Ocular adverse events associated with chimeric antigen receptor T-cell therapy: a case series and review.

BACKGROUND/AIMS: Chimeric antigen receptor T-cell (CAR T) therapy has been shown to improve the remission rate and survival for patients with refractory haematological malignancies. The aim of this study is to describe ocular adverse effects associated with CAR T therapy in patients with haematological malignancies. METHODS: This is a retrospective, single-institution, case series. Patients aged 18 years or older who received standard of care CAR T therapy for relapsed/refractory large B-cell lymphoma with a documented ophthalmic evaluation were included. The primary outcome was clinician ophthalmic examination findings. RESULTS: A total of 66 patients received CAR T-cell therapy from February 2018 to October 2019 with 11 receiving an ophthalmic examination. Eleven patients (n=22 eyes) who received CAR T-cell therapy were included in review. The median time from CAR T-cell infusion date to ocular examination was 57.5 days. The median patient age at the time of examination was 60.5 years. Ten patients had subjective symptoms prompting ophthalmic examination. Two patients reported floaters and photopsias. One patient had worsening ocular graft-versus-host disease. Two patients were identified with possible reactivation of viral infections, including herpes zoster ophthalmicus and regressing acute retinal necrosis. CONCLUSIONS: The increasing use of CAR T therapy for malignancies underscores the importance of ophthalmologists and oncologists understanding the potential toxicities associated with its use, particularly ocular toxicities and when to refer for an ophthalmic examination.

Automated Retroillumination Photography Analysis for Objective Assessment of Fuchs Corneal Dystrophy.

PURPOSE: Retroillumination photography analysis is an objective tool for the assessment of the number and distribution of guttae in eyes affected with Fuchs corneal dystrophy (FCD). Current protocols include manual processing of images; here, we assess validity and interrater reliability of automated analysis across various levels of FCD severity. METHODS: Retroillumination photographs of 97 FCD-affected corneas were acquired, and total counts of guttae were previously summated manually. For each cornea, a single image was loaded into ImageJ software. We reduced color variability and subtracted background noise. Reflection of light from each gutta was identified as a local area of maximum intensity and counted automatically. Noise tolerance level was titrated for each cornea by examining a small region of each image with automated overlay to ensure appropriate coverage of individual guttae. We tested interrater reliability of automated counts of guttae across a spectrum of clinical and educational experience. RESULTS: A set of 97 retroillumination photographs was analyzed. Clinical severity as measured by a modified Krachmer scale ranged from a severity level of 1 to 5 in the set of analyzed corneas. Automated counts by an ophthalmologist correlated strongly with Krachmer grading (R = 0.79) and manual counts (R = 0.88). Intraclass correlation coefficients demonstrated strong correlation at 0.924 (95% CI, 0.870-0.958) among cases analyzed by 3 students, and 0.869 (95% CI, 0.797-0.918) among cases for which images were analyzed by an ophthalmologist and 2 students. CONCLUSIONS: Automated retroillumination photography analysis allows for grading of FCD severity with high resolution across a spectrum of disease severity.

Retroillumination Photography Analysis Enhances Clinical Definition of Severe Fuchs Corneal Dystrophy.

PURPOSE: Retroillumination photography analysis (RPA) provides an objective assessment of the number and distribution of guttae in Fuchs corneal dystrophy. Here, we assess its correlation with clinical grading using slit-lamp biomicroscopy across varying levels of severity. METHODS: Retroillumination photographs were conducted for 95 affected corneas with slit-lamp flash photography after pupillary dilation. Individual guttae were counted manually and the position of individual points recorded. Clinical grading using the Krachmer scale was documented for each eye during examination, and regression analyses were performed to identify the strength of association with number of guttae. We assessed range at each stage of clinical grading and used the Mann-Whitney U test to assess whether clinical grading levels demonstrated successively higher numbers of guttae. RESULTS: Krachmer score ranged from 1 to 5, with mean of 2.6. Mean numbers of guttae at each level of severity were 289 (1+), 999 (2+), 2669 (3+), 5474 (4+), and 7133 (5+). Each stage demonstrated significantly higher numbers of guttae than its preceding level except from 4+ to 5+ (P = 0.30), consistent with the definition of 4+ as the highest level defined by the presence of guttae. Higher levels of clinical grading were associated with larger ranges of guttae (P < 0.01). A linear regression model resulted in a strong fit between RPA and Krachmer score (r = 0.81). CONCLUSIONS: In this largest study of RPA data and comparison with subjective clinical grading of Fuchs dystrophy severity, RPA correlates strongly and demonstrates enhanced definition of severity at advanced stages of disease.