Cytomegalovirus (CMV) retinitis is an opportunistic infection that has traditionally affected those who have HIV/AIDS or immunosuppressed individuals. CMV retinitis previously infected one-third of AIDS patients in the pre-highly active antiretroviral therapy (HAART) era, but since HAART, Western countries have seen an 80% decrease in the incidence of the disease. More recently, CMV retinitis has been reported in patients who are immunosuppressed, often due to chemotherapy or immunomodulatory medications. The diagnosis of CMV retinitis is often suspected based on clinical findings, with polymerase chain reaction for confirmation of CMV, especially in atypical cases. Highly active antiretroviral therapy and anti-CMV medications (systemic or local) remain the mainstay of treatment. However, for those who are not responsive to HAART, CMV retinitis remains a challenge, and can still lead to significant vision loss. Moreover, a regimen of anti-CMV medications can sometimes lead to viral resistance or organ toxicity. Complications such as immune recovery retinitis and rhegmatogenous retinal detachments continue to threaten the vision of patients who develop CMV retinitis. These complications can arise following initiation of treatment or if patients show disease progression. Proper vision screening for CMV retinitis in immunosuppressed patients at-risk is necessary for early detection and treatment.

To determine whether the addition of an unbiased test, metagenomic sequencing of intraocular fluid, compared to standard-of-care diagnostics alone, leads to better patient outcomes in presumed infectious intraocular inflammatory eye diseases. A randomized controlled trial was conducted from May 2022 through February 2024. Eligible participants had intraocular inflammation concerning for an infectious etiology, were 18 years or older, and had vision better than no light perception (NLP). This study enrolled participants at 6 tertiary referral eye centers in the United States (5 sites) and Thailand (1 site). Participants were randomized to have their physician have access to deep sequencing results or not. The main outcomes were (1) clinical improvement on examination at 4 weeks after randomization and (2) appropriate therapy administered by the treating physician as determined by an independent expert panel. Among the 100 participants enrolled (median [IQR] age, 62.0 [47.5-71.0] years; 57 [57.0%] were women), 92 participants completed the study. Forty-one (41.0%) participants had resolution of inflammation at their 2-week follow-up and 23 (23.0%) participants had a pathogen identified with routine diagnostics and exited the study. Twenty-one (21.0%) participants met the criteria for randomization. At the primary endpoint, 8 (88.9%) patients in the metagenomic sequencing group had clinical improvement compared to 7 (63.6%) patients in the no metagenomic sequencing group (risk difference, 30% [95% CI: 0.6%-59.1%]; relative risk [RR] = 1.35 [95% CI: 1.01-1.81]; P = 0.045). Eight (88.9%) patients were considered to receive the appropriate therapy in the metagenomic sequencing group compared to 11 (100%) patients in the no metagenomic sequencing group (risk difference, -12.0% [95% CI: -38.0%-14.0%]; RR = 0.89 [95% CI: 0.68-1.15]; P = .37). There were 3 nonstudy related adverse events. Having access to metagenomic sequencing results modestly improved clinical outcomes in a subset of patients with suspected intraocular infections. Larger studies are needed to determine the long-term impact on management and clinical outcomes. https://clinicaltrials.gov/ct2/show/NCT05286203.

Introduction: Vogt–Koyanagi–Harada (VKH) syndrome is an inflammatory condition characterized by bilateral, granulomatous panuveitis with or without systemic manifestations, and accounts for up to 18% of referrals for panuveitis at tertiary centers in the United States of America. Despite ongoing research, there is limited evidence and no clear consensus on how to diagnose and treat patients with VKH, leading to variations in practice patterns among uveitis specialists.Methods: An anonymous, online survey was distributed to uveitis specialists in the American Uveitis Society (AUS). The survey included 21 questions that asked for non-identifiable demographics and covered topics such as preferred imaging modalities, treatment for the first episode of VKH, and perceived efficacy of immunomodulatory therapy (IMT).Results: A total of 104 surveys were included for analysis, representing a 38.4% response rate from the AUS listserv. A majority of respondents were uveitis fellowship trained and practiced in North America in an academic setting. Fluorescein angiography and enhanced depth imaging with optical coherence tomography were rated as the most consistently useful methods for the diagnosis of VKH. For treatment of acute initial-onset VKH, responses were divided between a preference for high-dose systemic corticosteroids with IMT (61.5%) and without IMT (37.5%). Methotrexate and mycophenolate mofetil were the most common IMTs to be used as first-line therapies, but adalimumab and infliximab were perceived to be the most effective for the treatment for VKH.Discussion: While there are some common trends in the practice patterns for the diagnosis and treatment of patients with VKH, there was no clear consensus on the topic of IMT. There was a slight preference among uveitis specialists to use both IMT and systemic corticosteroids for the first episode of acute VKH.

Purpose: To evaluate clinical trials in the literature that focus on suprachoroidal drug delivery for the treatment of noninfectious uveitis and other posterior segment diseases. Methods: A synthesis of the literature was performed. Results: In 2021, suprachoroidal space triamcinolone acetonide, a corticosteroid delivery system used for the treatment of uveitic macular edema (ME), was approved by the US Food and Drug Administration. The drug-delivery system targets the suprachoroidal space using a microneedle-based device and has a favorable pharmacokinetic profile. Suprachoroidally administered investigational therapies have also been assessed in clinical trials for other posterior segment diseases, including diabetic ME, retinal vein occlusion, age-related macular degeneration, and choroidal melanoma. Conclusions: The safety and efficacy of suprachoroidal corticosteroid injections to treat uveitic ME have been shown in recent phase III clinical trials. Multiple programs are also investigating this modality of drug delivery for use in many other retinal and choroidal pathologies.