Systemic Diseases and the Eye
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Direct answer
The eye is affected by many systemic diseases, and ocular signs may be the first clue to a systemic diagnosis. Diabetes causes retinopathy, early cataract, cranial nerve palsies and refractive fluctuations; hypertension produces the Keith-Wagener retinopathy grades and is a major driver of vascular occlusions; thyroid disease causes orbitopathy; and sarcoidosis, tuberculosis and syphilis cause uveitis. Metabolic and storage diseases give pathognomonic corneal findings (Kayser-Fleischer ring in Wilson disease, corneal verticillata in Fabry disease, corneal crystals in cystinosis), while haematological and connective tissue diseases produce retinopathy, uveitis, scleritis and dry eye. Recognising these patterns converts an eye examination into a systemic screening tool.
What you must remember
- Diabetes: retinopathy (the leading microvascular complication), early-onset cataract, refractive shifts with glycaemic change, cranial nerve palsies (usually microvascular third or sixth), neurotrophic and infectious keratitis risk, xanthelasma and accelerated atheromatous vascular disease.
- Hypertension and atherosclerosis: Keith-Wagener-Barker retinopathy grades I to IV, retinal arteriolar emboli (Hollenhorst plaques), branch and central retinal vein and artery occlusions, and retinal macroaneurysms.
- Thyroid disease: Graves orbitopathy with lid retraction, proptosis and restrictive myopathy; hypothyroidism rarely gives xanthelasma and keratopathy.
- Wilson disease (hepatolenticular degeneration): Kayser-Fleischer ring, a golden-brown copper deposit in the peripheral Descemet membrane, best seen on gonioscopy; associated with sunflower cataract; reverses with chelation therapy.
- Storage and metabolic: Fabry disease gives cornea verticillata (whorl-like vortex keratopathy from amiodarone-like deposition), cystinosis gives corneal crystal deposits with photophobia, mucopolysaccharidoses (Hurler, Scheie) give corneal clouding, and albinism gives iris transillumination with foveal hypoplasia and nystagmus.
- Sarcoidosis: bilateral granulomatous uveitis with mutton-fat keratic precipitates, candle-wax drippings (periphlebitis), retinal granulomas, lacrimal gland enlargement and dry eye; chest radiograph and serum angiotensin-converting enzyme support the diagnosis.
- Tuberculosis and syphilis: TB causes chronic granulomatous uveitis, choroidal tubercles in miliary disease and Eales disease-like vasculitis in young Indian men; syphilis gives Argyll Robertson pupil, interstitial keratitis in congenital disease and uveitis.
- HIV and immunosuppression: CMV retinitis (pizza Fundus: necrotising retinitis with haemorrhage along vessels) is the commonest ocular opportunistic infection, plus herpes zoster ophthalmicus, Kaposi sarcoma of lids and conjunctiva, cotton-wool spots and neuro-ophthalmic disease.
- Connective tissue and vasculitis: rheumatoid arthritis (dry eye, scleritis, peripheral ulcerative keratitis), granulomatosis with polyangiitis (necrotising scleritis and orbit disease), systemic lupus erythematosus (cotton-wool spots, dry eye), ankylosing spondylitis (acute anterior uveitis) and Behcet disease (recurrent hypopyon uveitis with retinal vasculitis and oral-genital ulcers).
- Haematological disorders: anaemia and leukaemia give retinal haemorrhages including Roth spots (white-centred haemorrhages), hyper-viscosity syndromes such as Waldenstrom macroglobulinaemia give venous dilatation and haemorrhages, and sickle cell disease gives salmon-patch haemorrhages, sea-fan neovascularisation and angioid streaks.
- Phakomatoses for exams: neurofibromatosis (Lisch nodules, plexiform neurofibroma), tuberous sclerosis (retinal astrocytic hamartoma), Sturge-Weber syndrome (glaucoma, choroidal haemangioma) and von Hippel-Lindau disease (retinal haemangioblastoma).
Common confusion
Examiners contrast conditions with overlapping signs: corneal verticillata occur in Fabry disease but also with amiodarone and chloroquine, so the drug history is essential; Roth spots occur in leukaemia and anaemia but also in bacterial endocarditis; and Lisch nodules of neurofibromatosis must not be confused with Brushfield spots of Down syndrome (which sit peripherally on a pale iris). Also remember that uveitis work-ups always include syphilis, tuberculosis and sarcoidosis serology or imaging in Indian practice.
Exam-focused takeaway
MCQs are typically single-best-answer associations: Kayser-Fleischer ring with Wilson disease and its gonioscopic visibility, sunflower cataract with Wilson disease or copper intraocular foreign body, cornea verticillata with Fabry disease and amiodarone, Roth spots with endocarditis and leukaemia, cherry-red spot with Tay-Sachs and central retinal artery occlusion, and Lisch nodules with neurofibromatosis type 1. The viva often starts with a sign and demands the systemic differential and the next investigation.
Frequently asked questions
What is the Kayser-Fleischer ring and which disease does it signify?
It is a golden-brown to greenish ring of copper deposited in the peripheral Descemet membrane, usually widest at the superior and inferior limbus and best detected by gonioscopy. It is a hallmark of Wilson disease, correlates with neurological involvement, and fades with chelation treatment.
Which ocular signs suggest sarcoidosis?
Bilateral granulomatous anterior uveitis with large mutton-fat keratic precipitates and iris nodules, periphlebitis with candle-wax exudates, chorioretinal granulomas, bilateral lacrimal gland enlargement and dry eye suggest sarcoidosis. Chest imaging, serum angiotensin-converting enzyme and lysozyme support the diagnosis, confirmed by histology when accessible.
What are Roth spots and what do they indicate?
Roth spots are retinal haemorrhages with white centres, classically representing microabscesses or leucocyte collections within nerve fibre layer haemorrhages. They occur in bacterial endocarditis, leukaemia, severe anaemia, diabetes and hypertension, and always warrant a systemic work-up.
How does HIV infection affect the eye?
The commonest sight-threatening lesion is cytomegalovirus retinitis, a necrotising retinitis with yellow-white necrosis and haemorrhage along vascular arcs. Other manifestations include herpes zoster ophthalmicus, cotton-wool spots, Kaposi sarcoma of the adnexa, toxoplasmosis and neuro-ophthalmic lesions.
Which connective tissue diseases present with scleritis or keratitis?
Rheumatoid arthritis causes scleritis (including necrotising scleromalacia perforans) and peripheral ulcerative keratitis; granulomatosis with polyangiitis causes necrotising scleritis with orbital involvement; relapsing polychondritis causes scleritis with auricular cartilage inflammation. These signal systemic vasculitis needing urgent immunosuppression.