Diabetic%20retinopathy Treatment

• Choice of treatment should be individualized
• Treatment options and follow-up interval for DR are based on the types and severity of DR and presence and type of DME

Goals of Therapy

• Improve or stabilize visual function
• Preserve vision
• Reduce rate of progression and frequency of retinopathy, vitreous hemorrhage and macular edema
• Improve or stabilize vision-related quality of life
• Achieve optimal control of blood glucose, blood pressure and other metabolic risk factors

Intravitreal Anti-Vascular Endothelial Growth Factor (Anti-VEGF)

• Eg Aflibercept, Bevacizumab, Ranibizumab
• Studies show that it inhibits the increase in retinal vascular permeability mediated in part by protein kinase C
• Reduces progression of disease and preserve visual function in patients with DME
• Preferred initial treatment option for patients with center-involved DME without evidence of macular traction
  • Meta-analysis has shown that Aflibercept and Ranibizumab have superior efficacy for DME treatment compared to conventional laser
• Combined anti-VEGF therapy and panretinal photocoagulation should be considered in patients with PDR and concurrent center-involved DME
• A meta-analysis has shown that anti-VEGF therapy before vitrectomy may reduce the duration of surgery, the number or retinal breaks and the amount of intra-operative bleeding
  • Preoperative or intraoperative Bevacizumab has been shown to decrease the incidence of postoperative vitreous hemorrhage

Aflibercept 

•  A recombinant fusion protein which binds to VEGF-A and VEGF-B thereby preventing activation of VEGF receptor 1 and 2
• Has been shown to provide the best treatment outcomes over 1 year in patients with center-involved DME with visual acuity of ≥20/50
  • DME and VEGF Trap-Eye: Investigation of Clinical Impact (DA VINCI) study showed better treatment outcomes in patients with center-involved DME who received Aflibercept compared to those who underwent laser treatment
  • A study has shown that Aflibercept may have superior visual acuity outcomes compared to panretinal photocoagulation in patients with PDR without center-involved DME

Bevacizumab and Ranibizumab

• Recombinant humanized antibodies
• Studies have shown that these drugs reduce OCT macular thickness, PDR activity and severity, and improve visual acuity (1-2 lines on a Snellen chart)
• Have shown similar treatment outcomes as Aflibercept by 2 years in patients with center-involved DME with visual acuity of ≤20/40
• Bevacizumab is used off-label for DR treatment
  • Bevacizumab or Laser Treatment (BOLT) in the management of diabetic macular edema study showed better treatment outcomes in patients with center-involved DME who received Bevacizumab compared to those who underwent macular laser treatment
  • Has been used as adjunctive treatment to vitrectomy to minimize postoperative complications such as recurrent hemorrhage
• Ranibizumab is currently being used in the treatment of DME
  • More effective than Bevacizumab in reducing retinal thickening
  • Ranibizumab for Edema of the Macula in Diabetes-2 (READ-2) study showed better treatment outcomes for patients receiving Ranibizumab with or without laser treatment compared to laser alone
  • RIDE and RISE trial has shown that Ranibizumab improved the severity of all types of DR with the greatest improvement in patients with moderately severe to severe NPDR

Intravitreal Corticosteroids

Intravitreal Dexamethasone Implant

• Treatment option for adult patients with DME
• A study have shown improved visual acuity in patients with naive center-involved DME
• Studies have shown that intravitreal Dexamethasone implant improves vision and vascular leakage from DME in victrectomized patients

Intravitreal Fluocinolone Implant

• Studies have shown that they reduce neovascularization and retinal inflammation and may restore the integrity of the blood-retina barrier by increasing tight-junction protein expression
• May be used as 2nd-line treatment option for patients with DME
• May cause high risk rates of increased IOP, cataract formation and endophthalmitis

Intravitreal Triamcinolone Acetonide (IVTA) 

• Studies showed that IVTA inhibits VEGF-induced breakdown of the blood retinal barrier
• Also, studies have shown that although IVTA resulted in some reduction of macular edema, the long-term (2 years) effect was not as good as focal laser photocoagulation
• Used in visualization during vitrectomy
• May be considered in patients with center-involved DME with persistent retinal thickening after 24 weeks of anti-VEGF treatment
• May be considered in patients with refractory DME
• Under investigation for use in DME that persists after focal/grid laser treatment, in cases of extensive macular hard exudate deposition and adjunct to panretinal photocoagulation treatment of PDR
• Complications may include increased intraocular pressure and cataract