RISK FACTORS OF DIABETIC RETINOPATHY AND VISION

THREATENING DIABETIC RETINOPATY BASED ON DIABETIC

RETINOPATHY SCREENING PROGRAM IN
GREATER BANDUNG, WEST JAVA

Astriviani Switania, Aldiana Halim

Department of Ophthalmology, Faculty of Medicine Universitas Padjadjaran
Cicendo Eye Hospital, National Eye Center

ABSTRACT
Introduction : Diabetic retinopathy (DR) is a major microvascular complication of
diabetes. The disease has become the fifth leading cause of permanent visual impairment
in working aged population worldwide. The estimated rising number of people with
diabetes is associated with increased incidence of diabetic complication, including DR and
vision threatening diabetic retinopathy (VTDR). Development and progression of DR and
VTDR is associated with several risk factors, such as duration of diabetes, hyperglycemia,
hypertension, and hyperlipidemia. Strict control of those risk factors is recommended to
minimize disease progression.
Purpose : To identify risk factors associated with DR and VTDR and the prevalence of
DR in PROLANIS member with diagnosed diabetes in Greater Bandung, West Java based
on data from DR screening program.
Methods : Cross-sectional study was conducted. Data was collected retrospectively from
the registry of DR screening program in all community health centers in Greater Bandung,
West Java. Logistic regression model were used to analyzed risk factors of DR and VTDR.
Results : A total of 1649 participants with diabetes were included in this study. The
prevalence of persons with any DR in this study was 24,7% (95% CI 22,5% – 27%), DME
was 8,8% (95% CI 7,4% – 10,2%) and VTDR was 9% (95% CI 7,6% – 10,5%)
respectively. Duration of diabetes was found to be a significant risk factor for development
of VTDR and DME. Diastolic blood pressure was associated with increased risk of any DR
and systolic blood pressure was associated with increased risk of DME. Blood glucose
level 2 hours after glucose load was associated with increased risk of VTDR.
Conclusion : This study explored the risk factors and the prevalence of person with DR
and VTDR, which provide some insights for DR progression in Indonesian population with
diabetes in Greater Bandung, West Java. Findings in this study could be fundamental to
improvement of DR screening program and the development of eye care system.

Keywords : diabetic retinopathy, vision threatening diabetic retinopathy, risk factor

INTRODUCTION population. The number of persons

Diabetic retinopathy (DR) is a with moderate or severe visual
major microvascular complication of impairment affected by DR is
diabetes.1 The disease can cause projected to rise to 3,3 million in
severe permanent visual impairment 2020.2 A meta-analysis study
and blindness among working aged reported that global prevalence of any
population.2 DR has become the fifth DR in persons with diabetes was
leading cause of moderate or severe 34,6%, vision threatening diabetic
visual impairment among global retinopathy (VTDR) was 10,2% and

1
diabetic macular edema (DME) was hypertension and type 2 diabetes in
6,81% respectively.1 community health center.9 The main
International Diabetes Federation objective of PROLANIS is to reduce
(IDF) in 2017 reported that there are the risk of complications and achieve
326,5 million people of working age a better quality of life.9
group living with diabetes worldwide. Implementation of PROLANIS begin
The estimated number of people with with identification of person with type
diabetes will likely exceed half a 2 diabetes and hypertension in the
billion by 2030 with the greatest community health center coverage
increase will occur in developing followed by healthcare and risk factor
countries.3 This estimation will be monitoring provided by the
109
associated with an increase in the community health care provider.
incidence of diabetic complications, Community ophthalmology
including DR and VTDR.4 The division of Cicendo Eye Hospital,
estimated number of persons with DR National Eye Center has been
and VTDR in 2030 are 191 million conducting DR screening program for
and 56,3 million respectively.43 PROLANIS member with diagnosed
IDF report in 2017 revealed that diabetes in every community health
the prevalence of people with diabetes center in Greater Bandung, which
age 20-79 years in Indonesia was comprise of Bandung City, Bandung
6,3%. Indonesia has become the sixth Regency, West Bandung Regency,
countries with largest number of and Cimahi City, West Java since
people age 20-79 years with diabetes 2016. The purpose of this screening
in 2017.3 A recent community-based program is to provide referral system
study reported that the prevalence of for those with VTDR for
DR and VTDR in Indonesian ophthalmology treatment and for
population with type 2 diabetes was assessment of the retinal status in
43,1% and 26,3% respectively.5 those with poor quality photograph.
Development and progression of This study conducted to identify risk
DR and VTDR is associated with factors associated with DR and
several risk factors. Studies revealed VTDR and the prevalence of DR in
that duration of diabetes, PROLANIS member with diagnosed
hyperglycemia, hypertension and diabetes in Greater Bandung, West
hyperlipidemia are major risk factors Java based on data from DR screening
for development of DR. Strict control program.
of those risk factors have been
recommended to minimize DR MATERIAL AND METHODS
progression.678 Study design and participants
Indonesian government has This was a cross-sectional
developed strategies to manage analytical study. Data was collected
diabetes in Indonesia, one of them is retrospectively from the registry of
management program of chronic DR screening program for
disease (PROLANIS). This program PROLANIS member with diagnosed
is a system of governance of health diabetes in all community health
services for social health insurance centers in Greater Bandung, West
participants who suffer from Java in 2016 to 2017. Study

2
participants were recruited from discernible). All fundus photograph
PROLANIS member in which was graded at the screening site by
diabetes was already diagnosed from one certified grader for the
blood glucose testing according to retinopathy status and the DR
The American Diabetes Association severity. Grading confirmation was
(ADA) criteria (fasting blood glucose performed by Vitreoretina specialists
of ≥ 126 mg/dl or blood glucose of ≥ for all fundus photograph.
200 mg/dl 2 hour after glucose load). DR severity was assigned for each
Fundus photograph were obtained eye according to the Early Treatment
from all participants to evaluate the Diabetic Retinopathy Study (ETDRS)
retinal status. Poor quality and graded as follow: 0 as no DR, 1
photograph, in which the retinal status as mild NPDR, 2 as moderate NPDR,
cannot be evaluate due to media 3 as severe NPDR and PDR. DME is
opacity were excluded from this said to be present when there is hard
study. exudate within one disc diameter of
the center of the fovea or
Screening procedure and microaneurysm or dot hemorrhage
assessment of risk factors within one disc diameter of the center
All participants underwent of fovea. VTDR was defined as the
standard screening procedure. Fundus presence of DME at any stages of DR
photograph were obtained on both and/or grade 3.
eyes. Assessment of risk factors was
carried out by fasting blood glucose Data management and statistical
and/or 2 hours after glucose load analysis
testing and blood pressure Data was documented in Microsoft
measurement. Excel Office 2011. Statistical analysis
was performed using STATA 15.1
Fundus photograph and software. Descriptive analysis was
assessment of DR severity conducted and data is presented as
All participants underwent fundus prevalence and 95% confidence
photography performed by one interval. Risk factors analysis was
trained ophthalmic photographer. performed using logistic regression
One field dilated 45o digital fundus model and data is presented as Odd
photograph, centered at the macula ratio (OR) with p value of < 0,05
with the optic disc, superior and considered significant.
inferior vascular arcades in view,
were obtained on both eyes after RESULTS
instillation of 1% tropicamide eye Characteristics of study
drop with Smartscope Pro portable participants are shown in Table 1. A
fundus camera (Optomed, Oulu, total of 1649 participants with
Finland). diabetes were included in this study,
The quality of the photograph was in which 72,8% among them are
assessed as “good” (lesions well women. Most of the study
discernible as present or not), “fair” participants were in 51 - 60 years age
(lesions discernible with difficulty), group (34,6%) and 61 - 70 years age
or “poor” (presence of lesions not group (37,2%). Shorter duration of

3
diabetes (< 5 years) were found in load of < 200 mg/dl (63,4%). Systolic
63,92% of the participants. Most of blood pressure of < 140 mmHg and
the study participants had fasting diastolic blood pressure of < 90
blood glucose of £ 125 mg/dl mmHg were found in 64,83% and
(52,03%) and 2 hours after glucose 66,22% of the study participants.

Table 1. Characteristics of study participants

Characteristics Male Female Total
n (%) n (%) n (%)
Age (years)
£ 20 1 (0,2) 2 (0,2) 3 (0,2)
21 – 30 3 (0,7) 3 (0,2) 6 (0,4)
31 – 40 5 (1,1) 17 (1,4) 22 (1,3)
41 – 50 40 (8,9) 184 (15,3) 224 (13,6)
51 – 60 123 (27,5) 447 (37,2) 570 (34,6)
61 – 70 186 (41,5) 427 (35,6) 613 (37,2)
71 – 80 87 (19,4) 114 (9,5) 201 (12,2)
> 80 3 (0,7) 7 (0,6) 10 (0,6)
Period of diabetes (years)
<5 274 (16,6) 780 (47,3) 1054 (63,92)
5–9 87 (5,28) 225 (13,6) 312 (18,92)
≥ 10 87 (5,28) 196 (11,9) 283 (17,16)
Fasting blood glucose (mg/dl)
£ 125 255 (15,5) 603 (36,6) 858 (52,03)
126 – 199 152 (9,22) 407 (24,7) 559 (33,9)
≥ 200 41 (2,49) 191 (11,6) 232 (14,07)
2 hours after glucose load (mg/dl)
< 200 302 (67,4) 744 (61,9) 1046 (63,4)
≥ 200 146 (32,6) 457 (38,1) 603 (36,6)
Systolic blood pressure (mmHg)
< 140 310 (18,3) 768 (46,6) 1069 (64,83)
140 – 159 109 (6,61) 312 (18,9) 421 (25,53)
160 – 179 30 (1,82) 93 (5,64) 123 (7,46)
≥ 180 8 (0,49) 28 (1,7) 36 (2,18)
Diastolic blood pressure (mmHg)
< 90 297 (18) 795 (48,2) 1092 (66,22)
≥ 90 151 (9,16) 406 (24,6) 557 (33,78)

Table 2 shows the estimated VTDR in this study population. The

prevalence of any DR, DME and prevalence of eyes with any DR was

4
11,5% (95% confidence interval [CI] 4,6% (95% CI 3,9% - 5,3%) and of
10,4% – 12,6%), whereas the eyes with VTDR was 5,1% (95% CI
prevalence of eyes with DME was 4,3% – 5,8%) respectively.

Table 2. Prevalence of diabetic retinopathy and its severity in study population

Male Female Total
Prevalence (%) Prevalence (%) Prevalence (%)
n (95% CI) n (95% CI) n (95% CI)
Eyes
Any DR 138 15,4 (13,0 - 17,8) 380 15,8 (14,4 - 17,3) 518 11,5 (10,4 - 12,6)
DME 51 5,7 (4,2 - 7,2) 152 6,3 (5,4 - 7,3) 203 4,6 (3,9 - 5,3)
VTDR 54 6 (4,5 - 7,6) 167 7 (5,9 - 8,0) 221 5,1 (4,3 - 5,8)
Persons
Any DR 111 24,8 (20,4 - 29,1) 297 24,7 (22,1 - 27,4) 408 24,7 (22,5 - 27,0)
DME 34 7,6 (5,1 – 10,1) 111 9,2 (7,6 - 10,9) 145 8,8 (7,4 - 10,2)
VTDR 38 8,5 (5,8 - 11,1) 111 9,2 (7,6 - 10,9) 149 9 (7,6 - 10,5)

The prevalence of persons with 8,8% (95% CI 7,4% – 10,2%) and of

any DR among the study participants persons with VTDR was 9% (95% CI
was 24,7% (95% CI 22,5% – 27%), 7,6% – 10,5%) respectively. Higher
with similar prevalence were found prevalence of DME and VTDR was
among men and women. The found in women.
prevalence of persons with DME was

Table 3. Risk factors associated with any DR

Variable Odd Ratio 95% CI p value
Age (years)
< 50 Reference
≥ 50 1,04 (0,72 - 1,48) 0,94
Gender
Male Reference
Female 0,99 (0,76 - 1,29) 0,82
Duration of diabetes (years)
<5 Reference
5–9 1,31 ( 0,97 - 1,78) 0,08
≥ 10 1,36 (0,99 - 1,86) 0,06
Fasting blood glucose (mg/dl)
£ 125 Reference
126 – 199 1,13 (0,85 - 1,50) 0,39
≥ 200 1,15 (0,76 - 1,73) 0,52

5
 2 hours after glucose load (mg/dl)
< 200 Reference
≥ 200 1,3 (0,97 - 1,74) 0,08
Systolic blood pressure (mmHg)
< 140 Reference
140 - 159 0,82 (0,60 - 1,11) 0,20
160 - 179 0,96 ( 0,60 - 1, 56) 0,88
≥ 180 1,93 (0,90 - 4,14) 0,09
Diastolic blood pressure (mmHg)
< 90 Reference
≥ 90 1,35 (1,02 - 1,79) 0,04

Risk factors for any DR analysed with increased risk of having any DR
using multivariate regression analysis (p = 0,04). Diastolic blood pressure is
are shown in Table 3. Diastolic blood a significant risk factor for any DR as
pressure of ≥ 90 mmHg were shown in figure 1.
significantly associated (OR = 1,35)

Figure 1. Association of risk factors for any DR

6
 Multivariate regression analysis on years (OR = 2,18; p = 0,00) were
risk factors for DME are shown in significantly associated with
Table 4. Duration of diabetes of 5-9 increased risk of having DME.
years (OR = 1,81; p = 0,01) and ≥ 10

Table 4. Risk factors associated with DME

Variable Odd Ratio 95% CI p value
Age (years)
< 50 Reference
≥ 50 0,87 (0,51 - 1,47) 0,44
Gender
Male Reference
Female 1,19 (0,77 - 1,82) 0,59
Duration of diabetes (years)
<5 Reference
5-9 1,81 (1,15 - 2,84) 0,01
≥ 10 2,18 (1,39 - 3,42) 0,00
Fasting blood glucose (mg/dl)
£ 125 Reference
126 - 199 1,15 (0,74 - 1,78) 0,55
≥ 200 1,39 (0,77 - 2,53) 0,28
2 hours after glucose load (mg/dl)
< 200 Reference
≥ 200 1,41 (0,91 - 2,21) 0,13
Systolic blood pressure (mmHg)
< 140 Reference
140 - 159 0,99 (0,61 - 1,59) 0,95
160 - 179 1,34 (0,66 - 2,70) 0,42
≥ 180 2,77 (1,04 - 7,37) 0,04
Diastolic blood pressure (mmHg)
< 90 Reference
≥ 90 0,91 (0,59 - 1,42) 0,69

Systolic blood pressure of ≥ 180 Duration of diabetes and systolic

mmHg was also significantly blood pressure are significant risk
associated (OR = 2,77) with increased factors for DME as shown in figure 2.
risk of having DME (p = 0,04).

7
 Figure 2. Association of risk factors for DME

Multivariate regression analysis on years (OR = 1,95; p = 0,01) were

risk factors for VTDR are shown in significantly associated with
Table 5. Duration of diabetes of 5-9 increased risk of having VTDR.
years (OR = 1,97; p = 0,00) and ≥ 10

Table 5. Risk factors associated with VTDR

Variable Odd Ratio 95% CI p value
Age (years)
< 50 (ref) Reference
≥ 50 0,76 (0,45 - 1,27) 0,21
Gender
Male Reference
Female 1,33 (0,86 - 2,07) 0,29
Duration of diabetes (years)
<5 Reference
5-9 1,97 (1,26 -3,07) 0,00
≥ 10 1,95 (1,22 - 3,12) 0,01
Fasting blood glucose (mg/dl)
£ 125 Reference
126 - 199 0,86 (0,54 - 1,35) 0,50
≥ 200 1,14 (0,63 - 2,05) 0,67

8
 2 hours after glucose load (mg/dl)
< 200 Reference
≥ 200 1,60 (1,02 - 2,52) 0,04
Systolic blood pressure (mmHg)
< 140 Reference
140 - 159 1,05 (0,65 - 1,68) 0,85
160 - 179 1,31 (0,65 - 2,66) 0,45
≥ 180 2,02 (0,71 - 5,72) 0,19
Diastolic blood pressure (mmHg)
< 90 Reference
≥ 90 1,11 (0,72 - 1,72) 0,63

Blood glucose level 2 hours after (p = 0,04). Duration of diabetes and

glucose load of ≥ 200 mg/dl was also post prandial blood glucose are
significantly associated (OR = 1,60) significant risk factors for VTDR as
with increased risk of having VTDR shown in figure 3.

Figure 3. Association of risk factors for VTDR

9
DISCUSSION to be 13,1%.6 In India, Raman et al.
In this study, we found data on the reported prevalence of VTDR and
prevalence and risk factors of DR and DME among people with type 2
its severity in Indonesian population diabetes living in rural area to be
with diabetes in Greater Bandung, 3,8% and 2,1%, whereas among
West Java. The prevalence of any DR people with type 2 diabetes living in
in this study was 24,7%, whereas the urban area to be 4,3% and 1,4%
prevalence of VTDR and DME was respectively.1213 Sasongko et al.
9% and 8,8% respectively. Higher reported prevalence of VTDR in adult
prevalence of DME and VTDR in with type 2 diabetes in Jogjakarta to
women were found in this study. be 26,3% (95%CI 23,1 – 29,5).5
A meta-analysis involving 35 Lower prevalence of VTDR were
studies reported global prevalence of reported in United Kingdom (3,4%)
any DR, DME and VTDR among and The United States (4,4%)
patients with diabetes to be 34,6% compared to other study.1514
(95% CI 34,5 – 34,8), 6,81% (95% CI In this study, we found lower
6,74 – 6,89) and 10,2% (95% CI 10,1 prevalence of any DR compare to
– 10,3) respectively.1 This meta- global estimates and other studies.
analysis highlighted the burden of DR Prevalence of VTDR and DME in this
worldwide, however the result limited study is comparable to global
by the different time points, different estimates and other studies from
methodologies and population Asian countries. Lower prevalence of
characteristics of the pooled studies.1 VTDR were reported by Thomas et al.
There are several DR population- and Zhang at al. in Western countries.
based studies to compare. In China, This implies that most DR cases may
Liu et al. reported higher prevalence have been detected only when
of DR in people with type 2 diabetes, symptomatic or complications have
with overall prevalence of DR to be occured. Different result from these
34%.11 In India, Raman et al. reported studies could be due to several
prevalence of DR among people with factors, as such different methods of
type 2 diabetes living in rural area to recruitment of study participants,
be 10,3% and 18% in urban area.1213 different tools and procedure in
Sasongko et al. reported prevalence of obtaining fundus photograph, and
DR in adult with type 2 diabetes in grading system of DR used.
Jogjakarta to be 43,1% (95% CI 39,6 The only significant risk factor
– 46,6).5 These finding is comparable associated with any DR in this study
to prevalence of DR in western was diastolic blood pressure.
countries. Thomas et al. reported Significant risk factors associated
overall prevalence of DR in United with VTDR in this study were
Kingdom to be 32,4%, with higher duration of diabetes and blood
prevalence of DR in type 1 diabetes, glucose level 2 hours after glucose
whereas the prevalence of DR in The load. Duration of diabetes was also
United States reported by Zhang et al. become a significant risk factor
to be 28,5%.1415 associated with DME along with
Estimation of overall prevalence of systolic blood pressure.
VTDR in China reported by Liu et al.

10
 The United Kingdom Prospective Hyperglycemia is one of the most
Diabetes Study (UKPDS) was the important risk factor for DR and its
first randomized clinical trial that progression. The Diabetes Control
showed the importance of tight blood and Complication Trial (DCCT) and
pressure control in reducing UKDPS revealed that tight glycemic
retinopathy. After 9 years of follow control could reduce the risk of DR
up, patients with type 2 diabetes with development and progression in type
tight blood pressure control had a 1 and type 2 diabetes patients.722 Liu
reduction of risk in DR progression et al. reported that fasting blood
by 34% and visual acuity glucose, post prandial blood glucose
deterioration by 47%.16 The and HbA1C were all risk factors for
Wisconsin Epidemiologic Study of DR and VTDR.6 HbA1C has been
Diabetic Retinopathy (WESDR) on reported to be independent risk factor
type 1 diabetes patients revealed that for DR and its progression. It
every 10 mmHg increase in systolic represents the management condition
blood pressure was associated with of blood glucose.6 There is little
10% increased risk of early DR and evidence on the role of post prandial
15% risk of PDR or DME.817 blood glucose in DR progression.
Rajalakshmi at al. reported that Eriksson et al. reported that post
diastolic blood pressure is a prandial blood glucose was abnormal
significant risk factor for DR (OR = in 31% of patients with diabetes
1,36).18 Other study by Jee et al. whose fasting blood glucose was
revealed that both systolic (OR = normal, so it was considered to be an
1,02) and diastolic blood pressure important diagnostic factor for
(OR = 0,97) to be significant risk diabetes.23
factor for DR.19 One possible mechanism of post
Duration of diabetes has become prandial blood glucose in the
one of the most significant risk factor progression of DR might be that it
in DR progression. WESDR cohort reflects the capacity of insulin
reported that almost all patients with secretion, the peak of which was
type 1 diabetes develop some degree shown to be delayed in type 2
of retinopathy if duration of disease diabetes.11 High levels of post
exposure is long enough.8,17 Thomas prandial blood glucose indicate that
et al. reported an increased risk DR in insulin secretion is relatively
patients with type 2 diabetes with 5 – insufficient, which might result in a
9 years (OR = 1,29) and 10 years (OR blood glucose fluctuation after food
= 1,68) duration of diabetes.14 Other intake and subsequent harm to the
study by Jones et al. also reported an targeted organs.11
increased risk of DR with 10 – 20 The strength of this study was
years duration of diabetes (OR = large number of study population and
1,21).20 Longer duration may recruitment of participants from
represent a longer period of retinal community. This study also had some
toxicity induced by high glucose limitations. First, analysis in this
levels, which is believed to be study obtained from retrospective
associated with both vascular and data and randomization was not done
neural death in the retina.21 in recruitment of study participant,

11
therefore the result of this study Future studies could be conducted
cannot be generalized into with larger sample size using
population. Second, the use of one randomization in selection of study
field digital non stereoscopic fundus participant. Other risk factors for DR
photograph to identify DR lesions and VTDR have to be evaluated to
may reduce the sensitivity in require more information, which may
detection of mild DR cases, decrease DR progression.
peripheral lesion, and the presence of
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