In the sixth and final article in our series, Sophia Pathai and Andrew McNaught highlight some diseases and drugs that can affect the eye

The saying that the eyes are the window to the soul is more than purely metaphorical; a variety of systemic disorders are associated with eye conditions that are either direct or indirect manifestations of the underlying disease process. On the ward, this scenario may present in two ways: the patient may be known to have a general condition such as diabetes, and is concurrently suffering from a related eye problem. Alternatively, and more rarely, a presenting eye problem may be the first indication of underlying systemic disease. It's worth being aware of ophthalmic conditions that are associated with generalised disorders as you will be alerted to look out for some of the potentially serious eye complications when looking after these patients on the general wards. And maybe occasionally, you will be able to dazzle your colleagues by diagnosing a systemic condition based on your examination of the eye.

Diabetes and the eye

Diabetes can have a whole host of complications affecting the eye. Starting from the outside in, the eyelids can be affected by styes and lid cellulitis due to the increased susceptibility to infection. Moving on to the lens, the prevalence of cataract is higher in diabetics, and they tend to develop at an earlier age.

Microvascular disease can affect the vascular supply to the extraocular muscles, which can lead to a muscle palsy usually manifest as diplopia. The palsy usually resolves of its own accord within 4-6 weeks. Beware of assuming that diabetic microvascular disease is responsible for an acute IIIrd nerve palsy in a diabetic. Generally, vasculopathic IIIrd nerve palsies are pupil sparing, whereas compressive lesions (for example, posterior communicating artery aneurysm) have pupillary involvement. However, this is not always the case, as compressive lesions can occur without pupil involvement and so have a low threshold for neurological referral.

Haemorrhages in retina in Cytomegalo virus retintis

• Features of mild and moderate non-proliferative retinopathy arise mainly from loss of capillary integrity. These include microaneurysms, dot and blot haemorrhages, and hard exudates. Cotton wool spots are also seen.
• Features of more severe non- proliferative retinopathy are related to early signs of ischaemia. In addition to features present in mild to moderate disease, the fundus shows venous beading and more extensive intraretinal haemorrhage.
• In proliferative diabetic retinopathy features are related to retinal capillary non-perfusion. The fundus may exhibit features of non-proliferative retinopathy along with the development of neovascularisation of the optic disc, or elsewhere on the retina. Vitreous haemorrhage can occur as a consequence of new vessel formation.

The most common manifestation of microvascular disease in the eye is diabetic retinopathy--this is also the most serious as the complications can be sight threatening. Risk factors for the development of diabetic retinopathy include the duration of diabetes--more than 75% of diabetic patients develop retinopathy after 15 years of diabetes. Poor glycaemic control accelerates the development of retinopathy, as can pregnancy. Diabetic retinopathy is classified as non-proliferative or proliferative. Non-proliferative retinopathy is further subdivided into mild, moderate, and severe.

Visual loss occurs because of disease at the macula (the area of retina responsible for fine vision) or from the complications of proliferative retinopathy. It's important to remember that progression of diabetic retinopathy is related not only to diabetic control but also to other factors such as hypertension, hyperlipidaemia, and smoking.

Cardiovascular disease and the eye

Cardiovascular disease affects not only the major arteries in the systemic circulation--retinal vascular disease can be a manifestation of generalised atherosclerosis or a result of embolic disease originating from the cardiovascular system.

• Central retinal artery occlusion may occur secondary to emboli from the carotid artery, or from the heart.
• Hypertension is a major risk factor for central retinal vein occlusion.
• Atherosclerosis, hypertension and diabetes are all thought to be possible risk factors for non-arteritic ischaemic optic neuropathy (sudden, painless visual loss not associated with temporal arteritis).

Remember that patients with cerebrovascular disease can also develop eye problems. These may be directly related, such as a cortical stroke affecting the visual pathway, or amaurosis fugax, indicating compromise of the anterior cerebral circulation, or problems may arise indirectly, such as corneal exposure secondary to a seventh nerve palsy affecting the obicularis oculi muscle (which aids lid closure).

HIV and the eye

It is common to come across eye problems in HIV positive patients. In fact, almost three quarters of patients with HIV develop ocular complications. These may be related to opportunistic infection, neoplasia, or drug toxicity, and can affect all structures of the eye from the lids to the fundus.

A common complaint affecting the lids and anterior segment is that of blepharitis and dry eyes. In addition, molluscum contagiosum is more common in these patients and may be present on the eyelids. This can cause a chronic conjunctivitis, as discussed in our article on gritty, irritable eyes.1 Kaposi's sarcoma can also affect the eyelids and conjunctiva, so beware of an apparent subconjunctival haemorrhage that is not resolving.

An acutely painful red eye may also be seen. Again, a thorough history and examination of the eye (and the patient) should point you in the right direction. Viral infections (such as herpes simplex and herpes zoster) in immunocompromised patients can cause serious corneal pathology, and in addition atypical organisms such as fungi may also be able to breach the host defences. The painful, red eye of uveitis may be seen, and this may have an infective aetiology or in some cases may be related to drug toxicity.

Key messages

• If a patient has an ocular complaint, make sure you take a general medical history as well as the ophthalmic history
• When examining the patient, look at the patient as well as their eyes
• You will see a lot of diabetes and cardiovascular disease on the medical wards, so you may well come across associated ocular problems
• Remember that many drugs can have ocular side effects, either acutely or after long-term treatment

Opportunistic infection accounts for many of the problems seen in the retina; examples include cytomegalovirus, toxoplasmosis, and herpes simplex. Involvement of the macula in any of these problems will lead to a reduction in visual acuity or visual distortion. If you suspect posterior segment disease, have a good look at the (dilated) fundus. You may be surprised at what you see, and even if you don't know what it is you're looking at, have a go at describing it--even ophthalmologists have been known to call severe cytomeagolovirus retinitis "pizza retinopathy."

Diabetic maculopathy

Other causes of reduced visual acuity may be related to neuro-ophthalmic manifestations of HIV. Optic neuritis may occur secondary to opportunistic infections. In addition, the posterior visual pathway (beyond the optic chiasm) may be affected by space occupying lesions such as lymphoma or toxoplasmosis. Cranial nerve palsies can also occur as well as other disturbances of ocular motility.

Rheumatological disease and the eye

Patients with rheumatological disease are often encountered as inpatients on medical wards; as well as the musculosketelal features, ocular problems may also be present. Again, the ocular structures from the eyelids to the fundus can be affected. However, the most common condition that you probably see is that of dry eyes, which occurs due to a deficiency in the aqueous component of the tear film--this is known as keratoconjunctivitis sicca. Dry eyes are seen in several autoimmune conditions,1 treatment is generally symptomatic with supplementation of the tear film in the form of artificial tears.

A significant ocular association of rheumatoid arthritis is scleritis--we discussed this condition in the article on painful red eyes. Scleritis presents with a red eye, associated with pain that is often described as deep and boring. Patients with dry eyes may suffer from ocular discomfort but not severe pain, which is more likely to be seen in scleritis. Peripheral corneal ulceration is another ocular condition associated with rheumatoid arthritis, and other systemic conditions that can also lead to a painful red eye. If your patient develops a painful, red eye, it is wise to obtain an ophthalmology review to exclude any potentially sight-threatening conditions.

Non-proliferative diabetic retino

Drugs and the eye

It's important to remember that many drugs can have ocular side effects ranging from mild ocular discomfort to precipitating angle closure glaucoma. If you are making a referral to the ophthalmologist it's always helpful to provide a drug history as it may provide valuable clues to the diagnosis. The number of drugs that have ocular side effects is endless, but some of the drugs commonly prescribed on the ward merit special attention.

Steroids can cause early cataract if patients are having long term treatment. They also cause the type of cataract that leads to "glare" when driving, so beware of this association in young and middle aged asthmatic patient taking long term systemic steroids. Intraocular pressure may also rise in patients having long term treatment with steroids.

Anticholinergics and other drugs that dilate the pupils can lead to precipitation of angle closure glaucoma.2 In particular side effects of drugs for Parkinson's disease and tricyclic antidepressants include pupillary dilatation and failure of accommodation, so keep this at the back of your mind if you are faced with a patient with a painful red eye who has recently started taking new medication.