전안부 conference Scleritis 2012.4.23 R3 정현진/ Ap. 나경선

Case presentation 69/F C.C :Red eye, lid swelling(OD) onset) 20days ago ocular pain(+), bloody discharge(+) Local에서 R/O episcleritis(OD)로 퀴노비드, 네 오덱스 안연고 점안하였으나 악화되어본원 전원 됨 DM(-), rheumatic disease Hx.(-) ocular op./trauma Hx.(-/-) 2001.8.7 scleral mass/sclerouevitis(OS)로 본원 systemic steroid Tx. 당시 공막염 원인에 대한evaluation(-) 10년전 아산병원에서 enucleation(OS)시행받음 안구적출후에도 좌안염증으로 고생, 의안도 못 함. 2.8 Arthralgia(-), oral & genital ulcer(-), back pain(-) 약물치료 일시적인 호전과 악화 반복

Ocular evaluation VA 0.08 ref. error IOP 15mmHg lid mild swelling c mild erythema Conj. mod. injected scleral edema thinning of defect at inf(x2) (1.5mm, 1.0mm sized) Cornea rl .clear AC deep & cell(+) Pupil round & nl sized, LR(+) Lens mod cortical opacity/OD 박창현 charting mod. injected c melted necrotizing conj defect(x2)(1.5mm, 1.0mm sized) c Pus(+) at temporal side B-scan: 안구안쪽으로는 염증소견 없음, scleral thickining, eyeball은 유지됨(T-sign(-)) 여의도 post. Scleritis: O-LVF x 4, O-LON x q1hr, O-DCF x 4 Uveitis lab(-), CSF study(-) Add 1AT x 2, H-LON 40mg, IPF20(ibuprofen 200mg) 3T

Plan Impression Necrotizing scleritis(OD) R/O bacterial infection(OD) Last eye(OD) Plan Culture(bacterial & fungus) Immunology lab -> Rheumatology consultation Admission H-LON 60mg start Ceftriaxone 1g iv qd O-CS x q 1hr O-MOX x q 1hr O-1AT x 2(OD) Scleral patch를 대는 것은 위험

입원다음날, 내원 3일후 S: 좀 좋아진거 같아요 VA 0.16 Lid sl. erythematous swelling Conj. mild injected c thinning defect (x2) at inf. & temp. side(dec.) Cornea some SPE's(+) c microbullae AC deep & cell(+) Pupil post. synechiae at inf. Half Lens mod cortical opacity c NS Fd nl. Optic disc c flat post. Pole, tigroid app. /OD Plan : keep eyedrops & H-LON 60mg, IV anti 유 지 2.10 H-LON 60mg for 3days

Lab finding Autoimmune study(-) by Rheumatology (RA factor, SLE profile, ANA, ANCA, UA, CBC, BC, ACE) Infection study(-) (VZV, HSV, syphilis, Toxoplasma, Toxocariosis, CNV) Culture :propionibacterium acnes(+) 5일 Rheumatology consultation Rheumatic disease소견은 없으나 면역억제제 복용량 조절해주기로함 (METHOTREXATE 10MG Q WEEK + FOLIC ACID 1MG QD 추가, steroid는 tapering하거나 daily 5mg씩 줄이시되, maintanence dose는 유지)

입원8일후, 내원 9일후 S: 분비물 많이 줄어 들었어요 VA 0.25 Conj. mild injected c thinning defect (x2) at inf. & temp. side(dec.) Cornea some SPE's(+) AC deep & cell(rare) Pupil post. synechiae at inf. Half Lens mod cortical opacity c nucleosclerosis Fd nl. Optic disc c flat post. Pole, tigroid app./OD 2.17 Plan: 금일 퇴원 O-CS x 2, O-MOX x 4, O-1AT x 2, O-LON x 4, (O-CS, O-MOX 감량) H-LON 60mg for 8days-> H-LON x 40mg for 2days,MTX 10mg q1wk, folic acid 1mg QD, ->H-LON x 30mg for 1wk예정

plan 금일 퇴원 MTX 10mg q 1wk H-LON 30mg for 1wk Folic acid 10mg qd O-CS x 2 O-LON x 4 O-MOX x 4 O-1AT x2 (OD) O-LON은 12일 부터 추가

퇴원 12일후, 내원 21일후 S : 많이 좋아짐 VA OD 0.125 IOP OD 19mmHg sclerae & Conj. mild injected c inf. thinning defect (x2) at inf. & temp. side(dec.) Cornea some SPE's(+) AC deep & cell(rare) Pupil synechia at inf. Half Lens mod cortical opacity c nucleosclerosis, PSCO(+) Fd nl optic disc c flat post pole, tigroid app. /OD 2.29 H-LON 25mg for 1wk->H-LON 20mg for 1wk류마티스내과 조절예정 O-MOX x 4 O-LON x 4 백내장 수술고려

plan MTX 10mg q 1wk H-LON 25mg for 1wk -> 20mg for 1wk로 tapering Folic acid 10mg qd O-MOX x 4 O-LON x 4(OD)

퇴원 한달후, 내원 6주후 S : 많이 좋아짐 VA 0.1 IOP 20mmHg 퇴원 한달후, 내원 6주후 S : 많이 좋아짐 VA 0.1 IOP 20mmHg sclerae & Conj. not injected c inf. thinning defect (x2) at inf. & temp. side(dec.) Cornea some SPE's(+) AC deep & cell(rare) Pupil synechia at inf. Half Lens mod cortical opacity c nucleosclerosis, PSCO(+) Fd nl optic disc c flat post pole, tigroid app. /OD 여기까지는 좋아지고 있음 백내장 수술고려

plan MTX 10mg q 1wk H-LON 10mg for 1wk-> 7.5mg for 1wk -> 5mg for 1wk-> 2.5mg 1wk로 tapering Folic acid 10mg qd O-MOX x 2 O-LON x 2(OD)

내원 2개월 후 S: ocular pain, tearing(OD) onset )5days ago VA OD 0.04 ref. error sclerae & Conj. mild injected c thinning defect (x2) at inf. & temp. side(dec.) Cornea some SPE's(+) AC deep & cell(rare) Pupil synechia at inf. Half Lens mod cortical opacity c nucleosclerosis, PSCO(+) 악화 4.6 현재까지 약 2.8 H-LON 60mg for 8day -> H-LON 40mg for 2day(MTX 10mg q1wk) -> H-LON 30mg for 1wk(MTX 10mg q1wk) -> H-LON 25mg for 1wk(MTX)-> H-LON 20mg for 1wk(MTX)->H-LON x 15mg for 1wk(MTX)-> H-LON x 12.5mg for 1wk(MTX)-> H-LON x 10mg for 1wk(MTX)-> H-LON 7.5mg for 1wk(MTX)(이때부터악화)->H-LON 5.0mg for 2days(내원)-> H-LON 60mg으로 증량 -> 4.13 45mg감량, 4.20 30mg으로 감량

plan Culture H-LON 60mg 증량 O-MOX x 6 O-TOB x 6 (OS) Adm. recommand

1주일후 S: 많이 편해졌어요. 중간에 고름 안났어요. VA OD 0.125 ref. error sclerae & Conj. mild injected c thinning defect (x2) at inf. & temp. side(dec.) scleromalatic area at inferotemporal-stationarly Cornea some SPE's(+) AC deep & cell(trace) Pupil synechia at inf. Half Lens mod cortical opacity c nucleosclerosis, PSCO(+) Culture(-) 4.134.20마지막

Plan H-LON 60mg(for 1wk) O-MOX x 4 O-TOB x 4(OD) FU 1wk(호전되면 H-LON 45mg으로 감량예정)

Review Cornea Krachmer 3rd edition, Ch.104

Anatomy

Applied anatomy of vascular coats 상공막염 : 염증이 episclera와 tenon’s capsule에 구한 공막염 공막에 염증

Causes and systemic associations of scleritis 1. Rheumatoid artharitis 2. Connective tissue disease Wegener granulomatosis Polyarteritis nodosa SLE Miscellaneous Relapsing polychondritis Herpes zoster ophthalmicus Surgically induced

Pathogenesis Immune-mediated leading to vessel and tissue damage genetically controlled mechanisms environmental factors(infectious or endogenous) Type III hypersensitivity – immune complex inflammatory microangiopathy. Type IV hypersensitivity – systemic autoimmune disease associated with circulating immune complexes(SLE, rheumatoid arthritis, and polyarteritis nodosa.) Antigen – possibly scleral tissue(collagen), scleral blood vessel. Posterior scleritis – CD4+ lymphocytes, intercellular adhesion molecule-1(ICAM-1) and LFA-1) on sclera and conjunctiva

Epidemiology Scleritis Episcleritis more frequent in middle-aged and elderly Peak in fifth decade Diffuse, nodular > necrotizing 25~50%-associated systemic disease(RA>WG>relapsing polychondritis> spondylopathies, SLE.) Episcleritis young and middle-aged women Simple>>nodular 26~36%-associated disease, 5~14% collagen vascular disease No known geographic, racial, or genetic associations.

Classsification * Immune mediated * infectious Surv Ophthalmol 50 (4) July–August 2005 * infectious

Episcleritis gradually subsiding over a period usually 5~10days rapid onset, reaching peak in a few hours Start upper temporal or upper nasal quadrants gradually subsiding over a period usually 5~10days Frequently asymptomatic Mild ocular discomforts, FB sensation, mild photophobia Redness mild pinkish to fiery red (dilatation of episcleral blood vessels) May be bilateral (not frequently simultaneous) Recurrence (1 / 3, not necessarily in the same location) fluid extravasuclar space Tx: Topical steroids Systemic NSAID : flurbiprofen (100 mg tid if unresponsive or recurrent) 그림 1 smple diffuse episcleritis

Nodular episcleritis Less common inflammation is confined well-circumscribed, raised, red-pink, mobile nodule D/Dx with conjunctival phlyctenula - freely movable overlying conjunctiva 그림 1Localized nodule which can be moved over sclera 그림 2 Deep scleral part of slit-beam not displaced Nodular episcleritis

Scleritis Insidious Moderate~severe penetrating pain refered to forehead, jaw, sinuses Tearing, mild to moderate photophobia globe tenderness Necrotising scleritis-Intense, chronic, debilitating pain Bilateral: 34~50% (simultaneous or sequential) Recurrence Anterior scleritis Scleral edema, dilatation of deep episcleral vasculatures Injection with bluish to violaceous tinge Scleromalaciaperforans no pain, redness

Diffuse anterior scleritis Most benign and common Comprising btw 40 % ~ 64 % of ant. Scleritis 12 of 30, progression to nodular type 3 of 30, progression to necrotizing type. Btw 45 % ~ 62 % - associated systemic disease, typically RA Insidious onset of generalized inflammation, Last several months Superficial and deep vessel distorted and tortuous, Losing the radial pattern Relatively benign - does not progress to necrosis Widespread scleral and episcleral injection Tx : oral NSAIDs oral steroid if unresponsive

Nodular anterior scleritis Tender and immobile, firm to touch, yellow deep red or violaceous scleral nodule. Usually localized to the interpalpebral zone, approximately 3 ~ 4 mm from the limbus. Progression to necrotizing scleritis – 20 % 45 % - associated systemmic disease, typically RA 그림 1 On cursory examination resembles nodular episcleritis 그림 2 Scleral nodule cannot be moved over underlying tissue Treatment - similar to diffuse non-necrotizing scleritis

Anterior necrotizing scleritis with inflammation Most severe form of scleritis Sign of systemic vascular diseases (50~81% ) Intense pain, worsen at night White avascular area surrounded by the sw elling of sclera Become thinned sclera or choroid bare, st aphyloma may form FAG : venular obstruction Necrotizing scleritis – proteoglycans is stripped from the collagens by MMP from fibroblast – Antigenicity Most severe form of scleritis and ominous sign of systemic vascular diseases (50~81%) Intense pain, worsen at night White avascular area surrounded by the swelling of sclera Become thinned sclera or choroid bare, staphyloma may form FAG : venular obstruction Painful and most severe type Complications - uveitis, keratitis, cataract and glaucoma Tx. Oral steroids Immunosuppressive agents (cyclophosphamide, azathioprine, cyclosporin) Combined intravenous steroids and cyclophosphamide if unresponsive 그림 1 : avascular patchs 그림 2 scleral necrosis and visiblity of uvea 그림 3: Spread and coalescence Most destructive form of scleritis Extension of the inflammatory process led to – anterior uveitis (69 %), peripheral ulcerative keratitis (41 %), glaucoma (23 %), significant loss of visual acuity (82 %). 50 % ~ 81 % - associated with systemic connective tissue disease and/or potentially lethal systemic vasculitic disease. of necrosis

Ocular complication Corneal Involvement Stromal keratitis Sclerosing keratitis Corneal thinning –peripheral Peripheral ulcerative keratitis Posterior Segment Involvement Uveitis Optic disc edema Glaucoma Hypotonia Cataract Orbital involvement

Anterior scleritis without inflammation (scleromalacia perforans) Insidious onset, slow progression and lack of symptom Thinned, avascular area of sclera Ass with longstanding rheumatoid arthritis FAG : arteriolar obstruction Insidious onset, slow progression and lack of symptom Thinned, avascular area of sclera Ass with longstanding rheumatoid arthritis FAG : arteriolar obstruction Asymptomatic and untreatable 그림들 Progressive scleral thinning with exposure of underlying uvea Rare, bilateral condition, occurring predominantly among elderly females with a history of severe, progressive, long-standing rheumatoid arthritis with extra-articular manifestations. Caused by arteriolar obliteration as evidenced by FA, as opposed to venular non-perfusion, which is more prominent in necrotizing scleritis.

Ocular exam Level of inflammation Examine under daylight, slit lamp(diffuse, narrow, red-free) Under daylight Pink~red - epislceritis Deep-bluish red or violaceous - scleritis If scleral necrotitis, blue-gray to dark-brown areas of underlying uvea

Diagnostic Evaluation Comprehensive medical, ophthalmic history, review of system Ocular and physical exam Chest X-ray, blood test, serum chemistries, urine analysis ANCAs for systemic vasculitides c-ANCA: sensitive and specific for Wegener’s granulomatosis p-ANCA: microscopic polyarteritis nodosa, relapsing polychondritis, renal vasculitis HLA-B27, RA FTA-abs (syphilis) Scleral biopsy Infectious scleritis, foreign body, masquerade syndrome

Surgically induced scleritis Uninfectious - underlying 전신질환이 있는 경우가 많다 Infectious - Rare -Exogenous - 외상, 수술후, 각막염에서 침범(m/c) - Endogenous - 전신 감염와 연관

Infectious scleritis Pseudomonas - m/c cause - scleritis without keratitis 도 유발 가능 익상편 수술시 MMC 혹은 irradiation과 관련하여 잘 발생 m/c cause : Pseudomonas, Pneumococcus

Posterior scleritis Inflammation of sclera posterior of the ora serrata Frequently extends to choroid, retina, optic nerve, extraocular muscles, orbital tissues Up to 60%, present with anterior inflammation diseases In about 29% , systemic associations

Symptoms & signs Pain Visual loss Redness severe, radiating Visual loss Mild & correctable with convex lens transient hyperopia d/t reduction in AL Moderate to uncorrectable(17~84%) Choroidal folds or retinal striae Annular cilioretinal detachment Disc and macular edema Fundus or orbit mass lesions Reversible c good prognosis, if early Dx. & appropriate Tx. provided Redness Proptosis, lid swelling, painful LOM MRI Posterior scleral thickening a - Thickening of posterior sclera b -Fluid in Tenon space (‘T’ sign) ERD Ring choroidal detachment Subretinal mass

Ocular Exam Fundoscopic findings Ultrasonographic findings Common findings Optic disc swelling Exudative retinal detachment Choroidal folds Less common Focal subretinal mass-like lesions Ultrasonographic findings “T” sign Scleral & choroidal thickening Edema in Tenon’s space Computed tomography Essential in excluding orbital inflammatory diseases, tumors, thyroid eye disease, sinus diseases Extension into adjacent structures

Treatment Episcleritis Scleritis Simple – observation or topical NSAIDS. Episcleritis with connective tissue disease. – oral NSAIDs Scleritis 30.4 % - required oral NSAIDs, 60 % - oral corticosteroids or immunosuppressive drugs (90 ~ 100 % - necrotizing or posterior scleritis) Diffuse or nodular scleritis not associated with an underlying systemic vasculitis. oral NSAIDs, c/s topical corticosteroids  Failure – systemic corticosteroids(1 to 1.5 mg/kg per day) Oral NSAIDS 반응 없으면 우선 다른종류 NSAIDs써본다. -> NON necro Oral steroid : severe NON-ne Necrotizing Systemic immunosuppressant” severe necro/ c Wegeners/ c pollyarterytis nodosa Topiac cyclosporine: effective

Treatment Oral NSAIDs Systemic corticosteroids 1st line if not associated with systemic vasculitis Treatment response within 2~3 weaks For a minimum of 1 year Systemic corticosteroids Treatment failure with oral NSAIDs or severe scleritis Prednisone 1~1.5mg/kg/day with tapering High-dose methylprednisolone(1g/day x3) with tapering Safe and effective in the induction Immunosuppressive therapy Failed systemic corticosteroids or for“steroid-sparing” Underlying systemic vasculitis Cyclophosphamide-1st line for scleritis with Wegener’s granulomatosis or polyarteritis nodosa Specific antimicrobial therapy For infectious scleritis

Findings epi Red Superficial episcleral vs. engorgement scl. Violet, blue (translucent sclera) Superficial and deep episcleral vascular engorgement Avascular area with vascular occlusion Peripheral corneal ulceration Tx : topica (oral NSAIDs).oral 전신질환 관련(-) (+)

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