Intravitreal Bevacizumab Pretreatment for Reducing Preretinal Hemorrhage in Diabetic Vitrectomy
Condition: Proliferative Diabetic Retinopathy
MeSH terms: Retinal Diseases; Diabetic Retinopathy; Hemorrhage
Study type: Observational

Summary: 
      Treatment of severe proliferative diabetic retinopathy (PDR) may require the use of silicone
      oil for long-term retinal tamponade to prevent recurrent retinal detachment. Massive bleeding
      during surgery before proper release of traction and peri-silicone oil proliferation after
      surgery were major causes of surgical failure. The likelihood of reproliferation rises in the
      presence of significant preretinal blood. It is therefore crucial to reduce intraoperative
      and postoperative preretinal hemorrhage in complicated diabetic vitrectomy with silicone oil
      infusion.

      Intravitreal avastin has been noted to induce rapid regression of retinal and iris
      neovascularization in proliferative diabetic retinopathy. Further, presurgical administration
      of intravitreal avastin may reduce intraoperative bleeding during membrane dissection in PDR
      with traction retinal detachment. The pretreatment of avastin may be particularly beneficial
      in the treatment of severe active fibrovascular proliferation by decreasing the severity of
      intraoperative and postoperative intraocular hemorrhage, leading to better surgical outcome
      and early visual rehabilitation.

      We conduct a prospective study to evaluate the effect of avastin on the severity of intra-
      and post-operative bleeding, frequency of recurrent bleeding, and anatomical and functional
      outcome in eyes with severe active PDR undergoing vitrectomy with silicone oil infusion.
    

Detailed description: 
      From January 2007 to June 2007, consecutive patients undergoing primary pars plana vitrectomy
      with silicone oil infusion for complications of proliferative diabetic retinopathy will be
      recruited for the prospective study. The selection criteria are: 1) anticoagulant therapy has
      not been used prior to surgery or during post-operative follow-up period; 2) no medical
      history of blood diseases associated with abnormal blood coagulation is present. Active PDR
      is defined as visible large new vessels within the proliferative tissue with fresh preretinal
      and/or vitreous hemorrhage. Decision of silicone oil infusion will be made before surgery
      when potential creation of multiple breaks or incomplete traction release is anticipated
      during surgery due to severe vitreoretinal adhesion. The morphological criteria set for
      silicone oil infusion are: severe active fibrovascular proliferation with broad vitreous
      attachment around the disc, arcade and extending to the periphery in at least 2 quadrants
      (≥grade 5 in Eliott's grading system);8 presence of macular-off traction or combined traction
      and rhegmatogenous retinal detachment.

      Individual recruited patient will be randomly assigned to one of the two groups: group 1 will
      receive intravitreal injection of 1.25 mg of avastin (0.05 ml) 7 to 9 days before vitrectomy;
      group 2 will not receive avastin pretreatment. Standard 3 port pars plana vitrectomy will be
      performed followed by silicone oil (5000 CS) infusion. A total of 30 cases (15 in each group)
      will be recruited.

      After surgery, patients will be kept in a prone position overnight, then allowed to lie on
      either side during sleep thereafter, but maintained a head-down position during waking hours
      for 2 weeks. Ophthalmological examinations will be performed in the first 4 days after
      surgery, then weekly for 4 weeks, biweekly for 1 month, and then monthly for at least 3
      months.

      The preoperative, intraoperative, and postoperative data will be collected for each patient.
      These demographics and clinical findings include age, gender, study eye, types and duration
      of diabetes mellitus, systemic diseases such as hypertension, renal insufficiency (24 hours
      creatinine clearance estimated by Cockcroft and Gault equation), degree of intraoperative
      bleeding, duration of the surgery, combined lens extraction, and the use of scleral buckle.
      Data regarding the extent of preretinal blood in the first postoperative day; time, duration,
      frequency and treatment of recurrent vitreous hemorrhage; and the duration of postoperative
      follow-up will also be compiled. Results of ophthalmological examinations, including best
      corrected visual acuity, intraocular pressure, and lens status will be recorded.

      Intraoperative bleeding will be graded in 3 levels: grade 1 is defined as minor bleeding
      stopped either spontaneously or by transient bottle elevation; grade 2 is defined as moderate
      bleeding resulting in broad sheaths of clots requiring endodiathermy to the bleeding sites to
      stop the bleeding; grade 3 is defined as thick clot formation covering half or more of the
      posterior pole or interfering with the surgical plane. Postoperative preretinal blood will be
      separated into 3 grades: isolated clots with total area less than 10 disc area and without
      involvement of the posterior pole (grade1); broad sheaths of clots with total area more than
      10 disc area without involving the posterior pole (grade2); broad sheaths of clots with total
      area more than 10 disc area and with involvement of the posterior pole (grade3). Any
      noticeable increase of preretinal blood will be defined as recurrent hemorrhage.

      The severity of intraoperative bleeding, the extent of immediate postoperative preretinal
      blood, reabsorption time of blood around the disc area, total reabsorption time of preretinal
      blood, the rate and treatment of recurrent vitreous hemorrhage, and the change of
      best-corrected visual acuity will be compared between groups 1 and 2. Visual acuity will be
      graded into three levels: low (≤1 meter counting fingers), moderate (>1 meter counting
      fingers, but < 20/200), and good (≥ 20/200).
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Consecutive patients undergoing primary pars plana vitrectomy with silicone oil infusion
        for complications of proliferative diabetic retinopathy will be recruited for the
        prospective study.
      
Keywords: proliferative diabetic retinopathy; bevacizumab (Avastin); vitreous hemorrhage; silicone oil