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

Measuring progression in glaucoma

Background: Primary open angle glaucoma is characterised by progressive optic neuropathy associated with characteristic visual field loss. The ability to measure disease progression is of vital importance in the management of patients with glaucoma. Conventionally, disease progression has been monitored using static automated perimetry. Recently, devices which image the optic nerve head quantifiably have been introduced. This thesis sets out to compare structural and functional progression in ocular hypertensive subjects followed longitudinally using novel progression algorithms. Plan of research: The investigations may be considered in three parts. Firstly, the factors affecting the test-retest variability of the Heidelberg Retina Tomograph (HRT) are identified and methods to improve repeatability are investigated. Secondly, novel HRT trend and event analyses, based on the findings of the test-retest studies, are compared with established field progression techniques in ocular hypertensive and control subjects. Thirdly, a previously described novel spatial filter is assessed in terms of its impact on the monitoring of visual field progression and in terms of its agreement with a previously described 'structural' map. Results: Rim area was identified as the most repeatable HRT parameter its variability can be improved by using the 320pm reference plane and by using only good quality images. Agreement as regards structural and functional progression was poor, regardless of the estimated specificities of the algorithms used or technique adopted. The novel spatial filter appeared to confer some advantage in terms of specificity, comparable to the effect of confirmatory testing. The functional relationship between test-points, characterised by the filter, correlated well with the expected structural pattern. Clinical significance: The poor agreement suggests that the monitoring of both structure and function is essential to provide the best chance of detecting progression at all stages of the disease. Spatial filtering techniques may provide some additional benefit in the monitoring of progression, particularly once structural data are incorporated

Heavy metal toxicity and the aetiology of glaucoma

Despite recent advances, our understanding of the aetiological mechanisms underlying glaucoma remains incomplete. Heavy metals toxicity has been linked to the development of neurodegenerative diseases and various ocular pathologies. Given the similarities in pathophysiology between glaucoma and some neurodegenerative disorders, it is plausible that heavy metal toxicity may play a role in the development of glaucoma. Heavy metal exposure may be occupational, or through water or dietary contamination. In this report, we review mechanisms for systemic and neurotoxicity for arsenic, cadmium, chromium, cobalt, lead, mercury, and manganese, and weigh the evidence for an association between glaucoma and the accumulation of heavy metals either in ocular tissues or in the central nervous system

Detecting abnormality in optic nerve head images using a feature extraction analysis

Imaging and evaluation of the optic nerve head (ONH) plays an essential part in the detection and clinical management of glaucoma. The morphological characteristics of ONHs vary greatly from person to person and this variability means it is difficult to quantify them in a standardized way. We developed and evaluated a feature extraction approach using shiftinvariant wavelet packet and kernel principal component analysis to quantify the shape features in ONH images acquired by scanning laser ophthalmoscopy (Heidelberg Retina Tomograph [HRT]). The methods were developed and tested on 1996 eyes from three different clinical centers. A shape abnormality score (SAS) was developed from extracted features using a Gaussian process to identify glaucomatous abnormality. SAS can be used as a diagnostic index to quantify the overall likelihood of ONH abnormality. Maps showing areas of likely abnormality within the ONH were also derived. Diagnostic performance of the technique, as estimated by ROC analysis, was significantly better than the classification tools currently used in the HRT software – the technique offers the additional advantage of working with all images and is fully automated

Long-Term Outcomes of Trabeculectomy Augmented with Mitomycin C Undertaken within the First 2 Years of Life

To evaluate the long-term effectiveness and safety of mitomycin C (MMC)–augmented trabeculectomy undertaken within the first 2 years of life for the surgical management of glaucoma. DESIGN: Retrospective, consecutive, noncomparative case series. PARTICIPANTS: All children who underwent MMC-augmented trabeculectomy within 2 years of birth between May 2002 and November 2012. METHODS: The medical records of 40 consecutive eyes of 26 children who underwent surgery by a single surgeon were reviewed. Data collected during routine clinical care were analyzed. MAIN MEASURE OUTCOMES: Assessment of clinical outcomes included intraocular pressure (IOP), final visual acuity, bleb morphology, surgical complications (early and late), postoperative interventions, and further glaucoma surgery performed. Surgical success was defined as final IOP of 5 mmHg or more and of 21 mmHg or less, with anti-glaucoma medications (qualified success) and without (complete success), stable ocular dimensions and optic disc cupping, and no further glaucoma surgery (including needling) or loss of light perception. Surgical outcomes were evaluated using Kaplan-Meier life table analysis. RESULTS: Forty eyes of 26 children were studied over a mean follow-up period of 62.8 months. Most cases (80%) were of primary congenital glaucoma after failed goniotomy surgery. Cumulative probabilities of survival at 1, 5, and 7 years were 78%, 67%, and 60%, respectively. Of eyes regarded as successful, 96% (25/26 eyes) had controlled IOP without topical medication and 44% achieved visual acuity of 20/40 or better. In only 1 of the 40 eyes did a cystic avascular bleb develop, with all the other eyes being non-cystic in nature (diffuse and elevated or flat) at final follow-up. Sixty-four percent (9/14 eyes) of cases regarded as failures ultimately underwent glaucoma drainage device implantation. CONCLUSIONS: A contemporary pediatric trabeculectomy technique augmented with MMC is an effective procedure in the management of glaucoma within the first 2 years of life, as shown by the successful long-term outcomes and low incidence of sight-threatening complications. Trabeculectomy after failed goniotomy surgery or as a primary surgical intervention may offer a phakic infant with glaucoma an excellent opportunity to achieve long-term control of IOP without medications and may be associated with optimal visual outcomes

Teleglaucoma: ready to go?

Telemedicine technologies and services allow today's ophthalmic clinicians to remotely diagnose, manage and monitor several ophthalmic conditions from a distance. But is this the case for glaucomas? There has been a proliferation of telemedicine friendly devices in recent years that improves the capabilities of the clinician in managing glaucomas. The existing instruments still need to align themselves with accepted industry standards. There are successful programmes running in several areas of the world. The safety and efficacy of these programmes needs further exploration. The inability of a single device or test to diagnose glaucomas satisfactorily has also hampered progress in remotely diagnosing these conditions. There is, however, significant potential for telemedicine-friendly devices to remotely monitor the progress of glaucoma and, thereby, reduce some of the workload on an overstretched health service

Analysis of HRT Images: Comparison of Reference Planes

PURPOSE. The values of Heidelberg Retinal Tomograph (HRT; Heidelberg Engineering, Heidelberg, Germany) stereometric parameters depend on the reference plane (RP), the instability of which results in parameter variability. Identification of change depends on RP stability. This study was undertaken to evaluate the influence of various RPs on rim areas (RAs) in a longitudinal image series. METHODS. A longitudinal image series of 31 subjects with ocular hypertension who had reproducible visual field loss and 19 normal subjects was analyzed using five different RPs: the standard RP (HRT software version 3.1.2.0), two 320-m RPs (software ver. 3.1.2.0 and 1.7.0), a previously described experimental RP, and a new Moorfields RP. The Moorfields RP takes the standard RP at baseline and then is fixed relative to the reference ring for subsequent images. Classic methods, such as ophthalmoscopy and stereophotography, are widely used and are still important. These techniques involve the clinical examination of the ONH, to detect abnormalities associated with glaucoma, such as rim narrowing and notching, and recognition of large or asymmetric cup-to-disc ratios. However, these methods have limitations, since they rely on subjective judgment, and agreement between even expert observers on the presence of glaucoma or progressive change is not optimal. 5-10 Objective and reproducible measurements of the ONH surface topography are possible with scanning laser tomography. 11,12 Although scanning laser tomography appears to be reproducible, The HRT software applies two approaches to detection of change. The first is topographic change analysis, 14 in which the surface height in groups of pixels (super pixels) in follow-up images is compared with the surface height in the baseline image. Statistically significant change in surface height is color coded (red for relative depression, and green for relative elevation, compared to baseline). The second approach is to plot stereometric data, such as rim area (RA), over time. Currently, there is no statistical support in the software for this latter approach, but the potential value of quantifying RA over time to identify progression has been reported. Many different reference surfaces have been proposed

The Relationship Between Ambient Atmospheric Fine Particulate Matter (PM₂.₅) and Glaucoma in a Large Community Cohort

PURPOSE: Glaucoma is more common in urban populations than in others. Ninety percent of the world's population are exposed to air pollution above World Health Organization (WHO) recommended limits. Few studies have examined the association between air pollution and glaucoma. Questionnaire data, ophthalmic measures, and ambient residential area air quality data for 111,370 UK Biobank participants were analyzed. Particulate matter with an aerodynamic diameter < 2.5 μm (PM₂.₅) was selected as the air quality exposure of interest. Eye measures included self-reported glaucoma, intraocular pressure (IOP), and average thickness of macular ganglion cell–inner plexiform layer (GCIPL) across nine Early Treatment Diabetic Retinopathy Study (ETDRS) retinal subfields as obtained from spectral-domain optical coherence tomography. We examined the associations of PM₂.₅ concentration with self-reported glaucoma, IOP, and GCIPL. RESULTS: Participants resident in areas with higher PM₂.₅ concentration were more likely to report a diagnosis of glaucoma (odds ratio = 1.06, 95% confidence interval [CI] = 1.01–1.12, per interquartile range [IQR] increase P = 0.02). Higher PM₂.₅ concentration was also associated with thinner GCIPL (β = −0.56 μm, 95% CI = −0.63 to −0.49, per IQR increase, P = 1.2 × 10^{-53}). A dose–response relationship was observed between higher levels of PM₂.₅ and thinner GCIPL (P < 0.001). There was no clinically relevant relationship between PM₂.₅ concentration and IOP. CONCLUSIONS: Greater exposure to PM₂.₅ is associated with both self-reported glaucoma and adverse structural characteristics of the disease. The absence of an association between PM₂.₅ and IOP suggests the relationship may occur through a non–pressure-dependent mechanism, possibly neurotoxic and/or vascular effects

Comparison of neuroretinal rim area measurements made by the Heidelberg Retina Tomograph I and the Heidelberg Retina Tomograph II

To investigate the agreement between neuroretinal rim area (RA) measurements using the Heidelberg Retina Tomograph I (HRT Classic) and Heidelberg Retina Tomograph II (HRT II). To compare apparent RA changes in follow-up series of HRT II topographies when using either an HRT Classic or HRT II mean topography as baseline