Landmark Trials in Ophthalmology

Shawn Lin MD, Benjamin Lin MD

Many high-quality trials have been published in the field of Ophthalmology. Their findings drive our everyday practice, and their conclusions are important to know for OKAPs and the boards. Here, we have assembled a listing of all major clinical trials in a consistent, easy-to-read tabular format.

PubMed references are available for each one at the bottom of the page.

Let us know if you have suggestions for additional trials to include in this page!

Cornea

HEDS (1994)

Herpetic Eye Disease Study

The HEDS trial had 5 main study arms spread across 2 studies (HEDS1 and HEDS2). Below is an organized table of the results:

HEDS 1 (1989)
Disease Entity	Study Groups	Result	Primary Conclusion
Stromal Keratitis (HEDS-SKS) 104 patients with stromal keratitis	10 week oral ACV (Acyclovir) 400mg 5x / day vs. placebo (topical steroids / trifluridine given to both groups)	Oral ACV for stromal keratitis did not improve treatment failures, time to resolution or 6 month BCVA	Oral ACV not useful as adjunctive therapy for stromal keratitis
Stromal Keratitis (HEDS-SKN) 106 patients with stromal keratitis	10 week topical prednisolone taper vs. placebo (trifluridine initial QID then taper given to both groups)	Decreased persistent / progressive stromal keratitis by 68% and shorted duration of keratitis	Topical steroids useful in treatment of stromal keratitis
Iridocyclitis (HEDS-IRT) 50 patients with HSV iritis	10 week ACV 400mg PO 5x / day vs. placebo (topical corticosteroids and trifluridine given to both groups)	Trial stopped due to slow enrollment. Of the collected data, treatment failure lower in ACV group (50%) vs placebo (68%)	No statistical significance but trend suggests possible benefit for oral ACV for Herpes iridocyclitis
HEDS 2 (1992)
Disease Entity	Comparison	Result	Conclusion
Progression from Epithelial Keratitis to Stromal Keratitis / Iritis (HEDS-EKT)287 patients with epithelial keratitis	3 week ACV 400mg 5x / day vs. placebo (topical trifluridine given to both groups)	Rates of stromal keratitis or iritis were 11% in ACV group and 10% in placebo group	For epithelial keratitis, a 3-week course of oral ACV has no apparent benefit in preventing progression to stromal disease or iritis
Recurrent Ocular HSV (HEDS-APT)703 patients with inactive disease and off medications	12 month ACV 400mg BID vs. placebo	Oral ACV reduced recurrent ocular disease (19% recurrence in ACV group vs. 32% in placebo group)	Oral ACV significantly reduces risk of recurrent disease (by approx 50%), recommend long-term prophylaxis (esp. for recurrent stromal keratitis)
Recurrent Ocular HSV risk factors (HEDS-RFS)2 populations of 308 and 346 patients who had experienced HSV eye disease in the past year	No association between stress, systemic infection, sunlight exposure, menstruation, contact lens wear, eye injury and ocular HSV recurrence. History of HSV epithelial keratitis does NOT predict future recurrence of epithelial keratitis History of HSV stromal keratitis DOES increase risk of recurrence of stromal keratitis.

SCUT (2006)

Steroids for Corneal Ulcers

“To determine whether there is a benefit in clinical outcomes with the use of topical corticosteroids as adjunctive therapy in the treatment of bacterial corneal ulcers.”

Disease Entity	Comparison	Result	Conclusion
Bacterial corneal ulcers 500 patients with culture-positive corneal ulcers	Patients received prednisolone 1% as adjunctive therapy vs. placebo (moxifloxacin given to all patients for 48 hours prior to randomization)	With treatment, no significant differences in infiltrate / scar size, time to reepithelization or corneal perforation. Subgroup: Patients with vision of count fingers or worse had better visual acuity (~2-3 Snellen chart lines) with corticosteroids (p=0.03), along with patients with completely central corneal ulcers (p=0.02).	No difference in 3 month BSCVA and no safety concerns with adjunctive corticosteroid therapy for bacterial ulcers. Subgroup: Patients with CF or worse vision had significantly better visual acuity at 3 months, along with those with completely central corneal ulcers.

CDS (2013)

Corneal Donor Study

“To determine whether the 10-year success rate of penetrating keratoplasty for corneal endothelial disorders is associated with donor age.”

Disease Entity

Study Group

Result

Conclusion

Patients undergoing corneal transplantation for Fuchs, Pseudophakic corneal edema, and other endothelial dystrophies

1090 patients

Donor age range:
12 to 75 yo

Endothelial cell density:
2300 to 3300 cells / mm2

Subjects observed for 10 years

10 year survival: 77% in 12-65 yo donor group vs. 71% in 66-75 yo donor group (p=0.11)

Analyzed as a continuous variable, higher donor age was associated with lower graft success beyond 5 years (p<0.001)

There was no significant difference in 10 years success rates comparing donors aged 12 to 65 yo with those aged 66 to 75 yo.

However, there was evidence of donor age effect at the extremes of the age range.

Retina

AREDS (2001)

AMD Vitamins

“To evaluate the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on AMD progression and visual acuity.”

AREDS Study Grading System

Stage	Findings
No AMD	No drusen or <5 small drusen (<63 um)
Early	Many small drusen (<63 um) or few medium-sized drusen (63-125 um)
Intermediate	Many medium-sized drusen (63-125 um) or at least 1 large drusen (>125 um)
Advanced	Wet AMD or center involving geographic atrophy
Estimating drusen size: remember that 125 um is approximately equal to the diameter of the superior and inferior vascular arcades.

Disease Entity

Study Groups

Result

Conclusion

Age-related macular degeneration

4757 Patients

1) Vitamin A, C, E, Beta-carotene and Zinc

2) Zinc alone

3) Antioxidants alone

4) Placebo

1) Reduced risk of advanced AMD by 25%, reduced vision loss by 19%

2) Reduced risk of advanced AMD by 21%, reduced vision loss by 11%

3) Reduced risk of advanced AMD by 17%, reduced vision loss by 10%
Vs. Placebo

AREDS vitamins are useful in reducing vision loss in high-risk AMD (Intermediate with many medium drusen or at least 1 large drusen).

Caution in smokers with high dose beta-carotene due to increased risk of lung cancer
Treatment no benefit in patients with no AMD or early AMD (small / intermediate drusen)

AREDS2 (2013)

AMD Vitamins

The concern with AREDS1 were genitourinary tract side effects with zinc and increased risk of cancer in current / former smokers with beta-carotene. Thus the AREDs trial looked at adjusting the formulation of the vitamin. The AREDS2 formulation is most commonly found in the supplements on the market today.

“To determine whether adding lutein + zeaxanthin, DHA + EPA, or both to the AREDS formulation decreases the risk of developing advanced AMD and to evaluate the effect of eliminating beta carotene, lowering zinc doses, or both in the AREDS formulation.”

Disease Entity

Study Groups

Result

Conclusion

Age-related macular degeneration

4203 Patients

1) Vitamin A, C, E, Lutein / Zeaxanthin

2) Vitamin A, C, E, DHA + EPA

3) Vitamin A, C, E, Lutein / Zeaxanthin + DHA + EPA (Omega 3 fatty acids)

4) Placebo

Cartenoids lutein and zeaxanthin are safe alternative to beta-carotene, and may even work better.

Omega-3 fatty acids did not enhance outcomes.

Lowering zinc did not lead to statistically significant worsening, and likely lowers incidence of side effects.

AREDS2 formulation:
Vitamin E (400IU)
Vitamin C (500mg)
Lutein (10mg)
Zeaxanthin (2mg)
Zinc (25-80mg)
Copper 2mg
Examples:
PreserVision
ActiveEyes
Pro-Optic

MARINA (2006)

AMD Lucentis Efficacy

Disease Entity

Study Groups

Result

Conclusion

Age-related macular degeneration patients with minimally classic and occult CNV (wet AMD)

716 Patients

1) 0.3 mg monthly
Ranibizumab

2) 0.5 mg monthly Ranibizumab

3) Sham injection monthly

1) 15+ letter improvement in 24.8% of 0.3mg group, mean increase 6.5 letters.

2) 15+ letter improvement in 33.8% of 0.3mg group, mean increase 7.2 letters.

3) 15+ letter improvement in 5.0% of sham injection group, mean decrease 10.4 letters.

Ranibizumab prevented vision loss and improved visual acuity in patients with minimally classic and occult CNV

ANCHOR (2009)

AMD Lucentis vs. PDT

Disease Entity	Study Groups	Result	Conclusion
Age-related macular degeneration patients with classic CNV (wet AMD) 423 Patients	1) Verteporfin PDT plus monthly sham injection 2) Sham verteporfin PDT plus monthly 0.3mg or 0.5mg ranibizumab	1) 65.7% lost <15 letters, 6.3% gained >15 letters 2) 90% lost <15 letters, 34-41% gained >15 letters	Ranibizumab of greater clinical benefit than verteporfin PDT in patients with AMD with classic CNV

BRAVO (2010)

BRVO Lucentis Efficacy

Disease Entity

Study Groups

Result

Conclusion

Macular edema secondary to branch retinal vein occlusion (BRVO)

397 Patients

1) 0.3mg monthly Ranibizumab

2) 0.5mg monthly Ranibizumab

3) Sham injection monthly

1) 55.2% gained >15 letters. 67.9% with 20/40 or better vision.

2) 61.1% gained >15 letters. 64.9% with 20/40 or better vision.

3) 28.8% gained > 15 letters. 41.7% with 20/40 or better vision.

Ranibizumab leads to rapid improvement in 6 month visual acuity and macular edema following BRVO

CRUISE (2010)

CRVO Lucentis Efficacy

Disease Entity

Study Groups

Result

Conclusion

Macular edema secondary to central retinal vein occlusion (CRVO)

392 Patients

1) 0.3mg monthly Ranibizumab

2) 0.5mg monthly Ranibizumab

3) Sham injection monthly

1) 46.2% gained >15 letters. 43.9% with 20/40 or better vision.

2) 47.7% gained >15 letters. 46.9% with 20/40 or better vision.

3) 16.9% gained > 15 letters. 20.8% with 20/40 or better vision.

Ranibizumab leads to rapid improvement in 6 month visual acuity and macular edema following CRVO

BVOS (1984)

BRVO PRP Laser Efficacy

Disease Entity	Study Groups	Result	Conclusion
Macular edema secondary to central retinal vein occlusion (BRVO) 139 Patients	1) Grid argon laser photocoagulation 2) Control	1) Treated eyes +6.7 letters. 2) Untreated eyes +1 letter	Perform PRP for >5 disc diameters of nonperfusion IF neovascularization develops. Treatment decreases risk of neovascularization and vitreous hemorrhage

CVOS (1995)

CRVO Prophylactic PRP Efficacy

Disease Entity	Study Groups	Result	Conclusion
Central retinal vein occlusion (CRVO) 181 Eyes	1) Immediate prophylactic PRP 2) Frequent close observation with PRP if NVI / NVA	1) No statistically significant difference between NVI / NVA development in prophylactically treated and untreated eyes. 2) When NVI / NVA did develop, better regression with PRP in untreated eyes (56%) vs. prophylactically treated eyes (22%). 3) NVI / NVA correlated with the amount of nonperfused retina and hemorrhage.	Prophylactic PRP does not prevent NVI / NVA, and prompt regression is more likely in untreated eyes. Recommend careful observation with frequent follow up, and prompt PRP of eyes in which NVI / NVA develops.

DCCT (1995)

Diabetic Retinopathy A1C Management

Disease Entity

Study Groups

Result

Conclusion

Diabetic Retinopathy and Macular Edema in Type 1 Diabetics

1441 patients with type 1 diabetes

1) Conventional treatment group (1-2 daily insulin injections, daily blood glucose, quarterly clinic visits)

2) Intensive treatment group (3+ daily insulin injections, pump, monitoring and frequent MD, NP, or dietary monitoring)

Progression of diabetic retinopathy
Absolute risk per 100 patient years

A1C 11.0 – 12.69
A1C 7.0 – 1.17
A1C 6.0 – 0.52
Continued reduction in risk with decrease in A1C

Intensive treatment 10 times more effective than conventional.

Reduction of progression risk continues to decrease with lower A1Cs, and must be weighed against the threefold increase in risk of severe hypoglycemia.

10% lower A1C (8 vs 7.2%) associated with ~43% lower risk of progression

UKPDS (2001)

Diabetic Retinopathy A1C Management

Disease Entity

Study Groups

Result

Conclusion

Diabetic Retinopathy and Macular Edema in Type 2 Diabetics

5357 patients with newly diagnosed type 2 diabetes

1) Conventional control BS / BP, mean A1C 7.9%, BP 154/87

2) Tight control of BS / BP, mean A1C 7.0%, BP 144/82

8-fold relative progression reduction with A1C <6.2 vs. >7.5

2.5-fold relative incidence reduction with A1C <6.2 vs. >7.5

2.8-fold relative incidence reduction with systolic BP<125 vs. >140

Smoking associated with reduced risk of retinopathy with current smokers relative incidence risk of 0.63 and progression risk of 0.50

Blood sugar and blood pressure reduction are both beneficial to reducing the incidence and progression of diabetic retinopathy.

The reduction of incidence and progression risk from smoking could be accounted for by lower blood pressure, or due to pharmacological effect of nicotine, but does not justify advising smoking in patients with retinopathy.

ETDRS (1991)

Diabetic Retinopathy Grading and Photocoagulation

Disease Entity	Study Groups	Result	Conclusion
Diabetic Macular Edema 3711 patients with mild to severe NPDR or early PDR	1) One eye early photocoagulation 2) Other eye deferred photocoagulation, photocoagulated if high risk proliferative retinopathy detected	Early photocoagulation associated with small reduction in incidence of severe visual loss at 5 years (2.6% vs 3.7%). Focal photocoagulation effective in reducing visual loss for macular edema but scatter photocoagulation is not.	Focal laser decreases vision loss from macular edema. In addition, ETDRS defined the grading of NPDR and PDR which is still used to this day! CSME was also defined, but is less widely used today with the advent of OCT

DRS (1981)

Diabetic Retinopathy PRP Efficacy

Disease Entity	Study Groups	Result	Conclusion
Diabetic Retinopathy and Macular Edema in Type 2 Diabetics 1727 patients with severe NPDR in both eyes or PDR in at least 1 eye	1) One eye scatter photocoagulation 2) Other eye no treatment	Photocoagulation reduces risk of severe visual loss by 50%+ Decreases of visual acuity of one or more lines and constriction of peripheral visual fields also observed.	Perform PRP for patients with high-risk PDR. The two year risk of severe visual loss without treatment outweighs the risk of harmful treatment effects for two groups of eyes: 1) New preretinal hemorrhage or VH 2) New NVD / NVE / NVI

DRVS (1990)

Diabetic Retinopathy Vitreous Hemorrhage

Disease Entity

Study Groups

Result

Conclusion

Diabetic Retinopathy and Vitreous Hemorrhage in Type 1 and 2 diabetics

1) Observation

2) Early vs delayed surgery with neovascularization or fibrovascular proliferation

3) Early vs delayed surgery with severe DR and vitreous hemorrhage within 6 months

Early vitrectomy increased chance of 20/40 vision from 12% to 36% in type 1 diabetics.

No advantage seen for type 2 diabetics.

Early vitrectomy for nonclearing vitreous hemorrhage (at least 1 month) is helpful in type 1 diabetics and monocular patients.

EDIC (1999)

Diabetic Retinopathy A1C Management

Disease Entity	Study Groups	Result	Conclusion
Diabetic Retinopathy and Macular Edema follow up of DCCT study 1208 patients from DCCT followed for an additional 4 years	1) Conventional treatment group (1-2 daily insulin injections, daily blood glucose, quarterly clinic visits) 2) Intensive treatment group (3+ daily insulin injections, pump, monitoring and frequent MD, NP, or dietary monitoring)	Intensive therapy resulted in: 75% decreased progression of retinopathy 58% decreased macular edema 52% decreased need for laser treatment	Tight blood sugar control is useful long term for decreasing progression of retinopathy

EVS (1999)

Endophthalmitis Vitrectomy Study

Disease Entity

Study Groups

Result

Conclusion.

Post-operative endophthalmitis

420 patients with post-operative endophthalmitis (cataract or secondary IOL)

1) Vitrectomy with systemic antibiotics

2) Vitrectomy without systemic antibiotics

3) Tap / Inject with systemic antibiotics

4) Tap / Inject without systemic antibiotics

No difference in final visual acuity with or without systemic antibiotics

In patients with VA HM or better, no difference between vitrectomy and tap / inject.

In subgroup with LP or worse vision, vitrectomy had 3-fold increase in achieving 20/40 or better acuity

Intravenous antibiotics do not add benefit once already injected with intravenous antibiotics

Immediate vitrectomy only beneficial for LP vision or worse on presentation

69% with positive cultures, 94% gram positive (70% coagulase-negative Staph, 10% Staph Aureus, 9% Strep)

DRCR T (2016)

DRCR.net Protocol T: Avastin vs. Lucentis vs. Eylea for Diabetic Macular Edema

To compare relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema.

Disease Entity

Study Groups

Result

Conclusion

Diabetic macular edema involving the macular center

660 patients

1) Avastin 1.25mg

2) Lucentis 0.3mg

3) Eylea 2.0mg

Thus far, no statistical difference in the 3 drugs in mild vision loss (20/32 to 20/40).

Subgroup 20/50 or worse::
At 1 year:
Eylea significantly better than Avastin AND Lucentis (p

At 2 years:
Eylea significantly better vision than Avastin ( but not Lucentis)

In eye 20/50 or worse, Eylea has some advantages over Avastin (year 1 and 2) and Lucentis (year 1).
Half as many injections were needed in year 2 compared with year 1

Glaucoma

AGIS (1994)

Advanced Glaucoma Intervention Study – Trab vs. Laser

“To present for black and white patients with medically uncontrolled glaucoma 10-year results of treatment with 1 of 2 randomly assigned surgical intervention sequences.”

Disease Entity

Study Groups

Result

Conclusion

Medically uncontrolled glaucoma

451 black patients
249 white patients

Randomly assigned to 1 of 2 sequences:

1) ATT – ALT, trab, trab

2) TAT – Trab, ALT, trab

In black patients, VF loss was decreased with ATT sequence

In white patients, VF loss was decreased with TAT sequence

This effect was sustained through a 10 year follow up

IOP lowered in both sequences in black and white patients

Long term visual function outcomes better for:
ATT – black patients
TAT – white patients

GLT (1995)

Glaucoma Laser Trial – ALT vs. Meds

“To determine differences between the two treatment groups (ALT vs. topical medication) of the Glaucoma Laser Trial with respect to intraocular pressure, visual fields, optic disk cupping, and therapy for primary open-angle glaucoma.”

Disease Entity	Study Groups	Result	Conclusion
Newly diagnosed primary open angle glaucoma 271 patients	1) Topical medication 2) Argon laser trabeculoplasty	Eyes treated initially with argon laser trabeculoplasty had lower IOP and better VF / optic disc status 1.2 mm Hg greater IOP reduction in ALT group 0.6dB better VF in ALT group	Initial treatment with argon laser trabeculoplasty was at least as efficacious as initial treatment with topical medication

CNTGS (1999)

Collaborative NTG Study – 30% IOP reduction vs. Observation

“To determine if intraocular pressure plays a part in the pathogenic process of normal-tension glaucoma.”

Disease Entity

Study Groups

Result

Conclusion

Normal tension glaucoma

140 patients

All enrolled patients met criteria for normal-tension glaucoma. They were randomized into two groups:

1) Reduction of IOP by 30% or more

2) Observation

Progression of optic disc or visual field loss (p<0.0001):

1. Reduced IOP group: 12%

2. Control group: 35%

IOP lowering therapy beneficial in normal-tension glaucoma patients at risk for disease progression.

Lowering IOP by 30% reduced rate of VF loss in NTG from 35% to 12%

CIGTS (2001)

Collaborative Initial Glaucoma Treatment Study – Trab vs. Observation

“To determine whether patients with newly diagnosed open angle glaucoma are better treated by initial treatment with medications or immediate filtration surgery.”

Disease Entity

Study Groups

Result

Conclusion

Newly diagnosed open angle glaucoma

607 patients

1) Medications, stepped regimen

2) Immediate trabeculectomy

At 5 year follow up, VF loss did not differ significantly between the groups

Surgical patients had a greater risk of substantial visual acuity loss compared with medical patients

Rate of cataract formation greater in surgical group

Average IOP:
Medical: 17-18
Surgical: 14-15

Both medical and surgical groups result in about the same VF outcome after 9 years of follow up

In patients with advanced VF loss at baseline, initial surgery led to less VF progression than initial medication regimen

Subjects with diabetes had more VF loss over time if treated initially with surgery.

EMGT (2002)

Early Manifest Glaucoma Trial – POAG laser and meds vs. Observation

To determine the effect of IOP reduction in early previously untreated open angle glaucoma

Disease Entity

Study Groups

Result

Conclusion.

Early open angle glaucoma

255 patients

1) Treatment with laser trabeculoplasty and topical betaxolol BID

2) Observation

Treatment reduced IOP by 5% or 25%

Progression:
1) Treatment: 45%
2) Controls: 62%

Treatment group progression occurred significantly later

First adequately powered randomized trial to demonstrate benefit to IOP reduction in open angle glaucoma patients

Every 1mm Hg lower IOP reduced chance of progression by 10%

OHTS (2002)

Ocular Hypertension Treatment Study – 20% IOP reduction vs. Observation

“To determine the safety and efficacy of topical ocular hypotensive medication in delaying or preventing the onset of primary open angle glaucoma in patients with no evidence of glaucoma at enrollment.”

Disease Entity

Study Groups

Result

Conclusion

High IOP without evidence of glaucomatous damage

1636 patients

All enrolled patients with IOP 24-32 in one eye and between 21 and 32 in other eye.
1) Reduction if IOP by 20% or more
2) Observation

Treatment reduced IOP by 22.5%

Glaucoma Incidence at 5 years:
1) Treatment: 4.4%
2) Controls: 9.5%Minimal systemic or ocular risk in treatment group

Topical ocular hypotensive medication effective in delaying or preventing onset of POAG in individuals with elevated IOP

Decrease in IOP of 22.5% decreased glaucoma incidence by 50% from 9.5% to 4.4%

Thinner CCT identified as strongest predictor for glaucoma.

AVB (2011)

Ahmed vs. Baerveldt Study

“To compare 2 commonly used aqueous drainage devices for the treatment of refractory glaucoma.”

Disease Entity

Study Groups

Result

Conclusion

Uncontrolled or high-risk glaucoma refractory to maximal medical therapy.

Patients with previous trab or tube included.

238 patients

Randomized into two groups:

1) Ahmed-FP7

2) Baerveldt-350

At 3 years

Failure Rate:
51% Ahmed vs. 34% Baerveldt (p=0.03)

IOP:
15.7 Ahmed vs. 14.4 Baerveldt (p=0.09)

# Glaucoma meds:
1.8 Ahmed vs. 1.1 Baerveldt (p=0.002)

Complication rate:
52% Ahmed, 62% Baerveldt (p=0.12)

Both devices effective at lowering IOP.
Baerveldt group had lower failure rate and required fewer medications, but it experienced more hypotony-related vision-threatening complications.

TVT (2012)

Tube vs. Trab Study

“The Tube Versus Trabeculectomy (TVT) Study will compare the safety and efficacy of nonvalved tube shunt surgery to trabeculectomy with mitomycin C in patients with previous intraocular surgery.”

Disease Entity

Study Groups

Result

Conclusion

Uncontrolled glaucoma with IOP>18 on maximum tolerated medical therapy.

Patients with previous trab or cataract surgery included.

212 patients

Randomized into two groups:

1) Trabeculectomy with mitomycin C

2) Tube shunt implant (350mm Baerveldt)

At 5 years:

IOP reduction:
14.4 in tube group vs. 12.6 in trab group (p=0.12)

Failure probability: 29.8% in tube group vs 46.9% in trab group (p=0.002)

Rate of reoperation:
9% in tube group vs 29% in trab group.

Tube has higher success rate compared to trabeculectomy during 5 years of follow-up in TVT study. IOP reduction was similar.

More frequent reoperations after trab than with tube (though this is confounded as re-op after failed trab (tube, or repeat trab) may be less complex than re-op after failed tube (additional tube vs. CPC)

UKGTS (2013)

Latanoprost vs. Placebo

“The UKGTS is the first randomized, placebo-controlled trial to evaluate the efficacy of medical treatment in reducing VF deterioration in OAG.”

Disease Entity

Study Groups

Result

Conclusion

Newly diagnosed primary open angle glaucoma.

516 patients

Randomized into two groups:

1) Prostaglandin Analog (ie Latanoprost)

2) Placebo

Visual field preservation hazard ratio:
0.44 in Latanoprost group vs. 1 in placebo group

IOP lowering effect:
3.8mm Hg in Latanoprost group vs. 0.9mm Hg in placebo group.

First randomised placebo-controlled trial to demonstrate preservation of visual field with IOP lowering drug in patients with open-angle glaucoma

Neuro-ophthalmology

IONDT (1998)

Ischemic Optic Neuropathy Decompression Trial

“To assess the safety and efficacy of optic nerve decompression surgery compared with careful follow-up alone in patients with nonarteritic anterior ischemic optic neuropathy (NAION).”

Disease Entity	Study Groups	Result	Conclusion.
Nonarteritic Ischmic Optic neuropathy (NAION) with VA 20/64 or worse 244 patients	1. Optic nerve decompression surgery 2. Observation	Gain of 3+ lines: 32.6% of surgical group vs. 42.7% of observation group Loss of 3+ lines: 23.9% in surgical group vs. 12.4% in observation group	Optic nerve decompression surgery for NAION is not effective, may be harmful, and should be abandoned. The spontaneous improvement rate is better than previously reported. The 5-year risk of contralateral involvement in patients with NAION is 14.7%

CRASH (2005)

Corticosteroid Randomization After Significant Head Injury

“MRC CRASH is a randomised controlled trial (ISRCTN74459797) of the effect of corticosteroids on death and disability after head injury. “

Disease Entity	Study Groups	Result	Conclusion
Head injury and a Glasgow Coma Scale of 14 or less 10,008 patients	1. 48h infusion of methylprednisolone 2. Observation	Risk of death: 25.7% in corticosteroids group vs. 22.3% in observation group Risk of death or severe disability: 38.1% in corticosteroids group vs. 36.3% in observation group	Corticosteroids should not be used routinely in the treatment of head injury. Often, traumatic head injury is coincident with traumatic optic neuropathy (TON). Given the lack of clinical efficacy for TON and the risk of harm, steroids should not be used in these cases.

ONTT (2008)

Optic Neuritis Treatment Trial

“To determine the efficacy of corticosteroids as treatment for acute demyelinative optic neuritis. To assess the risk of developing multiple sclerosis (MS) after optic neuritis and the factors predictive of high and low risk.”

Disease Entity

Study Groups

Result

Conclusion

Acute optic neuritis treatment and follow up for development of multiple sclerosis over 15 years.

389 patients

1. IV 3-day course of methylprednisolone 250mg q6h followed by oral prednisone 1mg/kg/day for 2 weeks

2. Oral prednisone 1mg/kg/day for 2 weeks

3. Oral placebo

Visual recovery:
IV group experienced accelerated visual recovery at 2 weeks. Neither treatment improved final visual outcome

Recurrence:
Oral prednisone alone resulted in increased rate of recurrence!

MS risk at 15 years:
Overall: 50%
No MRI lesions: 25%
1+ MRI lesion: 72%

Protective features:
Male gender
Optic disc swelling
Absence of pain

IV steroids accelerate visual recovery but do not change final visual outcome.

Oral steroids result in INCREASED rate of recurrent optic neuritis.

MRI lesions at the time of attack are a strong predictor of 15-year MS risk.

IIHTT (2014)

Idiopathic Intracranial Hypertension Treatment Trial

“To determine whether acetazolamide is beneficial in improving vision when added to a low-sodium weight reduction diet in patients with IIH and mild visual loss.”

Disease Entity

Study Groups

Result

Conclusion

Intracranial hypertension and mild visual loss who recieved a low-sodium weight reduction diet

165 patients

1. Acetazolamide group (maximally tolerated up to 4 grams / day) for 6 months

2. Placebo group

Primary outcome was change in perimetric mean deviation (PMD) on Humphrey 24-2.

PMD improvement 1.43 Acetazmolade vs. 0.71 Placebo
(p=0.5)

Papilledema grade
-1.31 Acetazolamide vs -0.70 Placebo

NEI Quality of life survey VFQ-25:
8.33

In patients with IIH and mild visual loss, the use of acetazolamide with a low-sodium weight-reduction diet compared with diet alone resulted in modest improvement in visual field function.

Pediatrics

PEDIG (2002)

Pediatric Eye Disease Investigative Group (Amblyopia)

To compare patching and atropine as treatments for moderate amblyopia in children younger than 7 years.

Disease Entity	Study Groups	Result	Conclusion
Amblyopia with visual acuity from 20/40 to 20/100 419 patients (3-7yo) 507 patients (7-17yo)	3-7yo group: 1. Patching 2. Atropine 7-17yo group: 1. Patching + atropine 2. Optical correction alone	3-7yo group: Visual Acuity Improvement: 3.16 in patching group vs. 2.84 in atropine group 7-17yo group: Patching and near vision exercise can improve visual acuity from 7-12 yo even if previously treated. This is less effective for the 13-17yo age group.	Atropine and patching produce improvement of similar magnitude, and both are appropriate modalities for the initial treatment of moderate amblyopia in children aged 3 to less than 7 years. For kids 7-12 yo, a combined program of patching and near vision exercise can improve visual acuity. This technique is less effective in age 13-17 year olds

Infant Aphakia (2010)

Infant Aphakia Treatment Study

To compare the visual outcomes and adverse events of contact lens to primary intraocular lens (IOL) correction of monocular aphakia during infancy.

Disease Entity	Study Groups	Result	Conclusion
Unilateral congenital cataract underoing cataract surgery between 1 to 6 months of age. 114 patients	1. IOL implantation 2. Contact lens correction	Median logMAR: 0.80 in contact lens group vs. 0.97 in IOL group (p=0.20) Additional surgeries: 12% in contact lens group vs. 63% in IOL group	Until longer term follow-up data are available, caution should be exercised when performing IOL implantation in children 6 months of age or younger given the higher incidence of adverse events and the absence of an improved short-term visual outcome compared to contact lens use.

Uveitis

SITE (1995)

Systemic Immunosuppressive Therapy and Malignancy

To compare the occurrence of malignancy in patients with severe ocular inflammatory disease treated with systemic corticosteroids alone or with systemic immunosuppressive drugs with or without systemic corticosteroids.

Disease Entity	Study Groups	Result	Conclusion
Ocular inflammatory disease treated with systemic steroids or immunosuppressive chemotherapy (retrospective cohort study) 543 patients	1. Systemic immunosuppressives +/- corticosteroids 2. Systemic corticosteroids alone	The rate of malignancy in the immunosuppressant group was not significantly different from the rate in the corticosteroids alone group (p>0.90)	These findings do not support the hypothesis of an increased risk of malignancy in patients with severe ocular inflammatory disease who are treated with systemic immunosuppressive agents compared with patients treated with systemic corticosteroids.

MUST (2011)

Multicenter Uveitis Steroid Treatment

To compare the relative effectiveness of systemic corticosteroids plus immunosuppression when indicated (systemic therapy) versus fluocinolone acetonide implant (implant therapy) for noninfectious intermediate, posterior, or panuveitis (uveitis).

Disease Entity

Study Groups

Result

Conclusion

Active or recently active uveitis
255 patients

1. Systemic corticosteroids

2. Retisert Implant (fluocinolone acetonide)

Change in BCVA:
+6.0 letters in implant vs. +3.2 letters in systemic groups
(p=0.16)

Vision related quality of life:
+11.4 implant vs. +6.8 systemic (p=0.43)

Residual active uveitis:
12% implant vs. 29% systemic group (p=0.001)

Cataract surgery:
3.3 Hazard ratio in implant-eyes over 2 years (p=0.0001)

Glaucoma:
4.2 Hazard ratio (p=0.0008)

Systemic Infections:
0.6 / person-year systemic group vs. 0.36 / person-year implant group

Both treatments improve visual acuity, and the specific advantages and disadvantages should dictate selection between treatments on a case by case basis.

4 Responses...

Tung Hoang says:
June 9, 2018 at 12:53 pm
Terrific! Thank you for this great work.
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Ankur Mehta says:
February 18, 2021 at 10:56 am
I think you should consider adding the Eagle study in the glaucoma section
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Jacob Wanon says:
March 15, 2022 at 11:11 am
Is there a PDF form to print this fantastic summary ?
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shannon mike says:
April 28, 2023 at 7:49 pm
Cured from herpes with the herbal medicine from,.. R o b i n sonbu ckler11 ( @ ) gmail. com,
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Cornea

HEDS (1994)

SCUT (2006)

CDS (2013)

Retina

AREDS (2001)

AREDS2 (2013)

MARINA (2006)

ANCHOR (2009)

BRAVO (2010)

CRUISE (2010)

BVOS (1984)

CVOS (1995)

DCCT (1995)

UKPDS (2001)

ETDRS (1991)

DRS (1981)

DRVS (1990)

EDIC (1999)

EVS (1999)

DRCR T (2016)

Glaucoma

AGIS (1994)

GLT (1995)

CNTGS (1999)

CIGTS (2001)

EMGT (2002)

OHTS (2002)

AVB (2011)

TVT (2012)

UKGTS (2013)

Neuro-ophthalmology

IONDT (1998)

CRASH (2005)

ONTT (2008)

IIHTT (2014)

Pediatrics

PEDIG (2002)

Infant Aphakia (2010)

Uveitis

SITE (1995)

MUST (2011)

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