Diabetic macular edema (DME) is the leading cause of blindness in the diabetic population. However, there is limited understanding of the epidemiology of DME with visual impairment (VI) and treatment in patients with diabetes in Canada. This observational, retrospective study used records from the Southwestern Ontario database to observe the demographics, prevalence, and treatment characteristics of VI due to DME compared to a healthy population in a real-world Canadian setting. Data was compared between a cohort of 8,368 diabetic (type 1 or 2) patients, who were ≥18 years old and had a diagnosis of DME with VI (visual acuity <20/40 in Snellen equivalent), and 76,077 age- and gender-matched subjects representing a healthy population. Among diabetic patients, prevalence of DME was 15.7%, and prevalence of VI due to DME was 2.56%. Laser monotherapy was the most frequently used treatment. Public funding covered costs for 85% of persons with DME while 18% were paid for with private funds. This study provides insight into the demographics, prevalence, and treatment of VI due to DME in a representative Canadian cohort. This data can help to inform evaluation of current DME treatment patterns and of proposed new treatment on drug plan budgets in Canada.
Diabetic macular edema (DME), a complex disease of multifactorial origin, is the leading cause of blindness in the diabetic population [
The Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) reported the 25-year cumulative incidence of ME to be 29%, with annualized incidences of ME at 2.3%, 2.1%, 2.3%, and 0.9% in the first, second, third, and fourth follow-up periods of the study, respectively [
In a systematic review of epidemiology of diabetic retinopathy and macular edema (ME) Williams et al. (2004) found that a majority of the 359 articles included in the review were dominated by large studies like the WESDR, DCCT, ETDRS, and the United Kingdom Prospective Diabetes Study (UKPDS) [
There is very limited understanding of the epidemiology and disease burden of DME and information on the current state of DME with visual impairment (VI) and treatment in patients with diabetes in Canada. This study examines the prevalence, demographics, and treatment characteristics of VI due to DME in a real-world Canadian setting.
An observational, retrospective, noninterventional study was conducted using records from the Southwestern Ontario (SWO) database—a longitudinal population-based database of more than 170,000 patients in 53 family practice clinics in Southwestern Ontario, Canada.
The study cohort was identified using the following inclusion criteria: patients with diabetes (type 1 or type 2) and diagnosis of DME with visual impairment (defined as best corrected visual acuity <20/40 in Snellen equivalent) made by an ophthalmologist between January 1, 2008 and December 31, 2009, or the latest data available in the database with complete data for three months and after the index date (the date of the first diagnosis of DME during the study period until December 31, 2009); subjects of 18 years and older.
Exclusion criteria were as follows: patients without follow-up data to 1 year; patients diagnosed with age-related macular degeneration; patients diagnosed with a nondiabetes retinal vascular disease (i.e., retinal disease with a vascular origin including atherosclerosis or hypertension); patients who were participating in an ophthalmological clinical trial during the study period (if we have access to this information in the southwestern Ontario database).
Data included in this study comprised patient characteristics and demographics, prevalence, cardiovascular comorbidity and events, and medication coverage. Visual acuity was performed by a trained ophthalmologist or optometrist.
In order to compare characteristics and comorbidities of patients with DME to those of the general population, a control cohort was extracted by random selection of age- and gender-matched subjects >18 years by clinic location.
Initial extractions of control cohort, and the cohort of patients with diabetes and DME with VI, were accomplished utilizing International Classification of Disease codes (ICD9/ICD10), reviewing patient charts for text entries of symptoms that supported a diagnosis of diabetes and DME and concomitant comorbidity, and reviewing patient treatment records unique to DME with VI, including consultation notes and hospital discharge summaries. Demographic characteristics, comorbidities, and treatment were reported. In total, data from 8,368 patients with type 1 or 2 diabetes and from 76,077 people comprising the control cohort were extracted for this analysis.
The SWO database has recorded patient level data on the clinical diagnoses at each visit, symptoms corroborating the diagnoses, clinical data, prescribed treatments including lifestyle interventions and medications, physician visits, hospitalizations, and diagnostic/laboratory test results, allowing for the conduct of patient level analyses, since 2000. Data from the 53 practices participating in the SWO database cohort are routinely updated on a quarterly basis with immediate reconciliation at the point of care. The quarterly activity is triggered by chart entry and billed activity for patient encounters. All practices included in the SWO database are part of a family practice research network involved in various audit and clinical research activities. Practices have consented to centralized accrual of clinical data from the patient record (UWO IRB 09572). All records are anonymous and conform to current confidentiality industry standards. Each patient’s Ontario Health Insurance Plan (OHIP) number is assigned a unique patient identification number in the SWO database. To protect the privacy of patient’s medical information, a 128-bit SSL certificate is installed on the production SWO Web Server. The industry standard data protection method ensures the security of data during transmission across the Internet. Validation studies of the SWO database confirming the quality and completeness of the recorded data show good agreement between estimates of the prevalence of cardiovascular risk factors obtained from the SWO database and other published estimates [
All subjects meeting inclusion/exclusion criteria were analyzed to understand the demographics and treatment patterns of care. For treated patients, the treatment choices were characterized for each cell. The treatment pattern was related to clinical characteristics of patients, including type of coverage.
For continuous variables, the mean, standard deviation, median, minimum, and maximum values were estimated. For categorical variables, the number and percentage of each category within an assessment were calculated for nonmissing data.
Please refer to Table
Demographics of the populations investigated.
Control cohort |
Patients with DME |
Patients with DME (<20/40) |
|
---|---|---|---|
Average age (years) | 69 | 63 | 64 |
Average duration of diabetes (years) | n/a | 19 | 21 |
Average age at diagnosis of DME (years) | n/a | 52 | 48 |
Age distribution [ |
|||
Males <40 | 14,455 (19%) | 92* (7%) | 6 (3%) |
Males 40–59 | 1,932 (17%) | 236* (18%) | 26 (12%) |
Males 60–69 | 3,803 (5%) | 263* (20%) | 67 (31%) |
Males 70+ | 6,086 (8%) | 92 (7%) | 11 (5%) |
Females <40 | 14,454 (19%) | 158* (12%) | 24 (11%) |
Females 40–59 | 11,411 (15%) | 184 (14%) | 38 (18%) |
Females 60–69 | 3,804 (5%) | 234* (8%) | 34 (16%) |
Females 70+ | 9,129 (12%) | 53* (4%) | 9 (5%) |
Sex [ |
|||
Male | 37,551 (49%) | 671 (51%) | 116 (54%) |
Female | 38,526 (51%) | 645 (49%) | 99 (44%) |
Ethnicity [ |
|||
Caucasian | 59,340 (76%) | 934 (71%) | 131** (61%) |
Aboriginal | 6,847 (9%) | 158 (12%) | 47** (22%) |
Hispanic | 3,043 (4%) | 92* (7%) | 0 |
South Asian | 3,055 (5%) | 79 (6%) | 37 (17%) |
Asian | 1,521 (2%) | 39 (3%) | 0 |
African descent | 1,506 (2%) | 13 (1%) | 0 |
*Significantly different from cohort. 1-tail test.
**Significantly different from DME cohort. 1-tail test.
A smaller percentage of patients with VI due to DME were Caucasian compared with control or those with DME (61%,
Please refer to Table
Disease characteristics of the populations investigated.
Control cohort |
Patients with type 2 diabetes on oral meds |
Patients with type 1 diabetes |
Patients with DME |
|
---|---|---|---|---|
Overweight (BMI = 25–29.9 kg/m2) [ |
3,799 (5%) | 1,095* (18%) | 208 (9%) | 250* (19%) |
Obesity (BMI ≥30 kg/m2) [ |
1,522 (2%) | 791* (13%) | 92 (4%) | 158* (12%) |
BMI, male (mean ± SD) | 25 ± 13.9 | 29 ± 14.0 | 24 ± 9 | 29 ± 9 |
BMI, female (mean ± SD) | 24 ± 14.1 | 28 ± 14.7 | 26 ± 11 | 30 ± 7 |
Family history, type 2 diabetes [ |
782 (1%) | 487* (8%) | 274* (2%) | 132* (10%) |
Smoking [ |
3,804 (5%) | 1,339* (22%) | 416* (18%) | 276* (21%) |
Hypertension [ |
10,650 (14%) | 4,138* (68%) | 1,529* (67%) | 868* (66%) |
Systolic blood pressure (mean ± SD) | 131 ± 15.4 | 133 ± 15.3 | 133 ± 14 | 136 ± 11 |
Diastolic blood pressure (mean ± SD) | 77 ± 8.5 | 76 ± 8.5 | 81 ± 3 | 82 ± 9 |
Dyslipidemia [ |
7,603 (10%) | 2,921* (48%) | 251 (11%) | 166* (12%) |
History of impaired fasting glucose (IFG) [ |
0 (0%) | 791* (13%) | 16 (1%) | 154* (12%) |
History of impaired glucose tolerance (IGT) [ |
780 (1%) | 1,095* (18%) | 11 (1%) | 160* (12%) |
Hb1Ac (mean ± SD) | 5.1 ± 0.6 | 6.7 ± 1.8 | 6.5 ± 1.1 | 7.3 ± 1.3 |
History of vascular disease (coronary, cerebrovascular, or peripheral) [ |
9,129 (12%) | 1,643* (27%) | 319 (14%) | 368* (28%) |
Acute coronary syndrome (ACS) [ |
4,567 (6%) | 1,947* (32%) | 479* (21%) | 276* (21%) |
Acute | ||||
Myocardial infarction (MI) [ |
799 (1%) | 487* (8%) | 387* (17%) | 237* (18%) |
Stroke [ |
714 (1%) | 182 (3%) | 12 (1%) | 91* (7%) |
Percutaneous coronary transluminal arthroplasty (PCTA) |
689 (1%) | 61 (1%) | 25 (1%) | 27 (2%) |
Coronary artery bypass graft (CABG) [ |
701 (1%) | 65 (1%) | 32 (1%) | 13 (1%) |
Peripheral arterial disease (PAD) [ |
215 (<1%) | 121 (2%) | 10 (1%) | 66* (5%) |
Congestive heart failure (CHF) [ |
755 (1%) | 426* (7%) | 46 (2%) | 105* (8%) |
History gestational diabetes (females) [ |
181 (<1%) | 60 (1%) | 50 (2%) | 26 (2%) |
Chronic kidney disease [ |
||||
Stage 1 | 0 (0%) | 88 (1%) | 12 (1%) | 29 (2%) |
Stage 2 | 0 (0%) | 92 (1%) | 68 (3%) | 55 (4%) |
Stage 3 | 737 (1%) | 118 (2%) | 161 (7%) | 79 (6%) |
Stage 4 | 2,282 (3%) | 212 (4%) | 114 (5%) | 75 (6%) |
Stage 5 (end stage renal disease) | 766 (1%) | 109 (2%) | 42 (2%) | 37 (3%) |
Dialysis | (<1%) | 175 (3%) | 37 (2%) | 39 (3%) |
Microvascular complications [ |
||||
Amputations | 281 (1%) | 177 (3%) | 35 (2%) | 28 (2%) |
Peripheral neuropathy | 741 (2%) | 365 (6%) | 17 (1%) | 77 (6%) |
Nephropathy | 1,521 (2%) | 28 (4%) | 71 (3%) | 94 (7%) |
*Significantly different from control. 1-tail test.
Please refer to Table
Incidence and prevalence.
Patients with DME |
Patients with DME |
|
---|---|---|
Visual impairment |
|
|
Prevalence | 15.7% |
|
Incidence | — |
|
Visual impairment (VI) is defined as visual acuity <20/40.
Please refer to Table
Visual impairment in patients with DME.
Control ( |
Patients with DME ( |
Patients with DME (<20/40) ( |
|||
---|---|---|---|---|---|
Age (years) | 69 | 63 | 64 | ||
HbA1c at diagnosis (mean ± SD) | 6.3 ± 0.3 | 7.4 ± 1.7 | 7.6 ± 2.2 | ||
Right eye affected [ |
n/a | 486 (37%) | 96 (45%) | ||
Left eye affected [ |
n/a | 632 (48%) | 92 (43%) | ||
Both eyes affected [ |
n/a | 197 (15%) | 26 (12%) | ||
| |||||
Type* | n/a | Focal | Diffuse | Focal | Diffuse |
750 (57%) | 566 (43%) | 114 (53%) | 101 (47%) |
*Diffuse edema is associated with a paucity of lipid exudates. Focal edema is associated with the presence of lipid and lipid rings [
Please refer to Table
Treatment characteristics of patients with VI due to DME.
Patients with VI due to DME ( |
||
---|---|---|
Average time to treatment (days) (mean ± SD) |
|
|
Lag to second treatment (days) (mean ± SD) |
|
|
| ||
Type | Focal | Diffuse |
| ||
Number of patients |
114 (53%) | 101 (47%) |
| ||
Treatment type (% of all treatments recorded in patients’ charts)* | ||
| ||
Anti-VEGF monotherapy | 18.2% | 15.0% |
Intravitreal Triamcinolone Acetonide (IVTA) | 1.0% | 3.0% |
Other | 0.5% | 1.9% |
Laser mono | 69.3% | 53.3% |
Laser combo | ||
Laser—anti-VEGF | 7.8% | 12.1% |
Laser—IVTA | 3.1% | 15.0% |
*Some patients received more than one type of treatment; anti-VEGF: anti-vascular endothelial growth factor.
Public funding covered costs for 85% of persons with DME, 18% were paid for with private funds, and 1% from out-of-pocket resources.
DME is a chronic disease. The natural progression of DME leads to a significant vision loss within 2 years in half of individuals [
This study has some limitations. DME can be associated with severity of hypertension alone. Given that blood pressure levels and % of patients with hypertension were similar between those with and without DME, we do not believe that hypertension would contribute differently to outcomes in those with DME although this remains a possibility. Treatment timelines were taken from chart records and were not verified with patients, and adherence with treatment could not be captured. Furthermore, the validity of the diagnostic algorithms relies on the premise that the coding ophthalmologist accurately diagnosed the presence or absence of DME as well as the classification and treatment of focal and diffuse types of edema in patients with DME. Although classification of macular edema into focal and diffuse types is a common practice, a critical review by Browning et al. (2008) found little evidence that characteristics of macular edema described by the terms focal and diffuse are of clinical significance in that they do not adequately help to explain variation in visual acuity or response to treatment [
Overall, however, unlike pharmaceutical administrative databases which use service diagnosis codes to correlate with prescription use, this database allows for a linkage to be made between prescribed medications and disease correlates. As well, previously conducted validation studies of the SWO database confirming the quality and completeness of the recorded data show good agreement between estimates of the prevalence of cardiovascular risk factors obtained from the SWO database and other published estimates [
This study in a real-world setting among patients with diabetes provides insight into the prevalence, demographics, and treatment characteristics of visual impairment due to DME in a representative Canadian cohort. As such, it can help to inform evaluation of the current DME treatment patterns and help to populate budget impact models evaluating the impact of introducing new treatment on drug plan budgets in Canada.
This project was funded by an unrestricted educational grant from Novartis.