Autosomal Dominant Retinitis Pigmentosa Secondary to TOPORS Mutations: A Report of a Novel Mutation and Clinical Findings.

Purpose: Mutations in Topoisomerase I-binding RS protein (TOPORS) have been previously documented and have been described to result in pathological autosomal dominant retinitis pigmentosa (adRP). In our study, we describe the various genotypes and clinical/phenotypic manifestations of TOPORS-related mutations of our unique patient population in Rural Appalachia. Methods: The medical records of 416 patients with inherited retinal disease at the West Virginia University Eye Institute who had undergone genetic testing between the years of 2015-2022 were reviewed. Patients found to have pathologic RP and mutations related to TOPORS were then analyzed. Results: In total, 7 patients (ages 12-70) were identified amongst three unique families. All patients were female in our study. The average follow-up period was 7.7 years. A mother (70 yr) and daughter (51 yr) had a novel heterozygous nonsense point mutation in TOPORS c.2431C > T, p.Gln811X (Exon 3) that led to premature termination of the desired protein resulting in early onset vision loss, cataract formation, and visual field restriction. The mother developed a full-thickness macular hole which was successfully repaired. Five other patients were found to have previously described TOPORS mutations. Visual field loss was progressive with age in both cohorts. Conclusions: Seven patients at our institution were identified to have mutations in TOPORS resulting in autosomal dominant retinitis pigmentosa. Two patients were found to have novel truncating mutations in the TOPORS gene resulting in profound night blindness and visual field loss, recurrent macular edema, and in one individual, epiretinal membrane formation leading to a macular hole which was able to be successfully repaired.

Rising Incidence of Syphilitic Uveitis-Related Hospitalizations in the US.

Importance: The number of syphilis cases continues to increase in the US every year since 2001 with a 74% increase observed since 2017. In addition, there remains a national shortage of injectable penicillin G. Despite the increase in reported cases, to the authors' knowledge, there has been no recent nationwide study investigating the trends in incidence of syphilitic uveitis. Objective: To evaluate the national and regional incidence of syphilitic uveitis-related hospitalizations in the US. Design, Setting, and Participants: This was a retrospective, cross-sectional study. The Nationwide Inpatient Sample was queried to identify all inpatient admissions with a diagnosis of syphilitic uveitis in the US between the years 2010 and 2019. Analyses were performed to determine baseline sociodemographic characteristics and identify national and regional trends in incidence. All patients hospitalized with a diagnosis of syphilis, uveitis, and/or syphilitic uveitis were eligible for inclusion. Statistical analysis of study data took place in June 2023. Exposure: Diagnosis of syphilis, uveitis, and/or syphilitic uveitis on inpatient admissions during the years 2010 to 2019 in the Nationwide Inpatient Sample. Main Outcome Measures: The primary outcome was to determine trends in the national and regional incidence of syphilitic uveitis-related hospitalizations in the US. Secondary outcome measures included sociodemographic characteristics of patients with syphilitic uveitis, incidence stratified by sex and race and ethnicity, and median charge per syphilitic uveitis hospital admission. Results: From the Nationwide Inpatient Sample, inpatient data from 444 674 patients (median [IQR] age, 53 [37-67] years; 54.8% male) were analyzed. There were an estimated 5581 syphilitic uveitis-related hospitalizations during the 10-year study period. The median (IQR) age of individuals with syphilitic uveitis was 45 (35-55) years, and 4395 patients (78.9%) were male. Syphilitic uveitis disproportionately affected African American individuals (1787 patients [32%], although they compose 13.6% of the population) and those belonging to the lowest median household income quartile (2163 [38.8%]). The national incidence was 0.15 per 100 000 population and showed an increasing trend over the years, with the lowest incidence in 2011 (0.08 per 100 000 population) and the highest incidence in 2019 (0.23 per 100 000 population; P = .04). Regional analysis showed an increase in incidence across all 4 US geographical regions. A total of 1293 patients (23.2%) had comorbid AIDS. Conclusion and Relevance: Although this cross-sectional study only captured inpatient diagnosis, an increasing incidence of syphilitic uveitis-related hospitalizations was observed in the US between 2010 and 2019. Given the concomitant national shortage of injectable penicillin G, results suggest that clinicians should maintain a high index of suspicion for syphilis when evaluating patients with intraocular inflammation.

Ocular syphilis on the rise: a 10-year analysis from 2010 to 2020.

PURPOSE: The purpose of the study was to evaluate the incidence of ocular syphilis as well as diagnostic parameters, comorbidities, and visual outcomes over a 10-year time period in West Virginia. METHODS: A retrospective chart review included 25 eyes of 17 patients with ocular syphilis between 2010 and 2020. RESULTS: The incidence of systemic syphilis at a large tertiary referral center has increased from 27 cases in 2010 to 105 cases in 2020. Seventeen patients were identified with ocular syphilis. Bilaterality was present in 47.1% of cases. In this study, 70.6% of patients were male and 29.4% were female. The median age of presentation was 40.2 years (range 21-63). Panuveitis was the most common (60.0%) followed by isolated anterior uveitis (16.0%), chorioretinitis (12.0%), inner retinitis (4.0%), and papillitis (8.0%). Forty percent of patients had visual acuity worse than 20/400 on presentation. Post-treatment visual acuity improved in all patients. Rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TP-PA) tests were positive in 84.6% and 100% of cases, respectively. CSF venereal disease research laboratory (VDRL) was positive in 36.4%, CSF pleocytosis was present in 72.7%, and elevated CSF protein was observed in 81.8%. Human immunodeficiency virus (HIV) co-infection was present in 31.3%. A majority of patients experienced maculopapular rash and/or history of genital chancre. The anatomic classification of presenting uveitis (anterior, intermediate, posterior, and panuveitis) did not correlate with clinical variables including age, gender, HIV status, serologic test, presence of rash, or year of diagnosis (p > 0.05). CONCLUSION: Ocular syphilis is becoming increasingly prevalent and can present with a variety of ocular findings; therefore, it should be considered in the differential diagnosis for patients with ocular inflammation. Visual prognosis is excellent with timely diagnosis and treatment.

NONSURGICAL RESOLUTION OF FULL-THICKNESS MACULAR HOLES WITHOUT VITREOMACULAR TRACTION.

BACKGROUND/PURPOSE: The purpose of this study was to report a case series of full-thickness macular holes without vitreomacular traction that resolved without surgery. METHODS: This study is a retrospective case series of 11 patients who demonstrated closure of full-thickness macular holes without surgical intervention. RESULTS: All full-thickness macular holes closed, with all patients having improvement in visual acuity. All but one of the cases had visual acuity better than 20/40 at last recorded visit. Most cases presented with associated epiretinal membrane (73%), cystoid changes (64%), defects <150 µ m (80%), and resolved within 2 months (91%). Topical anti-inflammatory drops were used in 7 of 11 cases, and dorzolamide was used in one case. CONCLUSION: Full-thickness macular holes can develop in eyes without the presence of vitreomacular traction. Topical therapy without vitrectomy may be particularly helpful in closure of full-thickness macular holes with associated cystoid macular edema. Holes with a lamellar hole component may spontaneously resolve as part of a retinal remodeling process.

The microbiological spectrum, antimicrobial resistance pattern, and visual outcomes of endogenous endophthalmitis in West Virginia 2009-2019.

PURPOSE: To report the microbiological spectrum, antimicrobial resistance patterns, and visual outcomes in patients with endogenous endophthalmitis (EE). METHODS: This was a retrospective study of 50 patients with culture-positive EE managed in a tertiary referral center between October 2009 and 2019. Clinical, microbiology analysis, and antimicrobial resistance were reviewed. A multivariable linear regression analysis was used for identifying risk factors associated with worse visual outcomes. RESULTS: Fifty organisms were identified, 62% bacterial and 38% fungal. The most common bacterial organism was Staphylococcus aureus (75% methicillin resistant), and Candida was the most common fungal species. Multidrug resistance was observed in methicillin-resistant Staphylococcus aureus (MRSA) isolates against clindamycin, daptomycin, and fluoroquinolones. The distributions of the final visual acuity (VA) between the bacterial and fungal groups were significantly different, and the visual outcomes in the bacterial group tended to be worse (p = 0.01). The distributions of enucleation status were significantly higher in bacterial EE (35%) than fungal EE (5.3%) (p = 0.02). Results from the multivariable linear regression analysis revealed that older age was significantly associated with worse visual outcome (coef = 0.03; p = 0.02), while fungal infections were associated with better outcomes (coef = - 0.87; p = 0.01). Intravenous drug use (coef = 0.87; p = 0.054) was a marginally significant factor associated with worse visual outcomes. CONCLUSION: There was a higher prevalence of bacterial organisms than fungal species among EE. Bacterial EE was associated with worse visual outcomes and higher enucleation rates than fungal EE. Multidrug resistance was prevalent among MRSA isolates. Older age and intravenous drug use may be factors associated with poor prognosis.

Mortality risk associated with endophthalmitis in West Virginia.

PURPOSE: To explore how endophthalmitis presented from 2009 to 2019 in a West Virginia population particularly affected by the national opioid crisis. The analysis explores the relationship between the type of endophthalmitis and mortality, accounting for factors including age, gender, type of organism, and intravenous drug use (IVDU). METHODS: The electronic health record of West Virginia University (WVU) Medicine was queried for all patients managed for endophthalmitis from October 2009 to October 2019. For each of the included subjects, age, gender, history of IVDU, culture results, concomitant endocarditis, type of endophthalmitis, and the date of diagnosis were extracted. Mortality data were obtained from WVU's electronic medical record, the Social Security Death Index, and public obituaries. Mortality results were represented by a Kaplan-Meier Survival curve following each patient for one year from the date of diagnosis. Results were analyzed using unadjusted and adjusted Cox Proportional Hazard models. RESULTS: One-year mortality was 14 out of 113 endogenous cases (12.4%) compared to 6 out of 173 exogenous cases (3.5%). Endogenous endophthalmitis cases had significantly higher mortality than exogenous ones within one year of diagnosis (p = 0.0034). The unadjusted Cox proportional hazards model revealed that the type of endophthalmitis (endogenous vs. exogenous) was the only variable with a significant impact on 1-year mortality with a hazard ratio of 3.78 (p = 0.01). However, the hazard ratio for endogenous infections rose to 10.91 (CI 3.544-33.595) when the other variables of age, gender, organism, and IVDU were controlled (p < 0.01). The Cox proportional hazard ratios for age group, gender, organism type, and history of IVDU were not significantly different when adjusted for all other variables. CONCLUSION: Endogenous cases, which were significantly overrepresented in West Virginia, were associated with a significantly higher 1-year mortality rate than the exogenous ones. Age, gender, organism type, and history of IVDU have less, if any, modifying effect on mortality.

New Insights Into Pentosan Polysulfate Maculopathy.

BACKGROUND AND OBJECTIVE: To provide new insights into toxic maculopathy secondary to pentosan polysulfate (PPS) utilizing multimodal testing. PATIENTS AND METHODS: Retrospective case-series of four patients from two academic centers evaluated with multimodal imaging, electrophysiology, dark adaptometry (DA), and genetic testing. RESULTS: Median age was 58 years, exposure to PPS was 18.5 years, and cumulative dose of was 2,025 grams. Seven of eight eyes had visual acuity of 20/40 or better. Optical coherence tomography (OCT) angiography demonstrated increased choriocapillaris flow voids (54.25%) in cases compared to controls (13.2%). Two subjects had abnormal foveal avascular zone configurations. Two subjects demonstrated collapse of the retinal pigment epithelium nodular excrescences and progressive retinal thinning over 4 to 5 years on OCT. Electrophysiology was normal (3/3 patients), but DA was delayed (2/2 patients). CONCLUSIONS: The authors describe novel findings of PPS maculopathy, including flow voids in the choriocapillaris. Progressive retinal thinning may suggest a secondary retinal effect. These findings may improve understanding of the pathophysiology. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:13-22.].

Syphilitic retinitis presentations: punctate inner retinitis and posterior placoid chorioretinitis.

PURPOSE: To describe two distinct presentations of syphilitic fundus features in a series of patients with ocular syphilis. METHODS: This is a retrospective, interventional case series of 22 eyes from 16 serology confirmed cases. Clinical examination, fluorescein angiography, and optical coherence tomography were performed at presentation and following high-dose intravenous penicillin G. RESULTS: In our cohort, the mean age was 47.6 years (range 24-59 years) and 14 patients were male (87.5%), 11 patients were positive for human immunodeficiency virus (68.8%), and 6 had bilateral involvement (37.5%). Mean best-corrected visual acuity improved from 0.99 ± 0.79 logarithm of the minimal angle of resolution (LogMAR) at the time of presentation to 0.29 ± 0.36 LogMAR on final visit (P < 0.01). Posterior segment examinations in eyes with retinitis showed two distinct types (1) discrete, placoid lesions in the macula consistent with acute syphilitic posterior placoid chorioretinitis or (2) punctate inner retinitis with corresponding fluorescein pooling in a segmental pattern. These findings rapidly resolved after antibiotic therapy. CONCLUSION: In the era of resurgence, ocular syphilis may present with two phenotypes of discrete retinal lesions. Recognition of the characteristic ocular features may help make the diagnosis and monitor treatment response.

Incidence of Drug Use-Related Endogenous Endophthalmitis Hospitalizations in the United States, 2003 to 2016.

Importance: Complications arising from the nationwide opioid epidemic led to an increase in health care use. Few studies have investigated whether this is reflected in hospital admissions for endogenous endophthalmitis. Objective: To report changing trends in epidemiology, risk factors, hospital course, and costs associated with drug use-related endogenous endophthalmitis hospitalizations in the United States from 2003 to 2016. Design, Setting, and Participants: Nationwide, retrospective cross-sectional study using the National Inpatient Sample. A total of 56 839 patients admitted with a diagnosis of endogenous endophthalmitis were included. Data were analyzed between 2003 and 2016. Exposures: Inpatient admission for endogenous endophthalmitis during the years 2003 to 2016. Main Outcomes and Measures: The Nationwide Inpatient Sample was queried to identify all inpatient admissions with a diagnosis of endogenous endophthalmitis in the United States between the years 2003 and 2016. Analyses were performed to identify national and regional trends in incidence and prevalence of associated infectious and noninfectious comorbidities in patients with or without a history of drug dependence or use. Median and cumulative inflation-adjusted costs for admissions were calculated. Results: Of all patients, 55.6% were White, 13.6% were Black, and 10.6% were Hispanic. There were an estimated 56 839 endogenous endophthalmitis-related hospitalizations; 13.7% of these patients (n = 7783) had a history of drug dependence or use. The drug-using population was significantly younger (49.6 vs 57.5 years; difference, 7.9; 95% CI, 6.93-8.88; P < .001) and more likely to be male (61.8% [n = 35 127] vs 49.0% [n = 21 712]; difference, 12.8%; 95% CI, 11.6%-14.0%; P < .001). The incidence of endogenous endophthalmitis associated with drug dependence or use increased from 0.08 per 100 000 in 2003 to 0.32 per 100 000 population in 2016 across all 4 US geographic regions. Conclusions and Relevance: A 4-fold increase in drug use-related endogenous endophthalmitis hospitalizations was observed in the United States from 2003 to 2016, resulting in substantial health care use burden. These findings support the hypothesis that clinicians should maintain a high index of suspicion for endophthalmitis when evaluating patients with intraocular inflammation in the setting of drug dependence or use.

Subepithelial Corneal Deposits Associated with Exemestane.

This is a case report of corneal deposits noted in a 69-year-old female patient taking the aromatase inhibitor, exemestane, after undergoing a mastectomy and chemotherapy for breast cancer. The patient presented to our eye clinic for a new-onset floater in one eye, and bilateral subepithelial opacities were found incidentally on exam. The patient completed a 5-year course of the medication shortly after her initial visit with us and was noted to have a slight improvement in the density of the opacities on a follow-up visit 3 months later. We believe these corneal changes were most likely secondary to exemestane. The effect of aromatase inhibitors on the eye deserves further exploration as an increasing number of patients are prescribed these medications.

Trends in Infantile Endogenous Endophthalmitis Hospitalizations in the United States: An Analysis from 2007 through 2014 Using the National Inpatient Sample.

PURPOSE: To determine the annual change in incidence of neonatal and infantile endogenous endophthalmitis in the United States between 2007 and 2014 and identify associated risk factors for development of endophthalmitis and mortality. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Neonates (<28 days; n = 1650) hospitalized for endogenous endophthalmitis between 2003 and 2014 and infants (age range, 28 days-1 year; n = 1850) hospitalized between 2007 and 2014 across United States community hospitals were analyzed. METHODS: The Nationwide Inpatient Sample database was queried to identify neonates hospitalized for endogenous endophthalmitis between 2003 and 2014 and infants hospitalized between 2007 and 2014 across the United States. National and regional incidence of neonatal and infantile endogenous endophthalmitis and comorbidities as well as risk factors in the development of the disease and predictive factors for mortality from the years 2007 through 2014 were calculated. MAIN OUTCOMES AND MEASURES: National incidence, regional incidence, and risk factors for development of neonatal and infantile endogenous endophthalmitis. RESULTS: The rate of decline in incidence of neonatal endogenous endophthalmitis was 4% from 2003 through 2014. The rate of decline in the infantile population was 7% from 2007 through 2014. In 2007, an estimated 291 total cases of infantile endophthalmitis were identified, in comparison with 140 cases in 2014. Comorbidities prevalent in the endophthalmitis population included prematurity, respiratory disorders, perinatal infections, and retinopathy of prematurity (ROP). Significant positive predictors for the development of endogenous endophthalmitis based on multivariate logistic regression were perinatal infections, candidemia, bacteremia, very low birth weight, prematurity, respiratory disorders, and ROP. Descriptive analyses showed that the in-hospital mortality rate for patients identified with endophthalmitis was 1.55% in comparison with infants without endophthalmitis. CONCLUSIONS: The incidence of endogenous endophthalmitis declined in both the neonatal and infantile population from 2007 through 2014. Odds of endogenous endophthalmitis were higher for premature and low-birthweight infants and those identified with perinatal infections, candidemia, bacteremia, respiratory disorders, or ROP. These findings are consistent with the decline observed in pediatric infectious disease-related hospitalizations in general.

Transient mydriasis in toxoplasmosis retinochoroiditis.

PURPOSE: To report a case of transient anisocoria and mydriasis in a 14 year old boy with toxoplasmosis retinochoroiditis. OBSERVATION: The patient presented with panuveitis and mydriasis which persisted for 18 days and spontaneously resolved. CONCLUSIONS AND IMPORTANCE: Mydriasis is a rare potential neurological manifestation of toxoplasmosis retinochoroiditis. Clinicians should be aware of this rare cause of anisocoria.

Acute Vascular Ischemic Events in Patients With Central Retinal Artery Occlusion in the United States: A Nationwide Study 2003-2014.

PURPOSE: Central retinal artery occlusion (CRAO) confers a high risk of acute vascular ischemic events, including stroke and myocardial infarction (MI). Understanding the burden and risk factor profile of these ischemic events can serve as a valuable guide for ophthalmologists in the management and appropriate referral of these patients. DESIGN: Retrospective cross-sectional study. METHODS: The Nationwide Inpatient Sample (NIS) was queried to identify all inpatient admissions with a diagnosis of CRAO in the United States between the years 2003 and 2014. The primary outcome measure was the incidence of in-hospital acute vascular ischemic events. RESULTS: There were an estimated 17 117 CRAO inpatient admissions. The mean age was 68.4 ± 0.1 years and 53% of patients were female. The incidence of in-hospital stroke and acute MI were 12.9% and 3.7%. The incidence of stroke showed an increasing trend over the years, almost doubling in 2014 in comparison to 2003 (15.3% vs 7.7%). The combined risk of in-hospital stroke, transient ischemic attack, acute MI, or mortality was 19%. Female sex, hypertension, carotid artery stenosis, aortic valve disease, smoking, and alcohol dependence or abuse were positive predictors of in-hospital stroke. CONCLUSION: There is a significant burden of vascular risk factors, associated with an increased risk of in-hospital stroke, acute MI, and death in CRAO patients. The risk of CRAO-associated stroke is highest in women and in those with a history of hypertension, carotid artery stenosis, aortic valve disease, smoking, or alcohol abuse.

Astrocyte-specific DJ-1 overexpression protects against rotenone-induced neurotoxicity in a rat model of Parkinson's disease.

DJ-1 is a redox-sensitive protein with several putative functions important in mitochondrial physiology, protein transcription, proteasome regulation, and chaperone activity. High levels of DJ-1 immunoreactivity are reported in astrocytes surrounding pathology associated with idiopathic Parkinson's disease, possibly reflecting the glial response to oxidative damage. Previous studies showed that astrocytic over-expression of DJ-1 in vitro prevented oxidative stress and mitochondrial dysfunction in primary neurons. Based on these observations, we developed a pseudotyped lentiviral gene transfer vector with specific tropism for CNS astrocytes in vivo to overexpress human DJ-1 protein in astroglial cells. Following vector delivery to the substantia nigra and striatum of adult Lewis rats, the DJ-1 transgene was expressed robustly and specifically within astrocytes. There was no observable transgene expression in neurons or other glial cell types. Three weeks after vector infusion, animals were exposed to rotenone to induce Parkinson's disease-like pathology, including loss of dopaminergic neurons, accumulation of endogenous α-synuclein, and neuroinflammation. Animals over-expressing hDJ-1 in astrocytes were protected from rotenone-induced neurodegeneration, and displayed a marked reduction in neuronal oxidative stress and microglial activation. In addition, α-synuclein accumulation and phosphorylation were decreased within substantia nigra dopaminergic neurons in DJ-1-transduced animals, and expression of LAMP-2A, a marker of chaperone mediated autophagy, was increased. Together, these data indicate that astrocyte-specific overexpression of hDJ-1 protects neighboring neurons against multiple pathologic features of Parkinson's disease and provides the first direct evidence in vivo of a cell non-autonomous neuroprotective function of astroglial DJ-1.

Moxifloxacin Concentration and Proteomic Analysis of Aqueous Humor in Human Uveitis Associated with Oral Moxifloxacin Therapy.

PURPOSE: The aim was to report the aqueous humor moxifloxacin concentration and proteome profile of an individual with bilateral uveitis-like syndrome with pigment dispersion. METHODS: Multiple reactions monitoring mass spectrometry quantified the aqueous concentration of moxifloxacin in the affected individual. Shotgun proteomic analysis performed via liquid chromatography tandem mass spectrometry (LC-MS/MS) defined the protein profile in the affected individual and unaffected control samples. RESULTS: Moxifloxacin was present at higher than expected levels in aqueous humor 18 days following oral administration. One-third of the proteins were identified by significantly lower spectral counts in the aqueous of the individual with moxifloxacin associated uveitis compared to the unaffected control. CONCLUSION: Moxifloxacin was detected in aqueous humor 18 days following the completion of oral administration. These results suggest that moxifloxacin toxicity may be responsible for the uveitis-like syndrome with pigment dispersion syndrome induced by moxifloxacin therapy.

Uveitis and Systemic Inflammatory Markers in Convalescent Phase of Ebola Virus Disease.

We report a case of probable Zaire Ebola virus-related ophthalmologic complications in a physician from the United States who contracted Ebola virus disease in Liberia. Uveitis, immune activation, and nonspecific increase in antibody titers developed during convalescence. This case highlights immune phenomena that could complicate management of Ebola virus disease-related uveitis during convalescence.

Human papilloma virus vaccine associated uveitis.

PURPOSE: To report a possible association between human papilloma virus (HPV) vaccination and uveitis. METHODS: Spontaneous reports from the National Registry of Drug-Induced Ocular Side effects, World Health Organization and Food and Drug Administration were collected on uveitis associated with human papilloma virus vaccination. A MEDLINE search was performed using keywords "uveitis," "iritis," "iridocyclitis," "human papilloma virus," "Cervarix", and "Gardasil." MAIN OUTCOME MEASURES: Data garnered from spontaneous reports included the age, gender, adverse drug reaction (ADR), date of administration, concomitant administration of other vaccinations, time until onset of ADR, other systemic reactions, and dechallenge and rechallenge data. RESULTS: A total of 24 case reports of uveitis associated with human papilloma virus vaccination were identified, all cases were female, and the median age was 17. Median time from HPV vaccination to reported ADR was 30 days (range 0-476 days). DISCUSSION: According to World Health Organization criteria, the relationship between human papilloma virus vaccination and uveitis is "possible." Causality assessments are based on the time relationship of drug administration, uveitis development and re-challenge data. CONCLUSIONS: Clinicians should be aware of a possible bilateral uveitis and papillitis following HPV vaccination.

Biologic agents in experimental autoimmune uveitis.

Experimental uveitis models were developed in an effort to elucidate the pathogenesis of human uveitis. The therapeutic effects of numerous anti-inflammatory agents including corticosteroids and immunomodulatory agents including biologic response modifiers have been investigated in both experimental and human uveitis. Monoclonal antibodies to tumor necrosis factor alpha and anti-interleukins, among others, demonstrate efficacy and are employed in the treatment of uveitis refractory to conventional immunomodulatory agents.