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Show The Annual Meeting of the Association for Research in Vision and Ophthalmology ( ARVO), Fort Lauderdale, Florida, May 1- 4, 2005 Some 5,730 abstracts were presented at the Annual Meeting of the Association for Research in Vision and Ophthalmology ( ARVO) on May 1- 5, 2005 in Ft. Lauderdale, Florida. Available on www. arvo. org, the abstracts are referenced by program number (#). In his keynote address, Elias A. Zerhouni, MD, director of the National Institutes of Health, laid emphasis on eye diseases related to aging and stressed that more research was needed in the field of nanotechnology NEUROPROTECTION AND RETINAL GANGLION CELLS New approaches to neuroprotection that target the optic nerve or the retinal ganglion cells ( RGCs) in patients and animal models of optic nerve damage were presented. An experimental optic nerve crush model in rats was shown to produce an early increase in superoxide levels in RGCs, and the authors concluded that scavenging superoxide or inhibiting its intracellular targets may be a useful approach for RGC neuroprotection (# 154). Sprague- Dawley rats were exposed to optic nerve crush at different time intervals after traumatic brain injury ( TBI) to the contralateral hemisphere to study the effect of TBI on RGC survival. TBI is anticipated to cause immune- mediated neuroprotection and to salvage dying RGCs if performed one to two weeks before optic nerve crush but not concomitantly with the crush. The authors believe that TBI at a distant site may have a neuroprotective effect on the RGCs. This neuroprotective effect is probably immune mediated ( secondary to an increased level of brain- derived neurotrophic factor [ BDNF]); systemic corticosteroids may aid this neuroprotective effect (# 666). Culture of immuno- purified RGCs was performed to screen for compounds promoting RGC survival. The authors found more than 30 candidate compounds of 1,200 screened and identified a novel pharmacologic compound that promoted RGC survival and neurite outgrowth in a dose-dependent manner (# 170). Neuroprotective agents like LINGO- 1 ( a new member of the myelin receptor complex), estrogen, copolymer- 1, pituitary adenylate cyclase- activating polypeptide, pigment epithelium derived growth factor, inactivation of Rho, and pitavastatin ( a statin with high affinity to vascular endothelium) were found to prevent RGC degeneration or promote survival of retinal ganglion and pigment epithelial cells in animal models (# 157,158,160,164,167,174,179). OPTIC NEUROPATHY The relative risk for obstructive sleep apnea ( OSA) was found to be five times higher in patients with non-arteritic anterior ischemic optic neuropathy ( NAION) compared to the general population (# 644). The rate of OSA was 1.5- 2 times more frequent than other risk factors associated with NAION. The relationship between visual field loss and intraocular pressure ( IOP) was studied in patients with optic disc drusen (# 658). In 22 patients with intraocular pressure > 22 mm Hg, 91% had visual field loss. In 81 patients with normal IOP (< 22 mm Hg), 66% had visual field loss. Histopathologic evidence of subclinical involvement of peripheral neurons was found in a patient with Leber hereditary optic neuropathy ( LHON) (# 661). Neurodegenerative morphological changes affecting most nerve fibers in the brachial plexus were identified. Optic nerve crush leads to an increase in hydrogen peroxide levels in cultured RGCs with a peak level 3 days after injury (# 154). Antioxidant protein superoxide dismutase gene transfer to mitochondria in an experimental model for optic neuritis transiently protects against oxidative injury to RGC axons (# 1197). The gene defective in dominant optic atrophy ( DOA) is OPA1, which encodes a mitochondrial protein implicated in mitochondrial fusion and maintenance of cristae function. OPA1 is a dynamin- related GTPase and may act as a mechano- enzyme or regulatory GTPase. Knockout of OPA1 protein expression in mice triggered a dramatic breakdown in the filamentous interconnected mitochondrial network into multiple isolated organelles (# 5188). This was accompanied by partial inhibition of respiration, a decrease in cellular adenosine triphosphate level, and mitochondrial ultrastructural abnormalities, which may impair normal neuronal function and lead to degeneration. VISUAL CORTEX The use of optical coherence tomography to image the retinal nerve fiber layer to identify transsynaptic degeneration in occipital infarcts was explored (# 616). Loss of the nerve fiber layer in the nasal hemi- fovea temporally and the horizontal projections nasally was observed in one eye, whereas thinning in the superior and inferior temporal arcades was observed in the other eye in a patient with a homonymous hemianopia. BLEPHAROSPASM Modulation of photophobia in essential blepharospasm with chromatic lenses was studied (# 617). Of seven lenses tested, the FL41 lenses, which block the highest wavelength in the visible spectrum, did not result in the highest intensity of light tolerance compared to other chromatic lenses. However, FL41 lenses were subjectively preferred by most patients with blepharospasm. The authors concluded that photophobia may be related more to wavelength than intensity of light exposure. NEUROIMAGING Diffusion tensor imaging ( DTI) was used to investigate apparent diffusion coefficient ( ADC), a measure of diffusion magnitude, and fractional anisotropy ( FA), a measure of preferential directionality, as part of MRI scanning of four patients with optic neuritis (# 639). Three patients with a good prognosis for visual recovery had high ADC and low FA within one week of visual symptom onset. At three- month follow- up, ADC returned to normal. DTI may provide information useful for predicting the prognosis for visual recovery in optic neuritis. Eyes with high ADC during the acute phase had a good prognosis. PSEUDOTUMOR CEREBRI The localization of retinoic acid receptors and cellular retinoic acid- binding protein in human arachnoid granulation tissue in vivo and in tissue culture suggests a role for vitamin A in cerebrospinal fluid ( CSF) flow regulation (# 627). An in vitro model of CSF flow accurately replicated one- way CSF flow and may be used to study idiopathic intracranial hypertension (# 629). LEBER HEREDITARY OPTIC NEUROPATHY A separate session dedicated to LHON detailed the results of a comprehensive 2- year follow- up examination of the 300- member homoplasmic 11778 LHON pedigrees of seven generations described in rural Brazil. Studies of the asymptomatic carriers of the LHON mutation in the Brazilian pedigree reveal that subtle defects, such as nerve fiber layer swelling and telangiectasias, precede the onset of severe vision loss (# 1199). In a rodent model of LHON, an adenovirus was intra-vitreally injected to deliver a vector containing a mutated form of the ND4 subunit of mitochondrial complex I (# 1198). Three months after injection, the rodent had developed optic disc pallor, apoptotic RGC loss, retinal thinning, gliosis, and demyelination. These findings support a role for reactive oxygen species- related injury to mitochondrial proteins in the pathogenesis of LHON. ELECTROPHYSIOLOGY Near- infrared spectroscopy, which measures changes in hemoglobin concentration evoked by brain activity, showed decreased activation of the visual cortex in patients with unilateral optic neuritis (# 640). Multifocal visual evoked potential testing ( MfVEP) was able to demonstrate subclinical episodes of optic neuritis (# 641). MfVEP was also used to compare latencies in patients with ischemic optic neuropathy and optic neuritis (# 642). Both groups of patients had significantly delayed latencies compared with normal controls. In cluster analysis, the latencies were greater in optic neuritis than in ischemic optic neuropathy. PUPIL As measured by an automatic pupillometer, pupillary light reflex latencies were greater and amplitudes were lower in the active and recovery phases of patients with retrobulbar neuritis as compared with control subjects (# 634). PERIMETRY In patients with NAION, the number of abnormal points was greater with the frequency doubling than with the Swedish Interactive Thresholding Algorithm technique (# 643). EYE MUSCLES/ MOVEMENTS A ring- sling computational model of active rectus muscle pulleys confirmed the active pulley hypothesis and Listing's law of ocular torsion that proposes that the rectus pulleys receive insertions of orbital layers of rectus extraocular muscles ( EOMs) to shift pulleys anteroposteriorly during EOM activity so as to maintain a constant distance from pulleys to scleral insertions (# 4675). In another paper, this " active pulley hypothesis" was refuted by clinical, imaging, and physiological evidence (# 4766). Novel drug delivery techniques, such as single injections of growth factors into rabbit rectus muscles, resulted in an increase in force generation that can potentially be used clinically to increase EOM strength. It is known that EOMs remain clinically and pathologically spared, even in advanced cases of Duchenne muscular dystrophy ( DMD). Quantification of stem cell fractions in mice EOMs and tibialis anterior demonstrated that the proportion of stem cells was increased 5- to 20- fold in EOMs as compared with tibias anterior muscles. This finding supports the hypothesis that EOM stem cells contribute to sparing of EOMs in DMD (# 5726). In another experimental study in rabbits, the authors found a greater preponderance of stem cells and satellite cells in the EOMs than in limb muscles (# 4679). To study the mechanisms of complement- induced neuromuscular junction injury in myasthenia gravis ( MG), the authors induced experimental autoimmune MG in mice by injecting rat anti- acetylcholine receptor monoclonal antibodies. They found a significant change in the expression of 204 genes in the experimental mice that encode for immunoglobulin chains, transcription factors, and transport proteins. These pathways may thus be used to study sites for future intervention (# 5729). Ultrastructural and immunohistologic studies in experimentally induced hyperthyroid EOMs in mice demonstrated an interstitial protein- like infiltrate, cyclooxygenase- deficient-succinate dehydrogenase- positive muscle cell infiltration, and numerous abnormal mitochondria. These results suggest that mitochondria may play a significant role in the pathogenesis of ophthalmic manifestations in hyperthyroidism (# 5730). ORBIT Porous polyethylene implants containing embedded titanium mesh were found to be an excellent alternative to traditional porous polyethylene implants when postoperative imaging of the implant was important (# 5717). Swaraj Bose, MD University of California Irvine Irvine, California Howard D. Pomeranz, MD, PhD North Shore Long Island Jewish Health System Great Neck, New York |
