Choroidal neovascularization future treatment may be combination therapy

November 15, 2008
Lynda Charters

Adjuvant use of bromfenac ophthalmic solution 0.09% (Xibrom, ISTA Pharmaceuticals) with ranibizumab (Lucentis, Genentech) reduced the reduced the number of ranibizumab injections needed to control choroidal neovascularization secondary to age-related macular degeneration. Use of the two drugs together resulted in better visual acuity outcomes than those achieved with ranibizumab alone.

Key Points

The results of the study indicated that bromfenac reduced the number of ranibizumab injections needed to control the disease, he said. In addition, the two drugs together resulted in better visual acuity (VA) outcomes than those achieved with ranibizumab alone, Dr. Grant added.

An increasing body of knowledge suggests that inflammation is the cause of and maintains the pathologic neovascular state of AMD, he said.

"Unfortunately, the current data have suggested an increased incidence of cerebral vascular accident and myocardial infarction in those with a . . . history of these events on long duration of ocular non-selective anti-VEGF therapy," he continued. "Intravitreal injections also carry risks of complications such as endophthalmitis, retinal detachments, and vitreous floaters. COX-2 has numerous roles in inflammation, endothelial cell maintenance, and the VEGF pathway."

In light of those factors, Dr. Grant conducted this study to determine whether adjuvant use of bromfenac, a non-steroidal anti-inflammatory agent, had any effect on the duration of the treatment. The bromfenac was injected 3 to 4 mm posterior to the limbus in the inferotemporal quadrant through the pars plana, he explained.

Sixty patients in this retrospective case control series had received intravitreal injections of ranibizumab to treat CNV membranes with (n = 30) and without (n = 30) combined bromfenac twice daily. The two patient groups were similar in terms of disease, as seen on optical coherence tomography (OCT).

The patients underwent evaluations with fluorescein angiography, OCT, and VA assessment for 6 months. If active leakage was seen on OCT, they received subsequent injections of ranibizumab.

Dr. Grant found that over the 6-month course of the study, more patients who received bromfenac and ranibizumab had increases in VA compared with the patients who were only treated with ranibizumab. Twenty-two patients (71%) who received combination therapy gained one or more lines of vision on the Early Treatment Diabetic Retinopathy Study scale compared with six patients (19%) who were treated with ranibizumab. Ten patients (32%) treated with combination therapy gained three or more lines of vision in 6 months compared with no patients who received monotherapy.

The increases in VA were correlated with a greater reduction in the macular thickness in association with the bromfenac adjunctive treatment. The macular thickness decreased a mean of about 27 μm with combination therapy compared with a mean of about 10 μm with monotherapy.

"The VA changes in logMAR showed a statistically significant difference, with patients on the combination therapy gaining an average of 1.6 lines of vision [0.12 logMAR] versus less than one line for monotherapy alone [0.06 logMAR]," Dr. Grant said. "More surprisingly, these patients gained this VA with fewer mean injections of ranibizumab, 1.6 injections in 6 months versus 4.5 in the monotherapy group (p < 0.0001).

"The data strongly suggested a beneficial adjunctive role for bromfenac in the management of wet AMD and, indeed, possibly to other retinal indications where anti-VEGF therapy is indicated. A well-controlled prospective trial should be performed to confirm these data," he said.

Another noteworthy finding of this study included the fact that bromfenac increased the number of patients who responded to ranibizumab, Dr. Grant said.

Similar unpublished data support the use of bromfenac in combination with bevacizumab (Avastin, Genentech), he said.