Diabetic Retinopathy

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.

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 (HbA_1c, 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

• 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.

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.

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.