George Kong

Mitochondrial dysfunction in glaucoma and emerging bioenergetic therapies

The similarities between glaucoma and mitochondrial optic neuropathies have driven a growing interest in exploring mitochondrial function in glaucoma. The specific loss of retinal ganglion cells is a common feature of mitochondrial diseases - not only the classic mitochondrial optic neuropathies of Lebers Hereditary Optic Neuropathy and Autosomal Dominant Optic Atrophy - but also occurring together with more severe central nervous system involvement in many other syndromic mitochondrial diseases. The retinal ganglion cell, due to peculiar structural and energetic constraints, appears acutely susceptible to mitochondrial dysfunction. Mitochondrial function is also well known to decline with aging in post-mitotic tissues including neurons. Because age is a risk factor for glaucoma this adds another impetus to investigating mitochondria in this common and heterogeneous neurodegenerative disease. Mitochondrial function may be impaired by either nuclear gene or mitochondrial DNA genetic risk factors, by mechanical stress or chronic hypoperfusion consequent to the commonly raised intraocular pressure in glaucomatous eyes, or by toxic xenobiotic or even light-induced oxidative stress. If primary or secondary mitochondrial dysfunction is further established as contributing to glaucoma pathogenesis, emerging therapies aimed at optimizing mitochondrial function represent potentially exciting new clinical treatments that may slow retinal ganglion cell and vision loss in glaucoma.

The effect of different doses of intracameral bevacizumab on surgical outcomes of trabeculectomy for neovascular glaucoma.

Purpose To prospectively evaluate the effect of 1.25 mg and 2.5 mg intracameral bevacizumab on surgical outcomes of trabeculectomy for neovascular glaucoma (NVG), with primary outcome measures being the regression of neovascularization of iris (NVI) and reduction of intraocular pressure (IOP). Methods Consecutive patients with neovascular glaucoma from December 2006 to March 2007 were randomized into two cohorts assigned to receive 1.25 mg (Group 1) or 2.5 mg (Group 2) intracameral bevacizumab prior to undergoing mitomycin C (MMC) trabeculectomy. Surgical outcome measures were evaluated following initial injection and during follow-up post-surgery. Results The most common causes for iris neovascularization were central retinal vein occlusion (47.3%) and proliferative diabetic retinopathy (36.8%). Following intracameral bevacizumab, there was a reduction in IOP compared to baseline in both treatment groups (Group 1, n=9: −10.4±4.5 mmHg, p=0.57; Group 2, n=10: −12.1±5.5 mmHg, p=0.1). The reduction in IOP was not statistically significant between the two groups (p=0.55). None of the eyes underwent further retinal ablation post trabeculectomy. Reappearance of NVI was seen in three eyes (Group 1, n=2; Group 2, n=1) after 3 months. There was no statistically significant difference in regression of NVI grade between the treatment groups (p=0.1). Conclusions The efficacy of an intracameral dose of 2.5 mg of bevacizumab prior to trabeculectomy for eyes with NVG is not significantly different from a 1.25 mg dose. Intracameral bevacizumab followed by trabeculectomy results in good surgical outcomes. Longer follow-up would be needed to evaluate differences in recurrence rates of iris neovascularization using different dosages.

Optic Disc Evaluation in Optic Neuropathies: The Optic Disc Assessment Project

OBJECTIVE Optic nerve morphology is affected by genetic and acquired disease. Glaucoma is the most common optic neuropathy; autosomal-dominant optic atrophy (ADOA) and Lebers hereditary optic neuropathy (LHON) are the most prevalent hereditary optic neuropathies. These 3 entities can exhibit similar topographical changes at the optic nerve head. Both ADOA and LHON have been reported to be misdiagnosed as glaucoma. Our aim was to determine whether glaucoma subspecialists and neuro-ophthalmologists can distinguish these diagnoses on optic disc assessment alone. DESIGN Observational study. PARTICIPANTS Twenty-three optic nerve experts. METHODS We randomized and masked 60 high-resolution stereoscopic optic disc photographs (15 ADOA images, 15 LHON, 15 glaucoma, and 15 normal controls). Experts were asked to assess the discs on 12 conventional topographic features and assign a presumptive diagnosis. Intra- and interanalysis was performed using the index of qualitative variation and absolute deviation. MAIN OUTCOME MEASURES Can glaucoma specialists and neuro-ophthalmologists distinguish among the disease entities by optic nerve head phenotype. RESULTS The correct diagnosis was identified in 85%, 75%, 27%, and 16% of the normal, glaucoma, ADOA, and LHON disc groups, respectively. The proportion of correct diagnoses within the ADOA and LHON groups was significantly lower than both normal and glaucomatous (P<0.001). Where glaucoma was chosen as the most likely diagnosis, 61% were glaucomatous, 34% were pathologic but nonglaucomatous discs, and 5% were normal. There was greater agreement for individual parameters assessed within the normal disc set when compared with pathologic discs (P<0.05). The only parameter to have a significantly greater agreement within the glaucomatous disc set when compared with ADOA or LHON disc sets was pallor, whereby experts agreed on is absence in the glaucomatous discs but were not in agreement on its presence or its absence in the ADOA and LHON discs (P<0.01). CONCLUSIONS Optic neuropathies can result in similar topographic changes at the optic disc, particularly in late-stage disease, making it difficult to differentiate ADOA and LHON from glaucoma based on disc assessment alone. Other clinical parameters such as acuity, color vision, history of visual loss, and family history are required to make an accurate diagnosis.