The retina clinical trials included in the following tables as landmark trials were selected because they meaningfully changed how we treat patients—these trials introduced new therapies, shifted treatment strategies, or established standards still used in daily practice. This list is not exhaustive; priority was given to large, randomized control trials, although some negative and/or smaller trials were included to be as comprehensive as possible.

Table 1. Clinical Trials in Wet AMD
Trial PMID Population/ Subtype Drug/ Modality Regimen/ Design Comparator Primary Endpoint Key Outcome(s)
TAP (1999) 10532441 Predominantly classic CNV Verteporfin PDT Fixed PDT Placebo < 15 ETDRS letter loss First effective therapy; slowed vision loss prior to advent of anti-VEGF therapy
VIP (2001) 11336929 Occult CNV
(no classic)		 Verteporfin PDT Fixed PDT Placebo VA loss Benefit in selected occult CNV
VISION (2004) 15625332 Wet AMD Pegaptanib Every 6 weeks Sham < 15 ETDRS letter loss First anti-VEGF approval; modest benefit
MARINA (2006) 17021318 Occult/ minimally classic CNV Ranibizumab Monthly Sham ≥ 15 ETDRS letter gain Major VA gains; FDA approval
ANCHOR (2006) 19118696 Predominantly classic CNV Ranibizumab Monthly PDT ≥ 15 ETDRS letter gain Anti-VEGF superior to PDT
PIER (2008) 18222192 Wet AMD Ranibizumab Monthly for 3 months;
then quarterly		 Sham VA change Quarterly dosing lost early VA gains
EXCITE (2011) 21146229 Wet AMD Ranibizumab Monthly vs quarterly Active Noninferiority Quarterly inferior; need frequent dosing
SUSTAIN (2011) 21459217 Wet AMD Ranibizumab PRN after loading Single arm VA change, CST PRN viable with close monitoring
CATT (2011) 21526923 Wet AMD Ranibizumab vs bevacizumab Monthly vs PRN Head-to-head Mean VA Bevacizumab noninferior
IVAN (2012) 22578446 Wet AMD Ranibizumab vs bevacizumab Continuous vs discontinuous Head-to-head Mean VA Confirmed CATT findings (UK): bevacizumab noninferior
VIEW 1/2 (2012) 23084240 Wet AMD Aflibercept Every 8 weeks after loading Ranibizumab monthly Noninferiority VA Enabled dosing every 8 weeks
GEFAL (2013) 23916488 Wet AMD Bevacizumab Monthly Ranibizumab VA change Bevacizumab noninferior
MANTA (2013) 23292928 Wet AMD Bevacizumab Monthly Ranibizumab VA change No significant difference
HARBOR (2013) 23352196 Treatment-naïve wet AMD Ranibizumab 0.5 vs 2 mg Monthly vs PRN Active VA change Higher dose not superior
LUCAS (2015) 25227499 Wet AMD Bevacizumab vs ranibizumab Treat-and-extend Head-to-head Mean VA Noninferiority under treat-and-extend
TREX-AMD (2015) 26391465 Wet AMD Ranibizumab Treat-and-extend vs monthly Active VA change Treat-and-extend comparable with fewer injections
CATT (5-year) (2016) 27156698 Wet AMD Long-term anti-VEGF – – Long-term VA outcomes Decline over time; atrophy relevance
BRAMD (2016) 27203434 Wet AMD Bevacizumab Monthly Ranibizumab VA change Bevacizumab noninferior but more frequently observed retinal fluid on SD-OCT at 12 months
TREND (2017) 28893454 Wet AMD Ranibizumab Treat-and-extend vs monthly Active VA change Ranibizumab treat-and-extend noninferior
CANTREAT (2019) 30677465 Wet AMD Ranibizumab Treat-and-extend vs monthly Active Noninferiority VA Formal randomized control trial supporting treat-and-extend
FLUID (2019) 30502372 Wet AMD Ranibizumab Treat-and-extend
(SRF tolerant vs strict)		 Active Noninferiority VA Some SRF can be tolerated
HAWK/ HARRIER (2019) 30986442 Treatment-naïve wet AMD Brolucizumab Every 12 weeks/every 8 weeks Aflibercept Noninferiority VA Strong drying; similar safety
ALTAIR (2020) 32016788 Wet AMD Aflibercept Treat-and-extend
(2-week vs 4-week steps)		 Active VA change/ anatomic outcomes Flexible interval extension effective
ARIES (2021) 33782365 Wet AMD Aflibercept Early vs late treat-and-extend Active Noninferiority Early treat-and-extend acceptable
ARCHWAY (2021) 34597713 Previously treated wet AMD Port delivery system with ranibizumab Refill every 24 weeks Monthly injections Noninferiority VA Long-acting surgical delivery of ranibizumab noninferior to monthly ranibizumab
Prophylactic Aflibercept Trial (2021) 33734306 High-risk fellow eyes
(intermediate AMD with contralateral wet AMD)		 Aflibercept Quarterly intravitreal injections; single-masked RCT (24 months) Sham Conversion to wet AMD No significant reduction in conversion rate; does not support prophylactic anti-VEGF strategy
TENAYA/ LUCERNE (2022) 35085502 Treatment-naïve wet AMD Faricimab Up to 16 weeks Aflibercept every 8 weeks Noninferiority VA Dual Ang-2/VEGF targeting enables longer intervals
Prophylactic Ranibizumab Trial (2022) 35121216 Fellow eyes at high risk for neovascular AMD Ranibizumab Prophylactic intravitreal injections every 3 months; RCT Sham/ observation Conversion to wet AMD No reduction in conversion to wet AMD; does not support preventive anti-VEGF strategy
Abbreviations: Ang-2, angiopoietin-2; CNV, choroidal neovascularization; CST, central subfield thickness; PDT, photodynamic therapy; RCT, randomized control trial; SD-OCT, spectral-domain OCT; SRF, subretinal fluid.
Table 2. Clinical Trials in Dry AMD
Trial PMID Population/ Subtype Drug/Modality Regimen/ Design Comparator Primary Endpoint Key Outcome(s)
AREDS (2001) 11594942 Intermediate AMD; advanced AMD in fellow eye Antioxidants + zinc Oral supplements Placebo Progression to advanced AMD ~25% reduction in progression in high-risk patients; foundation of supplementation
GATE (2008) 26310670 GA secondary to AMD Tandospirone Topical Placebo GA lesion growth No clear efficacy
OT-551 (2010) 20574018 GA secondary to AMD Topical antioxidant (OT-551) Topical Vehicle VA change Well tolerated; no clear slowing of GA progression
Fenretinide Trial (2012) 23023528 GA secondary to AMD Fenretinide Oral Placebo GA lesion growth Dose-dependent biologic signal; no definitive efficacy
AREDS2 (2013) 23644932 Intermediate AMD Lutein/ zeaxanthin + omega-3 Oral supplements Original AREDS Progression to advanced AMD Lutein/ zeaxanthin a safe substitute for beta-carotene; omega-3 ineffective
MAHALO (2017) 28637922 GA secondary to AMD Lampalizumab (factor D inhibitor) Monthly
intravitreal		 Sham GA lesion growth Signal in subgroup; advanced to phase 3
CHROMA/ SPECTRI (2017) 29801123 GA secondary to AMD Lampalizumab Monthly
intravitreal		 Sham GA lesion growth No reduction in GA lesion growth/ Confirmed phase 3 failure
Emixustat (2018) 29716784 GA secondary to AMD Emixustat (visual cycle modulator) Oral Placebo GA lesion growth Negative; visual side effects prominent
FILLY (2019) 31474439 GA secondary to AMD Pegcetacoplan (C3 inhibitor) Monthly/every other month intravitreal Sham GA lesion growth Significant reduction in GA lesion growth; higher risk of CNV
GATHER1 (2020) 36964259 GA secondary to AMD Avacincaptad pegol (C5 inhibitor) Monthly
intravitreal		 Sham GA lesion growth Significant reduction in GA lesion growth at 12 to 18 months
Brimo DDS Gen 1 (2020) 32134802 GA secondary to AMD Brimonidine Drug Delivery System Intravitreal implant Sham GA lesion growth Suggested
neuroprotective signal
OAKS (2023) 37865470 GA secondary to AMD Pegcetacoplan Monthly/every other month Sham GA lesion growth Met primary endpoint;
FDA approval
DERBY (2023) 37865470 GA secondary to AMD Pegcetacoplan Monthly/every other month Sham GA lesion growth Directionally positive;
pooled efficacy
GATHER2 (12 months) (2023) 37696275 GA secondary to AMD Avacincaptad pegol Monthly Sham GA lesion growth Confirmed efficacy; FDA approval
LIGHTSITE I/II (2023) 37542463 GA secondary to AMD Photobiomodulation Multi-session light therapy Sham VA change, contrast sensitivity Functional signal without GA reduction
GATHER2 (24 months) (2024) 41407269 GA secondary to AMD Avacincaptad pegol Monthly/every other month Sham GA lesion growth
(long-term)		 Sustained GA
reduction;
safety update
Abbreviations: GA, geographic atrophy.
Table 3. Clinical Trials and Literature on Polypoidal Choroidal Vasculopathy
Trial PMID Population/ Subtype Drug/ Modality Regimen/Design Comparator Primary Endpoint Key Outcome(s)
EVEREST 22426346 Symptomatic macular PCV
(ICGA-confirmed)		 Verteporfin PDT ± ranibizumab RCT (6 months) Ranibizumab monotherapy Complete polyp regression (ICGA-confirmed) PDT (alone or with ranibizumab) achieved higher complete polyp regression vs ranibizumab alone; established concept that PDT closes polyps
LAPTOP (12 months) 23876867 Treatment-naïve PCV Ranibizumab RCT Verteporfin PDT VA change, anatomic outcomes Ranibizumab superior to PDT in BCVA and CRT
LAPTOP (24 months) 24484991 PCV Ranibizumab vs PDT 24-month
follow-up report		 Active comparator Long-term
outcomes		 Longer-term comparative
outcomes extending LAPTOP findings
FUJISAN 25830698 PCV Ranibizumab + PDT RCT; initial vs deferred
PDT with ranibizumab		 Timing
strategy comparison		 VA change, anatomic
outcomes		 Similar VA/anatomic gains; initial PDT needed fewer additional treatments
EVEREST II (12 months) 28983556 Treatment-naïve PCV Ranibizumab + verteporfin PDT RCT Ranibizumab monotherapy VA change, polyp
regression		 Combination therapy superior BCVA and higher complete polyp regression with fewer injections
PLANET 29801063 Treatment-naïve PCV Aflibercept RCT; fixed
dosing
early then
protocolized		 Aflibercept + rescue PDT vs aflibercept + sham rescue VA change Aflibercept produced strong vision/anatomic outcomes; few needed rescue PDT, supporting anti-VEGF-first strategy in many PCV eyes
EVEREST II (24 months) 32672800 PCV Ranibizumab + verteporfin PDT RCT extension Ranibizumab monotherapy VA change, anatomic
outcomes		 24-month data
supported sustained efficacy/safety; combination maintained advantages, including polyp outcomes
PLANET (Japanese subgroup) (2021) 33474611 PCV in Japanese subgroup of PLANET Aflibercept Subgroup analysis Aflibercept + rescue PDT vs aflibercept + sham rescue VA change, anatomic outcomes Reinforced PLANET conclusions in Japanese cohort
Vyas et al (2021) 34266844 PCV Aflibercept + reduced-fluence PDT Multicenter RCT Aflibercept monotherapy Trial-defined efficacy and safety Direct evidence on reduced-fluence PDT add-on to aflibercept from an RCT
Teo et al (2021) 33574033 Treatment-naïve PCV Aflibercept Prospective regimen
strategy study		 Fixed
regimen (study-defined)		 Regimen efficacy (trial-defined) ICGA/polyp-inactivation informed dosing strategy; supports individualized anti-VEGF approaches
ATLANTIC (2022) 34348351 PCV (multi-center) Aflibercept treat-and-extend RCT; treat-and-extend + verteporfin PDT vs treat-and-extend + sham PDT Sham PDT Trial-defined efficacy and safety Aflibercept treat-and-extend safe and effective, benefit of combining with PDT unclear
Cho et al (2023) 37504966 PCV Brolucizumab Comparative study Aflibercept 12-month
outcomes (study-defined)		 Comparable VA;
higher reported polyp regression in this cohort; safety monitoring important (IOI risk class consideration)
Chong et al (2025) 40146166 ICGA-confirmed symptomatic PCV Aflibercept + reduced-fluence PDT
(single baseline PDT) + PRN aflibercept		 Double-masked RCT Sham PDT + PRN aflibercept VA change Underpowered
(recruitment issues); no VA change; higher early polyp closure signal (secondary endpoint)
Abbreviations: CRT, central retinal thickness; ICGA, indocyanine green angiography; IOI, intraocular inflammation; PDT, photodynamic therapy; PCV, polypoidal choroidal vasculopathy; RCT, randomized control trial.