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Table of Contents 1. Introduction 2. Diabetic disease o 2.1 Screening for diabetic retinopathy o 2.2 Treatment of diabetic retinopathy 3. Sickle cell anaemia 4. Hypertension o 4.1 Arteriolar sclerosis o 4.2 Elevated blood pressure o 4.3 Screening for hypertensive retinopathy 5. Inflammatory conditions 6. Systemic infections 7. Thyroid disease 8. Myasthenia gravis 9. Cancer and the eye References 1. Introduction An understanding of the significance and implications of ocular presentation of systemic disease is vitally important in primary care practice. Some patients suffering from systemic disease are at particular risk of ocular complications, many of which are sight threatening. General practitioners play an important role in ensuring that these patients have regular ophthalmic review. Diabetes, hypertension and autoimmune disorders in particular predispose patients to complications. Golden Rule! Patients with systemic infections or autoimmune diseases presenting with red eye, decreased vision, photophobia or floaters should be referred ASAP to look for intraocular inflammation. Systemic disorders may present initially with ocular symptoms and signs. An awareness of the possible presentations of systemic disease is essential to diagnosis. Golden Rule! Remember, rare diseases present to common doctors. [ top ] 2. Diabetic disease Eye disease resulting from diabetes mellitus is the predominant cause of onset of blindness from the ages of 25-74 years. Only 2/3 of high risk diabetic retinopathy patients receive adequate care. 21-36% of people suffering from diabetes mellitus have retinopathy (6-13% have vision threatening retinopathy). Diabetes, hypertension and atherosclerosis are the most common causes of III and VI nerve palsies and the second most common cause (after trauma) of IV nerve palsy. III nerve palsy presenting with periorbital pain may in fact be the first clinical sign if diabetes and further diagnostics (eg blood glucose) are warranted. Trauma, aneurysms, neoplasms and inflammation may also cause nerve palsies. Diabetic retinopathy risk factors Duration of diabetes - Type 1 (IDDM) sufferers are retinopathy free for the first 5 years or to puberty, after that retinopathy increases with time. - Type 2 (NIDDM) sufferers also demonstrate increased retinopathy with duration of diabetes. 10-15% present with significant retinopathy at diagnosis. Poor glycaemic control - Good glycaemic control in IDDM patients has been shown to have a significant effect in reducing retinopathy risk. Hypertension Hyperlipidaemia Nephropathy [ top ] 2.1 Screening for diabetic retinopathy All patients with diabetes mellitus should have regular fundus examination, even if their vision is normal. Patients with retinopathy requiring laser treatment may still have normal vision. NIDDM patients should be examined at diagnosis, and yearly thereafter. IDDM patients should have an ophthalmological exam 5 yrs after diagnosis followed by an annual check-up. Patients complaining of new visual symptoms should be seen sooner than these recommended intervals. Reflect! How many diabetic patients do you look after? Do they all have regular ophthalmic examination? Do you routinely check this when you see them? Classification Features Minimal Nonproductive Diabetic Retinopathy (NPDR) Microaneurysms only Mild NPDR Microaneurysms + haemorrhages Hard exudates ModerateSevere NPDR As above + venous beading Proliferative Diabetic Retinopathy or macular oedema Fundus obscured due to vitreous haemorrhage Retinal detachment involving macula [ top ] 2.2 Treatment of diabetic retinopathy Management of diabetic retinopathy involves control of the underlying diabetes, and optimisation of blood pressure and cholesterol (if elevated). Laser treatment of diabetic retinopathy is primarily to stabilise vision due to macular oedema, and to prevent haemorrhage and tractional retinal detachment complicating proliferative retinopathy. Caution! Early diagnosis and referral of diabetic retinopathy is crucial to eventual success of treatment. [ top ] 3. Sickle cell anaemia Like diabetes mellitus, sickle cell anaemia can cause vitreous haemorrhage and retinal detachment. Patients with the SC and S Thal form of the disease are more likely to have ocular complications then the SS form. Ocular manifestations generally result from intravascular sickling, haemolysis, haemostasis and resultant thrombosis leading to arteriolar occlusion. This arteriolar occlusion causes restricted capillary perfusion and compensatory neovascularization results. Identification of preliminary signs such as thrombi and vascular occlusion are important for early referral. [ top ] 4. Hypertension Ocular manifestations of systemic hypertension are best understood if divided into two classifications: those due to arteriolar sclerosis; and those due to elevated blood pressure. [ top ] 4.1 Arteriolar sclerosis Systemic hypertension (with a diastolic pressure higher then 100mm Hg) accelerates the normal process during aging of thickening and sclerosis of the arterioles. These changes in the walls of the retinal arterioles can be readily observed during a routine fundus examination. In a normal eye, ophthalmoscopic examination of the retina displays the retinal arterioles as transparent tubes of blood with a streak of light reflected from the convex side of the vessel (the central light reflex). As the retinal arterioles thicken due to the sclerosis, the light reflex from these vessels also increases in width. As the arteriolar sclerosis advances and the light reflex comes to occupy most of the with of the vessels; at this stage the vessels are called copper-wire arterioles. Changes in the arteriovenous crossing may also indicate systemic hypertension. The arterioles and veins within the retinal tissue share a common sheath at crossing sites. Zones of concealment (where the vein is hidden in the region it crosses underneath the artery) may indicate hypertension. The vein may also be elevated or depressed by the arteriole and in more severe cases may change direction up to 90 degrees as it reaches the arteriole. Compression or constriction at the A/V crossing may result in dilation of the portion of the vein distal to the crossing or other changes in vein integrity. The changes in arteriovenous crossings listed above are most serious when located at or beyond the second bifurcation of the arteriole (~1 disc diameter form the optic disc margin). They can potentially lead to a decrease in visual acuity via occlusion of branch retinal veins. [ top ] 4.2 Elevated blood pressure A moderate, acute increase in blood pressure causes a compensatory constriction of retinal arterioles. If the rise in blood pressure is severe (diastolic pressure over 120mm Hg), fibrinoid necrosis of the vessel wall may result with exudates, flame-shaped haemorrhages, cottonwool spots and occasionally whitish swelling and oedema of significant portions of the retina. An optic disc resembling the swelling present in papilloedema may also be seen in the most severe form of hypertensive retinopathy. [ top ] 4.3 Screening for hypertensive retinopathy The thickening of vessel walls in arteriolar sclerosis guards against fibrinoid necrosis. Because of this, changes due to acute hypertension are best seen in previously normal arterioles. Differentiation between normal age related changes and chronic hypertensive vascular changes are difficult. The best indicators of hypertension are, in order of importance; changes in the retinal arterioles; focal narrowing; changes in arterioventricular crossing. Caution! If blood pressure must be lowered (eg due a severe acute increase in blood pressure), it is imperative to do so in a controlled fashion to reduce risk of optic nerve infarction. [ top ] 5. Inflammatory conditions A number of systemic inflammatory conditions may have clinical implications in the eye. They include: ankylosing spondylitis Reiter's syndrome psoriatic arthritis sarcoidosis juvenile rheumatoid arthritis all of which may cause uveitis and other ocular complications. Juvenile rheumatoid arthritis is a childhood inflammatory disease with serious ocular implications. Iritis is present in 10% of sufferers and if not recognised can lead to complications such as glaucoma, cataract and corneal calcification. Golden Rule! Patients who have juvenile rheumatoid arthritis should have quarterly visits with the ophthalmologist. Other inflammatory conditions, such as rheumatoid arthritis and systemic lupus erythematosus, may also appear in the eye. They primarily present as dry eye with symptoms of grittiness and burning in the eye. Lubricating ointment or artificial tears is adequate treatment in all but the most severe cases. [ top ] 6. Systemic infections AIDS AIDS has various manifestations in the eye. Amongst the most common are cotton-wool spots (AIDS retinopathy), cytomegalovirus retinitis and Kaposi's sarcoma of the eyelids. Cotton-wool spots are the sole ocular finding in approx 50% of AIDS patients. They occur due to occlusions of retinal capillaries that result in accumulation of axoplasm in the retinal nerve fibre layer. Occasionally, herpes zoster, herpes simplex, conjunctival microangiopathy, luetic and toxoplasmic uveitis and CNS involvement causing visual field and oculomotor defects are seen. (Illustration: Kaposi's sarcoma of the eyelid. Photo courtesy of Alex Mackay) Golden Rule! Any patient diagnosed with HIV should be referred to an ophthalmologist for a complete ophthalmological examination. Other Systemic Infections and Infestations All of the following may cause significant ocular complications: tuberculosis, leprosy, toxoplasmosis, herpes zoster herpes simplex Herpes zoster and simplex are dealt with in detail elsewhere. [ top ] 7. Thyroid disease Thyroid diseases, eg Graves' disease, are important autoimmune diseases that present clinical features in the eye. A common characteristic of thyroid disease is exophthalmos (protrusion of the globes), presenting with retraction of the upper and lower eyelid with upperlid lag on downgaze. The resulting appearance is commonly called the "Thyroid stare". Upper and lower eyelid retraction and exophthalmos can cause the patient to complain of irritation, foreign body sensation and tearing as a result of corneal exposure and drying. These symptoms can be remedied with artificial tear preparations and lubricating eye ointment at night. [ top ] 8. Myasthenia gravis Myasthenia gravis is an autoimmune disease caused by an abnormality at the neuromuscular junction. It is characterized by abnormal and excessive fatigability of skeletal muscles and usually presents in women aged 20-40. Around 60% of patients suffering from myasthenia gravis show ocular symptoms as their primary presentation so it is important not to overlook the clinical features involved. Clinical features: Bilateral but asymmetrical ptosis, worse towards the end of the day or when the patient is tired Test for the 'twitch sign of Crogan' by asking the patient to rapidly redirect his/her gaze from the downward position to the primary position. A positive twitch test will be indicated by the upper lid twitching upward and then slowly resettling to its ptotic position. Diplopia - extraocular muscle involvement appears to follow no set pattern by all fields of gaze should be examined to check for diplopia. [ top ] 9. Cancer and the eye Primary cancer in the eye is uncommon. Most ocular cancers arise secondarily. At autopsy, approximately 5% of cancer patients have ocular or orbital metastases. Approximately 3% of systemic lymphoma sufferers have proptosis or reduced eye motility. Leukaemic infiltration of ocular tissues can occur in children and patients with leukaemia commonly develop superficial retinal, pre-retinal or subconjunctival haemorrhages as a result of thrombocytopenia. Cancer treatments may have deleterious effects on the eye. Radiation of tumours close to the eye may produce cataract, as the lens is sensitive to radiation in the 2000 rads range. Some types of cancer chemotherapy may have ocular repercussions. Vincristine injections may cause optic neuropathy. Superficial keratitis may develop from cytosine arabinoside BCNU injection into the carotid may cause retinal artery occlusion. [ top ] References 1. Hunyor, A.P., 2001, Age related macular degeneration and diabetic eye disease, Chatswood Retinal Service. 2. Bradford, C.A.,1999, Basic ophthalmology for medical students and primary care residents, 7th edn., American Academy of Ophthalmology, San Francisco, CA .