Glaucoma drops may help in refractory AMD

By Lorraine L. Janeczko

NEW YORK (Reuters Health) - When age-related macular degeneration (AMD) is refractory to intravitreous anti-vascular endothelial growth factor (anti-VEGF), adding dorzolamide-timolol eye drops may be helpful, according to a small pilot study.

In 10 elderly patients, the drops, used twice daily, reduced central subfield thickness and subretinal fluid in 10 eyes with persistent exudation despite regular, fixed-interval intravitreous anti-VEGF treatment, researchers reported online February 25 in JAMA Ophthalmology.

"Our study suggests that a commonly available prescription glaucoma drop may help boost the effectiveness of the anti-VEGF medications we currently use to treat patients with wet AMD," corresponding author Dr. Jason Hsu at Thomas Jefferson University in Philadelphia told Reuters Health by email.

"I was surprised at how well it worked on average and especially in a few patients who had complete resolution of edema that had been chronic for months to years despite regular anti-VEGF injections. It was almost like we had discovered a novel drug for AMD," he said.

Dr. Hsu and colleagues tested their intervention over eight months in 2015 at two academic retina treatment centers. They enrolled 14 patients, but four patients did not complete the trial.

The researchers obtained baseline spectral-domain optical coherence tomography (SD-OCT) and clinical data, including visual acuity and intraocular pressure, at one visit before enrollment and at enrollment.

Of the 10 eyes that completed the study (mean age 78.2), eight were treated with intravitreous aflibercept and two were given intravitreous ranibizumab; the mean number of injections prior to the study was 22. Patients took the same anti-VEGF medication and were seen by their doctors at the same interval between injections as before enrollment. During the study, they added dorzolamide-timolol eye drops twice a day.

At each of at least two visits, central subfield thickness, maximum subretinal fluid height, and maximum pigment epithelial detachment height from spectral-domain optical coherence tomography were recorded. Eight patients completed three visits.

Between enrollment and the final visit, the mean central subfield thickness decreased from 419.7 micrometers to 334.1 micrometers (p=0.01). The mean maximum subretinal fluid height decreased from 126.6 micrometers to 49.5 micrometers (p=0.02). The mean maximum pigment epithelial detachment height decreased from 277.4 micrometers to 239.9 micrometers (p=0.12); and the mean logMAR chart visual acuities changed from 0.54 to 0.48 (p=0.60).

Dr. Rohit Varma, professor and chair of the Department of Ophthalmology at Keck School of Medicine of the University of Southern California in Los Angeles, told Reuters Health by phone, "These findings are surprising and interesting. About 15% of patients don't respond to anti-VEGF treatment, so finding ways to improve their outcomes is very important."

"Physicians who use dorzolamide-timolol eye drops should be aware of the potential side effects of these drugs," Dr. Varma advised. "These drops are not benign because they include a beta blocker and a carbonic anhydrase inhibitor. Ophthalmologists who use these drugs should watch for their potential side effects, including slowed heart rate, particularly in the 75-plus age group, exercise-induced asthma exacerbation, allergies, rashes, and so on."

Dr. Jacque L. Duncan, professor of ophthalmology at the University of California, San Francisco, agreed that doctors may consider adding dorzolamide-timolol eye drops to regular anti-VEGF injections for these patients.

"Also, the study looked at only two visits prior to adding eyedrops to the anti-VEGF treatments," Dr. Duncan added. "During the seven to 12 visits prior to starting the eye drops, variation in fluid may have been as great or greater than the effect reported in the current study, suggesting that the results were not caused by the addition of eye drops."

Dr. Ronald C. Gentile, professor of ophthalmology at New York Eye and Ear Infirmary of Mount Sinai in New York City, told Reuters Health by phone, "The treatment burden with intravitreal injections is one of the most significant challenges facing all retina specialists and their patients undergoing these treatments. If the drug decreases the treatment burden, patients can potentially need fewer injections, so in the long run the system can save money."

"Because of the small number of eyes enrolled, the lack of controls, and the high dropout rate where five eyes out of the original 15 never completed the study, questions remain, the most significant being whether the findings are the result of some bias," Dr. Gentile said. "Nonetheless, this study represents a potential new tool in our toolbox, a step in the right direction in our search for ways to decrease intravitreal treatment burden, something every retina specialist has been looking for."

This study was funded in part by the J. Arch McNamara, MD, Fund for Retina Research and Education at Wills Eye Hospital.

SOURCE: http://bit.ly/21KwHQZ

JAMA Ophthal 2016.

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