Retinal Nerve Fibre Layer OCT for Glaucoma Diagnosis – Gold Standard or Just a Piece of the Puzzle?

Abstract

Early diagnosis and accurate monitoring are essential in treating glaucoma effectively and avoiding further irreversible loss of retinal ganglion cells. Glaucoma is a complex disease; initial progression is usually asymptomatic, and regular clinical and imaging examinations are extremely important. Imaging the retinal nerve fibre layer (RNFL) using spectral domain optical coherence tomography (SD-OCT) has established itself in recent years as an easy-to-perform and reproducible diagnostic method. This imaging technique allows precise analysis of the RNFL in monitoring retinal nerve fibre thickness. The present article will discuss the anatomical principles, changes to be expected in the RNFL with glaucoma compared to normal control scans, and options in analysing disease progression. We will also be discussing limitations to the method as well as additional OCT imaging techniques available. Awareness of potential sources of error makes it easier to achieve an accurate analysis of RNFL scans. Tips on interpreting RNFL scans should help ophthalmologists using the available data effectively towards reaching informed decisions on disease treatment and management in glaucoma patients.

Keywords

Glaucoma - OCT - RNFL - diagnosis - progression

Publication History

Received: 25 October 2024

Accepted: 05 December 2024

Article published online:
24 July 2025

• References/Literatur

• 1 Weinreb RN, Aung T, Medeiros FA. The Pathophysiology and Treatment of Glaucoma. JAMA 2014; 311: 1901
• 2 Tham YC, Li X, Wong TY. et al. Global prevalence of glaucoma and projections of glaucoma burden through 2040: A systematic review and meta-analysis. Ophthalmology 2014; 121: 2081-2090
• 3 Coleman AL, Sommer A, Enger C. et al. Interobserver and Intraobserver Variability in the Detection of Glaucomatous Progression of the Optic Disc. J Glaucoma 1996; 5: 384-389
• 4 Hangai M, Ikeda HO, Akagi T. et al. Paracentral scotoma in glaucoma detected by 10–2 but not by 24-2 perimetry. Jpn J Ophthalmol 2014; 58: 188-196
• 5 Wang DL, Raza AS, de Moraes CG. et al. Central Glaucomatous Damage of the Macula Can Be Overlooked by Conventional OCT Retinal Nerve Fiber Layer Thickness Analyses. Transl Vis Sci Technol 2015; 4: 4
• 6 Hood DC, Slobodnick A, Raza AS. et al. Early Glaucoma Involves Both Deep Local, and Shallow Widespread, Retinal Nerve Fiber Damage of the Macular Region. Invest Ophthalmol Vis Sci 2014; 55: 632-649
• 7 Mwanza JC, Chang RT, Budenz DL. et al. Reproducibility of peripapillary retinal nerve fiber layer thickness and optic nerve head parameters measured with cirrus HD-OCT in glaucomatous eyes. Invest Ophthalmol Vis Sci 2010; 51: 5724-5730
• 8 Heijl A, Lindgren G, Olsson J. The Effect of Perimetric Experience in Normal Subjects. Arch Ophthal 1989; 107: 81
• 9 Hood DC, De Cuir N, Blumberg DM. et al. A single wide-field OCT protocol can provide compelling information for the diagnosis of early glaucoma. Transl Vis Sci Technol 2016; 5: 1-15
• 10 Parikh RS, Parikh SR, Sekhar GC. et al. Normal Age-Related Decay of Retinal Nerve Fiber Layer Thickness. Ophthalmology 2007; 114: 921-926
• 11 Leung CKS, Yu M, Weinreb RN. et al. Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: A prospective analysis of age-related loss. Ophthalmology 2012; 119: 731-737
• 12 Grewal DS, Sehi M, Paauw JD. et al. Detection of progressive retinal nerve fiber layer thickness loss with optical coherence tomography using 4 criteria for functional progression. J Glaucoma 2012; 21: 214-220
• 13 Sung KR, Wollstein G, Bilonick RA. et al. Effects of Age on Optical Coherence Tomography Measurements of Healthy Retinal Nerve Fiber Layer, Macula, and Optic Nerve Head. Ophthalmology 2009; 116: 1119-1124
• 14 Hood DC. Improving our understanding, and detection, of glaucomatous damage: An approach based upon optical coherence tomography (OCT). Prog Retin Eye Res 2017; 57: 46-75
• 15 Hood DC, Raza AS. On improving the use of OCT imaging for detecting glaucomatous damage. Br J Ophthalmol 2014; 98 (Suppl. 2) ii1-ii9
• 16 Garway-Heath DF, Poinoosawmy D, Fitzke FW. et al. Mapping the visual field to the optic disc in normal tension glaucoma eyes. Ophthalmology 2000; 107: 1809-1815
• 17 Jansonius NM, Schiefer J, Nevalainen J. et al. A mathematical model for describing the retinal nerve fiber bundle trajectories in the human eye: average course, variability, and influence of refraction, optic disc size and optic disc position. Exp Eye Res 2012; 105: 70-78
• 18 Hood DC, Raza AS, de Moraes CG. et al. Glaucomatous damage of the macula. Prog Retin Eye Res 2013; 32: 1-21
• 19 Gmeiner JMD, Schrems WA, Mardin CY. et al. Comparison of Bruchʼs Membrane Opening Minimum Rim Width and Peripapillary Retinal Nerve Fiber Layer Thickness in Early Glaucoma Assessment. Invest Ophthalmol Vis Sci 2016; 57: OCT575-OCT584
• 20 Leite MT, Rao HL, Zangwill LM. et al. Comparison of the diagnostic accuracies of the Spectralis, Cirrus, and RTVue optical coherence tomography devices in glaucoma. Ophthalmology 2011; 118: 1334-1339
• 21 Harizman N, Oliveira C, Chiang A. et al. The ISNT rule and differentiation of normal from glaucomatous eyes. Arch Ophthalmol 2006; 124: 1579-1583
• 22 Sayed MS, Margolis M, Lee RK. Green disease in optical coherence tomography diagnosis of glaucoma. Curr Opin Ophthalmol 2017; 28: 139-153
• 23 Mwanza JC, Durbin MK, Budenz DL. Cirrus OCT Normative Database Study Group. Interocular symmetry in peripapillary retinal nerve fiber layer thickness measured with the cirrus HD-OCT in healthy eyes. Am J Ophthalmol 2011; 151: 514-521.e1
• 24 Mwanza JC, Oakley JD, Budenz DL. et al. Ability of Cirrus HD-OCT optic nerve head parameters to discriminate normal from glaucomatous eyes. Ophthalmology 2011; 118: 241-248.e1
• 25 Wu H, de Boer JF, Chen TC. Diagnostic Capability of Spectral-Domain Optical Coherence Tomography for Glaucoma. Am J Ophthalmol 2012; 153: 815-826.e2
• 26 Budenz DL, Michael A, Chang RT. et al. Sensitivity and specificity of the StratusOCT for perimetric glaucoma. Ophthalmology 2005; 112: 3-9
• 27 Medeiros FA, Zangwill LM, Bowd C. et al. Evaluation of retinal nerve fiber layer, optic nerve head, and macular thickness measurements for glaucoma detection using optical coherence tomography. Am J Ophthalmol 2005; 139: 44-55
• 28 Tatham AJ, Medeiros FA. Detecting Structural Progression in Glaucoma with Optical Coherence Tomography. Ophthalmology 2017; 124: S57-S65
• 29 Hood DC, Raza AS, De Moraes CG. et al. Evaluation of a One-Page Report to Aid in Detecting Glaucomatous Damage. Transl Vis Sci Technol 2014; 3: 8
• 30 Yu M, Lin C, Weinreb RN. et al. Risk of Visual Field Progression in Glaucoma Patients with Progressive Retinal Nerve Fiber Layer Thinning A 5-Year Prospective Study. Ophthalmology 2016; 123: 1201-1210
• 31 Wu H, de Boer JF, Chen L. et al. Correlation of localized glaucomatous visual field defects and spectral domain optical coherence tomography retinal nerve fiber layer thinning using a modified structure–function map for OCT. Eye (Lond) 2015; 29: 525-533
• 32 Bradley C, Hou K, Herbert P. et al. Evidence-Based Guidelines for the Number of Peripapillary OCT Scans Needed to Detect Glaucoma Worsening. Ophthalmology 2023; 130: 39-47
• 33 Miki A, Medeiros FA, Weinreb RN. et al. Rates of retinal nerve fiber layer thinning in glaucoma suspect eyes. Ophthalmology 2014; 121: 1350-1358
• 34 Hwang YH, Kim YY, Kim HK. et al. Changes in retinal nerve fiber layer thickness after optic disc hemorrhage in glaucomatous eyes. J Glaucoma 2014; 23: 547-552
• 35 Tsamis E, Bommakanti NK, Sun A. et al. An Automated Method for Assessing Topographical Structure–Function Agreement in Abnormal Glaucomatous Regions. Transl Vis Sci Technol 2020; 9: 14
• 36 Liu Y, Simavli H, Que CJ. et al. Patient characteristics associated with artifacts in Spectralis optical coherence tomography imaging of the retinal nerve fiber layer in glaucoma. Am J Ophthalmol 2015; 159: 565-576.e2
• 37 Yang H, Lee HS, Bae HW. et al. Effect of image quality fluctuations on the repeatability of thickness measurements in swept-source optical coherence tomography. Sci Rep 2020; 10: 13897
• 38 De Clerck EEB, Schouten JSAG, Berendschot TTJM. et al. Loss of Temporal Peripapillary Retinal Nerve Fibers in Prediabetes or Type 2 Diabetes Without Diabetic Retinopathy: The Maastricht Study. Invest Ophthalmol Vis Sci 2017; 58: 1017-1027
• 39 Verma S, Singh VK, Rana J. et al. Quantitative measurement of retinal nerve fiber layer thickness and its correlation with optical coherence tomography angiography vascular biomarker changes in preclinical diabetic retinopathy. Indian J Ophthalmol 2024; 72 (Suppl. 1) S11-S15
• 40 Abalo-Lojo JM, Treus A, Arias M. et al. Longitudinal study of retinal nerve fiber layer thickness changes in a multiple sclerosis patients cohort: A long term 5 year follow-up. Mult Scler Relat Disord 2018; 19: 124-128
• 41 Kang SH, Hong SW, Im SK. et al. Effect of myopia on the thickness of the retinal nerve fiber layer measured by cirrus HD optical coherence tomography. Invest Ophthalmol Vis Sci 2010; 51: 4075-4083
• 42 Mwanza JC, Kim HY, Budenz DL. et al. Residual and dynamic range of retinal nerve fiber layer thickness in glaucoma: Comparison of three OCT platforms. Invest Ophthalmol Vis Sci 2015; 56: 6344-6351
• 43 Mwanza JC, Budenz DL, Warren JL. et al. Retinal nerve fibre layer thickness floor and corresponding functional loss in glaucoma. Br J Ophthalmol 2015; 99: 732-737