TOA Summit
Autoimmune Disease and the Eye Items in BOLD discussed in detail at the bottom of outlineIntroductionImportant for Optometrist to recognize what ocular complications can manifest from autoimmune disease for appropriate treatment, testing, and referral.GoalsRecognize signs/symptoms of autoimmune disease affecting the eyeUnderstand systemic complications of autoimmune diseaseLearn how/when to refer to specialistThis lecture is designed to examine the eye (anterior to posterior) and learn how autoimmune disease affects each structure. This is similar to how an Optometrist would discover autoimmune related disease in the eye.ExternalPtosisMyasthenia GravisChronic autoimmune neuromuscular disease causing muscle weaknessAntibodies destroy or alter receptors for acetylcholine. This prevents muscle contraction from occurring. Some patients develop thymoma - need to check thymus glandEyelid muscles first affected in most casesTestTensilonIce-pack testAcetylcholine receptor antibodiesAnti-MuSK antibodyTreatNeostigminePyridostigmineExophthalmosGraves’ DiseaseDiplopiaGraves’ DiseaseMyasthenia GravisMultiple SclerosisInflammatory (? infectious) disease that causes nerve demylenationCan cause many problems including optic neuropathy and diplopiaTypically recover from diplopia without treatmentIf diplopia appears atypical or combined with other symptoms (numbness, tingling, heat intolerance) - may consider MS testingGiant Cell ArteritisEpiscleraNot as likely as Scleritis to have systemic associationIf nodular and/or recurrent, consider list given with ScleritisScleraScleritisRheumatoid ArthritisInflammatory damage to small joints in hands and feetLeads to pain, swelling and possible deformityCan cause pain in larger joins such as hip, shoulder, knees, ankles, and elbowsOften diagnosed with a combination of blood work, x-ray, and clinical signs/symptomsTreated with NSAIDs for mild casesCan use steroids, DMARDs, and/or immune modulating drugsMost likely systemic cause of scleritis is RAKeep in mind that only 50% of patients with scleritis have associated conditionPatients with RA and scleritis have a more widespread and aggressive systemic disease and may need more aggressive therapyLupusLupus is an autoimmune disease that can affect: joints, skin, kidneys, blood cells, brain, heart and lungsSigns and symptoms often include: fatigue, shortness of breath, chest pain, classic “butterfly” rash on cheeks and noseMost commonly seen in women of childbearing ageDifficult to diagnoseTreated with NSAID, steroid, Plaquenil, immune suppression HLA-B27 Disease (not as likely) - see discussion on Uveitis for diagnosis strategyUlcerative ColitisAnkylosing SpondylitisReactive ArthritisPsoriatic ArthritisCornea/Dry EyeSjogren’sAutoimmune disease that mainly causes: dry eye and dry mouthCan also have joint pain, fatigue, persistent coughTypically in women over 40Can have association with RA or LupusDiagnosis is made by signs/symptoms, blood test, lip biopsy?Treat specific symptomsTreat salivation (pilocarpine), may also use PlaquenilGraves’ DiseaseLupusRheumatoid ArthritisUvea/UveitisUlcerative ColitisAnkylosing SpondylitisReactive ArthritisPsoriatic ArthritisRarely LupusSarcoidosisRetinaVasculitisHow to recognize vasculitisWho to refer toPlaquenil RetinopathyArterial DiseaseGiant Cell ArteritisOptic NerveMultiple SclerosisSarcoidosisLupusGiant Cell Arteritis1. Graves’ DiseaseGraves Disease (GD) is an autoimmune disease that targets 3 tissuesOrbitThyroidSkinPrevious thinking was that GD damaged the thyroid gland which led to ophthalmic complicationsCurrent knowledge states that GD is an autoimmune disease that can affect orbit, thyroid, and skin independently. It is not the thyroid directly leading to ocular damage.PathogenesisBody produces autoantibodies to TSH receptor which chronically stimulates synthesis. Leads to abnormally high T3 and T4Negative feedback loop decreases TSH which increases T3 and T4Simultaneously affects orbit fat and muscleFibroblastsMyofibroblastsOcular Signs and SymptomsExophthalmos – always bilateral though often asymmetricMost common cause at 50%Dry eyeForeign body sensation, EpiphoraIf severe enough can lead to corneal complicationsEye PainDiplopia – possible muscle restrictionEyelid retraction - from overactive sympathetic innervations to upper eyelidRednessRarely Optic Nerve CompressionThyroid LabsHyperthyroidism Majority of patients with GD get this ~80%NervousnessHeat Intolerance/SweatingTremorIncreased appetiteHypothyroidismUncommon in GD – but up to 15%LethargicLow appetiteLow sex driveWeight gainCold, clammyEuthyroidUncommon in GD ~ 5%No thyroid symptomsSkin Manifestations Pre-tibialTreatmentMost patients stabilize over 8-36 monthsSystemic SteroidsRadiotherapyAnti-thyroid medicationThyroidectomyPsychiatric MedicationQuality of LifeOrbital DecompressionLikely need strabismus surgery also due to diplopiaAs high as 64% after decompressionTopical LubricationTreating exposure keratopathySmoking cessation!Helps progression of diseaseHelps prognosis for recoveryNon-smokers (or those who quit) do better with treatmentWeight lossNeuropsychological and Mental HealthOften overlooked symptom of Graves’DepressionTensionAnxiety2. Giant Cell ArteritisGiant Cell Arteritis (GCA) is an Immune-Mediated VasculitisAffects Medium and Large ArteriesIn eye mostly Posterior Ciliary Artery (PCA), then Central Retinal Artery (CRA), rarely Ophthalmic Artery (OA)Explain why GCA affects eyesCalled GCA because of granulomatous inflammation. Arteries lined with multinucleated giant cells: macrophages, lymphocytes, and fibroblastsIncidence of 2.3/100,000 in 6th decade. Increases with Age.Happens mostly to those > 50 years oldAge rangePredilection for North European, Scandinavian descent. Typically Caucasian though can happen in other racesWhy is it important?Profound vision lossCauses A-AIONCan become bilateral in 14 days in 1/3 if untreatedTreatableCRAO and Cilioretinal artery occlusion can occurA-AIONSudden painless vision lossUnilateral Optic Disc Edema1/10 patients (> 50 years old) with optic disc edema are A-AION. Other 9/10 NA-AIONSystemic SymptomsJaw Claudication (Odds Ratio 9.0)Neck Pain (Odds Ratio 3.4)AnorexiaLess predictable symptomsHeadacheFeverScalp TendernessMalaiseAverage number of symptoms = Visual Symptoms/SignsSudden, painless vision loss31% had amaurosis fugax 1-2 weeks beforeThis can be misleading. Not saying 31% of patients with Amaurosis Fugax have GCA6% diplopia8% ocular painOptic Disc Edema “chalky white pallor”Lab TestingESR – 86% sensitiveCRP – 100% sensitive, 82% specificCombined ESR and CRP – 99% sensitive, 97% specificCBC with differential looking for disease that can affect Red Blood Cells (i.e. Anemia, Polycythemia Vera)Other Diagnostic TestingFluorescein Angiography (FA) – characteristic late filling of choroid in the 2 weeks after Optic Disc Edema startsUltrasound, PET, MRI of limited benefitTemporal Artery Biopsy – especially indicated if clinical symptoms highly suggestive but either ESR or CRP are inconclusiveContralateral optic nerve can give us clues to A-AION vs. NA-AIONGo through Bayesian analysisIf C/D is > 0.4 1/5 have A-AIONIf C/D is < 0.3 1/15 have A-AIONTreatmentMost studied and likely still most effective is oral steroid80-100 mg/day until labs normalizeThen taper for VERY long (years!)Evidence still lacks because not ethical to have a placebo groupNo evidence that IV steroid in mega dose any more effectiveLimited evidence for TNF blockers, Methotrexate and other immune modulators3. UveitisThe Goal of Treatment Improve patient’s quality of lifeAssociated ConditionsWhat is the purpose of evaluating for associated conditions?Find something that once found will help alleviate uveitis and prevent recurrence. Correctly name a condition that was previously named incorrectly – leading to better treatment of non-ophthalmic conditionShould leave the patient better after the testingWe need a thoughtful approach that matches the description of uveitis with patient’s symptoms. A “scatter” approach is not good medical care because:It is no more beneficial to patient than tailored approachThere is added expenseThere is added anxietyIncrease in false positivesA tailored workup should be specific to your patient. It requires that you know:A working list of common associated conditionsThe characteristics of the uveitis of those conditionsAcute vs. Chronic – Can be acute and recur. Recurrent does not mean ChronicAnterior vs. Posterior (or Panuveitis)Unilateral vs. Bilateral (or Alternating)Granulomatous vs. Non-Granulomatous – Often difficult to distinguish. Look for Granulomas, Bussaca nodules or Mutton Fat KPThe history and physical findings that might manifest in a patient with one of these conditionsWhat specialized testing used to identify these conditions (if indicated)The appropriate referral/treatment when a condition is diagnosed or suspectedMeshing these five areas will allow for appropriate testing and eliminate unnecessary tests. (e.g. a patient with acute, unilateral, non-granulomatous uveitis should not be tested for Sarcoid.)Common associated conditions and their characteristicsAnkylosing Spondylitis, Reactive Arthritis, Psoriasis - Acute, anterior, unilateral, nongranulomatous.Inflammatory Bowel Diseases– Typically unilateral and non-granulomatous. However, some report up to 50% bilateral. Forty percent of uveitis is anterior (40% is panuveitis, 20% posterior) Juvenile Idiopathic Arthritis– Chronic, anterior, unilateral or bilateral, nongranulomatous, asymptomatic. “White eye uveitis.”Sarcoid – Chronic, anterior (can be posterior or pan), bilateral, granulomatousSigns/Symptoms, Follow-up Testing, and Treatment of Associated ConditionsAnkylosing SpondylitisLower back pain/stiffness in morning > 30 minutes, back pain improves with exercise, awakening in second half of night from back pain. All back pain is worse with rest.Sacro-iliac joint x-ray and referralTreatment typically NSAID. TNF Blockers work very well but are very expensiveReactive ArthritisMost patients with Reactive Arthritis lack the full triad of “Reiter’s Syndrome.” Acute, asymmetric oligoarthritis (typically knee, ankle, foot). Can also have symptoms of urethritis, diarrhea, or cutaneous lesions (usually soles of hands or palms of hands). Musculoskeletal symptoms follow GI or GU symptoms by 2-4 weeks.Refer to Rheumatology. Laboratory tests are not indicated for diagnosis.Treatment is pain management. This includes, but not limited to, Physical Therapy, NSAID, Steroid, Anti-rheumatic medication.Inflammatory Bowel DiseaseGI symptoms such as stomach cramps, diarrhea, bloody stoolsRefer to GITreatment has a multi-step approach: Fiber, Aminosalicylates, and Corticosteroids Psoriasis Plaques on skin - red with white scaly topCan affect scalp, skin near jointsRefer to dermatologyTreatment includes shampoos, ointments, immune modulationJuvenile Idiopathic ArthritisSuspect in children with non-traumatic iritis. Usually found with unilateral cataract and white eye uveitis. Possible joint pain/stiffnessRefer to pediatricianTreatment typically NSAID.SarcoidSkin involvement (Macules, Papules, Granulomas), pulmonary symptoms such as dyspnea or coughOrder chest x-ray. Refer. ACE is a non-specific test with a poor sensitivity. Treatment: Immune suppression. Typically Corticosteroids.4. Plaquenil RetinopathyHydroxychloroquine (Plaquenil)Used forLupusRheumatoid ArthritisSjogren’sLyme arthritisSeveral side effects. Mostly worried about vision changesDamages Ganglion cells, Photoreceptors, RPELeads to atrophy of macular tissue 5-10 degrees from foveaParacentral scotomaIrreversible damageRisk FactorsAge > 60*Retinal Disease? – possiblyRenal and/or Liver DiseaseDaily DoseCumulative DosageDaily DoseTypically 400 mg/dayUsed to worry about weightDoes not store in fatty tissueConcern now with height/ideal weightCumulative Dosage1000 g = 400 mg/day for >5-7 yearsIf patient takes for less than 5 years, risk is 1/1000If patient takes for greater than 5 years risk is 1/100TestingShould not be confused with “screening”Several tests are widely usedAmsler GridColor vision10-2 Visual FieldMultifocal ERG (MFERG)Fundus Autofluoresence (FAF)OCTFundus examinationThe following tests are not recommendedTime domain OCTFluorescein AngiographyFull Field ERGEOGAmsler Grid/Color Vision – not sensitive enoughMFERGProsObjective ReliableTargets maculaConsInterpretationExpenseHassleAccessibilityFAFProsObjectiveView changes over timeConsInterpretationAvailabilityNot as reliable as 10-2, SD-OCT, ERG10-2 Visual FieldProsAvailableInexpensiveEasy interpretationConsSubjectivePatients dislikeFalse positives!!SD-OCT – Look for Flying Saucer signProsAvailableObjectiveInterpretation easyGood SpecificityConsEarly detection may be difficultPoor sensitivityCostAmerican Academy of Ophthalmology 2002 recommendationsPatient is high risk if > 6.5 mg/kg/dayColor vision10-2 or Amsler GridAmerican Academy of Ophthalmology 2011 recommendationsHigh risk if 1000g cumulative doseConsider heightNo color vision or Amsler Grid testingShould do 10-2 combined with SD-OCT, FAF, mfERGRecommend baseline examIf high risk, test yearlyIf low risk, test again after 5 yearsFrustrations with diagnosing and managing Plaquenil MaculopathyFalse positivesThere is no gold standardWe are the authority – often the eye doctor will dictate who gets taken off medsDifficult to balance risks/benefits of PlaquenilIt is possible that we are taking many patients off Plaquenil that would greatly benefit from the medication. These patients may have discontinued it due to our recommendations. We may have arrived at the recommendation from false positive testing. Optometrists need to understand our role in this diagnosis and management and be very careful before recommending stopping a potentially very helpful medicine.Autoimmune disease can affect every part of the eye. It is important for optometrists to recognize what ocular complications can manifest from autoimmune disease for appropriate treatment, testing, and referral.Objectives:Understand which eye diseases are associated with autoimmune diseaseUnderstand how autoimmune disease manifests systemicallyDevelop a strategy for evaluating patients who manifest ocular complications consistent with autoimmune diseaseLearn what tests/referral are appropriateDiscuss how to treat eye disease related to autoimmune disease ................
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