs do not mention international rotations on their official websites. Those that do tend to offer rotations to senior residents with India being the most common location. This study contrasts prior surveys which reported that a majority of programs offer or are developing international rotations. This discrepancy may exist because PDs with international rotations may be more likely to respond to surveys on this subject or residency program websites may not accurately reflect current initiatives.

PURPOSE:To compare the corticosteroid sparing efficacy of frequently used antimetabolites to tumor necrosis factor (TNF) inhibitors in the management of noninfectious ocular inflammation. METHODS:Retrospective analysis of patients with noninfectious uveitis on conventional antimetabolite (methotrexate, mycophenolate mofetil, azathioprine,or leflunomide, "CONV") or a TNF inhibitor (adalimumab or infliximab, "TNFi") with active inflammation or more than 7.5 mg daily prednisone. Eyes were assessed in three groups: CONV only, TNFi only and combination of both (COMB). Cox regression models compared treatment success, adjusted for age, race, smoking, anatomic location of uveitis, duration of uveitis and visual acuity. Corticosteroid sparing success was defined as: inactive or slightly active uveitis on <=7.5 mg daily oral prednisone and <=2 drops of prednisolone acetate 1%. RESULTS:There were 1475 eligible patients in the analysis. By 6 and 12 months, respectively, the Cox model-predicted, percentage success was 27.6% and 44.9% for the CONV group; 34.2% and 53.9% in the TNFi group and 39.9% and 61.1% for the COMB group. COMB was more likely than CONV to achieve success (adjusted HR 1.58 (95% confidence interval (CI), 1.28, 1.95, p < 0.0001). Factors associated with lower success were age under 18 years, smoking, visual acuity worse than 20/50 at cohort entry, over 4-year duration of uveitis and daily baseline prednisone 7.5 mg or higher (all p < 0.05). CONCLUSION:Our results suggest COMB is more effective than CONV at achieving disease quiescence and corticosteroid sparing success among patients with active noninfectious uveitis. More research is needed to determine if TNFi alone is superior to CONV for uveitic corticosteroid-sparing.

To report a case of chronic unilateral nodular anterior scleritis as a rare, isolated presentation of IgG4-related ophthalmic disease. A fifty-two-year-old patient was evaluated for painful, nodular scleral injection of the right eye, diagnosed as nodular anterior scleritis. There was only a partial response to topical corticosteroid and systemic immunomodulatory therapy. This, in combination with a sharp delineation between normal and abnormal sclera lead to the decision to perform a diagnostic biopsy of the lesion. Histopathology showed an IgG4 lymphoplasmacytic infiltration of the scleral tissue. There are few documented reports of scleritis as the presenting manifestation of IgG4-related disease. IgG4-related disease is an increasingly recognized etiology to be considered in evaluating and managing scleritis.

Evidence regarding suppressive valacyclovir treatment on postherpetic neuralgia is necessary to guide care. To test the hypothesis that suppressive treatment with 1000 mg/d of oral valacyclovir for 12 months reduces the prevalence, severity, and duration of postherpetic neuralgia compared with placebo at 12 and 18 months in participants with herpes zoster ophthalmicus (HZO). Multicenter, placebo-controlled randomized clinical trial including 527 immunocompetent, nonpregnant adults with history of HZO rash, documented keratitis, or iritis within 1 year and an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or greater. The study was conducted at 95 participating sites (in Canada, New Zealand, and the US) from November 2017 to June 2024 and participant visits occurred every 3 months. Treatment with 1000 mg/d of valacyclovir or placebo for 12 months. Prevalence of postherpetic neuralgia, severity as determined by pain score (a score of ≥3 on a scale of 1-10), pain duration (≥3 months after HZO onset), and total daily dose of pain medication. Of the 527 participants (490 completed 12 months of treatment and 460 completed 18 months), 73 (14%) had postherpetic neuralgia and were analyzed by age at HZO onset (<60 years or ≥60 years) and disease duration (recent [<6 months] or chronic [≥6 months]). Of the 73 participants with postherpetic neuralgia (34 in the valacyclovir group and 39 in the placebo group), the mean age was 62.4 years (SD, 13.6 years), 59% were female, 5% were Black or African American, and 10% were Hispanic. The prevalence of postherpetic neuralgia at 12 months was not reduced by valacyclovir (12/32 [38%]) compared with placebo (14/35 [40%]) (between-group difference, 2.5% [95% CI, −20.8% to 25.8%]; P>.99). The participants who were younger than 60 years at HZO onset and had a chronic disease duration had lower pain scores in the valacyclovir group (mean score, 0.3 [SD, 0.9]) vs the placebo group (mean score, 0.8 [SD, 1.9]) at 12 months (P = .045) and at 18 months (mean score, 0.2 [SD, 0.9] vs 1.0 [SD, 2.3], respectively; P = .02). There was a decrease in pain duration in the valacyclovir group at 18 months (mean, 13.6 [SD, 11.4] months) vs the placebo group (mean, 18.7 [SD, 29.5] months) (linear mixed-effects model between-group difference, −3.39 months [95% CI, −6.73 to −0.04 months]; P = .046). The total daily dose of neuropathic pain medication was lower in the valacyclovir group (mean, 271.4 [SD, 593.8] mg/d) vs the placebo group (mean, 363.4 [SD, 592.2] mg/d) at 12 months (linear mixed-effects model P = .006) and at 18 months (mean, 209.0 [SD, 412.8] mg/d vs 286.2 [SD, 577.9] mg/d, respectively; linear mixed-effects model P = .01). One year of suppressive treatment with valacyclovir was associated with a lower dosage of neuropathic pain medication. Participants in the valacyclovir group, who were younger at HZO onset and had a chronic disease duration, had lower pain scores. These secondary outcomes support consideration of 1 year of suppressive treatment with valacyclovir to reduce dosage of pain medications and pain due to HZO. ClinicalTrials.gov Identifier: NCT03134196

High-quality evidence regarding suppressive valacyclovir treatment in herpes zoster ophthalmicus (HZO) is necessary to guide care. To determine whether suppressive valacyclovir compared with placebo delays the occurrence of new or worsening stromal keratitis (SK), endothelial keratitis (EK), iritis, or dendriform epithelial keratitis (DEK) during 12 months of treatment and if treatment benefit persisted at 18 months (secondary end point). The Zoster Eye Disease Study (ZEDS) was a randomized clinical trial conducted in 95 sites from November 2017 to June 2024. Immunocompetent, nonpregnant adults with a history of an HZO rash, documented active keratitis or iritis within 1 year, and an estimated glomerular filtration rate of 45 mL/min/1.73 m2 or greater were eligible. After determined to be eligible, participants were randomized in 4 strata: age at onset (<60 years vs ≥60 years) and disease duration (<6 months vs ≥6 months). A total of 12 months of double-masked daily valacyclovir, 1000 mg, or placebo. The primary outcome was time to first occurrence within 12 months of new or worsening SK, EK, iritis, or DEK. A total of 527 participants (median [IQR] age, 60 [50-68] years; 266 female [50.5%]; 266 in the valacyclovir group; 261 in the placebo group) were randomized in 4 strata; 481 completed 12 months, and 460 completed 18 months. Data were analyzed by intention to treat. At 12 months, primary end points occurred in 86 participants (33%) assigned to placebo and 74 (28%) assigned to valacyclovir, and at 18 months in 104 participants (40%) assigned to placebo and 86 (32%) assigned to valacyclovir. The hazard ratio (HR) of the primary end point at 12 months was 0.77 for participants taking valacyclovir vs placebo (HR, 0.77; adjusted 95% CI, 0.56-1.05; P = .09) and 0.73 at the secondary end point at 18 months (HR, 0.73; adjusted 95% CI, 0.55-0.97; P = .03). There was a reduction of multiple other secondary end points at 12 months (HR, 0.70; 95% CI, 0.52-0.95; P = .02) and 18 months (HR, 0.72; 95% CI, 0.55-0.95; P = .02). Although the primary outcome did not show a benefit of suppressive valacyclovir treatment, secondary study outcomes showed treatment superiority at the 18-month end point and reduced number of multiple episodes of keratitis or iritis at both 12 and 18 months. These results support consideration of 1 year of suppressive valacyclovir treatment for HZO. ClinicalTrials.gov Identifier: NCT03134196

The development of acute anterior uveitis is usually associated with a lowering of intraocular pressure, as inflammation of the ciliary body results in a decrease in aqueous production while aqueous outflow is enhanced by increased uveoscleral outflow. When faced with a case of acute anterior uveitis with increased intraocular pressure, the ophthalmologist must consider several possibilities. I prefer to begin thinking broadly, narrowing down the possibilities with the pertinent positives and negatives of the details of the existing case. The mechanisms by which intraocular pressure can be elevated include 2 possibilities: 1) an increase in aqueous inflow, or 2) a decrease in aqueous outflow. I am unaware of uveitic diseases that result in an increase in aqueous production, so all relevant causes to be considered focus on impaired outflow. Consideration of this clinical scenario is well suited to an algorithmic approach, presented via outline form to follow. Determining the presence or absence of each of the possibilities presented is relatively straightforward using standard ophthalmologic examination techniques, including slitlamp biomicroscopy, gonioscopy, and dilated fundus examination.

This issue of the Journal includes 2 articles dealing with risk factors for cataract among people with various forms of chronic, noninfectious uveitis, populations with a particularly high prevalence of cataract. 1 Jabs DA Sugar EA Burke AE et al. Cataract surgery in patients with uveitis treated with systemic therapy in the MUST Trial & Follow-up Study: risk factors and outcomes. Am J Ophthalmol. 2023; Abstract Full Text Full Text PDF Google Scholar ,2 Papaliodis GN Rosner BA Dreger KA et al. Incidence of and risk factors for cataract in anterior uveitis. Am J Ophthalmol. 2023; Abstract Full Text Full Text PDF PubMed Google Scholar Cataract, in general, is the leading cause of visual impairment worldwide for those 50 years of age and older, with an estimated 15.2 million individuals affected, 3 GBD 2019 Blindness and Vision Impairment Collaborators; Vision Loss Expert Group of the Global Burden of Disease StudyCauses of blindness and vision impairment in 2020 and trends over 30 years, and prevalence of avoidable blindness in relation to VISION 2020: the Right to Sight: an analysis for the Global Burden of Disease Study. Lancet Glob Health. Feb 2021; 9: e144-e160https://doi.org/10.1016/S2214-109X(20)30489-7 Abstract Full Text Full Text PDF PubMed Scopus (855) Google Scholar and carries with it a substantial economic burden. 4 Marques AP Ramke J Cairns J et al. The economics of vision impairment and its leading causes: a systematic review. EClinicalMedicine. 2022; 46101354https://doi.org/10.1016/j.eclinm.2022.101354 Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar ,5 Pascual-Prieto J Nieto-Gomez C Rodriguez-Devesa I. The carbon footprint of cataract surgery in Spain. Arch Soc Esp Oftalmol (Engl Ed). 2023; 98: 249-253https://doi.org/10.1016/j.oftale.2023.01.005 Crossref PubMed Google Scholar There are well-established risk factors for cataract development, some of which cannot be modified, such as advancing age and genetic factors, 6 Kessel L Bach-Holm D Al-Bakri M Roos L Lund A Gronskov K Genetic disease is a common cause of bilateral childhood cataract in Denmark. Ophthalmic Genet. 2021; 42: 650-658https://doi.org/10.1080/13816810.2021.1941128 Crossref PubMed Scopus (3) Google Scholar but there are also potentially modifiable factors that influence cataract development, such as environmental exposures 7 Millen AE Dighe S Kordas K Aminigo BZ Zafron ML Mu L. Air pollution and chronic eye disease in adults: a scoping review. Ophthalmic Epidemiol. March 2, 2023; (Published online)https://doi.org/10.1080/09286586.2023.2183513 Crossref PubMed Scopus (1) Google Scholar and associated diseases. 8 Ang MJ Afshari NA. Cataract and systemic disease: a review. Clin Exp Ophthalmol. 2021; 49: 118-127https://doi.org/10.1111/ceo.13892 Crossref PubMed Scopus (41) Google Scholar , 9 Cicinelli MV Buchan JC Nicholson M Varadaraj V Cataracts Khanna RC. Lancet. 2023; 401: 377-389https://doi.org/10.1016/S0140-6736(22)01839-6 Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar , 10 Drinkwater JJ Davis WA Davis TME. A systematic review of risk factors for cataract in type 2 diabetes. Diabetes Metab Res Rev. 2019; 35: e3073https://doi.org/10.1002/dmrr.3073 Crossref PubMed Scopus (52) Google Scholar , 11 Al-Ani HH Sims JL Niederer RL. Long term complications and vision loss in HLA-B27 uveitis. Eye (Lond). 2023; 37: 1673-1677https://doi.org/10.1038/s41433-022-02216-x Crossref PubMed Scopus (2) Google Scholar , 12 AlBloushi AF Alfawaz AM Al-Dahmash SA et al. Incidence, risk factors and surgical outcomes of cataract among patients with uveitis in a university referral hospital in Riyadh, Saudi Arabia. Ocul Immunol Inflamm. 2019; 27: 1105-1113https://doi.org/10.1080/09273948.2018.1504970 Crossref PubMed Scopus (10) Google Scholar , 13 Minkus CL Pistilli M Dreger KA et al. Risk of cataract in intermediate uveitis. Am J Ophthalmol. 2021; 229: 200-209https://doi.org/10.1016/j.ajo.2021.02.032 Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar People with uveitis have additional, unique risk factors, related to inflammation and its treatment.

PURPOSE:To determine the incidence of all-cause and cancer mortality (CM) in association with immunosuppression. DESIGN:Retrospective cohort study at ocular inflammatory disease (OID) subspecialty centers. We harvested exposure and covariate data retrospectively from clinic inception (earliest in 1979) through 2010 inclusive. Then we ascertained overall and cancer-specific mortalities by National Death Index linkage. We constructed separate Cox models to evaluate overall and CM for each class of immunosuppressant and for each individual immunosuppressant compared with person-time unexposed to any immunosuppression. PARTICIPANTS:Patients with noninfectious OID, excluding those with human immunodeficiency infection or preexisting cancer. METHODS:Tumor necrosis factor (TNF) inhibitors (mostly infliximab, adalimumab, and etanercept); antimetabolites (methotrexate, mycophenolate mofetil, azathioprine); calcineurin inhibitors (cyclosporine); and alkylating agents (cyclophosphamide) were given when clinically indicated in this noninterventional cohort study. MAIN OUTCOME MEASURES:Overall mortality and CM. RESULTS:Over 187 151 person-years (median follow-up 10.0 years), during which 15 938 patients were at risk for mortality, we observed 1970 deaths, 435 due to cancer. Both patients unexposed to immunosuppressants (standardized mortality ratio [SMR] = 0.95, 95% confidence interval [CI], 0.90-1.01) and those exposed to immunosuppressants but free of systemic inflammatory diseases (SIDs) (SMR = 1.04, 95% CI, 0.95-1.14) had similar mortality risk to the US population. Comparing patients exposed to TNF inhibitors, antimetabolites, calcineurin inhibitors, and alkylating agents with patients not exposed to any of these, we found that overall mortality (adjusted hazard ratio [aHR] = 0.88, 0.89, 0.90, 1.11) and CM (aHR = 1.25, 0.89, 0.86, 1.23) were not significantly increased. These results were stable in sensitivity analyses whether excluding or including patients with SID, across 0-, 3-, or 5-year lags and across quartiles of immunosuppressant dose and duration. CONCLUSIONS:Our results, in a cohort where the indication for treatment was proven unassociated with mortality risk, found that commonly used immunosuppressants-especially the antimetabolites methotrexate, mycophenolate mofetil, and azathioprine; the TNF inhibitors adalimumab and infliximab, and cyclosporine-were not associated with increased overall and CM over a median cohort follow-up of 10.0 years. These results suggest the safety of these agents with respect to overall and CM for patients treated with immunosuppression for a wide range of inflammatory diseases. FINANCIAL DISCLOSURE(S):Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Objective Evaluate the association between cancer incidence and immunosuppressive treatment in patients with ocular inflammatory disease (OID). Methods and analysis We performed a retrospective cohort study of patients from 10 US OID subspecialty practices. Patients with non-infectious OID were included; HIV-infected patients were excluded. Time-dependent exposure to drug classes (ie, antimetabolites, calcineurin inhibitors, alkylating agents, tumour necrosis factor (TNF) inhibitors) and drugs were evaluated. Cancer incidence was ascertained by linkage to 12 state cancer registries from 1996 to 2015. Cancer incidence was analysed using Cox regression survival analysis, using 0-year, 3-year and 5-year lags after immunosuppression began. Results The cancer incidence cohort comprised 10 872 individuals at risk of incident cancer and residing in one of the 12 states covered; 812 primary cancers were identified through cancer incidence tracing with median follow-up time of 10 years. Neither TNF inhibitor, antimetabolite, calcineurin inhibitor nor alkylating agent classes were associated with statistically significant increases in cancer incidence adjusting for covariates. We found statistically significant reduced hazards in the systemic inflammatory disease (SID)-including cohort for adalimumab and chlorambucil, increased hazards for tacrolimus and etanercept in the non-SID cohort and reduced hazards for methotrexate in both. Other immunosuppressive drugs were not associated with overall cancer incidence. Conclusions We found no increased risk of overall or site-specific cancer incidence associated with short-term (non-transplant) therapy with most commonly used immunosuppressive drug classes and many specific drugs. Further research may clarify potentially protective or harmful effects of specific agents that were not consistently associated with reduced or increased cancer incidence. Trial registration number NCT00116090 .

PURPOSE:To report and illustrate the main clinical presentations of posterior herpetic uveitis.METHODS:Narrative review.RESULTS:The ocular manifestations of posterior herpetic uveitis include different clinical presentations. Herpes simplex and varicella zoster can cause acute retinal necrosis, progressive outer retinal necrosis, and non-necrotizing herpetic retinopathies. Cytomegalovirus has been associated with fulminant retinitis with confluent areas of retinal necrosis and retinal hemorrhages, indolent/granular retinitis, and frosted branch angiitis. These diverse clinical presentations are often associated with specific risk factors and different immunological profiles of the host.CONCLUSIONS:Herpetic viruses can cause posterior uveitis, presenting various clinical findings. Specific ocular manifestations and the immunological status of the host can help to differentiate the various herpetic entities before laboratory tests confirm the diagnosis.

PURPOSE: To determine classification criteria for Behcet disease uveitis. DESIGN: Machine learning of cases with Behcet disease and 5 other panuveitides. METHODS: Cases of panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation set. RESULTS: One thousand twelve cases of panuveitides, including 194 cases of Behcet disease with uveitis, were evaluated by machine learning. The overall accuracy for panuveitides was 96.3% in the training set and 94.0% in the validation set (95% confidence interval 89.0, 96.8). Key criteria for Behcet disease uveitis were a diagnosis of Behcet disease using the International Study Group for Behcet Disease criteria and a compatible uveitis, including (1) anterior uveitis; (2) anterior chamber and vitreous inflammation; (3) posterior uveitis with retinal vasculitis and/or focal infiltrates; or (4) panuveitis with retinal vasculitis and/or focal infiltrates. The misclassification rates for Behcet disease uveitis were 0.6% in the training set and 0% in the validation set, respectively. CONCLUSIONS: The criteria for Behcet disease uveitis had a low misclassification rate and seemed to perform sufficiently well for use in clinical and translational research. (C) 2021 Elsevier Inc. All rights reserved.

PURPOSE: To determine classification criteria for multifocal choroiditis with panuveitis (MFCPU). DESIGN: Machine learning of cases with MFCPU and 8 other posterior uveitides. METHODS: Cases of posterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the posterior uveitides. The resulting criteria were evaluated on the validation set. RESULTS: One thousand sixty-eight cases of posterior uveitides, including 138 cases of MFCPU, were evaluated by machine learning. Key criteria for MFCPU included (1) multifocal choroiditis with the predominant lesions size >125 mu m in diameter; (2) lesions outside the posterior pole (with or without posterior involvement); and either (3) punched-out atrophic chorioretinal scars or (4) more than minimal mild anterior chamber and/or vitreous inflammation. Overall accuracy for posterior uveitides was 93.9% in the training set and 98.0% (95% confidence interval 94.3, 99.3) in the validation set. The misclassification rates for MFCPU were 15% in the training set and 0% in the validation set. CONCLUSIONS: The criteria for MFCPU had a reasonably low misclassification rate and seemed to perform sufficiently well for use in clinical and translational research. (C) 2021 Elsevier Inc. All rights reserved.

PURPOSE: The purpose of this study was to determine classification criteria for multiple sclerosis-associated intermediate uveitis. DESIGN: Machine learning of cases with multiple sclerosis-associated intermediate uveitis and 4 other intermediate uveitides. METHODS: Cases of intermediate uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used in the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated in the validation set. RESULTS: A total of 589 cases of intermediate uveitides, including 112 cases of multiple sclerosis-associated intermediate uveitis, were evaluated by machine learning. The overall accuracy for intermediate uveitides was 99.8% in the training set and 99.3% in the validation set (95% confidence interval: 96.1-99.9). Key criteria for multiple sclerosis-associated intermediate uveitis included unilateral or bilateral intermediate uveitis and multiple sclerosis diagnosed by the McDonald criteria. Key exclusions included syphilis and sarcoidosis. The misclassification rates for multiple sclerosis-associated intermediate uveitis were 0 % in the training set and 0% in the validation set. CONCLUSIONS: The criteria for multiple sclerosis-associated intermediate uveitis had a low misclassification rate and appeared to perform sufficiently well enough for use in clinical and translational research. ((C) 2021 Elsevier Inc. All rights reserved.)

PURPOSE: The purpose of this study was to determine classification criteria for sympathetic ophthalmia. DESIGN: Machine learning of cases with sympathetic ophthalmia and 5 other panuveitides. METHODS: Cases of panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used in the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the panuveitides. The resulting criteria were evaluated in the validation set. RESULTS: A total of 1,012 cases of panuveitides, including 110 cases of sympathetic ophthalmia, were evaluated by machine learning. The overall accuracy for panuveitides was 96.3% in the training set and 94.0% in the validation set (95% confidence interval: 89.0-96.8). Key criteria for sympathetic ophthalmia included bilateral uveitis with 1) a history of unilateral ocular trauma or surgery and 2) an anterior chamber and vitreous inflammation or a panuveitis with choroidal involvement. The misclassification rates for sympathetic ophthalmia were 4.2% in the training set and 6.7% in the validation set. CONCLUSIONS: The criteria for sympathetic ophthalmia had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research. ((C) 2021 Elsevier Inc. All rights reserved.)

PURPOSE: To determine classification criteria for intermediate uveitis, non-pars planitis type (IU-NPP, also known as undifferentiated intermediate uveitis). DESIGN: Machine learning of cases with IU-NPP and 4 other intermediate uveitides. METHODS: Cases of intermediate uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation set. RESULTS: Five hundred eighty-nine of cases of intermediate uveitides, including 114 cases of IU-NPP, were evaluated by machine learning. The overall accuracy for intermediate uveitides was 99.8% in the training set and 99.3% in the validation set (95% confidence interval 96.1, 99.9). Key criteria for IU-NPP included unilateral or bilateral intermediate uveitis with neither snowballs in the vitreous humor nor snowbanks on the pars plana. Other key exclusions included multiple sclerosis, sarcoidosis, and syphilis. The misclassification rates for IU-NPP were 0% in the training set and 0% in the validation set. CONCLUSIONS: The criteria for IU-NPP had a low misclassification rate and seemed to perform well enough for use in clinical and translational research. (C) 2021 Elsevier Inc. All rights reserved.

PURPOSE: To determine classification criteria for Vogt-Koyanagi-Harada (VKH) disease. DESIGN: Machine learning of cases with VKH disease and 5 other panuveitides. METHODS: Cases of panuveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the panuveitides. The resulting criteria were evaluated on the validation set. RESULTS: One thousand twelve cases of panuveitides, including 156 cases of early-stage VKH and 103 cases of late-stage VKH, were evaluated. Overall accuracy for panuveitides was 96.3% in the training set and 94.0% in the validation set (95% confidence interval 89.0, 96.8). Key criteria for early-stage VKH included the following: (1) exudative retinal detachment with characteristic appearance on fluorescein angiogram or optical coherence tomography or (2) panuveitis with >= 2 of 5 neurologic symptoms/signs. Key criteria for late-stage VKH included history of early-stage VKH and either (1) sunset glow fundus or (2) uveitis and >= 1 of 3 cutaneous signs. The misclassification rates in the learning and validation sets for early-stage VKH were 8.0% and 7.7%, respectively, and for late-stage VKH 1.0% and 12%, respectively. CONCLUSIONS: The criteria for VKH had a reasonably low misclassification rate and seemed to perform sufficiently well for use in clinical and translational research. ((C) 2021 Elsevier Inc. All rights reserved.)

PURPOSE: To determine classification criteria for bird-shot chorioretinitis. DESIGN: Machine learning of cases with birdshot chorioretinitis and 8 other posterior uveitides. METHODS: Cases of posterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving super-majority agreement on diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the infectious posterior uveitides / panuveitides. The resulting criteria were evaluated on the validation set. RESULTS: One thousand sixty-eight cases of posterior uveitides, including 207 cases of birdshot chorioretinitis, were evaluated by machine learning. Key criteria for birdshot chorioretinitis included a multifocal choroiditis with (1) the characteristic appearance of a bilateral multifocal choroiditis with cream-colored or yellow-orange, oval or round choroidal spots ("birdshot" spots); (2) ab-sent to mild anterior chamber inflammation; and (3) ab-sent to moderate vitreous inflammation; or multifocal choroiditis with positive HLA-A29 testing and either classic "birdshot spots" or characteristic imaging on indocyanine green angiography. Overall accuracy for posterior uveitides was 93.9% in the training set and 98.0% (95% confidence interval 94.3, 99.3) in the validation set. The misclassification rates for birdshot chorioretinitis were 10% in the training set and 0% in the validation set. CONCLUSIONS: The criteria for birdshot chorioretinitis had a low misclassification rate and seemed to perform sufficiently ((C) 2021 Elsevier Inc. All rights reserved.)

center dot PURPOSE: To determine classification criteria for pars planitis. center dot DESIGN: Machine learning of cases with pars planitis and 4 other intermediate uveitides. center dot METHODS: Cases of intermediate uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the intermediate uveitides. The resulting criteria were evaluated on the validation set. center dot RESULTS: Five hundred eighty-nine cases of intermediate uveitides, including 226 cases of pars planitis, were evaluated by machine learning. The overall accuracy for intermediate uveitides was 99.8% in the training set and 99.3% in the validation set (95% confidence interval 96.1, 99.9). Key criteria for pars planitis included unilateral or bilateral intermediate uveitis with either 1) snowballs in the vitreous or 2) snowbanks on the pars plana. Key exclusions included: 1) multiple sclerosis, 2) sarcoidosis, and 3) syphilis. The misclassification rates for pars planitis were 0% in the training set and 1.7% in the validation set, respectively. center dot CONCLUSIONS: The criteria for pars planitis had a low misclassification rate and appeared to perform sufficiently well for use in clinical and translational research. (Am J Ophthalmol 2021;228: 268-274. (c) 2021 Elsevier Inc. All