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.
- 1 Disease Entity
- 2 Diagnosis
- 3 Management
- 4 Additional Resources
- 5 References
Retinal disease that occurs in patients with diabetes mellitus.
- Uncontrolled glucose or blood pressure levels are associated with increased risk (see NHANES, UKDPS, WESDR references below)
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
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).
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.
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.
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.
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.
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.
- See references.
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- 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.
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- 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.
- 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.
- 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.
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