Safety, Efficacy and Cost-efficacy of Ranibizumab (Monotherapy or Combination With Laser) in the Treatment of Diabetic Macular Edema (DME)

Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of BCVA (EDTRS) is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement.

Time frame: Baseline and 12 months

Population: ITT defined as all patients receiving at least one dose of either study treatment for monotherapy treatment arms, or one of the two study treatments for the combination therapy arm, and having at least 1 post-baseline assessment. Patients from one study site were excluded from ITT. patients with both baseline and 12 month data were included.

OCT is a diagnostic imaging technique using low-coherence interferometry to produce cross-sectional tomograms of the posterior segment eye structures. OCT was performed prior to study treatment to assess CRT, presence of fluid in the macula (intra-retinal cyst or fluid) and evaluation of image to monitor disease progression/treatment effect and to determine the need to stop/re-initiate ranibizumab treatment

Time frame: Baseline, 3, 6, 9 and 12 months

Population: The ITT population was defined as all patients receiving at least one dose of either study treatment for monotherapy treatment arms, or one of the two study treatments for the combination therapy arm, and having at least 1 post-baseline assessment. Patients from one site were excluded from ITT.

The Euro Quality of Life Questionnaire (EQ-5D) standardized instrument was utilized to measure health outcomes related to 5 dimensions, namely: mobility, self-care, usual activities, pain-discomfort, and anxiety/depression. The possible range for each dimension was 1 to 3, where 1=no problems, 2=some problems and 3=extreme problems. Missing values were not imputed. Using the scoring algorithm derived from the Canadian value sets (Bansback et al., 2012), a utility score for a patient was calculated based on the EQ-5D responses for a given time-point at which the questionnaire was presented to the patient. This mean EQ-5D utility score ranged between 0 (worst health) to 1 (perfect health).

Time frame: 12 month

Population: ITT defined as all patients receiving at least one dose of either study treatment for monotherapy treatment arms, or one of the two study treatments for the combination therapy arm, and having at least 1 post-baseline assessment. Patients from one study site were excluded from ITT. Patients with both baseline and 12 month data were included

Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of BCVA (EDTRS)is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement.

Time frame: Baseline, 3, 6 and 9 months

Population: The ITT population was defined as all patients receiving at least one dose of either study treatment for monotherapy treatment arms, or one of the two study treatments for the combination therapy arm, and having at least 1 post-baseline assessment. Patients from one site were excluded from ITT.

The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) was used to measure the influence of visual disability and visual symptoms on general health domains. The 12 subscales in the VFQ-25 are general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision. For each question, the patient was asked to rate their condition on a scale of 1-5 or 1-6, where a low number reflects a better outcome. A composite score for a patient is calculated by aggregating and averaging the scores from the 11 sub-scales (excluding general health sub-scale), and an algorithm is apply to give equal weight to each sub-scale. Sub-scales and composite scores are calculated by converting the response from questionnaires into a 0-100 scale, with 0 as the worst possible outcome and 100 as the best. Missing data was not imputed

Time frame: 12 month

Population: ITT defined as all patients receiving at least one dose of either study treatment for monotherapy treatment arms, or one of the two study treatments for the combination therapy arm, and having at least 1 post-baseline assessment. Patients from one study site were excluded from ITT. Patients with both baseline and 12 month data were included

Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of BCVA (EDTRS) is 0 to 100 letters. A higher percent of patients achieving a gain of ≥15 letters BCVA indicates a better response.

Time frame: Baseline, 3, 6, 9 and 12 months

Population: The ITT population was defined as all patients receiving at least one dose of either study treatment for monotherapy treatment arms, or one of the two study treatments for the combination therapy arm, and having at least 1 post-baseline assessment. Patients from one site were excluded from ITT

Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of BCVA (EDTRS) is 0 to 100 letters. A gain of 5,10,15 or more BCVA letters from baseline indicates improvement.

Time frame: 12 months

Population: ITT defined as all patients receiving at least one dose of either study treatment for monotherapy treatment arms, or one of the two study treatments for the combination therapy arm, and having at least 1 post-baseline assessment. Patients from one study site were excluded from ITT. Patients with 12 month data were included

(TTO) questionnaire was used to help determine the patients' health utility. Reported health utility represents the patients' quality of life at the current health state, and is a cardinal value that ranges from 0 (worst possible health or death) to 1 (best possible health). In this questionnaire, patients were first asked to estimate their remaining life expectancy. Second, the patients were presented with a hypothetical situation where a technology existed that could permanently return their vision to normal. This technology would always work, but would decrease their length of survival. Patients were then asked how much of their remaining life expectancy, if any, they would be willing to trade in return for use of the technology and thus for normal vision. The principle of this measure is that if patients were content with their current vision status (i.e., have a utility value of 1.0), they would not want to trade any of their remaining life years to improve their vision.

Time frame: 12 month

Population: ITT defined as all patients receiving at least one dose of either study treatment for monotherapy treatment arms, or one of the two study treatments for the combination therapy arm, and having at least 1 post-baseline assessment. Patients from one study site were excluded from ITT. Patients with both baseline and 12 month data were included