Photopsias are related in part to perceived stress and positive mood in retinitis pigmentosa.

PURPOSE: We measured the relationship between the occurrence of photopsias (spontaneous phosphenes), and retinitis pigmentosa (RP) subjects' level of vision, light exposure, and psychosocial factors to attempt to confirm RP patients' previous reports of these associations. METHODS: A total of 36 RP subjects self-administered PC-based binocular visual acuity, contrast sensitivity, and visual field tests at home twice a week, for 16 sessions in 2-3 months. After each session, subjects reported photopsias during the vision tests and completed questionnaires: Epworth Sleepiness Scale, Stanford Sleepiness Scale, Perceived Stress Scale, and Positive and Negative Affect Schedules. RESULTS: Across all subjects, photopsias occurred during 47% of sessions. Five (14%) subjects never noted photopsias, while five others noted photopsias at every session. Two-thirds of subjects experienced photopsias frequently (>20% of sessions). On average, the odds of noticing photopsias increased by 57% for every 1-point increase in mean perceived stress (OR = 1.57; 95% CI: 1.04, 2.4; P = 0.03) or reduced by 38% for every 1-point increase in positive mood (OR=0.62; 95% CI: 0.39, 0.98; P = 0.04), after adjusting for age, gender, and vision. Similarly, the odds of experiencing photopsias during a session increased by 16% for every 3-point increase in perceived stress and decreased by 17% for every 3-point increase in positive mood, after adjusting for age and gender (OR = 1.16; 95% CI: 1.01, 1.33; P = 0.048)(OR = 0.83; 95% CI: 0.73, 0.94; P = 0.004), respectively. Frequency of photopsias was not statistically significantly related to other factors measured. CONCLUSIONS: Increased photopsias appear to be related to times when subjects report increased perceived stress and/or decreased positive mood, rather than RP patients' age, level of vision, reported light exposure, or sleepiness.

Blind subjects implanted with the Argus II retinal prosthesis are able to improve performance in a spatial-motor task.

BACKGROUND/AIMS: To determine to what extent subjects implanted with the Argus II retinal prosthesis can improve performance compared with residual native vision in a spatial-motor task. METHODS: High-contrast square stimuli (5.85 cm sides) were displayed in random locations on a 19″ (48.3 cm) touch screen monitor located 12″ (30.5 cm) in front of the subject. Subjects were instructed to locate and touch the square centre with the system on and then off (40 trials each). The coordinates of the square centre and location touched were recorded. RESULTS: Ninety-six percent (26/27) of subjects showed a significant improvement in accuracy and 93% (25/27) show a significant improvement in repeatability with the system on compared with off (p<0.05, Student t test). A group of five subjects that had both accuracy and repeatability values <250 pixels (7.4 cm) with the system off (ie, using only their residual vision) was significantly more accurate and repeatable than the remainder of the cohort (p<0.01). Of this group, four subjects showed a significant improvement in both accuracy and repeatability with the system on. CONCLUSION: In a study on the largest cohort of visual prosthesis recipients to date, we found that artificial vision augments information from existing vision in a spatial-motor task. Clinical trials registry no NCT00407602.

Repeated mobility testing for later artificial visual function evaluation.

The study investigates the utility of a newly designed mobility test for repeated testing of visual function in patients with severe visual impairment and future application in evaluating functional progress in patients with artificial vision. Ten subjects divided into three groups based on visual acuity (VA) ranging from light perception to 20/200 and reduced visual field (VF) were included in the study. The mobility test consisted of using a set of four different but structurally similar and relatively short mazes having a constant number of obstacles of various sizes. The subjects, divided into three groups by acuity, passed through each course several times. In general, the patients with better VA had a larger extent of VF. Average speed and number of contacts were recorded as measures of performance. The average passing times of the groups through the courses were significantly different (p = 0.03), which was influenced by VA and VF. There was no significant difference in average number of contacts between the groups (p = 0.15). The mobility test proved to be appropriate for gaining statistically relevant results in repeated individual testing of patients with severe vision impairment. Results show promise for use this mobility test as a tool for assessing visual function of patients undergoing implantation of a visual prosthesis for artificial vision.

Simulating auditory and visual sensorineural prostheses: a comparative review.

Microelectronic vision prosthesis proposes to render luminous spots (so-called phosphenes) in the visual field of the otherwise blind subject by way of an implanted array of stimulating electrodes, and in doing so restore some spatial vision. There are now many research teams worldwide working towards a therapeutic device, analogous to the cochlear implant, for the profoundly blind. Despite the similarities between the cochlear implant and vision prostheses, there are few instances in the literature where the two approaches are compared and contrasted with a mind to informing the science and engineering of the latter. This is the focus of the present review; specifically, our interest is psychophysics and signal processing. Firstly, we examine the cochlear implant, and review a handful of psychophysical work: the acoustic simulation of cochlear implants and the method used. We focus on the use of normally hearing subjects (played coloured noise bands or sine waves) as a means of investigating cochlear-implant efficacy and speech processing algorithms. These results provide guidance to vision researchers, for they address the interpretation of simulation data, and flag key areas, such as 'artificial' perception in the presence of noise, that require experimental work in coming years. Secondly, we provide an up-to-date review of the body of analogous psychophysical work: the visual simulation, involving normal observers, of microelectronic vision prosthesis. These simulations allow predictions as to the likely clinical efficacy of the prosthesis; indeed, results to date suggest that a number on the order of 100 implanted electrodes will afford subjects mobility and recognition of faces (and other complex stimuli), while even fewer electrodes facilitate reading printed text and very simple visuomanual tasks. Further, the simulations allow investigations of image and signal processing strategies, plus they provide researchers in the field, and other interested persons, a perceptual experience that approximates what a prosthesis will likely afford implantees.

Thermal imaging aid for the blind.

To explore the efficacy of using a far infrared thermal camera with a haptic display to assist blind people in identifying humans, we performed experiments with a prototype device on five low-vision (functionally blind) subjects. Infrared allows for easy detection of human shape due to typically high contrast in temperatures from a person against their surrounding environment. Infrared cameras can be made small and inexpensive with uncooled microbolometer technology. Our study showed a great willingness by the blind subjects to use such a device after a short training session and both successful and unsuccessful operation. Future work will further develop the technology and undertake more expansive testing.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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).

Theoretical interpretation and derivation of flash-on-flash threshold parameters in visual system diseases.

Visual increment thresholds measured on backgrounds flashed on simultaneously with the test flash exhibit saturation rather than following Weber's law. These flash-on-flash thresholds have been modeled with saturating nonlinearities similar to those used to describe intensity-response functions of retinal neurons. Recently, the flash-on-flash technique has been used to assess the mechanisms of threshold elevations in visual system diseases. However, the results were interpreted in a qualitative way. This paper extends the clinical application of flash-on-flash threshold measures by providing a theoretically derived algorithm for estimating nonlinear model parameters from flash-on-flash threshold data. The performance of the algorithm is evaluated with Monte Carlo techniques, and the theoretical interpretations of the model parameters are tested experimentally. Published clinical flash-on-flash threshold data are reanalyzed using the algorithm. A previously unappreciated decrease in the half-saturation constant of retinitis pigmentosa patients was revealed by this analysis.