Systemic disease and the eye Common systemic diseases

Systemic disease and the eye

Common systemic diseases affecting the eye Infectious Toxoplasmosis Toxocariasis TB Syphilis Leprosy HIV CMV Non-infectious Endocrine – diabetes, thyroid Connective tissue disease – RA/ SLE/ Wegeners/ PAN/ Systemic sclerosis Vasculitides (GCA) Sarcoidosis Behcet’s Disease Vogt Koyanagi Harada syndrome Phakomatoses

THYROID EYE DISEASE 1. Soft tissue involvement • • 2. 3. 4. 5. Periorbital and lid swelling Conjunctival hyperaemia Chemosis Superior limbic keratoconjunctivitis Eyelid retraction Proptosis Optic neuropathy Restrictive myopathy

Soft tissue involvement Periorbital and lid swelling Chemosis Conjunctival hyperaemia Superior limbic keratoconjunctivitis

Signs of eyelid retraction Occurs in about 50% • Bilateral lid retraction • No associated proptosis • Bilateral lid retraction • Bilateral proptosis • Unilateral lid retraction • Unilateral proptosis • Lid lag in downgaze

Proptosis • Occurs in about 50% • Uninfluenced by treatment of hyperthyroidism Axial and permanent in about 70% May be associated with choroidal folds Treatment options • Systemic steroids • Radiotherapy • Surgical decompression

Optic neuropathy • Occurs in about 5% • Early defective colour vision • Usually normal disc appearance Caused by optic nerve compression at orbital apex by enlarged recti Often occurs in absence of significant proptosis

Restrictive myopathy • Occurs in about 40% • Due to fibrotic contracture Elevation defect - most common Abduction defect - less common Depression defect - uncommon Adduction defect - rare

SARCOIDOSIS Idiopathic multisystem disorder Characterised by non-caseating granulomata More common in women 20 -50 yrs More common in blacks and Asians ? Related to mycobacteria

SARCOIDOSIS Systemic Involvement Lung lesions – 95% Thoracic lymph nodes – 50% Skin lesions – 30% Eyes – 30%

SARCOIDOSIS Ocular Involvement Anterior segment lesions (30%) n n Conjunctival granuloma Lacrimal gland involvement/dry eye Acute or chronic uveitis KPs described as ‘mutton fat’ because they are large and greasy

SARCOIDOSIS Ocular Involvement Posterior segment lesions (20%) n n n Patchy venous sheathing Cellular infiltrate around vessels Chorioretinal granulonmas Vasculitis including occlusive causing: Neovascularisation Infiltrate in vitreous (vitritis) including cell clumps (snowballs)

SARCOIDOSIS Ocular Involvement Sheathing of the retinal veins Fluorescein angiography showing leakage and staining at sites of sheathing

SARCOIDOSIS Granuloma in Fundus Retinal and pre-retinal Choroidal

SARCOIDOSIS Granuloma in Fundus Optic nerve head granuloma Normal optic nerve head

SARCOIDOSIS Systemic Signs Lupus pernio affecting the nose – a chronic progressive cutaneous sarcoid that most commonly affects face and ears

SARCOIDOSIS Systemic signs Facial palsy Salivary gland enlargement

SARCOIDOSIS Systemic signs Hilar adenopathy on chest x-ray Lung infiltrate Erythema nodosum Arthritis

SARCOIDOSIS Investigations (1) CXR – to detect pulmonary signs Bilateral hilar lymphadenopathy Pulmonary mottling

SARCOIDOSIS Investigations (2) Serum angiotensin-converting enzyme (ACE) – elevated in active sarcoidosis Mantoux test – caution in patients who have had BCG vaccination. Test may be negative Lung function tests

SARCOIDOSIS Investigations (3) Gallium scan showing increased uptake in the lacrimal and parotid glands and pulmonary regions in a patient with active sarcoidosis

SARCOIDOSIS Treatment Systemic steroids may be necessary in patients with posterior segment disease where vision is threatened, especially if optic nerve is involved

PHACOMATOSES 1. Neurofibromatosis • Type I (NF-1) - von Recklinghausen disease • Type II (NF-2) - bilateral acoustic neuromas 2. Tuberous sclerosis (Bourneville disease) 3. von-Hippel-Lindau syndrome 4. Sturge-Weber syndrome

Neurofibromatosis type-1 - (NF-1) • • Most common phacomatosis Affects 1: 4000 individuals Presents in childhood Gene localized to chromosome 17 q 11 Café-au-lait spots Appear during first year of life Increase in size and number throughout childhood

Fibroma molluscum in NF-1 Appear at puberty • Pedunculated, flabby nodules consisting of neurofibromas or schwannomas • Increase in number throughout life • Usually widely distributed •

Plexiform neurofibroma in NF-1 • • Appear during childhood Large and ill-defined • May be associated with overgrowth of skin

Skeletal defects in NF-1 • Facial hemiatrophy • • Mild head enlargement - uncommon Other - scoliosis, short stature, thinning of long bones

Orbital lesions in NF-1 Optic nerve glioma in 15% Spheno-orbital encephalocele • Sagittal MRI scan of optic nerve glioma invading hypothalamus • Axial CT scan of congenital absence of left greater wing of sphenoid bone • Glioma may be uni or bilateral • Pulsating proptosis without bruit!

Eyelid neurofibromas in NF-1 Nodular Plexiform May cause mechanical ptosis May be associated with glaucoma

Intraocular lesions in NF-1 Lisch nodules Very common - eventually present in 95% of cases Congenital ectropion uveae Uncommon - may be associated with glaucoma Choroidal naevi Retinal astrocytomas Common - may be Multifocal and bilateral Rare - identical to those seen In tuberous sclerosis

Ocular features of NF-2 Very common p- resenile cataract Common - combined hamartomas of RPE and retina

Tuberous sclerosis (Bourneville disease) • • Autosomal dominant Triad - mental handicap, epilepsy, adenoma sebaceum Adenoma sebaceum • • Around nose and cheeks Appear after age 1 and slowly enlarge Ash leaf spots • • Hypopigmented skin patches In infants best detected using ultraviolet light (Wood’s lamp) Shagreen patches • • Diffuse thickening over lumbar region Present in 40%

Systemic hamartomas in tuberous sclerosis Astrocytic cerebral hamartomas Visceral and subungual hamartomas • Slow-growing periventricular tumours • Usually asymptomatic and innocuous • May cause hydrocephalus, epilepsy and • Kidneys (angiomyolipoma), mental retardation heart (rhabdomyoma)

Retinal astrocytomas in tuberous scleritis • • Innocuous tumour present in 50% of patients May be multiple and bilateral Early Semitranslucent nodule White plaque Advanced Dense white tumour Mulberry-like tumour

Systemic features of v-H-L syndrome Autosomal dominant CNS Haemangioblastoma MRI-spinal cord tumour • Tumours - renal carcinoma and phaeochromocytoma • Angiogram of cerebellar tumour Visceral tumours • Cysts - kidneys, liver, pancreas, epididymis, ovary and lungs Polycythaemia

Retinal capillary haemangioma in v-H-L syndrome • • Vision-threatening tumour present in 50% of patients May be multiple and bilateral Early Tiny lesion between Small red nodule arteriole and venuole Advanced dilatation and Round orange-red mass Associated tortuosity of feeder vessels

Systemic features of Sturge-Weber syndrome Naevus flammeus • • Congenital, does not blanche with pressure Associated with ipsilateral glaucoma in 30% of cases Meningeal haemangioma • • CT scan showing left parietal haemangioma Complications –mental retard, epilepsy and hemiparesis

Ocular features of Sturge-Weber syndrome Glaucoma Buphthalmos in 60% May be associated with episcleral haemangioma Diffuse choroidal haemangioma Normal eye Affected eye

Peripheral corneal involvement in rheumatoid arthritis Without inflammation With inflammation • Chronic and asymptomatic • Acute and painful • Circumferential thinning with intact • Circumferential ulceration and epithelium (‘contact lens cornea’) infiltration Treatment - systemic steroids and/or cytotoxic drugs

Peripheral corneal involvement in Wegener granulomatosis and polyarteritis nodos Circumferential and central ulceration similar to Mooren ulcer Unlike Mooren ulcer sclera may also become involved Treatment - systemic steroids and cyclophosphamide

Ocular manifestations of HIV infection

Introduction AIDS is an infectious disease caused by the gradual decrease in CD 4+ T lymphocytes causing subsequent opportunistic infections and neoplasia. It is a blood borne and sexually transmitted infection caused by the HIV (Human Immunodeficiency Virus) Approximately 36 million persons around the world are infected. Up to 70% of patients infected with HIV will develop some form of ocular involvement, ie: direct infection by HIV, opportunistic infections and neoplasia. HIV infection progresses though different phases

Ophthalmic Manifestations of HIV Infection AROUND THE EYE n Molluscum Contagiosum n Herpes Zoster Ophthalmicus n Kaposi’s Sarcoma n Conjunctival Squamous Cell Carcinoma n Trichomegaly FRONT OF THE EYE n Dry Eye n Anterior Uveitis BACK OF THE EYE n Retinal Microvasculopathy n CMV Retinitis n Acute Retinal Necrosis n Progressive Outer Retinal Necrosis n Toxoplasmosis Retinochoroiditis n Syphilis Retinitis n Candida albicans endophthalmitis NEURO-OPHTHALMIC

Molluscum Contagiosum Molluscum contagiosum is a viral infection of the skin. Affects up to 20% of symptomatic HIV infected patients. Clinically appears like painless, small, umbilicated nodules, which produce a waxy discharge when pressured. Treatment consists on excision of the lesion, curettage or cryotherapy

Herpes Zoster Ophthalmicus Due to the reactivation of a latent infection by Varicella Zoster Virus in the dorsal root of trigeminal nerve ganglion. It manifests with a maculo-papulo-vesicular rash which often is preceded by pain. Usually involves the upper lid and does not cross the midline Treatment consists on oral Aciclovir 800 mg 5 times /day. In immunocompromised patients Aciclovir is given intravenously for two weeks. Ocular manifestations such as anterior uveitis, are treated with topical steroids and mydriatics.

Kaposi’s Sarcoma Kaposi’s sarcoma is a vascular neoplasm which is almost exclusively seen in patients with AIDS. KS is the commonest anterior segment lesion seen in AIDS; appears as a violaceous non-tender nodule on the eyelid or conjunctiva. Typically KS involves only the skin but when there is a reduced CD 4 count it can progress rapidly to other sites such as the gastrointestinal tract and CNS Treatment of ocular adnexal KS may be necessary for cosmesis and to relieve functional difficulties. The mainstay of treatment is radiotherapy. Other options include cryotherapy or chemotherapy.

Conjunctival Squamous Cell Carcinoma Squamous cell carcinoma (SCC) is the third most common neoplasm associated to HIV infection. This may be due to an interaction between HIV, sunlight and Human Papilloma Virus infection. SCC appears as a pink, gelatinous growth, usually in the interpalpebral area. Often an engorged blood vessel feeding the tumour is seen. It may extend onto the cornea, but deep invasion and metastasis are rare. The treatment of choice is local excision and cryotherapy but the presence of orbital invasion is an indication of exenteration

Trichomegaly or hypertrichosis is an exaggerated growth of the eye lashes found in the later stages of the disease The cause is not known When symptomatic or for cosmetic reasons the eyelashes can be trimmed or plucked

Dry Eye Sicca syndrome is common with HIV infection Patients complain of burning uncomfortable red eyes. There are several causes of dry eye in HIV infection from blepharitis to destruction of the lacrimal glands. Treatment is with tear supplements

Anterior Uveitis HIV related anterior uveitis can be: n Direct manifestation of the HIV infection n autoimmnune in origin n drug induced ie: rifabutin, secondary to direct toxic effect upon the nonpigmented epithelium of the ciliary body. n Any of the different infections associated with AIDS : Herpes Zoster Virus, Herpes Simplex Virus, Cytomegalovirus, Toxoplasma gondii Syphilis

Rifabutin induced anterior uveitis

Retinal microvasculitis Retinal microvasculopathy occurs in more than half of the patients with HIV It is seen as transient cotton wool spots (CWS), intra-retinal haemorrhages and microaneurysm, Occurs in 50 -70% of patients. It is usually asymptomatic. Unclear pathogenesis, but thought to be HIV infection of retinal vascular cells. Serological test for HIV will confirm the diagnosis. Treatment is based in delaying the progression of the disease associated with HIV.

Cotton Wool Spots

CMV Retinitis Introduction n n CMV Retinitis is the commonest intraocular opportunistic infection seen in patients with AIDS Antibodies are found in almost 95% of adults, causing a trivial illness in immunocompetent adults, however severe immunosuppression causes viral reactivation and tissue invasive disease Pathogenesis n Reactivation from extraocular sites leads to seeding in other sites such as the retina Epidemiology n The number of newly diagnosed cases of CMVR has decreased since the introduction of the HAART Highly Active Antiretroviral Therapy

CMV Retinitis Clinical manifestations n n Patients may complain of minor visual symptoms such as floaters, flashing lights or mild blurred vision, or be totally asymptomatic. It presents with a wide range of clinical appearances. From cotton wool spots which may look like HIV Retinopathy to confluent areas of full thickness retinal necrosis and vasculitis. CMVR can progress in a “brushfire” pattern from the active edge of an active lesion. The retinal vessels in an affected area show attenuation, becoming ghost vessels eventually. Treatment n n The treatment of CMVR in patients with AIDS requires the use of specific antiviral agents, ganciclovir, foscarnet or cidovir in conjunction with HAART. These treatments can be administered orally, intravenously or intravitreally. Systemic treatment has the advantage of treating infection elsewhere in the body as well as the other eye but has the disadvantages of systemic side effects.

CMV Retinitis

Acute Retinal Necrosis ARN is a confluent peripheral whitening of the retina with marked vitritis and blood vessel closure. Optic neuritis and retinal detachment are frequent complications. ARN is usually due to Varicella-Zoster infection, but it can also be caused by Herpes Simplex virus or Cytomegalovirus. Initially described in the immunocompetent, it has also been described in the immunosuppressed. The diagnosis is mainly clinical and is confirmed by PCR assays on vitreous samples. Patients are treated with high doses of intravenous aciclovir or famciclovir, combined with laser treatment to prevent retinal detachment.

Acute Retinal Necrosis

Progressive Outer Retinal Necrosis (Varicella-Zoster Retinitis) PORN is a devastating viral retinitis caused by Varicella-Zoster virus, without vitritis or retinal vasculitis. The retinitis can be located anywhere but it is common for the lesions to coalesce and spread posteriorly in a rapid fashion. The main symptom is rapid loss of vision. The retina shows typically a white lesion with no haemorrhages or exudates. Treatment is often unsatisfactory (Ganciclovir and Aciclovir). The prognosis is very poor and retinal detachment is common. Resolution may leave a white plaque with the appearance of “cracked mud”.

Toxoplasma Retinochoroiditis Toxoplasmosis retinochoroiditis is an uncommon infection of the eye in AIDS. Ocular toxoplasmosis in HIV positive patients is different in appearance from immunocompetent patients. HIV infected patients often have bilateral and multifocal disease associated with anterior uveitis and vitritis No pigmented scars adjacent to the areas of retinal necrosis. (unlike in immunocompetent patients) Retinochoroiditis is not self-limiting as it is in imunocompetent patients.

Toxoplasma Retinochoroiditis When testing patients for antibodies to toxoplasmosis both Ig. G and Ig. M levels may be raised, but in immunocompromised patients these tests may be negative. Often associated with toxoplasma lesions in the Central Nervous System. Treatment in immunocompromised patients sulphadiazine or clindamycin +/- pyrimethamine and folinic acid (triple therapy). Long term maintenance to prevent relapses.

MRI T 1 showing an uniformly enhancing lesion in the midbrain One week later, the lesion showing ring enhancement

Immunocompetent Immunocompromised

Syphilis Retinitis There is a strong association between syphilis and HIV infection. It can manifest as a retinitis with dense vitritis, retinal vasculitis, serous retinal detachment or neuroretinitis, conjunctivitis, anterior uveitis, cranial nerve palsies and optic neuritis. Treatment high dose of intravenous Penicillin for 2 weeks.

Candida albicans endophthalmitis Infection with candida albicans is rare. Candida albicans is the commonest cause of fungal endophthalmitis Affected patients usually have a history of drug abuse or indwelling central lines or immuno-compromised. In the initial stages, floaters are the main symptom. As the condition progresses, whitish “puff-balls” and vitreous strands develop (‘string of pearls’) The treatment depends on the severity of the ocular involvement and systemic disease. The original foci should be removed. The drugs of choice are Amphotericin B and Fluconazole

Candida albicans endophthalmitis

Glossary CD 4: Director of the immune response. When activated it releases cytokines which in turn will activate the immune system Cotton Wool Spots: Light-coloured deposits in the retina secondary to infarcts of the nerve fibre layer HAART: Highly Active Antiretroviral Therapy Immunoblogulin: Protein in charge of fighting foreign substances in our body. Ig. G is the commonest type of immunoglobulin and Ig. M is the earliest class of immunoglobulin. PCR: Polymerase Chain Reaction is a technique used to make numerous copies of an specific portion of DNA VDRL: Venereal Disease Research Laboratory. The test becomes negative after successful treatment of the disease.