1 망막 Conference Behcet’s disease R3 정현진/AP. 박영훈

2 Case ( OPD) M/19 Chief complaint : red eye (OD) onset) 3wks ago Dec. VA(OS) onset) 1wk ago 상환 수능이 끝난 이후 가끔 밤 새고 무리하는 경우가 있었다고 하며, 가끔 뿌옇게 보이는 증상이 있었다고 함. 3주전 부터 우안 충혈되어 한양대 병원에서 우안 포도막염 진단받고 스테로이드 경구약 및 안약 처방받고 호전 되었다고 함. 1주일 전부터 좌안 시력 저하 발생하여 local안과에서 방문, R/O ARN, R/O retinal vasculitis 의심하에 큰 병원 권유받고 본원 내원함.

3 Past History No systemic disease Ocular op/trauma(-/-)Eye drop (+ ): 옵타낙, 프레드 포르테 x 2~3(OU) Medication(+): 압구정 성모안과에서 처방받은 약, 미상

4 Ocular exam VA OD 0.04(0.8 x -4.25Ds =-1.00Dc Ax180) OS FC 50cm(N-C)IOP OD 18 mmHg OS 11 mmHg at 13:55 EOM straight at 1 position by ACT, no LOM Orbit OU no exophthalmos Lid OU no swelling Conj. OD not injected OS ciliary injection Cornea OU clear AC OD deep & cell(-) OS deep & cell(+++) Pupil OD round & nl. sized, LR(+) OS round & nl. sized, LR(+). RAPD(-/-) Lens OD mild cortical opacity OS mild cortical opacity c iris pigments at ant. capsule

5 Ocular exam Fd OD nl. optic disc c flat but retinal hemorrhage & sheathining OS blurry visible d/t vit opacity but seems nl. optic disc c vit. cell(+++) peripheral retinal infiltrate esp. inf. Circumferencial like

6 타병원 FAG(OD) ( ) 0:52

7 타병원 FAG(OD) ( ) 3:38 FAG broom-shapled dye leakage from capillary wall

8 타병원 FAG(OS) ( ) 0:12

9 타병원 FAG(OS) ( ) 0:13

10 타병원 FAG(OS) ( ) 2:39

11 타병원 FAG(OS) ( ) 5:46

12 Cue list retinal necrotic infiltration at pph. rapid progressioncircumferential spread occlusive vasculopathy with arteriolar involvement prominent inflammatory reaction in the vitreous and AC

13 Impression R/O ARN R/O viral retinitis R/O Behcet’s diseaseR/O Intermediate uveitis R/O Sarcoidosis R/O Syphilis R/O Tuberculosis R/O primary ocular lymphoma PORN progressive outer retinal necrosis-> immunocompromised pt. extensive repidly progressving full thickness necrosis, AC. Vitreous recation d연과 없음 베쳇: FAG broom-shapled dye leakage from capillary wall 사코이도시스: nodular periphlebitis 톡소: elevated lesion in chorioretinitis 매독: diffuse, patchy necrotizing retinitis, 특히 vitritis and vasculitis

14 Initial plan Diagnositc Therapeutic Vasculitis lab for serumAqauous humor PCR for VZV, HSV 등 Therapeutic Intravit. Ganciclovir inj(OS) Acylovir IV start. O-LON x4, O-MOX x 4, O-1AT x2(OS) Aspirin H-LON 복용여부는 다음날 결정하기로 함.

15 Treatment of ARN

16 Acyclovir To limit the direct cytopathic effect of virus on retinal tissue 용량 1500mg/m2/day #3 IV for 5~10days 이후 oral acyclovir( 800mg, five times daily)for 6wks 치료시작 3.9일 후 new lesion did not develop and existing lesions did not progress Side effect : decreased renal function, GI irritation, phlebitis, CNS dysfunction, hypersensitivity reactions Alternative antivirals should be considered if the retinitis does not respond in a timely fashion to acyclovir within 3-5 days

17 Lab of Aquous humor(2012.1.16) VZV (-) HSV type I PCR(-) CMV RQ-PCR(-)Toxoplasma Ig G & Ig M (-/-) Toxocariosis Ig G(-) Micro ELISA Test(-)

18 Lab of blood(2012.1.16~19) Rheumatoid factor EBV Ig G(+), Ig M(-)PRP, quan(-) Toxoplasma Ig G, Ig M(-/-) HSV Ig G, Ig M(-/-) VZV Ig G, Ig M(-/-) Toxocariosis Ig G(-) ESR 80 C3, C4, ACE, immunoglobulin E: WNL

19 Progression note( ) 금일 intravit. Gancyclovir inj(OS)

20 Progression note( ) Acyclovir iv Tx 중 환자 Cr 4.60으로 상승 acute kidney insufficiency로 신장내과협진의뢰 및 전과 -> hydration & acyclovir iv dose modification (2500mg350mg) 및 H-LON po복용 중단함. 2차례 seizure로 신경과 협진의뢰, EEG상 특이소견 보이지 않고 brain MRI diffuse상 posterior reversible encephalopathy syndrome(PRES)소견보여 valproic acid loading함 -> CSF tapping : pressure 16.5cmH2O protein 49, glucose 70, WBC 0, RBC 0

21 Laboratory Exam. (2012.1.18) Rheumatoid factor(-)Anti cardiolipin Ab IgM(-) Anti ss DNA Ab IgG(-), SLE profile(-) Infectious origin에 대한 검사는 꽝

22 Progression( ) Fd : OD new retinal infiltrate at sup. Retina & vascular sheathing OS sl. Inc. retinal infiltrate and stationary vit. Opacity - Intravit. ganciclovir inj+AC paracentesis(OD) Intravit. ganciclovir inj+AC paracentesis(OS)

23 Progression(2012.1.25) HLA B 27(-) HLA B 51(+) Behcet 가족력  고모Recurrent oral ulcer Pathergy test(-) TEE, abdominal CT, chest CT, brain image에서는 다른 장기의 vasculitis소견은 보이지 않음  Behcet’s disease suspected

24 Progression(2012.1.27) AC OU cell(trace)Fd vit opaicty & cell(trace/+) but much dec. vit opacity(OS) retinal infiltrate and snow-ball like lesion-> stationary -> Acyclovir 1950mg # 3 O-MOX x 6, O-LON x q2hrs, O-1AT x 2 (OU) H-LON po 복용 경과보면서 diagnostic ppV(OS)고려예정

25 Diagnostic ppV(2012.2.4) OP title :ppV+endolaser+FAE+C3F8 gas inj. (OS) OP findings Snow ball like materials Lattice deg. c R. hole at 1 o/c Peripheral vascular occlusion

26 Lab of vitreous fluid Bacterial & fungal culture(-)Cytokine : IL-VI : 61.6pg/ml 6배 증가 (IL-X : 4.7 normal range) Toxoplasma DNA PCR(-) PCR HSV type I & CMV (-) VZV(-)

27 Progression note(2012.3.2) Mycophenolate mofetil 2000mg #3H-LON 20mg #2 Famciclovir 250mg #1 O-LON x 4, O-COST x 2(OS) VA OD (0.5)/OS(0.5) IOP OD 22mmHg/OS 22mmHg AC cell/flare (+) (OS) Fd : flat

28 망막 Conference Review R3 정현진/AP. 박영훈

29 General considerationa multiorgan disease characterized by an immune-mediated occlusive vasculitis Sx. Triad - oral ulcers(m/c), genital ulcers, hypopyon uveitis Geographic - m/c in the Middle and Far East Genetic - HLA type and HLA B51 ,52, ICAM-1 gene More common in men than in women (2nd to 4th decade)

30 Features & Frequency

31 Fluorescein angiography is an essential test in Behcet’s screening( Several patients with normal fundus  Angiographic alterations)

32 FAG findings Perivascular staining Leakage of the dilatedretinal capillaries Occlusion of retinal vessels Early & profuse leakage from ONH in early transit Diffuse fluorescein leakage from capillaries

33 Ocular manifestation In 60–80% of patientsMost serious manifestation due to its association to a permanent visual loss The initial symptom in 10~25% of Behcet’s patients Often present at the onset of the disease or within the first 2 years (quite rare for patients to develop ocular BD after the initial 5 years) Ocular BD occurs in up to 70% of males aged less than 25 years A recurrent non-granulomatous uveitis with necrotizing obliterative retinal vasculitis Either in the anterior segment or the posterior segment, or both Initially, unilateral affecting mostly the anterior uvea With time in 75% of patients, bilateral panuveitis with a chronic relapsing course is present

34 Anterior segment lesionHypopyon iritis 20~30% of patients Hypopyon uveitis: a bad prognosis of visual outcome Severe vasculitis Optic atrophy (about half of cases)(Pazarli et al, 1986) Keratic Precipitate (KP) Anterior or posterior synechiae Lead to secondary glaucoma, cataract formation

35 Posterior segment lesionCell infiltration of the vitreous body Retinal vasculitis Occlusive and necrotizing vasculitis Mostly involves the retinal veins Acute periphlebitis or thrombangiitis obliterans Perivascular sheathing with inflammatory whitish yellow exudates Neovascularization at retina or optic disc Choroidal vascular involvement Optic nerve inflammation: at least 25% of patients

36 Posterior segment lesionMost often bilateral and asymmetric Retinal vasculitis - Vein and artery with arterial occlusion and retinal necrosis Sparse perivascular infiltrate with round cells (lymphocytes and plasma cells)  associated with retinal necrosis Extensive loss of retinoarchitecture with neovascularization Blind, Secondary glaucoma, RD (End stage)

37 Treatment options

38 Treatment Chlorambucil (0.1~0.2mg/kg per day)Cyclophosphamide(1~2mg/kg per day) Systemic corticosteroid (1mg/kg per day) Oral prednisone + immunosuppressive agent control acute disease Once disease has been controlled Corticosteroids are tapered and discontinued, immunosuppressive drug is continued for 12~18months and then tapered

39 Treatment Cyclosporin reduction in the frequency and severity of attacks (but 25% no benefit) - Drug toxicity  Low dose (4~5mg/kg) + Steroid Azathioprine  Prevent contralateral eye involvement (But, 22% required additional Tx.)

40 Prognosis Natural history of ocular disease is poor.Loss of vision (all or part) within 5 yrs. - 74% of eye had vision <20/200 - 3.6yrs  25 eyes LP(-) /(described by Mamo) Corticosteroid therapy delayed the progression but not alter the ultimate outcome.

41 감사합니다

42 전형적인 ARN 망막소견