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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.

Abstract Background The antimetabolites methotrexate (MTX) and mycophenolate mofetil (MMF) are commonly used as initial corticosteroid-sparing treatment for uveitis. There is little data examining risk factors for failing both MTX and MMF. The objective of this study is to determine risk factors for failing both MTX and MMF in patients with non-infectious uveitis. Main body This is a sub-analysis of the First-line Antimetabolites as Steroid-sparing Treatment (FAST) uveitis trial, which was an international, multicenter, block-randomized, observer-masked, comparative effectiveness trial comparing MTX and MMF as initial treatments for non-infectious uveitis. This study was undertaken at multiple referral centers in India, the United States, Australia, Saudi Arabia and Mexico between 2013 and 2017. A total of 137 patients who completed all 12 months of follow-up from the FAST trial, were included in this study. The primary outcome was failing both antimetabolites over the 12 months of the trial. Potential predictors included: age, sex, bilateral involvement, anatomic location of the uveitis, presence of cystoid macular edema (CME) and retinal vasculitis at baseline visit, uveitis duration, and country/study sites as risk factors for failing both MTX and MMF. The presence of retinal vasculitis posterior to the equator on fluorescein angiogram was associated with failing both MTX and MMF. Conclusion Retinal vasculitis may be a risk factor for failing multiple antimetabolites. Clinicians could consider more quickly advancing these patients to other medication classes, such as biologics.

Purpose: To describe a case of unilateral Acanthamoeba-associated retinitis in the absence of concomitant corneal infection in an immunocompetent host without risk factors. Observations: A 37-year-old woman presented with unilateral multifocal retinitis with minimal vitritis. Anterior segment was normal. Conventional diagnostics of bacterial, fungal, viral, Toxoplasma and Toxocara etiologies all returned negative. Empiric treatments were unsuccessful, including oral valacyclovir, oral fluconazole, as well as intravitreal injection of vancomycin and ceftazidime. Metagenomic deep sequencing (MDS) identified Acanthamoeba genomic fragments in the vitreous sample. Multiple intravitreal voriconazole injections were performed and achieved partial suppression of lesion growth. Subsequent dual therapy of oral voriconazole and trimethoprim-sulfamethoxazole led to resolution of the lesions and vision improvement without further injections. Conclusions and importance: This is an unusual case of unilateral Acanthamoeba-associated retinitis without concomitant corneal infection, diagnosed via unbiased DNA and RNA deep sequencing, with other etiologies ruled out by conventional approaches. Treatment with systemic and intravitreal therapy led to a successful resolution of retinitis and vision improvement. Our case demonstrates the potential of MDS as an unbiased diagnostic tool for rare ocular pathogens and the therapeutic effect of oral voriconazole with trimethoprim-sulfamethoxazole for Acanthamoeba intraocular infection.