Retinal Microstructural Changes Reflecting Treatment-Associated Cognitive Dysfunction in Patients with Lower-Grade Gliomas

Purpose: To determine whether microstructural retinal changes, tumor features, and apolipoprotein E (APOE) e4 polymorphism are correlated with clinically detectable treatment-associated cognitive dysfunction (TACD) in patients with lower-grade gliomas. 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 e2/e3 (13%), 10 e3/e3 (63%), and 1 e3/e4 (6%). Conclusions: Retinal microstructural changes may serve as biomarkers for TACD in patients with lowergrade 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 e4 and Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. Ophthalmology Science 2024;4:100577 (c) 2024 by the American Academy of Ophthalmology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/