Vrundaben Patel1, Elijah M. Munachonga1, Grace Mutati1,2, Jessie Nyalazi2, Kangwa I. M. Muma1,2
1University of Zambia, School of Medicine, Lusaka
2University Teaching Hospitals – Eye hospital, Lusaka Zambia
Abstract
Purpose:
Diabetic retinopathy (DR) is a blinding complication of diabetes mellitus and a leading cause of visual impairment in people aged 20–64 years. Retinopathy develops overtime in all diabetics and controlling the modifiable risk factors delays its onset and reduces progression. This study was carried out to assess DR; its prevalence and associated clinical and demographic characteristics among patients attending the UTHs-Adult Hospital medical clinic in Lusaka, Zambia
Methods:
This was a hospital-based cross-sectional study carried out from 18th December, 2018 to 16th April, 2019 at the adult medical diabetic clinic. Snellen visual acuity (VA), blood pressure, weight and height were measured as well as relevant demographic and medical information collected. Retinal images were captured after pupil dilatation and used for grading retinopathy using the International classification of DR scale. The worse eye was used to grade for DR.
Results:
A total of 213 participants were studied with a female to male ratio of 2.3:1. The median age was 53 years and majority (183=85.2%) had type 2 diabetes. Median duration of diabetes was five years. Median glycated haemoglobin level was high at 8.1%. One hundred sixty-three participants (76.5%) had normal VA and six (2.8%) were blind.
The prevalence of DR in this study was 47.4%; 95% CI 40.8%-54.2% (101 participants), with 8.9% (19 participants) having proliferative diabetic retinopathy. Diabetic macula oedema was present in 24 (11.3%; 95% CI 7.5%-16.1%). Duration of diabetes was the most significant (p<0.0001) association found with retinopathy.
Even though 104 participants (51.1%) had the knowledge that diabetes affects the eyes, only 55 (25.8%) had had a dilated eye examination in the preceding twelve months.
Conclusion:
A high prevalence of DR among patients attending the adult medical diabetic clinic was found in this study, with only about a quarter of them having had dilated eye examination in the preceding twelve months. The study findings suggest that better advocacy for retinopathy screening and diabetes control needs to be implemented at the UTHs-Adult Hospital in Lusaka.
Introduction
Diabetic retinopathy is a common microvascular complication of diabetes mellitus (DM) [1] and also a leading cause of visual impairment in people aged 20–64 years affecting 1 in 3 persons with diabetes ([2]. The International Agency for Prevention of Blindness (IAPB) reports that 75% of diabetes burden is in low to middle income countries and that DR is emerging among the top causes of vision loss globally [3]. Risk factors for visual impairment that have been identified from studies such as the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) include poor glycaemic control, hypertension, smoking and severity of baseline retinopathy [4]. Controlling blood sugar levels reduces the annual incidence of DR but not the lifetime risk of developing DR as it usually develops over time in all diabetes patients [2]. In most cases of DR, an actual decrease in visual acuity is not noticed until progression to very advanced disease occurs [2]. This delays the presentation to any eye health care personnel [5].
A study from the Copperbelt province of Zambia based on a screening programme found a prevalence rate of DR of 52%, which was higher than average from other studies [6]. In a Malawian cohort of patients from diabetic clinics, DR was the most common primary cause of vision loss (38.6%), followed by cataract (16.5%), and both DR and cataract (3.9%) [7]. Cleland et al. looked at a DR screening programme in Tanzania and of the 3463 people analysed, DR was found in 27.9% of people, maculopathy in 16.1%, Proliferative diabetic retinopathy (PDR) in 2.8%, non-proliferative diabetic retinopathy (NPDR) in 25.1% [8]. In the capital city of Zambia – Lusaka, there was a lack of data on the level of retinopathy in diabetic patients and whether the patients are having regular dilated eye examination done by a health worker trained to perform fundoscopy. This study aimed at ascertaining what the prevalent severity of DR was in patients at UTHs adult hospital medical clinic to determine if there was as high a prevalence of DR at UTHs as seen in the Copperbelt. It also assessed risk factors that were associated with DR and whether diabetes patients were having dilated fundoscopy regularly.
Methodology
This was a hospital-based cross sectional study carried from 18th December, 2018 to 16th April, 2019 at the University Teaching Hospitals (UTHs) in Lusaka. The UTHs include the Adult and Emergency Hospital, Eye hospital, Cancer Diseases Hospital, Children’s Hospital, and Women and New Born Hospital. Participants were DM patients recruited weekly into the study from the Adult Hospital medical diabetes clinic. Eye examination equipment was set up in a designated room during the clinic and information collected by ophthalmic personnel from the Eye Hospital and the principle investigator. The sample size was 213 participants; calculated using the prevalence formula for a finite population. Inclusion criteria were known DM patients who consented to take part in the study. Exclusion criteria included patients with ocular media not clear for classifying fundus photos in both eyes and patients found to have retinal co-morbidities, during fundus imaging, affecting the grading of DR. Every consecutive diabetic patient meeting inclusion criteria was included in the study.
A researcher-administered questionnaire for information regarding the demographic characteristics of the patients, the relevant diabetes medical and ocular history and a section for the findings of blood pressure (BP), Body Mass Index (BMI), pin hole visual acuity (VA) and retinopathy grading was used for data collection. Other tools used included Snellen chart, pin hole, Digital Retinography System (DRS) fundus camera by Centervue, Italy, Sphygmomanometer, weighing scale and height scale, and blood collection consumables. Patients were identified as they were waiting for the physician’s review and informed consent was obtained. Those found to have ocular media not clear enough to get gradable retinal images in both eyes were excluded from the study and referred to a consultant ophthalmologist at the eye hospital for further assessment and management. After measurement of VA, BP and BMI, the participants’ pupils were dilated with one drop of a mydriatic eye drop that had a combination of tropicamide 0.8% and phenylephrine 5%. DRS fundus camera was used once the pupils were dilated to capture retinal images. Both colour and red-free retinal images were captured from both eyes and graded to assess the severity of retinopathy. The worse eye or the only eye with a gradable image was used in the analysis. The principle investigator read all retinal images and graded using the international classification of DR. One consultant ophthalmologist randomly reviewed selected images to ensure quality and adherence to the international standard and protocol for the study.
Figure 1: Procedure flow chart
Data was collected and entered in a Microsoft Excel spread sheet. Analysis was done using STATA version 13.1. Continuous variables were tested for normality using Shapiro-Wilk test. The chi square and Mann-Whitney tests were used to compare no DR to DR depending on the type of variable. To determine the correlation between two normally distributed independent variables Pearson coefficient was used; while Spearman coefficient was used for non-normally distributed variables. In the final analysis to rule out confounders, a multiple logistic regression model was constructed using a cut off of 20% for the variables. Age, HbA1c and use of Anti-HTN medication were included in the final analysis due to significant associations found in several other studies. The model helped identify factors that were associated with DR after adjusting for baseline characteristics. A p-value <0.05 was regarded as significant.
Results
The socio-demographic characteristics of participants in the study are shown in table 1 below:
Table 1: Socio-demographic characteristics of participants
| Variable | Category | Proportion (%) |
| Age | Median IQR (25%-75%) | 53 years44-63 years |
| Sex | FemaleMale | 150 (70.4)63 (29.6) |
| Occupation | Not employedInformal employmentFormal employment | 47 (22.07)109 (51.17)57 (26.76) |
| Education | None PrimarySecondaryTertiary | 35 (16.43)50 (23.47)45 (21.13)83 (38.97) |
| Smoking | YesNo | 7 (3.29)206 (96.71) |
| Alcohol intake | YesNo | 33 (15.49)180 (84.51) |
Of the 213 study participants, 30 (14.8%) had type 1 DM and 183 (85.2%) had type 2 DM. The median duration of DM was 5 years (IQR = 2-10 years). The median duration of attendance at UTHs adult hospital medical clinic was 3 years (IQR = 6 months to 7 years).
One hundred fifteen (54.5%) participants were taking insulin for DM control while 80 (37.6%) were taking oral hypoglycaemic medication. Twelve (5.6%) participants were taking both insulin and oral hypoglycaemics with 87 (40.8%) participants also taking anti-hypertensive medication.
One hundred twenty four (58.2%) participants did not report any complications arising from diabetes. However, 13 (6.1%) gave a history of diabetic foot, 67 (31.5%) had peripheral neuropathy and 3 (1.4%) had kidney-related complications.
Systolic BP measurements were normal in 117 (54.9%) participants, with 61 (28.6%) having stage 1 hypertension and 35 (16.4%) having stage 2 hypertension levels. Diastolic blood pressure measurements were normal in 142 (66.7%) participants, with 41 (19.2%) having stage 1 hypertension and 30 (14.1%) stage 2 hypertension. The BMI was normal for 78 (37.7%) participants, 69 (33.3%) participants were overweight and 60 (29.0%) of the participants were obese.
When asked if they had had a dilated eye examination in the preceding 12 months, 55 (25.8%) responded positively. The median age of participants who had the examination (58 years) was significantly higher than those who did not (52 years). Univariate logistic regression analysis revealed that those with tertiary level of education (p=0.038), longer duration of medical diabetes clinic attendance (p=0.009), and those with knowledge that diabetes has eye complications (p=0.034) were more likely to have had a dilated eye examination in the preceding 12 months.
Regarding knowledge about the ocular complications of DM, 104 (51.2%) participants had some idea with poor vision and blindness being the most common responses. There was no statistically significant difference in terms of gender (p=0.203) nor education level (p=0.114) in relation to knowledge about the ocular complications of DM.
Diabetic retinopathy and maculopathy were classified using the ICO international classification of
DR. DR was present in 101 (47.4%; 95% CI 40.7% – 54.2%) participants while 112 (52.6%; 95% CI 45.8% – 59.3%) participants had no DR. Eighty two (38.5%; 95% CI 32.1% – 45.3%) had NPDR and 19 (8.9%; 95% CI 5.7% – 13.6%) had PDR. 24 (11.3% with 95% CI 7.6% – 16.3%) participants had DME. No participant had had previous laser treatment for DR.
In the univariate analysis (table 2) the factors significantly associated with DR included duration of DM (p=0.001), duration of clinic 5 attendance (p=0.040), type of DM medication used (p=0.010), DM related illnesses (p=0.001), BMI class (p=0.030) and alcohol intake (p=0.002).
In the multiple logistic regression analysis (table 3), duration of DM (p<0.0001), having diabetic foot (p=0.006) and alcohol intake (p=0.005) were maintained as factors found to be statistically significant associations of DR.
For maculopathy, only duration of DM was found to be a statistically significant association (Odds ratio=1.10 with 95% CI 1.03-1.18).
Figure 2: Distribution of DR among participants
Table 2: Univariate analysis of associations of Diabetic retinopathy and maculopathy
| Variable | No DR | NPDR | PDR | p-value | No DME | DME | p-value | |
| Age (median years) | 51.5 | 54 | 52 | 0.712 | 53 | 57.5 | 0.027 | |
| Sex (n)FemaleMale | 4072 | 1864 | 514 | 0.110 | 5613 | 717 | 0.963 | |
| Occupation (n)NoneInformal Formal | 265728 | 174322 | 397 | 0.847 | 409652 | 6135 | 0.762 | |
| Education level (n)None PrimarySecondaryTertiary | 18332239 | 15111937 | 2647 | 0.241 | 30424176 | 5847 | 0.501 | |
| Smoking (n)No Yes | 1102 | 774 | 181 | 0.424 | 1836 | 231 | 0.766 | |
| Alcohol (n)NoYes | 10012 | 6813 | 118 | 0.002 | 16128 | 195 | 0.387 | |
| Type of DM (n)Type 1Type 2 | 1894 | 1072 | 217 | 0.670 | 30159 | 024 | 0.035 | |
| Duration of DM (years) | 3 | 7 | 10 | <0.0001 | 5 | 10.5 | <0.0001 | |
| DM medication (n):NoneInsulinOral hypoglycaemicBothAnti-HTN medication (n)YesNo Other DM-related illnesses (n):Renal diseaseDiabetic footPeripheral neuropathyNoneDuration of medical diabetes clinic attendance (years)BMI class (n)NormalOverweightObese HbA1c (%)SBP (n)NormalStage 1 HTNStage 2 HTNDBP (n)NormalStage 1 HTNStage 2 HTN | 562441 4567 0338652 3931397.5 662818 732415 | 143317 3646 2524514 3226218.17 412912 551413 | 01054 613 15583 71209.3 10415 1432 | 0.010 0.603 0.001 0.040 0.030 0.2580.378 0.889 | 5105727 76113 18621122 6460608.0 1075527 1273725 | 11085 1113 255123.5 14909.2 1068 1545 | 0.007 0.598 <0.0001 0.071 0.003 0.2500.058 0.595 |
Table 3: Multiple logistic regression analysis of risk factors associated with diabetic retinopathy
| Variable | Odds ratio | 95% Confidence interval | p-value |
| Age | 1.00 | 0.97 1.02 | 0.836 |
| Alcohol | 3.48 | 1.46 8.26 | 0.005 |
| Duration of DM | 1.12 | 1.05 1.19 | < 0.0001 |
| DM medication:InsulinOral hypoglycaemicBoth | 15.77 23.72127.48 | 0.47 524.550.71 791.373.16 5147.44 | 0.1230.080 0.010 |
| Anti HTN medication | 1.33 | 0.66 2.66 | 0.420 |
| Other DM-related illnesses:Renal diseaseDiabetic footPeripheral neuropathy | 23.026.283.00 | 1.57 337.681.68 23.540.430 1.63 | 0.0220.0060.601 |
| Duration of medical diabetes clinic attendance HbA1c | 0.98 1.05 | 0.91 1.06 0.90 1.22 | 0.591 0.558 |
Glycated haemoglobin (HbA1c) findings showed a median value of 8.1%, with the lowest being 4.6% and highest 13%. The median HbA1c level increased with the severity of DR as shown in figure 2 below.
Figure 3: HbA1c levels in different grades of DR
Using the International Classification of Diseases 11 (ICD 11) VA was graded, upon which classification of visual impairment and blindness was determined. One hundred sixty three (76.5%) participants had normal visual acuity, 44 (20.7%) had visual impairment and 6 (2.8%) were blind.
Table 4: ICD 11 class of visual acuity of participants
| ICD 11 Class | Visual acuity | Proportion (%) |
| Normal vision | ≥ 6/12 | 163 (76.53) |
| Visual impairmentMild ModerateSevere | < 6/12<6/18<6/60 | 24 (11.27)17 (7.98)3 (1.41) |
| Blindness | <3/60 | 6 (2.82) |
DISCUSSION
This was a cross sectional study looking at the prevalence of DR and its associated risk factors. Duration of DM, microvascular complications and alcohol intake were found to be associated with DR. The prevalence of DR was found to be 47.42% (95% CI 40.75% – 54.18%) in this study. This result reaffirms the findings of the Copperbelt province study where prevalence of DR was found to be 52% [6].
The median age of participants in this study was 53 years (IQR=44 to 63 years) which was consistent with many studies looking at patients with both type 1 and type 2 diabetes [6,9]. This study had a high ratio of female to male participants (2.3:1). Generally, females are more than males in study populations of type 2 DM or type 1 and 2 combined [10,11]. The number of smokers was very small in this study and no association was found with DR. Smoking is not an established known risk factor for DR, particularly type 2 DM, though it has been associated with DR in type 1 DM [12].
In studies involving the adult population, type 2 DM is more prevalent than type 1 DM [13,14] and this was the case in this study too. The type of DM had no impact on DR in this study. Type 1 DM participants had a median duration of DM of 5 years while for type 2 DM participants it was 5.5 years.
Among the participants, 40.85% were taking anti- hypertensive medication. Among those found to have stage 2 hypertension level systolic and diastolic BP, less than 70% were taking anti-hypertensive medication. However, no significant association was found with any of these three BP parameters and DR in this study. This is comparable to findings from studies by Akpalu (2011) and by Rotimi et al., (2003) from Africa [15,16]. However, major epidemiological studies such as the UKPDS have shown that strict control of BP is associated with reduced risk of DR and it’s progression though the effect wears off with cessation of such control [17]. Other studies also show an association with stage 1 or 2 hypertension level of blood pressure and DR [8,18]. Findings from a review done by Do et el in 2015 showed that strict hypertension control had a modest effect in reducing the incidence of DR by 4 to 5 years but lack of effect on progression of DR over the same time period [19]. Thus, hypertension control in DM patients is advised to reduce the overall morbidity associated cardiovascular disease rather than to reduce progression of DR [20].
Retinopathy, nephropathy and neuropathy are all microvascular complications of DM and have been shown to be present simultaneously in an individual. Three patients had nephropathy in this study and 2 of these had NPDR while 1 had PDR. Having a DM-related complication was also found to be significantly associated with DR in this study (p<0.0001).
The University Teaching Hospitals are tertiary level referral hospitals for the whole of Zambia. As such most of the DM patients seen are those that were poorly controlled from local health centres or have severe comorbidities. Type 1 DM patients require insulin for adequate glycaemic control while for type 2 DM patients oral hypoglycaemic medication may be enough but about one third need insulin [21]. These two factors can explain the high number of participants using insulin in this study. Unadjusted p-value suggested an association between medication used and DR though this was not significant in the multiple analysis. Some studies report majority of participants taking oral hypoglycaemics [6] while others report higher rate of insulin use, particularly in hospital patients [14,22].
Strict glycaemic control has been shown to reduce the occurrence of DR as presented in the UKPDS study where mean HbA1c was 7.0% in the strict glycaemic control group and 7.9% in the conventional group [23]. A systematic review looking at HbA1c and DM showed significant association with DR at HbA1c levels of 5.8% to 7.3% and suggest a threshold of 6.5% for diabetes-specific retinopathy [24]. In this study, there was no statistically significant association between the overall median HbA1c level and DR. However, the box and whisker plot shown in figure 3 indicates the median HbA1c was progressively higher from the ‘no DR’ to ‘PDR’ groups. The median for the ‘no DR group’ (7.5%) was higher than that of the ‘no DR groups’ in other studies showing generally poor glycaemic control in this study sample [18]. Other studies with similar samples of mostly type 2 DM patients also did not find association between HbA1c and DR [25,26]. Generally, when looking at glycaemic control and DR, evidence is available to show intensive glycaemic control lowers risk of incidence and, to a lesser extent, risk of progression of DR in patients with younger-onset or type 1 disease [27]. For older or type 2 patients, this is not so apparent [28].
A little more than half of the participants (51.1%) in this study had some knowledge about diabetes affecting the eyes though the knowledge was not specific to retinopathy. Sadly, this knowledge gap was seen even among the participants who had a positive medical background. The most common responses were visual impairment and blindness. Other studies have shown a much higher percentage of diabetic patients with knowledge that diabetes affects the eye; 75.62% from a Saudi Arabian study and 89.0% from a Tanzanian study [29,30]. This highlights gaps in sensitisation and dissemination of information at the primary health care level as well as during specialized medical diabetic clinic visits in this setting.
Despite about half of participants knowing that diabetes affects vision, only 28.8% had had a dilated fundal eye examination in the preceding twelve months. This low rate is consistent with other studies- 28.8% in the study by Mumba et al. in Tanzania [29]. Yearly eye screening for DR is the current recommended practice for all diabetics, particularly those with no DR on initial screening [2]. This could be a proxy indicator of physicians eventually referring diabetic patients for fundoscopy overtime though this could also be attributed to patients developing visual complaints.
As seen with other hospital-based studies, the prevalence of DR (47.42%) in this study was higher than findings from population-based studies. This value was closer to the 49% prevalence of DR found in the study by Akpalu et al in Ghana [15] and the 52.0% in the Copperbelt province of Zambia [6]. In contrast, DR was found in only 27.9% in a population-based Tanzanian study on enrolment into a screening programme [8]. The systematic review by Burgess et al had a range of DR from 9.55% to 62.4%, with maculopathy ranging from 1.2% to 31.1% across East and Southern Africa [7]. Grading of DR by means of retinal photographs (used in this study) as opposed to ophthalmoscopy has been found to produce higher frequency of DR detected [31].
Final risk factor analysis revealed duration of DM as the most important risk factor for DR in this study. This is consistent with all studies done analysing risk factors and it is known that all diabetics develop DR overtime [32]. Alcohol intake and diabetic foot were also found to be associated with DR in our study; though the 95% confidence intervals were not even and slightly wide suggesting less significance than indicated by the p-value. A UK primary-care based study did find an association of alcohol intake with DR [33]. According to a meta-analysis study in 2016 by Zhu et al., alcohol intake was not associated with increased risk of DR, even in subgroup analysis of type of alcohol [34]. No African study was part of the meta-analysis though. In our study, no quantification of type and frequency of alcohol intake was done and this would need to be further studied to explore any real association with DR.
CONCLUSION
From this study, a high prevalence rate of DR at 47.42% (95% CI 40.75% – 54.18%) was seen among patients attending the UTHs-Adult Hospital medical diabetic clinic in Lusaka. NPDR was present in 38.5% and PDR in 8.92% while 11.27% (95% CI 7.46%-16.13%) had diabetic macula oedema. Duration of diabetes was the most significant association found with retinopathy. Median HbA1c was 8% which showed poor average glycaemic control among participants. Even though 51.1% had the knowledge that diabetes affects the eyes, only 25.82% had had a dilated eye examination in the preceding twelve months.
RECOMMENDATIONS
From these findings, it is recommended that more sensitisation programmes in the primary health care facilities on need for regular retinal examinations in diabetic patients are needed. Also, regular HbA1c testing needs to be used as a means to assess glycaemic control in patients attending the medical diabetic clinic. This includes advocating for supportive laboratory services. Another recommendation is to scale up country wide DR screening using retinal photography across Zambia. This includes use of telemedicine for interpretation of images from areas with trained photographers but not trained image graders or ophthalmologists. Further studies are also needed with larger sample sizes for a definite risk factor analysis in both hospital-and community-based settings in Lusaka.
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