Cone Density Research Articles

Intergrader agreement of foveal cone topography measured using adaptive optics scanning light ophthalmoscopy.

The foveal cone mosaic can be directly visualized using adaptive optics scanning light ophthalmoscopy (AOSLO). Previous studies in individuals with normal vision report wide variability in the topography of the foveal cone mosaic, especially the value of peak cone density (PCD). While these studies often involve a human grader, there have been no studies examining intergrader reproducibility of foveal cone mosaic metrics. Here we re-analyzed published AOSLO foveal cone images from 44 individuals to assess the relationship between the cone density centroid (CDC) location and the location of PCD. Across 5 graders with variable experience, we found a measurement error of 11.7% in PCD estimates and higher intergrader reproducibility of CDC location compared to PCD location (p < 0.0001). These estimates of measurement error can be used in future studies of the foveal cone mosaic, and our results support use of the CDC location as a more reproducible anchor for cross-modality analyses.

Photoreceptor and Retinal Pigment Epithelium Relationships in Eyes With Vitelliform Macular Dystrophy Revealed by Multimodal Adaptive Optics Imaging.

PurposeTo assess the structure of cone photoreceptors and retinal pigment epithelial (RPE) cells in vitelliform macular dystrophy (VMD) arising from various genetic etiologies.MethodsMultimodal adaptive optics (AO) imaging was performed in 11 patients with VMD using a custom-assembled instrument. Non-confocal split detection and AO-enhanced indocyanine green were used to visualize the cone photoreceptor and RPE mosaics, respectively. Cone and RPE densities were measured and compared across BEST1-, PRPH2-, IMPG1-, and IMPG2-related VMD.ResultsWithin macular lesions associated with VMD, both cone and RPE densities were reduced below normal, to 37% of normal cone density (eccentricity 0.2 mm) and to 8.4% of normal RPE density (eccentricity 0.5 mm). Outside of lesions, cone and RPE densities were slightly reduced (both to 92% of normal values), but with high degree of variability in the individual measurements. Comparison of juxtalesional cone and RPE measurements (<1 mm from the lesion edge) revealed significant differences in RPE density across the four genes (P < 0.05). Overall, cones were affected to a greater extent than RPE in patients with IMPG1 and IMPG2 pathogenic variants, but RPE was affected more than cones in BEST1 and PRPH2 VMD. This trend was observed even in contralateral eyes from a subset of five patients who presented with macular lesions in only one eye.ConclusionsAssessment of cones and RPE in retinal locations outside of the macular lesions reveals a pattern of cone and RPE disruption that appears to be gene dependent in VMD. These findings provide insight into the cellular pathogenesis of disease in VMD.

Impact of Reference Center Choice on Adaptive Optics Imaging Cone Mosaic Analysis.

PurposeFoveal center marking is a key step in retinal image analysis. We investigated the discordance between the adaptive optics (AO) montage center (AMC) and the foveal pit center (FPC) and its implications for cone mosaic analysis using a commercial flood-illumination AO camera.MethodsThirty eyes of 30 individuals (including 15 healthy and 15 patients with rod–cone dystrophy) were included. Spectral-domain optical coherence tomography was used to determine the FPC, and flood-illumination AO imaging was performed with overlapping image frames to create an AO montage. The AMC was determined by averaging the (0,0) coordinates in the four paracentral overlapping AO image frames. Cone mosaic measurements at various retinal eccentricities were compared between corresponding retinal loci relative to the AMC or FPC.ResultsAMCs were located temporally to the FPCs in 14 of 15 eyes in both groups. The average AMC–FPC discordance was 0.85° among healthy controls and 0.33° among patients with rod-cone dystrophy (P < 0.05). The distance of the AMC from the FPC was a significant determinant of the cone density (β estimate = 218 cells/deg2/deg; 95% confidence interval [CI], 107–330; P < 0.001) and inter-cone distance (β estimate = 0.28 arcmin/deg; 95% CI, 0.15–0.40; P < 0.001), after adjustment for age, sex, axial length, spherical equivalent, eccentricity, and disease status.ConclusionsThere is a marked mismatch between the AMC and FPC in healthy eyes that may be modified by disease process such as rod–cone dystrophy. We recommend users of AO imaging systems carefully align the AO montage with a foveal anatomical landmark, such as the FPC, to ensure precise and reproducible localization of the eccentricities and regions of interest for cone mosaic analysis.

Investigating Biomarkers for USH2A Retinopathy Using Multimodal Retinal Imaging.

Pathogenic mutations in USH2A are a leading cause of visual loss secondary to non-syndromic or Usher syndrome-associated retinitis pigmentosa (RP). With an increasing number of RP-targeted clinical trials in progress, we sought to evaluate the photoreceptor topography underlying patterns of loss observed on clinical retinal imaging to guide surrogate endpoint selection in USH2A retinopathy. In this prospective cross-sectional study, twenty-five patients with molecularly confirmed USH2A-RP underwent fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy (AOSLO) retinal imaging. Analysis comprised measurement of FAF horizontal inner (IR) and outer (OR) hyperautofluorescent ring diameter; SD-OCT ellipsoid zone (EZ) and external limiting membrane (ELM) width, normalised EZ reflectance; AOSLO foveal cone density and intact macular photoreceptor mosaic (IMPM) diameter. Thirty-two eyes from 16 patients (mean age ± SD, 36.0 ± 14.2 years) with USH2A-associated Usher syndrome type 2 (n = 14) or non-syndromic RP (n = 2) met the inclusion criteria. Spatial alignment was observed between IR-EZ and OR-ELM diameters/widths (p < 0.001). The IMPM border occurred just lateral to EZ loss (p < 0.001), although sparser intact photoreceptor inner segments were detected until ELM disruption. EZ width and IR diameter displayed a biphasic relationship with cone density whereby slow cone loss occurred until retinal degeneration reached ~1350 μm from the fovea, beyond which greater reduction in cone density followed. Normalised EZ reflectance and cone density were significantly associated (p < 0.001). As the strongest correlate of cone density (p < 0.001) and best-corrected visual acuity (p < 0.001), EZ width is the most sensitive biomarker of structural and functional decline in USH2A retinopathy, rendering it a promising trial endpoint.

Cone Photoreceptor Loss in Light-Damaged Albino Rats.

We investigated the etiology of decreased cone-driven vision in a light damage (LD) model of retinal degeneration. To induce slow, moderate degeneration, albino rats underwent low-intensity light exposure for 10 days. Electroretinography was utilized to assess physiologic function of the rod- and cone-driven retinal function in LD and control rats. Immunohistochemistry targeting cone arrestin allowed for quantification of cone density and for comparison of the decline in function. Photoreceptor loss was quantified by outer nuclear layer thickness decreases, as observed by optical coherence tomography and histology. The LD rats showed decreased rod- and cone-driven function with partial recovery 30 days after cessation of light exposure. In addition, LD rats showed decreased cone photoreceptor densities in the central retinal region compared to control rats. Our results demonstrate that the loss of cone-driven visual function induced by light damage is at least partially due to the death of cone photoreceptors.

Cone Photoreceptors in Diabetic Patients.

PurposeCones in diabetic patients are at risk due to metabolic and vascular changes. By imaging retinal vessel modeling at high magnification, we reduced its impact on cone distribution measurements. The retinal vessel images and retinal thickness measurements provided information about cone microenvironment.MethodsWe compared cone data in 10 diabetic subjects (28–78 yr) to our published norms from 36 younger and 10 older controls. All subjects were consented and tested in a manner approved by the Indiana University Institutional Review Board, which adhered to the Declaration of Helsinki. Custom adaptive optics scanning laser ophthalmoscopy (AOSLO) was used to image cones and retinal microcirculation. We counted cones in a montage of foveal and temporal retina, using four non-contiguous samples within 0.9–7 deg that were selected for best visibility of cones and least pathology. The data were fit with a two parameter exponential model: ln(cone density) = a * microns eccentricity + b. These results were compared to retinal thickness measurements from SDOCT.ResultsDiabetic cone maps were more variable than in controls and included patches, or unusually bright and dark cones, centrally and more peripherally. Model parameters and total cones within the central 14 deg of the macula differed across diabetic patients. Total cones fell into two groups: similar to normal for 5 vs. less than normal for 2 of 2 younger diabetic subjects and 3 older subjects, low but not outside the confidence limits. Diabetic subjects had all retinal vascular remodeling to varying degrees: microaneurysms; capillary thickening, thinning, or bends; and vessel elongation including capillary loops, tangles, and collaterals. Yet SD-OCT showed that no diabetic subject had a Total Retinal Thickness in any quadrant that fell outside the confidence limits for controls.ConclusionsAOSLO images pinpointed widespread retinal vascular remodeling in all diabetic eyes, but the SDOCT showed no increased retinal thickness. Cone reflectivity changes were found in all diabetic patients, but significantly low cone density in only some. These results are consistent with early changes to neural, glial, or vascular components of the retinal without significant retinal thickening due to exudation.

Phenotype Heterogeneity and the Association Between Visual Acuity and Outer Retinal Structure in a Cohort of Chinese X-Linked Juvenile Retinoschisis Patients

Purpose: X-linked juvenile retinoschisis (XLRS), caused by mutations in the RS1 gene, is an X-linked recessive inherited disease that typically involves both eyes in the first 2 decades of life. Recently, the phenotype heterogeneity of this condition has drawn increasing attention. We reported various phenotypes caused by RS1 gene mutations in eleven patients from ten Chinese families. Methods: Data on the medical history of the patients from ten Han families of central China were collected. Ophthalmic examinations including best-corrected visual acuity (BCVA), fundus photography, ultra-wide-angle sweep source optical coherence tomography (SS-OCT), and electroretinography (ERG) were performed. Adaptive optics (AO) images were acquired to evaluate the cone photoreceptor mosaic when applicable. Venous blood of the probands and their family members was collected, and DNA was subjected to sequencing based on next-generation sequencing with a custom-designed targeted gene panel PS400 for inherited retinal diseases. Validation was performed by Sanger sequencing and cosegregation. Pathogenicity was determined in accordance with the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Ten RS1 mutations, including eight missense mutations and two terminator mutations, were identified in 10 XLRS families. c.657C > A (p.C219X) was a novel mutation in this cohort. These patients showed a variety of clinical phenotypes, including fovea schisis, bullous retinoschisis, and macular or peripheral atrophy. Fifteen eyes of eight patients exhibited macular retinoschisis, and twelve eyes of seven patients exhibited peripheral retinoschisis. In addition, three patients showed asymmetrical fundus manifestations. Of importance, three patients without macular retinoschisis were misdiagnosed until genetic testing results were obtained. AO showed a decrease in cone density and loss of regularity in the cystic schisis macular of XLRS. Furthermore, the BCVA was associated with the photoreceptor inner segment and outer segment (IS/OS) thickness. Conclusion: With complicated clinical manifestations, a considerable portion of XLRS patients may present various phenotypes. It should be noted that asymmetry in fundus appearance in both eyes could lead to misdiagnosis easily. Thus, genetic testing is crucial for making a final diagnosis in those patients who are suspected of having amblyopia, bilateral or unilateral macular atrophy, or conditions presenting an asymmetric fundus appearance. In addition, the residual cone photoreceptor structure was critical for the maintenance of useful vision.

Demographic processes underpinning post-fire resilience in California closed-cone pine forests: the importance of fire interval, stand structure, and climate

The resilience of serotinous obligate-seeding plants to fire may be compromised if increasing fire frequency curtails time available for canopy seed bank accumulation (i.e., immaturity risk), but how various drivers affect seed availability at the time of fire is poorly understood. Using field data from California closed-cone pine (Pinus attenuata and P. muricata) stands, we assess two critical demographic processes during the inter-fire period—reproductive capacity and mortality. At tree- and stand-levels, we test how these processes are affected by stand age and are mediated by biotic and abiotic factors. We found that stand age was the key driver of reproductive capacity; older stands had a greater proportion of reproductively mature individuals and greater closed cone density. Stand density mediated the effect of age; greater stand density resulted in greater closed cone density and a lower proportion of reproductively mature individuals, but reproductive capacity in low- and high-density stands converged over time. Increased moisture stress reduced the stand-level proportion reproductively mature trees but had no effect on closed cone density. Mortality was strongly associated with density-dependent thinning and increased in stands with high moisture stress. Reproductive capacity began to increase sharply 10 years post-fire and by 20 years immaturity risk was low. However, prior to 20 years, low-density stands with high moisture stress may be more susceptible to immaturity risk. Understanding these relationships is critical to predicting serotinous population persistence under changing climate and disturbance conditions.

Human Foveal Cone and RPE Cell Topographies and Their Correspondence With Foveal Shape.

PurposeTo characterize the association between foveal shape and cone and retinal pigment epithelium (RPE) cell topographies in healthy humans.MethodsMultimodal adaptive scanning light ophthalmoscopy and optical coherence tomography (OCT) were used to acquire images of foveal cones, RPE cells, and retinal layers in eyes of 23 healthy participants with normal foveas. Distributions of cone and RPE cell densities were fitted with nonlinear mixed-effects models. A linear mixed-effects model was used to examine the relationship between cone and RPE inter-cell distances and foveal shape as obtained from the OCT scans of retinal thickness.ResultsThe best-fit model to the cone densities was a power function with a nasal–temporal asymmetry. There was a significant linear relationship among cone and RPE cell spacing, foveal shape, and foveal cell topography. The model predictions of the central 10° show that the contributions of both the cones and RPE cells are necessary to account for foveal shape.ConclusionsThe results indicate that there is a strong relationship between cone and RPE cell spacing and the shape of the human adolescent and adult fovea. This finding adds to the existing evidence of the critical role that the RPE serves in fetal foveal development and through adolescence, possibly via the imposition of constraints on the number and distribution of foveal cones.

Invited Session II: Retinal mechanisms mediating vision: Light adaptation in primate fovea

Our visual performance varies remarkably across space. For instance, our central vision exhibits the highest spatial and chromatic sensitivity, whereas temporal sensitivity is higher for our peripheral than central vision. Our high-acuity central vision is initiated in the cone photoreceptors which are packed in a dense array in the fovea. The density and morphology of cones differ remarkably between foveal and peripheral primate retina, but our knowledge about their functional differences remain quite poor. In the past we have shown that cone signals in the fovea are two-fold slower than in the peripheral retina consistent with the difference in the temporal sensitivity of cone-mediated vision to high-frequency flicker. But we are far from understanding the full breadth of these topographic differences in cone signaling across primate retina over a wide range of light inputs. I will present recent results of a detailed comparison of functional properties - such as kinetics, gain and cellular noise - of cones in the fovea with that in rest of the primate retina. I will show how foveal cones adapt across a wide range of lumice and if they exhibit differences in the amplitude, kinetics or timescales of adaptation when compared to cones in the peripheral primate retina. Lastly, I will share our findings on the relative contribution of cone vs circuit mechanisms towards lumice adaptation in the domit neural circuit in the fovea - the midget ganglion cell pathway.

Asymmetries around the visual field: From retina to cortex to behavior.

Visual performance varies around the visual field. It is best near the fovea compared to the periphery, and at iso-eccentric locations it is best on the horizontal, intermediate on the lower, and poorest on the upper meridian. The fovea-to-periphery performance decline is linked to the decreases in cone density, retinal ganglion cell (RGC) density, and V1 cortical magnification factor (CMF) as eccentricity increases. The origins of polar angle asymmetries are not well understood. Optical quality and cone density vary across the retina, but recent computational modeling has shown that these factors can only account for a small percentage of behavior. Here, we investigate how visual processing beyond the cone photon absorptions contributes to polar angle asymmetries in performance. First, we quantify the extent of asymmetries in cone density, midget RGC density, and V1 CMF. We find that both polar angle asymmetries and eccentricity gradients increase from cones to mRGCs, and from mRGCs to cortex. Second, we extend our previously published computational observer model to quantify the contribution of phototransduction by the cones and spatial filtering by mRGCs to behavioral asymmetries. Starting with photons emitted by a visual display, the model simulates the effect of human optics, cone isomerizations, phototransduction, and mRGC spatial filtering. The model performs a forced choice orientation discrimination task on mRGC responses using a linear support vector machine classifier. The model shows that asymmetries in a decision maker's performance across polar angle are greater when assessing the photocurrents than when assessing isomerizations and are greater still when assessing mRGC signals. Nonetheless, the polar angle asymmetries of the mRGC outputs are still considerably smaller than those observed from human performance. We conclude that cone isomerizations, phototransduction, and the spatial filtering properties of mRGCs contribute to polar angle performance differences, but that a full account of these differences will entail additional contribution from cortical representations.

Influence of nanoclay on the fresh and rheological behaviour of 3D printing mortar

Additive manufacturing is rapidly influencing the construction industry and designing good quality concrete for printing our homes remain a challenge. New materials are being tested for its suitability in a concrete mix. The purpose of this study is to investigate the influence of nanoclay (nC) on fresh and rheological properties of 3D printing concrete. The 3D printing concrete used in this study is prepared by mixing of cement (OPC), fly-ash (FA), basalt fibre (BA), nanoclay (nC) and superplasticizer (SP) with sand at constant water/cement ratio of 0.41. Fresh and rheological properties of this mixture is evaluated with the help of slump flow, cone penetration and cylindrical slump. The amount of nanoclay (nC) in the cementitious mixture is increased from zero to 6 kg/m3. Addition of nanoclay in the cementitious mixture for 3D printing concrete caused an important loss of workability but increased the yield stress of the material, which is attributed to higher cohesiveness of the mix. Adding more nanoclay (nC) in the cementitious mixture not only maintained the desired shape during and after extrusion, but also demonstrated more stable layers, which prevented it from collapsing under gravity and weight of the subsequent layers. A good linear correlation between slump flow, cone penetration test, yield stress and density of the material is established. The aesthetic effect of nanoclay on the cementitious mixture is demonstrated via the extrusion of layers utilising 3D printing mortar.

Effect of protein homeostasis modulation in primary cone degeneration

AbstractPurposeDegenerative cone disorders are an important group of inherited retinal degenerations as they severely disable visual acuity and color vision, causing a major impact on the quality of life of affected patients. These disorders are commonly classified as cone dystrophies and achromatopsia. The cone photoreceptor function loss‐1 (cpfl1) mutant mouse is a model for primary cone degeneration and shares a similar phenotype to patients with complete achromatopsia. Cpfl1 mutation affects the cone‐specific PDE6 gene, leading to a cGMP accumulation, increased Ca+ influx, and cell death. Moreover, M‐, S‐opsin and cone‐specific transducin mislocalization to the cell body have been reported (Trifunovic et al., 2016). Previously, the inhibition of valosin‐containing protein (VCP, an ATPase involved in the (ERAD)) has proven to be protective in different models of autosomal dominant retinitis pigmentosa restoring protein trafficking (Arango‐Gonzalez et al., 2020; Sen et al., 2021). This study aims to assess whether VCP inhibition can also be protective against cone photoreceptor cell death in a cpfl1 retinal organotypic culture system.MethodsCpfl1 retinal explants were maintained in serum‐free conditions and treated with two VCP inhibitors, ML240 and NMS‐873, from PN14 until PN24 (peak of cone degeneration). Photoreceptor cell survival, cone morphology, and opsin expression were evaluated by TUNEL staining, cell row quantification, and immunostaining.ResultsVCP inhibition resulted in an increased number of cell rows in the ONL of the treated explants compared with the control groups. The treated retinas also showed an improved cone morphology and a significant restoration of cone density up to levels similar to those observed in the wild type.ConclusionsOur results suggest that modulation of protein homeostasis through VCP inhibition is protective in primary cone degeneration.

Superconductivity in the two-dimensional nonbenzenoid biphenylene sheet with Dirac cone

During the past decade, two-dimensional materials have attracted much attention in superconductivity due to their feasible physical properties and easy chemical modifications. Herein, we use a recently literature reported novel biphenylene sheet (BP sheet) for investigating superconductivity-related physical properties. The electronic states of BP sheet that appeared near the Fermi level are composed of p z orbital of carbon due to sp2 hybridization. Also, an anisotropic Dirac cone is formed just above the Fermi level by crossing two bands comprised of different carbon atoms. One of the two bands is quasi-flat thus leading to a peak of electronic density of states above the Fermi level. In addition, the rotational-vibration phonon mode of the six-membered carbon ring is strongly coupled with electrons. The electron-phonon coupling induces the superconductivity of 6.2 K in BP sheet. Furthermore, both small uniaxial strains and electronic doping can take the Dirac cone and high electronic density of state close to the Fermi level and further raise the superconducting critical temperature to 27.4 K and 21.5 K, respectively. The obtained result suggests that BP sheet with Dirac fermions and superconductivity can be a potential material for the development of future superconducting devices.

High-Resolution Image Analysis Reveals a Decrease in Lens Thickness and Cone Density in a Cohort of Young Myopic Patients.

Purpose: To study the association between axial length (AL) and the thickness of the lens, retina, choroid, and cone density with swept-source optical coherence tomography (SS-OCT) and an adaptive optics (AO) fundus camera.Design: A prospective cross-sectional study.Methods: This study included 136 eyes in 68 subjects. SS-OCT was used to quantify the thickness of the lens, ganglion cell complex (GCC) layer, inner nuclear layer (INL), outer retinal layer (ORL), and choroid layer. Adaptive optics was used to quantify spatial features of the cone photoreceptors, including density, spacing, regularity, and dispersion. The associations among the AL and the thickness of lens, retina, choroid, and cone features were evaluated with linear regression.Results: With the severity of myopia, the increased AL was associated with thinning of the lens (P < 0.001, 95% CI: −100.42 to −49.76). The thickness of the ORL and choroid decreased significantly (all P < 0.001), whereas the thickness of the GCC and INL decreased only in the outer ring (both P < 0.01). There was a significant correlation between the cone density/spacing and AL (both P < 0.001). Although cone density was reduced from 25,160/mm2 to 19,134/mm2 in the inner region and from 17,458/mm2 to 13,896/mm2 in the outer region, the best-corrected visual acuity (BCVA) was 20/20 or greater.Conclusions: We found that the lens thickness (LT), ORL, and cone density decreased in myopia. While decreasing cone density and ORL thickness should be related to axial elongation, decreasing of LT might imply intrinsic physical accommodation. These results provide further morphological changes of myopia.

Short-Term Parafoveal Cone Loss Despite Preserved Ellipsoid Zone in Rod Cone Dystrophy.

PurposeRod–cone dystrophy (RCD) is characterized by centripetal loss of rod followed by cone photoreceptors. In this prospective, observational cohort, we used flood-illumination adaptive optics (AO) imaging to investigate parafoveal cone loss in regions with preserved ellipsoid zone (EZ) in patients with RCD.MethodsEight patients with RCD and 10 age-matched healthy controls underwent spectral-domain optical coherence tomography and AO imaging. The RCD cohort underwent a follow-up examination after 6 months. Cone density (CD) and intercone distance (ICD) measurements were performed at 2° temporal from the fovea. Baseline CD and ICD values were compared between the control and patient groups, and longitudinal changes were calculated in the patient group. Residual EZ span in patients was measured in horizontal foveal B-scans.ResultsBetween the control and patient groups, there was no significant difference in the baseline CD (2094 vs. 1750 cells/deg2, respectively; P = 0.09) and ICD (1.46 vs. 1.62 arcmin, respectively; P = 0.08). Mean CD declined by 198 cells/deg2 (−11.3%; P < 0.01), and mean ICD increased by 0.09 arcmin (+5.6%; P = 0.01) at the 6-month follow-up in the patient group. Mean baseline and follow-up residual EZ spans in the six patients with EZ defect were 3189 µm and 3065 µm, respectively (−3.9%; P = 0.08).ConclusionsAO imaging detected significant parafoveal cone loss over 6-month follow-up even in regions with preserved EZ. Further studies to refine AO imaging protocol and validate cone metrics as a structural endpoint in early RCD are warranted.Translational RelevanceCD and ICD may change prior to EZ span shortening in RCD.

Multimodal Imaging of Torpedo Maculopathy With Fluorescence Adaptive Optics Imaging of Individual Retinal Pigmented Epithelial Cells.

Torpedo maculopathy (TM) is a rare congenital defect of the retinal pigment epithelium (RPE). The RPE is often evaluated clinically using fundus autofluorescence (AF), a technique that visualizes RPE structure at the tissue level from the intrinsic AF of RPE fluorophores. TM lesions typically emit little or no AF, but this macroscopic assessment is unable to resolve the RPE cells, leaving the organization of the RPE cell mosaic in TM unknown. We used fluorescence adaptive optics scanning laser ophthalmoscopy (AOSLO) to show here for the first time the microscopic cellular-level structural alterations to the RPE cell mosaic in TM that underlie the tissue-level changes seen in conventional clinical imaging. We evaluated two patients with TM using conventional clinical imaging techniques and adaptive optics (AO) infrared autofluorescence (IRAF) in AOSLO. Confocal AOSLO revealed relatively normal cones outside the TM lesion but altered cone appearance within it and along its margins in both patients. We quantified cone topography and RPE cell morphometry from the fovea to the margin of the lesion in case 1 and found cone density to be within the normal range across the locations imaged. However, RPE morphometric analysis revealed disrupted RPE cells outside the margin of the lesion; the mean RPE cell area was greater than two standard deviations above the normative range up to approximately 1.5 mm from the lesion margin. Similar morphometric changes were seen to individual RPE cells in case 2. Multi-modal imaging with AOSLO reveals that RPE cells are abnormal in TM well beyond the margins of the characteristic TM lesion boundary defined with conventional clinical imaging. Since the TM fovea appears to be fully formed, with normal cone packing, it is possible that the congenital RPE defect in TM occurs relatively late in retinal development. This work demonstrates how cellular level imaging of the RPE can provide new insight into RPE pathologies, particularly for rare conditions such as TM.

Long-term retinal imaging of a case of suspected congenital rubella infection

PurposeMany retinal disorders present with pigmentary retinopathy, most of which are progressive conditions. Here we present over nine years of follow up on a case of stable pigmentary retinopathy that is suspected to stem from a congenital rubella infection. Parafoveal cone photoreceptors were tracked through this period to gain insight into photoreceptor disruption in this pigmentary retinopathy. MethodsThe patient was examined at 8 visits spanning a total of 111 months. Examination at baseline included clinical fundus examination, full-field electroretinography (ERG), kinetic visual field assessment (Goldmann), and best corrected visual acuity; all of these except ERG were repeated at follow up visits. Imaging was performed with fundus photography, spectral-domain optical coherence tomography (SD-OCT) and confocal adaptive optics scanning light ophthalmoscopy (AOSLO). For the latter four time points AOSLO imaging also included split-detector imaging. ResultsThere were no defects in hearing or cardiac health found in this patient. There were minimal visual deficits found at baseline, with mild rod suppression on ERG; best corrected visual acuity was 20/25 OD and 20/20 OS at baseline, which was stable throughout the follow-up period. Retinal thickness as measured by OCT was within the normal range, though foveal hypoplasia was present and outer nuclear layer thickness was slightly below the normal range at all time points. Cone density was relatively stable throughout the follow-up period. A number of cones were non-reflective when observed with confocal AOSLO imaging and density was markedly lower than expected values (foveal cone density was 43,782 cones/mm2 on average). Genetic analysis revealed no causative variations explaining the phenotype. Conclusions and ImportanceThis patient appears to have a stable pigmentary retinopathy. This case is likely due to a congenital insult, rather than progressive retinal disease. This finding of stability agrees with other reports of rubella pigmentary retinopathy. Imaging with AOSLO enabled observation of two notable phenotypic features. First is the observation of dark cones, which are seen in many retinal disorders including color vision defects and degenerative retinal disease. Second, the cone density is well below what is expected – this is especially interesting as this patient has near-normal visual acuity despite this greatly decreased number of normally-waveguiding cones in the fovea.

Hydrodynamic performance of a cone falling into waves in 3DOFs free fall motion

This paper concentrates on the 3DOFs water entry of a cone into an incident wave. Undisturbed free surface is modeled with nonlinear 5th Stokes wave. Based on velocity potential theory, fully nonlinear boundary element method is used to simulate fluid field. Fluid-solid interaction between body's free fall motion and fluid loads is decoupled by auxiliary function method. Stretched coordinate system is constructed to make grids match the dramatically changing wetted surface. Distorted free surface is traced with improved Eulerian method. Water entries with different incident wave heights, initial vertical velocities and cone's densities are simulated respectively. 3DOFs motions including vertical, horizontal and rotational motion of cone with different initial conditions are compared and investigated. Pressure on the wetted surface is given, and discussions of pressure distribution along the cone's generatrices are provided.

Fixational eye movements in passive versus active sustained fixation tasks.

Human fixational eye movements are so small and precise that high-speed, accurate tools are needed to fully reveal their properties and functional roles. Where the fixated image lands on the retina and how it moves for different levels of visually demanding tasks is the subject of the current study. An Adaptive Optics Scanning Laser Ophthalmoscope (AOSLO) was used to image, track and present a variety of fixation targets (Maltese cross, disk, concentric circles, Vernier and tumbling-E letter) to healthy subjects. During these different passive (static) or active (discriminating) tasks under natural eye motion, the landing position of the target on the retina was tracked in space and time over the retinal image directly with high spatial (<1 arcmin) and temporal (960 Hz) resolution. We computed both the eye motion and the exact trajectory of the fixated target's motion over the retina. We confirmed that compared to passive tasks, active tasks elicited a partial inhibition of microsaccades, leading to longer drift periods compensated by larger corrective saccades. Consequently, the overall fixation stability during active tasks was on average 57% larger than during passive tasks. The preferred retinal locus of fixation was the same for each task and did not coincide with the location of the peak cone density.