At ARVO this year, research gravitated toward some of the many gray areas of our understanding of glaucomanamely, testing and diagnosing, glaucoma progression, medication and management, and patient compliance.

 

Make a Positive Diagnosis

Researchers in Switzerland presented the results of the first in vivo measure of human IOP with a wireless soft contact lens-based sensor.687/D960 The lens includes a strain gauge, antenna and microchip. Non-glaucomatous patients were tested with the lens while experiencing induced IOP fluctuations. The sensor recorded IOP correlative to Goldmann tonometry. Researchers note potential use for minimally invasive continuous monitoring of IOP, regardless of patient activity.

Massachusetts researchers set out to develop an implantable IOP monitor that provides an uninterrupted measurement, 24 hours a day.686/D959 The prototype implant was tested with air pressure simulations from 0mm Hg to 100mm Hg, and is coated with parylene for biocompatibility. Researchers note a need for revision before live trials, but state that the minimal daily upkeep needed for the device will improve quality of life.

Both new instruments in the aforementioned studies may allow us to accurately measure daily diurnal variation and circadian variation. And, the next two studies point out the usefulness of this information.

Researchers based in Italy and Spain asked, Can circadian IOP fluctuations really be estimated during office hours?1054/D997 Their answer: Nearly always. The retrospective study analyzed 144 24-hour IOP curves of healthy and glaucomatous patients. They found that, during office hours, mean IOP had only been slightly overestimated when approximating 24-hour fluctuation; however, there was a statistically significant difference between estimates and actual measurements of IOP in cases of undiagnosed glaucoma patients.

Researchers in Brazil also examined IOP measurements outside the office, and found that, at 6:00 a.m., the IOP of a poorly-controlled glaucoma patient tends to spike.1051/D994 Of the study cohort of glaucoma suspects and patients, 66.5% of IOP curves peaked at 6:00 a.m., signifying either a definitive diagnosis or inadequate therapeutic management, say researchers.

Identifying risk factors and additional tests to help predict glaucoma is always helpful. The following three studies do just that. 

A study led by researchers in Brazil and New York compared the water-drinking test with the 30 inverted body position test to determine their impact on patients IOP.1059/D1002 The 71 eyes examined in the study were categorized as normal, glaucoma suspect or diagnosed with early glaucoma.

Patients fasted before the water-drinking test, in which they drank one liter of water in five minutes. Measurements were taken at 15, 30 and 45 minutes. For the 30 inversion test, patients IOP was recorded after five minutes of lying in this position. Results showed that the 30 inversion test was as effective as the water drinking test for peak IOP detection, and researchers note that it is faster and more comfortable for practitioners and patients.

Philadelphia researchers examined the role of asymmetric IOP as an indicator of open-angle glaucoma.1064/D1007 Of the 198 patients examined, 100 were normal and 98 had open-angle glaucoma. IOP symmetry was nonexistent in glaucomatous patients, while 34% of healthy patients experienced symmetry. Further, 17% of the glaucomatous cohort demonstrated an IOP difference greater than 6mm Hg.

Similarly, researchers in Korea examined latent asymmetric IOP as a predictor of visual field deterioration secondary to glaucoma.1065/D1008 Every two hours over a period of 24 hours, 53 patients with open-angle glaucoma were examined to detect IOP asymmetry while supine, but not while sitting. Of the population, researchers found that nearly 30% demonstrated latent asymmetric IOP, and that this same group demonstrated worse visual fields than the other patients. Researchers note the need for further research.

 

Progression and Evaluation

Researchers in Spain set out to evaluate the ability of the Topographic Change Analysis feature of the Heidelberg Retinal Tomograph (HRT) to detect structural changes secondary to glaucoma.3651/D1042 For at least three years, 54 eyes with glaucomatous optic neuropathy were examined every six months, and progression had to be confirmed in at least two fields. At the conclusion of the study, 29 eyes were eligible for analysis due to image clarity. Results demonstrated that, within this cohort, HRT found 80% of the eyes undergoing disease progression.

In Israel, researchers found that optical coherence tomography (OCT) was able to better identify retinal nerve fiber layer (RNFL) loss than standard visual fields tests.733/D1071 After comparing RFNL thickness of unaffected quadrants of glaucomatous eyes to corresponding quadrants in healthy eyes, researchers found that glaucomatous RNFL was significantly thinner than that of the control RNFL. OCT detected 76% of these thin retinal nerve fiber layers.

One study examined the Glaucoma Progression Analysis (GPA) tool of the Humphrey Field Analyzer. Researchers in Spain compared its abilities to expert field analysis and found that GPA detected progression in 86% of progressing cases, and it detected the lack of progression in 97% of non-progressing cases.1094/D1037

 

Treatment

Making the best recommendation on secondary and tertiary treatment can be difficult. But, the following studies provide some guidance in this murky area.

Researchers in Greece and South Carolina compared the efficacy of a dorzolamide/timolol fixed combination (DTFC) as a second-line therapy to latanoprost monotherapy, DTFC as a first-line therapy and a latanoprost/timolol fixed combination (LTFC).1210/A52 The 31 patients who completed the study were rotated through the three treatment options for three months each.

Each treatment regimen resulted in a lower IOP than latanoprost monotherapy, but the DTFC-and-latanoprost regimen resulted in the lowest mean 24-hour IOP, as well as the lowest IOP at each measurement. But, this treatment also resulted in the most stinging upon instillation.

Researchers in New York examined the inflammatory response by surface epithelia upon exposure to prostaglandin analogs.3820/A187 In comparing the effects of travoprost Z 0.004%, travoprost 0.004% with BAK 0.015% and latanoprost 0.005% with BAK 0.02% on human conjunctival and corneal epithelial cell cultures, researchers found that travoprost Z incited the least inflammatory response and that latanoprost 0.005% with BAK 0.02% elicited the greatest. They note that the preservative appeared to induce nearly 70% of the response.

Two studies examined selective laser trabeculoplastys (SLTs) effects on IOP and primary open-angle glaucoma. New York researchers found that SLT resulted in significantly lower IOP one year after the procedure in patients with primary open-angle glaucoma who were already taking maximum medical therapy.1235/A109 In this retrospective study, the mean pre-treatment IOP was 18.97mm Hg, and at the one-year post-SLT follow-up, IOP was reduced by a mean of 2.48mm Hg.

But, another group of New York researchers assessed the efficacy of third and fourth repeat SLT procedures, and their ability to control IOP, and found that the efficacy of SLT declined with the amount of repeat procedures.1241/A115 The retrospective study found that 30% of third SLT procedures failed at three months and that nearly 50% did so by six months. And, researchers found that nearly 60% of fourth SLT procedures failed at one month and nearly 75% failed at five months.

Should we become more aggressive in our treatment? Can a single IOP measurement really indicate treatment failure? Yes, say New York researchers, if it is measured at a mean of 6mm Hg above target.3605/D888 Researchers posit, after examination, that an acceptable range of variability extends 1.05 standard deviations above the maximum target goal, and that, with a 95% confidence rate, a patient with a single IOP reading 6mm Hg above goal is 99.5% likely to fail therapy.

 

Compliance

Do you know how many of your patients adhere to their care regimens? Maybe not, according to researchers in Belgium and Switzerland.1579/A79 A survey of 635 glaucoma patients and their eye-care practitioners showed that patients reported 38% non-adherence, while practitioners reported that only 2.2% of their patients were non-adherent.

And, researchers in Germany and France contend that non-compliance may lessen the efficacy of glaucoma treatment. They measured patient compliance by recording self-dosing regimens electronically.1582/A82 Nearly 10% of patients used more than one drop per application, while another subset of patients instructed to instill one drop t.i.d. showed a mean rate of 1.8 drops per day.

Perhaps patients use too many drops per application because they require aid for instillation. New York researchers examined a new positioning aid and found that patients responded well.1581/A81 Participants instillation technique prior to aid use was examined for duration of process and location of the applied drop, and special note was taken if the dropper tip touched ocular or periocular tissue. Of the 110 patients in the study, 82.4% found instillation was easier with the aid, and contact with the ocular or periocular surface was lessened. Researchers point to the aids usefulness post-surgeryrisk of infection from contamination may be lessened, and patients may be more comfortable with drop application. This device may also help patients use the proper amount of medication.

Dr. Cole is in private practice in Bridgeton, N.J., and he is an assistant professor at Pennsylvania College of Optometry.

 

687/D960. Pitchon EM, Leonardi M, Renaud P, et al. First in vivo human measure of the intraocular pressure fluctuation and ocular pulsation by a wireless soft contact lens sensor.

686/D959. Dresher RP, Chow EY, Fogle BN, et al. Improving glaucoma treatment: an implantable IOP monitor providing uninterrupted measurements.

1059/D1002. Kanadani FN, Moreira TCA, Melo FH, et al. A new provocative test for glaucoma?

1054/D997. Orzalesi N, Fogagnolo P, Ferreras A, Rossetti L. Circadian intraocular pressure fluctuations: Can we really estimate them during office hours?

1051/D994. Cronemberger A, Silva ACL, Calixto S. The importance of intraocular pressure at 6:00am in bed and darkness in suspects and glaucomatous patients.

1064/D1007. Spaeth GL, Wang Y, Barros DSMd, et al. Asymmetric intraocular pressure in subjects with or without glaucoma.

1065/D1008. Hong S, Kang S, Kim EK, et al. Latent asymmetric intraocular pressure as a predictor of glaucomatous visual field deterioration.

3651/D1042. Ayala E, Anton A, Martin B, et al. Detection of progression with HRTs topographic change analysis.

733/D1071. Geyer O, Fishelson-Arev T, Mathalone N, et al. Optical coherence tomography (OCT) can identify retinal nerve fiber layer (RNFL) loss, beyond visual field defect in glaucoma.

1094/D1037. Bardavio J, Pazos M, Castany M, et al. Glaucoma progression detection: comparison of expert visual field evaluation and glaucoma progression analyzer.

1210/A52. Konstas AG, Mikropoulos D, Dimopoulos AT, et al. Second-line therapy with dorzolamide/timolol or latanoprost/timolol fixed combination versus added dorzolamide/timolol fixed combination to latanoprost monotherapy.

3820/A187. Epstein SP, Chen D, Asbell PA. Inflammatory response by ocular surface epithelia upon exposure to prostaglandin analogs.

1241/A115. Basile M, Ostrovsky A, Danias J, et al. Effect of third and fourth SLT on IOP.

1235/A109. Malen M, Lai P. Effects of SLT on IOP in POAG in maximum medical therapy.

3605/D888. Patel S, Young J, Nissan E. A single intraocular pressure measurement of 6mm Hg above goal indicates glaucoma treatment failure.

1579/A79. Vanderbroek S, Dobbels F, De Geest S, et al. Ophthalmologists poorly predict patient non-adherence.

1582/A82. Hermann MM, Bron AM, Creuzot-Garcher CP, Diestelhorst M. Electronic compliance monitoring in glaucoma patients used to topical therapy.
1581/A81. Papachristou GC, Radcliffe NM, Sbeity Z, et al. A new positioning aid for eye drop instillation.