Summary

Diabetic retinopathy is an important public health concern and is one of the most common causes of blindness. The causes of visual loss in diabetic retinopathy include macular oedema, vitreous haemorrhage, tractional retinal detachment and neovascular glaucoma. With appropriate screening and treatment, more than 90% of visual loss resulting from diabetic retinopathy can be prevented. This article reviews the pathophysiology, clinical signs and course of diabetic retinopathy that may help the general practitioner in screening for diabetic patients with a high risk of diabetic retinopathy. Early detection of diabetic retinopathy and referral to an ophthalmologist is the key to prevention of blindness in the management of diabetic mellitus.

摘要

糖尿病性視網膜病是重要的公共衛生問題，也是失明的最常見原因之一。糖尿病性視網膜病人失明的原因包括黃斑水腫、玻璃體出血、牽拉性視網膜脫離和新生血管性青光眼。適當的篩選檢查和治療可以預防90%以上由糖尿病性視網膜病引起的失明。本文回顧了糖尿病性視網膜病的病理生理學、臨床表現和病程，有助全科醫生為易發生糖尿病性視網膜病的高危糖尿病人進行篩選檢查。預防失明的關鍵是早期診斷和及時轉診予眼科醫生診斷。

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Introduction

Diabetic retinopathy is one of the most common causes of blindness in the world. Advances in the screening techniques and treatment over the past 40 years have greatly reduced the risk of blindness resulting from this disease. Unfortunately diabetes mellitus is so prevalent that diabetic retinopathy still remains an important health problem. Prevention of diabetic blindness relies on a co-operation between the physicians or general practitioners who manage the systemic disease and who screen for retinopathy, and the ophthalmologists who manage the diabetic retinopathy. This article reviews the clinical features and classification of diabetic retinopathy and the screening methods for the primary care practitioners.

Epidemiology

Diabetes mellitus (DM) is a major medical problem throughout the world. Diabetic retinopathy is the leading cause of new cases of legal blindness among the Americans between the age of 20 and 74 years.¹ There are two distinct forms of DM: type 1, the juvenile-onset or insulin-dependent diabetes mellitus (IDDM), is generally diagnosed before the age of 30, while type 2 is primarily diagnosed at or after the age of 30. Patients with type 1 diabetes are at higher risk of developing the more severe retinal complications leading to visual loss.^2,3 Type 2 diabetic patients have a lower prevalence of diabetic retinopathy and the retinopathy that developes is generally of a lesser severity.^4,5 However, type 2 DM is more common and a large proportion of patients with diabetic retinopathy belong to this type of DM.

The risk of developing diabetic retinopathy is related to the duration of the DM. Nearly all type 1 DM and about 60% type 2 DM patients have certain degree of retinopathy after acquiring the disease for more than 20 years.^2,4 For those who have developed diabetic retinopathy, about 50% type 1 DM patients progress to proliferative retinopathy compared with less than 10% in type 2 patients.^2,4

Clinical features of diabetic retinopathy

Diabetic retinopathy is caused by microangiopathy affecting the retinal precapillary arterioles, capillaries and venules. The pathophysiology includes microvascular leakage and microvascular occlusion (Figure 1). The microvascular leakage manifests clinically as haemorrhages and hard exudates deposition in the retina and causes visual loss if the macula is involved (Figure 2). The microvascular occlusion leads to retinal ischaemia which in turn stimulates new vessel formation and eventually progresses to vitreous haemorrhage, tractional retinal detachment and neovascular glaucoma (Figure 3).

Diabetic retinopathy is broadly classified into non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). Diabetic macular oedema, a common cause of decreased central vision, can occur at any stage of the diabetic retinopathy.

Non-proliferative diabetic retinopathy

Fundal examination in NPDR reveals micro-aneurysms, retinal haemorrhages, hard exudates, cotton wool spots, venous beading and intraretinal microvascular abnormalities (Figures 4-6).

Microaneurysms are small capillary dilatations, seen as small red dots with the direct ophthalmoscope. They are often the first clinically detectable sign of diabetic retinopathy. They leak lipoproteinaceous fluid from the blood into the retina resulting in retinal oedema or lipid deposition known as hard exudates.

Retinal haemorrhages appear as dots or blots. The shape is due to their location in the outer retinal layers, where the arrangement of cells is perpendicular to the surface of the retina. The haemorrhages are generally larger than microaneurysms, with indistinct margins in contrast to the sharp borders of microaneurysms. Extensive retinal haemorrhages is a strong predicting factor for progression to proliferative retinopathy.⁶

Hard exudates are lipid and liproprotein deposits in the retina. They are leaked out from abnormally permeable retinal microaneurysms and capillaries. They have a waxy appearance with discrete margins. The extent of hard exudates is not associated with an increased risk of progression to proliferative retinopathy. Raised blood cholesterol levels are associated with a more extensive hard exudates formation.⁷

Cotton wool spots are fluffy white lesions in the inner retina. They are axonal swelling of the ischaemic or infarcted nerve fibres due to interruption of axoplasmic flow in areas of retinal capillary closure. They are signs of poor retinal perfusion but they have poor predictive value for progression of retinopathy to more severe levels.⁶

Venous beading refers to irregular constriction and dilatation of the lumen of retinal venules. It occurs in areas of retinal ischaemia. It is associated with an increased risk of progression to PDR.⁶

Intraretinal microvascular abnormalities (IRMA) are shunt vessels or enlarged capillaries adjacent to the areas of occluded capillaries. They appear as dilated, telangiectatic capillaries and they strongly indicate the likelihood of progression to proliferative retinopathy.⁷

Classification of non-proliferative diabetic retinopathy

NPDR is graded as mild, moderate and severe.⁹ Mild NPDR is defined as the presence of at least one microaneurysm with or without the presence of retinal haemorrhages, hard exudates, cotton wool spots or venous loops (Figure 7). Patients with mild NPDR have a 4% risk for progression to PDR within 1 year.⁹

Moderate NPDR is characterized by the presence of more numerous microaneurysms and retinal haemorrhages (Figure 8). Cotton wool spots and a limited amount of venous beading can also be seen. Patients with moderate NPDR have a risk of 12 to 27% for progression to PDR within 1 year.

Severe NPDR is characterized by any one of the following (4-2-1 rule):⁶ (1) numerous haemorrhages and microaneurysms in 4 quadrants of the retina (2) venous beading in 2 or more quadrants (3) IRMA in at least 1 quadrant. Severe NPDR carries a 50% chance of progression to PDR in one year. Patients with 2 or more of these features are graded as very severe NPDR (Figure 9).

Diabetic macular oedema is retinal thickening within 2 disc diameters of the centre of the macula. It is rarely visible with the direct ophthalmoscope unless it is so severe that cystic changes have developed. It is a common cause of decreased visual acuity in patients with DM. It can be seen at any stage of diabetic retinopathy and does not predict the risk of retinopathy progression. If retinal thickening threatens or involves the fovea, it is termed clinically significant macular oedema (CSME). Laser treatment to the macula in these patients reduces moderate visual loss by 50% in 3 years.⁸

Proliferative diabetic retinopathy

Proliferative diabetic retinopathy (PDR) is characterized by an extra-retinal fibrovascular proliferation that is presumably due to vascular endothelial growth factor released from widespread ischaemic retina.¹⁰ Young type 1 diabetic patients or patients with poor control of glucose level, renal disease, hypertension, dyslipidemia, anaemia and pregnancy are particularly at risk of PDR development.^11,12

In the early stage of PDR there are new vessels on the optic disc (NVD) or on the retina (NVE). NVD is readily visible with direct ophthalmoscope. It appears as irregular new vessels growing from the optic disc on or into the vitreous gel. Without laser treatment, NVD is associated with a high risk of haemorrhage and severe visual loss. NVE is new vessels arising from the retina away from the optic nerve, commonly seen along the temporal vascular arcades (Figure 10). NVE has slightly less risk of severe visual loss than NVD but it still requires monitoring and treatment.

Haemorrhage from NVD or NVE often assumes a classic boat shape with a horizontal upper edge if the blood is located at the space between the retina and the posterior hyaloid face (Figure 11). If the haemorrhage breaks through the posterior hyaloid, it becomes vitreous haemorrhage (Figure 12). The fundus becomes blurred and if the vitreous blood is dense, the fundal details are obscured. These patients usually present with sudden painless loss of vision. The vitreous haemorrhage may persist for weeks or months before resolving.

In the more advanced stage the abnormal vascular component can cause preretinal and vitreous haemorrhage and subsequent contraction of the fibrous component leading to tractional retinal detachment (Figure 13).

New vessels may also develop on the iris and in the anterior chamber angle in advanced PDR that may lead to neovascular glaucoma (Figure 14). This kind of glaucoma is often refractory to treatment and frequently results in painful blind eye.

Treatment of diabetic retinopathy

Diabetes is a multi-system disease. Proper control of the blood sugar level, blood pressure, renal function and serum lipid profile positively impacts on the onset, progression and prognosis of diabetic retinopathy.^13-17

In general, the indications for treatment of diabetic retinopathy are CSME and PDR. Macular laser for CSME can reduce moderate visual loss by 50% compared to no treatment¹⁸ and improve vision by 15%.¹⁸ Laser photocoagulation to the retina in PDR reduces the risk of severe visual loss by approximately 50% (Figure 15).^19,20 Vitrectomy, that is, surgical removal of vitreous jelly, is indicated when there is non-clearing vitreous haemorrhage or tractional retinal detachment near the macula. Table 1 summarizes the classification and treatment of diabetic retinopathy.

Screening of diabetic retinopathy

The purpose of screening is to identify patients at risk of developing diabetic retinopathy, patients with asymptomatic diabetic retinopathy and to refer for specialist management in order to prevent visual loss. With appropriate screening and timely treatment, >90% of visual loss resulting from diabetic retinopathy can be prevented.¹²

The usual screening methods in primary health care include direct ophthalmoscopy and retinal photography. Direct ophthalmoscopy should be performed with the pupils dilated. However, the sensitivity of this method is only around 65% even with experienced ophthalmologists due to the inherent limitation of the direct ophthalmoscope.^21,22 It only provides a limited peripheral view and is difficult to detect macula oedema due to monocular viewing.

Retinal photography with standard polaroid or digital imaging, non-mydriatic or mydriatic camera, single or multiple pictures has a sensitivity ranging from 65-90% and a specificity ranging from 85-90%.^22,23 However, macular oedema or fine-caliber new vessels may be missed.

Initial eye screening and referral to ophthalmologists

The recommended timing for first diabetic retinopathy screening in diabetic patients is summarized in Table 2. For type 1 patients, the onset of vision-threatening retinopathy is rare before puberty.² It is also rare for severe retinopathy to be found in patients within 5 years after diagnosis of type 1 diabetes once patients are 10 years of age or older.²⁴

For type 2 patients, however, the onset date of diabetes is frequently not precisely known, and thus more severe disease can be found soon after diagnosis.²⁵ Initial eye screening is recommended at the time of diagnosis of type 2 diabetes.²⁶

Diabetic retinopathy can progress rapidly during pregnancy.²⁷ Initial eye screening is recommended prior to pregnancy and during the first trimester. Close follow-up throughout pregnancy is indicated, with subsequent examinations determined by the findings present at the first trimester examination.²⁶

It is controversial whether primary care providers or ophthalmologists be responsible for subsequent screening and monitoring. It is also controversial concerning the optimum time for patient referral to ophthalmologists. Some suggested routine referral of diabetic patients to ophthalmologists regardless of whether diabetic retinopathy is present or not.^28,29 Some argued that only those with severe NPDR, PDR or diabetic macula oedema be referred to ophthalmologists.^30,31 In practice, the timing of referral to ophthalmologists depends on the availability of trained primary care providers, effective screening methods like retinal photography, health care resources, and availability of ophthalmologists. Nowadays most government outpatient clinics and hospital medical clinics are equipped with retinal cameras. With the availability of the camera, trained primary care providers can play a significant role in diabetic retinopathy screening.^22,32 It is recommended that diabetic patients with any degree of diabetic retinopathy or if they have a poor media for fundal examination, e.g., cataract, should be referred to ophthalmologists. The urgency of referral to ophthalmologists for different stages of retinopathy is suggested in Table 3. In general, the more severe the retinopathy the earlier the referral should be. Urgent referral to ophthalmologists is suggested when there is acute visual loss, when PDR is found or when there is macular oedema. Patients should be educated to the fact that diabetic retinopathy can develop without any visual disturbance in the early stage and that early treatment if needed can prevent permanent damage to their vision.

Conclusions

Diabetic retinopathy is a common cause of visual loss in Hong Kong. Primary care doctors should have adequate knowledge on its clinical features and provide proper screening with appropriate methods. Early detection and timely referral to ophthalmologists can prevent severe visual loss.

Key messages

1. Diabetic retinopathy is one of the most common causes of blindness.
2. The risk of diabetic retinopathy is associated with the duration of the diabetes mellitus.
3. Type 1 diabetes mellitus has higher risk of development into proliferative diabetic retinopathy than type 2.
4. Early detection and treatment is the key to the prevention of permanent visual loss.
5. Urgent referral to ophthalmologists is indicated when there is acute visual loss, macular oedema or proliferative diabetic retinopathy.

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References