Abstract Refractory inflammatory ocular diseases—uveitic macular edema (UME), acute retinal necrosis (ARN), and vitreoretinal lymphoma (VRL)—pose significant diagnostic and therapeutic challenges due to their vision- or life-threatening nature and limited treatment options. UME, a leading cause of vision loss in intermediate, posterior, and panuveitis, affects approximately 40% of such cases, particularly in elderly patients and those with prolonged inflammation. Despite its prevalence, effective treatment is still being explored. ARN, caused by herpes viruses such as herpes simplex virus (HSV)-1, HSV-2, and varicella-zoster virus, ranks among the retinal diseases with the poorest visual prognosis; nearly half of patients experience a visual acuity (VA) of ≤ 0.1 within six months. However, a standardized treatment regimen has not yet been established. VRL, one of the ocular malignancies with the lowest overall survival rate, is frequently misdiagnosed as uveitis. Given the diagnostic delay and high frequency (60–85%) of central nervous system involvement—which is often directly life-threatening—early detection and comprehensive systemic management are essential. This review highlights recent advances in the diagnosis, clinical trials, and management of these three challenging ocular inflammatory diseases, emphasizing unmet needs and emerging therapeutic strategies.
Takeda et al. (2025) studied this question.