1. Systemic disease and the eye

2. 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

Behcets Disease

Vogt Koyanagi Harada syndrome

Phakomatoses

3. 1. Soft tissue involvement

Periorbital and lid swelling

Conjunctival hyperaemia

Chemosis

Superior limbic keratoconjunctivitis

2.Eyelid retraction 3.Proptosis 4.Optic neuropathy 5.Restrictive myopathy THYROID EYE DISEASE 4. Soft tissue involvement Periorbital and lid swelling Chemosis Conjunctival hyperaemia Superior limbickeratoconjunctivitis 5. Signs of eyelid retraction Occurs in about 50%

Bilateral lid retraction

No associated proptosis

Bilateral lid retraction

Bilateral proptosis

Lid lag in downgaze

Unilateral lid retraction

Unilateral proptosis

6. Proptosis Treatment options

Systemic steroids

Radiotherapy

Surgical decompression

Occurs in about 50%

Uninfluenced by treatment of hyperthyroidism

Axial and permanent in about 70%May be associated with choroidal folds 7. Optic neuropathy

Occurs in about 5%

Early defective colour vision

Usually normal disc appearance

Caused by optic nerve compression atorbital apex by enlarged rectiOften occurs in absence of significantproptosis 8.

Occurs in about 40%

Due to fibrotic contracture

Restrictive myopathy Elevation defect - most common Abduction defect - less commonDepression defect -uncommon Adduction defect - rare 9. 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

10. SARCOIDOSIS Systemic Involvement

Lung lesions 95%

Thoracic lymph nodes 50%

Skin lesions 30%

Eyes 30%

11. SARCOIDOSIS Ocular Involvement

Anterior segment lesions (30%)

• Conjunctival granuloma

• Lacrimal gland involvement/dry eye

• Acute or chronic uveitis

• KPs described as mutton fat because they are large and greasy

12. SARCOIDOSIS Ocular Involvement

Posterior segment lesions (20%)

• Patchy venous sheathing

• Cellular infiltrate around vessels

• Chorioretinal granulonmas

• Vasculitis including occlusive causing:-

• Neovascularisation

• Infiltrate in vitreous (vitritis) including cell clumps (snowballs)

13. SARCOIDOSIS Ocular Involvement

Sheathing of the retinal veins

Fluorescein angiography showing leakage and staining at sites of sheathing

14. SARCOIDOSIS Granuloma in Fundus

Retinal and pre-retinal

Choroidal

15. SARCOIDOSIS Granuloma in Fundus

Optic nerve head granuloma

Normal optic nerve head

16. SARCOIDOSIS Systemic Signs

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

17. SARCOIDOSIS Systemic signs

Facial palsy

Salivary gland enlargement

18. SARCOIDOSIS Systemic signs

Hilar adenopathy on chest x-ray

Lung infiltrate

Erythema nodosum

Arthritis

19. SARCOIDOSIS Investigations (1)

CXR to detect pulmonary signs

Bilateral hilar lymph-adenopathy

Pulmonary mottling

20. 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

21. SARCOIDOSIS Investigations (3)

Gallium scan showing increased uptake in the lacrimal and parotid glands and pulmonary regions in a patient with active sarcoidosis

22. SARCOIDOSIS Treatment

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

23. PHACOMATOSES 1.Neurofibromatosis 2.Tuberous sclerosis (Bourneville disease) 3.von-Hippel-Lindau syndrome 4.Sturge-Weber syndrome

Type I (NF-1) - von Recklinghausen disease

Type II (NF-2) - bilateral acoustic neuromas

24. Neurofibromatosis type-1 -(NF-1) Appear during first year of life Caf-au-lait spots

Most common phacomatosis

Increase in size and numberthroughout childhood

Affects 1:4000 individuals

Presents in childhood

Gene localized to chromosome 17q11

25. Fibroma molluscum in NF-1

Appear at puberty

Pedunculated, flabby nodules consisting of

neurofibromas or schwannomas

Increase in number

throughout life

Usually widely distributed

26. Plexiform neurofibroma in NF-1

May be associated with

overgrowth of skin

Appear during childhood

Large and ill-defined

27. Skeletal defects in NF-1

Mild head enlargement - uncommon

Other - scoliosis, short stature, thinning

of long bones

Facial hemiatrophy

28. Orbital lesions in NF-1 Spheno-orbital encephalocele Optic nerve glioma in 15%

Sagittal MRI scan of optic nerve

glioma invading hypothalamus

Glioma may be uni or bilateral

Axial CT scan of congenital absence

of left greater wing of sphenoid bone

Pulsating proptosis without bruit!

29. Eyelid neurofibromas in NF-1 Nodular Plexiform May cause mechanical ptosis May be associated with glaucoma 30. Intraocular lesions in NF-1 Lisch nodules Very common - eventually present in 95% of cases Congenital ectropion uveae Uncommon - may beassociated with glaucoma Retinal astrocytomas Rare - identical to those seenIn tuberous sclerosis Choroidal naevi Common - may beMultifocal and bilateral 31. Ocular features of NF-2 Common - combined hamartomas ofRPE and retinaVery common - presenile cataract 32. Tuberous sclerosis (Bourneville disease)

Diffuse thickening over

lumbar region

Present in 40%

Shagreen patches

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 (Woods lamp)

33. Systemic hamartomas in tuberous sclerosis Astrocytic cerebral hamartomas

Slow-growing periventricular tumours

May cause hydrocephalus, epilepsy and

mental retardation

Usually asymptomatic and

innocuous

Kidneys (angiomyolipoma),

heart (rhabdomyoma)

Visceral and subungual hamartomas 34. Retinal astrocytomas in tuberous scleritisDense white tumour Mulberry-like tumour Early

Innocuous tumour present in 50% of patients

May be multiple and bilateral

Semitranslucent nodule White plaque Advanced 35. Systemic features of v-H-L syndrome Autosomal dominant

Tumours - renal

carcinoma and

phaeochromocytoma

Cysts - kidneys, liver,

pancreas, epididymis,

ovary and lungs

Polycythaemia

CNS Haemangioblastoma MRI-spinal cord tumour Angiogram of cerebellartumour Visceral tumours 36. Retinal capillary haemangiomain v-H-L syndrome Round orange-red mass Early

Vision-threatening tumour present in 50% of patients

May be multiple and bilateral

Tiny lesion betweenarteriole and venuole Small red nodule Associated dilatation andtortuosity of feeder vessels Advanced 37. Systemic features of Sturge-Weber syndrome

Congenital, does not

blanche with pressure

Associated with ipsilateral

glaucoma in 30% of cases

Naevus flammeus

CT scan showing left

parietal haemangioma

Complications mental retard,

epilepsy and hemiparesis

Meningeal haemangioma 38. Ocular features of Sturge-Weber syndrome Normal eye Buphthalmos in 60% May be associated withepiscleral haemangioma Affected eye Diffuse choroidal haemangioma Glaucoma 39. Peripheral corneal involvement inrheumatoid arthritis

Chronic and asymptomatic

Circumferential thinning with intact

epithelium (contact lens cornea)

Acute and painful

Circumferential ulceration and

infiltration

Treatment- systemic steroids and/or cytotoxic drugs Without inflammationWith inflammation 40. Peripheral corneal involvement inWegener granulomatosis and polyarteritis nodosa Circumferential and central ulceration similar to Mooren ulcer Unlike Mooren ulcer sclera may also become involved Treatment- systemic steroids and cyclophosphamide 41. Ocular manifestations of HIV infection 42. Introduction

AIDS is an infectious disease caused by the gradual decrease inCD4+ T lymphocytescausing 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 thoughdifferent phases

43. 44. Ophthalmic Manifestations of HIV Infection

AROUND THE EYE

• Molluscum Contagiosum

• HerpesZoster Ophthalmicus

• KaposisSarcoma

• ConjunctivalSquamousCell Carcinoma

• Trichomegaly

FRONT OF THE EYE

• Dry Eye

• Anterior Uveitis

BACK OF THE EYE

• RetinalMicrovasculopathy

• CMVRetinitis

• Acute Retinal Necrosis

• Progressive Outer Retinal Necrosis

• Toxoplasmosis Retinochoroiditis

• SyphilisRetinitis

• Candida albicans endophthalmitis

NEURO-OPHTHALMIC

45. Molluscum Contagiosum

Molluscum contagiosum is a viral infection of the skin.

Affects up to 20% ofsymptomatic 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

46. 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 800mg 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.

47. 48. Kaposis Sarcoma

Kaposis 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 CD4 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.

49. 50. 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

51. 52. Trichomegaly

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

53. 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

54. Anterior Uveitis

HIV related anterior uveitis can be:

• Direct manifestation of the HIV infection

• autoimmnune in origin

• drug induced ie: rifabutin, secondary to direct toxic effect upon the non-pigmented epithelium of the ciliary body.

• Any of the different infections associated with AIDS :-Herpes Zoster Virus,Herpes Simplex Virus, Cytomegalovirus,Toxoplasma gondiiSyphilis

55. Rifabutin induced anterior uveitis 56. 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.

57. Cotton Wool Spots 58. CMV Retinitis

Introduction

• CMV Retinitis is the commonest intraocular ocular 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

• Reactivation from extraocular sites leads to seeding in other sites such as the retina

Epidemiology

• The number of newly diagnosed cases of CMVR has decreased since the introduction of the HAART

Highly Active Antiretroviral Therapy 59. CMV Retinitis

Clinical manifestations

• Patientsmay 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

• 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.

• Intravitreal implants release the drug over a six-month period, achieving prolonged high intravitreal levelsof drug.

60. CMV Retinitis 61. 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.

62. Acute Retinal Necrosis 63. 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.

64. 65. Toxoplasma Retinochoroiditis

Toxoplasmosis retinochoroiditis is an uncommon infection of the eye in AIDS.

Oculartoxoplasmosisin HIV positive patients is different in appearancefrom immunocompetent patients .

HIV infected patients often have bilateral and multifocal disease associated with anterior uveitis and vitritis

No pigmentedscars adjacent to the areas of retinal necrosis. (unlike in immunocompetent patients)

Retinochoroiditis is not self-limiting as it is in imunocompetent patients.

66. Toxoplasma Retinochoroiditis

When testing patients for antibodies to toxoplasmosis both IgG and IgM 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.

67. MRI T1 showing an uniformly enhancing lesion in the midbrain One week later, the lesion showing ring enhancement 68.

Immunocompetent Immunocompromised

69. 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.

70. 71. 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

72. Candida albicans endophthalmitis 73. Glossary

CD4 : Director of the immune response. When activated it releasescytokines which in turn will activate the immune system

Cotton Wool Spots : Light-coloured deposits in the retina secondaryto infarcts of the nerve fibre layer

HAART : Highly Active Antiretroviral Therapy

Immunoblogulin : Protein in charge of fighting foreign substances inour body.IgGis the commonest type ofimmunoglobulin andIgMis the earliest class of immunoglobulin.

PCR : Polymerase Chain Reaction is a technique used to makenumerous copies of an specific portion of DNA

VDRL : Venereal Disease Research Laboratory. The test becomesnegative after successful treatment of the disease.

74. 75. 76. 77. 78.