Faculty Bibliography

PURPOSE: To examine the 12-month results of a group of patients treated with 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 (newly treated group). Thirteen patients with prior PDT therapy who experienced visual loss while being treated with PDT alone comprised the remainder (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: In the newly treated group, the mean acuity change was an improvement of 2.5 lines (last observation carried forward [LOCF], +2.4 lines; P = 0.011, Wilcoxon signed ranks test, as compared with baseline acuity) for patients completing the 12-month follow-up. In the prior PDT group, the mean change was an improvement of +0.44 lines (LOCF, +0.31 lines; P = 0.53). Retreatment rates were 1.24 for the newly treated group and 1.2 for the prior PDT group over the first year. Ten patients (38.5%) developed an intraocular pressure (IOP) of >24 mmHg during follow-up, a threshold used to institute pressure reduction therapy. No patient developed endophthalmitis. CONCLUSION: Although the number of patients in this pilot study was limited, the improvement of acuity and the reduced treatment frequency in these patients suggest that combination therapy with PDT and intravitreal triamcinolone acetonide, particularly when used as first-line therapy, merits further investigation. Elevated IOP seems to be the most frequent early side effect of the 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 clarify the frequency and nature of ICG angiographic 'hot spots' seen in patients with neovascular age-related macular degeneration (ARMD). METHODS: A consecutive series of newly diagnosed patients with neovascular ARMD and fluorescein angiographic evidence of occult choroidal neovascularization (occult CNV) was imaged with ICG angiography. Eyes with ICG angiographic 'hot spots' were identified and further classified. A hot spot was defined as any area of abnormal hyperfluorescence, in the mid to late stages of ICG angiography, measuring less than 1 disk area in size. RESULTS: From a total of 190 patients (220 eyes) with neovascular ARMD, 30 patients and 34 eyes (16%) with hot spots were identified. Hot spots were noted to be of three distinct patterns: polypoidal choroidal neovascularization (polypoidal CNV) in 21 of 34 eyes, or 62%; retinal angiomatous proliferation (RAP) in 11 of 34 eyes, or 30%; and focal occult CNV in 2 of 34 eyes, or 8%. CONCLUSIONS: A focal area of intense hyperfluorescence or so-called hot spot seen on ICG angiography in neovascular ARMD is due to one of three possible forms of neovascularization: most frequently polypoidal CNV, less commonly RAP, and infrequently nonspecific, focal occult CNV. Since neovascular ARMD may be caused by different types of neovascularization, each with distinct clinical manifestations, natural course, visual prognosis, and response to treatment, it is important to identify the precise nature of hot spots to establish an accurate diagnosis and, when appropriate, a specific form of management

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 study the effects of photodynamic therapy (PDT) using verteporfin on the treatment of patients with subfoveal choroidal neovascularization (CNV) secondary to multifocal choroiditis and panuveitis (MCP), an uncommon disorder with no proven forms of therapy. METHODS: A retrospective chart review of seven consecutive patients with subfoveal CNV secondary to MCP treated with PDT using verteporfin was performed. RESULTS: The mean age of the 7 patients (all myopic women) was 41.4 years. A mean of 1.86 treatments was performed, and the mean follow-up time was 10 months. Four of the seven patients were treated unsuccessfully with corticosteroids before referral for PDT. The mean improvement of visual acuity was 0.86 line; 3 patients (42.8%) had an improvement in visual acuity representing at least a halving of their visual angle, while the other 4 patients remained stable. There were no treatment-related side effects. CONCLUSIONS: Although the follow-up time and the number of patients in this study were limited, the use of PDT was associated with stabilization or improvement of visual acuity in patients with subfoveal CNV secondary to MCP. Further study of this treatment modality is indicated