Please select the eligibility criteria that correspond to the clinical trial below.
Title: Intravitreous Anti-VEGF vs. Prompt Vitrectomy for Vitreous Hemorrhage From Proliferative Diabetic Retinopathy
Brief Summary: Although vitreous hemorrhage (VH) from proliferative diabetic retinopathy (PDR) can cause acute and dramatic vision loss for patients with diabetes, there is no current, evidence-based clinical guidance as to what treatment method is most likely to provide the best visual outcomes once intervention is desired. Intravitreous anti-vascular endothelial growth factor (anti-VEGF) therapy alone or vitrectomy combined with intraoperative PRP each provide the opportunity to stabilize or regress retinal neovascularization. However, clinical trials are lacking to elucidate the relative time frame of visual recovery or final visual outcome in prompt vitrectomy compared with initial anti-VEGF treatment. The Diabetic Retinopathy Clinical Research Network Protocol N demonstrated short-term trends consistent with a possible beneficial effect of anti-VEGF treatment in eyes with VH from PDR, including greater visual acuity improvement and reduced rates of recurrent VH as compared with saline injection. It is possible that a study with a longer duration of follow-up with structured anti-VEGF retreatment would demonstrate even greater effectiveness of anti-VEGF for VH to avoid vitrectomy and its attendant adverse events while also improving visual acuity. On the other hand, advances in surgical techniques leading to faster operative times, quicker patient recovery, and reduced complication rates may make prompt vitrectomy a more attractive alternative since it results in the immediate ability to clear hemorrhage and to perform PRP if desired, often as part of one procedure. This proposed study will evaluate the safety and efficacy of two treatment approaches for eyes with VH from PDR: prompt vitrectomy + PRP and intravitreous aflibercept injections.


Options:
A: Inclusion Criteria:

Age \>= 18 years -Individuals \< 18 years old are not being included because proliferative diabetic retinopathy (PDR) is so rare in this age group that the diagnosis of PDR may be questionable.

Diagnosis of diabetes mellitus (type 1 or type 2)

Any one of the following will be considered to be sufficient evidence that diabetes is present:

* Current regular use of insulin for the treatment of diabetes
* Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes
* Documented diabetes by American Diabetes Association (ADA) and/or World Health Organization (WHO) criteria (see Procedures Manual for definitions) Able and willing to provide informed consent.

Meets at least all of the following ocular criteria criteria:

* Presence of PDR which the investigator intends to manage with PRP alone but for which PRP can be deferred for at least 4 weeks in the setting of intravitreal ranibizumab, in the investigator's judgment.
* Best corrected Electronic-Early Treatment Diabetic Retinopathy Study (E-ETDRS) visual acuity letter score \> 24 (approximate Snellen equivalent 20/320) on the day of randomization.
* Media clarity, pupillary dilation, and study participant cooperation sufficient to administer PRP and obtain adequate fundus photographs and optical coherence tomography (OCT).

  * Investigator must verify accuracy of OCT scan by ensuring it is centered and of adequate quality

Exclusion Criteria:

Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant.

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).

* Individuals in poor glycemic control who, within the last 4 months, initiated intensive insulin treatment (a pump or multiple daily injections) or plan to do so in the next 4 months should not be enrolled.

Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval for the indication being studied.

* Study participants cannot receive another investigational drug while participating in the study.

Known allergy to any component of the study drug.

Blood pressure \> 180/110 (systolic above 180 or diastolic above 110).

* If blood pressure is brought below 180/110 by anti-hypertensive treatment, individual can become eligible.

Myocardial infarction, other acute 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.

* These drugs should not be used during the study.

For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 3 years.

* Women who are potential study participants should be questioned about the potential for pregnancy. Investigator judgment is used to determine when a pregnancy test is needed.

Individual is expecting to move out of the area of the clinical center to an area not covered by another Diabetic Retinopathy Clinical Research Network (DRCR.net) certified clinical center during the 3 years of the study.

Individual has any of the following ocular characteristics:

* History of prior panretinal photocoagulation (prior PRP is defined as ≥ 100 burns outside of the posterior pole)
* Tractional retinal detachment involving the macula.

  -- A tractional retinal detachment is not an exclusion if it is outside of the posterior pole (not threatening the macula) and in the investigator's judgment, is not a contraindication to intravitreal ranibizumab treatment and also does not preclude deferring PRP for at least 4 weeks in the setting of intravitreal ranibizumab
* Exam evidence of neovascularization of the angle (neovascularization of the iris alone is not an exclusion if it does not preclude deferring PRP for at least 4 weeks in the investigator's judgment).
* If macular edema is present, it is considered to be primarily due to a cause other than diabetic macular edema.

  -- An eye should not be considered eligible if:
  * macular edema is present that is considered to be related to ocular surgery such as cataract extraction or
  * clinical exam and/or OCT suggest that vitreoretinal interface abnormalities disease (e.g., a taut posterior hyaloid or epiretinal membrane) is the primary cause of any macular edema.
* An ocular condition is present (other than diabetic retinopathy) that, in the opinion of the investigator, might alter visual acuity during the course of the study (e.g., retinal vein or artery occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.).

  -- A vitreous or preretinal hemorrhage is not an exclusion if it is out of the visual axis and in the investigator's judgment is not having any affect on visual acuity.
* Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye were otherwise normal).
* History of intravitreal anti-VEGF treatment at any time in the past 2 months.
* History of corticosteroid treatment (intravitreal or peribulbar) at any time in the past 4 months.

  --If the investigator believes that there may still be a substantial effect 4 months after prior treatment (e.g., dose of intravitreal triamcinolone higher than 4 mg), the eye should not be included.
* History of major ocular surgery (including vitrectomy, cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or anticipated within the next 6 months following randomization.
* History of (yttrium-aluminum-garnet) YAG 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:

1. Age \>= 18 years Participants \<18 years old are not being included because proliferative diabetic retinopathy is so rare in this age group that the diagnosis may be questionable.
2. Diagnosis of diabetes mellitus (type 1 or type 2)

Any one of the following will be considered to be sufficient evidence that diabetes is present:

* Current regular use of insulin for the treatment of diabetes
* Current regular use of oral anti-hyperglycemia agents for the treatment of diabetes
* Documented diabetes by American Diabetes Association and/or World Health Organization criteria 4. Able and willing to provide informed consent. 5. Patient is willing and able to undergo vitrectomy within next 2 weeks and the vitrectomy can be scheduled within that time frame.

  6. Vitreous hemorrhage causing vision impairment, presumed to be from proliferative diabetic retinopathy, for which intervention is deemed necessary.
  * Note: Prior panretinal photocoagulation is neither a requirement nor an exclusion.
  * Subhyaloid hemorrhage alone does not make an eye eligible; however, presence of subhyaloid hemorrhage in addition to the criteria above will not preclude participation provided the investigator is comfortable with either treatment regimen.

    7. Immediate vitrectomy not required (investigator and participant are willing to wait at least 4 months to see if hemorrhage clears sufficiently with anti-vascular endothelial growth factor without having to proceed to vitrectomy).

    8. Visual acuity letter score ≤78 (approximate Snellen equivalent 20/32) and at least light perception.

    9. Investigators should use particular caution when considering enrollment of an eye with visual acuity letter score 69 to 78 (approximate Snellen equivalent 20/32 to 20/40) to ensure that the need for vitrectomy and its potential benefits outweigh the potential risks.

Exclusion Criteria:

* A potential participant is not eligible if any of the following exclusion criteria are present:

  1. History of chronic renal failure requiring dialysis (including placement of fistula if performed in preparation for dialysis) or kidney transplant.
  2. 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).
  3. Initiation of intensive insulin treatment (a pump or multiple daily injections) within 4 months prior to randomization or plans to do so in the next 4 months.
  4. A condition that, in the opinion of the investigator, would preclude participant undergoing elective vitrectomy surgery if indicated during the study.
  5. Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval for the indication being studied.

     • Note: participants cannot receive another investigational drug while participating in the study.
  6. Known allergy to any component of the study drug or any drug used in the injection prep (including povidone iodine).
  7. Blood pressure \> 180/110 (systolic above 180 or diastolic above 110).
  8. If blood pressure is brought below 180/110 by anti-hypertensive treatment, potential participant can become eligible.
  9. Systemic anti-vascular endothelial growth factor or pro-vascular endothelial growth factor treatment within 4 months prior to randomization.

     • These drugs cannot be used during the study.
  10. For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next two years.

      • Women who are potential participants should be questioned about the potential for pregnancy. Investigator judgment is used to determine when a pregnancy test is needed.
  11. Potential participant is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the two years.
  12. Evidence of traction detachment involving or threatening the macula.

      • If the density of the hemorrhage precludes a visual assessment on clinical exam to confirm eligibility, then it is recommended that assessment be performed with ultrasound as standard care.
  13. Evidence of rhegmatogenous retinal detachment.

      • If the density of the hemorrhage precludes a visual assessment on clinical exam to confirm eligibility, then it is recommended that assessment be performed with ultrasound as standard care.
  14. Evidence of neovascular glaucoma (iris or angle neovascularization is not an exclusion).
  15. Known diabetic macular edema (DME), defined as either
  16. Optical coherence tomography central subfield thickness (microns):
  17. Zeiss Cirrus: ≥290 in women; ≥305 in men
  18. Heidelberg Spectralis: ≥305 in women; ≥320 in men OR
  19. Diabetic macular edema on clinical exam that the investigator believes currently requires treatment.
  20. History of intravitreous anti-vascular endothelial growth factor treatment within 2 months prior to current vitreous hemorrhage onset or after onset.
  21. History of intraocular corticosteroid treatment within 4 months prior to current vitreous hemorrhage onset or after onset.
  22. 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.
  23. History of vitrectomy.
  24. History of YAG capsulotomy performed within 2 months prior to randomization.
  25. Aphakia.
  26. Uncontrolled glaucoma (in investigator's judgment).
  27. Exam evidence of severe external ocular infection, including conjunctivitis, chalazion, or substantial blepharitis.
C: Inclusion Criteria:

* vitreous haemorrhage
* tractional retinal detachment
* active proliferative diabetic retinopathy.

Exclusion Criteria:

* neovascular glaucoma
* cataract
* combined traction and rhegmatogenous RD
D: 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

Answer: B