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.


METHODS
Phase 2, multicenter, double-masked, placebo-controlled, randomized clinical trial.


METHODS
Nineteen ophthalmology practices in North America and Europe.


METHODS
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.
Azab
Mohammad
M
Boyer
David S
DS
Bressler
Neil M
NM
Bressler
Susan B
SB
Cihelkova
Ilona
I
Hao
Young
Y
Immonen
Ilkka
I
Lim
Jennifer I
JI
Menchini
Ugo
U
Naor
Joel
J
Potter
Michael J
MJ
Reaves
Al
A
Rosenfeld
Philip J
PJ
Slakter
Jason S
JS
Soucek
Peter
P
Strong
H Andrew
HA
Wenkstern
Andrea
A
Su
Xiang Yao
XY
Yang
Yit C
YC
D000368:Aged; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005451:Fluorescein Angiography; D005584:Fovea Centralis; D006801:Humans; D008268:Macular Degeneration / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use*; D012449:Safety; D000077362:Verteporfin; D014792:Visual Acuity / Q000502:physiology
D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin