Vogt-Koyanagi-Harada-like Syndrome Induced by Checkpoint Inhibitor Cemiplimab.

Checkpoint inhibition targeting programmed cell-death protein 1 has demonstrated efficacy for a wide range of indications including cutaneous malignancy. However, immune-related adverse events (irAEs), including infrequent but visually impactful ocular irAEs, require careful consideration of treatment options, including medication withdrawal, local corticosteroids, or rarely immunomodulation. This case presents a 53-year-old woman who developed uveitis and mucous membrane ulcers after treatment for numerous cutaneous neoplasms, primarily squamous cell carcinoma, with the programmed cell-death protein 1 inhibitor cemiplimab. Ophthalmic examination revealed diffuse choroidal depigmentation consistent with a Vogt-Koyanagi-Harada-like syndrome. Topical and periocular steroids were used to treat the intraocular inflammation, and cemiplimab was discontinued. Because of ongoing severe uveitis, systemic corticosteroids and corticosteroid-sparing immunosuppression were initiated. Specifically, azathioprine and methotrexate were introduced, but each was stopped due to side effects, prompting the initiation of adalimumab (ADA) treatment. While ADA controlled intraocular inflammation, the squamous cell carcinomas were noted to progress, resulting in the discontinuation of ADA. However, a uveitis recurrence was observed. After a discussion of risks and benefits of biologic immunosuppressive therapy, including the risk of vision loss, ADA was restarted with successful disease quiescence at a 16-month follow-up. The cutaneous neoplasms were managed with topical and intralesional therapies, such as 5-fluorouracil. Recent dermatologic examinations suggested no new cutaneous lesions. This scenario presents the effective use of ADA in an ocular irAE that balances the management of sight-threatening ocular inflammation with the risk of promoting recurrent or de novo neoplastic disease.

Mycobacterial ocular inflammation: delay in diagnosis and other factors impacting morbidity.

IMPORTANCE: The reported outcomes of ocular mycobacterial infection are commonly unfavorable. This study is among the first to elucidate factors associated with poor outcomes, as well as highlight the continued controversies in therapy, particularly the role of oral corticosteroids. OBJECTIVE: To describe presentations and outcomes of mycobacterial ocular disease in the Midwestern United States. DESIGN Retrospective case series. SETTING: A university-based uveitis clinic. PARTICIPANTS: Twenty-six eyes of 17 patients with mycobacterial ocular inflammatory disease seen at University of Illinois at Chicago from 1995 to 2010. MAIN OUTCOME MEASURES: Bivariate and regression analyses were performed to assess factors associated with delay in referral, relapse, and irreversible visual acuity loss (≤ 20/200). RESULTS: Of 17 patients, 13 had isolated ocular disease, 1 had miliary tuberculosis (TB), 2 had TB lymphadenopathy, and 1 had active pulmonary TB. Fourteen had Mycobacterium tuberculosis and 3 had nontuberculous mycobacterial infection. Chest imaging was consistent with granulomatous disease in 46.7%. Average delay from ocular disease onset to uveitis service referral was 755.3 days. Posterior uveitis and non-Hispanic white race were associated with increased delay. A relapsing course was observed in posterior uveitis (odds ratio [OR], 20.0; 95% CI, 1.39-287; P = .03) and those treated with systemic steroids for eye disease (OR, 10.1; 95% CI,1.60-64.0; P = .01). Disease control was achieved in 81%, although 38.5% had profound visual loss, associated with age older than 50 years and delay in diagnosis. Patients diagnosed after 500 days from initial ocular symptoms were more likely to lose vision (OR, 20.0; 95% CI, 1.41-282; P = .03). CONCLUSIONS: Ocular mycobacterial infection occurs in nonendemic areas and cannot be ruled out with negative chest imaging. Tuberculosis and atypical mycobacterial infection should be in the differential diagnosis of ocular inflammation, regardless of patient ethnicity. Significant delays exist in instituting antimicrobial treatment, associated with increased morbidity. Early referral is necessary for patients not responding appropriately to anti-inflammatory therapy.

Dexamethasone for ocular inflammation.

INTRODUCTION: Corticosteroids, administered systemically and periocularly, have long been used to treat intermediate and posterior segment noninfectious uveitis. In addition to systemic immunosuppressive medications, these therapies are used to reduce inflammation, prevent structural complications and prevent long-term visual loss in patients with uveitis. While systemic immunosuppressive therapies carry their own set of side effects, treatment with local steroids is associated with the risk of development of cataract and glaucoma. AREAS COVERED: Intravitreal delivery of fluocinolone acetonide via a sustained-release implant (Retisert) was approved by the FDA in 2005 for the treatment of noninfectious intermediate and posterior uveitis. Recently, the FDA also approved the biodegradable dexamethasone implant (Ozurdex) for the treatment of noninfectious uveitis involving the posterior segment. EXPERT OPINION: The single injection, 26-week data indicate that the implant is well tolerated and produces meaningful improvements in intraocular inflammation and visual acuity that persist through 6 months. The available 6-month data also indicate that this implant confers much less of a risk of ocular hypertension than other forms of intraocular steroid therapy. However, future longer-term trials are needed to evaluate the efficacy and safety data in patients who receive multiple injections. The newly approved dexamethasone implant, Ozurdex, is a useful addition to our local armamentarium in the treatment of noninfectious intermediate and posterior uveitis given its efficacy, safety, and ease of use in the outpatient setting.