DrT1
EDITORIAL
Screening for Diabetic Retinopathy Using Non-mydriatic Fundus Photography In their recent review of health care screening in the United Kingdom, Holland and Stewart’ restate the view that the principles underlying screening for disease have not changed since they were defined by Wilson and Jungner in 1968.’ The condition sought should be an important problem with a recognizable latent or presymptomatic stage. A suitable screening test should be available which is acceptable both to the public and to health care professionals. There should be effective treatment for patients with recognized disease and an agreed policy on whom to treat. Finally the costs of early diagnosis and treatment should be economically balanced in relation to total expenditure on health care. Unfortunately, in spite of these well established principles, few screening tests have been adequately evaluated prior to their implementation and this has led to difficulties in determining their overall public health impact, for instance the cervical cancer screening programme. The case of screening for diabetic retinopathy is ~ t r o n g j , ~ but as yet there i s no general agreement as to what is the most appropriate screening method. The first problem is that there is no agreed consensus on the gold standard against which potential screening methods can be compared. Fluorescein angiography has been used5 and a recent IDFiWHO workshop recommended seven field stereoscopic fundus photography.6 However, for practical reasons most studies have so far utilized the diagnosis obtained by an ophthalmologist by fundoscopy after mydriasis.’ Given that the screening test i s to be used to determine those patients to be referred for consideration of laser therapy, the most important attribute of a test i s its sensitivity, because the consequences of missing treatable disease are high compared with those of unnecessary false positive referrals. Specificity, which determines the number of false positives, will predominantly affect the cost-effectiveness. Comparison with the gold standard i s vital when assessing the effectiveness of screening tests. Studies which do not utilize such a comparison are of limited value and may serve to confuse the issue. Few of the studies published on non-mydriatic fundus photography have utilized a full c o m p a r i ~ o n . ~8-12 , Williams et a / . , 7 comparing this method with an ophthalmologist’s assessment, calculated the sensitivity of the test to be 96 % with a specificity of 98 % . However this was a small study of only 62 patients. The study by Buxton et a/.’ is of considerable interest not only because it involved a much larger number of patients in several centres but also because comparison was made with a reference screening test, ophthalmoscopy by an
0742-3071 191/070607-02$05.00 Wiley & Sons, Ltd.
0 1991 by john
ophthalmic clinical assistant. In the five centres the calculated sensitivity of fundus photography varied between 35 and 67 %. If the appropriate 2 x 2 tables are combined the overall sensitivity can be calculated as 56 % with a specificity of 97 %. As the authors acknowledge, this is a poor result and will be a disappointment to those who hoped that fundus photography could be used alone as a test for a national screening programme. Equally worrying are the poor results of primary care ophthalmoscopy, especially since sensitivity is likely to be better in a trial than in routine use. If these results were repeated in a national screening programme, then the impact on the burden of blindness due to diabetes would be more limited than the one-third reduction suggested as a public health target in the St Vincent d e ~ l a r a t i o n . ’ ~ It i s possible that alternative approaches may improve the sensitivity. Screening modalities could be combined, for example ophthalmoscopy and fundus photography. Alternatively, the technique of non-mydriatic fundus photography could be modified by the use of mydriasis and of colour transparencies rather than Polaroid film. Instead of a single 45 degree non-mydriatic photograph of each eye, an additional picture of the nasal retina, as recommended by the IDFiWHO workshop6 may allow the detection of more retinal disease. These technical improvements might improve sensitivity,” although there may be a trade-off in terms of cost-effectiveness and patient acceptability. A more rewarding strategy might be to target high-risk groups, for example patients who are not attending either hospital diabetic or ophthalmology clinics, as they are known to be at increased risk of late referral. Economic evaluation of potential screening programmes is necessary to answer important questions of efficiency. Cost-benefit analysis attempts to determine social efficiency, whereas cost-effectiveness analysis is directed at the question of technical efficiency, the delivery of the greatest output at a given cost or, conversely, a given output at the least cost. There i s little doubt that a screening programme for diabetic retinopathy would be cost-beneficial because the value of sight and therefore the cost of blindness i s high, although this has not been quantified. The question of technical efficiency is addressed by the cost-effectiveness analysis by Sculpher et in this issue. They compared hospital- and community-based non-mydriatic fundus photography with ophthalmoscopic examinations by a variety of primary screeners (general practitioners, hospital physicians and ophthalmic opticians). The outcome measure
’
607 DIABETIC MEDICINE, 1991 ; 8 : 607-608
Dm
EDITORIAL used was the cost per true positive case detected, in contrast to other studies that have used cost per year of sight saved. ' 1 3 Hospital-based screening proved t o be relatively expensive because of high hospital overheads whilst community-based non-mydriatic fundus photograp h y was relatively inexpensive. As the sensitivity analysis shows, the cost per true positive case detected is dependent on the incidence of retinopathy in the screened population and is therefore related t o the age-structure of the population and the ratio of Type 1 t o Type 2 patients. The marginal reduction in cost per true positive case detected as throughput increases suggests that units that screen less than 1000 patients a year are unlikely t o be efficient. Using data from the Wisconsin Epidemiologic Study, Dasbach et al.'" suggested that the cost of screening c o u ld b e recovered b y preventing blindness in those diabetic patients taking insulin b u t not necessarily in older Type 2 diabetic patients, presumably due to their reduced life expectancy. However, this finding i s highly dependent on the demographic features of the population studied and the figures for sensitivity used. It m i g h t b e argued that it may be more cost-effective to screen Type 2 diabetic patients i n the UK because they are less likely to be regularly examined and therefore niore likely to have a higher incidence of treatable eye disease."j On the other hand non-mydriatic fundus photography m a y b e less technically satisfactory i n older patients because lens opacities and small pupils may reduce sensitivity? W e must therefore conclude that the present evidence o n the sensitivity of non-mydriatic fundus photography is insufficient to a l l o w recommendation of its usage as the sole screening tool in a nationwide screening programme for diabetic retinopathy. There is an urgent need for properly designed studies of a variety of photographic and other techniques using validated reference methods i n clearly defined populations before w e can hope to persuade health authorities and other health care purchasers that screening for diabetic retinopathy offers good value for money, even though it w o u l d certainly benefit significant numbers of patients who m i gh t otherwise lose their vision.
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Nick Wareham, Richard Greenwood Department of Public Health M e d i c i n e a n d Bertram Diabetes Centre, Norwich, U K
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References 20. 1.
608
Holland WW, Stewart S. Screening in Health Care. Benefit or Bane! London: The Nuffield Provincial Hospitals Trust, 1990.
Wilson JMG, Jungner G . The Principles and Practice of Screening for Disease. Public Health Papers 34. Geneva: WHO, 1968. Kohner EM, Barry PJ. Prevention of blindness in diabetic retinopathy. Diabetologia 1984; 26: 173-1 79. Rohan TE, Frost CD, Wald NJ. Prevention of blindness by screening for diabetic retinopathy: a quantitative assessment. Br M e d 1 1989; 299: 1 198-1 201. Jones D, Dolben J, Owens DR, et a/. Non-mydriatic Polaroid photography in screening for diabetic retinopathy: evaluation in a clinical setting. Br M e d / 1988; 296: 1029-1 030. Retinopathy Working Party. A protocol for screening for diabetic retinopathy in Europe. Diabetic Med 1991; 8 : 263-267. Williams R, Nussey S, Humphry R, Thompson G . Assessment of non-mydriatic fundus photography in detection of diabetic retinopathy. Br Med / 1986; 293: 1140-1 142. Klein R, Klein BEK, Neider M W , etal. Diabetic retinopathy as detected using ophthalmoscopy, a non-mydriatic camera and a standard fundus camera. Ophthalmology 1985; 92: 485-491. Ryder REJ, Young S, Vora JP, et a/. Screening for diabetic retinopathy using Polaroid retinal photography through undilated pupil5. Practical Diabetes 1985; 2: 34-39. Barrie T, MacCuish AC. Assessment of non-mydriatic fundus photography in detection of diabetic retinopathy. Br M e d 1 1986; 293: 1304. Mohan R, Kohner EM, Aldington SJ, et a / . Evaluation of a non-mydriatic camera in Indian and European diabetic patients. Br / Ophthalmol 1988; 72: 841-845. Taylor R, Lovelock L, Tunbridge WMC, etal. Comparison of non-mydriatic retinal photography with ophthalmoscopy in 2159 patients: mobile retinal camera study. Br M e d 1 1990; 31 0: 1243-1 247. Buxton MJ, Sculpher MJ, Ferguson BA, et a/. Screening for treatable diabetic retinopathy: a comparison of different methods. Diabetic M e d 1991; 8 : 371-377. WHO/IDF Europe. Diabetes care and research in Europe: The Saint Vincent Declaration. Diabetic M e d 1990; 7: 360. Moss SE, Klein R, Kessler SD, Ritchie KA. Comparison between ophthalmoscopy and fundus photography in determining the severity of diabetic retinopathy. Ophthalmology 1985; 92: 485-491. Jones RB, Larizgoitia I, Casado L, Barrie T. H o w effective i s the referral chain for diabetic retinopathy? Diabetic Med 1989; 6: 262-266. Sculpher MJ, Buxton MJ, Ferguson BA, et a/. A relative cost-effectiveness analysis of different methods of screening for diabetic retinopathy. Diabetic M e d 1991; 8 : 644-65 0. Javitt JC, Canner JK, Sommer A. Cost-effectiveness of current approaches to the control of retinopathy in type I diabetics. Ophthalmology 1989; 96: 255-264. Dasbach EJ, Frybach DG, Newcomb PA, et a/. Costeffectiveness of strategies for detecting diabetic retinopathy. Medical Care 1991 ; 29: 20-39. Higgs ER, Harney B, Kelleher A, et a/. Limitations of the non-mydriatic camera in screening for diabetic retinopathy in the community (Abstract). Diabetic Med 1990; 7 (suppl 1): 9A.
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EDITORIAL
EDITORIAL
Screening for Diabetic Retinopathy Using Non-mydriatic Fundus Photography In their recent review of health care screening in the United Kingdom, Holland and Stewart’ restate the view that the principles underlying screening for disease have not changed since they were defined by Wilson and Jungner in 1968.’ The condition sought should be an important problem with a recognizable latent or presymptomatic stage. A suitable screening test should be available which is acceptable both to the public and to health care professionals. There should be effective treatment for patients with recognized disease and an agreed policy on whom to treat. Finally the costs of early diagnosis and treatment should be economically balanced in relation to total expenditure on health care. Unfortunately, in spite of these well established principles, few screening tests have been adequately evaluated prior to their implementation and this has led to difficulties in determining their overall public health impact, for instance the cervical cancer screening programme. The case of screening for diabetic retinopathy is ~ t r o n g j , ~ but as yet there i s no general agreement as to what is the most appropriate screening method. The first problem is that there is no agreed consensus on the gold standard against which potential screening methods can be compared. Fluorescein angiography has been used5 and a recent IDFiWHO workshop recommended seven field stereoscopic fundus photography.6 However, for practical reasons most studies have so far utilized the diagnosis obtained by an ophthalmologist by fundoscopy after mydriasis.’ Given that the screening test i s to be used to determine those patients to be referred for consideration of laser therapy, the most important attribute of a test i s its sensitivity, because the consequences of missing treatable disease are high compared with those of unnecessary false positive referrals. Specificity, which determines the number of false positives, will predominantly affect the cost-effectiveness. Comparison with the gold standard i s vital when assessing the effectiveness of screening tests. Studies which do not utilize such a comparison are of limited value and may serve to confuse the issue. Few of the studies published on non-mydriatic fundus photography have utilized a full c o m p a r i ~ o n . ~8-12 , Williams et a / . , 7 comparing this method with an ophthalmologist’s assessment, calculated the sensitivity of the test to be 96 % with a specificity of 98 % . However this was a small study of only 62 patients. The study by Buxton et a/.’ is of considerable interest not only because it involved a much larger number of patients in several centres but also because comparison was made with a reference screening test, ophthalmoscopy by an
0742-3071 191/070607-02$05.00 Wiley & Sons, Ltd.
0 1991 by john
ophthalmic clinical assistant. In the five centres the calculated sensitivity of fundus photography varied between 35 and 67 %. If the appropriate 2 x 2 tables are combined the overall sensitivity can be calculated as 56 % with a specificity of 97 %. As the authors acknowledge, this is a poor result and will be a disappointment to those who hoped that fundus photography could be used alone as a test for a national screening programme. Equally worrying are the poor results of primary care ophthalmoscopy, especially since sensitivity is likely to be better in a trial than in routine use. If these results were repeated in a national screening programme, then the impact on the burden of blindness due to diabetes would be more limited than the one-third reduction suggested as a public health target in the St Vincent d e ~ l a r a t i o n . ’ ~ It i s possible that alternative approaches may improve the sensitivity. Screening modalities could be combined, for example ophthalmoscopy and fundus photography. Alternatively, the technique of non-mydriatic fundus photography could be modified by the use of mydriasis and of colour transparencies rather than Polaroid film. Instead of a single 45 degree non-mydriatic photograph of each eye, an additional picture of the nasal retina, as recommended by the IDFiWHO workshop6 may allow the detection of more retinal disease. These technical improvements might improve sensitivity,” although there may be a trade-off in terms of cost-effectiveness and patient acceptability. A more rewarding strategy might be to target high-risk groups, for example patients who are not attending either hospital diabetic or ophthalmology clinics, as they are known to be at increased risk of late referral. Economic evaluation of potential screening programmes is necessary to answer important questions of efficiency. Cost-benefit analysis attempts to determine social efficiency, whereas cost-effectiveness analysis is directed at the question of technical efficiency, the delivery of the greatest output at a given cost or, conversely, a given output at the least cost. There i s little doubt that a screening programme for diabetic retinopathy would be cost-beneficial because the value of sight and therefore the cost of blindness i s high, although this has not been quantified. The question of technical efficiency is addressed by the cost-effectiveness analysis by Sculpher et in this issue. They compared hospital- and community-based non-mydriatic fundus photography with ophthalmoscopic examinations by a variety of primary screeners (general practitioners, hospital physicians and ophthalmic opticians). The outcome measure
’
607 DIABETIC MEDICINE, 1991 ; 8 : 607-608
Dm
EDITORIAL used was the cost per true positive case detected, in contrast to other studies that have used cost per year of sight saved. ' 1 3 Hospital-based screening proved t o be relatively expensive because of high hospital overheads whilst community-based non-mydriatic fundus photograp h y was relatively inexpensive. As the sensitivity analysis shows, the cost per true positive case detected is dependent on the incidence of retinopathy in the screened population and is therefore related t o the age-structure of the population and the ratio of Type 1 t o Type 2 patients. The marginal reduction in cost per true positive case detected as throughput increases suggests that units that screen less than 1000 patients a year are unlikely t o be efficient. Using data from the Wisconsin Epidemiologic Study, Dasbach et al.'" suggested that the cost of screening c o u ld b e recovered b y preventing blindness in those diabetic patients taking insulin b u t not necessarily in older Type 2 diabetic patients, presumably due to their reduced life expectancy. However, this finding i s highly dependent on the demographic features of the population studied and the figures for sensitivity used. It m i g h t b e argued that it may be more cost-effective to screen Type 2 diabetic patients i n the UK because they are less likely to be regularly examined and therefore niore likely to have a higher incidence of treatable eye disease."j On the other hand non-mydriatic fundus photography m a y b e less technically satisfactory i n older patients because lens opacities and small pupils may reduce sensitivity? W e must therefore conclude that the present evidence o n the sensitivity of non-mydriatic fundus photography is insufficient to a l l o w recommendation of its usage as the sole screening tool in a nationwide screening programme for diabetic retinopathy. There is an urgent need for properly designed studies of a variety of photographic and other techniques using validated reference methods i n clearly defined populations before w e can hope to persuade health authorities and other health care purchasers that screening for diabetic retinopathy offers good value for money, even though it w o u l d certainly benefit significant numbers of patients who m i gh t otherwise lose their vision.
2.
3. 4.
5.
6. 7.
8.
9.
10.
11. 12.
13.
14.
15.
16.
17.
Nick Wareham, Richard Greenwood Department of Public Health M e d i c i n e a n d Bertram Diabetes Centre, Norwich, U K
18.
19.
References 20. 1.
608
Holland WW, Stewart S. Screening in Health Care. Benefit or Bane! London: The Nuffield Provincial Hospitals Trust, 1990.
Wilson JMG, Jungner G . The Principles and Practice of Screening for Disease. Public Health Papers 34. Geneva: WHO, 1968. Kohner EM, Barry PJ. Prevention of blindness in diabetic retinopathy. Diabetologia 1984; 26: 173-1 79. Rohan TE, Frost CD, Wald NJ. Prevention of blindness by screening for diabetic retinopathy: a quantitative assessment. Br M e d 1 1989; 299: 1 198-1 201. Jones D, Dolben J, Owens DR, et a/. Non-mydriatic Polaroid photography in screening for diabetic retinopathy: evaluation in a clinical setting. Br M e d / 1988; 296: 1029-1 030. Retinopathy Working Party. A protocol for screening for diabetic retinopathy in Europe. Diabetic Med 1991; 8 : 263-267. Williams R, Nussey S, Humphry R, Thompson G . Assessment of non-mydriatic fundus photography in detection of diabetic retinopathy. Br Med / 1986; 293: 1140-1 142. Klein R, Klein BEK, Neider M W , etal. Diabetic retinopathy as detected using ophthalmoscopy, a non-mydriatic camera and a standard fundus camera. Ophthalmology 1985; 92: 485-491. Ryder REJ, Young S, Vora JP, et a/. Screening for diabetic retinopathy using Polaroid retinal photography through undilated pupil5. Practical Diabetes 1985; 2: 34-39. Barrie T, MacCuish AC. Assessment of non-mydriatic fundus photography in detection of diabetic retinopathy. Br M e d 1 1986; 293: 1304. Mohan R, Kohner EM, Aldington SJ, et a / . Evaluation of a non-mydriatic camera in Indian and European diabetic patients. Br / Ophthalmol 1988; 72: 841-845. Taylor R, Lovelock L, Tunbridge WMC, etal. Comparison of non-mydriatic retinal photography with ophthalmoscopy in 2159 patients: mobile retinal camera study. Br M e d 1 1990; 31 0: 1243-1 247. Buxton MJ, Sculpher MJ, Ferguson BA, et a/. Screening for treatable diabetic retinopathy: a comparison of different methods. Diabetic M e d 1991; 8 : 371-377. WHO/IDF Europe. Diabetes care and research in Europe: The Saint Vincent Declaration. Diabetic M e d 1990; 7: 360. Moss SE, Klein R, Kessler SD, Ritchie KA. Comparison between ophthalmoscopy and fundus photography in determining the severity of diabetic retinopathy. Ophthalmology 1985; 92: 485-491. Jones RB, Larizgoitia I, Casado L, Barrie T. H o w effective i s the referral chain for diabetic retinopathy? Diabetic Med 1989; 6: 262-266. Sculpher MJ, Buxton MJ, Ferguson BA, et a/. A relative cost-effectiveness analysis of different methods of screening for diabetic retinopathy. Diabetic M e d 1991; 8 : 644-65 0. Javitt JC, Canner JK, Sommer A. Cost-effectiveness of current approaches to the control of retinopathy in type I diabetics. Ophthalmology 1989; 96: 255-264. Dasbach EJ, Frybach DG, Newcomb PA, et a/. Costeffectiveness of strategies for detecting diabetic retinopathy. Medical Care 1991 ; 29: 20-39. Higgs ER, Harney B, Kelleher A, et a/. Limitations of the non-mydriatic camera in screening for diabetic retinopathy in the community (Abstract). Diabetic Med 1990; 7 (suppl 1): 9A.
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EDITORIAL
