Journal of Neuro-Ophthalmology, December 2003, Volume 23, Issue 4

Annual Meeting of the Association for Research in Vision and Ophthalmology

NEURO- OPHTHALMOLOGY AT LARGE Annual Meeting of the Association for Research in Vision and Ophthalmology ( ARVO), Fort Lauderdale, Florida, May 4- 9, 2003 Approximately 5250 abstracts were presented at the Annual Meeting of the Association for Research in Vision and Ophthalmology ( ARVO), Fort Lauderdale, FL, May 4- 9, 2003. The abstracts, available on www. arvo. org, are referenced by program number (#). NEURO- PROTECTION New approaches to neuro- protection targeted the op­tic nerve or the retinal ganglion cells ( RGCs) in animal models of optic nerve damage and in patients. Lomerizine, a diphenylmethylpiperazine calcium antagonist, was shown to enhance retinal ganglion cell survival induced by optic nerve damage (# 108). In another study, trans- corneal electrical stimulation was shown to enhance the survival of axotomized retinal ganglion cells in adult rats (# 109). In another study from Germany, the authors concluded that there was inhibition of calcium- activated neutral cysteine proteases by calpain inhibitor MDL- 28170, which may of­fer neuroprotective effects after an excitotoxic lesion (# 110). Copolymer 1 ( Copaxone), an FDA- approved drug for multiple sclerosis ( MS), was shown to rescue at least 50% of the potentially doomed retinal ganglion cells fol­lowing intraocular pressure- induced death. This drug has the potential for use as a therapeutic vaccination in cases of acute optic nerve damage following high intraocular pres­sure (# 112). Theanine, topical brimonidine purite ( Al-phagan- P), and minocycline were found to protect retinal ganglion cell damage in rats (# 119, # 120, # 124). Neuropro­tective effects of the potent anti- inflammatory cytokine in-terleukin- 10 ( IL- 10) were shown to inhibit apoptosis of reti­nal ganglion cells. It was postulated that IL- 10 may exert its effect by modulating nuclear factor kappa- B activity or by inhibiting the synthesis of proinflammatory cytokines such as TNF- alpha, both of which play an important role in cell survival (# 125). OPTIC NEUROPATHY Sleep apnea was suggested as one of the risk factors in patients with ischemic optic neuropathy (# 625). A rat model of photoembolically- induced non- arteritic ischemic optic neuropathy ( NAION) appeared to spare the retinal vasculature, as evidenced by normal electroretinogram ( ERG) recordings (# 622). Gene expression studies in a similar rat model were shown to correlate with retinal gan­glion cell loss (# 624). Serum uric acid, a natural antioxi­dant, was found to be lower in patients with acute optic neuritis and MS than in controls; it may be a marker to dis­tinguish optic neuritis from other optic neuropathies (# 630). Among patients with sarcoid optic neuropathy, early with­drawal of corticosteroid treatment was associated with re­lapse and the need for additional immunosuppressive therapy to maintain vision (# 637). RETINAL GANGLION CELLS/ APOPTOSIS Experimental models used retinal ganglion cell ( RGC) death created by transecting the optic nerve, raising the intraocular pressure, or direct laser ablation. The retinal ganglion cells were labeled retrogradely by injecting fluo-rogold into the superior coUiculus region. Several recent reports have suggested that reactive oxygen species play an important role in neuro- degeneration following ischemia or perfusion injury. A study from Japan concluded that the use of MCI- 186, a radical scavenger, had a neuroprotective ef­fect in the rat retina. Reactive oxygen species evidently play a role in the early phase of retinal ganglion cell degenera­tion following ischemia (# 128). Fibroblast growth factor- 2 gene delivery using recombinant adeno- associated virus was shown to stimulate extensive axonal regeneration of adult retinal ganglion cells in vivo (# 129). Ginexin ( Gingko biloba extract) increased the survival of retinal ganglion cells in the rat optic nerve crash injury model. This did not significantly influence the intravitreal glutamate concentra­tion (# 130, # 146). 2- deoxy- D- glucose ( 2DG), a non-metabolizable glucose analog that mimics caloric restric­tion, was shown to protect retinal ganglion cells against NMDA- mediated excitotoxicity (# 133). Survival of puri­fied retinal ganglion cells in culture after withdrawal of brain- derived neurotrophic factor and ciliary neurotrophic factor was significantly improved by co- culture with cloni-dine or timolol. Demonstration of in vivo RGC apoptosis was possible using intravitreal staurosporine and fluores-cein- labeled annenxin- 5, a marker for apoptosis, and using confocal scanning laser ophthalmoscopy with an argon la­ser (# 2150). Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 298 JNeuro- Ophthalmol, Vol. 23, No. 4, 2003 Neuro- Ophthalmology At Large JNeuro- Ophthalmol, Vol. 23, No. 4, 2003 IMAGING There were several papers that discussed the repro­ducibility of optic nerve head parameters and retinal nerve fiber layer thickness ( RNFL) measurements using the new optical coherence tomography 3 device ( OCT 3) (# 3384, # 3394, # 3396, # 3639). The OCT 3 has the potential of de­tecting changes prior to their detection with achromatic au­tomated perimetry (# 3392). Retinal thickness was found to be 10% greater when measured histologically in rabbits as compared with OCT measurements and this variation re­sulted from the fact that the OCT measures the optical prop­erties of the retina rather than the actual thickness of the RNFL (# 3639). Mean muscle index of all six extraocular muscles using A and B scan USG and the BVI Quantel Cinescan S program aids in the differential diagnosis of pa­tients with thyroid eye disease; the authors found a high incidence of involvement of the superior rectus mus­cle (# 3657). PSEUDOTUMOR CEREBRI In a retrospective study of 72 eyes with pseudotumor cerebri ( PTC), the authors found sequential disc photo­graphs to be a sensitive method in monitoring disease pro­gression (# 610). Measurements of optic nerve sheath diam­eter using B- scan USG seemed to be a good non- invasive and indirect measure of raised intracranial pressure in pa­tients with PTC (# 611). Analysis of perfusion- weighted MRI and MRA in patients with PTC revealed marked hy­poperfusion of subcortical white matter (# 612). Positron emission tomography ( PET) can provide functional infor­mation not attainable with MRI or MRA. PET imaging in a patient with PTC and vision loss ( with normal brain MRI) revealed a bilateral decrease in the glucose uptake in the visual association areas ( Broca's area 19, dorsal visual stream). Postoperative PET scans following optic nerve sheath fenestration surgery demonstrated a bilateral in­crease in uptake along the occipital, temporal, and parietal visual association areas that correlated with significant vi­sual improvement (# 2725). OPTIC NERVE Quantitative analysis of optic disc parameters using Heidelberg retinal tomography in patients with optic nerve head drusen with and without visual field loss demonstrated that the disc and rim areas were significantly larger in pa­tients with visual field loss than in those without visual field loss. It was hypothesized that the drusen reach a critical size at which compression damage of axons and corresponding field defects finally occur (# 615). Analysis of visual field defects in patients with congenital optic nerve tilting or en­larged optic nerve cups disclosed features typically seen in patients with optic nerve hypoplasia(# 617). Optic nerve hy­poplasia was found in about 10% of patients with aniridia with or without foveal hypoplasia (# 620). Strabismus and anisometropia were the most common clinical signs in 20 patients with Morning Glory syndrome, and B- scan USG demonstrated a new finding called the " overhanging glial tissue sign" (# 621). Chronic ischemia in the monkey optic nerve induced by infusion of endothelin- 1 to the nasal su­perior optic nerve resulted in a preferential damage to the temporal superior region of the optic nerve (# 3325). Immu-nohistochemical studies of cadaver optic nerves in the re­gion of the lamina cribrosa demonstrated increased mito­chondrial density; the authors suggested that this finding indicates increased energy requirements in this region. It may also why optic neuropathy occurs in mitochondrially-inherited diseases (# 626). In an experimental study in pigs, intravenous acetazolamide, in addition to carbogen breath­ing ( 95% 02+ 5% C02), significantly increased oxygen­ation of the optic disc, probably due to the vasodilatory ef­fect of elevated systemic PaC02 (# 1298). LEBER HEREDITARY OPTIC NEUROPATHY A separate session dedicated to Leber's Hereditary Optic Neuropathy ( LHON) detailed the results of a compre­hensive one- year follow- up examination of the 300- member homoplasmic 11778 LHON pedigrees of seven generations described in rural Brazil. The authors found that carriers of LHON had subtle findings including disc edema, blood vessel telangiectasias, nerve fiber layer edema, reduced nerve fiber layer measurements (# 939), mild visual field defects (# 935), tritan or deutan color vision defects (# 940), and prolonged latencies in the pat­tern- reversal visual evoked potentials (# 936). Patients with severe visual loss continued to demonstrate low grade de­terioration over time. Administration of complex II substrates or the human gene for mitochondrial superoxide dismutase ( SOD2) did not significantly improve LHON cybrid cell survival and suggested that other reactive oxygen species or reduced ATP synthesis may play a role in cellular injury and optic neuropathy in LHON (# 941). In another paper, the authors showed that the oxidative injury induced by Complex I de­ficiency is protected with adeno associated virus- mediated gene transfer of human SOD2 and concluded that that this approach may be used in the future to treat patients with diseases like LHON or MS (# 627, # 628). Segregation analysis of 128 maternally- related individuals with LHON indicated the existence of a nuclear modifier gene that could explain variable penetrance within the same family (# 937). There were no significant differences in the circulat­ing levels of total antioxidants, lipids peroxidation prod­ucts, IL- 3 and TNF- alpha in male and female LHON pa­tients and non- affected carriers. However, there was a significant elevation of circulating and neuron- specific enolase levels in male carriers when compared with normal Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 299 JNeuro- Ophthalmol, Vol. 23, No. 4, 2003 Bose male controls. Neuron- specific enolase levels may be a good indicator of retinal ganglion cell and optic nerve stress degeneration (# 938). EYE MOVEMENTS In an attempt to find a reproducible and standard mea­sure of ocular motor ductions in clinical trials, the Kesten-baum test ( using a ruler to measure the ductions) was found to be less variable than a cervical range of motion device ( CROM) (# 1931). Deep brain stimulation of the thalamus in patients with Parkinson's disease minimized the tremor and improved fixation stability and eye- head coordination movements (# 1935). In a prospective study, all 25 CPEO patients with cytochrome c oxidase ( COX)- deficient fibers presented with exotropia, relative sparing of downgaze, and the degree of diplopia was proportional to the proportion of COX- deficient fibers in the muscle biopsy (# 1947). ELECTRORETINOGRAPHY Multifocal electroretinography ( mfERG) may emerge as the best method to detect early retinal toxicity in clinically symptomatic and asymptomatic patients on long-term chloroquine/ hydroxychloroquine retinopathy. MfERG showed a significant decrease in the PI amplitude in the foveal and paracentral rings (# 2701). The ERG pho-tostress test, using focal 41 Hz ERG, was found to be effec­tive for early detection of macular disease and was unaf­fected by media changes (# 1899). PUPIL Alterations in the pupil size were shown to alter the temporal modulation sensitivity ( TMS) and absolute light sensitivity ( ALS) across the central visual field. Dilated pu­pils ( 6mm) resulted in higher sensitivities than did smaller pupils ( 3, 4.3mm) for both of these visual assessment pa­rameters (# 4095). The relationship between parameters of the pupillary light reflex and the corneal illuminance after 20 minutes of adaptation for each illuminance level was in­vestigated in 23 normal subjects. The authors found that the amplitude of pupillary constriction changed with the adap­tation illuminace level significantly in the adaptation light range from 60- 400 ft- cd. It was concluded that the adapta­tion illuminance ( in ft- cd) must be considered when quan­titatively measuring the parameters of the pupillary light reflex (# 4077). Alterations of the pupil diameter ( using my­driatics and miotics in normal subjects) influenced the la­tency but not the amplitude of multifocal visual evoked potentials ( mfVEP). The results suggest that even with pharmacologically altered pupil size, the mfVEP can be used to assess diseases that affect signal amplitude, but the interpretation of latency must be used with caution as a bor­derline conduction defect with a dilated pupil may appear normal (# 4118). PERIMETRY The new frequency doubling perimetry ( FDT2) 24- 2 testing strategy provides a screening and quantitative visual field parameter for optic nerve, chiasmal, and post chiasmal disorders, and was found to correlate well with HVF II SITA Standard 24- 2 program (# 1951, 1956). Patients with recovered optic neuritis showed better visual fields than predicted by nerve fiber layer thickness, perhaps as a re­sult of a compensatory mechanism not present in other op­tic neuropathies like glaucoma, AION, and compres­sion (# 1959). SCANNING LASER OPHTHALMOSCOPY The scanning laser ophthalmoscope was found to be a useful tool in the evaluation of suspected psychogenic vi­sual loss as it could document patient fixation and test vi­sual acuity under direct visualization (# 1963). ORBIT The integrated hydroxyapatite implant reduced im­plant migration but increased the rate of conjunctival dehis­cence when compared with the non- integrated implants (# 2216). In another study, extrusion of the implant was only seen with the glass sphere implants when compared with porous polyethylene and hydroxyapatite implants (# 2219). In an experimental study using pediatric porcine anoph-thalmic sockets, the hydrogel autoexpansile orbital im­plants provided safer and more reliable stimulation of bony orbital development than did dermis fat grafting (# 2226). A graded approach to orbital decompression for dysthyroid orbitopathy resulted in a fairly predictable proptosis reduc­tion; the greatest reduction was seen with a three- wall de­compression through a lateral and transcaruncular approach (# 2223). Orbital endoscopy using free electron laser al­lowed better visualization of media using carbon dioxide and it was possible to perform optic nerve sheath fenestra­tion in cadaver eyes using this technique (# 613, 614). Swaraj Bose, MD Department of Ophthalmology University of California Irvine Irvine, California Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 300 © 2003 Lippincott Williams & Wilkins