Retinal Ganglion Cell Loss and Patterns of Neuroretinal Rim Thinning at the Onset of Visual Field Defects in Glaucoma.

Purpose: To compare retinal ganglion cell (RGC) loss in glaucoma suspect eyes with diffuse versus localized neuroretinal rim loss at the time of the first confirmed visual field defect.

Design: Prospective observational cohort study.

Subjects: Fifty-three glaucoma suspect eyes and 124 healthy eyes.

Methods: Fifty-three glaucoma suspect eyes were followed until development of repeatable glaucomatous visual field defects. Estimated RGC counts were derived using a validated model combining standard automated perimetry and optical coherence tomography measurements. Conversion was defined as the first confirmed abnormal field, with RGC estimates taken within three months. Neuroretinal rim loss was classified as diffuse or localized through masked grading of optic disc stereophotographs. A normative cohort of 124 healthy eyes provided reference RGC values.

Main Outcome Measures: Estimated RGC counts at perimetric conversion.

Results: Of the 53 eyes, 36 (68%) showed diffuse and 17 (32%) localized rim loss. Eyes with diffuse loss had significantly lower RGC counts at conversion (613,543 ± 114,886) than those with localized loss (733,614 ± 65,776, P < 0.001), corresponding to a 32.6% and 19.4% mean reduction relative to healthy controls, respectively. Mean deviation differed modestly between groups (-2.44 ± 1.36 dB vs -1.62 ± 1.13 dB, P = 0.033) at time of conversion. Multivariable analysis identified diffuse rim loss, older age, and Black race as independent predictors of lower RGC counts.

Conclusions: Diffuse rim thinning at the earliest stage of functional loss is associated with substantially greater RGC loss than localized thinning. These findings support incorporating structural features into early glaucoma assessment.