Optical Coherence Tomography Interpretation for Glaucoma

Structural glaucomatous changes occur more frequently in the earlier stages of glaucoma than functional defects so we should give special care on oct (optical coherence tomography) importance as the best current method. RNFL change detection are more useful in early glaucoma, GCC in moderate to advanced glaucoma while visual field test is more useful in advanced stages but overall using a combination of RNFL, ONH and macular measurement modalities is recommended for glaucoma evaluation because each of these parameters may be affected earlier than the others so, taking into account the findings from the RNFL, ONH and macula enhances early diagnosis of glaucoma

Adaptive optics: principles and applications in ophthalmology

This is a comprehensive review of the principles and applications of adaptive optics (AO) in ophthalmology. It has been combined with flood illumination ophthalmoscopy, scanning laser ophthalmoscopy, as well as optical coherence tomography to image photoreceptors, retinal pigment epithelium (RPE), retinal ganglion cells, lamina cribrosa and the retinal vasculature. In this review, we highlight the clinical studies that have utilised AO to understand disease mechanisms. However, there are some limitations to using AO in a clinical setting including the cost of running an AO imaging service, the time needed to scan patients, the lack of normative databases and the very small size of area imaged. However, it is undoubtedly an exceptional research tool that enables visualisation of the retina at a cellular level

An in vivo investigation of optic nerve head microstructure in primary open angle glaucoma

Glaucoma remains the leading cause of irreversible blindness in the world. Since retinal ganglion cell (RGC) axonal degeneration precedes permanent vision loss, identification of ONH parameters affected in the earliest stages of primary open angle glaucoma (POAG) is critical to ensure early diagnosis. This cross-sectional study used enhanced-depth imaging optical coherence tomography (EDI-OCT; 1040/70nm) to acquire 10° and 20° scans centred on the ONH (glaucomatous; n=128 or healthy controls; n=60). Regional measures of prelamina and LC depth and thickness, nerve fibre layer thickness at ONH border (bNFL) and peripapillary (pNFL), neuroretinal minimum rim width; (MRW) and area; (MRA) were analysed. This is the first study to quantify volumetric parameters including optic cup, prelamina and LC volume, and also Bruch’s membrane opening (BMO) surface area. Furthermore, LC connective tissue alignment was probed regionally and depth-wise within the LC. Statistical modelling was performed to identify ONH parameters that best contributed to characterisation of ONHs in the earliest stages of POAG. Regional measures of prelamina depth and thickness, and LC thickness were able to differentiate between control eyes and preperimetric (PG), and early glaucoma (EG) (P<0.05). Additionally, EG LC volume was significantly less than in controls (P<0.05). Significant associations of these parameters with loss of VF sensitivity (VF Mean deviation [MD]) were identified. Border and pNFL thickness, MRW (but not MRA) significantly differed between controls and PG and EG (P<0.05); and decreased with VF MD. Lamina cribrosa connective tissue alignment altered in a region and depth specific manner between PG LC and controls, or EG LCs (P<0.05), providing an original in vivo indicator of disease. In conclusion, in vivo ONH and NFL parameters are able to discriminate between healthy ONHs and early POAG ONHs; providing a group index with potential as a novel biomarker for early diagnosis, critical to personalised clinical decision making

The use of 1050nm OCT to identify changes in optic nerve head pathophysiology in glaucoma

Glaucoma is a progressive optic neuropathy that causes irreversible vision loss and is the second leading cause of blindness worldwide. Glaucoma is characterised by loss of retinal ganglion cells (RGC) and the proposed site of primary damage is the lamina cribrosa (LC), where RGC axonal transport is disrupted causing subsequent RGC damage and eventual cell death. Current detection for primary open angle glaucoma (POAG) is based upon clinical measures such as intraocular pressure (IOP), visual field loss and changes to the optic nerve head (ONH). However, for there to be an indication that there is a problem using these measures, often RGC damage has already occurred. Therefore it is crucial to determine ocular parameters that alter in the earliest stage of disease, prior to vision loss occurring. In this thesis optical coherence tomography (OCT) was used to assess the optic nerve heads and maculae of control eyes and eyes with preperimetric, early and advanced glaucoma in order to characterise changes that could potentially be used as biomarkers for the earliest stages of the disease. A custom built 1050 nm research OCT was used to acquire datasets from the macula and optic nerve heads of eyes glaucomatous and control eyes in vivo. Analysis of the inner retinal layers at the macula was performed to indirectly assess RGC integrity. At the ONH the prelamina and LC volume and regional depth and thicknesses were investigated. Additionally, nerve fibre layer and Bruch’s membrane parameters were assessed. Finally, LC beam coherence and orientation were probed in order to determine whether regional or glaucomatous changes ould be detected at the LC connective tissue microstructure. Prelamina depth and thickness was shown to be an indicator of early and preperimetric glaucoma (p0.01). Border nerve fibre layer revealed significant thinning in early glaucoma compared to control, and the superior peripapillary nerve fibre layer was thinner in preperimetric glaucoma than control. The ratio of inner plexiform layer (IPL) : ganglion cell layer (GCL) showed significant differences between control eyes and preperimetric glaucoma, and as such has potential to be a useful biomarker for indicating the earliest stages of disease. Both the GCL and IPL were thinner in early glaucoma than control (p<0.01), a hypothesis that cell body shrinkage and death occurs in preperimetric glaucoma and dendritic loss occurs in early glaucoma, when vision loss is first apparent, is suggested. Additionally, LC beams showed greater coherence in the superior and inferior poles than the temporal region, indicating that the shows regional variation but that further research is required to characterise changes. In conclusion, 1050 nm OCT was used to probe microstructural parameters of the optic nerve head in vivo to characterise changes that could be used as a potential biomarker for early glaucoma. ONH and retinal parameters have been identified that, with further research, may be used to differentiate between control eyes and those with preperimetric and early glaucoma. These have the potential to help identify those ONHs at risk of glaucoma damage

Three-dimensional optical coherence tomography imaging of the optic nerve head

Background: the primary site of injury in glaucoma is likely to be at the lamina cribrosa (LC), deep within the optic nerve head (ONH). Optical coherence tomography (OCT) in glaucoma has, to date, focused on the detection of nerve fibre loss. Spectral domain OCT (SDOCT) has improved speed and axial resolution, allowing acquisition of three-dimensional ONH volumes and may capture targets deep within the ONH. This thesis explores the capabilities and potential of deep SDOCT imaging in the monkey ONH. Plan of research: an investigation was conducted into the detection of key landmarks that would be necessary for future quantification strategies. In particular, detection of the neural canal opening (NCO) was assessed and how the NCO relates to what is clinically identified as the disc margin. The next phase involved clarifying the anatomical and histological basis of ONH structures observed within SDCOT volumes, by comparison with histological sections and disc photographs. Finally, quantification strategies for novel parameters based on deep targets were developed and used to detect chronic longitudinal changes in experimental glaucoma and acute changes following IOP manipulation. Results: SDOCT reliably detects the NCO, which can be used as an anchoring structure for reference planes. Usually the NCO equates to the disc margin but disc margin architecture can be complex and highly variable. SDOCT captures the prelaminar tissue and anterior LC surface. Prelaminar thinning and posterior LC displacement were both detected longitudinally in experimental glaucoma. Prelaminar thinning was observed with acute IOP elevation; posterior LC movement was rare. Significance: deep ONH structures, including the LC, are realistic targets for clinical imaging. These imaging targets may be useful in the detection of glaucoma progression and in the verification of ex-vivo models of ONH biomechanical behaviour

Crimp, Microstructure, and Biomechanics: Analyzing the Eye Using Polarized Light Microscopy

Glaucoma is the second leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is the main risk factor for glaucoma, though sensitivity to IOP varies widely. A leading theory states that the breadth of sensitivity is due to the biomechanical variability between eyes. According to this theory, biomechanically weak eyes suffer glaucoma at lower IOPs whereas robust eyes withstand higher IOPs without glaucomatous neural tissue damage. Therefore, in order to prevent, diagnose, and treat glaucoma, we need to have a better understanding of ocular biomechanics. Ocular biomechanics are intimately tied to the anisotropy and nonlinearity of eye tissue. Both of these macroscale properties are largely determined by the organization of collagen, the main load-bearing component of the eye. The anisotropy is related to the mesoscale collagen structure, whereas the nonlinearity is related to the microstructural collagen fiber waviness or crimp. Although many have studied the collagen anisotropy, few studies of ocular crimp exist. Hence, the microstructural basis for eye biomechanics remains unclear, precluding a mechanistic assessment and understanding of individual sensitivity to IOP. The main goal of this project was to characterize the collagen crimp in the eye. The lack of information on ocular crimp stems largely from the absence of a suitable imaging technique that can quantify ocular crimp with high resolution over a wide field-of-view. We established a method using polarized light microscopy (PLM) to quantify collagen fiber orientation in the eye and characterized the accuracy, repeatability, and robustness of our method. We then used PLM to characterize the crimp distribution in the eye. We also characterized how the crimp differed in eyes fixed at different IOPs and tracked how ocular crimp changed with stretch. Our studies revealed many complex aspects of collagen architecture in the eye, including the existence of fibers that are arranged radially around the optic nerve head and highly uniform crimp in the lamina cribrosa and cornea. Our findings helped elucidate the role of crimp in determining eye biomechanics and provided insight into collagen patterns that play a central role in the pathophysiology of glaucoma

IN VIVO BIOMECHANICAL STRAIN RESPONSE OF THE LAMINA CRIBROSA TO INTRAOCULAR PRESSURE CHANGE AS A RESULT OF GLAUCOMA MEDICATION CHANGE

The aim of the present pilot study was to evaluate the feasibility of a method for characterizing the short-term, in vivo biomechanical response of the lamina cribrosa (LC) in the eyes of patients starting glaucoma medication as a potential biomarker for primary open angle glaucoma (POAG). Radial optical coherence tomography (OCT) image volumes were acquired and intraocular pressure (IOP) was measured for 23 eyes from 15 patients before starting glaucoma medication and after a duration of 7.3 ± 1.4 days. Pre- and post-treatment image volumes were compared using digital volume correlation (DVC) to determine the anterior LC (ALC) strains and anterior LC depth (ALD) change. After the one-week treatment period, IOP decrease caused significant tensile Ezz greater than baseline error, compressive Err greater than baseline and correlation error, and small but significant posterior ALD change in Group 1 (eyes which had an IOP decrease of at least 4 mmHg). In Group 2 (eyes with 0-1 mmHg IOP change), there was a significant tensile Ezz, however its magnitude was approximately three times smaller than that of the Group 1 eyes and it did not exceed baseline or correlation error. Strain magnitudes were more highly correlated with percent IOP decrease than IOP decrease. Strains did not vary by quadrant of the LC and did not relate to ALD change. ALD change did not increase with increased IOP decrease. Strains and strain compliance increased with decreasing mean deviation (MD) and visual field index (VFI), but decreased with thinner average retinal nerve fiber layer (RNFL). Strains, strain compliance response, ALD change, RNFL, MD, and VFI were not significantly related to patient age. The results of the present study suggest the current method is a promising method for measuring repeatable LC strains and depth change in the eyes of patients subjected to IOP change as a result of glaucoma medication change

Relación de las características biomecánicas de la córnea con parámetros morfológicos de las estructuras profundas de la cabeza del nervio óptico en el glaucoma primario de ángulo abierto

La cubierta ocular externa está formada por la córnea, la esclera y la lámina cribosa (LC), siendo ésta última considerada la estructura fundamental donde se localiza el daño axonal en el glaucoma. Se trata de estructuras muy interrelacionadas en cuanto a su composición, origen embriológico y genética. Las propiedades biomecánicas de la córnea (histéresis corneal, HC; y factor de resistencia corneal, FRC) reflejan la capacidad viscoelástica y de resistencia a las fuerzas de deformación de su matriz extracelular de colágeno. Por tanto, tratándose de estructuras con similitudes importantes en la composición de su matriz extracelular, es probable que la córnea pueda compartir características biomecánicas con la lámina cribosa, siendo las propiedades de la córnea un reflejo del comportamiento de la misma. Por ello, diseñamos un estudio observacional transversal para evaluar las posibles asociaciones entre las propiedades biomecánicas de la córnea y la morfología de la cabeza del nervio óptico (CNO) y la LC, así como un estudio observacional longitudinal para valorar los cambios biomecánicos y morfológicos que se producen en la córnea, en la CNO y en la LC 3 meses después de realizar una esclerectomía profunda no perforante en pacientes con glaucoma primario de ángulo abierto (GPAA). Aunque las asociaciones observadas en el estudio transversal no son concluyentes, en el estudio longitudinal hemos observado que, aunque el factor que ha demostrado tener una mayor influencia en la reversibilidad de la excavación papilar fue la disminución de la PIO tras la cirugía, el FRC fue el parámetro preoperatorio independiente más influyente sobre la reversibilidad de la excavación papilar. Mayores cifras del FRC se asociaron con una mayor reversibilidad de la excavación papilar y un mayor engrosamiento del tejido prelaminar tras la cirugía. Los datos reflejados en el estudio apoyan la existencia de una asociación entre las propiedades biomecánicas de la córnea y el comportamiento de las CNO con las variaciones de la PIO en pacientes con GPAA