Ten Emerging Trends in the Epidemiology of Diabetic Retinopathy · 2017-11-24 · Table 1. List of emerging trends in the epidemiology of diabetic retinopathy. 1 There is a global

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Ophthalmic Epidemiology

ISSN 0928-6586 (Print) 1744-5086 (Online) Journal homepage httpwwwtandfonlinecomloiiope20

Ten Emerging Trends in the Epidemiology ofDiabetic Retinopathy

Charumathi Sabanayagam WanFen Yip Daniel S W Ting Gavin Tan amp TienY Wong

To cite this article Charumathi Sabanayagam WanFen Yip Daniel S W Ting Gavin Tan amp TienY Wong (2016) Ten Emerging Trends in the Epidemiology of Diabetic Retinopathy OphthalmicEpidemiology 234 209-222 DOI 1010800928658620161193618

To link to this article httpdxdoiorg1010800928658620161193618

Published online 29 Jun 2016

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MINI REVIEW

Ten Emerging Trends in the Epidemiology of Diabetic RetinopathyCharumathi Sabanayagamabc WanFen Yipa Daniel S W Tinga Gavin Tana and Tien Y Wongacd

aSingapore Eye Research Institute Singapore National Eye Centre Singapore bCenter for Quantitative Medicine Duke-NUS Medical SchoolSingapore cYong Loo Lin School of Medicine National University of Singapore Singapore dOphthalmology and Visual Sciences AcademicClinical Program Duke-NUS Medical School Singapore

ABSTRACTPurpose Diabetes is a major public health problem affecting 415 million people worldwide Withthe increasing prevalence of diabetes diabetic retinopathy (DR) is emerging as the leading causeof avoidable blindness worldwideMethods We reviewed previous and recent literature to provide an overview of emerging trendson the burden epidemiology risk factors and prevention of DRResults First there is clear evidence of a global increase in the prevalence of diabetes Secondthere is a decline in the incidence of blindness due to DR particularly in developed countriesThird diabetic macular edema (DME) rather than proliferative diabetic retinopathy (PDR) is theincreasingly common cause of visual impairment Fourth DR awareness remains patchy and lowin most populations Fifth hyperglycemia remains the most consistent risk factor for DR in type 1diabetes across different studies and populations Sixth in contrast blood pressure is an impor-tant risk factor for DR in type 2 diabetes Seventh the relationship between dyslipidemia and DRremains unclear with inconsistent results from different studies and trials Eighth the utility ofpredictive models incorporating multiple risk factors for assessing DR risk requires evaluationNinth photographic screening of DR using tele-ophthalmology platforms is increasingly recog-nized as being feasible and cost-effective Finally DR prevention in low-resource settings cannotfollow models developed in high-resource countries and requires different strategiesConclusions The ten trends we observed in the current review may guide planning of publichealthcare strategies for the management of DR and prevention of blindness

ARTICLE HISTORYReceived 29 January 2016Revised 15 March 2016Accepted 19 March 2016

KEYWORDSAwareness burden diabeticretinopathy prevention riskfactors

Introduction

Diabetes currently affects an estimated 415 millionpeople worldwide and the number is expected to riseto 642 million by 20401 With the rising prevalence ofdiabetes the number of persons with diabetic retino-pathy (DR) has also increased In view of the increasingburden of diabetes and DR there has been substantialglobal public attention and research in recent years onunderstanding the epidemiology risk factors and bur-den of diabetes and DR in an effort to develop long-term strategies to manage this major public healthproblem1ndash8

Over the last decade there have been somemajor devel-opments in the diagnosis and care of patients with diabetesand DR For example the results of landmark clinical trialsin the 1980s and 1990s such as the Diabetes Control andComplications Trial (DCCT) and the United KingdomProspective Diabetes Study (UKPDS) showed that thedevelopment and progression of DR can be significantlyreduced by controlling blood glucose9ndash11 and blood

pressure (BP)12 Other major trials demonstrated the effec-tiveness of laser photocoagulation in preventing vision lossin patients with DR1314 In the last decade three develop-ments are particularly important First the development ofthe non-invasive optical coherence tomography (OCT) hasimproved the assessment of DR particularly diabeticmacular edema (DME) Second the introduction of intrao-cular administration of anti-vascular endothelial growthfactor (anti-VEGF) agents has changed the paradigm inthe management of DME from ldquopreventing vision lossrdquo toldquoimproving visionrdquo15 Finally the increasing use of photo-graphic screening of DR with the development of highquality digital fundus cameras and the transmission ofimages and information over the internet has allowed thedevelopment of tele-ophthalmology as an increasinglyused viable and cost-effective option in the screening ofDR16ndash19 These developments have reduced the prevalenceof DR and occurrence of new cases of blindness due to DRglobally and improved the diagnosis and management ofDME For example with the increasing availability of OCTdevices together with their improved accuracy and

CONTACT Charumathi Sabanayagam charumathisabanayagamsericomsg Singapore Eye Research Institute The Academia 20 College RoadDiscovery Tower Level 6 Singapore 169856 Tel +65 6576 7286 Fax +65 6225 2568

OPHTHALMIC EPIDEMIOLOGY2016 VOL 23 NO 4 209ndash222httpdxdoiorg1010800928658620161193618

copy 2016 Taylor amp Francis

precision for identification of subclinical DME OCT hasbeen recognized as the new reference standard for assess-ment of DME and proven valuable for monitoring pro-gression and treatment response for DME2021

Implementation of telemedicine-based DR screeningresulted in improved screening rates and less vision lossfrom DR22 Treatment with anti-VEGF drugs haveimproved vision outcomes and reduced the worsening ofDR in patients withDME2324 In this article we review pastand current literature to understand and highlight emer-ging trends in the epidemiology of DR with a particularfocus on the burden awareness risk factors and screeningof DR

Materials and methods

We searched Medline (PubMed) and EMBASE databasesup to December 2015 Gray literature was searched usingGoogle and citation lists of relevant publications weremanually searched Search terms included ldquodiabetesrdquo ldquoreti-nopathyrdquo or ldquodiabetic retinopathyrdquo ldquomacular edemardquo orldquodiabetic macular edemardquo in combination with searchterms related to epidemiology (eg ldquoprevalencerdquo ldquoinci-dencerdquo ldquoawarenessrdquo) risk factors (eg ldquoblood pressurerdquoldquoglucoserdquo ldquoglycated hemoglobinrdquo ldquoHbA1crdquo ldquocholesterolrdquoldquopredictive modelrdquo) and screening (eg ldquotelemedicinerdquo)Only studies published in English were included in thisreview

Results and discussion

Our study findings listed in Table 1 may guide futureresearch and planning of public healthcare strategiesfor the management of DR and prevention of blindness

Trend 1 There is a global increase in theprevalence of diabetes

The total number of persons with diabetes continues toincrease worldwide from 135 million in 199525 to 171million in 200026 to 415 million in 20151 This number isprojected to increase dramatically to 642 million by 204027

with the greatest increases expected in developing coun-tries particularly in Asia and Africa28 Diabetes estimatesfrom developing countries show marked trends towardyounger ages of onset and rural communities beingaffected as much as urban ones While the majority ofthose with diabetes in developed countries were agedover 64 years most people with diabetes in developingcountries were found to be much younger between theages of 45 and 64 years29 In addition risk factors contri-buting to the increased prevalence of diabetes have beenshown to be different between developed and developing

countries In developing countries weight gain and obesitydue to sedentary lifestyle unhealthy diet (eg easier accessto fast food) high BP and high cholesterol have beenshown to contribute to the rising prevalence of diabetes330

On the other hand the main reason for the increasingprevalence of diabetes in developed countries has beenattributed to the increased life expectancy of thepopulation31 These differences suggest that healthcare sys-tems of countries with different economic status shouldfocus on different strategies to control the prevalence ofdiabetes While many studies have reported on the preva-lence of diabetes there is still a lack of data in certaindeveloping regions such as Eastern Europe Africa andSoutheast Asia30 Understanding the prevalence of diabetesin these regions is important for relevant authorities toestimate the needs of medical facilities and to plan resourceallocation for managing the increasing number of patientswith diabetes In addition as the prevalence of diabeticmicro- and macrovascular complications including retino-pathy nephropathy foot complications and cardiovascu-lar disease are set to increase paralleling the risingprevalence of diabetes organized public health efforts areneeded to detect diabetes early in the course of the diseasethrough screening programs and to educate the public ondiabetes-related risk factors and complications in order totackle the epidemic However this will require politicalwill commitments at all levels and adequate resources

Trend 2 There is a decline in the incidence ofblindness due to proliferative diabetic retinopathyparticularly in developed countries

With increasing prevalence of diabetes and increasing lifeexpectancy of those with diabetes DR is set to be theleading cause of vision loss in many countries32 In 2010of an estimated 285 million people worldwide with

Table 1 List of emerging trends in the epidemiology ofdiabetic retinopathy1 There is a global increase in the prevalence of diabetes2 There is a decline in the incidence of blindness due to PDR

particularly in developed countries3 DME rather than PDR is an increasingly common cause of visual

impairment4 Awareness of DR remains poor in most communities5 Hyperglycemia remains the most consistent risk factor for DR in type

1 diabetes6 In contrast BP is an important risk factor for DR in type 2 diabetes7 The relationship between dyslipidemia and DR remains unclear8 Photographic screening of DR using a tele-ophthalmology platform

is increasingly being recognized as a feasible and cost-effectivescreening strategy

9 An accurate predictive model of patients at risk of DR remains to bedeveloped

10 DR prevention in low-resource settings requires different publichealthcare models and strategies

BP blood pressure DME diabetic macular edema DR diabetic retinopathyPDR proliferative diabetic retinopathy

210 C SABANAYAGAM ET AL

diabetes over one-third were found to have signs of DR8

Despite the increasing prevalence of diabetes across allcountries epidemiological evidence from developed coun-tries (Table 2) suggested a declining trend in the prevalenceof DR-related blindness in people with both type 1533ndash35

and type 236 diabetes due to concerted public health effortsIn the Wisconsin Epidemiologic Study of DiabeticRetinopathy (WESDR) a population-based prospectivestudy of diabetic persons living in 11 counties of the stateofWisconsin in the US with 25-year follow-up the annual-ized estimates for the progression of DR and the incidence

of proliferative diabetic retinopathy (PDR) was higher inthe first 12 years of the study (1980ndash1992) than in the later13 years of the study (1994ndash2007)5 Similarly in theLinkoumlping Diabetes Complications Study33 the cumulativeincidence of severe retinopathy was reported to havedeclined from 47 in the 1961ndash1965 cohort to 28 inthe 1966ndash1970 cohort and 24 in the 1971ndash1975 cohort33

Similar findings were observed in a Danish study where thecumulative incidence of PDR declined progressively from312 in participants whose onset of diabetes was in1965ndash1969 to 125 in participants whose onset of diabeteswas in 1979ndash198434 and in the Pittsburgh Epidemiology ofDiabetes Complications Study from 38 in the earliercohort to 265 in the latter cohort although the declinewas not statistically significant35 In a meta-analysisincluding 28 studies and 27120 type 1 and type 2 diabeticparticipants the pooled incidence of PDRwas found to belower in participants in 1986ndash2008 (26) compared toparticipants in 1975ndash1985 (195)37 and in thePittsburgh Epidemiology of Diabetes ComplicationsStudy from 38 in the 1965ndash1969 cohort to 265 inthe 1975ndash1980 cohort35 A similar decline was alsoobserved in the pooled incidence of non-proliferativeDR (NPDR 47 in 1975ndash1985 to 205 in1986ndash2008)37 Additional evidence to support this trendcomes from screening studies conducted in Europe whichhave shown more than two-thirds reduction in the pre-valence of visual impairment and blindness after theintroduction of free screening services38

Although developed countries have documented adecreasing trend in the prevalence and progression ofsevere DR despite increasing prevalence of diabetes asimilar trend was not observed in developing countrieswhere public health programs targeting diabetes pre-vention and management face significant challengesdue to poor healthcare systems and lack of resourcesIn addition to diabetes as the prevalence of other riskfactors of DR including hypertension and high choles-terol are on the rise in developing countries such asChina and India3940 it will be important to investigatethe trend of DR in these countries394142

Trend 3 Diabetic macular edema rather thanproliferative diabetic retinopathy is anincreasingly common cause of visual impairment

With the rising prevalence of type 2 diabetes the preva-lence of DME (commonly seen in type 2 diabetes) is also onthe rise43ndash45 In a recent study in the US DME was shownto be twice as common as PDR suggesting DME to be amore common cause of vision loss in persons with type 2diabetes43 In the WESDR the overall prevalence of DMEwas shown to be 111 and 84 in the younger and older

Table 2 Trends in the incidence and prevalence of diabeticretinopathy (DR)Authoryear ref no Definition of retinopathy Findings

Type 1 diabetesKlein andKlein 20105

Modification of the EarlyTreatment DiabeticRetinopathy Study

Annual incidence ofproliferativeretinopathy1980ndash1982 to1990ndash1992 cohort351994ndash1996 to2005ndash2007 cohort15

Pambiancoandcolleagues2006 35

Modified Airlie House System Cumulative incidenceof proliferativeretinopathy1965ndash1969 cohort381975ndash1980 cohort265

Nordwall andcolleagues200433

Graded by ophthalmologistusing independentDR grading protocol

Cumulative incidenceof severe retinopathy(laser-treatedretinopathy)1961ndash1965 cohort47 (95 CI 34ndash61)1966ndash1970 cohort28 (95 CI 15ndash40)1971ndash1975 cohort24 (95 CI 12ndash36)

Hovind andcolleagues200334

Graded by ophthalmologist Cumulative incidenceof proliferativeretinopathy1965ndash1969 cohort312 (95 CI 222ndash398)1970ndash1974 cohort303 (95 CI 222ndash384)1975ndash1979 cohort193 (95 CI 112ndash274)1979ndash1984 cohort125 (95 CI 52ndash198)

Type 2 diabetesCugati andcolleagues200636

Modified Airlie HouseClassification

Prevalence ofmoderate-severe NPDRBMES I (1992ndash1994)83BMES II (1997-2000)45 Prevalence ofPDRBMES I 14BMES II 12

CI confidence interval BMES Blue Mountains Eye Study

OPHTHALMIC EPIDEMIOLOGY 211

onset groups respectively In the same cohort the 10-yearincidence of DME was highest in the older-onset patientson insulin (254) followed by the younger-onset patientson insulin (201) and older-onset patients not requiringinsulin (139)46 Nevertheless the incidence of DMEamong those with type 1 diabetes was lower in the laterfollow-ups compared to the earlier ones largely attributedto better glycemic and BP control54647 However theWESDR data needs to be interpreted with caution as thedata was collected in the early 1980s It is therefore unclearwhether the reduction in incidence is due to early detectionor recent medical advances in diabetes care Incidence ofDME in type 1444648ndash53 and type 2 diabetes44515254ndash56 arelisted in Table 3 In addition the decline in the incidence ofDME was reported among those with type 1 diabetes only-4648 and no data is available to support this trend in thosewith type 2 diabetes515556 As the number of persons withDME is expected to increase with the rising prevalence oftype 2 diabetes worldwide large population-based studieswith recent data are needed to understand the epidemiol-ogy and treatment pattern of DME

Trend 4 Awareness of diabetic retinopathy remainspoor in most communities

Early detection and timely treatment can prevent DR-related blindness However lack of patient awareness isa major hurdle to patients attending eye screenings andreceiving treatment Surprisingly poor awareness ofDR has been reported in both developed and develop-ing countries In the 2005ndash2008 National Health andNutrition Examination Survey (NHANES) in the US73 of individuals with DR57 and 553 of those withDME58 were unaware of their condition In Tokyo 32of those with type 2 diabetes were unaware of their DRstatus59 In Singapore while 90 of those with diabeteswere aware of their diabetic status more than 80 ofthose with DR were unaware of their DR status includ-ing 25 of those with sight-threatening DR60 Fewstudies have documented awareness of DR in develop-ing countries Awareness of DR among those withdiabetes was reported to be 2761 in the AndhraPradesh Eye Disease Study in India and 63 amongnewly diagnosed diabetic patients who presented to atertiary eye care center in Nepal62 In Egypt 602 ofparticipants presenting with advanced DR were notaware that diabetes could be sight-threatening63

These findings suggest that despite the high prevalenceof diabetes and impact of DR on vision awareness ofDR remains low As a consequence these patients areless likely to be detected early or receive timely inter-ventions for DR64 which is important for the preven-tion of visual impairment and blindness

Lack of awareness of DR has been shown to be asso-ciated with poor health literacy low socioeconomic statusand poor control of HbA1c and BP levels65ndash67 Thesefindings indicate that public health education should bemore targeted towards persons with lower educationallevels and lower socioeconomic status In addition itshould also be highlighted that more follow-up sessionscould be set aside by primary care professionals forpatients with poorly controlled HbA1c and BP levels

Trend 5 Hyperglycemia remains the mostconsistent risk factor for diabetic retinopathy intype 1 diabetes

Hyperglycemia has consistently been shown to be a riskfactor for DR and DME in both type 1414849 and type 2diabetes6869 In theWESDR higher HbA1c at baseline andan increase in HbA1c level between baseline and follow-upwere associated with progression of DR and incidence ofPDR at both 14 and 25 years of follow-up4149 BaselineHbA1c was associated with incidence of DME at both timepoints and an increase inHbA1c level between baseline andfollow-upwas associatedwith incidence ofDMEat 25 yearsin those with type 1 diabetes48 Data from several rando-mized controlled trials provided strong evidence support-ing the effectiveness of tight glycemic control in reducingthe risk of DR in those with type 1 diabetes The DCCTdemonstrated that intensive therapy reduced the risk of DRby 75 and progression of DR by 54 over a mean follow-up of 65 years in patients with type 1 diabetes70ndash73 In ameta-analysis of 16 trials from 12 cohorts of type 1 diabeticpatientsWang and colleagues reported that intensive treat-ment decreased risk ofDRprogression by 51compared toconventional treatment74 Although tight glycemic controlreduces the risk of microvascular complications it has twoclinically important adverse effects namely early worseningof DR and hypoglycemia In the DCCT tight glycemiccontrol led to risk of early worsening of DR75 which wassubsequently reversed after 18 months with no cases ofserious vision loss reported subsequently75 A similar find-ing was also reported in the meta-analysis by Wang andcolleagues74 In another meta-analysis of 14 randomizedcontrolled trials (RCT) of type 1 diabetic participantsintensive treatment was found to be associated with a 3-fold increased risk of hypoglycemia and a nearly 2-foldincreased risk of ketoacidosis76

Hyperglycemia has been shown to be a risk factor forDRin those with type 2 diabetes in several cross-sectionalstudies77ndash81 In addition higher HbA1c was associatedwith both incidence and progression of DR over a 4-yearfollow-up in patients with type 2 diabetes in a Hong Kongstudy69 However the benefits of tight glycemic control inreducing the risk of DR in patients with type 2 diabetes is

Table3

Incidenceof

diabeticmacular

a(DME)

Authoryearrefno

pulatio

Definition

Follow-up

Martin

-Merinoand

colleagues2014

51Type

1amp2diabetesU

minusMaculop

athyinclusive

ofMEexud

ativemaculop

oranyotherno

n-specificmaculop

mulativeincidence

1-year

follow-up

1diabetes0

2diabetes0

9-year

follow-up

1diabetes4

2diabetes3

Jonesandcolleagues

55Type

2diabetesU

Independ

entgradingscale

EnglishNationalS

creening

mulativeincidenceof

5-year

follow-up

10-yearfollow-up

asandcolleagues

56Type

2diabetesU

Maculop

athyexudateswith

in1disc

ofthefovea

Referableretin

opathy

pre-proliferativeor

proliferativeretin

opathy

orwith

outmaculop

athy)or

maculop

backgrou

ndretin

opathy

nualincidenceof

Referable

opathy

Romero-Arocaand

colleagues2011

50Type

1diabetesSpain

DMEretin

althickening

andhard

inthemacular

mulativeincidenceof

aandcolleagues2010

44UnitedStates

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

tocoagulationscarsinthe

macular

mulativeincidenceof

Kleinandcolleagues

48Type

1diabetesU

nitedStates

Stereoscop

sMEretin

althickening

inthemacular

nualized

incidences

Follow-up1

Follow-up2

Follow-up3

Follow-up4

Leskeandcolleagues

52Type

1amp2diabetesBarbado

sStereoscop

sClinicallysign

ificant

macular

(1)thickening

oftheretin

orwith

in500μm

ofthecenter

ofthemacula(2)hard

in500μm

ofthecenter

ofthemaculaassociated

thickening

oftheadjacent

notresidu

alhard

remaining

afterthedisapp

earanceof

althickening

)and(3)a

orzonesof

althickening

orlarger

insize

anypartof

in1disc

ofthecenter

ofthemacula

mulativeincidenceof

isandcolleagues

53Type

1diabetesU

yMaculop

athyringof

atewith

inmaculage1disc

insize

ofcenter

ofmaculaor

in1disc

offixation

presence

offocalo

photocoagu

nscars

mulativeincidenceof

isandcolleagues

54Type

2diabetesU

yMaculop

athyringof

atewith

inmaculage1disc

insize

ofcenter

ofmaculaor

in1disc

offixation

presence

offocalo

photocoagu

nscars

mulativeincidenceof

tinued)

Table3

tinued)

Authoryearrefno

pulatio

Definition

Follow-up

Kleinandcolleagues1998

49Type

1diabetesU

nitedStates

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

CSMEretin

althickening

in500microm

thecenter

ofthemaculaor

in500microm

ofthecenter

thickening

oftheadjacent

orzonesof

althickening

atleast1disc

insize

atleastpartof

is1disc

thecenter

ofthemaculaor

focalp

hotocoagulationtreatm

mulativeincidenceof

DME261

Cumulativeincidenceof

CSME170

46Type

1amp2diabetesU

States

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

nualincidenceof

DMEover

4years

ger-on

Older-onset1

alincidenceof

DMEover

6years

ger-on

Older-onset2

MEmacular

aCSMEclinicallysign

ificant

macular

fluorescein

angiog

pticalcoherencetomog

not clear In the UKPDS trial involving patients with newlydiagnosed type 2 diabetes the group that received intensivetherapy had 25 reduced risk of microvascular end points(retinopathy requiring photocoagulation vitreous hemor-rhage andor fatal or non-fatal renal failure) compared tothe conventional treatment group82 A similar finding wasalso observed in two Japanese studies8384 In the Action toControl Cardiovascular Risk in Diabetes (ACCORD) trialinvolving type 2 diabetic patients85 although intensive gly-cemic control (HbA1c lt60) did not reduce the progres-sion of DR defined by development of ldquoneed for retinalphotocoagulation or vitrectomy to treat retinopathyrdquointensive control did reduce deterioration of visual acuitydefined by ldquo3-line change in visual acuityrdquo associated withDR86 In contrast in the Action in Diabetes and VascularDisease (ADVANCE) trial87 aggressive glycemic control(HbA1c lt65) showed no significant benefit in terms ofonset or progression of retinopathy in type 2 diabetes Arecent meta-analysis involving participants with type 2diabetes from seven trials showed that intensive glycemiccontrol reduced the risk of DR by 2088 but increased therisk of hypoglycemia by 30 In addition an increasedrisk of death due to cardiovascular causes was reportedwith intensive glycemic control in the ACCORD and theVeterans Affairs Diabetes trials89

In summary while hyperglycemia is a risk factor for DRin both type 1 and type 2 diabetes benefits of tight glycemiccontrol were more evident in type 1 diabetes It should benoted that strict glycemic control may be effective in pre-venting or delaying the onset of DR in patients with dia-betes but rapid reductions in HbA1c should be cautionedconsidering the adverse effects

Trend 6 Blood pressure is an important risk factorfor diabetic retinopathy in persons with type 2diabetes

BP has been shown to be associated with DR in severalprospective studies506890ndash95 In theWESDR type 1 diabetescohort baseline hypertensionwas associatedwith incidenceof PDR at 14 years follow-up49 higher systolic BP at base-line with incidence of PDR at 25 years follow-up andbaseline systolic BP with incidence of DME at 25 yearsfollow-up41 Higher diastolic BP between baseline and 4-year follow-up was associated with progression of DR atboth 14 years and 25 years follow-up4149 and baselinesystolic BP was associated with 25-year DME incidence48

Interestingly this finding was not observed in those withtype 2 diabetes in the WESDR cohort92 possibly due toselective mortality of those with both DR and high BP asthose with type 2 diabetes are older than those with type 1diabetes92 In a 5-year community-based prospective studyconducted among Chinese adults with type 2 diabetes in

Shanghai high BP was independently associated with inci-dent DR68

Evidence from RCTs have consistently shown the effec-tiveness of BP control in reducing the risk of DR TheUKPDS96 including hypertensive patients with type 2 dia-betes reported that patients allocated to tight BP control(lt15085 mmHg) had 37 reduced risk of microvasculardisease 34 decreased risk of DR progression and 47reduced risk of deterioration in visual acuity of three linesover a 9-year period9798

In addition to the effect of BP on DR risk the effect ofanti-hypertensive medication use on DR has also beeninvestigated In the EURODIAB Controlled Trial ofLisinopril in Insulin-Dependent Diabetes Mellitus99 aftera 2-year follow-up the group assigned to treatment withlisinopril an angiotensin-converting enzyme (ACE) inhi-bitor had a 50 reduction in the risk of progression ofretinopathy compared to participantswhowere on placeboIn the Diabetic Retinopathy Candesartan Trial (DIRECT)the group assigned to candesartan an angiotensin II recep-tor antagonist had 18 reduction in incidence of retino-pathy and 35 reduction in progression of retinopathy inpersonswith type 1 diabetes and 34 increase in regressionof retinopathy in those with type 2 diabetes100101 In theRenin-Angiotensin System Study treatment with ACEinhibitors enalapril and losartan was reported toreduce retinopathy progression by 70 after 5 years offollow-up102 In the ADVANCE Preterax andDiamicron MR Controlled Evaluation RetinalMeasurement Study while lowering BP with an ACEinhibitor and diuretic combination (perindoprilndashinda-pamide) did not significantly reduce the incidence orprogression of retinopathy in patients with type 2 dia-betes fewer patients experienced new or worsening DRin the BP lowering treatment group compared withplacebo after 45 years of follow-up103 Although severalclinical trials have shown that ACE inhibitors are effec-tive in controlling BP in patients with diabetes ACEinhibitors were not found to be superior to other anti-hypertensive agents for controlling BP in patients withhypertension and DR91

In summary while well-controlled BP was associatedwith decreased incidence and progression of DR morestudies are needed to establish a clear BP cut-off beforeBP targets are incorporated into clinical practice

Trend 7 The relationship between dyslipidemia anddiabetic retinopathy remains unclear

Several population-based studies have examined theassociation between dyslipidemia and DR81104ndash107

In the Madrid Diabetes Study including 3443 per-sons with type 2 diabetes higher levels of low

density lipoprotein (LDL) cholesterol increased the4-year risk of DR 8-fold106 Findings from cross-sectional studies were inconsistent While higherlevels of triglycerides were marginally associatedwith DR in those with type 2 diabetes in an Indianstudy105 higher levels of total and LDL cholesterolwere found to be protective of any retinopathy in aSingapore study81 and serum lipids (high densitylipoprotein cholesterol LDL cholesterol triglycer-ides) failed to show significant associations withDR in a US study107

In contrast to observational studies evidence fromtwo major RCTs show that fenofibrate a peroxisomeproliferator activatedndashreceptor alpha (PPARα) agonistused to reduce cholesterol levels mainly in patients atrisk of cardiovascular disease had an effect on DR pro-gression A retrospective study comparing the progres-sion of DR in persons with type 2 diabetes treated withand without fibrates in the UK reported a 22 reductionin rates of new onset of DR in the fibrate-treated group-108 In the Fenofibrate Intervention and Event Loweringin Diabetes (FIELD) Study109 36 of participants withtype 2 diabetes who received fenofibrate required lasertherapy for retinopathy compared to 52 in the placebogroup (p = 00003) over a 5-year period In the ACCORDEye Study110 therapy with 160 mg of fenofibrate plussimvastatin daily in those with type 2 diabetes reducedthe progression of DR by 40 compared to placebo plussimvastatin However in these trials the mechanism ofthe beneficial effect of fenofibrate did not appear to beattributable to the observed changes in the circulatinglevels of lipid Mechanisms unrelated to lipids havecurrently been postulated to be attributable to the ben-eficial effect on DR Fenofibrate has been hypothesizedto protect the retina from the adverse effects of oxidativestress by preventing lipid deposition and lipotoxicity byupregulating apolipoprotein A-1 production111 and bypromoting expression of antioxidant enzymes (such assuperoxide dismutase and glutathione)112 by activatingPPARα There is also evidence to suggest that fenofibricacid an active metabolite of fenofibrate prevents apop-tosis (programmed cell death) of retinal endothelialcells113 by downregulating stress-mediated signalingand induction of autophagy and survival pathways ofthe retinal pigment epithelium114 and prevents inflam-matory disruption of the retinal epithelium pigment bysuppressing the activation of adenosine monopho-sphate-activated protein kinase (AMPK)115

In summary although fenofibrate has been shown tobe effective in reducing the progression of DR in type 2diabetes it is unclear if the same effect will be observedin patients with type 1 diabetes116 and the mechanismsof action are not well understood

Trend 8 Photographic screening of diabeticretinopathy using a tele-ophthalmology platform isincreasingly being recognized as a feasible andcost-effective screening strategy

AsDR remains asymptomatic until advanced and there isstrong evidence that laser treatment prevents vision lossregular eye examinations are recommended for peoplewith diabetes In the long term early detection of DRalso motivates patients to better manage their diabeteswith improved glycemic and BP control117 Compellingdata from Sweden and England where a DR screeningservice is offered for free showed that vision loss fromDRcould largely be prevented by regular eye screening38118

Incidence of vision loss from DR has been shown to bereduced by more than a third in Stockholm county118 andby more than two-thirds in the Newcastle district inEngland38 a decade after the introduction of the DRscreening service The American Diabetes Associationand the American Academy of Ophthalmology recom-mend that people with type 2 diabetes should have aninitial dilated eye examination at the time of their diabetesdiagnosis and subsequent examinations should be yearlyor more frequently if retinopathy is progressing119

Despite the recommendations and guidelines adherenceto DR screening has been reported to be low possibly dueto lack of awareness lack of healthcare resources or pooraccess to care Telemedicine-based DR screening wheredigital retinal photographs taken with non-mydriaticcameras at the point-of-care are transmitted for remoteinterpretation by trained readers and consultation byophthalmologists is gaining popularity due to improvedaccess with wider coverage improved accuracy effi-ciency and cost-effectiveness16ndash19

Trend 9 An accurate predictive model of patientsat risk of diabetic retinopathy remains to bedeveloped

While large epidemiological studies have identifiedpoor glycemic control higher BP and dyslipidemia asimportant risk factors associated with progression ofDR studies integrating these risk factors into a DR riskscore to improve prediction of DR are scarce A preciseprediction model is important as it allows clinicians toidentify individuals at high risk for early treatment andcounseling thereby reducing the risk of progressionfrom non-proliferative DR to vision-threateningDR120 In addition risk scores help efficient allocationof healthcare resources for example in initiating treat-ment or to schedule follow-up121 Using data fromhealth insurance enrollees of a large managed care net-work in the US Harris and colleagues attempted to

construct a risk model based on risk factors such as ageat first diagnosis of non-proliferative DR sex racecomorbid hypertension dyslipidemia diabetic nephro-pathy neuropathy non-healing foot ulcers HbA1c

level and treatment with ACE inhibitors statins sul-phonylureas metformin and insulin122 The 5-yearprobability of DR progression from non-proliferativeDR to PDR was reported to be as low as 5 for thosewith few risk factors and as high as 38 for those withmultiple risk factors122 However the findings of thisstudy should be interpreted with caution as the studywas limited by lack of information on other importantrisk factors of DR such as diabetes duration BP bodymass index etc and the authors did not performempirical testing for the efficacy of their predictionmodel

Trials that examined the effect of intensive treat-ment against multiple risk factors in patients withdiabetes have also shown inconsistent findings withrespect to DR In the Steno-2 Study long-termintensive treatment against multiple factors includinghyperglycemia hypertension dyslipidemia andmicroalbuminuria in patients with type 2 diabetesreduced the risk of macro- and microvascular eventsincluding DR by about 50123 Nonetheless thesame benefits of multifactorial treatment (medica-tions targeting hyperglycemia hypertension anddyslipidemia together with promotion of a healthylifestyle) on microvascular complications were notobserved in a subsequent multicenter cluster RCTconducted across 343 primary care practices inEurope124 Compared to routine care target-drivenmultifactorial intervention failed to show significantreductions in the prevalence of any of the threemicrovascular outcomes including nephropathy neu-ropathy and DR at 5 years124 Clearly there is apaucity of prediction models for DR and more stu-dies developing accurate models for predicting riskof DR in multiple diverse populations and validatingthe developed equations are needed before being putto clinical use

Trend 10 Diabetic retinopathy prevention in low-resource settings requires different publichealthcare models and strategies

Although the prevalence of diabetes is increasingworldwide the overwhelming burden of diabetes hasbeen shown to affect lowndashmiddle income countrieswhere four out of five people with diabetes are livingand is a major concern27 Despite the increasing burdenof diabetes in lowndashmiddle income countries epidemio-logical data for DR in these countries is limited or non-

existent Available estimates suggest that the estimates ofDR in these countries are comparable to those reportedfrom developed countries The prevalence of any DRamong those with diabetes in lowndashmiddle income coun-tries has been shown to range from 18ndash22 in India125

23 in China126 30 in Latin America and 30ndash32 inAfrica2 Prevalences in rural populations were reportedto be 18 in rural India127 and 43 in rural China128

Prevention of DR in lowndashmiddle income countries facesignificant challenges due to lack of resources TheWorld Health Organization (WHO) and InternationalDiabetes Federation have initiated programs and pro-jects to improve prevention of blindness from diabetesglobally and in particular in lowndashmiddle income coun-tries by supporting the adoption of effective measures forthe surveillance prevention and control of blindness dueto DR7129ndash132 These include (1) Establishing and main-taining a web-based source to assist policy makers in theimplementation of national diabetes programs includingeducational materials treatment guidelines trainingmanuals developed in different settings evidence-basedinformation and online access to expert advice (2)educating diabetic patients about risk factors of DRand promoting a healthy lifestyle at primary care level(3) adding dilated ophthalmoscopic exams to assess themagnitude of DR to Rapid Assessment of AvoidableBlindness (RAAB) studies a screening method originallydesigned to enumerate causes of avoidable blindness dueto cataract refractive error trachoma and corneal scar-ring in low-resource settings (4) capacity building byempowering and training primary healthcare workerswith skills to perform screening and counseling (5) useof low-cost screening technologies such as digital retinalimaging and remote grading (6) strengtheningsecondary-level centers for laser photocoagulation andtertiary-level facilities for retinal surgery (7) improvingaccess to care using mobile health vans or health-careservices that move closer to patientsrsquo homes (8) toensure sustainability integrating DR screening programsinto existing public health programs such as the healthylifestyle initiative primary health care disease controlprogram etc (9) encouraging the commitment and sup-port of nongovernmental organizations and private sec-tors in strengthening and promoting DR controlprograms Although adopting the public health approachhas been accepted as a priority by several member coun-tries of WHO131133ndash135 challenges in implementationremain including poor health-care systems lack ofawareness about DR among persons with diabetes lackof well-trained personnel lack of tertiary eye-care ser-vices logistical constraints for screening treatment andfollow-up and difficulty in ensuring compliance withtreatment

Conclusion

In conclusion we provide a current overview of thetrends in the epidemiology of DR in the last few decadesAn epidemic of diabetes is imminent consequently theabsolute numbers of DR cases will increase worldwide inparticular in lowndashmiddle income countries Awareness ofDR remains alarmingly low and concerted efforts areneeded to educate patients physician policy makersand the population The decline in blindness due to DRin the last decade in developed countries in the US andEurope suggest comprehensive and well-organized publichealth efforts may help curtail the burden of blindnessdue to DR Public health initiatives in lowndashmiddleincome and low resource setting countries are gainingmomentum but significant challenges remain

Declaration of interest

The authors report no conflicts of interest The authors aloneare responsible for the writing and content of this article

References

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2 Burgess PI MacCormick IJ Harding SP et alEpidemiology of diabetic retinopathy and maculopathyin Africa a systematic review Diabet Med201330399ndash412

3 Cockram CS The epidemiology of diabetes mellitus inthe Asia-Pacific region Hong Kong Med J 2000643ndash52

4 Khandekar R Screening and public health strategies fordiabetic retinopathy in the EasternMediterranean regionMiddle East Afr J Ophthalmol 201219178ndash184

5 Klein R Klein BE Are individuals with diabetes seeingbetter A long-term epidemiological perspectiveDiabetes 2010591853ndash1860

6 Lee R Wong TY Sabanayagam C Epidemiology ofdiabetic retinopathy diabetic macular edema andrelated vision loss Eye Vis (Lond) 2015217

7 World Health Organization Global initiative for theelimination of avoidable blindness Action Plan2006ndash2011 Vision 2020 Report 2007

8 Yau JW Rogers SL Kawasaki R et al Global preva-lence and major risk factors of diabetic retinopathyDiabetes Care 201235556ndash564

9 The Diabetes Control and Complications Trial ResearchGroup Progression of retinopathy with intensive versusconventional treatment in the Diabetes Control andComplications Trial 1995102647ndash661

10 The Diabetes Control and Complications Trial ResearchGroup The effect of intensive treatment of diabetes onthe development and progression of long-term compli-cations in insulin-dependent diabetes mellitus N Engl JMed 1993329977ndash986

11 UK Prospective Diabetes Study (UKPDS) GroupIntensive blood-glucose control with sulphonylureasor insulin compared with conventional treatment andrisk of complications in patients with type 2 diabetes(UKPDS 33) Lancet 1998352837ndash853

12 UK Prospective Diabetes Study Group Tight bloodpressure control and risk of macrovascular and micro-vascular complications in type 2 diabetes UKPDS 38BMJ 1998317703ndash713

13 The Diabetic Retinopathy Study Research GroupPhotocoagulation treatment of proliferative diabetic reti-nopathy Clinical application of Diabetic RetinopathyStudy (DRS) findings DRS Report Number 8Ophthalmology 198188583ndash600

14 Early Treatment Diabetic Retinopathy Study ResearchGroup Focal photocoagulation treatment of diabeticmacular edema Relationship of treatment effect tofluorescein angiographic and other retinal characteris-tics at baseline ETDRS report no 19 Arch Ophthalmol19951131144ndash1155

15 Mitchell PWong TYManagement paradigms for diabeticmacular edema Am J Ophthalmol 2014157505ndash513

16 Shi L Wu H Dong J et al Telemedicine for detectingdiabetic retinopathy a systematic review and meta-analysis Br J Ophthalmol 201599823ndash831

17 Kirkizlar E Serban N Sisson JA et al Evaluation oftelemedicine for screening of diabetic retinopathy inthe Veterans Health Administration Ophthalmology20131202604ndash2610

18 Jones S Edwards RT Diabetic retinopathy screening asystematic review of the economic evidence DiabetMed 201027249ndash256

19 Mansberger SL Sheppler C Barker G et al Long-termcomparative effectiveness of telemedicine in providingdiabetic retinopathy screening examinations a rando-mized clinical trial JAMA Ophthalmol 2015133518ndash525

20 Virgili G Menchini F Casazza G et al Optical coher-ence tomography (OCT) for detection of macularoedema in patients with diabetic retinopathyCochrane Database Syst Rev 20151CD008081

21 Adhi M Duker JS Optical coherence tomography ndash cur-rent and future applications Curr Opin Ophthalmol201324213ndash221

22 Zimmer-Galler IE Kimura AE Gupta S Diabetic reti-nopathy screening and the use of telemedicine CurrOpin Ophthalmol 201526167ndash172

23 Boyer DS Hopkins JJ Sorof J et al Anti-vascularendothelial growth factor therapy for diabetic macularedema Ther Adv Endocrinol Metab 20134151ndash169

24 Agarwal A Afridi R Hassan M et al Novel therapiesin development for diabetic macular edema Curr DiabRep 20151575

25 King H Aubert RE Herman WH Global burden ofdiabetes 1995ndash2025 prevalence numerical estimatesand projections Diabetes Care 1998211414ndash1431

26 World Health Organization Diabetes ProgrammeGeneva WHO 2015

27 International Diabetes Federation IDF Diabetes atlas7th ed Brussels Belgium Author 2015 AccessedDecember 20 2015 from httpwww diabetesatlas org

28 Foundation ID IDF Diabetes atlas 6th ed 2014Accessed December 22 2015 from httpswww idf

orgsitesdefaultfilesAtlas-poster-2014_EN pdf [serialonline]

29 Shaw JE Sicree RA Zimmet PZ Global estimates ofthe prevalence of diabetes for 2010 and 2030 DiabetesRes Clin Pract 2010874ndash14

30 Wild S Roglic G Green A et al Global prevalence ofdiabetes estimates for the year 2000 and projectionsfor 2030 Diabetes Care 2004271047ndash1053

31 Stovring H Andersen M Beck-Nielsen H et al Risingprevalence of diabetes evidence from a Danish phar-maco-epidemiological database Lancet 2003362537ndash538

32 Cheung N Mitchell P Wong TY Diabetic retinopathyLancet 2010376124ndash136

33 Nordwall M Bojestig M Arnqvist HJ et al Decliningincidence of severe retinopathy and persisting decreaseof nephropathy in an unselected population of Type 1diabetes ndash The Linkoping Diabetes ComplicationsStudy Diabetologia 2004471266ndash1272

34 Hovind P Tarnow L Rossing K et al Decreasingincidence of severe diabetic microangiopathy in type1 diabetes Diabetes Care 2003261258ndash1264

35 Pambianco G Costacou T Ellis D et al The 30-yearnatural history of type 1 diabetes complications thePittsburgh Epidemiology of Diabetes ComplicationsStudy experience Diabetes 2006551463ndash1469

36 Cugati S Kifley A Mitchell P et al Temporal trends inthe age-specific prevalence of diabetes and diabeticretinopathy in older persons population-based surveyfindings Diabetes Res Clin Pract 200674301ndash308

37 Wong TY Mwamburi M Klein R et al Rates ofprogression in diabetic retinopathy during differenttime periods a systematic review and meta-analysisDiabetes Care 2009322307ndash2313

38 Arun CS Ngugi N Lovelock L et al Effectiveness ofscreening in preventing blindness due to diabetic reti-nopathy Diabet Med 200320186ndash190

39 Hu FB Globalization of diabetes the role of diet life-style and genes Diabetes Care 2011341249ndash1257

40 Ibrahim MM Damasceno A Hypertension in develop-ing countries Lancet 2012380611ndash619

41 Klein R Knudtson MD Lee KE et al The WisconsinEpidemiologic Study of Diabetic Retinopathy XXII thetwenty-five-year progression of retinopathy in personswith type 1 diabetes Ophthalmology 20081151859ndash1868

42 Reddy KS Yusuf S Emerging epidemic of cardiovas-cular disease in developing countries Circulation199897596ndash601

43 Zhang X Saaddine JB Chou CF et al Prevalence ofdiabetic retinopathy in the United States 2005ndash2008JAMA 2010304649ndash656

44 Varma R Choudhury F Klein R et al Four-yearincidence and progression of diabetic retinopathy andmacular edema the Los Angeles Latino Eye Study AmJ Ophthalmol 2010149752ndash761

45 Minassian DC Owens DR Reidy A Prevalence ofdiabetic macular oedema and related health and socialcare resource use in England Br J Ophthalmol201296345ndash349

46 Klein R Klein BE Moss SE et al The WisconsinEpidemiologic Study of Diabetic Retinopathy XVThe long-term incidence of macular edemaOphthalmology 19951027ndash16

47 Ding J Wong TY Current epidemiology of diabeticretinopathy and diabetic macular edema Curr DiabRep 201212346ndash354

48 Klein R Knudtson MD Lee KE et al The WisconsinEpidemiologic Study of Diabetic Retinopathy XXIIIthe twenty-five-year incidence of macular edema inpersons with type 1 diabetes Ophthalmology2009116497ndash503

49 Klein R Klein BE Moss SE et al The WisconsinEpidemiologic Study of Diabetic Retinopathy XVIIThe 14-year incidence and progression of diabetic reti-nopathy and associated risk factors in type 1 diabetesOphthalmology 19981051801ndash1815

50 Romero-Aroca P Baget-Bernaldiz M Fernandez-Ballart J et al Ten-year incidence of diabetic retino-pathy and macular edema Risk factors in a sample ofpeople with type 1 diabetes Diabetes Res Clin Pract201194126ndash132

51 Martin-Merino E Fortuny J Rivero-Ferrer E et alIncidence of retinal complications in a cohort of newlydiagnosed diabetic patients PLoS One 20149e100283

52 Leske MC Wu SY Hennis A et al Nine-year inci-dence of diabetic retinopathy in the Barbados EyeStudies Arch Ophthalmol 2006124250ndash255

53 Younis N Broadbent DM Harding SP et al Incidenceof sight-threatening retinopathy in Type 1 diabetes in asystematic screening programme Diabetic Med200320758ndash765

54 Younis N Broadbent DM Vora JP et al Incidence ofsight-threatening retinopathy in patients with type 2diabetes in the Liverpool Diabetic Eye Study a cohortstudy Lancet 2003361195ndash200

55 Jones CD Greenwood RH Misra A et al Incidenceand progression of diabetic retinopathy during 17 yearsof a population-based screening program in EnglandDiabetes Care 201235592ndash596

56 Thomas RL Dunstan F Luzio SD et al Incidenceof diabetic retinopathy in people with type 2 dia-betes mellitus attending the Diabetic RetinopathyScreening Service for Wales retrospective analysisBMJ 2012344e874

57 Gibson DM Diabetic retinopathy and age-relatedmacular degeneration in the US Am J Prev Med20124348ndash54

58 Bressler NM Varma R Doan QV et al Underuse ofthe health care system by persons with diabetes melli-tus and diabetic macular edema in the United StatesJAMA Ophthalmol 2014132168ndash173

59 Funatsu H Hori S Shimizu E et al Questionnairesurvey on periodic ocular examination in Japanesediabetic patients Am J Ophthalmol 2003136955ndash957

60 Huang OS Tay WT Ong PG et al Prevalence anddeterminants of undiagnosed diabetic retinopathy andvision-threatening retinopathy in a multiethnic Asiancohort the Singapore Epidemiology of Eye Diseases(SEED) study Br J Ophthalmol 2015991614ndash1621

61 Dandona R Dandona L John RK et al Awareness ofeye diseases in an urban population in southern IndiaBull World Health Organ 20017996ndash102

62 Thapa R Paudyal G Maharjan N et al Awareness ofdiabetic retinopathy among diabetic patients in NepalActa Ophthalmol 201290e242

63 Abueleinen KG El-Mekawey H Saif YS et alSociodemographic factors responsible for blindness indiabetic Egyptian patients Clin Ophthalmol201151593ndash1598

64 Wang S Tikellis G Wong N et al Lack of knowledgeof glycosylated hemoglobin in patients with diabeticretinopathy Diabetes Res Clin Pract 200881e15ndashe17

65 Tajunisah I Wong P Tan L et al Awareness of eyecomplications and prevalence of retinopathy in the firstvisit to eye clinic among type 2 diabetic patients Int JOphthalmol 20114519ndash524

66 Huang OS Tay WT Tai ES et al Lack of awarenessamongst community patients with diabetes and dia-betic retinopathy the Singapore Malay eye study AnnAcad Med Singapore 2009381048ndash1055

67 Islam FM Chakrabarti R Islam SZ et al Factorsassociated with awareness attitudes and practicesregarding common eye diseases in the general popula-tion in a rural district in Bangladesh The BangladeshPopulation-based Diabetes and Eye Study (BPDES)PLoS One 201510e0133043

68 Jin P Peng J Zou H et al The 5-year onset andregression of diabetic retinopathy in Chinese type 2diabetes patients PLoS One 20149e113359

69 Tam VH Lam EP Chu BC et al Incidence and pro-gression of diabetic retinopathy in Hong Kong Chinesewith type 2 diabetes mellitus J Diabetes Complications200923185ndash193

70 The Diabetes Control and Complications TrialResearch Group The effect of intensive treatment ofdiabetes on the development and progression of long-term complications in insulin-dependent diabetes mel-litus N Engl J Med 1993329977ndash986

71 Diabetes Control and Complications Trial ResearchGroup Progression of retinopathy with intensive ver-sus conventional treatment in the Diabetes Control andComplications Trial Ophthalmology 1995102647ndash661

72 The Diabetes Control and Complications TrialResearch Group The relationship of glycemic exposure(HbA1c) to the risk of development and progression ofretinopathy in the diabetes control and complicationstrial Diabetes 199544968ndash983

73 The Diabetes Control and Complications TrialEpidemiology of Diabetes Interventions andComplications Research Group Retinopathy andnephropathy in patients with type 1 diabetes fouryears after a trial of intensive therapy N Engl J Med2000342381ndash389

74 Wang PH Lau J Chalmers TC Meta-analysis of effectsof intensive blood-glucose control on late complica-tions of type I diabetes Lancet 19933411306ndash1309

75 Early worsening of diabetic retinopathy in the DiabetesControl and Complications Trial Arch Ophthalmol1998116874ndash886

76 Egger M Davey SG Stettler C et al Risk of adverseeffects of intensified treatment in insulin-dependentdiabetes mellitus a meta-analysis Diabet Med199714919ndash928

77 Cheng YJ Gregg EW Geiss LS et al Association ofA1C and fasting plasma glucose levels with diabeticretinopathy prevalence in the US population

implications for diabetes diagnostic thresholdsDiabetes Care 2009322027ndash2032

78 Chiang PP Lamoureux EL Cheung CY et al Racialdifferences in the prevalence of diabetes but not dia-betic retinopathy in a multi-ethnic Asian populationInvest Ophthalmol Vis Sci 2011527586ndash7592

79 Dowse GK Humphrey AR Collins VR et alPrevalence and risk factors for diabetic retinopathy inthe multiethnic population of Mauritius Am JEpidemiol 1998147448ndash457

80 Pradeepa R Anjana RM Unnikrishnan R et al Riskfactors for microvascular complications of diabetesamong South Indian subjects with type 2 diabetes ndash theChennai Urban Rural Epidemiology Study (CURES) EyeStudy-5 Diabetes Technol Ther 201012755ndash761

81 Wong TY Cheung N Tay WT et al Prevalence andrisk factors for diabetic retinopathy the SingaporeMalay Eye Study Ophthalmology 20081151869ndash1875

83 Ohkubo Y Kishikawa H Araki E et al Intensiveinsulin therapy prevents the progression of diabeticmicrovascular complications in Japanese patients withnon-insulin-dependent diabetes mellitus a randomizedprospective 6-year study Diabetes Res Clin Pract199528103ndash117

84 Shichiri M Kishikawa H Ohkubo Y et al Long-termresults of the Kumamoto Study on optimal diabetescontrol in type 2 diabetic patients Diabetes Care200023(Suppl 2)B21ndashB29

85 Action to Control Cardiovascular Risk in DiabetesStudy Group Gerstein HC Miller ME et al Effectsof intensive glucose lowering in type 2 diabetes N EnglJ Med 20083582545ndash2559

86 Ismail-Beigi F Craven T Banerji MA et al Effect ofintensive treatment of hyperglycaemia on microvas-cular outcomes in type 2 diabetes an analysis of theACCORD randomised trial Lancet 2010376419ndash430

87 Group AC Patel A MacMahon S et al Intensive bloodglucose control and vascular outcomes in patients withtype 2 diabetes N Engl J Med 20083582560ndash2572

88 Hemmingsen B Lund SS Gluud C et al Intensiveglycaemic control for patients with type 2 diabetessystematic review with meta-analysis and trial sequen-tial analysis of randomised clinical trials BMJ2011343d6898

89 Duckworth W Abraira C Moritz T et al Glucosecontrol and vascular complications in veterans withtype 2 diabetes N Engl J Med 2009360129ndash139

90 Harris MI Klein R Cowie CC et al Is the risk ofdiabetic retinopathy greater in non-Hispanic blacksand Mexican Americans than in non-Hispanic whiteswith type 2 diabetes A US population study DiabetesCare 1998211230ndash1235

91 Klein R Moss SE Klein BE et al The Wisconsin epide-miologic study of diabetic retinopathy XI The incidence ofmacular edema Ophthalmology 1989961501ndash1510

92 Klein R Klein BE Moss SE et al Is blood pressure apredictor of the incidence or progression of diabeticretinopathy Arch Intern Med 19891492427ndash2432

93 Stratton IM Kohner EM Aldington SJ et al UKPDS50 risk factors for incidence and progression of retino-pathy in Type II diabetes over 6 years from diagnosisDiabetologia 200144156ndash163

94 Tudor SM Hamman RF Baron A et al Incidence andprogression of diabetic retinopathy in Hispanics andnon-Hispanic whites with type 2 diabetes San LuisValley Diabetes Study Colorado Diabetes Care19982153ndash61

95 van Leiden HA Dekker JM Moll AC et al Bloodpressure lipids and obesity are associated with retino-pathy the Hoorn study Diabetes Care 2002251320ndash1325

96 Matthews DR Stratton IM Aldington SJ et alRisks of progression of retinopathy and vision lossrelated to tight blood pressure control in type 2diabetes mellitus UKPDS 69 Arch Ophthalmol20041221631ndash1640

98 Estacio RO Jeffers BW Gifford N et al Effect of bloodpressure control on diabetic microvascular complica-tions in patients with hypertension and type 2 diabetesDiabetes Care 200023(Suppl 2)B54ndashB64

99 Chaturvedi N Sjolie AK Stephenson JM et al Effect oflisinopril on progression of retinopathy in normotensivepeople with type 1 diabetes The EUCLID Study GroupEURODIAB Controlled Trial of Lisinopril in Insulin-Dependent Diabetes Mellitus Lancet 199835128ndash31

100 Chaturvedi N Porta M Klein R et al Effect of cande-sartan on prevention (DIRECT-Prevent 1) and pro-gression (DIRECT-Protect 1) of retinopathy in type 1diabetes randomised placebo-controlled trials Lancet20083721394ndash1402

101 Sjolie AK Klein R Porta M et al Effect of candesartanon progression and regression of retinopathy in type 2diabetes (DIRECT-Protect 2) a randomised placebo-controlled trial Lancet 20083721385ndash1393

102 Mauer M Zinman B Gardiner R et al Renal andretinal effects of enalapril and losartan in type 1 dia-betes N Engl J Med 200936140ndash51

103 Beulens JW Patel A Vingerling JR et al Effects ofblood pressure lowering and intensive glucose controlon the incidence and progression of retinopathy inpatients with type 2 diabetes mellitus a randomisedcontrolled trial Diabetologia 2009522027ndash2036

104 Lyons TJ Jenkins AJ Zheng D et al Diabetic retinopathyand serum lipoprotein subclasses in the DCCTEDICcohort Invest Ophthalmol Vis Sci 200445910ndash918

105 Rema M Srivastava BK Anitha B et al Association ofserum lipids with diabetic retinopathy in urban SouthIndians ndash the Chennai Urban Rural Epidemiology Study(CURES) Eye Study ndash 2 Diabet Med 2006231029ndash1036

106 Salinero-Fort MA San Andres-Rebollo FJ de Burgos-Lunar C et al Four-year incidence of diabetic retino-pathy in a Spanish cohort the MADIABETES studyPLoS One 20138e76417

107 Wong TY Klein R Islam FM et al Diabetic retino-pathy in a multi-ethnic cohort in the United States AmJ Ophthalmol 2006141446ndash455

108 Morgan CL Owens DR Aubonnet P et al Primary pre-vention of diabetic retinopathy with fibrates a retrospec-tive matched cohort study BMJ Open 20133e004025

109 Keech A Simes RJ Barter P et al Effects of long-termfenofibrate therapy on cardiovascular events in 9795 peo-ple with type 2 diabetes mellitus (the FIELD study) ran-domised controlled trial Lancet 20053661849ndash1861

110 Group AS Group AES Chew EY et al Effects ofmedical therapies on retinopathy progression in type2 diabetes N Engl J Med 2010363233ndash244

111 Staels B Dallongeville J Auwerx J et al Mechanism ofaction of fibrates on lipid and lipoprotein metabolismCirculation 1998982088ndash2093

112 Bordet R Ouk T Petrault O et al PPAR a newpharmacological target for neuroprotection in strokeand neurodegenerative diseases Biochem Soc Trans2006341341ndash1346

113 Kim J Ahn JH Kim JH et al Fenofibrate regulatesretinal endothelial cell survival through the AMPKsignal transduction pathway Exp Eye Res200784886ndash893

114 Miranda S Gonzalez-Rodriguez A Garcia-Ramirez Met al Beneficial effects of fenofibrate in retinal pigmentepithelium by the modulation of stress and survivalsignaling under diabetic conditions J Cell Physiol20122272352ndash2362

115 Villarroel M Garcia-Ramirez M Corraliza L et alFenofibric acid prevents retinal pigment epitheliumdisruption induced by interleukin-1beta by suppressingAMP-activated protein kinase (AMPK) activationDiabetologia 2011541543ndash1553

116 Wong TY Simo R Mitchell P Fenofibrate ndash a potentialsystemic treatment for diabetic retinopathy Am JOphthalmol 20121546ndash12

117 Owens DR Gibbins RL Kohner E et al Diabeticretinopathy screening Diabet Med 200017493ndash494

118 Backlund LB Algvere PV Rosenqvist U New blind-ness in diabetes reduced by more than one-third inStockholm County Diabet Med 199714732ndash740

119 American Diabetes Association Executive summaryStandards of medical care in diabetes ndash2014 DiabetesCare 2014 37(Suppl1)S5ndash13

120 Harris NK Talwar N Gardner TW et al Predictingdevelopment of proliferative diabetic retinopathyDiabetes Care 2013361562ndash1568

121 Fante RJ Gardner TW Sundstrom JM Current andfuture management of diabetic retinopathy a persona-lized evidence-based approach Diabetes Manag (Lond)20133481ndash494

123 Gaede P Vedel P Larsen N et al Multifactorial inter-vention and cardiovascular disease in patients withtype 2 diabetes N Engl J Med 2003348383ndash393

124 Sandbaek A Griffin SJ Sharp SJ et al Effect of earlymultifactorial therapy compared with routine care onmicrovascular outcomes at 5 years in people withscreen-detected diabetes a randomized controlled

trial the ADDITION-Europe Study Diabetes Care2014372015ndash2023

125 Rema M Premkumar S Anitha B et al Prevalence ofdiabetic retinopathy in urban India the ChennaiUrban Rural Epidemiology Study (CURES) eye studyI Invest Ophthalmol Vis Sci 2005462328ndash2333

126 Liu L Wu X Liu L et al Prevalence of diabetic retino-pathy in mainland China a meta-analysis PLoS One20127e45264

127 Rani PK Raman R Chandrakantan A et al Risk factorsfor diabetic retinopathy in self-reported rural populationwith diabetes J Postgrad Med 20095592ndash96

128 Wang FH Liang YB Zhang F et al Prevalence ofdiabetic retinopathy in rural China the Handan EyeStudy Ophthalmology 2009116461ndash467

129 World Health Organization International DiabetesFederation Diabetes action now 2004 AccessedDecember 15 2015 from httpwww who intdiabetesactionnowbookleten

130 World Health Organization Prevention of blindnessfrom diabetes mellitus Report of a WHOConsultation in Geneva 2006

131 Tso MO Changing scenery of eye care in China fromcataract to diabetic retinopathy Arch Ophthalmol2012130243ndash245

132 World Health Organization Universal Eye Health Aglobal action plan 2014ndash2019 Prevention of blindnessand visual impairment 2013

133 Khandekar R Screening and public health strategies fordiabetic retinopathy in the eastern Mediterraneanregion Middle East Afr J Ophthalmol 201219178ndash187

134 Manperumalsamy Guidelines for the comprehensivemanagement of diabetic retinopathy in India AravindEye Care System Madurai India A VISION 2020 TheRight to Sight India Publication 2008

135 von-Bischhoffshausen FB Castro FM Gomez-Bastar PPlanning diabetic retinopathy services ndash lessons fromLatin America Community Eye Health 20112414ndash16

Abstract

Introduction

Trend 1 There is a global increase in the prevalence of diabetes

Trend 2 There is a decline in the incidence of blindness due to proliferative diabetic retinopathy particularly in developed countries

Trend 3 Diabetic macular edema rather than proliferative diabetic retinopathy is an increasingly common cause of visual impairment

Trend 4 Awareness of diabetic retinopathy remains poor in most communities

Trend 5 Hyperglycemia remains the most consistent risk factor for diabetic retinopathy in type 1 diabetes

Trend 6 Blood pressure is an important risk factor for diabetic retinopathy in persons with type 2 diabetes

Trend 7 The relationship between dyslipidemia and diabetic retinopathy remains unclear

Trend 8 Photographic screening of diabetic retinopathy using a tele-ophthalmology platform is increasingly being recognized as a feasible and cost-effective screening strategy

Trend 9 An accurate predictive model of patients at risk of diabetic retinopathy remains to be developed

Trend 10 Diabetic retinopathy prevention in low-resource settings requires different public healthcare models and strategies

Conclusion


References

MINI REVIEW

Ten Emerging Trends in the Epidemiology of Diabetic RetinopathyCharumathi Sabanayagamabc WanFen Yipa Daniel S W Tinga Gavin Tana and Tien Y Wongacd

aSingapore Eye Research Institute Singapore National Eye Centre Singapore bCenter for Quantitative Medicine Duke-NUS Medical SchoolSingapore cYong Loo Lin School of Medicine National University of Singapore Singapore dOphthalmology and Visual Sciences AcademicClinical Program Duke-NUS Medical School Singapore

ABSTRACTPurpose Diabetes is a major public health problem affecting 415 million people worldwide Withthe increasing prevalence of diabetes diabetic retinopathy (DR) is emerging as the leading causeof avoidable blindness worldwideMethods We reviewed previous and recent literature to provide an overview of emerging trendson the burden epidemiology risk factors and prevention of DRResults First there is clear evidence of a global increase in the prevalence of diabetes Secondthere is a decline in the incidence of blindness due to DR particularly in developed countriesThird diabetic macular edema (DME) rather than proliferative diabetic retinopathy (PDR) is theincreasingly common cause of visual impairment Fourth DR awareness remains patchy and lowin most populations Fifth hyperglycemia remains the most consistent risk factor for DR in type 1diabetes across different studies and populations Sixth in contrast blood pressure is an impor-tant risk factor for DR in type 2 diabetes Seventh the relationship between dyslipidemia and DRremains unclear with inconsistent results from different studies and trials Eighth the utility ofpredictive models incorporating multiple risk factors for assessing DR risk requires evaluationNinth photographic screening of DR using tele-ophthalmology platforms is increasingly recog-nized as being feasible and cost-effective Finally DR prevention in low-resource settings cannotfollow models developed in high-resource countries and requires different strategiesConclusions The ten trends we observed in the current review may guide planning of publichealthcare strategies for the management of DR and prevention of blindness

ARTICLE HISTORYReceived 29 January 2016Revised 15 March 2016Accepted 19 March 2016

KEYWORDSAwareness burden diabeticretinopathy prevention riskfactors

Introduction

Diabetes currently affects an estimated 415 millionpeople worldwide and the number is expected to riseto 642 million by 20401 With the rising prevalence ofdiabetes the number of persons with diabetic retino-pathy (DR) has also increased In view of the increasingburden of diabetes and DR there has been substantialglobal public attention and research in recent years onunderstanding the epidemiology risk factors and bur-den of diabetes and DR in an effort to develop long-term strategies to manage this major public healthproblem1ndash8

Over the last decade there have been somemajor devel-opments in the diagnosis and care of patients with diabetesand DR For example the results of landmark clinical trialsin the 1980s and 1990s such as the Diabetes Control andComplications Trial (DCCT) and the United KingdomProspective Diabetes Study (UKPDS) showed that thedevelopment and progression of DR can be significantlyreduced by controlling blood glucose9ndash11 and blood

pressure (BP)12 Other major trials demonstrated the effec-tiveness of laser photocoagulation in preventing vision lossin patients with DR1314 In the last decade three develop-ments are particularly important First the development ofthe non-invasive optical coherence tomography (OCT) hasimproved the assessment of DR particularly diabeticmacular edema (DME) Second the introduction of intrao-cular administration of anti-vascular endothelial growthfactor (anti-VEGF) agents has changed the paradigm inthe management of DME from ldquopreventing vision lossrdquo toldquoimproving visionrdquo15 Finally the increasing use of photo-graphic screening of DR with the development of highquality digital fundus cameras and the transmission ofimages and information over the internet has allowed thedevelopment of tele-ophthalmology as an increasinglyused viable and cost-effective option in the screening ofDR16ndash19 These developments have reduced the prevalenceof DR and occurrence of new cases of blindness due to DRglobally and improved the diagnosis and management ofDME For example with the increasing availability of OCTdevices together with their improved accuracy and

CONTACT Charumathi Sabanayagam charumathisabanayagamsericomsg Singapore Eye Research Institute The Academia 20 College RoadDiscovery Tower Level 6 Singapore 169856 Tel +65 6576 7286 Fax +65 6225 2568

OPHTHALMIC EPIDEMIOLOGY2016 VOL 23 NO 4 209ndash222httpdxdoiorg1010800928658620161193618

copy 2016 Taylor amp Francis

Table3

Incidenceof

diabeticmacular

a(DME)

Authoryearrefno

pulatio

Definition

Follow-up

Martin

-Merinoand

colleagues2014

51Type

1amp2diabetesU

minusMaculop

athyinclusive

ofMEexud

ativemaculop

oranyotherno

n-specificmaculop

mulativeincidence

1-year

follow-up

1diabetes0

2diabetes0

9-year

follow-up

1diabetes4

2diabetes3

Jonesandcolleagues

55Type

2diabetesU

Independ

entgradingscale

EnglishNationalS

creening

mulativeincidenceof

5-year

follow-up

10-yearfollow-up

asandcolleagues

56Type

2diabetesU

Maculop

athyexudateswith

in1disc

ofthefovea

Referableretin

opathy

pre-proliferativeor

proliferativeretin

opathy

orwith

outmaculop

athy)or

maculop

backgrou

ndretin

opathy

nualincidenceof

Referable

opathy

Romero-Arocaand

colleagues2011

50Type

1diabetesSpain

DMEretin

althickening

andhard

inthemacular

mulativeincidenceof

aandcolleagues2010

44UnitedStates

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

mulativeincidenceof

Kleinandcolleagues

48Type

1diabetesU

nitedStates

Stereoscop

sMEretin

althickening

inthemacular

nualized

incidences

Follow-up1

Follow-up2

Follow-up3

Follow-up4

Leskeandcolleagues

52Type

sStereoscop

sClinicallysign

ificant

macular

(1)thickening

oftheretin

orwith

in500μm

ofthecenter

ofthemacula(2)hard

in500μm

ofthecenter

thickening

oftheadjacent

notresidu

alhard

remaining

afterthedisapp

earanceof

althickening

)and(3)a

orzonesof

althickening

orlarger

insize

anypartof

in1disc

ofthecenter

ofthemacula

mulativeincidenceof

isandcolleagues

53Type

1diabetesU

yMaculop

athyringof

atewith

inmaculage1disc

insize

ofcenter

ofmaculaor

in1disc

offixation

presence

offocalo

photocoagu

nscars

mulativeincidenceof

isandcolleagues

54Type

2diabetesU

yMaculop

athyringof

atewith

inmaculage1disc

insize

ofcenter

ofmaculaor

in1disc

offixation

presence

offocalo

photocoagu

nscars

mulativeincidenceof

tinued)

Table3

tinued)

Authoryearrefno

pulatio

Definition

Follow-up

49Type

1diabetesU

nitedStates

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

CSMEretin

althickening

in500microm

thecenter

ofthemaculaor

in500microm

ofthecenter

thickening

oftheadjacent

orzonesof

althickening

atleast1disc

insize

atleastpartof

is1disc

thecenter

ofthemaculaor

focalp

mulativeincidenceof

DME261

CSME170

46Type

1amp2diabetesU

States

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

nualincidenceof

DMEover

4years

ger-on

Older-onset1

alincidenceof

DMEover

6years

ger-on

Older-onset2

MEmacular

aCSMEclinicallysign

ificant

macular

fluorescein

angiog

Conclusion

References

Abstract

Introduction











Conclusion


References

Table3

Incidenceof

diabeticmacular

a(DME)

Authoryearrefno

pulatio

Definition

Follow-up

Martin

-Merinoand

colleagues2014

51Type

1amp2diabetesU

minusMaculop

athyinclusive

ofMEexud

ativemaculop

oranyotherno

n-specificmaculop

mulativeincidence

1-year

follow-up

1diabetes0

2diabetes0

9-year

follow-up

1diabetes4

2diabetes3

Jonesandcolleagues

55Type

2diabetesU

Independ

entgradingscale

EnglishNationalS

creening

mulativeincidenceof

5-year

follow-up

10-yearfollow-up

asandcolleagues

56Type

2diabetesU

Maculop

athyexudateswith

in1disc

ofthefovea

Referableretin

opathy

pre-proliferativeor

proliferativeretin

opathy

orwith

outmaculop

athy)or

maculop

backgrou

ndretin

opathy

nualincidenceof

Referable

opathy

Romero-Arocaand

colleagues2011

50Type

1diabetesSpain

DMEretin

althickening

andhard

inthemacular

mulativeincidenceof

aandcolleagues2010

44UnitedStates

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

mulativeincidenceof

Kleinandcolleagues

48Type

1diabetesU

nitedStates

Stereoscop

sMEretin

althickening

inthemacular

nualized

incidences

Follow-up1

Follow-up2

Follow-up3

Follow-up4

Leskeandcolleagues

52Type

sStereoscop

sClinicallysign

ificant

macular

(1)thickening

oftheretin

orwith

in500μm

ofthecenter

ofthemacula(2)hard

in500μm

ofthecenter

thickening

oftheadjacent

notresidu

alhard

remaining

afterthedisapp

earanceof

althickening

)and(3)a

orzonesof

althickening

orlarger

insize

anypartof

in1disc

ofthecenter

ofthemacula

mulativeincidenceof

isandcolleagues

53Type

1diabetesU

yMaculop

athyringof

atewith

inmaculage1disc

insize

ofcenter

ofmaculaor

in1disc

offixation

presence

offocalo

photocoagu

nscars

mulativeincidenceof

isandcolleagues

54Type

2diabetesU

yMaculop

athyringof

atewith

inmaculage1disc

insize

ofcenter

ofmaculaor

in1disc

offixation

presence

offocalo

photocoagu

nscars

mulativeincidenceof

tinued)

Table3

tinued)

Authoryearrefno

pulatio

Definition

Follow-up

49Type

1diabetesU

nitedStates

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

CSMEretin

althickening

in500microm

thecenter

ofthemaculaor

in500microm

ofthecenter

thickening

oftheadjacent

orzonesof

althickening

atleast1disc

insize

atleastpartof

is1disc

thecenter

ofthemaculaor

focalp

mulativeincidenceof

DME261

CSME170

46Type

1amp2diabetesU

States

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

nualincidenceof

DMEover

4years

ger-on

Older-onset1

alincidenceof

DMEover

6years

ger-on

Older-onset2

MEmacular

aCSMEclinicallysign

ificant

macular

fluorescein

angiog

Conclusion

References

Abstract

Introduction











Conclusion


References

Table3

Incidenceof

diabeticmacular

a(DME)

Authoryearrefno

pulatio

Definition

Follow-up

Martin

-Merinoand

colleagues2014

51Type

1amp2diabetesU

minusMaculop

athyinclusive

ofMEexud

ativemaculop

oranyotherno

n-specificmaculop

mulativeincidence

1-year

follow-up

1diabetes0

2diabetes0

9-year

follow-up

1diabetes4

2diabetes3

Jonesandcolleagues

55Type

2diabetesU

Independ

entgradingscale

EnglishNationalS

creening

mulativeincidenceof

5-year

follow-up

10-yearfollow-up

asandcolleagues

56Type

2diabetesU

Maculop

athyexudateswith

in1disc

ofthefovea

Referableretin

opathy

pre-proliferativeor

proliferativeretin

opathy

orwith

outmaculop

athy)or

maculop

backgrou

ndretin

opathy

nualincidenceof

Referable

opathy

Romero-Arocaand

colleagues2011

50Type

1diabetesSpain

DMEretin

althickening

andhard

inthemacular

mulativeincidenceof

aandcolleagues2010

44UnitedStates

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

mulativeincidenceof

Kleinandcolleagues

48Type

1diabetesU

nitedStates

Stereoscop

sMEretin

althickening

inthemacular

nualized

incidences

Follow-up1

Follow-up2

Follow-up3

Follow-up4

Leskeandcolleagues

52Type

sStereoscop

sClinicallysign

ificant

macular

(1)thickening

oftheretin

orwith

in500μm

ofthecenter

ofthemacula(2)hard

in500μm

ofthecenter

thickening

oftheadjacent

notresidu

alhard

remaining

afterthedisapp

earanceof

althickening

)and(3)a

orzonesof

althickening

orlarger

insize

anypartof

in1disc

ofthecenter

ofthemacula

mulativeincidenceof

isandcolleagues

53Type

1diabetesU

yMaculop

athyringof

atewith

inmaculage1disc

insize

ofcenter

ofmaculaor

in1disc

offixation

presence

offocalo

photocoagu

nscars

mulativeincidenceof

isandcolleagues

54Type

2diabetesU

yMaculop

athyringof

atewith

inmaculage1disc

insize

ofcenter

ofmaculaor

in1disc

offixation

presence

offocalo

photocoagu

nscars

mulativeincidenceof

tinued)

Table3

tinued)

Authoryearrefno

pulatio

Definition

Follow-up

49Type

1diabetesU

nitedStates

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

CSMEretin

althickening

in500microm

thecenter

ofthemaculaor

in500microm

ofthecenter

thickening

oftheadjacent

orzonesof

althickening

atleast1disc

insize

atleastpartof

is1disc

thecenter

ofthemaculaor

focalp

mulativeincidenceof

DME261

CSME170

46Type

1amp2diabetesU

States

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

nualincidenceof

DMEover

4years

ger-on

Older-onset1

alincidenceof

DMEover

6years

ger-on

Older-onset2

MEmacular

aCSMEclinicallysign

ificant

macular

fluorescein

angiog

Conclusion

References

Abstract

Introduction











Conclusion


References

Table3

Incidenceof

diabeticmacular

a(DME)

Authoryearrefno

pulatio

Definition

Follow-up

Martin

-Merinoand

colleagues2014

51Type

1amp2diabetesU

minusMaculop

athyinclusive

ofMEexud

ativemaculop

oranyotherno

n-specificmaculop

mulativeincidence

1-year

follow-up

1diabetes0

2diabetes0

9-year

follow-up

1diabetes4

2diabetes3

Jonesandcolleagues

55Type

2diabetesU

Independ

entgradingscale

EnglishNationalS

creening

mulativeincidenceof

5-year

follow-up

10-yearfollow-up

asandcolleagues

56Type

2diabetesU

Maculop

athyexudateswith

in1disc

ofthefovea

Referableretin

opathy

pre-proliferativeor

proliferativeretin

opathy

orwith

outmaculop

athy)or

maculop

backgrou

ndretin

opathy

nualincidenceof

Referable

opathy

Romero-Arocaand

colleagues2011

50Type

1diabetesSpain

DMEretin

althickening

andhard

inthemacular

mulativeincidenceof

aandcolleagues2010

44UnitedStates

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

mulativeincidenceof

Kleinandcolleagues

48Type

1diabetesU

nitedStates

Stereoscop

sMEretin

althickening

inthemacular

nualized

incidences

Follow-up1

Follow-up2

Follow-up3

Follow-up4

Leskeandcolleagues

52Type

sStereoscop

sClinicallysign

ificant

macular

(1)thickening

oftheretin

orwith

in500μm

ofthecenter

ofthemacula(2)hard

in500μm

ofthecenter

thickening

oftheadjacent

notresidu

alhard

remaining

afterthedisapp

earanceof

althickening

)and(3)a

orzonesof

althickening

orlarger

insize

anypartof

in1disc

ofthecenter

ofthemacula

mulativeincidenceof

isandcolleagues

53Type

1diabetesU

yMaculop

athyringof

atewith

inmaculage1disc

insize

ofcenter

ofmaculaor

in1disc

offixation

presence

offocalo

photocoagu

nscars

mulativeincidenceof

isandcolleagues

54Type

2diabetesU

yMaculop

athyringof

atewith

inmaculage1disc

insize

ofcenter

ofmaculaor

in1disc

offixation

presence

offocalo

photocoagu

nscars

mulativeincidenceof

tinued)

Table3

tinued)

Authoryearrefno

pulatio

Definition

Follow-up

49Type

1diabetesU

nitedStates

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

CSMEretin

althickening

in500microm

thecenter

ofthemaculaor

in500microm

ofthecenter

thickening

oftheadjacent

orzonesof

althickening

atleast1disc

insize

atleastpartof

is1disc

thecenter

ofthemaculaor

focalp

mulativeincidenceof

DME261

CSME170

46Type

1amp2diabetesU

States

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

nualincidenceof

DMEover

4years

ger-on

Older-onset1

alincidenceof

DMEover

6years

ger-on

Older-onset2

MEmacular

aCSMEclinicallysign

ificant

macular

fluorescein

angiog

Conclusion

References

Abstract

Introduction











Conclusion


References

Table3

Incidenceof

diabeticmacular

a(DME)

Authoryearrefno

pulatio

Definition

Follow-up

Martin

-Merinoand

colleagues2014

51Type

1amp2diabetesU

minusMaculop

athyinclusive

ofMEexud

ativemaculop

oranyotherno

n-specificmaculop

mulativeincidence

1-year

follow-up

1diabetes0

2diabetes0

9-year

follow-up

1diabetes4

2diabetes3

Jonesandcolleagues

55Type

2diabetesU

Independ

entgradingscale

EnglishNationalS

creening

mulativeincidenceof

5-year

follow-up

10-yearfollow-up

asandcolleagues

56Type

2diabetesU

Maculop

athyexudateswith

in1disc

ofthefovea

Referableretin

opathy

pre-proliferativeor

proliferativeretin

opathy

orwith

outmaculop

athy)or

maculop

backgrou

ndretin

opathy

nualincidenceof

Referable

opathy

Romero-Arocaand

colleagues2011

50Type

1diabetesSpain

DMEretin

althickening

andhard

inthemacular

mulativeincidenceof

aandcolleagues2010

44UnitedStates

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

mulativeincidenceof

Kleinandcolleagues

48Type

1diabetesU

nitedStates

Stereoscop

sMEretin

althickening

inthemacular

nualized

incidences

Follow-up1

Follow-up2

Follow-up3

Follow-up4

Leskeandcolleagues

52Type

sStereoscop

sClinicallysign

ificant

macular

(1)thickening

oftheretin

orwith

in500μm

ofthecenter

ofthemacula(2)hard

in500μm

ofthecenter

thickening

oftheadjacent

notresidu

alhard

remaining

afterthedisapp

earanceof

althickening

)and(3)a

orzonesof

althickening

orlarger

insize

anypartof

in1disc

ofthecenter

ofthemacula

mulativeincidenceof

isandcolleagues

53Type

1diabetesU

yMaculop

athyringof

atewith

inmaculage1disc

insize

ofcenter

ofmaculaor

in1disc

offixation

presence

offocalo

photocoagu

nscars

mulativeincidenceof

isandcolleagues

54Type

2diabetesU

yMaculop

athyringof

atewith

inmaculage1disc

insize

ofcenter

ofmaculaor

in1disc

offixation

presence

offocalo

photocoagu

nscars

mulativeincidenceof

tinued)

Table3

tinued)

Authoryearrefno

pulatio

Definition

Follow-up

49Type

1diabetesU

nitedStates

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

CSMEretin

althickening

in500microm

thecenter

ofthemaculaor

in500microm

ofthecenter

thickening

oftheadjacent

orzonesof

althickening

atleast1disc

insize

atleastpartof

is1disc

thecenter

ofthemaculaor

focalp

mulativeincidenceof

DME261

CSME170

46Type

1amp2diabetesU

States

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

nualincidenceof

DMEover

4years

ger-on

Older-onset1

alincidenceof

DMEover

6years

ger-on

Older-onset2

MEmacular

aCSMEclinicallysign

ificant

macular

fluorescein

angiog

Conclusion

References

Abstract

Introduction











Conclusion


References

Table3

tinued)

Authoryearrefno

pulatio

Definition

Follow-up

49Type

1diabetesU

nitedStates

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

CSMEretin

althickening

in500microm

thecenter

ofthemaculaor

in500microm

ofthecenter

thickening

oftheadjacent

orzonesof

althickening

atleast1disc

insize

atleastpartof

is1disc

thecenter

ofthemaculaor

focalp

mulativeincidenceof

DME261

CSME170

46Type

1amp2diabetesU

States

Stereoscop

sMEthickening

oftheretin

orwith

artiallossof

transparency

in1disc

macular

center

orthepresence

offocalpho

macular

nualincidenceof

DMEover

4years

ger-on

Older-onset1

alincidenceof

DMEover

6years

ger-on

Older-onset2

MEmacular

aCSMEclinicallysign

ificant

macular

fluorescein

angiog

Conclusion

References

Abstract

Introduction











Conclusion


References

Conclusion

References

Abstract

Introduction











Conclusion


References

Conclusion

References

Abstract

Introduction











Conclusion


References

Conclusion

References

Abstract

Introduction











Conclusion


References

Conclusion

References

Abstract

Introduction











Conclusion


References

Abstract

Introduction











Conclusion


References

Abstract

Introduction











Conclusion


References

Abstract

Introduction











Conclusion


References

Abstract

Introduction











Conclusion


References

Documents

Ten Emerging Trends in the Epidemiology of Diabetic Retinopathy · 2017-11-24 · Table 1. List of emerging trends in the epidemiology of diabetic retinopathy. 1 There is a global