We found that the management of modifiable risk factors in the majority of patients with sight-threatening diabetic retinopathy referred by our eye department to a dedicated diabetic retinopathy clinic was suboptimal. Changes to the medical management of these patients were made in 75% of the patients who attended the diabetic retinopathy clinic, which suggests that input from diabetes specialists is beneficial to patients with worsening retinopathy. Our results support a report published by Diabetes UK which recommends that patients with diabetes and retinopathy requiring active management or complex monitoring should be managed by specialist teams .
Eye specialist input in the treatment of diabetic retinopathy is ultimately limited without the optimization of medical diabetes treatment [10, 11]. Poor glycemic control, together with other cardiovascular risk factors, including high blood pressure, an abnormal lipid profile, and a high BMI, accelerate the progression of diabetic retinopathy and are associated with a poorer prognosis [2–4, 12–17]. Physicians are best placed to manage medical risk factors and early medical input in patients, and particularly in those with significant retinopathy it is vital to reduce morbidity and mortality. Ideally eye clinics would be combined with physician input, but such treatment strategies are complex to organize and represent an inefficient use of physician time .
A HbA1c level of >8.0% has been associated with STDR . Numerous randomized control trials have shown that optimal long-term control of blood glucose reduces the risk of retinopathy. The Diabetes Control and Complications Trial (DCCT) and the UK Prospective Diabetes Study (UKPDS) both showed statistically highly significant reductions in the incidence and progression of retinopathy in patients who were randomized to tight blood glucose control . Among the patients in our study, 84% had an HbA1c of >8% at their initial appointment at the diabetic retinopathy clinic, and changes were made immediately in 31% of these patients to hyperglycemic medication.
The use of pioglitazone has been associated with macular edema [21, 22]. Two patients in our study with diabetic maculopathy were on pioglitazone at presentation; this medication was stopped in both patients and an alternative glycemic agent prescribed. Stopping pioglitazone without the substitution of an alternative agent may lead to a deterioration in glycemic control .
The UKPDS found that tight control of blood pressure led to a 34% reduction in the rate of progression of retinopathy; more specifically, this trial found that for each 10 mmHg decrease in systolic blood pressure there was a 13% reduction in the risk of retinopathy [3, 5]. The UKPDS also showed that in patients with T2D, systolic blood pressure was strongly linked to the incidence of diabetic retinopathy . The Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) found diastolic blood pressure to be a significant indicator of progression of diabetic retinopathy in patients with younger onset T1D. The WESDR also found that in patients with T1D and T2D, elevated diastolic blood pressure was associated with a significantly increased 4-year risk of developing macular edema [25–27].
In our study 72% patients had a blood pressure that surpassed the target of 130/80 mmHg at the initial clinic visit, and changes to blood pressure management were made in 57% (13/23) of these. A further three patients were referred for 24-h blood pressure monitoring. These findings suggest that blood pressure, a very easily measured parameter, may be a strong determining factor in identifying patients who would benefit from referral to the diabetologist. One study has suggested that blood pressure should be measured in all patients at every diabetes clinic appointment with the ophthalmologist . However, in another study blood pressure recordings at an eye clinic were found to be significantly higher than comparative diabetes clinic measurements, possibly secondary to the white-coat effect . Clearly, the benefits of one-off blood pressure measurements at eye clinics is of debatable value, and home and ambulatory blood pressure monitoring can provide objective data regarding individual blood pressure control.
Hypertension worsens with the progression of diabetes . In our study, after 12 months of follow-up, blood pressure improvements were less consistent than those for glycemic control (Table 5). Only one additional patient had a combined target blood pressure. Three patients had an increase in their diastolic blood pressure such that it was no longer possible to achieve the target. The reasons for this increase are likely multifactorial and include the possibility of white-coat hypertension. Of 28 patients, seven (25%) had a drop in their diastolic blood pressure that was ≥10 mmHg at the follow-up visit as compared to the initial visit; 12 patients (43%) had an equivalent drop in their systolic blood pressure.
No patients in this study were prescribed fenofibrate either prior to or at the initial clinic visit. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study group highlighted that fenofibrate may reduce the rate of progression of diabetic retinopathy . The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study noted a 37% reduction in the need for laser treatment in patients with T2D who were taking fenofibrate . Following this study, Australia’s Therapeutic Goods Association approved its use to slow the progression of diabetic retinopathy in patients with T2D . The use of fenofibrate alongside statins is associated with an increased risk of myopathy and rhabdomyolysis . NICE guidance recommends against the use of fibrates for the prevention of cardiovascular disease in patients with T1D and T2D , but in the UK there is no current guidance on the use of fenofibrate in patients with diabetic retinopathy.
Statins have been shown not to have a significant effect on the progression of diabetic retinopathy despite being effective in treating hyperlipidemia [33–35]. Of the 32 patients in our study, 72% had changes made to their management which involved the prescription of statins with the aim to reduced overall systemic risk.
A pre-determined protocol was used to determine which patients should be referred to the diabetologist, which resulted in all patients with STDR being referred to the dedicated diabetic physician clinic. An alternate strategy of only referring patients with suboptimal diabetes control or management could be considered, as recommended by the UK Royal College of Ophthalmologists; however, key information, such as HbA1c and current medical management, is often unknown or unavailable [36, 37]. Ultimately, ophthalmologists need to weigh advice from both the Royal College of Ophthalmologists and Diabetes UK against their knowledge of the capacity of local services when deciding which patients would benefit most from specialist input in their diabetes care. Improved collaboration with GPs and local protocols could prevent unnecessary referrals and enhance monitoring of modifiable risk factors in patients with STDR such that early specialist input can be achieved as required.
Failure to attend outpatient appointments is a particularly prevalent issue in the diabetic population and is associated with poorer outcomes [38, 39]. Of the 54 patients referred by our eye department to the diabetic retinopathy clinic, 22 failed to attend their initial clinic appointment. One study found that the presence of major diabetic complications was associated with improved clinic attendance . Only three of the 32 patients who presented to the diabetic retinopathy for their initial appointment failed to attend their first follow up appointment after 12 months, possible due to an increased understanding of the importance of improvements to their systemic control.
A strength of the study was our ability to access data from both the eye department and the diabetes clinics. Limiting factors include the retrospective nature of our study and our small sample size. The longest period of follow-up data was from the first clinic appointment up to 12 months following the initial visit. The availability of additional follow-up data was limited due to the high turnover of patients in the clinic. Patients who require longer term follow-up are referred to a general diabetes clinic for ongoing management, and those who are on maximal medical therapy are discharged to the care of their GP with the option of re-referral if required.