OCULAR MANIFESTATIONS OF SYSTEMIC DISEASES

Jeannette TTH Semmelweis University, Budapest Dept. of Ophthalmology

INTRODUCTION
The eyes are frequently involved in diseases affecting the rest of the body Ocular manifestations in certain multisystem disorders may offer a diagnostic clue Sometime the eye involvement may be subtle enough to avoid detection unless the clinicians knows to look for it

THE CORNEA RELATED TO SYSTEMIC DISEASES

DISEASES OF THE SKIN AND MUCOUS MEMBRANES Atopic dermatitis, cicatricial pemphigoid, epidermolysis bullosa, erythema multiforme DISORDERS OF COLLAGEN METABOLISM Ehlers-Danlos syndrome, Marfan syndrome

THE CORNEA RELATED TO SYSTEMIC DISEASES

COLLAGEN DISEASES Dermatomyositis, periarteritis nodosa, rheumatoid arthritis, SLE METABOLIC DISEASES Amyloidosis, cystinosis, glycogen storage disease, gout, hyperlipidemia

CATARACT RELATED TO SYSTEMIC DISEASES

CHROMOSOMAL DISORDERS Alport syndrome, Crouzon syndrome, myotonic dystrophy,Trisomy 18, Turner syndrome DISEASES OF THE SKIN AND MUCOUS MEMBRANES Atopic dermatitis, pemphigus

CATARACT RELATED TO SYSTEMIC DISEASES

METABOLIC AND NUTRITION DISEASES Aminoaciduria, diabetes mellitus, galactosemia, hypoparathyroidism, hypothyroidism, Wilsons disease INFECTIOUS DISEASES Congenital HSV, syphylis, CMV, rubella TOXIC SUBSTANCES

THE RETINA RELATED TO SYSTEMIC DISEASES

CARDIOVASCULAR DISEASES
Aortic arch syndrome, hypertension and toxaemia of pregnancy, occlusive vascular disease

COLLAGEN DISEASES
Dermatomyosistis, periarteritis nodosa, SLE, temporal arteritis, Wegener granulomatosis

ENDOCRINE DISEASES
Diabetes mellitus, Cushing syndrome, hyperthyroidism, hypothyroidism, hypoparathyroidism

THE RETINA RELATED TO SYSTEMIC DISEASES

DISEASES OF THE SKIN AND MUCOUS MEMBRANES
Pseudoxanthoma elasticum

GASTROINTESTINAL AND NUTRITIONAL DISEASES

Regional enteritis, vitamin A deficiency

HEMATOLOGIC DISEASES
Anaemias, leukemias, sickle cell disease, thrombocytopenia

INFECTIOUS DISEASES
Candida retinitis, parasites, viral infections, tuberculosis, HIV, HSV, HZV, CMV

PHAKOMATOSES METABOLIC DISEASES

THYROID EYE DISEASE (Graves ophthalmopathy)

The diagnosis may not be obvious, although it is quite common! The severity of the eye changes does not always relate to the severity of the endocrine problem It is not known why some patients with thyroid imbalance have eye features and others do not The link is immunological, though the details are unclear Often the eye features develop out of phase with the thyroid

FEATURES OF THYROID EYE DISEASE

Not all patients have all the signs and symptoms! Puffiness of lids and conjunctiva, often worse in the morning Discomfort and redness Watering Upper lid Retraction due to overaction of Mllers muscle (Dalrymples sign) Lag (Von Graefes sign)

FEATURES OF THYROID EYE DISEASE

Infiltrative ophthalmopathy
Enlargement of extraocular muscles Proliferation of orbital fat and connective tissue Protrusion (with poor eyelid closure, if severe corneal damage) Double vision, often worse in the morning Visual failure from optic nerve compression (rare, but needs urgent treatment)!

PATHOGENESIS OF THYROID EYE DISEASE

The disease is not completely understood The existing knowledge suggests that the disease is likely to be autoimmune in origin and linked to autoimmune thyroid disease Cigarette smoking is commoner among patients with Graves disease and smokers have a more severe ophthalmopathy Orbital fibroblasts synthesize more glycosaminoglycans when cultured under hypoxic conditions. Glycosaminoglycans attract water swelling of extraocular muscles Infiltration of orbital tissue by immune cells ant their activation, with subsequent cytokine release leads to local cell proliferation

OPHTHALMIC PROBLEMES IN NEUROLOGICAL DISORDERS

Multiple sclerosis Stroke Intracranial tumors Benign intracranial hypertension Facial palsy

MULTIPLE SCLEROSIS (demyelinisation)

Optic (ON) neuritis is the most common manifestation (usually unilateral, but may be bilateral) and the presenting feature in about 25% of MS patients About 60% of patients in the 2040 years age group who present with ON will subsequently develop evidence of systemic demyelinisation!

SYMPTOMS OF OPTIC NEURITIS

Decreased visual acuity Afferent pupillary defect (if unilateral or asymmetric) Impairment of color vision Pain with eye movements or pressure on the globe Central or ceco-central visual field defect

STROKE
Homonymous hemianopia is the commonest finding Often not recognized by the patient Lesion within the optic path behind the chiasm (usually in the radiation passing through temporal and parietal areas to the occipital cortex) Occlusion of the vertebrobasilar circulation may cause bilateral cortical lesions and marked visual disability Many patients have reading difficulties

INTRACRANIAL TUMORS
A tumor close to the optic nerve, chiasm or radiation may affect visual acuity or visual field Check both visual field and visual acuity in patients with vague, but persistent and progressive complaints Headache is not always present! Look for papilloedema or atrophy of one or both optic nerve heads

PAPILLOEDEMA
Is caused by impairment of axonic flow in the optic nerve Does not impair visual acuity but increases the size of the blind spot Optic atrophy implies death of nerve fibers and is associated with impairment of visual acuity, field or color vision

BENIGN INTRACRANIAL HYPERTENSION

Papilloedema Raised intracranial pressure No tumor Syndrome found in plump young women with persistent headache and menstrual irregularities Cause unknown Therapy: diuretics Long-term monitoring by a specialist

FACIAL PALSY
Weakness of eye closure Patients at risk of corneal ulceration Depending on severity of malfunction therapy consists of topical antibiotics (for lubrication and prevention of secondary infections), taping or temporary suturing of the eyelids

EYE PROBLEMS IN JOINT DISORDERS

Some patients with joint disorders have inflammation of the coats of the eye (e.g. episcleritis, scleritis), other condition are associated with internal inflammation (iritis), some are a cause of dryness of the eye (sicca) Rheumatoid arthritis Ankylosing spondylitis Reiter syndrome Sjgren syndrome Juvenile arthritis

RHEUMATOID ARTHRITIS
Dry eye (discomfort, burning sensation) Scleritis (necrosis of the sclera may occur) Refer urgently the rheumatoid arthritis patient with a painful eye even if it is not particularly red!

EYE PROBLEMS IN JOINT DISORDERS

ANKYLOSING SPONDYLITIS Occurs in younger patients with HLA B27 positivity, causes sacroiliitis Patients have recurrent anterior uveitis REITERS SYNDROME Ocular inflammation with oligoarticular arthritis and urethritis Chlamydia, Yersinia, Salmonella may be the causative agent

SJGRENS SYNDROME
Typically affects conjunctiva and oral mucosa The ophthalmologist is frequently the first doctor to see the patient DRY EYE!

JUVENILE IDIOPATHIC ARTHRITIS

Low grade iritis, that may lead to blindness, if not recognized and treated Children with inflammatory arthritis under 12 years of age are at risk Screening! COMPLICATIONS:
Cataract Glaucoma Band keratopathy Phthisis bulbi

EYE PROBLEMS IN SKIN DISORDERS

ALLERGIC REACTIONS Acute allergic reaction in atopic patients Cell-mediated allergy (e.g. topical treatment)

SEBORRHOEIC DERMATITIS Blepharitis

EYE PROBLEMS IN SKIN DISORDERS

ROSACEA BLEPHARITIS Severe corneal changes PSORIASIS Iritis in some patients

BLISTERING DISORDERS
STEVENS-JOHNSON SYNDROME PEMPHIGOID EPIDERMOLYSIS BULLOSA

STEVENS-JOHNSON SYNDROME
Acute hypersensitivity vesiculobullous reaction of the skin and mucous membranes Immune complex deposition incited by medications or infectious agents Corneal ulceration and severe pseudomembranous conjunctivitis Symblepharon, entropion, ectropion, trichiasis, dry eye, persistent conjunctival inflammation, corneal opacification

OCULAR CICATRICIAL PEMPHIGOID

Slowly progressive, chronic cicatrizing conjunctivitis Idiopathic, possibly a type II hypersensitivity reaction Presents in women over 60 with recurrent attacks of nonspecific conjunctival inflammation There may be associated oral, pharyngeal or urethral mucosal lesions

INFECTIONS OF THE SKIN INVOLVING THE EYE

HERPES ZOSTER
Often involves the eyelid Cornea and uvea may be involved (secondary glaucoma)

VARICELLA
Lid and corneal lesions

IMPETIGO WARTS MOLLUSCUM CONTAGIOSUM PUBIC LICE

HERPES ZOSTER (HZ)

Incidence: between 40 and 70 years Healthy and immunocompromized patients are affected HZ ophthalmicus represents 10 - 15% of cases

HERPES ZOSTER
Any branch of the Vth cranial nerve may be affected Ocular complications are related to infection of the nasociliary nerve
Eyelid cicatrization Symblepharon Keratitis

ANTERIOR UVEITIS WITH SECONDARY GLAUCOMA!

AIDS
TWENTY MILLION CASES WORLDWIDE IN 2000! Retrovirus (HIV) which infects immunocompetent CD4+ cells RESULTS IN CELLULAR IMMUNODEFICIENCY (T-CELL AND MACROPHAGE DEFICIT)
Complications due 1) to the virus itself 2) to superinfection by opportunistic pathogens

OCULAR INVOLVEMENT IN AIDS

Ocular manifestations have been reported in up to 70% of individuals infected with HIV Ocular manifestations almost invariably reflect systemic disease and may be the first sign of disseminated systemic infection The most common ocular finding is HIV retinopathy, occurring in about 50%-70% of cases HIV has been isolated from human retina, and its antigen has been detected in retinal endothelial cells Endothelial infection may be responsible for the vascular alterations

INFECTIOUS AGENTS THAT AFFECT THE EYE IN AIDS

Cytomegalovirus (CMV) - retinitis Herpes Zoster - retinal necrosis Toxoplasma gondii - retinochoroiditis Mycobacterium tuberculosis - multifocal choroiditis Cryptococcus neoformans - multifocal choroiditis Pneumocystis carinii- choroiditis These agents can infect the ocular adnexa, anterior or posterior segment Multifocal choroiditis is an alarming sign, since it frequently represents disseminated infection!

OCULAR MANIFESTATIONS OF AIDS

Clinically 75% of patients have ocular signs or symptoms ANTERIOR SEGMENT COMPLICATIONS
Conjunctival teleangiectasia, giant molluscum, High grade malignant lymphoma/Burkitt lymphoma Kaposi sarcoma Keratitis, keratoconjunctivitis (HZ)

OCULAR MANIFESTATIONS OF AIDS

POSTERIOR SEGMENT COMPLICATIONS Vasculitis (direct effect of the virus)
VIRUS INFECTIONS (MULTIPLE)

CMV retinitis HSV acute retinal necrosis

MYCOTIC AND PARASITIC INFECTIONS

Pneumocystis carinii

EYE PROBLEMS IN VASCULAR DISORDERS

Hypertension Diabetes mellitus Hyperlipidaemia Hematological disorders Vasculitis Ischaemic optic nerve disease Retinal vascular occlusions

RETINAL FEATURES OF HYPERTENSION

Vessels (especially arterioles) Narrowing Thickening with silvering or tortuosity
Arteriovenous crossing change (nipping in of the vein)

RETINAL FEATURES OF HYPERTENSION

Hemorrhages Cotton wool spots (microinfarcts) Retinal edema and disc swelling Hard exudates (lipid) Macroaneurysms

DIABETIC RETINOPATHY
A sight-threatening chronic process based primarily on damage to the retinal capillaries (microangiopathy) Later the process involves larger vessels: venules, arterioles and arteries A certain degree of retinopathy develops in virtually every diabetic patient

DIABETIC RETINOPATHY
In type -1 (insulin-dependent) diabetes the first ophthalmologic examination should be performed 3 to 5 years after the diagnosis In type -2 diabetes (NIDDM) the beginning of the disease is usually not known, ophthalmologic examination is mandatory, as retinopathy or macular edema may already be present at diagnosis!

DIABETIC RETINOPATHY (pathogenic mechanisms)

Capillary hypertension Systemic hypertension Insulin resistance Increased vascular permeability Endothelial dysfunction Hyperglycemic pseudohypoxia Non-enzymatic glycosylation

Capillary damage
Endothelial damage

Capillary non-perfusion

Pericyte necrosis (capillaries and veins)

Retinal ischaemia

Growth factors

New vessels

Vasoactive factors

Hypertension

Hyperperfusion

Abnormal autoregulation

Hyperglycemia

NON-PROLIFERATIVE DIABETIC RETINOPATHY

MICROANEURYSMS and blot-and-dot hemorrhages INCREASED VASCULAR PERMEABILITY (hard exudates) ISCHAEMIA (cotton-wool spots: damage to axoplasmic flow in the nerve fiber layer)

NON-PROLIFERATIVE DIABETIC RETINOPATHY

Venous beading

IRMA (intraretinal microvascular anomalies) Extensive capillary occlusion and ischaemia

PROLIFERATIVE DIABETIC RETINOPATHY

IS CHARACTERIZED BY NEWLY FORMED VESSELS (neovascularisation) which originate from vessels of the optic nerve or from the surface of the retina Newly formed vessels are abnormal, extremely fragile vessels!

PROLIFERATIVE DIABETIC RETINOPATHY

Vascular buds grow into the vitreous cortex through the damaged internal limiting membrane of the retina Shrinkage and retraction of the vitreous is complicated by vitreous hemorrhage and/or retinal detachment

ANTERIOR SEGMENT COMPLICATIONS OF DIABETES

Recurrent, non-healing corneal epithelial defects Neovascular glaucoma (related to rubeosis iridis ang anterior chamber angle neovascularization)

HYPERLIPIDAEMIA
OCULAR SYMPTOMS
Corneal arc

Eruptive xanthoma

VASCULITIS
PERIARTERITIS NODOSA WEGENER GRANULOMATOSIS

VASCULITIS
ARTERITIS TEMPORALIS (GIANT CELL ARTERITIS) Arteritic ischemic optic neuropathy Painless visual loss with altitudinal visual field defect Age more than 55 years! Elevated ESR!

PHAKOMATOSES
Phakomatoses or neurocutaneous syndromes are a group of disorders featuring multiple discrete lesions of one or a few histologic types that are found in two or more organ systems, including skin or central nervous system or both. Eye involvement is frequent, and may constitute an important source of morbidity or provide information critical to diagnosis Neurofibromatosis (von Recklinghausen disease) Tuberous sclerosis (Bourneville disease) Angiomatosis of retina and cerebellum (von Hippel-Lindau) Encephalotrigeminal angiomatosis (Sturge-Weber syndrome)

NEUROFIBROMATOSIS
Two genetically distinct form are recognized NF-1, one of the commonest autosomal dominant disorders. Variation in the spectrum and severity of expression are prominent features. NF-1 gene is a tumor suppressor gene (chromosome 17q12) Diagnostic features Caf au lait spots Skin neurofibromas Lisch nodules

NEUROFIBROMATOSIS 1 (NF-1)
Associated ocular features Neurofibroma of eyelid and orbit Uveal melanocytic nevi Retinal glial hamartoma Congenital glaucoma Optic nerve glioma

NEUROFIBROMATOSIS 2 (NF-2)
The gene maps to chromosome 22 Diagnostic features Schwannoma of VIII cranial nerve Meningioma Spinal nerve root tumors Cutaneous neurofibroma (relatively rare) Associated ocular features Lens opacities - posterior capsular cataract developing during adolescence or young adulthood

TUBEROUS SCLEROSIS
Autosomal dominant trait, the responsible gene maps to chromosome 9q34 Skin lesions Angiofibroma (adenoma sebaceum) Seizures Mental retardation in 50% of cases Eye lesions Astrocytic hamartoma (composed of nerve fibers and glial cells) may be flat or mulberry-like

VON HIPPEL-LINDAU DISEASE Autosomal dominant disease, maps to chromosome 3p25

Diagnostic features Retinal angioma supplied by dilated tortuous arteriole and venule, may be multiple Cerebellar angioma Associated ocular conditions Retinal exudates, hemorrhage, retinal detachment

Associated general conditions Kidney tumors (renal carcinoma) Pheochromocytoma Cysts in different organs

STURGE-WEBER SYNDROME
Is not genetically transmitted Diagnostic features Facial cutaneous angioma (consists of excessively numerous dilated capillaries in the dermis) Cerebral calcification Seizures

STURGE-WEBER SYNDROME
OCULAR FEATURES
Choroidal involvement increased number of choroidal vessels Glaucoma is the most serious complication seen in children with SWS