External Ocular Signs of Systemic Disease

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In the realm of ophthalmology and systemic disease, the focus traditionally lies on retinal findings obtained through fundoscopy.

However, this article takes a different approach, shifting the spotlight to ocular features apparent from a general examination without needing specialised ophthalmic equipment.

This perspective is particularly relevant for medical students and general practitioners, who often rely on more general examination techniques in their initial patient assessments. By exploring these observable ocular signs and their associations with various systemic diseases, this guide aims to provide a comprehensive understanding of how the eyes can reflect broader systemic diseases.

This article will cover various body systems, illustrating how simple observations of the eyes can offer valuable insights into a patient’s systemic health.

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Cardiovascular system



Cholesterol deposits under the skin.

Xanthelasma in hyperlipidaemia
Figure 1. Xanthelasma.

Corneal arcus

Lipid deposits on the outer cornea.

Corneal arcus
Figure 2. Corneal arcus.

Gastrointestinal system

Wilson’s disease

Kayser-Fleischer rings

These form on the peripheral border of the cornea due to copper deposition.

Kayser-Fleischer ring
Figure 3. Kayser-Fleischer ring

Crohn’s disease and ulcerative colitis

Uveitis and episcleritis

The image shows an irregularly shaped pupil due to posterior synechiae in uveitis.

Posterior synechiae uveitis
Figure 4. Posterior synechiae in uveitis

Nervous systemΒ 

Neurofibromatosis type 1

Lisch nodules

Lisch nodules (iris hamartomas) are pathognomonic of neurofibromatosis type 1.Β 

Lisch nodules
Figure 5. Lisch nodules

Endocrine system

Thyroid eye disease


There may also be lid lag on examination.Β 

Figure 6. Exophthalmos

Dermatological conditions


Ocular rosacea

Ocular rosacea
Figure 7. Ocular rosacea.

Autoimmune conditions

Systemic lupus erythematosus (SLE), rheumatoid arthritis, BehΓ§et’s disease and ankylosing spondylitis can cause dry, inflamed red eyes.

They are also associated with episcleritis, scleritis and uveitis. From general inspection, these likely appear as a non-specific, painful red eye.

Sarcoidosis can also be associated with conjunctival nodules.

Connective tissue diseases

Osteogenesis imperfecta and Ehler’s-Danlos syndrome

Blue sclera

Blue sclerae osteogenesis imperfecta
Figure 8. Blue sclerae

Marfan syndrome

Lens subluxation

Marfan syndrome is associated with lens subluxation (ectopia lentis) when the lens is off-centre. It can occur in up to 75% of patients with Marfan syndrome. Lens subluxation is also associated with trauma and other ocular disease such as retinitis pigmentosa, high myopia and congenital glaucoma.

Lens subluxation marfan syndrome
Figure 9. Lens subluxation


  • American Academy of Ophthalmology. Ocular Manifestations of Systemic Disease. Published in 2009. Available from: [LINK]
  • Patient.info. The Eye and Systemic Disease. Published in 2021. Available from: [LINK]
  • Jacob J. Yunker, MD. Ocular Manifestations of Systemic Disease. Available from: [LINK]

Image references

  • Figure 1. Oleg Tymofii. Adapted by Geeky Medics. Eyelid Xanthelasma. License: [CC BY-SA]
  • Figure 2. Afrodriguezg. Arcus Senilis. License: [CC BY-SA]
  • Figure 3. Herbert L. Fred, MD, Hendrik A. van Dijk. Kayser-Fleicher rings. License: [CC BY]
  • Figure 4. Community Eye Care Journal. Posterior synechiae – a sign of uveitis. License: [CC BY-NC]
  • Figure 5. Dimitrios Malamos. Lisch nodules. License: [CC BY]
  • Figure 6. Emergency Medicine Clinical Images. Exophthalmos. License: [CC BY-NC-SA]
  • Figure 7. Dermnet. Ocular rosacea. License: [CC BY-NC-ND]
  • Figure 8. Herbert L. Fred, MD and Hendrik A. van Dijk. Characteristically blue sclerae of patient with osteogenesis imperfecta. License: [CC BY-SA]
  • Figure 9. Anselmuccifederico. Subluxation of the lens in human eye. License: [CC BY]


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