Case Chorioretinal lesion in Immunocompromised Patient

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1 Case Chorioretinal lesion in Immunocompromised Patient
Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea. R3 SY Kim/ Ap.KS Kim Immunocompromised patient 에서 chorioretinal lesion 에 대한 case 발표하겠습니다. Let us begin the case on “chorioretinal lesion in Immunocompromised patient”.

2 C/C Visual defect (OS) on sup.temporal side
Case (M/35) Aug C/C Visual defect (OS) on sup.temporal side 5days ago accompanied with visual acuity decline Aug BMT d/t ALL at Yeoido Sung-mo H. Ocular GVHD(OU) Tx Ocular trauma/op.(-/-) Eyedrop (-) 35세 남자환자가 월 12일에 방문하였다. 5일전부터 superotemporal side부위 visual defect 가 생겼다고 말하였다. 그는 손등에 얼굴을 받친채로 엎드려 자고 나서 부터 발생하였다고 하였고 시력도 저하되었다고 했다. 그는 1년전 ALL 로 BMT 를 받은 환자로 안과는 Ocular GVHD 치료 받은기왕력 이외 없었다. A 35 year-old male visited on August 12th, The chief complaint was visual defect on the superotemporal side, which occured 5days ago. It was also accompanied with visual acuity decline. He had received BMT 1 year ago ,due to ALL. He had no other Ocular Hx other than Ocular GVHD treatment.

3 PAST HISTORY He was diagnosed of ALL , BMT was done 1yr ago (Aug.2008)
Continuous diarrhea which started 4months ago (April~Jun 2009.) R/O Gut GVHD, R/O CMV colitis He had taken Foscarnet Tx still on oral Steriod treatment for GVHD 1 month ago, he was diagnosed of AVN on left hip joint pain 그는 5일전부터 잘 안보이는 증상 외에 다른 전신증상도 가지고 있었다. 4달전부터 지속적인 설사로 R/O GUT GVHD, R/O CMV colitis 가 의심되어 Foscarnet 투여를 받았었으며 GVHD 로 steroid PO 복용 계속하고 있었다. 1달전부터는 좌측 hip joint pain으로 OS 방문하였다 AVN 을 진단받았다. 최근에는 General weakness, anemia URI Sx 동반되어 있었다. He also had systemic symptoms other than visual defect. Due to continuous diarrhea which started 4months ago, he was suspected of having GUT GVHD or CMV colitis. He had taken Foscarnet treatment, and was still on oral Steriod treatment for GVHD. 1 month ago, he was diagnosed of AVN after visiting the orthopedic department on left hip joint pain

4 (OD) (OS) VA (0.8 x ) (n-c x Ax71) IOP 20 mmHg mmHg Cornea Clear AC Deep & clear Pupil round & nl sized, PAS (-) Lens mild nucleosclerosis c PSCO Fds nl optic disc c flat post pole nl optic disc c 1DD sized ovoid, yellowish elevated lesion c serous detachment c Hemorrhage at macula His visual acuity was Slit lamp examination at the anterior segment showed nonspecific finding. But on the fundus examination, 1disc diameter sized ovoid yellowish elevated lesion, serous detachment blot Hemorrhage was found at the macular lesion.

5 Findings of Funduscopy
이 형태는 전형적인 chorioretinitis 소견이 아니어서 원인을 알수가 없었다. This figure is not a typical chorioretinitis finding, so the cause was not clear. 1DD sized ovoid, yellowish elevated lesion c serous detachment c blot Hemorrhage

6 Findings of Macular OCT
Elevated RPE Findings of Macular OCT 는 Elevated RPE Findings of Macular OCT showed Elevated RPE

7 PLAN? Chest PA Lab FAG ICG (OS-OD) 1 week later CBC, BC, ESR, CRP
ACE, C3, C4 Immunoglobulin A, M, D, G, E Viral marker (HBV, HCV, HIV, CMV IgM, IgG, FTA-ABS IgM IgG, Toxoplasma IgM, IgG, HSV IgM, IgG, VZV IgM, IgG) 그래서 환자에게 CBC BC ESR CRP ACE C3Cr, Immunoglobulin, viral marker 검사를 하였다. Chest PA 도 시행하였다. FAG ICG 를 일주일뒤 시행하기로 하였다. So The exam was done included CBC BC ESR CRP ACE C3Cr, Immunoglobulin, and viral markers. Chest PA was also taken. FAG ICG were to be done 1 week later.

8 AFTER 1wk VA 0.06 (0.2x-2.00Ds) IOP 17/12 AC cell (rare) Fundus
increased retinal hemorrhage subretinal yellowish lesion SSRD at parafoveal area /(OS) 일주일뒤 corrected visual acuity 는 0.2 로 떨어졌다. Anterior cell 이 관찰되었다. Fundus exam 에서 retinal hemorrhage 가 증가하였다. After 1 week, corrected visual acuity dropped to 0.2. Anterior chamber cell was found. Retinal hemorrhage increased.

9 AFTER 1wk Findings of FAG
이것은 좌안이다. . The chorioretinal lesions appeared hypofluorescent in the early phases of the study; leakage occurs in the later phases. This is the left eye FAG, leakage occurs in the later phases.

10 AFTER 1wk Findings of ICG
좌안의 ICG 이다. 여기도 FAG 처럼 The chorioretinal lesions appear hypofluorescent in the early phases of the study; leakage occurs in the later phases. Choroid 에도 병변이 있음을 알수 있었다. ICG of the left eye. As in the FAG, the chorioretinal lesions appear hypofluorescent in the early phases of the study; leakage occurs in the later phases. Choroid lesion could be concluded.

11 AFTER 1wk Lab CMV renitis ?? Ocular Tuberculosis ??
CBC & Automated WBC Differertial Count WBC Count 4.31 4.0~10.0 RBC Count 2.78▼ 4.5~5.5 Hemoglobin 8.2▼ 13.0~18.0 Hematocrit 25.8▼ 40.0~54.0 Platelet count 22▼ 150~450 WBC Diff. Count Seg.-neutrophils 64.1 50~75 Lymphocytes 21.1 20~44 Monocytes 14.4 2~9 Eosinophils 0.2 0~5 Basophils 0~2 ANC 계산 2.76 Mean Corp Index MCV 92.8 80~99 MCH 29.5 27~33 MCHC 31.8 33~37 ESR 29 0~15 CRP 0.49▲ 0.01~0.47 Urea Nitrogen 36.8▲ 7.0~20.0 Creatinine 1.42▲ 0.6~1.2 MDRD-GFR 60.301 AST(GOT) 45▲ 14~40 ALT(GPT) 91▲ 9~45 Sodium 141 136~146 Potassium 4.9 3.5~5.1 CMV IgG 14 <6 CMV IgM Positive(3.32) negative FTA-ABS, IgG FTA-ABS, IgM Toxoplasma IgG <10.5 Toxoplasma IgM HSV IgG Positive(1.81) HSV IgM VZV IgG VZV IgM HBs Ag Negative(0.062) Negative(<0.9) HBs Ab 113.1▲ <10 Anti-HCV Ab Negative(0.373) HIV Ag/Ab Negative ACE 23.7 18~55 C3 113 76~139 C4 32.9 12~37 Immunoglobulin G 721▼ Immunoglobulin A 129 Immunoglobulin M 147 33-190 Immunoglobulin D 0.3 1.0~5.1 Immunoglobulin E < 30 <100 ANA 일주일전 시행한 lab 결과는 CMV IgM positive 였다. Chest PA 에서도 atelectasis 가 관찰되었다. 이외에 HemoHema가 떨어져 있었고 plateletl count도 밖에 안되었다. The Lab result 1 week ago showed CMV IgM positive & Toxoplasma antibody and other viral marker antibody negative. So CMV retinitis was suspected. Atelectasis was found in Chest PA. so Ocular tuberculosis could be guessed. Hemo/Hema(?) was low, and platelet count was merely Ocular Tuberculosis ?? Chest PA Linear subsegmental atelectasis in the LLLf.

12 Chorioretinitis of Unknown cause?
In case of chorioretinitis with no prior injury nor surgery Hx, the cause could be ; Idiopathic Inflammation (Infection, hematogenous spread) , - CMV - Tuberculosis - Toxoplasmosis - Fungal endophthalmitis Malignancy (lymphoma or metastasis, leukemic infiltration) EVALUATION Patient systemic symptoms, underlying disease, systemic laboratory testing, clinical finding, response to treatment 이처럼 chorioretinitis 가 있을때 , 외상이나 수술력이 없다면 원인은 Idiopathic, inflammation 특히 hematogenous spread 되는 systemin infection, lymphoma, metastasis 같은 malignancy 를 생각해 볼수 있다. 그래서 원인을 평가할때 Patient systemic symptom,,,등을 고려해야한다. In case of chorioretinitis with no prior injury nor surgery Hx,// the cause could be Idiopathic,// or inflammation, especially systemic infection that could be hematogenously spread,// or malignancy such as lymphoma and leukemic infiltration.// Thus, the Patient’s systemic symptoms.. Etc must be considered in evaluating the cause.

13 Chorioretinitis of Unknown cause?
In case of chorioretinitis with no prior injury nor surgery Hx, the cause could be ; Idiopathic Inflammation (Infection, hematogenous spread) , - CMV - Tuberculosis - Toxoplasmosis - Fungal endophthalmitis Malignancy (lymphoma or metastasis, leukemic infiltration) EVALUATION Patient systemic symptoms, underlying disease, systemic laboratory testing, clinical finding, response to treatment He is immunocompromised state 이처럼 chorioretinitis 가 있을때 , 외상이나 수술력이 없다면 원인은 Idiopathic, inflammation 특히 hematogenous spread 되는 systemin infection, lymphoma, metastasis 같은 malignancy 를 생각해 볼수 있다. 그래서 원인을 평가할때 Patient systemic symptom,,,등을 고려해야한다. In case of chorioretinitis with no prior injury nor surgery Hx,// the cause could be Idiopathic,// or inflammation, especially systemic infection that could be hematogenously spread,// or malignancy such as lymphoma and metastasis.// Thus, the Patient’s systemic symptoms.. Etc must be considered in evaluating the cause.

14 PLAN AC paracentesis (OS) for CMV & Tuberculosis PCR was scheduled
Pulmonology consult for atelectasis , R/O Tuberculosis AC paracentesis (OS) for CMV & TB PCR Negative result Another AC paracentesis(OS) for toxoplasmosis PCR test was scheduled, but the patient was admitted to the Hematology department owing to severe abdominal pain. the Hip joint pain aggravated and Orthopedic surgery was suggested. Colitis, Pneumonia was also diagnosed, Ceftriaxone start CMV titer high & CMV viremia, GCV Tx. ( ~ 9.22 ) Blood culture : Negative 그래서 Anterior chamber paracentesis 를 하여 CMV 와 Tuberculosis PCR 을 검사하기로 하였다. 그리고 호흡기 내과에 consult의뢰하여 tuberculosis evaluation 하기로 하였다. 8월 25일 CMV 와 Tuberculosis PCR 을 위한 Anterior chamber paracentesis 를 시행하였고 2009 년 9월 4일 결과는 negative 였다. 그래서 toxoplasmosis PCR 에 대한 검사를 위해 다시 anterior paracentesis 를 하기로 하였는데 그 사이 환자가 복통으로 혈액내과에 입원하게 되었다. 그 사이 고관절 부위 통증 악화되어 정형외과 수술을 권유받았고 .colitis, pneumonia 진단되어 ceftriaxone 주사를 시작하였따. CMV titer 가 높아 CMV viremia 로 2009년 9월 5일부터 gancyclovir 를 주사맞기 시작하였다. Thus, Anterior paracentesis for CMV and Tuberculosis PCR test was scheduled. And Tuberculosis evaluation was to be done through Pulmonary department consultation. On Aug. 25th, Anterior chamber paracentesis for CMV and Tuberculosis PCR was taken and the result on Sep. 4th was Negative. Therefore, another anterior paracentesis for toxoplasmosis PCR test was scheduled, but he was admitted to the Hematology department owing to severe abdominal pain. During this period, the Hip joint pain aggravated and Orthopedic surgery was suggested. Colitis and Pneumonia was also diagnosed, and Ceftriaxone injection was started. Because of the CMV viremia showing high CMV titer, he took Gancyclovir injection from Sep. 5th to 22th . Blood culture result was negative.

15 Retinal Hemorrhage increased
PROGRESS Sep. 5th AC paracentesis (OS) for Toxo PCR Negative result Sep. 11th while waiting for the result, Visual acuity declined to FC 50cm. Fd increased yellowish choroidal lesion OS Toxoplasmosis 검사를 anterior chamber paracentesis로 하였고 그 검사를 기다리던중 9.11 시력이 FC 50cm 으로 악화되었다. Fundus examination은 incrased yellowish choroidal lesion and retinal Hemorrhage 을 보였고 OCT 에서 ME 가 증가하였다. Toxoplasmosis exam was done by anterior chamber paracentesis.and the result was also negative. // On Sep. 11th, while waiting for the toxo PCR test result, Visual acuity declined to FC 50cm. Fundus exam showed increased yellowish choroidal lesion and retinal Hemorrhage. Retinal Hemorrhage increased

16 PROGRESS General condition worsened R/O Fungal endophthalmitis FC50cm
0.06 General condition worsened AC paracentesis & Intravitreal Amphotericin injection (OS) Gram stain & fungus culture : Negative R/O Fungal endophthalmitis 환자의 전신상태는 점점 악화되었다. 그즉시 바로 intravitreal amphotericin injection 을 시행하였다. 왜냐하면 choroidal lesion 을 포함한다는 점과 환자의 면역억제 상태인점, macula를 침범하는 hemorrhage 가 동반된 whitish plaque를 보이는 망막소견이 이를 시사하기 때문이다. AC paracentesis 한 fluid 를 검사하였다. Gram stain 과 fungus culture 는 negative 였다. 주사 후 4일뒤 환자 시력이 0.06 으로 호전되었다. 그래서 2번째 intravitreal amphotericin injection 을 시행하였고 역시 경과가 더 호전되었다. Toxo PCR 결과는 Negative 였다. 그래서 fungus endophthalmitis 로 추측되었다. His general condition worsened. because of the choroidal lesion, the immuno-compromised state, and the fundus exam that showed whitish plaque with hemorrhage invading the macula suggested Fungal endophthalmitis. Intravitreal amphotericin injection was carried out immediately AC paracentesis fluid was examined. Gram stain and fungus culture result was negative. after the 1st injection , choroioretinal lesion was improved

17 PROGRESS R/O Fungal endophthalmitis
FC50cm 0.06 nd Intravit. Amphotericin inj. (OS) : Sx improved !! So the 2nd intravitreal amphotericin injection was done and the progess showed more improvement after 2 injecton, visual acuity was improved to Thus, fungal endophthalmitis was suspected. R/O Fungal endophthalmitis

18 PROGRESS 2009.10.5. OS Adm for Op. d/t AVN
Consultation from OS VA 0.04 Choroidal lesion clearly decreased 10월 5일 정형외과 수술을 받기 위해 입원하였다. consultation was requested the day befor2번의 주사로 choroidal lesion 은 분명히 감소하였다. He was admitted to the Orthopedic department for surgery on Oct. 5th and consultation was requested the day before the surgery choroidal lesion clearly decreased after the 2 injections.

19 PROGRESS 2009.10.8. OS Adm for THRA : During the operation,
synovium whitish pus gush out culture yeast Post op Wx oozing tip culture yeast pus culture : Candida tropicalis Transferred to the Hematology department Amphotericin B IV ( ~10.21) 다음날 그는 수술을 받았다. 수술중 정형외과의사들은 깜짝 놀랐다. 그들은 AVN이라 생각했으나 예기치 않는 일이 벌어졌다. incision 을 가하자 마자 whitish pus 가 gush out 했기 때문이다. Pus culture 결과는 candida tropicalis 였다. 혈액내과로 전과되었고 환자는 systemic amphotericinB intravenous injection 을 시행받았다. MRI 사진에서 보면 femur head 형체가 분명하지 않고 염증이 심해보이는 상태이다. 이후 한달 뒤 previous lesion 은 줄었으나 but yellow whitish lesion 이 새로 발생하였다. He was operated the next day, and during the operation, Orthopedic surgeons were surprised. They had been thinking of AVN, but as soon as the synovium incision was made, whitish pus gushed out. Pus culture result was Candida tropicalis. He was transferred to the Hematology department and took systemic intravenous amphotericinB injection..

20 PROGRESS Fungal endophthalmitis !!!!!!!!! 08.11.21. MRI : Synovitis
MRI : AVN  in both hips & Lt joint effusion 그는 1년전부터 지속적인 고관절 부위 통증을 호소하였다 찍은 MRI 판독은 단순 synovitis 였고 치료는 NSAID였다 다시 MRI 찍었을때는 정형외과에서는 only AVN, hip Lt. 로 진단되었다. 정형외과는 전신마취하에 수술을 권유하였고 전신상태 악화로 수술을 하지 못하고 있다가 이번에 수술을 하였고 only AVN 이 아니라 candida 로 인한 septic arthritis 였던 것이다. 그래서 그는 fungal endophthalmitis 였던 것이다. He complained of continuous Hip joint pain which started 1 year ago.MRI reading on November 21st, 2008 was Simple synovitis, and was treated with only NSAID. And the MRI was taken again on Aug 19th, 2009, the diagnosis (made by the Orthopedic department) was AVN, hip Lt, and Lt. joint effusion. The Orthopedic department recommended surgery under general anesthesia, but was being delayed due to poor general condition. During the surgery, Not only AVN but also septic candida arthritis was found. Therefore final diagnosis was fungal endophthalmitis. Fungal endophthalmitis !!!!!!!!!

21 PROGRESS R/O Combined CMV retinitis & Blood CMV titer high
POSTOP F/U Fds more decreased previous lesion(OS) but yellow whitish lesion increased (OU) R/O Combined CMV retinitis & Blood CMV titer high Tx : start Antiviral agent again (Gancyclovir (IV))) He already had been taking fluconazole After the orthopedic surgery he visited opthalmology department again. And then We found newly developed lesions on both eyes. It seemed to be CMV retinits. He already had been taking fluconazole. And we added antiviral agent.

22 After 6 months po valgancyclovir & fluconazole Full recovery Whitish retinal lesion Atrophic change at macula (OS) After 6 months, Atrophic change at macula could be seen. The inflammation has all gone, but the final Visual acuity was Finger count.

23 After 6 months Whitish retinal lesion Atrophic change at macula (OS)
VA FC 30cm 이것은 6개월뒤 환자 fundus photography 이다. Atrophic change at macula 이며 염증은 모두 사라졌으나 최종시력은 Finger count 30cm 이었다. After 6 months, Atrophic change at macula could be seen. The inflammation has all gone, but the final Visual acuity was Finger count.

24 Subsequent event Pygenic spondylitis antibiotics , culture (-)
Blood culture (-) Lt knee jt pain synovial fluid culture : Candida tropicalis After 6 mo He had suddenly died of pneumonia. Pygenic spondylitis was also found , he took antibiotics, and the pus culture / blood culture result was (-) He also showed Lt knee joint pain, and the synovial fluid culture result was Candida tropicalis, while Blood culture was (-).