EVIDENCE BASED OPHTHALMOLOGY

LANDMARK TRIALS IN OPHTHALMOLOGY

CORNEA
HEDS (1994) – Herpetic Eye Disease Study

The HEDS trial had 5 main study arms spread across 2 studies (HEDS1 and HEDS2).

HEDS 1 (1994-1997)

Disease Entity Study Groups Result Primary Conclusion

Stromal Keratitis 10-week oral ACV
(HEDS-SKN) (Acyclovir) 400mg 5x / day
104 patients with stromal vs. placebo
keratitis
(topical steroids /
trifluridine given to both
groups)
Oral ACV for stromal Oral ACV not useful as adjunctive
keratitis did not improve therapy for stromal keratitis
treatment failures, time to
resolution or 6-month
BCVA

Stromal Keratitis 10-week topical Decreased persistent / Topical steroids useful in

(HEDS-SKS) prednisolone taper vs. progressive stromal treatment of stromal keratitis
106 patients with stromal placebo keratitis by 68% and
keratitis shorted duration of
(trifluridine initial QID then
keratitis
taper given to both groups)

Iridocyclitis 10-week ACV 400mg PO 5x
(HEDS-IRT) / day vs. placebo (topical
50 patients with HSV iritis corticosteroids and
trifluridine given to both
groups)
Trial stopped due to slow No statistical significance but
enrollment. Of the trend suggests possible benefit
collected data, treatment for oral ACV for Herpes
failure lower in ACV group iridocyclitis
(50%) vs placebo (68%)

HEDS 2 (1997-2001)

Disease Entity Comparison Result Conclusion

Progression from 3-week ACV 400mg 5x / day Rates of stromal keratitis or For epithelial keratitis, a 3-week
Epithelial Keratitis to vs. placebo iritis were 11% in ACV course of oral ACV has no
Stromal Keratitis / Iritis group and 10% in placebo apparent benefit in preventing
(topical trifluridine given to
(HEDS-EKT)287 patients group progression to stromal disease or
both groups)
with epithelial keratitis iritis

Recurrent Ocular HSV 12-month ACV 400mg BID Oral ACV reduced recurrent Oral ACV significantly reduces risk
(HEDS-APT)703 patients vs. placebo ocular disease (19% of recurrent disease by 50%, and
with inactive disease and recurrence in ACV group vs. is recommended for long-term
off medications 32% in placebo group)
 prophylaxis (esp. for recurrent
stromal keratitis)

Recurrent Ocular HSV risk No association between stress, systemic infection, sunlight exposure, menstruation, contact
factors lens wear, eye injury and ocular HSV recurrence.
(HEDS-RFS)2 populations
History of HSV epithelial keratitis does NOT predict future recurrence of epithelial keratitis
of 308 and 346 patients
who had experienced History of HSV stromal keratitis DOES increase risk of recurrence of stromal keratitis.
HSV eye disease in the
past year

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 Patients received With treatment, no significant differences No difference in 3 month BSCVA
corneal ulcers prednisolone 1% as in infiltrate / scar size, time to and no safety concerns with
adjunctive therapy vs. reepithelization or corneal perforation. adjunctive corticosteroid therapy
500 patients
placebo for bacterial ulcers.
with culture- Subgroup: Patients with vision of count
positive (moxifloxacin given to fingers or worse had better visual acuity Subgroup: Patients with CF or
corneal ulcers all patients for 48 (~2-3 Snellen chart lines) with worse vision had significantly
hours prior to corticosteroids (p=0.03), along with patients better visual acuity at 3 months,
randomization) with completely central corneal ulcers along with those with completely
(p=0.02). 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: 10 year survival: 77% in 12-65 There was no significant
12 to 75 yo donor group vs. 71% in 66- difference in 10 years success
yoEndothelial cell 75 yo donor group (p=0.11) rates comparing donors aged
density: 12 to 65 yo with those aged 66
Analyzed as a continuous
2300 to 3300 cells / to 75 yo.
variable, higher donor age
mm2Subjects
was associated with lower However, there was evidence
observed for 10
graft success beyond 5 years of donor age effect at the
years
(p<0.001) 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 1) Vitamin A, C, E, 1) Reduced risk of AREDS vitamins are useful in reducing vision loss
macular Beta-carotene and advanced AMD by 25%, in high-risk AMD (Intermediate with many
degeneration Zinc reduced vision loss by 19% medium drusen or at least 1 large drusen).

4757 Patients 2) Zinc alone 2) Reduced risk of Caution in smokers with high dose beta-carotene
advanced AMD by 21%, due to increased risk of lung cancer
3) Antioxidants
reduced vision loss by 11% Treatment has no benefit in patients with no
alone
AMD or early AMD (small / intermediate drusen)
3) Reduced risk of
4) Placebo
advanced AMD by 17%,
reduced vision loss by 10%
Vs. Placebo

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 1) Vitamin A, C, E, Lutein / Cartenoids lutein and zeaxanthin are safe AREDS2
degeneration Zeaxanthin alternative to beta-carotene, and may even formulation:
work better. Vitamin E
4203 Patients 2) Vitamin A, C, E, DHA + EPA
(400IU)
Vitamin C
(500mg)
 3) Vitamin A, C, E, Lutein / Omega-3 fatty acids did not enhance Lutein (10mg)
Zeaxanthin + DHA + EPA (Omega outcomes. Zeaxanthin
3 fatty acids) (2mg)
Lowering zinc did not lead to statistically
Zinc (25-80mg)
4) Placebo significant worsening, and likely lowers
Copper 2mg
incidence of side effects.
Examples:
PreserVision
ActiveEyes
Pro-Optic

MARINA (2006) – AMD Lucentis Efficacy

Disease Entity Study Groups Result Conclusion

Age-related macular
degeneration patients with
classic and occult CNV (wet
AMD)
716 Patients
1) 0.3 mg monthly 1) 15+ letter improvement in Ranibizumab prevented vision
Ranibizumab2) 0.5 mg 24.8% of 0.3mg group, mean loss and improved visual acuity
monthly Ranibizumab3) increase 6.5 letters. in patients with classic and
Sham injection monthly occult CNV
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.

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 1) 65.7% lost <15 Ranibizumab of greater clinical
monthly sham injection letters, 6.3% benefit than Verteprofin PDT in
gained >15 letters patients with AMD with classic CNV
2) Sham verteporfin PDT
2) 90% lost <15
plus monthly 0.3mg or
letters, 34-41%
0.5mg Ranibizumab
gained >15 letters

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 1) 55.2% gained >15 Ranibizumab leads to rapid improvement
Ranibizumab letters. 67.9% with 20/40 in 6-month visual acuity and macular
or better vision. edema following BRVO
2) 0.5mg monthly
Ranibizumab 2) 61.1% gained >15
letters. 64.9% with 20/40
3) Sham injection
or better vision.
monthly
 3) 28.8% gained > 15
letters. 41.7% with 20/40
or better vision.

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 1) 46.2% gained >15 Ranibizumab leads to rapid improvement
Ranibizumab letters. 43.9% with 20/40 in 6 month visual acuity and macular
or better vision. edema following CRVO
2) 0.5mg monthly
Ranibizumab 2) 47.7% gained >15
letters. 46.9% with 20/40
3) Sham injection
or better vision.
monthly
3) 16.9% gained > 15
letters. 20.8% with 20/40
or better vision.

BVOS (1984) – BRVO PRP Laser Efficacy

Disease Entity Study Groups Result Conclusion

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

CVOS (1995) – CRVO Prophylactic PRP Efficacy

Disease Entity Study Groups Result Conclusion

Central retinal 1) Immediate 1) No statistically significant difference
vein occlusion prophylactic PRP between NVI / NVA development in
(CRVO) prophylactically treated and untreated
2) Frequent close
eyes.
181 Eyes observation with PRP
if NVI / NVA 2) When NVI / NVA did develop, better
regression with PRP in untreated eyes
(56%) vs. prophylactically treated eyes
(22%).
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.

3) NVI / NVA correlated with the amount

of nonperfused retina and hemorrhage.
DCCT (1995) – Diabetic Retinopathy A1C Management

Disease Entity Study Groups Result Conclusion

Diabetic Retinopathy 1) Conventional treatment group Progression of Intensive treatment 10 times more
and Macular Edema (1-2 daily insulin injections, daily diabetic effective than conventional.
in Type 1 Diabetics blood glucose, quarterly clinic retinopathy
Risk of progression continues to
visits) Absolute risk per
1441 patients with decrease with lower A1Cs, and must be
100 patient years
type 1 diabetes 2) Intensive treatment group (3+ weighed against the threefold increase
daily insulin injections, pump, A1C 11.0 – 12.69 in risk of severe hypoglycemia.
monitoring and frequent MD, NP, A1C 7.0 – 1.17
10% lower A1C (8 vs 7.2%) associated
or dietary monitoring) A1C 6.0 – 0.52
with ~43% lower risk of progression
Continued
reduction in risk
with decrease in
A1C

UKPDS (2001) – Diabetic Retinopathy A1C Management

Disease Entity Study Groups Result Conclusion

Diabetic 1) Conventional 8-fold relative progression Blood sugar and blood pressure reduction are
Retinopathy and control BS / BP, reduction with A1C <6.2 vs. both beneficial to reducing the incidence and
Macular Edema in mean A1C 7.9%, BP >7.5 progression of diabetic retinopathy.
Type 2 Diabetics 154/87
2.5-fold relative incidence The reduction of incidence and progression risk
5357 patients with 2) Tight control of reduction with A1C <6.2 vs. from smoking could be accounted for by lower
newly diagnosed BS / BP, mean A1C >7.5 blood pressure, or due to pharmacological
type 2 diabetes 7.0%, BP 144/82 effect of nicotine, but does not justify advising
2.8-fold relative incidence
smoking in patients with retinopathy.
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

ETDRS (1991) – Diabetic Retinopathy Grading and Photocoagulation

Disease Entity Study Groups Result Conclusion

Diabetic Macular 1) One eye early photocoagulation Early photocoagulation associated Focal laser decreases
Edema with small reduction in incidence of vision loss from macular
2) Other eye deferred
severe visual loss at 5 years (2.6% vs edema.
3711 patients photocoagulation, photocoagulated
3.7%).
with mild to if high risk proliferative retinopathy In addition, ETDRS defined
severe NPDR or detected Focal photocoagulation effective in the grading of NPDR and
early PDR reducing visual loss for macular PDR which is still used to
this day!
 edema but scatter photocoagulation CSME was also defined,
is not. 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 1) One eye scatter Photocoagulation reduces risk of Perform PRP for patients with high-risk
and Macular Edema photocoagulation severe visual loss by 50%+ PDR. The two-year risk of severe visual
in Type 2 Diabetics loss without treatment outweighs the
2) Other eye no Decreases of visual acuity of one
risk of harmful treatment effects for two
1727 patients with treatment or more lines and constriction of
groups of eyes:
severe NPDR in both peripheral visual fields also
eyes or PDR in at least observed. 1) New preretinal hemorrhage or VH
1 eye 2) New NVD / NVE / NVI

DRVS (1990) – Diabetic Retinopathy Vitreous Hemorrhage

Disease Entity Study Groups Result Conclusion

Diabetic Retinopathy and 1) Observation Early vitrectomy Early vitrectomy for nonclearing
Vitreous Hemorrhage in better vision than vitreous hemorrhage (at least 1
2) Early vs delayed surgery with
Type 1 and 2 diabetics deferred for type 1 month) is helpful in type 1 diabetics
neovascularization or
diabetics. and monocular patients.
fibrovascular proliferation
No advantage seen
3) Early vs delayed surgery with
for type 2 diabetics.
severe DR and vitreous
hemorrhage within 6 months

EDIC (1999) – Diabetic Retinopathy A1C Management

Disease Entity Study Groups Result Conclusion

Diabetic Retinopathy and 1) Conventional treatment group (1-2 Intensive therapy Tight blood sugar control is
Macular Edema follow up daily insulin injections, daily blood resulted in: useful long term for
of DCCT study glucose, quarterly clinic visits) 75% decreased decreasing progression of
progression of retinopathy
1208 patients from DCCT 2) Intensive treatment group (3+ daily
retinopathy
followed for an additional insulin injections, pump, monitoring and
58% decreased
4 years frequent MD, NP, or dietary monitoring)
macular edema
52% decreased
need for laser
treatment
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 No difference in final visual Systemic antibiotics are not effective
with systemic acuity with or without systemic for endophthalmitis
antibiotics antibiotics
Immediate vitrectomy only beneficial
2) Vitrectomy In patients with VA HM or for LP vision or worse on
without systemic better, no difference between presentation
antibiotics vitrectomy and tap / inject.
69% with positive cultures, 94%
3) Tap / Inject In subgroup with LP or worse gram positive (70% coagulase-
with systemic vision, vitrectomy had 3-fold negative Staph, 10% Staph Aureus,
antibiotics increase in achieving 20/40 or 9% Strep)
better acuity
4) Tap / Inject
without systemic
antibiotics

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 Result Conclusion

Groups

Diabetic macular edema 1) Avastin Thus far, no statistical difference in In eye 20/50 or worse, Eylea has some
involving the macular 1.25mg the 3 drugs in mild vision loss (20/32 advantages over Avastin (year 1 and 2)
center to 20/40). and Lucentis (year 1).
2) Lucentis
Half as many injections were needed in
660 patients 0.3mg Subgroup 20/50 or worse::
year 2 compared with year 1
At 1 year:
3) Eylea
Eylea significantly better than
2.0mg
Avastin AND Lucentis (p

At 2 years:
Eylea significantly better vision than
Avastin ( but not Lucentis)
 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 Randomly assigned to 1 In black patients, VF loss was IOP lowered in both sequences in
uncontrolled of 2 sequences: decreased with ATT sequence black and white patients
glaucoma
1) ATT – ALT, trab, trab In white patients, VF loss was Long term visual function
451 black patients decreased with TAT sequence outcomes better for:
2) TAT – Trab, ALT, trab
249 white patients This effect was sustained through ATT – black patients
a 10 year follow up 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 1) Topical Eyes treated initially with argon Initial treatment with argon laser
primary open angle medication laser trabeculoplasty had lower IOP trabeculoplasty was at least as
glaucoma and better VF / optic disc status efficacious as initial treatment with
2) Argon laser
topical medication
271 patients trabeculoplasty 1.2 mm Hg greater IOP reduction in
ALT group
0.6dB better VF in ALT group

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 All enrolled patients met criteria for Progression of optic disc IOP lowering therapy is beneficial in
tension normal-tension glaucoma. They were or visual field loss normal-tension glaucoma patients at
glaucoma randomized into two groups: (p<0.0001): risk for disease progression.

140 patients 1) Reduction of IOP by 30% or more 1. Reduced IOP group: Lowering IOP by 30% reduced rate of
12% VF loss in NTG from 35% to 12%
2) Observation
2. Control group: 35%
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 1) Medications, At 5 year follow up, VF loss did Both medical and surgical groups result in
open angle stepped regimen not differ significantly between about the same VF outcome after 5 years of
glaucoma the groups follow up
2) Immediate
607 patients trabeculectomy Surgical patients had a greater At 8 year follow up, initial surgery led to
risk of substantial visual acuity less VF progression than initial medication
loss compared with medical regimen in subjects with advanced VF loss
patients at baseline

Rate of cataract formation greater Subjects with diabetes had more VF loss over
in surgical group time if treated initially with surgery.
Average IOP:
Medical: 17-18
Surgical: 14-15

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 Study Groups Result Conclusion

Entity

Early open 1) Treatment with laser Treatment reduced IOP by 5% or 25% First adequately powered
angle trabeculoplasty and Progression: randomized trial to demonstrate
glaucoma topical betaxolol BID 1) Treatment: 45% benefit to IOP reduction in open
2) Controls: 62%Treatment group angle glaucoma patients
255 patients 2) Observation
progression occurred significantly
laterEvery 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 All enrolled patients with IOP Treatment reduced IOP Topical ocular hypotensive
evidence of 24-32 in one eye and by 22.5 medication effective in delaying or
glaucomatous damage between 21 and 32 in other Glaucoma Incidence at 5 preventing onset of POAG in
eye. years:: individuals with elevated IOP
1636 patients
1) Reduction if IOP by 20% or 1) Treatment: 4.4%
2) Controls: 9.5%Minimal
 more systemic or ocular risk in Decrease in IOP of 22.5% decreased
2) Observation treatment group 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 At 3 years Both devices effective at lowering IOP.
two groups: Baerveldt group had lower failure rate and
Failure Rate:
required fewer medications, but it experienced
1) Ahmed-FP7 51% Ahmed vs. 34%
more hypotony-related vision-threatening
Baerveldt (p=0.03)
2) Baerveldt-350 complications.
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)

TVT (2012) – Tube vs. Trab Study

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

Disease Entity Study Groups Result Conclusion

Uncontrolled glaucoma Randomized into At 5 years: Tube has higher success rate compared to
with IOP>18 on two groups: trabeculectomy during 5 years of follow-up in
IOP reduction:
maximum tolerated TVT study. IOP reduction was similar.
1) Trabeculectomy 14.4 in tube group vs.
medical therapy.
with mitomycin C 12.6 in trab group More frequent reoperations after trab than with
Patients with previous (p=0.12) tube (though this is confounded as re-op after
2) Tube shunt
trab or cataract surgery failed trab (tube, or repeat trab) may be less
implant (350mm Failure probability:
included. complex than re-op after failed tube (additional
Baerveldt) 29.8% in tube group vs
tube vs. CPC)
212 patients 46.9% in trab group
(p=0.002)

Rate of reoperation:
9% in tube group vs
29% in trab group.
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 Randomized into Visual field preservation First randomized placebo-controlled trial to
primary open angle two groups: hazard ratio: demonstrate preservation of visual field with
glaucoma. 0.44 in Latanoprost group IOP lowering drug in patients with open-angle
1) Prostaglandin
vs. 1 in placebo groupIOP glaucoma
516 patients Analog (ie
lowering effect:
Latanoprost)
3.8mm Hg in Latanoprost
2) Placebo group vs. 0.9mm Hg in
placebo group.

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 1. Optic nerve Gain of 3+ lines: Results from the IONDT indicate that optic nerve
Optic neuropathy decompression 32.6% of surgical decompression surgery for NAION is not effective,
(NAION) with VA surgery group vs. 42.7% of may be harmful, and should be abandoned. The
20/64 or worse 2. Observation observation groupLoss spontaneous improvement rate is better than
of 3+ lines: previously reported.
244 patients
23.9% in surgical
group vs. 12.4% in
observation group

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 1. 48h infusion of
a Glasgow Coma methylprednisolone
Scale of 14 or 2. Observation
less
10,008 patients
Risk of death: Corticosteroids should not be used routinely in
25.7% in corticosteroids the treatment of head injury.
group vs. 22.3% in
Often, traumatic head injury is coincident with
observation groupRisk of
traumatic optic neuropathy (TON). Given the
death or severe disability:
lack of clinical efficacy for TON and the risk of
38.1% in corticosteroids
harm, steroids should not be used in these
group vs. 36.3% in
cases.
observation group
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 1. IV 3-day course of Visual recovery: IV steroids

treatment and follow up methylprednisolone 250mg q6h
for development of followed by oral prednisone
multiple sclerosis over 15 1mg/kg/day for 2 weeks
years.
2. Oral prednisone 1mg/kg/day
389 patients for 2 weeks
3. Oral placebo
IV group experienced accelerated accelerate visual
visual recovery at 2 weeks. Neither recovery but do not
treatment improved final visual change final visual
outcomeRecurrence: outcome.
Oral prednisone alone resulted in
Oral steroids result
increased rate of recurrence!
in INCREASED rate of
MS risk at 15 years:
recurrent optic
Overall: 50%
neuritis.
No MRI lesions: 25%
1+ MRI lesion: 72%Protective MRI lesions at the
features: time of attack are a
Male gender strong predictor of
Optic disc swelling 15-year MS risk.
Absence of pain

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 1. Acetazolamide group Primary outcome was In patients with IIH and mild visual loss,
and mild visual loss who (maximally tolerated up change in perimetric the use of acetazolamide with a low-
recieved a low-sodium to 4 grams / day) for 6 mean deviation (PMD) sodium weight-reduction diet compared
weight reduction diet months on Humphrey 24-2. with diet alone resulted in modest
improvement in visual field function.
165 patients 2. Placebo group 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
 PEDIATRIC OPHTHALMOLOGY

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 Result Conclusion

Groups

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

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 1. IOL Median logMAR: Until longer term follow-up data are available, caution
cataract underoing implantation 0.80 in contact should be exercised when performing IOL implantation in
cataract surgery 2. Contact lens lens group vs. children 6 months of age or younger given the higher
between 1 to 6 months correction 0.97 in IOL group incidence of adverse events and the absence of an
of age. (p=0.20) improved short-term visual outcome compared to contact
114 patients Additional lens use.
surgeries:
12% in contact
lens group vs.
63% in IOL group
 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 1. Systemic The rate of malignancy in the These findings do not support the
disease treated with immunosuppressives immunosuppressant group hypothesis of an increased risk of
systemic steroids or +/- corticosteroids was not significantly malignancy in patients with severe
immunosuppressive different from the rate in the ocular inflammatory disease who are
2. Systemic
chemotherapy corticosteroids alone group treated with systemic
corticosteroids alone
(retrospective cohort (p>0.90) immunosuppressive agents
study) compared with patients treated with
543 patients 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 1. Systemic Change in BCVA: Both treatments improve visual acuity, and the
recently corticosteroids +6.0 letters in implant vs. specific advantages and disadvantages should
active uveitis +3.2 letters in systemic dictate selection between treatments on a case by
2. Retisert Implant
255 patients groups (p=0.16) case basis.
(fluocinolone
Vision related quality of
acetonide)
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