| OCR Text |
Show NEURO- OPHTHALMOLOGY AT LARGE Annual Meeting of the Association for Research in Vision and Ophthalmology ( ARVO) Fort Lauderdale, Florida May 6- 10, 2007 More than 6,000 abstracts were presented at the annual meeting of the Association for Research in Vision and Ophthalmology ( ARVO), Fort Lauderdale, FL, May 6- 10, 2007. Available at www. arvo. org, the abstracts are referenced by program number (#). This year the focus was on the ' Aging Eye.' In their keynote address, William Novelli, director of American Association of Retired Persons ( AARP), and Paul Lee, MD, of Duke University emphasized the rising ophthalmic health care costs in the aging population and the importance of early recognition and treatment. The Proctor Medal was awarded to Nicolas Bazan, MD, PhD, for his work on neuroprotection signaling in retinal pigment epithelium. The Weisenfeld Award went to David Guyton, MD, for his seminal work on cyclovertical strabismus. The Friedenwald Award winner was Ilene Gipson, PhD, who presented her work on the importance of the ocular surface. The Cogan Award was given to Wolfgang Drexler, PhD, for his pioneering work on optical coherence tomography ( OCT). NEUROPROTECTION In a placebo- controlled animal study using pigmented rabbits, a single dose of oral memantine was found to normalize the sweep visual evoked potential ( VEP) deficit after an acute elevation of intraocular pressure ( IOP) (# 96). Prophylactic administration of simvastatin was shown to produce neuroprotective effects against ischemic reperfusion- dependent deficits in retinal function demonstrated by using a rat acute glaucoma model and quantitated by recording scotopic electroretinograms ( ERGs) before and 1 week after the ischemic insult (# 208). Brimonidine, an a2 receptor agonist, provided rescue and protection from stress- induced loss of mitochondrial membrane production and reactive oxygen species ( ROS) production in rat retinal ganglion cells ( RGCs). This study suggests that brimonidine exerts a direct protective effect on RGCs apart from its role in lowering IOP (# 620). Intravitreal injections of activators of SIRT1, an enzyme involved in cellular stress resistance and survival, attenuated RGC loss in a dose- dependent manner in a mouse model of optic neuritis. The neuroprotective effect was blocked by sirtinol, a SIRT1 inhibitor. This model suggests that SIRT1 activators may be beneficial as additives with current multiple sclerosis ( MS) immunomodulatory therapies (# 563). Bacterial DNAwas shown to provide neuroprotection after optic nerve crush injury by suppressing CD4 and CD5 regulatory T cell activities (# 1539). NAP is an 8- amino acid peptide derived from activity- dependent neuroprotective protein and plays an important role in neuronal differentiation and survival of neurons. Injected intraperitoneally in a retinal ischemia rat model, NAP increased the number of surviving RGCs by 30%- 40% after optic nerve crush and retinal ischemia in vitro (# 565). Tempol ( 4- hydroxy- 2,2,6,6- tetramethylpiperidine- l- oxyl), a superoxide dismu-tase mimetic, attenuated RGC loss in an optic nerve crush trauma model (# 3286). OPTIC NEUROPATHY Rodent anterior ischemic optic neuropathy ( rAION) induced in Wistar rats showed a regional loss of RGCs by apoptosis (# 4197). Although some RGCs die soon after induction of AION, demonstrable apoptosis occurs for nearly 1 month after induction with two major peaks of cell death. The earliest apoptotic peak is the longest, with a major loss of cells occurring between 7 and 15 days. Apoptosis was nearly complete by 31 days, suggesting that a measure of retinotopic organization occurs in the rodent optic nerve as in primates and humans (# 4197). Because there are considerable differences between rodent and primate retina and optic nerves, a primate model of non-arteritic anterior ischemic optic neuropathy ( pNAION) that closely resembled clinical NAION was produced using rhesus monkeys (# 4410). In a clinical study, investigators determined that the severity of visual field loss ( mean deviation) in the first eye was a risk factor for developing NAION in the second eye (# 3172). Nuclear gene OPA1 encodes a mitochondrial inner membrane protein, a GTPase in the dynamin family, and J Neuro- Ophthalmol, Vol. 27, No. 4, 2007 317 J Neuro- Ophthalmol, Vol. 27, No. 4, 2007 Bose and Pomeranz maintains the integrity of mitochondrial inner membrane. OPA1 is expressed in all retinal layers including the RGC. Immunohistochemical and electron microscopic studies on mouse retina, optic nerve, and tracts were performed using OPA1 and ATP synthase antibodies. The mitochondrial structure in RGC axons posterior to the lamina cribrosa is tubular with dark content. Anterior to the lamina cribrosa, mitochondria are round with clear content. The transformation from spherical to tubular mitochondria involves OPA1 function. OPA1 activity is also important in distribution of mitochondria along the axon during retinal development and maintenance of the mitochondrial membrane potential. A study found that OPA1 in the cell soma is required to prevent apoptosis (# 1540). In a clinical study, retinal nerve fiber layer ( RNFL) thickness measurements using OCT were performed in 30 patients with OPA1- dominant optic atrophy ( DOA), showing that OPA1 influences the anatomical conformation. Findings included decreased nerve fiber layer thickness in all four quadrants around the optic nerve, decreased disc area, vertical and horizontal disc diameter, decreased rim area, and increased cup- to- disc ratio. There was diffuse thinning of the RNFL in all four quadrants (# 3170). Conventional VEP latency did not reveal a significant difference between optic disc drusen group and control subjects, but multifocal VEP ( mfVEP) latency was greater in the drusen group, being abnormal in up to 70% of eyes (# 3174). The G- to- A transition at nucleotide 11778 in mitochondrial DNA in the gene specifying the NADH dehydrogenase subunit 4 ( ND4) of complex I leads to Leber hereditary optic neuropathy ( LHON). In a model for LHON, vitreal injection of wild- type human ND4 in rats containing the mutant human ND4 gene did not protect against retinal ganglion cell loss induced by mutant ND4. Wild- type ND4 injected 1 month before induction of optic neuropathy suppressed apoptosis by 33% and suppressed optic nerve head swelling at 6 months by 27%. Wild- type ND4 did not suppress optic neuropathy if injected at 6 months before induction of optic neuropathy. The lack of rescue was probably due to the dominant effect of the mutant human ND4 in the mouse (# 3171). Some small- caliber unmyelinated efferent fibers were demonstrated in the optic nerves obtained at autopsy from patients with Leber hereditary optic neuropathy. These noradrenergic fibers were more numerous in the peripheral portion of the optic nerve (# 2450). In a case- control retrospective review of patients in whom traumatic optic neuropathy was diagnosed between January 2003 and May 2006, 30 of 38 patients with indirect traumatic optic neuropathy received megadoses of intravenous methylprednisolone ( 30 mg/ kg loading dose followed by 5.4 mg/ kg/ h for 24- 48 h), whereas eight patients were not treated. The corticosteroid- treated group on average had better visual acuity than the untreated group. These very preliminary results suggest that corticosteroid treatment may be beneficial in this form of traumatic optic neuropathy, but larger numbers are needed (# 2479). In a retrospective United Kingdom study involving 124 patients with giant cell arteritis ( GCA), the authors found no difference in ischemic complications between patients with GCA who were treated with aspirin and those not so treated (# 922). OPTIC NERVE IMAGING In 23 patients with MS who underwent RNFL and optic nerve head measurements using scanning laser polar-imetry ( GDx- VCC) and scanning laser ophthalmoscopy ( HRT), significant differences between affected and fellow eyes were found for some GDx and mean RNFL HRT parameters. No significant correlation was observed between clinical assessment and imaging techniques. The results suggested that GDx and HRT measurements are an important tool in measuring axonal damage in MS (# 908). VISUAL PATHWAYS A combination of self- assembly peptide nanofiber scaffold and chondroitinase ABC appears to create a more permissive environment in optic tract lesion repair, resulting in return of vision. The addition of self- assembly peptide Arg- Ala- Asp- Ala together with chondroitinase ABC increased the number of re- innervations after incisions in the optic tract of a hamster (# 3168). Intraventricular hemorrhage ( IVH) is a major cause of adverse neurologic outcome after premature birth. VEP recordings were used to study visual cortex function in low-birth- weight infants with IVH. The study included 72 infants who demonstrated lower contrast and spatial frequency swept parameters, a finding that may reflect neuronal loss by injury to germinal matrix, subclinical damage, or developmental delay (# 3169). Visual rehabilitation using Luebeck software in three patients with homonymous hemianopia ( HH) resulted in an increase in the visual fields varying from 2 to 10. This resulted in an improved ability to read and walk (# 952). RGC function was studied in three patients with pathologic cupping of the optic nerve but normal vision and IOP who also underwent resection of non- secreting pituitary tumors. Before surgery, all six eyes showed pattern ERG ( PERG) dysfunction with an average reduction of amplitude of 42.5% and average phase delay of 4.4%. After tumor resection, PERG amplitudes progressively recovered to normal. The authors hypothesized that there is blockage of retrograde axonal transport of neurotrophins in chiasmal compression. Interference in axonal flow was attributed to local ischemia of the optic chiasm in non- compressive 318 © 2007 Lippincott Williams & Wilkins ARVO Meeting J Neuro- Ophthalmol, Vol. 27, No. 4, 2007 cases. A potential candidate for this hemodynamic perturbation is the vasoactive peptide endothelin- 1 released by pituitary tumor (# 928). IDIOPATHIC INTRACRANIAL PRESSURE ( IIH, PSEUDOTUMOR CEREBRI) 11- Hydroxysteroid dehydrogenase 1 ( HBHSDl) has been previously identified in the ciliary body as an intraocular regulator of Cortisol. A similar mechanism has been hypothesized for the control of cerebrospinal fluid ( CSF) dynamics. Immunohistochemical analyses of postmortem human choroid plexus and arachnoid granulation tissue identified the presence of 11BHSD1. These results suggest that manipulating 11BHSDI and CSF Cortisol may have important therapeutic implications in regulating CSF dynamics and possibly intracranial pressure ( ICP) (# 927). Inflammatory and adiposity- related cytokine profiles were studied using serum and CSF samples from patients with IIH and others undergoing lumbar puncture. Higher levels of serum and CSF leptin and lower levels of adiponectin were detected in patients with IIH than in other groups, suggesting a novel abnormality of the adipokine profile in IIH (# 926). A retrospective study of 110 patients with IIH showed that about 25% had an identifiable cerebral venous thrombosis detected by brain MRI ( 35.7%) and magnetic resonance venogram ( MRV) ( 82%) and also had coagulopathies. The authors suggested that evaluation of a coagulopathy is mandatory in these patients and that they should not be classified as having IIH unless such studies are normal (# 925). In a prospective study, CSF and serum were obtained from six patients with IIH and six control subjects to analyze for retinoic acid, retinol, retinyl esters, retinol-binding protein, and transthyretin, a transport protein for vitamin A. There was an increase in retinoic acid levels in CSF compared with serum levels in patients with IIH compared with control subjects. The results may explain the role of vitamin A metabolites, which may reduce permeability at the arachnoid granulations, thereby contributing to increased CSF pressure (# 924). Based on an earlier finding that IOP is reflective of ICP, the authors analyzed data obtained from 35 patients with IIH, 7 with NAION, and 5 with other conditions. No substantial correlation was seen between average IOP and ICP (# 938). THYROID EYE DISEASE A session dedicated to thyroid- associated orbitopathy ( TAO) focused on new directions for unifying basic and clinical science. Orbital fibroblasts in patients with Graves disease have been shown to be different from fibroblasts elsewhere in the body. Insulin growth factor ( IGF- 1) and interleukin- 1 play important roles in the regulation of fibroblast proliferation and the inflammatory components of thyroid orbitopathy. Potential targets for treatment of Graves orbitopathy include antibodies to the IGF- 1 receptor and cytokine antagonists. Several immunologic and hypothyroid animal models of Graves disease ( including mutants) were discussed, and the tree shrew was thought to be an appropriate model as it is a primate with a well-formed orbital cavity (# 359). In an in vitro study, mouse extraocular muscles ( EOMs) cultured with the addition of thyroid hormone ( T3) demonstrated an increased level of caspase 8 and 3 activity compared with control EOMs. The results suggested that T3- induced hyperthyroidism in cultured EOMs is associated with apoptosis involving mitochondria and caspase pathways (# 5276). In another in vivo hypothyroid mouse model, the EOMs demonstrated an increase in myofibril thickness and mitochondrial density. This study highlighted the role of confocal scanning laser microscopy in the quantitative assessment of EOM changes and showed that it was comparable to the more time- consuming light and electron microscopy (# 5626). Hypothyroid rats were used in an experimental study to evaluate the effect of thyroid hormone on the expression of thyroid hormone receptor- 1 ( TRbl) on the lacrimal gland. The authors concluded that the lacrimal gland expresses TRb 1 and that hypothyroidism induces a higher expression of this receptor, confirming the fact that the lacrimal gland is a target organ for thyroid hormone and suggesting a mechanism for dry eyes in hypothyroidism (# 416). PUPILS In a study of relative afferent pupillary defects ( RAPDs) in amblyopia, horizontal pupil diameters and amplitude of contractions were studied in 12 patients with unilateral amblyopia ( from ametropia or strabismus) using binocular infrared pupillography Only one patient with moderate amblyopia was found to have an RAPD in the amblyopic eye, suggesting that only a small percentage of patients with unilateral amblyopia have a RAPD (# 4878). Pupillary responses ( amplitude, latency, constriction, and dilation velocity) to a graded light source over a standard ambient background were evaluated in 14 patients with RAPD to quantify and compare the asymmetry of the pupil reflex in ischemic to various other optic neuropathies. The authors found that the abnormally reacting pupil caused by ischemic optic neuropathy showed a slower maximum and mean constriction velocity and concluded that the comparison of the difference in amplitude constriction might distinguish the RAPD seen in ischemic versus other etiologies of RAPD (# 5538). Pupil contractions in response to chromatic stimuli ( red and blue light) as a function of brightness were studied 319 J Neuro- Ophthalmol, Vol. 27, No. 4, 2007 Bose and Pomeranz in 13 patients with photoreceptor disease ( retinitis pigmentosa and rod- cone dystrophy) to differentiate the photoreceptor- mediated pupil responses from those of melanopsin- containing retinal ganglion cells. The diseased eyes demonstrated a relative decrease in the transient pupil response at low and medium intensities to both red and blue light stimuli. They also found that pupil dilation after a 10- second light exposure was slower after blue light than after red light stimulation. Thus, in eyes with photoreceptor disease, there is a relative decrease in the transient pupil response, indicating that the initial component of pupil contraction is mediated by photoreceptors in humans. The rapid pupil dilation after termination of light stimulation is probably mediated by a light- off signal from photoreceptors, which inhibits sustained firing on the pupil light reflex by the melanop sin- containing retinal ganglion cells. This study clearly demonstrates that patients with photoreceptor disease have abnormal transient and sustained pupil contractions that correlate with the physiologic response properties of melanopsin- containing retinal ganglion cells (# 5535). 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 320 © 2007 Lippincott Williams & Wilkins |
