Diabetic Retinopathy

From EyeWiki

Sponsored in part by Boehringer Ingelheim International GmbH

Diabetic retinopathy refers to retinal changes that occur in patients with diabetes mellitus. These changes affect the small blood vessels of the retina and can lead to vision loss through several different pathways.

Disease Entity



Retinal disease that occurs in patients with diabetes mellitus.

Risk Factors

  • Diabetes
  • Uncontrolled glucose or blood pressure levels are associated with increased risk (see NHANES, UKDPS, WESDR references below)

General Pathology

The main types of diabetic retinopathy are non-proliferative and proliferative diabetic retinopathy. The main distinguishing feature between these two categories is the presence (proliferative) or absence (non-proliferative) of abnormal new (neovascular) blood vessels (retinal or optic disc neovascularization).


Vascular endothelial growth factor (VEGF) is secreted bythe ischemic retina. VEGF leads to a) increased vascular permeability resulting in retinal swelling/edema and b) angiogenesis- new blood vessel formation

Primary prevention

Control of glucose and blood pressure. Each 1% reduction in updated mean HbA(1c) was associated with reductions in risk of 21% for any end point related to diabetes(95% confidence interval 17% to 24%, P<0.0001), 21% for deaths related to diabetes (15% to 27%, P<0.0001), 14% for myocardial infarction (8% to 21%, P<0.0001), and 37% for microvascular complications (33% to 41%, P<0.0001). (UKDPS report 35).



Ask for symptoms of decreased vision or fluctuating vision, presence of floaters (vitreous hemorrhage) or defects in the field of vision. It is important to know the hemoglobin A1c and whether the patient’s blood pressure is under control.

Physical examination and Signs

Slit lamp examination and dilated fundus examination should be performed. One should look carefully for the presence of abnormal blood vessels on the iris (rubeosis or NVI), cataract (associated with diabetes) and vitreous cells (blood in the vitreous or pigmented cells if there is a retinal detachment with hole formation). Intraocular pressure (IOP) should be checked especially when NVI is seen. Dilated fundus examination should include a macular examination (contact lens or non-contact examination lens) to look for microaneurysms, hemorrhage, hard exudates, cotton wool spots, retinal swelling (edema)/ cystoid macular edema. The optic disc and area surrounding it (for one disc diameter) should be examined for presence of abnormal new blood vessels (neovascularization of the disc, NVD), optic nerve head pallor or glaucomatous changes. The remainder of the retina should also be examined for presence of abnormal new blood vessels (neovascularization elsewhere, NVE).


Clinical diagnosis

The central retina area that located between the main branches (superior and inferior arcades) of the central retinal vessels (central retinal artery and central retinal vein) in the eye is known as the “macular area”. The retina beyond this is considered “peripheral retina”. The central retinal area can develop abnormal findings in diabetic retinopathy. These findings can be present in the non-proliferative or the proliferative forms of the disease. These changes in the macula include the presence of abnormally dilated small vessel outpouchings (called microaneurysms), retinal bleeding (retinal hemorrhages) and yellow lipid and protein deposits (hard exudates). The macula can get thicker than normal- referred to as macular edema. Non-proliferative retinopathy can be classified into mild, moderate or severe stages based upon the presence or absence of retinal bleeding, abnormal venous beading of the vessel wall (venous beading) or abnormal vascular findings (intraretinal microvascular anomalies or IRMA). No treatment is usually done at this stage.

Proliferative retinopathy is progressive and requires treatment to prevent bleeding and scar tissue formation.

Diagnostic procedures

Fluorescein angiography is used to determine the degree of ischemia or the presence of retinal vascular abnormalities. The areas of microaneurysms appear as hyperfluorescent spots and may leak on the late frames resulting in areas of retinal edema clinically. The areas of NVD/ NVE show leakage on the FA.

Ocular coherence tomography (OCT) is useful to determine the retinal thickness measurements. The OCT can be sequentially obtained to determine whether the macular thickening is responding (swelling/ edema is decreasing) to therapy.

Laboratory test

Hemoglobin A1c is a measure of the degree of glycemic control over the past 3 months. A goal of 5.5 % - 6.0 % is ideal, although difficult to achieve in some patients. Generally, a HgbA1c </= 7 is the goal. Sometimes, for older patients (age 70's plus), diabetologists aim for a slightly higher A1C since A1C's below 7 are associated with increased morbidity in that age group.

Differential diagnosis

Macular edema from radiation retinopathy (history of radiation), vein occlusion (occluded vessel seen, telangiectasia present), parafoveal telangiectasia (telangiectatic vessels seen).

NVD/NVE from vein occlusion, retinal vasculitis, sarcoidosis, ocular ischemic syndrome, sickle cell retinopathy.

NVI from vein occlusions, ocular ischemia.

Sickle cell retinopathy, although in sickle cell , the NV is generally peripheral.


General treatment

Systemic control of diabetes, hypertension, hyperlipidemia, hypercholesterolemia, nephropathy and other diseases are of paramount importance.

Medical therapy and follow up

Treatment of macular edema is usually needed in order to prevent loss of vision or to try to improve vision. Treatment includes the use of lasers or injection of drugs that cause the retinal swelling/macular edema (from leaking blood vessels) to resolve. Patients are seen monthly if being injected or every 3 months post-laser for macular edema. (DRCR, RIDE, RISE, DAVINCI and ETDRS studies). Several studies indicate that anti-VEGF drugs are more effective than focal laser (DRCR, READ2, RIDE, RISE, DAVINCI). A recent study by the DRCR network has shown all three drugs (bevacizumab, ranibizumab and aflibercept) are effective for macular edema therapy. Recently, the DRCR has shown that for very good visual acuity (20/25 or better), watchful and careful observation compared well with those treated with anti-VEGF therapy. ( Baker CW, Glassman AR, Beaulieu WT, Antoszyk AN, Browning DJ, Chalam KV, Grover S, Jampol LM, Jhaveri CD, Melia M, Stockdale CR, Martin DF, Sun JK; DRCR Retina Network. Effect of Initial Management With Aflibercept vs Laser Photocoagulation vs Observation on Vision Loss Among Patients With Diabetic Macular Edema Involving the Center of the Macula and Good Visual Acuity: A Randomized Clinical Trial. JAMA. 2019 May 21;321(19):1880-1894. )For observed eyes, prompt treatment with anti-VEGF once sustained visual acuity decline was found, resulted in good visual acuity outcomes. Treatment of PDR is laser photocoagulation of the peripheral retina/panretinal photocoagulation (PRP). The laser is used to create scars on the peripheral retina. If successful, vitreous bleeding may be averted. Sometimes the proliferative disease is advanced and there is bleeding filling the eye (and preventing laser to be done) or scar tissue that wrinkles the retina or pulls it off the eyewall surface. In these situations, surgery is necessary (see vitrectomy for more information). In cases of NVD/ NVE with NVI, anti-VEGF injections into the eye can also be used. DRCR protocol S showed that anti-VEGF drug ranibizumab was noninferior to PRP in PDR. Anti-VEGF injections are sometimes used in concert with laser when rubeosis and neovascular glaucoma are present. Anti-VEGF are also given prior to vitrectomy surgery in selected cases. Follow-up is crucial for these patients. Thus, in a patient who is for any reason unliely to return for follow-up, anti-VEGF is not the treatment of choice and PRP should be done.

Surgery and Surgical follow up

The goal of surgery is to remove blood and scar tissue from the retinal surface and to place laser treatment as needed. Intraoperatively, intraocular gas or silicone oil may be needed to reattach the retina to the underlying layers and eyewall.


There is always the low, but real, risk of infection of the eyeball (endophthalmitis) with any injection of drugs into the eye or with eye surgery. There is also the risk of cataract progression with retinal surgery- vitrectomy accelerates the rate of cataract formation.


ETDRS studies show that the stage of retinopathy is correlated with progression to more advanced stages or retinopathy and visual loss.

Additional Resources


  1. Brown DM1, Nguyen QD, Marcus DM, Boyer DS, Patel S, Feiner L, Schlottmann PG, Rundle AC, Zhang J, Rubio RG, Adamis AP, Ehrlich JS, Hopkins JJ; RIDE and RISE Research Group.Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE.Ophthalmology. 2013 Oct;120(10):2013-22. doi: 10.1016/j.ophtha.2013.02.034. Epub 2013 May 22.
  2. Davis MD, Fisher MR, Gangnon RE, Barton F, Aiello LM, Chew EY, Ferris FL 3rd, Knatterud GL. Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: Early Treatment Diabetic Retinopathy Study Report #18. Invest Ophthalmol Vis Sci. 1998 Feb; 39:233-52
  3. Diabetes Control and Complications Trial Research Group. Clustering of long-term complications in families with diabetes in the diabetes control and complications trial. Diabetes. 1997 Nov; 46:1829-39.
  4. Diabetic Retinopathy Clinical Research Network. A randomized trial comparing intravitreal triamcinolone acetonide and focal/grid photocoagulation for diabetic macular edema. Ophthalmology. 2008 Sep;115(9):1447-9, 1449.e1-10. Epub 2008 Jul 26.
  5. Diabetic Retinopathy Clinical Research Network (DRCR.net), Beck RW, Edwards AR, Aiello LP, Bressler NM, Ferris F, Glassman AR, Hartnett E, Ip MS, Kim JE, Kollman C. Three-year follow-up of a randomized trial comparing focal/grid photocoagulation and intravitreal triamcinolone for diabetic macular edema. Arch Ophthalmol. 2009 Mar;127(3):245-51.
  6. Diabetic Retinopathy Clinical Research Network, Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, Ferris FL 3rd, Friedman SM, Glassman AR, Miller KM, Scott IU, Stockdale CR, Sun JK. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010 Jun;117(6):1064-1077.e35. Epub 2010 Apr 28.
  7. Do DV1, Nguyen QD, Boyer D, Schmidt-Erfurth U, Brown DM, Vitti R, Berliner AJ, Gao B, Zeitz O, Ruckert R, Schmelter T, Sandbrink R, Heier JS; da Vinci Study Group. One-year outcomes of the da Vinci Study of VEGF Trap-Eye in eyes with diabetic macular edema. Ophthalmology. 2012 Aug;119(8):1658-65. doi: 10.1016/j.ophtha.2012.02.010. Epub 2012 Apr 24.
  8. Early Treatment Diabetic Retinopathy Study Research Group. Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Ophthalmology. 1991 May;98(5 Suppl):823-33.
  9. Early Treatment Diabetic Retinopathy Study Research Group. Classification of diabetic retinopathy from fluorescein angiograms. ETDRS report number 11. Ophthalmology. 1991 May;98(5 Suppl):807-22.
  10. Early Treatment Diabetic Retinopathy Study Research Group Early photocoagulation for diabetic retinopathy. ETDRS report number 9.. Ophthalmology. 1991 May;98(5 Suppl):766-85.
  11. Early Treatment Diabetic Retinopathy Study Research Group. Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 2. Ophthalmology. 1987 Jul; 94:761-74.
  12. Diabetic Retinopathy Clinical Research Network Writing Commttee. Comparison of the modified Early Treatment Diabetic Retinopathy Study and mild macular grid laser photocoagulation strategies for diabetic macular edema. Arch Ophthalmol. 2007 Apr; 125:469-80.
  13. The Diabetic Retinopathy Clinical Research Network. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema. February 18, 2015DOI: 10.1056/NEJMoa1414264
  14. Flynn HW Jr, Chew EY, Simons BD, Barton FB, Remaley NA, Ferris FL 3rd. Pars plana vitrectomy in the Early Treatment Diabetic Retinopathy Study. ETDRS report number 17. The Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1992 Sep; 99:1351-7.
  15. Focal photocoagulation treatment of diabetic macular edema. Relationship of treatment effect to fluorescein angiographic and other retinal characteristics at baseline: ETDRS report no. 19. Early Treatment Diabetic Retinopathy Study Research Group. Arch Ophthalmol. 1995 Sep; 113:1144-55.
  16. Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XVII. The 14-year incidence and progression of diabetic retinopathy and associated risk factors in type 1 diabetes. Ophthalmology. 1998 Oct;105(10):1801-15.
  17. Liang JC, Goldberg MF. Treatment of diabetic retinopathy. Diabetes. 1980 Oct; 29(10):841-51. Review.
  18. Matthews DR, Stratton IM, Aldington SJ, Holman RR, Kohner EM; UK Prospective Diabetes Study Group. Risks of progression of retinopathy and vision loss related to tight blood pressure control in type 2 diabetes mellitus: UKPDS 69. Arch Ophthalmol. 2004 Nov; 122(11):1631-40.
  19. Nguyen QD, Shah SM, Heier JS, Do DV, Lim J, Boyer D, Abraham P, Campochiaro PA; READ-2 Study Group. Primary End Point (Six Months) Results of the Ranibizumab for Edema of the mAcula in diabetes (READ-2) study. Ophthalmology. 2009 Nov; 116:2175-81.e1.
  20. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol. 1985 Dec; 103:1796-806.
  21. Puklin JE, Tamborlane WV, Felig P, Genel M, Sherwin RS. Influence of long-term insulin infusion pump treatment of type I diabetes on diabetic retinopathy. Ophthalmology. 1982 Jul; 89:735-47.
  22. Sinclair SH, Alaniz R, Presti P. Laser treatment of diabetic macular edema: comparison of ETDRS-level treatment with threshold-level treatment by using high-contrast discriminant central visual field testing. Semin Ophthalmol. 1999 Dec; 14:214-22.
  23. Scott IU, Danis RP, Bressler SB, Bressler NM, Browning DJ, Qin H; Diabetic Retinopathy Clinical Research Network. Effect of focal/grid photocoagulation on visual acuity and retinal thickening in eyes with non-center-involved diabetic macular edema. Retina. 2009 May; 29:613-7.
  24. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000 Aug 12;321(7258):405-12.
  25. Stratton IM, Kohner EM, Aldington SJ, Turner RC, Holman RR, Manley SE, Matthews DR. UKPDS 50: risk factors for incidence and progression of retinopathy in Type II diabetes over 6 years from diagnosis. Diabetologia. 2001 Feb;44(2):156-63.
  26. Williams KV, Erbey JR, Becker D, Orchard TJ. Improved glycemic control reduces the impact of weight gain on cardiovascular risk factors in type 1 diabetes. The Epidemiology of Diabetes Complications Study. Diabetes Care. 1999 Jul;22(7):1084-91.