LAPORAN KASUS - ristekdikti

44 • JURNAL ILMIAH KEDOKTERAN

LAPORAN KASUS

A 7 YEAR-7-MONTH OLD BOYWITH LEUKEMIC RETINOPATHY

Ni Made Rini Suari1, Widnyana1, Putu Budhiastra2

Departments of Child Health1 and Ophthalmology2, Medical School, Udayana University Sanglah Hospital Denpasar

ABSTRACT

Ocular problems in patient with leukemia which are called leukemic retinopathy and subhyaloid hemorrhageis one of its feature. Subhyaloid hemorrhage in children with acute lymphoblastic leukemia (ALL) is rarelyhappened. We reported a boy 7 year 7 month old, complained sudden blurred vision on his both eyes anddiagnosed with acute lymphoblastic leukemia. When patient had complained his vision, result of routinehematology showed anemia, thrombocytopenia, and leukocytosis. Treatment of leukemic retinopathy inthis patient was supportive and causal therapy with transfusion of thrombocyte concentrate, hydration forleukocytosis, giving chemotherapy intrathecal methotrexate and systemic (vincristine, daunorubicin, L-asparginase). We found gradually undergone resolution of subhyaloid hemorrhages, visible fl ame shapedthin, and his vision recovered nearly completely to 6/6 OD and 6/20 OS. [MEDICINA 2013;44:44-49]

Keywords: children, leukemic retinopathy, acute lymphoblastic leukemia

SEORANG ANAK LAKI USIA 7 TAHUN 7 BULANDENGAN RETINOPATI LEUKIMIA

Ni Made Rini Suari1, Widnyana1, Putu Budhiastra2

Bagian/SMF Ilmu Kesehatan Anak1 dan Mata2 Fakultas Kedokteran Universitas Udayana/Rumah Sakit UmumPusat Sanglah Denpasar

ABSTRAK

Gangguan penglihatan pada pasien dengan leukemia disebut retinopati leukemia dan salah satu kejadianyang ditemui adalah perdarahan subhyaloid. Perdarahan subhyaloid jarang terjadi pada anak denganleukemia limfoblastik akut (LLA). Kami melaporkan seorang anak laki usia 7 tahun 7 bulan dengan LLAyang mengalami keluhan penglihatan kabur pada kedua mata. Pada pemeriksaan oftalmoskopi ditemukanadanya perdarahan pada subhyaloid. Ketika keluhan muncul, pasien dalam kondisi anemia, trombositopeni,dan leukositosis sesuai sebagai penyebab terjadinya retinopati leukemia. Tata laksana yang diberikan padapasien ini adalah suportif dan kausal, yaitu dengan tranfusi trombosit konsentrat, hidrasi pada leukositosis,kemoterapi sistemik, dan kemoterapi intratekal (vincristine, daunorubicin, L-asparginase). Secara bertahapditemukan resolusi pada perdarahan suhyaloid, penipisan pada lapisan perdarahan, dan perbaikan visuspenglihatan mendekati normal OD 6/6 dan OS 6/20 [MEDICINA 2013;44:44-49]

Kata kunci : anak, retinopati leukemia, leukemia limfoblastik akut

INTRODUCTION

Leukemia is defi nedas a neoplastic blooddisorder characterizedby the overproduction ofabnormal white blood cells.It can be divided into twotypes; myelogenous andlymphoblastic. At least 50%

all leukemias manifest someocular involvement.1 The ocularcomplications of leukemia maybe due to a direct involvementby leukemic infi ltrates orsecondary to concomitantanemia or thrombocytopenia.

Leukemic retinopathyis a common manifestationof leukemia and found

in both acute and chronicforms. Features of leukemicretinopathy include multiplepreretinal and intraretinalhemorrhages are mostcommonly found in theposterior pole. Other features

wool spots, exudates,retinal venous tortuosity,

JURNAL ILMIAH KEDOKTERAN • 45

perivascular sheathing, andneovascularization are alsofound.1

Ocular involvement inleukemia is either due to directinfi ltration of the orbit andother tissues (iris, choroid, opticnerve), vascular abnormalitiesaff ecting the retina (intraretinalhemorrhages, white centralretinal hemorrhages,

hemorrhages, subhyaloidhemorrhages, vitreoushemorrhages), or neuroophthalmic signs (papilloedemasecondary to raised intracranialpressure, isolated cranial nervepalsies) of central nervoussystem (CNS) disease.2

In leukemic case, the timeappearance of ocular evaluationis not specifi ed. It is possiblethat the ocular evaluation isperformed at any time duringthe course of illness, only whenthe patient demonstrated ocularsymptoms, or in patient withhigh risk factors such as centralnervous system leukemia,severe thrombocytopenia ormarked leucocytosis.2,3

Before the era ofeff ective antileukemic therapy,retinopathy is believed to hasno prognostic signifi cance inacute leukemia. However, itis important to consider anocular evaluation at the time ofdiagnosis of acute leukemia inadults and children since recentreports have demonstratedthat the presence of ocularinvolvement is associatedwith poor prognosis in acutechildhood leukemias.4

We reported a casethat demonstrates theappearance of leukemicretinopathy associated with

extensive retinal hemorrhages(subhyaloid hemorrhages)occurring in the absenceof trauma in a patient withALL. We reported the clinicalfeatures, relevant literature,and suggested mechanismsfor subhyaloid hemorrhages insuch a situation.

CASE REPORT

A 7 year 7 month oldboy who was born and livedin Mengwi, was referred fromKapal Hospital with suspectleukemia. He came to KapalHospital with chief complaintsfever, pale, and distendedabdomen. He suff eredfrom fever 3 weeks beforehospitalized. Fever withoutcoughing, diarrhea, dyspneu,dysuria, and convulsion. Othersymptom was pale since 2weeks before hospitalized,started from eyelids and lipsand spread on his hands andfoots. There were no history ofbleeding on skin and gum norredness urine or blackish stool.

When treated at RSUDKapal on September 22nd, 2011,he had undergone routinehematology and blood smearevaluation. Result of routinehematology was leukocyte 41.6x (neutrophil 4.79, lymphocyte34.7, monocyte 1.72) 103/µL, hemoglobine 8.71 g/dL,hematocrite 25.8%, MCV 70.6fl , MCH 23.8 pg, MCHC 33.80g/dL, RDW 14.70, platelets 21.7k/uL, and blood smear resultwas suspicious for ALL.

On September 26th 2011,he came again to Kapal Hospitalwith severe pale, fever, andpain of his leg. When he arrivedat Kapal Hospital, his doctor

gave advice to go to SanglahHospital in order to do followthrough examination.

Blood examinationwas taken when he wentto Sanglah Hospital, andshowed similar results, highWBC count with lymphocytepredominance, normochromicnormositic anemia with lowplatelet count (leukocyte60.20 k/µL, neutrophil 4.14k/µL, lymphocyte 50.32 k/µL, monocyte 4.14 k/µL,hemoglobine 5.77 g/dL,hematocrite 17.78, MCV 68.40fl , MCH 23.11 pg, MCHC 33.79g/dL, RDW 14.06, platelets 20 k/uL. Blood smear was evaluatedand showed erythrocytenormochromic, anisocytosis,normoblast, leukocyteincrease, homogen lymphoblastpredominance, decrease ofplatelets, and was concludedwith suspicion ALL (L1). AtSanglah hospital patient waslater undergone bone marrowaspiration (BMA) to confi rmthe diagnosis. Therapy appliedwas hydration for leukocytosis,transfusion of packed red cell(PRC), transfusion of platelets,and nutritional therapy.

After 12 days of treatment,

appetite and bone marrow wasdone. Laboratory result showedleukocyte 67.40 k/µL neutrophil3.49 k/µL, lymphocyte 58.63k/µL, monocyte 3.34 k/µL, hemoglobine 8.1 g/dL,hematocrite 22.48%, MCV73.49 fl , MCH 26.52 pg, MCHC36.09 g/dL, RDW 17.66,platelets 24.29 k/uL. Resultof bone marrow aspirationwas hypercellularity, eritroidsystem decreased activity,mieloid system decreased

A 7 Year-7-month Old Boy With Leukemic Retinopathy | Ni Made Rini Suari, Widnyana, Putu Budhiastra

MEDICINA • VOLUME 44 NOMOR 4 • JANUARI 2013


activity, megakariocyte systemdecreased activity, other cellshowed >50% infi ltration oflymphoblast with homogenmorphology small size, andconclusion appropriate ALL(L1).

On-day 19 (October15th, 2011) he started to hasblurred vision and fl aresensation on both eyes.There was no ocular or headtrauma, no history of blackishstool, nose bleeds nor easybruising. In that time, routinehematology was leukocyte139.50 k/µL, neutrophil 2.69k/µL, lymphocyte 116.40k/µL, monocyte 0.41 k/µL,hemoglobin 6,30 g/dL (MCV77,0 fl , MCH 28,40 pg, MCHC36,80 g/dL), hematocrite 17.10%,RDW 18.10, platelets 11 k/µL,LUC 14.30%.

Patient then consulted toOphthalmology Departmentand examination was doneat the bedside secondary topatient’s weakness and nausea.Visual acuity was 5/60 oculidextra (OD) and 3/60 oculisinistra (OS), pupils were 4mm and reactive, with noevidence of a relative aff erentpapillary defect. Anteriorsegment examination wasgrossly normal. Conclusionfrom ophthalmologist wasleukemic retinopathy on botheyes and later examined withfunduscopic.

On-day 23 of treatment(October 19th, 2011) funduscopicwas done and showed anteriorsegment ODS were normal.Posterior segment OD showedpale retina, subhyaloidhemorrhages in inferior maculawith Roth spots at inferonasalquadrant, fl ame shaped at

Figure 1. Funduscopic examination at October 19th 2011, showed manifestationhemorrhages was fl ame shaped with fl uid level.

Ocular dextra Ocular sinistra

Figure 2. Funduscopic at November 17th 2011.

superotemporal, and superiorquadrant. Posterior segment OSshowed pale retina, subhyaloidhemorrhages in inferiormacula, and fl ame shaped at

superotemporal (Figure 1).Acute lymphoblastic

leukemia treatment started fromOctober 22nd 2011 using high risk2006 protocol. On October 26th

2011, methothrexate intrathecalwas administered, accompaniedwith liquor cerebrospinalis(LCS) analysis to examinewhether blast cell invade CNS.Liquor cerebrospinalis analysiswas performed to diff erentiateblurring vision from blastinvasion to CNS especiallyoptic nerves. Result from LCSanalysis found no blast cell.

On November 17th

2011, we made secondevaluation for blurring vision.Ophthalmologist found VA OD6/30 OS 6/60, anterior segment

ODS was normal. Posteriorsegment OD showed volumeof hemorrhages of subhyaloidwas decreased without Rothspots and thin fl ame shaped.

Posterior segment OS showeddecreased of volume subhyaloidhemorrhages (Figure 2).

Third evaluation thatmade on November 25th

2011 found improvementon vision capability withVA 6/12 and 6/30 (Figure 3).Ophthalmologist evaluationon December 22nd 2011 foundno blurring vision with VA 6/6,anterior segment was normal,and posterior segment showedsubhyaloid hemorrhageswith improvement. On lefteye we found visus 6/20 withnormal anterior segment andimprovement of subhyaloidhemorrhages on posteriorsegment (Figure 4). UntilDecember, patient had 6 times


chemotherapy L-Asp 6000µ/m2, 5 times of Daunorubicin 30mg/m2, 7 times of vincristine1,5 mg/m2, and 4 times ofmethothrexate intrathecal.Routine hematology was doneand showed leukocyte 2.27 k/µl,neutrofi l 35.4 k/µL, lymphocyte49,98 k/µL, hemoglobin 10.6 g/dL (MCV 83.10; MCHC 37.90),hematocrite 32.10%, platelets501 k/µL.

DISCUSSION

Leukemia is an abnor-mal proliferation of one ormore cell lines in the blood atthe expense of the normal celllines. Diff erentiation of leuke-mic type is determined by theline of hematopoiesis (lympho-blastic versus myelocytic) andthe rate of progression (acuteversus chronic), with acute leu-kemias making up the majorityin those under 20 years of age.Acute lymphoblastic leukemia(ALL) accounts for approxi-

mately 80% of acute leukemias,which acute myeloid leukemia(AML) responsible for the re-maining 20%.5

The retina is involved inleukemia more often than anyother ocular tissue. The earlymanifestations (because of he-matological disturbance) arevenous dilatation and tortuos-ity. Hemorrhages may occur inall levels of the retina, usuallyin the posterior pole, and mayextend into the vitreous.6

Ocular involvement inleukemia is either due to di-rect infi ltration of the orbit andother tissue (iris, choroid, opticnerve), or vascular abnormali-ties aff ecting the retina (intra-retinal hemorrhages, whitecentered retinal hemorrhag-

lar hemorrhages, subhyaloidhemorrhages, vitreous hemor-rhages), or neuro ophthalmicsigns (papilloedema secondaryto raised intracranial pressure,isolated cranial nerve palsies)

of CNS disease.6,7 In our case,patient was a boy aged 7 year 7month old and diagnosed withALL according to the clinical

pathologic feature. He had sud-denly blurred vision.

Leukemic retinopathy ismost often manifestation usedto denote the ocular manifesta-tion of anemia, thrombocytope-nia and increased blood viscos-ity seen in patients with leuke-mia. Prevalence of leukemicretinopathy was 49%.8 It hasbeen suggested that leukemicinfi ltration of the ocular is re-lated to high leukocyte countsand that ocular hemorrhagesare associated to anemia and/orthrombocytopenia.9,10

Ocular hemorrhages arethe most striking feature ofleukemia. They tend to occurmost commonly at the poste-rior pole, may be at any level ofthe retina and may extend intothe subretinal or vitreous spac-es.10 Retinal hemorrhages havebeen described as dot and blot,or fl ame-shaped, or, classically,as white-centered hemorrhages(Roth’s Spot). It has been pro-posed that these white centredhemorrhages represent an ac-cumulation of leukemic cells,or platelet fi brin aggregates.9,10

The role of anemia in thecase of retinal hemorrhageshad focused by several authors.The critical blood levels belowwhich retinal hemorrhagesmay occur are stated to be ahemoglobin concentration of40 percent and an erythrocytecount of 1,500,000/mm. Severeanemia may result in hypoxia.This is a potent stimulus to thedilatation of retinal veins. Suchvenous dilatation contributes to

Figure 4. Funduscopic at December 22nd 2011.

Figure 3. Funduscopic at November 25th 2011.


MEDICINA • VOLUME 44 NOMOR 4 • JANUARI 2013


capillary engorgement and in-creased fragility, thus, the stageis set for easy bleeding. Capil-lary fragility may be further in-creased by thrombocytopenia,hypoxia or by bacterial toxins,and those combination of sev-eral factors which may produceretinal hemorrhages, and it isquite diffi cult to evaluate theindividual role of any one of theformed elements of the blood.10

In our case, we found whenpatient had complained his vi-sion, result of routine hematol-ogy showed anemia, thrombo-cytopenia, and leukocytosis.That time, patient confi rmedwith ALL (L1). Funduscopicshowed there was bleedingfl ame shaped with Roth spotsas well as subhyaloid hemor-rhages in inferior macular onright eye. On the left eye seenany hemorrhages fl ame shapedand subhyaloid hemorrhagemore spacious if compared tothe right eye. This picture waslikely caused by anemia and/orthrombocytopenia.

Hyperviscosity conditioncan cause venous occlusioncharacterized by the formationof microaneurysma, hemor-rhages of the retina, and neo-vascularisation. Blockage ofvein leads to hypoxia of retinaltissue layer and nerve fi bers of

wool spots.10 In our case, sub-hyaloid hemorrhage can causeof hyperviscosity of blood otherthan thrombocytopenia condi-tion with level of leukocyte 139k/µL (leukocytosis).

The funduscopic appear-ance of preretinal blood de-pends on its age and the size andshape of the blood fi lled space.Fresh preretinal blood usually

look like a fl ame shaped, semi-lunar, crescentic, or geographicaccumulation of dark red bloodoverlying and obscuring itssource. Within time the sameaccumulation of blood canshowed semilunar or crescen-tic in shape, with a fl uid level

of the formed elements.10

Flame shapedhemorrhages are bright red, andlozenge shaped with a striatedor serrated outline on at leastone margin, and they follow thecourse of the retinal nerve fi brelayer. They occur in the posteriorpole of the fundus and areassociated with disorders of thesuperfi cial radial peripapillarycapillaries.10

Various modalities oftreatment for subhyaloidhemorrhage are availableincluding pars plana vitrectomyand pneumatic displacementby intravitreal use of gas andtissue plasminogen, Nd: YAGor green argon laser posteriorhyaloidotomy is safe andeasy alternative for releasingthe entrapped subhyaloidblood into the vitreous andby this way absorption ofblood cells in facilitated.The need for unnecessarygeneral anaesthesia in alreadycompromised leukemicchildren and vitrectomy and itscomplications are avoided.7

Vitrectomy in childrenis an alternative treatment forsubhyaloid hemorrhage butgeneral anaesthesia in alreadycompromised. Child is riskyand may be associated withnumerous complications;cataract, intraoperative retinalbreaks and proliferativevitreoretinopathy. Perforate

the posterior hyaloid face orinternal limiting membraneby use of pulsed Nd: YAGlaser has been described asa practical substitution tovitrectomy. The only drawbackparticularly in children is lackof cooperation.7 In comparisonto vitrectomy, the laserprocedure is the ambulatoryand painless procedure. TheNd: YAG laser hyaloidotomywill not aff ect the outcome ofdeferred vitrectomy. In ourcase, we did not performedvitrectomy and posterior Nd:YAG laser hyaloidotomy. Wehave known that subhyaloidhemorrhages happeneddue to ALL. The precisemanagement was intrathecaland systemic chemotherapy.Ophthalmologist decided toobserved the VA and frequentlyfunduscopic examination. If,there is no development ofvisual acuity and resorptionof hemorrhage for 6 weeks,they will be undergoneintervention.

Leukemic retinopathyis usually not treated directly.Systemic treatment involvesthe use of chemotherapy,immunotherapy, andradiotherapy. Intraocularleukemic infi ltrate is besttreated with chemotherapy thatis appropriate for the type andstage of leukemia.10 Supportivetherapy with transfusions,antibiotics, and hematopoieticgrowth factors are alsoimportant. Although there is nosystematic treatment protocolfor cases of ocular leukemicinfi ltration, many oncologistsand ophthalmologists supportorbital irradiation as a necessarycomponent of treatment for the


best chance of cure.10 This isbecause the eye is thought tobe part of the central nervoussystem, which is often resistantto systemic chemotherapy.The central nervous system isconsidered a pharmacologicsanctuary for leukemic cells,and prophylactic irradiationwith or without intrathecalchemotherapy is given in manycases.7 In our case, after beinggiven chemotherapy intrathecalmethotrexate and systemic(vincristine, daunorubicin,L-asparginase) graduallyundergone resolution ofsubhyaloid hemorrhages,visible fl ame shaped thin.His vision recovered nearlycompletely to 6/6 OD and 6/20OS.

Ridgway (quoted from10)reported that 80% of childrenwith acute leukemia diedwithin 10 months followingocular complications. Someliterature found a signifi cant(P < 0.05) decrease in the 5-year survival rate (21.4%versus 45.7%) in children withacute leukemia and ocularinvolvement compared tothose without ocular disease.3

They reported that 96.4% ofchildren with acute leukemiadied within 28 months from theonset of ocular manifestation.10

In our case, prognosis patient isunknown because his treatmentfor ALL it is still in progress. Thepresence of ocular involvementin children with ALL is usuallya poor prognostic indicator

SUMMARY

IPA 7 year 7 month oldboy from Mengwi with chiefcomplaint fever, pale, and

distended of his abdomen. Hediagnosed with ALL (L1) sinceOctober 8th 2011 with bonemarrow aspiration. At October15th 2011 he had blurred visionand fl are. He got examinationfrom ophthalmologist. Resultof ocular examination, visualacuity was 5/60 OD and 3/60OS, pupils were 4 mm andreactive. Conclusion fromophthalmologist was leukemicretinopathy on both eyesand later examination withfunduscopic. ALL treatmentstarted from October 22nd

2011 using high risk 2006protocol. After treated with 6time L-Asp 6000 µ/m2, 5 timeof Daunorubicin 30 mg/m2, 7times of vincristine 1,5 mg/m2,and 4 time of methothrexateintrathecal until December 2011and funduscopic examinationevaluation was done showedgradually occurring resolutionof subhyaloid hemorrhagesand visible fl ame shaped thin.His vision recovered nearlycompletely to 6/6 OD and 6/20OS.

REFERENCES

1. Conter V, Rizzari C, Sala

M, Biondi A. Acutelymphoblastic leukemia.Orphanet Encyclopedia.2004;14:1-13.

2. Sharma1 T, Grewal J,Gupta S, Murray P.Ophthalmic manifestationsof acute leukaemias : Theophthalmologist’s role.Eye. 2004;18:663–72.

3. Levin AV. Retinalhemorrhages: Advancesin understanding. PediatrClin N Am. 2009;56:333–44.

4. Schmidt D. The mystery of

of recent and historicaldescriptions. Eur J MedRes. 2008;13:231-66.

5. Parija S, Roy AK, editors.Ocular manifestationsof acute leukemia inchildhood – A prospectivestudy. Proceeding of the12th MEACO InternationalCongress; 2012 16-20February; Abu Dhabi.United Arab Emirates:WOC; 2012.

6. Park SW, Seo MS.Subhyaloid hemorrhagetreated with SF6 gasinjection. Ophthalmicsurg lasers imaging.2004;35:335-7.

7. Rennie CA, Newman DK,Snead MP, Flanagan DW.Nd:YAG laser treatmentfor premacular subhyaloidhemorrhage. Eye.2001;15:519–24.

8. Tonotsuka T, Imai M, SaitoK, Iijima H. Visual prognosisfor symptomatic retinalarterial macroaneurysm.Japan J Ophthalmol.2003;47:498–502.

9. Durukan Ah, KerimogluH, Erdurman C, DemirelA, Karagul S. Long-term results of Nd:Yag laser treatment forpremacular subhyaloidhemorrhage owing tovalsalva retinopathy. Eye.2008;22:214–8.

10.Reddy SC, Jackson N, MenonBS. Ocular involvement inleukemia – A study of 288cases. Ophthalmologica.2003;217:441-5.


Documents

LAPORAN KASUS - ristekdikti