mohamed soliman pgy-2 ophthalmology lsuhsc shreveport
TRANSCRIPT
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
ET DRSEarly treatment Diabetic Retinopathy Study
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
ET DRSEarly treatment Diabetic Retinopathy Study
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
ET DRSEarly treatment Diabetic Retinopathy Study
Results for focal photocoagulation for DME
Decreased risk of MVL
Increased chance of visual gain (halving of Visual angle)
Decreased retinal thickening
ET DRSEarly treatment Diabetic Retinopathy Study
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)
COMSCollaborative Ocular Melanoma Study
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
COMSCollaborative Ocular Melanoma Study
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
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