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.

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.

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.

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.

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.

Cytomegalovirus retinitis in immunocompetent patients: case reports and literature review.

PURPOSE: The purpose of this study was to examine 2 cases of cytomegalovirus (CMV) retinitis, occuring in 2 immunocompentent adult patients. METHODS: Case selection and literature review. RESULTS: Both patients cited significantly decreased vision despite systemic, topical, and/or local corticosteroid use. Neither patient was using high-dose immunosuppressant therapy at the time of diagnostic testing. Both patients exhibited confirmed CMV infection via polymerase chain reaction DNA testing. Oral antivirals were employed and have stabilized both patients. CONCLUSION: The cases described herein serve to inform ophthalmologists of the urgent need to include CMV in their differential when encountering an immunocompetent adult with significant comorbidities or with a history of previous exposure. Proper treatment is heavily reliant on proper diagnosis.

Acute unilateral toxoplasma retinochoroiditis associated with adalimumab, a tumor necrosis factor-α antagonist.

PURPOSE: The purpose of this study was to report a case of a patient with unilateral toxoplasma retinochoroiditis while on treatment with adalimumab, an anti-tumor necrosis factor α agent for ulcerative colitis. METHODS: This is a descriptive case report. RESULTS AND DISCUSSION: In addition to the patient with toxoplasma retinochoroiditis, there is one published report of two patients who developed toxoplasma chorioretinitis while on anti-tumor necrosis factor α therapy for rheumatoid arthritis: one was on adalimumab and methotrexate and the other one was on etanercept and methotrexate. CONCLUSION: The authors need to be aware of this potentially vision threatening risk with anti-tumor necrosis factor α therapy.

Bilateral uveitis associated with fluoroquinolone therapy.

CONTEXT: Retrospective case series, database study and literature review. Forty case reports are described. OBJECTIVE: To report a possible association between fluoroquinolones and uveitis. MATERIALS AND 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 systemic fluoroquinolone therapy. A literature review was performed using keywords "uveitis", "fluoroquinolones", and each individual fluoroquinolone name. Additional case reports were collected from the practices of six uveitis subspecialists and one neuro-ophthalmologist. MAIN OUTCOME MEASURES: Data garnered from the reports include the type of fluoroquinolone, age, gender, adverse drug reaction (ADR), dosage, duration of therapy until onset of uveitis, concomitant drugs, systemic disease, dechallenge and rechallenge data. RESULTS: A total of 40 case reports of uveitis associated with fluoroquinolones were identified including 12 men, 27 women, and 1 case in which the gender was not specified. The median age was 54 years. Dosage varied between the different fluoroquinolone drugs, with the median dosage within the range recommended in the package insert for each different fluoroquinolone. Median time from beginning of therapy to appearance of the ADR was 13 days (range 0-20 days). Thirteen patients were 60 years or older, and one patient was taking systemic anti-inflammatory steroids. There were five positive dechallenge case reports. DISCUSSION: According to World Health Organization criteria, the relationship between fluoroquinolone therapy and uveitis is "possible". Causality assessments are based on the time relationship of drug administration, uveitis development, and dechallenge data. CONCLUSIONS: Clinicians should be aware of a possible bilateral fluoroquinolone-associated uveitis, particularly the finding of iris transillumination and pigment dispersion.

Drug-induced graves disease from CTLA-4 receptor suppression.

Monoclonal antibody, ipilimumab, useful for treatment of metastatic melanoma, blocks CTLA-4 mediated T-cell suppression and can also cause a Graves ophthalmopathy like syndrome. Epidemiologic study has linked variant polymorphisms of CTLA-4 receptor gene to the presence of thyroid eye disease. The combination of these observations suggests CTLA-4 mediated T-cell functions are important to the pathogenesis of thyroid-associated eye disease.

Current treatments for radiation retinopathy.

BACKGROUND: to review the currently available therapeutic modalities for radiation retinopathy (RR), including newer investigational interventions directed towards specific aspects of the pathophysiology of this refractory complication. METHODS: a review of the literature encompassing the pathogenesis of RR and the current therapeutic modalities available was performed. RESULTS: RR is a chronic and progressive condition that results from exposure to any source of radiation. It might be secondary to radiation treatment of intraocular tumors such as choroidal melanomas, retinoblastomas, and choroidal metastasis, or from unavoidable exposure to excessive radiation from the treatment of extraocular tumors like cephalic, nasopharyngeal, orbital, and paranasal malignancies. After the results of the Collaborative Ocular Melanoma Study, most of the choroidal melanomas are being treated with plaque brachytherapy increasing by that the incidence of this radiation complication. RR has been reported to occur in as many as 60% of eyes treated with plaque radiation, with higher rates associated with larger tumors. Initially, the condition manifests as a radiation vasculopathy clinically seen as microaneurysms and telangiectases, with posterior development of retinal hard exudates and hemorrhages, macular edema, neovascularization and tractional retinal detachment. Regrettably, the management of these eyes remains limited. Photodynamic therapy, laser photocoagulation, oral pentoxyphylline and hyperbaric oxygen have been attempted as treatment modalities with inconclusive results. Intravitreal injections of anti-vascular endothelial growth factor such as bevacizumab, ranibizumab and pegaptanib sodium have been recently used, also with variable results. DISCUSSION: RR is a common vision threatening complication following radiation therapy. The available therapeutic options are limited and show unsatisfactory results. Further large investigative studies are required for developing better therapeutic as well as preventive treatment strategies.

Local treatment for lymphoid malignancies of the eye.

Lymphoid malignancies may affect the eye either as primary intraocular lymphomas (PIOL), or by secondary involvement of a nodal lymphoma. PIOL is a subtype of primary central nervous system (CNS) lymphoma and in up to 98% of the cases are non-Hodgkin's B cell lymphomas. PIOL may occur in isolation, without involvement of the CNS. They may affect both the vitreous and the retina, while secondary invasion predominantly affects the uvea. Both forms frequently masquerade as intraocular inflammation or uveitis. Systemic chemotherapy, alone or in combination with radiotherapy has been used in the past for the treatment of PIOL. Methotrexate and rituximab are immunomodulatory agents used in the treatment of cancer and autoimmune diseases. Recent reports have shown the intraocular safety and efficacy of both of these agents for the treatment of PIOL.