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Show NEURO- OPHTHALMOLOGY AT LARGE The Annual Meeting of the Association for Research in Vision and Ophthalmology, Fort Lauderdale, Florida April 30- May 4, 2006 Some 5,920 abstracts were presented at the Annual Meeting of the Association for Research in Vision and Ophthalmology ( ARVO), Fort Lauderdale, Florida, April 30- May 4, 2006. Available on www. arvo. org, the abstracts are referenced by program number. In their keynote address, Paul Sieving, MD, PhD, Director of the National Eye Institute and G. N. Rao, MD, President, International Agency for the Prevention of Blindness ( IAPB), emphasized the importance of building global partnerships in performing vision research as a vital method for the control of avoidable worldwide blindness. Among this year's presentations, well over half were multi-country collaborations. The Proctor Medal winners were Trevor D. Lamb, BE, ScD, FRS ( Cambridge, U. K.) and Edward N. Pugh, Jr., PhD ( Philadelphia, PA), who, in an elegant joint presentation, discussed their work on " The Vision Cycle." The Weisenfeld, Friedenwald, and Cogan awards were given to S. Evangelos Gragoudas, MD ( Boston, MA), David Williams, PhD ( Rochester, NY), and Joshua L. Dunaief, MD, PhD ( Philadelphia, PA) for their contributions to the field of uveal melanomas, human vision, and pathogenesis of age- related macular degeneration, respectively. NEUROPROTECTION AND OPTIC NERVE PHYSIOLOGY When investigating the cellular and molecular mechanisms underlying optic nerve degeneration after axotomy, it was concluded that cell invasion ( microglia, oligoden-drogliocytes, astrocytes), semaphorin induction, the presence of myelin debris, and disruption of the internal organization of the optic nerve contribute to the generation of the nonpermissive environment that prevents axonal regeneration and leads to neuronal loss (# 727). Optic nerve crush induced a slower rate of retinal ganglion cell ( RGC) progressive degeneration than did optic nerve transection (# 1248). Nicotinamide adenine dinucleotide may be neuroprotective for tumor necrosis factor alpha- induced small fiber optic nerve axonal death and may hold potential for the treatment of some optic neuropathies (# 730). Transpupillary thennotherapy led to greater survival of RGCs at 2 weeks in comparison to the control group after optic nerve crush produced at a distance of 1 mm from the disc by an aneurysm clip for 60 seconds (# 1571). Treatment with minocycline was found to inhibit neuroglial cell activation and increase neuronal survival, inhibit caspase-dependent and caspase- independent pathways of neuronal death, and increase survival of retinal neurons up to two weeks after ischemic injury to the optic nerve (# 1572). Therapeutic doses of insulin- like growth factor, a central nervous system neuroprotective agent, can reach the retina and optic nerve of rats by intranasal delivery (# 728). OPTIC NEUROPATHY Two studies suggest a possible link between coagulation abnormalities and ischemic optic neuropathy. In the first study, 5 patients with optic neuropathy and elevated alpha- 2 antiplasmin levels were reported. Patients' ages ranged from 45 to 76 years. Acuity ranged from 20/ 20 to counting fingers. All patients showed gradual improvement on repeat visual field administration, but no defects completely resolved. All patients had painless vision loss with either optic disc pallor or segmental nerve fiber layer hemorrhages (# 731). In the second study, 8 patients with optic neuropathy and alpha- 1 antitrypsin deficiency were identified. Alpha- 1 antitrypsin is a major circulatory serine protease inhibitor involved in the coagulation cascade, including the protein C pathway. Visual acuity ranged from 20/ 25 to hand motions. All patients presented with varying degrees of bilateral optic pallor and were found to have low alpha- 1 fraction ( alpha- 1 globulin) on protein electrophoresis ranging from 0.04 g/ dL to 0/ 13 g/ dL ( normal, 0.14- 0.26 g/ dL). No patients were noted to have lung disease or clotting abnormalities. All patients had normal neuro-imaging studies (# 732). The mechanism for indirect traumatic optic neuropathy is not well established. Previous work has postulated that force is conducted through the sphenoid bone to the optic canal and induces structural deformation of the surrounding bone. The authors propose that optic nerve injury is at least in part the result of soft tissue ( rather than bone) energy transmission, which is amplified within the conical space of the orbit. An impact hammer was designed to deliver a blunt force to a human cadaver head. Accelerometers were placed within the orbit 220 J Neuro- Ophthalmol, Vol. 26, No. 3, 2006 Neuro- Ophthalmology at Large J Neuro- Ophthalmol, Vol. 26, No. 3, 2006 and on the superior scalp. Movement was recorded after impact directed to the forehead and back of the skull. Frontal impact resulted in high- frequency oscillations, which were not seen with posterior impacts, consistent with a reverberation effect within the orbit (# 741). ISCHEMIC OPTIC NEUROPATHY In a rat model of ischemic optic neuropathy, optic nerve segments were cultured in vitro in oxygen and glucose- deprived conditions for 2 hours. Connexin 43 gap junction specific antisense oligodeoxynucleotides were shown to reduce cell death and tissue swelling in the cultures. The degree of upregulation of connexin 43 was directly correlated with the severity of tissue damage (# 740). In a different rat model of ischemic optic neuropathy, bone marrow- derived stem cells were injected intravenously or intravitreally after induction of optic nerve ischemia. Stem cells were injected one day before, immediately, or one day after ischemia induction. Stem cells were incorporated at both retinal and optic nerve injury sites within 3 days of injury and survived for at least 30 days (# 1772). In 3 patients with nonarteritic ischemic optic neuropathy and 2 patients with traumatic optic neuropathy, transcorneal electrical stimulation for 30 minutes led to the appearance of isopters to dimmer light stimulus intensities 1 to 3 months after treatment (# 733). OPTICAL COHERENCE TOMOGRAPHY The effect of optic nerve compression on amplitude and phase of pattern electroretinogram ( ERG) and retinal nerve fiber layer ( RNFL) thickness was studied in 36 patients with compressive optic neuropathies. The patients were tested with pattern ERG ( PERG), visual- evoked potentials ( VEPs), perimetry, and optical coherence tomography ( OCT) to measure RNFL thickness and were compared with 20 normal subjects. The study concluded that compression of the intraorbital part of the optic nerve can cause abnormalities in amplitude and/ or phase of the PERG even before axonal loss occurs. Abnormalities in PERG latency may consist of prolongation or shortening of the conduction time. Factors that influence whether the latency time is longer or shorter may relate to which populations of ganglion cell axons are affected by compression in a given person. PERG amplitude but not latency appears to correlate with RNFL thickness (# 663). The RNFL and macular thickness were studied in 40 patients with band atrophy of the optic nerves and temporal hemianopic visual field defects resulting from chiasmal compression. Macular and RNFL thickness were assessed with a Stratus OCT. The severity of visual field defects was evaluated by the mean defect from automated perimetry. Macular thickness parameters related to the nasal hemiretina could best detect pathologic damage in eyes with band atrophy. Macular thickness measurements in eyes with band atrophy were significantly lower than those in healthy eyes. Macular thickness measurements represent a surrogate indicator of ganglion cell loss in patients with band atrophy and could prove to have clinical value for detection of damage and for long- term monitoring (# 748). PERIMETRY RNFL measured by OCT and visual field sensitivity were correlated in 30 eyes with compressive optic neuropathy. The study demonstrated that the papillomacular bundle was most frequently affected ( 73%) and had the most significant loss ( 54%) of RNFL thickness. The authors demonstrated that RNFL thinning topographically correlated with decreased visual field sensitivity in compressive optic neuropathy and that this structure- function relationship suggested that RFNL thickness as assessed by OCT predominantly measures irreversible axonal loss (# 1084). LEBER HEREDITARY OPTIC NEUROPATHY Two studies showed that the optic disc in unaffected carriers of Leber hereditary optic neuropathy ( LHON) is larger than the mean size in the general population and that the clinical expression of LHON may be influenced by the size of the optic disc (# 753). A smaller vertical optic disc diameter as determined by OCT was correlated with a lack of recovery of vision in patients with LHON (# 756). A fundamental paradox of LHON is that although all cells in the body have the same mtDNA mutations, the disease is almost exclusively manifested in RGCs. RGCs use superoxide as a mitochondrial- derived intracellular messenger for signaling the initiation of apoptosis after neuronal injury. Some investigators have speculated that differences in reactive oxygen species production and sensitivity to oxidative stress among cell types may explain the timing and specificity of LHON. The authors examined superoxide production in isolated RGC mitochondria using a novel RGC cell line and brain from rats. The rate of superoxide production was 7 times lower in the cell line mitochondria than in brain mitochondria corrected for protein. There was a dramatic difference in superoxide production when electrons were shunted to complex I using mitochondrial electron transport chain complex I and III substrates and inhibitors. Mitochondrial DNA mutations of specific components of NADH- ubiquinone oxidoreductase in LHON may disrupt the cell type- specific handling of superoxide in RGC mitochondria and lead to premature cell death (# 2571). OPTIC DISC DRUSEN There are two possible explanations for blind spot enlargement associated with optic disc drusen: physical 221 J Neuro- Ophthalmol, Vol. 26, No. 3, 2006 Bose and Pomeranz enlargement of the optic disc by drusen and peripapillary serous retinal elevation. Quantitative analysis in one study suggested that physical enlargement of the optic disc by drusen is the cause. This study revealed a statistically significant greater disc area as detected by OCT. Average optic disc area measured by OCT was 65% greater than normal. This difference is not explained by refractive error, axial length, or corneal curvature (# 744). OCT can detect RNFL defects in patients with optic disc drusen. OCT detected a defect in more hemifields ( 65%) than did automated perimetry ( 54%) or multifocal VEP ( 38%). Although OCT tended to be abnormal when both automated perimetry and multifocal VEP were abnormal ( 94%), it was abnormal 48% of the time when both perimetry and visual- evoked potentials were normal and 51% of the time when one or both of these tests were normal. Given the low false- positive rate ( 1.7%), OCT may be useful in detecting RNFL damage in patients with optic disc drusen (# 754). In a prospective study, 31 ( 39%) of 80 eyes with optic disc drusen showed visual field deterioration after a mean follow- up time of 77 months. The older the patients with disc drusen, the higher the degree of visual field loss and the higher the amount of progression of visual field loss (# 764). ORBIT AND OCULAR ADNEXAE In patients with large periocular skin defects, the use of acellular human dermal matrix ( AlloDerm) was shown to be very useful in situations in which autologous skin grafting may be extremely difficult (# 3774). In patients with traumatic medial canthus tendon avulsion involving the inferior canaliculus, a new technique of repair was illustrated that emphasized reapproximation of the posterior cms of the medial canthal tendon (# 3773). High- resolution MRI of the upper eyelid with surface coils was found to be useful in the preoperative identification of the upper eyelid skin crease, position of the septum, levator, and the orbital fat pads that resulted in better preoperative planning of ptosis surgery (# 3777). Precision studies were conducted in an experimental orbit model to localize the electromag-netically tracked orbital endoscope for use with the free electron laser. Accuracy studies in the phantom trials revealed that the error was consistently between 2 and 3 mm, suggesting the need for further development (# 3784). A study of surgical orbital decompression in 12 pediatric patients with Graves ophthalmopathy found that children have a relatively benign course and a lower surgical risk and morbidity than adults (# 3785). EXTRAOCULAR MUSCLES AND EYE MOVEMENTS The polymerase chain reaction test substitutes for a muscle biopsy or lumbar puncture in confirming the diagnosis of a common deletion at 4977 bp in Kearns- Sayre syndrome (# 4619). Surprisingly, the extraocular muscles ( EOMs) seem to be spared in Duchenne muscular dystrophy that results in widespread muscle damage. An experimental study using C57BL/ 10 mice found that there were 15 times more stem cells per gram of tissue in extraocular muscles than in tibialis anterior. This greater stem cell density may be responsible for EOM- sparing and has the potential of leading to treatment strategies (# 5059). In another experimental study, EOM mitochondrial ultra-structure and function was compared in hyperthyroid C57BL/ 6 mice and another hyperthyroid transgenic strain ( adenosine nucleotide translocator 1- deficient [ ANT1-/-], a mitochondrial- deficient model). Electron and confocal microscopy demonstrated a significant alteration in the number and function of mitochondria in the ANT1-/- mice, demonstrating that mitochondria are probably the site of derangement in thyroid- related eye disease and allowing determination of future therapeutic strategies (# 5401). A session was devoted to the functional anatomy, computational and primate modeling, and central neural adaptations of superior oblique palsy (# 449). In an experimental study using force generation as an end point in the rabbit superior rectus muscles that received a combination of injection borulinum toxin and ricin- m- Ab35, the authors concluded that this combination may be beneficial in extending the duration of the drug effect to weaken the EOM (# 5395). PUPIL A clinical study involving 73 patients with isolated third cranial nerve palsy caused by microvascular ischemia ( group 1) and 45 patients with a palsy caused by unruptured posterior communicating artery aneurysm ( group 2) showed that the only clinical features that distinguished the two groups were a complete palsy of the somatic portion of the nerve ( EOMs and lid) and normal pupil function ( ischemia) (# 781). 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 222 © 2006 Lippincott Williams & Wilkins |
