diabetic retinopathy (DR, proliferative {PDR} & non-proliferative)
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Classification
Etiology
- hypertension increases risk[4]
- aspirin therapy does not adversely affect course of diabetic retinopathy[1]
Epidemiology
- non-proliferative stage
- eventually occurs in virtually all type-1 diabetics
- rarely occurs in type 1 diabetes < 5 years duration
- prevalence is 50% in type 1 diabetes > 10-15 years duration
- progression to proliferative stage
- 40-60% of type-1 diabetics
- 10-20% of type-2 diabetics in 10 years
- most common cause of blindness in USA
- 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
- non-proliferative stage
- vascular dilation & tortuosity
- capillary leakage
- retinal hemorrhages
- in both nerve fiber & mid-retinal layers
- hard liquid exudates*
- retinal hemorrhages
- ischemia
- soft exudates (nerve layer infarcts)
- new vessel formation within the retina
- cotton wool spots (nerve fiber layer infarcts)
- proliferative stage
- more ischemia & angiogenesis
- proliferation of larger, but fragile new blood vessels
- vitreous hemorrhage
- retinal detachment
- hyperlipidemia & hypertension also contribute to pathology
- retinal hypoxia may stimulate production of angiogenic factors
- retinal & macular edema
- most common cause of visual impairment
- may occur in either phase
- retinal vein occlusion[19]
- may be role for AKR1B1 (aldehyde reductase)
Clinical manifestations
- non-proliferative stage
- cotton wool spots (nerve fiber layer infarcts)
- dot & blot intraretinal hemorrhages
- hard exudates*
- microvascular abnormalities
- dilated retinal veins
- microaneurysms
- proliferative stage
- may be asymptomatic even in advanced stages
* hard exudates surrounding & close to the fovea suggest macular edema
Diagnostic procedures
- 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
- aggressive control of blood sugar
- prevents or retards non-proliferative retinopathy
- 10% of patients respond to intensive insulin therapy with transient (generally reversible) worsening of retinopathy
- number needed to treat: 30 for 4 years with target HgbA1c < 6.0% to prevent 1 case of worsening retinopathy[6]
- does not prevent significant vision loss[6]
- long-chain omega-3 fatty acids > 500 mg/day within a Mediterranean diet reduces risk of diabetic retinopathy (RR=0.52)[11]
- control of hypertension & hyperlipidemia
- ARB of marginal benefit in prevention &/or preventing progression[5]
- addition of fenofibrate to statin
- number needed to treat: 30 for 4 years to prevent 1 case of worsening retinopathy[6]
- does not prevent significant vision loss[6]
- screening examination by ophthalmologist:
- stereoscopic photography of the fundus (gold standard)[13]
- dilated ophthalmoscopy
- screening schedule
- < 30 years of age (diabetes mellitus type 1)
- 1st examination within 5 years of diagnosis[14] or at puberty[17]
- examination yearly
- no retinopathy: every 4 years[16]
- mild nonproliferative retinopathy: every 3 years
- moderate nonproliferative retinopathy: every 6 months
- severe nonproliferative retinopathy: every 3 months
- more frequent screening with increased HgbA1c
- web application to calculate screening frequency[16]
- > 30 years of age (or diabetes mellitus type 2)
- 1st examination at the time of diagnosis
- examination yearly
- if retinopathy is present, depends on the degree of retinopathy[10]
- prior to pregnancy
- 1st examination prior to conception or in 1st trimester
- examination every 3 months
- < 30 years of age (diabetes mellitus type 1)
- 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]
- 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]
- indications for urgent referral to an ophthalmologist
- acute blurring of vision
- sudden onset of visual floaters
- laser phototherapy or photocoagulation[1]
- indications:
- reduces visual loss by 50%
- does NOT restore visual loss already present
- see pan-retinal photocoagulation
- 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
- pregnancy: see diabetics who become pregnant
- aspirin is NOT contraindicated[1]
More general terms
- retinopathy
- diabetic eye disease; diabetic oculopathy
- microvascular complication of diabetes mellitus
More specific terms
- diabetic macular edema (DME)
- non-proliferative diabetic retinopathy (NPDR)
- preproliferative diabetic retinopathy (PPDR)
- proliferative diabetic retinopathy (PDR)
Additional terms
References
- ↑ 1.0 1.1 1.2 1.3 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2006, 2009, 2012, 2015, 2018, 2022.
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 274
- ↑ 3.0 3.1 Mangione C. In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ 4.0 4.1 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/18728082 (<Internet> 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: https://www.ncbi.nlm.nih.gov/pubmed/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: https://www.ncbi.nlm.nih.gov/pubmed/2044441 - ↑ 5.0 5.1 Sjolie AK et al. Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): A randomised placebo-controlled trial. Lancet 2008 Oct 18; 372:1385. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18823658
Chaturvedi N et al. Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: Randomised, placebo-controlled trials. Lancet 2008 Oct 18; 372:1394. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18823656 - ↑ 6.0 6.1 6.2 6.3 6.4 Prescriber's Letter 17(8): 2010 ACCORD Eye Study: Therapies to Slow Progression of Diabetic Retinopathy Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260805&pb=PRL (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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20587587 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20587586 <Internet> http://content.nejm.org/cgi/content/full/NEJMe1005667 - ↑ 7.0 7.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/2286883 <Internet> http://annals.org/article.aspx?articleid=1305508
- ↑ Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010 Jul 10;376(9735):124-36 PMID: https://www.ncbi.nlm.nih.gov/pubmed/20580421
- ↑ 9.0 9.1 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
- ↑ 10.0 10.1 10.2 Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022 - ↑ 11.0 11.1 Sala-Vila A, Diaz-Lopez A, Valls-Pedret C et al Dietary Marine omega-3 Fatty Acids and Incident Sight- Threatening Retinopathy in Middle-Aged and Older Individuals With Type 2 Diabetes. Prospective Investigation From the PREDIMED Trial. JAMA Ophthalmol. Published online August 18, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27541690 <Internet> http://archopht.jamanetwork.com/article.aspx?articleid=2543478
Larsen M Eat Your Fish or Go for Nuts. JAMA Ophthalmol. Published online August 18, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27541163 <Internet> http://archopht.jamanetwork.com/article.aspx?articleid=2543475 - ↑ 12.0 12.1 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27898976 <Internet> 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27898977 <Internet> http://jamanetwork.com/journals/jama/fullarticle/2588762
Beam AL, Kohane IS. Translating Artificial Intelligence Into Clinical Care. JAMA. Published online November 29, 2016. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/27898974 <Internet> http://jamanetwork.com/journals/jama/fullarticle/2588761 - ↑ 13.0 13.1 13.2 13.3 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28223445 <Internet> http://care.diabetesjournals.org/content/40/3/412
- ↑ 14.0 14.1 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28334336 <Internet> 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28334299 <Internet> http://jamanetwork.com/journals/jamaophthalmology/article-abstract/2613115 - ↑ 15.0 15.1 15.2 15.3 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28346590 <Internet> 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. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28346579 <Internet> http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2612113 - ↑ 16.0 16.1 16.2 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28423305 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28423293 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMe1701820
Optimal Frequency Retinopathy (Calculator) https://extapps.bsc.gwu.edu/shinypub/edic/retinopathy/ - ↑ 17.0 17.1 Hooper P, Boucher MC, Cruess A, et al. Excerpt from the Canadian Ophthalmological Society evidence- based clinical practice guidelines for the management of diabetic retinopathy. Can J Ophthalmol. 2017 Nov;52 Suppl 1:S45-S74 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29074014 <Internet> http://www.canadianjournalofophthalmology.ca/article/S0008-4182(17)31047-5/fulltext
- ↑ 18.0 18.1 Brooks M FDA OKs AI Device to Detect Diabetic Retinopathy in Primary Care. Medscape - Apr 11, 2018. https://www.medscape.com/viewarticle/895061
- ↑ 19.0 19.1 19.2 NEJM Knowledge+ Ophthalmology
- ↑ ElSayed NA, Aleppo G, Aroda VR, et al. 12. Retinopathy, neuropathy, and foot care: standards of care in diabetes - 2023. Diabetes Care. 2023;46:S203-S215. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36507636
- ↑ Morrison JL, Hodgson LA, Lim LL, Al-Qureshi S. Diabetic retinopathy in pregnancy: a review. Clin Exp Ophthalmol. 2016 May;44(4):321-34. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27062093 Review.
- ↑ Diabetic Retinopathy: What you should know http://www.nei.nih.gov/health/diabetic/retinopathy.asp