Lens Dislocation in Marfan syndrome <Pediatric Ophthalmology Case Conference> Lens Dislocation in Marfan syndrome 12999346 서울성모병원 안과 Ap.박신혜/R2박진형

임 O 욱 M/4 C/C TV를 볼 때 고개를 들고 가까이서 본다 onset) 1년 전부터

Ocular exam Lens OU Clear VA OD 0.02(n-c) OS 0.25(n-c) Ref) OD -11.75Ds -8.25Dc Ax122’ OS -1.50Ds -6.25Dc Ax35’ Sensory test Ocular Lang II E (-) C (-) M (-) Titmus Fly(-) Animal (0/3) Circle (0/9) EOM Ortho at N&F by ACT, no LOM Orbit OU No exophthalmos Lid OU No swelling Conj. OU Not injected Cornea OU Clear AC OU Deep & cell(-) Pupil OU Round & nl. sized, LR(+/+), RAPD(-/-) Lens OU Clear

Fundus OD nl. Optic disc c flat macula OS nl. Optic disc c flat macula OD OS

Imp. Anisometropia Plan PEG 한 달 후 좌안 가림 치료시작

OPD F/U 1mo. Lens OU mild lens dislocation to superonasally Plan) VA OD 0.06(n-c) OS 0.5(n-c) Ref) OD -12.25Ds -4.75Dc Ax126’ OS -1.25Ds -4.50Dc Ax32’ Ker) OD 45.25/43.50 (WTR1.75) OS 45.75/43.25 (WTR2.50) AL OD 24.20 mm OS 21.97 mm EOM Ortho at N&F by ACT, no LOM Orbit OU No exophthalmos Lid OU No swelling Conj. OU Not injected Cornea OU Clear AC OU Deep & cell(-) Pupil OU Round & nl. sized, LR(+/+), RAPD(-/-) Lens OU mild lens dislocation to superonasally Plan) 좌안 가림 3시간 시작 F/U 1mo.

OPD F/U 6mo. <OD> Stretched Zonule <OS> VA OD (0.32) Ref.) OD -10.00Ds -8.50Dc Ax 129’ OS -1.50Ds -5.75Dc Ax 35’ Iridodonesis (-) Phacodonesis (-) /OU <OD> Stretched Zonule Plan) PD consult for Marfan Synd. F/U 6mo. <OS>

Review : Marfan syndrome Ref. Cornea 3rd edition, Krachmer

Introduction Systemic connective tissue disorder Mutations in the fibrillin-1 gene Originally believed - production of abnormal fibrillin-1 - structurally weaker connective tissue 15번 염색체

Introduction Recent molecular studies - Fibrillin-1 haploinsufficiency - Dysregulated TGF-β signaling altered morphogenetic and homeostatic programs ★ TGF-β antagonism : prevent and possibly reverse aortic root dilatation, mitral valve prolapse, lung disease, and skeletal muscle dysfunction 15번 염색체 조작으로 또는 돌연변이로 한쪽의 유전자가 망가진 경우, 정상적인 단백질을 만들고 아무 이상이 없으면 haplosufficiency라고 부르고 다른점이 있다면 이것을 haploinsufficiency라고 부른다. morphogenetic 한글:  형태형성

Abnormalities in three systems Ocular Ectopia lentis Cardiovascular Dilation of the aortic root Aneurysm of the ascending aorta Aortic aneurysm Skeletal Dolichostenomelia Upper segment/lower segment ratio two standard deviations below mean for age Pectus excavatum Kyphoscoliosis Ectopia lentis수정체 편위 Dolichostenomelia 거미팔다리증 Upper segment/lower segment ratio two standard deviations below mean for age Pectus excavatum 오목가슴 Kyphoscoliosis 척추측후만증

Ocular abnormality Subluxation of the crystalline lens Defective fibrillin component Lens zonules are abnormally weak Degree of subluxation varies Evident only on maximal pupillary dilation Superior and temporal displacement : M/C Inferior, nasal, or lateral movement No progression of the displacement is noted over the years : M/C Total dislocation into the Vit. cavity : unusual in young patients In most patients

Ocular abnormality Zonular rupture straightening of the lens contour : coloboma of the lens Cornea is flat with keratometric readings high 30s in about 20% of patients 40.8 D Marfan vs 43.3 D controls associated with corneal thinning 543.5 microns (µm) Marfan vs 564.2 microns (µm) controls Clinical diagnostic criterion Strabismic and/or anisometropic or ametropic amblyopia responds surprisingly well to optical correction Open-angle glaucoma Cataracts develop earlier microspherophakia 한글:  공모양작은수정체(증) Ametropic 굴절이상 녹내장은 연령에 비례

Operation indications No correction with glasses Posterior dislocation into vitreous Secondary glaucoma (anterior dislocation) or corneal endothelial damage Uveitis or monocular diplopia Cataracts Poor vision : high astigmatic errors Early age to avoid amblyopia Dislocation into the AC

Fatality Dissection / enlargement of the aortic root M/C of premature death Mouse models : mitigated by treatment with TGF-β antagonists - also studied in humans