J. Jason McAnany

The relative capabilities of the upper and lower visual hemifields

Visual performance is better in the lower visual hemifield than in the upper field for many classes of stimuli. The origin of this difference is unclear. One theory associates it with finer-grained attention in the lower field, an idea consistent with a change in relative efficacy with task difficulty. The first experiment in this study confirmed a lower hemifield advantage for discriminating a range of stimuli, including those that differ in contrast, hue, and motion. An identical paradigm revealed an upper field advantage when stimuli differed in their apparent distances from the observer. Presentations of stimuli in the upper or lower hemifield were interlaced to reduce the likelihood of possible artifacts or biases. A second experiment varied the difficulty of these discriminations, showing that difficulty does not determine field preference. Thus, an attentional mechanism is not a likely explanation for these preferences.

Assessing Rod, Cone, and Melanopsin Contributions to Human Pupil Flicker Responses

PURPOSE We determined the relative contributions of rods, cones, and melanopsin to pupil responses in humans using temporal sinusoidal stimulation for light levels spanning the low mesopic to photopic range. METHODS A four-primary Ganzfeld photostimulator controlled flicker stimulations at seven light levels (-2.7 to 2 log cd/m(2)) and five frequencies (0.5-8 Hz). Pupil diameter was measured using a high-resolution eye tracker. Three kinds of sinusoidal photoreceptor modulations were generated using silent substitution: rod modulation, cone modulation, and combined rod and cone modulation in phase (experiment 1) or cone phase shifted (experiment 2) from a fixed rod phase. The melanopsin excitation was computed for each condition. A vector sum model was used to estimate the relative contribution of rods, cones, and melanopsin to the pupil response. RESULTS From experiment 1, the pupil frequency response peaked at 1 Hz at two mesopic light levels for the three modulation conditions. Analyzing the rod-cone phase difference for the combined modulations (experiment 2) identified a V-shaped response amplitude with a minimum between 135° and 180°. The pupil response phases increased as cone modulation phase increased. The pupil amplitude increased with increasing light level for cone, and combined (in-phase rod and cone) modulation, but not for the rod modulation. CONCLUSIONS These results demonstrate that cone- and rod-pathway contributions are more predominant than melanopsin contribution to the phasic pupil response. The combined rod, cone, and melanopsin inputs to the phasic state of the pupil light reflex follow linear summation.

Assessing retinal structure in complete congenital stationary night blindness and oguchi disease

PURPOSE To examine retinal structure and changes in photoreceptor intensity after dark adaptation in patients with complete congenital stationary night blindness and Oguchi disease. DESIGN Prospective, observational case series. METHODS We recruited 3 patients with complete congenital stationary night blindness caused by mutations in GRM6, 2 brothers with Oguchi disease caused by mutations in GRK1, and 1 normal control. Retinal thickness was measured from optical coherence tomography images. Integrity of the rod and cone mosaic was assessed using adaptive optics scanning light ophthalmoscopy. We imaged 5 of the patients after a period of dark adaptation and examined layer reflectivity on optical coherence tomography in a patient with Oguchi disease under light- and dark-adapted conditions. RESULTS Retinal thickness was reduced in the parafoveal region in patients with GRM6 mutations as a result of decreased thickness of the inner retinal layers. All patients had normal photoreceptor density at all locations analyzed. On removal from dark adaptation, the intensity of the rods (but not cones) in the patients with Oguchi disease gradually and significantly increased. In 1 Oguchi disease patient, the outer segment layer contrast on optical coherence tomography was 4-fold higher under dark-adapted versus light-adapted conditions. CONCLUSIONS The selective thinning of the inner retinal layers in patients with GRM6 mutations suggests either reduced bipolar or ganglion cell numbers or altered synaptic structure in the inner retina. Our finding that rods, but not cones, change intensity after dark adaptation suggests that fundus changes in Oguchi disease are the result of changes within the rods as opposed to changes at a different retinal locus.

Clinical value, normative retinal sensitivity values, and intrasession repeatability using a combined spectral domain optical coherence tomography/scanning laser ophthalmoscope microperimeter

PurposeTo establish normative values for macular light sensitivity and to determine the intrasession fluctuation of perimetric responses using the OPKO/OTI microperimeter.MethodsA total of 32 visually normal subjects participated in the study. A standardized grid pattern was used for testing, which consisted of 28 points arranged concentrically in three circles that occupied an area of 11° (in diameter) within the central macula. Each subject participated in at least two tests. Parameters evaluated included: overall mean macular sensitivity for test 1 and 2, overall difference in mean macular sensitivity between tests, and the mean sensitivity for each circle. The relationship between sensitivity and age was also examined.ResultsThe overall median sensitivity for test 1 was 16.8 decibels (dB) and for test 2 was 16.9 dB. The median sensitivities for test 1 and test 2 were not significantly different (P=0.72). The mean intrasession sensitivity difference was 0.13 dB. The variability of the sensitivity difference between tests decreased as mean sensitivity increased. The sensitivity values averaged across the two tests for inner, middle, and outer circles ranged from 14.3 to 18.8 dB (median value of 16.9 dB), 13.8–18.3 dB (median value of 17.2 dB), and 11.3–18.3 dB (median value of 16.6 dB), respectively. Linear regression analysis showed a 0.5 dB sensitivity loss for each decade of life.ConclusionWe documented a narrow range of intrasession fluctuation using the OPKO/OTI microperimeter. The establishment of normative sensitivity values will facilitate monitoring the loss of macular visual function in patients with retinal disease.

Magnocellular and parvocellular visual pathway contributions to visual field anisotropies

It is well established that sensitivity is not necessarily equivalent at isoeccentric locations across the visual field. The focus of this study was a psychophysical examination of the spatial sensitivity differences between the upper and lower visual hemifields under conditions biased toward the presumed magnocellular or parvocellular visual pathway. Experiment 1 showed higher contrast sensitivity in the lower visual field when visual sensitivity was biased toward the parvocellular pathway; no visual field anisotropy was found when sensitivity was biased toward the magnocellular pathway. Experiment 2 showed that the magnitude of the contrast sensitivity anisotropy within the presumed parvocellular pathway increased when test targets of higher spatial frequency were used. The results of this study have relevance for the design both of psychophysical paradigms and clinical training programs for patients with heterogeneous visual field loss.

Contrast sensitivity for letter optotypes vs. gratings under conditions biased toward parvocellular and magnocellular pathways

This study examined the extent to which letter optotypes and grating stimuli provide equivalent measures of contrast sensitivity under conditions designed to favor the magnocellular (MC) and parvocellular (PC) pathways. The contrast sensitivity functions (CSFs) of three visually normal observers were measured for Sloan letters and Gabor patches, using steady- and pulsed-pedestal paradigms to bias processing toward MC and PC pathways, respectively. CSFs for Gabor patches were low-pass for the steady-pedestal paradigm and band-pass for the pulsed-pedestal paradigm, in agreement with previous reports. However, CSFs for letters were low-pass for both testing paradigms. CSFs for letters restricted in frequency content by spatial filtering were equivalent to those for Gabor patches for both testing paradigms. Results indicate that conventional letter optotypes can provide a misleading measure of contrast sensitivity, especially under conditions emphasizing the PC pathway. The use of spatially band-pass filtered letters can provide a more appropriate evaluation of spatial contrast sensitivity while maintaining some of the potential advantages of letters.

Topical Dorzolamide for Treatment of Cystoid Macular Edema in Patients with Choroideremia

Purpose: To determine the value of a topical carbonic anhydrase inhibitor on the macular thickness and function in choroideremia patients with cystoid macular edema. Methods: Two choroideremia patients with cystoid macular edema, observed by spectral-domain optical coherence tomography, were treated with a topical form of carbonic anhydrase inhibitor. Examinations performed before and during treatment included best-corrected visual acuity by using the Early Treatment Diabetic Retinopathy Study charts and contrast sensitivity measured with briefly presented grating targets and the Pelli–Robson letter contrast sensitivity chart, microperimetry, and spectral-domain optical coherence tomography. Results: The 2 choroideremia patients treated with dorzolamide 2% formulation had a noticeable reduction in macular thickness by spectral-domain optical coherence tomography. This reduction was found in both eyes after 2 months of treatment. After an additional 3 months of the same treatment regimen, a more noticeable reduction in macular thickness was observed. The two study patients had improvement of their visual acuity, in at least one eye, on Early Treatment Diabetic Retinopathy Study charts, but no clinically significant changes for the other measures of visual function. Conclusion: The present study shows the potential efficacy of topical dorzolamide for treating choroideremia patients with cystoid macular edema.

Effect of stimulus size and luminance on the rod-, cone-, and melanopsin-mediated pupillary light reflex

This study determined if the pupillary light reflex (PLR) driven by brief stimulus presentations can be accounted for by the product of stimulus luminance and area (i.e., corneal flux density, CFD) under conditions biased toward the rod, cone, and melanopsin pathways. Five visually normal subjects participated in the study. Stimuli consisted of 1-s short- and long-wavelength flashes that spanned a large range of luminance and angular subtense. The stimuli were presented in the central visual field in the dark (rod and melanopsin conditions) and against a rod-suppressing short-wavelength background (cone condition). Rod- and cone-mediated PLRs were measured at the maximum constriction after stimulus onset whereas the melanopsin-mediated PLR was measured 5-7 s after stimulus offset. The rod- and melanopsin-mediated PLRs were well accounted for by CFD, such that doubling the stimulus luminance had the same effect on the PLR as doubling the stimulus area. Melanopsin-mediated PLRs were elicited only by short-wavelength, large (>16°) stimuli with luminance greater than 10 cd/m(2), but when present, the melanopsin-mediated PLR was well accounted for by CFD. In contrast, CFD could not account for the cone-mediated PLR because the PLR was approximately independent of stimulus size but strongly dependent on stimulus luminance. These findings highlight important differences in how stimulus luminance and size combine to govern the PLR elicited by brief flashes under rod-, cone-, and melanopsin-mediated conditions.

Evaluation of retinal nerve fiber layer thickness in patients with retinitis pigmentosa using spectral-domain optical coherence tomography

Purpose To measure the peripapillary retinal nerve fiber layer (RNFL) thickness using spectral-domain optical coherence tomography in patients with retinitis pigmentosa. Methods Fifty eyes of 30 patients with retinitis pigmentosa underwent a complete ocular examination, including best-corrected visual acuity using a Snellen chart, slit-lamp biomicroscopic examination, and Goldmann applanation intraocular pressure measurement. Dilated fundus examination was performed using both direct and indirect ophthalmoscopy. In addition, all patients underwent peripapillary RNFL thickness measurements using an OPKO spectral-domain optical coherence tomography (OPKO Instrumentations, Miami, FL). Results The mean (±SD) age of the study cohort was 45.8 (±16.3) years. Of the 50 eyes, 18 (36%) showed a thinning of the peripapillary RNFL in 1 or more quadrants and 21 (42%) showed a thickening of the peripapillary RNFL in 1 or more quadrants. Four eyes (8%) showed both thinning and thickening of the peripapillary RNFL thickness. The overall circumferential RNFL thickness of the 14 eyes that showed only thinning in at least 1 quadrant was 78.78 &mgr;m. For the 17 eyes that showed only thickening in at least 1 quadrant, the RNFL thickness was 119.69 &mgr;m. The values of the eyes with thinning and the eyes with thickening were significantly different from normal (t = 6.31 and P < 0.01 for thickening; t = 3.62 and P < 0.01 for thinning). Conclusion Using spectral-domain optical coherence tomography testing, we demonstrated in the current study that the peripapillary RNFL thickness in patients with RP can be decreased, increased, or maintained within normal limits. Assessment of the RNFL thickness seems prudent in these patients, particularly for identifying notable degrees of RNFL thinning in those being considered for future therapeutic trials.

Spatial contrast sensitivity in dynamic and static additive luminance noise

The purpose of this study was to define the quantitative relationship between the temporal characteristics of additive luminance noise and the properties of the spatial contrast sensitivity function (CSF). CSFs were obtained from two observers using Gabor patch targets of short duration that were added to white luminance noise with a range of root-mean-square contrasts (c(rms)). The noise was either dynamic or static and was either of the same duration as the test target (synchronous) or of longer duration (asynchronous). For targets presented in asynchronous dynamic, synchronous dynamic, and synchronous static noise, the CSFs became increasingly band-pass with increasing c(rms), whereas the CSFs were low-pass at all levels of c(rms) for targets presented in asynchronous static noise. For all noise types, the properties of the CSFs were well-predicted by the linear amplifier model (LAM), in which the signal energy at threshold (E(t)) is related linearly to noise spectral density (N). The fundamentally different characteristics of CSFs obtained in asynchronous static noise can be accounted for by a previous proposal that this noise type biases contrast sensitivity toward transient (inferred magnocellular) mechanisms. The other three modes of noise presentation appear to emphasize detection by sustained (inferred parvocellular) mechanisms.