Depression scores are associated with retinal ganglion cells loss.

BACKGROUND: Light is a known factor affecting mood and the circadian system. Light deficit is linked to deteriorated transduction of photic information to the brain, and reduced amplitude of the perceived circadian light signaling. Retinal ganglion cells (RGCs) loss due to advanced glaucoma can be a factor compromising light perception, with consequences for circadian rhythms, sleep and mood. This study aimed to estimate associations of RGCs loss with a depression score by multiple regression, accounting for other features of glaucoma. METHODS: One hundred and fifteen patients diagnosed with primary open-angle glaucoma completed the Beck Depression Inventory II questionnaire. The damage to their RGCs was assessed by high-definition optical coherence tomography (HD-OCT) and their function by pattern electroretinogram (PERG). On fifteen of these patients, 24-h salivary melatonin patterns were determined under light-controlled laboratory conditions, and analysis of eight clock related gene polymorphisms was performed. RESULTS: Backward stepwise multiple regression revealed that the BDI score was the strongest factor that was most closely associated with the HD-OCT-based percentage of global RGCs loss (standardized coefficient, b* = 0.784, p < 0.001), surpassing other related factors, including age, intraocular pressure, visual field loss, and PERG amplitude. A high BDI score was associated with the GNß3 825C > T polymorphism (dbSNP rs5443). LIMITATIONS: This study did not specifically address damage to intrinsically photoreceptive RGCs. The gene study is based on a limited number of volunteers. CONCLUSIONS: Depression scores are strongly associated with RGCs loss, increasing abruptly above a threshold of 15 %, supporting the hypothesis that RGCs loss in advanced glaucoma may affect non-visual photic transduction and lead to mood disturbances.

Melatonin mitigates disrupted circadian rhythms, lowers intraocular pressure, and improves retinal ganglion cells function in glaucoma.

Glaucoma is a progressive optic neuropathy associated with damage to retinal ganglion cells (RGCs) and disrupted circadian rhythms. Melatonin is a promising substance to ameliorate glaucoma-associated compromised circadian rhythms, sleep, mood, and retinal cells function. However, studies estimating melatonin effects in glaucoma are currently lacking. Therefore, In this study, we investigated the effect of long-term (daily at 10:30 pm for 90 days) oral melatonin administration on systemic (Tb) and local to the organ of vision (IOP) circadian rhythms, pattern electroretinogram (PERG), sleep, and mood, depending on glaucoma stage in patients diagnosed with stable or advanced primary open-angle glaucoma. In a laboratory study in 15 of them, 24-hour records of salivary melatonin were obtained and MTNR1B receptor gene polymorphism was assessed. Melatonin increased the stability of the Tb circadian rhythm by improving its phase alignment and alignment with IOP. Melatonin time-dependently decreased IOP and IOP standard deviation (SD). IOP 24-hour mean and IOP SD decreases were more pronounced in individuals with the higher initial 24-hour IOP mean. Melatonin improved RGCs function in advanced glaucoma; N95 amplitude increase correlated positively with RGCs loss. The beneficial effects of melatonin on sleep and mood were greater in advanced glaucoma. Finally, delayed salivary melatonin and Tb phases were observed in MTNR1B G-allele carriers with advanced glaucoma. Combined, these results provide evidence for melatonin efficiency in restoring disrupted circadian rhythms in glaucoma with different effects of melatonin on systemic vs. local circadian rhythms, indicating that a personalized strategy of melatonin administration may further refine its treatment benefits.

Disruption of 24-Hour Rhythm in Intraocular Pressure Correlates with Retinal Ganglion Cell Loss in Glaucoma.

Parameters of 24-h rhythm in intraocular pressure (IOP) were assessed in patients with stable or advanced primary open-angle glaucoma (S-POAG/A-POAG) and referenced to the phase of "marker" circadian temperature rhythm of each patient. Body temperature and IOP were measured over a 72-h span in 115 participants (65 S-POAG and 50 A-POAG). Retinal Ganglion Cell (RGC) damage was assessed by high-definition optical coherence tomography. The 24-h IOP rhythm in A-POAG patients peaked during the night, opposite to the daytime phase position in S-POAG patients (p < 0.0001). The 24-h IOP phase correlated with RGC loss (p < 0.0001). The internal phase shift between IOP and body temperature gradually increased with POAG progression (p < 0.001). Angiotensin converting enzyme Alu-repeat deletion/insertion (ACE I/D) emerged as a candidate gene polymorphism, which may play a role in the alteration of the circadian IOP variability in advanced glaucoma. To conclude, a reliable estimation of the 24-h rhythm in IOP requires the degree of RGC damage to be assessed. In advanced POAG, the 24-h phase of IOP tended to occur during the night and correlated with RGC loss, being progressively delayed relative to the phase of temperature.

Five Keratoplasties From One Donor Cornea.

PURPOSE: To describe the feasibility of same-day, consecutive use of a single donor cornea in 5 patients with corneal pathology, who required anterior lamellar and endothelial keratoplasties. METHODS: Descemet membrane (DM) with endothelium was completely stripped from a single corneoscleral button and punched out from the endothelial side with a circular, standard punch. Using a custom-made punch for linear cutting of DM, we obtained 4 quarter-grafts (Q-graft). The denuded and punched-out corneal stroma was transplanted in 1 patient with keratoconus, using the big-bubble deep anterior lamellar keratoplasty (DALK) technique. The 4 DM Q-grafts were consecutively transplanted to 4 patients with Fuchs dystrophy using the quarter Descemet membrane endothelial keratoplasty (Q-DMEK or 1/4 DMEK) technique. RESULTS: All surgical procedures were performed successfully during 1 surgical session. No intraoperative or postoperative complications requiring intervention were observed. Six months after surgery, the decimal best-corrected visual acuity achieved was 0.66 after DALK and 0.95 ± 0.1 (range, 0.8-1.0) in the 4 Q-DMEK cases; the endothelial cell density was 1680 ± 254 cells/mm (range, 1492-2039 cells/mm). Six months postoperatively, all corneas were clear. CONCLUSIONS: In this limited series, we demonstrate that 1 donor cornea can be successfully used for 5 recipients. Although performing DALK and Q-DMEK on a single day is technically challenging, it is feasible and can dramatically reduce the shortage and the cost of corneal tissue. Strict case selection is necessary. Further study on this approach is required.