Photodynamic therapy appears to be a dynamic therapy to many retina researchers, especially when combined with other agents, such as triamcinolone acetonide, to treat choroidal neovascularization (CNV). Numerous presentations at this years ARVO meeting discussed these ongoing studies.
In other research, investigators continue to hone the use of anti-angiogenic agents, and papers on diabetic macular edema report promising results with various applications of Kenalog injections.
Several studies indicate that photodynamic therapy (PDT) in combination with Kenalog (triamcinolone acetonide, Bristol-Myers Squibb) results in a more pronounced reduction in subretinal fluid, better restoration of vision and the need for fewer retreatments when compared with PDT alone.
Researchers in Germany conducted a prospective study of 199 patients with CNV due to age-related macular degeneration (AMD).3567 About 80% of patients had subfoveal lesions, 10% had juxtafoveal lesions and 10% had extrafoveal lesions. Baseline acuity averaged 20/125 but ranged from 20/100 to hand movement. Patients received intravitreal triamcinolone injection 16 hours after PDT. At follow-up (mean 30.5 weeks), patients had an average improvement of 1.14 lines of vision, and required an average of 1.25 treatments to achieve persistent inactivation of CNV. The treatment was well tolerated, although researchers noted transient but controllable increases in IOP.
Researchers at the Cleveland Clinic and four other centers used data from the Visudyne Patient Registry to perform a retrospective analysis of patients treated for CNV due to AMD. Patients received at least one intravitreal triamcinolone injection in conjunction with PDT. At six months, the mean change in visual acuity (VA) from baseline was -8.6 letters (-1.8 lines) in patients who had better VA at baseline (mean 20/100+2), and +10.0 letters (+2.0 lines) in patients who had poorer baseline VA (mean 20/640+2).3568
Anti-VEGF for AMD
Several studies evaluated treatments that target vascular endothelial growth factor (VEGF), which is involved in the early development of CNV in AMD patients:
Retaane (anecortave acetate, Alcon). Open-label studies of two concentrations of anecortave acetate, administered as a periocular posterior juxtascleral depot, enrolled AMD patients who had predominantly classic, mixed or occult classic CNV lesions.1375 About half of all patients received concomitant PDT. All lesion types performed equally well, and as many as 81% of patients maintained vision after one year of treatment. And, when researchers considered reflux, patients had an even more beneficial outcome.
Macugen (pegaptanib sodium injection, Eyetech/Pfizer). This injection remains effective in CNV eyes two years after treatment with a favorable safety profile, according to the VEGF Inhibition Study in Ocular Neovascularization (VISION) Clinical Trial Group.2309 Researchers randomized nearly 1,200 patients with all angiographic subtypes of AMD into two double-masked, sham-controlled, multicenter studies. Patients who received two years of treatment had 67% fewer events of three-line vision loss than patients who received just one year of treatment.
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| Researchers are working on several anti-angiogenic drugssome combined with PDTto treat neovascular AMD. |
Lucentis (ranibizumab, Genentech). After more than one year of extended follow-up, subjects who received intravitreal ranibizumab for subfoveal CNV secondary to AMD had stable VA and stable lesion characteristics, despite a reduced frequency of injections.1393 In this study, researchers increased the initial 0.3mg dose to 0.5mg, and changed the dosing interval from one injection every four weeks to a median rate of 0.22 injections every four weeks. Common adverse events in the study eyes were conjunctival hemorrhage (29% of treated patients), eye pain (11%), blurred vision (11%), iris and uveal tract inflammation (11%), and increased IOP (11%). The ongoing study is testing a less frequent dosing strategy in patients who have neovascular AMD.
Avastin (bevacizumab, Genentech). Bevacizumab is currently FDA approved only for treating patients who have metastatic colorectal cancer. However, researchers from the Bascom Palmer Eye Institute and the University Eye Hospital in Vienna are studying its off-label use as an anti-VEGF agent for patients who have wet AMD.2310 Unlike other ophthalmic anti-VEGF drugs, bevacizumab is administered as a systemic infusion.
After the first dose, investigators noted significant visual acuity improvements in one week. By three months, visual acuity in the study eyes of nine patients increased by a median of eight letters and a mean of 12 letters. In the nine fellow eyes (eight of which were diagnosed with CNV at baseline), acuity increased by a median of 27 letters and a mean of 16 letters.
Diabetes and the Retina
Researchers in Australia reported on intravitreal triamcinolone acetonide injection for diabetic macular edema (DME) that persists or recurs after laser treatment.4672 More than half the treated eyes (eight eyes) gained at least five letters of vision and one-third (five eyes) stayed the same. However, significant adverse events accompanied the treatment, including elevated IOP (64% of treated eyes), significant cataract progression (36% of treated eyes), and one case of infectious endophthalmitis (treated without loss of acuity).
Several studies compared anterior sub-Tenons triamcinolone injection against intravitreal triamcinolone injection. One notable study comes from the National Eye Institute, which found that the anterior sub-Tenons injection had a modest therapeutic effect on DME.1431 NEI researchers performed a retrospective review of nine eyes (eight patients) that had DME and received anterior sub-Tenons injections of 20mg of Kenalog. Six out of nine eyes showed a decrease in retinal thickening, which indicates improvement of DME. Three of those six showed improved visual acuity, and the other three showed stable visual acuity. The researchers conclude that anterior sub-Tenons triamcinolone injection may offer an alternative to intravitreal steroid injection with a different morbidity profile.
Macugen appears to be an emerging new treatment for DME. Researchers conducted a study of 172 patients with DME whose visual acuity ranged from 20/50 to 20/320.4674 Patients were randomized into four groups that each received a different dosage (0.3mg, 1mg, 3mg or sham) of Macugen every six weeks for a 12-week period. Those who received the 0.3mg dose showed better visual acuity, a greater reduction in central retinal thickness and less need for laser therapy.
Dr. Dunbar is director of optometric services at Bascom Palmer Eye Institute in Miami, and author of Review of Optometrys Retina Quiz column.
1375. Hudson HL, Fish GE, Dahlin D, et al. Clinical outcomes of two open-label pharmacokinetic studies with anecortave acetate in patients with exudative age-related macular degeneration (AMD).
1393. Heier JS, Rosenfeld PJ, Antoszyk AN, et al. Long-term experience with Lucentis (ranibizumab) in patients with neovascular age-related macular degeneration (AMD).
1431. Dahr SS, Rosenthal J, Gilmer W, et al. Anterior sub-Tenons triamcinolone acetonide (ASTA) injection for the treatment of diabetic macular edema: 4 to 6 month clinical follow-up.
2309. DAmico DJ, VEGF Inhibition Study in Ocular Neovascularization (VISION) Clinical Trial Group. VEGF Inhibition Study in Ocular Neovascularization (VISION): second year efficacy data.
2310. Rosenfeld PJ, Puliafito CA, Michels S, et al. Systemic bevacizumab (Avastin) therapy for Neovascular Age-Related Macular Degeneration (SANA) Study: visual acuity outcomes.
3567. Augustin AJ, Offermann I, Schmidt-Erfurth U. Verteporfin in combination with intravitreal triamcinolone for CNV due to AMD.
3568. Kaiser PK, Boyer DS, Mittra RA, et al. Verteporfin photodynamic therapy and intravitreal triamcinolone acetate for CNV due to AMD: results from the Visudyne Patient Registry Database.
4672. Gillies MC, Zhu M, Simpson JM, Sutter FK. A randomized, placebo-controlled trial of intravitreal triamcinolone acetonide for diabetic macular edema that persists or recurs after laser treatment 2-year results.
4674. Singerman LJ, Macugen Diabetic Retinopathy Study Group. Findings of the phase 2 trial of the safety and efficacy of pegaptanib sodium (Macugen) in patients with diabetic macular edema.
