UC Davis

PURPOSE: To determine whether microstructural retinal changes, tumor features, and apolipoprotein E (APOE) ε4 polymorphism are correlated with clinically detectable treatment-associated cognitive dysfunction (TACD) in patients with lower-grade gliomas. DESIGN: Cohort study. PARTICIPANTS AND CONTROLS: Sixteen patients with lower-grade glioma at a United States academic ophthalmology department between January 2021 and November 2023. Normal controls were recruited from convenient sampling. METHODS: Montreal Cognitive Assessment (MoCA) scores and retinal changes were assessed in 6-month intervals. Apolipoprotein E genotyping was performed, and tumor details were recorded. Partial least-squares discriminant (PLSD) model was established to evaluate the association between TACD with APOE genotype, ophthalmic, and tumor features. MAIN OUTCOME MEASURES: The main outcome measure was cognitive status as measured by the MoCA score and analyzed in relation to ophthalmic measurements, tumor features, and APOE genotype. RESULTS: Median time to first eye examination was 34 months (2-266) from tumor diagnosis and 23 months (0-246) from radiation. Nine patients (56%) had abnormal cognition (MoCA <26/30). Montreal Cognitive Assessment scores were significantly worse in patients with temporal (22 ± 7.2) than frontal lobe tumors (26 ± 3.1, P = 0.02) and those with oligodendrogliomas (22 ± 4.1) than astrocytomas (26 ± 3.6, = 0.02). Patients with TACD had significant radial peripapillary capillary density loss (45% ± 4.6) compared with those with normal cognition (49% ± 2.6, P = 0.02). A PLSD model correlated MoCA scores with retinal nerve fiber thickness, intraocular pressure, foveal avascular zone, best-corrected visual acuity, months since first diagnosis, and tumor pathology (oligodendroglioma or not). Using these features, the model identified patients with TACD with 77% accuracy. Apolipoprotein E genotyping showed: 2 ε2/ε3 (13%), 10 ε3/ε3 (63%), and 1 ε3/ε4 (6%). CONCLUSIONS: Retinal microstructural changes may serve as biomarkers for TACD in patients with lower-grade gliomas. Temporal lobe tumors and oligodendrogliomas may increase susceptibility to TACD. Utilization of retinal markers may enhance TACD diagnosis, progression monitoring, and inform management of lower-grade patients with glioma. A larger study with serial eye examinations is warranted to evaluate the role of APOE ε4 and develop a predictive model. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.