Experimental demonstration of ray-rotation sheets.

We have built microstructured sheets that rotate, on transmission, the direction of light rays by an arbitrary, but fixed, angle around the sheet normal. These ray-rotation sheets comprise two pairs of confocal lenticular arrays. In addition to rotating the direction of transmitted light rays, our sheets also offset ray position sideways on the scale of the diameter of the lenticules. If this ray offset is sufficiently small so that it cannot be resolved, our ray-rotation sheets appear to perform generalized refraction.

Experimental demonstration of ray-optical refraction with confocal lenslet arrays.

We observe imaging through windows comprising pairs of confocal lenslet arrays that have different focal lengths but that are otherwise identical. Image space is stretched in the longitudinal direction only. Such windows are examples of METATOYs, optical components that can change light-ray direction in ways that appear wave-optically forbidden.

Measured double-pass intensity point-spread function after adaptive optics correction of ocular aberrations.

The double-pass intensity point-spread function was recorded in four subjects using a monochromatic source emitting at 543 nm, through a 6.7-mm diameter pupil i) at the fovea after adaptive optics correction of the ocular aberrations, ii) at the fovea without adaptive optics correction, and iii) at 2 degrees of eccentricity with adaptive optics correction. The half-width at half-maximum of the double-pass point-spread function was narrower after correction of the ocular aberrations. At 2 degrees of eccentricity this width was larger than at the fovea. The minimum widths were about 1.1 arcmin in dark pigmented eyes and 1.6 arcmin in light pigmented eyes. These values are 6 to 9 times larger than the width expected from diffraction alone.

Regulation of subfoveal choroidal blood flow in age-related macular degeneration.

PURPOSE: To assess the capability of the subfoveal choroidal circulation to regulate its blood flow in response to an acute increase in ocular perfusion pressure in the eyes of healthy elderly persons or of subjects with neovascular age-related macular degeneration (AMD). METHODS: Changes of subfoveal choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBF) induced by isometric exercise were determined using laser Doppler flowmetry (LDF) in 19 young healthy volunteers (group 1), 24 elderly healthy volunteers with mild macular pigment distribution changes (group 2), and 23 subjects with subfoveal classic neovascularization caused by AMD (group 3). RESULTS: Isometric exercise induced significant increases in mean ocular perfusion pressure (PPm) of 19.5% +/- 4.9%, 20.2% +/- 3.8%, and 23.2% +/- 4.2%, for groups 1, 2, and 3, respectively (mean +/- 95% confidence interval). In groups 1 and 2, the increase in PPm did not induce significant changes in the mean values of the different LDF parameters. In group 3, however, ChBF increased significantly by 12.4% +/- 5.0%. No significant correlations were found between age and the changes of each of the LDF parameters and of PPm at the end of squatting for the young and elderly healthy groups. CONCLUSIONS: In response to an acute, moderate increase in PPm induced by isometric exercise, subfoveal choroidal blood flow behaves similarly in young and elderly healthy persons and is not significantly different from its value at rest. In contrast, in patients with neovascular AMD, this flow increases, indicating altered regulation in response to the increase in PPm.

Visually evoked hemodynamical response and assessment of neurovascular coupling in the optic nerve and retina.

The retina and optic nerve are both optically accessible parts of the central nervous system. They represent, therefore, highly valuable tissues for studies of the intrinsic physiological mechanism postulated more than 100 years ago by Roy and Sherrington, by which neural activity is coupled to blood flow and metabolism. This article describes a series of animal and human studies that explored the changes in hemodynamics and oxygenation in the retina and optic nerve in response to increased neural activity, as well as the mechanisms underlying these changes. It starts with a brief review of techniques used to assess changes in neural activity, hemodynamics, metabolism and tissue concentration of various potential mediators and modulators of the coupling. We then review: (a) the characteristics of the flicker-induced hemodynamical response in different regions of the eye, starting with the optic nerve, the region predominantly studied; (b) the effect of varying the stimulus parameters, such as modulation depth, frequency, luminance, color ratio, area of stimulation, site of measurement and others, on this response; (c) data on activity-induced intrinsic reflectance and functional magnetic resonance imaging signals from the optic nerve and retina. The data undeniably demonstrate that visual stimulation is a powerful modulator of retinal and optic nerve blood flow. Exploring the relationship between vasoactivity and metabolic changes on one side and corresponding neural activity changes on the other confirms the existence of a neurovascular/neurometabolic coupling in the neural tissue of the eye fundus and reveals that the mechanism underlying this coupling is complex and multi-factorial. The importance of fully exploiting the potential of the activity-induced vascular changes in the assessment of the pathophysiology of ocular diseases motivated studies aimed at identifying potential mediators and modulators of the functional hyperemia, as well as conditions susceptible to alter this physiological response. Altered hemodynamical responses to flicker were indeed observed during a number of physiological and pharmacological interventions and in a number of clinical conditions, such as essential systemic hypertension, diabetes, ocular hypertension and early open-angle glaucoma. The article concludes with a discussion of key questions that remain to be elucidated to increase our understanding of the physiology of ocular functional hyperemia and establish the importance of assessing the neurovascular coupling in the diagnosis and management of optic nerve and retinal diseases.

Flicker-evoked response measured at the optic disc rim is reduced in ocular hypertension and early glaucoma.

PURPOSE: To determine in patients with ocular hypertension (OHT) or early glaucoma (EOAG) the change in blood flow measured at the neuroretinal rim of the optic disc in response to a 15-Hz diffuse green luminance flicker, a stimulus that activates predominantly the ganglion cell magnocellular pathway. METHODS: Thirteen patients with EOAG, 29 with OHT, and 16 age-matched control subjects, all with excellent fixation, were examined. Blood flow (F(onh)) at the neuroretinal rim of the optic disc was continuously monitored by laser Doppler flowmetry before and during exposure to a 15-Hz, 30 degrees field green luminance flicker. The response of F(onh) to this stimulus (RF(onh)) was expressed as percentage change in F(onh) between baseline and the last 20 seconds of flicker. Two to three temporal sites of the disc were tested, and the highest RF(onh) was considered for further analysis. RF(onh) results in patients were correlated with morphologic (cup-to-disc area ratio, cup shape neuroretinal rim area) and functional (perimetric mean deviation and pattern electroretinogram amplitude) clinical parameters. RESULTS: In the patients with OHT or EOAG, F(onh) and RF(onh) were both reduced compared with their respective values in the control group. Both quantities decreased significantly with neuroretinal rim area when the patients' data were pooled. No significant correlation was found between F(onh) or RF(onh) and the other morphometric and functional parameters. The group-averaged time course of RF(onh) was not significantly different from that in the normal subjects. CONCLUSIONS: Luminance flicker-evoked RF(onh) is abnormally reduced in patients with OHT or EOAG, indicating an impairment of neurally mediated vasoactivity. The data suggest that PERG-derived neural activity and flicker-evoked RF(onh) can be independently altered early in the disease process.

Temporal dynamics and magnitude of the blood flow response at the optic disk in normal subjects during functional retinal flicker-stimulation.

Near-infrared laser Doppler flowmetry was applied in 15 normal volunteers to record the time course and magnitude of changes in the velocity (Vel), volume (Vol) and flow (F) of blood and tissue reflectance (R) at the optic disk in response to 40 and 50 s of increased retinal neural activity. This activity was evoked by diffuse luminance flicker of the retinal posterior pole. After 20 s of flicker, the group averages of Vel, Vol, and F were significantly higher than at baseline (pre-flicker) by 12, 24 and 38%. Time constants of the increases in Vel, Vol, and F were 3.4, 12.7 and 9.1 s, respectively. The group average change in R of 1% was not significant. However, in one subject, 15 recordings from the same site of the optic disk showed a significant increase in R of 8%, with a time course similar to that of Vol. Our findings show that, in the human optic nerve, a white matter tissue, the temporal dynamics and magnitude of the response of blood flow to an increase in retinal neural activity are similar to those reported for brain gray matter. Furthermore, although the R-response could be due, in part, to changes in blood volume, other factors, such as activity-evoked tissue scattering changes, may also affect this response.

Flicker-evoked changes in human optic nerve blood flow: relationship with retinal neural activity.

PURPOSE: Visual flicker induces a response in human optic nerve blood flow (F(onh)) and inner retinal activity, as assessed by laser Doppler flowmetry and electroretinogram (ERG), respectively. In this study the relationship was examined between the flicker-evoked changes in F(onh) (RF(onh)) and ERG when various parameters of the stimulus were varied. METHODS: In five normal observers (mean age, 41; range, 25-62 years) F(onh) and ERG were recorded simultaneously in response to pure red (R) or pure green (G) flicker, as well as heterochromatic R-G flicker (30 degrees field at the posterior pole). RF(onh) and the changes in the first (1F) and second (2F) harmonic amplitudes of the ERG were documented as a function of the frequency of pure luminance and equiluminant R-G flicker, the mean illuminance of 10-Hz luminance flicker, and the color ratio r = R/(R + G) of a 15-Hz heterochromatic R-G flicker. RESULTS: Frequency-dependent changes in RF(onh) were similar to those in both 1F and 2F amplitudes for equiluminant R-G flicker. RF(onh) and 2F amplitude increased and then saturated with increasing mean illuminance of luminance flicker. They both decreased similarly as the R-G flicker approached the r value corresponding to equiluminance. RF(onh) was positively correlated with both 1F and 2F amplitudes (r = 0.55 and 0.31, respectively, P < 0.05) when these quantities were recorded as a function of frequency of R-G equiluminant flicker. RF(onh) was positively correlated with 2F amplitudes when both quantities were recorded as a function of mean illuminance of luminance flicker and r of heterochromatic R-G flicker (r = 0.52 and 0.48, respectively, P < or = 0.01). CONCLUSIONS: Under specific experimental conditions, changes in human RF(onh) are similar to and correlated with those of the flicker ERG 1F and 2F amplitudes. These findings support a relationship between vaso- and neural activity changes in the neural tissue of the human eye.

Relationship of blood flow changes of the human optic nerve with neural retinal activity: a new approach to the study of neuro-ophthalmic disorders.

BACKGROUND: The relationship between the flicker-evoked changes in optic nerve blood flow (F onh ) and neural retinal activity was investigated by laser Doppler flowmetry and electroretinogram (ERG), respectively. MATERIAL AND METHODS: In five normal subjects F onh was continuously recorded before, during and after exposure to green flicker modulation (30 degrees field at the posterior pole), at different levels of mean illuminance between 0.9 and 13.5 lux. During flicker stimulation, ERGs were simultaneously recorded with F onh. The flicker-evoked changes in F onh ( RF onh ) and the amplitudes of the first (1F) and second (2F) harmonic component of the ERG were measured. RESULTS: By increasing mean flicker illuminance, RF onh and ERG 2F, but not 1F amplitude first increased and then saturated beyond 10 lux. RF onh and the corresponding 2F amplitudes, recorded at the various mean illuminances, showed a significant positive correlation (r = 0.79, p < 0.01). CONCLUSIONS: Under specific experimental conditions, changes in human RF onh are quantitatively correlated with those of the flicker ERG 2F amplitudes. Since the 2F component reflects, unlike 1F, a strong contribution from inner retina, the present findings support the presence of an association between vasoactivity and inner retinal activity changes in the human eye. This finding may provide a new approach to the study of neuro-ophthalmic disorders.