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Editors

PaulaSummanen
MattiSeppänen

Diabetic Retinopathy

Essentials

  • Diabetes causes diabetic retinopathy, i.e. changes in the ocular fundi. It is the most important preventable cause of visual disability in working-age people.
  • The changes develop gradually and remain asymptomatic for a long time.
  • Good glycaemic control and treatment of all risk factors prevent the development of retinopathy and its progression to a sight-threatening disease.
  • Regular examination of the ocular fundi in asymptomatic patients with diabetes (screening and follow-up) helps to find out whether there are changes due to retinopathy and to refer patients to further examinations and treatment, as necessary.
  • Screening may be carried out by fundus photography performed according to recommendations or by biomicroscopy performed by an ophthalmologist. Ophthalmoscopy or partial fundus photography are not adequately accurate screening methods.
  • Monitoring of the ocular fundi can be performed by the patient's general practitioner if the changes are quite mild. As the changes progress, decisions about monitoring as well as the need for any treatment should be made by an ophthalmologist.
  • Treatment options include fundus laser therapy, vitreoretinal surgery and intravitreal injection of VEGF inhibitor and glucocorticoid.
  • Rehabilitation should be started as soon as sight-threatening changes are noted in the ocular fundi.

Clinical picture and natural course of the disease

  • In the initial phase, the disease is completely asymptomatic.
  • Before detectable retinopathy changes appear, symptoms may include reduced contrast sensitivity and disturbances of colour vision (especially in the blue-yellow range).
  • As the disease progresses, internal haemorrhages, oedema, lipid accumulations and neovascularization may appear in the retina. The new blood vessels bleed easily and may cause haemorrhage on the retinal surface and in the vitreous chamber and cause impaired vision.

Nonproliferative (background) retinopathy

  • In nonproliferative retinopathy, the following retinal changes can be found:
    • Local dilatation of capillaries (microaneurysms) and haemorrhages
    • retinal oedema and lipid deposits left behind after the oedema has been reabsorbed (so-called hard exudates)
    • microinfarcts (so-called cotton wool spots or soft exudates)
    • Venous beading (venopathy)
    • Extensive capillary damage (intraretinal microvascular abnormalities, IRMA) appearing as areas of reticular vascular structures.
  • The first retinopathy findings are often microaneurysms or small haemorrhages. The number of aneurysms varies: some may disappear and new ones may appear. An increase in their number indicates progression of the capillary damage.
  • Microinfarcts and haemorrhages disappear with time and do not necessarily lead to permanent capillary occlusion.
  • IRMA and venous changes indicate permanent capillary occlusion.
  • Nonproliferative retinopathy is divided into various degrees of severity. Mild or moderate nonproliferative retinopathy does not require topical treatment of the eye.
  • In severe nonproliferative retinopathy (i.e. preproliferative retinopathy) there are scattered IRMA and/or venous abnormalities or several large haemorrhages in the entire fundus. In such cases, the need for laser treatment of the fundus should be individually assessed. If central oedema is also present, a VEGF inhibitor may have a beneficial effect on both.

Maculopathy and macular oedema

  • Diabetic maculopathy (sight-threatening nonproliferative retinopathy, primarily macular oedema) may develop at any stage of the disease and is more likely the more retinopathy changes there are.
  • Macular changes often heal spontaneously.
  • Macular oedema can be divided into mild, moderate and severe depending on how far from the fovea the lipid exudates and the oedema are situated.
    • Two-dimensional follow-up pictures cannot be used to assess oedema; clinical examination is needed for this, today complemented by optical coherence tomography (OCT).
  • Even mild maculopathy may affect the ability to distinguish colours and impair contrast sensitivity.
  • In severe maculopathy, vision that allows for general mobility is preserved, but when central visual acuity falls below 0.3, near vision is no longer adequate for reading a newspaper, for example. Various magnifiers may be of benefit at this stage.

Proliferative retinopathy

  • In proliferative retinopathy, neovascularization is observed on the retina and/or the optic disc in addition to nonproliferative retinopathy.
    • Neovascularization is due to extensive vascular occlusion and resulting retinal ischaemia and hypoxia.
  • Unless the posterior vitreous body has already become detached from the retina Vitreous Detachment, new vessels attach to the posterior surface of the vitreous membrane. As the vitreous body contracts, new vessels are pulled towards the centre of the eye, causing the vessels to easily bleed onto the retina, into the space between the retina and the vitreous membrane and/or directly into the vitreous body.
  • Vitreous haemorrhage Vitreous Haemorrhage (Vh) is the most common cause of sudden loss of vision in type 1 diabetes. The haemorrhage usually heals spontaneously over a few weeks or months, unless it recurs.
    • As vitreous haemorrhage is rarely associated with straining, there is usually no need to restrict exercising in a patient with retinopathy. However, extreme straining should be avoided as long as active neovascularisation is apparent, i.e. for a few weeks after laser treatment.
  • Neovasculature attached to the posterior surface of the vitreous membrane, and associated scar tissue, may cause retinal traction and detachment of the vitreous body from the retina Retinal Detachment. Small peripheral detachments do not affect visual acuity but they may require surgical treatment if there is a tear in the retina or traction on the macula.
  • Severe untreated retinal hypoxia may also lead to neovascularisation of the surface of the iris (rubeosis iridis) and the iridocorneal angle, leading to neovascular glaucoma which is difficult to treat.

Epidemiology

  • One in two patients with type 1 diabetes, and one in four with type 2 diabetes, have diabetic retinopathy.
  • Within 20 years from diagnosis, 80-100% of patients developing type 1 diabetes before the age of 30 will develop nonproliferative retinopathy and 15-50% proliferative retinopathy.
  • Only a few patients developing type 1 diabetes after the age of 30 or having type 2 diabetes develop proliferative retinopathy (approximately 20% of those treated with insulin and less than 5 % of those treated with diet or oral antidiabetic drugs).
  • Twenty years after diagnosis, 10-25% of patients have sight-threatening maculopathy, or clinically significant macular oedema. Maculopathy is the most common cause of visual impairment due to diabetes in patients with type 2 diabetes.

Risk factors

  • Good glycaemic control and good management of blood pressure decrease the risk of diabetic retinopathy and slow down its progression Glycaemic Control for Slowing the Progression of Microvascular Complications in Diabetes Mellitus.
    • Retinopathy starts to occur when HbA1c levels exceed 48 mmol/mol (6.5%). Fluctuations in the levels also add to the risk of progressive retinopathy.
    • Hypertension also increases the incidence of macular oedema, particularly that of refractory macular oedema.
  • Pregnancy increases the risk of retinopathy temporarily but is not likely to influence the course of the disease in the long run. Retinopathy is not a contraindication to normal delivery.
  • Other risk factors include dyslipidaemia, abdominal obesity and anaemia, as well as microalbuminuria and diabetic nephropathy. A family history of diabetic retinopathy is associated with an increased risk of retinopathy.
    • The role of hereditary protective or risk factors is not fully understood but severe forms of the disease appear to run in families.

Screening methods

  • The patient's family doctor may monitor visual acuity, for example in connection with annual check-ups. This will help to detect the development of cataracts, for example. However, the monitoring of visual acuity alone is not sufficient to exclude retinopathy or to determine its severity. Regular examinations of the fundi are therefore needed.
  • To examine the ocular fundi, tropicamide must be used to dilate the pupils. It takes 20-30 minutes to achieve pupillary dilatation (mydriasis). Driving is not recommended for 2-3 hours after pupillary dilatation on account of the reduced ability to tolerate glare.

Ophthalmoscopy

  • Requires experience and regular practice.
  • Examination is complicated by the presence of severe refractive error, media opacities, and a small pupil.
  • No permanent record remains of ophthalmoscopy for future comparison or for attachment to a referral.
  • Ophthalmosocopy is not sufficiently accurate method for screening. A carefully, through a dilated pupil performed ophthalmoscopy may, however, be helpful in recognizing retinal changes that require urgent treatment (advanced diabetic retinopathy, age-related degeneration of the central vision area, arterial and venous occlusions).

Fundus photography Screening and Monitoring Tests for Diabetic Retinopathy

  • Fundus photography is a cost-efficient method of carrying out screening. It requires a sufficiently good imaging equipment and familiarity with taking these images. A single, below 50°, low-resolution colour photograph is not adequate for screening.
  • Mydriasis is required even if a special non-mydriatic fundus camera is used.
  • In screening photography, at least the following should be obtained of both eyes:
    • a 50° image with the macula at the centre (centred on the centre of the macula or slightly temporally of it)
    • a 50° image with the optic disk at the centre (centred on the optic nerve head or slightly nasally of it)
  • When monochromatic black and white film is used the camera must be equipped with a green filter. Plain digital pictures should be viewed through a green filter.
  • The advantage of photographic screening is the speed of interpretation and the fact that the images will provide a permanent record of the stage of retinopathy and the vasculature. The images should be attached to the referral.
  • Fundus photography can be carried out at a regular check-up or separate photography appointment or as a part of a mass screening programme. Photography can be organized as part of an institution's own activity, purchased externally, or by several organizations jointly purchasing a camera which is then shared.
  • The pictures should be viewed by a trained health care professional (the ophthalmic photographer, nurse or doctor) at the treatment or screening unit. Any pictures that show more than mild changes suggestive of retinopathy or other abnormality should be sent to an ophthalmologist specialized in diabetic retinal lesions. Referral for evaluation should include a short medical history as well as information on the main risk factors (HbA1c, blood pressure, lipid values). The patient's family doctor should be informed about the results of the fundus examination, which are shared with the patient at the treatment unit.
  • If monitoring is done by photography, neither the patient's family doctor nor the ophthalmologist necessarily sees the patient at the appointment. If so, particular attention should be paid to the flow of information. Patients should be informed in advance that, should the images show anything needing further investigations or treatment, they will be referred to the treatment unit that will invite them directly for examinations and treatment.

Follow-up frequency

  • See table T1

Follow-up frequency of fundus abnormalities in patients with diabetes

Type of diabetesFirst examination of the fundiSubsequent examinations
Type 1, age at onset < 10 yrsAt the age of 10Every 2 years, and annually or more frequently as soon as abnormalities are noted
Type 1, age at onset > 10 yrsAt the time of diagnosisEvery 2 years, and annually or more frequently as soon as abnormalities are noted
Type 2At the time of diagnosisEvery 3 years; every two years once slight abnormalities are noted; annually or more frequently if there are more abnormalities
  • Sight-threatening fundus abnormalities, particularly signs of development of severe nonproliferative retinopathy, poor glycaemic control, a rapid improvement of glycaemic control after intensification of treatment, or nephropathy, may be indications for more frequent examinations than specified in the Table.
  • The fundi should be examined in patients planning pregnancy, or at least as soon as pregnancy has begun, and during pregnancy, particularly in patients who have been diagnosed with retinopathy.

Treatment

Laser treatment Laser Photocoagulation for Diabetic Retinopathy

  • Laser treatment started without delay is the basis of the treatment of severe proliferative retinopathy. Its effect is good and lasting.
  • Indications for treatment
    • Diabetic maculopathy which has developed into clinically significant macular oedema
      • Laser treatment is administered locally either directly into leaking microaneurysms or vascular areas or indirectly, i.e. by grid laser treatment.
      • The visual loss stops in 50% of patients.
      • Macular oedema should preferably be treated before panretinal photocoagulation either by laser or injection therapy.
    • Severe nonproliferative retinopathy (preproliferative retinopathy)
      • N.B.! Laser treatment is not indicated in mild to moderate nonproliferative retinopathy, but an individual monitoring programme must be planned, taking into account the degree of retinopathy and risk factors.
    • Proliferative retinopathy
  • Extensive, i.e. panretinal photocoagulation is started without delay in severe proliferative retinopathy (and in the presence of rubeosis iridis or neovascular glaucoma). Scatter treatment is given as several burns and divided into two or more sessions, using a sufficient size and number of burns, the total number of burns always being defined individually.
    • The aim of the treatment is to create scarring over the ischaemic and hypoxic retina, thus reducing the retinal oxygen demand and consumption and the production of vascular endothelial growth factor, and increasing oxygen uptake from the choroid.
    • Extensive panretinal laser photocoagulation has been shown to reduce severe visual loss to less than 2-5% five years after the treatment (without treatment up to 50% of patients become blind). A good treatment result is long-lasting. The disadvantages of the treatment are deterioration of night vision and a narrowing of the visual field, if frequent treatment is required.
  • In patients with mild or moderate proliferative retinopathy who are regularly monitored, laser treatment should be regional or sectoral and continued as necessary.
  • In severe nonproliferative retinopathy, scatter photocoagulation of the midperiphery and/or areas with vascular occlusion, locally, slows down both disease progression and visual loss as well as reducing the need for vitreal surgery. Effects on macular oedema vary individually, i.e. the treatment may either increase oedema or help to reduce it, which should be taken into consideration.

Intravitreal injections

  • Intravitreal injections are a new treatment alternative for central macular oedema.
  • The availability of injection therapies has significantly increased, and short-term effect also on small new vessels has been described. There is, however, no evidence on long-term effects and cost-effectiveness in proliferative retinopathy yet. Combined with laser therapy they have a beneficial effect on macular oedema which may be temporarily increased because of panretinal laser therapy.
  • When planning treatments, risk of infection must be considered and laser therapy should still be considered as an alternative when it is feasible.
  • Often considered
    • if laser therapy does not provide adequate effect or if for other reasons intravitreal injection is regarded as the primary treatment option
    • for central macular oedema, if visual acuity is below 0.5 and if retinal thickness is over 300 µm (individual assessment).
  • To the extent possible should be avoided if there are findings suggestive of severe macular ischaemia.

Types of intravitreal injections

  • Injections of anti-VEGF antibodies that inhibit vascular endothelial growth factor
    • At 1-month intervals, often as series of three injections; repeated if effect can be observed
    • Effective in two out of three
    • Not during pregnancy
  • Glucocorticoid injections
    • May be used if response to anti-VEGF antibodies is weak
    • Intraocular pressure must be controlled 2 weeks after the injection. Notice! Also a general practitioner should check pressures if a patient who has recently been treated with glucocorticoid injection seeks medical help.
    • A new injection may be considered 2 months after the previous one.
  • Intraocular glucocorticoid implant
    • Long-term effect (3-4 months); should also be considered as a potential cause of increased intraocular pressure.

Adverse effects

  • Risk of endophthalmitis (general infection of the inside structures of the eyeball) is associated with all intravitreal injections (about 0.05%).
  • Anti-VEGF antibody injection may cause short-term increase in intraocular pressure.
  • Intravitreal glucocorticoid therapy causes cataract and may lead to increased intraocular pressure.

Surgical treatment

  • Vitreoretinal surgery requires particular familiarity with the techniques.
  • Indications for surgery are, among others,
    • vitreous haemorrhage that does not clear up during follow-up
    • retinal detachment threatening the macula
    • pull on the retina caused by intravitreous neovascularisation and vitreous condensation.
  • Surgery should be carried out without delay if the macula is at risk of tractional detachment or if detachment due to a tear in the retina (rhegmatogenous detachment) is observed.
  • The timing of surgery for vitreous haemorrhage that fails to clear is determined by the vision in the fellow eye. In young patients, an observation period of several months should be avoided particularly if no laser treatment has been administered to the ocular fundus. If the fundus cannot be visualised, the status of the retina should be checked with ultrasound.
  • If macular oedema is accompanied by problems affecting the vitreous body (vitreofoveal traction, absence of posterior vitreous detachment), vitrectomy may be of benefit.
  • If the macula has been detached for a long period of time, the retina and/or the optic nerve have atrophied or the macula is damaged by severe capillary damage, visual acuity may remain poor even if the optic media clear and the retina can be reattached.
  • An anti-VEGF antibody injection may be combined with the surgery
    • some days prior to surgery to reduce bleeding risk during or after the operation
    • within the operation, if severe macular oedema has been detected before the surgery.

Low vision rehabilitation of patients with diabetes

  • After a patient's rehabilitation needs have been assessed, low vision rehabilitation consists of vocational rehabilitative measures, adjustment training, introduction to low vision skills as well as advice on the use and purchase of appropriate aids.
  • A rehabilitation plan should be drawn up at the treatment unit. Adjustment training courses for patients and relatives are arranged by specialized care units and patient organizations.
  • Patients with diabetes should be encouraged to study in order to increase the scope of available employment alternatives.
  • Social insurance institutions finance vocational rehabilitation for people whose working ability is at risk. A vocational rehabilitation and investigation plan should be drawn up. A statement by an ophthalmologist is needed for assessing working ability.
  • Rehabilitation evaluation may be carried out at the patient's workplace (visual performance necessary for the work tasks, aids required, appropriate lighting, ergonomic needs and whether it is possible to tailor the job description).
  • If profound visual impairment occurs suddenly, the patient should be provided with crisis therapy at the ophthalmology unit as a part of the initial treatment. In patients with profound visual impairment, rehabilitation usually starts with adjustment training.
  • The cost of any necessary aids is usually reimbursed to the patient. Some basic aids (such as white canes) may be available at the local health centre.

Evidence Summaries