. 2024 Jun 10;18:1701–1716. doi: 10.2147/OPTH.S464371

Table 1.

Summary of Select Clinical Trials of vPDT for the Treatment of Choroidal Neovascularization Associated with Age-Related Macular Degeneration

Study and Design	Patient Population	Treatments	Efficacy Outcomes	Safety Outcomes
vPDT vs placebo
TAP 12 mo²⁷ 24 mo³⁰ R, MC, DM, PBO-C US (11 sites) Canada (2 sites) Europe (9 sites) N=609 (609 eyes) Age: ≥50 y	Pts with CNV associated with AMD	vPDT (n=402) vs PBO (n=207)	vPDT vs PBO % eyes with <15 letters lost (<3 lines) of VA from baseline 12 mo: 61.2% vs 46.4% (P<0.001) 24 mo: 53% vs 38% (P<0.001)	12 mo (vPDT vs PBO) Tx-related AEs: 46% vs 36% Photosensitivity reactions with vPDT 12 pts (3.0%), with 2 pts not related to tx; transient, mild-to-moderate sunburns caused by direct exposure to sunlight Tx-related discontinuation (only with vPDT) 7 pts (1.7%); allergy to fluorescein dye, GI bleeding, subretinal hemorrhage, possible allergic reaction to tx, severe back pain possibly due to infusion, suprachoroidal hemorrhage with retinal detachment and vitreous hemorrhage, injection site reaction 24 mo (vPDT vs PBO) Tx-related AEs: 47.8% vs 33.8% Photosensitivity reactions with vPDT 14 pts (3.5%) No additional tx-related discontinuations
VIP²⁹ R, MC, DM, PBO-C Europe and North America (28 sites) N=339 (339 eyes)	Pts with CNV associated with AMD	vPDT (n=225) vs PBO (n=114)	vPDT vs PBO % eyes with ≥15 letters lost of VA from baseline 12 mo: 51% vs 54% (P=0.5) 24 mo: 54% vs 67% (P=0.02)	vPDT 10 pts (4%) had severe decrease in VA within 7 d of tx; some pts experienced subsequent improvement in VA <1% pts had photosensitivity reactions
VEGF inhibitor vs sham
MARINA³¹ R, MC, DM, Sham-C US (96 sites) N=716	Pts with CNV associated with AMD	Ranibizumab 0.5 mg (n=240) Ranibizumab 0.3 mg (n=238) Sham injection (n=238)	Ranibizumab 0.5 mg and 0.3 mg vs sham injection % pts losing <15 letters of VA from baseline 12 mo: 94.6% and 94.5% vs 62.2% (P<0.001 for both ranibizumab groups vs sham) 24 mo: 90.0% and 92.0% vs 52.9% (P<0.001 for both ranibizumab groups vs sham)	Ranibizumab 0.5 mg and 0.3 mg vs sham injection AEs at 24 mo Serious ocular AEs Presumed endophthalmitis: 1.3%, 0.8%, 0% Uveitis: 1.3%, 1.3%, 0% Vitreous hemorrhage: 0.4%, 0.4%, 0.8% Retinal tear: 0.4%, 0.4%, 0% Lens damage: 0.4%, 0%, 0% Rhegmatogenous retinal detachment: 0%, 0%, 0.4%
vPDT vs VEGF inhibitor
ANCHOR 12 mo³² 24 mo³³ R, MC, DM 83 sites N=423 Age: ≥50 y	Pts with CNV associated with AMD	Ranibizumab 0.5 mg (n=140) Ranibizumab 0.3 mg (n=140) vPDT (n=143)	Ranibizumab 0.5 mg and 0.3 mg vs vPDT % pts losing <15 letters of VA from baseline 12 mo: 96.4% and 94.3% vs 64.3% (P<0.001 for both ranibizumab groups vs vPDT) 24 mo: 89.9% and 90.0% vs 65.7% (P<0.0001 for both ranibizumab groups vs vPDT)	Ranibizumab 0.5 mg and 0.3 mg vs vPDT AEs at 12 mo Serious ocular AEs Presumed endophthalmitis: 1.4%, 0%, 0% Uveitis: 0.7%, 0%, 0% Rhegmatogenous retinal detachment: 0%, 0.7%, 0.7% Vitreous hemorrhage: 0%, 0.7%, 0% Lens damage: 0%, 0%, 0% Retinal tear: 0%, 0%, 0% AEs at 24 mo Pooled ranibizumab groups: 1.1% pts developed presumed endophthalmitis (rate per injection: 3/5921 [0.05%])
vPDT combination therapy
FOCUS 1 yr³⁴ 2 yr³⁵ R, SM, MC US (25 sites) N=162	Pts with CNV associated with AMD	vPDT + ranibizumab 0.5 mg (n=106) vPDT + sham injection (n=56)	vPDT + ranibizumab 0.5 mg vs vPDT % pts losing <15 letters of VA from baseline 1 y: 90.5% vs 67.9% (P<0.001) 2 y: 87.6% vs 75.0% (P=0.04)	vPDT + ranibizumab 0.5 mg vs vPDT Nonocular AEs more common with combination therapy vs vPDT at 1 y Hypertension: 12.4% vs 7.1% Pain in an extremity: 7.6% vs 3.6% Anxiety: 6.7% vs 1.8% Combination therapy vs vPDT at 2 y Serious ocular AEs: 17.1% vs 14.3% Endophthalmitis: 2.9% vs 0% Intraocular inflammation: 12.4% vs 0% Vascular systemic serious AEs: 13.3% vs 10.7% Other systemic serious AEs: 20.0% vs 19.6%
DENALI³⁶ R, MC, DM, ph 3b N=321	Pts with CNV associated with AMD	vPDT + ranibizumab 0.5 mg (n=104) vPDT (reduced fluence) + ranibizumab 0.5 mg (n=105) Ranibizumab 0.5 mg (n=112)	vPDT + ranibizumab 0.5 mg vs vPDT (reduced-fluence) + ranibizumab 0.5 mg vs ranibizumab 0.5 mg Mean change from baseline in BCVA at 12 mo: 5.3, 4.4, vs 8.1 letters Noninferiority of either combination tx vs ranibizumab not demonstrated % pts with ranibizumab tx-free interval of ≥3 mo after third consecutive monthly ranibizumab injection: 92.6% and 83.5% (combination tx only)	vPDT + ranibizumab 0.5 mg vs vPDT (reduced-fluence) + ranibizumab 0.5 mg vs ranibizumab 0.5 mg Ocular AEs at 12 mo: 60.6%, 52.8%, 54.1% Eye pain: 19.2%, 12.3%, 12.6% Conjunctival hemorrhage: 11.5%, 14.2%, 13.5% VA reduced: 11.5%, 6.6%, 6.3%
MONT BLANC³⁷ R, MC, DM Europe (45 sites) N=255 Age: ≥50 y	Pts with CNV associated with AMD	vPDT + ranibizumab 0.5 mg (n=122) Ranibizumab 0.5 mg (n=133)	vPDT + ranibizumab 0.5 mg vs ranibizumab 0.5 mg Mean change from baseline in BCVA at 12 mo: 2.5 vs 4.4 letters (P=0.005) Noninferiority of combination tx vs ranibizumab demonstrated (margin of 7 letters) % pts with ranibizumab tx-free interval ≥3 mo after 2 mo: 96% and 92%	vPDT + ranibizumab 0.5 mg vs ranibizumab 0.5 mg Ocular AEs at 12 mo: 41.8% vs 40.6% Increased IOP: 6.6% vs 5.3% Eye pain: 5.7% vs 5.3% Ocular hyperemia: 5.7% vs 6.0%
RADICAL³⁸ R, MC, SM, ph 2 N=162 (162 eyes) Age: ≥50 y	Pts with CNV associated with AMD	vPDT (half-fluence) + ranibizumab 0.5 mg + dexamethasone 0.5 mg (n=39) vPDT (quarter-fluence) + ranibizumab 0.5 mg + dexamethasone 0.5 mg (n=39) vPDT (half-fluence) + ranibizumab 0.5 mg (n=43) Ranibizumab 0.5 mg (n=41)	vPDT (half-fluence) + ranibizumab + dexamethasone vs vPDT (quarter-fluence) + ranibizumab + dexamethasone vs vPDT (half-fluence) + ranibizumab vs ranibizumab Retreatments 12 mo: 3.2, 4.0, 4.1, 5.7 (P values vs ranibizumab alone: P<0.001, P=0.02, P=0.03) 24 mo: 4.3, 5.9, 5.9, 8.7 (P values vs ranibizumab alone: P<0.001, P=0.03, P=0.02) Mean change (95% CI) from baseline in VA letter score 12 mo: 6.8 (2.4 to 11.1), 3.6 (–0.9 to 8.1), 5.0 (0.6 to 9.3), 6.5 (1.7 to 11.4) (P≥0.4 vs ranibizumab alone) 24 mo: 1.1 (–4.3 to 6.4), –0.2 (–5.7 to 5.4), –0.3 (–6.2 to 5.6), 4.4 (–1.5 to 10.2)	vPDT (half-fluence) + ranibizumab + dexamethasone vs vPDT (quarter-fluence) + ranibizumab + dexamethasone vs vPDT (half-fluence) + ranibizumab vs ranibizumab Tx-related AEs at 24 mo: 44%, 49%, 47%, 27% Ocular AE: 36%, 38%, 30%, 27% Infusion-related back pain: 5%, 3%, 9%, 0% Intravenous injection site extravasation: 3%, 3%, 7%, 0% Intravenous injection site pain: 3%, 3%, 7%, 0% Photosensitivity reaction: 0%, 3%, 2%, 0% Tx-associated SAEs: 5% (increased IOP, vision decreased, SAE-related withdrawal), 5% (retinal tear, vitreous hemorrhage), 2% (retinal detachment, vision decreased, visual field defect, vitreous hemorrhage), 0%

Abbreviations: AE, adverse event; AMD, age-related macular degeneration; ANCHOR, Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration; BCVA, best-corrected visual acuity; CI, confidence interval; CNV, choroidal neovascularization; DM, double-masked; FOCUS, RhuFab V2 Ocular Treatment Combining the Use of Visudyne to Evaluate Safety; GI, gastrointestinal; IOP, intraocular pressure; MARINA, Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age-Related Macular Degeneration; MC, multicenter; PBO, placebo; PBO-C, placebo-controlled; ph, phase; pt, patient; R, randomized; RADICAL, Reduced Fluence Visudyne-Anti-VEGF-Dexamethasone in Combination for AMD Lesions; SAE, serious adverse event; Sham-C, sham-controlled; SM, single-masked; TAP, Treatment of Age-Related Macular Degeneration With Photodynamic Therapy; Tx, treatment; VA, visual acuity; VEGF, vascular endothelial growth factor; VIP, Verteporfin in Photodynamic Therapy; vPDT, verteporfin PDT.