| 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.
•Spondyloarthropathies.
•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) •Episcleritis •Scleritis •Ulcerative keratitis (corneal ulcer) •Uveitis |
■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. •Skin: ◊“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) •Scleritis •Peripheral ulcerative keratitis •Retinal vasculitis •Optic neuropathy |
Investigations
To ascertain diagnosis, following investigations are performed:
•Complete blood count (CBC).
•ESR (raised).
•Urine analysis.
•Antinuclear antibody (ANA) test.
•Ultrasonography.
•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 •Headache •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. |
■Sarcoidosis
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).
Investigations
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). | •Poliosis. •Uveitis (bilateral and granulomatous). •Choroiditis. •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. Kidney: • Necrotizing glomerulonephritis. • Renal failure. Polyneuritis Cutaneous vasculitis | •Sclera—necrotizing scleritis. •Cornea—peripheral ulcerative keratitis (marginal corneal ulcers). •Uvea—uveitis. •Retina—retinitis and occlusive retinal periarteritis. •Optic nerve—optic neuritis. •Lacrimal system—dacryocystitis. •nasolacrimal obstruction. •Orbit—proptosis. |
■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. •Scoliosis •Diaphragmatic hernia | •Ocular fragility to mild trauma •High myopia •Keratoconus •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 •Myopia •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
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 |
•Arthritis •Urethritis •Cystitis, cervicitis, orchitis and prostatitis •Mucocutaneous lesions (mouth ulcer) | •Conjunctivitis •Acute anterior uveitis •Keratitis •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. •Neurological—peripheral 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.) •Renal—nephropathy 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. •Conjunctiva—conjunctivitis. •Cornea—keratitis. •Iris—uveitis and rubeosis iridis. •Lens—cataract. •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). ◊Amaurosis. |
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: •Tachycardia •Palpitations •Tremors •Increased basal metabolic rate leading to heat production, weight loss, and warm and sweaty skin. | Ocular features include: Symptoms— •Retrobulbar discomfort. •Red eyes. •Puffy lids. •Lacrimation. •Photophobia. •Tear insufficiency with grittiness. Signs— 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 neuropathy—retrobulbar edema and infiltration may cause severe visual impairment. |
■Hypoparathyroidism
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.
■Homocystinuria
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 •Papilloedema |
▃Eye in Infectious Diseases
The infective diseases may be:
Bacterial:
•TB.
•Leprosy.
Viral:
•H. simplex.
•H. zoster.
•AIDS.
•Cytomegalovirus.
•Rubella.
Fungal:
•Candida.
•Cryptococcus.
Spirochaetal:
•Syphilis.
■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) •Malaise •Granuloma of lung •Weight loss •Cough •Lymphadenopathy | Adnexal manifestations: •Lupus vulgaris •Eyelid tuberculous granulomas manifestations Anterior segment manifestations: •Conjunctivitis •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 •Papilloedema •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. Nose—saddle-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. Conjunctiva—conjunctivitis. 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. |
■Syphilis
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. •Lymphadenopathy. •Condyloma latum in the anal region. | Secondary: •Eye lid rash. •Madarosis. •Dacryoadenitis. •Dacryocystitis. •Orbital periostitis. Anterior segment: •Conjunctivitis. •Interstitial keratitis. •Episcleritis. •Scleritis. •Uveitis. Posterior segment: •Chorioretinitis. •Neuroretinitis. •Retinal vasculitis. •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. | Tertiary: •Lens subluxation. •Horners syndrome. •Argyll Robertson pupil. •Optic atrophy (Relative Afferent Pupillary Defect). •Cranial nerve palsies. •Ptosis. •Nystagmus. •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 |
Symptoms: •Fever •Headache •Malaise •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. •Conjunctivitis. •Episcleritis. •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. | |
■Cytomegalovirus
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: •Fever •Hepatitis •Pneumonitis •Encephalitis | •Microphthalmos. •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 |
•Microcephaly •Mental retardation •Congenital heart disease •Deafness (sensorineural) •Hepatosplenomegaly | •Microphthalmos •Cataract •Glaucoma •Anterior uveitis •Iris atrophy •Keratitis •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 •Fever •Encephalitis •Middle ear infection •Diarrhea •Precipitates malnutrition | •Keratoconjunctivitis •Keratitis •Xerophthalmia •Optic neuritis |
■Mumps
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.
Diagnosis
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 •Lymphoma •Tuberculosis •Pneumocystis infection •Toxoplasma infections •CMV retinitis •Varicella zoster retinitis •Cryptococcus •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: Tumors: •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: •Telangiectasia. •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. Neoplasms: •Kaposi sarcoma of lids and conjunctiva. •Burkitt’s lymphoma. Neuro-ophthalmological features—these include: •Papilloedema. •Optic atrophy. •Cranial nerve palsies. |
•Vasculopathies.
•Opportunistic infections.
•Neoplasms.
•Neuro-ophthalmic disorders.
▃Eye in Parasitic Diseases
■Toxoplasmosis
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 •Hydrocephalus •Mental retardation •Encephalitis Acquired toxoplasmosis: •Lymphadenopathy •Hepatosplenomegaly | •Retinochoroiditis (bilateral) •Vitritis •Macular scarring •Nystagmus •Strabismus. |
■Toxocariasis
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 |
•Liver—hepatosplenomegaly •Lungs—pulmonary infiltrates and recurrent respiratory infections. •Brain—seizures | •Choroiditis •Vitritis •Vitreoretinal granuloma •Endophthalmitis •Cataract |
■Cysticercosis
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 |
•Pruritus •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 | •Keratitis •Microfilariae in the aqueous •Anterior uveitis •Chorioretinitis |
▃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). •Hepatosplenomegaly. •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 •Hyphema •Hypopyon •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 |
•Hepatosplenomegaly •Bleeding •Infection •Vascular occlusion •Weakness and fatigue | •Retinal hemorrhages •Retinal edema •Neovascularization in retina •Orbital chloroma causing proptosis. |
■Polycythemia
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 |
•Headache •Dizziness •Signs of cerebrovascular insufficiency •Red skin of nose, lips and cheeks •Bleeding from nose and gums | •Amaurosis fugax •Retinal hemorrhages •Papilloedema •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 |
•Anemia •Jaundice •Pain in back, chest, and extremities •Acute chest syndrome •Stroke •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 |
•Pallor •Fatigue •Dyspnea on exertion •Anemia •Purpura •Pathological fractures •Multiple osteolytic lesions •Hyperglobulinemia and classical punched-out lesions in skull, vertebrae, and ribs. | •Proptosis •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 •Cardiomyopathy •Low intelligence | •Ptosis •External ophthalmoplegia •Early-onset cataract (Christmas-tree cataract) •Pigmentary retinopathy •Pupillary light near dissociation •Low IOP |
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. •Ataxia •Deafness •Short stature •Hypoparathyroidism | •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 •Keratoconus •Cataract |
■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 |
Face: •Facial naevus flammeus (port wine stain) distributed over the area corresponding to one or more branches of Vth nerve. Leptomeninges: •Angiomas of ipsilateral parietal or occipital meninges. | •Arteriovenous malformations of episclera. •Choroidal hemangioma. •Glaucoma (ipsilateral). •Iris heterochromia. |
■Neurofibromatosis
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. |
■Albinism
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 | •Nystagmus. •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
Sources
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:
Infants | 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. | |
Absorption
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
Functions
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).
•Embryogenesis.
•Hematopoiesis.
•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). •Hematopoiesis. •Skeletal growth. •Fertility (male and female). •Embryogenesis. •Antioxidants. | •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). ◊Diarrhea. •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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