The largest age group was in the 51 to 60 years old range, with more females than males (58.9%) and the population was predominantly Malay (consistent with the district and national population breakdown). Most patients had DM of less than 10 years (61.9%), and the mean duration of DM was 9.4 ± 7.4 years. Thirty patients (8.8%) had DM of less than one year. The mean serum HbA1c level was 8.5% ± 1.9% with 150 patients (44.0%; 95% CI, 38.9%-49.4%) categorized as having good control (HbA1c ≤7.5%). Hypertension (86.8%) and dyslipidemia (84.5%) were common and 22.6% had microalbuminuria or worst. Patients’ demographics and profiles are shown in Table 1.

The prevalence of DR was 22.6% (95% CI, 18.8-27.1). Among patients with DR, 14 patients (18.2%; 95% CI, 9.8-28.4) had PDR with overall prevalence of PDR being 4.1% (95% CI, 2.1%-6.5%). Macular oedema occurred in 17 patients (5.0%; 95% CI, 2.9-7.7) and VTDR occurred in 9.7% (95% CI, 6.8%-13.3%) of all patients. The breakdown is shown in Table 2.

In univariate analysis, age groups (p = 0.030 for trend), longer duration of DM (p = 0.002 for trend), DM control (p < 0.0001 for trend) and presence of any microalbuminuria (p < 0.05) were significantly associated with DR (Table 3). Sex, hypertension, and dyslipidemia did not show significant associations (all p > 0.05). When these variables were entered into multivariate analysis, duration of DM, poor control of DM, and presence of microalbuminuria remained significantly associated with presence of any DR (Table 4). Duration of DM for 11 years or more, having poor DM control, and microalbuminuria were associated with any DR. Compared to the youngest age group (<40 years), the 61 to 70 and over 70 age groups had 80% to 90% lower risk for DR (p = 0.006).

Our study showed that DR is common among patients with type 2 DM in Brunei Darussalam with one in five affected and that certain variables were associated with the presence of DR. The prevalence of DR at 22.6% in our study is within the range reported across continents in the literature as shown in Table 5 [7-9,11-25]. Globally, reported rates range from those in Spain (12.3%) [15], India (15.4%) [18], and Korea (15.8%) [24] to high rates reported in Indonesia (43.1%) [23], Malaysia (39.3%) [20], and Saudi Arabia (36.4%) [17]. Studies from China, UK, and US all reported rates of above 30% [11,14,19]. Overall, there seems to be no definite correlations with the relative development of the countries. These variations can be accounted by several factors especially the patient population studied in these publications. Generally, studies tend to be done in academic or large centers and this can result in over representations of more severe cases. Milder or controlled cases are usually followed up in peripheral clinics and such patients may not be included in the population samples. Availability of healthcare and its’ infrastructure are also important. With greater accessibility, the proportion of patients diagnosed with DM early is higher and the proportion of undiagnosed cases is expected to be lower. On the other hand, in less developed countries where prevalence of obesity is low or just beginning to increase, the prevalence of DM may similarly be low or just increasing. Therefore, the true prevalence of complications related to diabetes such as DR is likely to be lower in less developed countries when compared to developed countries. Despite this, reported figures represent major universal public health concern with one in eight to almost one in two having DR [11-26]. This is particularly important given that DR is the main cause of visual impairment and blindness in adults and that the prevalence of DM is increasing [1].

Similarly, there is also heterogeneity in the reported prevalence of VTDR globally (Table 5) [7-9,11-25]. Interestingly, the prevalence of VTDR is generally low in developed nations and high in developing countries. This may be related to better control of DM and timely treatment of DR in the more developed world. On the other hand, changing food habits, increasing prevalence of non-communicable diseases such as obesity, hypertension, and dyslipidemia, and non-availability of timely and appropriate treatment of retinopathy may be reasons for increased rates of VTDR in developing countries. Further research is required to ascertain the reasons.

The current rate of 22.9% for any DR in Brunei Darussalam is slightly higher than the rates (18.0%-19.0%) reported in the previous local studies from nearly two decades ago [7-9]. The combined rate of severe DR and PDR (6.3%) in the current study is also higher than the last study of 3.7% carried out more than 5 years ago [9]. The study by Da and Nyunt [7] which was conducted in the same institution as the current study provided a unique opportunity for comparison. The proportion of patients with good control of DM (HbA1c <8.0%) has declined from 48.6% in the year 2003 to 60.1% at present. In contrast, the proportion of patients with hypertension has increased from 61.7% to 86.8% and likewise dyslipidemia has increased, reflecting changes to the patient demographic over time [7]. Retinopathy has increased from 18.0% to 22.9%. These differences may be a true reflection of increasing prevalence of DR in Brunei Darussalam. Perhaps the prevalence of non-communicable diseases including DM has been increasing with greater awareness and understanding, contributing to the increasing number of patients being diagnosed with DM.

Our study showed several factors to be significantly associated with DR. Among the known risk factors for development of DR, duration of DM is the most important non-modifiable factor. According to large epidemiological studies, the risk of developing DR increased several folds after a latent period of 8 to 10 years’ duration of DM [4,25]. We showed that patients who had DM of more than 10 years were significantly associated with DR: 11 to 15 years (odds ratio [OR], 3.88), 16 to 20 years (OR, 3.39) and over 20 years (OR, 5.43). Among the patients in this study, 61.9% have DM of less than 10 years duration. This indicates a likely increase in the prevalence of DR in the population in the coming years.

In the management of DM, good control of diabetes is very important to reduce the risk of future complications. However, even with good control, complications do occur due to the chronic nature of the disease. Our study showed a linear correlation between DR and levels of control: good control (14.3%), suboptimal control (20.3%) and poor control (35.9%). Poor control was significantly associated with development of DR (OR, 2.01). The American Diabetes Association recommends 7% as target of HbA1c level for good control [26]. The Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study showed that increasing levels of HbA1c correlated well with occurrence and progression of DR [27,28]. However, later studies demonstrated that strict control of DM does not give clear benefits in controlling macro-vascular diseases, unlike in microvascular diseases [29-31]. The Action to Control Cardiovascular Risk in Diabetes study showed that intensive control of DM increased the risk of mortality especially in type 2 DM [32]. In our setting, we use HbA1c ≤7.5% as a target value for good control. Later analysis of the above mentioned and similar studies suggest that HbA1c targets should be individualized based on the duration of the DM and existing comorbidities [33]. Generally, younger individuals with DM who are otherwise healthy should aim for a lower target value whereas older individuals with cardiovascular comorbidities should have a higher target level of HbA1c.

Albuminuria in DM is a wide spectrum ranging from micro to macroalbuminuria, which usually correlates with duration and severity of the disease. It is an important predictor of DM nephropathy. Not unexpectedly, our study showed a positive association between microalbuminuria and DR (OR, 2.00). Therefore, it is important that interval screening for microalbuminuria be carried out.

Interestingly, we found that among the age groups, the older patients had a lower risk for DR, (61-70 years group with OR 0.22, p = 0.006 and >70 years group with OR 0.09, p = 0.007) when compared to the over 40 years group. This probably indicates for uncertain reason that the younger age groups were at higher risk for DR. At first sight, this may seem contradictory to our finding that a longer duration of DM was significantly associated with DR. We found that the older groups (61-70 and >70), despite having a longer duration of DM, had better mean HbA1c levels and good DM control when compared to the younger age groups. Furthermore, factors that were not considered in our study may contribute, such as genetic predisposition and lifestyle. The phenomenon of young DM patients having more complications is probably a reflection of the changing demographic in DM, with more young people developing DM, corresponding with the increasing prevalence of obesity and metabolic syndromes.

Among the factors assessed, hypertension and hyperlipidemia were not associated with DR. Hypertension can cause retinopathy and nephropathy and is often correlated with severe and chronic hypertension. In DM, the management of hypertension is more aggressive with lower target levels making contribution of hypertension less important than DM itself [34,35]. There have been several studies examining the effect of hypertension and hyperlipidemia in relation to diabetic complications. A meta-analytic review published in Cochrane patients concluded that there is only weak evidence for beneficial effects of reduction in blood pressure with respect to preventing DR [36]. The Action to Control Cardiovascular Risk in Diabetes Eye Study showed that intensive glycemic control together with control of dyslipidemia using fenofibrate and simvastatin reduced the proportion of eyes that had progression of DR by one-third [37]. However, the beneficial effect may be due to the intensive management of DM rather than lipid control. Similar to the management of hypertension, the recommendation for initiating treatment for dyslipidemia in patients with DM is also more aggressive. All our patients with diagnosis of hypertension and hyperlipidemia were receiving treatment.

There are several limitations to our study that need to be considered when interpreting the study findings. First, our study was a retrospective study and there are inherent limitations with retrospective studies such as incomplete data and selection bias. Our study looked into already known risk factors for DR in the context of Brunei Darussalam. Second, this study was conducted in a single hospital and might not accurately represent the whole country. However, the patient population breakdown in our study is consistent with that of the national breakdown and previous studies from different districts have reported comparable results [7,8]. Third, we only included patients over a 3-month period, and it is possible that more patients with significant DR would be included, given their shorter follow-up intervals. This may inflate the prevalence of DR. However, the total number of patients with significant PDR who will have shorter follow-up interval of 3 months is small. Fourth, our study population excluded patients with complicated diseases such as diabetic foot disease, cardiac, or renal disease, as they typically received treatment and are followed up in the tertiary hospital. Such patients are likely to have DR and not captured in our study. Hence, the prevalence of DR could be higher than our estimate. However, the proportion of such patients is estimated to be small.

We showed that DR in Brunei Darussalam is common with a rate of 22.6%, which is comparable to what has been reported in the literature. DR affects one in five patients with type 2 DM in Brunei Darussalam, comparable to rates reported for other Asian populations. A third of those with DR had either PDR or VTDR. Longer duration of DM, poor control of diabetes, and presence of microalbuminuria are significantly associated with DR. Interestingly, age groups were not linearly associated with DR, and this requires further study. Since a large percentage of DR occurs in young and middle-aged patients, it is worthwhile to advocate strict control of DM from the outset. Public and targeted awareness programs are needed, especially in countries with young and growing population, like Brunei Darussalam.