Screening for Diabetic Retinopathy

14.1 Introduction

Screening is worthwhile when certain criteria are met: a disease has public health importance; an effective treatment exists; an interval exists within which treatment can effect benefit; and the disease is neither too rare nor too common.1 Screening for diabetes mellitus in those over 40 years of age and screening for diabetic retinopathy (DR) in those with known diabetes mellitus fulfill these criteria.2,3

Beyond improving health-related outcomes, treatment of diabetes and DR is cost effective.4,5,6 Thus,

the value of screening for DR is widely recognized. There is, however, controversy regarding the best screening method and screening intervals.7

In the United States, the gold standard for screening to detect DR is a dilated fundus examination with stereoscopic biomicroscopy and indirect ophthalmoscopy annually from diagnosis of diabetes in type 2

diabetes and annually beginning 5 years after diagnosis in type 1 diabetes.8–10 The failure of this ideal as a

practical standard is exemplified by the statistic that 30–50% of patients with diabetes are not screened annually, and that 10–36% of known diabetics have

never had a dilated eye examination, depending on the country.7,11–17 In the United States, approxi-

mately half of those never having had a dilated eye examination have eye disease.18 Across the world, failure in screening is related to economic status; worse poverty is associated with worse screening

D.J. Browning (*)

Charlotte Eye Ear Nose & Throat Associates, Charlotte, NC 28210, USA

e-mail: dbrowning@ceenta.com

outcomes.16,14 For example, among Chinese populations, rates of undiagnosed diabetes due to failure to screen are lower in Hong Kong and Taiwan than mainland China19. In the United States too, poverty

is associated with lower rates of eye examinations for DR.16,14,20 Among the poor, minorities, migrants,

and others with limited access to health-care annual screening rates for DR are as low as 10%.14,21

A correlation exists between failure of screening for diabetes and DR and a preventable proportion of societal blindness. In Bristol, UK, 5.5% of blind registrations were due to DR, and of these, 50% had never had an eye examination and 22% were not known to be diabetic.22 Screening for DR implies a more basic need to screen for diabetes. If diabetes has not been diagnosed, there is no possibility of screening for DR. Screening for DR should be focused on known diabetics, as the rate of referable retinopathy in newly diagnosed diabetics from screening is negligible.23

The goal of screening all diabetic patients has not

been met in most societies across the world with the exception of Iceland.3,11,24,25 The reasons besides

poverty vary, but include inadequate numbers and regional maldistribution of ophthalmologists and optometrists, poor ability of non-eye care health professionals to recognize referable DR, lack of education and awareness of the importance of screening eye examinations in diabetes, advanced patient

age, requirement to dilate the pupils, and burden of undiagnosed diabetes.3,24,26,27 As a result, interest

in screening methods is worldwide and the literature is large. The topic is complex because the optimal techniques in screening for diabetic macular edema (DME), nonproliferative diabetic retinopathy

(NPDR), and proliferative diabetic retinopathy (PDR) are not the same. The retinal lesions are often more peripheral in PDR and detection of

DME is compromised by nonstereoscopic meth- ods.9,26,28–30 Nor are the techniques necessarily the

same for types 1 and 2 diabetes. Some studies use more complicated protocols for type 1 diabetics because of their greater probability of having PDR requiring more peripheral retinal examination.27 Comparing the results of studies is difficult because of different definitions of referable retinopathy, ungradable photographic images, gold standards, and protocols for screening.3,9 Moreover, cameras have improved limiting comparability across studies over time.26 Film versus digital media, red-free versus color images for grading, and grading on screens versus prints further cloud comparability of studies.31 Despite these complexities, in this chapter we will try to identify the broad themes, while making no claim to exhaustive coverage of the topic.

The effectiveness of a screening program depends on four variables – the prevalence of the disease, the percentage of the target population actually screened (the compliance), the performance statistics of the screening method (the sensitivity and specificity), and the cost.32 Estimates of the prevalence of sightthreatening eye disease among diabetics range from 6.0 to 14.1%.9,32 Compliance with opportunistic screening by general practitioners and diabetologists in daily practice versus systematic photographic screening in pilot trials in the United Kingdom has been reported to be 38–85% and 80–93%, respectively.10,32 Compliance with ophthalmic screening in the United States is 50–65%.17 Factors that limit compliance include housebound patients, percentage of patients in rural areas, social deprivation score based on unemployment, distribution of doctors, crowding, car ownership, socioeconomic status, and rapid population turnover in mobile urban societies.32,33 Published benchmark targets for compliance are 90–95%.10 Sensitivity and specificity for screening by primary care physicians have been esti-

mated to be 38–63% and 92–97%, respectively.32,34,35 For photographic screening methods,

these estimates are generally >80% and >90%, respectively (Table 14.2). As a reference benchmark,

an acceptable screening technique needs to have a sensitivity for the detection of DR of 80%.9,36

Cost estimates vary over time and on many

assumptions such as method of screening and valuation for degrees of visual impairment.7 We will compare the performance of the various methods of screening on these variables below.

14.2 Who Does Not Need to Be Screened

Type 1 diabetics of age less than 9–12 years do not

need to be screened, because the risk of DME and PDR is near zero.37–40 Type 1 diabetics who have

been diagnosed less than 3–5 years previously also do not need to be screened for similar reasons.8,39

14.3Screening for Diabetic Retinopathy by Adjunctive or Stand-Alone Visual Acuity Testing

Given the challenge of primary care providers learning ophthalmoscopic skills, there has been an interest in determining if detection of DR by simply screening for subnormal corrected visual acuity is feasi-

ble.17 Evidence suggests that this is not the case.35,36,41,42 The sensitivity of visual acuity testing

for retinopathy as severe or more severe than moderate NPDR was 43.8% because many patients with more severe DR continue to have good visual acuity.35 Its sensitivity for the detection of DME was 7.5–38.5%. The specificity of visual acuity screening is also low because other causes of reduced

vision, such as cataract, corneal pathology, or macular degeneration, are common. 35–36,41–43 Neverthe-

less, because DME is 4–5 times as common as PDR, its detection is difficult for all methods, and a check of visual acuity is simple and inexpensive to perform, adding a vision check to the other methods of screening is a good strategy for reducing false negatives and prioritizing referral.9,22,35

14.4Screening with Undilated Direct Ophthalmoscopy by Non-eye Care Professionals

Direct ophthalmoscopy performed by nonophthalmologist physicians has sensitivity and specificity for detecting PDR of 30–67% and 97%,

respectively.35,44,45 Experience affects the screening statistics; physicians in fellowship training performed worse than attendings with >8 years experience.35 For DME detection by nonophthalmologists, the sensitivity and specificity were 0% and 100%, respectively.35 For DR retinopathy detection without further subclassification, the sensitivity and specificity were 52 and 91% for a general practitioner and 67 and 97% for an endocrinologist.46 The sensitivity and specificity of a physician’s assistant for detection of DR compared to seven-field stereo fundus photography were 14 and 99%, respectively.47 The sensitivity and specificity of experienced technicians to detect PDR compared to seven-field stereo fundus photography were 50 and 90%, respectively.29

The practicality of non-eye care professionals

screening for DR has been in turn defended and deprecated.17,35 The best case scenario has been

studied using the photographic files of the Early Treatment Diabetic Retinopathy Study (ETDRS).17 Bresnick and colleagues assumed that such professionals could be trained to correctly identify retinal lesions of DR in the area covered by ETDRS photographic fields 1–3 (roughly the posterior pole and peripapillary retina). If this were the case, in the older onset diabetic population, the best case sensitivity and specificity for detecting PDR were 87 and 80%, respectively.17 The fundus characteristic associated with this level of performance was the presence of hemorrhages and microaneurysms temporal to the macula as severe as or more severe than ETDRS standard photograph 3 (see chapter 5). For clinically significant macular edema (CSME), the sensitivity and specificity were 94 and 54%, respectively.17 The characteristic associated with this performance was presence of any hard exudates within 1 disk diameter of the center of the macula. Assuming it were practical and that nonophthalmologists could detect vision-threatening retinopathy (PDR and DME) reliably, the number of referrals for ophthalmologic examination would drop an estimated 47% for younger onset patients and 62% for older onset patients.17 The bulk of the evidence suggests that actual performance by nonophthalmic physicians will continue to fall far short of this best case scenario.48

14.5Screening with Dilated Ophthalmoscopy by Ophthalmic Technicians or Optometrists

With special training and unrestricted ability to consult among themselves, an optometrist and an ophthalmic technician were able to perform on par with an ophthalmologist in detecting DR by direct ophthalmoscopy and indirect ophthalmoscopy as needed.49 DR severity was collapsed into three categories: none, NPDR, and PDR. The agreement between all three examiner types and graded sevenfield stereo fundus photographs was 85.7% and the chance-corrected agreement (kappa) was 0.749. There was no important difference between the performance of the ophthalmologist, the optometrist, or the technician.49 Studies using various gold standards (e.g., ophthalmologist or retina specialist diagnosis) and levels of retinopathy detection (e.g., referable or sight threatening) have reported sensitiv-

ity and specificity for optometric detection of DR of 52–94% and 90–100%, respectively.10,46,50,51 The

sensitivity of British ophthalmic opticians for detecting any DR was 73%.45

14.6Screening with Dilated Ophthalmoscopy by Ophthalmologists

With seven-field stereoscopic photography as a gold standard, the sensitivity and specificity for

ophthalmologists detecting DR have ranged from 28 to 76% and 91 to 100%, respectively.5,35,47,52,53

The wide range of sensitivity reflects differences in study designs and types of retinopathy assessed. Chance-corrected agreement has been poor (0.38–0.40), primarily because ophthalmoscopy is

insensitive to the presence of microaneurysms and small intraretinal hemo-rrhages.5,47,54 For DME,

the sensitivity and specificity are 40 and 100%, respectively.35 For detecting PDR, these statistics were 61–80% and 98–99%, respectively.53,55 Whether direct plus indirect ophthalmoscopy or slit-lamp biomicroscopy with a fundus non-con- tact lens plus indirect ophthalmoscopy is employed

seems not to matter.47 Although a few studies disagree, most suggest that dilated ophthalmoscopy is inferior to single-field nonmydriatic photography

for detecting DR, although ophthalmoscopy and

the attendant co-examination have co-advantages not found with photographic screening.5,47,55,56

14.7Screening with Dilated Ophthalmoscopy by Retina Specialists

The chance adjusted agreement for a retina specialist’s detection of DR by dilated indirect and direct ophthalmoscopy versus grading by a trained photographic grader at a reading center of sevenfield stereoscopic fundus photographs has been reported to be 0.49.54 The kappa for assessing

severity of retinopathy has been reported to be 0.55–0.62.54,58 The sensitivity and specificity of a retina specialist for detecting PDR were 50 and 100%, respectively.34 Using direct and indirect ophthalmoscopy and contact lens stereoscopic biomicroscopy through a dilated pupil, the sensitivity and specificity for detection of CSME by retina specialists compared to reading center grading of stereo fundus photographs were 82 and 79% in the ETDRS.59