Development and application of magnetoencephalographic methods in the investigation of the human visual system

This thesis is an exploration of the organisation and functioning of the human visual system using the non-invasive functional imaging modality magnetoencephalography (MEG). Chapters one and two provide an introduction to the ‘human visual system and magnetoencephalographic methodologies. These chapters subsequently describe the methods by which MEG can be used to measure neuronal activity from the visual cortex. Chapter three describes the development and implementation of novel analytical tools; including beamforming based analyses, spectrographic movies and an optimisation of group imaging methods. Chapter four focuses on the use of established and contemporary analytical tools in the investigation of visual function. This is initiated with an investigation of visually evoked and induced responses; covering visual evoked potentials (VEPs) and event related synchronisation/desynchronisation (ERS/ERD). Chapter five describes the employment of novel methods in the investigation of cortical contrast response and demonstrates distinct contrast response functions in striate and extra-striate regions of visual cortex. Chapter six use synthetic aperture magnetometry (SAM) to investigate the phenomena of visual cortical gamma oscillations in response to various visual stimuli; concluding that pattern is central to its generation and that it increases in amplitude linearly as a function of stimulus contrast, consistent with results from invasive electrode studies in the macaque monkey. Chapter seven describes the use of driven visual stimuli and tuned SAM methods in a pilot study of retinotopic mapping using MEG; finding that activity in the primary visual cortex can be distinguished in four quadrants and two eccentricities of the visual field. Chapter eight is a novel implementation of the SAM beamforming method in the investigation of a subject with migraine visual aura; the method reveals desynchronisation of the alpha and gamma frequency bands in occipital and temporal regions contralateral to observed visual abnormalities. The final chapter is a summary of main conclusions and suggested further work.

Transversal and longitudinal images from the retina of the living eye using low coherence interferometry

An optical coherence tomography (OCT) system to produce both longitudinal and transversal images of the in vivo human eye is presented. For the first time, OCT transversal images collected from the living eye at 50-µm depth steps show details unobtainable with the state-of-the-art scanning laser ophthalmoscope. Images of up to 3×3?mm are produced from the retina in less than a second. For images larger than 1.6×1.6?mm, a path modulation is introduced by the galvanometric scanning mirror and is used as an effective phase modulation method.

Simultaneous en-face imaging of two layers in human retina by low-coherence reflectometry

We show that with a fiberized multiple Michelson-interferometer-type configuration, transverse images from several layers in the human eye can be simultaneously obtained. We demonstrate the principle by producing simultaneous 100×100 pixel en-face images of a 4 mm×4 mm region on a postmortem retina for two depth positions 250 µm apart.

Optical imaging of retina in response to grating stimuli in cats

We examined the intrinsic signals in response to grating stimuli in order to determine whether the light-evoked intrinsic signals of the retina are due to changes in the photoreceptor activities induced by the image projected on to the retina or are due to neural activities of the inner retina. The retinas of the left eye of 12 cats under general anesthesia were examined by a functional imaging fundus camera. Near infrared light was used to monitor the reflectance changes (RCs) of the retina. Vertical grating were used to stimulate the retina at 4 Hz. The spatial frequencies of the gratings were 0.05, 0.11, 0.22, 0.43, 0.86, 1.73, and 3.46 cycles/degree (cpd). Ten images were averaged and used to analyze the RCs to obtain the peak value (PV) of a two dimensional fast Fourier transfer of the RCs. The wavefront aberrations (WA) were measured with a compact wavefront aberrometer and the spatial modulation transfer function (MTF) of the eye was calculated. The retinal reflectance image had a grating pattern. The PV of the spatial sensitivity curve was highest at low spatial frequencies (0.05 and 0.11 cpd), and the sensitivity decreased steeply with an increase in the spatial frequency. RCs were not detectable at 3.46 cpd. The MTF decreased gradually with increases in the spatial frequencies and was 0.68 at 3.46 cpd. The reflectance pattern of the retinal intrinsic signal elicited by grating stimuli of different spatial frequencies was different from that of the MTF. This suggests that the intrinsic signal represents not only the response of the photoreceptors but also other neuronal or vascular changes in the retina.

25th RCOphth Congress, President's Session paper:25 years of progress in medical retina

The quarter century since the foundation of the Royal College of Ophthalmologists has coincided with immense change in the subspecialty of medical retina, which has moved from being the province of a few dedicated enthusiasts to being an integral, core part of ophthalmology in every eye department. In age-related macular degeneration, there has been a move away from targeted, destructive laser therapy, dependent on fluorescein angiography to intravitreal injection therapy of anti-growth factor agents, largely guided by optical coherence tomography. As a result of these changes, ophthalmologists have witnessed a marked improvement in visual outcomes for their patients with wet age-related macular degeneration (AMD), while at the same time developing and enacting entirely novel ways of delivering care. In the field of diabetic retinopathy, this period also saw advances in laser technology and a move away from highly destructive laser photocoagulation treatment to gentler retinal laser treatments. The introduction of intravitreal therapies, both steroids and anti-growth factor agents, has further advanced the treatment of diabetic macular oedema. This era has also seen in the United Kingdom the introduction of a coordinated national diabetic retinopathy screening programme, which offers an increasing hope that the burden of blindness from diabetic eye disease can be lessened. Exciting future advances in retinal imaging, genetics, and pharmacology will allow us to further improve outcomes for our patients and for ophthalmologists specialising in medical retina, the future looks very exciting but increasingly busy.

Simultaneous en-face imaging of two layers in human retina by low-coherence reflectometry

We show that with a fiberized multiple Michelson-interferometer-type configuration, transverse images from several layers in the human eye can be simultaneously obtained. We demonstrate the principle by producing simultaneous 100×100 pixel en-face images of a 4 mm×4 mm region on a postmortem retina for two depth positions 250 µm apart.

Transversal and longitudinal images from the retina of the living eye using low coherence interferometry

An optical coherence tomography (OCT) system to produce both longitudinal and transversal images of the in vivo human eye is presented. For the first time, OCT transversal images collected from the living eye at 50-µm depth steps show details unobtainable with the state-of-the-art scanning laser ophthalmoscope. Images of up to 3×3?mm are produced from the retina in less than a second. For images larger than 1.6×1.6?mm, a path modulation is introduced by the galvanometric scanning mirror and is used as an effective phase modulation method.