Ranibizumab and Peripheral Scatter Laser in Patients With Diabetic Macular Edema and Peripheral Nonperfusion
Condition: Diabetic Macular Edema
MeSH terms: Macular Edema; Edema
Intervention: intravitreal injection of ranibizumab; peripheral laser; intravitreal injection of triamcinolone acetonide; macular laser
Intervention description: intravitreal injection of 0.5 mg ranibizumab; ultra-widefield fluorescein angiography guided peripheral laser; intravitreal injection of 4.0 mg triamcinolone acetonide; macular laser to areas of retinal thickening or leakage
Intervention MeSH terms: Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Ranibizumab; Triamcinolone diacetate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: diabetic macular edema

Summary:

      To investigate the role of ranibizumab and angiographically-directed peripheral scatter laser
      therapy in patients with clinically-significant diabetic macular edema (CSME) and peripheral
      nonperfusion. We propose a novel treatment of CSME in a subgroup of patients defined by a
      combination of ultrawide-field angiography (UWFA) and optical coherence tomography (OCT).
      Within this classification scheme, patients with CSME are subdivided by the presence of: 1)
      focal macular leakage, 2) vitreomacular interface traction, and/or 3) peripheral
      nonperfusion. The successful treatment of diabetic macular edema would be dictated by
      pathophysiology-directed therapy based on this classification.

      The subgroup of interest for this clinical trial is characterized by diabetic macular edema,
      peripheral nonperfusion on UWFA, and the absence of macular traction on OCT. This group of
      patients has previously not been well recognized or characterized due to limitations in
      previous, standard angiographic evaluation of the retinal periphery.

      We postulate that this subcategory represents one with a high rate of failure of accepted
      therapies given persistence of the basic pathophysiologic mechanism for CSME, namely
      ischemia-induced production of Vascular Endothelial Growth Factor (VEGF) from the retinal
      periphery. This also represents a population of patients with likely recurrence of CSME
      despite treatment with anti-VEGF therapy alone for the same reason.
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects will be eligible if the following criteria are met:

          -  Ability to provide written informed consent and comply with study assessments for the
             full duration of the study

          -  Age > 18 years

        Patient related considerations:

        • Patients with Type I or Type II diabetes

        Disease related considerations:

          -  Study eye with clinically significant diabetic macular edema characterized by macular
             edema, peripheral nonperfusion, and absence of macular traction on clinical exam,
             UWFA, and OCT.

          -  Study eye with best corrected visual acuity between 20/40 (≤ 73 letters on Early
             Treatment of Diabetic Retinopathy Study (ETDRS) chart and 20/320 (≥ 19 letters on
             ETDRS chart) Other considerations

          -  Patient able to complete all study visits

          -  Female patients must be using two forms of contraception

        Exclusion Criteria:

          -  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 Intra Uterine
             Device, or contraceptive hormone implant or patch.

          -  Prior enrollment in the study

          -  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

          -  Therapy with intravitreal triamcinolone, pegaptanib, ranibizumab, or bevacizumab
             within the previous 3 months

          -  Previous panretinal scatter laser photocoagulation

          -  Previous pars plana vitrectomy

          -  Visually-significant significant cataracts as primary reason for vision loss

          -  Uncontrolled or advanced glaucoma

          -  Patients on more than one anti-glaucoma agent

          -  Myocardial infarction or cerebrovascular accident within 6 months

          -  Subjects with poor glycemic control that have initiated intensive insulin treatment or
             plan to do so in the next 4 months