Diabetes mellitus is caused due to lack or diminished effectiveness of endogenous insulin and is characterised by hyperglycaemia.
There are two broad types:
Type I: This is known as insulin-dependent diabetes mellitus (IDDM). It is characterised by insulin deficiency. Usually it has juvenile onset but may occur at any age. Patients are prone to ketoacidosis and weight loss.
Type II: This is known as non insulin-dependent diabetes mellitus (NIDDM) or maturity onset diabetes mellitus. It occurs in middle aged/ older people who are often obese. There is impaired insulin secretion and/or insulin resistance. Patients may be managed with oral hypoglycaemic agents (drugs which lower blood sugar level). Patients may eventually need insulin especially those with ketonuria or dehydration. This does not mean that IDDM has developed.
Diabetic retinopathy (DR) is characterised by changes in retinal blood vessels that occur in patients with diabetes mellitus. DR is a retinal microangiopathy affecting arterioles, capillaries and the venules. However, larger vessels may be involved as well.
Central retina or macular area is located between main superior and inferior retinal artery and vein. The area beyond these main vessels is the peripheral retina.
Retinopathy has features of both micro-vascular occlusion and micro-vascular leakage of plasma constituents due to breakdown of the blood-retinal barrier. Micro-vascular occlusion leads to arteriovenous shunts with capillary blockage and neovascularisation (new vessel formation). Micro-vascular leakage may cause haemorrhage and diffuse or localised retinal oedema. This disease can affect vision.
Diabetic retinopathy is broadly divided as:
- Background Diabetic retinopathy.
- Pre-proliferative Diabetic retinopathy.
- Proliferative Diabetic retinopathy (PDR).
Kanski,Jack J. Clinical Ophthalmology, A Systematic Approach .Third Edition.UK. Butterworth Heinemann, 1994.
Longmore Murray; Wilkinson Ian; Torok Estee. Oxford handbook of clinical medicine. Fifth Edition.UK. Oxford University Press, 2001.
Patients are generally asymptomatic in the initial stages of the disease.
In advanced stages of disease, patient may experience:
- Blurring of vision.
- Progressive reduction of visual acuity.
- Fluctuation of vision.
- Presence of floaters.
- Distortion of images.
- Flashes of light (photopsia).
- Defects in the field of vision.
Diabetic retinopathy occurs in patients with Diabetes mellitus, more so in IDDM.
Risk factors for development of Diabetic retinopathy:
- Duration of Diabetes: Probability and incidence of developing Diabetic retinopathy is related to the duration of Diabetes. This is the most important factor.
- Control of Diabetes: Though control of Diabetes mellitus will not prevent Diabetic retinopathy, it delays development by few years.
- Other factors having adverse effect on DR:
- Systemic hypertension.
- Renal disease.
Ischaemic retina secretes Vascular Endothelial Growth Factor (VEGF).
VEGF leads to:
- Retinal oedema due to increased vascular permeability.
- Angiogenesis or formation of new blood vessels.
Patients have increased fasting and postprandial (taken two hours after meals) blood sugar levels. Glycosylated or glycated haemoglobin (HbA1c) is a measure of glycaemic control over the last three months. Besides, patients have systemic features of Diabetes mellitus.
Features of Background Diabetic retinopathy:
- Micro-aneurysms: Micro-aneurysms appear as small round dots, usually seen temporal to the macula. Micro-aneurysms coated with blood are indistinguishable from dot haemorrhages.
- Haemorrhages: Superficially placed haemorrhages appear as Flame-shaped haemorrhages. Haemorrhages in the deeper layers of retina appear as ‘dot’ and ‘blot’ haemorrhages.
- Hard exudates: Exudates are composed of lipoprotein and lipid filled macrophages and typically surround leaking micro-vascular lesions and may take circinate (circular or ring shaped) pattern. These may be absorbed over a period of time.
- Retinal oedema: Retinal oedema is characterised by retinal thickening which obscures underlying layers of retina. Fovea (point of retina through which an object is seen) may assume cystoid appearance due to progressive retinal oedema. Retinal oedema may present as ‘macular oedema’ or as ‘clinically significant macular oedema’.
Macular oedema: Macular oedema is the presence of retinal thickening or hard exudates within one disc diameter (disc is the point of exit of optic nerve and is 1500µm in size) of the center of fovea.
Clinically significant macular oedema (CSMO): This is characterised by the presence of one or more of the following features.
- Retinal oedema within 500µm of the center of fovea.
- Hard exudates within 500µm of the fovea, associated with adjacent retinal thickening, which may be outside the limit of 500µm.
- Retinal oedema of one disc diameter or larger, any part of which is within one disc diameter of the center of fovea.
Features of Pre-proliferative Diabetic retinopathy: Retinal changes in Pre-proliferative DR are produced due to ischaemia and consists of:
- Vascular appearance: Venules show beading, looping or sausage like segmentation. Arterioles may be narrowed or even obliterated.
- Retinal infarcts: These appear as dark blot haemorrhages.
- Cotton wool spots: Ischaemia due to capillary occlusion may cause damage to nerve fiber layer appearing as cotton wool spots in multiple areas.
- Intra-retinal micro-vascular abnormality (IRMA): IRMAs are located within retina and do not cross major retinal blood vessels. These appear similar to flat retinal neovascularisation.
Proliferative Diabetic Retinopathy (PDR): PDR is more common in IDDM and show features of:
- Neovascularisation: New vessels may appear on the optic nerve head (new vessels at disc or NVD) or along major temporal vessels (new vessels elsewhere or NVE). Over one-quarter of the retina has to be non-perfused before NVD develops. Later, there may be formation of fibro-vascular epiretinal membrane in the potential vitreoretinal space.
- Vitreous detachment or separation: Formation of fibro-vascular epiretinal membrane in potential vitreoretinal space may lead to total or partial posterior vitreous detachment. The fibro-vascular tissue may become adherent to posterior vitreous face. Pull on fibro-vascular tissue by the vitreous detachment may lead to haemorrhage in vitreoretinal space or within the vitreous. PDR is asymptomatic until the onset of vitreous haemorrhage.
- Haemorrhage: Haemorrhage may occur in potential vitreoretinal space (retrohyaloid space) as pre-retinal haemorrhage or into the vitreous gel (intravitreal haemorrhage).Intravitreal (Intra-gel) haemorrhage takes longer to clear as compared to pre-retinal haemorrhage. Pre-retinal haemorrhage takes crescentic shape along the posterior vitreous detachment.
Complications of Proliferative Diabetic retinopathy: PDR may lead to retinal detachment, persistent vitreous haemorrhage, rubeosis iridis (formation of new vessels on iris) or formation of opaque membrane on posterior surface of detached vitreous.
Laboratory tests for Diabetic Retinopathy:
- Fluorescein Angiography (FA): Fluorescein is a fluorescent dye. Fluorescein Angiography helps in assessing degree of retinal ischaemia and delineates retinal vascular abnormalities. Microaneurysms appear as hyper-fluorescent spots which leaks the dye in late phases of FA. ‘Blot’ and ‘Dot’ haemorrhages appear hypo-fluorescent in contrast to micro-aneurysms. Nonperfused areas appear as dark patches or homogeneous hypo-fluorescent areas. NVD and NVE also show leakage of dye on FA. Intra-retinal micro-vascular abnormalities do not leak dye.
- Optical Coherence Tomography (OCT): OCT generates cross-sectional image of the retina with light. OCT helps in measuring retinal thickening. Periodic OCT determine whether the retinal thickening in macular area due to oedema is regressing or not with treatment. Any vitreomacular traction can also be assessed.
- B-scan ultrasonography: B-scan ultrasonography evaluates retina when the media is not clear e.g. vitreous haemorrhage.
Diabetic retinopathy should be distinguished from conditions like retinal vein occlusion, retinal vasculitis, sickle cell retinopathy or ocular ischaemic syndrome.
It should be strictly carried out under medical supervision.
Goals of management of Diabetes mellitus and Diabetic retinopathy are the good control of disease process and maintaining HbA1c level within a range of 6-7 %.
Change in lifestyle with regular exercise helps in controlling Diabetes mellitus which in turn reduces complications including DR.
Drug therapy for Diabetes mellitus: Drugs may be from various groups like biguanides, sulfonylureas, meglitinide derivatives, thiazolidinediones, alpha- glucosidase inhibitors, dipeptidyl peptidase IV inhibitors or insulin.
Drug therapy for Diabetic retinopathy:
- Intravitreal triamcinolone: Intravitreal injection of triamcinolone may be used in cases of Diabetic macular oedema.
- Intravitreal Anti-Vascular Endothelial Growth Factor (Anti-VEGF): Intravitreal injection of Anti-VEGF help in reducing diabetic macular oedema, NVD and NVE. Bevacizumab (Avastin) and Ranibizumab (Lucentis) are VEGF antibodies and antibody fragments (Anti-VEGF) respectively, being used as intravitreal injection. Intravitreal Aflibercept (Eylea) may also be given to patients with diabetic macular oedema.
Laser Photocoagulation for Diabetic retinopathy:
Laser photocoagulation is a non-invasive technique that has relatively low rate of complication and a significant success rate. Highly focused beam of laser causes coagulation in the target tissue.
Background Diabetic retinopathy: All eyes with CSMO are treated with laser photocoagulation. Prior fluorescein angiography delineates the area and extent of oedema. The technique of laser photocoagulation may be:-
- Direct laser photocoagulation: Laser burns are applied to microaneurysms and micro-vascular lesions in the center of hard exudates located between 500µm to 3000µm from center of the fovea.
- Grid photocoagulation: Grid photocoagulation is applied in areas of diffuse retinal thickening located at posterior pole of eye, 500µm each from the center of the fovea and from the temporal margin of the optic disc.
Pre-proliferative Diabetic retinopathy: Photocoagulation is done when fluorescein angiography shows extensive areas of capillary non-perfusion in patients who had proliferative DR in the fellow eye.
Proliferative Diabetic retinopathy: Patients with high risk of vision loss should be treated. Features of high risk are:-
- NVD or neovascularisation more than one-quarter disc in area within 1500µm of the disc.
- Less extensive NVD associated with vitreous or retrohyaloid haemorrhage.
- NVE more than one-half disc in size associated with vitreous or retrohyaloid haemorrhage.
Panretinal Photocoagulation (PRP) is given in scatter pattern extending from posterior fundus to the peripheral retina.
Recurrence is further treated with photocoagulation or cryotherapy.
Surgical management in the form of pars plana vitrectomy may be done in complicated cases like persistent vitreous haemorrhage, tractional retinal detachment or rubeosis iridis.