Peripheral blood mononuclear cell respiratory function is associated with progressive glaucomatous vision loss.

Intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma and all licensed treatments lower IOP. However, many patients continue to lose vision despite IOP-lowering treatment. Identifying biomarkers for progressive vision loss would have considerable clinical utility. We demonstrate that lower peripheral blood mononuclear cell (PBMC) oxygen consumption rate (OCR) is strongly associated with faster visual field (VF) progression in patients treated by lowering IOP (P < 0.001, 229 eyes of 139 participants), explaining 13% of variance in the rate of progression. In a separate reference cohort of untreated patients with glaucoma (213 eyes of 213 participants), IOP explained 16% of VF progression variance. OCR is lower in patients with glaucoma (n = 168) than in controls (n = 50; P < 0.001) and is lower in patients with low baseline IOP (n = 99) than those with high baseline IOP (n = 69; P < 0.01). PBMC nicotinamide adenine dinucleotide (NAD) levels are lower in patients with glaucoma (n = 29) compared to controls (n = 25; P < 0.001) and strongly associated with OCR (P < 0.001). Our results support PBMC OCR and NAD levels as new biomarkers for progressive glaucoma.

Eccentric Viewing Training for Age-Related Macular Disease: Results of a Randomized Controlled Trial (the EFFECT Study).

Purpose: Eccentric viewing training for macular disease has been performed for > 40 years, but no large studies including control groups have assessed the benefits of this training. The EFFECT (Eccentric Fixation From Enhanced Clinical Training) study is a large randomized controlled trial of 2 types of eccentric viewing training. Design: Randomized controlled trial. Participants: Two hundred adults with age-related macular disease. Methods: Participants were randomized to either of the following: (1) a control group; (2) a group receiving supervised reading support; (3) a group receiving 3 sessions of training to optimize the use of their own preferred retinal locus; or (4) a group receiving 3 sessions of biofeedback training of a theoretically optimal trained retinal locus. All participants received standard low-vision rehabilitation. Main Outcome Measures: The primary outcome was patient-reported visual task ability measured on the Activity Inventory instrument at goal level. Secondary outcomes included reading performance and fixation stability. Results: There was no difference between groups on change in task ability (F(3,174) = 1.48, P = 0.22) or on any of the secondary outcome measures. Visual acuity and contrast sensitivity fell in all groups, suggesting that disease progression outweighed any benefit of training. Conclusions: Eccentric viewing training did not systematically improve task ability, reading performance, or fixation stability in this study. Our results do not support the routine use of eccentric viewing training for people with progressing age-related macular disease, although this training may help people with end-stage disease. Rehabilitation of an inherently progressive condition is challenging. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The Role of Mitophagy in Glaucomatous Neurodegeneration.

This review aims to provide a better understanding of the emerging role of mitophagy in glaucomatous neurodegeneration, which is the primary cause of irreversible blindness worldwide. Increasing evidence from genetic and other experimental studies suggests that mitophagy-related genes are implicated in the pathogenesis of glaucoma in various populations. The association between polymorphisms in these genes and increased risk of glaucoma is presented. Reduction in intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma, while clinical trials highlight the inadequacy of IOP-lowering therapeutic approaches to prevent sight loss in many glaucoma patients. Mitochondrial dysfunction is thought to increase the susceptibility of retinal ganglion cells (RGCs) to other risk factors and is implicated in glaucomatous degeneration. Mitophagy holds a vital role in mitochondrial quality control processes, and the current review explores the mitophagy-related pathways which may be linked to glaucoma and their therapeutic potential.

Neuroprotection in Glaucoma: NAD+/NADH Redox State as a Potential Biomarker and Therapeutic Target.

Glaucoma is the leading cause of irreversible blindness worldwide. Its prevalence and incidence increase exponentially with age and the level of intraocular pressure (IOP). IOP reduction is currently the only therapeutic modality shown to slow glaucoma progression. However, patients still lose vision despite best treatment, suggesting that other factors confer susceptibility. Several studies indicate that mitochondrial function may underlie both susceptibility and resistance to developing glaucoma. Mitochondria meet high energy demand, in the form of ATP, that is required for the maintenance of optimum retinal ganglion cell (RGC) function. Reduced nicotinamide adenine dinucleotide (NAD+) levels have been closely correlated to mitochondrial dysfunction and have been implicated in several neurodegenerative diseases including glaucoma. NAD+ is at the centre of various metabolic reactions culminating in ATP production-essential for RGC function. In this review we present various pathways that influence the NAD+(H) redox state, affecting mitochondrial function and making RGCs susceptible to degeneration. Such disruptions of the NAD+(H) redox state are generalised and not solely induced in RGCs because of high IOP. This places the NAD+(H) redox state as a potential systemic biomarker for glaucoma susceptibility and progression; a hypothesis which may be tested in clinical trials and then translated to clinical practice.