Proliferative Diabetic Retinopathy (Grand Rounds)

From EyeWiki
Original article contributed by: Jesse L. Berry, MD
All contributors: Jennifer I Lim MD and Jesse L. Berry, MD
Assigned editor: Leo A. Kim, MD
Review: Assigned status Up to Date by Jesse L. Berry, MD on February 27, 2017.

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  • 31-year-old man with type 2 diabetes presenting with one day of right eye “red floater”

Exam Findings

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Differential Diagnosis

  • Retinal vein occlusion
  • Proliferative diabetic retinopathy
  • Thrombocytopenia
  • Severe anemia
  • Hypertensive retinopathy
  • Hyperviscosity syndrome (leukemias)
  • Sickle cell retinopathy

Additional Investigations

  • Fluorescein angiography
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  • Proliferative diabetic retinopathy


  • Microvascular diabetic disease causes ischemia of the retina. Hypoxia-induced growth factors, most notably but not limited to VEGF, are secreted. These growth factors stimulate neovascularization out of the retina. These new vessels use the posterior vitreous as a scaffold. There is a high risk of hemorrhage from these vessels causing diabetic hemorrhages into the vitreous and subhyaloid spaces. There is also a proliferation of fibrous tissue along with neovascularization. The regression of the vessels with persistent fibrous proliferation can lead to complications including tractional retinal detachments.


  • Panretinal photocoagulation (PRP) has been the mainstay of therapy for proliferative diabetic retinopathy for > 35 years. The Diabetic Retinopathy Study (1981) showed that the rate of severe vision loss was reduced by 50% in eyes treated with PRP. There are several side effects of PRP, including post-procedural macular edema, decreased night vision, and loss of peripheral vision.
  • As shown by the Diabetes Control and Complications Trial and UK Prospective Diabetes Study, intensive blood sugar control reduces microvascular complications including diabetic retinopathy.

Prognosis and Future Directions

  • Anti-VEGF therapy, widely used for diabetic macular edema, has recently been suggested as a potential alternate treatment to PRP for proliferative diabetic retinopathy. Protocol S of the Diabetic Retinopathy Clinical Research Network compared initial PRP to a series of ranibizumab injections and monthly monitoring with deferred PRP. This study found that the peripheral visual field[CAC1] sensitivity loss was worse, DME more frequent and vitrectomy more often required in the PRP group. The primary outcome-mean visual acuity letter improvement at 2 years-was +2.8 in the ranibizumab group and +0.2 in the PRP group (95% CI of difference – -0.5 to +5.0). Overall, it was determined that ranibizumab with monthly visits was non-inferior to PRP. The use of anti-VEGF agents as primary treatment, with PRP for rescue, remains an exciting new area of development for PDR treatment with appropriate patient selection.
  • We had an extensive discussion of the risks, benefits and options of anti-VEGF injections with monitoring or prompt PRP. The patient indicated that he may not follow-up as advised and elected prompt PRP therapy. This illustrates one of the greatest practical limitations to Protocol S, the importance of close follow-up. This limitation is especially germane in any patient population where close, reliable follow-up is not possible.


  • Progression of retinopathy with intensive versus conventional treatment in the Diabetes Control and Complications Trial. Diabetes Control and Complications Trial Research Group. Ophthalmology. 1995 Apr;102(4):647-661.
  • Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998;317(7160):703-713.
  • Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. Diabetic Retinopathy Study Research Group. Ophthalmology.1981 Jul;88(7):583-600.
  • Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial. Diabetic Retinopathy Clinical Research Network. JAMA. 2015; 314(20):2137-2146.


  • Andrew Moshfeghi, MD, MBA, Associate Professor of Clinical Ophthalmology,
  • Luv Patel, MD, PGY-2 Ophthalmology resident,