A Safety and Efficacy Trial of a Treat and Extend Protocol Using Ranibizumab With and Without Laser Photocoagulation for Diabetic Macular Edema

This research study will compare the visual outcomes between a group of patients who are
treated with monthly injections of Ranibizumab 0.3 mg and two groups of patients who are
treated with the "Treat and Extend" regimen. One of the "Treat and Extend" groups will also
receive laser therapy to determine if this has any additional beneficial effects.

Inclusion Criteria:

- Ability to provide written informed consent and comply with study assessments for the
full duration of the study

- Age > 18 years of age Patient related considerations

- For sexually active women of childbearing potential, agreement to the use of an
appropriate form of contraception (or abstinence) for the duration of the study

- Although no birth control method is 100% effective, the following are considered
effective means of contraception: surgical sterilization, use of oral contraceptives,
barrier contraception using either a condom or diaphragm with spermicidal gel, an
intrauterine device, or contraceptive hormone implant or patch. A patient's primary
care physician, obstetrician, or gynecologist should be consulted regarding an
appropriate form of birth control.

- Ability and willingness to return for all scheduled visits and assessments

Disease related considerations

- The presence of center-involving diabetic macular edema on clinical exam and SDOCT

- Best corrected visual acuity in the study eye, using ETDRS testing, between 20/25 and
20/320 (Snellen equivalent), inclusive.

- Clear ocular media and adequate pupillary dilation to permit good quality fundus
imaging.

Exclusion Criteria:

- General Exclusion Criteria

- Pregnancy (positive urine 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 (Intrauterine Device) , 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

Ocular Exclusion Criteria Prior Ocular Treatment

- History of active proliferative diabetic retinopathy in the study eye on clinical exam

- History of vitrectomy surgery, submacular surgery, or other intraocular surgical
intervention for diabetic macular edema in the study eye

- Any previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection,
anti-VEGF drugs including ranibizumab, or device implantation) in the study eye within
90 days of the screening visit.

- History of prior laser macular photocoagulation more than 90 days prior to screening
will be eligible for study inclusion. However, if the investigator does not feel that
additional laser photocoagulation can be safely performed or would benefit the
patient, then the eye in consideration will be excluded.

- Evidence of vitreomacular interface abnormality or epiretinal membranes which may be
responsible for macular edema

Concurrent Ocular Conditions

• Any concurrent intraocular condition in the study eye (e.g., cataract or macular
degeneration) that, in the opinion of the investigator, could either: Require medical or
surgical intervention during the 24-month study period to prevent or treat visual loss that
might result from that condition; or if allowed to progress untreated, could likely
contribute to loss of at least 2 Snellen equivalent lines of BCVA (Best Corrected Visual
Acuity) over the 24-month study period.

- Active intraocular inflammation (grade trace or above) in the study eye

- Current vitreous hemorrhage in the study eye

- History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the
study eye

- Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either
eye

- Aphakia or absence of the posterior capsule in the study eye

- Intraocular surgery (including cataract surgery) in the study eye within 3 months
preceding Day 0

- Uncontrolled glaucoma in the study eye (defined as IOP (Intraocular Pressure) ≥ 30
mmHg despite treatment with anti-glaucoma medication)

- History of glaucoma-filtering surgery in the study eye

- History of corneal transplant in the study eye

- History of pars plana vitrectomy

Concurrent Systemic Conditions

- Any history of use of systemic anti-VEGF (Vascular Endothelial Growth Factor) agents

- Uncontrolled blood pressure (defined as systolic > 180 mmHg and/or diastolic > 110
mmHg while patient is sitting) If a patient's initial reading exceeds these values, a
second reading may be taken 30 or more minutes later. If the patient's blood pressure
needs to be controlled by antihypertensive medication, the patient can become eligible
if medication is taken continuously for at least 30 days prior to Day 0.

- Atrial fibrillation not managed by patient's primary care physician or cardiologist
within 3 months of screening visit

- Women of childbearing potential not using adequate contraception (as defined in the
inclusion criteria).

A woman is considered not to be of childbearing potential if she is postmenopausal, defined
by amenorrhea for at least 1 year in a woman > 45 years old; or has undergone hysterectomy
and/or bilateral oophorectomy.

- History of stroke within the last 3 months of screening visit

- History of other disease, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use an investigational drug or that might affect interpretation of
the results of the study or renders the patient at high risk for treatment
complications

- Current treatment for active systemic infection

- Active malignancy

- History of allergy to fluorescein, not amenable to treatment

- Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality
to be analyzed and graded by the reading center

- Inability to comply with study or follow-up procedures

- Previous participation in any studies of investigational drugs within 1 month
preceding Day 0 (excluding vitamins and minerals)