Landmark Trials in Ophthalmology: High-Yield Summary
Last updated: October 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. |
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. |
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. |
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. |
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. |
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. |
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.
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