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Uveoscleral outflow received attention from Dr. Robert Weinreb of San Diego in an exceptional First Pharmacia and Upjohn Lecture, which has been established to allow distinguished basic scientists and clinician scientists to share their research and place it in a clinical perspective. In his lecture entitled The Other Outflow Pathway, Dr. Weinreb reported on changes in the extracellular matrix of ciliary body smooth muscle cells induced by high doses of prostaglandin derivatives in tissue culture and in animal models. He hypothesized that these changes could in part account for the increase in uveoscleral outflow with this new class of ocular hypotensive agents. He also summarized past studies examining the role of uveoscleral in the normal human eye as well as in glaucoma. He speculated that uveoscleral outflow represents a larger percentage of the total outflow in the normal physiological state and may take on even greater significance when conventional trabecular outflow is obstructed.
Dr. M. Bruce Shields from New Haven, Connecticut, beautifully delivered the Tenth American Glaucoma Society Lecture, which was entitled Reflections and Projections on Crossing the Millennium: A Tribute to Dr. Marvin L. Sears. Dr. Shields summarized the many contributions that Dr. Sears has made, including his work on aqueous physiology and adrenergic pharmacology of the eye. Dr. Shields also reviewed the most significant advances in the field of glaucoma during the 20th century, and he concluded that the cognitive advances in our understanding of glaucoma will have greater long-term impact than the technological advances, since they will provide the foundation on which continued progress in the 21st century will be based. In looking forward to the 21st century, he predicted that genetic research will play an even greater role, not only diagnostically, but also therapeutically in glaucoma management.
Two of the free papers focused on differences in the incidence of glaucoma and corneal thickness in black compared to white persons, respectively. Dr. David Friedman reported that, in East Baltimore, the age-adjusted incidence of open-angle glaucoma for blacks was nearly double that for whites. Incidence increased with age in both groups, with nearly five times the incidence in individuals over the age of 70 years at baseline compared to those of 40-49 years old. In a study performed in Houston, Drs. Silvia, Orengo and Nania found that, in African American patients with and without glaucoma, mean central corneal thickness was approximately 30 µm thinner (530 µm) than in whites (558 µm). The authors suggested that this observation, which I found somewhat surprising, may result in an underestimation of the actual level of intraocular pressure (IOP) in African Americans. Given what we already know about corneal thickness in ocular hypertension and normal-tension glaucoma, this paper will likely lead me and others to perform corneal pachymetry on a more regular basis.
Surgical management of leaking or overfunctioning filtering blebs, an increasingly common challenge to glaucoma surgeons, was addressed by three papers. Dr. Donald Budenz of Miami found that conjunctival advancement for leaking blebs was more effective than amniotic membrane transplantation, as the latter was more frequently associated with recurrent leaks and the need for repeat glaucoma surgery. In a series from Chicago, Dr. David Palmer reported that, after bleb revision (excision of necrotic bleb followed by conjunctival advancement) in 13 eyes, a high percentage (85%) maintained IOPs <18 mmHg with or without medical therapy. Similarly, Dr. Harry Quigley from Baltimore described a series of 32 eyes in which bleb revision, including rotational or free conjunctival graft placement, generally resulted in improved symptoms and IOPs, without loss of IOP control. In view of the all-too-common need to consider some form of bleb revision in patients with bleb leaks and/or hypotony, I found these data to be quite encouraging.
Dr. Paul Kaufman from Madison, Wisconsin, presented data showing that uveoscleral outflow as a proportion of total aqueous humor flow dramatically declined in five rhesus monkeys aged 25-29 years (0.9±4.0%) versus 19 animals aged 3-23 years (24.9±4.9%). Based on existing human data, he suggested that this difference may be similarly age-dependent in humans.
With regard to trabecular meshwork-induced glucocorticoid response protein/myocilin (TIGR/MYOC), Dr. Doug Johnson of Rochester, Minnesota, described results of localizing studies of the trabecular meshwork, in which cell labelling was present in most trabecular cells of the uveal, corneoscleral, and juxtacanalicular regions, but only variably present in the endothelial cells of Schlemm's canal. He concluded that most cells in the meshwork, but only a few cells in the endothelial lining of Schlemm's canal, produce TIGR and suggested that TIGR's effect on IOP may involve the extracellular matrix rather than the internal cytoskeleton of cells. Of note, dexamethasone treatment increased the number and intensity of labelled cells in the meshwork, and also the number of labelled cells in the endothelial lining of Schlemm's canal.
Some free papers and several scientific posters addressed research in medical therapies for glaucoma. In a free paper, Dr. Monte Dirks from Rapid City, South Dakota, revealed the results of a preliminary study of 106 patients comparing latanoprost to AGN-192024. The latter agent, known as a 'hypotensive lipid', appeared to have similar efficacy to latanoprost in lowering IOP. Additional studies on this new drug are under way.
As some controversy has existed regarding response rates to medical treatment with latanoprost, response rates to timolol and latanoprost (TM and LP, resp.) were reviewed in a poster presented by Dr. Carl Camras from Omaha, Nebraska. Based on data from the United States Latanoprost Study Group, Dr. Camras evaluated responsiveness based on four different criteria: 1. >30% reduction; 2. >20% reduction; 3. >3 mmHg reduction; and 4. IOP <20 mmHg. He reported response rates (LP/TM) of: 1. 40/18% (p<0.01); 2. 78/47% (p<0.01); 3. 88/78% (p<0.10); and 4. 79/67% (p<0.06).
The role of ophthalmologists in caring for the needs of our low vision patients also received attention in the program. In a presentation entitled The Responsibility and Reward of Vision Rehabilitation, Dr. David Gieser of Wheaton, Illinois, reported on his involvement and experiences with a comprehensive Center for Vision Rehabilitation, which is located in a re-modelled home and has served more than 10,000 adults and 1800 children since 1986. I applaud Dr. Gieser for his presentation, which provided information regarding the impact of this center but, even more importantly, emphasized the vital role that glaucoma specialists and other ophthalmologists play in the vision rehabilitation process.
In a study designed to identify possible multifocal electroretinography (MERG) abnormalities in glaucoma, Dr. Chris Johnson of Portland found that the most distinguishing characteristic was a change in the MERG responses within the central 10°. However, abnormalities of MERG responses to several different stimuli do not correspond topographically to even advanced visual field changes.
An outstanding mini-symposium on Imaging in Glaucoma was moderated by Drs. Jeff Liebmann of New York City and Robert Weinreb of San Diego, included many leaders in this area of glaucoma research, and reviewed the rationale for imaging of the optic disc and retinal nerve fiber layer; the principles of confocal scanning laser ophthalmoscopy, scanning laser polarimetry, and optical coherence topography; and the clinical assessment of disc topography and the retinal nerve fiber layer. While these technologies may provide useful information, particularly with respect to the long-term follow-up of glaucoma, their role continues to evolve, and it is still difficult to determine which of these technologies will be the most useful in the future diagnosis and management of glaucoma. Perhaps the most important messages from the mini-symposium were the realization that each of these technologies requires validation via reproducibility studies and evaluation in longitudinal studies of glaucoma patients.
In the equally impressive AGS Surgical Mini-Symposium entitled Non-Penetrating Glaucoma Surgery and moderated by Drs. Mark Sherwood of Gainesville, Florida, and Ted Krupin of Chicago, several speakers reviewed developments with viscocanalostomy and the deep sclerectomy/wick procedure. Dr. Robert Stegmann from South Africa summarized the evolution of viscocanalostomy, details of the technique, and surgical results in a series of 266 eyes. In this black African population, he reported a drop in mean IOP from 49.9-19.1 mmHg, with an average follow-up of approximately 34 months. A summary of the deep sclerectomy/wick procedure was provided by Dr. Alan Crandall of Salt Lake City.
With respect to these newer procedures and viscocanalostomy in particular, Drs. Richard Wilson of Philadalphia, Ronald Fellman of Dallas, and Paul Palmberg of Miami emphasized that, after successful viscocanalostomy, IOPs tend to be higher than after trabeculectomy with antiproliferative agents. A select group of American patients, including those with past complications associated with standard trabeculectomy with antifibrotic agents, those at high risk for complications with trabeculectomy, and those with minimal glaucomatous damage for whom IOPs in the high teens may be acceptable, may benefit from viscocanalostomy. While surgeons seeking surgical alternatives to current techniques are to be highly commended, the role of both viscocanalostomy and the deep sclerectomy/wick procedure continues to evolve. I agree with some of the speakers in their view that carefully performed studies comparing trabeculectomy to newer procedures will be critical to better defining their long-term place in the surgical management of glaucoma.
Uveoscleral outflow appears to represent a larger percentage
of total outflow in the normal state than previously thought, and
may be even greater when conventional outflow is obstructed.
Glaucoma genetics will likely play an even greater role, both
diagnostically and therapeutically, in the 21st century.
Mean central corneal thickness is approximately 30 µm thinner
in African Americans than in whites.
Glaucoma control can usually be maintained, even after bleb revision.
Localizing studies of the trabecular meshwork suggest that TIGR's
effect on IOP may involve the extracellular matrix rather than the
internal cytoskeleton of trabecular cells.
A new 'hypotensive lipid' appears to show efficacy similar to
latanoprost.
Glaucoma specialists play a vital role in the vision rehabilitation
process.
It is still unclear which of the new technologies for assessing
the optic nerve and retinal nerve fiber layer will be the most useful
in the future.
Emerging procedures such as viscocanalostomy show promise, but will require continued careful study to better define their role in the surgical management of glaucoma.
As program chair for the 2000 meeting of the American Glaucoma Society, I was extremely pleased with the very high quality of the free papers, scientific posters, and mini-symposia; the nice blend of basic and clinical sciences; Dr. Bruce Shields' superb Tenth AGS Lecture; an outstanding inaugural Pharmacia and Upjohn Lecture by Dr. Robert Weinreb; and our continued progress in achieving methods to better serve our patients with glaucoma. Congratulations to all of the meeting participants!
I am greatly looking forward to the Eleventh AGS Annual Meeting.