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.

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.

Clinical evaluation and cost analysis of mitomycin-C-augmented PreserFlo MicroShunt versus trabeculectomy. Retrospective cohort study across 3 teaching hospitals. A total of 134 consecutive eyes of 129 patients (70 undergoing MicroShunt, 64 trabeculectomy). Primary and secondary glaucoma cases with uncontrolled intraocular pressure (IOP) were included. Neovascular glaucoma and surgery combined with cataract extraction were excluded. The cost analysis used results from the clinical study to estimate operative costs (equipment and staff costs) and postoperative costs (follow-up visits, nonglaucoma medications, and postoperative procedures) per eye for PreserFlo and trabeculectomy. The primary clinical outcome measure was surgical failure (defined as IOP > 21 mmHg or < 20% reduction from baseline, IOP ≤ 5 mmHg, reoperation, or loss of light perception) or qualified and complete success (with or without medication) at 18 months. Secondary measures were IOP, glaucoma medications, visual acuity, mean deviation, time to cessation of steroid drops, complications, surgical time, follow-up visits, postoperative interventions, and reoperations. The cost analysis evaluated costs of PreserFlo compared with trabeculectomy. Baseline characteristics were similar, except for more non-White patients in the trabeculectomy group (51% Black and Asian vs. 32% MicroShunt, P = 0.02) and more cases with prior ab externo glaucoma surgery in the MicroShunt group (19% vs. 3% in the trabeculectomy group, P = 0.004). Overall, 59% of eyes had primary open-angle glaucoma. Mean follow-up was 19.9 months for both groups. At 18 months, surgical failure was 25% for MicroShunt compared with 35% for trabeculectomy (P = 0.18). Failure in MicroShunt cases was due to inadequate IOP reduction (84%) or reoperation for glaucoma (16%). Failure in trabeculectomy cases was due to inadequate IOP reduction (58%), persistent hypotony (29%), or reoperation for glaucoma (13%). Combined blebitis and endophthalmitis rate was 1.4% for MicroShunt and 3.1% for trabeculectomy. Cost analysis showed a savings of £245 to £566 per eye in the MicroShunt group, driven mostly by reduced postoperative procedures and follow-up visits. This is in contrast to prior randomized controlled trial data reporting the incremental cost of $2058 of PreserFlo over trabeculectomy. Our experience of introducing PreserFlo MicroShunt surgery showed it was safer than trabeculectomy and is a cost-saving and effective option that offers potential to free up highly limited National Health Service resources. Proprietary or commercial disclosure may be found after the references.

Aim: For accurate intraocular pressure (IOP) measurement in very young children examination under anaesthesia (EUA) may be necessary. Most anaesthetic agents used for EUA have some effect on IOP. We compared IOPs in children after ketamine and sevoflurane anaesthesia. Methods: Consecutive patients with definite or suspected glaucoma, uncooperative for reliable IOP measurement in clinic and requiring EUA, were included in this study. IOPs were measured after intramuscular injection (5 mg/kg) or intravenous injection (2 mg/kg) of ketamine using a Perkins applanation tonometer. Three measurements were taken from each eye. The IOPs were rechecked after sevoflurane, given for maintenance anaesthesia. Mean IOPs were used for analysis. Paired t test was used to assess the differences in IOPs for the whole group and one-way ANOVA for the three subgroups (ketamine IOP 30 mmHg). Results: The records of eight patients (16 eyes) were available for review. The mean age was 55.42 (SD 25, range 26–89) months. Seventy data-points from both eyes (35 EUAs) were used for the analysis. The mean IOP after sevoflurane (17 (SD 10) mmHg) was statistically lower than after ketamine (24.4 (SD 12.7) mmHg, p<0.001). The percentage difference was 28.5 (SD 20.8; 95% CI 23.5 to 33.4)). The difference between the subgroups was not statistically significant (p = 0.192). Conclusion: Sevoflurane lowers the IOP significantly compared with the IOP measured after ketamine. This difference is independent of the IOP level. It may be important to use ketamine as the induction anaesthetic agent when accurate IOP measurement is necessary during EUA for children.

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.