Abstract :
PURPOE: To determine if photodynamic therapy with verteporfin (Viudyne; Novarti AG, Bülach, witzerland), termed verteporfin therapy, can afely reduce the rik of viion lo compared with a placebo (with ham treatment) in patient with ubfoveal choroidal neovacularization caued by age-related macular degeneration who were identified with a leion compoed of occult with no claic choroidal neovacularization, or with preumed early onet claic choroidal neovacularization with good viual acuity letter core.
METHOD: Thi wa a double-maked, placebo-controlled (ham treatment), randomized, multicenter clinical trial involving 28 ophthalmology practice in Europe and North America. The tudy population wa patient with age-related macular degeneration, with ubfoveal choroidal neovacularization leion meauring no greater than 5400 μm in greatet linear dimenion with either 1) occult with no claic choroidal neovacularization, bet-corrected viual acuity core of at leat 50 (nellen equivalent approximately 20/100), and evidence of hemorrhage or recent dieae progreion; or 2) evidence of claic choroidal neovacularization with a bet-corrected viual acuity core of at leat 70 (better than a nellen equivalent of approximately 20/40); aigned randomly (2:1) to verteporfin therapy or placebo therapy. Verteporfin (6 mg per quare meter of body urface area) or placebo (5% dextroe in water) wa adminitered by mean of intravenou infuion of 30 ml over 10 minute. Fifteen minute after the tart of the infuion, a laer light at 689 nm delivered 50 J/cm2 by application of an intenity of 600 mW/cm2 over 83 econd uing a pot ize with a diameter 1000 μm larger than the greatet linear dimenion of the choroidal neovacularization leion on the retina. At follow-up examination every 3 month, retreatment with the ame regimen wa applied if angiography howed fluorecein leakage. The main outcome meaure wa at leat moderate viion lo, that i, a lo of at leat 15 letter (approximately 3 line), adhering to an intent-to-treat analyi with the lat obervation carried forward to impute for miing data.
REULT: Two hundred ten (93%) and 193 (86%) of the 225 patient in the verteporfin group compared with 104 (91%) and 99 (87%) of the 114 patient in the placebo group completed the month 12 and 24 examination, repectively. On average, verteporfin-treated patient received five treatment over the 24 month of follow-up. The primary outcome wa imilar for the verteporfin-treated and the placebo-treated eye through the month 12 examination, although a number of econdary viual and angiographic outcome ignificantly favored the verteporfin-treated group. Between the month 12 and 24 examination, the treatment benefit grew o that by the month 24 examination, the verteporfin-treated eye were le likely to have moderate or evere viion lo. Of the 225 verteporfin-treated patient, 121 (54%) compared with 76 (67%) of 114 placebo-treated patient lot at leat 15 letter (P = .023). Likewie, 67 of the verteporfin-treated patient (30%) compared with 54 of the placebo-treated patient (47%) lot at leat 30 letter (P = .001). tatitically ignificant reult favoring verteporfin therapy at the month 24 examination were conitent between the total population and the ubgroup of patient with a baeline leion compoition identified a occult choroidal neovacularization with no claic choroidal neovacularization. Thi ubgroup included 166 of the 225 verteporfin-treated patient (74%) and 92 of the 114 placebo-treated patient (81%). In thee patient, 91 of the verteporfin-treated group (55%) compared with 63 of the placebo-treated group (68%) lot at leat 15 letter (P = .032), wherea 48 of the verteporfin-treated group (29%) and 43 of the placebo-treated group (47%) lot at leat 30 letter (P = .004). Other econdary outcome, including viual acuity letter core wore than 34 (approximate nellen equivalent of 20/200 or wore), mean change in viual acuity letter core, development of claic choroidal neovacularization, progreion of claic choroidal neovacularization and ize of leion, favored the verteporfin-treated group at both the month 12 and month 24 examination for both the entire tudy group and the ubgroup of cae with occult with no claic choroidal neovacularization at baeline. ubgroup analye of leion compoed of occult with no claic choroidal neovacularization at baeline uggeted that the treatment benefit wa greater for patient with either maller leion (4 dic area or le) or lower level of viual acuity (letter core le than 65, an approximate nellen equivalent of 20/50−1 or wore) at baeline. Propectively planned multivariable analye confirmed that thee two baeline variable affected the magnitude of treatment benefit. Of the 123 verteporfin-treated patient and 64 placebo-treated patient with either viual acuity core le than 65 or leion ize 4 dic area or le at baeline, 60 (49%) and 48 (75%) lot at leat 15 letter (P < .001), repectively, and 26 (21%) and 31 (48%) lot at leat 30 letter (P < .001), repectively, at the month 24 examination. Converely, treatment may not be beneficial for patient with both larger leion and good viual acuity (both greater than 4 dic area and letter core 65 or greater, an approximate nellen equivalent of 20/50 or better). With repect to afety for the entire tudy group, 10 of 225 verteporfin-treated patient (4.4%) and none of the placebo-treated patient had a evere decreae of viion (at leat 20 letter compared with the viual acuity jut before the treatment) within 7 day after treatment, judged to be the reult of the development of ubretinal pigment epithelial blood, marked ubretinal fluid aociated with choroidal hypofluorecence, or no obviou caue. Five of thee 10 patient had recovery of viion to le than a 20-letter lo compared with the pretreatment viion core at 3 month after thi event. Photoenitivity reaction occurred in only one patient in each group.
CONCLUION: In thi trial of patient with age-related macular degeneration and ubfoveal choroidal neovacularization leion compoed of occult with no claic choroidal neovacularization, verteporfin therapy ignificantly reduced the rik of moderate and evere viual acuity lo. ubgroup analye ugget that a greater benefit wa achieved in patient preenting with either maller leion (4 dic area or le) or lower level of viual acuity (letter core le than 65, an approximate nellen equivalent of 20/50−1 or le). The Verteporfin In Photodynamic Therapy tudy Group recommend that thi therapy hould be conidered for the treatment of patient with age-related macular degeneration with ubfoveal leion compoed of occult with no claic choroidal neovacularization who are preumed to have recent dieae progreion. Patient to be treated hould be aware of a mall (4%) rik of acute, evere viion decreae.
