Function Of Retinal Eccentricity Research Articles

Enhanced S-Cone Syndrome: Elevated Cone Counts Confer Supernormal Visual Acuity in the S-Cone Pathway.

To measure photoreceptor packing density and S-cone spatial resolution as a function of retinal eccentricity in patients with enhanced S-cone syndrome (ESCS) and to discuss the possible mechanisms supporting their supernormal S-cone acuity. We used an adaptive optics scanning laser ophthalmoscope (AOSLO) to characterize photoreceptor packing. A custom non-AO display channel was used to measure L/M- and S-cone-mediated visual acuity during AOSLO imaging. Acuity measurements were obtained using a four-alternative, forced-choice, tumbling E paradigm along the temporal meridian between the fovea and 4° eccentricity in five of six patients and in seven control subjects. L/M acuity was tested by presenting long-pass-filtered optotypes on a black background, excluding wavelengths to which S-cones are sensitive. S-cone isolation was achieved using a two-color, blue-on-yellow chromatic adaptation method that was validated on three control subjects. Inter-cone spacing measurements revealed a near-uniform cone density profile (ranging from 0.9-1.5 arcmin spacing) throughout the macula in ESCS. For comparison, normal cone density decreases by a factor of 14 from the fovea to 6°. Cone spacing of ESCS subjects was higher than normal in the fovea and subnormal beyond 2°. Compared to the control subjects (n = 7), S-cone-mediated acuities in patients with ESCS were normal near the fovea and became increasingly supernormal with retinal eccentricity. Beyond 2°, S-cone acuities were superior to L/M-cone-mediated acuity in the ESCS cohort, a reversal of the trend observed in normal retinas. Higher than normal parafoveal cone densities (presumably dominated by S-cones) confer better than normal S-cone-mediated acuity in ESCS subjects.

Local Progression Kinetics of Geographic Atrophy Depends Upon the Border Location.

PurposeTo assess the influence of lesion morphology and location on geographic atrophy (GA) growth rate.MethodsWe manually delineated GA on color fundus photographs of 237 eyes in the Age-Related Eye Disease Study. We calculated local border expansion rate (BER) as the linear distance that a point on the GA border traveled over 1 year based on a Euclidean distance map. Eye-specific BER was defined as the mean local BER of all points on the GA border in an eye. The percentage area affected by GA was defined as the GA area divided by the total retinal area in the region.ResultsGA enlarged 1.51 ± 1.96 mm2 in area and 0.13 ± 0.11 mm in distance over 1 year. The GA area growth rate (mm2/y) was associated with the baseline GA area (P < 0.001), perimeter (P < 0.001), lesion number (P < 0.001), and circularity index (P < 0.001); in contrast, eye-specific BER (mm/y) was not significantly associated with any of these factors. As the retinal eccentricity increased from 0 to 3.5 mm, the local BER increased from 0.10 to 0.24 mm/y (P < 0.001); in contrast, the percentage of area affected by GA decreased from 49.3% to 2.3%.ConclusionsUsing distance-based measurements allows GA progression evaluation without significant confounding effects from baseline GA morphology. Local GA progression rates increased as a function of retinal eccentricity within the macula which is opposite of the trend for GA distribution, suggesting that GA initiation and enlargement may be mediated by different biological processes.

Morphological properties of the axon initial segment-like process of AII amacrine cells in the rat retina.

Signal processing within the retina is generally mediated by graded potentials, whereas output is conveyed by action potentials transmitted along optic nerve axons. Among retinal neurons, amacrine cells seem to be an exception to this general rule, as several types generate voltage-gated Na+ (Nav ) channel-dependent action potentials. The AII, a narrow-field, bistratified axon-less amacrine cell found in mammalian retinas, displays a unique process that resembles an axon initial segment (AIS), with expression of Nav channels colocalized with the cytoskeletal protein ankyrin-G, and generates action potentials. As the role of spiking in AIIs is uncertain, we hypothesized that the morphological properties of the AIS-like process could provide information relevant for its functional importance, including potential pre- and/or postsynaptic connectivity. For morphological analysis, we injected AII amacrine cells in slices with fluorescent dye and immunolabeled the slices for ankyrin-G. Subsequently, this enabled us to reliably identify AII-type processes among ankyrin-G-labeled processes in wholemount retina. We systematically analyzed the laminar localization, spatial orientation, and distribution of the AIS-like processes as a function of retinal eccentricity. In the horizontal plane, the processes displayed no preferred orientation and terminal endings were randomly distributed. In the vertical plane, the processes displayed a horizontal preference, but also ascended and descended into the inner nuclear layer and proximal inner plexiform layer, respectively. These results suggest that the AII amacrine AIS-like process is unlikely to take part in conventional synaptic connections, but may instead be adapted to respond to volume neurotransmission by means of extrasynaptic receptors.

Detection of occluding targets in natural backgrounds.

Detection of target objects in the surrounding environment is a common visual task. There is a vast psychophysical and modeling literature concerning the detection of targets in artificial and natural backgrounds. Most studies involve detection of additive targets or of some form of image distortion. Although much has been learned from these studies, the targets that most often occur under natural conditions are neither additive nor distorting; rather, they are opaque targets that occlude the backgrounds behind them. Here, we describe our efforts to measure and model detection of occluding targets in natural backgrounds. To systematically vary the properties of the backgrounds, we used the constrained sampling approach of Sebastian, Abrams, and Geisler (2017). Specifically, millions of calibrated gray-scale natural-image patches were sorted into a 3D histogram along the dimensions of luminance, contrast, and phase-invariant similarity to the target. Eccentricity psychometric functions (accuracy as a function of retinal eccentricity) were measured for four different occluding targets and 15 different combinations of background luminance, contrast, and similarity, with a different randomly sampled background on each trial. The complex pattern of results was consistent across the three subjects, and was largely explained by a principled model observer (with only a single efficiency parameter) that combines three image cues (pattern, silhouette, and edge) and four well-known properties of the human visual system (optical blur, blurring and downsampling by the ganglion cells, divisive normalization, intrinsic position uncertainty). The model also explains the thresholds for additive foveal targets in natural backgrounds reported in Sebastian et al. (2017).

Relationship of Topographic Distribution of Geographic Atrophy to Visual Acuity in Nonexudative Age-Related Macular Degeneration

To investigate the topographic distribution of geographic atrophy (GA) and to identify an anatomic endpoint that correlates with visual acuity (VA) in eyes with GA. Retrospective analysis of a multicenter, prospective, randomized controlled trial. The Age-Related Eye Disease Study participants with GA secondary to nonexudative age-related macular degeneration. We manually delineated GA on 1654 fundus photographs of 365 eyes. We measured GA areas in 9 subfields on the Early Treatment Diabetic Retinopathy Study (ETDRS) grid and correlated them with VA via a mixed-effects model. We determined the optimal diameter for the central zone by varying the diameter from 0 to 10 mm until the highest r2 between GA area in the central zone and VA was achieved. We estimated the VA decline rate over 8 years using a linear mixed model. Geographic atrophy area in macular subfields and VA. The percentage of area affected by GA declined as a function of retinal eccentricity. GA area was higher in the temporal than the nasal region (1.30 ± 1.75 mm2 vs. 1.10 ± 1.62 mm2; P= 0.005) and in the superior than the inferior region (1.26 ± 1.73 mm2 vs. 1.03 ± 1.53 mm2; P < 0.001). Total GA area correlated poorly with VA (r2= 0.07). Among GA areas in 9 subfields, only GA area in the central zone was associated independently with VA (P < 0.001). We determined 1 mm as the optimal diameter for the central zone in which GA area correlated best with VA (r2= 0.45). On average, full GA coverage of the central 1-mm diameter zone corresponded to 34.8 letters' decline in VA. The VA decline rate was comparable between eyes with initial noncentral and central GA before GA covered the entire central 1-mm diameter zone (2.7 letters/year vs. 2.8 letters/year; P= 0.94). The prevalence of GA varies significantly across different macular regions. Although total GA area was associated poorly with VA, GA area in the central 1-mm diameter zone was correlated significantly with VA and may serve as a surrogate endpoint in clinical trials.

Measurement of Carotenoids in Perifovea using the Macular Pigment Reflectometer.

The macular pigment reflectometer (MPR) objectively measures the overall macular pigment optical density (MPOD) and further provides the lutein optical density (L-OD) and zeaxanthin optical density (Z-OD) in the central 1 degree of the fovea. A modification of the technique was developed to evaluate in vivo carotenoid density eccentric to the fovea. An adjustable track system with red LED lights was placed 6.1 m away from the participant to facilitate ocular fixation. Lights were spaced appropriately to create increments of 1 degree retinal disparity during the reflectometry measurements. All reflectometry measurements were obtained with pupillary dilation. The mean MPR-MPOD value for the central measurement was 0.593 (SD 0.161) with an L-OD to Z-OD ratio of 1:2.61. The MPR-MPOD value at 1 degree was 0.248 and the mean MPR-MPOD value at 2 degrees in the parafoveal region was 0.143. The L-OD to Z-OD ratio at 1 degree and 2 degrees off center was 1.38:1.0 and 2.08:1.0, respectively. The results demonstrate that MPOD measurements obtained using the MPR decrease as a function of retinal eccentricity and that there is a higher concentration of zeaxanthin centrally compared to lutein. The L-OD to Z-OD ratio changes with foveal eccentricity, with twice more lutein than zeaxanthin at 2 degrees off center. Our technique successfully provides a quick in vivo method for the measurement of macular pigment optical density at various foveal eccentricities. The results agree with prior published in vivo and in vitro xanthophyll carotenoid density distribution measurements.

Comparing Parafoveal Cone Photoreceptor Mosaic Metrics in Younger and Older Age Groups Using an Adaptive Optics Retinal Camera

To analyze cone mosaic metrics on adaptive optics (AO) images as a function of retinal eccentricity in two different age groups using a commercial flood illumination AO device. Fifty-three eyes of 28 healthy subjects divided into two age groups were imaged using an AO flood-illumination camera (rtx1; Imagine Eyes, Orsay, France). A 16° × 4° field was obtained horizontally. Cone-packing metrics were determined in five neighboring 50 µm × 50 µm regions. Both retinal (cones/mm2 and µm) and visual (cones/degrees2 and arcmin) units were computed. Results for cone mosaic metrics at 2°, 2.5°, 3°, 4°, and 5° eccentricity were compatible with previous AO scanning laser ophthalmoscopy and histology data. No significant difference was observed between the two age groups. The rtx1 camera enabled reproducible measurements of cone-packing metrics across the extrafoveal retina. These findings may contribute to the development of normative data and act as a reference for future research. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:45-50.].

Crowding in the S-cone pathway

The spatial extent of interference from nearby object or contours (the critical spacing of “crowding”) has been thoroughly characterized across the visual field, typically using high contrast achromatic stimuli. However, attempts to link this measure with known properties of physiological pathways have been inconclusive. The S-cone pathway, with its ease of psychophysical isolation and known anatomical characteristics, offers a unique tool to gain additional insights into crowding. In this study, we measured the spatial extent of crowding in the S-cone pathway at several retinal locations using a chromatic adaptation paradigm. S-cone crowding was evident and extensive, but its spatial extent changed less markedly as a function of retinal eccentricity than the extent found using traditional achromatic stimuli. However, the spatial extent agreed with that of low contrast achromatic stimuli matched for isolated resolvability. This suggests that common cortical mechanisms mediate the crowding effect in the S-cone and achromatic pathway, but contrast is an important factor. The low contrast of S-cone stimuli makes S-cone vision more acuity-limited than crowding-limited.

A Novel Approach to Measuring the Useful Field of View in Simulated Real-World Environments Using Gaze Contingent Displays: The GC-UFOV.

The Useful Field of View (UFOV) task assesses attentional breadth within a single glance. The UFOV has successfully predicted changes in attention that have real-world consequences (e.g. automobile collision likelihood), however its design prevents it from being incorporated into simulated environments (e.g. driving/flight simulators). Additionally, the UFOV task and other attentional breadth measures (e.g. the peripheral detection task) do not disentangle attention from hard-wired perceptual properties that change with retinal eccentricity (e.g., spatial resolution via cortical magnification). We therefore developed an alternative method of measuring attentional breadth using gaze-contingent (GC) displays, the GC-UFOV. Thirteen participants completed four sessions of testing to determine the effect of a secondary task (auditory N-back) on Gabor patch orientation discrimination at four retinal eccentricities (0o, 3o, 6o, and 9o). Gabor patches were occasionally presented gaze-contingently for single eye fixations while participants completed a scene recognition memory task. Gabors were size-thresholded under single-task conditions to disentangle eccentricity-dependent acuity from changes in attention occurring between single and dual-task conditions, while N-back levels were thresholded to ensure that cognitive load was equivalent across participants. RESULTS showed a significant decrease in orientation sensitivity in the dual-task condition, but not as a function of retinal eccentricity. We conclude that interference with executive attention produces general interference with visual attention equally across retinal eccentricity. N-back sensitivity was only minimally impaired under dual-task conditions compared to single-task trials. Picture recognition memory was no different between N-back single and dual tasks, but was significantly better in the Gabor single task condition. Thus, the Gabor task did not interfere with processing picture information, making this method ideal for use in simulated real-world tasks. Furthermore, we propose that future adaptations of this method employ other ecologically valid sources of cognitive load (e.g., stress, traffic density) to observe their effects on attentional breadth. Meeting abstract presented at VSS 2015. Language: en

Eccentricity dependent changes of density, spacing and packing arrangement of parafoveal cones

To investigate the distribution of cone density and spacing as well as the preferred packing arrangement of the cone mosaic as a function of retinal eccentricity. An adaptive optics retinal camera (rtx1, www.imagine-eyes.com) was used to obtain images of the parafoveal cone mosaic in nineteen healthy volunteers. Cone density and spacing were estimated for each subject (both eyes) using a sampling window of 80×80 pixels, at 250-, 450-, 650- and 1100-μm eccentricities from the fovea along the nasal and temporal retina of both eyes. The inter-subject and intra-subject variation of cone density and spacing were calculated via Coefficient of Variation (CoV). Cone packing arrangement was assessed using Voronoi analysis; calculations were done over 1024×128 pixels image sections of the cone mosaic across the horizontal meridian from 200- to 1050-μm eccentricities. The inter-subject variation of parafoveal cone density ranged between 10% and 15% (p<0.001) and the intra-subject variation of cone density was lower than 8% in all subjects, except for two. The cone spacing values showed a moderate inter-subject (CoV<7%; p<0.001) and a low intra-subject variation (CoV<4% in all subjects, except for two cases). In the parafoveal region, 40-50% of cones were hexagonally arranged; the percentage of non-hexagonal Voronoi tiles increased at greater eccentricities. The use of multiple and complementary metric descriptors allows for a more detailed description of packing distribution and preferred arrangement of cone photoreceptors across the parafoveal retina.

A study of factors affecting the human cone photoreceptor density measured by adaptive optics scanning laser ophthalmoscope

To investigate the variation in human cone photoreceptor packing density with various demographic or clinical factors, cone packing density was measured using a Canon prototype adaptive optics scanning laser ophthalmoscope and compared as a function of retinal eccentricity, refractive error, axial length, age, gender, race/ethnicity and ocular dominance. We enrolled 192 eyes of 192 subjects with no ocular pathology. Cone packing density was measured at three different retinal eccentricities (0.5 mm, 1.0 mm, and 1.5 mm from the foveal center) along four meridians. Cone density decreased from 32,200 to 11,600 cells/mm2 with retinal eccentricity (0.5 mm to 1.5 mm from the fovea, P < 0.001). A trend towards a slightly negative correlation was observed between age and density (r = −0.117, P = 0.14). There was, however, a statistically significant negative correlation (r = −0.367, P = 0.003) between axial length and cone density. Gender, ocular dominance, and race/ethnicity were not important determinants of cone density (all, P > 0.05). In addition, to assess the spatial arrangement of the cone mosaics, the nearest-neighbor distances (NNDs) and the Voronoi domains were analyzed. The results of NND and Voronoi analysis were significantly correlated with the variation of the cone density. Average NND and Voronoi area were gradually increased (all, P ≤ 0.001) and the degree of regularity of the cone mosaics was decreased (P ≤ 0.001) with increasing retinal eccentricity. In conclusion, we demonstrated cone packing density decreases as a function of retinal eccentricity and axial length and the results of NND and Voronoi analysis is a useful index for cone mosaics arrangements. The results also serve as a reference for further studies designed to detect or monitor cone photoreceptors in patients with retinal diseases.

Topography of Cone Dark Adaptation Deficits in Age-Related Maculopathy

Despite widespread agreement that dark adaptation is abnormal in age-related maculopathy (ARM), the optimal retinal location for detection of this deficit is unclear. We quantified the diagnostic potential of cone dark adaptation as a function of retinal eccentricity and compared this with the diagnostic potential of the time to the rod-cone-break (RCB). Cone dark adaptation was monitored after an 80% cone photopigment bleach in 10 subjects with ARM and 10 age-matched controls, using four achromatic annuli (0.5, 2, 7, and 12° radius) centered on the fovea. Threshold recovery data were modeled and the time constant of cone recovery (τ), final cone threshold, and time to RCB were determined. Diagnostic potential was evaluated by constructing receiver operating characteristic curves for these parameters. Cone τ was significantly longer for the ARM group at 2, 7, and 12°. The greatest difference between groups was observed at 12° from fixation. At this location, the mean τ was 3.49 (±2.02) min and 0.64 (±0.38) min for ARM and control subjects, respectively (p = 0.002), and time to RCB was 17.68 (±5.37) min and 9.05 (±2.11) min for ARM and control subjects, respectively (p = 0.001). Correspondingly, receiver operating characteristic curves showed that the diagnostic potential of dark adaptometry is greatest for stimuli presented 12° from fixation; for cone τ, the area under the curve = 0.99 ± 0.02 and for time to RCB, area under the curve = 0.96 ± 0.04. This study has shown cone-mediated dark adaptation to be significantly impaired in ARM. Our results provide compelling evidence in support of the diagnostic potential of cone dark adaptation and the use of annular stimuli at 12°. The observation that cone τ is highly diagnostic at this eccentricity is significant clinically because this parameter may be quantified within a few minutes.

ERG signals driven by chromatic and luminance processing: Variation as a function of retinal eccentricity

ERG signals driven by chromatic and luminance processing: Variation as a function of retinal eccentricity

Parafoveal Magnification

Models of eye guidance in reading rely on the concept of the perceptual span-the amount of information perceived during a single eye fixation, which is considered to be a consequence of visual and attentional constraints. To directly investigate attentional mechanisms underlying the perceptual span, we implemented a new reading paradigm-parafoveal magnification (PM)-that compensates for how visual acuity drops off as a function of retinal eccentricity. On each fixation and in real time, parafoveal text is magnified to equalize its perceptual impact with that of concurrent foveal text. Experiment 1 demonstrated that PM does not increase the amount of text that is processed, supporting an attentional-based account of eye movements in reading. Experiment 2 explored a contentious issue that differentiates competing models of eye movement control and showed that, even when parafoveal information is enlarged, visual attention in reading is allocated in a serial fashion from word to word.

Adaptive Optics Retinal Imaging

<b>Invest Ophthalmol Vis Sci</b> <b>High-Resolution Imaging With Adaptive Optics in Patients With Inherited Retinal Degeneration</b> Jacque L. Duncan; Yuhua Zhang; Jarel Gandhi; Chiaki Nakanishi; Mohammad Othman; Kari E. H. Branham; Anand Swaroop; Austin Roorda <h3></h3> <b>Purpose:</b>To investigate macular photoreceptor structure in patients with inherited retinal degeneration using high-resolution images and to correlate the findings with clinical phenotypes and genetic mutations. <b>Methods:</b>Adaptive optics scanning laser ophthalmoscopy (AOSLO) images of photoreceptors were obtained in 16 eyes: 5 with retinitis pigmentosa (RP), 3 with cone-rod dystrophy (CRD), and 8 without retinal disease. A quadratic model was used to illustrate cone spacing as a function of retinal eccentricity. Cone spacing at 1° eccentricity was compared with standard measures of central visual function, including best-corrected visual acuity (BCVA), foveal threshold, and multifocal electroretinogram (mfERG) amplitude and timing. Intervisit variations were studied in 1 patient with RP and 1 patient with CRD. Screening of candidate disease genes identified mutations in 2 patients, one with RP (a rhodopsin mutation) and the other with CRD (a novel<i>RPGR</i>-ORF15 mutation). <b>Results:</b>Cone spacing values were significantly different from normal for patients with RP (<i>P</i> = .01) and CRD (<i>P</i> &lt; .0001) and demonstrated a statistically significant correlation with foveal threshold (<i>P</i> = .0003), BCVA (<i>P</i> = .01), and mfERG amplitude (<i>P</i> = .008). Although many RP patients showed normal cone spacing within 1° of fixation, cones could not be unambiguously identified in several retinal regions. Cone spacing increased in all CRD patients, even those with early disease. Little variation was observed in cone spacing measured during 2 sessions fewer than 8 days apart. <b>Conclusions:</b>AOSLO images can be used to study macular cones with high resolution in patients with retinal degeneration. The authors present the first report of cone structure in vivo in patients with mutations in rhodopsin and<i>RPGR</i>-ORF15 and show that macular cones display distinct characteristics, depending on the underlying disease. AOSLO imaging, therefore, can provide new insight into possible mechanisms of cone vision loss in patients with retinal degeneration. <i>Invest Ophthalmol Vis Sci.. 2007;48(7):3283-3291.</i>

New equally readable charts based on anisotropy of peripheral visual acuity1

Abstract: Anstis’ equally readable chart for visual acuity has been widely quoted in textbooks on visual perception. However, this chart does not reflect the anisotropy of peripheral visual acuity that has been reported by previous studies. Here, the authors reexamined peripheral visual acuity by measuring resolution thresholds for Landolt rings and recognition thresholds for hiragana letters as a function of retinal eccentricity across two principal retinal meridians: horizontal and vertical. Observers were required to identify the orientation of a gap in the Landolt ring or recognize a hiragana letter while the stimulus was moved slowly from the periphery toward the fovea across each of four meridians: nasal, temporal, superior, and inferior. The results revealed the horizontal‐vertical anisotropy of visual acuity in accordance with the results of previous studies. The mean thresholds obtained in the vertical meridian were approximately 1.51‐fold (for Landolt rings) and 1.42‐fold (for hiragana letters) higher than those obtained in the horizontal meridian at the same retinal eccentricity. The authors propose new equally readable charts for Landolt rings and hiragana letters.

Foveal Fine Structure in Retinopathy of Prematurity: An Adaptive Optics Fourier Domain Optical Coherence Tomography Study

To describe the fine structure of the fovea in subjects with a history of mild retinopathy of prematurity (ROP) using adaptive optics-Fourier domain optical coherence tomography (AO-FDOCT). High-speed, high-resolution AO-FDOCT videos were recorded in subjects with a history of ROP (n = 5; age range, 14-26 years) and in control subjects (n = 5; age range, 18-25 years). Custom software was used to extract foveal pit depth and volume from three-dimensional (3-D) retinal maps. The thickness of retinal layers as a function of retinal eccentricity was measured manually. The retinal vasculature in the parafoveal region was assessed. The foveal pit was wider and shallower in ROP than in control subjects. Mean pit depth, defined from the base to the level at which the pit reaches a lateral radius of 728 microm, was 121 microm compared with 53 microm. Intact, contiguous inner retinal layers overlay the fovea in ROP subjects but were absent in the control subjects. Mean full retinal thickness at the fovea was greater in the subjects with ROP (279.0 microm vs. 190.2 microm). The photoreceptor layer thickness did not differ between ROP and control subjects. An avascular zone was not identified in the subjects with ROP but was present in all the control subjects. The foveas of subjects with a history of mild ROP have significant structural abnormalities that are probably a consequence of perturbations of neurovascular development.

A central performance drop with luminance stimuli requiring spatial integration

This study reports four experiments that analyzed detection performance for luminance contrasts as a function of retinal eccentricity in order to find further support and explanations for the central performance drop (CPD) in the fovea. In the first experiment, 10 participants (16-37 years of age) had to detect a target patch in a stimulus consisting of bright and dark pixels. Luminance differences between target and context areas were achieved by placing a different number of bright (and dark) pixels in the target and the context area. Results showed a marked CPD; that is, performance did not peak in the fovea but in the parafovea. A spatial integration hypothesis was proposed to explain this CPD. Alternative explanations were tested in three further experiments with a total of 28 participants from 19-46 years of age (using the decision criterion effect, the selective masking effect, and inhibition by high frequencies). The findings did not contradict the spatial-integration hypothesis.

High-Resolution Imaging with Adaptive Optics in Patients with Inherited Retinal Degeneration

To investigate macular photoreceptor structure in patients with inherited retinal degeneration using high-resolution images and to correlate the findings with clinical phenotypes and genetic mutations. Adaptive optics scanning laser ophthalmoscopy (AOSLO) images of photoreceptors were obtained in 16 eyes: five with retinitis pigmentosa (RP), three with cone-rod dystrophy (CRD), and eight without retinal disease. A quadratic model was used to illustrate cone spacing as a function of retinal eccentricity. Cone spacing at 1 degrees eccentricity was compared with standard measures of central visual function, including best-corrected visual acuity (BCVA), foveal threshold, and multifocal electroretinogram (mfERG) amplitude and timing. Intervisit variations were studied in one patient with RP and one patient with CRD. Screening of candidate disease genes identified mutations in two patients, one with RP (a rhodopsin mutation) and the other with CRD (a novel RPGR-ORF15 mutation). Cone spacing values were significantly different from normal for patients with RP (P = 0.01) and CRD (P < 0.0001) and demonstrated a statistically significant correlation with foveal threshold (P = 0.0003), BCVA (P = 0.01), and mfERG amplitude (P = 0.008). Although many RP patients showed normal cone spacing within 1 degrees of fixation, cones could not be unambiguously identified in several retinal regions. Cone spacing increased in all CRD patients, even those with early disease. Little variation was observed in cone spacing measured during two sessions fewer than 8 days apart. AOSLO images can be used to study macular cones with high resolution in patients with retinal degeneration. The authors present the first report of cone structure in vivo in patients with mutations in rhodopsin and RPGR-ORF15 and show that macular cones display distinct characteristics, depending on the underlying disease. AOSLO imaging, therefore, can provide new insight into possible mechanisms of cone vision loss in patients with retinal degeneration.

Multifocal visual evoked potentials to cone specific stimuli in patients with retinitis pigmentosa

Our aim was to determine whether patients with retinitis pigmentosa show differences in L- and M-cone multifocal visual evoked potential (mfVEP) responses that are eccentricity dependent, as has been shown for control subjects. Second, we compared the losses for mfVEPs to losses on achromatic visual field and multifocal electroretinogram (mfERG) measures in the patients. Monocular mfVEPs were recorded to a pattern reversing display that modulated only the L- or M-cones. Also, standard automated achromatic visual fields and mfERGs were obtained. For the control subjects, the ratio of L-cone to M-cone mfVEP amplitudes increased as a function of retinal eccentricity. For the patients, the ratio did not vary with eccentricity. For all measures, responses were least affected for the first ring (central 2.4°) and most affected for the third ring (11.6°–44.4°). For the first ring, mfERG amplitudes were more impaired than were the mfVEPs or the visual field thresholds. For most of the patients, there was local response correspondence among our measures of visual function.