ARVO researchers evaluate glaucoma diagnosis, treatment options

Issue: July 2005

ByMurray Fingeret, OD

FT. LAUDERDALE, Fla. — The annual meeting of the Association for Research in Vision and Ophthalmology, held here every year in early May, brings together many of the best minds from around the world who are involved in eye and vision research. ARVO has 13 different sections, and any member of ARVO may submit one research project in the form of a paper or poster for presentation at the annual meeting.

Each section has its own acceptance criteria, and not every submission is accepted. One of most stringent is the glaucoma section, in which approximately 20% of submissions are rejected annually. While each section’s program committee screens every entry, the entry is not peer reviewed, as it would be if it were submitted to a journal for publication. This results in the quality of posters varying widely. For this column, I will describe a few of the papers and posters that were presented within the glaucoma section at this year’s meeting.

Risk assessment and modeling

Risk assessment and risk modeling are important tools that internists use in the management of cardiovascular disease. This concept is in the developmental stages for ocular hypertension and glaucoma. Felipe Medeiros and colleagues at the Hamilton Glaucoma Center at the University of California in San Diego (UCSD) have developed one risk assessment model for the conversion from ocular hypertension (OHT) to glaucoma (“Validation of a predictive model for the conversion from ocular hypertension to glaucoma”). Predictive models for the 5-year risk of conversion to glaucoma were developed from the previously published results of the Ocular Hypertension Treatment Study (OHTS) using Cox proportional hazards regression.

Murray Fingeret, OD [photo]
Murray Fingeret

The performance of these models was assessed in an independent population of 126 untreated OHT subjects from a longitudinal study (Diagnostic Innovations in Glaucoma Study [DIGS]) that is being performed at UCSD. Thirty-one (25%) patients developed glaucoma during follow-up, and average follow-up time was 86 months, with a range of 14 to 198 months. Hazard ratios for DIGS- and OHTS-derived predictive models were similar for age, IOP, central corneal thickness, vertical cup/disc ratio (VCD) and pattern standard deviation (PSD), but were significantly different for the presence of diabetes mellitus. When applied to the DIGS population, the OHTS-derived predictive models had reasonably good discrimination and calibration.

From this study, a simple risk scoring system has been developed, which will be published soon. This system allows calculation of the 5-year risk of glaucoma development for an individual patient.

Response to medications

Several studies were presented using data from the OHTS. Steve Mansberger and colleagues examined the IOP response to topical beta-blockers and prostaglandins in a monocular trial (“Comparison of IOP response to topical beta-adrenergic antagonists and prostaglandin analogues in African Americans and Whites: the Ocular Hypertension Treatment Study [OHTS]”). In the multivariate analysis, both baseline IOP and corneal thickness were associated with the magnitude of IOP reduction. There appeared to be no difference between African Americans’ and Whites’ IOP response to either beta-blockers or prostaglandins after adjusting for baseline IOP and corneal thickness.

In another study from OHTS, Michael Kass and colleagues examined the question of whether topical ocular hypotensive medication was associated with the development of cataracts (“Is there an association of topical ocular hypotensive medication with lens opacification and visual function? Evidence from the Ocular Hypertension Treatment Study”). After analysis, the rates of cataract surgery and lens opacification were found to be similar between the observation and medication arms of the study. There appears to be little proof that the use of medication leads to the development of cataract.

Optic disc analysis

Richard Parrish examined the reproducibility of optic disc analysis using stereo photographs (“Test-retest reproducibility of determining optic disc deterioration in the Ocular Hypertension Treatment Study”). Over a period of 5 years, the examiners reviewed test photographs that showed no change along with a different set that had confirmed change. The specificity of recognizing the unchanged eyes was 98% or better over a 5-year period with sensitivity of 64% to 81%.

In another study based on OHTS data, baseline confocal scanning laser ophthalmoscopy measurements were evaluated to see if any were associated with the development of primary open-angle glaucoma (“Baseline topographic optic disc measurements are associated with the development of primary open angle glaucoma: The Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the OHTS”).

In this study, 865 eyes from 438 participants from OHTS were tested with the HRT II (Heidelberg Engineering, Vista, Calif.) performed at the time of their entry into the study. From this group, 41 eyes from 36 individuals developed glaucoma. Several baseline HRT optic disc measurements were associated with the development of primary open-angle glaucoma, including larger C/D ratio, mean cup depth, mean height contour, cup volume, smaller rim area, rim to disc area and rim volume.

Comparing imaging technologies

Christopher Girkin, MD, and colleagues evaluated the ability of the GDx-VCC (Carl Zeiss Meditec, Dublin, Calif.), the HRT II and the OCT 3 (Carl Zeiss Meditec) to detect glaucomatous damage (“Discrimination between glaucomatous and non-glaucomatous Eyes of Black and White subjects using quantitative optic disc topography [OCT 3 and HRT II], retinal nerve fiber layer analysis [OCT 3 and GDx-VCC] and subjective optic disc assessment”). Examination findings from one eye of 65 glaucomatous individuals and 162 normal subjects were evaluated. The investigators found no difference among the best performing parameters for each of the imaging methods.

Take-home pearls

There appeared to be no difference between African Americans’ and Whites’ IOP response to either beta-blockers or prostaglandins after adjusting for baseline IOP and corneal thickness.
There appears to be little proof that the use of glaucoma medication leads to the development of cataract.
Investigators found no difference between the best performing parameters of three imaging instruments: the HRT II, the GDx-VCC and the OCT 3.

The imaging methods also compared well with the subjective evaluation of photographs. Interestingly, the age-adjusted receiver operator characteristic (ROC) curves were lower for blacks for all tests, indicating that glaucoma may be more difficult to diagnose in this patient group. The imaging instrument performed as well as expert assessment of photographs, which — while not surprising because it has been reported before — shows how far imaging has come. The concept that imaging is experimental, as put forth by some insurance carriers, is ridiculous and not based upon evidence. The best parameters for each instrument were GDx VCC RNFL average, HRT II Rim Disc Area Ratio, OCT 3 Disc Vertical Rim Area and OCT 3 RNFL Inferior Quadrant Average.

N. Strouthidis and colleagues examined how well a single test performs in detecting glaucoma (“Do we need both structure and function for measuring glaucomatous progression?”). In this study, individuals with ocular hypertension as well as normals were followed using HFA perimetry (Carl Zeiss Meditec) and HRT II imaging. The mean follow-up was more than 6 years.

Poor agreement occurred between the two tests in regard to detecting the majority of patients who developed glaucoma. HRT II rim sector analysis alone found 33 individuals, visual field alone discovered 19 and 14 people converted on both tests. Fairly good agreement occurred on congruity for the individuals converting on both tests, but these results indicate that the best way to detect the greatest number of cases is to combine a structural and functional assessment.

The European Glaucoma Prevention Study (EGPS) is similar to OHTS in that it also investigated the question of whether reducing IOP prevents individuals with ocular hypertension from converting to glaucoma. Stalmans and colleagues, using data from the EGPS, looked at the frequency of optic disc hemorrhages and the development of glaucoma (“Optic disc hemorrhages and progression to glaucoma in the European Glaucoma Prevention Study [EGPS]”). Over a 5-year period, they evaluated the rate of detection of optic disc hemorrhages based upon the clinical evaluation of the optic nerve as well as the evaluation of stereo optic disc photographs.

Of the 1,342 eyes (750 individuals), 30 (2.2%) developed optic disc hemorrhages. Of these, 24 (80%) were detected using stereo photography, five (16.7%) with fundoscopy and stereo photography and only one (3.3%) with fundoscopy only. The percentage of eyes that converted from ocular hypertension to glaucoma was 7.9%. Of the 30 eyes that developed optic disc hemorrhages, seven (23.3%) developed glaucoma.

New technology

As new technology becomes part of the equipment commonly used in practice, one important question is how it compares to the instrumentation it replaced. William Swanson examined the question of how similar conventional perimetric visual field analyzers compare to new forms of perimetry that use sinusoidally modulated stimuli (frequency-doubling technology) (“Cortical pooling analysis of perimetric sensitivity for conventional and sinusoidal stimuli”).

Using a computational modeling of contrast sensitivity, simulations found that perimetric sensitivity declined at a similar rate between the tests as ganglion cell number declined to a 90% ganglion cell loss. When loss exceeded 90%, perimetric sensitivity decreased more rapidly than ganglion cell number for conventional perimetry.

Ron Harwerth, using psychophysical and histological measurements, published a mathematical model in 2004 that linked visual sensitivity and ganglion cell density. Knighton and colleagues conducted a fascinating study using the OCT 3 to evaluate this model (“The relation between ganglion cell layer thickness and visual sensitivity in the glaucomatous human macula”).

They evaluated the central 10º in individuals with mild to moderate stages of glaucoma. Stratus OCT images were taken, and ganglion cell density was calculated from these images. Visual sensitivity was measured using 10-2 HFA full-threshold algorithms. For eccentricities outside 4º, ganglion cell densities obeyed the model developed by Ron Harwerth. Within 4º, there were differences, as the measured values were less than predicted.

ARVO is a fascinating meeting that provides views into new and exciting areas of glaucoma. Risk modeling, new medications and diagnostic tests are just a few of the areas explored at this meeting.

For Your Information:

Murray Fingeret, OD, is chief of the optometry section at the Department of Veterans’ Affairs Medical Center in Brooklyn and Saint Albans, N.Y., and a professor at SUNY College of Optometry. He is also a member of the Primary Care Optometry News Editorial Board. He may be contacted at St. Albans VA Hospital, Linden Blvd. and 179th St., St. Albans, NY 11425; (718) 526-1000; fax: (516) 569-3566; e-mail: murrayf@optonline.com. Dr. Fingeret has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.