Ranibizumab and PRP in Patients With CSDME and Peripheral Nonperfusion (RaScaL)

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 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.

• Other: intravitreal injection of ranibizumab + peripheral laser
  a single injection of 0.5 mg ranibizumab plus wide field peripheral laser
  Other Name: treatment arm
• Drug: triamcinolone acetate
  4 mg/0.1 cc triamcinolone acetate
  Other Name: control arm 1
• Other: intravitreal injection of triamcinolone and macular laser
  4 mg/0.1 cc triamcinolone acetate plus macular focal laser
  Other Name: control group 2

• Active Comparator: Treatment group 1
  ranibizumab and scatter laser
  Intervention: Other: intravitreal injection of ranibizumab + peripheral laser
• Comparative group 1
  Intravitreal triamcinolone acetate
  Intervention: Drug: triamcinolone acetate
• Comparative Group 2
  Intravitreal triamcinolone with macular laser
  Intervention: Other: intravitreal injection of triamcinolone and macular laser

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 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 IUD, 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