6, 7, 8 As apoptosis has such a major role in glaucoma, its early identification in vivo would be a key goal for biomedical research that will certainly enhance clinical diagnostics and could be an end point for novel neuroprotective strategies. 3 Although apoptosis is a key component of homoeostasis in normal development and aging, its dysregulation is implicated in a vast range of leading ophthalmic and systemic disorders, including age-related macular degeneration, retinitis pigmentosa, cancer, neurodegeneration, and automimmune diseases. 4, 5 Increased RGC apoptosis and axonal loss within the inner retina is the earliest form of cell death in glaucoma, and it directly correlates with clinical severity of the disease. Glaucoma is a neurodegenerative disorder characterised by the progressive loss of retinal ganglion cells (RGCs). 2 It is expected to affect 79.6 million people worldwide by 2020, of which 11.2 million will be bilaterally blind. Clinically, patients classically experience the progressive loss of their peripheral visual field, with eventual complete blindness. 1 The disease's asymptomatic nature impedes any forewarning prior to its disabling progression. Glaucoma, commonly termed the ‘silent thief of sight', is a leading cause of blindness worldwide. This review will illustrate the challenges of imaging RGCs, the main retinal imaging modalities, the in vivo techniques to augment these as specific RGC-imaging tools and their potential for translation to the glaucoma clinic. Although many of these advances have not yet been introduced to the clinical arena, their successes in animal studies are enthralling. It may confirm the presence of healthy RGCs, such as in transgenic models or retrograde labelling, or detect subtle changes in the number of unhealthy or apoptotic RGCs, such as detection of apoptosing retinal cells (DARC). However, an ideal imaging technique to diagnose and monitor glaucoma would image RGCs non-invasively with high specificity and sensitivity in vivo. Recent advances in retinal imaging, including optical coherence tomography, confocal scanning laser ophthalmoscopy, and adaptive optics, have propelled both glaucoma research and clinical diagnostics and therapeutics. To propel the efficacy of therapeutics in glaucoma, an earlier diagnostic tool is required. Current diagnostic tools require significant RGC or functional visual field loss before the threshold for detection of glaucoma may be reached. One of its most devastating features is its late diagnosis and the resulting irreversible visual loss that is often predictable. It is caused by the progressive loss of retinal ganglion cells (RGCs), predominantly via apoptosis, within the retinal nerve fibre layer and the corresponding loss of axons of the optic nerve head. Glaucoma is one of the leading causes of blindness worldwide and will affect 79.6 million people worldwide by 2020.
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