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Highlights of the ARVO Meeting

April 30-May 4, 2006, Fort Lauderdale, Florida, USA

Glaucoma New Ideas session

Claude Burgoyne

  • Spada et al. described the first use of metabolic mapping to clinically measure retinal mitochondrial function in monkeys which were either bilaterally normal or had been given severe experimental glaucoma in one eye. While inter-eye differences were minimal in the bilaterally normal monkeys, profound differences were detected in the experimental glaucoma eyes which suggests that changes in the metabolism of RGCs and their axons may be clinically detectable prior to RGC apoptosis.
  • Chen et al. presented the first simultaneous, ultra-high speed, ultra high resolution spectral domain OCT images of the optic nerve head and retina of human patients with early to severe glaucoma, suggesting clinical OCT imaging with greater speed and higher resolution is in development.
  • Poeschla et al. reported the first injection of eFGP fluorescence encoding, FIV-based lentiviral vectors into the anterior chambers of four monkeys with good (up to nine months) long-term eGFP expression, without evidence for IOP elevation or active inflammation - moving glaucoma gene therapy closer to clinical reality.
  • Dahlman et al. described a novel system for simultaneously imaging and micro-culture force manipulating ocular fibroblasts so as to monitor and manipulate the mechanisms of matrix contraction and one day influence ocular healing. This experimental system may allow the controlled study of pharmacologic manipulations of glaucoma filtration surgery.
  • Cordeiro et al. reported the expression of Beta Amyloid in hypertensive rat retinas, as well as apoptotic death of retinal ganglion cells following Beta Amyloid injection into the vitreous in a separate group of eyes. Their studies suggest a role for Beta Amyloid in glaucomatous damage to the rat retinal ganglion cell.
  • Di Polo et al. evaluated the neuroprotective effects of intraperitoneal Galantamine (currently approved as an oral agent for Alzheimer's Disease) in the rat experimental glaucoma model and found protection of both RGC stroma and RGC axons (counted in the optic nerve) at five weeks. While preservation of visual function remains to be determined, this is the first demonstration of Galantamine neuroprotection in glaucoma.
  • Schmidt et al. measured antioxidative activity in serum and aqueous samples of 50 POAG and 50 normal control patients undergoing cataract surgery and found no changes in serum levels, but aqueous anti-oxidative activity to be increased in early phase POAG and unchanged in late phase POAG patients compared to control. Their work suggests that treatment of POAG patients with anterior chamber anti-oxidants, particularly late in the disease, may be important.

ARVO Top-Ten

Mingguang He

  • Based on the five-year and ten-year incidence data of open-angle glaucoma in a cohort from Blue Mountain Eye Study, the incidence was found as 4.5% (95%CI: 3.5~5.5), higher in female (5.6%) than male (3.0%), increasing markedly with age. Higher IOP, cup disc ratio > 0.5, disc hemorrhage and reduced corneal thickness were all associated with increasing risk of glaucoma.
  • IOP was stable up to six years among untreated patients in EMGT trials. Only exfoliation was associated with more elevation of IOP. About 67.8% of control patients progressed in six years. Progression was associated with exfoliation, higher IOP, having both eye eligible, older age and worse baseline MD.
  • After integrating a novel spatial filter to the traditional visual field progression based on point-wise linear regression (PROGRESSOR for windows software), the specificity improved from 85.7-95.4% to 96.8-100% in the identification of subjects without progression. About one third of those identified as progression by either filtered or unfiltered VF also demonstrated progression by HRT.
  • The More Flow Surgery Study in Moorfields demonstrated that both degree of reduction and variability of IOP were important in the progression of structural optic nerve head damage identified by HRT after trabeculectomy.
  • A prototype system spectral domain OCT obtained images at a speed of 73 times faster than commercially available OCT system. The prototype requires less optical power into the eye and allows a high-resolution delineation of the optic nerve head.
  • By a comparison of three normal and three POAG human donors, extracellular matrix (ECM)/fibroticgene expression in lamina cribrosa cells was found to be markedly different. Hypoxia, mechanical sketch and TGF-b1 induced glaucomatous gene clusters in normal lamina cribrosa cells.
  • Using immunized Lewis rats, the study suggests that RGC death in selected glaucoma patients likely involves failure of immunoregulation of the microglia/T-cell/RGC axis. This is perhaps through the pro-apoptosis and protective pathways.
  • Using a simultaneous imaging and micro-culture force monitor system, ocular fibroblasts are involved in the scarring of the eye. The system is promising for quantitative assessment of matrix contraction and perhaps the contraction-modulating effect of new drugs in the future.
  • An international collaborative project suggests differences between ethnic groups in HRT parameters, both in the absolute values and correlation with disc size and age. This finding underscores the needs for generating ethnic-specific databases.
  • By examining 484 population-based subjects (after excluding those with established occludable angle at baseline), a study demonstrated 20.2% of subjects with an ACD < 2.53 mm will develop occludable angles over six years.

ARVO Top-Ten

Keith Martin

  • Combining 5-FU with hyaluronic acid markedly prolongs drug release from tissue and has the potential to improve the treatment of bleb failure.
  • In rat and mouse models of glaucoma, IOP measurements  using the TonoLab tonometer match manometric IOP more closely than TonoPen measurements. The TonoLab also requires fewer applications to acquire readings and reduces IOP less when multiple measurements are taken.
  • Rat retinal microglia increase in number and reactivity in response to IOP elevation and respond differently to duration and fluctuations in IOP.
  • In Singapore patients with unilateral acute primary angle closure, the risk of developing glaucoma in the fellow eye was 5.1% at a mean follow up of six years.
  • Retinal ganglion cell loss in the DBA/2J model of glaucoma is sectoral with a pattern that suggests damage to optic nerve bundles at the optic nerve head.
  • Reductions in the size and complexity of dendritic trees of rat retinal ganglion cells were observed following induction of ocular hypertension with mean, peak and fluctuation in IOP influencing the degree of dendritic pruning.
  • Encapsulated cell technology (ECT) is a promising method for long-term drug delivery to the posterior segment of the eye.
  • Selective inhibition of c-Jun N-terminal kinase (JNK) is strongly neuroproctective in cultured retinal ganglion cells exposed to either excitotoxic injury or neurotrophin withdrawal.
  • Annexin V labelling, combined with scanning laser ophthalmoscopy allows in vivo imaging of apoptosis in the mouse eye.
  • Secondary degeneration in the optic nerve appears to involve activation of the MAP kinase and p53 signal transduction cascades, as also occurs in glaucoma and after complete optic nerve transection.

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