405CASE REPORT

Received for publication 02/06/2015 - Accepted for publication 27/10/2015The authors declare no conflicts of interests.

1 Ophthalmology Department of Universidade Federal do Paraná, Curitiba, PR, Brazil.2 Hospital de Olhos de Curitiba, PR, Brazil.3 Medicine School of Universidade Federal do Paraná, Curitiba, PR, Brazil.

Manifestações oftalmológicas deSíndrome de Klippel Trenaunay

Ophthalmological manifestation ofthe Klippel Trenaunay Syndrome

Carlos Augusto Moreira Júnior1, Carlos Augusto Moreira Neto2, Nicole Tássia Amadeu3, Mariela Regina Dalmarco Ghem3

ABSTRACT

The Klippel-Trenaunay Syndrome (KTS) is a rare congenital disease, which the prevalence is higher in males, and its incidence of 2-5:100,000. It is presented in its classic form as the triad of port-wine stains, enlarged limbs and venous and / or lymphatic malformation.The diagnosis is essentially clinical and due to the complexity of the syndrome, the progressive characteristic and the wide variety ofclinical presentations, a multidisciplinary team should treat patients individually. The ocular changes associated with KTS includevascular, orbit, iris, retina, choroid and optic nerve abnormalities. Case report: A 23-year-old female patient, carrier KTS, being followedat Vision Center - Federal University of Paraná, complaining of decreased visual acuity in the right eye. The patient had port-wine stainsin right hemibody and hypertrophy of ipsilateral members. Glaucoma was diagnosed and eye exams were performed to assess the degreeof impairment of visual fields and fundus. The best correction was checked at 20/100 OD and 20/20 OS. At fundoscopy, there wasincreased excavation of the optic nerve right - 0.75 x 0.90 mm. Clinical treatment was chosen with Dorzolamide Hydrochloride,Latanoprost, Brimonidine and Timolol, presenting good long-term results - the tonometry showed 19 mmHg OD and 15 mmHg OS,despite the difficulty in stabilizing the disease. Conclusion: Reports have shown that the results of clinical and surgical treatments ofglaucoma in association with KTS are unsatisfactory compared to other types of glaucoma - clinical control is not possible in about 1/3 of patients and the surgical management has a high rate of complications. Significant studies are needed to establish the correlationbetween glaucoma and KTS, and base the treatment of choice.

Keywords: Glaucoma/complications; Glaucoma/diagnosis; Klippel-Trenaunay-Weber syndrome; Capillaries/abnormalities

RESUMO

A Síndrome de Klippel-Trenaunay (SKT) é uma doença congênita rara, com maior prevalência no sexo masculino e incidência de 2-5:100.000. Apresenta-se, na forma clássica, como a tríade de manchas vinho porto, hipertrofia de membros e malformação venosa e/oulinfática. O diagnóstico é essencialmente clínico e devido à complexidade da síndrome, de natureza progressiva e ampla variedade deapresentações clínicas, os pacientes devem ser tratados de forma individualizada por uma equipe multidisciplinar. .Alteraçõesoftalmológicas associadas à SKT incluem anormalidades vasculares da órbita, íris, retina, coroide e nervo óptico. Relato de caso: Pacientede 23 anos, sexo feminino, portadora de SKT, em acompanhamento no Centro da Visão – Universidade Federal do Paraná, com queixade diminuição da acuidade visual em olho direito. A paciente apresentava manchas vinho porto em dimidio direito e hipertrofia demembros ipsilateral. Foi diagnosticado glaucoma e realizados exames complementares oftalmológicos a fim de avaliar o grau decomprometimento dos campos visuais e o fundo de olho. A visão com a melhor correção foi de 20/100 OD e foi de 20/20 OE. Àfundoscopia, constatou-se aumento da escavação do nervo óptico à direita – 0,75 x 0,90 mm. Optou-se por tratamento clínico comCloridrato de Dorzolamida, Latanoprosta, Brimonidina e Timolol, com bons resultados a longo prazo – a tonometria de aplanaçãomostrou 19 mmHg OD e 15 mmHg OE, apesar da dificuldade na estabilização da doença. Conclusão: Relatos demonstram que osresultados dos tratamentos clínico e cirúrgico do glaucoma em associação à SKT são insatisfatórios quando comparados a outros tiposde glaucoma – o controle clínico não é possível em cerca de 1/3 dos pacientes, e o manejo cirúrgico tem alto índice de complicações. Sãonecessários estudos mais expressivos que estabeleçam a correlação entre glaucoma e SKT e embasem o tratamento de escolha.

Descritores: Glaucoma/complicações; Glaucoma/diagnóstico; Síndrome de Klippel-Trenaunay-Weber; Capilares/anormalidades.

Study carried out at Centro da Visão do Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, PR, Brazil.

Rev Bras Oftalmol. 2016; 75 (5): 405-8

Rev RBO _Set_Out_2016 _Inglês_Com Revisão Final.pmd 29/9/2016, 21:08405

DOI 10.5935/0034-7280.20160082

406 Júnior C A M , N eto C A M , A m adeu N T, G hem M R D

IN TRO D U C TIO N

In 1900, K lippel and Trenaunay described a rare congenitalm alform ation characterized by abnorm alities in m esoderm alcom ponents.The incidence of SK T, m ore prevalent in m ales,

is 2-5:100,000, and its pathogenesis has not yet been com pletelyclarified.(1) Studies suggest that the m ajority of cases results fromsom atic m utations involving genes responsible for em bryonicangiogenesis.

The classic description of K lippel-TrenaunaySyndrom e(K T S) is clinically defined by the triad:(1) capillary m alform ation,often port w ine stain, in the affected extrem ity or at anotherlocation other than the hypertrophied lim b; (2) bone or softtissue hypertrophy, or both; (3) varicose veins and venousm alform ations, som etim es w ith persistent em bryogenic lateralveins.Tw o of the three m anifestations are necessary for thediagnosis of K T S.The lesions shall be present at birth, and inabout 75% of patients it appears before 10 years of age, w ith notendency to involution.(1-5)

O phthalm ologic changes associated to K T S includevascular abnorm alities of the orbit, iris, retina, choroid, and opticnerve.T he findings include:orbital varices, retinalvaricoses,choroidal and m elanom aangiom a, persistent fetal vasculature,heterochrom ia iridum , strabism us and glaucom a.(5-7)

C A SE R EPO RT

F.M .P, fem ale, 23 years old, from Irati, Paraná,w ent to C en-tro da V isão da U niversidade Federal do Paraná (U FPR ) inC uritiba, Paraná, in order to re-evaluate the visual acuity andglaucom a.

T he patient reported previous diagnosis of glaucom a inR E associated to asym m etry of low er lim bs and w ine-coloredstains in the right hem ibody since childhood.She denies othercom orbidities or fam ily history of glaucom a or sim ilar cases.Inuse of ophthalm ic solutionsof D orzolam ide H ydrochloride,L atanoprost and C om bigan (B rim onidine + Tim olol).

T he physical exam ination show ed port w ine stains on righthem ibody(F igures 1A , 1B and 1C ) and left low er lim bhypertrophy.

Figure 1A : Portw ine stains in the right hem iface, including the right earSource: The author (2015)

Figure 1B : Portw ine stains in the right low er lim bSource: The author (2015)

Figure 1C : Portw ine stains on the right upper lim bSource: The author (2015)

O n exam ination, the patient show ed buphthalm os in R E(Figure 2), w ith extrinsic m otility preserved.In the exam inationof m otor skills and eye sensitivity, the pupils w ere isochoric andphotoreactive, and reflections of pairs of N C III, IV, V and V Iw ere preserved.T he endoscopy show ed the presence of bilate-ral red reflex and increased excavation of the optic nerve to theright – 0.75 x 0.90 m m (Figure 3).

T he R E had the best correction of 20/100, and the L Ew as 20/20. A pplanation tonom etry show ed 19 m m H g in R Eand 15 m m H g in L E .B iom icroscopy evaluation of the opticnerve show ed asym m etry betw een the excavations of both eyes,w ith increased excavation / disc ratio in R E , denudation ofcircunlinear vessel, diffuse arteriolar narrow ing, peripapillaryatrophy, and located pallor in the neuroretinal rim .

P erim etry show ed peripheral loses of visual field inR E .In order to evaluate the functional dam age of glaucom a,L inear C om puterized Perim etry, strategy Fastpav 24-2 w asused (Figure 4).

T he m easurem ent of the retinal nerve thickness in R E w ithnerve fibers analyzer O C T-G D x show ed loss of D ouble hum p(physiological peaks in the upper and low er regions), w ith areasoutside norm al lim its, and decreased thickness in the upper,bottom and central areas (95% C I); tem poral region w ithin thenorm al range (Figure 5).

Figure 2: B uphthalm os in the right eyeSource: The author (2015)

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407

D ISC U SSIO N

SK T has been used as a synonym of K lippel-Trenaunay-Weber Syndrome (KTWS)(2) The Sturge-W eber Syndrom e (SW S),also a sporadic and rare neuro-oculocutaneous congenitalm alform ation, is characterized by encefalofacialangiom atosis -. portw ine stains of the face, m ost com m only follow ing the distributionof N C III; glaucom a and vascular lesions of the ipsilateral side ofthe brain and m eninges.(2) H ow ever, the K T W S is considered aseparate entity, consisting of the triad K lippel-Trenaunayaccom panied by a clinically apparent arteriovenousfistula characteristic of SW S, a com ponent indicating the w orstprognosis.(4, 5) The incidence of SW S is 1:50,000(8), and there is noracial or gender difference (9), w hereas K T S is m ore prevalent inm ales, 2-5: 100,000. The association betw een SW S and K T S resultingin K T W S is not usual.(2)

In 1956, Schnyder et al.(10) correlated K lippel-Trenaunay,Sturge-W eber and K lippel-Trenaunay-W eber syndrom es, alsocalled Parkes-W eber syndrom e.They suggested that the threesyndrom es are variants w ith the sam e m ain characteristic - localgigantism and hem angiom a.T he involvem ent of the head andneck, w ith m eningeal angiom atosis, causing epileptic seizures andchoroidal hem angiom a or glaucom a, results in SW S.G igantismand hem angiom a in the lim bs w ith bone hypertrophy arecharacteristic of K T S, K T W S,in case of significant arteriovenousm alform ation.D ue to the sim ilar behavior of the syndrom es, it issuggested that they have the sam e basic pathophysiology, show ingdifferent m anifestations due to the involvem ent typical of eachone of them .T he other characteristics should be secondary to theprim ary involvem ent of neuro-ectoderm al vascularity.(2)

T he pathogenesis of these syndrom es has not beencom pletely explained yet.Studies suggest that the m ajority ofcases results from som atic m utations involving genes responsiblefor em bryonic angiogenesis.U ntil now, no locus or specific genew as identified as the source of the m alform ation.(2,5) R ecentstudies have show n som e evidence that K T W S is associated tothe translocation t(8;14) (q 22.3; q13). M en and w om en are equallyaffected in K T W S, and the occurrence is not lim ited nor has apreferred racial group.(11)

C linical presentations can be extrem ely varied.(12) A studyw ith 252 patients w ith K lippel-Trenaunay-W eber Syndrom efound the classic triad in 63% of patients.A lm ost all (98% ) thecases had capillar m alform ations w ith portw ine stains, 72%show ed arteriovenous m alform ations, and 67% had lim bhypertrophy.(13)

T he lesions shall be present at birth, and in about 75% ofpatients it appears before 10 years of age.T he portw ine stain ispresent at birth and does not show any tendency to develop.It isoften unilateral and segm ented -in general respecting the m idline- and increases proportionally to the grow th, besides thepossibility to be present in any part of the body, being m orecom m on in the face and neck of patients w ith SW S.(14) The m ostfrequent findings are isolated to one lim b in K T S.H ow ever, thereare reports of cases involving m ore than one lim b, hem ibody,and even the w hole body.(12)

O phthalm ologic changes associated to K T S and K T W Sinclude vascular abnorm alities of the orbit, iris, retina, choroid, andoptic nerve.The findings include:orbital varices, retinal varicoses,choroidal and m elanom a angiom a, persistent fetal vasculature,heterochrom ia iridum , strabism us and glaucom a.(5-7)

Several other abnorm alities involving the optic nerve havebeen described in association w ith K T W S.G ood and H oyt(15)

Figure 3: Fundoscopy of the right eyeSource: The author (2015)

Figure 5: M easurem ent of the retinal nerve thickness in R E w itnverve fibers analyzer O C T-G D XSource: The author (2015)

Figura 4: L inear com puter perim etry of R ESource: The author (2015)

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O phthalm ological m anifestation of the K lippel Trenaunay Syndrom e

408

reported in 1989 the case of a patient, fem ale, 10 years of age, w ithK T W S and increased shade of the optic nerve atecography(thickening of the optic nerve).Spoor et al.(16) describedin 1981 the case of a patient, fem ale, 18 years of age, w ith K TW S andbilateral m eningeom a in the optic nerve.B othun et al.(5) reported in2011 the case of a 16-year-old girl w ith K TS associated to bilateralgliom a of the optic chiasm and optic nerves, druses in the optic disc,and acquired m yelinationof the retinal nerve fibers.In addition, ca-ses of optic nerve hypoplasia, reverse papilla, and conjunctivallinfangiectasia have already been docum ented.(17)

Fundus abnorm alities associated to K lippel-Trenaunay-W eber syndrom e are not com m on, and include retinal vasculartortuosity and diffuse choroidal hem angiom a.(18)

D ue to the com plexity of the syndrom e, its progressivenature and w ide variety of clinical presentations, patients m ustbe treated individually by a m ultidisciplinary m edical team .(12)

T he m anagem ent of SK T is predom inantly conservative,including com pressive therapies such as the use of com pressionstockings and even interm ittent pneum atic com pression of thelim b affected.(12, 13, 19) These therapies help to reduce sym ptom sof venous insufficiency and lym phedem a, but they are noteffective to decrease the size of the hypertrophied lim b.(8) Surgery,laser therapy, sclerotherapy and em bolic therapy can also beused.T he prognosis of the disease can be reserved in som e cases- the presence of im portant arteriovenous m alform ation in K T W Sindicates severity and risk of loss of the affected lim b.(12)

In patients w ith functional lim bs, little or no edem a, bleeding,ulceration or pain, the treatm ent of choice is conservative focusedon relief of sym ptom s.Pulsed laser light therapy w as used w ithexcellent clinical efficacy and good aesthetic results in the treatm entof portw ine stains on the face and neck.T he surgical indication isreserved for an increase greater or equal to 2 cm of thehypertrophied lim b, in com parison w ith the contralateral lim b.(12)

A bout the ocular repercussions, the standard treatm ent forglaucom a has been the continued drug treatm ent com bined w ithsurgeries(20) in order to control the intra ocular pressure and preventdam age to the optic nerve.N evertheless, the initial treatm ent iscarried out only w ith beta-blockers, carbonic anhydrase inhibitors,alpha-agonists, and analogues of prostaglandins.(21)

Surgical procedures are only for patients w ho do not respondto clinical treatm ent, but the abnorm ality in the vasculature andhigh episcleral venous pressure com prom ise the success of thesurgery.(20) In the case of large circum scribed choroidalhem angiom as w ith subretinal fluid, treatm ent w ithepiscleralbrachytherapy plate is often considered effective.(22)

H ow ever, researchers report results of clinical and surgical treatm entforglaucom a in SW S patients as unsatisfactory com pared to othertypes of glaucom a.The clinical control is not possible in about 1/3 ofthe patients, and the surgical m anagem ent can be difficult.

T he surgical technique is still debatable, a challenge forophthalm ologists because of the high rate of postoperativecom plications such as choroidal hem orrhage in these patients.(23)

REFEREN CES

1. Forbes N , W alw yn M , R ao G , E llis D , L ee M G . K lippel-Trenaunaysyndrom e. W est Indian M ed J. 2013;62(3):254-6.

2. Purkait R , Sam anta T, Sinham ahapatra T, C hatterjee M . O verlapof Sturge-W eber syndrom e and K lippel-Trenaunay syndrom e.Indian J D erm atol. 2011;56(6):755-7.

3. G eske JB , Jouni H , H oyt JR . Im ages in vascular m edicine. Them ystery of a crim son leg: a case of K lippel-Trenaunay-W ebersyndrom e. V asc M ed. 2013;18(1):49-50.

4. M eier S. K lippel-Trenaunay syndrom e: a case study. A dv N eona-tal C are. 2009;9(3):120-4.

5. B othun E D , K ao T, G uo Y , C hristiansen SP. B ilateral optic nervedrusen and gliom as in K lippel-Trenaunay syndrom e. J A A PO S.2011;15(1):77-9.

6. D hir L , Q uinn A G . Persistent fetal vasculature and spontaneoushyphem a in a patient w ith K lippel-Trénaunay-W eber syndrom e.J A A PO S. 2010;14(2):190-2.

7. B rodsky M C . C ircum papillary choroidal “haem orrhoid” in K lippel-Trenauney-W eber syndrom e. B r J O phthalm ol. 2007;91(3):394.

8. D i R occo C , Tam burrini G . Sturge-W eber syndrom e. C hilds N ervSyst. 2006;22(8):909-21.

9. Pascual-C astroviejo I, D íaz-G onzalez C , G arcía-M elian R M ,G onzalez-C asado I, M uñoz-H iraldo E . Sturge-W eber syndrom e:study of 40 patients. Pediatr N eurol. 1993 1993;9(4):283-8.

10. Schnyder U W , L andolt E , M artz G . Syndrom e de K lippel-Trenaunay avec colom be irien atypique. J G enet 1956;5:1-8.

11. D utt R , D utt C . K lippel - trenaunay - w eber syndrom e. J C linN eonatol. 2012;1(3):160-1.

12. K ihiczak G G , M eine JG , Schw artz R A , Janniger C K . K lippel-Trenaunay syndrom e: a m ultisystem disorder possibly resultingfrom a pathogenic gene for vascular and tissue overgrow th. Int JD erm atol. 2006;45(8):883-90.

13. Jacob A G , D riscoll D J, Shaughnessy W J, Stanson A W , C lay R P,G loviczki P. K lippel-Trénaunay syndrom e: spectrum and m an-agem ent. M ayo C lin Proc. 1998;73(1):28-36.

14. G ontijo B , Pereira L B, Silva C M . M alform ações vasculares. A nB ras D erm atol. 2004;79(1):7-25.

15. G ood W V , H oyt C S. O ptic nerve shadow enlargem ent in theK lippel-Trenaunay-W eber syndrom e. J Pediatr O phthalm ol Stra-bism us. 1989;26(6):288-9.

16. Spoor T C , K ennerdell JS, M aroon JC , H epler R , K rohel G .Pneum osinus D ilatans, K lippel-Trenaunay-W eber syndrom e, andprogressive visual loss. A nn O phthalm ol. 1981;13(1):105-8.

17. B elliveau M J, B row nstein S, Jackson W B , Y ücel Y H . B ilateralconjunctival lym phangiectasia in K lippel-Trénaunay-W eber syn-drom e. A rch O phthalm ol. 2009;127(8):1057-8.

18. B rod R D , Shields JA , Shields C L , O berkircher O R , Sabol L J. U n-usual retinal and renal vascular lesions in the K lippel-Trenaunay-W eber syndrom e. R etina. 1992;12(4):355-8.

19. G loviczki P, D riscoll D J. K lippel-Trenaunay syndrom e: currentm anagem ent. Phlebology. 2007;22(6):291-8.

20. B odensteiner JB ; R oach E .S. Sturge-W eber syndrom e. N J: TheSturge-W eber Foundation, 1999.

21. van E m elen C , G oethals M , D ralands L , C asteels I. Treatm ent ofglaucom a in children w ith Sturge-W eber Syndrom e. J PediatrO phthalm ol Strabism us, 2000;37(1):29-34.

22. Franco N eto N B, Franchini SP, Foletto Junior V G , Pom blum V J.Síndrom e de Sturge-W eber. Saúde (Santa M aria), v.37, n.2, p.0918, 2011.

23. Figueiredo L R , Silva Filho SJ, R ehder JR . Sturge-W eber syn-drom e and its ocular effects: a review . R ev B ras O ftalm ol.2011;70(3):194-9.

C orresponding author:C arlos A ugusto M oreira N etoC entro da Visão:Rua Pasteur, 26, D istrict: Batel, C uritiba, Paraná,Brazil, ZIP C ode:80250-080 -Phone: (41) 3360-1800Em ail:m oreiraguto@ hotm ail.comN icole TássiaA m adeuEm ail:niam adeu@ gm ail.com

Júnior C A M , N eto C A M , A m adeu N T , G hem M R D

R ev B ras O ftalm ol. 2016; 75 (5): 405-8