Primary open angle glaucoma (POAG) is defined as a “genetically complex trait”, where modifying factors act on a genetic predisposing background. For the majority of glaucomatous conditions, DNA variants are not sufficient to explain pathogenesis. Some genes are clearly underlying the more “Mendelian” forms, while a growing number of related polymorphisms in other genes have been identified in recent years. Environmental, dietary, or biological factors are known to influence the development of the condition, but interactions between these factors and the genetic background are poorly understood. Several studies conducted in recent years have led to evidence that epigenetics, that is, changes in the pattern of gene expression without any changes in the DNA sequence, appear to be the missing link. Different epigenetic mechanisms have been proven to lead to glaucomatous changes in the eye, principally DNA methylation, post-translational histone modification, and RNA-associated gene regulation by non-coding RNAs. The aim of this work is to define the principal epigenetic actors in glaucoma pathogenesis. The identification of such mechanisms could potentially lead to new perspectives on therapeutic strategies.

This case-control study aims to compare the efficacy, safety, and postoperative burden of MicroShunt versus trabeculectomy. The first consecutive cohort of MicroShunt procedures (n = 101) was matched to recent historical trabeculectomy procedures (n = 101) at two London hospital trusts. Primary endpoints included changes in intraocular pressure (IOP) and glaucoma medications. Secondary outcome measures included changes in retinal nerve fibre layer (RNFL) thickness, rates of complications, further theatre interventions, and the number of postoperative visits. From the baseline to Month-18, the median [interquartile range] IOP decreased from 22 [17–29] mmHg (on 4 [3–4] medications) to 15 [10–17] mmHg (on 0 [0–2] medications) and from 20 [16–28] mmHg (on 4 [3–4] medications) to 11 [10–13] mmHg (on 0 [0–0] medications) in the MicroShunt and trabeculectomy groups, respectively. IOP from Month-3 was significantly higher in the MicroShunt group (p = 0.006), with an increased number of medications from Month-12 (p = 0.024). There were greater RNFL thicknesses from Month-6 in the MicroShunt group (p = 0.005). The rates of complications were similar (p = 0.060) but with fewer interventions (p = 0.031) and postoperative visits (p = 0.001) in the MicroShunt group. Therefore, MicroShunt has inferior efficacy to trabeculectomy in lowering IOP and medications but provides a better safety profile and postoperative burden and may delay RNFL loss.