Defects of the Lamina Cribrosa in Eyes with Localized Retinal Nerve Fiber Layer Loss Ophthalmology 2013 Oct 18. pii: S0161-6420(13)00762-8 서울성모병원 Pf.안명덕.

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Defects of the Lamina Cribrosa in Eyes with Localized Retinal Nerve Fiber Layer Loss Ophthalmology 2013 Oct 18. pii: S0161-6420(13)00762-8 서울성모병원 Pf.안명덕 / R3 신지영

Introduction Lamina cribrosa (LC) a meshwork of connective tissue through which retinal ganglion cell axons pass as they exit the eye through the scleral canal Deformation of the LC is a manifestation of IOP-related connective tissue damage and that axonal damage is likely to occur concurrently with LC damage Burgoyne CF, Downs JC, Bellezza AJ, et al. The optic nerve head as a biomechanical structure: a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage. Prog Retin Eye Res 2005;24:39–73. LC는 retinal ganglion cell axons 이 scleral canal을 통해 안구를 빠져나가는 곳에 있는 connective tissue meshwork 입니다. 과거 LC의 변형이 안압으로 인한 connective tissue의 손상의 증상일 수 있으며 Axonal damage가 이와 동시에 발생할 수 있다는 보고도 있었습니다.

Introduction Regional differences in the LC may make specific portions of the optic nerve particularly susceptible to neural loss Superior & inferior poles of the optic nerve head LC pores are larger Connective tissue septae thinner → less structural support for retinal ganglion cell axons and less resistance to mechanical deformation LC의 부분적인 변화가 시신경 손상에 더욱 specific한 부위를 만들 수 있다는 실제 optic nerve head 부위에 sup. & inf. Pole은 LC pore가 더 크고 connective tissue septae 가 거 얇아 retinal ganglion cell axon에 대해 구조적인 지지가 더 약하고 기계적인 손상에 더 취약한 것으로 알려져 있습니다. 따라서 녹내장이 localized neural loss가 관찰되는 지에 대해 해답이 될수 있다는 주장이 제기된 것이 있습니다.

Introduction The aim of this study To use EDI-OCT Evaluate the LC of glaucomatous eyes with localized RNFL defects, compared with age-matched, healthy controls Frequency and location of LC defects Relationship with RNFL defects were assessed in glaucomatous eyes 이 논문은 EDI OCT 를 사용하여 localized RNFL defect가 있는 녹내장 환자와 age-matched 정상 대조군에서 LC 이상여부를 확인하고 LC defect 의 위치와 발생빈도, RNFL defect 와의 연관성에 대해 연구해 보고자 하였습니다.

Methods 24 glaucomatous eyes of 14 with localized RNFL defects repeatable (2 consecutive) abnormal visual field test results pattern standard deviation with P<5% a glaucoma hemifield test result outside normal limits presence of documented progressive optic disc damage based on masked grading of optic disc stereophotographs Both eyes of 25 healthy subjects IOP of <21 mmHg No history of increased IOP Normal standard automated perimetry (SAP) result Matched for age using optimal bipartite matching 사용하여 localized RNFL defect가 있는 녹내장 환자 14명의 24안과 정상 대조군 25명의 양안을 대상으로 하였습니다. 녹내장 환자는 시야검사상에서 2반 이상의 반복적인 이상을 나타내며 시신경 사진상에서 progressive한 시신경 손상이 관찰되어야 하며 정상 대조군은 안압이 21 mmHg 이하이고 안압이 올라갔던 과거력이 없고 시야검사가 정상인 경우를 inclusion criteria로 삼았습니다. 양군간은 양자간의 age-matching 을 시행하였다.

Methods Exclusion criteria Best-corrected visual acuity of <20/40 Spherical refraction outside 5.0 diopters Cylinder correction outside 3.0 diopters Any other ocular or systemic disease that could affect the optic nerve or the visual field Exclusion criteria 는 BCVA가 0.5 미만이거나 Spherical이 5.0 diopter 이상이거나 Cylinder가 3.0 이상인 경우 그리고 시신경이나 시야에 영향을 미칠수 있는 눈 이나 전신의 질환을 가진경우로 하였다.

Methods Comprehensive ophthalmologic examination Review of medical history Best-corrected visual acuity Slit-lamp biomicroscopy IOP measurement Gonioscopy Dilated funduscopic examination Stereoscopic optic disc photography SAP(SITA Standard 24-2; Carl Zeiss Meditec, Inc., Dublin, CA)

Stereophotograph Grading Reviewed with a stereoscopic viewer Masked to the subject’s identity and to the other test results Eyes with localized RNFL defects were identified by 2 masked graders RNFL defects Wider than twice the width of an arteriole Extending from close to the disc margin into the parapapillary area Image of lamina cribrosa without a focal lamina cribrosa defect. There are multiple small, full-thickness lamina perforations (<100 m in diameter) likely corresponding with lamina pores (arrows). The anterior lamina surface is indicated by the green line and the Bruch’s membrane terminations by the yellow dots.

Enhanced Depth SD-OCT The Spectralis SD-OCT (software version 5.4.7.0; Heidelberg Engineering, Dossenheim, Germany) using the automated EDI setting Imaging was performed within 6 months of stereoscopic photography and SAP Obtained using 48 radial line B-scans centered on the optic disc, each at an angle of 3.75 to the last. A, Optic disc photograph of an eye with an inferior localized retinal nerve fiber layer (RNFL) defect. B, C, The infrared en face radial line enhanced depth imaging optical coherence tomography (EDI-OCT) image for the same eye was superimposed on the optic disc photograph, with 4.7 of rotation required for alignment. D, Each of the 48 radial line EDI-OCT images were examined for lamina cribrosa defects.

Enhanced Depth SD-OCT Focal LC defect Anterior laminar surface irregularity violating the normal smooth curvilinear U- or W-shaped contour >100 um in diameter and >30 um in depth present in 2 neighboring radial line scans Central defects : defects where the anterior LC was visible on either side of the defect Peripheral defects : defects where the anterior LC was visible on only 1 side of the defect

Enhanced Depth SD-OCT

Enhanced Depth SD-OCT

Results Poor visibility of the anterior LC 20 eyes of 14 patients with localized RNFL defects 40 eyes of 25 healthy subjects 나이 성별 인종 각막두께 안축장 간에는 통계적으로 유의한 차이가 없었으며 MD RNFL thickness LC defect 가 있는 안구의 숫자에서는 차이가 있었다.

Results Location of RNFL Defects 18 eyes : inferotemporal RNFL defect 1 eye : superotemporal RNFL defect 1 eye : 2 noncontiguous RNFL defects affecting the inferotemporal and superotemporal sectors

Results Number of LC Defects Fifteen of 20 eyes with a localized RNFL defect (75%) had more than 1 focal LC defect detected 13 : 1 LC defect, 1 : 2 LC defects, 1: 3 LC defects 12 : central LC defect, 6 : peripheral LC defects Only 1 healthy eye (of a 72-year-old subject) with a focal LC defect

Results 15 LC defect of 20 eyes with a localized RNFL defect vs. 5 no LC defects Mean RNFL thickness (P = 0.002) sectors with a focal LC defect : 59.5±25.3 mm sectors without a focal LC defect : 78.7±10.5 mm Eyes with focal LC defects : lower mean RNFL thickness There was no difference in SAP mean deviation, axial length, central corneal thickness

Results LC defects location 13 in the inferotemporal sector 3 defects in the superotemporal sector 1 in the inferonasal sector 1 in the in superonasal sector 15/18 focal LC defects in eyes with localized RNFL defects (83%) were in an EDI- OCT radial line scan transecting a localized RNFL defect 13 eyes : closest to the visible RNFL defect 2 eyes : the sector opposite the RNFL defect

Discussion Focal LC defects are common in glaucomatous eyes LC defects might also develop with age Good spatial agreement between the location of the focal LC defects and the location of RNFL defects The LC defects were associated with significant RNFL thinning

Discussion The greatest number of LC defects in the eyes included in this study was in the inferotemporal followed by superotemporal sectors The inferior and superior regions of the LC are known to contain larger pores and thinner connective tissue septae than the nasal and temporal sectors, which might render these areas of the LC particularly susceptible to deformation from IOP-related stresses and explain a susceptibility to focal defects in the LC There were no focal LC defects detected in the nasal or temporal sectors

Discussion The number of focal LC defects is higher in eyes with more severe glaucoma The eyes with localized RNFL defects had an average mean deviation of -4.8 dB and an average of only 1 LC defect There was 1 eye in this study with 3 LC defects, and this eye had a mean deviation of -11.18 dB

Discussion Limitation The LC defects may have been missed because of poor visibility of the LC Due to the difficulty of visualizing the insertion of the LC peripheral to the BMO, we did not distinguish peripheral LC defects from disinsertions Need for accurate alignment of photographs and EDI-OCT images

Summary A high prevalence of focal LC defects in glaucomatous eyes with localized RNFL defects Good spatial correlation between the location of LC defects and the location of RNFL loss, suggesting that damage to the LC might contribute to damage to retinal ganglion cell axons

Thank you for your attention