Combination therapy provides quick visual recovery for CME patients, study shows

Contrast sensitivity also improved with combination therapy.

ByMichelle Stephenson

ORLANDO, U.S.A. — Both combination therapy and ketorolac (Acular; Allergan) alone are efficacious for the treatment of acute pseudophakic cystoid macular edema (CME). However, visual recovery is quickest with combination therapy, according to a recent study.

“The reported incidence of clinical CME ranges from 1% to nearly 7%, depending on the definition of CME. This could result in 20,000 to almost 140,000 new cases of pseudophakic CME annually. This obviously can have a significant impact, both on surgeons and patients,” said Jeffrey S. Heier, MD, at the recent meeting of the American Academy of Ophthalmology held here.

Combination therapy

Dr. Heier and his colleagues conducted a prospective, randomized study to evaluate prednisolone, ketorolac and combination therapy for the treatment of acute pseudophakic CME. “Inclusion criteria included patients who had characteristic angiographic CME and acuity of 20/40 or worse and who were 3 weeks to 3 months post-cataract extraction and lens implantation,” he explained.

Exclusion criteria included the use of nonsteroidal anti-inflammatory drugs within 7 days, the use of any anti-inflammatory other than systemic aspirin or topical prednisolone in the postoperative period and any ocular disease that could have resulted in decreased acuity, which would have confounded the study results.

“Our outcome criteria included improvement in visual acuity, improvement in contrast sensitivity and improvement in the angiographic appearance of CME,” he added.

Patients were randomized on postoperative day 1. If they were already on topical prednisolone, the steroids were stopped, and study medications were begun immediately without a washout period.

Medications tapered

Treatment was four times a day and was maintained until patients had stable acuity for 1 month. Then, medications were tapered over 3 weeks at the rate of one drop per week.

Twenty-eight patients were enrolled, 26 of whom completed the study. One patient in the ketorolac group was excluded after developing a neovascular membrane 3 months postoperatively. Additionally, one patient in the combination group was removed from the study after developing a branch retinal vein occlusion.

Patients were enrolled an average of 7 weeks post-cataract extraction, with a range of 3 to 12 weeks. There were no significant differences in the study groups with respect to time of enrollment or initial visual acuity. Eleven patients were on topical steroids at the time of enrollment, and these were spread out over the three groups.

“We evaluated the data and felt that the most important evaluation was that of average improvement in acuity over baseline. The reason was that this corrected for any differences in initial visual acuity. The prednisolone group improved an average of 1.1 lines. The ketorolac group improved an average of 1.6 lines, and the combination group improved an average of more than 3 lines,” he explained.

Sixty-one percent of patients improved two lines or more. Fifty percent of those in the prednisolone group improved two lines or more, and 66% of the ketorolac patients improved two lines or more. With combination therapy, 90% improved two lines or more.

Faster improvement

The ketorolac group and the combination group improved twice as fast as the prednisolone group.

“When contrast sensitivity and improvement in fluorescein angiography were evaluated, we found that these results seemed to mirror the improvements noted in visual acuity. Recurrences in the postoperative period were detected in two patients, one in the ketorolac group and one in the combination group. Both patients had experienced an improvement in acuity once treatment was re-started, but the patient in the combination group only improved one line, and this actually represented the single treatment failure in the combination group,” Dr. Heier said.

“While the majority of CME patients resolve on their own, treatment is still important. It is not uncommon to see a patient who develops CME have total resolution and improve to 20/20, yet still complain of significant differences when compared to the non-CME eye. It is possible that these differences are measured not necessarily by Snellen acuity, but perhaps by contrast sensitivity or Amsler grid changes. It has been previously shown that treatment with topical nonsteroidals can result in improvements in contrast sensitivity,” he said.

Additionally, improvements in visual acuity are expected rapidly. Acute CME may delay these improvements and may permit them from occurring completely. The treatment of acute CME may, at the minimum, hasten this recovery.

“We showed that combination nonsteroidal and steroid therapy resulted in greater gains in acuity, faster improvements with these gains and improvements in contrast sensitivity. However, this study had weaknesses, such as the lack of a control arm and a relatively small sample size. Perhaps a longer follow-up would have resulted in more recurrences,” he added.

Preoperative use of corticosteroids

According to Allan J. Flach, MD, who discussed the study at the AAO meeting, “This study is confused to an extent by the preoperative use of corticosteroids. As the authors have suggested, corticosteroids were used in some patients until 7 days prior to the initiation of the treatment regimen. This provides at least for the possibility of corticosteroid activity in all patients, at least in the early part of the study.”

He said that this study’s greatest strength is its demonstration of the synergism between nonsteroidal anti-inflammatory agents and steroids in the treatment of CME. “Whether or not there is a short-term benefit for visual acuity will remain to be seen after we analyze the individual data within this study. Of course, neither this study nor any existing study shows that the early treatment of CME or the prophylactic treatment of CME following cataract surgery has a proven, long-term benefit for visual acuity or that it prevents the ultimate onset of chronic CME in the future,” he added.

For Your Information:

Jeffrey S. Heier, MD, can be reached at Ophthalmic Consultants of Boston, 50 Staniford St., Ste. 600, Boston, MA 02114 U.S.A.; +(1) 617-367-4800; fax: +(1) 617-723-7028. Dr. Heier has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Allan J. Flach, MD, can be reached at P.O. Box 219, Corte Madera, CA 94976 U.S.A.; +(1) 415-476-3709; fax: +(1) 415-502-6195. Dr. Flach did not participate in the preparation of this article.