C L I N I C A L
A N D
E X P E R I M E N T A L
OPTOMETRY cxo_628
563..567
RESEARCH PAPER
Incidence of diabetic retinopathy in a Hong Kong Chinese population Clin Exp Optom 2011; 94: 6: 563–567 HaiYan Song*† MScMed LongQian Liu† MMed PhD Rita Sum* BOptom Mavis Fung* BOptom Maurice KH Yap* PhD MCOptom FAAO *School of Optometry, The Hong Kong Polytechnic University, Hong Kong, China † West China School of Medicine, Sichuan University, China E-mail:
[email protected]
Submitted: 26 August 2010 Revised: 16 March 2011 Accepted for publication: 2 April 2011
DOI:10.1111/j.1444-0938.2011.00628.x Background: The aim was to examine the progression and regression of diabetic retinopathy within a four-year period in a Chinese population with type 2 diabetes mellitus in a community optometry clinic in Hong Kong. Methods: During the period May 2005 to November 2009, 5,160 patients with type 2 diabetes mellitus who had attended at least two diabetic retinopathy screening sessions at a community optometry clinic were included as subjects in this study. All had retinal photographs taken of both eyes, which were of sufficiently good quality for grading. For the purpose of this study, diabetic retinopathy grading was based on the results of the worst eye. The main outcomes were the within four-year incidence of diabetic retinopathy and the incidence of progression and regression of diabetic retinopathy. Results: Of the 5,160 subjects in this study, 3,647 had no diabetic retinopathy, while 1,513 had diabetic retinopathy at the baseline visit. Of those 3,647 subjects with no diabetic retinopathy, the within four-year cumulative incidence of any diabetic retinopathy, mild or moderate non-proliferative diabetic retinopathy and sight-threatening diabetic retinopathy was 15.16 per cent, 14.45 per cent, 0.69 per cent and 0.03 per cent, respectively. Of those 1,513 subjects with diabetic retinopathy at baseline, the within four-year progression incidence of diabetic retinopathy was 6.61 per cent and the regression incidence of diabetic retinopathy was 45.54 per cent. Conclusion: The high regression incidence of diabetic retinopathy suggests that it might not be necessary for all patients with diabetes to be screened annually. Other methods to determine the screening frequency for an individual patient should be explored.
Key words: diabetes mellitus, Hong Kong, incidence, retinopathy
In the year 2000, the prevalence of type 2 diabetes mellitus in Hong Kong Chinese people was estimated at 9.8 per cent.1 With increasing prevalence of type 2 diabetes mellitus in the community, diabetic retinopathy-related visual impairment has become a serious public health issue; however, diabetic retinopathy is amenable to treatment and early detection is the key.
Planned screening for diabetic retinopathy in people with diabetes has been proposed in the UK2 and in the USA.3 In fact, a nationwide systematic screening program for diabetic retinopathy has been operating in the UK since 2003.4 The incidence of diabetic retinopathy has been reported for many communities in various countries.5–14 The four-year
© 2011 The Authors Clinical and Experimental Optometry © 2011 Optometrists Association Australia
cumulative incidence of diabetic retinopathy reported in these studies ranges from 16.8 per cent to 34 per cent. For sightthreatening diabetic retinopathy, which includes diabetic maculopathy, severe non-proliferative or proliferative diabetic retinopathy, the four-year cumulative incidence reported was between 0.7 per cent and 2.1 per cent. Direct comparison
Clinical and Experimental Optometry 94.6 November 2011
563
Incidence of diabetic retinopathy Song, Liu, Sum, Fung and Yap
between studies is problematic because of different patient selection criteria and methodologies.15 There have been two previous reports on the incidence of diabetic retinopathy in Hong Kong Chinese.7,9 One reported a four-year cumulative incidence of 20.3 per cent. This study7 was conducted in a hospital setting. The second study9 recruited subjects mainly from primary care clinics and reported a six-year incidence of 13.8 per cent; however, both of these studies graded retinopathy based on a single 45° fundus photograph centred on the macula. It has been suggested that this single central 45° image is sufficient to determine the presence or absence of diabetic retinopathy but not the grading of the level of diabetic retinopathy.16 In our study, we investigated the within four-year incidence and progression/ regression rates of diabetic retinopathy in a large population with type 2 diabetes mellitus enrolled in a diabetic retinopathy screening program in one district in Hong Kong. Nine-field digital fundus photography was used to screen for diabetic retinopathy in this screening program. METHOD This is a retrospective study of a population with type 2 diabetes mellitus enrolled in a diabetic retinopathy screening program.
Diabetic retinopathy screening program The diabetic retinopathy screening program is a collaborative project between the School of Optometry of The Hong Kong Polytechnic University, the Kwai Tsing Safe Community and Healthy City Association and the Princess Margaret Hospital in Kowloon, Hong Kong. The screening program, which started in 2005, primarily receives referrals from general outpatient clinics in the Kwai Tsing district and to a lesser extent the surrounding districts. The Kwai Tsing district has an estimated population of approximately half a million people and on this basis is estimated to have approximately 25,000 patients with diagnosed diabetes.17
On arrival at the screening centre, each patient was asked to provide his or her general health history, which included the duration since diabetes had been diagnosed as well as medications taken, blood pressure and blood sugar control. After a test of presenting vision and assessment of the anterior angle, the pupils were dilated with 1% tropicamide hydrochloride. Nine 45° field digital fundus photographs of each eye were then taken using a Topcon fundus camera (Model TRCNW65, Topcon Inc, Tokyo, Japan). Images were graded by optometrists trained in the use of the Early Treatment Diabetic Retinopathy Study classification system (EDTRS).18 At the end of the screening procedure, patients were invited to return for screening annually or earlier if they had moderate non-proliferative diabetic retinopathy or if blood sugar and blood pressure control were poor. Those with sight-threatening diabetic retinopathy were referred for ophthalmological attention but were also invited back for an annual screening. All the baseline and follow-up examinations followed a similar protocol that was approved by the institutional human subjects committee of The Hong Kong Polytechnic University and was conducted in accordance with the Declaration of Helsinki.
Subjects Subjects who were included in the study were patients with type 2 diabetes mellitus aged over 30 years. All attended for diabetic retinopathy screening at least twice between the period May 2005 and November 2009 (‘the study period’). Patients who did not have gradable photographs or had non-diabetes-related eye disease were excluded.
Procedures A search of the patient information system using the criteria for subjects described in the previous section returned 5,160 cases who had attended at least two screenings during the study period. The grading of retinopathy for the worst eye of each subject was used. ‘Onset of new diabetic retinopathy’ was defined as subjects who had no diabetic
Clinical and Experimental Optometry 94.6 November 2011
564
retinopathy at baseline (that is, first visit) but had developed retinopathy in subsequent examinations within the study period. For subjects who had attended more than one follow-up screening within the four-year period, the data from the visit that yielded the most severe diabetic retinopathy grading was used for analysis. The ‘within four-year cumulative incidence of diabetic retinopathy’ was defined as the percentage of subjects who had no diabetic retinopathy at baseline but had developed retinopathy in subsequent examinations within the study period. The ‘within four-year cumulative progression incidence of diabetic retinopathy’ was defined as the percentage of subjects who had diabetic retinopathy at baseline and at least a one-step increment in the grading scale within the study period. The ‘within four-year cumulative regression incidence of diabetic retinopathy’ was defined as the percentage of subjects who had diabetic retinopathy at baseline and at least a onestep decrement in the grading scale within the study period.
RESULTS
Baseline characteristics of subjects Between May 2005 and November 2009 a total of 14,019 patients attended for diabetic retinopathy screening, of whom 5,160 subjects with gradable retinopathy at both baseline and follow-up visits were included for analysis. The baseline demography of the 5,160 subjects is shown in Table 1.
Within four-year cumulative incidence of diabetic retinopathy Table 2 shows the results of the within four-year cumulative incidence of diabetic retinopathy in subjects with no retinopathy at the baseline visit. For the 3,647 subjects who have no diabetic retinopathy at baseline, subsequent screenings within a four-year period revealed that 553 had developed some retinopathy. This gave a within four-year cumulative incidence of any retinopathy © 2011 The Authors
Clinical and Experimental Optometry © 2011 Optometrists Association Australia
Incidence of diabetic retinopathy Song, Liu, Sum, Fung and Yap
Within four-year cumulative progression/regression incidence of diabetic retinopathy
of 15.2 per cent. One subject developed sight-threatening diabetic retinopathy during the four-year follow-up period, giving a within four-year cumulative incidence of sight-threatening diabetic retinopathy of 0.03 per cent.
Table 3 shows the within four-year grading changes in subjects with diabetic retinopathy at baseline.
No diabetic retinopathy at baseline Diabetic retinopathy at baseline (n = 3,647)
(n = 1,513)
Age (mean ⫾ standard deviation) (years)
62.60 ⫾ 9.58
63.42 ⫾ 11.00
Females (n, %)
1,967 (54%)
804 (53%)
Males (n, %)
1,680 (46%)
709 (47%)
Table 1. Baseline characteristics of the 5,160 subjects
The overall progression incidence of diabetic retinopathy was 6.6 per cent (100/1,513) and the overall regression incidence of diabetic retinopathy was 45.8 per cent (693/1,513). For subjects with mild non-proliferative diabetic retinopathy, the progression incidence was 6.2 per cent (86/1387) and the regression incidence was 46.5 per cent (645/1,387). For subjects with moderate nonproliferative diabetic retinopathy at baseline, the progression incidence was 12.4 per cent (14/113) and the regression incidence was 38.9 per cent (44/113). For subjects with baseline sightthreatening diabetic retinopathy, the regression incidence was 30.8 per cent (4/13).
DISCUSSION Number of cases
Incidence (%)
Any retinopathy
553
15.16
Mild non-proliferative diabetic retinopathy
527
14.45
25
0.69
1
0.03
Moderate non-proliferative diabetic retinopathy Sight-threatening retinopathy
Table 2. Within four-year cumulative incidence in the worst eye of 3,647 subjects with type 2 diabetes mellitus but no diabetic retinopathy at baseline
Baseline level
Our overall four-year cumulative incidence of any diabetic retinopathy of 15.16 per cent is somewhat lower than other reported four-year cumulative incidences, which range from 19.2 per cent to 34 per cent.5,6,8,11-13 There might be methodological differences between the studies. For instance, the Liverpool study used 45° or 50° non-stereoscopic photographs from dilated eyes,5 while the Barbados study6
No retinopathy
Mild non-proliferative diabetic retinopathy
Moderate non-proliferative diabetic retinopathy
Sight-threatening diabetic retinopathy
645
656
81
5
Moderate non-proliferative diabetic retinopathy (n = 113)
4
40
55
14
Sight-threatening diabetic retinopathy (n = 13)
0
1
3
9
Mild non-proliferative diabetic retinopathy (n = 1,387)
Table 3. Within four-year incidence and progression of retinopathy in the worst eye of 1,513 subjects with type 2 diabetes mellitus and baseline diabetic retinopathy as assessed at the follow-up © 2011 The Authors Clinical and Experimental Optometry © 2011 Optometrists Association Australia
Clinical and Experimental Optometry 94.6 November 2011
565
Incidence of diabetic retinopathy Song, Liu, Sum, Fung and Yap
and the Melbourne Visual Impairment Project10 used 30° colour stereoscopic fundus photographs centred on the disc and macula. We used a 45° non-mydriatic retinal photography (nine views) of both eyes to grade retinopathy. There are other confounding factors, such as the age of subjects, body mass index, waist/hip ratio, treatment differences and patient awareness of diabetes complications. These factors are known to be significant risk factors associated with the development of diabetic retinopathy. Among those without diabetic retinopathy at baseline, just one subject developed sight-threatening diabetic retinopathy during the four-year period. Our within four-year incidence of sight-threatening diabetic retinopathy of 0.03 per cent is low compared with the six-year cumulative incidence of sight-threatening diabetic retinopathy of 0.7 per cent reported by another study in Hong Kong9 and 3.9 per cent reported for the five-year cumulative incidence by the Liverpool Diabetic Eye study.5 For proliferative diabetic retinopathy alone, the four-year incidence was reported to be 2.0 per cent in the Barbados eye study,6 0.47 per cent (one of 212) in a Hong Kong study7 and the five-year incidence of proliferative diabetic retinopathy was 2.9 per cent in the Melbourne Visual Impairment Project.10 We note that the incidence of serious diabetic retinopathy in Hong Kong reported in the present and previous studies from Hong Kong are not high compared with those reported elsewhere. For subjects with baseline diabetic retinopathy of any grade, there was a higher regression incidence (45.54 per cent) than progression incidence (6.61 per cent). Subjects with baseline mild nonproliferative diabetic retinopathy have a higher regression incidence of 46.5 per cent than progression incidence of 6.2 per cent. Subjects with baseline moderate non-proliferative diabetic retinopathy also have a higher regression rate of 38.94 per cent than progression incidence of 12.39 per cent. Our cumulative progression incidence of 6.2 per cent was lower than that published in most other studies.9–11,14,19,20
Compared with other populations, the Hong Kong Chinese population seems to show a lower incidence of serious diabetic retinopathy. We speculate that a number of factors such as genetic pre-disposition, severity of the diabetes, timely access to medical care, frequency of health checks, dietary differences, provision of diabetes health education and level of health consciousness might be relevant and warrant further study. Regression of diabetic retinopathy is well documented. For instance, in 1962 Caird and Garrett21 noted that in a group of 168 diabetic patients after five years, 36 per cent of eyes showed regression of microaneurysms and 27 per cent of eyes showed regression of haemorrhages and/ or exudates. A recent report from the Wisconsin Epidemiologic Study of Diabetic Retinopathy22 found that regression of diabetic retinopathy is more likely in patients with lower glycosylated haemoglobin and diastolic blood pressure. We do not have HbA1c and blood pressure data for our subjects; however, the Hong Kong government has been engaging the public on diabetes prevention for over a decade and has produced clinical guidelines for physicians, which advocate tight glycaemic and blood pressure control in the management of diabetes.23 Such measures might have contributed to the higher regression rates of diabetic retinopathy observed in our subjects. Our findings for the progression and regression rates might indicate the frequency of diabetic retinopathy screening necessary for an individual patient in Hong Kong. Although our data do not enable us to recommend an optimum period between diabetic retinopathy screenings, it is clear that an annual screening might not be necessary, especially in the case of no diabetic retinopathy or mild non-proliferative diabetic retinopathy at baseline. If resources are limited, as is usually the case with publicly funded screening programs, a patient with mild non-proliferative diabetic retinopathy at baseline might not have to be screened annually, as typically advocated, particularly if the patient has good glycaemic control and blood pressure within the
Clinical and Experimental Optometry 94.6 November 2011
566
normal range. An online calculator is available to estimate the risk of an individual patient developing sight-threatening retinopathy and based on this estimate the period for the next diabetic retinopathy screening can be recommended (http:// www.risk.is/index.php?page=calculator). Our study has some strengths and some limitations. One strength is the relatively large number of subjects who returned for follow-up within the four-year period. Another is the use of nine-field fundus photography compared with two-field fundus photography used in other studies. More comprehensive coverage of the fundus enables more precise grading of the diabetic retinopathy. As the level of HbA1c and blood pressure have been identified as important risk factors affecting the progression of diabetic retinopathy,22,24–26 one limitation of the current study is that we do not have access to our subjects’ HbA1c and blood pressure data. Without these data we are unable to associate our findings of progression and regression rates to treatment received by the subjects. Another limitation is that the subjects in the present study reside predominantly in one district in Hong Kong (Kwai Tsing district) where the educational and income levels are generally lower than average. Their access to health care is primarily at government-funded medical facilities. Our findings might not be applicable to other groups of people in Hong Kong who have access to private health care and educational materials. A third limitation of this study is the fact that the fundus photographs were read by several optometrists. Although steps were taken to minimise criterion bias, such as ensuring that all new readers had to demonstrate competency in using the ETDRS grading system and demonstrate alignment of grading with more experienced readers, we cannot rule out criterion bias, particularly in borderline cases. The total number of subjects seen in our screening centre between May 2005 and November 2009 was 14,019. Of these, 5,160 subjects had more than one screening episode. On the basis that each patient should be screened annually, we estimate that there should be around 9,000 subjects © 2011 The Authors
Clinical and Experimental Optometry © 2011 Optometrists Association Australia
Incidence of diabetic retinopathy Song, Liu, Sum, Fung and Yap
who had more than one screening episode. Our subject sample is only slightly more than half of the potential sample but it is unclear how this would affect the incidence findings. In conclusion, the present study provides data on the within four-year cumulative incidence of any retinopathy, mild or moderate non-proliferative diabetic retinopathy and sight-threatening diabetic retinopathy in subjects with type 2 diabetes mellitus. For subjects with baseline mild non-proliferative diabetic retinopathy, regression of retinopathy at a subsequent visit is more likely than progression of retinopathy. Even for baseline moderate non-proliferative diabetic retinopathy, regression is more likely than progression. These findings add some support to the view that an annual screening for all patients with type 2 diabetes might not be the most efficient way to identify those most likely to have sight-threatening retinopathy. An individualised approach, taking into consideration risk factors such as the patient’s blood pressure, HbA1c and duration of diabetes, might be a more efficient way to estimate the interval before the next diabetic retinopathy screening for the patient. ACKNOWLEDGEMENTS
The diabetic retinopathy screening program at Lai King was championed by Dr Lily Chiu, Mr Chow Yick Hay, Ms Adela Lai, Dr Yiu Yuk-kwan and Dr Liang Jun from the Kwai Tsing Safe Community and Healthy City Association. We thank the primary care doctors and nurses in the Kwai Tsing district and at the Princess Margaret Hospital for their support. Professor David Wong of the Eye Institute, University of Hong Kong, provided invaluable insight and inspiration to further diabetic retinopathy research in Hong Kong. GRANTS AND FINANCIAL SUPPORT
The research was supported by a grant from the Hong Kong Polytechnic University (1-BBZD). REFERENCES 1. Cockram CS. The epidemiology of diabetes mellitus in the Asia-Pacific region. Hong Kong Med J 2000; 6: 43–52.
2. Garvican L, Clowes J, Gillow T. Preservation of sight in diabetes: developing a national risk reduction programme. Diabet Med 2000; 17: 627–634. 3. National Eye Health Education Program, Congressional record, National Departments of Labor, Health and Human Services, Education, and related agencies, Appropriation Bill 1988. Senate report 100–189: 121. 4. Department of Health (UK), National Service Framework for Diabetes: Delivery Strategy. Product No: 29895, 2003, Crown Copyright. 5. Younis N, Broadbent DM, Vora JP, Harding SP. Incidence of sight threatening retinopathy in patients with type 2 diabetes in the Liverpool Diabetic Eye Study: a cohort study. Lancet 2003; 361: 195–200. 6. Leske MC. Wu, A. Wu SY, Heannis A, Nemesure B, Hyman L, Schachat A. Incidence of diabetic retinopathy in the Barbados Eye Studies. Ophthalmology 2003; 110: 941–947 7. Tam VHK, Lam EPK, Chu BCY, Tse KK, Fung LM. Incidence and progression of diabetic retinopathy in Hong Kong Chinese with type 2 diabetes mellitus. J Diabetes Complications 2009; 23: 185–193. 8. Klein R, Klein BEK, Moss SE, Davis MD, DeMets DL. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. X. Four-year incidence and progression of diabetic retinopathy when age at diagnosis is 30 years or more. Arch Ophthalmol 1989; 107: 244–249. 9. Tam Tk, Lau CM, Tsang LCY, Ng KK, Ho KS, Lai TC. Epidemiological study of diabetic retinopathy in a primary care setting in Hong Kong. Hong Kong Med J 2005; 11: 438–444. 10. McCarty DJ, Fu CL, Harper CA, Taylor HR, McCarty CA. Five-year incidence of diabetic retinopathy in the Melbourne Visual Impairment Project. Clin Experiment Ophthalmol 2003; 31: 397– 402. 11. Chen MS, Kao CS, Fu CC, Chen CJ, Tai TY. Incidence and progression of diabetic retinopathy among non-insulin dependent diabetic subjects: a 4-year follow-up. Int J Epidemiol 1995; 24: 787–795. 12. Agardh E, Agardh CD, Koul S, Torffvit O. A fouryear follow-up study on the incidence of diabetic retinopathy in older onset diabetes mellitus. Diabet Med 1994; 11: 273–278. 13. Tudor SM, Hamman RE, Baron A, Johnson DW, Shetterly SM. Incidence and progression of diabetic retinopathy in Hispanics and non-Hispanic whites with type 2 diabetes. San Luis Valley Diabetes Study, Colorado. Diabetes Care 1998; 21: 53–61 14. Looker HC, Krakoff J, Knowler WC, Bennett PH, Klein R, Hanson RL. Longitudinal studies of incidence and progression of diabetic retinopathy assessed by retinal photography in Pima Indians. Diabetes Care 2003; 26: 320–326. 15. Williams R, Airey M, Baxter H, Forrester J, Kennedy-Martin T, Girach A. Epidemiology of diabetic retinopathy and macular oedema: a systematic review. Eye 2004; 18: 963–983. 16. Vujosevica S, Benettib E, Massignanb F, Pilotto E, Varano M, Cavarzeran F, Avogaro A, et al. Screening for diabetic retinopathy: 1 and 3 nonmydriatic 45-degree digital fundus photographs vs 7 standard early treatment diabetic retinopathy study fields. Eur J Cardiovasc Prev Rehab 2009; 148: 111– 118. 17. Chan JCN, Yeung VTF, Chow CC, Cockram CS. Diabetes mellitus—Epidemiology and pathogenesis. HK Pract 1996; 18: 270–279.
© 2011 The Authors Clinical and Experimental Optometry © 2011 Optometrists Association Australia
18. Early Treatment Diabetic Retinopathy Study Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs: an extension of the modified Airlie House classification. ETDRS Report No. 10. Ophthalmology 1991; 98: 786–806. 19. Stratton IM, Kohner EM, Aldington SJ, Turner RC, Holman RR, Manley SE, Matthews DR. UKPDS 50: risk factors for incidence and progression of retinopathy in Type II diabetes over 6 years from diagnosis. Diabetologia 2001; 44: 156–163. 20. Kim HK, Kim CH, Kim SW, Park JY, Hong SK, Yoon YH, Lee KU. Development and progression of diabetic retinopathy in Koreans with NIDDM. Diabetes Care 1998; 21: 134–138. 21. Caird FI, Garrett CJ. Progression and regression of diabetic retinopathy. Proc R Soc Med 1962; 55: 477– 479. 22. Klein R, Knudtson MD, Lee KE, Gangnon R, Klein BEK. The Wisconsin Epidemiologic Study of Diabetic Retinopathy: XXII the twenty-five-year progression of retinopathy in persons with type 1 diabetes. Ophthalmology 2008; 115: 1859–1868. 23. Guideline on management of Type 2 diabetes mellitus in primary care in Hong Kong. Department of Health, The Government of Hong Kong Special Administrative Region. Available from: http:// www.pdqa.gov.hk/textonly/english/primary care/clinical/files/dmquideline_3rded_2009.pdf. Accessed 3 June 2011. 24. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998; 317: 703–713. 25. Shiraiwa T, Kaneto H, Miyatsuka T, Kato K, Yammamoto K, Kawashima A, Kanda T, et al. Postprandial hyperglycemia is a better predictor of the progression of diabetic retinopathy than HbA1c in Japanese Type 2 diabetic subjects. Diabetes Care 2005; 28: 2806–2807. 26. Fujisawa T, Ikegami H, Yamato E, Kawaguchi Y, Ueda H, Shintani M, Nojima K, et al. Association of plasma fibrinogen level and blood pressure with diabetic retinopathy and renal complications associated with proliferative diabetic retinopathy in Type 2 diabetes mellitus. Diabet Med 1999; 16: 522– 526.
Corresponding author: Professor Maurice Yap School of Optometry The Hong Kong Polytechnic University Hong Kong CHINA E-mail:
[email protected]
Clinical and Experimental Optometry 94.6 November 2011
567