Mohamed Soliman PGY-2 Ophthalmology LSUHSC Shreveport.

Clinical Trials in Ophthalmology

Mohamed SolimanPGY-2 OphthalmologyLSUHSC Shreveport

Diabetic Retinopathy

ET DRSEarly treatment Diabetic Retinopathy Study

Study Questions

Effectiveness of Photocoagulation DR and DMEEffectiveness of Asprin in preventing progresion of DR

Outcome Variables

SVL (Severe Visual Loss) : VA < 5/200 for at least 4 monthsMVL (Moderate Visual Loss) : Doubling of Visual angleProgression of DR


Results for Early Scatter Photocoagulation

Did not reduce the risk of SVLNot indicated in Mild / Moderate NPDRMore effective for Type 2 DM

Moderate NPDRMild NPDR Early PDR


Defined CSME as :

Retinal edema within 500 µm of center of macula

HE within 500 µm of center of macula if associated with thickening of adjacent retina

A zone of thickening larger than 1 DD if located within 1 DD of the center of the macula


Results for focal photocoagulation for DME

Decreased risk of MVL

Increased chance of visual gain (halving of Visual angle)

Decreased retinal thickening


Results for Asprin

Did not alter progression of DRDid not affect VA

Did not increase Vitreous HemorrhageDid decrease the risk of Cardiovascular Morbidity and mortality

DRSDiabetic Retinopathy Study

Study QuestionIs Photocoagulation (argon or xenon arc) effective in treating DR

EligibiltyPDR or Severe NPDR

Outcome variablesSVL ( VA < 5/200 )

DRSDiabetic Retinopathy Study

Results

Photocoagulation decreased the risk of SVLGreatest benefit to High Risk PDR

Recommended prompt treatment of “High Risk PDR”

Mild NVD + Vitreous HemorrhageModerate NVE + Vitreous HemorrhageMod/Severe NVD (1/4 – 1/3 NVD) with or without Vitreous Hemorrhage

High Risk PDR

3 months after laser

DCCTDiabetes Control and Complications Trial

Study questionWill intensive control of Blood sugar (BS) in Type 1 DM slow the development of DR or slow its progression

Results Intensive control of BSDecreased risk of developing DR (76%)Slowed progression of DR (54%)Decreased risk of Neuropathy (60%) Albuminuria (54%)

But …

Early worsening of DR in 1st yearIncreased risk of Hypoglycemic events

UKPDSUnited Kingdom Prospective Diabetes Study

Study QuestionsWill intensive control of Blood Sugar (BS) in Type 2 DM decrease the microvascular complications of Diabetes Will intensive control of Blood Pressure (BP) in Type 2 DM decrease the microvascular complications of Diabetes (including DR progression)

ResultsIntensive control of BS slowed the progression of DR and decreased the risk of micro vascular complications

Intensive control of BP slowed the micro and macrovacular complications of DM

DVSDiabetic Vitrectomy Study

Objective Natural course and effect of surgical intervention on severe PDR

ResultsType 1 DM with Dense Vitreous Hemorrhage (VH) and SVL in 1 eye :

Early Surgery (1-6 m after visual loss)

Type 2 DM with dense VH: No difference between early and late vitrectomy

Note: Endolaser was not yet available during this study 1988 and microsurgical techniques have greatly improved so outcomes in PPV may be better than those reported in the DVS

AMD and CNV

AREDSAge-Related Eye Disease Study

Objective To evaluate whether antioxidants or zinc supplements can reduce development or progression of AMD

ResultsPatients with intermediate, dry AMD, or unilateral advanced AMD benefited from antioxidants and zinc supplementation with respect to vision loss and progression of AMD

MPSMacular Photocoagulation Study

ObjectiveDoes laser treatment to leaking CNVs prevent significant visual loss compared to observation

Study designPhotocoagulation of Extrafoveal, juxtfoveal and subfoveal leaking CNVs

Outcome variablesSevere Visual loss (SVL) = loss of 6 or more lines, or quadrupling of the visual angle

MPSMacular Photocoagulation Study

Results

Laser decreased the risk of SVL in eyes with Extrafoveal and Juxtafoveal CNV (AMD,POHS and idopathic)compared to no treatment

In Subfoveal CNVs there was an initial drop in VA but after 1 year resulted in a decrease in SVL compared to observed eyes. Persistent or recurrent CNV was noted in 51% of lasered eyes in 24 months

The Photodynamic Thearpy (PDT) Era

TAPTreatment of AMD with PDT study

Objective

To determine if PDT with verteporfin can reduce visual loss in patients with subfoveal CNV

Results

Patients treated with PDT+Verteporfin sustained less MVL. This was mainly in seen in predominantly classic CNV (>50% of area is classic).

VIPVerteporfin in PDT Trial (AMD and Myopia)

ObjectiveTo determine if PDT + Verteporfin can reduce visual loss in Patients with subfoveal CNV

ResultsDecreased MVL and SVL

Note : PDT use has dropped significantly with the advent of pharmacotherapy, it may be used in combination with antiangiogenisis treatments.

The Anti-VEGF Era

VISIONVEGF inhibition Study in Ocular Neovascularization

Objective To determine if pegaptanib (Macugen) can reduce the risk of visual loss in subfoveal CNVs

Results70% of patients lost < 3 lines6% showed visual gainEndophthalmitis after injection

(1.3 risk/patient/year)

Note: Use of this drug has dropped as newer antiangiogenesis agents have been developed

ANCHORAnti-VEGF for the tretment of Predominantly Classic CNV in AMD

ObjectiveTo determine if monthly intravitreal Ranibizumab (Lucentis) can reduce visual loss in patients with predominantly classic CNV 2ry to wet AMD

Study designPatients were given Lucentis every month for 24 months and compared to PDT with verteporfin

Results95% of patients given Lucentis maintained or improved their vision after 12 months64% treated with PDT+ Verteporfin over 12 months

MARINAMinimally classic/Occult Trial of Ranibizumab in Neovascular

AMD

ObjectiveTo determine if monthly Ranibizumab (Lucentis) can reduce visual loss in Patients with occult Subfoveal CNV 2ry to wet AMD .

Study designPatients were given Lucentis every 4 weeks for 24 months and compared to placebo

Results95% of patients experienced visual improvement or stabilization after 12 months

Post-operative Endophthalmitis

EVSEndophthalmitis Vitrectomy Study

ObjectiveEvaluate the role of PPV and Intravenous antibiotics in post-operative bacterial endophthalmitis

ParticipantsPatients with bacterial endophthalmitis within 6 weeks of onset of infection

Study designPatients randomized to systemic antibiotics or not, and to immediate PPV or to immediate tap/inject

EVSEndophthalmitis Vitrectomy Study

Results

Systemic Antibiotics not effective : No difference in VA whether or not systemic antibiotics (Amikacin/Ceftazidime) were employed

Tap/inject for better than LP vision : No difference in outcomes between PPV and tap/inject group for VA better than LP

Immediate PPV for LP vision: showed much better results

Note : Revolutionized treatment of post-cataract surgery endophthalmitis making it an office procedure of tap and inject for most eyes

Vein Occlusions

CVOSCentral Vein Occlusion Study

ObjectiveTo determine if grid laser improve VA with CRVO and perfused ME.

To determine if early PRP prevents NVI/NVA

Results

Grid laser treatment in the macula reduced FA evidence of macular edema, yet yielded no benefit in VA (might be beneficial in younger patients with macular edema)

Most important risk factor for NVI is poor VA and larger areas of retinal capillary nonperfusion

PRP should be done after 2 clock hours of NVI

Prophylactic PRP does not decrease the incidence of NVI

(not done in clinical practice)

BVOSBranch Vein Occlusion Study

ObjectiveCan focal macular laser improve VA in BRVOs with ME and VA ≤ 20/40.

Can scatter laser prevent NV and VH in BRVOs.

Results

Improved VA after laser for ME with intact foveal vasculature and VA ≤ 20/40

BVOSBranch Vein Occlusion Study

Results

PRP to the area of nonperfusion caused regression of new vessels with retinal or disc neovascularization

Ischemia alone is not an indication for scatter laser

Patients should be observed for the development of neovascularization

Scatter laser reduced the risk of VH in eyes with recent BRVO that developed neovascularization

Retinopathy of PrematurityROP

STOP-ROPSupplemental Therapeutic Oxygen for Prethreshold ROP

Objective

To test whether supplemental oxygen would decrease the progression from prethreshold to threshold disease.

Results

Supplemental oxygen did not cause further progression of prethershold ROP but also did not reduce the number of infants requiring ablative therapy

Oxygen increased the risk of adverse pulmonary events

CROPTrial of Cryotherapy for ROP

Objective

To determine if Cryotherapy to theperipheral avascular retina in severe ROP prevented cicatricial changes and RD.

Results

Cryotherapy to the avascular anterior retina in ROP eyes with thershold disease showed a reduction by half in unfavourable outcomes at 1 year

Threshold disease Zone 1 or Zone 2 Stage 3 (5 contiguous or 8 total clock hours) With plus disease

At 10 years eyes that received Cryotherapy were still much less than control eyes to be blind

ET-ROPEarly Treatment for Retinopathy of Prematurity Study

Determined that earlier laser therapy can improve visual and anatomic outcomes in ROP

Recommended laser therapy for

Type 1 Prethreshold diseaseZone 1 with plus diseaseZone 1 with stage 3Zone 2 , stage 2/3 with plus Disease

oImplied treating an additional 50% more patients than with CROP guidlines

Herpetic Eye Disease

HEDSHerpetic Eye Disease Study

Objective:To evaluate the efficacy of topical steroids and oral acyclovir in treating HSV stromal keratitis and iridocyclitis in conjunction with topical trifluridine (Viroptic).

Results

Do topical steroids treat stromal keratitis ?

Yes. They treat stromal inflammation and shorten the duration of keratitis

HEDSHerpetic Eye Disease Study

Question and Answer

Is oral acyclovir helpful in:

A) treating stromal keratitis (in addition to trifluridine and steriods)…………….. No

B)treating HSV iritis ……………………………….…..Not sure. Probably

C)prevent development of Stromal keratitis and iritis in patients with epithelial keratitis…….… No

D)prophylaxis against HSV recurrences……………...Yes

Choroidal Melanoma

COMSCollaborative Ocular Melanoma Study

COMS large Choroidal Melanoma trial

Large Apex > 10 Base >16

Compared Enucleation alone to Enucleation preceeded by External beam RT

ResultsEstablished appropriateness of primary enucleation alone (RT did not improve overall survival)


COMS Medium Choroidal Melanoma trial

Medium Apex <10 Base <16

Compared Standardized enucleation and brachytherapy (iodine 125)

Results

Enucleation Brachytherapy

All cause mortality

18% 19%

Metastasis at 5 y

11% 9%

Other complications

Misdiagnosis in 0.3% of cases

Decline in VA to 20/200 in 3 years


COMS Small Choroidal Melanoma trial

Small Apex 1-2.4 Base 4-8

Observational study for small tumors

Melanoma specific mortality 1 % at 5 y

Clinical Risk factors: -Greater initial thinckness-presence of orange pigment-absence of Drusen &/or RPE changes

Audio-Visual tour

Mohamed Soliman PGY-2 Ophthalmology LSUHSC Shreveport.

Documents

Transcript of Mohamed Soliman PGY-2 Ophthalmology LSUHSC Shreveport.