Combining photodynamic therapy (PDT) using verteporfin (Visudyne; Novartis, East Hanover, NJ) with intravitreal bevacizumab (Avastin; Genentech, San Francisco) may be useful in treating neovascular age-related macular degeneration (AMD).

We, along with our colleagues from the Barnes Retina Institute in St. Louis and Vitreoretinal Surgery in Edina, Minn., reported in a recent issue of Retina1 that this combination treatment may reduce retreatment rates and improve visual acuity. Previous reports have shown a beneficial effect of PDT with verteporfin combined with triamcinolone for choroidal neovascularization (CNV) secondary to AMD. The average improvement in visual acuity seen with this combination, however, comes with need for frequent injections on regular 4- to 6-week intervals. Retreatment requires frequent follow-up visits and exposes patients to repeated risk of endophthalmitis.

Treatment with bevacizumab, a potent anti-vascular endothelial derived growth factor (VEGF) antibody, may have a beneficial synergistic effect that could reduce the need for retreatment and cyclic injections.

RETROSPECTIVE SERIES
We performed a retrospective series of 24 eyes that had juxtafoveal or subfoveal CNV secondary to AMD (lesion sizes >6 disk areas were excluded); the patients were treated with verteporfin PDT and 1.25 mg intravitreal bevacizumab. We included only patients with 7 months of follow-up; all of the patients included were naïve to treatment and had either treatment within a 14-day interval.

The main measures of outcome were visual acuity and retreatment rates; stabilization of visual acuity was defined as no loss or an improvement in visual acuity. We used a standard Snellen chart to measure visual acuity and converted the values to logMAR in order to calculate means. The need for retreatment was based on the findings of persistent subretinal fluid by ocular coherence tomography or leakage by fluorescein angiography. Retreatments consisted of combined PDT and bevacizumab.

At the 7-month follow-up, 20 of 24 (83%) patients had stabilization of visual acuity. An improvement in visual acuity was seen in 16 (67%) eyes, and the mean improvement in visual acuity was 2.04 Snellen lines. We found that, among all lesion types, 15 eyes required only a single initial combined treatment for CNV resolution (63%).

NO COMPLICATIONS, MEAN IMPROVEMENT
There were no complications of treatment noted in this series, including endophthalmitis, ocular hypertension, uveitis, and nonocular complications.

The mean improvement of 2.04 lines in our series is similar to what has been previously described in newly treated patients who received monthly bevacizumab as monotherapy. Our results appear to be superior, in the short term at least, to those who received PDT alone where patients had an average loss of vision of 2.2 lines (Treatment of Age-Related Macular Degeneration with Photodynamic Therapy2 [TAP]) and 3.1 lines (Verteporfin in Photodynamic Therapy [VIP]3) study.

While the use of adjunctive triamcinolone may limit the gradual decline in vision over the course of therapy, there are drawbacks to using the agent in conjunction with PDT. For example, ocular hypertension, increased susceptibility to infection, and cataract progression are well known complications associated with intraocular steroid use. It is possible that the benefits in visual acuity seen in our series may have been predominantly from intravitreal bevacizumab, but comparative, controlled studies are needed to clarify this.

FEWER TREATMENTS NEEDED?
PDT in combination treatment may play a role in reducing the number and frequency of treatments needed to eradicate CNV. Patients treated with PDT alone in the TAP study required an average of 3.3 retreatments in the first year, and patients treated with anti-VEGF agents often receive intravitreal injections on regular 4- to 6-week intervals. This puts patients at a low, but repeated risk of endophthalmitis. The need for frequent follow-up also puts a significant burden on the health care system. Either treatment, taken separately, seems to require multiple treatments that result in little improvement in visual function, according to long-term studies. Ranibizumab (Lucentis; Genentech), an antibody fragment that inhibits VEGF, has been found to be an effective treatment with visual improvement for exudative AMD, but these patients still required frequent periodic injections.

The use of nonthermal laser in conjunction with VEGF inhibition may be necessary to achieve complete and persistent resolution of CNV. The results of the current study affirm the need for further investigation with larger controlled trial that will outline the appropriate treatment paradigm for approaching neovascular AMD.

Mandeep S. Dhalla, MD, and Gaurav K. Shah, MD, are from the Barnes Retina Institute, and the Department of Ophthalmology, Washington University School of Medicine, St. Louis, Mo. Dr. Shah may be reached at gkshah1@gmail.com.

1. Dhalla MS, Shah GK, Blinder KJ, et al. Combined photodynamic therapy with verteporfin and intravitreal bevacizumab for choroidal neovascularization in age-related macular degeneration. Retina. 2006;26:988-993.
2. Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials—TAP report. Arch Ophthalmol. 1999;117:1329-1345.
3. Verteporfin in Photodynamic Therapy Study Group. Verteporfin therapy for subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesion with occult and no classic choroidal neovascularization—Verteporfin in Photodynamic Therapy report 2. Am J Ophthalmol. 2001;131:541-560.