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{{Short description|Diabetes-induced damage to the retina of the eye}}
{{Infobox medical condition (new)
| name = Diabetic retinopathy
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}}
<!-- Definition and symptoms -->
'''Diabetic retinopathy''' (also known as '''diabetic eye disease'''), is a [[medical condition]] in which damage occurs to the [[retina]] due to [[diabetes]]. It is a leading cause of [[blindness]] in developed countries.
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==Pathogenesis==
[[File:Blausen 0312 DiabeticRetinopathy.png|thumb|Illustration depicting diabetic retinopathy]]
Diabetic retinopathy is the result of damage to the small blood vessels and neurons of the retina. The earliest changes leading to diabetic retinopathy include narrowing of the retinal arteries associated with [[Ischemia|reduced retinal blood flow]]; dysfunction of the neurons of the inner retina, followed in later stages by changes in the function of the outer retina, associated with subtle changes in visual function; dysfunction of the [[blood-retinal barrier]], which protects the retina from many substances in the blood (including toxins and [[immune cells]]), leading to the leaking of blood constituents into the retinal [[neuropile]].<ref name="XuCurtisStitt">{{cite journal| vauthors = Xu H, Curtis T, Stitt A |title=Pathophysiology and Pathogenesis of Diabetic Retinopathy [internet] |journal= Diapedia|date=13 August 2013 |volume=7104343513 |issue=14 |doi=10.14496/dia.7104343513.14|doi-broken-date=2024-
An experimental study suggests that pericyte death is caused by blood glucose persistently activating [[protein kinase C]] and [[mitogen-activated protein kinase]] (MAPK), which, through a series of intermediates, inhibits signaling through [[platelet-derived growth factor receptor]]s—signaling that supports cellular survival, proliferation, and growth. The resulting withdrawal of this signaling leads to the programmed cell death ([[apoptosis]]) of the cells in this experimental model.<ref>{{cite journal | vauthors = Geraldes P, Hiraoka-Yamamoto J, Matsumoto M, Clermont A, Leitges M, Marette A, Aiello LP, Kern TS, King GL | display-authors = 6 | title = Activation of PKC-delta and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy | journal = Nature Medicine | volume = 15 | issue = 11 | pages = 1298–1306 | date = November 2009 | pmid = 19881493 | pmc = 3290906 | doi = 10.1038/nm.2052 }}</ref>
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==Management==
There are four common treatments for diabetic retinopathy: [[anti-VEGF]] injections, [[steroid]] injections, panretinal [[laser photocoagulation]], and [[vitrectomy]].<ref>{{Cite journal |last1=Martinez-Zapata |first1=Maria José |last2=Salvador |first2=Ignacio |last3=Martí-Carvajal |first3=Arturo J. |last4=Pijoan |first4=José I. |last5=Cordero |first5=José A. |last6=Ponomarev |first6=Dmitry |last7=Kernohan |first7=Ashleigh |last8=Solà |first8=Ivan |last9=Virgili |first9=Gianni |date=2023-03-20 |title=Anti-vascular endothelial growth factor for proliferative diabetic retinopathy |journal=The Cochrane Database of Systematic Reviews |volume=2023 |issue=3 |pages=CD008721 |doi=10.1002/14651858.CD008721.pub3 |issn=1469-493X |pmc=10026605 |pmid=36939655
Although these treatments are very successful (in slowing or stopping further vision loss), they do not cure diabetic retinopathy. Caution should be exercised in treatment with laser surgery since it causes a loss of retinal tissue. It is often more prudent to inject triamcinolone or anti-VEGF drugs. In some patients it results in a marked increase of vision, especially if there is an [[macular edema|edema of the macula]].<ref name=":0">{{cite journal | vauthors = Mitchell P, Wong TY | title = Management paradigms for diabetic macular edema | journal = American Journal of Ophthalmology | volume = 157 | issue = 3 | pages = 505–13.e1–8 | date = March 2014 | pmid = 24269850 | doi = 10.1016/j.ajo.2013.11.012 }}</ref>
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===Mild or moderate NPDR===
For those with mild to moderate non-proliferative diabetic retinopathy, the American Academy of Ophthalmology recommends only more frequent retinal exams—every six to twelve months—as these people are at an increased risk of developing proliferative retinopathy or macular edema.{{sfn|Flaxel|Adelman|Bailey|Fawzi|2020|loc="Mild to moderate NPDR without macular edema"}} Injection of [[anti-VEGF]] drugs or steroids can reduce diabetic retinopathy progression in around half of eyes treated; however, whether this results in improved vision long term is not yet known.{{sfn|Brownlee|Aiello|Sun|Cooper|2020|loc="Treatment of nonproliferative diabetic retinopathy”}} The lipid-lowering drug [[fenofibrate]] also reduces progression of disease in people with mild to moderate disease.<ref>{{Cite journal |last1=Ngah |first1=Nor Fariza |last2=Muhamad |first2=Nor Asiah |last3=Abdul Aziz |first3=Roslin Azni |last4=Mohamed |first4=Shelina Oli |last5=Ahmad Tarmizi |first5=Nor Azita |last6=Adnan |first6=Azian |last7=Asnir |first7=Zalifah Zakiah |last8=Hussein |first8=Zanariah |last9=Siew |first9=Hui Foo |last10=Mohamed |first10=Masni |last11=Lodz |first11=Noor Aliza |last12=Valayatham |first12=Vijayamala |date=2022-12-18 |title=Fenofibrate for the prevention of progression of non-proliferative diabetic retinopathy: review, consensus recommendations and guidance for clinical practice |journal=International Journal of Ophthalmology |volume=15 |issue=12 |pages=2001–2008 |doi=10.18240/ijo.2022.12.16 |issn=2222-3959 |pmc=9729076 |pmid=36536974}}</ref><ref>{{Cite web |title=Trial: Fenofibrate Slows Diabetic Retinopathy Progression |url=https://www.medscape.com/viewarticle/trial-fenofibrate-slows-diabetic-retinopathy
===Diabetic macular edema===
Those at highest risk of vision loss – that is, with edema near the center of the macula – benefit most from eye injections of [[anti-VEGF]] therapies [[aflibercept]], [[bevacizumab]], or [[ranibizumab]].{{sfn|Flaxel|Adelman|Bailey|Fawzi|2020|loc="Anti-Vascular Endothelial Growth Factor Therapy"}} There is no widely accepted dosing schedule, though people typically receive more frequent injections during the first year of treatment, with less frequent injections in subsequent years sufficient to maintain remission.{{sfn|Lin|Hsih|Lin|Wen|2021|loc="Treatments"}} Those whose eyes don't improve with anti-VEGF therapy may instead receive laser photocoagulation, typically in the form of short laser pulses.{{sfn|Kuroiwa|Malerbi|Regatieri|2021|loc="Laser"}}
Those with macular edema but no vision loss do not benefit from treatment; the American Academy of Ophthalmology recommends deferring treatment until visual acuity falls to at least 20/30.{{sfn|Flaxel|Adelman|Bailey|Fawzi|2020|loc="Treatment Deferral"}} The diabetic macular edema manifestation is difficult to predict. Autoantibodies against [[hexokinase 1]] are commonly associated with diabetic macular edema manifestation. Nearly one-third of patients with diabetic macular edema were found to be positive for anti-hexokinase 1 autoantibodies. Importantly, these autoantibodies were rare in patients with diabetic retinopathy only or diabetes mellitus only. However, these autoantibodies fail to predict disease onset. They likely manifest secondary to the tissue-damaging stimulus at diabetic macular edema onset and cannot be used to predict diabetic macular edema before its onset.<ref name="Simcikova et al. 2024">{{Cite journal | last1 = Simcikova | first1 = D. | last2 = Ivancinova | first2 = J. | last3 = Veith | first3 = M. | last4 = Dusova | first4 = J. | last5 = Matuskova | first5 = V. | last6 = Nemcansky | first6 = J. | last7 = Kuncicky | first7 = P. | last8 = Chrapek | first8 = O. | last9 = Jiraskova | first9 = N. | last10 = Gojda | first10 = J. | last11 = Heneberg | first11 = P. | doi = 10.1016/j.diabres.2024.111721 | title = Serum autoantibodies against hexokinase 1 manifest secondary to diabetic macular edema onset. | journal = Diabetes Research and Clinical Practice | volume = 212 | issue = 1 | pages = 111721 | date = 2024 | pmid = 38821414 }}</ref>
===Laser photocoagulation===
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===Medications===
====Intravitreal triamcinolone acetonide====
[[Triamcinolone]] is a long acting steroid preparation. Treating people with DME with intravitreal injections of triamcinolone may lead to a some degree of improvement in visual acuity when compared to eyes treated with placebo injections.<ref name=":3">{{cite journal | vauthors = Rittiphairoj T, Mir TA, Li T, Virgili G | title = Intravitreal steroids for macular edema in diabetes | journal = The Cochrane Database of Systematic Reviews | volume = 2020 | issue = 11 | pages = CD005656 | date = November 2020 | pmid = 33206392 | pmc = 8095060 | doi = 10.1002/14651858.CD005656.pub3 }}</ref> When injected in the vitreous cavity, the steroid decreases the macular edema (thickening of the retina at the macula) caused due to diabetic maculopathy, and that may result in an increase in visual acuity. The effect of triamcinolone is not
====Intravitreal anti-VEGF====
[[Aflibercept]] may have advantages in improving visual outcomes over bevacizumab and [[ranibizumab]], after one year, longer term advantages are unclear <ref>{{Cite journal |last1=Virgili |first1=Gianni |last2=Curran |first2=Katie |last3=Lucenteforte |first3=Ersilia |last4=Peto |first4=Tunde |last5=Parravano |first5=Mariacristina |date=2023-06-27 |editor-last=Cochrane Eyes and Vision Group |title=Anti-vascular endothelial growth factor for diabetic macular oedema: a network meta-analysis |journal=Cochrane Database of Systematic Reviews |language=en |volume=2023 |issue=6 |pages=CD007419 |doi=10.1002/14651858.CD007419.pub7 |pmc=10294542 |pmid=38275741
===Surgery===
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Vitrectomy may be done under general or [[local anesthesia]]. The doctor makes a tiny incision in the [[sclera]], or white of the eye. Next, a small instrument is placed into the eye to remove the vitreous and insert the saline solution into the eye.
Patients may be able to return home soon after the vitrectomy, or may be asked to stay in the [[hospital]] overnight. After the operation, the eye will be [[red]] and sensitive, and patients usually need to wear an eyepatch for a few days or weeks to protect the eye. Medicated eye drops are also prescribed to protect against [[infection]]. There is evidence which suggests anti-[[VEGF]] drugs given either prior to or during vitrectomy may reduce the risk of posterior vitreous cavity haemorrhage .<ref>{{cite journal | vauthors = Dervenis P, Dervenis N, Smith JM, Steel DH | title = Anti-vascular endothelial growth factors in combination with vitrectomy for complications of proliferative diabetic retinopathy | journal = The Cochrane Database of Systematic Reviews | volume = 2023 | issue = 5 | pages = CD008214 | date = May 2023 | pmid = 37260074 | pmc = 10230853 | doi = 10.1002/14651858.CD008214.pub4
==Epidemiology==
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===Blood pressure control===
A [[Cochrane (organisation)|Cochrane review]] examined 29 randomized controlled trials to determine whether interventions that sought to control or reduce blood pressure in diabetics had any effects of diabetic retinopathy.<ref name=":5">{{cite journal | vauthors = Do DV, Han G, Abariga SA, Sleilati G, Vedula SS, Hawkins BS | title = Blood pressure control for diabetic retinopathy | journal = The Cochrane Database of Systematic Reviews | volume = 2023 | issue = 3 | pages = CD006127 | date = March 2023 | pmid = 36975019 | pmc = 10049880 | doi = 10.1002/14651858.CD006127.pub3
=== Fundoscopic image analyses ===
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