Purpose. To assess the integrity of intrinsically photosensitive retinal ganglion cells (ipRGCs) using the pupillary light reflex in glaucoma patients. Methods. A cross-sectional study was conducted, including 76 eyes from 38 patients with primary open-angle glaucoma and 36 eyes from 18 control subjects. The patients were tested in the dark with light stimuli using the Ganzfeld system, and the pupil diameter was measured with the assistance of an eye tracker consisting of two infrared cameras fit to an eyeglass frame. To preferentially stimulate ipRGCs, we used a 1-second 470-nm flash with a luminance of 250 cd/m². To stimulate different retinal photoreceptors (cones and rods), we used a 1-second 630-nm flash with a luminance of 250 cd/m². Standard automated perimetry (SAP), matrix frequency-doubling technology (FDT), and high-definition optical coherence tomography (Cirrus HD-OCT) were also performed. The correlation between the ipRGC-mediated sustained response following the pupillary light reflex and the structural and functional changes in glaucoma patients was analyzed using generalized estimating equation. Results. An association was observed between the average retinal nerve fiber layer (RNFL) thickness, as measured by Cirrus HD-OCT, and the sustained pupillary response to the blue flash (P = 0.024). The severity of glaucoma, based on the mean deviation of SAP (Hodapp-Anderson-Parrish system), was also associated with the sustained response to the blue flash (P = 0.006). Conclusions. This study showed a correlation between the mean RNFL thickness and the pupillary light response. A decrease in the number of ipRGCs is potentially related to the reduced RNFL thickness.

The effect of cross-regional or cross-cultural differences on color appearance ratings and memory colors of familiar objects was investigated in seven different countries/regions – Belgium, Hungary, Brazil, Colombia, Taiwan, China and Iran. In each region the familiar objects were presented on a calibrated monitor in over 100 different colors to a test panel of observers that were asked to rate the similarity of the presented object color with respect to what they thought the object looks like in reality (memory color). For each object and region the mean observer ratings were modeled by a bivariate Gaussian function. A statistical analysis showed significant (p < 0.001) differences between the region average observers and the global average observer obtained by pooling the data from all regions. However, the effect size of geographical region or culture was found to be small. In fact, the differences between the region average observers and the global average observer were found to of the same magnitude or smaller than the typical within region inter-observer variability. Thus, although statistical differences in color appearance ratings and memory between regions were found, regional impact is not likely to be of practical importance.

Patients with glaucoma showed to have higher daytime sleepiness measured by Epworth sleepiness scale. In addition, this symptom was associated with pupillary reflex and polysomnography parameters. These ipRGC functions might be impaired in patients with glaucoma, leading to worse quality of life.

Purpose: To evaluate in patients with primary open-angle glaucoma (POAG) the contribution of the inner and outer retinal photoreceptors to the pupillary light responses (PLRs) correlated with both functional (color vision and visual field perimetry) and morphologic (optical coherence tomography) parameters. Methods: In total, 45 patients with POAG and 25 healthy control participants were evaluated. The PLR was measured as pupil diameter with an eye tracker; stimuli were presented in a Ganzfeld. Pupil responses were measured monocularly, to 1 second blue (470 nm) and red (640 nm) flashes with −3, −2, −1, 0, 1, 2, and 2.4 log cd/m² luminance levels. Color vision was evaluated with the Cambridge Color Test, visual field was measured by standard automatic perimetry, and retinal nerve fiber layer thickness was evaluated by optical coherence tomography. Results: Patients with moderate and severe POAG have a significantly decreased PLR that depends on the severity of POAG, for both the 470 and 640 nm stimuli, revealing the reduction of the contributions of the rods, cones, and intrinsically photosensitive retinal ganglion cells to PLR. A significant loss of color discrimination along the blue-yellow axis was observed in all stages of POAG. Correlations among standard automatic perimetry, retinal nerve fiber layer thickness, Cambridge Color Test, PLR, and melanopsin parameters were found. Conclusions: The results provide evidence that in moderate and severe stages of POAG, both the inner and outer retinal contributions to PLR are affected. Also, a worsening in color vision was correlated with reduced PLR responses at high-intensity stimuli. These findings may enhance the clinical management of POAG patients.

Glaucoma is traditionally defined as an ocular disease characterized by progressive retinal ganglion cell degeneration, in some cases with elevated intraocular pressure (IOP), and optic nerve damage. However, growing evidence indicates that glaucoma shares critical features with neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. This study aimed to explore the systemic nature of primary open-angle glaucoma (POAG) by integrating visual function, cognitive performance, and transcriptomic profiling. We conducted a multidimensional assessment of POAG patients and age-matched controls, accounting for demographic factors. Structural parameters included retinal nerve fiber layer (RNFL) thickness, measured using optical coherence tomography (OCT), and visual field indices mean deviation (MD) and pattern standard deviation (PSD). Cognitive function was evaluated across multiple domains, encompassing visual memory, executive function, processing speed, and verbal fluency. Additionally, transcriptomic analysis was performed from conjunctival samples to identify differentially expressed genes (DEGs) and enriched pathways. POAG patients exhibited significant RNFL thinning, which correlated with both visual field loss and cognitive impairments, particularly in terms of visual memory and executive function. Transcriptomic profiling revealed a distinct gene expression signature in POAG, including upregulation of TTBK1 and CCN2 (CTGF), genes associated with tau phosphorylation and extracellular matrix remodeling. Functional enrichment analysis indicated the involvement of neurodegenerative pathways, such as glutamate signaling, calcium signaling, and cell adhesion. Our findings support the reclassification of glaucoma as a neurodegenerative disease with both ocular and cognitive manifestations. Furthermore, biomarkers such as TTBK1 and CCN2 may serve as potential targets for early detection and neuroprotective therapy.