Faculty Bibliography

PURPOSE: To examine the 12-month results for a group of patients with nonsubfoveal choroidal neovascularization who were treated with combined photodynamic therapy (PDT) with verteporfin and intravitreal triamcinolone acetonide. METHODS: Patients with nonsubfoveal choroidal neovascularization, which was defined as either juxtafoveal or extrafoveal neovascularization, were treated with PDT immediately followed by an intravitreal injection of 4 mg of triamcinolone acetonide. Need for retreatment was based on fluorescein angiographic evidence of leakage at 3-month follow-up intervals. The main outcome measures were visual acuity and the proportion of patients developing subfoveal extension. RESULTS: Of the 15 patients, 9 were women and 6 were men (mean age +/- SD, 80 +/- 7.5 years). The mean baseline visual acuity was almost 20/60 (mean logMAR = 0.46), and 14 of the 15 eyes had juxtafoveal choroidal neovascularization. At 3, 6, and 9 months, the patients had significant improvement in the mean visual acuity (P = 0.002, 0.001, and 0.007, respectively), but at the end of the 12-month follow-up period, the mean visual acuity was slightly worse than 20/40 (mean logMAR = 0.34), which was not statistically significant at an alpha level adjusted for multiple comparisons of .013 (P = .057) as compared with the baseline visual acuity. One patient had subfoveal extension of choroidal neovascularization. The mean number of treatments was 1.9. Three patients (20%) developed an intraocular pressure of >24 mmHg during follow-up, a threshold used to institute pressure reduction therapy. No patient developed endophthalmitis. CONCLUSION: The number of patients in this pilot study was limited; however, the visual acuity response and the low incidence of subfoveal extension suggest that PDT combined with intravitreal triamcinolone for the treatment of nonsubfoveal choroidal neovascularization merits further investigation as a first-line treatment

PURPOSE: We sought to evaluate the detailed safety profile of photodynamic therapy with verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration (ARMD) from the combined analysis of three multicenter, double-masked, placebo-controlled, randomized 24-month clinical trials of similar design (TAP Investigation Studies A and B and the VIP ARMD Trial), and to clarify the adverse reaction information in the current verteporfin product prescription information approved in the United States. METHODS: Nine hundred forty-eight patients were randomly assigned to verteporfin or placebo. Treatment was administered as described in previous reports. All general entry criteria were similar, so systemic safety results were combined for this analysis. Entry criteria for CNV lesion composition and visual acuity in the two TAP Investigation trials was different from those used in the VIP ARMD trial, so ocular safety results for the treated eye were not combined. RESULTS: The percentage of patients who experienced at least one ocular or nonocular adverse event, regardless of relationship to therapy, was similar between the verteporfin and placebo groups (92.3 and 89.1%, respectively, P = 0.114). The overall incidence of study eye adverse events was not significantly different between verteporfin and placebo. The only clinically relevant ocular adverse events reported with higher incidence after verteporfin compared with placebo were visual disturbances (22.1 versus 15.5% in TAP [P = 0.054] and 41.7 and 22.8% in VIP [P < 0.001]). Acute severe visual acuity decrease (defined as a visual acuity letter score decrease of at least 20, equivalent to at least four-line decrease, within 7 days of therapy) occurred in 3 patients treated with verteporfin in the TAP Investigation (0.7%) and 11 in the VIP ARMD trial (4.9%). Systemic adverse events with increased incidence after verteporfin compared with placebo, most of which were transient and mild or moderate, were injection site reactions (13.1 versus 5.6%; P < 0.001), photosensitivity reactions (2.4 versus 0.3%; P = 0.016), and infusion-related back pain (2.4 versus 0%; P = 0.004). No clinically relevant difference was observed between the verteporfin and placebo groups in any other adverse event. CONCLUSION: In 948 ARMD patients, verteporfin therapy had an overall safety profile similar to that for placebo, with a few exceptions. Visual disturbances, including acute severe visual acuity decrease, did not affect the net vision outcome benefits associated with treatment that has been reported previously. This detailed safety profile of verteporfin therapy clarifies the adverse reaction information in the current verteporfin product prescription information

PURPOSE: To examine combined photodynamic therapy (PDT) with verteporfin and intravitreal triamcinolone acetonide for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). DESIGN: Noncomparative case series. PARTICIPANTS: Twenty-six eyes of 26 patients with CNV secondary to AMD. Thirteen with CNV, without restriction to type, were not treated with prior PDT and were called the Newly Treated group. Thirteen patients with prior PDT therapy who experienced visual loss during treatment with PDT alone comprised the remainder and were termed the Prior PDT group. METHODS: Patients with CNV were treated with PDT immediately followed by an intravitreal injection of 4 mg of triamcinolone acetonide. Visual acuity was measured by Early Treatment Diabetic Retinopathy Study protocol refraction. Need for retreatment was based on fluorescein angiographic evidence of leakage at 3-month follow-up intervals. MAIN OUTCOME MEASURES: Visual acuity and retreatment rate. RESULTS: Of the 13 patients in the Newly Treated group the mean visual acuity change at 3 months was an improvement of 1.9 lines, and 4 (30.8%) had an improvement of at least 3 lines. Two patients (15.4%) required retreatment at 3 months. At the 6-month follow-up, available for 12 patients in the Newly Treated group, the mean visual acuity change from baseline was an improvement of 2.4 lines, 4 patients (33%) had an improvement of at least 3 lines and 1 patient required retreatment. At both time points the visual acuity was significantly greater than at baseline (P = 0.023 and P = 0.007, at the 3-month and 6-month time points, Wilcoxon signed ranks test) for patients in the Newly Treated group. Among the 13 patients in the Prior PDT group, the mean change in visual acuity from baseline at the 3-month follow-up was 0.31 lines and 1 patient (7.7%) had an improvement of at least 3 lines. Six-month follow-up was available for 11 patients in the Prior PDT group and the mean change from baseline visual acuity was 0.1 lines and 1 patient (9.1%) experienced an improvement of 3 or more lines. No patient in the Prior PDT group required retreatment at 3 or 6 months. At the 3-month and 6-month time points the visual acuity was not significantly different than the baseline acuity in the Prior PDT group. No patient in either group at any time point experienced a loss of visual acuity of 3 or more lines. Five patients (19.2%), 3 in the Newly Treated group and 2 in the Prior PDT group, required monodrop therapy to control their intraocular pressure. No patient developed endophthalmitis. CONCLUSION: Although the number of patients in this pilot study was limited, the improvement of acuity and the lack of fluorescein leakage in these patients suggest combination therapy with PDT and intravitreal triamcinolone acetonide, particularly when used as first-line therapy, merits further investigation

PURPOSE: To study the effects of photodynamic therapy using verteporfin in the treatment of patients with subfoveal polypoidal choroidal vasculopathy (PCV). METHODS: A retrospective chart review of 16 consecutive patients with subfoveal PCV treated with photodynamic therapy using verteporfin was performed. RESULTS: The mean age of the patients involved was 70.5 years. The mean follow-up time was 12 months. The visual acuity improved in 9 (56.3 %), remained the same in 5 (31.3 %), and decreased in 2 (12.5 %). The mean change in visual acuity was an improvement of 2.38 lines, a difference that was highly significant ( = 0.004). The change in visual acuity was negatively correlated with increasing age. The final visual acuity was positively correlated with initial acuity and negatively correlated with age. These results were confirmed by multiple linear regression. No patient had any lasting complication from the treatment. CONCLUSIONS: Subfoveal PCV has no proven method of treatment. Although the follow-up time and the number of patients in this pilot study were limited, the encouraging results and lack of complications suggest that further study is indicated

PURPOSE: To report the effects of photodynamic therapy using verteporfin in the treatment of patients with subfoveal idiopathic choroidal vascularization (CNV). DESIGN: Interventional case series. METHODS: In a retrospective study, eight eyes of eight consecutive patients aged 55 years or younger with subfoveal idiopathic CNV treated with photodynamic therapy using verteporfin were evaluated. Visual acuity was considered to be improved if the visual angle was halved, while acuity was thought to be worse if the visual angle doubled. RESULTS: The eight patients included three men and five women with a mean (+/- SD) age of 34.6 (+/- 9.7) years (range 25-53 years). The mean follow-up time was 13.5 months. At the end of the follow-up period the visual acuity improved in five eyes (62.5%), remained unchanged in one (12.5%), and decreased in two (25%). The mean acuity improvement was 3.6 lines of Snellen acuity by the end of the follow-up period, a change that was statistically significant (P =.027, Wilcoxon signed-rank test). No patient had any complication from the treatment. CONCLUSIONS: There is no widely accepted method for treating subfoveal idiopathic CNV and all previously investigated methods have had a significant number of serious side effects. Although the follow-up time and the number of patients in this pilot study were limited, the encouraging results and lack of complications suggest that further study is indicated

PURPOSE: To determine if oral hydration decreases the incidence of verteporfin infusion-associated pain and to find out if other factors play a role in predisposing to this undesired complication. METHODS: Nonrandomized clinical trial. We prospectively examined 250 consecutive patients who have been diagnosed with subfoveal choroidal neovascularization secondary to age-related macular degeneration and received photodynamic therapy using verteporfin. One hundred twenty-five patients were assigned to receive 500 ml of water orally administered 30 minutes before beginning the verteporfin infusion, and the remaining 125 consecutive patients were used as controls. Historical and clinical factors in these patients were evaluated for their association with the presence of verteporfin infusion-associated pain. RESULTS: Out of 125 patients receiving water before treatment 12 (9.6%) experienced verteporfin infusion-associated pain. Among the 125 patients who did not get hydration before therapy 12(9.6%) experienced verteporfin infusion-associated pain. There was no statistical difference between the incidence of pain in the two groups (P = 1.0). No statistically significant association was evidenced between the presence of pain and participant's baseline characteristics, except for pain on previous administration of verteporfin (P < .001). Out of 250 total patients 24 (9.6%) developed verteporfin infusion-associated pain. Back pain was the most common and occurred in 21 (8.4%) patients, but other sites included leg, groin, chest, buttock, arm, and shoulder pain concurrently or independently. All patients had resolution of their pain, including chest pain, on cessation of the infusion. CONCLUSIONS: Verteporfin infusion-associated pain may be more common than has been previously reported and is not limited to the back area. It appears to be an idiosyncratic reaction to the drug. It does not seem to be prevented by oral hydration before infusion of verteporfin, and no baseline characteristics, other than a history of pain on previous infusion, seem to be predictive of verteporfin infusion-associated pain