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Biomedical subjects

G Dagnelie

Publications and source records attributed to G Dagnelie.

At least 19 recordsLinked to original sources

Are lutein and zeaxanthin conditionally essential nutrients for eye health?

The carotenoids lutein and zeaxanthin are found in the macula in high concentrations and may play a role in the pathogenesis of age-related macular degeneration (ARMD). Lutein and zeaxanthin may protect the macula and photoreceptor outer segments throughout the retina from oxidative stress and play a role in an antioxidant cascade that safely disarms the energy of reactive oxygen species. Although lutein and zeaxanthin are not essential nutrients, studies are beginning to suggest that they fit the criteria for conditionally essential nutrients. Low plasma lutein and zeaxanthin concentrations or dietary intake are associated with low macular pigment density and increased risk of ARMD. Dietary deprivation of lutein and zeaxanthin in primates causes pathological changes in the macula. Should controlled clinical trials show lutein and/or zeaxanthin supplementation protects against the development or progression of ARMD and other eye diseases, then lutein and zeaxanthin could be considered as conditionally essential nutrients for humans.

Aging↗

Human neural retinal transplantation.

PURPOSE: A pilot study of human neural retinal transplantation was undertaken to investigate three major issues: whether a safe surgical procedure could be devised for transplantation of neural retinal tissue into the subretinal space, whether the transplant would be accepted in the subretinal space, and whether an improvement in vision could be achieved. METHODS: Eight patients with bare light perception (LP) vision due to retinitis pigmentosa (RP) and one patient with bare LP vision due to advanced neovascular age-related macular degeneration (AMD) received subretinal transplants of human fetal retinal microaggregate suspensions without postoperative systemic immunosuppression. The patient with AMD also received a fetal retinal sheet transplant. The ages of the patients ranged from 31 to 94 years (median, 55 years). The pre- and postoperative evaluations included visual function testing, detailed fundus examinations, fundus photography, fluorescein angiography, macular perimetry using a scanning laser ophthalmoscope (SLO), and full field and focal electroretinograms (ERGs). RESULTS: Three of the eight RP patients demonstrated possible improved light sensitivity during the initial months of follow-up. However, visual improvement disappeared between 3 and 13 months of follow-up. After transplantation, no subject showed any changes in the ERG recordings or SLO macular perimetry relative to their preoperative baseline. No patient experienced a retinal detachment, infection, or extensive bleeding. None of the patients developed retinal vasculitis or intraocular inflammation. In one RP patient, fluorescein angiography and fundus photography documented the formation and maturation of new host retinal vessels in the area of the transplant. CONCLUSIONS: Transplantation of fetal retinal photoreceptor suspensions into the subretinal space was achieved safely in nine subjects. Although a definite positive effect on visual function could not be demonstrated, the apparent high tolerance for graft tissue is promising for future efforts in the field of neural retinal transplantation.

Adult↗

Lutein improves visual function in some patients with retinal degeneration: a pilot study via the Internet.

PURPOSE: The purpose of this article is to examine the effects of lutein supplementation on visual acuity, central visual-field area, and subjective visual disturbances in retinitis pigmentosa (RP) and related retinal degenerations, in an international study population recruited via an Internet mailing list. METHODS: Sixteen participants (13 with RP, three with other retinal degenerations) completed a 26-week program of lutein supplementation (40 mg/day for 9 weeks, 20 mg/day thereafter); 10 participants also took 500-mg docosahexaenoic acid (DHA)/day, vitamin B complex, and digestive enzymes. Ten participants previously taking vitamin A and/or beta-carotene continued those supplements throughout the study. Participants self-tested their visual acuity on their computer screen and their central visual-field extent on a wall chart, weekly for 14 weeks, bi-weekly thereafter. RESULTS: Mean visual acuity improved by 0.7 dB and mean visual-field area by 0.35 dB. Improvements started 2 to 4 weeks after supplementation began, and plateaued at 6 to 14 weeks. Visual acuity gains were strongly correlated with eye color: 1.2 dB in seven blue-eyed participants, but 0.3 dB in seven dark-eyed participants. Participants who received previous supplements showed greater benefits in central visual-field area (0.55 dB) than those not receiving previous supplements (no change). No significant effects of age, sex, disease stage, or study supplement were found. CONCLUSIONS: Short-term vision improvements after lutein supplementation--previously reported in age-related macular degeneration--also occur in RP, especially in blue-eyed individuals; vitamin A may increase visual field benefits.

Administration, Oral↗

Understanding the origin of visual percepts elicited by electrical stimulation of the human retina.

BACKGROUND: The success of a retinal prosthesis for patients with outer retinal degeneration (ORD) depends on the ability to electrically stimulate retinal cells other than photoreceptors. Experiments were undertaken in human volunteers to ascertain whether electrical stimulation of cells other than photoreceptors will result in the perception of light. METHODS: In two subjects, two areas of laser damage (argon green and krypton red) were created in an eye scheduled for exenteration due to recurrent cancer near the eye. In the operating room prior to exenteration, under local anesthesia, a hand-held stimulating device was inserted via the pars plana and positioned over the damaged areas and normal retina. Subjects' psychophysical responses to electrical stimulation were recorded. RESULTS: In both subjects, electrical stimulation produced the following perceptions. Normal retina: dark oval (subject 1), dark half-moon (subject 2); krypton red laser-treated retina: small, white light (both subjects); argon green laser treated retina: thin thread (subject 1), thin hook (subject 2). Histologic evaluation of the krypton red-treated retina showed damage confined to the outer retinal layers, while the argon green-treated area evinced damage to both the outer and the inner nuclear layers. CONCLUSION: The perception produced by electrical stimulation was dependent on the retinal cells present. Electrical stimulation of the krypton red-ablated area best simulated the electrically elicited visual perceptions of our blind, ORD patients, suggesting that the site of stimulation in blind patients is the inner retinal neurons.

Aged↗

Pattern electrical stimulation of the human retina.

Experiments were conducted to study if electrical stimulation of the retinal surface can elicit visual sensation in individuals blind from end-stage retinitis pigmentosa (RP) or age-related macular degeneration (AMD). Under local anesthesia, different stimulating electrodes were inserted through the eyewall and positioned over the surface of the retina. Subjects' psychophysical responses to electrical stimulation were recorded. Subjects perceived simple forms in response to pattern electrical stimulation of the retina. A non-flickering perception was created with stimulating frequencies between 40 and 50 Hz. The stimulation threshold was dependent on the targeted retinal area (macular versus extramacular).

Blindness↗

Allogenic fetal retinal pigment epithelial cell transplant in a patient with geographic atrophy.

PURPOSE: To test the hypothesis that healthy fetal retinal pigment epithelium (RPE) can rescue the remaining viable RPE and choriocapillaries and thereby the photoreceptors in non-neovascular age-related macular degeneration (ARMD) (geographic atrophy [GA]). METHODS: A 65-year-old legally blind woman with non-neovascular ARMD underwent fetal RPE transplantation. Best-corrected visual acuity testing, detailed fundus examination, fundus photography, fluorescein angiography, scanning laser ophthalmoscope macular perimetry, and humoral and cellular immune response testing were performed. A suspension of RPE was infused into the subretinal space through a retinotomy along the superotemporal arcade at the edge of the area of GA. The patient did not take systemic immunosuppressants. RESULTS: The patient's vision remained unchanged for 5 months after the surgery. Fluorescein angiography after transplantation showed leakage and staining at the level of the outer retina. There was progressive subretinal fibrosis in the area of the transplant. Immune response studies showed a weakly positive mixed lymphocyte response against phosducin and rhodopsin. CONCLUSION: Although it is surgically feasible to transplant fetal RPE to the subretinal space of patients with GA, such an allogenic RPE transplant without immunosuppression leads to leakage on fluorescein angiography and eventual fibrosis. A very weak immune response against proteins associated with photoreceptors is also of concern.

Aged↗

Visual perception elicited by electrical stimulation of retina in blind humans.

OBJECTIVE: To evaluate the feasibility of bypassing damaged photoreceptors and electrically stimulating the remaining viable retinal layers to provide limited visual input to patients who are blind because of severe photoreceptor degeneration. METHODS: In the operating room with the patient under local anesthesia, focal electrical stimulation of the retinal surface with brief biphasic pulses was performed using small probes inserted through the sclera. The procedure was performed in five subjects who had little or no light perception. Three subjects had retinitis pigmentosa, one had age-related macular degeneration, and one had unspecified retinal degeneration from birth. RESULTS: Stimulation elicited visual perception of a spot of light (phosphene). Subjects who previously had useful vision accurately localized the phosphenes according to the retinal area stimulated. Two subjects could track the movement of the stimulating electrode by reporting movement of the elicited phosphene, and could perceive two simultaneous phosphenes on independent stimulation with two electrodes. In a resolution test, one of the subjects with no light perception in his left eye resolved phosphenes at 1.75 degrees center-to-center distance (ie, 4/200 OS visual acuity). CONCLUSIONS: Local electrical stimulation of the retinal surface in patients blind from outer retinal disease results in focal light perception that seems to arise from the stimulated area. Such findings in an acute experiment warrant further research into the possibility of prolonged retinal stimulation, improved resolution, and ultimately, an intraocular visual prosthesis.

Adult↗

Visual stabilization of posture in persons with central visual field loss.

PURPOSE: To determine whether people with central visual field loss (CFL) show a smaller visual contribution to posture stabilization than people with normal vision and to determine the visual factors that predict the magnitude of visual stabilization in people with central visual field loss. METHODS: Posture information was recorded in 19 subjects with CFL and in 20 subjects with normal vision. Data were collected as the subject stood in a dark environment and also as he or she viewed a stationary visual display. In both conditions, somatosensory feedback was concurrently altered. The central visual fields of the subjects with CFL were measured by static perimetry with the confocal scanning laser ophthalmoscope. Binocular visual acuity and contrast sensitivity were measured on all subjects using the ETDRS and Pelli-Robson charts, respectively. Image-displacement thresholds were measured in a subset of the subjects. RESULTS: On average, subjects with central field loss showed a smaller visual contribution to posture stabilization than subjects with normal vision. The reduction in sway caused by visual stimuli was only 29% for the subjects with CFL compared to 41% for the subjects with normal vision. Displacement thresholds accounted for 45% of the variance in the visual stabilization magnitude of the subjects with CFL. No other visual factor significantly increased the coefficient of determination. CONCLUSIONS: The visual self-motion cues generated by small body oscillations may be undetectable and, thus, unusable as cues to postural sway by people with central field loss.

Aged↗

Landmark-driven fundus perimetry using the scanning laser ophthalmoscope.

PURPOSE: To present a new method of performing scanning laser ophthalmoscope perimetry that compensates for eye movements so that the correct retinal location is tested even if fixation changes. This allows for accurate testing of patients with central scotomas and for repeating testing longitudinally at the same retinal locations even if central fixation is lost. METHODS: The operator views the retina and selects a retinal landmark, such as a vessel bifurcation, that can be identified easily. A testing strategy is preselected, and the computer saves the landmark and stimulus coordinates. To present each stimulus, the operator positions a cursor over the retinal landmark, and the computer adjusts the site of presentation of the stimulus for any change in landmark position caused by an eye movement. At the conclusion of the testing, the results are displayed in the proper retinal location on a fundus image. RESULTS: Sixty-seven eyes with macular disease were tested with the landmark-driven method, using the same preplanned strategy for each eye for both a bright and a dim stimulus. There was a low rate of inconsistent points (seen with dim but not bright stimuli), and virtually all of these bordered a dense scotoma. Those eyes with more inconsistent points had a significantly greater percentage of dense scotoma points and significantly lower visual acuity. The technique significantly corrected error in retinal localization resulting from large eye movement. There is no significant rotation or magnification change during the procedure, so specifying the change in location of one landmark is sufficient to describe movement of the retina. The technique is rapid and easy to administer to elderly patients and to children. CONCLUSIONS: This technique allows for accurate and repeatable measures of retinal sensitivity in specific locations. It is useful in following change over time. It can be developed further to allow for fully automated, retinally correct testing.

Adolescent↗

Visual stabilization of posture in retinitis pigmentosa and in artificially restricted visual fields.

PURPOSE: To investigate the relationship between retinitis pigmentosa (RP) progression and the visual contribution to posture stabilization; to examine the extent to which visual-field diameter affects the visual contribution to posture stabilization. METHODS: Posture information was recorded in 35 subjects with well-characterized RP and in 20 subjects with normal vision. Data were collected as each subject stood in a dark environment and as each subject viewed a stationary visual display. In both conditions, somatosensory feedback was concurrently altered. Data were also collected on 10 additional subjects with normal vision wearing field-restricting goggles (visual-field diameters ranged from 26.5 down to 6 degrees). RESULTS: RP progression is accompanied by a steady decrease of the visual stabilization of posture, from normal values at the onset of the disease to the absence of visual stabilization and, eventually, to visual destabilization of posture. Decreasing visual field diameter in the subject with normal vision resulted in a linear decrease of the visual stabilization of posture. However, subjects with RP with comparable visual-field loss showed significantly lower visual stabilization than normal subjects with artificially restricted fields. Moreover, subjects with normal vision with restricted visual fields as small as 6 degrees failed to show visual destabilization of posture. CONCLUSIONS: Most likely, the additional reduction in the visual stabilization of posture shown in subjects with RP, as well as the visual destabilizing effect manifest in the late stages of RP, is caused by anomalous processing of visual information in the remaining visual field.

Adult↗

Foveal cone involvement in retinitis pigmentosa progression assessed through flash-on-flash parameters.

PURPOSE: To compare psychophysical Naka-Rushton parameters in retinitis pigmentosa (RP) patients and healthy controls using a flash-on-flash increment threshold paradigm, and to measure changes of these parameters with RP progression. METHODS: Sixty-six RP patients and 10 normal subjects were tested, and their maximum response (Rmax), half-saturation intensity (sigma), and slope (n) parameters were estimated. RESULTS/CONCLUSIONS: Rmax in RP patients is decreased significantly with respect to the range in normal controls and continues to decrease (0.024 log units/yr) with disease progression. The distribution of sigma in RP patients differs from that in normal subjects, showing lower values in general, but no progression. Small differences in parameter distributions among genetic or pathophysiologic RP subcategorizations were found, but these do not fulfill stricter statistical criteria required for multiple comparisons. Measurement noise, inherent in the flash-on-flash paradigm, exert considerable influence on the quality of the data, as was demonstrated through repeated measures and a Monte Carlo simulation.

Adolescent↗

Foveal cone involvement in retinitis pigmentosa progression assessed through psychophysical impulse response parameters.

PURPOSE: To compare psychophysical impulse response parameters in retinitis pigmentosa (RP) patients and healthy controls using a temporal contrast sensitivity threshold paradigm, and to measure changes in these parameters with RP progression. METHODS: Sixty-six RP patients and 10 healthy control subjects were tested, and the amplitude and timing parameters of the psychophysical impulse response function were computed through time-domain transformation under assumption of minimum-phase properties. RESULTS/CONCLUSIONS: The initial rise time of the impulse response, ta, was significantly lengthened in RP patients compared to controls, as was the fall time from peak to trough, tp-->t. The log peak-to-trough amplitude, log R, was significantly reduced. With disease progression, all impulse response parameters continued to move away from the normal range. Only minor distinctions according to RP pathophysiologic subtype or mode of inheritance were found, supporting the hypothesis of a common course of the secondary retinal degeneration across different RP subcategories.

Adolescent↗

Temporal impulse responses from flicker sensitivities: practical considerations.

The application of the transformation technique of Stork and Falk [J. Opt. Soc. Am. A 4, 1130 (1987)] to the temporal contrast sensitivity functions of patients and normal subjects brings out several pitfalls that resulted from their choices for low- and high-frequency extrapolation. Other choices, more closely reflecting the known properties of human flicker sensitivity, are proposed, and the improved recovery of the impulse response function under the improved procedure is demonstrated.

Contrast Sensitivity↗

Topography and homogeneity of monkey V1 studied through subdurally recorded pattern-evoked potentials.

Using small checkerboard stimulus fields, we have recorded visually evoked potentials (VEPs) in an alert rhesus monkey from an array of 35 electrodes chronically implanted between dura and arachnoid to study mass neuronal activity in striate and peristriate visual cortex. Although the principal purpose of this work was to study in detail cortical mapping in this particular animal for future intracortical recordings, we report here the usefulness of our approach for the non-invasive study of cortical processing, in particular of cortical magnification and receptive-field properties over the central 6 degrees of the visual field. The striate and extrastriate components in the pattern onset VEP both have a double negative-going waveform, with N-P-N peak latencies of 75-100-135 ms and 90-115-160 ms, respectively, for small element sizes and moderate contrasts; latencies may be 5 ms shorter for large element sizes and high contrast. We found little activity at electrode locations over visual areas beyond V2. The waveforms and timing permit some careful speculation concerning intracortical processing and VEP generation. The complex logarithmic form of the retinotopical projection provides a satisfactory model for our data, if a value of 1-1.2 degrees is used for the offset parameter a. Our data suggest that the most abundant receptive-field size in foveal striate cortex has a center diameter of 12'. This size remains constant up to 2 degrees eccentricity, and increases only slowly up to 4 degrees. The smallest receptive-field sizes seem to be independent of eccentricity throughout the central 4 degrees of V1, with a value of 4-8', in agreement with single-cell data reported by Dow et al. (1981) and Van Essen et al. (1984).

Animals↗

Principal components analysis for source localization of VEPs in man.

This study defines and compares the topologies of the visual evoked potentials to various stimuli such as pattern onset/offset, pattern reversal, pattern motion and high frequency luminance flicker. The responses recorded from 24 occipital derivations were examined using a three sphere conductance model to represent the head, with the assumption that activity from an underlying cortical source is equivalent to a single dipole. Principal components analysis was used to find the dimensionality of the data space. From this analysis could be concluded that all stimuli evoked responses in the primary visual cortex. Only pattern onset, and to a lesser degree pattern offset and pattern reversal, yielded activity in higher visual areas. In particular it has been shown that the CI, CII interval of the pattern onset response has its origins in two different cortical regions. A fast positive (CI)-negative (part of the CII) component arises from area 18 (or 19), a slower negative (initial part of CII) component comes from area 17.

Evoked Potentials, Visual↗

Pattern reversal stimuli: motion or contrast?

Pattern reversal stimuli are widely used for electrophysiological examination of the visual system. To investigate the mechanisms contributing to the pattern reversal EP (PREP) we performed experiments with a trained alert macaque monkey, using both contrast and motion stimuli. It was found that, as in man, for parafoveal and peripheral stimulation the PREP can be constructed from the EPs to the onset and offset of pattern motion. On the other hand foveal stimulation activates the contrast mechanism only. Our conclusion is that pattern reversal data should be considered with caution since pattern reversal can activate motion as well as contrast mechanisms. This ambiguity is not present in the pattern appearance-disappearance stimulus.

Animals↗

Flicker and movement constituents of the pattern reversal response.

A counterphase-modulated (i.e. contrast reversing) pattern will affect hypothetical neural elements sensitive to motion as well as hypothetical elements sensitive to changes in contrast and other elements sensitive to local luminance. Attempts to describe visual evoked potentials (VEPs) to contrast reversal entirely in terms of luminance change or entirely in terms of contrast change have been unsuccessful; strong interactions between responses to contrast decrease and increase had to be postulated ad hoc in order to account for the contrast reversal VEP, and no explanation for these interactions has been proposed. Rather than attempting to separate the reversal VEP into responses to contrast decrease and increase, we attempt here to analyze the reversal VEP into responses to motion onset and offset. We find that VEPs to an abrupt displacement of less than one square's width of a checkerboard pattern are qualitatively similar to the contrast reversal VEP, and that the displacement VEP can be seen as the limiting case of a motion onset response shortly followed by a motion offset response. When displacement occurs during steady motion, the displacement and motion responses interact. We conclude that the contrast reversal VEP is better described in terms of motion onset and offset response than in terms of contrast onset and offset responses.

Adaptation, Ocular↗

Subdurally recorded pattern and luminance EPs in the alert rhesus monkey.

Two rhesus monkeys (Macaca mulatta) were trained to fixate a TV screen on which checkerboard and bar patterns could be presented. Stainless steel skull electrodes and electrode bundles under the dura, each containing 7 leads permitting 7 recording sites at 5 mm intervals, were placed over the temporal-occipital cortex and used to obtain visually evoked potentials (VEPs). The following conclusions were reached: VEPs recorded with skull electrodes resemble scalp recorded VEPs. Subdural electrodes may yield larger VEP amplitudes than skull or scalp electrodes. Subdural VEPs vary more in shape with recording site than scalp or skull recorded VEPs. Apart from differences in shape there are topographical differences between luminance and pattern EPs; the luminance EP is localized near the occiput and the pattern EP is most pronounced at the temporal site overlying the foveal projection area. For a given recording site it can be seen that: (a) the amplitude of the pattern reversal EP is smaller than that of the pattern onset EP; (b) the shape of the reversal EP resembles the pattern offset EP; and (c) the shape of the pattern onset EP is rather invariant to check size and bar width. On the basis of the pattern EP the striate and prestriate cortical areas can be distinguished as follows: (a) the prestriate cortex yields a positive-negative-positive (PNP) response complex to pattern onset and the striate cortex a PN response complex; and (b) the striate cortex responds to finer patterns than the prestriate cortex.

Animals↗