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Ocular Associations of Diabetes Other ThanDiabetic RetinopathyV. SWETHA E. JEGANATHAN, MBBS1,2

JIE JIN WANG, PHD1,3

TIEN YIN WONG, MD, PHD1,3,4

Diabetic retinopathy is the most well-known ocular complication of dia-betes and the leading cause of

blindness among people 2064 years ofage in the U.S. (1). Up to 4 million Amer-icans with diabetes, 40 years of age andolder, have retinopathy, and nearly 1 mil-lion have sight-threatening retinopathy(2). In major clinical trials, tight control ofblood glucose and blood pressure hasbeen demonstrated to reduce the risk of

retinopathy and associated blindness (3).A range of ocular diseases is also as-

sociated with diabetes, which may lead tovisionloss. However, some of these ocularconditions may not be familiar to noneyeclinicians (4 6). In this review, we aim tohighlight the frequencies, clinical presen-tations, natural histories, and manage-m e n t o f t h e s e o c u l a r c o n d i t i o n s .Physicians who manage patients with di-abetes may benefit from knowledge ofthese associated conditions and are thusable to ensure adequate and timely refer-

ral and treatment. Routine eye screeningfor retinopathy of individuals with diabe-tes offers the opportunity to detect theseother ocular diseases early, many ofwhich are sight threatening. Physician ed-ucation remains an important publichealth strategy in the prevention of visionloss in patients with diabetes.

OCULAR CONDITIONS

DIRECTLY ASSOCATED

WITH DIABETES

1. Cataracts and cataract surgeryCataract is a major cause of vision impair-ment in people with diabetes. Numerous

studies have documented an associationbetween diabetes and cataracts. This asso-ciation is supported by an abundance ofdata from clinical epidemiological studiesand basic science studies (722). Bothcross-sectional and prospective data fromthree population-based studies, the Bea-ver Dam Eye Study, the Blue MountainsEye Study, and the Visual ImpairmentProject, have documented associationsbetween diabetes and both prevalent and

incident posterior subcapsular cataractand, less consistently, with prevalent andincident cortical cataracts but not nuclearcataract (812,1419,23,25). The BlueMountains Eye Study showed that im-paired fasting glucose, in the absence ofclinical diabetes, was also a risk factor forthe development of cortical cataract (7).There is additional evidence that the riskof cataract increases with increasing dia-betes duration and severity of hyperglyce-mia (26). De posit ion of a dva nc e dglycation end products in the lens has

been postulated as one possible patho-genic mechanism for diabetic cataract(27).

Cataract surgery is the standard treat-ment for patients with cataract and signif-icant vision impairment. In individualswith diabetes, cataract occurs at a youngerage and progresses more rapidly, result-ing in higher rates of cataract surgery at arelatively young age (28). In the Wiscon-sin Epidemiologic Study of Diabetic Reti-n o p a t h y , t h e 1 0 - y e a r c u m u l a t i v eincidence of cataract surgery was 8% inthose with type 1 diabetes and 25% inthose with type 2 diabetes. Predictors ofcataract surgery included older age,

greater severity of diabetic retinopathy,and baseline proteinuria in type 1 diabe-

tes and older age and use of insulin in type2 diabetes (25).While the overall outcomes of cata-

ract surgery are excellent, patients withdiabetes may have poorer vision out-comes than those without diabetes, andthe worst outcomes may occur in oper-ated eyes with active proliferative retinop-athy (29) and/or preexisting macularedema. To improve cataract surgical out-comes in patients with diabetes, adequatecontrol of diabetic retinopathy with lasertreatment before cataract surgery is nec-essary (30).

The most devastating postoperativecomplication is endophthalmitis, a severeintraocular infection, with several studiesshowing that patients with diabetes havean increased risk of developing this com-plication (3134), resulting in pooreroutcomes (35). Patients with endoph-thalmitis characteristically present withpain, redness, discharge, decreased vi-sion, eyelid edema, proptosis, and con-

junctival injection, with anterior chamberinflammation and vitritis. Management ofendophthalmitis consists of inpatient ad-

mission for a combination of intravitreal,subconjunctival, and topical antibioticsand steroids and possibly ocular surgery.In patients with diabetes, treatment mayneed to be more aggressive, with surgeryperformed earlier rather than later (35).

2. Anterior ischemic opticneuropathy

Ante rior is chemic optic ne uropat hy(AION) is an acute vascular condition ofthe optic nerve. Studies suggest that up to25% of patients with AION have a history

of diabetes (36). In patients with diabetes,diabetic microvascular disease affectingthe anterior part of the optic nerve isthought to cause the ischemia (37, 38).

The optic disc in the contra-lateraleye of patients with AION is typicallysmall in diameter with a small or absentcup, referred to as a disc at risk. Patientswith AION usually present with moderateloss of vision upon awakening, presum-ably related to nocturnal systemic hypo-tension (39). Visual acuity is better than20/200 in 60% of cases at presentation(40). Untreated, AION generally remains

From the1Centrefor Eye Research Australia,University of Melbourne,Victoria,Australia; the 2Singapore EyeResearch Institute, Singapore National Eye Centre, Singapore; the 3Centre for VisionResearch, Universityof Sydney, New South Wales, Australia; and the 4Department of Ophthalmology, Yong Loo Lin School ofMedicine, National University of Singapore, Singapore.

Corresponding author: Tien Yin Wong, [email protected] 17 February 2008 and accepted 29 May 2008.DOI: 10.2337/dc08-0342 2008 by the American Diabetes Association. Readers may use this article as long as the work is properly

cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be herebymarked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

R e v i e w s / C o m m e n t a r i e s / A D A S t a t e m e n t s

R E V I E W A R T I C L E

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stable, and recurrence in the same eye isunusual (41). Good recovery of visionwas observed in 43% of patients in theIschemic Optic Neuropathy Decompres-sion Trial (42).

There are no proven treatments forAION, and the Ischemic Optic Neuropa-thy Decompression Trial revealed no ben-

efit of optic nerve decompression surgery(43). Currently, neuroprotective agentsare being investigated for nonarteritic

AION (NAION) and appear to be benefi-cial against secondary neuronal degener-ation in animal models of ischemic retinalganglion cell damage and optic nervecrush injury (44). There is no proven pro-phylaxis for AION, and the evidence forthe efficacy of aspirin therapy is limited(45).

3. Diabetic papillopathy

Diabetic papillopathy is an uncommonoptic nerve condition characterized byacute disc edema and mild vision loss(46). Diabetic papillopathy is a risk factorfor the progression of diabetic retinopa-thy (47); and, in rare instances, papillopa-thy can precede the development of

AION (48). Early investigators postulateda toxic effect of abnormal glucose metab-olism on the optic nerve in individualswith diabetes; subsequent studies havesuggested that diabetic papillopathy maybe a mild and reversible form of AION(49).

The significance of this condition istwofold. First, this condition may be mis-diagnosed as papilledema (50). Second,telangiectasia at the optic disc in diabeticpapillopathy may be mistaken as neovas-cularization in the opitc disc as part ofproliferative diabetic retinopathy, leadingto unnecessary laser photocoagulation.Diabetic papillopathy spontaneously im-proves within a year, and vision prognosisis usually good. In most patients, visionrecovers to a level 20/30 (51). Tighten-ing diabetes control and treating coexis-

tent hypertension and renal dysfunctionmay help with resolution of this condi-tion. There is anecdotal evidence that in-traocular steroid injection may benefitpatients with vision impairment (52).

4. Ocular movement disordersExtraocular motility disorders may occurin patients with diabetes, secondary to di-abetic neuropathy, involving the third,fourth, or sixth cranial nerve. Rarely, si-multaneous palsies of multiple extraocu-lar nerves can occur (53,54). Diabetes isthe underlying cause in 2530% of pa-

tients aged 45 years and older who de-velop acute extraocular muscle palsy(55). In one study (56), 1% of patientswith diabetes were found to have cranialnerve palsies, compared with only 0.13%of control subjects. Of these cases, 41%had a third nerve palsy. In another popu-lation-based study, patients with sixth

cranial nerve palsy were six times morelikely to have diabetes (57).

Patients with extraocular palsiespresent with binocular diplopia. Pupilsparing is an important diagnostic featurein diabetes-related third cranial nervepalsy, distinguishing it from surgicalcauses, such as intracranial aneurysm ortumor. In diabetic cranial nerve palsies,recovery of extraocular muscle functiongenerally occurs within 3 months (58).Recurrences can be common and may in-volve the same or other cranial nerves.

The presence of other focal neurologicalsigns, progressive deterioration, or palsyin a patient younger than 45 years shouldbe investigated to exclude a compressivelesion. In these instances, a neurology orneuro-ophthalmology consultation is rec-ommended.

OCULAR CONDITIONS FOR

WHICH DIABETES IS A

KNOWN RISK FACTOR

1. GlaucomaGlaucoma is a progressive optic neuropa-thy associated with typical optic discchanges and visual field defects. Elevatedintraocular pressure is the major risk fac-tor for glaucoma, although a proportionof patients with glaucoma do not haveraised intraocular pressure. Patients withdiabetes are at risk of two major types ofglaucoma: primary glaucoma and neovas-cular glaucoma.a. Primary glaucoma. Several large epi-demiological studies have reported posi-tive associations between diabetes withprimary open angle glaucoma (POAG),the most common form of primary glau-coma, or elevated intraocular pressure inthe absence of glaucoma optic neuropa-thy (5963). Glaucoma occurs more of-ten in patients with diabetes (5%) thanin the general population (2%) (64). Therisk of glaucoma has been reported to be1.6 4.7 times higher in individuals withdiabetes than in nondiabetic individuals(6568). In the Blue Mountains and Bea-ver Dam Eye studies, participants with di-abetes were twice as likely to have

glaucoma as those without. However, notall population-based studies have identi-fied such an association (6973).

There are clear biologically plausiblemechanisms supporting an associationbetween diabetes and POAG. First, mi-crovascular damage from diabetes couldimpair blood flow to the anterior optic

nerve, resulting in optic nerve damage(37,38). Diabetes also impairs the auto-regulation of posterior ciliary circulation,which may exacerbate glaucomatous op-tic neuropathy (74). Second, patientswith diabetes often have concomitant car-diovascular risk factors (e.g., hyperten-sion) that may affect vascular perfusion ofthe optic nerve head (75). Finally, relativeto those without diabetes, individualswith diabetes may be more vulnerable toelevated intraocular pressure (76), withmore severe visual field loss at the same

intraocular pressure level (77).It is important to screen for POAGamong individuals with diabetes, asPOAG can be asymptomatic until the latestages, when decreased vision and/or con-stricted visual fields are noted. Treatmentinvolves lowering intraocular pressurethrough topical eye drops and laser andsurgical procedures. Primary angle clo-sure glaucoma (PACG), the other com-mon primary glaucoma, is characterizedby narrow or closed anterior chamber an-gles, which impedes drainage of aqueoushumor and leads to raised intraocular

pressure. Patients with PACG appear tobe more likely to have abnormal glucosetolerance than those with POAG or thosewithout glaucoma (78). Diabetes may beassociated with PACG via systemic auto-nomic dysfunction or increased lensthickness as a result of sorbitol overload(79,80). Patients with PACG may presentwith an acute attack, which is associatedwith severe ocular pain, headaches, andnausea, with substantially elevated in-traocular pressure. Acute PACG requiresurgent referral and treatment.

b. Neovascular glaucoma. Studies haveshown a consistent association betweendiabetes and neovascular glaucoma (81),with proliferative retinopathy the leadingcause of this type of secondary glaucoma.Between 32 and 43% of neovascular glau-coma cases are caused by proliferativediabetic retinopathy (82,83). Neovascu-larization of the iris, an early precursor ofneovascular glaucoma, is commonly seenin patients with long-standing poorlycontrolled diabetes (84). Hypoxia in theretina and other ocular tissue causes anincreased expression of vascular endothe-

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lial growth factor (VEGF), which stimu-lates new vessel formation in the iris (85)or in the anterior chamber angle (86).Neovascular glaucoma requires aggres-sive intervention to lower intraocularpressure with medication, followed bysurgery (87). Regression of neovascular-ization following pan-retinal laser photo-

coagulation can occur if treated early(37,38).

2. Ocular ischemic syndromeOcular ischemic syndrome (OIS) is an un-common vascular problem that resultsfrom chronic hypo-perfusion of the eye,most commonly caused by ipsilateral in-ternal carotid or ophthalmic artery occlu-sion (88). Patients with OIS typicallypresent with vision loss and dull ocularpain (87). The prevalence of diabetes inpatients with OIS is higher than in the

general population (69), with one studyreporting that more than 50% of patientswith OIS have diabetes (89). Diabetes is amajor risk factor for carotid artery steno-sis and plaque formation, the underlyingcauses of OIS (90).

The 5-year mortality rate among pa-tients with OIS has been reported to be40%or higher (91). Coexisting cardiovas-cular and cerebrovascular diseases are themain causes of death. Carotid ultrasonog-raphy is useful to delineate the presenceand severity of carotid artery stenosis. Al-though carotid endarterectomy lowers

the risk of stroke in patients with symp-tomatic carotid stenosis (92), it is unclearwhether this procedure alters vision prog-nosis in eyes with OIS (93,94). The coex-istence of diabetes with OIS may be anindicator of poorer vision prognosis, dueto the higher incidence of secondary glau-coma (94). Pan-retinal laser photocoagu-lation is indicated in eyes with ocularneovascularization.

OCULAR CONDITIONS

WHERE DIABETES IS A

POSSIBLE RISK FACTOR

1. Retinal vein occlusionRetinal vein occlusion (RVO) is a retinalvascular condition characterized by di-lated tortuous retinal veins with retinalhemorrhages, cotton wool spots, andmacular edema. Central RVO occurs atthe optic disc (95), whereas branch RVOoccurs at retinal venular branches, usu-ally at the site of arterio-venous crossing(96). Central RVO may be subdivided fur-ther into nonischemic and ischemictypes, the latter associated with poorer vi-

sion prognosis (97). Although it has beenthought that diabetes is a major risk fac-tor for RVO, epidemiological studieshave not shown a consistent relation-ship between diabetes and the presenceof RVO, with some studies reporting apositive association (98102) and oth-ers finding no association (103106).

The importance of RVO in patients withdiabetes is that the retinal signs (e.g.,hemorrhages or cotton wool spots) maymimic diabetic retinopathy. Thus,when patients with diabetes presentwith acute vision loss and asymmetricsigns of diabetic retinopathy, RVOshould be considered.

The management of RVO dependsupon the site of occlusion (central orbranch), degree of ischemia, presence ofmacular edema, visual acuity level, andcomplications. Approximately 30% of

central RVO cases are initially nonisch-emic, but 10% progress to ischemiawithin 6 months (107). The two majorcomplications of RVO are secondary neo-vascular glaucoma and macular edema.Pan-retinal laser photocoagulation hasbeen shown to prevent neovascular glau-coma (108). No treatment has proven ef-fective for macular edema in patients withcentral RVO, although focal laser treat-ment may be useful in patients with mac-ular edema and branch RVO (109).Clinical trials are on-going to assess the

intraocular administration of pharmaceu-tical agents, such as steroids (110) or an-tivascular endothelial growth factoragents (111,112).

The vision prognosis with centralRVO, particularly ischemic central RVO,is poor, but that of branch RVO is rela-tively good, with nearly half of patientsmaintaining visual acuity better than20/40 (113). Patients with diabetes whodevelop RVO are more likely than theirnondiabetic counterparts to develop reti-nal neovascularization (114), neovascular

glaucoma, and vitreous hemorrhage(112). More importantly, recent studiessuggest that, among those with diabetes4369 years of age, the presence of RVOis associated with double the risk of car-diovascular mortality (115).

Management of concomitant medicalconditions (e.g., hypertension and dyslip-idemia) may be important to prevent arecurrence of RVO (116). There is nogood evidence that tight glycemic controlcan alter the course or improve the prog-nosis of RVO.

2. Retinal arteriolar emboliRetinal arteriolar emboli are discreteplaque-like lesions lodged in the lumen ofretinal arterioles. The majority of emboliare asymptomatic and transient, althoughpatients infrequently present with epi-sodes of sudden, painless, monocularblindness (amaurosis fugax), a transient

ischemic attack, or stroke (117).Population-based studies show that

asymptomatic retinal emboli occur in1.31.4% of adults 40 years of age andolder (61,118). Studies show that retinalarteriolar emboli are associated with ca-rotid artery disease, hypertension, othercardiovascular risk factors (117), and anincreased risk of stroke and stroke-related(119,120) and all-cause (121) mortality.However, there are no consistent data onwhether retinal arteriolar emboli occurmore commonly in people with diabetes.

In theBeaver Dam Eye Study, participantswith type 2 diabetes were found to have atwofold higher prevalence of retinal em-boli (60), but two other population-basedstudies have failed to confirm this associ-ation (61,105).

Once an embolus has been detected, afull cardiovascular and cerebrovascularrisk assessment is recommended, includ-ing carotid artery ultrasound and echo-cardiography to assess the source of theemboli. Treatment of concomitant car-diovascular risk factors is vital and shouldinclude improved control of hyperglyce-

mia, hypertension, and hyperlipidemia,cessation of smoking, and carotid endar-terectomy, if indicated. Low-dose aspirincan be recommended to prevent retinalartery occlusion (122).

3. Retinal artery occlusionRetinal artery occlusion (RAO) is a retinalvascular condition similar to emboli. Thehallmark of RAO is sudden, unilateral,painless loss of vision associated with avisual field defect. Patients with central

RAO usually present with a dramatic lossof vision, an afferent pupillary defect, dif-fuse retinal whitening, and the resultantclassic cherry spot on the macula. Thefundoscopic findings with branch RAO,which occur at a branch, usually consistof a focal wedge-shaped area of retinalwhitening; vision loss also tends to bemuch milder. As for emboli, there is noclear evidence that patients with diabetesare at higher risk of RAO. However, theprevalence of diabetes among patientswith RAO has been reported to be as highas 21%, which is higher than in the gen-

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e r a l p o p u l a t i o n o f t h e s a m e a g e(123,124).

Patients with RAO should be referredimmediately to an ophthalmologist formanagement. In the acute phase (within24 h), a variety of treatments have beenproposed, such as ocular massage (to dis-lodge the embolus) and intravenous acet-

azolamide injection (to lower intraocularpressure) (125). However, there is no ev-idence from randomized trials regardingthe efficacy of these treatments (126). It isimportant for physicians to measure theerythrocyte sedimentation rate to excludegiant cell arteritis (127). Regardless oftreatment, however, the vision prognosisof central RAO is poor (128).

4. Corneal diseasesPatients with diabetes are known to ex-hibit abnormalities of the corneal epithe-

l ium, le a ding t o c orne a l e rosion,persistent epithelial defect, or corneal ul-cers. Recurrent corneal erosions in pa-t i e n t s w i t h d i a b e t e s a r e u s u a l l yposttraumatic and the result of apparentlymild epithelial breakdown following cat-aract or vitreoretinal surgery (129131).

A reduction in hemidesmosomes maycontribute to a weakness in the adhesionof diabetic corneal epithelium to the un-derlying stroma (132). In addition, eryth-rocyte aldose reductase increase has beenreported in patients with type 2 diabetes,leading to high accumulation of sorbitol,

which can damage the corneal epithelium(133). In one study, corneal abnormali-ties (gerontoxon, limbal vascularization,punctate keratopathy, endothelial dystro-phy, recurrent erosion, and ulcers) weredetected in up to 73.6% patients with di-abetes (134). Patients with corneal dis-e as e o f te n p r es en t w it h p ai n ,photophobia, blurred vision, and hyper-emia. However, patients with diabetes of-ten have reduced corneal sensitivity aspart of diabetes complication in periph-eral nerves and limbal vasculopathy

(135).Patients with diabetes who wear con-tact lenses must take extra hygiene careand be warned to seek advice early if anyirritation symptom develops to preventvision loss from microbial keratitis. Treat-ment of corneal disease includes topicalantibiotics and topical cycloplegic (shortterm), and corneal patching for 24 h isindicated if the original insult is of nonor-ganic nature (not from plant or soilsources), for large corneal lesions (2cm), and in noncontact lens users. Con-tact lensrelated conditions including

corneal ulcers and large abrasions needurgent referral to the ophthalmologist. Allother corneal cases need to be reviewedt h e n e x t d a y b y t h e p r i m a r y c a r ephysician.

CONDITIONS

MASQUERADING AS

DIABETIC RETINOPATHYThere are a range of common ocular andsystemic conditions that can mimic dia-betic retinopathy in patients with diabetes(136).

1. Age-related macular degenerationAlthough many population-based studieshave shown that people with diabetes arenot at higher risk of age-related maculardegeneration (AMD) (137143), there aresimilarities between AMD and diabeticretinopathy. First, retinal signs (e.g.,

hemorrhages and hard exudates) of neo-vascular or wet AMD are sometimesconfused with diabetic macular edema,particularly among older patients with di-abetes. Second, the key pathogenic pro-cess in neovascular AMD and proliferativeretinopathy is an increased expression of

VEGFs. Chronic inflammation is also apossible common pathophysiologicmechanismof both conditions (144,145).

Advanced glycation end products, for ex-ample, have been found in drusen, a typ-ical lesion of early-stage AMD (146).Third, there is now good evidence that

anti-VEGF treatment is effective for bothneovascular AMD and proliferative reti-nopathy (147149).

2. Hypertensive retinopathySigns of hypertensive retinopathy are fre-quently seen in adults over 40 years of ageand may include arteriosclerotic changes(arteriolar narrowing, arterio-venouscrossing changes, or arterio-venous nick-ing), arteriolar wall changes (copper/s i lve r wiring), c ot t on wool spot s,hemorrhages, or edema. Many patients

with diabetes have hypertension, andsome of the more severe signs of hyper-tensive retinopathy are similar to diabeticretinopathy. Like diabetic retinopathy,the presence of hypertensive retinopathysignals widespread microvacular damageand predicts subsequent events of stroke,congestive heart failure, and cardiovascu-lar mortality, independently of traditionalrisk factors (150153). Early recognitionof the ocular effects of blood pressurecould allow physicians to better managepatients with hypertension and to moni-tor its end-organ effects (154).

3. Radiation retinopathyRadiation retinopathy presents progres-sively degenerative and proliferative vas-cular changes, primarily affecting themacula, ranging from microaneurysm totelangiectasia, intraretinal hemorrhages,and neovascularization (155). Radiationretinopathy can have a delayed onset

months to years after radiation treatment,and patients with diabetes and hyperten-sion are more susceptible to radiation ret-inopathy (156) due to intensifyingoxygen-derived free-radical assault on thevascular cells (155). Patients with mini-mal diabetic retinopathy undergoing che-motherapy may suffer vision loss fromradiation retinopathy resulting from low-dose radiation that is considered to be safeand properly fractionated (157). Since ra-diation retinopathy and diabetic retinop-a t h y a r e i d e n t i c a l c l i n i c a l l y a n d

histopathologically, treatment for thiscondition has been based on establishedtherapy for diabetic retinopathy such aslaser photocoagulation (158).

4. Other causes of retinopathyTypical diabetic retinopathy lesions suchas cotton wool spots, retinal microaneu-rysms, and retinal hemorrhage are alsoseen in eyes with branch RVO. Other sys-temic conditions that may resultin similarsigns include HIV/AIDS (159), variousconnective tissue diseases (Bechets dis-ease, temporal arteritis, systemic lupus

vasculitis, sarcoidosis, sickle cell retinop-athy, and Wegeners granulomatosis),and retinal telangiectasias (Lebers miliaryaneurysm, Coats disease, and idiopathic

juxtafoveal telangiectasia), a group ofrare, idiopathic, congenital retinal vas-cular anomalies affecting the retinalcapillaries.

CONCLUSIONS A wide spectrumof ocular conditions other than diabeticretinopathy is associated with diabetes.Some of these conditions appear to be

causally linked to hyperglycemia and di-abetes (e.g., cataract), whereas diabetesmay be only one of many risk factors forother conditions (e.g., RVO and retinalarteriolar emboli). In addition, there are arange of retinal conditions (e.g., hyper-tensive and radiation retinopathy) thatmimic common diabetic retinopathysigns.

The management of diabetes-relatedeye diseases is primarily preventative, andregular eye examinations and appropriateophthalmology referral remains the keystrategy to reduce the impact of diabetes-



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related vision loss. In many instances, vi-sion loss associated with most of theconditions discussed is gradual. Occa-sionally, however, more urgent referral toan ophthalmologist is needed, as acutesurgical or laser intervention can save apatients vision. While clinical trials havedemonstrated that good glycemic control

reduces the incidence and progression ofdiabetic retinopathy (3), it is unclearwhether the same beneficial effect appliesto other diabetes-related ocular condi-tions (160). It is also unclear whethercontrolling for relevant risk factors (e.g.,blood pressure and lipids) can alter thecourse of these ocular conditions.

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