Diabetic Retinopathy

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Disease Entity

Diabetes mellitus as a disease was identified as far back as 250-300 BC and was characterized by the sweet properties of urine. In 1889 Mering and Minkowski discovered the relevance of the pancreas in this disease process after inducing a severe and fatal form of diabetes in a dog following removal of the pancreas. Since then, advancements in medicine have led to multiple new medication therapies and approaches to treat diabetes mellitus.

Despite this, diabetes remains one of the top ten most prevalent and important non-infectious causes of morbidity and mortality worldwide. An estimated 34.1 million Americans aged 18 years or older, 13.0% of all U.S. adults, had diabetes in 2018. This prevalence, in concert with the associated diseases that usually coincide with (and result from) diabetes should solidify the importance of being familiar with this disease process.


Diabetic retinopathy represents microvascular end-organ damage as a result of diabetes. It ranges from non-proliferative diabetic retinopathy (NPDR) and its stages to proliferative diabetic retinopathy (PDR). As the disease progresses, associated diabetic macular edema (DME) may also become apparent.

Among patients aged 25-74, diabetic retinopathy is a leading cause of vision loss worldwide. By 2030 an estimated 191.0 million people globally will have diabetic retinopathy, and approximately 56.3 million will have vision-threatening diabetic retinopathy. The Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) Cohort showed that after 20 years of diabetes mellitus, 99% of patients with type 1 and 60% of patients with type 2 show some degree of retinopathy. There are several other key risk factors for the development of diabetic retinopathy beyond years since diagnosis and type of diabetes. Additionally, elevated hemoglobin A1c (HbA1c) levels and blood pressure are associated with increased risk of diabetic retinopathy.


Type 1 diabetes mellitus (T1DM) is characterized by the destruction of beta cells in the pancreas by an autoimmune mechanism, whereas type 2 diabetes mellitus (T2DM) is a relationship between lifestyle and genetics. Etiology of these two subtypes describes the etiology of diabetic retinopathy, as retinal disease is an end-organ manifestation of the principal disease.

There is a stronger genetic association between T2DM compared to T1DM. Multiple genetic factors have been named in the development of T2DM including TCF7L2 , NOTCH2, KCNQ1, JAZF1, and MODY (a heterogeneous disorder with autosomal dominant transmission). Poor lifestyle, in conjunction with genetic influences, increases the risk of developing T2DM.

Over 90% of people with a new diagnosis of T1DM have measurable antibodies against specific pancreatic β-cell proteins (insulin, islet antigen 2, zinc transporter 8, etc.). These antibodies lead to a chain of progressive loss of β-cells, decreased insulin release, and recognizable diabetes.

Risk Factors

  • Diabetes duration
  • Uncontrolled glucose or blood pressure levels are associated with increased risk (see NHANES, UKDPS, WESDR references below)
  • Hypertension
  • Dyslipidemia
  • Ethnicity
  • Pregnancy
  • Smoking

General Pathology

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

Of primary concern are the factors that lead to visual impairment in this patient population.  The three items listed below are the foundation of this disease process, and the presence of them can be correlated with disease severity.

1.    Capillary leakage (DME)

2.    Capillary occlusion

3.    Sequelae of retinal ischemia (retinal neovascularization, vitreous hemorrhage, tractional retinal detachment, neovascular glaucoma)


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

Diabetic retinopathy pathophysiology

Primary Prevention

Control of glucose and blood pressure. Each 1% reduction in updated mean HbA1c was associated with a reduction 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).



Symptoms of decreased vision or fluctuating vision (lens or macular edema), presence of floaters (vitreous hemorrhage), or visual field defects (tractional detachment). It is important to know the hemoglobin A1c and whether or not 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 [neovascularization of the iris (NVI) or rubeosis], 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 lens) to look for microaneurysms, hemorrhage, hard exudates, cotton wool spots, and retinal swelling (DME). 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 retinal area that is 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, which is referred to as macular edema.

Classification of Non-proliferative diabetic retinopathy

Non-proliferative diabetic retinopathy can be classified into mild, moderate or severe stages based upon the presence or absence of retinal bleeding, abnormal beading of the venous wall (venous beading) or abnormal vascular findings (intraretinal microvascular anomalies or IRMA).

  • Mild: few microaneurysms
  • Moderate: increased number of microaneurysms and dot-blot hemorrhages. Cotton wool spots and hard exudates may be present.
  • Severe: "4-2-1 rule" -- 4 quadrants of diffuse retinal hemorrhages and microaneurysms, 2 or more quadrants of venous beading, or 1 or more quadrant of IRMA

No treatment is usually done at this stage though there is evidence that anti-vascular endothelial growth factor (VEGF) injections may help decrease the severity of retinopathy and lower the risk of vision complications.

Proliferative diabetic retinopathy

High Risk Characteristics
  • NVD > 1/4 to 1/3 disc area
  • Any NVD associated with vitreous or preretinal hemorrhage
  • Any NVE associated with vitreous or preretinal hemorrhage

This is progressive and often requires treatment to prevent bleeding and scar tissue formation, especially in patients who meet high risk characteristics.

Diagnostic Procedures

Fluorescein angiography (FA) may be 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 also show leakage on the FA. Areas of capillary dropout and non-perfusion will appear hypofluorescent.

Optical coherence tomography (OCT) is useful to determine the presence and location of intraretinal and/or subretinal fluid as well as retinal thickness measurements. The OCT can be sequentially obtained to determine whether the macular edema is responding 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, HbA1c ≤ 7 is the goal. Sometimes, for older patients (≥70 years), diabetologists aim for a slightly higher HbA1C since levels below 7 have been associated with increased morbidity in that age group.

Differential Diagnosis

Macular edema with retinal hemorrhages

Retinal neovascularization

Iris neovascularization

  • Vein occlusion
  • Ocular ischemic syndrome


General Treatment

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

Medical Therapy and Follow-up

Diabetic Macular Edema

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 (anti-VEGF therapies or corticosteroids) that decrease the retinal swelling/macular edema. Patients may be initially 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 study by the DRCR network (Protocol T) has shown all three drugs (bevacizumab, ranibizumab and aflibercept) are effective for macular edema therapy with similar visual outcomes in eyes with better vision (20/32 to 20/40).[1] If visual acuity was 20/50 or worse, aflibercept had superior visual outcomes compared to bevacizumab (at year 1 and year 2) and ranibizumab (at year 1 only). A corollary DRCR study (Protocol AC) explored step therapy by comparing initial bevacizumab treatment with a switch to aflibercept only if certain criteria for improvement were not met versus immediately starting aflibercept in eyes with visual acuity of 20/50 or worse.[2] No significant difference in visual outcomes were seen with either treatment algorithm. Another study by the DRCR (Protocol V) has shown that for eyes with very good visual acuity (20/25 or better), watchful and careful observation compared well to those treated with immediate anti-VEGF therapy.[3] For observed eyes, prompt treatment with anti-VEGF once sustained visual acuity decline was found, resulted in good visual acuity outcomes. In 2022, two new drugs were FDA approved for the treatment of DME: brolucizumab[4] and faricimab.[5] The phase 3 clinical trials demonstrated similar visual acuity outcomes to aflibercept with the potential for less frequent dosing intervals of up to 12-16 weeks.

Proliferative Diabetic Retinopathy

The primary treatment option for PDR is laser photocoagulation of the peripheral retina, known as panretinal photocoagulation (PRP). The laser is used to obliterate some of the ischemic peripheral retina in order to decrease VEGF release and induce regression of neovascularization. If successful, vitreous hemorrhage and tractional retinal detachment may be averted. Sometimes the proliferative disease is advanced and there is blood filling the eye (and preventing application of laser) or scar tissue that wrinkles the retina or pulls it off the eyewall (tractional retinal detachment). In these situations, surgery may be necessary (see vitrectomy for more information).

In some cases, anti-VEGF injections into the eye can also be used to induce regression of neovascularization. DRCR protocol S showed that the anti-VEGF drug ranibizumab was noninferior to PRP in managing patients with PDR. In situations where PRP is not possible, such as in the presence of vitreous hemorrhage, anti-VEGF injections may help to improve the likelihood of clearance of the hemorrhage. Follow-up is crucial for patients receiving anti-VEGF injections alone as this therapy does not appear to provide long-term involution of the neovascularization after the injections are halted, whereas PRP generally has long-lasting effects. Thus, in a patient who is, for any reason, unlikely to return for follow-up, anti-VEGF injections alone should not be the treatment of choice and PRP should be done. However, a large case-control study has demonstrated no difference between injections alone vs. PRP alone in the odds of TRD.[6]

Anti-VEGF injections may sometimes be used in concert with PRP when rubeosis and neovascular glaucoma are present. Another common scenario is using anti-VEGF injections initially in eyes with vitreous hemorrhage that is too dense to permit PRP then later performing laser once the hemorrhage has adequately cleared. Anti-VEGF injections are also sometimes given prior to vitrectomy surgery in selected cases to lower the risk of intraoperative hemorrhage.

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 maintain reattachment of 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


Cited References

  1. Wells JA, Glassman AR, Ayala AR, Jampol LM, Bressler NM, Bressler SB, Brucker AJ, Ferris FL, Hampton GR, Jhaveri C, Melia M, Beck RW; Diabetic Retinopathy Clinical Research Network. Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema: Two-Year Results from a Comparative Effectiveness Randomized Clinical Trial. Ophthalmology. 2016 Jun;123(6):1351-9. doi: 10.1016/j.ophtha.2016.02.022. Epub 2016 Feb 27. PMID: 26935357; PMCID: PMC4877252.
  2. Jhaveri CD, Glassman AR, Ferris FL 3rd, Liu D, Maguire MG, Allen JB, Baker CW, Browning D, Cunningham MA, Friedman SM, Jampol LM, Marcus DM, Martin DF, Preston CM, Stockdale CR, Sun JK; DRCR Retina Network. Aflibercept Monotherapy or Bevacizumab First for Diabetic Macular Edema. N Engl J Med. 2022 Aug 25;387(8):692-703. doi: 10.1056/NEJMoa2204225. Epub 2022 Jul 14. PMID: 35833805; PMCID: PMC9714135.
  3. 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.
  4. Brown DM, Emanuelli A, Bandello F, Barranco JJE, Figueira J, Souied E, Wolf S, Gupta V, Ngah NF, Liew G, Tuli R, Tadayoni R, Dhoot D, Wang L, Bouillaud E, Wang Y, Kovacic L, Guerard N, Garweg JG. KESTREL and KITE: 52-Week Results From Two Phase III Pivotal Trials of Brolucizumab for Diabetic Macular Edema. Am J Ophthalmol. 2022 Jun;238:157-172. doi: 10.1016/j.ajo.2022.01.004. Epub 2022 Jan 14. PMID: 35038415.
  5. Wykoff CC, Abreu F, Adamis AP, Basu K, Eichenbaum DA, Haskova Z, Lin H, Loewenstein A, Mohan S, Pearce IA, Sakamoto T, Schlottmann PG, Silverman D, Sun JK, Wells JA, Willis JR, Tadayoni R; YOSEMITE and RHINE Investigators. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): two randomised, double-masked, phase 3 trials. Lancet. 2022 Feb 19;399(10326):741-755. doi: 10.1016/S0140-6736(22)00018-6. Epub 2022 Jan 24. PMID: 35085503.
  6. Tsui JC, Yu Y, VanderBeek BL. Association of Treatment Type and Loss to Follow-up With Tractional Retinal Detachment in Proliferative Diabetic Retinopathy [published online ahead of print, 2022 Dec 1]. JAMA Ophthalmol. 2022;10.1001/jamaophthalmol.2022.4942. doi:10.1001/jamaophthalmol.2022.4942

General References

  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.
  27. Sapra A, Bhandari P. Diabetes Mellitus. In: StatPearls. Treasure Island (FL): StatPearls Publishing; June 7, 2020
  28. The top 10 causes of death. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death. Published May 24, 2018. Accessed August 23, 2020.
  29. National Diabetes Statistics Report 2020. DiabetesResearch.org. https://www.diabetesresearch.org/file/national-diabetes-statistics-report-2020.pdf. Published 2020. Accessed August 23, 2020.
  30. Zheng Y, He M, Congdon N. The worldwide epidemic of diabetic retinopathy. Indian J Ophthalmol. 2012;60(5):428-431. doi:10.4103/0301-4738.100542
  31. Klein R, Lee KE, Knudtson MD, Gangnon RE, Klein BE. Changes in visual impairment prevalence by period of diagnosis of diabetes: the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Ophthalmology. 2009;116(10):1937-1942. doi:10.1016/j.ophtha.2009.03.012
  32. Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35(3):556-564. doi:10.2337/dc11-1909
  33. Sladek R, Rocheleau G, Rung J, et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature. 2007;445(7130):881-885. doi:10.1038/nature05616
  34. DiMeglio LA, Evans-Molina C, Oram RA. Type 1 diabetes. Lancet. 2018;391(10138):[[1]]. doi:10.1016/S0140-6736(18)31320-5
  35. Zheng, Y., Ley, S. H., & Hu, F. B. (2018). Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nature Reviews.Endocrinology, 14(2), 88-98. doi:http://dx.doi.org.wrnmmc.idm.oclc.org/10.1038/nrendo.2017.151
  36. Ning Cheung MD, Paul Mitchell Prof and Tien Yin Wong ProfLancet, The, 2010-07-10, Volume 376, Issue 9735, Pages 124-136, Copyright © 2010 Elsevier Ltd
  37. 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.