It has long been realized that today's science fiction is tomorrow's reality. This premise represents the driving force by which investigators exchange new findings in an effort to impact positively on patient care. At this year's meeting of the Association for Research in Vision and Ophthalmology, this enthusiasm was obvious at the "New ideas in Glaucoma" session. Moderated by Robert Weinreb, MD and Carlo Traverso, MD, the session was clearly "standing room only". This report summarizes the seven papers presented on May 13, 1997.

Earlier this year, a breakthrough study (Stone EM, Fingert JH, Alward WLM, et al: Identification of a gene causing primary open angle glaucoma (GLC1A). Science, 1997;275:668-670) reported the first identification of a genetic mutation found in 2.9% of patients with autosomal dominant juvenile open-angle glaucoma and some cases of adult-onset primary (idiopathic) open-angle glaucoma (POAG). The TIGR (Trabecular meshwork Inducible Glucocorticoid Response) molecule, the location of the gene for which (GLC1A gene) was narrowed to a 3 cM region of chromosome lq between markers D1S3665 and D1S3664, was cloned from human trabecular meshwork (HTM) cells and evaluated by Dr. Thai Nguyen et al (UCSF) for its potential role as a candidate gene in glaucoma. TIGR promoter was characterized as having glucocorticoid response elements with increased TIGR gene expression in glaucomatous HTM tissue compared to normals. They speculated that the TIGR gene product interacts with the extracellular matrix of trabecular cells resulting in outflow obstruction and subsequent IOP elevation. Hormonal and stress response elements were identified in the TIGR promoter. They suggested that in some individuals, the TIGR gene may represent the molecular link between the corticosteroid response observed in many patients with juvenile and adult-onset POAG.

Dr. Keith Barton and colleagues (Moorfields Eye Hospital and Bascom Palmer Eye Institute) presented their experience with the use of preserved human amniotic membrane in an animal model of conjunctival filtering bleb reconstruction. Amniotic membrane grafting, obtained from human placenta and subsequently sterilized and separated from the underlying chorion, has recently been reported effective for treatment of persistent corneal epithelial defects with ulceration. In this investigation, clinical and histopathological results were described in 12 rabbit eyes which underwent excision of a limbus-based conjunctival flap at the time of trabeculectomy and replaced with an acellular amniotic membrane graft. 12 controls underwent fornix-based trabeculectomy. Tissue from both groups was analyzed at 14 and 36 days postoperatively. Significantly longer bleb survival and reduced fibroblast proliferation was observed in eyes receiving the grafts compared with controls, although differences in IOP were statistically insignificant. Although there was considerable granulomatous inflammation in the xenografts, this finding has not been observed in human eyes which have received this new grafting material at the time of filtering bleb reconstruction.

Dr. Michael Eichhorn et al (University of Erlangen, Germany) described a novel technique for growing human scleral spur cells in monolayer culture. Scleral spur cells in primates contain a ring of myofibroblast-like cells which, when stimulated, may influence outflow facility. Cells from trabecular meshwork, ciliary muscle and scleral spur were dissected from human donor eyes and subsequently cultured. Both ciliary muscle and scleral spur cells exhibited "hill-valley" growth characteristics. However, using immunohistochemistry, the authors found that scleral spur cells could be differentiated by using a,§-crystalline markers. The authors suggested that pharmacological stimulation of these scleral spur cells may augment outflow facility and provided a model for isolation of these cells in future biochemical investigations.

Recent attention has focused on the role of vascular endothelial growth factor (VEGF) as the vasoproliferative agent responsible for neovascularization in eyes with proliferative diabetic retinopathy and advanced ocular ischemia. Dr Ramesh Tripathi et al (University of South Carolina and the University of Illinois at Chicago) presented a quantitative analysis of the aqueous humor concentration of VEGF in 12 human eyes with neovascular glaucoma compared with 28 eyes with POAG and 20 age-matched controls with cataracts. Significantly greater mean levels of VEGF were present in eyes with NVG than in eyes with POAG or cataracts. Interestingly, eyes with POAG had significantly greater mean levels of VEGF than controls. The authors speculated that this may reflect alterations in the blood-aqueous barrier with leakage from serum. Based upon these data, they suggested that ischemic retina is the source of VEGF, which may be the most important vasoproliferative agent responsible for neovascular glaucoma.

We are becoming increasingly aware that a variety of pressure-independent pathogenic variables (e.g., ocular blood flow abnormalities, excitotoxic injury) may be present in eyes with glaucoma and may facilitate the final common pathway of retinal ganglion cell (RGC) death. These non-pressure-dependent pathways may cause damage in the presence of a normal IOP or may act in concets with an elevated IOP to produce damage. Dr. Mary Pease and colleagues (Wilmer Eye Institute) evaluated the hypothesis that neurotrophin deprivation may be associated with RGC death in eyes with experimental glaucoma. They compared the amount and distribution of the trkB neurotrophin receptor in ten monkey optic nerves after either induction of experimental glaucoma or optic nerve transection. In glaucomatous eyes, immunohistochemical evidence of focal heavy trkB staining was observed in RGC axons within neural bundles adjacent to and within the lamina cribrosa. In comparison, diffuse staining was observed proximal to the level of optic nerve axotomy in eyes following optic nerve transection. This experimental model suggests that axonal transport blockade at the level of the lamina cribrosa may result in functional neurotrophin deprivation and subsequent RGC death in eyes with glaucoma.

Dr. D.S. Kamal and colleagues (Moorfields Eye Hospital) evaluated the ability of the confocal scanning laser ophthalmoscope to detect glaucomatous optic nerve head change in ocular hypertensive eyes prior to the development of achromatic visual field abnormalities. Segmental stereometric topographic parameters were evaluated using the Heidelberg Retinal Tomograph in 13 ocular hypertensive eyes which subsequently developed glaucomatous visual field abnormalities. Although decreases in the superonasal rim area and increases in cup area were identified, the most commonly observed change was a decrease in the inferotemporal rim volume. The authors speculate that scanning laser ophthalmoscopy may provide stereometric evidence of glaucomatous change in some ocular hypertensive eyes prior to the onset of detectable achromatic threshold visual field abnormalities.

Lastly, Drs. Ronald Harwerth and Earl Smith (University of Houston) presented data regarding the relationship of IOP and visual field defects in an experimental model of glaucoma. Unilateral glaucoma was induced in 18 monkeys which underwent "behavioral modification", such that automated perimetry could be performed and evaluated using a 24-2 threshold algorithm. As in humans, there was considerable variation in development of visual field defects following IOP elevation. Although 10/18 eyes developed significant nerve fiber bundle defects at IOP above 30 mmHg, a subgroup showed no correlation between mean deviation and IOP. Although the interpretation of animal psychophysical data is limited by numerous factors, this experimental model may provide useful information in longitudinally evaluating the relationship between structure and visual function.

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