Leading glaucoma experts from the World Glaucoma Association launched the group"s first consensus on intraocular pressure at last month"s World Glaucoma Congress in Singapore. The panel recognized that elevated IOP is the leading risk factor for glaucoma progression and accurate measurement of IOP plays a key role in assessing glaucoma risk and disease management. The panel"s goal is to define more clearly the relationship between IOP and the optic nerve to minimize permanent damage, a leading cause of blindness worldwide.
The consensus panel represents 70 of the world"s principal glaucoma societies. "It is vital to define clearly how IOP relates to optic nerve damage to improve patient care and to achieve consistency in glaucoma management across the globe," said Robert N. Weinreb, MD, past president of the WGA (formerly AIGS: Association of International Glaucoma Societies), chair of the WGA Consensus Committee, and director of the Hamilton Glaucoma Center at the University of California, San Diego. "Our goal is to minimize glaucoma progression to preserve sight and maintain the overall quality of life of our patients."
The consensus report was based on more than two decades of groundbreaking research, which confirmed that IOP is a primary modifiable risk factor for glaucoma. Lowering IOP has been shown to be the only approach demonstrated to prevent and delay glaucoma progression.
The panel emphasized that IOP should be evaluated on an individual basis depending on where the patient is along the glaucoma disease continuum. The target levels for IOP should be defined as the estimated range where the risk of progressive disease is unlikely to affect the patient"s quality of life. Clinicians should consider the amount of glaucoma damage that has already occurred, the IOP at which the initial optic nerve damage occurred, life expectancy, the status of the fellow eye and family history of glaucoma.
The panel also considered ways to measure IOP accurately. In particular, the measurement of central corneal thickness was identified as crucial. The time of day, how long people have been awake and contact lens use all affect the precision of measurement of CCT.
The panel highlighted other important parameters in the outcome of glaucoma; the management of peak and mean IOP were seen as key factors to improve current standards of care.
"The WGA is working constantly to improve the global management of glaucoma in an effort to prevent what should be unnecessary vision loss," said Ivan Goldberg, FRANZCO, WGA president and clinical associate professor of ophthalmology at the University of Sydney, Australia. "The WGA has created the consensus process to achieve better patient care for those with glaucoma, and the panel"s report is respected globally."
Early Data on Anecortave Acetate for OAG
Alcon released the three-month interim results of the first controlled clinical study of anecortave acetate administered as an anterior juxtascleral depot in the sub-Tenon"s space to reduce IOP in patients with open-angle glaucoma.
The results, presented in a poster at the World Glaucoma Congress in Singapore, were from the 12-month proof of concept study that randomly assigned 85 patients to one of four arms: 3 mg, 15 mg or 30 mg of anecortave acetate or vehicle. All patients enrolled were diagnosed with open-angle glaucoma, had experienced glaucomatous visual field changes and had off-therapy IOPs between 24 mmHg and 36 mmHg. One injection of drug or vehicle was administered to each patient, and IOPs were assessed at two weeks, six weeks and at three months. The study will continue with full clinical assessments through the six-month period, with safety follow-up through the conclusion of the study.
The primary conclusion of the poster was that anecortave acetate demonstrated potential for prolonged reduction of IOP in a significant percentage of patients following a single administration of the drug for all concentrations versus vehicle at month three (ANOVA, p<0.05). On a combined basis, 38 percent of patients in the active arms were classified as treatment successes at three months, compared to 24 percent of patients in the vehicle arm. In the highest dose (30 mg), 50 percent of patients were defined as treatment successes at three months. On a combined basis, the mean IOP reduction in the three active arms at three months was 7.2 mmHg, compared to 1.4 mmHg for the vehicle arm (p=0.0014).
Additional data from the poster revealed that mean IOP declined in all three active arms and the vehicle arm at the two-week point, although there were no statistical differences at this time point. However, the mean intraocular pressure decline in the three active arms was maintained at the three-month time point, while mean intraocular pressure in the vehicle arm essentially returned to baseline by month three. Mean IOPs at month three declined 2 percent for the vehicle arm compared to 15 percent for the 3-mg arm (p=0.0536), 16 percent for the 15-mg arm (p=0.0526) and 19 percent for the 30-mg arm (p=0.0120).
The poster noted that the study was designed very conservatively to ensure patient safety in a study that involved glaucoma patients with confirmed vision loss and included a vehicle group. This study used a pre-defined intraocular pressure target for continuation in the study (¡Ü 21 mmHg), which imparted a negative bias toward demonstrating an overall beneficial treatment effect. This resulted in some patients exiting the study because their IOPs rose above 21 mmHg, even when IOPs were much lower than when they entered the study. This conservative design reduced the number of patients who reached the three-month endpoint, thereby preventing the achievement of the pre-defined primary endpoint of this small study.
The most frequent adverse events included eye pain, foreign body sensation and blurred vision. Nine of the 14 reports of eye pain were associated with the injection, and no patients discontinued from the study due to an adverse event. The four serious adverse events reported were stroke, irregular heart rate, uterine polyp and kidney stone, none of which was related to the study drug or procedure, and there was no dose relationship evident in the safety data.
"The results of this first controlled clinical study of anecortave acetate for glaucoma are encouraging because they show that with one injection the drug works for at least three months in a significant number of glaucoma patients to lower pressure by clinically relevant amounts," said Scott Krueger, PhD, Alcon"s vice president of R&D, Pharmaceutical Development. "In addition to these positive indications, we also learned more about the drug that will help us design additional studies that we believe will become the basis for filing an anticipated new drug application with the FDA in 2009."
Eye Test Causes Severe Lethargy in Infants
New research suggests that an eye drop used to diagnose Horner syndrome in infants can cause severe lethargy lasting up to 10 hours and requiring hospital admission and oxygen administration. In the article, "Adverse Effects of Apraclonidine Used in the Diagnosis of Horner Syndrome in Infants," published in the June issue of Journal of the American Association for Pediatric Ophthalmology and Strabismus, Patrick Watts, MD, and coauthors described five cases of extreme drowsiness or unresponsiveness after infants under 6 months of age were administered 1% apraclonidine eye drops.
Apraclonidine was developed to lower IOP and minimize the systemic side effects associated with the use of its parent drug, clonidine. An investigation of the site of action of apraclonidine incidentally uncovered a reversal of anisocoria in patients with Horner syndrome, a neurologic condition that causes a small pupil and a drooping eyelid on one side of the face. Though the syndrome is very rare in infants, testing occurs frequently.
While no deaths or permanent injuries occurred, the authors recommend against using apraclonidine in infants. If apraclonidine must be used in infants younger than 6 months of age, the patient should be observed for at least two hours after instillation of the drops, with admission to a pediatric ward prompted by lethargy, bradycardia or a reduced respiratory rate. No problems were reported with use of the medication in older children or adults.
AMO Sets Return To Multipurpose Solution Market
Advanced Medical Optics plans to begin shipping a multipurpose solution in the United States in the first half of August and expects the product will be widely available to consumers in this country by early September. The company had previously projected the product would not be available until late September.
The new product will focus on comfort and disinfection efficacy, incorporating the importance of proper handling and care of contact lenses, per guidelines set forth by major professional eye-care associations. AMO plans to ship to other global regions in a phased-in approach throughout the fall.