Peripheral ulcerative keratitis associated with tralokinumab therapy: a case report and review of IL-13 inhibitor-associated ocular surface disease.

BACKGROUND: Dupilumab and tralokinumab are interleukin-binding monoclonal antibodies used to treat systemic atopic disease. Use of these medications in management of atopic dermatitis (AD) is known to cause conjunctivitis. Dupilumab therapy has also been associated with more severe ocular surface disease, which has not previously been described in association with tralokinumab. This report describes a case of tralokinumab-associated conjunctivitis and peripheral ulcerative keratitis and reviews the spectrum and proposed mechanisms of ocular surface disease triggered by these medications. CASE PRESENTATION: A 61-year-old male with no rheumatologic or ocular history presented with bilateral papillary conjunctivitis and right eye peripheral ulcerative keratitis (PUK). PUK was arrested using oral corticosteroids and doxycycline, and long-term control of papillary conjunctivitis was achieved using topical tacrolimus ointment, allowing continuation of effective AD management with tralokinumab. CONCLUSION: This case report documents ulcerative keratitis occurring in association with tralokinumab therapy for AD, which has previously been described with dupilumab but not tralokinumab. This report demonstrates the need for vigilant ocular surface monitoring for patients on tralokinumab and illustrates successful management and long-term control of adverse ocular events associated with this medication.

Association of Metformin With the Development of Age-Related Macular Degeneration.

Importance: Age-related macular degeneration (AMD) is a leading cause of blindness with no treatment available for early stages. Retrospective studies have shown an association between metformin and reduced risk of AMD. Objective: To investigate the association between metformin use and age-related macular degeneration (AMD). Design, Setting, and Participants: The Diabetes Prevention Program Outcomes Study is a cross-sectional follow-up phase of a large multicenter randomized clinical trial, Diabetes Prevention Program (1996-2001), to investigate the association of treatment with metformin or an intensive lifestyle modification vs placebo with preventing the onset of type 2 diabetes in a population at high risk for developing diabetes. Participants with retinal imaging at a follow-up visit 16 years posttrial (2017-2019) were included. Analysis took place between October 2019 and May 2022. Interventions: Participants were randomly distributed between 3 interventional arms: lifestyle, metformin, and placebo. Main Outcomes and Measures: Prevalence of AMD in the treatment arms. Results: Of 1592 participants, 514 (32.3%) were in the lifestyle arm, 549 (34.5%) were in the metformin arm, and 529 (33.2%) were in the placebo arm. All 3 arms were balanced for baseline characteristics including age (mean [SD] age at randomization, 49 [9] years), sex (1128 [71%] male), race and ethnicity (784 [49%] White), smoking habits, body mass index, and education level. AMD was identified in 479 participants (30.1%); 229 (14.4%) had early AMD, 218 (13.7%) had intermediate AMD, and 32 (2.0%) had advanced AMD. There was no significant difference in the presence of AMD between the 3 groups: 152 (29.6%) in the lifestyle arm, 165 (30.2%) in the metformin arm, and 162 (30.7%) in the placebo arm. There was also no difference in the distribution of early, intermediate, and advanced AMD between the intervention groups. Mean duration of metformin use was similar for those with and without AMD (mean [SD], 8.0 [9.3] vs 8.5 [9.3] years; P = .69). In the multivariate models, history of smoking was associated with increased risks of AMD (odds ratio, 1.30; 95% CI, 1.05-1.61; P = .02). Conclusions and Relevance: These data suggest neither metformin nor lifestyle changes initiated for diabetes prevention were associated with the risk of any AMD, with similar results for AMD severity. Duration of metformin use was also not associated with AMD. This analysis does not address the association of metformin with incidence or progression of AMD.

Redefining the Spectrum of Pentosan Polysulfate Retinopathy: Multimodal Imaging Findings from a Cross-Sectional Screening Study.

PURPOSE: There is growing evidence of a direct association between pentosan polysulfate (PPS) therapy and the development of macular changes. Using standardized visual acuity (VA) testing and multimodal imaging, we investigated the impact of PPS therapy on vision and described an expanded spectrum of imaging findings among PPS users. DESIGN: Cross-sectional screening study. PARTICIPANTS: Thirty-nine patients who were current or recent users of PPS. METHODS: The participants underwent a brief eye examination and answered a comprehensive medical and ophthalmic history questionnaire. Color fundus photography, fundus autofluorescence (FAF), and spectral-domain OCT (SD-OCT) were performed. The images were evaluated by expert graders at Wisconsin Reading Center. Abnormalities were categorized as definite toxicity (DT) if seen on both FAF and SD-OCT and as questionable toxicity (QT) if seen on either FAF or SD-OCT. MAIN OUTCOME MEASURES: ETDRS and Snellen VA, the dosage and duration of PPS exposure, and the prevalence of retinal toxicity on imaging. RESULTS: The mean ETDRS and Snellen VA of the study cohort were 85 letters and 20/22, respectively. The mean PPS daily dose was 282 mg (range, 88-400 mg), whereas the mean cumulative dose was 915 g (range, 19-3650 g) over a mean period of 8.8 years (range, 2 months-25 years). There was evidence of retinopathy in 41% of the eyes; DT was identified in 24 eyes (31%) and QT in 8 eyes (10%). Retinal pigment epithelium (RPE) abnormalities (thickening or thinning or both) were present in all eyes with DT. Retinal pigment epithelium atrophy was seen in 7 eyes (9%). In addition to well-established findings, the unique SD-OCT features of this cohort included interdigitation zone abnormalities and the presence of a flying saucer-type defect. Fundus autofluorescence abnormalities were seen in 24 eyes (30.8%), with 20 (66.7%) of these exhibiting abnormalities located outside the central subfield and extending beyond the arcades. CONCLUSIONS: Findings from the masked grading of multimodal imaging at a centralized reading center suggest a wider phenotypic spectrum of structural abnormalities among patients taking PPS. Macular changes selectively involve the RPE and outer retina, with a range of findings often seen beyond the arcades. The subtle and atypical findings in this cohort should prompt clinicians to consider lowering the threshold for diagnosing PPS retinopathy.

Investigating skin age analysis to reduce tanning intentions among adolescents: A pilot study.

As skin cancer rates continue to rise, targeted efforts to reduce excessive exposure to ultraviolet radiation are crucial. Adolescents are a high-risk population for intentional tanning; thus, we sought to determine whether the novel use of skin age analysis with ultraviolet (UV) photography would be an effective tool for reducing intentions to tan in adolescents with a calculated skin age (measured by complexion analysis software) that exceeds their actual age. Surveying 85 students in this study, skin age difference above zero was associated with reduced intentions to tan (P = 0.006) and high-risk sun exposure behaviors were identified. This provides rationale for skin age analysis as a potentially effective intervention in decreasing intentions to tan in this high-risk young population.