The Diabetic Retinopathy Clinical Research NetworkThe Diabetic Retinopathy

Clinical Research Network

DRCR.net Prompt PRP vs Ranibizumab+Deferred PRP for

PDR Study

Jeffrey G. Gross, M.D. – Protocol Chair

Supported through a cooperative agreement from the National Eye Institute and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and

Human Services EY14231, EY14229, EY018817 

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BackgroundBackground

Current treatment for PDR is panretinal photocoagulation (PRP)• Inherently destructive• Adverse effects on visual function

Some eyes with PDR+DME now receive anti-VEGF as standard care for DME

Would initial treatment of PDR with intravitreal anti-VEGF delay or prevent need for PRP?

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Study Objective and Treatment GroupsStudy Objective and Treatment Groups

Prompt PRP

To determine if visual acuity outcomes at 2 years in eyes with PDR (with or without concurrent DME) that receive anti-VEGF therapy with deferred PRP are non-

inferior to those in eyes that receive prompt PRP therapy.

(Note: Study ranibizumab may be given as needed for DME using Protocol I retreatment as guidelines.)

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0.5mg ranibizumab with deferred

PRP

Important Secondary Objectives(assuming visual acuity outcomes are non-inferior)Important Secondary Objectives(assuming visual acuity outcomes are non-inferior)

Compare visual function outcomes (including Humphrey visual field testing and study participant self-reports of visual function)

Determine percent of eyes not requiring PRP when intravitreal anti-VEGF is given in the absence of prompt PRP

Compare safety outcomesPerform cost effectiveness analysis

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Sample Size Sample Size

Minimum of 380 eyes

Subjects may have one or two study eyes

316 participants assuming 20% have two study eyes

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Major Inclusion CriteriaMajor Inclusion CriteriaAge ≥ 18 yearsType 1 or 2 diabetesPDR for which PRP is planned but in the

investigator’s opinion can be deferred for at least 4 weeks if an intravitreal anti-VEGF injection is given

Visual acuity (Snellen equivalent) 20/320 or better

Note: eyes with or without DME may be enrolled 6

Major Exclusion CriteriaMajor Exclusion Criteria

Systemic• Significant renal disease• BP > 180/110• Cardiac event or stroke within 4 months

Study eye• Prior PRP• Tractional retinal detachment involving the macula• NV of the angle• History of intravitreal anti-VEGF within past 2 months• History of corticosteriod in the past 4 months

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Testing Procedures – Undilatedwithin 14 days of randomization

Testing Procedures – Undilatedwithin 14 days of randomization

Questionnaires (except in participants with two study eyes)• NEI-VFQ, UAB-LLQ, WPAI, and TTO

Humphrey visual field testing (30-2 and 60-4) – dilation may be needed depending on pupil size• Required at sites with certified HVF equipment

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Testing Procedures – UndilatedDay of Randomization

Testing Procedures – UndilatedDay of Randomization

E-ETDRS best-corrected visual acuity in each eye

Binocular E-ETDRS using the participant’s everyday glasses or contacts

IOP in the study eye

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Testing Procedures - DilatedTesting Procedures - Dilated

OCT of study eye (within 8 days) Fundus photographs of study eye (within 21

days)• If NV is not captured on 7F or 4W, additional fields

should be taken to capture NV• This is documented on protocol specific form

Ocular exam in both eyes (day of randomization)

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PRP TreatmentPRP Treatment

Prompt PRP group receives 1200 to 1600 burns initiated on day of randomization (or within 14 days of baseline if injection for DME given) and completed within 8 weeks.

Anti-VEGF+Deferred PRP may receive PRP only if failure/futility criteria are met • Protocol chair approval MUST be obtained

before PRP is given in some cases of failure/futility

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Follow-up ScheduleFollow-up Schedule

Baseline to 1 Year

1 Year to 3 Years

• Assessment Visits every 16 weeks in both groups

• PDR Treatment Visits every 4 weeks (deferred PRP group only)…interval may only be extended if PRP is given

• Assessment Visits every 16 weeks in both groups

• PDR Treatment Visit every 4-16w (deferred PRP group only)…interval is extended if injections for PDR continually deferred

• Primary outcome visit at 2 years

• Annual visits for data collection only• Treatment as part of usual care

4 to 5Years

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Non-Annual Testing ProceduresNon-Annual Testing Procedures E-ETDRS best-corrected visual acuity in both eyes Ocular exam and IOP in the study eye (extended

ophthalmoscopy in deferred PRP group) OCT only if eye

• 1) has initiated DME treatment, • 2) will be evaluated for initial DME treatment, or • 3)10 letter unexplained loss since last visit.

Fundus photography only if PRP will be initiated in an eye assigned to IVR+deferred PRP

WPAI questionnaire at 16-week interval visits (except in OU participants)

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Annual Testing ProceduresAnnual Testing Procedures

Binocular E-ETDRS using the participant’s everyday glasses or contacts

Questionnaires (except in OU participants)• NEI-VFQ, UAB-LLQ, WPAI, and TTO• May be completed at home prior to visit (within 14

days)

Fundus photography Humphrey visual field testing (30-2 and 60-4)• Required at sites with certified HVF equipment

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Anti-VEGF Injections for PDR (Deferred PRP Group)

Anti-VEGF Injections for PDR (Deferred PRP Group)

Injections every 4 weeks through 12- week visit• NV status does not matter• Injection can only be skipped if an adverse event

occurs

If at anytime the investigator thinks PRP is needed within 1 week to avoid substantial vision loss, PRP may be given once protocol chair approval obtained

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Injection Retreatment Criteria for PDR (Deferred PRP Group)

Injection Retreatment Criteria for PDR (Deferred PRP Group)

Starting at the 16-week visit, each eye will be categorized into one of the following 5 groups:

1. Resolved NV of the retina, disc, and iris/angle* is absent. Decision to re-inject is at investigator

discretion. PRP should not be given.

*if angle is examined16

2. Improved NV of the retina, disc, or iris/angle* still

persists, but there is evidence of “improvement” since the last visit.

“Improvement” defined as a decrease in the size of NV or diminished density of NV

An injection is given. PRP should not be given.

*if angle is examined 17

Injection Retreatment Criteria for PDR (Deferred PRP Group)

Injection Retreatment Criteria for PDR (Deferred PRP Group)

3. Stable NV of the retina, disc, and iris/angle* is

clinically unchanged since the last visit. Once the eye meets criteria for stability, at

least 2 more injections must be given, each one month apart.  Further reinjection is then at investigator discretion as long as the eye remains stable.  PRP should not be given. 

*if angle is examined18

Injection Retreatment Criteria for PDR (Deferred PRP Group)

Injection Retreatment Criteria for PDR (Deferred PRP Group)

4. Not fully treated Failure/futility criteria not met and recurrent or

worsening NV of the retina, disc, or iris is present in an eye that has had fewer than 4 injections over the previous 4 months or there is vitreous or preretinal hemorrhage precluding assessment. 

An injection is given.  PRP should not be given. 

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Injection Retreatment Criteria for PDR (Deferred PRP Group)

Injection Retreatment Criteria for PDR (Deferred PRP Group)

5. Failure/futility One of the following criteria are met:

• NV worse than last visit such that it is greater in extent than baseline and at least 4 injections given over previous 4 months• NV of the angle• PRP needed within 1 week to avoid substantial

vision loss and protocol chair approval obtained• Persistent NV after 1.5 years of follow-up despite

anti-VEGF and protocol chair approval obtained

Decision to re-inject is at investigator discretion.  PRP may be given. 20

Injection Retreatment Criteria for PDR (Deferred PRP Group)

Injection Retreatment Criteria for PDR (Deferred PRP Group)

Follow-Up Treatment for DMEFollow-Up Treatment for DME

If DME develops during follow-up, treatment is at investigator discretion using study ranibizumab and/or focal/grid laser with Protocol I retreatment criteria as guidelines

Additional follow-up visits for DME retreatment are at the discretion of the investigator (not part of visit schedule)

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