RGC Counts in Early Glaucomatous Damage Relate to Neuroretinal Rim Thinning

This study’s findings suggest that eyes with diffuse neuroretinal rim thinning sustain significantly greater neural loss before reaching the threshold for visual field defect detection, highlighting the critical need for complementary structural assessments and the development of new functional strategies that are more sensitive to diffuse glaucomatous damage. Photo: Henrietta Wang, BOptom, MPH, and Jack Phu, OD, PhD. Click image to enlarge. Glaucomatous damage to the neuroretinal rim and retinal nerve fiber layer (RNFL) typically manifests as diffuse thinning or as localized defects, which may reflect distinct pathophysiological mechanisms or different stages of disease progression. Understanding how these patterns of structural damage correlate with the extent of retinal ganglion cell (RGC) loss could offer critical insights into the disease process and help identify patients at higher risk of rapid progression and vision loss.Researchers from Bascom Palmer Eye Institute in Miami believe that by combining OCT-derived retinal ganglion cell estimates with perimetry-derived ones into a metric called the RGC index can offer a more comprehensive and robust estimate of neural damage in glaucoma. This combined structure-function index significantly outperformed isolated structural and functional metrics in staging glaucoma and monitoring progression and has been validated in multiple external cohorts.They hypothesized that differences in RGC loss at the time of initial visual field defect detection are driven by the pattern of neuroretinal rim or RNFL thinning, specifically whether the thinning is diffuse or localized. They proposed that classifying glaucomatous eyes based on these thinning patterns and estimating RGC counts using the RGC index can help shed light on why some eyes exhibit greater RGC loss than others at the time of earliest visual field defect detection. Their study determined that diffuse rim thinning at the earliest stage of functional loss was associated with substantially greater RGC loss than localized thinning. These findings support incorporating structural features into early glaucoma assessment. For advice on recognizing the clinical signs of glaucoma, see this recent article. “These findings suggest that the amount of underlying neural damage at the onset of detectable visual field loss differs depending on the pattern of structural injury,” the study authors wrote in their paper. “Recognizing these differences is important for clinicians, as reliance on visual field sensitivity alone may underestimate disease severity in eyes with diffuse rim loss, potentially leading to earlier and more accurate identification of glaucomatous damage.”Their prospective observational cohort study, which was published in American Journal of Ophthalmology, included 53 glaucoma suspect eyes and 124 healthy eyes. 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) than those with localized loss (733,614), corresponding to a 32.6% and 19.4% mean reduction relative to healthy controls, respectively. Mean deviation differed modestly between groups (-2.44dB vs -1.62dB) at time of conversion. Multivariable analysis identified diffuse rim loss, older age and Black race as independent predictors of lower RGC counts.Black patients exhibited significantly lower estimated RGC counts at the time of perimetric conversion, suggesting that greater neural loss had already occurred by the time visual field defects became detectable. This disparity may contribute to the higher rates of glaucoma-related visual impairment observed in Black populations.“Estimating RGC counts at perimetric conversion provides additional insight into the severity of underlying neural damage and may help clinicians identify glaucoma suspect eyes at higher risk for progression, beyond what is apparent from structural or functional testing alone,” the researchers concluded.Click here for the journal source. Rabinowitz AS, Vilasboas-Campos V, Filho MG, Medeiros FA. Retinal ganglion cell loss and patterns of neuroretinal rim thinning at the onset of visual field defects in glaucoma. Am J Ophthalmol. September 6, 2025. [Epub ahead of print].This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.