망막 CONFERENCE R2 이지영/St.전소희

M/47 조 O 영 History C/C : floater(OD) for 1 week P/I DM/HBP (-/-) 상기 환자 severe aplastic anemia로 본원 혈액종양내과에서 2012.4 골수이식예정인 환자로 내원 1주일 전부터 우안 비닐막이 씌운 것 같고 물방울이 보이는 증상 발생하여 내원 History DM/HBP (-/-) Severe Aplastic anemia: 2011년 10월 진단 ATG 3.5mg/kg for 5days : 2011.12.13 ~ 12.17 G-CSF : 2011.12.18 ~ 12.26 (9 times) Cyclosporin 300mg /d : 2011.12.18~ Oral candidiasis, Herpes zoster 2012.1.13 진단 Ocular op/trauma(-/-) Eye drop (-)

Ocular exam VA OD 0.4(N-C) / OS 1.0 IOP OD 9 / OS 13 mmHg Conj. OU mild injected Cornea OD mild edematous, KP’s AC OD deep & cell(rare) OS deep & cell (-) Pupil OD round & dilated, LR(+, slugguish) Lens OD mild cortical opaticy, iris pigment on ant. surface Fd OD nl optic disc c dot & blot Hm. c multiple whitish-yellow lesion at inf. some exudates c multiple sheathed vessels OS CDR 0.6 c flat post pole

Fundus photo retinal vascular sheathing : neutrophilic perivascular infiltration Perivascular hemorrhage granular patches Confluent areas of retinal whitening associated with venous sheathing and hemorrhages along the major retinal vascular arcades irregular granular borders with small, isolated satellite lesions adjacent to retinal vessels with hemorrhage

Lab findings(2012.2.27) CBC WBC: 940 /µl seg neu: 53% lymph: 42% Mono : 5% Eosino: 0 Baso: 0 ANC 500 Plt 47000 Hb/Hct 6.9/19.8

Impression CMV retitis ? R/O ARN (OD) R/O CMV retinitis (OD) Immunocomprimised pt. Mild AC reaction Fd : granular patches, confluent areas of retinal whitening associated with venous sheathing and hemorrhages

Fundus photo retinal vascular sheathing : neutrophilic perivascular infiltration Perivascular hemorrhage granular patches Confluent areas of retinal whitening associated with venous sheathing and hemorrhages along the major retinal vascular arcades irregular granular borders with small, isolated satellite lesions adjacent to retinal vessels with hemorrhage

Impression ARN>CMV retinitis R/O ARN (OD) R/O CMV retinitis (OD) Peripheral retinal necrosis Vessel 따라서 spread 되는 양상이 아님.

DDx. Progressive outer retinal necrosis (PORN) toxoplasmosis chorioretinitis syphilitic retinitis acute multifocal hemorrhagic retinal vasculitis toxocariasis fungal or bacterial retinitis Behcet’s disease sarcoidosis commotio retinae central retinal artery or ophthalmic artery occlusion ischemic ocular syndrome collagen-vascular disases intraouclar leukemia / lymphoma retinoblastoma

Plan Diagnositc test Therapeutic plan Daily f/u CMV, HSV, VZV, EBV IgM/G CMV, HSV, VZV, EBV RQ PCR Therapeutic plan IV acyclovir 1800mg #3 O-1AT x2, O-LON xq2, O-MOX x4, O-GC x5 / OD Intravit. ganciclovir inj.(OD) Daily f/u

Viral titer CMV RQ PCR <500 VZV RQ PCR (+) HSV type I PCR (-) CMV RQ PCR (-) at blood EBV RQ PCR 6393 copy/mL at blood CMV IgM (-) IgG (+) at serum HSV IgM (-), IgG (+) at serum VZV IgM (-), IgG (+) at serum

O-1AT x2, O-LON xq2, O-MOX x4, O-GC x5(OD) Progression note trace ++ + - AC cell Vit cell intravitreal ganciclovir inj.(OD) O-1AT x2, O-LON xq2, O-MOX x4, O-GC x5 IV acyclovir 1800mg Po acy 4000mg H-LON 60mg H-LON 50mg O-1AT x2, O-LON xq2, O-MOX x4, O-GC x5(OD)

2012.3.2 2012.2.27

2012.2.27 2012.3.5

O-1AT x2, O-LON xq2, O-MOX x4, O-GC x5(OD) Progression note trace ++ + - AC cell Vit cell intravitreal ganciclovir inj.(OD) intravitreal foscarnet inj.(OD) O-1AT x2, O-LON xq2, O-MOX x4, O-GC x5 IV acyclovir 1800mg Po acy 4000mg H-LON 60mg H-LON 50mg O-1AT x2, O-LON xq2, O-MOX x4, O-GC x5(OD)

2012.2.27 2012.3.5 2012.3.9

2012.3.12 Plan - acyclovir 4000mg#5, H-LON 50 mg - keep eye drops VA OD (0.5) IOP OD 12 mmHg Conj OD not injected Cornea OD clear AC OD deep & cell(+) Pupil OD round & mild dilated d/t cycloplegics Lens OD mild cortical opacity c mod. NS Fds OD nl. optic disc c perifoveal whitish confluent lesion - decreased Vit cell (+) vitreous opacity (+) multiple retinal Hm. c multiple sheathed vessels at inf. arcade multiple whitish-yellow lesion at inf. - decreased Plan - acyclovir 4000mg#5, H-LON 50 mg - keep eye drops - discharge 후 OPD f/u , intravit. foscarnet inj

Acute Retinal Necrosis Review Acute Retinal Necrosis

Introduction Definition Epidemiology characterised by confluent, peripheral, necrotizing retinitis, peripheral occlusive arteritis and moderate-to-severe vitritis Epidemiology No association between gender, race, age Typically occur in healthy, immunocompetent pts But also be found in immunocompromised pts.

Etiology multiple members of the Herpes virus family Varicella-zoster virus(m/c) Herpes simplex virus 1 Herpes simplex virus 2 Cytomegalovirus Epstein-Barr virus HLA haplotypes HLA-DQw7, HLA-Bw62, DR4 Bilateral involvement occurs in 2/3 of the patients frequently in the first six weeks, but sometimes months to years later. no correlation between the severity of ARN in the first eye

Clinical presentation Symptom mild to moderate ocular or periorbital pain red eye visual symptom floaters, blurred vision decreased vision vitreous opacification, necrotizing retinitis, optic neuritis or neuropathy

Clinical presentation Episcleritis or scleritis Anterior uveitis Mild to moderate anterior segment cellular reaction granulomatous or fine keratic precipitates Hypopyon, dendritic or stromal keratitis(rare) Acute necrotiziong retinitis Deep, multifocal, yellow-white patches typically beginning in the peripheral fundus(360 degrees) spreading toward the posterior pole the macula is frequently spared Active vasculitis perivascular hemorrhages, vascular sheathing terminal obliteration of arterioles by thrombi In early ARN, multifocal white patches of retinal necrosis occur in the peripheral retina With progression of ARN, the areas of retinal whitening begin to coalesce. Mild perivascular retinal hemorrhages are noted The peripheral retinal whitening becomes confluent with vascular obliteration.

Clinical presentation Vitritis (severe) Choroiditis Optic nerve involvement Optic nerve swelling Dyschromatopsia Relative afferent papillary defect Visual field defect Bilateral involvement occurs in 2/3 of the patients frequently in the first 6 weeks, but sometimes months to years later. no correlation between the severity of ARN in the first eye Bilateral involvement occurs in 2/3 of the patients frequently in the first six weeks, but sometimes months to years later. no correlation between the severity of ARN in the first eye

Clinical presentation Resolusion phase (4~6 weeks) the retinal areas appear thinned and atrophic underlying retinal pigment epithelial alterations (distinct scalloped pattern) Full-thickness retinal breaks large, irregular, and multiple at the junction of normal and affected retina accompanying vitreous fibrosis and traction Rhegmatogenous RD major cause of visual loss occurs in 50% to 75% of cases not treated with prophylactic laser photocoagulation high grade PVR, posterior located multiple break 6 days~ several months (4~6 weeks)

Clinical presentation Initial reports of ARN in healthy patients with normal systemic immunity no extraocular manifestations of herpetic infection Secondary to reactivation of a latent herpetic infection dermatomal VZV (herpes zoster) primary VZV (chickenpox) perioral blisters (HSV) reactivation of the viral genome from the trigeminal ganglion may result in the development of ARN after transneural spread uncommon for healthy individuals to develop ARN simultaneously with cutaneous VZV or HSV infection

Immunocompromised patients ARN subsequently has been reported in immunocompromised patients with HIV infection, autoimmune disorders, cancer, and organ transplants rapidly progressive necrotizing retinitis Bilateral involvement in 90% mild anterior segment cellular reaction decreased Involvement of retinal and choroidal vessels More commonly have retinal detachment poor responsive to acyclovir treatment worse visual outcome More recurrence Bilateral involvement in 90% More commonly have retinal detachment(80%) Worse response to the antiviral treatment More recurrence

Diagnosis American Uveitis Society diagnostic criteria 1. 진단기준 (한글판 망막) 1) 주변 망막에 하나 이상의 경계가 분명한 망막괴사 병소 2) 치료하지 않으면 급속히 진행 3) 병변의 진행방향이 측면으로 확산 4) 세동맥의 폐쇄혈관염 5) 유리체와 전방에 염증소견 (시신경증이나 공막염, 안구통은 필수요건이 아님) 위의 다섯 가지 소견이 모두 보여야 ARN 그렇지 않으면 necrotizing herpetic retinopathy The diagnosis of ARN is based on clinical examination characteristic funduscopic appearance

Laboratory evaluation Aqueous humor and/or vitreous fluid Qualitative PCR Quantitative PCR Presence of viral Ab in the pph. Blood not specific finding Serum Ab not necessarily elevated

FAG Not diagnostic arterial phase venous phase recirculation phase focal choroidal perfusion defects venous phase abrupt “cut off” of the intravascular F pattern recirculation phase staining of the optic disc staining of both retinal a & v d/t obliterative vasculitis

Diagnostic vitrectomy or retinal biopsy atypical cases evaluation of intraocular samples with various techniques, such as viral culture, serology, polymerase chain reaction, and histopathologic examination The viral cause of ARN often is difficult to determine in an end-stage atrophic or detached retinal specimens more readily identified in ocular specimens obtained during acute stages of the disease

Differential diagnosis Progressive outer retinal necrosis(PORN) Immunocompromised patients Varicella-zoster retinitis Extensive, rapidly progressing full-thickness necrosis of the retina involving posterior pole No associated AC or vitreous reaction, rare vascular inflammation Poor response of antiviral therapy

Differential diagnosis CMV retinitis immunocompromised individuals the clinical course is chronic and indolent minimal or absent vitreous inflammation initially with 1 or 2 patches of white granular retinal lesions at post. pole Hemorrhage is more common Hematogenous spread no response acyclovir

Differential diagnosis Behcet disease FAG : broom-shaped dye leakage from capillary wall Sarcoidosis Nodular periphlebitis Toxoplasmosis Elevated lesion in chorioretinitis dense yellow-white lesions with better defined borders Inflammation is usually more intense peripheral retina is usually less involved Syphilis Diffuse, patchy necrotizing retinitis, prominent vitritis and vaculitis

Treatment Anti-viral treatment Anti-inflammatory treatment Anti-thrombotic treatment Vitreous surgery

Treatment Anti-viral treatment Acyclovir Induction therapy IV Acyclovir : standard Tx. maintenance therapy Oral acyclovir : after IV acyclovir ( fellow eye에 대한 prophylaxis) Immunocomprimised pt. – more long term maintenance Ganciclovir first-choice of CMV retinitis acyclovir 에 효과 없는 경우에 효과가 있을 수 있음. BM suppression -> pancytopenia Valacyclovir : pro-drug of acyclovir, useful for the initial Tx. - maintenance therapy Alternative antivirals should be considered if the retinitis does not respond in a timely fashion to acyclovir within 3-5 days

Treatment Anti-inflammatory treatment Anti-thrombotic treatment for intraocular and vitreous inflammation IV acyclovir 투여 후 24- 48시간 뒤에 시작 for optic nerve dysfunction(바로 시작) Anti-thrombotic treatment d/t occlusive retinal arteritis and phlebitis Low dosage aspirin(100mg /day) for ischemic optic neuropathy IV acyclovir 투여 후 24- 48시간 뒤에 시작

Treatment Prophylactic Laser Photocoagulation The use of confluent laser photocoagulation posterior to active retinitis has been recommended to prevent retinal detachment. Retinal Detachment Surgery

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