Background: Neurodegenerative diseases, like multiple sclerosis, dementia and motor neurone disease, represent one of the major public health threats of our time. There is a clear persistent need for novel, affordable, and patient-acceptable biomarkers of these diseases, to assist with diagnosis, prognosis and impact of interventions. And these biomarkers need to be sensitive, specific and precise. The retina is an attractive site for exploring this potential, as it is easily accessible to non-invasive imaging. Remarkable technology revolutions in retinal imaging are enabling us to see the retina in microscopic level detail, and measure neuronal and vascular integrity. Aims and objectives: I therefore propose that retinal imaging could provide reliable and accurate markers of these neurological diseases. In this project, I aimed to explore the clinical utility of retinal imaging derived measures of retinal neuronal and vessel size and morphology, and determine their candidacy for being reliable biomarkers in these diseases. I also aimed to detail the methods of retinal imaging acquisition, and processing, and the principles underlying all these stages, in relation to understanding of retinal structure and function. This provides an essential foundation to the application of retinal imaging analysis, highlighting both the strengths and potential weaknesses of retinal biomarkers and how they are interpreted. Methods: After performing detailed systematic reviews and meta-analyses of the existing work on retinal biomarkers of neurodegenerative disease, I carried out a prospective, controlled, cross-sectional study of retinal image analysis, in patients with MS, dementia, and ALS. This involved developing new software for vessel analysis, to add value and maximise the data available from patient imaging episodes. Results: From the systematic reviews, I identified key unanswered questions relating to the detailed analysis and utility of neuroretinal markers, and diseases with no studies yet performed of retinal biomarkers, such as non-AD dementias. I recruited and imaged 961 participants over a two-year period, and found clear patterns of significance in the phenotyping of MS, dementia and ALS. Detailed analysis has provided new insights into how the retina may yield important disease information for the individual patient, and also generate new hypotheses with relation to the disease pathophysiology itself. Conclusions: Overall, the results show that retinal imaging derived biomarkers have an important and specific role in the phenotyping of neurodegenerative diseases, and support the hypothesis that the eye is an important window to neurological brain disease.

No description available.

Thesis (doctoral)--Lund University, 1994. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1994. / Added t.p. with thesis statement inserted.

Yes / Identification of glaucomatous damage and progression by perimetry are limited by measurement and response variability. This study tested the hypothesis that the glaucoma damage signal/noise ratio is greater with stimuli varying in area, either solely, or simultaneously with contrast, than with conventional stimuli varying in contrast only (Goldmann III, GIII). Thirty glaucoma patients and 20 age-similar healthy controls were tested with the Method of Constant Stimuli (MOCS). One stimulus modulated in area (A), one modulated in contrast within Ricco’s area (CR), one modulated in both area and contrast simultaneously (AC), and the reference stimulus was a GIII, modulating in contrast. Stimuli were presented on a common platform with a common scale (energy). A three-stage protocol minimised artefactual MOCS slope bias that can occur due to differences in psychometric function sampling between conditions. Threshold difference from age-matched normal (total deviation), response variability, and signal/noise ratio were compared between stimuli. Total deviation was greater with, and response variability less dependent on defect depth with A, AC, and CR stimuli, compared with GIII. Both A and AC stimuli showed a significantly greater signal/noise ratio than the GIII, indicating that area-modulated stimuli offer benefits over the GIII for identifying early glaucoma and measuring progression.

Purpose: To compare the safety and efficacy of intravitreal (IVT) and sub-Tenon (ST) triamcinolone acetonide for the treatment of refractory diffuse diabetic macular oedema. Method: 29 eyes of 22 patients with long-standing, diffuse diabetic macular oedema refractory to argon laser treatment were randomly assigned to a single 4mg injection of IVT triamcinolone acetonide or a 40mg sub-Tenon injection. Patients were subsequently monitored for six to nine months. Outcome measures were visual acuity, intraocular pressure, macular thickness on optical coherence tomography and adverse effects. Results: There was no significant improvement in visual acuity in either group. A transient decrease in macular thickness was found in the IVT group but not in the ST group. There were no significant adverse effects apart from a mild to moderate intra-ocular pressure rise found more frequently in the IVT group. Conclusion: IVT and ST triamcinolone acetonide injections for refractory diffuse diabetic macular oedema appear relatively safe and well-tolerated. IVT injection produces a significant temporary decrease in macular thickness in patients with long-standing diffuse diabetic macular oedema while ST injection does not. Neither intervention was shown to significantly improve visual acuity in this group of patients.

Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2008. / Full text also available online. Scroll down for electronic link.

Tingan Chen. / "March 2000." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (p. 100-142). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

Ng, Tsz Kin. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 151-185). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Hypothesis 1. MfERG is useful in the assessment of retinal dysfunction in patients following photodynamic therapy with verteporfin. / Hypothesis 2. MfERG is useful in the evaluation of retinal dysfunction in patients following safety-enhanced photodynamic therapy using half-dose verteporfin. / Hypothesis 3. MfERG is useful in the assessment of retinal dysfunction in patients receiving hydroxychloroquine therapy. / Hypothesis 4. MfERG findings correlate to certain extent with the visual field findings in patients receiving hydroxychloroquine therapy and mfERG might be more sensitive compared with 10-2 visual field testing in assessing retinal dysfunction associated with hydroxychloroquine therapy. / Hypothesis 5. MfERG is useful In the assessment of retinal dysfunction associated with intraoperative application of indocyaniue green for internal limiting membrane staining in epiretinal membrane surgery. / Multifocal electroretinography (mfERG) is an investigation which can provide objective assessment of retinal function, In contrast with full-field electroretinography which measures the mass electrical activity of the entire retina, mfERG allows simultaneous measurements of multiple retinal responses from the macula. / Several studies have demonstrated that mfERG might be useful in assessing retinal dysfunction caused by pharmacological agents and following laser therapy. This thesis aims to demonstrate the application of mfERG in the evaluation of retinal dysfunction associated with various ocular or systemic pharmacological agents. Three treatment modalities including photodynamic therapy with verteporfin, systemic use of hydroxychloroquine, and intraoperative application of indocyanine green dye were chosen for evaluation. These pharmacological agents were selected as they are associated with potential retinal dysfunction and are commonly encountered in the ophthalmic clinical practice. The thesis examines the following hypotheses: / Summary of studies arising from the thesis. Based on the findings from the above studies, it was demonstrated that mfERG can objectively evaluate the retinal dysfunction caused by a variety of ocular or systemic pharmacological agents. These included PDT with verteporfin, systemic therapy with hydroxychloroquine, as well as intraoperative application of ICG dye for ILM staining. The use of mfERG has enhanced the understanding of the underlying pathophysiology of drug-associated retinal toxicity. As mfERG becomes more widely available, its application will provide a valuable option for clinicians to assess toxic retinopathy objectively and enable safer administration of treatment to minimize potential retinal toxicity. (Abstract shortened by UMI.) / by Lai Yuk Yau, Timothy. / Source: Dissertation Abstracts International, Volume: 69-02, Section: B, page: 0951. / Thesis (M.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 161-183). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.