Objective: To examine the changes of visual field and retinal nerve fiber layer (RNFL) measurements and the risk of glaucoma progression before and after taking off intraocular pressure (IOP) lowering medication in Chinese patients with ocular hypertension. Design: Prospective study. Participants: 106 ocular hypertension patients (4 were excluded because there was no 1 year follow up examination). Method: All patients underwent visual field testing by Humphrey Field Analyser and Retinal Nerve Fiber Layer (RNFL) thickness measurement by a spectral-domain optical coherence tomography. Eyes without glaucomatous visual field defect and had an IOP ?30mmHg were instructed to stop taking IOP lowering medication and measurements of IOP, visual field and RNFL measurements were taken. Changes in the visual field mean deviation, average, superior and inferior RNFL thickness and the risk of developing glaucoma between the baseline and follow-up examinations were compared between the groups with and without stopping IOP lowering medications. Logistic regression was used to analyze the association between corneal hysteresis, ocular pulse amplitude and the onset of glaucoma. Results: There were 73 patients with IOP lowering medications taken off and 29 with continued medications. No significant differences were found in the changes of visual field mean deviation, average RNFL thickness and the risk of glaucoma progression (P=0.92, P=0.81, P=0.35, respectively) between the groups. Ocular pulse amplitude was a significant predictor of glaucoma development by functional (-0.61, P=0.047) and structural criteria (-0.74, P=0.024). Conclusion: There were no functional and structural changes in patients with ocular hypertension after stopping IOP lowering medications in one year. Low ocular pulse amplitude could be a predictive factor for the conversion from ocular hypertension to glaucoma. Clinicians should not prescribe IOP-lowering medication simply base on high IOP. / published_or_final_version / Medicine / Master / Master of Medical Sciences

Background Glaucoma is a major cause of blindness worldwide. The affected population was projected to increase from 60.5 million in 2010 to 79.6 million in 2020. Among the various types of glaucoma, primary open angle glaucoma will account for more than 70% of this population. Treatment by lowering the intraocular pressure is the only proven method to reduce progression. This can be achieved via medication, surgery and laser. Selective laser trabeculoplasty is a relatively new type of laser that is reported to be equally efficacious to a first line medication and other established laser trabeculoplasty, namely argon laser trabeculoplasty. The evidence available, however, is limited to single trials, which may not reach adequate power to detect the difference. A systematic review and meta-analysis would add evidence to consider selective laser trabeculoplasty as an alternative treatment option in open angle glaucoma through assessing its efficacy and effectiveness in lowering the intraocular pressure and through testing for its non-inferiority when compared with other conventional treatment modalities. Method Literature search of Pubmed, EMBASE, CENTRAL, dissertation and thesis databases and hand search of relevant journals was performed for the use of selective laser trabeculoplasty in the treatment of open angle glaucoma. English and Chinese articles were included. Meta-analysis of randomized controlled trials comparing treatment efficacy of selective laser trabeculoplasty and other treatment modalities were performed where appropriate. Results 80 articles were identified to be relevant and provided sufficient data for interpretation for efficacy or safety assessment. It was estimated that selective laser trabeculoplasty resulted in a weighted pooled mean intraocular pressure reduction of 21.9 to 23.8% at different follow-up durations. However, sensitivity analysis including only prospective studies with baseline IOP less than 21mmHg did not show significant IOP lowering effect. Review on side effects of selective laser trabeculoplasty showed a good safety profile in general. Rare occurrences of more severe or long-term complications included persistent intraocular pressure spike requiring surgery, persistent macular edema and corneal haze. Meta-analysis of randomized controlled trials showed that selective laser trabeculoplasty is non-inferior to argon laser trabeculoplasty and medication in intraocular pressure reduction and also in achieving treatment success. Number of medication reduction is similar between selective laser trabeculoplasty and argon laser trabeculoplasty. Conclusion This report demonstrated comparable efficacy of selective laser trabeculoplasty with argon laser trabeculoplasty and medication therapy in the treatment of open angle glaucoma. / published_or_final_version / Public Health / Master / Master of Public Health

Glaucoma is a devastating blinding disease, caused by retinal ganglion cell (RGC) loss via apoptosis and clinically associated with raised intraocular pressure (IOP). Mainstream theories of glaucoma's pathogenesis detail loss of RGCs via indirect links to lOP; including mechanodistortion of optic nerve axons, trophic factor deficiency, ischaemia or excitotoxicity. A novel concept in the pathogenesis of glaucoma is that pressure alone could be a direct stimulus for RGC loss. Currently available glaucoma treatments are solely aimed at lowering lOP. Reduction ofIOP has been shown to reduce glaucomatous progression however RGC losses continue. Neuroprotection is an emerging field of research offering hope to neurodegenerative diseases, including glaucoma. This thesis investigated known glaucoma therapeutics with suggested neuroprotective activity in an in vitro glaucoma model using the RGC-5 cell line. To evaluate therapies, a suitable in vitro model was initially evaluated. The RGC-5 cell line was immunochemically demonstrated to possess NSE, a neuronal marker and Thy-1, an RGC marker. Glutamate excitotoxicity was investigated however excessive concentrations were required to cause significant in vitro RGC-5 cytotoxicity. Using a modified hydrostatic pressure model, reproducible pressure-induced RGC-5 apoptosis was demonstrated. Apoptosis was detected using cell morphology and confirmed with both early (caspase-3 and annexin V) and late (TUNEL) apoptotic markers. Despite the advantages of rapid, objective quantification, results indicated that flow cytometry of RGC-5 cells was not technically possible. I defined a modified laser scanning cytometry protocol, allowing for objective apoptosis quantification of TUNEL stained cells. Brimonidine is postulated to mediate receptor mediated RGC protection. Experiments conducted for this thesis, were the first to immunochemically demonstrate alpha2 adrenergic receptor expression on human RGCs and the RGC-5 cell line, suggesting direct cell mediated protection on the target neuron of glaucoma is possible and that the RGC-5 line is a useful in vitro target for experimentation. Both brimonidine and betaxolol were shown to confer protection to the RGC-5 cell line from pressure-induced apoptosis, under defined conditions. These results suggest that these drugs may confer direct cell-mediated protection, rather than indirect protection conferred via other retinal or glial cells, the anterior segment, the vasculature or some other means.