Uveitis

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  • The main focus of treatment is to mitigate the irritation, ease agony, treat basic causes and prevent that could harm vision. Uveitis Treatment duration of time may vary depending on the degree of the disease. http://www.herbs-solutions-by-nature.com/Uveitis.php
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  • The main focus of treatment is to mitigate the irritation, ease agony, treat basic causes and prevent that could harm vision. Uveitis Treatment duration of time may vary depending on the degree of the disease. http://www.herbs-solutions-by-nature.com/Uveitis.php
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  • To help manage and treat uveitis, especially bilateral, recurrent, or recalcitrant uveitis, it is imperative that the underlying cause is found. Here is a brief overview on different disease and conditions that have been associated with uveitis.
  • Most common form of uveitis
  • Negative RFClass 1 surface antigen that presents to T suppressor cellsDisease are sometimes clinically indistinguishable5% of population, about ½ of pts with acute iritis
  • --improves with exertion, bamboo spine is conplete fusion of the spineis a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structuresNot all HLA-B27 develop the disease, only 1 in 4 will develop spondyloarthritis or eye diseaseShould be referred to rheumotologist, NSAIDs are mainstay of tx of AS, anti-TNF are gaining popularity-physical therapy and smoking cessation can slow down disease progression
  • triggered by an infection in another part of your body — most often your intestines, genitals or urinary tract.--in addition to classic triad they can have scaly, erythematous disorder of the palms and soles of feetConjunctivitis most common, uveitis -10% can become bilateral and chronic b/c of permanent breakdown of blood-aqueous barrier
  • IBD: may also develop slerouveitis, these pts are usually HLAB27 –ve compared to those with acute iritisPA: dx based on typicl cutaneous changes -erythematous hyperkeratotic rash
  • Symptoms are vague: discomfort,blurred vision, halos--recurrences are very common over many years--rare, dx of exclusion, other syndromes must be r/o such as herpetic uveitis
  • can occur following disruption of the lens capsule (traumatic or surgical) or leakage of lens protein in hypermature cataracts--other names include phacoanaphylacticendopthalmitis, phacotoxic uveitis and phacolytic glaucoma--unsure of mechanism but thought due to immune rxn to lens protein--now with modern IOL’s less complications
  • relatively rare occurrence and is reported to represent less than 0.5 % of cases in a tertiary referral uveitis clinic (1). The time between medication use and occurrence of symptoms varies, ranging from a few days to months.. The cause for drug-induced inflammation is not well known. Postulates include direct and indirect mechanisms. Direct mechanisms are typically seen soon after medication use, typically occurring with topical or intracamerally instilled drugs. Indirect mechanisms include immune complex deposition in uveal tissues, immune reactions to antigens released from antibiotic-induced death of microorganisms, or an alteration of melanin’s ability to scavenge free radicals (2).
  • Inflammation of the anterior segment persistent and relapses less than 3 months after d/c of therapy
  • --pauciarticular onset 85=90% of JIA that have uveitis: 4 or fewer joints are involved in 1st 6 months or disease, may have no joint symptoms--because of freq. asymptomatic nature of uveitis in these pts profound silent ocular damage can occur, long term prognosis often depends on extent of damage at time of dx--pts should be evaluated by rheumatologist and undergo ANA testing--joint pain can be minimal or absent at time of uveitis diagnosesDdx: fuchs, sarcoid, behcet, seronegativespondy., herpetic and lyme disease
  • Usually overlooked, 3% of cases referred to uveitis clinics are dx w fuchs--usually vague symptomsdx: made due to distribution of KP’s, lack of synechiae, lack of symptoms, and heterochromiafew require therapy, topical steroids can lessen inflammation but do not resolve itLighter colored eye indicated involved, although in blue eyed the darker b/c stromal atrophty and darker iris pig epith shows
  • 15% of all cases of uveitis’--inflammation in ant vitreous and the vitreous base overlying ciliary body and peripheral retina-pars plana complex--may aggregate in the vitreous “snow balls”, accumulate on inf pars plana –”snowbanking”
  • In older main complaint is floatersComplications: cataract (60%), glauc, CME(5)%), retinal neovas. (15%), VH, tractional or rhegmatogenous RD-- CME develops and becomes chronic and refractory in 10% of pts--ischemia from phlebitis with angiogenic stimuli from intraocular inflammation can lead to neovascularization 10% of casesthought to be autoimmune reaction against vitreous, peripheral retinal and CB
  • Can preceed dx of MS in 25% of pts and by 5-10yrs15% of pts with pars planitis may eventually develop MSME less common then pars planitis, also less mild interm. uveitis
  • SUN: Inflammation involving the retina and or choroid. Inflammatory cells may be observed diffusely throughout the vitreous cavity overlying foci of active inflammation
  • B lymphocyte hyperactivity, polyconal B-lymphocyte activation, hypergammaglobulinemia, autoantibody formation, and T-lymphocyte autoreactivity with immune complex deposition
  • KCS most common symptomLupus retinopathy is most well recognized post. Segment manifestation and is considered and important marker of systemic disease -3% to 29% in severe –w or w/o hemesVascular occlusiveLupus choroidopathy- choroidal infarction, CNV, serous elevations of RPE and retina
  • Consequence of Underlying vascular disease: Post pole: may manifest as HTN retinopathy, retinal arteriolar occlusive disease, choroidal infarcts, choroidaliscehmia, neuro-ophthmanifestions, scleritis, optic atrophy, peripheral ulcerative keratitis
  • 15% ocularinvolv. At presentation, 50% during course of disease
  • Level of retinal, RPE , choriocapillaris and choriodDdx: syphilis, DUSN (diffuse unilateral subacuteneuroretinitis, OHS, as well as non infectios: sarcoidosis, sympathetic ophthalmia, VKH, intraocular lymphoma
  • Many of these have viral or autoimmune component--Serpiginouschoroiditis is associated with HLA B-27
  • Involvement of all anatomical compartments of the eye –AC, vitreous, retina and choroidUsually bilateral
  • abnormal collections of chronic inflammatory cellsgranulomas) that can form as nodules in multiple organs.[1] The granulomas that appear are usually not of the caseating variety and are most often located in the lungs or the lymph nodes, but virtually any organ can be affected. uveitis being most frequent manifestation
  • Cutaneous invovment –orbital and eyelid granuloma’s, conj. Nodules, lacrimal gland infiltration -KCS2/3 pts with ocular sarcoidosis have ant. Uveitis-
  • Usually occurs 3 months after injury (80%) to 1 year (90%)--characteristic white, midequatorialchoridal lesions (Dalen nodules) that may become confluent, peripapillarychoridal lesionslymphocytic infiltration and the formation of granulomas. Deposition of these granulomas between Bruch's membrane and the RPE is termed a Dalen-Fuchs' nodule--injured eye “exciting eye” and noninjured is “sympathizing” eye--dx: clinical, ddx VKH
  • The prodromal stage is marked by flu-like symptoms. Patients present with headache, nauseadysacusia and tinnitus.
  • Sunset glow –resolution of exudative detachments,depigmentation of the choroid
  • Oral ulcers are the most frequent finding BD –recurrent mucosal ulcers the produce sign discomfort and pain (round white ulcerations with red rims, occur every 5-10 days or every month)
  • AO and VO’s, combination, vascular sheathing with variable amounts of vitirtis –becomes very ischemic--can look like ARN due to ischemic nature of vasculitis and accompanying retinitis.--can have papillitis, ischemic optic neuropathiesHLA associations: HLAB12, HLA B27, HLA B51IMT is essential due to chronic inflamm.
  • Based on maryland 2011 data from the CDC:Maryland ranked 3rd in the US in reports of primary and secondary syphilisMD reported 452 cases of primary and seconday syphilis in 201124 cases of congenital syphilis in 2011.
  • Short acting agents like tropicamide are useful for acute non-granulomatous anterior uveitis. Chronic uveitis and moderate flare anterior chamber reactions for disease like juvenile idiopathic arthritis (JIA) require chronic use of short acting agents to prevent further complications like synechiae. If there is a significant uveitic reaction like granulomatous inflammation, the use of long acting agents like atropine are useful to prevent the accumulation of inflammatory cells by stabilizing the ciliary body vascular system.Long acting agents like atropine are useful for
  • Corticosteroids have both direct and indirect inhibitory effects on the potent pro-inflammatory transcription factor NF-kB.
  • Periocular injections (either transseptal or sub-tenon approach) of triamcinolone acetonide or methylprednisolone should not be used in infectious uveitis cases such as toxoplasmosis. Also these injections can cause high IOP spikes with increased duration.
  • Suspension needs to be shaken, emulsion does not.
  • Higher concentration does not mean higher potency, only high corneal permeability or penetration into the anterior chamber,can yield higher potencies
  • COX1 and 2 inhibitors-commonly used in ocular inflammationCOX 2 only inhibitors (celecoxib,rofecoxib,valdecoxib)-increased risk of adverse cardiovascular events, therefore these are not used for ocular inflammation or are limited in scope-Systemic NSAIDS: useful for chronic iridocyclitis (ie. JIA-associated iridocyclitis) and potentially for CME to allow maintenance on a lower dose of topical NSAIDS.Topical NSAIDS: limited role in ocular inflammation, not used in the treatment of anterior uveitis, but only implicated in postoperative pseudophakic CME and episcleritis.
  • These medications take 2-4months for successful control of ocular inflammation. Therefore, it is necessary to start these medications while the corticosteroids are being tapered to not further delay of successful treatment.
  • Corticosteroid-induced side effects:pars planitis (int. uveitis), retinal vasculitis, panuveitis, and chronic iridocyclitis.
  • Low/no TPMT activitiy: do not use aziothioprineInt.:reduced dosage <50mg/dayNormal/High: higher doses
  • Can create dissemination of tuberculosis
  • Uveitis

    1. 1. Julie Jantzi, O.D. Mallory Cranmer, O.D. Neal Shastri, O.D. Noushin Ahmed, O.D. Seidenberg Protzko Eye Associates
    2. 2. Epidemiology • ~15 per 100,000 in U.S. each year • Causes 10% of blindness in U.S. • Third leading cause of blindness in developed countries • Prevalence varies by location, age, and date of study • Highest among >65 years of age • Females • Chronic and unilateral • Anterior Uveitis most common
    3. 3. Pathophysiology • Inflammation of the uvea • Infectious, traumatic, neoplastic, autoimmune, idiopathic • Inflammatory response: chemical mediators result in vasodilation, increased vascular permeability, and chemotaxis of inflammatory cells in eye.
    4. 4. Inflammatory Cascade Photo Credit: Studyblue.net
    5. 5. Classification Location Duration Type Anterior Uveitis Acute Granulomatous Intermediate Uveitis Chronic Nongranulomatous Posterior Uveitis Panuveitis
    6. 6. Symptoms • Redness • Pain • Photophobia • Epiphora • Blur • Scotoma • Floaters Photo Credit: www.sunglasswarehouse.com
    7. 7. Clinical Signs Anterior to Posterior
    8. 8. Eyelid • Vitiligo • Nodules • Lesions Photo credit: http://www.pcds.org.uk/clinical-guidance/vitiligo
    9. 9. Conjunctiva & Episclera • Ciliary Flush • Diffuse injection Photo credit: http://www.mastereyeassociates.com/eyediseases-treatments/iritis---anterior-uveitis/
    10. 10. Cornea • Keratic Precipitates • Granulomatous • Non-granulomatous • Fibrin • Pigment • Corneal Edema • Band Keratopathy* Photo Credit: http://www.optometricmanagement.com/articleviewer.aspx?artic leid=71765
    11. 11. Anterior Chamber • Cells • Flare (serous) • Pigment • Hypopyon (purulent) • Plasmoid (Fibrinous) • Hyphema + hypopyon (sanguinoid)
    12. 12. Grading
    13. 13. Iris • Nodules • Busacca • Koeppe • Posterior synechiae • Heterochromia • Granulomas • Atrophy (stromal)* • Cyclitic membrane formation*
    14. 14. Angle • Nodule (Berlin) • Vascularization • Peripheral anterior synechiae • Secondary Ciliary body detachment*
    15. 15. IOP • Hypotony • Secondary Glaucoma* (Van Bus-kirk EM: Clinical Atlas of Glaucoma. Philadelphia: WB Saunders, 1986.)
    16. 16. Vitreous • Cells • Flare • Snowball Opacities • Snowbanking • Active • Inactive • Vitreal Strands Photo credit: Mohawk Valley Retina
    17. 17. Retina • Retinal/choroidal inflammatory infiltrates • Sheathing of arteries/veins • Retinal detachment • Schwartz syndrome • RPE hypertrophy/atrophy • Atrophy/swelling of retina, choroid, optic nerve head • Macular edema Photo Credit: Oculist.net
    18. 18. Major Complications • Cataracts • Glaucoma • Band Keratopathy • Cystoid Macular Edema
    19. 19. Differential Diagnoses • Infections • Non-infectious • Masquerade syndromes • Large cell Lymphoma, retinoblastoma, leukemia, malignant melanoma • Juvenile Xanthogranuloma • Pigment dispersion syndrome • Retinal Detachment • Retinitis pigmentosa • Ocular Ishchemic Syndrome
    20. 20. Non-Infectious Uveitis
    21. 21. ANTERIOR UVEITIS: POSTERIOR UVEITIS: • • Collagen Vascular Disease • White Dot Syndromes • Acute nongranulomatous Iritis and Iridocyclitis Chronic Anterior Uveitis PANUVEITIS INTRMEDIATE UVEITIS: • • • • Sarcoidosis Sympathetic Ophthalmia • Vogt-Koyanagi-Harada Syndrome • Behcet Disease Pars Planitis Multiple Sclerosis
    22. 22. Acute Anterior Uveitis HLA-B27 diseases Glaucomatocyclitic crisis Lens associated uveitiis Postoperative inflammation: IOL associated
    23. 23. HLA-B27 DISEASES • Class 1 surface antigen • Seronegative spondyloarthropathies are strongly associated with acute anterior uveitis and HLA-B27 • spondylitis and sacroiliitis Include: • Ankylosing spondylitis • Reactive arthritis syndrome • Inflammatory bowel disease • Psoriatic arthritis
    24. 24. Ankylosing Spondylitis • lower back pain and stiffness • men, 20-40‟s • HLA-B27: 90% • dx: sacroiliac imaging studies - “bamboo spine” Ocular findings (40%): • acute anterior uveitis - fibrin and hypopon not uncommon
    25. 25. Reactive Arthritis Syndrome • Triad: nonspecific urethritis, polyarthritis, and conjunctivitis often accompanied by iritis • HLA-B27: 95%, young adult men • arthritis in knees, ankles, feet, sacroiliitis in 70% of pts Ocular findings: • Mucopurulent and papillary conjunctivits, acute nongranulomatous iritis in 10% Keratoderma blennorrhagicum
    26. 26. Psoriatic Arthritis • Inflammatory arthritis occurs in 30% of pts with chronic psoriasis Inflammatory Bowel Disease • cutaneous changes, distal phalangeal joint inflammation, ungula involvement • • 20% may have sacroiliitis • 25% develop iritis 12% of ulcerative colitis pts and 2.4% of Chrons disease pts develop acute anterior • 20% have sacroiliitis • 60% HLA-B27 positive
    27. 27. Glaucomatocyclitic Crisis • Recurrent unilateral mild acute iritis • Elevated IOP, corneal edema, fine KPs, low-grade cell and flare, slightly dilated pupil • Duration: hours to days • Associated with HLA-B54
    28. 28. Lens-associated Uveitis • • Immune reaction to lens material: granulomatous or nongranulmatous KPs can be small or large, cells mild to severe, hypopon, PS, elevated IOP, vitritis Postoperative inflammation: IOL-associated Mild inflammation to UGH syndrome (uveitis-glaucoma-hyphema) IOL implantation can activate complement cascade, cellular deposits on IOL, synechiae formation, capsular opacification • Retained lens material • Phthisis bulbi, persistent uveitis, or glaucoma often occurs in these eyes • iris chafing caused by the edges or loops of IOL – mechanical irritation and inflammation
    29. 29. Drug Induced Uveitis • Systemic Drugs 1. Rifabutin 2. Bisphosphonates • Topical Drugs 1. Metipranolol 2. Miotics 3. Prostaglandins 3. Sulphonamides 4. Diethylcarbamazine • Intracameral Drugs 1. Cidofovir 5. Cidofovir (intravenous) 2. Antibiotics 3. Urokinase • Vaccines
    30. 30. Chronic Anterior Uveitis Juvenile idiopathic arthritis Fuchs heterochromic iridocyclitis Idiopathic iridocyclitis
    31. 31. • most common systemic disorder associated with iridocyclitis in children • iritis develops within 5-7 yrs of onset of joint disease • RF: female, pauciarticular onset, ANA • negative RF • eye is usually white and uninflamed, some pts do not have pain • Ocular findings: fine KPS, flare and cells, posterior synechiae, cataract, glaucoma, band keratopathy, vitreous debris, ME, chronic hypotony, phthisis Juvenile Idiopathic Arthritis
    32. 32. Fuchs Heterochromic Iridocyclitis • Unilateral uveitis, heterochromia, iris stromal atrophy, small white stellate KPs scattered diffusely over endothelium • synechiae almost never forms but glaucoma and cataracts often occur • Associations with toxoplamosis, HSV, and CMV infections
    33. 33. Idiopathic Iridocyclitis • In many cases of chronic iridocyclitis the cause is unknown
    34. 34. Intermediate Uveitis Pars Planitis Multiple Sclerosis
    35. 35. • absence of infection and systemic disease • 85-90% of intermediate uveitis cases • 5-40 yrs, healthy individuals • associated with HLA-DR15 and HLADR51 alleles Pars Planitis Clinical Characteristics: • 80% bilateral • Ocular manifestations: spillover into anterior chamber, vitreous cells, snowballs, peripheral phlebitis and retinal venous sheathing • Ddx: Syphilis, lyme, sarcoidosis, MS, toxicarasis, lymphoma
    36. 36. Multiple Sclerosis • 30% of MS pts will get uveitis • 15% of pts with pars planitis will eventually develop MS • women, 20-50 yrs • HLA-DR2 and DR15 • Granulomatous anterior uveitis, intermediate uveitis, panuveitis
    37. 37. Posterior Uveitis Collagen Vascular Diseases Inflammatory Chorioretinopathies of Unknown Etiology
    38. 38. Collagen Vascular Disorders Systemic Lupus Erythematosus Polyarteritis Nodosa and Microscopic polyangiitis Wegener‟s Granulomatosis
    39. 39. Systemic Lupus Erythematosus • Multisystem autoimmune connective tissue disorder • Type 3 hypersensitivity reaction: Antibody-immune complexes precipitate and cause further immune response • Affects heart, nervous system, joints, skin, lungs, blood vessels, liver, and kidney • Women, 15-45 years • Labs: ANA • Malar “butterfly” rash -70-80%
    40. 40. Clinical findings Ocular manifestations in 50% • Keratoconjunctivitis sicca (20%) • Lupus retinopathy -CWS • Cutaneous lesions on the eyelids • Scleral inflammatory disease • Neuro-ophthalmic disorders • Retinal vasculopathy • In rare cases uveitis
    41. 41. Polyarteritis nodosa and microscopic polyangiitis • Systemic vasculitis – necrotizing inflammation of medium and small sized arteries • 40-60 yrs, men, hepatitis B • Ocular involvement in 20% • Mortality rate of untreated PAN is 90% by 5 yrs • Labs: p-ANCA, ESR, CRP, tissue biopsy
    42. 42. Wegener‟s Granulomatosis • Triad: necrotizing granulomatous vasculitis of upper and lower respiratory tract, glomerulonephritis, necrotizing vasculitis of small arteries and veins • Involvement of paranasal sinuses is most characteristic feature • Ocular involvement in 50%: -- orbital involvement: pseudotumor, cellulitis, dacryocystitis -- anterior, intermediate, or posterior uveitis --scleritis (necrotizing), uveitis, retinal vascular involvement Dx: tissue biopsy, chest x-ray, CRP, ESR, c-ANCA
    43. 43. White Dot Syndromes • Group of chorioretinopathies that are inflammatory in nature presenting with discrete, multiple, yellow-white lesions • Symptoms: photopsia, blurred vision, floaters, nyctalopia, enlarged blind spot • Young females
    44. 44. • Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) • Birdshot choroidopathy • Multiple evanescent white dot syndrome (MEWDS) • Acute zonal occult outer retinopathy (AZOOR) • Multifocal choroiditis (MCP) • Punctate inner choroidopathy (PIC) • Serpiginous choroiditis
    45. 45. Panuveitis Sarcoidosis Sympathetic Ophthalmia Vogt Koyanagi-Harada Syndrome Behcet Disease
    46. 46. Sarcoidoses • Multisystem non-caseating granulomatous disorder of unknown etiology • Intrathoracic : 90%, intraocular: 50% • Affect lymph nodes, skin, eyes, CNS, bones and joints, liver, and heart • African American, females, 20-50 years • Dx: chest x-ray, lymph node biopsy, elevated ACE and lysozyme levels
    47. 47. Ocular Findings • can involve any ocular tissue • most common: Anterior granulomatous uveitis –mutton fat KP‟s, koeppe and busacca iris nodules, synechiae • Posterior segment in 20% of ocular sarcoidosis --vitreous infiltration “string of pearls” or “snow balls” --granulomas seen in retinal, choroid --perivascular sheathing, occlusive vascular disease • Eyelid granulomas • Conjunctival nodules • Lacrimal gland infiltration
    48. 48. Sympathetic Ophthalmia • Bilateral, diffuse granulomatous, non-necrotizing panuveitis • Autoimmune inflammatory response toward ocular antigens – delayed hypersensitivity to melanin containing structures? • Occurs after surgery or trauma to an eye • 2% of uveitis cases • Anterior Uveitis: mutton fat KPs, PS, thickening of iris from lymphocytic infiltration • Posterior vitritis, dalen-fuchs nodules, peripapillary choroidal lesions, exudative RD
    49. 49. • Cell-mediated autoimmune process driven by T lymphocyctes directed against self-antigens associated with melanocytes of all organ systems • Higher association in darkly pigmented ethnic groups • 4% of uveitis referrals in US • Chronic, bilateral, diffuse, granulomatous panuveitis with integumentary, neurologic, and auditory involvement Vogt-KoyanagiHarada Syndrome
    50. 50. Stages Acute: bilateral granulomatous anterior uveitis, vitritis, thickening of choroid, edema and hyperemia of optic nerve, multiple serous retinal detachments Convalescent: “sunset glow” fundus, skin changes: vitiligo, alopecia, poliosis Chronic recurrent: repeated bouts of uveitis
    51. 51. Behcet Disease • chronic, relapsing, occlusive systemic nongranulomatous vasculitis of unknown etiology • recurrent oral ulcers, skin lesions, genital ulcers, ocular inflammatory disease (70%) • can affect all portions of uveal tract
    52. 52. Ocular Findings 80% bilateral • Anterior uveitis: hypopyon in 25% of cases • Posterior segment: necrotizing retinal vasculitis affects both veins and arteries • Optic nerve affected in 25% of pts • Visual prognosis is guarded -25% VA < 20/200
    53. 53. Infectious Uveitis •Viral – Herpetic, CMV •Fungal •Protozoal - Toxoplasmosis •Helminthic - Toxocara •Bacterial – Syphilis, Lyme, Tuberculosis, other
    54. 54. Viral • Herpes Simplex: • Usually iritis is a keratouveitis but can be: corneal, cutaneous, retinal • arborized • +/- KPs, +/- Hypopyon • HSV-1 is generally oral-labial HSV-2 generally genital infections, although crossover does occur. Image: C. Blake Perry. Source: http://webeye.ophth.uiowa.edu/eyeforum/atlas/pages/HSV-epithelial-keratitis.htm
    55. 55. Viral • Herpes Zoster • • • • 72 hours PHN ¼ ocular involvement Infiltrative pseudodendrites (negative stain) Typically elderly and immunocompromised Image:Yanoff, Myron, and Jay Duker. Ophthalmology. 3rdrd ed. N.p.: Mosby Elsevier, 2009. 223. Print.
    56. 56. • Viral ARN • • • • • • VZV>HSV>CMV Immunocompetent Starts unilateral but 36%Fellow eye Within 6 weeks of onset Painful, Floaters, LOV Peripheral „creamy‟ necrosis that spread, occlusive vascular involvement, Panuveitis • Poor Prognosis, RD in 75% • PORN • VZV mainly • Immunocompromised • Posterior pole involved early • Patchy confluent necrosis, weak or absent uveitis, no vascular involvement • Poor Prognosis, RD in 70% Images: Baumal, Caroline et al. Duane‟s Ophthalmology ,2006.‟Acute Retinal Necrosis and Progresive Outer Retinal Necrosis Syndromes Accessed online: http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v3/v3c028.html#ref
    57. 57. Viral • CMV • • • • • • • CD4 <50-100 Most common opportunistic infection in AIDS In congenital cases + birth defects Before HAART ~30% of CD4<50 After HAART incidence decreased 75-80% May start by looking like CWS (small infiltrates) Perivascular hemorrhages, white necrotic retina, frosted branches /vasculitis Image: Yanoff, Myron, and Jay Duker. Ophthalmology. 3rdrd ed. N.p.: Mosby Elsevier, 2009. 796. Print.
    58. 58. Protozoal • Toxoplasmosis • Toxoplasma gondii • Undercooked meat /cat feces • Most common posterior uveitis in immunocompetent individuals • Often acquired in utero (0.2-1% of pregnancies) • Further Trimester = increased chance of exposure, worst if acquired early (spontaneous abortion) • Majority do not develop ocular manifestations Image: Tabbara. Khalid. „Toxoplasmosis‟. Duane‟s Ophthalmology 2006. Accessed online: http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v4/v4c046.html
    59. 59. Protozoal • Toxoplasmosis • „Headlights in the fog‟ • Focal chorioretinal scar with adjacent necrosis and dense vitritis • With AIDS may have multiple lesions • Often self-resolving over months • May use sulfadiazine, pyramethamine, steroids. Image: Tabbara. Khalid. „Toxoplasmosis‟. Duane‟s Ophthalmology 2006. Accessed online: http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v4/v4c046.html
    60. 60. Helminthic Parasites • Toxocaraisis • Ingesting eggs of Toxocara • Dogs >cats • Acquired through soil, or uncooked food • Particularly affects kids with pica • Yellow white mass with tractional component, may have vitritis. • Often leads to TRD • Treat uveitis, consider anti-helminthics (albendazole) Image: Yanoff, Myron, and Jay Duker. Ophthalmology. 3rdrd ed. N.p.: Mosby Elsevier, 2009. 834. Print.
    61. 61. Bacterial • Syphilis • • • • • • Treponema pallidum „Great Mimicker/Masquerader/Imitator‟ Enters through intact mucosa Ocular Syphilis in 2‟ and 3‟ stages (2-6 mo after) Uveitis most common ocular manifestation (up to 10%) Affects immunocompetent or immunocompromised Image: „Syphilis‟. WebMD. Accessed Online: http://www.webmd.com/sexual-conditions/guide/syphilis
    62. 62. Bacterial • Syphilis • • • • • • • Dilated iris capillaries (iris roseola) Chorioretinitis, „salt and pepper‟ Vasculitis, vitritis, neuroretinitis, CNV, optic neuritis Granulomatous or non-granulomatous uveitis Argyll Robertson Interstitial Keratitis Tests: • Nontreponemal (VDRL / RPR) • Treponemal (FTA-ABS / MHA- TP) • Tx: Penicillin Image: Yanoff, Myron, and Jay Duker. Ophthalmology. 3rdrd ed. N.p.: Mosby Elsevier, 2009. 800. Print.
    63. 63. Bacterial • Lyme • • • • • Borrelia burgdorferi 1: rash (e. migrans) 2: dermatologic, neurologic, cardiac 3: Late arthritis, cranial and peripheral nerves 50% reported no hx of tick bite Image: Sources for Rashes: Poster: "Looking for a Bull's-Eye Rash? Look again - erythema migrans can take many forms. A collaborative effort between the Maryland Department of Health and Mental Hygeine and the Lyme Disease Research Foundation of Maryland Maryland.http://www.bayarealyme.org/get-help/lymes-many-symptoms
    64. 64. Bacterial • Lyme 1. Conjunctivitis early 2.Motility / CN palsies, optic neuropathy, PTC, chorioretinitis, uveitis 3. Stromal keratitis, symblepharon ELISA, Western Immuoblot Tx: Doxycycline, amoxicillin, if needed ceftriaxone Image: Pediatric Associates of Connecticut. „Tick Bites and Lyme Disease, Accessed Online: http://www.pediatricdoc.com/newsletter.cfm?nid=625
    65. 65. Bacterial • Tuberculosis • • • • • • • • • • Mycobacterium tuberculosis Incidence: Annually ~9.3 million patients worldwide Communicable: inhaled aerosolized droplets Primarily involves the lungs Uveitis is common Cough, fever, night sweats Caseating necrotic granulomas CXR PPD / Mantoux testing TB blood tests: interferon-gamma release assays (IGRAs) Images taken from wikipedia . Accessed online: http://en.wikipedia.org/wiki/Tuberculosis_diagnosis
    66. 66. Bacterial • Tuberculosis • • • • Granulomatous anterior, intermediate or posterior uveitis Vasculitis with choroiditis, or choroidal tubercles Phlyctenular conjunctivitis Tx: Rifampin, Isoniazid, Pyrazinamide, Ethambutol Image: Yanoff, Myron, and Jay Duker. Ophthalmology. 3rdrd ed. N.p.: Mosby Elsevier, 2009. 808. Print.
    67. 67. Infectious Endophthalmitis • Endogenous (<10%) • Systemic via blood stream • Organisms causing endocarditis and GI tract are primary sources, usually with sepsis, immunocompromise, IV drug abuse, catheders. • Typically less pain and inflammation, and can be bilateral • Exogenous • • • • Trauma, Surgery, Infection Acutely is usually gram + (normal flora) Decrease in occurrence over the last 30 years. Bleb-associated may occur at any time. • Acute 0.061-0.3% • Delayed 0.2-18% (variable reports) Image taken from „Endophthalmitis‟ by the American Academy of Ophthalmology 2013. Accessed Online: http://www.aao.org/theeyeshaveit/red-eye/endophthalmitis.cfm
    68. 68. Infectious Endophthalmitis • EVS • used <6 weeks, for cataract PO (Acute Onset) • Blur (94%), red eye (82%), pain (74%), hypopyon (86%) • No view of retinal vessels in 79% • Red reflex present in only 32% • Immediate vitrectomy if LP or worse. • B scan • Tx: culture, Vancomycin/Amikacin/Ceftazidime +/Dexamethasone
    69. 69. Masquerade Syndromes Accounts for nearly 5% of all patients with uveitis at tertiary referral. Neoplastic Masquerade • Lymphoma • Uveal melanoma • Retinoblastoma • Juvenile xanthrogranuloma • Metastatic tumors Nonneoplastic Masquerade • Retinitis Pigmentosa • Ocular Ischemic Syndrome • Retinal detachment • Intraocular Foreign Bodies • Pigment Dispersion Syndrome
    70. 70. Lymphoma • 5th to 7th decade of life • 25% ocular involvement • 15% ocular as initial presentation • 56% with ocular involvement develop CNS involvement • Variable uveitic presentations unresponsive to therapy • Can mimic chronic uveitis
    71. 71. Lymphoma: Ocular Findings • Benign reactive uveal lymphoid hyperplasia • Mobile, fleshy episcleral/conj mass • Retinal findings: classic creamy-yellow sub-retinal infiltrates with overlying RPE detachments mimicking sarcoid or birdshot • Anterior uveitis • CME
    72. 72. Lymphoma • Diagnosis • MRI • Cerebrospinal fluid analysis • Tissue diagnosis (definitive method) • Treatment • Intravenous and intravitreal methotrexate • Radiation & IV Cytarabine • >60 years = chemo only • <60 years = combination radiation & chemo • Prognosis = poor
    73. 73. Uveal Melanoma • 5% ocular inflammation • Episcleritis, ant/post uveitis, endophthalmitis Retinoblastoma • 1-3 % with ocular inflammation • White pseudohypopyon • Conjunctival chemosis • Ultrasound: low internal reflectivity • Diffuse infiltrating variant • 4-6 years old • Limited visibility of fundus
    74. 74. Juvenile Xanthogranuloma • Occurs before age 1 • Red-yellow skin lesions • Lesions can involve iris = spontaneous hyphemas • Skin of eyelid involved, globe usually spared • Treatment: topical, periocular, systemic steroids
    75. 75. Metastic Tumors • Adults • • Metastic melanoma: brown spherules in retina Most common: Cutaneous Melanoma • Others: white-yellow • Perivascular sheathing, necrotizing retinitis, retinal vasculitis • Lung, GI, breast • Vitritis, serous detachment, CME • Iris nodules, NVI, high IOP • Anterior uveitis • Bilateral and multifocal • Rare
    76. 76. Nonneoplastic Masquerade • RP • Waxy disc pallor, attenuation of arterioles, bone-spicule mid-periphery • +FHx • Nyctolopia • Vitritis, CME • ERG depressed early Source: http://www.rpfightingblindness.org.uk
    77. 77. Ocular Ischemic Syndrome • Males >65 • CC: decreased vision, mild pain • Corneal edema, A/C reaction, flare>cells, NVI, NVA, • decreased IOP (ischemia), high with NVG • Mild disc edema, dilated tortous veins • mid peripheral hemes • NVD/NVE • FA • Delayed arteriole filling • Diffuse leakage • Capillary non-perfusion • Carotid doppler > 90% diagnostic • Treatment • Endarterectomy • Topical corticosteroids & cycloplegics • PRP for neo • Anti-VEGF injection • 5 year mortality rate of patients 40% • Transient improvement, usually worsens
    78. 78. Retinal Detachment • Chronic Peripheral Rhegmatogenous • AC reaction • Vitreous inflammatory & pigment cells • Good vision, may worsen due to CME • Photoreceptor outer segments may be present in AC simulating inflammatory response • IOP elevated, OAG • Schwartz syndrome • DFE with scleral depression • Peripheral demarcation lines, subretinal fluid, retinal breaks, subretinal fibrosis, peripheral cysts http://gridironforgirls.blogspot.com
    79. 79. Intraocular FB • Chronic inflammation • Mechanical, chemical, toxic, or inflammatory inflammation of ciliary body • Gonio, ultrasound, CT of eye/orbits • Complications: proliferative vitreoretinopathy and endophthalmitis Pigment Dispersion Syndrome • Pigment released from iris and/or ciliary body • Simulates anterior uveitis
    80. 80. Management and Treatment Cycloplegics and mydriatics Corticosteriods Immunomodulating Agents Pressure-lowering medications
    81. 81. Cycloplegics Mydriatics • These opthalmic preparations block the responses of the iris sphincter and the accommodative muscle of the ciliary body to cholinergic stimulation, producing pupillary dilation (mydriasis) and paralysis of accommodation (cycloplegia) • Tropicamide 1%, cyclopentolate and atropine have both properties • Phenylephrine has only mydriasis. www.lookfordiagnosis.com/mesh_info.php?term=
    82. 82. Cycloplegics Purpose: •To break or prevent posterior synechiae and to relieve ciliary spasm induced photophobia. •Short acting vs. long acting cycloplegics •Dosing depends on the extent of inflammation •(1-2xdaily atropine, 3xdaily tropicamide and phenylephrine)
    83. 83. www.opsweb.org/?page=Scien tificExhibit portalcodgdh.minsaude.pt/index.php/Dissecção _ Posterior synechiae
    84. 84. Antigen-dependent lymphocyte activation and STEROID/NSAID activation sites Cunningham, Emmett. Practical approach to the use of corticosteroids in patients with uveitis. Can J Opthalmol 2010; 45:352-8
    85. 85. Corticosteroids: Produced through the hypothalamus, pituitary and adrenal axis (HPA) to control inflammation in uveitis http://pubs.niaaa.nih.gov/publications/arcr 344/images/stephens01.png
    86. 86. Common uses of corticosteroids -Mainstay of initial therapy Cunningham, Emmett. Practical approach to the use of corticosteroids in patients with uveitis. Can J Opthalmol 2010; 45:352-8
    87. 87. Ocular Surface Penetration Durezol>Pred Forte> FML larrazabaleye.com/cvep.html www.revoptom.com/content/c /216 www.revoptom.com/content/c /216 TOPICAL STEROIDS
    88. 88. Topical Steroids Cunningham, Emmett. Practical approach to the use of corticosteroids in patients with uveitis. Can J Opthalmol 2010; 45:352-8
    89. 89. Topical Steroids •Suspension vs. emulsion •Concentration vs. efficacy www.pharmainfo.net/reviews/microemulsionsnovel
    90. 90. Potency Cunningham, Emmett. Practical approach to the use of corticosteroids in patients with uveitis. Can J Opthalmol 2010; 45:352-8
    91. 91. Adverse Effects of Corticosteroids
    92. 92. Adverse Effects continued www.amardeepeyecare.com/ptosis.html
    93. 93. continued www.lpeyecare.com/eyeconditions/252-2
    94. 94. Intravitreal Injections Cunningham, Emmett. Practical approach to the use of corticosteroids in patients with uveitis. Can J Opthalmol 2010; 45:352-8
    95. 95. NSAIDS • www.uninet.edu/cin2001-old/conf/bala/bala.html • www.thedrugmonitor.com/coxi.html
    96. 96. Systemic NSAIDS • Complications of prolonged use: -myocardial infarction -hypertension -stroke (selective Cox-2 inhibitors) www.mayoclinic.com/health/medic www.ohioinjurylaw.com/ohioattorney/medical-mal
    97. 97. Immunomodulating Medications (IMT) • Antimetabolites • T cell signaling Inhibitors • Alkylating Agents • Biologic response modifiers www.riskindoc.com/new_psoria
    98. 98. Indications for IMT  inadequate response of uveitis to corticosteroid therapy for greater than 3 months with doses exceeding 5-10mg/day.  contraindications to corticosteroid use: 1. (diabetes, hypertension, peptic ulcer, GERD, immunocompromised state, psychiatric conditions) 2. exacerbated side effects 3.chronic corticosteroid dependence www.fortiusfitness.com/blog/steroi d-side-effects
    99. 99. Precautions  No infection present  No hepatic or hematologic contraindications  Close physician follow up  Teratogenic mamaprayed.blogspot.com/2012/08/if-you-give-m
    100. 100. Antimetabolites • Azathioprine, methotrexate, mycophenolate mofetil • Azathioprine (purine nucleoside analogue) -interferes with DNA replication and RNA transcription -found beneficial in VKHsyndrome, int. uveitis, Behcet uveitis, sympathetic opthalmia and necrotizing scleritis -GI side effects (nausea, upset stomach) are cause for D/C. -CBC, LFT every 4-6 weeks. -Thiopurine S-methyltransferase (TPMT) testing (metabolizes 6mercaptopurine,ie 6-MP) www.lookfordiagnosis.com/mesh_info.php?term
    101. 101. Methotrexate • Folic Acid analogue • Inhibitor of dihydrofolate reductase and it’s DNA replication • Causes extracellular accumulation of adenosine to create an anti-inflammatory effect. • Useful for JIA (first line choice IMT treatment for children), sarcoidosis, panuveiti s, various other types of uveitis • Prospective study for IV inj. for refractory uveitis and uveitic CME. www.humira.com/jia/what-is-jia.aspx
    102. 102. Mycophenolate Mofetil • Inhibits inosine monophosphate dehydrogenase and DNA replication • Side effects: reversible GI distress, diarrhea; 20%pt. pop. • CBC monthly • 85% effectivity in chronic uveitis patients and a good second choice IMT for children.
    103. 103. T Cell Signaling Inhibitors Cyclosporine and tacrolimus: • Calcineurin inhibitors- disrupt T-cell receptor signal transduction and down regulate IL-2 transcription and CD4 T lymphocyte receptor expression. Sirolimus: • Non-calcineurin inhibitordisrupts T cell signaling that inhibits Ab production and Blymphocytes. www.bdbiosciences.com/research/tcell/reg
    104. 104. Cyclosporine • SE: Nephrotoxicity and systemic hypertension; paresthesia,hypertrichosis. • BP, CBC, serum creatinine monthly. • Used for int. uveitis and posterior uveitis cases from Behcets and VKH. • Used in combination with corticosteroids for modest improvement
    105. 105. Tacrolimus • AE: nephrotoxicity • Low dose and increased potency to cyclosporine • Less risk of hypertension and hyperlipidemia • Useful for chronic int. and posterior uveitis.
    106. 106. Sirolimus • One open-label, prospective study it was found useful in treatment for refractory noninfectious uveitis • GI side effects • Under active investigation for use in treating uveitis
    107. 107. Alkylating Agents Cyclophosphamide • Active metabolites alkylate purines in DNA and RNA, creating impaired DNA replication and cell death • Cytotoxic to dividing and resting lymphocytes • AE:myelosuppression, hemorrhagic cystitis, sterility Chlorambucil • Interferes with DNA replication • AE:myelosuppression, sterility Treatment for int. uveitis, VKH, SO, Behcet Significant AE: increased risk for malignancy (leukemia, various cancers)
    108. 108. Infliximab Biologic Response Modifiers • Chimeric, monoclonal IgG1k antibody against TNFalpha • Treatment for Behcet, sarcoidosis and VKH. Some HLA B27 ant. uveitis • Drug induced toxicity (lupus, systemic vascular thrombosis, CHF, malignancy, demyelinating disease and vitreous hemorrhage) • +PPD, contraindication • Adalimumab, less AE, same effectiveness
    109. 109. Alternative Therapy Under FDA Investigation • Rituximab:chimeric monoclonal antibody against CD20 positive cells (B lymphocytes) • Daclizumab: monoclonal Ab to IL-2 • IFNalpha2a: antiviral, immunomodulatory and antiangiogenic effects (leukopenia and thrombocytopenia side effects)
    110. 110. Management/Follow up • Encounter visit determines extent of ocular inflammation (ant., int., panuveitis, etc). • Make a differential list and send out for further pertinent lab work to confirm/rule out differentials. super-trainer.com/fitness-business-becoming-a-bu
    111. 111. Anterior Uveitis • Cycloplegic • Steroid • Dosage depends on severity • Follow up in 2-3 days • If 2-3 additional follow up appt. prove no improvement, referral to uveitis specialist medlibes.com/entry/anterior-uveitis
    112. 112. Intermediate/Posterior Uveitis • Determine extent of inflammation, if anterior involvement, start on cycloplegic and steroid. • Refer to retinal specialist for periocular steroid injections (if deemed non-infectious) • Intravitreal injections for chronic anterior uveitis or inflammation not responsive to periocular injection www.retinaeye.com/uveitis.html
    113. 113. Uveitic Treatment Adverse Effects • Steroid responders: Need to lower IOP by utilizing beta blockers, alpha2 agonists,CAI, prostaglandins and their combinations where appropriate.
    114. 114. Case #1 • 70+ yr old cauc. male • Redness, mild pain, blurry vision in the right eye. • Slit lamp: 2+ AC WBC reaction; florrid NVI,NVA, corneal edema with descemet folds; IOP 16mmHg OD
    115. 115. Differentials? • Neovascular glaucoma • OIS • PDR
    116. 116. OIS! • DFE: mid-peripheral blot hemorrhages • No CME, NVD, NVE • Tx: Prednisolone Forte q2hrs, Atropine BID OD • Referral to retinal consult for PRP and possible injections of anti-vegf • Contact PCP for carotid doppler, echocardiogram, EKG
    117. 117. Case #2 • 17 yr cauc. female • CC: redness, pain, photophobia, bl urry vision • Review of systems was unremarkable • Second episode, first episode two years ago in GA.
    118. 118. Review of Systems • General - Weight loss, fatigue, fever Skin - Rash, nodules, changes in nails • Neck - Lymphadenopathy • Respiratory - Cough, wheezing • Cardiac - Chest pain/discomfort, dyspnea • Gastrointestinal - Hepatomegaly, diarrhea, frequent bowel movements • Genitourinary - Delayed secondary sexual characteristics • Musculoskeletal - Muscle or joint pain, arthritis, back pain, limitation of motion (refer to uveitis.org for more information and questionnaire)
    119. 119. Differentials? • JIA, lyme disease, lupus, sarcoid • ????? • Ran pertinent lab tests for her age (CBC c diff.,ANA, ACE, Lyme titer,ESR,RF, HLA B27) • Durezol q2hrs, Atropine BID OD. Pledget of 10% phenylephrine to break posterior synechiae • CBC with diff., lyme titre, RF, ANA, ACE, serum lysozyme • Blood results…negative. Consult with uveitis specialist.
    120. 120. Case 3
    121. 121. Chief Complaint • 46 year old WM • Redness OS x 5 days, gradually getting worse that is constant throughout the day • (+) photophobia, epiphora • ( - ) eye pain, flashes, floaters, cold sores • He was seen at Patient First 3 days ago where they diagnosed him with shingles over the left eyelid, noting ocular involvement • Treated with 20 mg Pred, mild pred taper and 1 gm of Valtrex tid x 10 days
    122. 122. History • Medical History • Hypertension, GERD • Treated with Omeprazole and Diovan • Family Medical History • Unremarkable
    123. 123. Examination • VA sc 20/25 OD, OS, OU • OD unremarkable findings • OS • Lid: vesicles along upper forehead & nose, lid erythema, small hordeolum • Conj: nasal injection
    124. 124. Examination • Cornea • Punctate Epithelial Keratitis • Inferior stromal haze • Anterior Chamber • Cells – WBC 2+ • ( - ) Flare • IOP 16, 19 mm Hg • Fundus • Unremarkable OU
    125. 125. Examination • Fundus Unremarkable, OU
    126. 126. Assessment 1. Redness/Discharge of Eye OS 1. Educated patient on findings 2. H. Zoster Keratoconjunctivitis OS 2. Neomycin ung on vesicles, BID 3. H. Zoster Iridocyclitis, OS 3. Pred Forte TID, OS 4. H. Zoster of Eyelid 4. Cool compresses and antibiotic ung on vesicles
    127. 127. Follow Up: 2 days later • Patient now complains of eye pain in the morning • Thinks it is getting worse • Currently taking pred forte tid OS and will finish Valtrex the following week
    128. 128. Examination: 2 days • VA sc 20/25 OD; 20/40 OS PHNI • OD unremarkable • OS Lid: Vesicles along upper forehead & nose with lid erythema, hordeolum on superior lid • Cornea • Prominent pseudodendrites • Anterior Chamber • 2+ WBC • IOP 16, 27 • Fundus: Unremarkable OU
    129. 129. Assessment: 2 days 1. Zoster, Eyelid OS 1. Continue ointment 2. Zoster Iridocyclitis, OS 2. Continue pred forte tid, atropine instilled in office Due to increased IOP: Combigan OS bid RTO 1 week
    130. 130. Follow up: 1 week later • Currently on pred forte TID, Combigan BID, OS only • Finished Valtrex • Feels improvement
    131. 131. Examination: 1 week • VA sc 20/25 OD, 20/40-2 PH 20/25-, OS • OD unremarkable • OS • Lids: healed vesicles, mild ptosis • Conjunctiva: Trace injection • Cornea: Pseudodendrites with endothelialitis inferiorly • Anterior Chamber: 2+ WBC • IOP 17, 20
    132. 132. Assessment: 1 week 1. Redness/discharge of eye OS 1. Injection improved, less tearing 2. H. Zoster of eyelid OS 2. Complete resolution 3. Zoster iridocyclitis 3. Durezol QID, atropine in office (increased IOP); continue combigan BID OS 4. H Zoster keratoconjunctivis 4. Pseudodendrites stable
    133. 133. Follow up 2 weeks later • Patient reports improvement • VA sc 20/30 PH 20/25 OD, OS • OD unremarkable • OS • • • • Lid: no vesicles Conjunctiva: trace injection Cornea: punctate staining Anterior chamber: KP‟s less evident • IOP 16, 18 mm Hg
    134. 134. Assessment: 2 weeks 1. H Zoster Iridocyclitis, OS 1. Improvement with quiet A/C, IOP stable --Continue Combigan BID OS --Taper durezol over 2 weeks, then D/C --RTO 5 weeks
    135. 135. Follow up 5 weeks later • Patient currently on Combigan BID OS only • VA sc 20/25 OD; 20/30 • OD unremarkable • OS • Conjunctiva: tr injection • Cornea: punctate staining • Anterior chamber: NO cells • IOP 16, 18 mm Hg • Assessment • H. Zoster Iridicyclitis • No signs of recurrent inflammation; IOP well • D/C combigan • Follow up 1 month for IOP check
    136. 136. References • Cunningham, Emmett. Practical approach to the use of corticosteroids in patients with uveitis. Can J Opthalmol 2010; 45:352-8 • Moorthy, Ramana. Intraocular Inflammation and Uveitis.American Academy of Opthalmology. Section 9. pgs 98-116. • http://www.uveitis.org/uveitis-questionnaire • http://emedicine.medscape.com/article/1209891-clinical • “Care of the Patient with Anterior Uveitis,” Optometric Clinical Practice Guideline. American Optometric Association.

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