B WHAT DO WE KNOW ABOUT DIABETIC RETINOPATHY?
1 SIGN Guidelines – The Evidence
The Scottish Intercollegiate Guidelines Network (SIGN; http://www.sign.ac.uk/) was established in 1993 by the Academy of Royal Colleges and their Faculties in Scotland, to develop evidence-based clinical guidelines for the National Health Service (NHS) in Scotland.
Clinical practice guidelines have been defined as “systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances.” They are designed to help practitioners assimilate, evaluate and implement the ever-increasing amount of evidence and opinion on best current practice. Clinical guidelines are intended as neither cookbook nor textbook. Where there is evidence of variation in practice, which affects patient outcomes and a strong research base providing evidence of effective practice, guidelines can assist doctors and other health care professionals in making decisions about appropriate and effective care for their patients.
The accepted criteria for validity of guidelines have evolved over the past decade from the essential elements of good guidelines identified by the US Institute of Medicine in 1990. These recommended attributes of good guidelines included validity, reliability, clinical applicability, clinical flexibility, clarity, multidisciplinary process, scheduled review, and documentation. The recommendations were underpinned by the twin themes of credibility and accountability: “The link between a set of guidelines and the scientific evidence must be explicit, and scientific and clinical evidence should take precedence over expert judgement.” SIGN’s original Criteria for Appraisal of Clinical Guidelines for National Use, and the more recent AGREE (Appraisal of Guidelines, Research and Evaluation for Europe www.agreecollaboration.org) guideline appraisal instrument are based on these founding principles of guideline development.
Management of Diabetes Section 6: Prevention of Visual Imparment
The following section is taken from SIGN publication No 55- the management of diabetes, November 2001.
Blindness is one of the most feared complications of diabetes with an incidence of 50-65 per 100,000 diabetic population per year in Europe.245, 246, 247 However, with good care, visual impairment due to diabetes can be avoided for the vast majority of patients.
6.1 RISK IDENTIFICATION AND PREVENTION
6.1.1 RISK FACTORS FOR DIABETIC RETINAL DISEASE
The following risk factors have been shown to determine the development and progression of diabetic retinal disease:
- poor glycaemic control18, 248, 249
- raised blood pressure 232
- increasing number of microaneurysms250, 251
- duration of diabetes252, 253
- microalbuminuria and proteinuria254, 255
- raised triglycerides and lowered haematocrit256
- pregnancy.257
Evidence level 1++, 2+
The evidence with regard to smoking as a risk factor for diabetic retinal disease is conflicting. The available evidence suggests that smoking may be a risk factor for retinopathy in type 1 diabetes;258, 259 however, in type 2 diabetes, the evidence is controversial, and smoking may protect against the progression of retinopathy in certain patients.260, 261 Smoking is an independent risk factor for cardiovascular disease in all patients with diabetes and should therefore be discouraged (see sections 3.4 and 4.2).
Patients with multiple risk factors should be considered at high risk of developing diabetic retinal disease.
See section 8 for specific guidance on assessment and referral during pregnancy.
Diabetic retinal disease is the commonest cause of visual impairment in type 1 diabetes, but not in type 2 diabetes.262 Patients with diabetes have approximately a twofold increased risk of cataract263, 264 and the risk is increased with poor glycaemic control.265 One study has indicated that intensive glycaemic control reduced the incidence of cataract extraction in type 2 diabetes. Evidence level 2++
6.1.2 RISK FACTOR MODIFICATION
The evidence that modifying risk factors has a beneficial outcome in diabetic retinal disease exists for only some of the risk factors identified above. Evidence level 1++
Tight control of blood glucose reduces the risk of onset and progression of diabetic eye disease in type 1 and 2 diabetes.231, 248, 266 Evidence level 1++
Reducing HbA1c by 1.5% and, if possible, to 7% in type 1 and 2 diabetes231, 248 and reducing blood pressure to 144/82 mm Hg in type 2 diabetes reduces the incidence and progression of sight-threatening diabetic eye disease232 and this is likely also to be the case for type 1 diabetes. Evidence level 1++
Reducing blood pressure and HbA1c below these targets is likely to reduce the risk of eye disease further.171, 172 Microvascular endpoints (including retinopathy) are decreased by 37% with each 1% reduction in HbA1c, and by 13% for each 10 mm Hg reduction in systolic blood pressure172, 174 indicating that any improvement in these parameters is beneficial. Evidence level 2++
Good glycaemic control (HbA1c ideally around 7%) and blood pressure control (< 140/80 mm Hg) should be maintained to prevent onset and progression of diabetic eye disease.
Rapid improvement of glycaemic control can result in short term worsening of diabetic retinal disease although the long term outcomes remain beneficial.248 Evidence level 2++
Sight-threatening retinal disease, if present, should be stabilised before rapid clinical improvements in glycaemic control are achieved.
There is an absence of good evidence for any additional benefit of ACE inhibitors in diabetic eye disease. One recent multicentered RCT which addressed this issue was methodologically flawed,267 however there are a number of ongoing trials involving ACE inhibitor therapy.
6.2 SCREENING
6.2.1 WHO SHOULD BE SCREENED?
Up to 39% of patients with type 2 diabetes have retinopathy at diagnosis, with 4-8% being sight-threatening.231, 268 Evidence level 1++
Screening for diabetic retinal disease is effective at detecting unrecognised sight-threatening retinopathy269, 270 Evidence level 2++, 4
In type 1 diabetes, pre-proliferative retinopathy has been identified 3.5 years after diagnosis in post-puberty patients271 and within two months of onset of puberty. Evidence level 2+
For patients with no retinopathy at baseline, the chance of developing sight-threatening retinopathy within two years is less than 1% in both type 1 and type 2 diabetes on preliminary data.272, 273 Patients with existing diabetic retinal disease may require more frequent retinal examination. Evidence level 2++
Systematic annual screening for diabetic retinal disease should be provided for all people with diabetes.
Patients with type 2 diabetes should be screened from diagnosis.
Patients with type 1 diabetes should be screened from age 12 years. If onset of type 1 diabetes is post-puberty, screening should start three years after diagnosis.
6.2.2 HOW SHOULD SCREENING BE PERFORMED?
Diabetes UK proposes that an effective system of screening should achieve a sensitivity of 80% and specificity of 95% with a technical failure rate of less than 5%.274 Visual acuity measurements help in interpretation of maculopathy.275 Evidence level 4
Retinal photography can frequently achieve a sensitivity of 80% and is a more effective screening method than direct ophthalmoscopy, which only rarely achieves 80% sensitivity even when carried out by properly trained operators.270 Evidence level 2++
Between 3% and 14% of retinal photographs are ungradeable269, 276 although this rate may be improved by digital imaging. Slit lamp biomicroscopes with dilated indirect ophthalmoscopy used by properly trained individuals can achieve sensitivities similar to,270 or greater than,277 retinal photography, with a lower technical failure rate. However, slit lamp biomicroscopy has only limited validation as a screening tool.278 Evidence level 2++
Patients prefer screening to be performed at a site convenient to them.279, 280 Evidence level 4
Retinal photography or slit lamp biomicroscopy used by trained individuals should be used in a programme of systematic screening for diabetic retinopathy.
Dilated direct ophthalmoscopy should only be used for opportunistic screening.
Screening modalities should aim to detect sight threatening retinal disease with a sensitivity >= 80% and specificity >= 95%.
Patients with ungradeable retinal photographs should receive slit lamp and indirect ophthalmoscopy examination where possible.
Where possible and practical, screening should be performed at a site convenient to patients.
6.2.3 GRADING AND QUALITY ASSURANCE
When grading retinal appearances, digital imaging is more sensitive than polaroid prints and probably similar to 35 mm film.281 Initial data indicates that high-resolution automated techniques can identify the absence of microaneurysms on digital images with a sensitivity of 85%, although further research is required in this area to validate the technique.282 Evidence level 2+
All screening modalities should undergo quality assurance checks. For retinal photography it has been suggested that this should happen in 1% of photographs.269 Evidence level 4
Retinal photographs should be graded using digital images or 35 mm film by an appropriately trained grader.
At least 1% of all screening events (photography or slit lamp) should be reviewed.
The Health Technology Board for Scotland (HTBS) is carrying out a health technology assessment to determine the most efficient, effective and comprehensive national screening programme for diabetic retinopathy in Scotland.
6.3 TREATMENT
6.3.1 LASER PHOTOCOAGULATION
Laser photocoagulation for high risk retinopathy and clinically significant macular oedema (CSMO) is of proven benefit.283, 284 Older patients with diabetes and those with type 2 diabetes in particular benefit from photocoagulation before high risk features develop.285 Laser treatment for CSMO helps to stabilise vision when used for focal or diffuse maculopathy, but was not shown to be helpful for ischaemic maculopathy.284, 286, 287 It has also been shown to be effective for iris neovascularisation (rubeosis) due to microvascular disease.288 Evidence level 1++, 3
There are no clinical trial data assessing the strategy of whether treatment should be deferred in diffuse maculopathy until visual acuity is affected. There is no evidence for the use of laser in ischaemic maculopathy.
All patients with sight-threatening retinopathy (moderate proliferative diabetic retinopathy or worse) should receive laser photocoagulation.
Patients with severe pre-proliferative or mild proliferative diabetic retinopathy should receive close follow up or laser photocoagulation.
Focal or modified grid laser photocoagulation should be used for patients with focal CSMO but not for patients with ischaemic maculopathy.
Diffuse maculopathy should be treated if there is a concern that the disease is progressing.
6.3.2 VITRECTOMY
Early vitrectomy is of proven value in patients with type 1 diabetes and persistent vitreous haemorrhage for improving long term vision. Its value in type 2 diabetes is less certain. Patients with type 1 or type 2 diabetes who have severe fibrovascular proliferation with or without retinal detachment threatening the macula also have better visual acuity after vitrectomy.289 Evidence level 1+
Vitrectomy for diffuse diabetic macular oedema has been shown to result in resolution of oedema and improvement in visual acuity.290, 291, 292 Evidence level 3
Patients with type 1 diabetes and persistent vitreous haemorrhage should be referred for early vitrectomy.
Vitrectomy should be performed for tractional retinal detachment threatening the macula and should be considered for severe fibrovascular proliferation.
Vitrectomy should be considered in patients with diffuse diabetic macular oedema.
Patients with type 2 diabetes and vitreous haemorrhage which is too severe to allow photocoagulation should be referred for consideration of a vitrectomy.
6.3.3 REFERRAL INTERVALS
Delay in treatment of greater than two years from diagnosis of sight-threatening diabetic retinopathy is associated with poor outcome and severe visual loss.283 When vitrectomy is required, a delay of over one year is associated with poorer visual outcome.293 Evidence level 1++
The Royal College of Ophthalmologists275 recommends the following referral intervals:
Assess by ophthalmologist within 4 weeks if:
- there is unexplained drop in visual acuity
- there are hard exudates within 1 disc diameter of the fovea
- macular oedema is present
- there are unexplained retinal findings
- pre-proliferative or more advanced (severe) retinopathy is present.
Evidence level 4
- Assess by ophthalmologist within 1 week if:
- there is new vessel formation
- there is evidence of pre-retinal and/or vitreous haemorrhage
- rubeosis iridis is present.
Evidence level 4
Assess by ophthalmologist within 1 day if:
- there is sudden loss of vision
- there is evidence of retinal detachment.
Evidence level 4
6.3.4 CATARACT EXTRACTION IN PATIENTS WITH DIABETES
Visual outcome following cataract surgery in patients with diabetes is closely linked to age and severity of retinopathy present before surgery.294, 295 Whilst postoperative progression of pre-existing proliferative diabetic retinopathy and CSMO has been documented, the balance of evidence does not show an increase in long-term incidence of CSMO following cataract extraction.294, 295, 296 Evidence level 1++, 2++
Cataract extraction should not be delayed in patients with diabetes.
Cataract extraction is advised when sight-threatening retinopathy cannot be excluded.
When cataract extraction is planned in the context of advanced disease which is not stabilised prior to surgery, the risk of progression and the need for close postoperative review should be fully discussed with the patient.
6.3.5 METHOD OF ASSESSING RETINOPATHY
Slit lamp biomicroscopy carried out by an appropriately experienced ophthalmologist is as good as the gold standard of 7-field stereoscopic photography for the assessment of CSMO.277, 284, 286 Evidence level 1+
Either good quality 7-field stereo photography or slit lamp biomicroscopy (both dilated) carried out by an appropriately experienced ophthalmologist should be used to investigate:
CSMO
proliferative diabetic retinopathy and severe non-proliferative diabetic retinopathy.
6.4 REHABILITATION
There is very little evidence relating to programmes of rehabilitation for patients with diabetic eye disease. Awareness of low vision aids is poor, but once available, patients benefit from being instructed in their use.
Low vision aid clinics297 and community self-help groups298, 299 as part of a low vision service300, 301 can improve the quality of life and functional ability for patients with visual impairment. Evidence level 3, 4
Community support, low vision aids and training in their use should be provided to people with diabetes and visual impairment.
Patients with visual impairment should be assisted to register as blind / partially sighted at an early stage.