Dengyi Zhou

Introduction

Ophthalmic symptoms are frequently encountered across acute, outpatient and ward-based settings. While many eye presentations are benign, the eye can also provide an early and accessible indication of systemic disease. Visual symptoms may precede, accompany or reflect the severity of underlying inflammatory, vascular, neurological or infectious pathology (1). Recognising when an ocular presentation represents more than a local eye problem is therefore an important clinical skill across specialties.

The Eye as a Window to Systemic Health

The eye is unique in allowing direct visualisation of blood vessels, neural tissue and inflammatory processes without invasive investigation. Retinal vasculature reflects systemic microvascular health, while the optic nerve can offer insight into neurological and intracranial pathology. As a result, ocular findings may be the first manifestation of systemic illness or signal disease progression elsewhere.

Visual symptoms should prompt broader consideration when they are:

• associated with reduced visual acuity
• painful or accompanied by photophobia
• bilateral, recurrent or progressive
• associated with neurological or constitutional symptoms

Inflammatory Disorders

Inflammatory and infective diseases can affect vision by targeting multiple ocular structures. Early recognition is important, as diagnosis frequently necessitates systemic evaluation and coordinated multidisciplinary care.

Uveitis and Retinal Vasculitis

Uveitis refers to inflammation of the uveal tract and may affect adults or children. Although it can be idiopathic, it is frequently associated with serious systemic disease, including tuberculosis, syphilis and HIV (infectious uveitis), sarcoidosis (non-infectious uveitis) and, less commonly, lymphoma (2).

Anterior uveitis is the most common subtype and typically presents with a red, painful eye, photophobia and blurred or cloudy vision. The pupil may appear small or irregular, and patients may complain of headache. Intermediate uveitis primarily affects the vitreous and is usually painless, presenting with floaters and blurred vision. Posterior uveitis affects the choroid and retina and often presents with painless visual loss, floaters and occasionally retinal detachment. Panuveitis involves multiple segments of the eye and can produce a combination of these symptoms (2).

Management depends on identifying the underlying cause through targeted laboratory investigations and imaging, such as chest X-rays. Control of intraocular inflammation is essential and frequently requires a multidisciplinary approach involving ophthalmology, rheumatology, infectious diseases or oncology.

Scleritis

Scleritis is a severe inflammatory condition affecting the sclera and is associated with intense ocular pain and a very red eye. It may be anterior or posterior, with posterior scleritis sometimes presenting with serous retinal detachment or choroidal folds. Importantly, scleritis is often associated with systemic inflammatory disease, particularly rheumatoid arthritis, and should prompt investigation for an underlying cause (2).

Behçet’s disease

Behçet’s disease is a multisystem vasculitis with a particular affinity for mucous membranes, most commonly presenting with recurrent oral ulcers. Ocular involvement is reported in 30-70% of patients with Behçet’s disease and may include recurrent uveitis and retinal vascular occlusion (3).

Sarcoidosis

Sarcoidosis is a multisystem granulomatous disease that can affect patients of all ages, with higher prevalence reported in individuals of African-American or Scandinavian descent. Ocular manifestations include dry eye, granulomatous anterior uveitis, conjunctival granulomas and retinal periphlebitis. Retinal neovascularisation may develop secondary to inflammation-induced vascular occlusion. Diagnosis is supported by clinical and radiographic findings alongside histological evidence of non-caseating granulomas. Investigations commonly include serum angiotensin-converting enzyme levels and chest X-ray. Treatment is centred on corticosteroids, with topical, periocular or systemic therapy chosen based on disease severity and location (4).

Vascular Disorders

Diabetic Retinopathy

Diabetic retinopathy is a leading cause of preventable visual impairment. Vision loss may result from macular oedema or from retinal ischaemia leading to neovascularisation, vitreous haemorrhage and retinal detachment. Management requires optimisation of systemic risk factors such as diabetes, hypertension and hyperlipidaemia, alongside ophthalmic treatments including laser photocoagulation and intravitreal anti-vascular endothelial growth factor injections. Screening programmes have enabled earlier detection and improved visual outcomes (5).

Retinal Vein Occlusion

Retinal vein occlusion represents the second leading cause of retinal vascular blindness after diabetic retinopathy and results from obstruction of the retinal venous system, most commonly related to atherosclerotic risk factors. Other causes include haematological disorders, hypercoagulable states and systemic inflammatory disease such as Behçet’s disease, sarcoidosis and vasculitis. Patients may be asymptomatic until complications such as macular oedema or vitreous haemorrhage develop. Ophthalmic management follows similar pathways to diabetic retinopathy (6).

Retinal Artery Occlusion

Retinal artery occlusion presents as sudden, painless visual loss in one eye and is an ophthalmic emergency. Causes include emboli, atherosclerosis, inflammation or vasospasm and may be associated with atrial fibrillation or carotid artery stenosis. Investigation may include vascular imaging, such as carotid Doppler ultrasound, cardiac assessment for atrial fibrillation or valvular disease, and, in younger patients, evaluation for hypercoagulable or autoimmune conditions.

Giant cell arteritis should be suspected in all patients over 50 years, particularly if systemic symptoms such as headache, jaw claudication or scalp tenderness are present. Inflammatory markers (ESR, CRP) are usually elevated, and high-dose corticosteroids should be initiated immediately, without waiting for temporal artery biopsy or imaging, to prevent further visual loss (7).

Severe carotid artery stenosis can also result in ocular ischaemic syndrome, a rare vision-threatening condition presenting with progressive visual loss, ocular pain, and visual field defects. This condition requires referral to vascular surgery alongside ophthalmic management (8).

Neurological Disorders

Optic Neuropathies

Distinguishing between arteritic and non-arteritic optic neuropathy is crucial. Arteritic ischaemic optic neuropathy, most commonly due to giant cell arteritis, results in profound visual loss and systemic complications. Elevated inflammatory markers support the diagnosis, and treatment with high-dose corticosteroids should be initiated urgently.

Non-arteritic ischaemic optic neuropaty is more common than the arteritic form and typically occurs in patients with vascular risk factors or an anatomically crowded optic disc, which predisposes the optic nerve head to ischaemic injury. Management focuses on identifying and treating underlying cardiovascular risk factors, with ophthalmic follow-up to monitor visual fields (9).

Optic Neuritis

Optic neuritis typically presents with painful eye movements, subacute visual loss, and impaired colour vision, often associated with multiple sclerosis. MRI of the brain and orbits is recommended to assess for demyelinating lesions. Atypical features such as bilateral involvement, severe vision loss, absence of pain, or optic disc haemorrhage, should prompt further evaluation for alternative causes, including ischaemic, inflammatory, infectious, or infiltrative optic neuropathies (10).

Papilloedema

Papilloedema reflects raised intracranial pressure and requires urgent investigation to exclude intracranial mass lesions, venous sinus thrombosis and malignant hypertension. Idiopathic intracranial hypertension should be considered, particularly in overweight women of childbearing age (11).

Thyroid Eye Disease

Thyroid eye disease has a wide range of ocular manifestations, including lid retraction, proptosis, restricted eye movements and optic nerve compression. Smoking is associated with increased disease severity. Management focuses on controlling thyroid dysfunction and providing supportive care, with immunosuppression or surgical intervention reserved for more severe disease (12).

Practical Considerations

A systematic approach to history-taking and examination, including assessment of both ocular and general systems, is essential. Reduced visual acuity, pain, photophobia and neurological symptoms should prompt further evaluation. Management should be multidisciplinary, targeting both the underlying systemic condition and its ophthalmic manifestations.

Conclusion

Ocular symptoms should not be viewed in isolation. Across specialties, understanding when eye findings indicate wider systemic disease is an essential clinical skill. Recognising red flags, maintaining a broad differential diagnosis and escalating appropriately can prevent irreversible visual loss and improve overall patient outcomes. The eye often provides the first indication that something more significant is occurring, and careful attention to ophthalmic presentations can make a meaningful difference.

References

1. Hazin R, Lum F, Daoud YJ. Ophthalmic features of systemic diseases. Annals of medicine. 2012 May 1;44(3):242-52.
2. Miller JR, Hanumunthadu D. Inflammatory eye disease: An overview of clinical presentation and management. Clinical Medicine. 2022 Mar 1;22(2):100-3.
3. Abbas MA, Yasir MB, Rasheed LS. Prevalence and Characteristics of Ocular and Systemic Manifestations in Iraqi Patients with Behçet’s Disease. The Open Ophthalmology Journal. 2025 Feb 17;19(1).
4. Jain R, Yadav D, Puranik N, Guleria R, Jin JO. Sarcoidosis: causes, diagnosis, clinical features, and treatments. Journal of clinical medicine. 2020 Apr 10;9(4):1081.
5. Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet. 2010 Jul 10;376(9735):124-36.
6. Ip M, Hendrick A. Retinal vein occlusion review. The Asia-Pacific Journal of Ophthalmology. 2018 Jan 1;7(1):40-5.
7. Smith JH, Swanson JW. Giant cell arteritis. Headache: The Journal of Head and Face Pain. 2014 Sep;54(8):1273-89.
8. Terelak-Borys B, Skonieczna K, Grabska-Liberek I. Ocular ischemic syndrome–a systematic review. Medical science monitor: international medical journal of experimental and clinical research. 2012 Aug 1;18(8):RA138.
9. Salvetat ML, Pellegrini F, Spadea L, Salati C, Zeppieri M. Non-arteritic anterior ischemic optic neuropathy (NA-AION): a comprehensive overview. Vision. 2023 Nov 9;7(4):72.
10. Toosy AT, Mason DF, Miller DH. Optic neuritis. The Lancet Neurology. 2014 Jan 1;13(1):83-99.
11. Rigi M, Almarzouqi SJ, Morgan ML, Lee AG. Papilledema: epidemiology, etiology, and clinical management. Eye and brain. 2015 Aug 17:47-57.
12. Weiler DL. Thyroid eye disease: a review. Clinical and experimental optometry. 2017 Jan 1;100(1):20-5.