Ocular complications

Clinically significant ocular complications associated with diabetes include:

IRMA, intraretinal microvascular anomaly.

Another commonly used grading system is the Early Treatment Diabetic Retinopathy Study (ETDRS) system (Table 5.2).

Table 5.2 The Early Treatment Diabetic Retinopathy Study (ETDRS) system

DD, disc diameter; HRC, high-risk changes; IRMA, intraretinal microvascular anomaly; NPDR, non-proliferative diabetic retinopathy; NVD, new vessels on the disc; NVE, new vessels elsewhere in the retina; PDR, proliferative diabetic retinopathy.

Screening

Diabetic retinopathy can progress significantly without the patient being aware of any problems. The primary aim of screening is the detection of potentially sight-threatening retinopathy in asymptomatic people so that treatment, where required, can be performed before visual impairment occurs.

Retinal screening is defined as the ongoing assessment of fundi with no diabetic retinopathy or non-sight-threatening diabetic retinopathy. Once sight-threatening eye disease develops, treatment is usually required. Diabetic retinopathy screening does not remove the need for a regular general eye examination to monitor changes in refraction and to detect other eye disease.

In patients with type 1 diabetes it takes 5–6 years for retinopathy to progress. In type 1 patients aged 11 years or older, it can take 1–2 years for retinopathy to progress. A population-based study demonstrated the prevalence of retinopathy to be 14.5% for any retinopathy and 2.3% for proliferative and pre-proliferative retinopathy in children and adolescents with insulin-dependent diabetes mellitus diagnosed before the age of 15 years and who were older than 9 years at the time of examination. Pre-proliferative retinopathy has been identified as early as 3.5 years after diagnosis in patients postpuberty, and within 2 months of onset of puberty.

General principles of management of diabetic retinopathy

Proliferative diabetic retinopathy

Proliferative diabetic retinopathy (PDR) affects about 5 –10% of the diabetic population and is more common in type 1 diabetes.

Neovascularization is the hallmark of PDR. New vessels are commonly seen along the retinal arcades, but can occur at the optic disc or elsewhere in the retina. As a general rule, the retina distal to the neovascularization should be considered as ischaemic, and it has been estimated that more than one-quarter of the retina has to be non-perfused before neovascularization occurs. Ischaemia upregulates the vascular endothelial growth factor (VEGF) that stimulates neovascularization. New vessels start as endothelial proliferations, and pass through the internal limiting membrane to lie in the potential plane between the retina and the posterior vitreous face. PDR can result in visual deterioration from ischaemia, haemorrhage and tractional retinal detachment involving the macula (Table 5.4).

Table 5.4 Guidelines for referral for specialist assessment of diabetic retinopathy

Diabetic maculopathy

Involvement of the macula with exudative or ischaemic changes has a potential to involve the fovea, thus threatening vision. Exudative maculopathy may be amenable to treatment but ischaemic changes are not.

Diabetic maculopathy can present in the following patterns:

Laser photocoagulation

The efficacy of photocoagulation has been demonstrated in the Diabetic Retinopathy Study (DRS) and ETDRS studies. It is believed that the regression of neovascularization is due to the destruction of ischaemic and hypoxic retina with the reduction in angiogenic factors.

Panretinal photocoagulation is now the main modality of treatment for proliferative diabetic retinopathy and severe non-proliferative diabetic retinopathy (NPDR). Clinically significant macular oedema (CSMO) can be treated with focal or grid photocoagulation.

Panretinal laser involves the application of 500 μm of Argon laser photocoagulation spots, each separated by an interval of a similar spot size to the mid-peripheral retina. A row of laser burns are initially placed approximately three disc diameters temporal to the fovea to avoid getting closer to the fovea. About 1500 burns are usually required (in two to three sessions). Severe cases may require further photocoagulation. The aim is to cover the ischaemic areas and regression of new vessels occurs in almost 80% of cases. Fundus fluorescein angiography (FFA) should be undertaken initially to delineate the ischaemic areas, or should be done to ensure coverage of ischaemic areas with laser if good regression of neovascularization is not achieved even with initial retinal photocoagulation.

Laser treatment can be associated with pain, transient visual loss, loss of visual field (inevitable) and, sometimes, reduced visual acuity and choroidal damage.

In very aggressive cases of PDR, an intravitreal injection of an anti-VEGF can give a valuable window period until the laser photocoagulation takes effect which can take up to 2 weeks.

Macular laser

Laser photocoagulation is considered primarily for clinically significant macular oedema. This can be applied focally to leaking microaneurysms or in a grid pattern over the macula in case of diffuse macular oedema. The spot sizes used vary from 50-100 μm and power just sufficient to cause a minimal blanch. Use of higher power can result in reduction of visual acuity. Utmost care should be taken to avoid the foveal avascular zone. Ideally macular laser should be undertaken only after angiographic assessment.

Other modalities of locally managing macular oedema are with intravitreal injections of triamcinolone acetonide or anti-VEGF. The effects of these injections, however, are usually only short-lived.

Vitrectomy

Early vitrectomy is of proven value for improving long-term vision in patients with type 1 diabetes and persistent vitreous haemorrhage. Its value in type 2 diabetes is less certain. Patients with type 1 or type 2 diabetes who have severe fibrovascular proliferation threatening the macula with or without retinal detachment also have better visual acuity after vitrectomy.

Cataract extractions 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. Although postoperative progression of pre-existing proliferative diabetic retinopathy and CSMO has been documented, the balance of evidence does not show an increase in diabetic retinopathy or in the long-term incidence of CSMO following cataract extraction.

When cataract extraction is planned in the context of advanced eye disease that is not stabilized prior to surgery, the risk of disease progression and the need for close postoperative review should be discussed fully with the patient.

Pharmacological therapy

Fenofibrate reduces the risk of progression of retinopathy and the need for laser treatment in patients with type 2 diabetes. The outcomes were not explained by a change in the serum lipid profile and the effect was independent of its lipid-lowering properties.

Intravitreal triamcinolone may provide a short-term reduction in retinal thickness and a corresponding improvement in visual acuity. In the long term it does not appear to have any benefit over laser treatment. Triamcinolone may be useful in patients who do not respond to laser. There is a risk of raising intraocular pressure: in one study, 68% of patients were affected, with 44% requiring glaucoma medication and 54% of patients requiring cataract surgery.

A randomized clinical trial of patients with type 2 diabetes and raised serum lipid levels at baseline, found that atorvastatin reduced the severity of hard exudates following laser therapy (P  =  0.007), although the clinical significance of this is not certain. A similar study showed a non-statistically significant improvement in visual acuity and reduction in clinically significant macular oedema in patients on simvastatin.

There is insufficient evidence to warrant routine usage of anti-VEGF therapies for the treatment of proliferative diabetic retinopathy or diabetic macular oedema, either as stand-alone therapy or as an adjuvant to laser therapy.

There is no good evidence for any additional benefit of angiotensin converting enzyme (ACE) inhibitors in diabetic eye disease.

An angiotensin receptor blocker (ARB) appeared to reduce significantly the incidence of new-onset retinopathy in patients with type 1 diabetes, by 35% when measured as a change of three steps in the ETDRS scale, rather than the two steps in the original study design. Treatment with the ARB enhanced regression of retinopathy by 34% in patients with type 2 diabetes with early retinopathy.

Rehabilitation

Patients should be registered by their ophthalmologist as partially sighted (best corrected acuity 6/60) or blind (3/60 or worse). They should be assisted to register as blind/partially sighted as soon as they fulfil the criteria. Recognized disability will allow direct referral to a local low-vision network and/or visual impairment team for assessment and ongoing support. Low-vision aids and adapted everyday appliances are available. Pen injectors and other devices may be useful for patients requiring insulin treatment. With instruction, self-monitoring of capillary glucose is possible; modified glucose meters are available, including devices providing an audible result.

Other potential support includes:

Depression is understandably common. Peer support organized through patient organizations can often be helpful.

Cataract

A cataract is an opacity of the crystalline lens of the eye. It is usually asymptomatic in the early stages of development, but may progress to cause significant visual impairment or even blindness. The commonest variety of cataract is the so-called senile cataract. Cataracts are features of certain syndromes or therapies that may also be associated with diabetes, for example:

Epidemiological studies indicate that diabetes mellitus is a significant risk factor for cataract formation in patients aged up to 70 years. The incidence of cataract is increased several-fold compared with incidence in the non-diabetic population; the opacity also progresses more rapidly in diabetic patients. Good glycaemic control reduces the risk of cataract extraction.

Rarely, diabetes is associated with the development of an acute form of rapidly developing lens opacity known as a ‘snowflake cataract’. This usually occurs in young insulin-dependent patients and typically, though not invariably, follows a period of particularly poor glycaemic control. The cataract may appear and mature within weeks.

Diabetic neuropathy

The wide variability in symmetrical diabetic polyneuropathy prevalence data is due to lack of consistent criteria for diagnosis, variable methods of selecting patients for study, and differing assessment techniques. In addition, because many patients with diabetic polyneuropathy are initially asymptomatic, detection is extremely dependent on careful neurological examination by the primary care clinician.

In the UK, the prevalence of diabetic neuropathy among the hospital clinic population is thought to be around 30%. Using additional methods of detection, such as autonomic or quantitative sensory testing, the prevalence may be higher.

Treatment

Despite advances in the understanding of the metabolic causes of neuropathy, treatments aimed at interrupting these pathological processes have been limited. Thus, with the exception of tight glucose control, treatments are for reducing pain and other symptoms.

Options for pain control include tricyclic antidepressants (TCAs), serotonin reuptake inhibitors (SSRIs) and antiepileptic drugs (AEDs). It is suggested that TCAs and traditional anticonvulsants are better for short-term pain relief than newer-generation anticonvulsants. A combination of medication may be superior to a single agent.

The only two drugs approved by the US Food and Drug Administration (FDA) for diabetic peripheral neuropathy are the antidepressant duloxetine and the anticonvulsant pregabalin (Fig. 5.1). Before trying a systemic medication, people with localized diabetic periperal neuropathy occasionally get relief from their symptoms with lidocaine patches.

Figure 5.1 Treatment algorithm for management of painful diabetic peripheral neuropathy. TCA, tricyclic antidepressant.

(Source: Wong et al (2007). Reproduced with permission.)

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