Study shows primary intravitreal bevacizumab provides stability, improvement in diffuse diabetic macular edema

August 1, 2008

A comparison of two doses of intravitreal bevacizumab (Avastin, Genentech) showed that both resulted in stability or improvement in visual acuity and central macular thickness in patients with diffuse diabetic macular edema (DME) over a 12-month period.

Key Points

Fort Lauderdale, FL-A comparison of two doses of intravitreal bevacizumab (Avastin, Genentech) showed that both resulted in stability or improvement in visual acuity and central macular thickness in patients with diffuse diabetic macular edema (DME) over a 12-month period. Juan G. Sanchez, MD, presented findings from this study on behalf of the Pan-American Collaborative Retina Study Group (PACORES) at the annual meeting of the Association for Research in Vision and Ophthalmology.

Because outcomes between the two doses do not seem to differ, the lower dose would be preferred, Dr. Sanchez added. He cautioned, however, that a longer follow-up period is needed to confirm the results. At the time of his presentation, he was a fellow at Clinica Oftalmologica Centro Caracas in Caracas, Venezuela, working with J. Fernando Arevalo, MD, FACS, director of the clinic and the Arevalo-Coutinho Foundation for Research in Ophthalmology.

Dr. Sanchez reported the anatomic and Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) results from an interventional retrospective review of the clinical records of 82 consecutive patients (101 eyes) who had received primary intravitreal bevacizumab in doses of 1.25 or 2.5 mg. Patients had been seen at six centers in Brazil, Costa Rica, Mexico, Puerto Rico, and Venezuela. All patients with at least 12 months of follow-up were included in the analysis; the mean was 57.6 weeks.

The mean age of the patients was 59.7 ± 9.3 years, 53.7% were female, and 79.3% were Hispanic. A majority of patients, 52.5%, had PDR. Dr. Sanchez reported that 48 eyes were treated with an injection of 1.25 mg and 53 eyes with 2.5 mg of bevacizumab. Patients underwent ETDRS BCVA testing, ophthalmoscopy, optical coherence tomography, and fluorescein angiography at baseline and follow-up visits.

The mean baseline BCVA was 0.87 logMAR, whereas the mean final BCVA was 0.68 logMAR, a statistically significant difference (p < 0.0001).

"At the 6-month follow-up time point, we noticed a worsening of vision with a mean logMAR of 0.77, but still a difference that was statistically significant from visual acuity at baseline," Dr. Sanchez said.

Analyzed by dosing group, the results showed that in the 1.25 mg group, an average gain of 3.2 ± 2.9 lines of BCVA was seen at 1 month, 2.7 ± 2.6 lines at 3 months, 2.1 ± 3.4 lines at 6 months, and 2.9 ± 3.6 lines at 12 months (p < 0.005). In the 2.5 mg group, the change in BCVA was 2 ± 4 lines at 1 month, 1.9 ± 2.9 lines at 3 months, 0.6 ± 5.5 lines at 6 months, and 0.7 ± 5.5 lines at 12 months (p < 0.05).

Analyzing the drop in BCVA at 6 months, the investigators found that the decrease occurred in eyes that had received one or two injections rather than those that had received three or more.

"This suggests the need for at least three injections a year to maintain the visual acuity results," Dr. Sanchez said.

The results for central macular thickness (CMT) showed an overall decline from a mean baseline of 401.8 to 290.2 µm at the final visit (p < 0.001).

No statistically significant difference existed between the two dosage groups.

In the 1.25 mg group, the mean CMT decreased from 419.1 ± 201.1 µm at baseline to 295.11 ± 91.5 µm at 1 month, 302.1 ± 124.2 µm at 3 months, 313.4 ± 96.3 µm at 6 months, and 268.2 ± 95.5 µm at 12 months. In the 2.5 mg group, the mean CMT decreased from 387.7 ± 162 µm at baseline to 287 ± 136 µm at 1 month, 316.9 ± 169.8 µm at 3 months, 306.7 ± 139.6 µm at 6 months, and 295.5 ± 113.9 µm at 12 months (p < 0.0001).

A total of 244 intravitreal bevacizumab injections were given during the study; the mean per eye was three (range one to six). No statistically significant difference was found in the number of injections between the two groups.

Adverse events were infrequent; Dr. Sanchez reported one incident each of transient high blood pressure, transient increased IOP, and tractional retinal detachment.

Limitations of the study include its nonrandomized, uncontrolled, and retrospective design and lack of a control group. Investigators cannot rule out the possibility that some of the improvement in macular edema might be associated with overall improvement in systemic health.

"However, the results were very promising and suggest the need for further investigation," Dr. Sanchez concluded.