Relationship of Optic Disc Cup with Lamina Cribrosa and Prelaminar Tissue in Healthy and Glaucomatous Eyes: In Vivo

Quantification with SpectralDomain Optical Coherence Tomography

Roberto M. Vessani 1; Vitor G.Prado 1; Paula D. Borba 1; Paula D.Silva1; Igor Matsubara 1; Augusto Paranhos 1; Tiago S. Prata1
1Glaucoma

A0063

Service, Ophthalmology Department, Paulista School of Medicine, So Paulo Hospital, Federal University of So Paulo, So Paulo, Brazil

Introduction The lamina cribrosa (LC) within the scleral canal in the optic nerve head (ONH) is thought to be the primary site of axonal insult in glaucoma. 1-3 It is of interest in glaucoma to understand the anatomy of the LC and surrounding tissues and how they change with aging and disease. The LC has been investigated using a variety of methods, including histologic section4,5,6 detergent digestion of surrounding tissues,6,7 and finite element modeling.8,9 In human glaucomatous eyes, LC alterations may include posterior deformation,7,10 compression and thinning,10,11 and molecular changes in astrocytes and other glial cells12,13, laminar beam and pore size alterations,14 and posterior migration of both the anterior and posterior laminar insertions from the sclera toward and sometimes into the pial sheath.15 Recent reports have suggested that spectral domain-optical coherence tomography (SD-OCT) imaging of the human ONH in vivo can visualize the lamina cribrosa.16-18 A new approach to SD-OCT, known as enhanced depth imaging (EDI) OCT, has been shown to improve anterior and posterior LC surface visibility compared with conventional SD-OCT. 19-22 The goal of this study was to investigate the relationship of optic disc cup with LC thickness and prelaminar tissue thickness in ONH using EDI modality of SD-OCT in healthy and glaucomatous eyes. Methods In this observational case-control study, participants were recruited from the Ophthalmology Department at Paulista School of Medicine, So Paulo Hospital, Federal University of So Paulo (Sao Paulo, Brazil). The study was part of a larger protocol approved by the Ophthalmology Department Institutional Review Board and in accordance with the Helsinki. Consecutive glaucomatous patients with a wide range of disease stage (glaucomatous optic neuropathy and reproducible visual field defect) and healthy individuals were prospectively enrolled from August 2012 to October 2012. Glaucomatous optic disc was defined by the presence of any of the following characteristics: vertical cup-to-disc ratio (VCDR) 0.6, asymmetry of VCDR 0.2 between eyes, presence of localized RNFL defects and/or neuroretinal rim defects in the absence of any other abnormalities that could explain such findings. Glaucomatous VF defect in the standard automated perimetry (Humphrey SITA tenets of Declaration of

Standard 242, Carl Zeiss Meditec, Dublin, CA) was defined by the presence of three or more points in clusters with p <5% on the pattern deviation plot, a pattern standard deviation index with p <5%, or a glaucoma hemifield test with results outside the normal limits. Healthy individuals required normal VF testing, normal appearance of the optic disc and untreated IOP<21mmHg. Exclusion criteria for both groups were significant media opacity, previous ocular surgery or trauma, use of oral or topical steroids and any ocular condition (other than glaucoma) that could interfere with visual field and imaging results. All participants underwent EDI-OCT imaging (SD-OCT; Spectralis, Wavelength: 870nm; Heidelberg Engineering Co., Heidelberg, Germany). An experienced examiner masked to patients clinical data measured the following ONH parameters: central lamina cribrosa (LC) thickness, prelaminar tissue thickness, Bruchs membrane opening and cup depth (image below). When both eyes were eligible, one was randomly selected. Multiple regression analysis (controlling for age and optic disc size) was used to investigate possible associations between cup depth, LC thickness and prelaminar neural tissue thickness. Figure 3. Association between prelaminar tissue thickness and lamina cribrosa thickness Figure 1. Association between cup depth and prelaminar tissue thickness Figure 2. Association between cup depth and lamina cribrosa thickness

Results A total 19 eyes of 19 patients were included (10 patients with glaucoma diagnosis and 9 healthy subjects). Baseline characteristics of study patients are provided in table. Multiple regression analysis revealed a significant negative association between cup depth and prelaminar neural tissue thickness (r=-0.64, p<0.01; Figure 1). Cup depth also correlated significantly with LC thickness (r=-0.44, p=0.02; Figure 2); eyes with deeper cups having thinner LCs. Finally, there was a positive correlation between prelaminar tissue thickness and LC thickness (r=0.51; p=0.04; Figure 3).
Financial Disclosure: Roberto M Vessani: Allergan (C,R); Augusto Paranhos: Allergan (C,R); Tiago S Prata: Allergan (C,R); other authors: none

Conclusions In this study, in vivo assessment of ONH structures in healthy subjects and glaucomatous patients revealed that eyes with deeper ONH cup presented less prelaminar tissue and thinner lamina cribrosa, independent of optic disc size and age.

References:1. Burgoyne CF, Downs JC, Bellezza AJ, Suh JK, Hart RT. 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;24:3973; 2. Quigley HA, Flower RW, Addicks EM, McLeod DS. The mechanism of optic nerve damage in experimental acute intraocular pressure elevation. Invest Ophthalmol Vis Sci. 1980;19:505517; 3. Hernandez MR. The optic nerve head in glaucoma: role of astrocytes in tissue remodeling. Prog Retin Eye Res. 2000;19: 297321; 4. Anderson DR. Ultrastructure of human and monkey lamina cribrosa and optic nerve head. Arch Ophthalmol. 1969;82(6):800-814; 5. Radius RL, Gonzales M. Anatomy of the lamina cribrosa in human eyes. Arch Ophthalmol. 1981;99(12):2159-2162; 6. Quigley HA, Addicks EM, Green WR, Maumenee AE. Optic nerve damage in human glaucoma, II: the site of injury and susceptibility to damage. Arch Ophthalmol. 1981;99:635649; 7. Quigley HA, Addicks EM. Regional differences in the structure of the lamina cribrosa and their relation to glaucomatous optic nerve damage. Arch Ophthalmol. 1981; 99(1):137-143; 8. Sigal IA, Flanagan JG, Tertinegg I, Ethier CR. Finite element modeling of optic nerve head biomechanics. Invest Ophthalmol Vis Sci. 2004;45(12):4378-4387; 9. Downs JC, Roberts MD, Burgoyne CF, Hart RT. Multiscale finite element modeling of the lamina cribrosa microarchitecture in the eye. Conf Proc IEEE Eng Med Biol Soc. 2009;2009:4277-4280; 10. Jonas JB, Berenshtein E, Holbach L. Anatomic relationship between lamina cribrosa, intraocular space, and cerebrospinal fluid space. Invest Ophthalmol Vis Sci. 2003;44:51895195; 11. Quigley HA, Hohman RM, Addicks EM, Massof RW, Green WR. Morphologic changes in the lamina cribrosa correlated with neural loss in open-angle glaucoma. Am J Ophthalmol. 1983;95:673691; 12. Hernandez MR, Andrzejewska WM, Neufeld AH. Changes in the extracellular matrix of the human optic nerve head in primary open-angle glaucoma. Am J Ophthalmol. 1990;109:180188; 13. Agapova OA, Yang P, Wang WH, et al. Altered expression of 3 alpha-hydroxysteroid dehydrogenases in human glaucomatous optic nerve head astrocytes. Neurobiol Dis. 2003;14:6373; 14. (Grimm J, et al. IOVS 2007;48:ARVO E-Abstract 3295); 15. Yang H, Williams G, Downs JC, et al. Posterior (outward) migration of the lamina cribrosa and early cupping in monkey experimental glaucoma. Invest Ophthalmol Vis Sci. 2011;52:71097121; 16. Vilupuru AS, Rangaswamy NV, Frishman LJ, Smith EL III, Harwerth RS, Roorda A. Adaptive optics scanning laser ophthalmoscopy for in vivo imaging of lamina cribrosa. J Opt Soc Am A Opt Image Sci Vis. 2007;24(5):1417-1425. 17. Kagemann L, Ishikawa H, Wollstein G, et al. Ultrahigh-resolution spectral domain optical coherence tomography imaging of the lamina cribrosa. Ophthalmic Surg Lasers Imaging. 2008;39(4)(suppl):S126-S131; 18. Strouthidis NG, Grimm J, Williams GA, Cull GA, Wilson DJ, Burgoyne CF. A comparison of optic nerve head morphology viewed by spectral domain optical coherence tomography and by serial histology. Invest Ophthalmol Vis Sci. 2010; 51(3):1464-1474; 19. Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol. 2008;146:496500; 20. Lee EJ, Kim TW, Weinreb RN, Park KH, Kim SH, Kim DM. Visualization of the lamina cribrosa using enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol. 2011;152(1):87-95, e1; 21. Park SC, De Moraes CG, Teng CC, Tello C, Liebmann JM, Ritch R. Enhanced depth imaging optical coherence tomography of deep optic nerve complex structures in glaucoma. Ophthalmology. 2012;119(1):3-9; 22. Park HY, Jeon SH, Park CK. Enhanced depth imaging detects lamina cribrosa thickness differences in normal tension glaucoma and primary open-angle glaucoma. Ophthalmology. 2012;119(1):10-20.