Acyclovir Resistant , VZV-ARN R3 김소윤/Pf.이원기

CASE 1

M/40 박O이 C.C) Dec.VA(OD) for 12 days ARN(OD) 진단하에 Zovirax 750mg i.v,(7days), Aspirin 100mg p.o 로 치료중이던 중 증상 호전없어 내원. P.Hx)N-S VA 0.04/0.63 IOP 20/10 mmHg Conj. OD mild injected OS not injected Cornea OD multiple mutton fat KP(+) OS clear AC OD deep & cell(+++) OS deep & cell(-) Pupil OD round & dilated d/t cycloplegics OS round & normal sized, LR(+) Lens OD mild cortical opacity OS mild cortical opacity Fds OD blurry visible . mottled app. macula.vit. cell(++), retinal Hm(+) OS nl optic disc c flat retina

Lab CMV, HIV, HBV, HSV, Toxoplasma,FTA-ABS: N-S Varicella Zoster Virus PCR + C3(151 ),C4(47.8 ) CRP(1.65 )

Imp : Acyclovir Resistant , VZV-ARN(OD) Plan : Intravenous Foscarnet + Intravitreal Ganciclovir(OD)

1 day later Bun/Cr 31.5 / 3.96 Acute Renal Failure !! Intravenous treatment 를 중단하고 Intravitreal Foscarnet inj.(OD) 를 1주간격으로 시행하기로 함

2010.3.9 Intravit. Ganciclovir inj.(OD) 2010.3.15 Intravit. Foscarnet inj.(OD) 2010.3.22 Intravit. Foscarnet inj. (OD) 2010.3.29 Intravit. Foscarnet inj. (OD) 2010.4.5 Intravit. Foscarnet inj. (OD) 2010.4.12 Intravit. Foscarnet inj. (OD) 1 1 week after 1st injection 1 week after 2nd injection

1 week after 5th injection 3 weeks after 5th injection 3 months after 5th injection 4 months after 5th injection

2010.8. 16 2일간 커튼처럼 우안이 가려보이는 증상으로 내원 Imp: ARN c RD c TRD(OD) Op.: ppV+MP+endolaser+PFCL inj. & removal+FAE +SO inj.(OD)

CASE 2

F/65 박O숙 C.C) Dec.VA(OS) for 6 days ARN(OS) 진단하에 Acyclovir iv1500mg/day x 2days, Ganciclovir iv 500mg/day x10days로 치료 받았으나 증상 호전없어 내원함. P.Hx)HBP(+) VA 1.0/0.08(N-C) IOP 16/7 mmHg Conj. OD mild injected OS subconj. Hm Cornea OD clear OS mod. Edematous c DM’s folding(+), diffuse SPK’s, microbullae(+) AC OD deep & cell(-) OS deep & cell(+) Pupil OD round & normal sized, LR(+) OS round & normal sized, LR(+) Lens OD mild cortical opacity OS mild cortical opacity Fds OD nl optic disc c ppa, flat retina OS nl optic disc c vit. opacity(++), yellow whitish exudative infiltration at sup. area, retinal Hm(+)

Lab CMV, HIV, HBV, HSV, Toxoplasma,FTA-ABS: N-S Varicella Zoster Virus PCR +

Imp : Acyclovir Resistant , VZV-ARN(OS) Plan : Intravenous Foscarnet + Intravitreal Ganciclovir(OS)

2010.7.19 Intravit. Ganciclovir inj.(OS) + Intravenous Foscarnet inj. (9g/day)X 14days

1 week after 1st injection 1 week after 2nd injection 12 days after 2nd injection 3 weeks after 3rd injection

2009.10.19 3일간의 좌안의 시력저하로 내원 Imp: TRD d/t ARN(OS) Op.: ppV+MP+tractional membrane removal+retinotomy+endodiathermy+FAE+PFCL inj. +AFE+PFCL removal+endolaser+SO inj.+encircling(OD)

Review

Diagnosis Diagnostic criteria (by American uveitis society) 1) Designation of ARN should be based only on clinical appearance and course of infection. A) one or more foci of retinal necrosis with discrete borders located in the peripheral retina. Macular lesions are uncommon but may be present. B) rapid progression of disease (advancement of lesion borders or development of new foci of necrosis) if antiviral therapy has not been given. C) circumferential spread of the disease . D) evidence of occlusive vasculopathy with arteriolar involvement. E) prominent inflammatory reaction in the vitreous and anterior chamber. 2) Characteristics that support but are not required for the diagnosis A) optic neuropathy/atrophy B) scleritis C) pain 3) The definition does not depend on the extent of the necrosis. 4) The definition does not depend on the immunologic status of the host. 5) The designation is not influenced by isolation of any virus or pathogen from ocular tissues or fluid.

Causes Varicella-zoster virus Herpes simplex virus 1 Cytomegalovirus Epstein-Barr virus

Progression -Episcleritis or scleritis, periorbital pain, and anterior uveitis -Decreased vision resulting from vitreous opacification, necrotizing retinitis(deep, multifocal, yellow-white patches, typically beginning in the peripheral fundus and t hen becoming concentrically confluent and spreading toward the posterior pole), optic neuritis or neuropathy. -Vasculitis with perivascular hemorrhages, sheathing, and terminal obliteration of a rterioles by thrombi. -Rhegmatogenous retinal detachment (75%) -Pigmentation of the peripheral lesions begins at their posterior margins, leaving a scalloped appearance ,frequently accompanied by retinal breaks at the junction of normal and necrotic retina. -Giant retinal pigment epithelial tears may develop.

has not been determined Optimal Treatment Intravenous Acyclovir 7-10 days  oral antiviral medication for several weeks Usually retinal lesions regress 3.9 days after treatment Alternative antivirals should be considered if the retinitis does not respond in a timely fashion to acyclovir within 3-5 days Optimal Treatment for Acyclovir Resistant ARN has not been determined

Foscarnet : Not activated by thymidine kinase : Effective in treating infections caused by virus mutants that do not induce thymidine kinase : Side Effects - renal toxicity - electrolyte abnormalities - alterations in calcium/phosphorus metabolism does not require virus-encoded TK to be functional.  This is the only FDA approved treatment not dependent on TK activity ACYCLOVIR 가 RESISTANCE 생기는 기전은 – 고유 enzyme 인 thymidine kinase 의 변화 때문.,

Treatment in ARN Traditional Acyclovir Intravenous treatment Adjunctive treatment with intravitreal antiviral drugs (Foscarnet + Ganciclovir) Oral antiviral drugs (Valacyclovir , Famciclovir)

Treatment in Acyclovir Resistant ARN Switch to Intravenous Foscarnet, Ganciclovir Combination antiviral therapy (Foscarnet + Acyclovir or Ganciclovir) Adjunctive treatment with intravitreal antiviral drugs (Foscarnet + Ganciclovir)

Good results with intravitreal injections in Acyclovir Resistant ARN Intravitreal injections of Ganciclovir (2000µg/0.05ml) and Foscarnet (1200µg/0.05ml) were administered every other day, 4 times Intravitreal injections of Ganciclovir (2000µg/0.05ml) 2 times , 3 days apart Intravenous Foscarnet & Acyclovir + intravitral Ganciclovir (2000µg/0.05ml) on alternate days for 3 times We cannot directly attribute clnical improvement to intravitreal ganciclovir it served as a safe adjunctive treatment, which we believe conributed to resolution of the patien’s retinitis Intravitreal Antiviral Injections as Adjunctive Therapy in the Management of Immunocompetent Patients with necrotizing Herpetic Retinopathy Am J Ophthalmol. 2000;129:811-3.

감사합니다.