Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

110th Annual Meeting of the American Academy of Ophthalmology

Las Vegas, Nevada / November 11-14, 2006

“Glaucoma management is far more successful when appropriate target pressures are used,” indicated Dr. Richard Parrish, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Florida, citing two studies that highlight the difference in outcomes achieved with and without the use of target pressures. By using aggressive target pressures (mean reduction of 35% intraocular pressure [IOP]), the CIGTS (Collaborative Initial Glaucoma Treatment Study) was able to reduce IOP by a mean of 37%. Conversely, a mean reduction in IOP of 29% was reported in the EMGT (Early Manifest Glaucoma Trial) that did not use target pressures.

According to Dr. Parrish, along with more successful glaucoma management when evidence-based target pressures are used, their use is also helpful to patients and physicians. “Patients are better prepared to accept changes in therapy when you have discussed how likely each step is to achieve the target pressure,” he explained, adding that “the proper use of target pressures does not prevent, but actually facilitates, treatment of the patient as an individual.”

Countered Dr. Kuldev Singh, Professor of Ophthalmology, Stanford University, Connecticut, “You do not need a target IOP to manage glaucoma patients. Baseline untreated IOP should replace target IOP as a reference parameter in glaucoma care.” In his view, several unknowns about IOP make it impractical to define an ideal target for a given patient. “We do not know the degree of IOP fluctuations over the 24-hour period, [because] continuous measurement is unavailable.” Also unknown are “the relative importance of mean IOP, peak IOP and fluctuations of variability of IOP,” he added, as is the “quality of IOP-lowering with various glaucoma therapies.”

Diurnal Curves: Measuring 24-hour IOP Fluctuations

Emerging as an important strategy to optimizing glaucoma control is the need to keep IOP at a constant pressure throughout the 24-hour cycle. The under-recognized danger of elevated nocturnal pressure was highlighted by Dr. Arthur J. Sit, Assistant Professor of Ophthalmology, Mayo Clinic College of Medicine, Rochester, Minnesota. He cited early studies of primary open-angle glaucoma (POAG) which suggested that IOP is highest in the morning and slightly lower at night. However, he, noted, these studies only measured IOP while patients were sitting. More recent studies that measure IOP in both a sitting position during the day and in a supine position at night found rapid increases in IOP in patients in the supine position. “Although most patients have peak IOPs during sleep,” he told delegates, “studies examining the efficacy of treatment have not typically evaluated nocturnal efficacy.”

Currently under investigation at the Mayo Clinic is the yet unknown reason behind nocturnal IOP increases. According to Dr. Sit, researchers are observing the role of outflow facility and position on nocturnal IOP.

He also suggested that there is a need for 24-hour IOP monitoring much like the Holter monitoring for EKG or ambulatory blood pressure. However, “nocturnal IOP measurement is not practical at this time,” he told the audience.

IOP and Potential Risk Factors for Glaucoma

Evidence suggests that reduced ocular diastolic perfusion pressure (DPP) may be a risk factor for POAG. According to Dr. Alon Harris, Letzter Endowed Professor of Ophthalmology, Indiana University School of Medicine, Indianapolis, foremost among the many different risk factors associated with glaucoma is low DPP. “Many prospective studies have shown ocular blood flow [OBF] is abnormal in glaucoma patients,” he confirmed. In these studies, OBF abnormalities have been found in several vascular locations, including the optic nerve head, choroid, retina, retrobulbar circulation, and the cerebral and peripheral vessels.

Dr. Harris presented data on advances in a number of imaging tools, including ultrasound, laser, computerized image analysis and Doppler technologies, which now permit objective measurement of OBF. Despite the availability of these tools, evaluation of OBF is not yet used in daily clinical practice because no single diagnostic tool or device can currently evaluate accurately all the relevant vascular beds in glaucoma. “Basically, we would like to see the development of a single device which would replace all the current separate devices,” he explained, adding that this is important so that OBF analysis can be available in clinics on a daily basis as needed rather than only in research centres. In the future, according to Dr. Harris, “patients that present with vascular risk factors and advancing disease would be referred for OBF examination in an attempt to determine whether this is an underlying reason for their disease progression.”

Another study presented by Dr. Ronald Eric P. Frenkel, Eye Research Foundation, East Florida Eye Institute, Stuart, found that low nocturnal DPP may be an even more sensitive risk factor for glaucoma compared to low daytime DPP. The study found significantly lower nocturnal DPP in patients with abnormal systolic dips (SD) and diastolic dips (DD) compared to non-dippers (SD: 52 ± 9 mm Hg non-dippers vs. 45 ± 8 mm Hg dippers; P=0.001; DD: 53 ± 9 mm Hg non-dippers vs. 44 ± 8 mm Hg dippers; P=0.00002). The study investigators recommended that daytime and nocturnal DPP should be further studied and incorporated into glaucoma risk factor models.

EXACCT Study Findings

For patients who fail first-line therapy, finding an effective second-line strategy is critical to provide optimal glaucoma control. Final results were presented from the multicentre, open-label EXACCT study, which examined the efficacy of second-line therapy of dorzolamide/timolol fixed combination (DTFC) either alone (switch group) or combined with latanoprost (add-on group) in patients who failed initial therapy with latanoprost. Findings showed a significant reduction in IOP in both groups, with a mean 23% pressure reduction at six and 12 weeks for the switched group and 28% for the add-on group (P=0.001).

As reported by investigator Dr. Mark R. Lesk, Université de Montréal, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, “In patients who were uncontrolled while on latanoprost, if you either switch them to dorzolamide/timolol or add dorzolamide/timolol, you will have excellent pressure reduction and excellent control of IOP.” Adherence to therapy was seen in 71% and 67% for DTFC at the second and third visits, respectively, and 77% and 73% for latanoprost, respectively.

The study also found that 85% of physicians felt that DTFC was helpful and 82% were satisfied with it compared to other IOP-lowering medications. “I think people who read this [study] and who participated in the study will be quite happy with the pressure reduction [attained] and are probably likely to use timolol-dorzolamide as second-line therapy,” Dr. Lesk concluded.

Dry Eye in Glaucoma Patients

It may be important for clinicians to ask about—and manage—symptoms of dry eye among glaucoma patients, as it would appear to be prevalent. A retrospective review of 2117 glaucoma patients and 2000 patients with dry eye presented here during the scientific sessions by Dr. Jenny Yu, University of Pittsburgh Medical Center Eye and Ear Institute, Pennsylvania, and colleagues, demonstrated that 9% of glaucoma patients were also being treated for dry eye. Of these patients, over 55% were using various forms of artificial tears to relieve dry eyes and almost 20% had also used topical cyclosporine. Most patients being treated for dry eye were using topical glaucoma therapy while approximately one-third of the group required treatment with two or more glaucoma compounds.

The study authors concluded that their retrospective review suggests that the incidence of dry eye may be quite high in glaucoma patients and physicians should therefore both inquire about and offer treatment for concomitant symptoms of dry eye when treating patients for glaucoma.