Retinal Microstructural Changes Reflecting Treatment-Associated Cognitive Dysfunction in Patients with Lower-Grade Gliomas
Bibliographic record
Abstract
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 lower-grade glioma patients at a U.S. 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-months intervals. APOE 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 exam was 34 months (2–266) from tumor diagnosis and 23 months (0–246) from radiation. Nine patients (56%) had abnormal cognition (MoCA <26/30). MoCA 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 to 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. APOE genotyping showed: two ε2/ε3 (13%), ten ε3/ε3 (63%) , and one ε3/ε4 (6%). Conclusion 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 glioma patients. A larger study with serial eye exams is warranted to evaluate the role of APOE ε 4 and develop a predictive model.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".