Glaucoma is characterised by loss of retinal ganglion cells, and their axons and many pathophysiological processes are postulated to be involved. It is increasingly understood that not one pathway underlies glaucoma aetiology, but rather they occur as a continuum that ultimately results in the apoptosis of retinal ganglion cells. Oxidative stress is recognised as an important mechanism of cell death in many neurodegenerative diseases, including glaucoma. NADPH oxidase (NOX) are enzymes that are widely expressed in vascular and non-vascular cells, and they are unique in that they primarily produce reactive oxygen species (ROS). There is mounting evidence that NOX are an important source of ROS and oxidative stress in glaucoma and other retinal diseases. This review aims to provide a perspective on the complex role of oxidative stress in glaucoma, in particular how NOX expression may influence glaucoma pathogenesis as illustrated by different experimental models of glaucoma and highlights potential therapeutic targets that may offer a novel treatment option to glaucoma patients.

Glaucoma filtration surgery is regularly performed for the treatment of glaucoma and trabeculectomy is often regarded as the 'gold standard' glaucoma operation. The biggest risk of failure of the operation is bleb scarring. The advent of anti-fibrotic agents, such as mitomycin C (MMC) and 5-fluorouracil (5FU) has vastly prolonged the longevity of the bleb, but concerns remain regarding the potential increase in postoperative complications. More selective therapeutic targets have therefore been explored. One of these is vascular endothelial growth factor (VEGF) inhibition. Vascular endothelial growth factor inhi bition has a role not only in sub conjunctival angiogenesis inhi bition but also it has direct anti-fibrotic properties. Newer phar macological compounds and materials have also been developed in recent years in attempt to modulate the wound healing in different ways after glaucoma surgery. These include physical barriers to scarring and vehicles for sustained release of pharmacological agents, and early promising results have been demonstrated. This two-part review will provide a discussion of the application of anti-fibrotic agents in glaucoma filtration surgery and evaluate the newer agents that have been developed. How to cite this article: Fan Gaskin JC, Nguyen DQ, Ang GS, O'Connor J, Crowston JG. Wound Healing Modulation in Glaucoma Filtration Surgery-Conventional Practices and New Pers pectives: The Role of Antifibrotic Agents (Part I). J Curr Glaucoma Pract 2014;8(2):37-45.

To analyse the clinical and microstructural changes during the course of acute corneal hydrops in keratoconus. A prospective study of consecutive patients presenting with acute corneal hydrops over 12 months was performed. Patients were examined with slit-lamp biomicroscopy and in vivo confocal microscopy (IVCM) at 2-weekly intervals until resolution of hydrops. 10 consecutive patients (mean age 23.6±7.5 years) were recruited. All were of Maori or Pacific Island Nations origin. All affected eyes exhibited extensive grade 3 acute corneal hydrops. Mean best corrected vision in hydrops eyes was 2/60 at presentation and 6/48 at resolution. Mean time to resolution of hydrops was 9.9±4.3 weeks. On IVCM, four corneas exhibited hyper-reflective round cells in the epithelium and stroma. Elongated branching cells with small cell bodies were noted in the anterior stroma in two cases at 6 and 12 weeks, respectively. Three months after presentation, both cases also exhibited unusual stromal cells with large speckled cell bodies and elongated branching cell processes. Both cases subsequently developed corneal neovascularisation. Corneal neovascularisation occurred in 20% of eyes in this pilot study and prolonged presence of presumed inflammatory cells was observed in these eyes. Further study of this potential association may enable identification of patients at risk of neovascularisation.

To evaluate the efficacy and safety of combined cataract surgery with insertion of an ab interno trabecular microbypass device (iStent Inject, Glaukos Corporation) compared to cataract surgery alone in patients with mild-to-moderate glaucoma. Prospective, randomized, assessor-masked controlled trial at a single centre. Eyes with visually-significant cataract and mild-to-moderate glaucoma with preoperative intraocular pressure (IOP) of 12 - 30 mmHg on 0 to 3 ocular hypotensive medications. Participants eyes were randomised (2017-2020) 1:1 to combined cataract surgery with iStent Inject (treatment group, n= 56) or cataract surgery alone (control group, n=48), and followed up for two years. The co-primary effectiveness endpoints were the number of ocular hypotensive medications and IOP at 24-months post-surgery. The secondary effectiveness endpoints were ocular comfort as measured by the Ocular Surface Disease Index (OSDI) and vision-related quality of life as measured by the Glaucoma Activity Limitation Questionnaire (GAL-9) at 24-months. Safety measures included postoperative visual acuity, any unplanned return to the operating theatre, adverse events, and complications. Participants (67.3% male) were aged 53-85 years and treatment groups were similar in terms of mean medicated IOP (treatment group 17.7 mmHg ± 4.0; control group 17.1 mmHg ± 3.1), and number of ocular hypotensive medications (treatment group 1.69 ± 1.05; control group 1.80 ± 1.22) at baseline. At 24 months, the number of ocular hypotensive medications were 0.7 ± 0.9 in the treatment groups compared to 1.5 ± 1.9 in the control group, with an adjusted difference of 0.6 fewer medications per eye in the treatment group (95% CI 0.2 to 1.1, p=0.008). 57% of eyes in the treatment group were on no glaucoma medications compared to 36% in the control group. There was no significant difference in IOP between the two groups beyond the 4-weeks. There were no differences in patient-reported outcomes between the two groups. The visual outcomes and safety profiles were similar between the two groups. Combined cataract surgery with iStent Inject achieved a clinically- and statistically-significantly greater reduction in ocular hypotensive medication usage at 24-months compared to cataract surgery alone, with no significant difference in IOP.

Glaucoma filtration surgery is regularly performed for the treatment of glaucoma and trabeculectomy is often regarded as the 'gold standard' glaucoma operation. The biggest risk of failure of the operation is bleb scarring. The advent of antifibrotic agents, such as mitomycin C (MMC) and 5-fluorouracil (5FU) has vastly prolonged the longevity of the bleb, but concerns remain regarding the potential increase in postoperative complications. More selective therapeutic targets have therefore been explored. One of these is vascular endothelial growth factor (VEGF) inhibition. VEGF inhibition has a role not only in subconjunctival angiogenesis inhibition but also it has direct anti-fibrotic properties. Newer pharmacological compounds and materials have also been developed in recent years in attempt to modulate the wound healing in different ways after glaucoma surgery. These include physical barriers to scarring and vehicles for sustained release of pharmacological agents, and early promising results have been demonstrated. This two-part review will provide a discussion of the application of anti-fibrotic agents in glaucoma filtration surgery and evaluate the newer agents that have been developed. How to cite this article: Fan Gaskin JC, Nguyen DQ, Ang GS, O'Connor J, Crowston JG. Wound Healing Modulation in Glau coma Filtration Surgery-Conventional Practices and New Pers pectives: Antivascular Endothelial Growth Factor and Novel Agents (Part II). J Curr Glaucoma Pract 2014;8(2):46-53.

To study the clinical and histological manifestations of an extreme Descemet's membrane rupture as a result of keratoconus. Using Periodic acid-Schiff assay to study a keratoconic cornea with an extreme rupture showed that the ruptured Descemet's membrane had retracted and folded into scrolls and ridges. The dimensions of the rupture were estimated to be 3.7mm2, and the central cornea was extremely thinned with a thickness of only 260μm. Stromal scarring and loosely packed lamellae were present anterior to the scrolls and ridges. Antibodies targetting the major components of Descemet's membrane, Laminin and type IV collagen, displayed intense labelling adjacent to the scrolls where the stroma was denuded and differential expression patterns lined the ridges. Environmental scanning electron microscopy showed possible collagen deposition at the site of rupture. The specific staining patterns of laminin and type IV collagen suggest these components have an important role in re-endothelisation of the cornea. This is the first known report of spatial resolution of the topography of the Descemet's membrane rupture established by environmental scanning electron microscopic image montage.