Review of the epidemiology of diabetic retinopathy

According to the latest report of the Vision Loss Expert Group of the Global Burden of Disease Study, the crude prevalence (all ages) of visual impairment and blindness caused by diabetic retinopathy (DR) increased significantly between 1990 and 2015.¹

The number of people affected by blindness due to DR increased from 0.2 million to 0.4 million, and moderate to severe vision impairment increased from 1.4 million to 2.6 million.

An increase in age-standardised prevalence of blindness and visual impairment caused by DR was observed in the high income sub-regions-North Africa and the Middle East-whereas the prevalence of blindness and visual impairment due to DR has decreased in all regions of sub-Saharan Africa, Latin America, Oceania, Caribbean, central and eastern Europe.¹

DR is the leading cause of preventable blindness in working-age adults. The potential risk of blindness in an individual with diabetes is 2.4 times higher than that of an individual without diabetes.^2,3

In 2013, 382 million people had diabetes and this number is expected to rise to 592 million by 2035.⁴

Systematic screening of diabetic patients has the potential to reduce the incidence of sight-threatening visual impairment. Such programmes have been successfully implemented in many countries. Here, we review the results of the latest studies of DR in Europe and worldwide, which together included at least 10,000 participants.

Portugal

The Diabetic Retinopathy Screening Service for Lisbon and Tagus Valley-RETINODIAB-was commissioned and carried out in Portugal between July 2009 and October 2014.5 Data analysis included 52,739 patients with type 2 diabetes, diagnosed over the age of 40 years, 49.6% of whom were women.

The mean age of participants was 69.13 years (standard deviation [SD] 11.13) and the mean duration of diabetes was 8.5 years (SD 7.89). DR was detected in a total of 8,584 patients (16.3%). Of these, 5,484 patients (10.4%) had mild non-proliferative DR (NPDR), 1,457 (2.8%) had moderate NPDR, 672 (1.3%) had severe NPDR and 971 (1.8%) had proliferative DR.

Statistical analysis revealed that the presence of any DR, non-referable DR or referable DR was strongly associated with increasing duration of diabetes and earlier age at diagnosis.⁵

United Kingdom

In the United Kingdom, the Clinical Practice Research Datalink (CPRD) electronic health database was used to examine trends in the prevalence and relative risk of retinopathy by diabetes type, patient age, sex, ethnicity, socioeconomic deprivation and region.⁶ Data were analysed from 7,707,475 patients aged over 12 years from 601 general practices across the UK that contributed to the CRPD from 2004 to 2014.

Of these patients, 338,390 with type 2 diabetes and 30,657 with type 1 diabetes were identified. The prevalence of DR was 48.4% (14,846) in the population with type 1 diabetes mellitus and 28.3% (95,807) in the population with type 2 diabetes mellitus.

Statistical analysis revealed that relative risk of DR in patients with type 2 diabetes mellitus varied significantly with region and was increased for older age groups and in men compared with women, with the risk of severe DR increased in South Asian ethnic groups and more deprived groups. Relative risk of DR for patients with type 1 diabetes mellitus varied with age and region, but not by sex, ethnic group or socioeconomic status.⁶

Germany and Austria

In Germany and Austria, anonymous patient records accumulated from January 2000 to March 2013 within the German/Austrian Diabetes Prospective Documentation Initiative (DPV) were analysed.7 Complete data were available for 64,784 patients with type 2 diabetes from 166 recruiting centres in Germany and Austria.

Men represented 51.4% of the study population and the mean duration of diabetes was 9.2 years (standard error 0.03). The study showed that retinopathy was absent in 79.88% of patients (51,750) at the most recent visit; 10.26% (6,646) had mild to moderate retinopathy and 9.09% (5,887) had severe non-proliferative or proliferative retinopathy.

Diabetic macular oedema (DMO) was reported in 501 patients (0.77%). Statistical analysis with the Kaplan–Meier method revealed that, after a diabetes duration of 20 years, 38.2% of patients had DR; after 40 years the proportion had increased to 89.7%. The corresponding figures for severe non-proliferative or proliferative retinopathy were 19.7% and 67.5%, and for DMO 1.6% and 9.8%, respectively.⁷

Denmark

The Danish Registry of Diabetic Retinopathy (DiaBase) compiles data on all diabetes patients aged ≥18 years who attend screening for diabetic eye disease in hospital eye departments and private ophthalmological practices in Denmark.8 Statistical analysis included data from 77,968 DiaBase patients, collected in 2014–2015.

The prevalence of no DR, NPDR and proliferative DR, respectively, in the study population was 78%, 18% and 4%. However, the overall prevalence of patients in this registry without diabetic maculopathy was 97%.⁸

Spain

In Spain, a population-based prospective study of 15,396 patients with diabetes mellitus was conducted.9 Patients in sixteen Primary Health Care Areas were screened between January 2007 and December 2014.

There were no significant differences in mean age or in age groups between those Health Care Areas and the study sample included more men, which reflects the overall population prevalence of diabetes in Spain.

An increase in the incidence of DR and DMO was observed, especially in the patients aged between 31 and 70 years, and this was linked to bad metabolic control of diabetes mellitus. The incidence of any DR increased from 8.09% in 2007 to 8.99% in 2014, and DMO from 2.00% in 2007 to 2.49% in 2014.9

China

The Lifeline Express Diabetic Retinopathy Screening Program is a multi-hospital-based screening programme among patients with diabetes across mainland China.¹⁰ The recently published study used data collected in eight hospitals from April 2014 to July 2016.

In total, 16,305 patients with diabetes mellitus were screened: 1.07% had type 1 diabetes, 98.39% type 2 diabetes and 0.53% pregnancy-related diabetes. Fundus photographs were gradable for 92.5% of patients.

The age-standardised prevalence of any DR and sight-threatening DR was 27.9% and 12.6%, respectively. The mean age of participants was 63.23 years (SD 10.21) and the mean duration of diabetes was 7.45 years (SD 6.42).

In the multiple logistic regression analysis, younger age, longer duration of diabetes, higher haemoglobin A1c, higher fasting plasma glucose, higher systolic blood pressure, faster heart rate, higher low-density lipoprotein, lower triglycerides, higher blood urea nitrogen and elevated serum creatinine level were associated with the presence of any DR. Similar risk factors, except for blood urea nitrogen and triglycerides, were found for sight-threatening DR.10

Singapore

In Singapore, a total of 3,353 Chinese, 3,280 Malays and 3,400 Indians aged 40–80 years participated in The Singapore Epidemiology of Eye Diseases Study from 2004 to 2011.¹¹ Among 10,033 participants, 2,376 (23.7%) had diabetes mellitus, 805 (33.9%) of whom had DR and 212 (26.3%) vision-threatening DR.

The age-standardised prevalence of diabetes mellitus was highest in Indian participants (26.69%), followed by Malay (19.53%) and Chinese participants (12.89%). There was no significant difference in age-standardised prevalence of DR and vision-threatening DR across the ethnic groups. Among those with DR, 657 (81.6%) had minimal to moderate NPDR, 148 (18.4%) had severe NPDR or proliferative DR and 103 (12.8%) had clinically significant macular oedema.11

New Zealand

Finally, in the Greater Wellington region of New Zealand, data from 12,667 patients referred for their first diabetic retinal screening from 2006 to 2015 were evaluated.¹² Men made up 55% of the study cohort and the majority of patients were of European descent (56.6%).

Overall, the prevalence of any DR was 22.5%, including 20.2% with non-sight-threatening DR and 2.3% with sight-threatening DR. Statistical analysis revealed that type 1 diabetes and poor haemoglobin A1c control were strongly associated with any degree of DR. Old age (>65 years) increased the risk, and Asian and Pacific Island ethnicity had moderately greater odds compared with European ethnicity.12

Summary
In summary, while the global prevalence of diabetes mellitus is increasing, the awareness of DR remains poor in most communities. DMO, rather than proliferative DR, is an increasingly common cause of visual impairment.

Early recognition and timely management of these conditions would reduce the number of visually impaired people, which would have a beneficial impact on societies.

Photographic screening of DM patients using tele-ophthalmology platforms, risk stratification algorithms and fundus picture analysis based on deep learning automatic software might become cost-effective screening strategies.

Disclosures:

Dr Michal S. Nowak, PhD

E: michaelnovak@interia.pl
Dr Nowak is based at the Provisus Eye Clinic, Czestochowa, Poland. He reports no conflict of interest with the studies mentioned.

Dr Andrzej Grzybowski, PhD

E: ae.grzybowski@gmail.com
Dr Grzybowski is based in the Department of Ophthalmology at the University of Warmia and Mazury, Olsztyn, Poland and the Institute for Research in Ophthalmology, Foundation for Ophthalmology Development, Poznan, Poland. He reports no conflict of interest with the studies mentioned.

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