The Effect of Intravitreal Ranibizumab on Visual Acuity and Hard Exudate Resolution in the Treatment of Diabetic Macular Edema With Center Involved Edema and Lipid Exudates

Study Overview
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Brief Summary
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This is an open-label, Phase I/II study of intravitreally administered 0.3mg ranibizumab in subjects with diabetic macular edema and lipid exudates in the central subfield.

Detailed Description
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This is an open-label, Phase I/II study of intravitreally administered 0.3mg ranibizumab in subjects with diabetic macular edema and lipid exudates in the central subfield. Consented, enrolled subjects will receive multiple open-label intravitreal injections on 0.3mg ranibizumab administered every 30 days for 12 months per the treatment algorithm. The patients will be randomized to 1 of 2 treatment groups. Group 1: Treatment algorithm based on the Diabetic Retinopathy Clinical Research (DRCR) protocol I 4:2:7 strategy based on the presence of macular edema. Group 2: Continue treatment until not only the macular edema is resolved but also until the lipid exudate is resolved. Sample size: 30 eyes Follow-up Schedule: Every 4 weeks throughout the study.

Official Title
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The Effect of Intravitreal Ranibizumab on Visual Acuity and Hard Exudate Resolution in the Treatment of Diabetic Macular Edema With Foveal Involving Edema and Lipid Exudates

Conditions
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Diabetic Macular Edema, Hard Lipid Exudates

Intervention / Treatment
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* Drug: ranibizumab 0.3mg


Participation Criteria
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Eligibility Criteria
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Subjects will be eligible if the following criteria are met: Inclusion Criteria Ability to provide written informed consent and comply with study assessments for the full duration of the study Age ≥ 18 years Type 1 or Type 2 Diabetes mellitus Best corrected ETDRS visual acuity (20/32-20/320) or letter score 78 to 24 Diabetic macular edema on clinical examination involving the center of the macula assessed to be the main cause of visual loss Retinal thickness measured on spectral domain optical coherence tomography (OCT). Zeiss Cirrus: ≥290μm in women and ≥305 μm in men in the central subfield. Heidelberg Spectralis: ≥305μm in women and ≥320 μm in men in the central subfield Lipid exudates involving the central subfield on spectral domain OCT. Exclusion Criteria Subjects who meet any of the following criteria will be excluded from this study: Treatment for diabetic macular edema within the prior 4 months. Panretinal photocoagulation within the prior 4 months or anticipated need for panretinal photocoagulation within the next 6 months major ocular surgery within the prior 4 months myocardial infarction, other cardiac event requiring hospitalization, cerebrovascular accident, transient ischemic attack, or treatment for acute congestive heart failure occurred within 4 months before randomization Pregnancy (positive pregnancy test) or lactation Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an intrauterine device (IUD), or contraceptive hormone implant or patch. Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated Participation in another simultaneous medical investigation or trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Diabetic macular edema treatment group (Group 1)<br>Treatment using intravitreal ranibizumab 0.3mg based on the DRCR protocol I 4:2:7 strategy based on the presence of macular edema. | Drug: ranibizumab 0.3mg<br>* intravitreally administered<br>* Other names: Lucentis;|
| Active Comparator: Diabetic macular edema and lipid treatment group (Group 2)<br>Continued treatment with intravitreal ranibizumab 0.3mg until, not only the macular edema is resolved, but also until the lipid exudate is resolved. | Drug: ranibizumab 0.3mg<br>* intravitreally administered<br>* Other names: Lucentis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Corrected Visual Acuity as Measured by ETDRS at 6 and 12 Months | Compare Group 1 and Group 2 for best correct visual acuity (BCVA), as assessed by the number of letters read correctly on the ETDRS eye chart at a starting test distance of 4 meters. | 6-12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Eyes With Improvement of Lipid Deposits in the Central Subfield as Measured on OCT and Fundus Photography |  | 12 months | 
| Percentage of Eyes With Complete Resolution of Lipid Deposits in the Central Subfield as Measured on OCT and Fundus Photography |  | 12 months | 
| Number of Eyes With Complete Resolution in the Central Subfield as Measured on OCT and Fundus Photography |  | 12 months | 
| Percentage of Eyes With Improvement in Lipid Deposits Throughout the Macular Grid as Measured by OCT and Fundus Photography |  | 12 months | 
| Percentage of Patients With Complete Resolution of Lipid Deposits Throughout the Macular Grid as Measured on OCT and Fundus Photography |  | 12 months | 
| Number of Eyes With Complete Resolution of Lipid Deposits Throughout the Macular Grid as Measured by OCT and Fundus Photography |  | 12 months | 
| Incidence and Severity of Ocular Adverse Events as a Measure of Safety and Tolerability |  | 12 months | 
| Incidence and Severity of Other Adverse Events as a Measure of Safety and Tolerability |  | 12 months |