Sight-threatening Diabetic Retinopathy in a Swedish County – : Prevalence and Comparison of Patients with and without Sight-threatening Diabetic Retinopathy

(1)

Örebro University School of Medicine Degree Project, 30 ECTS 2018-01-04

Sight-threatening Diabetic Retinopathy in

a Swedish County –

Prevalence and Comparison of Patients with and without

Sight-threatening Diabetic Retinopathy

Version 2

Author: Sebastian Gustafsson, Bachelor of Medicine Supervisor: Karl-Johan Hellgren, M.D. Ph.D.

(2)

Abstract

Introduction

Diabetic retinopathy (DR) is the commonest complication of diabetes mellitus, the most frequent cause of blindness in working age people and is associated with increased risk of morbidity and mortality. Advanced stages are classified as sight-threatening diabetic retinopathy (STDR). The prevalence of DR and STDR in Sweden is unknown, and there is limited data on how STDR affects visual acuity.

Aim

Estimate the prevalence of confirmed STDR among adult diabetics in Värmland County in Sweden in 2008. Estimate trends of prevalence of possible DR and STDR, and proportion of STDR, among adult diabetics in Värmland 2008-2016. Investigate differences, including visual acuity, between patients with and without STDR in 2008.

Material and Methods

All patients with possible DR and STDR in Värmland 2008-2016 were included. Data was collected from two electronic medical records; Melina and Cambio Cosmic.

Results

The prevalence of confirmed STDR in 2008 was estimated to 6.8 %. The prevalence of possible STDR and DR was 11.7 % and 28.3 % in 2008, and decreased by 4.0 % and 8.2 % 2008-2016, respectively. Type 1 diabetes, longer diabetes duration, treatment with insulin, higher glycated hemoglobin (HbA1c) and visual acuity in best and worst eye was associated

with presence of STDR.

Conclusions

The estimated prevalence of confirmed STDR was 6.8 %, lower than a global estimate of 10.4 %. STDR was associated with lower visual acuity, as well as several unfavorable diabetic factors. Our study shows a possible decrease in the prevalence of STDR and DR in Värmland 2008-2016.

(3)

Abbreviations list

Anti-VEGF – Anti-Vascular Endothelial Growth Factor DME – Diabetic Macular Edema

DR – Diabetic Retinopathy HbA1c – Glycated Hemoglobin.

(4)

Introduction

Diabetes mellitus is a disease characterized by hyperglycemia because of absolute or relative insulin deficiency for type 1 and type 2, respectively [1]. The prevalence of diabetes around the globe is estimated to increase from 415 million in 2015 to 642 million in 2040 [2]. The prevalence of diabetes among adults (≥20 years) in Sweden increased from 5.8 % in 2007 to 6.8 % 2013 despite constant incidence, and is projected to rise to 10,4 % by 2050 with constant incidence and continued improvement in relative survival [3].

DR is one of several micro- and macrovascular complications of diabetes. It is the most common complication, with estimated prevalence at 34.6 % among diabetes subjects worldwide, although, there is considerable variability between individual studies [4]. Major risk factors include duration of diabetes, HbA1c and high blood pressure [4]. It is also the most

common cause of blindness in working age people [5]. The presence of DR is furthermore associated with all-cause mortality and cardiovascular events [6].

There are several morphological signs of DR. The first visible signs are microaneurysms, followed by leakage and intraretinal hemorrhages, and eventually, if untreated, progression to neovascularization and preretinal/vitreous hemorrhages [7]. Retinopathy of the macula is classified separately as diabetic macular edema (DME) [7]. Later stages of DR and DME are classified as STDR because of significant risk of visual impairment as a result of the

morphological changes. The prevalence of STDR among patients with diabetes is estimated at 10.2 % globally, but as with any DR there are significant variations among individual studies [4].

DR may be prevented by good metabolic control and sight-threatening vascular lesions can often be treated with photocoagulation or intravitreal injections of anti-VEGF and cortisone [8].

Retinal photocoagulation as a proven treatment to prevent blindness in patients with DR was established in the early 1990’s [9–11]. Screening programs was put in place as patients gained access to treatment, and the Swedish Agency for Health Technology Assessment and

Assessment of Social Services established recommended screening for DR in type 1 and type 2 diabetes in 1993, and the National Board of Health and Welfare publishes guidelines regarding screening for DR since 1999, which were last revised in 2015 [12,13].

(6)

2

Levels of blindness and need for low vision habilitation decreased in the 1990’s alongside implementation of screening and treatment of DR [14,15]. However, this coincided with significant improvements in diabetes care, e.g. better monitoring of blood glucose, better glycemic control and blood pressure treatment, which may have contributed to the observations stated above, as well as reports of slower progression of DR [16,17]. With regards to the continuous improvements in diabetes care, both systematic and

ophthalmological, it is necessary to have current data on prevalence and functional outcomes of DR and STDR. Prevalence of DR has been estimated in only a few recent studies, and there is even more limited data regarding how STDR impact visual acuity [18].

We hypothesized that the prevalence of DR in Värmland would be lower than global estimates, similar to a population-based study in a region of Norway [4,19]. We also

hypothesized that the prevalence of DR and STDR would decrease over an eight-year period as a possible result of the improvements in diabetes care. Finally, we hypothesized that patients with STDR would have worse visual acuity and more unfavorable diabetic factors than non-STDR patients.

Aims

Primary aims: Estimate the prevalence of confirmed STDR among adult diabetics (≥20 years) in Värmland County in Sweden in 2008. Estimate trends of prevalence of possible DR and STDR among adult diabetics in Värmland 2008-2016, as well as the proportion of STDR compared to any DR in the same time period.

Secondary aim: Investigate possible differences, including visual acuity, between 100 patients with confirmed STDR 2008 and an age- and sex-matched control group with diabetes but without STDR.

Material and Methods

Diabetic Retinopathy and Visual Acuity in Värmland 2008-2018

This study is a retrospective record study that is a pilot study of “Diabetic Retinopathy and Visual Acuity in Värmland 2008-2018”. The primary aims of that study is to describe the number of patients with STDR, their visual acuity, and if there has been any change over a ten-year period.

(7)

3

Study Population

To investigate the prevalence of confirmed STDR among adult diabetics we verified the grade of retinopathy of patients with possible STDR in 2008. Patients were identified as having confirmed STDR after re-evaluation of fundus photographs. In cases were photographs were missing because the degree of retinopathy was graded by ophthalmoscopy, the retinopathy grade was collected from the medical record.

To investigate trends of prevalence of possible, non-confirmed, STDR and DR among adult diabetics we included all diabetic subjects with a clinical diagnosis of possible STDR and DR in medical records.

Visual acuity and other patient characteristics in subjects with and without STDR were

compared in two subgroups. One STDR group consisting of 100 consecutive patients, starting 2008-01-01, with confirmed STDR. The control group was matched for gender and age. A requirement to be included in the control group was that there was no record of STDR and that visual acuity was accessible.

(8)

4

Data Collection and Definitions

Data was collected from two electronic medical records; Melina 1.0 (Know It, Karlstad, Sweden), which is the software used to register all screening visits for DR in Värmland County, and Cambio Cosmic 8.1 (Cambio Healthcare Systems, Sweden) in the case of missing data in Melina.

Retinopathy

DR was graded according to the “International Clinical Diabetic Retinopathy and Diabetic Macular Edema Disease Severity Scale” as follows: Not present, mild (microaneurysms only), moderate to severe non-proliferative (severe intraretinal hemorrhages in four quadrants, venous beading in at least 2 quadrants or intraretinal microvascular abnormalities), or proliferative (angiogenesis) [7]. DME was graded as absent, mild, moderate, or severe [7]. Proliferative DR treated with photocoagulation was still defined as proliferative DR, while DME treated with photocoagulation was not defined as DME post treatment.

Possible STDR was defined as presence of “severe non-proliferative” or “proliferative” DR, and/or presence of DME according to medical records.

Possible DR was defined as presence of any grade of DR and/or presence of DME according to medical records.

Prevalence

The prevalence of confirmed STDR in 2008 was estimated based on re-evaluation of 74.9 % (n=969) of cases planned for re-evaluation (n=1294), which included all possible cases of STDR except those registered as proliferative DR. In total, the estimation was based on re-evaluation of 63.9 % of all possible cases of STDR (n=1516), i.e. including cases registered as severe non-proliferative DR, proliferative DR and/or DME. The exclusion rate for those re-evaluated was extrapolated to all possible cases.

The prevalence of possible STDR 2008-2016 was calculated for every other year, i.e. 2008, 2010, 2012, 2014 and 2016. Patients with no diagnosis in medical registers in these years but were registered as having STDR in both surrounding years, i.e. 2007 and 2009 for 2008, were also included.

The prevalence of diabetes in Värmland 2008-2016 was based on results from a study on the prevalence of diabetes among individuals ≥20 years in Sweden 2007-2014 and projections to

(9)

5

2050[3]. The assumption that the prevalence of diabetes was the same in Värmland County as in Sweden in general was made in this study.

Statistics Sweden was used to ascertain the number of people ≥20 years old living in Värmland 2008-2016.

Variables

Diabetes

All patients registered in Melina have diabetes, classified as type 1, type 2 or unknown. If a patient was classified as unknown in Melina, the specified type was found in Cambio Cosmic. Data related to diabetes, e.g. duration, type of treatment and HbA1c was also collected.

Visual Acuity

The visual acuity with best correction, i.e. glasses, if present, was used. Visual acuity was defined using the decimal scale as being in the interval of 0.0 to 1.0. Patients who had a visual acuity that was registered as P (perception), P+L (perception and localization), or HR (hand movements) were converted to 0, 0 and 0.01 respectively.

HbA1c

HbA1c was presented in percent (%) in Melina in 2008 as Sweden used the Mono-S standard

prior to 2010. Starting 2010, Sweden uses the IFCC standard and the unit mmol/mol for HbA1c. HbA1c values were converted to mmol/mol before statistical analysis [20].

HbA1c was missing for 36 patients, 17 in the STDR group and 19 in the control group.

Statistics

A power analysis based on findings of differences in visual acuity in earlier studies was performed and showed a required population size of 100 in each group to achieve a power of 0.8[18,21]. Presence of STDR was used as dependent variable in all statistical analysis. Chi-square test was used for nominal variables. Student’s t-test was used for parametric

continuous variables and Mann Whitney-U for non-parametric continuous variables, respectively. Visual acuity, a non-parametric continuous variable, was described as median with minimum and maximum values as well as means. Linear regression was used to calculate trends over time. The software used for statistical analysis was SPSS version 21.

(10)

6

Ethics

This study was approved by Uppsala Ethics Vetting Committee (2017/092). Consent was not gathered from patients included in this study. All data was anonymized post collection by designating each patient a unique number with only the main author and supervisor having access to the key.

Results

Of the possible cases of STDR in 2008 that were manually re-evaluated 42.2 % did not meet criteria for STDR. Extrapolated to all cases of possible STDR in 2008, the prevalence of confirmed STDR among adult diabetics in Värmland in 2008 would be 6.8 % (n=876). The prevalence of possible STDR and DR among adult diabetic subjects was 11.7 % (n=1516) and 28.3 % (n=3668) in 2008, respectively. The prevalence of possible STDR and DR in

Värmland between 2008 and 2016 decreased by 4.0 % and 8.2 %, respectively (figure 2). Both trends were statistically significant, p=0.001 for STDR and p=0.004 for DR. The proportion of STDR to total DR, i.e. any grade of DR, decreased by approximately 3 % over the same time period, from 41 to 38 %.

Type of diabetes, diabetes duration, diet and insulin treatment, HbA1c and visual acuity in best

and worst eye were statistically different between the STDR group and the age- and sex matched control group, while treatment with oral antidiabetics and presence of hypertension

(11)

7

was not (table 1). Means for visual acuity for the better-seeing eye were 0.89 and 0.95, and 0.73 and 0.82 for the worst-seeing eye, in the STDR and non-STDR group, respectively.

Discussion

Diabetic retinopathy is still one of the most common causes of blindness in the world. This study estimates that the prevalence of confirmed STDR among diabetics ≥20 years in

Värmland in 2008 was 6.8 %. Another finding was that the prevalence of DR and STDR may have decreased in Värmland between 2008 and 2016, based on trends of possible cases. Patients with confirmed STDR in 2008 were found to have significantly longer diabetes duration, higher proportion of insulin treatment, higher HbA1c and lower visual acuity in both

the best- and worst-seeing eye, compared to non-STDR patients.

This study included all known diabetic patients ≥20 years with STDR in Värmland County by identifying patients with STDR in medical records. Värmland County, with its homogeneous health care system and stable population figures, is ideal for this purpose. To confirm possible cases of STDR, fundus photographs were re-evaluated by two experienced graders. The exclusion rate for both graders was similar, which indicate that their assessments were equivalent.

The estimated prevalence of confirmed STDR among diabetics ≥20 years in 2008 in this study was approximately two thirds, i.e. 3.4 percentage points lower, of the estimated

(12)

8

prevalence of STDR worldwide of 10.2 % presented in a meta-analysis, which pooled population based studies conducted between 1980 and 2008 [4]. However, there are several limitations with this comparison, the most essential being that STDR was not defined in the same way in the different studies. While our study defined STDR as severe non-proliferative or proliferative DR and/or DME, the meta-analysis defined STDR as proliferative DR and/or DME [4]. Thus, despite a wider definition, the prevalence of STDR estimated in this study was still lower than a global estimate. Finally, the prevalence of STDR reported in individual studies vary greatly, e.g. 6.7-34.9 % and 4.3-8.2 % in type 1 and type 2 diabetics, respectively [22].

The trends of prevalence of possible DR and STDR agree with trends presented in other studies, i.e. that the prevalence of DR has been decreasing in the western world in the 21st century [23,24]. The factors associated with STDR in this study, e.g. diabetes type 1, longer diabetes duration and higher HbA1c, are similar to findings in earlier studies [4,25,26].

A limitation of this study was the size of the cohort used to compare functional outcome between subjects with and without STDR. This might affect how the result are applicable. A greater generality could have been achieved by including a larger cohort, but as the re-evaluation process of fundus photographs was time consuming the cohort was limited. Furthermore, the power analysis was performed based on only a couple of studies, explained by the fact that there are not many studies addressing the differences in visual acuity between patients with and without STDR, upon which the power analysis was based [18,21].

Clinical grading lacks the consistency of research studies. Grading DR varies within and between individual graders, and over time. This may be the explanation as to why there was a discrepancy in the prevalence of confirmed STDR compared to possible STDR, and might affect the trend of STDR that was observed in this study. As mentioned above, two physicians conducted the re-evaluation process in this study. However, while manual grading of DR is considered the golden standard and the exclusion rate was similar for both evaluators, automated software grading of fundus photographs would create the most consistent grading and may be used in future studies [27].

This study did not consider the possible number of patients with undiagnosed diabetes with STDR, which theoretically could have affected the results. However, according to existing data, the frequency of STDR in type 2 diabetics is low at diagnosis [28].

(13)

9

The exclusion rate of possible STDR in 2008 during the re-evaluation process was 42.2 %, which suggest significant overdiagnosis. Overdiagnosis may be addressed through further training in evaluation of fundus photographs or an automated process. However, there may be a declining level of overdiagnosis as explanation of the trends of possible DR and STDR 2008-2016 found in this study, without or in combination with a real decline in prevalence. Information on incidence would contribute to the understanding of the decreasing prevalence on clinically diagnosed diabetic retinopathy, i.e. possible DR. In this pilot study we do not investigate incidence, but we recognize that it would be of great interest. Such data might be difficult to achieve since there is considerable variability in grading no/mild retinopathy. Thus, it would be necessary for a meticulously procedure for re-evaluation. Furthermore, regarding that most subjects have no or mild retinopathy, it would subsequently result in more than 50 000 retinal examinations to re-evaluate during our study period of eight years.

However, if an automated grading procedure could be used this might be possible. For future work using manual evaluation, it might be feasible to present data on the incidence of STDR. The current study adds to existing evidence regarding characteristics of diabetic subjects with DR and STDR, but also adds new evidence, specifically in the form of prevalence figures and possible trends for DR and STDR in a part of Sweden, as well as the finding that patients with STDR have worse visual acuity.

Conclusions

This retrospective study of STDR provides an updated estimate on the impact of DR and STDR. A knowledge of utmost importance to plan future health care from a cost – effectiveness perspective. The prevalence of STDR in a Swedish County in 2008 was estimated to 6.8 %, lower than a global estimate of 10.2 %. The lower proportion of STDR compared to DR over time might reflect the great improvements in diabetes care in the last decades. If the slightly but significant worse visual acuity among STDR patients found in this study are confirmed in the further analysis of this research, it will be informative for patients whose worry for blindness is based on older studies. Further research is needed on the prevalence of DR and visual outcome to plan the future need in health care and for adequate information to patients.

(14)

10

Acknowledgements

I want to give my sincerest thanks to my supervisor, ophthalmologist Karl-Johan Hellgren, for his constant support and optimism in the face of difficulties. I also want to thank Ali Sharif, resident in ophthalmology, tasked with the monumental mission to manually re-evaluate fundus photographs for over a thousand patients.

(15)

11

References

1. Diabetes [Internet]. [cited 2017 Oct 18]. Available from: https://medlineplus.gov/diabetes.html

2. IDF Diabetes Atlas, 7th ed., 2015. International Diabetes Federation [Internet]. [cited 2017 Oct 18]. Available from: http://www.diabetesatlas.org

3. Andersson T, Ahlbom A, Carlsson S. Diabetes Prevalence in Sweden at Present and Projections for Year 2050. PLoS ONE [Internet]. 2015 Nov 30 [cited 2017 Oct

18];10(11). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664416/ 4. Yau JWY, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, et al. Global Prevalence and Major Risk Factors of Diabetic Retinopathy. Diabetes Care. 2012 Mar;35(3):556–64.

5. Facts About Diabetic Eye Disease | National Eye Institute [Internet]. [cited 2017 Oct 18]. Available from: https://nei.nih.gov/health/diabetic/retinopathy

6. Kramer CK, Rodrigues TC, Canani LH, Gross JL, Azevedo MJ. Diabetic Retinopathy Predicts All-Cause Mortality and Cardiovascular Events in Both Type 1 and 2 Diabetes. Diabetes Care. 2011 May;34(5):1238–44.

7. Wilkinson CP, Ferris FL, Klein RE, Lee PP, Agardh CD, Davis M, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology. 2003 Sep;110(9):1677–82.

8. Mohamed Q, Gillies MC, Wong TY. Management of diabetic retinopathy: a systematic review. JAMA. 2007 Aug 22;298(8):902–16.

9. Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, DRS Report Number 8. The Diabetic Retinopathy Study Research Group. Ophthalmology. 1981 Jul;88(7):583–600. 10. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol Chic Ill 1960. 1985 Dec;103(12):1796–806.

(16)

12

11. Early photocoagulation for diabetic retinopathy. ETDRS report number 9. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991 May;98(5 Suppl):766–85.

12. Services S beredning för medicinsk och social utvärdering (SBU); SA for HTA and A of S. Diabetic retinopathy – the value of early detection [Internet]. 1993 [cited 2017 Oct 18]. Available from: http://www.sbu.se/en/publications/sbu-assesses/diabetic-retinopathy---the-value-of-early-detection/

13. National Guidelines for Diabetes Care – Support for governance and management [Internet]. [cited 2017 Oct 18]. Available from:

http://www.socialstyrelsen.se/publikationer2015/2015-4-12

14. Agardh E, Agardh CD, Hansson-Lundblad C. The five-year incidence of blindness after introducing a screening programme for early detection of treatable diabetic retinopathy. Diabet Med J Br Diabet Assoc. 1993 Jul;10(6):555–9.

15. Bäcklund LB, Algvere PV, Rosenqvist U. New blindness in diabetes reduced by more than one-third in Stockholm County. Diabet Med J Br Diabet Assoc. 1997

Sep;14(9):732–40.

16. Antonetti DA, Klein R, Gardner TW. Diabetic retinopathy. N Engl J Med. 2012 Mar 29;366(13):1227–39.

17. Wong TY, Mwamburi M, Klein R, Larsen M, Flynn H, Hernandez-Medina M, et al. Rates of progression in diabetic retinopathy during different time periods: a systematic review and meta-analysis. Diabetes Care. 2009 Dec;32(12):2307–13.

18. Lian JX, Gangwani RA, McGhee SM, Chan CKW, Lam CLK, Primary Health Care Group, et al. Systematic screening for diabetic retinopathy (DR) in Hong Kong:

prevalence of DR and visual impairment among diabetic population. Br J Ophthalmol. 2016 Feb;100(2):151–5.

19. Bertelsen G, Peto T, Lindekleiv H, Schirmer H, Solbu MD, Toft I, et al. Tromsø eye study: prevalence and risk factors of diabetic retinopathy. Acta Ophthalmol (Copenh). 2013 Dec;91(8):716–21.

(17)

13

20. hba1c-en.pdf [Internet]. [cited 2017 Nov 28]. Available from: http://users.mai.liu.se/andbj49/diabetes/hba1c-en.pdf

21. Attebo K, Mitchell P, Smith W. Visual acuity and the causes of visual loss in Australia. The Blue Mountains Eye Study. Ophthalmology. 1996 Mar;103(3):357–64. 22. Lee R, Wong TY, Sabanayagam C. Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss. Eye Vis [Internet]. 2015 Sep 30 [cited 2017 Dec 13];2. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4657234/ 23. Zhang X, Saaddine JB, Chou C-F, Cotch MF, Cheng YJ, Geiss LS, et al. Prevalence of diabetic retinopathy in the United States, 2005-2008. JAMA. 2010 Aug 11;304(6):649–56.

24. Andersen N, Hjortdal JØ, Schielke KC, Bek T, Grauslund J, Laugesen CS, et al. The Danish Registry of Diabetic Retinopathy. Clin Epidemiol. 2016 Oct 25;8:613–9.

25. Vujosevic S, Pucci P, Casciano M, Daniele A, Bini S, Berton M, et al. A

decade-long telemedicine screening program for diabetic retinopathy in the north-east of Italy. J Diabetes Complications. 2017 Aug;31(8):1348–53.

26. Scanlon PH, Aldington SJ, Leal J, Luengo-Fernandez R, Oke J, Sivaprasad S, et al. Development of a cost-effectiveness model for optimisation of the screening interval in diabetic retinopathy screening. Health Technol Assess Winch Engl. 2015 Sep;19(74):1–116. 27. Tufail A, Rudisill C, Egan C, Kapetanakis VV, Salas-Vega S, Owen CG, et al. Automated Diabetic Retinopathy Image Assessment Software: Diagnostic Accuracy and Cost-Effectiveness Compared with Human Graders. Ophthalmology. 2017 Mar;124(3):343– 51.

28. Looker HC, Nyangoma SO, Cromie D, Olson JA, Leese GP, Black M, et al. Diabetic retinopathy at diagnosis of type 2 diabetes in Scotland. Diabetologia. 2012 Sep;55(9):2335–42.

(18)

Populärvetenskaplig sammanfattning

Diabetes är en sjukdom som på lång sikt skadar små blodkärl i kroppen och ger upphov till olika komplikationer. Vanligaste komplikationen är diabetesretinopati, som innebär att blodkärlen i ögats näthinna skadas. Initialt har patienten inga symtom. Långt gången diabetesretinopati kallas synhotande diabetesretinopati och innebär en stor risk för

synnedsättning och blindhet. Synhotande förändringar kan ofta behandlas för att förhindra fortsatt försämring av synen.

Sverige har ett screeningprogram* för diabetesretinopati hos diabetiker för att kunna behandla i tid. Sedan detta infördes har synproblem minskat, åtminstone delvis förklarat av förbättrad diabetesbehandling.

Det saknas dock viktig kunskap på det här området. Studiens syften var att bland diabetiker i Värmland uppskatta (1) förekomsten av synhotande diabetesretinopati år 2008, (2)

förekomsten av möjlig** diabetesretinopati och förekomst, och proportion av, synhotande diabetesretinopati från år 2008 till 2016, samt (3) undersöka skillnader mellan diabetiker med och utan synhotande diabetesretinopati.

6,8 % av diabetikerna i Värmland 2008 uppskattas haft synhotande diabetesretinopati, jämfört med en uppskattning på 10,2 % globalt. Vi såg också en möjlig minskning av

diabetesretinopati och synhotande diabetesretinopati i Värmland 2008 och 2016. Diabetiker med synhotande diabetesretinopati hade sämre syn och mer ogynnsamma faktorer,

exempelvis haft diabetes under längre tid, än patienterna de jämfördes med.

Detta är den första av flera planerade studier, med långsiktigt mål att kunna utvärdera screeningprogrammet. De spännande resultaten som pekar på minskad förekomst av diabetesretinopati kommer studeras närmare i projektets fortsättning.

*Systematisk undersökning av individer med risk för en viss sjukdom. **Antal patienter som registrerats ha diabetesretinopati i journal.

(19)

Cover letter

Editor-in-Chief December 1st, 2017. British Journal of Ophthalmology

Dear Editor,

Please find enclosed a manuscript entitled “Sight-threatening Diabetic Retinopathy in a Swedish County – Prevalence and Comparison of Patients with and without Sight-threatening Diabetic Retinopathy”, which we hope will be considered for publication in the British Journal of Ophthalmology. It is a retrospective record study including all patients with diabetic retinopathy (DR) registered in medical records in Värmland County, Sweden. It investigates the prevalence of sight-threatening diabetic retinopathy (STDR) in 2008 and compares patients with and without STDR regarding visual acuity and diabetic factors.

Furthermore, the study estimates trends of prevalence of DR and prevalence and proportion of STDR over an eight-year period.

The estimated prevalence of STDR in Värmland in 2008 was 6.8 %, lower than the global estimate of 10.2 %. STDR was associated with worse visual acuity and unfavorable diabetic factors, e.g. longer duration, and the prevalence of DR and STDR, as well as the proportion of STDR to any DR, may have decreased from 2008 to 2016.

To our knowledge no previous population based study of diabetes in the western world has reported prevalence of both DR and STDR over time, as well as compared visual acuity of diabetics with and without STDR. The impact of the burden of diabetes is a pressing issue and of great interest for the readers of the BJO. This manuscript is not being considered for

publication elsewhere. Sincerely,

Sebastian Gustafsson, Bachelor of Medicine Örebro University

(20)

Ethical considerations

This study was approved by Uppsala Ethics Vetting Committee (2017/092). Consent was not gathered from patients included in this study. All data was anonymized post collection with only the main author and supervisor having access to the key.

Diabetes and its complications are prevalent and serious, which explains why there are several kinds of screening programs for diabetics in place. Studies based on present screening

programs are paramount as to evaluate and improve those screening procedures, and treatments, in the future.

Patients in this and similar studies, i.e. prevalence studies, are not exposed to different interventions, but merely observed. From an ethical standpoint, this might be superior, as no patient by design is exposed to an intervention that is hypothesized to be inferior to the intervention received by another patient.

Absence of patient consent is frequent in this type of study and presents an ethical issue. While consent may be impossible to retrieve in some cases, e.g. deceased patients, it is important to analyze available options and ethical arguments. The integrity of each patient must also be considered in all clinical studies on humans, with as few people as possible having access to a key to link data to specific patients.

The current study cannot be claimed to bring any direct advantages or disadvantages to the specific study population. However, it might be a part in improving the treatment of patients with diabetic retinopathy in the future and may therefore be motivated.