Intravitreal anti-VEGF may be useful in diabetic macular edema

A study indicated a greater benefit when bevacizumab was used in patients with no history of treatment for DME.

Issue: November 2009

Intravitreal bevacizumab appears to be a safe and effective therapy for diabetic macular edema, and results of a recent study suggest that it may prove most successful as a front-line therapeutic option.

Surgical intervention in patients with diabetic macular edema (DME), including grid laser photocoagulation, can reduce visual loss. However, long-term efficacy is limited, and studies have highlighted that laser photocoagulation does not address the vascular leakage induced by release of VEGF into the ischemic retina in patients with DME.

The role of VEGF may, therefore, point to a role for anti-VEGF therapy in DME. Although corticosteroids, specifically intravitreal triamcinolone acetonide, have proved effective in reducing VEGF activity in DME, associated complications, including IOP increase and cataract formation, have limited their clinical utility.

According to Dennis S.C. Lam, MD, FRCOphth, selective anti-VEGF therapy, such as Avastin (bevacizumab, Genentech), offers an alternative therapeutic option in DME. In a study led by Prof. Lam and co-investigator Timothy Y. Lai, MD, FRCOphth, bevacizumab improved best corrected visual acuity at 6 months in patients with DME, and no significant adverse events were reported. In addition, subgroup analysis showed a greater benefit from bevacizumab therapy in patients with no prior treatment history.

Dennis S.C. Lam

“Since bevacizumab appeared to be effective in treatment naïve cases and the safety profile is much better than corticosteroids, it should be considered as a front-line therapy if cost is not a major concern,” Prof. Lam said.

Study results

In the study, 52 eyes of 52 patients with DME were randomly assigned to receive a 1.25-mg dose or a 2.5-mg dose of bevacizumab. Patients were administered three monthly doses and were followed to 6 months, when 23 eyes in the 1.25-mg group and 25 eyes in the 2.5-mg group were available for analysis.

Compared with baseline, BCVA improved significantly in both groups. In the 1.25-mg group, BCVA improved from 0.63 logMAR to 0.52 logMAR, and in the 2.5-mg group, BCVA improved from 0.6 logMAR to 0.47 logMAR; there was no significant difference in BCVA between the two groups at any time point.

In the lower dose group, BCVA improved to 0.48 logMAR at 4 months, followed by a slight regression. This same pattern was not seen in the higher dose group.

“Although there appeared to be a small regression in BCVA in the 1.25-mggroup and no change in BCVA in the 2.5-mg group between 4 and 6 months, the differences between the two groups were not statistically significant. The small differences were likely to be due to individual variations,” Prof. Lam said.

According to Prof. Lam, peak improvement occurred at about 4 months, indicating that re-treatment or continuous treatment may be beneficial.

“Moreover, the optical coherence tomography results showed that there was recurrence of the edema after the injections were stopped and, therefore, re-treatment or continuous monthly injections might be useful to prevent edema recurrence,” he said.

Central foveal thickness

In subgroup analysis of 31 eyes that had full treatment history available, 17 had received previous therapy (photocoagulation in 14 eyes, and laser and triamcinolone in three eyes). In these patients, mean central foveal thickness improved from 452 µm at baseline to 416 µm at 6 months, and BCVA improved from 0.66 logMAR to 0.56 logMAR (P = .074).

However, in 14 patients with no treatment history, central foveal thickness was reduced from 466 µm at baseline to 354 µm at 6 months (P < .001), and BCVA improved from 0.58 logMAR to 0.46 logMAR at 6 months (P = .001).

“These preliminary results suggested that anti-VEGF is more useful in causing visual and anatomical improvements when used as a front-line therapy rather than treatment for recurrent cases. The results suggest that treatment other than bevacizumab should be considered for previously treated cases,” Prof. Lam said. “This might be due to lesser extent of damage to photoreceptors or retinal pigment epithelial cells caused by previous laser photocoagulation.”

He said his group has recently initiated a 2-year study with a larger population to compare the use of bevacizumab vs. laser vs. combined therapy for DME in an attempt to more precisely define the role of anti-VEGF therapy in DME. — by Bryan Bechtel

Reference:

Lam DS, Lai TY, Lee VY, et al. Efficacy of 1.2 mg versus 2.5 mg intravitreal bevacizumab for diabetic macular edema: six-month results of a randomized controlled trial. Retina. 2009;29(3):292-299.

Dennis S.C. Lam, MD, FRCOphth, can be reached at Hong Kong Eye Hospital, The Chinese University of Hong Kong, 3/F, 147K Argyle St., Kowloon, Hong Kong SAR, China; +852-2762-3157; fax: +852-2715-9490; e-mail: dennislam8@cuhk.edu.hk. Prof. Lam has no direct financial interest in the products discussed in this article, nor is he a paid consultant for any companies mentioned.