Uveitis and Systemic Disease - diabetic retinopathy
Uveitis and Systemic Disease Classification When to investigate ? Common Causes Systemic associations Uveitis and Systemic Disease Uveitis can be defined as inflammation of the uvea, the middle, vascular coat of the eye (Greek uva- grape) The uvea consists of the iris, ciliary body and the choroid. The
International Uveitis Study Group classification separates uveitis anatomically by location of observed disease according to visible signs- anterior posterior or intermediate. Iritis is a synonym for anterior uveitis.. Uveitis Uveitis, a term correctly used to describe inflammation of the uveal tract (iris, ciliary body, choroid) alone, in reality comprises a large group of diverse diseases affecting not only the uvea but also
the retina, optic nerve and vitreous. Uveitis is a major cause of severe visual impairment and has been estimated to account for 10-15% of all cases of total blindness in the USA. In surveys of the causes of blindness uveitis has usually not been included and is probably underestimated Uveitis and Systemic Disease International Classification of Uveitis Temporal- Acute versus Chronic ( >3 months) In acute uveitis symptoms and signs occur suddenly and typically lasts up to 6 weeks. In chronic uveitis the onset is usually gradual and
the inflammation lasts longer than three months. Anatomical Anterior Uveitis ( Iris and anterior ciliary body ) Intermediate Uveitis ( posterior ciliary body- pars plana ) Posterior Uveitis ( predominantly choroid) Complications from chronic uveitis Complications from chronic uveitis are common and may result in severe visual
loss.. Macular oedema can complicate any type of uveitis and can cause substantial visual loss. Cataract is common in chronic uveitis and its treatment with corticosteroids. Techniques for cataract surgery and perioperative management have improved greatly, and most patients with uveitis are now suitable for intraocular lens implantation and do well. 18 Glaucoma is the most overlooked complication of chronic uveitis and has several causes.19 Medical management with topical agents such as blockers control the elevation of intraocular pressure in most patients. Some patients also require oral carbonic anhydrase inhibitors, while surgical intervention is reserved for those who have progressive visual loss or uncontrollable intraocular
Uveitis and Systemic Disease Epidemiology of uveitis in the United Kingdom A uveitis register at the Leicester Royal Infirmary consisted of data collected on all uveitis patients except minor easily resolved, anterior uveitis cases. The diagnoses of these patients were classified by the aetiological method. A total of 712 patients was entered into the register over a period of 10 years starting from January 1985. In the study, 73.0% of the cases fit into named clinical syndromes while 27.0% of the cases were diagnosed as idiopathic or uncategorised. The commonest definable cause of anterior uveitis was HLA-B27-related acute anterior uveitis, comprising 15.2% of all uveitis cases ( in some series up to 50% of uveitis is related to
HLA B27 antigen ). Intermediate uveitis accounted for 7.9% of all cases while the commonest definable cause of posterior uveitis was toxoplasmosis, forming 4.6% of all uveitis cases. The annual incidence in Western countries is approximately 17/100,000 while the prevalence of uveitis is estimated as about 38/100,000. Ethnicity Ethnicity affects uveitis, for example- HLAB27 antigen is the commonest factor responsible for uveitis in Caucasians, in the Afro-Caribbean community sarcoid is common whist Bechets disease affects those of Asian and Middle Eastern origins (HLA B5 ).
Uveitis and Systemic Disease Uveitis and Systemic Disease Uveitis and Systemic Disease Uveitis and Systemic Disease Uveitis and Systemic Disease Uveitis and Systemic Disease -History and examination Overview of the Investigation and
Management of Uveitis The management of the patient with uveitis involves the following, History taking (ocular and general) Complete ocular examination General physical examination Investigations Specialist medical referral ( for further evaluation ) When to investigate One of the most pressing questions that arises in the
mind of every ophthalmologist who sees a new case of uveitis is "what is the cause of this disease?" In evaluating patients with uveitis, the ophthalmologist must consider that a lengthy list of infections, autoimmune systemic diseases, distinctive inflammatory conditions and masquerade syndromes may all cause uveal inflammation. Despite this array of potential diagnoses, the vast majority of patients have disease that defies categorisation. Uveitis and Systemic Disease-avoid a shotgun approach to investigation !!
Do not wade in like John Wayne !! General Investigations A recent retrospective review of patients with various types of uveitis showed the following abnormal results: full blood count: 23/113 (20.3%), plasma viscosity / ESR: 37/108 (34.2%), VDRL/TPHA: 3/70 (4.3%), angiotensin converting enzyme (ACE): 9/77 (10.8%) and chest x-ray (CXR): 15/103 (14.6%). Sarcoidosis was diagnosed in eight patients who had an abnormal CXR raised ACE. All patients with symptoms of other organ system dysfunction or general malaise should be investigated to
rule out under-lying systemic disease. Uveitis and Systemic Disease Table- Aetiology of Anterior uveitis HLA-B27 Positive or Seronegative Group Ankylosing spondylitis Reiters syndrome Inflammatory bowel disease (Ulcerative colitis, Crohns disease) Psoriatic arthritis Intraocular lens related Herpes simplex Herpes zoster
General Investigations ESR / Plasma Viscosity/ C Reactive Protein CXR FBC Syphilis Serology- TPHA, VDRL Urine analysis ( Diabetes Mellitus ) Specific Investigations HLA B27 Ag; HLA B29 ( birdshot retinochoroidopathy ) Angiotensin Converting Enzyme Rheumatoid Factor , Lupus Group Autoantibodies including anti-neutrophil cytopasmic antibody ( Wegeners Granulomatosis ) Anticardiolipin Antibody- ( the yield of these investigations is actually low except in children with Juvenile Chronic Arthritis ) Toxoplasma Serology / IgG antibodies ( if negative on undiluted serum to exclude
congenital toxoplasmosis ) Toxocara ELISA HIV Pathergy Test Mantoux Test, Sputum Acid Fast Bacilli X Ray Hands and SI Joints B Scan for Masquerade Leisions or Posterior Scleritis Kveim Test Immune Complexes -Polyethylene Glycol Method DNA Polymerase Chain Reaction ( Herpes virus, Propionebacter ) CT scan of chest ( sarcoidosis) MRI( non Hodgkins lymphoma, neurosarcoid, demyelination ) Choroidal biopsy ( Non Hodgkins Lymphoma )
Physician Referral Rheumatological Referral Broncho-alveolar lavage ( Sarcoid) CSF studies ( non Hodgkins lymphoma, neurosarcoid, VKH ) Venereological Referral HIV, Reiter's, Syphilis A recent retrospective review showed the following abnormal results, plasma viscosity/ esr 34.2%, VDRL/TPHA ( 4.3% ) Angiotensin converting enzyme (10.8%) Chest X ray ( 14.6%) Uveitis and Systemic Disease HLA-B27 Antigen The test can be useful in cases of recurrent anterior uveitis. HLA-B27 denotes a genotype
located on chromosome 6. It is present in 4% of the general population and up to 50% of patients with acute iritis. Many patients with acute iritis therefore have a genetic predisposition. Factors which may trigger the occurrence of acute iritis are often unknown. In general, the importance of tissue tying for HLA B27 is under appreciated, the investigation has a high yield, is inexpensive, and gives patients an explanation of an often recurrent problem. Ankylosing spondylitis, Reiters syndrome, psoriatic arthritis and inflammatory bowel disease are all associated with iritis, spondylitis and the presence of HLA-B27 positivity HLA-B27 disease. Debate exists as to whether patients with the commonest type of uveitis (acute anterior uveitis AAU) should be investigated. It is well recognised that
approximately 50% of patients with AAU are HLAB27 positive. A number of these patients will give a history of an associated HLA-B27 disease. HLA-B27-associated AAU often presents with a number of clinical clues which help in diagnosis: it is usually recurrent, unilateral but alternating, with severe anterior chamber inflammation (posterior synechiae, fibrin and hypopyon). Useful investigations for chronic uveitis
Chest x ray Diagnosis of tuberculosis, sarcoidosis, lymphoma, lung carcinoma Syphilis serologyDiagnosis of syphilis HLA-A29Diagnosis of birdshot chorioretinopathy Mantoux testAnergic response despite prior BCG vaccination is consistent with sarcoidosis. Strong positive response without prior vaccination suggests exposure to tuberculosis HIV serologyIf patient of high risk status or clinical picture suggests HIV
related uveitis such as cytomegalovirus retinitis Lyme disease serologyIf patient from endemic area or with history of exposure and suggestive symptoms Antinuclear antibodiesIf clinical picture suggests juvenile chronic arthritis ANF ANCA Rhem Factor Aqueous and vitreous biopsiesDiagnosis of infective endophthalmitis and intraocular lymphoma Uveitis and Systemic Disease Ankylosing Spondylitis 30% of AS patients develop iritis, especially if male; iritis may precede arthritis rarely retinal vasculitis / vitritis.
Acute anterior uveitis lasting 2-6 weeks, good prognosis Investigations in suspected ankylosing spondylitis X-ray sacroiliac joints HLA B27 (positive in more than 90% ) Uveitis and Systemic Disease Associations of Reiter's Syndrome
Occurs if genetically predisposed (HLA B27); 60 - 90% association M>F Exposure to certain urethritis / dysentery organisms: e.g. Chlamydia, Yersinia, Shigella, Salmonella, Campylobacter. The order of manifestation is normally: urethritis conjunctivitis arthritis. Ocular 20% anterior uveitis, 60% conjunctivitis, episcleritis, keratitis, post-uveitis. Reiters disease can sometimes result in hypopyon formation
Uveitis and Systemic Disease Intermediate uveitis Pars planitis
Sarcoidosis Sympathetic ophthalmia Behcets disease Idiopathic Uveitis and Systemic Disease Toxoplasmosis ELISA IgM in neonates, Rising IgG in adults (although not that helpful in adults). Fluorescein angiography (hypofluorescence in the early stages and then progressive leakage). Indocyanine angiography - multiple small dark spots
may be seen around the visible lesions implying the affected retina is greater than apparent initially. This sign may be useful in assessing the effect of treatment. Uveitis and Systemic Disease Uveitis and Systemic Disease Sarcoidosis This chronic non-caseating granulomatous systemic disease of unknown aetiology affects women more commonly than men and is more common in individuals of Afro-Caribbean ethnicity. In Britain sarcoidosis is the commonest systemic disease that presents as chronic uveitis. It has protean ocular manifestations and may present with
a spectrum of ocular signs, including anterior and posterior uveitis, retinal vascular sheathing, and optic disc abnormalities Ocular Manifestations About 30% of patients with sarcoidosis have ocular involvement. Iritis may be acute or chronic; it may be unilateral or bilateral. Patients with posterior uveitis usually have anterior uveitis as well. Vitritis is also common and tends to occur in older patients. There may be retinal periphlebitis; the vessels may display an exudative cuff (so called candle wax drippings). Inflammation of the retina may lead to macular oedema, retinal granuloma, preretinal nodules and retinal haemorrhage. Inflammation of the optic nerve may cause optic disc oedema, granuloma and neovascularization. Branch retinal vein occlusion and retinal neovascularisation are uncommon
Uveitis and Systemic Disease Sarciodosis - Investigations Chest X-ray Serum ACE (angiotensin converting enzyme)this is elevated in active disease urine and serum calcium levelshypercalciuria is common hypercalcaemia is less common Conjunctival biopsy may show granulomata Uveitis and Systemic Disease Uveitis and Systemic Disease Uveitis and Systemic Disease
Uveitis and Systemic Disease Uveitis and Systemic Disease Ocular Manifestations of Tuberculosis Affects 2% of sufferers of active tuberculosis , uveitis is commonest manifestation. Systemic disease is often apparent. Eyelids- lupus vulgaris (nodules surrounded by erythema) Orbit- cellulitis, dacryoadenitis, dacryocystitis, osteomyelitis, abscess Conjunctiva- rarely affected, chronic conjunctivitis Cornea- phlyctenular keratoconjunctivitis, interstitial keratitis (unilateral, sectorial, superficial vascularisation) Sclera- episcleritis, nodular scleritis
Uveitis- chronic granulomatous anterior uveitis, multifocal choroiditis, exudative retinitis, vasculitis, optic nerve oedema, papilloedema Uveitis and Systemic Disease Juvenile Chronic Arthritis Chronic AAU , usually bilateral Commoner in female patients, the young, ANF positive. Pauciarticular disease <5 joints. Complications Glaucoma (20%) Cataract (40%) Band Keratopathy (40%)
Uveitis and Systemic Disease Uveitis and Systemic Disease Uveitis and Systemic Disease Monitoring Children with Juvenile Chronic Arthritis High Risk Early Onset , < 6 years, Pauciarticular Disease , ANA Positive 3 months for first year , then 6 months for five years , then annually Medium Risk polyarticular disease ANA positive , pauciarticular -disease ANA negative 6 monthly intervals for 5 years then annually Low Risk
Systemic JCA , B27 associated arthritis , disease starting after age 11 Duration For ten years after onset of JCA or until age 12, whichever is shorter. Source RCOphth (UK), British Paediatric Association (1994) Masquerade Syndromes Intraocular lymphoma may present as a chronic uveitis in older patients, especially when there is vitritis and vitreous veils and a poor response to treatment. Intraocular tumours, particularly retinoblastoma in children, may also occasionally present in this manner. Differential Diagnosis Of Uveitis- It is of paramount importance to note that uveitis can be caused or mimicked by the following- Masquerade Syndromes- neoplasms mimicking uveitis
Ocular malignant melanoma Retinoblastoma Reticulum Cell Sarcoma ( Primary Intraocular Lymphoma ) Leukaemia Lymphoma Ocular Metastasis OtherEndophthalmitis Retinal detachment Intraocular foreign body Uveitis and Systemic Disease Uveitis and Systemic Disease
Uveitis and Systemic Disease Syphilis Uveitis may be acute or chronic, unilateral or bilateral. Interstitial keratitis affects a small percentage of acquired cases and is often unilateral. Chorioretinitis is bilateral in 50% of cases;multifocal or diffuse yellow exudate is seen. The chorioretinitis may resolve, leaving extensive bone spicule pigmentation. The appearance may resemble retinitis pigmentosa. There may be retinal oedema, haemorrhages, exudates, cotton wool spots and vascular sheathing. Optic disc oedema may also be seen. Investigations for suspected syphilitic uveitis include VDRL and FTA-ABS tests. The VDRL test is useful for screening; false positive results may occur. The FTA-ABS test remains positive for life, even after treatment.
Uveitis and Systemic Disease- about 5% of uveitis caused by syphilis in some series Therapeutics The aims of treatment are to control inflammation, prevent visual loss, and minimise long term complications of the disease and its treatment. Macular oedema is the commonest indication for treatment. Treatment is usually indicated if the visual acuity has fallen to less than 6/12, or if the patient is experiencing visual difficulties. In patients with longstanding macular oedema and poor vision or where it is not possible to determine easily the cause of visual loss, a trial of
immunosuppressive treatment is usually indicated to determine whether the visual loss is reversible. Many patients with unilateral chronic uveitis can be managed with topical corticosteroids to control anterior uveitis and periocular corticosteroids for macular oedema and visual loss. Patients with useful vision in only one eye must be managed aggressively to control inflammation and preserve vision. Systemic corticosteroids Corticosteroids are the mainstay of systemic treatment for patients with chronic uveitis, and the usual indication for treatment is the presence of macular oedema and visual acuity of less than 6/12.
Patients should be treated with appropriate doses to determine whether the macular oedema is reversible. Thus maximum treatment (1.0-1.5 mg/kg body weight/day of prednisone or prednisolone) should be used for two to three weeks. If there is no response at this dose, addition of a second line agent such as cyclosporin (or azathioprine or mycophenolate in older patients) for a further four to six weeks may be considered. In children the doses should be adjusted appropriately. Other systemic immunosuppressive therapy If macular oedema recurs and visual acuity decreases at an unacceptably high dose
of corticosteroid (>15 mg/day of prednisolone) an additional drug is necessary to help control the inflammation. Cyclosporin is the drug of choice for most patients aged under 50 years.The commonest dose limiting side effects of cyclosporin are hypertension and renal dysfunction, which are usually reversible if the drug is stopped. Several other drugs can be considered in patients who require additional immunosuppressive therapy when cyclosporin is not appropriate or not tolerated. Azathioprine, methotrexate, and, much less commonly, cyclophosphamide are the most used, but each is associated with important side effects and complications. Other agents such as mycophenolate, tacrolimus, and humanised Tac monoclonal antibodies have been usedThe decision to start treatment with immunosuppressive drugs is a long term commitment by both the clinician and patient, as treatment is likely to last for a minimum of six months and is often much longer.
Surgery Surgery may be required for complications such as cataract, glaucoma, and vitreoretinal problems, but, except in emergency situations, it should be contemplated only once the uveitis is controlled, ideally for at least three months. Intraocular surgery (cataract removal, vitrectomy, and retinal detachment surgery) is performed under the cover of systemic corticosteroids to prevent a relapse of uveitis. Removal of the vitreous body (vitrectomy) may be helpful when there is substantial opacity but also may improve disease control, particularly in younger patients.
Complications of chronic uveitis and their management
Macular oedema Periocular steroids Systemic steroids Immunosuppressive drugs Cataract Surgery once uveitis controlled for 3 months preoperatively Perioperative cover with corticosteroid Intraocular lens in most patients Glaucoma Management depends on type Topical drugs Short term treatment with systemic carbonic anhydrase inhibitors Surgery
Synechiae Minimise with regular mydriatics Band keratopathy Chelation with EDTA Excimer laser Vitreous opacities Observation Occasionally short course of corticosteroids Vitrectomy rarely required Vitreous haemorrhage Observation Exclude new vessels and retinal tear as cause Retinal neovascularisation
Control uveitis Laser photocoagulation if ischaemia present Subretinal neovascularisation Observation Laser photocoagulation Interferon a Surgical membranectomy Retinal detachment Determine whether exudative, rhegmatogenous, or traction Surgery usually involves vitrectomy Perioperative cover with corticosteroid Summary points
Intraocular inflammation has various causes and can be acute or chronic In either case the inflammatory process can be apparently localised to the eye or be part of a systemic disease such as sarcoidosis or Behet's disease The inflammation can occur in any part of the eyeanterior,
posterior, or bothand visual loss can occur with any type Treatment depends on the location and severity of the inflammation, with systemic drugs being reserved for sight threatening posterior disease Complications are common and include cataract, glaucoma, macular oedemaall of which can reduce vision Uveitis and Systemic Disease References Harvey RB, Practical Ophthalmology- CD ROM 1999 Birmingham; Palmtrees Publishing Jones NP, Uveitis an illustrated manual Oxford ; Butterworth ; Heinemann 1998 1-93
Nussenblatt RB, Whitcup SM, Palestine AG, Uveitis- Fundamentals and Clinical Practice 2nd Edition ; St Louis ; Mosby 1996 3-151 Marr JE, Stavrou P, Murray PI, Should we investigate uveitis ? Invest Ophthalmol Vis Sci 1998 ; 39: S608 Murray P, Serum Autoantibodies and Uveitis Br J Ophthalmol 1986; 70 :266-8 Murray PI, Stavrou P, Marr JE, Moradi P, Pattern of visual loss in patients with uveitis Invest Ophthalmol Vis Sci 1998 : 39 : S607 Barlie GR, Flynn TE Syphilis exposure in patients with uveitis Ophthalmology 1997 ; 104 1605-9 Murray PI, Uveitis, When to Investigate ? Focus- Occasional Update from the Royal College of Ophthalmologists 1998 ; 8 : 1-2 Uveitis and Systemic Disease
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