Landmark Trials in Ophthalmology: High-Yield Summary

Last updated: November 2026

Landmark trials are the backbone of evidence-based ophthalmology and a favourite of every viva examiner. This page condenses the trials residents are most often asked about into one line each: the question the trial asked, and the take-home message you need to remember.

How to use this page: for each trial, learn the question and the answer first. Numbers are given only where they are classic and frequently examined. For details, always go back to the original publication.

Glaucoma

Trial	Question	Take-home message
OHTS Ocular Hypertension Treatment Study	Does lowering IOP in ocular hypertension prevent glaucoma?	Lowering IOP by about 20% reduced 5-year conversion to POAG from 9.5% to 4.4%. Thin central corneal thickness emerged as an independent risk factor.
EMGT Early Manifest Glaucoma Trial	Does treating early glaucoma slow progression compared with no treatment?	Treatment (laser trabeculoplasty plus betaxolol) reduced progression (45% vs 62%). Each 1 mmHg of IOP lowering reduced progression risk by about 10%.
CNTGS Collaborative Normal-Tension Glaucoma Study	Does lowering IOP help normal-tension glaucoma?	A 30% IOP reduction slowed progression, but many untreated eyes did not progress over 5 years. Its methodology has recently been questioned — see our NTG page.
AGIS Advanced Glaucoma Intervention Study	Which surgical sequence works best in advanced glaucoma, and what IOP is safe?	Eyes whose IOP stayed below 18 mmHg at every visit showed almost no average visual field progression. Lower and more consistent IOP matters in advanced disease.
CIGTS Collaborative Initial Glaucoma Treatment Study	Medicines or trabeculectomy as initial treatment for newly diagnosed glaucoma?	Visual field outcomes were similar. Surgery achieved lower IOP but caused more cataract.
TVT Tube Versus Trabeculectomy Study	Tube or trabeculectomy with MMC in eyes with previous cataract or failed glaucoma surgery?	The tube (Baerveldt 350) had a higher success rate over 5 years, with similar final IOP.
LiGHT Laser in Glaucoma and Ocular Hypertension Trial	SLT first or drops first?	First-line SLT was at least as good as drops, was cost-effective, and about three-quarters of SLT eyes were drop-free at 3 years.
EAGLE	Clear lens extraction or laser iridotomy in primary angle closure?	In PACG, and in PAC with IOP ≥30 mmHg, clear lens extraction gave better IOP control and quality of life and was cost-effective.
ZAP Zhongshan Angle Closure Prevention trial	Should every primary angle-closure suspect get a prophylactic iridotomy?	Iridotomy reduced the risk of progression, but the absolute risk was so low that routine widespread prophylactic LPI was not recommended.
UKGTS United Kingdom Glaucoma Treatment Study	Does a single IOP-lowering drug preserve the visual field compared with placebo?	Latanoprost halved the risk of visual field deterioration over 24 months (hazard ratio 0.44): the first placebo-controlled trial to show that lowering IOP preserves vision in open-angle glaucoma.
ABC / AVB Ahmed Baerveldt Comparison / Ahmed Versus Baerveldt studies	Which glaucoma drainage device works better?	The Baerveldt implant gave slightly lower IOP with fewer medications and fewer failures, but more serious hypotony-related complications; the Ahmed valve controls pressure earlier with fewer complications.

Diabetic retinopathy and macular oedema

Trial	Question	Take-home message
DRS Diabetic Retinopathy Study	Does panretinal photocoagulation prevent vision loss in PDR?	PRP reduced severe vision loss by at least 50%, with the greatest benefit in eyes with high-risk characteristics.
ETDRS Early Treatment Diabetic Retinopathy Study	Focal laser for macular oedema? Early PRP? Aspirin?	Focal laser for clinically significant macular oedema (CSME) halved moderate vision loss. Early PRP is not advised for mild to moderate NPDR. Aspirin neither helped nor harmed retinopathy or vitreous haemorrhage. ETDRS also defined CSME.
DRVS Diabetic Retinopathy Vitrectomy Study	Early vitrectomy for severe vitreous haemorrhage?	Early vitrectomy benefited type 1 diabetics.
DRCR Protocol T	Aflibercept vs bevacizumab vs ranibizumab for centre-involving DME?	All three were similar when starting vision was 20/32 to 20/40. With vision of 20/50 or worse, aflibercept gave better vision at 1 year.
DRCR Protocol S	Anti-VEGF or PRP for proliferative diabetic retinopathy?	Ranibizumab was non-inferior to PRP at 2 years, with less peripheral field loss and less DME. Its weakness: patients who miss follow-up are at risk.
DRCR Protocol V	Does centre-involving DME with good vision (20/25 or better) need treatment immediately?	Observation (treating only if vision worsened), laser, and immediate aflibercept gave similar vision at 2 years.
DRCR Protocol I Ranibizumab with prompt or deferred laser for DME	Are anti-VEGF injections better than laser alone for centre-involving DME?	Ranibizumab (with prompt or deferred laser) gave better vision than laser alone, making anti-VEGF the first-line treatment for centre-involving DME.
DRCR Protocol W Aflibercept to prevent complications of NPDR	Does treating moderate to severe NPDR with aflibercept before complications improve outcomes?	At 4 years, aflibercept reduced progression to PDR or centre-involving DME (34% vs 57%) but gave no visual benefit over observation with treatment when needed.

AMD and vein occlusions

Trial	Question	Take-home message
AREDS / AREDS2	Can antioxidant supplements slow AMD?	Supplements reduced progression to advanced AMD by about 25% in intermediate AMD or advanced AMD in one eye. AREDS2 replaced beta-carotene with lutein and zeaxanthin because of the lung cancer risk in smokers.
MARINA / ANCHOR	Does monthly ranibizumab work for neovascular AMD?	Ranibizumab improved vision, compared with sham (MARINA) and with verteporfin PDT (ANCHOR). This began the anti-VEGF era.
CATT / IVAN	Is bevacizumab as good as ranibizumab?	Bevacizumab gave equivalent visual outcomes when used on the same dosing schedule.
BVOS Branch Vein Occlusion Study	Laser for BRVO?	Grid laser improved vision in macular oedema with VA 20/40 or worse. Scatter laser reduced vitreous haemorrhage once neovascularisation developed.
CVOS Central Vein Occlusion Study	Laser for CRVO?	Grid laser did not improve vision in CRVO macular oedema. Prophylactic PRP is not recommended; treat promptly once neovascularisation appears (2 clock hours of iris NV or any angle NV).
SCORE	Intravitreal triamcinolone for vein-occlusion oedema?	In CRVO, triamcinolone 1 mg was better than observation. In BRVO, it was no better than grid laser and had more side effects.
BRAVO / CRUISE	Ranibizumab for vein-occlusion oedema?	Ranibizumab gave rapid and significant visual gain in both BRVO and CRVO.
HAWK / HARRIER Brolucizumab vs aflibercept in neovascular AMD	Can a longer-acting anti-VEGF match aflibercept?	Brolucizumab was non-inferior for vision with more 12-weekly dosing, but post-marketing reports of intraocular inflammation and occlusive retinal vasculitis limited its use.
TENAYA / LUCERNE Faricimab vs aflibercept in neovascular AMD	Does dual Ang-2/VEGF inhibition allow longer intervals?	Faricimab at up to 16-weekly intervals was non-inferior to aflibercept every 8 weeks, with a similar safety profile.
LEAVO Lucentis, Eylea, Avastin in central retinal vein occlusion	Is bevacizumab as good as ranibizumab or aflibercept for macular oedema in CRVO?	Aflibercept was non-inferior to ranibizumab, but bevacizumab was not shown to be non-inferior, although many patients still did well on it.

Vitreoretina, endophthalmitis and ROP

Trial	Question	Take-home message
EVS Endophthalmitis Vitrectomy Study	Immediate vitrectomy or tap-and-inject after cataract surgery? Systemic antibiotics?	Immediate vitrectomy helped only when vision was light perception. With hand movements or better, tap-and-inject was enough. Systemic antibiotics added no benefit.
Silicone Study	Which tamponade for PVR?	Silicone oil and C3F8 gas were similar to each other and both better than SF6.
CRYO-ROP	Does cryotherapy help threshold ROP?	Cryotherapy reduced unfavourable structural outcomes.
ETROP	Should we treat before threshold?	Treat type 1 (high-risk prethreshold) ROP; observe type 2.
BEAT-ROP	Intravitreal bevacizumab or laser?	Bevacizumab reduced recurrence in zone I stage 3+ disease, but not in zone II. Late reactivation and long-term systemic safety need follow-up.
PIVOT Pneumatic retinopexy vs vitrectomy	Is pneumatic retinopexy as good as vitrectomy for suitable primary retinal detachments?	Pneumatic retinopexy gave better vision at 1 year (about 5 letters) and less vertical metamorphopsia, at the cost of a lower primary reattachment rate (81% vs 93%); final reattachment was similar.
RAINBOW Ranibizumab vs laser for ROP	Is a single ranibizumab injection as good as laser for ROP?	Ranibizumab 0.2 mg succeeded in 80% vs 66% with laser at 24 weeks, with fewer unfavourable structural outcomes; the difference just missed statistical significance.

Cornea, infection and cataract

Trial	Question	Take-home message
HEDS Herpetic Eye Disease Study	What helps herpes simplex keratitis and iritis?	Topical steroids (with antiviral cover) reduced persistence and progression of stromal keratitis. Long-term oral acyclovir 400 mg twice daily significantly reduced recurrences of ocular HSV.
SCUT Steroids for Corneal Ulcers Trial	Do adjunctive topical steroids help bacterial keratitis?	No overall difference in vision at 3 months. Some severe, non-Nocardia ulcers may benefit.
MUTT I	Natamycin or voriconazole for filamentous fungal keratitis?	Natamycin was better, especially for Fusarium.
MUTT II	Does adding oral voriconazole help severe fungal ulcers?	No overall benefit.
ESCRS Endophthalmitis Study	Does intracameral cefuroxime prevent post-cataract endophthalmitis?	Intracameral cefuroxime reduced endophthalmitis about fivefold.

Neuro-ophthalmology

Trial	Question	Take-home message
ONTT Optic Neuritis Treatment Trial	Should optic neuritis be treated with steroids?	IV methylprednisolone sped recovery but did not change final vision. Oral prednisone alone (standard dose) increased recurrences and should be avoided. Brain MRI lesions were the strongest predictor of MS: the 15-year risk was about 25% with a normal MRI and about 72% with one or more lesions.
IONDT Ischemic Optic Neuropathy Decompression Trial	Does optic nerve sheath decompression help NAION?	No benefit, and possibly harm. Abandon it.
IIHTT Idiopathic Intracranial Hypertension Treatment Trial	Does acetazolamide help mild visual loss in IIH?	Acetazolamide plus diet gave a modest improvement in visual field, papilloedema and quality of life compared with diet alone.

Uvea and ocular oncology

Trial	Question	Take-home message
COMS Collaborative Ocular Melanoma Study	Plaque brachytherapy or enucleation for choroidal melanoma?	For medium tumours, survival was the same with either. For large tumours, radiation before enucleation added no survival benefit. See our COMS page.
MUST Multicenter Uveitis Steroid Treatment trial	Fluocinolone implant or systemic therapy for non-infectious intermediate, posterior and panuveitis?	Both worked. The implant caused more cataract and glaucoma, and long-term follow-up favoured systemic therapy for vision.
VISUAL I Adalimumab in active non-infectious uveitis	Does adalimumab reduce treatment failure in active uveitis?	Adalimumab roughly doubled the median time to treatment failure (24 vs 13 weeks) in active intermediate, posterior and panuveitis, leading to its approval as a steroid-sparing agent.
SYCAMORE Adalimumab plus methotrexate in JIA-associated uveitis	Does adding adalimumab help children whose uveitis is active despite methotrexate?	Treatment failure fell from 60% with placebo to 27% with adalimumab; the trial was stopped early for benefit.

Paediatrics and strabismus

Trial	Question	Take-home message
PEDIG ATS Amblyopia Treatment Studies	How much patching or atropine is needed?	For moderate amblyopia, 2 hours of daily patching was as effective as 6 hours. Weekend atropine was as effective as daily atropine. Patching and atropine gave similar results. See our amblyopia page.
IATS Infant Aphakia Treatment Study	Primary IOL or contact lens after unilateral infant cataract surgery (1–6 months of age)?	Visual outcomes were similar, but the IOL group had more adverse events and reoperations. Contact lens aphakia remains reasonable in young infants.
LAMP Low-Concentration Atropine for Myopia Progression	Which low-dose atropine concentration controls myopia best?	Of 0.01%, 0.025% and 0.05%, the 0.05% concentration was the most effective and still well tolerated.
CITT Convergence Insufficiency Treatment Trial	Which treatment works for convergence insufficiency?	Office-based vergence/accommodative therapy with home reinforcement was the most effective.
CHAMP Childhood Atropine for Myopia Progression	Does low-dose atropine slow myopia in US and European children?	Over 3 years, 0.01% atropine slowed both refractive progression and axial elongation versus placebo; 0.02% slowed axial elongation only. No serious side effects.

Viva tip: examiners rarely want the exact percentages. They want the clinical decision the trial changed. Always end your answer with "…so in practice, we now …".

This is a revision summary. Before quoting figures in a paper or presentation, please verify them against the primary publications.

Reading trials critically: biostatistics for ophthalmologists.

📘 Want more exam-ready material? See Ophthalmology Explorer on Kindle, or browse all my books.

Sources for trials added in November 2026

Garway-Heath DF, et al. Latanoprost for open-angle glaucoma (UKGTS). Lancet. 2015;385:1295-1304
Elman MJ, et al; DRCR.net. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for DME (Protocol I). Ophthalmology. 2010;117:1064-1077
Maturi RK, et al; DRCR Retina Network. Four-year visual outcomes in the Protocol W randomized trial of intravitreous aflibercept for prevention of vision-threatening complications of diabetic retinopathy. JAMA. 2023;329:376-385
Dugel PU, et al. HAWK and HARRIER: phase 3 trials of brolucizumab for neovascular AMD. Ophthalmology. 2020;127:72-84
Heier JS, et al. Efficacy, durability and safety of faricimab in neovascular AMD (TENAYA and LUCERNE). Lancet. 2022;399:729-740
Hykin P, et al. Effect of intravitreal aflibercept, bevacizumab or ranibizumab on visual acuity in CRVO with macular oedema (LEAVO). JAMA Ophthalmol. 2019;137:1256-1264
Hillier RJ, et al. The Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT). Ophthalmology. 2019;126:531-539
Stahl A, et al. Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW). Lancet. 2019;394:1551-1559
Jaffe GJ, et al. Adalimumab in patients with active noninfectious uveitis (VISUAL I). N Engl J Med. 2016;375:932-943
Ramanan AV, et al. Adalimumab plus methotrexate for uveitis in juvenile idiopathic arthritis (SYCAMORE). N Engl J Med. 2017;376:1637-1646
Zadnik K, et al. Safety and efficacy of 0.01% and 0.02% atropine for the treatment of pediatric myopia progression over 3 years (CHAMP). JAMA Ophthalmol. 2023;141:990-999
Christakis PG, et al. The Ahmed Versus Baerveldt study: five-year treatment outcomes. Ophthalmology. 2016;123:2093-2102; Budenz DL, et al. Five-year treatment outcomes in the Ahmed Baerveldt Comparison study. Ophthalmology. 2015;122:308-316

Written and medically reviewed by Dr. Dhaval Patel, MD (Ophthalmology, AIIMS New Delhi) · Editorial policy

Consultant, Cataract & Refractive Surgery — among a small number of AIIMS-trained ophthalmologists practicing in Gujarat. Read full credentials & experience or view his 28 publications on ResearchGate.

📚 Also the author of OKAT Decoded, FRCOphth Decoded and other high-yield ophthalmology exam-prep books used by residents and PG aspirants.

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