Diabetic Retinopathy Management Guidelines

Rahul Chakrabarti; C Alex Harper; Jill Elizabeth Keeffe


Expert Rev Ophthalmol. 2012;7(5):417-439. 

In This Article

Assessment of DR: Frequency of Examination

While there was general consensus among published guidelines regarding the timing of the initial examination, there were differences between follow-up examination schedules (Table 4).

No Retinopathy

For patients without evidence of retinopathy, guidelines from South Africa, NICE, RCO, AAO and the Pacific Islands recommended annual follow-up. The AAO referenced the WESDR that demonstrated that at 1 year, 5–10% of patients with a normal retinal examination at baseline had progressed to some evidence of DR. The 4-year incidence of any DR was 59% in patients with Type 1 DM and 34% in Type 2 patients.[43] The NHMRC was the only publication that identified and recommended that patients at elevated risk (longer duration, poor glycemic control, hypertension, hyperlipidemia or from an indigenous background) required at minimum annual review. The necessity for greater vigilance particularly for the indigenous population is supported by recent evidence which demonstrated that indigenous people in Australia developed vision-threatening disease (particularly clinically significant macular edema [CSME]) from a normal baseline at an earlier stage than nonindigenous populations.[76,77] Extension of the examination schedule to 2-yearly intervals for most patients was recommended by the NHMRC, Scottish Intercollegiate Guidelines Network (SIGN), New Zealand and Malaysia. Evidence-based justification for the timing between examinations were based on findings from studies subsequent to WESDR, including the UKPDS, showed that 22% with a normal baseline examination developed DR after 6 years.[78] Comparable data showing ≤half the incidence in the WESDR was also demonstrated in the Blue Mountains Eye Study,[79] Melbourne Visual Impairment Project[80] and UKPDS.[78] In the context of these findings, The Liverpool Diabetic Eye Study concluded that the rate of progression to sight-threatening DR among people with normal baseline was so low that a conservative screening period of 2–3 years could be reliably adopted.[81] A more recent meta-analysis by Wong et al. demonstrated that for patients with nil retinopathy at baseline, the progression to PDR after 4 years was 2.6% in studies published between 1986 and 2008, compared with 6.3% in prior studies.[82] The authors concluded that this difference may be accounted for by optimization of risk-factor control among patients with DM. This was supported by a meta-analysis of health economic evidence that demonstrated that for patients with good glycemic control and no background retinopathy, biennial or triennial screening was more cost effective than annual examination.[83] Despite this evidence, guidelines developed for low-resource areas (South Africa, Kenya and the Pacific Islands) all recommend annual screening intervals. The rationale for annual screening in these areas can perhaps be contextualized by the differences in disease prevalence and 'high-risk' ethnic groups. Furthermore, it must be considered that findings from the Liverpool Diabetic Eye Study related to the end point of sight-threatening disease. The extension of the screening interval beyond 2 years failed to consider the effect that lower levels of DR severity impart on patient visual morbidity, and the additional benefits associated with clinician–patient continuity of care to opportunistically detect other associated eye conditions more frequent in DM (e.g., cataract and glaucoma).[84,85] Thus, at present, current evidence indicates that patients without an elevated risk of DR can safely be reviewed at 2-yearly intervals.

Mild-to-moderate NPDR Without Macular Edema

The recommended frequency of examination for patients with mild-to-moderate nonproliferative DR without macular edema varied between published guidelines. While all guidelines recommended annual examination, the AAO, WHO, Pacific Islands and Malaysia suggested patients could be reviewed more frequently, at 6–12 monthly intervals. The AAO referenced the WESDR that demonstrated that 16% of Type 1 DM patients with mild retinopathy (hard exudates and microaneurysms only at baseline examination) progressed to proliferative disease after 4 years.[52] For Type 2 DM, 34–47% experienced worsening of retinopathy over a similar period.[86] More conservative estimates of progression were demonstrated in the 6-year follow-up data from the UKPDS. This showed that 29% of patients with retinopathy at baseline progressed by at least two ETDRS levels of severity. Eighteen percent with mild-to-moderate NPDR at baseline progressed to need photocoagulation at 6 years.[78] Recently, a 4-year follow-up of patients with Type 2 DM demonstrated an escalation in incidence of DR from 5.8 to 20.3% between 1- and 2-year follow-ups.[87] This strongly supports the current recommendations for at least annual review in these patients.

Severe NPDR

In the context of patients with severe nonproliferative DR, all guidelines addressed the necessity for more frequent review of patients. Prompt referral within 4 weeks was advocated by NICE, New Zealand/Pacific Islands, Malaysian and South African guidelines. Comparatively, the WHO, AAO, NHMRC, RCO and SIGN while acknowledging the importance of early examination by an ophthalmologist, offered a range between 2 and 6 months. The rationale for at least four monthly examinations was derived from the ETDRS protocol, which reviewed patients with mild-to-severe NPDR. This demonstrated that 45% of patients with severe NPDR developed PDR within 1 year, increasing to 71% after 5 years.[3] Subsequent analyses from the ETDRS demonstrated that early referral for retinal photocoagulation for patients with severe NPDR reduced the risk of severe vision loss or need for vitrectomy by 50%, compared with deferring until high-risk PDR developed.[88] The difficulty in determining an 'optimal' period of review for severe NPDR rests with limitations in the literature. As highlighted by Wong et al., many of the 'landmark' studies had larger proportions of more advanced DR at baseline.[82] In addition, the advances and access to modern treatment modalities would therefore pose challenges to designing a new prospective study. Thus, given the evidence that suggests the propensity for severe NPDR to progress rapidly, current evidence supports a maximum of 4-monthly intervals.