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

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

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

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

Associations with Retinal Pigment Epithelium Thickness Measures in a Large Cohort: Results from the UK Biobank

PURPOSE: To describe associations of ocular and systemic factors with retinal pigment epithelium (RPE)-Bruch's membrane (BM) complex thickness as measured by spectral-domain (SD) optical coherence tomography (OCT). DESIGN: Multisite community-based study. This research has been conducted using the UK Biobank Resource. PARTICIPANTS: Sixty-seven thousand three hundred eighteen people 40 to 69 years old received questionnaires, physical examination, and eye examination, including macular SD OCT. Systematic selection process identified 34 652 eyes with high-quality SD OCT images from normal individuals for analysis. METHODS: We included people with no self-reported ocular disease, diabetes, or neurologic disorders; visual acuity of ≥20/25; refraction between -6 diopters (D) to 6 D, and IOP of 6 to 21 mmHg. Only high-quality, well-centered SD OCT images with central, stable fixation were included. Descriptive statistics, t tests, and regression analyses were performed. Multivariate regression modeling was used to adjust for covariates and to identify relationships between RPE-BM thickness and ocular and systemic features. MAIN OUTCOME MEASURES: Retinal pigment epithelium-BM thickness, as measured by SD OCT segmentation using Topcon Advanced Boundary Segmentation at 9 Early Treatment of Diabetic Retinopathy Study subfields. RESULTS: Mean RPE-BM thickness was 26.3 μm (standard deviation, 4.8 μm) at central subfield. Multivariate regression with age stratification showed that RPE thinning became apparent after age 45. Among those aged ≤45, RPE-BM was significantly thicker among those of black or mixed/other race (+3.61 and +1.77 μm vs. white, respectively; P 45, RPE-BM was significantly thinner with older age (-0.10 μm/year; P < 0.001), Asian ethnicity (-0.45 μm vs. white; P = 0.02), taller height (-0.02 μm/cm; P < 0.001), higher IOP (-0.03 μm/mmHg; P < 0.001), and regular smoking (-0.27 μm vs. nonsmokers; P = 0.02). In contrast, RPE-BM was significantly thicker among black or mixed/other race (+3.29 μm and +0.81 μm vs. white, respectively; P < 0.001) and higher hyperopia (+0.28 μm/D; P < 0.001). There was no significant association with sex or Chinese ethnicity. CONCLUSIONS: We describe novel findings of RPE-BM thickness in normal individuals, a structure that varies with age, ethnicity, refraction, IOP, and smoking. The significant association with IOP is especially interesting and may have relevance for the etiology of glaucoma, while the association between age and smoking may have relevance for the etiology of age-related macular degeneration

Relationships between retinal layer thickness and brain volumes in the UK Biobank cohort

BACKGROUND: Current methods to diagnose neurodegenerative diseases are costly and invasive. Retinal neuroanatomy may be a biomarker for more neurodegenerative processes and can be quantified in vivo using optical coherence tomography (OCT), which is inexpensive and noninvasive. We examined the association of neuroretinal morphology with brain MRI image derived phenotypes (IDPs) in a large cohort of healthy older people. METHODS: UK Biobank participants aged 40 to 69 years old underwent comprehensive examinations including ophthalmic and brain imaging assessments. Macular retinal nerve fibre layer (mRNFL), ganglion cell-inner plexiform layer (mGCIPL), ganglion cell complex (mGCC) and total macular thicknesses were obtained from OCT. MRI IDPs assessed included total brain, grey-matter, white-matter and hippocampal volume. Multivariable linear regression models were used to evaluate associations between retinal layers thickness and brain MRI IDPs, adjusting for demographic factors and vascular risk factors. RESULTS: A total of 2,131 participants (mean age 55 years; 51% women) with both gradable OCT images and brain imaging assessments were included. In multivariable regression analysis, thinner mGCIPL, mGCC, and total macular thickness were all significantly associated with smaller total brain (p<0.001), grey-matter and white-matter volumes (p<0.01), and grey-matter volume in the occipital pole (p<0.05). Thinner mGCC and total macular thicknesses were associated with smaller hippocampal volume (p<0.02). No association was found between mRNFL and the MRI IDPs. CONCLUSION: Markers of retinal neurodegeneration are associated with smaller brain volumes. Our findings suggest that retinal structures may be a biomarker providing information about important brain structures in healthy, older adults

Relationship between the magnitude of intraocular pressure during an episode of acute elevation and retinal damage four weeks later in rats

PURPOSE: To determine relationship between the magnitude of intraocular pressure (IOP) during a fixed-duration episode of acute elevation and the loss of retinal function and structure 4 weeks later in rats. METHODS: Unilateral elevation of IOP (105 minutes) was achieved manometrically in adult Brown Norway rats (9 groups; n = 4 to 8 each, 10-100 mm Hg and sham control). Full-field ERGs were recorded simultaneously from treated and control eyes 4 weeks after IOP elevation. Scotopic ERG stimuli were white flashes (-6.04 to 2.72 log cd.s.m(-2)). Photopic ERGs were recorded (1.22 to 2.72 log cd.s.m(-2)) after 15 min of light adaptation (150 cd/m(2)). Relative amplitude (treated/control, %) of ERG components versus IOP was described with a cummulative normal function. Retinal ganglion cell (RGC) layer density was determined post mortem by histology. RESULTS: All ERG components failed to recover completely normal amplitudes by 4 weeks after the insult if IOP was 70 mmHg or greater during the episode. There was no ERG recovery at all if IOP was 100 mmHg. Outer retinal (photoreceptor) function demonstrated the least sensitivity to prior acute IOP elevation. ERG components reflecting inner retinal function were correlated with post mortem RGC layer density. CONCLUSIONS: Retinal function recovers after IOP normalization, such that it requires a level of acute IOP elevation approximately 10 mmHg higher to cause a pattern of permanent dysfunction similar to that observed during the acute event. There is a 'threshold' for permanent retinal functional loss in the rat at an IOP between 60 and 70 mmHg if sustained for 105 minutes or more

Optic Nerve Head Quantification in Idiopathic Intracranial Hypertension by Spectral Domain OCT

Objective: To evaluate 3D spectral domain optical coherence tomography (SDOCT) volume scans as a tool for quantification of optic nerve head (ONH) volume as a potential marker for treatment effectiveness and disease progression in idiopathic intracranial hypertension (IIH). Design and Patients: Cross-sectional pilot trial comparing 19 IIH patients and controls matched for gender, age and body mass index. Each participant underwent SDOCT. A custom segmentation algorithm was developed to quantify ONH volume (ONHV) and height (ONHH) in 3D volume scans. Results:Whereas peripapillary retinal nerve fiber layer thickness did not show differences between controls and IIH patients, the newly developed 3D parameters ONHV and ONHH were able to discriminate between controls, treated and untreated patients. Both ONHV and ONHH measures were related to levels of intracranial pressure (ICP). Conclusion: Our findings suggest 3D ONH measures as assessed by SDOCT as potential diagnostic and progression markers in IIH and other disorders with increased ICP. SDOCT may promise a fast and easy diagnostic alternative to repeated lumba

Measures of socioeconomic status and self-reported glaucoma in the UK Biobank cohort

Purpose: To determine ocular, demographic, and socioeconomic associations with self-reported glaucoma in the UK Biobank.Methods: Biobank is a study of UK residents aged 40–69 years registered with the National Health Service. Data were collected on visual acuity, intraocular pressure (IOP), corneal biomechanics, and questionnaire from 112?690 participants. Relationships between ocular, demographic, and socioeconomic variables with reported diagnosis of glaucoma were examined.Results: In all, 1916 (1.7%) people in UK Biobank reported glaucoma diagnosis. Participants reporting glaucoma were more likely to be older (mean 61.4 vs 56.7 years, P&lt;0.001) and male (2.1% vs 1.4%, P=0.001). The rate of reported glaucoma was significantly higher in Black (3.28%, P&lt;0.001) and Asian (2.14%, P=0.009) participants compared with White participants (1.62%, reference). Cases of reported glaucoma had a higher mean IOP (18?mm?Hg both eyes, P&lt;0.001), lower corneal hysteresis (9.96 right eye, 9.89 left eye, P&lt;0.001), and lower visual acuity (0.09 logMAR right eye, 0.08 logMAR left eye, P&lt;0.001) compared with those without (16?mm?Hg both eyes, hysteresis 10.67 right eye, 10.63 left eye, 0.03 logMAR right eye, 0.02 logMAR left eye). The mean Townsend deprivation index was ?0.72 for those reporting glaucoma and ?0.95 for those without (P&lt;0.001), indicating greater relative deprivation in those reporting glaucoma. Multivariable logistic regression showed that people in the lowest income group (&lt;£18?000/year) were significantly more likely to report a diagnosis of glaucoma compared with any other income level (P&lt;0.01). We observed increasing glaucoma risk across the full range of income categories, with highest risk among those of lowest income, and no evidence of a threshold effect.Conclusions: In a large UK cohort, individuals reporting glaucoma had more adverse socioeconomic characteristics. Study of the mechanisms explaining these effects may aid our understanding of health inequality and will help inform public health interventions