Please select the eligibility criteria that correspond to the clinical trial below.
Title: Prospective, Randomized, Multicenter, Open Label, Phase II Study to Access Efficacy and Safety of Lucentis® Monotherapy (Ranibizumab 0.5 mg Intravitreal Injections) Compared With Lucentis® Plus Panretinal Photocoagulation (PRP) and PRP (Monotherapy) in the Treatment of Patients With High Risk Proliferative Diabetic Retinopathy
Brief Summary: The purpose of this trial is to evaluate safety and to compare the efficacy of intravitreous injection of ranibizumab alone (0.5 mg), versus combination of intravitreous injection of ranibizumab (0.5 mg) plus panretinal photocoagulation, versus panretinal photocoagulation alone in the regression of retinal neovascularization in eyes with high-risk proliferative diabetic retinopathy.


Options:
A: Subject-level Criteria

Inclusion

To be eligible, the following inclusion criteria must be met:

Age \>= 18 years Diagnosis of diabetes mellitus (type 1 or type 2) At least one eye meets the study eye criteria listed below Able and willing to provide informed consent.

Exclusion

A subject is not eligible if any of the following exclusion criteria are present:

A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control).

A condition that, in the opinion of the investigator, would preclude subject undergoing elective vitrectomy surgery if indicated during the study.

Participation in an investigational trial that involved treatment with any drug within 30 days of randomization that has not received regulatory approval at the time of study entry.

Known allergy to any component of the study drug. Blood pressure \> 180/110 (systolic above 180 or diastolic above 110). Myocardial infarction, other cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization.

Systemic anti-VEGF or pro-VEGF treatment within 4 months prior to randomization.

For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 4 months.

Subject is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the 12 months of the study.

Study Eye Criteria

The subject must have at least one eye meeting all of the inclusion criteria and none of the exclusion criteria listed below.

A subject can have only one study eye. If both eyes are eligible at the time of randomization, the study eye will be selected by the investigator and subject before randomization.

The eligibility criteria for a study eye are as follows:

Inclusion

Vitreous hemorrhage causing vision impairment, presumed to be from proliferative diabetic retinopathy, and precluding completion of panretinal photocoagulation (or precluding assessment of completeness of prior PRP).

Immediate vitrectomy not required (investigator and subject are willing to wait at least 8 weeks to see if hemorrhage clears sufficiently without having to proceed to vitrectomy).

Visual acuity is light perception or better.

Exclusion

Prompt vitrectomy indicated, such as because of signs of rhegmatogenous retinal detachment or traction detachment involving the macula present on ultrasound.

Exam evidence of neovascular glaucoma, angle neovascularization, or active neovascularization of the iris (small iris tufts not an exclusion).

History of intravitreal anti-VEGF treatment for vitreous hemorrhage at any time in the past or for an indication other than vitreous hemorrhage in the past 2 months.

History of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or major ocular surgery other than vitrectomy anticipated within the next 6 months following randomization.

History of vitrectomy. History of yttrium aluminum garnet capsulotomy performed within 2 months prior to randomization.

Aphakia. Uncontrolled glaucoma (in investigator's judgment). Exam evidence of severe external ocular infection, including conjunctivitis, chalazion, or substantial blepharitis.
B: Inclusion Criteria:

* Presence of PDR with the indication of full PRP according the intend of investigator
* Best corrected visual acuity of 20/320 or better
* Media clarity, pupillary dilation and patient's cooperation sufficient for full PRP, wide-field FAG and OCT

Exclusion Criteria:

* History of prior PRP with more than 100 burns outside the posterior pole
* Tractional retinal detachment involving the macula
* Evidence of neoplasia of angle on examination
* Macular edema due to a cause other than DME
* Any ocular condition which may change visual acuity during the study
* Substantial cataract which has declined the vision by 3 lines or more
* History of intravitreal injection of anti-VEGF agent in past 2 months
* History of any use of corticosteroid during past 4 months
* History of major intra-ocular surgery except cataract surgery
* History of YAG laser capsulotomy during past 2 months
* Aphakia and uncontrolled glaucoma according to investigator judgment
C: Inclusion Criteria:

* Macular edema associated with diabetic retinopathy
* Decreased visual acuity attributable primarily to DME
* Diagnosis of diabetes mellitus

Exclusion Criteria:

* High risk proliferative diabetic retinopathy
* Cataract surgery within 3 months of Baseline, or any other previous intraocular surgery
* Uncontrolled glaucoma
* Current or history of ocular disease in the study eye other than DME
* Major illness or major surgical procedure within 1 month prior to Day 1
* Uncontrolled blood pressure
* Glycosylated hemoglobin (HbA1c) greater than (\>) 12 percent (%) at screening
* Untreated diabetes mellitus or initiation of oral anti-diabetic medication or insulin within 4 months prior to Day 1
D: Inclusion Criteria:

* High-risk proliferative diabetic retinopathy (HR-PDR) eyes.
* Best Corrected-Visual Acuity at baseline \> 20/320 in the study eye.
* Clear ocular media and adequate pupillary dilatation to permit good quality fundus photography.
* Intraocular pressure \< 21 mmHg.
* Type I, or Type II diabetic subjects as defined by the World Health Organization criteria of either gender, and aged ≥ 18 years.
* Women must be using effective contraception, be post-menopausal for at least 12 months prior to trial entry, or surgically sterile.
* Ability to provide written informed consent.
* Ability to return for all trial visits.

Exclusion Criteria:

* Eyes with prior scatter (panretinal) or focal/grid photocoagulation, within the previous 6 months.
* Fibrovascular proliferation with retinal traction.
* Other cause of retinal neovascularization (retinal vein occlusion, radiation retinopathy or others).
* Atrophy/scarring/fibrosis/ hard exudates involving the center of the macula.
* Subjects who have received yttrium-aluminum-garnet laser, or peripheral retinal cryoablation, or laser retinopexy (for retinal tears only), or focal/grid photocoagulation, within the previous 6 months.
* Significant media opacities, which might interfere with visual acuity, assessment of toxicity or fundus photography.
* Subjects should not be entered if there is likelihood that they will require cataract surgery within the following 1 year.
* Any intraocular surgery within 6 months before trial enrollment.
* Previous vitrectomy.
* HbA1C level \>11% or recent signs of uncontrolled diabetes.
* Any of the following underlying systemic diseases:

  * History or evidence of severe cardiac disease.
  * History or evidence of clinically significant peripheral vascular disease such as intermittent claudication or prior amputation.
  * Clinically significant impaired renal function (serum creatinine \>2.5 mg/dL or s/p renal transplant or receiving dialysis).
  * Clinically significant impaired hepatic function.
  * Stroke (within 12 months of trial entry).
  * Any major surgical procedure within one month before trial enrollment.
* Previous radiation to the head in the region of the study eye.
* Any prior treatment with an investigational agent for diabetic retinopathy or anti-VEGF therapy (including intravitreal, subconjunctival or subtenons corticosteroids) during the past 90 days for any other condition.
* Known serious allergies to fluorescein used in angiography, or to components of Lucentis® formulation.
* Systolic Blood Pressure \> 170 (2 different readings) or diastolic Blood Pressure \> 100 (2 different readings).
* Acute ocular or periocular infection.
* Previous filtering surgery (e.g., trabeculectomy) or placement of a glaucoma drainage device (e.g., tube-shunt surgery).
* Use of other investigational drugs at the time of enrollment.
* History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.
* History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
* Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (\> 5 mIU/mL).
* Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant UNLESS they are: women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner; women whose partners have been sterilized by vasectomy or other means using a highly effective method of birth control. Periodic abstinence are not acceptable.

Answer: D