Thursday, June 1, 2023
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More than 6000 abstracts, a large proportion of which were related to all aspects of glaucoma, were presented at the 2007 meeting of the Association for Research in Vision and Ophthalmology (ARVO). From mice to molecules to clinical therapies to the larger socioeconomic impact of glaucoma, the 2007 ARVO Meeting offered a rich sampling of the ongoing research aimed at better understanding the world's second-leading cause of blindness.
A number of new ideas regarding how to best predict and monitor glaucoma damage have recently attracted the interest of clinicians and researchers. Since the Ocular Hypertension Treatment Study (OHTS)[1] reported central corneal thickness as an independent risk factor for progression from ocular hypertension to glaucoma, there has been a groundswell of interest in the noninvasive measurement of corneal factors that may have an impact on the risk of disease. Initial reports[2] indicated that lower hysteresis, a viscoelastic property of the cornea as measured by the Reichert noncontact tonometer, was correlated with glaucoma progression. This notion was confirmed by several papers at ARVO, including those from Bascom Palmer[3] and the Rothschild Institute in Paris.[4] Both papers found that eyes with worse glaucoma had a lower hysteresis, and concluded that this measurement has potential in the noninvasive assessment of glaucoma risk.
Perhaps the most interesting study examining the role of hysteresis in glaucoma risk took the next step in confirming the mechanism connecting corneal characteristics and glaucoma risk: Garway-Heath's group in London[5] reported that lower corneal hysteresis was associated with a greater deformation of the optic nerve surface as measured with Heidelberg Retinal Tomograph II (HRT II) during transient elevation of intraocular pressure (IOP) using a LASIK suction cup. This finding suggests that a more deformable cornea may be correlated with a more deformable, and hence perhaps more readily damaged, optic nerve. Basic research is ongoing which might offer a way to intervene on this problem. Investigators from University College of London[6] reported on animal studies attempting to transduce the optic nerve head with viral vectors to modulate the extracellular matrix makeup and thus modify the stiffness characteristics of the nerve. Sub-tenon injection appeared to be most effective in demonstrating proof of principle.
The water-drinking test (WDT) has received renewed attention in recent years as a potential predictor of glaucoma damage.[7] A number of posters from the University of California at San Diego and Brazil focused on water-drinking. Peak IOP during the WDT was found:
Because the test takes only half an hour and involves the consumption of only 1 liter of water, it may have potential in the noninvasive assessment of glaucoma risk, if reports of correlation with worse field outcomes can be confirmed.
Recently, work by Realini[11] has called into question the usefulness of 1-eyed trials of topical therapy in glaucoma, due to low observed correlation between the pressures in the 2 eyes. Three abstracts examined this question, with smaller studies by Spaeth at Wills Eye Hospital[12] and investigators at Yale[13] reporting relatively low correlation between success in a one-eyed trial and later response of the fellow eye to the same medication. A principal reason for this disparity appears to be regression to the mean. However, a large study from OHTS[14] found that, among 590 patients with a ≥ 20% response to beta-blockers, 78% had at least a 15% reduction in the fellow eye. Thus, the 1-eyed trial was effective in this setting.
Basic science studies of potential interest to clinicians at ARVO included a report of a study in mice[15] that supported the hypothesis that field damage in normal-tension glaucoma may be due to transient, asymptomatic elevations throughout the day in intracranial pressure. A report from Japan[16] indicated that intravitreal injection of Muller cells in the rat could significantly increase survival of retinal ganglion cells subjected to a model of glaucoma. Finally, a study in monkeys[17] reported IOP reductions of nearly 50% for 48 hours with the use of electro-acupuncture applied to points far from the eye according to the theories of traditional Chinese medicine. No significant reduction in IOP was observed in sham-treated controls.
Bolstered in many cases by new devices providing direct measurement of patient drop use, some of the most innovative abstracts in pharmacologic therapy focused on issues of compliance and adherence to therapy. A report by Robin from Baltimore[18] found that adherence measured with a "bottle in a bottle" electronic medications event monitoring system (MEMS) cap was higher (70% missing 0-2 drops per week) for a single prostaglandin analog than for a second, non-prostaglandin medication (43% with 0-2 drops missed). The device used is similar to that employed by Kass in his landmark study of drop adherence in the 1980s.[19] Robin[20] also reported on predictors of adherence using the Travatan dosing aid (Alcon, Ft. Worth, Texas). Overall rates of 80% were similar to the 76% reported by Kass. Divorced persons (40%), African Americans (63%), and younger patients (20-49 years, 66%) appeared to have lower adherence, although statistical tests of significance were not presented.
Traverso[21] reported that subjects with primary open-angle glaucoma were more compliant with drop use (50%) than were those with ocular hypertension (40%). The rate of missed drops for brimonidine[22] was reported to be 24% for twice-a-day dosing and 36% for three-times-a-day, while the figure for travopost using the Travalert device was 12% missed drops.[23] Both of these were small studies. Based on large datasets drawn from health maintenance organizations, Friedman and colleagues[24] have suggested that real-world adherence figures for glaucoma medications may be significantly lower, perhaps well under 50%. Stein[25] attempted to assess the proportion of subjects filling glaucoma prescriptions utilizing Medicare data and interviews for persons with a diagnosis of glaucoma or glaucoma suspect. Only 12% of glaucoma suspects, and only two-thirds of those diagnosed with glaucoma appeared to be receiving medicine. These figures are closer to those reported by Friedman and certainly provide cause for concern, although additional validation studies will be needed.
Another area of interest within pharmacology was the prevalence of medication side effects. A particularly interesting set of posters measured cystoid macular edema (CME) using ocular computed tomography (OCT) and other devices after cataract surgery in patients on glaucoma drop therapy. Preoperative[26] and postoperative[27,28] use of prostaglandin analogues was found to significantly increase the odds of CME after cataract surgery, as did the preoperative use of topical CAI/beta blocker preparation.[27]
A number of studies at this meeting looked beyond the treatment of individuals with glaucoma in an attempt to measure the larger costs of the disease to society. A study utilizing Medicare data[29] estimated the lifetime cost of glaucoma-related vision impairment at $9,200 per person. Of note, some 80% of this figure related to costs not directly related to visual impairment itself, including increased rates of depression, hip fractures, and home health care associated with glaucoma vision loss. In his talk during a workshop on healthcare disparities, Paul Foster[30] from the United Kingdom presented data indicating that persons with lower education and income tended to have higher IOP in studies in the United Kingdom. Although much of this disparity appeared to be explained by the mediating effect of systolic blood pressure, the point remains that, as with so many other diseases, patients with fewer resources often have poorer outcomes with glaucoma.
A number of studies sought to quantify the impact of glaucoma on patients' visual function and quality of life. A paper from the LALES study of Latinos in Los Angeles[31] found a significant decline in self-reported quality of life. The most noticeable decline among persons with abnormal visual fields was in the driving subcategory, even though 75% of the respondents did not know they had glaucoma. Central visual field defects had the greatest impact, although bilateral peripheral defects were also associated with worse self-reports.
Two other studies underscored the deleterious effect of glaucoma on driving. A study[32] of on-road performance of glaucoma patients driving with an instructor and a certified occupational therapist found 6 times the rate of critical interventions (such as the instructor's taking control of the steering or brake to prevent an accident) in drivers with modest glaucomatous field defects than in age-matched controls. A study by Garway-Heath's group[33] documented reduced saccadic distance, increased number of saccades, and failure to detect road hazards in glaucomatous subjects on a driving simulator.
Another study attempting to assess the impact of glaucoma on performance under "real world" conditions was Friedman's report from Maryland's Salisbury Eye Evaluation study.[34] The study documented slower walking speed and an increased number of bumps by persons with bilateral glaucomatous visual field defects on an obstacle course. Spaeth and the group[35,36] from Wills reported in a series of posters on results of the Assessment of Disability Related to Vision (ADREV), a module of real-world tests including matching socks, dialing a telephone, and recognition of facial expressions. Subjects with glaucoma had less variable decline in scores on the ADREV than they did in tests of self-reported visual function.
Broman and Quigley[37] from the Wilmer Eye Institute reported on the results of a study designed to assess the rate of progression of visual field loss in glaucoma patients from available population-based data. A total of 1066 white, black, Hispanic, and Chinese subjects were included. Though the rates of visual field progression (1 - 1.5 dB/year) did not differ significantly between races, black subjects had earlier onset and thus longer duration of disease (some 15 years) compared with whites (13 years), which meant that predicted rates of bilateral blindness in blacks (7%) were over 15 times higher than for whites (0.3%). The ADAGES study[38] of African Americans with glaucoma and ocular hypertension, which reported baseline results at ARVO, promises to have important insights into the reasons for worse glaucoma outcomes among persons of African descent.
Supported by an independent educational grant from Genentech
