Pathologic changes in the cornea and external eye are associated with a wide variety of systemic diseases. They may have different particular symptoms. Some changes are characteristic of the specifically underlying diseases. Some changes in some grouping cases are arbitrary. Some corneal findings may be secondary to problems of the eyelids, eyelashes, and other adnexal structures that are involved in a systemic disorder. These associated systemic diseases include congenital disorders, chromosomal abnormalities, inherited connective tissue disorders, metabolic disorders, and other ocular anatomical disorders.

　　Craniofacial malformation syndromes include Crouzon syndrome and Goldenhar syndrome. Chromosome disorders include Down syndrome (Trisomy 21), Turner syndrome, Patau syndrome (Trisomy 13), and Edward syndrome (Trisomy 18). Ocular manifestations in the congenital and chromosomal disorders comprise microphthalmos, microcornea, limbal dermoid, and ptosis. Connective tissue diseases include Marfan syndrome, osteogenesis imperfecta and Ehlers-Danlos syndrome. They may have ocular manifestation of megalocornea, keratoconus, keratoglobus, and blue sclera. Metabolic disorders include protein and amino acid metabolic defects, mucopolysaccharidoses, sphingolipidoses, dyslipoproteinemias, and mucolipidoses. Most of metabolic disorders are alternations in corneal clarity caused by abnormal storage of metabolic substances within the epithelium, stroma, or endothelium.

　　Other systemic disorders may have primary or secondary corneal changes. Rheumatoid arthritis and polyarteritis nodosa causes corneal melting and scleritis. Lupus erythematosus, scleroderma and Sjogren’s syndrome may have corneal erosion and dry eye. Graves’s disease may have exophthalmos, exposure keratitis and strabismus. Band keratopathy may be a presenting sign in hyperparathyloidism. Acne rosacea may cause blindness by corneal vascularization. Atopic dermatitis may have punctate keratitis, keratoconus, cataract, and retinal detachment.

　　These systemic diseases have widely variant manifestations of corneal and external eye. It is important for the clinician to be aware of the significance of certain corneal changes and their possible relationship to systemic disease processes.