The third glaucoma subspecialty day at the Annual Meeting of the American Academy of Ophthalmology in Chicago this year was entitled ‘100 Years of Progress In Glaucoma: Celebrating Our Heritage and Looking to the Future.’ The meeting provided a comprehensive review of many aspects of glaucoma diagnosis and therapy from the time of von Graefe to the present.

In his introductory remarks, Dr. M. Bruce Shields pointed out how poorly understood glaucoma was 100 years ago. Perimetry was limited to Bjerrum’s campimeter. The only available medical therapy consisted of pilocarpine and eserine, and surgical procedures were crude and fraught with complications. Gonioscopy had not yet been devised, so the broad classification of glaucoma into open-angle and closed-angle mechanisms was not appreciated. From this point, the expert panel of speakers added an historical perspective to the current thinking in glaucoma and to its future trends.

The morning session was devoted to reviewing our understanding of the etiology and pathophysiology of glaucoma. Some speakers entertained, others presented historical overviews of their topic, some personal and some didactic. Several speakers were particularly relevant and thought provoking. Dr. David Epstein described how the aqueous humor outflow pathways were discovered. He also talked about the debate as to the site at which resistance to aqueous humor outflow through the trabecular meshwork occurs. Most investigators agree that the primary site of resistance to conventional outflow is the juxtacanalicular trabecular tissue (JCT). This resistance is thought to be caused by either the deposition of a plaque-like material, altered glycosaminoglycans, or reduced surface area of aqueous channels near the JCT. Alternatively, the structure of the inner wall of Schlemm's canal may produce resistance through “giant vacuoles” in the wall of the canal (which have been demonstrated using electron microscopy) and by the overlying endothelial cells. Outflow resistance may be decreased by agents that modulate the inner wall endothelial cell cytoskeleton or cell adhesion, such as ethacrynic acid, EDTA, or cytochalasin B. These agents can separate the endothelial cells and promote outflow.

Dr. Harry Quigley discussed the mechanisms of glaucomatous optic nerve atrophy. Recent research indicates that ganglion cell death in glaucoma probably occurs via apoptosis, which is a genetically programmed mode of cell death (‘cell suicide’). For instance, one means of potential glaucomatous damage to retinal ganglion cell axons consists of interrupted axoplasmic transport in both directions, in turn leading to a decrease in the concentration of growth factors reaching those portions of the ganglion cell where they exert their activity. This relative reduction in growth factor availability is thought to initiate the apoptotic cascade. One possible direction in glaucoma therapy may be the prevention of apoptosis by replacing these growth factors pharmacologically (a form of ‘neuroprotective’ therapy). The question remains as to how seemingly different entities like idiopathic (primary) open-angle glaucoma and normal-tension glaucoma cause axoplasmic flow stasis. Dr. Quigley feels the answer may lie in the structure of the lamina cribrosa. Elastin is one component of the lamina which protects it from backward excavation. High IOP can damage elastin in the lamina and facilitate its backward stretching, in turn leading to poor capillary blood flow, which inhibits axonal transport. In normal-tension glaucoma, optic nerve vascular nutrition may be inherently compromised, leading to axoplasmic transport stasis, but this factor alone would not explain the excavation of the optic nerve head that occurs. Dr. Quigley believes patients with normal-tension glaucoma have not only a decrease in optic nerve blood flow but also an inherent abnormality in the lamina, such as defective elastin, which predisposes the lamina to excavation at intraocular pressures that are considered "normal".

Some of the most exciting trends in glaucoma research have evolved in the field of genetics. The talk given by Dr. Wallace (Lee) Alward explained how new discoveries concerning the genetic basis of glaucoma may redefine our understanding of the disease. Although much has been learned about the glaucomas over the last hundred years, our current classification system remains primarily descriptive. However, diseases with different phenotypic appearances may nevertheless have the same genetic basis. For example, Peters' anomaly and aniridia have both been localized to the PAX6 gene on chromosome 11p. Both syndromes are associated with glaucoma, and although their clincial appearances differ, they may merely represent different mutations of the same gene. Some forms of Rieger's anomaly and iris hypoplasia have been localized to chromosome 4q. Although Peters' and Rieger's anomalies were once classified together, a genetically based classification system would assign them different etiologies given their location on different chromosomes. Furthermore, some types of idiopathic (primary) open-angle glaucoma and juvenile open-angle glaucoma have been localized to Chromosome 1q. If other genes are discovered, we may find that idiopathic open-angle glaucoma is not one disease but a similar end result of many different genetic defects. When the products of normal and defective genes are compared, we may better understand the molecular etiologies of the glaucomas and provide more specific and possibly curative therapies.

The end of the morning session was highlighted by the Becker lecture given by Dr. Allan Kolker. Dr. Kolker first reviewed the accomplishments of Dr. Bernard Becker and the profound influence he has had on many of today's leading glaucomatologists. He then described the evolution of glaucoma filtration surgery which remains essentially a ‘plumbing operation’. Early filtration surgery consisted of full-thickness sceral excision, performed with crude instruments under low magnification, and, although it had a relatively high success rate, there was also an unacceptably high rate of complications, including flat anterior chambers and endophthalmitis. Guarded filtration procedures, such as trabeculectomy, evolved a generation ago, improving the complication rate, but also lowering the success rate. The advent of microsurgery and, later, antifibrotic agents, releasable sutures, and postoperative laser suture lysis, has markedly increased the success rate of filtration surgery while reducing such complications as flat anterior chamber and early postoperative endophthalmitis to an all-time low. 5-Fluorouracil temporarily inhibits fibroblast DNA synthesis by competitively inhibiting thymidylate synthetase, while mitomycin-C is an alkylating agent which permanently crosslinks DNA. Use of these agents leads to thin, ischemic filtration blebs which are prone to leakage, and leaking blebs can cause hypotony and late bleb-related endopthalmitis. Thus far, the rate of complications with antifibrotic agents has been far below that of full thickness procedures. However, because of their relatively recent introduction, the long term incidence remains uncertain. These drugs have brought guarded filtration surgery around full circle to equal the success of full-thickness procedures, but hopefully the complication rate will remain at an acceptable level.

The afternoon session addressed advances in "secondary" glaucomas, such as pigment dispersion syndrome and neovascular glaucoma, and reviewed medical and surgical therapy. In summary, the glaucoma symposium presented a stimulating, comprehensive review of the current trends in glaucoma management. It will be available through the Academy on CD-ROM.

[ About NYGRI ][ Education ][ Glaucoma Network ]
[ How You Can Help ][ Question Corner ][ Research ]