Ophthalmic manifestations of systemic disorders

Inflammatory disorders

Inflammatory and infective diseases can affect vision by targeting a variety of tissues in the eye.

Uveitis and retinal vasculitis

Uveitis refers to inflammation of the middle layer of the eye and can affect both adults and children. It may be idiopathic, but it can be linked to some serious systemic diseases such as tuberculosis, syphilis and HIV/AIDS (infectious uveitis), sarcoidosis (non-infectious uveitis) and lymphoma.

Anterior uveitis (the most common type of uveitis affecting the iris or/and the ciliary body) is associated with visible signs of anterior chamber inflammation such as red, painful eye with cloudy vision, as well as a small, or irregular-shaped pupil, photophobia and headaches. Intermediate uveitis predominantly affects the vitreous. It is mostly painless and presents with eye floaters, blurred vision and sometimes a mild redness of the eye. Posterior uveitis affects the choroid, it is also painless and usually causes decreased vision, eye floaters, and sometimes retinal detachment. Panuveitis can be a combination of all of these symptoms due to multiple areas of the eye being affected concurrently.

Management of uveitis and retinal vasculitis depends on identifying the underlying disease through laboratory investigations and X-rays. Control of intraocular inflammation is important, often requiring a multidisciplinary team approach.

Scleritis

Scleritis, is a form of inflammation affecting predominantly the sclera and can be anterior or posterior, both types causing a very red eye and intense ocular pain. Posterior scleritis can manifest as serous retinal detachment, choroidal folds or both. It’s important to investigate whether there is an associated underlying medical condition such as rheumatoid arthritis.

Specific inflammatory disorders

Behcet's disease

Behcet's disease is a multisystem vasculitis affecting nearly all organ systems, with a particular affinity for mucous membranes with oral ulcers being the main feature. Ophthalmic presentation can include intraocular inflammation with recurrent uveitis (in 10-20% of Behcet's cases) and vascular occlusion.

Sarcoidosis

This multisystem granulomatous disease can occur in all age groups and is strongly associated with racial and ethnic factors. Common ocular symptoms include dry eye, granulomatous anterior uveitis, conjunctival granulomas, sarcoid periphlebitis, and retinal neovascularization which stems from inflammation-induced vascular blockage and ischemia.

The sarcoidosis diagnosis is established when clinical and radiographic findings are supported by histological evidence of non-caseating granulomas on biopsy. Common investigations include serum angiotensin-converting enzyme and chest X-ray.

Ocular sarcoidosis is mainly treated with corticosteroids, with options including topical, peribulbar, or systemic administration depending on the location and severity of the disease.

Vascular disorders

Diabetic retinopathy

Diabetic retinopathy is a sight-threatening condition caused mainly by either the growth of new vessels, resulting in intraocular haemorrhage and/or retinal detachment, or macula oedema, with loss of central vision.

Management includes optimizing underlying health pathologies such as diabetes mellitus, hypertension and hyperlipidaemia. Ophthalmic treatment depends on how severe the eye problems are (new blood vessels or issues with the macula) and can include laser photocoagulation and intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections.

Screening programmes have enabled the early detection of diabetic retinopathy and early treatment, with increasingly good outcomes.

Retinal vein occlusion

Retinal vein occlusion is an obstruction of the retinal venous system, usually by thrombus formation and many cases are related to the risks of atherosclerosis. Other causes include blood coagulation disorders (leukaemia, myeloma, waldenstrom’s macroglobulinaemia, myelofibrosis, changes in the protein C pathway) and systemic inflammatory disorders (behcet's disease, polyarteritis nodosa, sarcoidosis, granulomatosis with polyangiitis and goodpasture’s syndrome).

Patients with retinal vein occlusion are only symptomatic if complications develop, such as visual impairment in macular oedema, and vitreous haemorrhage in retinal ischaemia and neovascularization. Ophthalmic treatment is similar to the diabetic retinopathy treatment pathways.

Retinal artery occlusion

A blockage in the retinal artery can cause sudden, painless vision loss in one eye. This blockage can happen due to various reasons like clots, cholesterol buildup, inflammation, or spasms in the blood vessels and can be linked to atrial fibrillation or carotid artery stenosis.

Giant cell arteritis must be considered in patients over 50 years of age. Carotid artery stenosis assessment typically involves carotid ultrasound, while echocardiography should be included to detect potential cardiac valve abnormalities. In younger patients, it's recommended to conduct a hypercoagulability evaluation, which should encompass screening for antiphospholipid antibodies as well as autoimmune and inflammatory conditions.

Multiple or recurrent branch retinal artery occlusions, signs of encephalopathy and hearing loss should highlight a possibility of Susac’s syndrome.

Ocular ischaemic syndrome

This is a very rare, vision-threatening disease usually linked with severe narrowing of the carotid artery, leading to reduced blood flow to the eyes. Symptoms include visual loss, light-induced transient visual loss and ischaemic ocular pain. On examination, there can be a reduction in visual acuity, ocular hypotony and 360% mid-peripheral haemorrhages. Risk factors in patients with ocular ischaemic syndrome are similar to those of atherosclerosis.

Eye treatment focuses on managing inflammation in the front part of the eye using corticosteroid eye drops and cycloplegic medications. This helps stabilize the barrier between the blood and the fluid inside the eye, and addresses issues like reduced blood flow to the retina and the development of abnormal blood vessels causing glaucoma. Patients should be referred to vascular surgeons.

Roth’s spots

These are traditionally considered to be a manifestation of infective endocarditis. However, the differential diagnosis and subsequent investigations for patients with Roth’s spots should include anaemia, leukaemia, retinal phlebitis, candida albicans infection, vascular diseases, bacterial sepsis and viral pneumonia.

Neurological disorders

Optic neuropathies

It is important to differentiate between arteritic and non-arteritic optic neuropathies as the former result in loss of vision and systemic complications.

Arteritic ischaemic optic neuropathy

Arteritic ischaemic optic neuropathy is often referred to as giant cell arteritis, a condition where medium-sized blood vessels throughout the body become inflamed and narrowed. The condition typically affects women over 60 years of age and it is often linked with polymyalgia rheumatica.

Clinical tests reveal elevated levels of inflammation markers: erythrocyte sedimentation rate and C-reactive protein. The preferred diagnostic method is a temporal artery biopsy, but ultrasound is becoming more common to detect a 'halo sign', indicating swelling in the artery wall. Treatment involves high doses of corticosteroids, which are carefully monitored and gradually reduced over a period of 6 months, usually in consultation with a rheumatologist.

Non-arteritic ischaemic optic neuropathy

Non-arteritic ischaemic optic neuropathy is the most common type of optic nerve damage among patients over 50 years of age. It occurs due to the blockage of small blood vessels supplying the optic nerve and is linked with risk factors related to blood vessel problems, such as those seen in atherosclerosis or an ‘at-risk disc’ - a small crowded optic disc with a small physiological cup.

Investigations aim to identify and treat patients with atherosclerosis-related conditions. The stability of vision loss is assessed through follow-up visual field exams with an ophthalmic specialist at 3 months.

Optic neuritis

Optic neuritis is an acute inflammation of the optic nerve that often leads to pain when moving the eyes and vision problems, including changes in color perception. While many cases have no known cause, it can sometimes be linked with multiple sclerosis. Other less common causes include post-viral infection and post-vaccination immunological responses.

In many cases, optic neuritis resolves by itself, vision typically starts to improve within the initial month. Unusual signs like no pain, significant swelling of the optic nerve with fluid and bleeding, or severe and persistent vision loss beyond 3 weeks, require additional investigations (such as lumbar puncture, spinal MRI, aquaporin-4 concentration) to exclude other possible causes of optic neuritis.

Papilloedema

Swelling of the optic nerves, known as papilledema, is due to heightened pressure inside the skull. Investigations aim to rule out conditions like brain tumours, blood clotting in the brain's veins, and severe high blood pressure by using imaging scans and monitoring blood pressure in all patients with papilledema symptoms.

Idiopathic intracranial hypertension

Idiopathic intracranial hypertension, a condition leading to papilledema, typically impacts overweight women in their childbearing years. If left untreated, it can cause gradual optic nerve damage and vision loss. Treatment often involves lifestyle changes like weight loss efforts and discontinuing certain medications such as oral contraceptives and doxycycline. In severe cases, surgical options like optic nerve decompression or ventriculoperitoneal shunts may be considered by a neurosurgeon.

Thyroid eye disease

Thyroid eye disease has a range of ocular manifestations including swelling around the eyes, redness in the conjunctiva, watery eyes, and inflammation of the upper part of the cornea, eyelid retraction, bulging eyes (proptosis), restrictions in eye movement due to muscle issues, optic nerve damage.

Smoking is associated with an increased severity of the disease. Investigations include measurements of thyroid-stimulating hormone, thyroxine (T4) and thyroid-stimulating immunoglobulin. Imaging techniques such as computed tomography and MRI show enlarged extraocular muscles and possible proptosis of the eye globe.

The primary approach to treating thyroid eye disease involves supportive care as it often improves on its own. It's important to effectively manage any underlying thyroid issues. For mild cases, simply using eye lubricants may suffice. In more active cases, treatment may involve intravenous methylprednisolone or medications that reduce the need for corticosteroids. Orbital radiation in combination with oral corticosteroids can be effective for relieving pressure on the optic nerve. Surgical intervention is occasionally necessary in severe cases after the inflammation has settled.

Source: Heng L.Z., Hamilton R. D. (2018). Medicine in ophthalmology. Medicine, 46 (5). https://doi.org/10.1016/j.mpmed.2018.09.007