Ocular Manifestations of Systemic Diseases

CHAPTER 24 Ocular Manifestations of Systemic Diseases

Numerous systemic diseases have ocular manifestations. Occasionally, the eye findings may be the first indication of underlying systemic diseases leading to diagnosis. The systemic diseases involving the eye include:

Connective tissue/Collagen disorders.


Endocrine/Metabolic disorders.

Eye in infectious diseases.

Eye in parasitic diseases.

Hematological diseases.

Muscular disorders.

Inherited disorders.

Connective Tissue Disorders

Various connective tissue disorders causing ocular manifestations are rheumatoid arthritis, systemic lupus erythematosus (SLE), giant cell arteritis, sarcoidosis, Vogt–Koyanagi–Harada (VKH) syndrome, Wegener’s granulomatosis, Ehlers–Danlos syndrome, Marfan syndrome, and Pseudoxanthoma elasticum.

Rheumatoid Arthritis

It is an autoimmune, inflammatory polyarthropathy. It is more common in females than males. Clinical features are described in Table 24.1.

Table 24.1 Systemic and ocular features of rheumatoid arthritis

Systemic features

Ocular manifestations

Joints swelling, usually of hands typically, involving the proximal interphalangeal (IP) joints and sparing the distal IP joints.

Ulnar deviation of metacarpophalangeal (MP) joints secondary to the chronic inflammation.

Dry eyes (keratoconjunctivitis sicca)



Ulcerative keratitis (corneal ulcer)


Systemic Lupus Erythematosus

It is an autoimmune disease of the body’s connective tissues. It occurs between the ages of 15 and 40 years. Systemic Lupus Erythematosus (SLE) can affect joints, skin, kidneys, heart, lungs, blood vessels, and blood. Clinical features are described in Table 24.2.

Table 24.2 Systemic and ocular features of systemic lupus erythematosus

Systemic features

Ocular manifestations

Joints—painful, swollen joints.


“Butterfly-shaped” facial rash over the cheeks below the eyes and across the bridge of the nose.

Alopecia (hair loss).

Kidneys—inflammation of kidneys (nephritis).

Heart—pericarditis, myocarditis, and endocarditis.

Lungs—pleurisy and shrinking lungs.

Blood vessels—inflammation (vasculitis) with arterial and venous occlusion. Raynaud’s phenomenon (fingers turn white and/or blue in the cold).

Blood—anemia, leucopenia, and thrombocytopenia.

Keratoconjunctivitis sicca (dry eye)


Peripheral ulcerative keratitis

Retinal vasculitis

Optic neuropathy


To ascertain diagnosis, following investigations are performed:

Complete blood count (CBC).

ESR (raised).

Urine analysis.

Antinuclear antibody (ANA) test.


X-ray chest.

Giant Cell Arteritis

It is systemic granulomatous vasculitis affecting medium- and large-sized vessels. It presents usually in 7th to 8th decades. Clinical features are described in Table 24.3.

Table 24.3 Systemic and ocular features of giant cell arteritis

Systemic features

Ocular manifestations

Scalp tenderness


Jaw claudication (pain in jaw when chewing).

Polymyalgia rheumatica (pain and stiffness in proximal muscle groups, typically the shoulders).

Anterior ischemic optic neuropathy (AION) resulting in blurred vision.

Extraocular muscle palsies resulting in diplopia.


It is a multisystem disorder characterized by noncaseating granuloma. The most affected organ is the lungs, liver, spleen, skin, parotid glands, phalangeal bones, and eyes. Sarcoidosis presents in one of the following ways (Table 24.4):

Table 24.4 Systemic and ocular features of sarcoidosis

Systemic features

Ocular manifestations

Lungs—bilateral hilar lymphadenopathy, alveolitis, and noncaseating granuloma in lungs is the characteristic lesion of sarcoidosis and fibrosis.

Skin—erythema nodosum, granuloma, and lupus pernio.

Liver—cholestasis, fibrosis, cirrhosis, portal hypertension, and the Budd chiari syndrome have been seen.

Anterior uveitis is most common.

Other manifestations are:

Lacrimal gland granuloma.

Conjunctival nodule.

Lofgren’s syndrome—acute triad of erythema nodosum, joint pains, and bilateral hilar adenopathy.

Heerfordt syndrome (uveoparotid fever)— it is characterized by uveitis, parotid gland enlargement, fever, and cranial nerve palsy (often VIIth).


To ascertain diagnosis, following investigations are performed:

Chest radiographs.

Serum angiotensin converting enzyme (ACE).

Lysozyme assay.

Biopsy (lacrimal gland, lymph nodes, and skin lesion).

Vogt–Koyanagi–Harada Syndrome

It is an idiopathic autoimmune disease against melanocytes. Therefore, inflammation of melanocytes tissues (skin, uvea, ear, and meninges) takes place. It is associated with HLA-DR1 and HLA-DR4. Clinical features are described in Table 24.5.

Table 24.5 Systemic and ocular features of Vogt-Koyanagi-Harada syndrome

Systemic features

Ocular manifestations

Skin—alopecia and vitiligo.

Ear—tinnitus, vertigo, and deafness.

Meninges—meningitis and encephalopathy (less frequent).


Uveitis (bilateral and granulomatous).


Exudative retinal detachment.

Focal depigmented fundus lesions (sunset glow fundus).

Depigmented limbal lesions (Sugiura sign).

Wegener’s Granulomatosis

It is an idiopathic, necrotizing granulomatous vasculitis of multiple organs, predominantly affecting the respiratory tract, kidney, and eye. Antineutrophil cytoplasmic antibodies (c-ANCA) are found in 90% of the patients. Clinical features are described in Table 24.6.

Table 24.6 Systemic and ocular features of Wegener’s granulomatosis

Systemic features

Ocular manifestations

Respiratory tract:

Destructive lesions of nose (perforation of nasal septum, saddle-shaped nasal deformity).

Bilateral infiltrates and cavities in the lung.


Necrotizing glomerulonephritis.

Renal failure.


Cutaneous vasculitis

Sclera—necrotizing scleritis.

Cornea—peripheral ulcerative keratitis (marginal corneal ulcers).


Retina—retinitis and occlusive retinal periarteritis.

Optic nerve—optic neuritis.

Lacrimal system—dacryocystitis.

nasolacrimal obstruction.


Ehlers–Danlos Syndrome

It is a disorder of collagen caused by deficiency of procollagen lysyl hydroxylase. Clinical features are described in Table 24.7.

Table 24.7 Systemic and ocular features of Ehlers–Danlos syndrome

Systemic features

Ocular manifestations

Skin—thin and hyperelastic.

Joints—hypermobile with lax ligaments.

Cardiovascular disease—dissecting aneurysm and mitral valve prolapse.


Diaphragmatic hernia

Ocular fragility to mild trauma

High myopia


Retinal detachment

Marfan’s Syndrome

It is a connective tissue disorder associated with mutation of gene on chromosome 15q. Its inheritance is autosomal dominant. Clinical features are described in Table 24.8.

Table 24.8 Systemic and ocular features of Marfan syndrome

Systemic features

Ocular manifestations

Musculoskeletal features—tall, scoliosis, and sternal deformity, disproportionately long limbs compared with the trunk, arachnodactyly (Long spider-like fingers and toes), and high-arched palate.

Cardiovascular—dilatation of the ascending aorta, leading to aortic incompetence and heart failure, mitral valve disease, and aortic dissection.

Subluxation of the lens


Retinal detachment

Pseudoxanthoma Elasticum

It is a hereditary disorder of connective tissue which involves skin, vessels, and eyes. It is characterized by progressive calcification, fragmentation, and degeneration of elastic fibers in these tissues. Clinical features are described in Table 24.9.

Table 24.9 Systemic and ocular features of Pseudoxanthoma elasticum

Systemic features

Ocular manifestations

Calcification of elastic media and intima of arteries and heart valves causes: renal artery stenosis, intermittent claudication, and mitral valve prolapse.

Gastric hemorrhage due to calcified submucosal vessels.

“Plucked chicken” appearance of skin due to small, yellowish macules, papules, or plaques.

Angioid streaks are the most characteristic sign.

Blue sclera.


Spondyloarthropathies are a family of chronic diseases of joints. These diseases occur in children and adults. They include ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and enteropathic arthritis.

Ankylosing Spondylitis

It is a spondyloarthropathy of the axial skeleton. It typically affects males, 90% of whom are HLA-B27 positive. The affected joints are sacroiliac, spine, ribs, and shoulders. Investigations to ascertain its diagnosis include ESR (raised), X-ray sacroiliac joints (juxta–articular osteoporosis and fusion of joints). Its systemic features include pain and stiffness in lower back, fixed spine in flexion, reduced mobility of the thoracic cage, and bamboo spine. Anterior uveitis is seen in 30 to 40% of the cases (Table 24.10).

Table 24.10 Systemic and ocular features of Ankylosing spondylitis

Systemic features

Ocular manifestation

Pain and stiffness in lower back, spine becomes fixed in flexion, reduced mobility of the thoracic cage, and bamboo spine.

Anterior uveitis in 30 to 40%

Reiter Syndrome (Reactive Arthritis)

It is characterized by triad of urethritis (nongonococcal), conjunctivitis, and arthritis (Table 24.11).

Table 24.11 Systemic and ocular features of Reiter syndrome

Systemic features

Ocular manifestations



Cystitis, cervicitis, orchitis and prostatitis

Mucocutaneous lesions (mouth ulcer)


Acute anterior uveitis


Episcleritis and scleritis

Retinal vasculitis

Endocrine/Metabolic Disorders

Endocrine disorders involve the body’s over production or under production of certain hormones while metabolic disorders affect the body’s ability to process certain nutrients and vitamins. Diabetes mellitus, hyperthyroidism, hypothyroidism, and hypoparathyroidism are some common endocrine disorders, while homocystinuria and Cushing’s syndrome are metabolic disorders.

Diabetes Mellitus

Ocular manifestations in diabetes mellitus depend much more on the duration and not the severity of the disease, commonly occurring in long-standing diabetes mellitus (Table 24.12). Diabetes lowers the resistance of patient to pyogenic infection.

Table 24.12 Systemic and ocular features of diabetes mellitus

Systemic features

Ocular manifestations

Vascular—atherosclerosis of lower limb arteries may result in ischemia and gangrene of feet and toes.

Neurologicalperipheral neuropathy affects the feet and may give rise to ulcer pressure points in the soles.

Cranial nerve palsies as a result of small vessel involvement, so the pupil is spared in IIIrd nerve palsy (Compressive lesions such as posterior communicating artery aneurysm have pupillary involvement.)

Renalnephropathy which may eventually result in renal failure.

Cutaneous—bacterial and fungal infections.

Necrobiosis lipoidica (waxy plaques with irregular margins and shiny centers involving the shins).

Diabetes can involve every structure of the eye.

Lid—recurrent stye.



Iris—uveitis and rubeosis iridis.


Retina—diabetic retinopathy.

Vitreous—intraocular and vitreous hemorrhage due to new vessel formation.

Glaucoma (IOP)—neovascular glaucoma due to rubeosis.

Hypotony in diabetic coma.

Optic nerve—retrobulbar neuritis (often bilateral).

Extra ocular muscles—paralysis (diplopia).

Vision—transient refractive changes

Weakness of accommodation.

(diabetes mellitus involving nerve supply of ciliary muscle causes peripheral neuritis and the ciliary muscle becomes weakened).


Abbreviation: IOP, intraocular pressure.

Hyperthyroidism (Thyrotoxicosis)

Graves’ disease, an autoimmune disorder, is the most common type of hyperthyroidism. IgG antibodies bind to TSH receptors in the thyroid gland and stimulate the secretion of thyroid hormones (Table 24.13).

Table 24.13 Systemic and ocular features of hyperthyroidism

Systemic features

Ocular manifestations

Systemic features of hyperthyroidism include:




Increased basal metabolic rate leading to heat production, weight loss, and warm and sweaty skin.

Ocular features include:


Retrobulbar discomfort.

Red eyes.

Puffy lids.



Tear insufficiency with grittiness.


Lid signs—these include:

Retraction of upper lid in primary gaze (Dalrymple sign).

Lid lag—upper lid lags behind the globe on down gaze (Von Graefe’s sign).

Puffy edematous eye lids (Enroth sign).

Infrequent blinking with staring look (Stellwag’s sign).

Joffroy’s sign—loss of forehead corrugation when looking up.

Defects of ocular movement:

Restrictive myopathy leads to diplopia.

Convergence deficiency (Moebius sign).

Exophthalmos—it is axial and may lead to exposure keratopathy, corneal ulceration, and infection.

Optic neuropathyretrobulbar edema and infiltration may cause severe visual impairment.


It is due to the deficiency of parathyroid hormone. It is characterized by hypocalcaemia and hyperphosphatemia. Systemic features include tetany and seizures. Cataract (bilateral), fasciculation, and disc edema could be seen as an ocular manifestation.


It is the disorder of methionine (amino acid) metabolism. It is caused by deficiency of cystathionine β-synthetase, leading to accumulation of homocysteine and methionine. This condition carries a thrombotic tendency. It has autosomal recessive inheritance (Table 24.14).

Table 24.14 Systemic and ocular features of homocystinuria

Systemic features

Ocular manifestations

Mental retardation.

Thromboembolic episodes.

Arachnodactyly (infrequent).

Bilateral subluxation of the lens (inferiorly and nasally).

Acute secondary glaucoma due to subluxation of lens in anterior chamber.

Retinal detachment and myopia may occur.

Cushing’s Syndrome

It is caused by prolonged elevation of plasma glucocorticoids. Glucocorticoids are secreted by adrenal cortex. Cushing’s disease is caused by hyper secretion of adrenocorticotrophic hormone (ACTH) by basophil cells of pituitary gland which, in turn, increases the secretion of glucocorticoids by adrenal cortex. Clinical features are described in Table 24.15.

Table 24.15 Systemic and ocular features of Cushing’s syndrome

Systemic features

Ocular manifestations

Obesity—it may be generalized or involve the trunk, abdomen, and neck (‘buffalo hump’).

Swollen face (moon face).

Hyperpigmentation of skin may develop.

Other features—depression, osteoporosis, poor wound healing, hypertension, and pathological fractures.

Hypertensive retinopathy


Eye in Infectious Diseases

The infective diseases may be:





H. simplex.

H. zoster.









Tuberculosis (TB)

TB primarily involves the lung. Other organs including the eye may be involved secondarily. Primary infection of the eye is rare. TB can affect all the ocular structures except lens. Active TB may not be associated with ocular involvement. Secondary ocular involvement occurs as a result of hematogenous spread or as a hypersensitive response to tubercular proteins. The hallmark of extrapulmonary TB is caseating granuloma and necrosis. Clinical features are listed in Table 24.16.

Table 24.16 Systemic and ocular features of tuberculosis

Systemic features

Ocular manifestations

Fever (evening rise)


Granuloma of lung

Weight loss



Adnexal manifestations:

Lupus vulgaris

Eyelid tuberculous granulomas manifestations

Anterior segment manifestations:


Conjunctival granuloma

Tubercular scleritis

Interstitial keratitis

Phlyctenular keratoconjunctivitis

Iridocyclitis (chronic granulomatous, anterior and intermediate uveitis)

Posterior segment manifestations—

Choroidal tubercles

Choroidal tuberculoma

Serpiginous like choroiditis

Retinal vasculitis

Eale’s disease


Optic neuritis papillitis, retrobulbar neuritis (RBN), and neuroretinitis

Leprosy (Hansen Disease)

It is a chronic granulomatous infection. The organism, Mycobacterium leprae, has the affinity for skin, peripheral nerves, and anterior segment of the eye. Tuberculoid leprosy is restricted to the skin and peripheral nerves. The eye is involved in lepromatous leprosy. Ocular involvement in leprosy is 70 to 75%. Lepromatous leprosy is a generalized infection involving skin, peripheral nerve, upper respiratory tract (URT), testes, and eyes. Clinical features are listed in Table 24.17.

Table 24.17 Systemic and ocular features of leprosy

Systemic features

Ocular manifestations

Skin—skin lesions appear as areas of impaired sensations or as macules (hypopigmented or erythematous).

Thickening of cutaneous sensory nerves.

Nosesaddle-shaped, nasal deformity due to destruction of nasal cartilage.

Peripheral nerves:

Motor neuropathy claw hand (due to ulnar nerve palsy).

Sensory peripheral neuropathy may result in shortening and loss of digits.

Autonomic neuropathy. It leads to dry, cracked, and infection-prone skin.

Lids—madarosis and trichiasis.

Lacrimal system—dacryocystitis, and chronic dacryoadenitis leading to keratoconjunctivitis sicca (KCS).

Sclera—episcleritis and scleritis.


Cornea—keratitis, thickened corneal nerves, corneal anesthesia, and superficial stromal keratitis.

Iris—anterior uveitis.

VII nerve paresis—lagophthalmos due to facial nerve involvement (zygomatic branch) and lower lid ectropion.


It is caused by the spirochaete, Treponema pallidum. It may be primary, secondary, or tertiary syphilis. Clinical features are listed in Table 24.18.

Table 24.18 Systemic and ocular features of syphilis

Systemic features

Ocular manifestations

Primary—chancre (painless ulcer at the site of infection). The most common site is the penis in males and the vulva in females.

Primary—conjunctival chancre.

Secondary—it begins a few weeks to months after the chancre heals. It is characterized by:

Rashes on palms and soles.


Condyloma latum in the anal region.


Eye lid rash.




Orbital periostitis.

Anterior segment:


Interstitial keratitis.




Posterior segment:



Retinal vasculitis.

Neuro ophthalmological:

Optic neuritis.

Cranial nerve palsies.

Tertiary—it occurs in approximately 40% of untreated cases and is characterized by:

Neurosyphilis—tabes dorsalis, general paresis of insane, and syphilitic meningitis.

Cardiovascular syphilis—aortitis with aortic regurgitation and aneurysms, and gummas (destructive lesions of bones, skin, or liver).

Congenital syphilis:

Hutchinson’s teeth.

VIII nerve deafness.

Interstitial keratitis.


Lens subluxation.

Horners syndrome.

Argyll Robertson pupil.

Optic atrophy (Relative Afferent Pupillary Defect).

Cranial nerve palsies.



Visual field defects.

Gummas of ocular structures.

Herpes Simplex

It is caused by herpes simplex virus (HSV–HSV1 and HSV2), a DNA virus. Clinical features are listed in Table 24.19.

Table 24.19 Systemic and ocular features of herpes simplex

Systemic features

Ocular manifestations

Primary infection: Primary infections are often subclinical and cause mild fever, malaise, and upper respiratory tract symptoms.

Recurrent infection (reactivation of infection): The pattern of disease depends on the site of reactivation which may be remote from the site of primary disease.

Primary infections in children may develop blepharoconjunctivitis and corneal micro dendrites in few cases.

The corneal lesions of recurrent herpes are characteristic and include:

Dendritic ulcer: the ends of the ulcer have characteristic terminal buds; the enlargement of ulcer may produce the geographical configuration.

Reduced corneal sensations.

Disciform keratitis.

Stromal necrotic keratitis.

Metaherpetic ulceration.

Herpes Zoster

It is caused by varicella-zoster virus (VZV). VZV causes chickenpox (varicella) and shingles (herpes zoster). Clinical features are listed in Table 24.20.

Table 24.20 Systemic and ocular features of herpes zoster

Systemic features

Ocular manifestations





Unilateral skin rash in the area supplied by a single sensory nerve and vesicles appear within 24 hours.

The trigeminal nerve (Vth), especially the ophthalmic division (V1), is commonly involved in herpes zoster; the ocular manifestations of herpes zoster ophthalmicus (HZO) are:

Lid margin vesicles.



Scleritis and sclerokeratitis.

Cornea Epithelial keratitis (dendritic lesions have tapered ends without terminal bulbs):

Nummular keratitis—stromal keratitis.

Disciform keratitis.

Anterior uveitis.

Trabeculitis may cause secondary glaucoma.

It may cause acute retinal necrosis (ARN) and anterior segment ischemia.

Optic neuritis is a rare and late complication.

HZO affecting 3rd, 4th, and 6th CN results in extraocular muscle palsy, while facial N (7th CN) involvement results in facial palsy (Bell’s palsy).

Abbreviation: CN, cranial nerve.


It is a β herpes virus. Clinical features are listed in Table 24.21.

Table 24.21 Systemic and ocular features of cytomegalovirus

Systemic features

Ocular manifestations

In newborns and immunocompromised adults, it causes:






Necrotizing chorioretinitis. It is more severe and associated with retinal necrosis and retinal hemorrhages, especially in AIDS patients.

Optic atrophy.

Rubella (German Measles)

It is caused by Rubella virus. It is transmitted from an infected mother to the fetus through placenta, usually during the first trimester of pregnancy. Risk to fetus is closely related to the stage of gestation at the time of maternal infection. Clinical features are listed in Table 24.22.

Table 24.22 Systemic and ocular features of Rubella

Systemic features

Ocular manifestations


Mental retardation

Congenital heart disease

Deafness (sensorineural)





Anterior uveitis

Iris atrophy


Retinopathy (salt and pepper)

Measles (Rubeola)

It is caused by a myxovirus, a RNA virus. Clinical features of measles are listed in Table 24.23.

Table 24.23 Systemic and ocular features of measles

Systemic features

Ocular manifestations

Rash (erythematous and maculopapular)

Koplik’s spot on buccal mucosa



Middle ear infection


Precipitates malnutrition




Optic neuritis


It is caused by paramyxovirus. Systemically, it presents as bilateral parotitis, epididymo-orchitis in adults and meningitis, while ocular manifestations include conjunctivitis and dacryoadenitis (bilateral), but episcleritis and peripheral keratitis are infrequent.

Acquired Immune Deficiency Syndrome

It is caused by human immunodeficiency virus (HIV), an RNA virus belonging to retrovirus family.

Acquired immune deficiency syndrome (AIDS) is transmitted by sexual intercourse, contaminated/infected blood, and transplacental or via breast milk. CD4+T (helper) lymphocytes are vital to the initiation of immune response to pathogens. HIV targets CD4+T lymphocytes. The disease is characterized by a deficiency of CD4+T lymphocytes, leading to progressive immune deficiency. Regular estimation of CD4+T count is, therefore, a useful measure of disease progression.


For making provisional diagnosis when blood test may not be available, WHO has recommended clinical diagnostic criteria of AIDS which is based on the presence of any two major and at least one minor systemic sign.

Major Signs

Loss of more than 10% of body weight.

Chronic fever.

Chronic diarrhea (>1 months’ duration).

Minor Signs

Chronic cough.

Itchy dermatitis.

Oropharyngeal candidiasis.

Chronic progressive herpes simplex infection.

Recurrent herpes zoster.

Generalized lymphadenopathy.

Demonstration of anti-HIV antibodies in the serum by ELISA and Western blot tests.

CD4+T lymphocyte counts are measured every three months. ACD4+T lymphocytes count < 200 cells/mm3 has high-risk of HIV infection (Table 24.24). AIDS is diagnosed when HIV-positive subject develops one or more of the indicator diseases.

Table 24.24 Associated infections with CD4+T count

CD4+T count

Associated infection

<500 cell/mm3

<250 cell/mm3

<100 cell/mm3

Kaposi sarcoma



Pneumocystis infection

Toxoplasma infections

CMV retinitis

Varicella zoster retinitis


HIV encephalopathy

Clinical Features

Approximately 3/4th of patients with HIV develop ocular manifestations affecting all the structures of eye from the lids to the retina. Ocular manifestations of AIDS can be (Table 24.25):

Table 24.25 Systemic and ocular features of AIDS

Systemic features

Ocular manifestations

Opportunistic infections:


Kaposi sarcoma.

NonHodgkin B cell lymphoma.

Squamous cell carcinoma of the cervix and anus.

HIV encephalopathy.

Microvasculopathy affect mainly the conjunctiva and retina. Conjunctival micro vasculopathy is characterized by:


Segmental dilatation of small conjunctival vessels.

Micro vasculopathy in retinal vessels produces cotton-wool spots, superficial and deep retinal hemorrhages, and microaneurysms in the retina.

Opportunistic infections—These include:

Cytomegalovirus retinopathy.

Herpes zoster ophthalmicus causing keratouveitis.

Progressive outer retinal necrosis (PORN).

Toxoplasmosis is the most common nonvirus opportunistic infection in AIDS.

Mycobacterial infections.

Fungal endophthalmitis.


Kaposi sarcoma of lids and conjunctiva.

Burkitt’s lymphoma.

Neuro-ophthalmological features—these include:


Optic atrophy.

Cranial nerve palsies.


Opportunistic infections.


Neuro-ophthalmic disorders.

Eye in Parasitic Diseases


It is caused by toxoplasma gondii, an obligate intracellular protozoan. Its definitive host is the cat, while the intermediate hosts are humans. Clinical features are listed in Table 24.26.

Table 24.26 Systemic and ocular features of toxoplasmosis

Systemic features

Ocular manifestations

Congenital toxoplasmosis:

Intracranial calcification


Mental retardation


Acquired toxoplasmosis:



Retinochoroiditis (bilateral)


Macular scarring




It is caused by toxocara canis, an intestinal round worm of dogs. The larvae of the worm penetrate the intestinal wall and travel to various organs, such as liver, lungs, skin, brain, and eyes. Clinical features are listed in Table 24.27.

Table 24.27 Systemic and ocular features of toxocariasis

Systemic features

Ocular manifestations


Lungs—pulmonary infiltrates and recurrent respiratory infections.




Vitreoretinal granuloma




It is caused by Cysticercus cellulosae, the larval form of pork tapeworm Taenia solium. Intermediate hosts are pigs, while the definitive hosts are humans. It often involves lungs, muscles, and brain. Clinical features are listed in Table 24.28.

Table 24.28 Systemic and ocular features of cysticercosis

Systemic features

Ocular manifestations

Subcutaneous cysts and nodules.

Seizures and neurological deficits (neuro cysticercosis).

Extraocular cysts (subconjunctival cysticerci).

Intraocular cysts (vitreous cysticerci).

Retinal detachment.

Onchocerciasis (River Blindness)

It is caused by Onchocerca volvulus, a parasitic helminth. The obligate intermediate host is a black fly which breeds in fast-flowing water. Clinical features are listed in Table 24.29.

Table 24.29 Systemic and ocular features of onchocerciasis

Systemic features

Ocular manifestations


Leopard skin (focal areas of hypo- and hyperpigmentation on the shins)

Lizard skin (skin becomes thickened and wrinkled with time as a result of constant scratching)

Subcutaneous nodules


Microfilariae in the aqueous

Anterior uveitis


Hematological Diseases

Lymphocytic Leukemia

Systemic and ocular features of lymphocytic leukemia are mentioned in Table 24.30.

Table 24.30 Systemic and ocular features of lymphocytic leukemia

Systemic features

Ocular manifestations

Enlargement of lymph nodes (lymphadenopathy).


Anemia resulting in tiredness, weakness, and dyspnoea.

Risk of secondary infection due to neutropenia.

Hemorrhages in oral cavity due to thrombocytopenia.

Retinal hemorrhages

Roths spots

Retinal edema



Leukemic infiltration may involve the uvea (iris nodules) and orbit (proptosis)

Myeloid Leukemia

Systemic and ocular features of myeloid leukemia are mentioned in Table 24.31.

Table 24.31 Systemic and ocular features of myeloid leukemia

Systemic features

Ocular manifestations




Vascular occlusion

Weakness and fatigue

Retinal hemorrhages

Retinal edema

Neovascularization in retina

Orbital chloroma causing proptosis.


Polycythemia is a disease state in which the hematocrit (the volume percentage of red blood cells in the blood) is elevated. Systemic and ocular features of polycythemia are mentioned in Table 24.32.

Table 24.32 Systemic and ocular features of polycythemia

Systemic features

Ocular manifestations



Signs of cerebrovascular insufficiency

Red skin of nose, lips and cheeks

Bleeding from nose and gums

Amaurosis fugax

Retinal hemorrhages


Central retinal vein occlusion

Sickle-cell Disease

It is an inherited group of disorders in which red blood cells contort into a sickle shape and breakdown, leaving a shortage of healthy red blood cells. Systemic and ocular features of sickle cell disease are mentioned in Table 24.33.

Table 24.33 Systemic and ocular features of sickle cell disease

Systemic features

Ocular manifestations



Pain in back, chest, and extremities

Acute chest syndrome


Painless hematuria

Leg ulcers

Comma-shaped conjunctival vessels.

Atrophy and neovascularization of iris.

Black sunburst chorioretinal scars.

Sea-fan neovascularization of retina.

Retinal capillary occlusion

Multiple Myeloma

Multiple myeloma is a cancer of plasma cell. Plasma cells are found in the bone marrow and are an important part of the immune system. In multiple myeloma, the overgrowth of plasma cells in the bone marrow can crowd out normal blood, forming cells and leading to low-blood counts that can cause anemia (low red blood cells), thrombocytopenia (low platelets), and leukopenia (low white blood cells). Systemic and ocular features of multiple myeloma are mentioned in Table 24.34.

Table 24.34 Systemic and ocular features of multiple myeloma

Systemic features

Ocular manifestations



Dyspnea on exertion



Pathological fractures

Multiple osteolytic lesions

Hyperglobulinemia and classical punched-out lesions in skull, vertebrae, and ribs.


Blood sludging

Infiltration of uvea, optic nerve, and lacrimal gland

Choroidal tumor

Hemorrhages and exudates in retina

Roths spots

Vascular occlusion

Muscular Disorders

Muscular disorders may be congenital or acquired.

Myasthenia Gravis

It is an autoimmune disease in which acetylcholine receptors in striated muscle are destroyed by antibodies. It leads to impairment of neuromuscular conduction, resulting in weakness and fatigue of skeletal muscle (not of cardiac and involuntary muscles) (Table 24.35).

Table 24.35 Systemic and ocular features of myasthenia gravis

Systemic features

Ocular manifestations

Voluntary muscle weakness which worsen after exercise or in the evening. It affects limbs, facial expression, speaking (dysarthria), swallowing (dysphagia), and mastication; difficulty with breathing is rare but serious.

Ptosis after exertion.

Diplopia after exercise or in the evening.

Myotonic Dystrophy

It is characterized by delayed muscular relaxation after cessation of voluntary effort (Table 24.36). It is inherited as autosomal dominant with gene locus on 19q 13.3.

Table 24.36 Systemic and ocular features of myotonic dystrophy

Systemic features

Ocular manifestations

Difficulty in releasing grip.

Muscle wasting and weakness.

Bilateral facial wasting with hollow cheeks (mournful facial expression).

Swallowing difficulties due to involvement of pharyngeal muscles.

Slurred speech due to involvement of tongue.

Frontal baldness

Testicular atrophy


Low intelligence


External ophthalmoplegia

Early-onset cataract (Christmas-tree cataract)

Pigmentary retinopathy

Pupillary light near dissociation


Abbreviation: IOP, intraocular pressure.

Kearns–Sayre Syndrome

It is characterized by abnormal mitochondria associated with mitochondrial DNA deletions. It is characterized by the classical triad of retinitis pigmentosa, progressive external ophthalmoplegia, and heart block (Table 24.37).

Table 24.37 Systemic and ocular features of Kearns–Sayre syndrome

Systemic features

Ocular manifestations

Cardiac conduction defects resulting in heart block.



Short stature


Bilateral ptosis with insidious onset

Progressive external ophthalmoplegia

Pigmentary retinopathy

Pendular nystagmus

Eye in Inherited Disorders

Down Syndrome (Trisomy 21)

It is a genetic chromosome 21 disorder, causing developmental and intellectual problems. Down syndrome is a genetic disorder caused when abnormal cell division results in extra genetic material from chromosome 21. Its systemic and ocular features are mentioned in Table 24.38.

Table 24.38 Systemic and ocular features of Down syndrome

Systemic features

Ocular manifestations

Mental retardation

Brachycephaly with flattening of occiput

Protruding tongue

Broad short hands

Upward slanting palpebral fissures

Epicanthic folds



Sturge–Weber Syndrome

It is a congenital phakomatoses and involves the face, leptomeninges, and eyes (Table 24.39).

Table 24.39 Systemic and ocular features of Sturge–Weber syndrome

Systemic features

Ocular manifestations


Facial naevus flammeus (port wine stain) distributed over the area corresponding to one or more branches of Vth nerve.


Angiomas of ipsilateral parietal or occipital meninges.

Arteriovenous malformations of episclera.

Choroidal hemangioma.

Glaucoma (ipsilateral).

Iris heterochromia.


It primarily affects the cell growth of neural tissues. It is of two types: neurofibromatosis-1 (von-Recklinghausen disease) and neurofibromatosis-2. Clinical features are listed in Table 24.40.

Table 24.40 Systemic and ocular features of neurofibromatosis

Systemic features

Ocular manifestations

Café-au-lait spots: these are light-brown macules commonly found on the trunk.

Subcutaneous neurofibromas along the course of peripheral or autonomic nerves but do not occur on purely motor nerves.

Absence of greater wing of sphenoid bone.

Orbital involvement:

Optic nerve glioma

Spheno-orbital encephalocele due to absence of greater wing of sphenoid bone and resulting in pulsating proptosis.

Eyelid neurofibromas:

These frequently cause a mechanical ptosis.

Iris lesions:

Lisch nodules.

Fundus lesions:

Choroidal naevi.

Retinal astrocytomas.


It is a genetically determined disorder of melanin synthesis which may involve the eyes alone (ocular albinism) or eyes, skin, and hair (oculocutaneous albinism) (Table 24.41).

Table 24.41 Systemic and ocular features of albinism

Systemic features

Ocular manifestations

Hypopigmented skin and hair


Translucent iris giving rise to a pink-eyed appearance.

Large choroidal vessels are seen due to lack of pigment in fundus.

Foveal hypoplasia.

Von Hippel–Lindau Disease

Von Hippel-Lindau disease (VHL) is a hereditary condition associated with tumors arising in multiple organs (brain, kidneys, pancreas, adrenal glands, and reproductive tract). It is characterized by angiomatosis of the central nervous system, kidneys, and also retinal angiomas.

Nutritional Deficiencies

Vitamin A

It is a fat-soluble vitamin and consists of retinol (preformed vitamin), retinal, retinoic acids, and carotene (pro-vitamin). Some of the carotene is converted to retinol in the intestinal mucosa.

1 IU of vitamin A = 0.3 mcg of retinol


The richest animal sources of vitamin A (retinol) are livers like beef liver and cod liver oil, egg, fish, meat, and milk.

Plant foods containing vitamin A are yellow–orange fruits (papaya, mango, and pumpkins), green leafy vegetables (spinach and amaranth), some roots (carrot), vegetables rich in carotenoids, specifically β-carotene, provide provitamin A precursors.

Daily Requirement

Daily requirement of retinol (pure vitamin A) is:


350 µg

1 to 6 years

400 µg

7 to 12 years

600 µg

Adults and pregnancy

600 µg

Requirement of carotene is four times higher than retinol.


Approximately 80 to 90% of ingested vitamin A is absorbed. It is passed along with fat through the lymphatic system into the blood stream. Absorption is poor in case of diarrhea, jaundice, and abdominal disorder, and increases if taken with fat. Unabsorbed vitamin A is excreted within 1 or 2 days in feces. The absorption of retinol requires the presence of bile salts.

Transport, Storage and Excretion

It is transported via chylomicrons from intestinal cells to the liver and from the liver to target tissue. The liver has enormous capacity to store it in the form of retinolpalmitate. Under normal conditions a well-fed person has sufficient vitamin A reserves to meet his need for 6 to 9 months or more. Vitamin A is not readily excreted


Vitamin A plays a critical role in:

Vision in dim light (vitamin A is a part of rhodopsin and visual pigment).

Maintaining the integrity and normal functioning of glandular and epithelial tissues which lines intestinal, respiratory, and urinary tracts as well as skin and eyes.

Supports skeletal growth.

Fertility (male and female).



Retinal and retinoic acid function as steroid hormones. They regulate the protein synthesis and are thus involved in cell growth and differentiation.

Synthesis of certain glycoproteins.

Essential for the maintenance of proper immune system.

Carotenoids function as antioxidants and reduce the risk of cancers.

Vitamin A Deficiency

It is common in poorer countries and is the leading cause of preventable childhood blindness. Each year, millions of children in the developing countries suffer from night blindness or go blind due to hypovitaminosis A.

Normal serum retinol level is 1 to 3 µmol/l (28 to 86 µg/dL).

Plasma vitamin level of ≤0.35 µmol/L (10 µg/dl) indicates vitamin A deficiency.

The major causes of vitamin A deficiency are inadequate intake, iron deficiency (it can affect vitamin A uptake), excess alcohol consumption (it can deplete vitamin A), fat malabsorption, and liver disorders. The signs of deficiency are more accentuated in the presence of protein-energy malnutrition (PEM) and gastrointestinal disorders (malabsorption). Vitamin A deficiency may become severe after a precipitating illness such as measles, respiratory tract infections (due to increased metabolic absorption), or diarrhea (due to decreased absorption). Loss of functionality due to vitamin A deficiency is highlighted in Table 24.42.

Table 24.42 Functions of vitamin A and features of its deficiency

Function of vitamin A

Deficiency of vitamin A

Vision (night vision).

Epithelial cell integrity against infections which line intestinal, respiratory and urinary tracts as well as skin and eyes.

Immune response (mucosal cells function as a barrier and defence against infections).


Skeletal growth.

Fertility (male and female).



Night blindness and xerophthalmia:

The skin becomes keratinized, scaly, and toad like (phrynoderma), and the mucus secretion is suppressed.

Alteration in mucosa of renal pelvis and urinary bladder, and formation of renal and vesical calculi.

Collections of keratin in the conjunctiva (Bitot’s spots).


Impaired immune function; deficiency leads to decreased resistance to infections:

Squamous metaplasia of respiratory mucosa and more prone to respiration infections.

Impaired hematopoiesis and leads to anemia.

Decreased bone development and growth rate.

Atrophy of germinal epithelium leading to infertility.

Birth defects.

Risk of cancers (lung, oral, and prostate cancers).

Age-related macular degeneration (ARMD).

Rhodopsin, the eye pigment responsible for sensing dim light, is composed of retinal (an active form of vitamin A) and opsin (a protein). Vitamin A deficiency has been associated with the loss of goblet cells in the conjunctiva. Goblet cells are responsible for secretion of mucus, and their absence results in xerophthalmia, a condition where the eyes fail to produce tears (Flowchart 24.1).

Flowchart 24.1 Vitamin A deficiency and its ocular effects.

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Nov 20, 2022 | Posted by in OPHTHALMOLOGY | Comments Off on Ocular Manifestations of Systemic Diseases

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