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At least 19 recordsLinked to original sources
PubMed2001

Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization--verteporfin in photodynamic therapy report 2.

PURPOSE: To determine if photodynamic therapy with verteporfin (Visudyne; Novartis AG, Bülach, Switzerland), termed verteporfin therapy, can safely reduce the risk of vision loss compared with a placebo (with sham treatment) in patients with subfoveal choroidal neovascularization caused by age-related macular degeneration who were identified with a lesion composed of occult with no classic choroidal neovascularization, or with presumed early onset classic choroidal neovascularization with good visual acuity letter score. METHODS: This was a double-masked, placebo-controlled (sham treatment), randomized, multicenter clinical trial involving 28 ophthalmology practices in Europe and North America. The study population was patients with age-related macular degeneration, with subfoveal choroidal neovascularization lesions measuring no greater than 5400 microm in greatest linear dimension with either 1) occult with no classic choroidal neovascularization, best-corrected visual acuity score of at least 50 (Snellen equivalent approximately 20/100), and evidence of hemorrhage or recent disease progression; or 2) evidence of classic choroidal neovascularization with a best-corrected visual acuity score of at least 70 (better than a Snellen equivalent of approximately 20/40); assigned randomly (2:1) to verteporfin therapy or placebo therapy. Verteporfin (6 mg per square meter of body surface area) or placebo (5% dextrose in water) was administered by means of intravenous infusion of 30 ml over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm delivered 50 J/cm(2) by application of an intensity of 600 mW/cm(2) over 83 seconds using a spot size with a diameter 1000 microm larger than the greatest linear dimension of the choroidal neovascularization lesion on the retina. At follow-up examinations every 3 months, retreatment with the same regimen was applied if angiography showed fluorescein leakage. The main outcome measure was at least moderate vision loss, that is, a loss of at least 15 letters (approximately 3 lines), adhering to an intent-to-treat analysis with the last observation carried forward to impute for missing data. RESULTS: Two hundred ten (93%) and 193 (86%) of the 225 patients in the verteporfin group compared with 104 (91%) and 99 (87%) of the 114 patients in the placebo group completed the month 12 and 24 examinations, respectively. On average, verteporfin-treated patients received five treatments over the 24 months of follow-up. The primary outcome was similar for the verteporfin-treated and the placebo-treated eyes through the month 12 examination, although a number of secondary visual and angiographic outcomes significantly favored the verteporfin-treated group. Between the month 12 and 24 examinations, the treatment benefit grew so that by the month 24 examination, the verteporfin-treated eyes were less likely to have moderate or severe vision loss. Of the 225 verteporfin-treated patients, 121 (54%) compared with 76 (67%) of 114 placebo-treated patients lost at least 15 letters (P =.023). Likewise, 67 of the verteporfin-treated patients (30%) compared with 54 of the placebo-treated patients (47%) lost at least 30 letters (P =.001). Statistically significant results favoring verteporfin therapy at the month 24 examination were consistent between the total population and the subgroup of patients with a baseline lesion composition identified as occult choroidal neovascularization with no classic choroidal neovascularization. This subgroup included 166 of the 225 verteporfin-treated patients (74%) and 92 of the 114 placebo-treated patients (81%). In these patients, 91 of the verteporfin-treated group (55%) compared with 63 of the placebo-treated group (68%) lost at least 15 letters (P =.032), whereas 48 of the verteporfin-treated group (29%) and 43 of the placebo-treated group (47%) lost at least 30 letters (P =.004). Other secondary outcomes, including visual acuity letter score worse than 34 (approximate Snellen equivalent of 20/200 or worse), mean change in visual acuity letter score, development of classic choroidal neovascularization, progression of classic choroidal neovascularization and size of lesion, favored the verteporfin-treated group at both the month 12 and month 24 examination for both the entire study group and the subgroup of cases with occult with no classic choroidal neovascularization at baseline. Subgroup analyses of lesions composed of occult with no classic choroidal neovascularization at baseline suggested that the treatment benefit was greater for patients with either smaller lesions (4 disc areas or less) or lower levels of visual acuity (letter score less than 65, an approximate Snellen equivalent of 20/50(-1) or worse) at baseline. Prospectively planned multivariable analyses confirmed that these two baseline variables affected the magnitude of treatment benefit. (ABSTRACT TRUNCATED)

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PubMed2004

Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: meta-analysis of 2-year safety results in three randomized clinical trials: Treatment Of Age-Related Macular Degeneration With Photodynamic Therapy and Verteporfin In Photodynamic Therapy Study Report no. 4.

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.

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PubMed2004

Selective photodynamic therapy by targeted verteporfin delivery to experimental choroidal neovascularization mediated by a homing peptide to vascular endothelial growth factor receptor-2.

OBJECTIVE: To evaluate the feasibility, efficacy, and selectivity of photodynamic therapy (PDT) using targeted delivery of verteporfin to choroidal neovascularization (CNV) in the rat laser-injury model of CNV. METHODS: We performed PDT in rat eyes on experimental CNV and normal retina and choroid using verteporfin conjugates. A targeted verteporfin conjugate was made by conjugating verteporfin (after isolation from its liposomal formulation) to a modified polyvinyl alcohol (PVA) polymer (verteporfin-PVA) followed by linkage to the peptide ATWLPPR known to bind the receptor for vascular endothelial growth factor, VEGFR2. The verteporfin-PVA conjugate served as a control. We performed fluorescent fundus angiography to determine the optimal timing of light application for PDT using the conjugates. Closure of CNV was assessed angiographically and graded in a masked standardized fashion. We used standardized histological grading to compare the effects on normal retina and choroid. RESULTS: The verteporfin-PVA conjugation ratio was on average 28:1. The conjugate retained typical emission/excitation spectra and photosensitizing activity and was as efficient as an equivalent amount of verteporfin. Peak intensity of targeted verteporfin in CNV was detected angiographically at 1 hour after intravenous injection. Photodynamic therapy using targeted verteporfin (3 or 4.5 mg/m2) with light application 1 hour after drug injection showed angiographic closure of all treated CNV (17/17) 1 day after treatment. Photodynamic therapy using verteporfin-PVA at the same drug dose achieved closure in 18 of 20 CNV. Histological examination after PDT of normal retina and choroid using targeted verteporfin and irradiation at 1 hour showed minimal effect on retinal pigment epithelium and no injury to photoreceptors, whereas PDT using verteporfin-PVA resulted in retinal pigment epithelium necrosis and mild damage to photoreceptors. CONCLUSIONS: Verteporfin bound to the targeting peptide, ATWLPPR, retained its spectral and photosensitizing properties. Angiography demonstrated localization of the targeted verteporfin 1 hour after injection. Photodynamic therapy using targeted verteporfin and the control conjugate were more effective in causing CNV closure than standard liposomal verteporfin. The targeted verteporfin resulted in more selective treatment than the control conjugate or standard verteporfin. These results suggest that targeted PDT strategies based on selective expression of receptors on CNV vasculature may improve current therapy. CLINICAL RELEVANCE: Targeted PDT for CNV is feasible and may offer a qualitative improvement in current treatments for patients with age-related macular degeneration. This study provides the basis for further preclinical studies of targeted PDT strategies and subsequent clinical trials.

Animals↗
PubMed2002

Verteporfin therapy for subfoveal choroidal neovascularization in age-related macular degeneration: three-year results of an open-label extension of 2 randomized clinical trials--TAP Report no. 5.

OBJECTIVE: To report vision and safety outcomes from an extension of a 2-year investigation evaluating verteporfin photodynamic therapy in patients with age-related macular degeneration with subfoveal choroidal neovascularization (CNV). DESIGN AND SETTING: Open-label extension of selected patients from 2 multicenter, double-masked, placebo-controlled, randomized clinical trials, the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) Investigation, at 22 ophthalmology practices in Europe and North America. PARTICIPANTS: Patients enrolled in the TAP Investigation and followed up for at least 24 months in whom verteporfin therapy to CNV might reduce the risk of further vision loss. METHODS: Before receiving verteporfin therapy in the extension, eligible patients signed a written informed consent form accompanied by an oral consent process approved by local institutional review boards. Methods were similar to those described for 1- and 2-year results, with follow-up examinations beyond 2 years continuing at 3-month intervals with a few exceptions, including that extension patients with fluorescein leakage from CNV were to receive open-label verteporfin therapy irrespective of their original treatment assignment. RESULTS: Of 402 patients in the verteporfin group, 351 (87.3%) completed the month 24 examination; 320 (91.2%) of these enrolled in the extension study. The enrolled participants included 124 (78.0%) of the 159 verteporfin-treated patients with lesions composed of predominantly classic CNV at baseline, of whom 105 (84.7%) completed the month 36 examination. Verteporfin-treated patients with this lesion composition at baseline who participated in the extension study, with or without a month 36 examination, appeared more likely to have a younger age, better level of visual acuity, absence of fluorescein leakage from classic CNV, or no progression of classic CNV beyond the baseline boundaries of the lesion at the month 24 examination compared with those who did not enroll in the extension. For the 105 patients with a predominantly classic baseline lesion composition who completed the month 36 examination, an average of 1.3 treatments were given from the month 24 examination up to, but not including, the month 36 examination. A letter score loss in the study eye of at least 15 from baseline for these patients occurred in 39 (37.5%) at the month 24 examination compared with 44 (41.9%) of these patients at the month 36 examination. Visual acuity changed little from the month 24 examination (mean, -1.9 lines) to the month 36 examination (mean, -2.0 lines) for these eyes. Verteporfin-treated patients had little change in the mean visual acuity lost and few or no additional instances of infusion-related back pain or photosensitivity reactions from month 24 to month 36. Two patients originally assigned to placebo had acute severe vision decrease within 7 days after verteporfin treatment during the extension. One patient originally assigned to verteporfin had acute severe vision decrease after verteporfin treatment of the fellow eye during the extension. CONCLUSIONS: Vision outcomes for verteporfin-treated patients with predominantly classic lesions at baseline remained relatively stable from month 24 to month 36, although only approximately one third of the verteporfin-treated patients originally enrolled with this lesion composition had a month 36 examination. From these results, the TAP Study Group identified no safety concerns to preclude repeating photodynamic therapy with verteporfin. Additional treatment was judged likely to reduce the risk of further vision loss. Caution appears warranted in the absence of comparison with an untreated group during the extension and since not all patients in the TAP Investigation participated in the TAP Extension.

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PubMed2003

Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia: 2-year results of a randomized clinical trial--VIP report no. 3.

PURPOSE: To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia. DESIGN AND SETTING: Multicenter, double-masked, placebo-controlled, randomized clinical trial at 28 ophthalmology practices in Europe and North America. PARTICIPANTS: Patients with subfoveal choroidal neovascular lesions caused by pathologic myopia measuring no more than 5400 micro m and best-corrected visual acuity (approximate Snellen equivalent) of 20/100 or better. METHODS: Similar to methods described for 1-year results with follow-up examinations beyond 1 year, continuing every 3 months (except Photograph Reading Center evaluations only at the month 24 examination). During the second year, the same regimen (with verteporfin or placebo as applied at baseline) was used if angiography showed fluorescein leakage from CNV. MAIN OUTCOME MEASURES: The primary outcome was the proportion of eyes with fewer than 8 letters (approximately 1.5 lines) of visual acuity loss at the month 24 examination, adhering to an intent-to-treat analysis and using the last observation carried forward method to impute for any missing data. RESULTS: Seventy-seven of 81 patients (95%) in the verteporfin group, compared with 36 of 39 patients (92%) in the placebo group, completed the month 24 examination. At this time point, 29 of 81 verteporfin-treated patients (36%) compared with 20 of 39 placebo-treated patients (51%) lost at least 8 letters (P = 0.11). The distribution of change in visual acuity at the month 24 examination was in favor of a benefit for the cases assigned to verteporfin (P = 0.05). This included improvement by at least 5 letters (equivalent to at least 1 line) in 32 verteporfin-treated cases [40%] vs. five placebo-treated cases (13%) and improvement by at least 15 letters (equivalent to at least 3 lines) in 10 verteporfin-treated cases (12%) vs. zero placebo-treated cases. No additional photosensitivity adverse reactions or injection site adverse events were associated with verteporfin therapy in the second year of follow-up. CONCLUSIONS: Verteporfin therapy for subfoveal CNV caused by pathologic myopia safely maintained a visual benefit compared with a placebo therapy through 2 years of follow-up. Although the primary outcome was not statistically significantly in favor of verteporfin therapy at 2 years as it had been at 1 year of follow-up, the distribution of change in visual acuity at the month 24 examination was in favor of the verteporfin-treated group and showed that this group was more likely to have improved visual acuity through the month 24 examination. The VIP Study Group recommends verteporfin therapy for subfoveal CNV resulting from pathologic myopia based on both the 1- and 2-year results of this randomized clinical trial.

Adult↗
PubMed2002

Verteporfin photodynamic therapy in the rat model of choroidal neovascularization: angiographic and histologic characterization.

PURPOSE: To develop a model of verteporfin photodynamic therapy (PDT) for experimental choroidal neovascularization CNV in the rat. METHODS: A laser injury model was used to induce experimental CNV in rats. The transit and accumulation of the photosensitizer verteporfin was assessed angiographically in CNV lesions, to determine the optimal time for delivery of light energy. The CNV lesions were then treated with verteporfin PDT, with two doses of verteporfin (3.0 and 6.0 mg/m(2)) and four activating doses of light energy (10, 25, 50, and 100 J/cm(2)). Closure of the CNV was assessed both angiographically and histologically. Verteporfin PDT was also performed on areas of normal choroid and retina at the two verteporfin doses and four light energy doses. The effect of these treatments on these structures was also assessed angiographically and histologically. RESULTS: Peak verteporfin intensities in the CNV were detected at 15 to 20 minutes after intravenous injection. Rates of closure of the CNV varied as a function of the dose of verteporfin and of the activating light energy. Angiographic closure of the CNV correlated with damage to the neovascular complex, as seen with light and electron microscopy. Damage to areas of normal choroid and retina treated with verteporfin PDT also varied as a function of the verteporfin and light energy doses. CONCLUSIONS: Verteporfin PDT for experimental CNV in the rat is a feasible, effective, and reproducible model that can be used for testing the efficacy of adjunctive therapy to verteporfin PDT.

Animals↗
PubMed2001

Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin. 1-year results of a randomized clinical trial--VIP report no. 1.

OBJECTIVE: To determine if photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, GA) can improve the chance of stabilizing or improving vision (<8 letter loss) safely in patients with subfoveal choroidal neovascularization (CNV) caused by pathologic myopia. DESIGN: Multicenter, double-masked, placebo-controlled, randomized clinical trial at 28 ophthalmology practices in Europe and North AMERICA: PARTICIPANTS: One hundred twenty patients with subfoveal CNV caused by pathologic myopia with a greatest linear dimension no more than 5400 microM and best-corrected visual acuity (Snellen equivalent) of approximately 20/100 or better. INTERVENTION: Patients were randomly assigned (2:1) to verteporfin (6 mg per square meter of body surface area; n = 81) or placebo (5% dextrose in water; n = 39) administered via intravenous infusion of 30 ml over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm was delivered at an intensity of 600 mW/cm(2) over 83 seconds to give a light dose of 50 J/cm(2) to a round spot size on the retina with a diameter of 1000, microM larger than the greatest linear dimension of the choroidal neovascular lesion. At follow-up examinations every 3 months, retreatment with either verteporfin or placebo (as assigned at baseline) was applied to areas of fluorescein leakage if present. MAIN OUTCOME MEASURES: The primary outcome was the proportion of eyes at the follow-up examination 12 months after study entry with fewer than eight letters (approximately 1.5 lines) of visual acuity lost, adhering to an intent-to-treat analysis. RESULTS: At baseline, more than 90% of each group had evidence of classic CNV (regardless of whether occult CNV was present) and only 12 (15%) and 5 (13%) cases in the verteporfin and placebo groups, respectively, had occult CNV (regardless of whether classic CNV was present). Seventy-nine of the 81 verteporfin-treated patients (98%) compared with 36 of the 39 placebo-treated patients (92%) completed the month 12 examination. Visual acuity, contrast sensitivity, and fluorescein angiographic outcomes were better in the verteporfin-treated eyes than in the placebo-treated eyes at every follow-up examination through the month 12 examination. At the month 12 examination, 58 (72%) of the verteporfin-treated patients compared with 17 (44%) of the placebo-treated patients lost fewer than eight letters (P < 0.01), including 26 (32%) versus 6 (15%) improving at least five letters (>/=1 line). Seventy (86%) of the verteporfin-treated patients compared with 26 (67%) of the placebo-treated patients lost fewer than 15 letters (P = 0.01). Few ocular or other systemic adverse events were associated with verteporfin therapy compared with placebo treatment. CONCLUSIONS: Because photodynamic therapy with verteporfin can safely increase the chance of stabilizing or improving vision in patients with subfoveal CNV from pathologic myopia compared with a placebo, we recommend ophthalmologists consider verteporfin therapy for treatment of such patients.

Adult↗
PubMed2002

Verteporfin infusion-associated pain.

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.

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PubMed2004

Spotlight on verteporfin in subfoveal choroidal neovascularisation.

UNLABELLED: Verteporfin (Visudyne) therapy (photodynamic therapy with intravenous liposomal verteporfin) is the first treatment to effectively prevent the loss of visual acuity in patients with subfoveal choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD), pathological myopia or presumed ocular histoplasmosis syndrome (POHS). In adult patients with classic subfoveal CNV or occult with no classic subfoveal CNV secondary to AMD, or subfoveal CNV secondary to pathological myopia or POHS, verteporfin therapy slows or prevents loss of visual acuity. In well designed clinical trials, verteporfin therapy was superior to placebo in patients with subfoveal classic-containing CNV and occult with no classic CNV secondary to AMD at 12 and/or 24 months (Treatment of Age-related macular degeneration with Photodynamic therapy [TAP] Investigation and Verteporfin In Photodynamic therapy [VIP-AMD] trial) and in patients with pathological myopia at 12 months (Verteporfin In Photodynamic therapy [VIP-PM] trial). Limited data suggest that verteporfin therapy also prevents loss of visual acuity in patients with subfoveal CNV secondary to POHS. Verteporfin therapy was generally well tolerated in clinical trials; most adverse events were mild to moderate in intensity and transient. The most frequently reported verteporfin therapy-related adverse events (incidence >2%) were visual disturbance, injection-site reactions, photosensitivity reactions and infusion-related back pain. Approximately 5% of patients with occult with no classic subfoveal CNV secondary to AMD reported severe vision decrease within 7 days of treatment in clinical trials; 3 months later, several patients had recovered some of this loss. CONCLUSION: Photodynamic therapy with verteporfin, the first photosensitiser approved for the treatment of subfoveal CNV, is a well tolerated treatment that stabilises or slows visual acuity loss in adult patients with predominantly classic or occult with no classic subfoveal CNV secondary to AMD, and subfoveal CNV secondary to pathological myopia or POHS. Thus, verteporfin therapy provides a valuable option for the management of these patients for whom treatment options are few, and should be considered as a first-line therapy in these difficult-to-manage conditions.

Adult↗
PubMed2003

Verteporfin : a review of its use in the management of subfoveal choroidal neovascularisation.

UNLABELLED: Verteporfin (Visudyne) therapy (photodynamic therapy with intravenous liposomal verteporfin) is the first treatment to effectively prevent the loss of visual acuity in patients with subfoveal choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD), pathological myopia or presumed ocular histoplasmosis syndrome (POHS). In adult patients with classic subfoveal CNV or occult with no classic subfoveal CNV secondary to AMD, or subfoveal CNV secondary to pathological myopia or POHS, verteporfin therapy slows or prevents loss of visual acuity. In well designed clinical trials, verteporfin therapy was superior to placebo in patients with subfoveal classic-containing CNV and occult with no classic CNV secondary to AMD at 12 and/or 24 months (Treatment of Age-related macular degeneration with Photodynamic therapy [TAP] Investigation and Verteporfin In Photodynamic therapy [VIP-AMD] trial) and in patients with pathological myopia at 12 months (Verteporfin In Photodynamic therapy [VIP-PM] trial). Limited data suggest that verteporfin therapy also prevents loss of visual acuity in patients with subfoveal CNV secondary to POHS. Verteporfin therapy was generally well tolerated in clinical trials; most adverse events were mild to moderate in intensity and transient. The most frequently reported verteporfin therapy-related adverse events (incidence >2%) were visual disturbance, injection-site reactions, photosensitivity reactions and infusion-related back pain. Approximately 5% of patients with occult with no classic subfoveal CNV secondary to AMD reported severe vision decrease within 7 days of treatment in clinical trials; 3 months later, several patients had recovered some of this loss. CONCLUSION: Photodynamic therapy with verteporfin, the first photosensitiser approved for the treatment of subfoveal CNV, is a well tolerated treatment that stabilises or slows visual acuity loss in adult patients with predominantly classic or occult with no classic subfoveal CNV secondary to AMD, and subfoveal CNV secondary to pathological myopia or POHS. Thus, verteporfin therapy provides a valuable option for the management of these patients for whom treatment options are few, and should be considered as a first-line therapy in these difficult-to-manage conditions.

Adult↗
PubMed2004

Verteporfin therapy in age-related macular degeneration (VAM): an open-label multicenter photodynamic therapy study of 4,435 patients.

PURPOSE: To provide broad clinical experience and to gather safety data on photodynamic therapy with verteporfin (Visudyne, Novartis AG, Basel, Switzerland), also termed verteporfin therapy, in patients with predominantly classic subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The Verteporfin in Age-related Macular Degeneration (VAM) Study was designed to provide expanded access to verteporfin therapy after beneficial results for these cases were reported but before regulatory approval in North America. METHODS: This open-label multicenter study from September 1999 through June 2000 enrolled among 222 centers patients 50 years or older in the United States, or 40 years or older in Canada, with age-related macular degeneration and subfoveal CNV with a lesion composition that was predominantly classic CNV on fluorescein angiography. Corrected visual acuity with habitual eyewear in the office setting was 20/40 to 20/200, inclusive. All patients received verteporfin therapy and returned for follow-up every 3 months. At those follow-up examinations, additional courses of treatment were recommended if any fluorescein leakage from CNV was identified. Safety information was collected from patient self-reporting, questioning (in person and by telephone), and physician evaluation. Safety was assessed by evaluating the effect of treatment on corrected distance visual acuity and by evaluating adverse events. RESULTS: A total of 4,435 patients were enrolled of whom 4,051 (91%) completed the study after receiving 6,701 treatments. Most patients received only one treatment in VAM before regulatory approval of verteporfin in the United States and Canada. Three hundred patients (6.8%) experienced an adverse event considered by the treating ophthalmologist to be associated with treatment, including 115 (2.6%) with abnormal or decreased vision, of whom 25 (0.6%) experienced acute severe visual acuity decrease, and 14 (0.3%) with transient infusion-related back pain. Patients were advised to avoid exposure to direct sunlight for 24 hours; however, after verteporfin administration only 2 (0.05%) reported a photosensitivity reaction. An additional course of verteporfin therapy was administered to 1,739 of 2,314 patients (75.2%) who had a month 3 examination that was not their close-out visit and 177 of 266 (66.5%) who had a month 6 examination that was not their close-out visit. CONCLUSIONS: Verteporfin therapy exhibited no additional or new safety concerns. The therapy associated with a low incidence of adverse events when expanded access was provided in a large, open-label, multicenter study, including a low incidence (0.05%) of reported photosensitivity reactions despite a short photosensitivity protection period (24 hours) following verteporfin administration.

Adult↗
PubMed2001

Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials-tap report 2.

OBJECTIVE: To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, Ga) in patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration (AMD). DESIGN: Two multicenter, double-masked, placebo-controlled, randomized clinical trials. SETTING: Twenty-two ophthalmology practices in Europe and North America. PARTICIPANTS: Patients with subfoveal CNV lesions caused by AMD with greatest linear dimension on the retina measuring 5400 micrometer or less, with evidence of classic CNV and best-corrected visual acuity (approximate Snellen equivalent) between 20/40 and 20/200. METHODS: The methods were similar to those described in our 1-year results, with follow-up examinations beyond 1 year continuing every 3 months (except for Photograph Reading Center evaluations, which occurred only at month 18 and month 24 examinations). During the second year, the same regimen (with verteporfin or placebo as applied at baseline) was used if angiography showed fluorescein leakage from CNV. The primary outcome was the proportion of eyes with fewer than 15 letters (approximately 3 lines) of visual acuity loss at the month 24 examination, adhering to an intent-to-treat analysis. The last observation was carried forward to impute for any missing data. RESULTS: Three hundred fifty-one (87%) of 402 patients in the verteporfin group compared with 178 (86%) of 207 patients in the placebo group completed the month 24 examination. Beneficial outcomes with respect to visual acuity and contrast sensitivity noted at the month 12 examination in verteporfin-treated patients were sustained through the month 24 examination. At the month 24 examination for the primary outcome, 213 (53%) of 402 verteporfin-treated patients compared with 78 (38%) of 207 placebo-treated patients lost fewer than 15 letters (P<.001). In subgroup analyses for predominantly classic lesions (in which the area of classic CNV makes up at least 50% of the area of the entire lesion) at baseline, 94 (59%) of 159 verteporfin-treated patients compared with 26 (31%) of 83 placebo-treated patients lost fewer than 15 letters at the month 24 examination (P<.001). For minimally classic lesions (in which the area of classic CNV makes up <50% but >0% of the area of the entire lesion) at baseline, no statistically significant differences in visual acuity were noted. Few additional photosensitivity adverse reactions and injection site adverse events were associated with verteporfin therapy in the second year of follow-up. CONCLUSIONS: The visual acuity benefits of verteporfin therapy for AMD patients with predominantly classic CNV subfoveal lesions are safely sustained for 2 years, providing more compelling evidence to use verteporfin therapy for these cases. For AMD patients with subfoveal lesions that are minimally classic, there is insufficient evidence to warrant routine use of verteporfin therapy.

Aged↗
PubMed2002

Effects of verteporfin therapy on contrast on sensitivity: Results From the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) investigation-TAP report No 4.

BACKGROUND: In the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy (TAP) investigation, verteporfin therapy reduced the risk of at least moderate vision loss (defined as a loss of at least 15 letters of visual acuity) in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (ARMD). This report presents detailed analyses of 24-month contrast sensitivity outcomes in these patients. METHODS: The patients included in the TAP investigation had subfoveal CNV secondary to ARMD and received verteporfin therapy (n = 402) or placebo (n = 207) at the first visit, with retreatment at each 3-month follow-up visit if angiography revealed fluorescein leakage from CNV. Contrast sensitivity was determined at each visit using a Pelli-Robson chart. RESULTS: At the month 24 examination, verteporfin-treated patients were less likely to lose at least 6 or 15 letters of contrast sensitivity than placebo-treated patients (86 [21%] versus 94 [45%], and 27 [7%] versus 24 [12%], respectively; P < 0.05 for both comparisons). The superiority of verteporfin therapy over placebo was greater in patients with predominantly classic CNV at baseline, although verteporfin-treated patients with minimally classic CNV also had better contrast sensitivity outcomes. CONCLUSIONS: Consistent with visual acuity outcomes, verteporfin therapy reduced the risk of a clinically relevant loss of contrast sensitivity in the total study population, with the greatest effect in patients with predominantly classic subfoveal CNV secondary to ARMD. Verteporfin-treated patients with minimally classic CNV also had better contrast sensitivity outcomes than patients who received placebo. Given the association between contrast sensitivity and visual disability, the beneficial effects of verteporfin therapy on contrast sensitivity outcomes are expected to have a favorable impact on patients' daily activities.

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PubMed1999

Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials--TAP report. Treatment of age-related macular degeneration with photodynamic therapy (TAP) Study Group.

OBJECTIVE: To determine if photodynamic therapy with verteporfin (Visudyne; CIBA Vision Corp, Duluth, Ga) can safely reduce the risk of vision loss in patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration (AMD). DESIGN: Two multicenter, double-masked, placebo-controlled, randomized clinical trials. SETTING: Twenty-two ophthalmology practices in Europe and North America. PARTICIPANTS: Patients with subfoveal CNV lesions caused by AMD measuring 5400 microm or less in greatest linear dimension with evidence of classic CNV and best-corrected visual acuity of approximately 20/40 to 20/200. METHODS: Six hundred nine patients were randomly assigned (2: 1) to verteporfin (6 mg per square meter of body surface area) or placebo (5% dextrose in water) administered via intravenous infusion of 30 mL over 10 minutes. Fifteen minutes after the start of the infusion, a laser light at 689 nm delivered 50J/cm2 at an intensity of 600 mW/cm2 over 83 seconds using a spot size with a diameter 1000 microm larger than the greatest linear dimension of the CNV lesion. At follow-up examinations every 3 months, retreatment with the same regimen was applied if angiography showed fuorescein leakage. The primary outcome was the proportion of eyes with fewer than 15 letters lost (approximately <3 lines of loss), adhering to an intent-to-treat analysis. RESULTS: In each group, 94% of patients completed the month 12 examination. Visual acuity, contrast sensitivity, and fluorescein angiographic outcomes were better in the verteporfin-treated eyes than in the placebo-treated eyes at every follow-up examination through the month 12 examination. At the month-12 examination, 246 (61%) of 402 eyes assigned to verteporfin compared with 96 (46%) of 207 eyes assigned to placebo had lost fewer than 15 letters of visual acuity from baseline (P<.001). In subgroup analyses, the visual acuity benefit (< 15 letters lost) of verteporfin therapy was clearly demonstrated (67% vs 39%; P<.001) when the area of classic CNV occupied 50% or more of the area of the entire lesion (termed predominantly classic CNV lesions), especially when there was no occult CNV. No statistically significant differences in visual acuity were noted when the area of classic CNV was more than 0% but less than 50% of the area of the entire lesion. Few ocular or other systemic adverse events were associated with verteporfin treatment, compared with placebo, including transient visual disturbances (18% vs 12%), injection-site adverse events (13% vs 3%), transient photosensitivity reactions (3% vs 0%), and infusion-related low back pain (2% vs 0%). CONCLUSIONS: Since verteporfin therapy of subfoveal CNV from AMD can safely reduce the risk of vision loss, we recommend verteporfin therapy for treatment of patients with predominantly classic CNV from AMD.

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PubMed2002

Simple, reliable and fast spectrofluorometric method for determination of plasma Verteporfin (Visudyne) levels during photodynamic therapy for choroidal neovascularization.

Photodynamic therapy with Verteporfin, a potent photosensitizer dye, is a very effective treatment for age related macular degeneration due to choroidal neovascularization. Photodynamic therapy offers the potential for selective tissue injury in part attributable to preferential localization of Verteporfin, administrated by intravenous infusion, to the choroidal neovascularization complex and irradiation of the complex with non-laser thermal light at 690 nm resulting in at least temporary thrombosis and vessel closure. Verteporfin is a benzoporphyrin derivative monoacid ring A formulated as a unilamellar liposome. In the blood Verteporfin is associated with lipoprotein fractions and is rapidly cleared via a receptor-mediated uptake mechanism due the high expression of LDL receptors in neovascular tissues. Verteporfin was undetectable in plasma 24 hr after infusion of the recommended dose: 6 mg/m2 of body surface area. The main side effect is photosensitivity of skin which is usually short-lived (24-48 hr) with a low incidence (2.3%). As skin photosensitivity depends on circulating rather than tissue drug levels, we investigate the possibility of developing a simple, fast and reliable spectrofluorometric method to measure plasma Verteporfin levels. Fluorescence emission spectrum (550-750 nm) of 1:10 saline diluted plasma with lambda exc=430 nm showed a characteristic emission peak at 692 nm, the height being proportional to the Verteporfin levels. The sensitivity is around 100 ng/ml and the pharmacokinetics of Verteporfin has been studied from 0 to 5 hr after infusion in six patients older than 65 years with age-related macular degeneration.

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PubMed2000

A preliminary study of photodynamic therapy using verteporfin for choroidal neovascularization in pathologic myopia, ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes.

OBJECTIVE: To evaluate short-term safety and the effects on visual acuity and fluorescein angiography of single or multiple sessions of photodynamic therapy with verteporfin for choroidal neovascularization (CNV) not related to age-related macular degeneration (AMD), including pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, and idiopathic causes. DESIGN: A nonrandomized, multicenter, open-label, dose-escalation phase 1 and 2 clinical trial. SETTING: Four ophthalmic centers in Europe and North America providing retinal care. PARTICIPANTS: Thirteen patients with subfoveal CNV due to pathologic myopia, the ocular histoplasmosis syndrome, angioid streaks, or idiopathic causes. METHODS: Standardized protocol refraction, visual acuity testing, ophthalmic examinations, color photographs, and fluorescein angiograms were used to evaluate the results of photodynamic therapy treatments with verteporfin. Follow-up ranged from 12 weeks for patients who were treated once to 43 weeks for patients who were treated up to 4 times. RESULTS: Verteporfin therapy was well tolerated in patients with CNV not related to AMD. No deterioration in visual acuity was observed; most patients gained at least 1 line of vision. Reduction in the size of leakage area from classic CNV was noted in all patients as early as 1 week after verteporfin therapy, with complete absence of leakage from classic CNV in almost half of the patients. Improvement in visual acuity after verteporfin therapy was greatest (+6, +8, and +9 lines) in 3 patients with relatively poor initial visual acuity (between 20/200 and 20/800). Up to 4 treatments were found to have short-term safety even with retreatment intervals as short as 4 weeks. CONCLUSIONS: Treatment of CNV not related to AMD with verteporfin therapy achieves short-term cessation of fluorescein leakage from CNV in a small number of patients without loss of vision. Further randomized clinical trials including a larger number of patients are under way to confirm whether verteporfin therapy is beneficial for subfoveal CNV not related to AMD.

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PubMed2005

Verteporfin therapy of subfoveal minimally classic choroidal neovascularization in age-related macular degeneration: 2-year results of a randomized clinical trial.

OBJECTIVE: To compare the treatment effect and safety of photodynamic therapy with verteporfin using a standard (SF) or reduced (RF) light fluence rate with that of placebo therapy in patients with subfoveal minimally classic choroidal neovascularization (CNV) with age-related macular degeneration. DESIGN: Phase 2, multicenter, double-masked, placebo-controlled, randomized clinical trial. SETTING: Nineteen ophthalmology practices in North America and Europe. PARTICIPANTS: Patients with initial best-corrected visual acuity of at least 20/250 and a lesion size of no greater than 6 Macular Photocoagulation Study (MPS) disc areas. METHODS: We randomly assigned 117 patients (1:1:1) to verteporfin infusion (6 mg/m(2)) and light application with an RF rate (300 mW/cm(2)) for 83 seconds (light dose of 25 J/cm(2)) or an SF rate (600 mW/cm(2)) for 83 seconds (light dose of 50 J/cm(2)) or to placebo infusion with RF or SF. Treatment was repeated every 3 months if the treating physician noted fluorescein leakage from CNV on angiography. Patients in whom a predominantly classic lesion developed could receive open-label standard verteporfin treatment. Best-corrected visual acuity was measured every 3 months, and angiographic changes were assessed by the Photograph Reading Center through the 3-month examination unless an ocular adverse event or conversion to a predominantly classic lesion was identified by an investigator. Safety was assessed throughout the study. All outcomes were on an intent-to-treat basis. RESULTS: One hundred three (88%) of 117 patients completed the 24-month examination. Twelve (30%) of 40 patients assigned to placebo received open-label standard verteporfin treatment after confirmation of presence of predominantly classic CNV. At month 12, a loss of at least 3 lines of visual acuity occurred in 5 (14%) of 36 eyes assigned to RF and 10 (28%) of 36 eyes assigned to SF, compared with 18 (47%) of 38 eyes assigned to placebo (RF, P = .002; SF, P = .08; RF + SF, P = .004). At month 24, this loss occurred in 9 (26%) of 34 eyes assigned to RF and 17 (53%) of 32 assigned to SF, compared with 23 (62%) of 37 eyes assigned to placebo (RF, P = .003; SF, P = .45; RF + SF, P = .03). Progression to predominantly classic CNV by 24 months was more common in the placebo group (11 [28%] of 39 patients compared with 2 [5%] of 38 in the RF group [P = .007] and 1 [3%] of 37 in the SF group [P = .002]). No unexpected ocular or systemic adverse events were identified. Treatment-related, usually transient visual disturbances were 13% with SF, 10% with placebo, and 5% with RF. CONCLUSIONS: Verteporfin therapy safely reduced the risks of losing at least 15 letters (> or =3 lines) of visual acuity and progression to predominantly classic CNV for at least 2 years in individuals with subfoveal minimally classic lesions due to age-related macular degeneration measuring 6 MPS disc areas or less. Based on the overall evidence available on verteporfin therapy for these lesions, the VIM Study Group would consider recommending verteporfin therapy for relatively small minimally classic lesions similar to those enrolled in the VIM Trial.

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