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diabetic retinopathy (DR, proliferative {PDR} & non-proliferative)

Classification: 1) non proliferative diabetic retinopathy 2) proliferative diabetic retinopathy (PDR) Etiology: 1) hypertension increases risk [4] 2) aspirin therapy does not adversely affect course of diabetic retinopathy [1] Epidemiology: 1) non-proliferative stage a) eventually occurs in virtually all type-1 diabetics b) rarely occurs in type 1 diabetes < 5 years duration c) prevalence is 50% in type 1 diabetes > 10-15 years duration 2) progression to proliferative stage a) 40-60% of type-1 diabetics b) 10-20% of type-2 diabetics in 10 years 3) most common cause of blindness in USA 4) racial differences - HbA1c levels at which the risk for retinopathy begins to increase are lower in black adults than in white adults [7] (5.5% vs 6.0%) Pathology: 1) non-proliferative stage a) vascular dilation & tortuosity - microaneurysms b) capillary leakage 1] retinal hemorrhages - in both nerve fiber & mid-retinal layers 2] hard liquid exudates* c) ischemia 1] soft exudates (nerve layer infarcts) 2] new vessel formation within the retina 3] cotton wool spots (nerve fiber layer infarcts) 2) proliferative stage a) more ischemia & angiogenesis b) proliferation of larger, but fragile new blood vessels c) vitreous hemorrhage d) retinal detachment e) hyperlipidemia & hypertension also contribute to pathology f) retinal hypoxia may stimulate production of angiogenic factors 3) retinal & macular edema a) most common cause of visual impairment b) may occur in either phase 4) retinal vein occlusion [19] 5) may be role for AKR1B1 (aldehyde reductase) Clinical manifestations: 1) non-proliferative stage a) cotton wool spots (nerve fiber layer infarcts) b) dot & blot intraretinal hemorrhages c) hard exudates* d) microvascular abnormalities 1] dilated retinal veins 2] microaneurysms 2) proliferative stage a) neovascularization 1] rubeosis 2] neovascular glaucoma b) vitreous hemorrhage c) floaters d) flashing lights e) macular edema 3) may be asymptomatic even in advanced stages * hard exudates surrounding & close to the fovea suggest macular edema Special laboratory: - ophthalmoscopy: - machine learning algorithms may detect diabetic retinopathy from retinal fundus photographs with > 87% sensitivity & specificity [12] - AI device for retinal imaging in primary care FDA-approved [18] Management: 1) aggressive control of blood sugar a) prevents or retards non-proliferative retinopathy b) 10% of patients respond to intensive insulin therapy with transient (generally reversible) worsening of retinopathy c) number needed to treat: 30 for 4 years with target HgbA1c < 6.0% to prevent 1 case of worsening retinopathy [6] d) does not prevent significant vision loss [6] e) long-chain omega-3 fatty acids > 500 mg/day within a Mediterranean diet reduces risk of diabetic retinopathy (RR=0.52) [11] 2) control of hypertension & hyperlipidemia a) ARB of marginal benefit in prevention &/or preventing progression [5] b) addition of fenofibrate to statin c) number needed to treat: 30 for 4 years to prevent 1 case of worsening retinopathy [6] d) does not prevent significant vision loss [6] 3) screening examination by ophthalmologist: a) stereoscopic photography of the fundus (gold standard) [13] b) dilated ophthalmoscopy c) screening schedule 1] < 30 years of age (diabetes mellitus type 1) a] 1st examination within 5 years of diagnosis [14] or at puberty [17] b] examination yearly c] no retinopathy: every 4 years [16] d] mild nonproliferative retinopathy: every 3 years e] moderate nonproliferative retinopathy: every 6 months f] severe nonproliferative retinopathy: every 3 months g] more frequent screening with increased HgbA1c h] web application to calculate screening frequency [16] 2] > 30 years of age (or diabetes mellitus type 2) a] 1st examination at the time of diagnosis b] examination yearly c] if retinopathy is present, depends on the degree of retinopathy [10] 3] prior to pregnancy a] 1st examination prior to conception or in 1st trimester b] examination every 3 months d) teleretinal screening program - medical assistants & nurses were trained in fundus photography - images uploaded to web-based screening software for analysis by optometrists - transmission of analysis electronically to the patients' primary care providers [15] - reduces median duration to screening (158 to 17 days) [15] - avoids unnecessary visits with eye care providers [15] 4) if diabetic retinopathy is diagnosed, ophthalmology follow-up depends on the degree of retinopathy & should be determined by the ophthalmologist [10] - exam at least once a year if evidence of retinopathy [13] - exam every two years if no evidence of retinopathy [13] 5) indications for urgent referral to an ophthalmologist a) acute blurring of vision b) sudden onset of visual floaters 6) laser phototherapy or photocoagulation [1] a) indications: 1] retinal neovascularization 2] macular edema b) reduces visual loss by 50% c) does NOT restore visual loss already present d) see pan-retinal photocoagulation 7) inhibitors of vascular endothelial growth factor [3] - intravitreal injection - VEGF inhibitor for proliferative diabetic retinopathy - aflibercept (Eylea) FDA-approved [9] - use bevacizumab (off label use) because it is much cheaper [19] - indications & caveats regarding visual loss similar to laser photocoagulation 8) pregnancy: see diabetics who become pregnant 9) aspirin is NOT contraindicated [1]

Related

Early Treatment of Diabetic Retinopathy Study (ETDRS)

Specific

diabetic macular edema (DME) non-proliferative diabetic retinopathy (NPDR) preproliferative diabetic retinopathy (PPDR) proliferative diabetic retinopathy (PDR)

General

retinopathy diabetic eye disease; diabetic oculopathy microvascular complication of diabetes mellitus

References

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  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 274
  3. Mangione C. In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
  4. Gallego PH et al. Role of blood pressure in development of early retinopathy in adolescents with type 1 diabetes: Prospective cohort study. BMJ 2008 Aug 26; 337:a918. PMID: 18728082 (http://dx.doi.org/10.1136/bmj.a918) - Klein R et al, The relation of ambulatory blood pressure and pulse rate to retinopathy in type 1 diabetes mellitus: the renin-angiotensin system study. Ophthalmology. 2006 Dec;113(12):2231-6. Epub 2006 Sep 25. PMID: 16996597 - Parving HH. Impact of blood pressure and antihypertensive treatment on incipient and overt nephropathy, retinopathy, and endothelial permeability in diabetes mellitus. Diabetes Care. 1991 Mar;14(3):260-9. Review PMID: 2044441
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  6. Prescriber's Letter 17(8): 2010 ACCORD Eye Study: Therapies to Slow Progression of Diabetic Retinopathy Detail-Document#: 260805 (subscription needed) http://www.prescribersletter.com - The ACCORD Study Group and ACCORD Eye Study Group Effects of Medical Therapies on Retinopathy Progression in Type 2 Diabetes N Eng J Med June 29, 2010 PMID: 20587587 http://content.nejm.org/cgi/content/full/NEJMoa1001288 - Klein BEK Reduction in Risk of Progression of Diabetic Retinopathy N Eng J Med June 29, 2010 PMID: 20587586 http://content.nejm.org/cgi/content/full/NEJMe1005667
  7. Tsugawa Y et al Should the Hemoglobin A1c Diagnostic Cutoff Differ Between Blacks and Whites?: A Cross-sectional Study Annals of Internal Medicine August 7, 2012, Vol. 157. No. 3 PMID: 2286883 http://annals.org/article.aspx?articleid=1305508
  8. Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010 Jul 10;376(9735):124-36 PMID: 20580421
  9. FDA News Release. March 25, 2015 FDA approves new treatment for diabetic retinopathy in patients with diabetic macular edema. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm439838.htm
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  12. Gulshan V, Peng L,Coram M et al Development and Validation of a Deep Learning Algorithm for Detection of Diabetic Retinopathy in Retinal Fundus Photographs. JAMA. Published online November 29, 2016. PMID: 27898976 http://jamanetwork.com/journals/jama/fullarticle/2588763 - Wong TY, Bressler NM Artificial Intelligence With Deep Learning Technology Looks Into Diabetic Retinopathy Screening. JAMA. Published online November 29, 2016. PMID: 27898977 http://jamanetwork.com/journals/jama/fullarticle/2588762 - Beam AL, Kohane IS. Translating Artificial Intelligence Into Clinical Care. JAMA. Published online November 29, 2016. PMID: 27898974 http://jamanetwork.com/journals/jama/fullarticle/2588761
  13. Solomon SD, Chew E, Duh EJ et al Diabetic Retinopathy: A Position Statement by the American Diabetes Association. Diabetes Care 2017 Mar; 40(3): 412-418 PMID: 28223445 http://care.diabetesjournals.org/content/40/3/412
  14. Wang SY, Andrews CA, Gardner TW et al Ophthalmic Screening Patterns Among Youths With Diabetes Enrolled in a Large US Managed Care Network. JAMA Ophthalmol. Published online March 23, 2017. PMID: 28334336 http://jamanetwork.com/journals/jamaophthalmology/article-abstract/2613117 - Garg S Diabetic Retinopathy Screening With Telemedicine. A Potential Strategy to Engage Our Youth. JAMA Ophthalmol. Published online March 23, 2017. PMID: 28334299 http://jamanetwork.com/journals/jamaophthalmology/article-abstract/2613115
  15. Daskivich LP, Vasquez C, Martinez C et al Implementation and Evaluation of a Large-Scale Teleretinal Diabetic Retinopathy Screening Program in the Los Angeles County Department of Health Services. JAMA Intern Med. Published online March 27, 2017. PMID: 28346590 http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2612116 - Lyles C, Sarkar U. Seeing the Effect of Health Care Delivery Innovation in the Safety Net. JAMA Intern Med. Published online March 27, 2017. PMID: 28346579 http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2612113
  16. The DCCT/EDIC Research Group Frequency of Evidence-Based Screening for Retinopathy in Type 1 Diabetes. N Engl J Med 2017; 376:1507-1516. April 20, 2017 PMID: 28423305 http://www.nejm.org/doi/full/10.1056/NEJMoa1612836 - Rosenberg JB, Tsui I. Screening for Diabetic Retinopathy. N Engl J Med 2017; 376:1587-1588. April 20, 2017 PMID: 28423293 http://www.nejm.org/doi/full/10.1056/NEJMe1701820 - Optimal Frequency Retinopathy (Calculator) https://extapps.bsc.gwu.edu/shinypub/edic/retinopathy/
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  18. Brooks M FDA OKs AI Device to Detect Diabetic Retinopathy in Primary Care. Medscape - Apr 11, 2018. https://www.medscape.com/viewarticle/895061
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