Cone Density Research Articles

Retinal adaptations of southern bluefin tuna larvae: Implications for culture

We examined Southern bluefin tuna, Thunnus maccoyii, larvae to identify specific retinal adaptations that would indicate both important parameters for culture and larval ecology in the wild. Plastic resin histology, microspectrophotometry and behavioural feeding responses were used to describe visual development. Thunnus maccoyii larvae reflected the visual morphogenesis template commonly observed in many other marine fish species exhibiting indirect development. First-feeding (3 days post-hatching, [dph], 3.4 mm standard length [SL]) larvae possessed tightly packed single cone photoreceptors. Rods and twin cones were present in the retina in post-flexion larvae (21 dph, 8.39 mm fork length [FL]) with cone mosaic patterns observed in juveniles (30 dph, 21 mm FL). Based on the spacing of adjacent photoreceptors and focal length, first feeding larvae had a maximum theoretical visual acuity of 1.23 ± 0.11° that decreased to 0.14 ± 0.02° at 30 dph. Thunnus maccoyii displayed high cell density in the ventral retinal region (cones, bipolar and horizontal cells), a low convergence of cone cells to ganglion cells throughout the retina during larval development (1.1 ± 0.2 to 1.4 ± 0.3 at 3 dph and 30 dph, respectively), and early development of retinal pigment epithelium (RPE) migration. Microspectrophotometry showed twin cone visual pigments maximally sensitive to light in the blue-green part of the visual spectrum (wavelength of maximum absorption [λmax] of 494 nm, 507 nm and 524 nm), and behavioural experiments showed they fed preferentially at these wavelengths. Increased retinal cone densities in the ventral region indicated a localized region specialized for acute vision for prey and predator detection in the upward direction (dorsal plane) at an early age, representing a possible adaptation to life in deeper oceanic waters. The apparent high acuity and photopic sensitivity observed in T. maccoyii is hypothesised to be associated with the ability to feed in low light conditions. This has important practical considerations in determining lighting regimes for culture of T. maccoyii and possibly for other tuna species.

A 2-Year Longitudinal Study of Normal Cone Photoreceptor Density.

PurposeDespite the potential for adaptive optics scanning light ophthalmoscopy (AOSLO) to quantify retinal disease progression at the cellular level, there remain few longitudinal studies investigating changes in cone density as a measure of disease progression. Here, we undertook a prospective, longitudinal study to investigate the variability of cone density measurements in normal subjects during a 2-year period.MethodsFourteen eyes of nine subjects with no known ocular pathology were imaged both at a baseline and a 2-year follow-up visit by using confocal AOSLO at five retinal locations. Two-year affine-registered images were created to minimize the effects of intraframe distortions. Regions of interest were cropped from baseline, 2-year manually aligned, and 2-year affine-registered images. Cones were identified (graded masked) and cone density was extracted.ResultsMean baseline cone density (cones/mm2) was 87,300, 62,200, 45,500, 28,700, and 18,200 at 190, 350, 500, 900, and 1500 μm, respectively. The mean difference (± standard deviation [SD]) in cone density from baseline to 2-year affine-registered images was 1400 (1700), 100 (1800), 300 (800), 400 (800), and 1000 (2400) cones/mm2 at the same locations. The mean difference in cone density during the 2-year period was lower for affine-registered images than manually aligned images.ConclusionsThere was no meaningful change in normal cone density during a 2-year period. Intervisit variability in cone density measurements decreased when intraframe distortions between time points were minimized. This variability must be considered when planning prospective longitudinal clinical trials using changes in cone density as an outcome measure for assessing retinal disease progression.

Early detection of cone photoreceptor cell loss in retinitis pigmentosa using adaptive optics scanning laser ophthalmoscopy.

The purpose of the study was to investigate the characteristics of the parafoveal cone density changes in patients with retinitis pigmentosa (RP) using adaptive optics scanning laser ophthalmoscopy (AO-SLO). A total of 14 eyes of RP patients and 10 eyes of control subjects were examined. High-resolution images of cone photoreceptor cells were obtained with a Canon AO-SLO system in the four retinal regions of the superior, inferior, temporal, and nasal areas located 1.0mm from the central fovea. The relationships of cone density with optical coherence tomography (OCT) findings and the visual sensitivity of the static perimetry tests were analyzed in RP patients. The averaged cone densities in RP patients were decreased at 1.0mm eccentricity from the fovea (11,899cells/mm2) compared with those in control subjects (16,647cells/mm2; P < 0.01). The cone density was substantially decreased even in RP patients with an intact interdigitation zone at the examined area (12,865cells/mm2; P < 0.01 vs. controls) and preserved visual sensitivity with > 35dB (13,019cells/mm2; P < 0.001 vs. controls). In RP, cone photoreceptor cell loss occurred in the parafoveal region with a preserved EZ/IZ or visual sensitivity. AO-SLO may be a useful modality to detect early changes of cone photoreceptor cells in RP patients.

Three-Dimensional Adaptive Optics-Assisted Visualization of Photoreceptors in Healthy and Pathologically Aged Eyes.

To visualize and characterize photoreceptor (PR) layers on a subcellular level in healthy and pathologically aged eyes using adaptive-optics optical coherence tomography technology (AO-OCT). AO-OCT scanning was performed within a 2° × 2° field of view, focused on the PR layer at different retinal regions in healthy aged eyes (n = 32 eyes/16 subjects; 62- to 85-years old), eyes with early to intermediate AMD (n = 16 eyes/8 subjects, 65- to 83-years old), and eyes with advanced nonneovascular AMD (n = 16 eyes/8 subjects, 61- to 84-years old). Areas of interest were determined by AO-fundus camera, which is part of the AO-OCT system and spectral-domain (SD)-OCT. PR integrity was evaluated in AO-OCT en face and cross-sectional images at the level of inner/outer segment junction (IS/OS) and cone/PR end tips (COST/ETPR). AO-OCT in healthy eyes showed clearly distinguishable and regular IS/OS and COST patterns and an inverse relation between cone density and eccentricity. In early to intermediate AMD, PR in between drusen showed more irregular patterns (P < 0.001) and slightly lower PR density (P ≤ 0.002). Drusen caused attenuated and distorted signals and a loss of PR mosaic. In advanced AMD, IS/OS and COST patterns were affected to different degrees between surrounding area, junctional zone, and atrophic area (P < 0.001), ranging from reduced PR densities to total signal loss. AO-OCT imaging allows the three-dimensional visualization of different PR layers in patients with AMD and age-matched healthy subjects. Thereby, AO-OCT provides a unique insight into PR morphology and shows potential to fill the gap between conventional OCT and histologic examination of the retina.

Adaptive Optics (rtx1) High-Resolution Imaging of Photoreceptors and Retinal Arteries in Patients with Diabetic Retinopathy.

Background Diabetic retinopathy (DR) is the leading cause of impaired vision in patients with diabetes mellitus. An adaptive optics retinal camera (rtx1™; Imagine Eyes, France) was used to capture images of cones and retinal arteries from patients with DR. Objective Cone parameters (density, interphotoreceptor distance, and regularity) and retinal artery parameters (wall thickness, lumen diameter, WLR, and WCSA) were analyzed in 36 patients with nonproliferative DR (NPDR; 22 with mild NPDR and 14 with moderate NPDR) and in 20 healthy volunteers (the control group). Results Cone density at 2° eccentricities was significantly lower in the DR compared to the control group (19822 ± 4342 cells/mm2 vs. 24722 ± 3507 cells/mm2, respectively). Cone density and regularity decreased with increasing severity of DR. The artery walls were significantly thicker in the DR group. The WLR and WCSA differed significantly between the DR and the control groups (WLR 0.339 ± 0.06 vs. 0.254 ± 0.04; WCSA 5567 ± 1140 vs. 4178 ± 944, respectively). Conclusions Decreased cone regularity and density are seen in patients with mild and moderate NPDR. Abnormalities of retinal arterioles show signs of arteriolar dysfunction in DR. Retinal image analysis with the rtx1 offers a novel noninvasive measurement of early changes in the neural cells and retina vasculature in diabetic eyes.

Evaluating seasonal changes of cone photoreceptor structure in the 13-lined ground squirrel

Cone photoreceptors of the 13-lined ground squirrel (13-LGS) undergo reversible structural changes during hibernation, including cone outer segment disc degeneration and inner segment mitochondria depletion. Here, we evaluated cone structure with adaptive optics scanning light ophthalmoscopy (AOSLO) before, during, and after hibernation. Also, intra-animal comparisons of cone structure were made at distinct physiological states (pre-hibernation, torpor, interbout euthermia, and post-hibernation) with AOSLO and transmission electron microscopy. Our results indicate that the 13-LGS cone mosaic is only transiently affected by structural remodeling during hibernation. Outer segment remodeling starts during torpid states during a period of fall transition in room temperature, with more severe structural changes during bouts of torpor in cold temperature. Cones return to euthermic-like structure during brief periods of interbout euthermia and recover normal waveguiding properties as soon as 24 h post-hibernation. Cone structure is visible with split-detector AOSLO throughout hibernation, providing evidence that intact outer segments are not necessary to visualize cones with this technique. Despite the changes to cone structure during hibernation, cone density and packing remained unchanged throughout the seasonal cycle. Pairing non-invasive imaging with ultrastructural assessment may provide insight to the biological origins of cone photoreceptor signals observed with AOSLO.

CELLULAR IMAGING OF THE TAPETAL-LIKE REFLEX IN CARRIERS OF RPGR-ASSOCIATED RETINOPATHY.

To examine the features of the tapetal-like reflex (TLR) in female carriers of RPGR-associated retinopathy by means of adaptive optics scanning light ophthalmoscopy (AOSLO) and spectral domain optical coherence tomography. Nine molecularly confirmed RPGR carriers and three healthy controls underwent ocular examination and the following retinal imaging modalities: color photography, near-infrared reflectance, fundus autofluorescence, spectral domain optical coherence tomography, and AOSLO. After identifying TLR areas across all imaging modalities, normalized local contrast of outer retinal bands on spectral domain optical coherence tomography was calculated and AOSLO-acquired photoreceptor mosaic analysis was performed. Seven carriers had TLR areas, which colocalized with increased rod photoreceptor reflectivity on confocal AOSLO and reduced cone photoreceptor densities. Parafoveal TLR areas also exhibited reduced local contrast (i.e., increased reflectivity) of the outer retinal bands on spectral domain optical coherence tomography (inner segment ellipsoid zone and outer segment interdigitation zone). Healthy controls did not show TLR. The cellular resolution provided by AOSLO affords the characterization of the photoreceptor mosaic in RPGR carriers with a TLR. Features revealed include reduced cone density, increased cone inner segment diameter, and increased rod outer segment reflectivity.

The Cone Photoreceptor Mosaic in Aniridia: Within-Family Phenotype–Genotype Discordance

Investigate invivo cone photoreceptor structure in familial aniridia caused by deletion in the PAX6 gene to elucidate the complexity of between-individual variation in retinal phenotype. Descriptive case-control study. Eight persons with congenital aniridia (40-66 yrs) from 1 family and 33 normal control participants (14-69 yrs), including 7 unaffected family members (14-53 yrs). DNA was isolated from saliva samples and used in polymerase chain reaction analysis to amplify and sequence exons and intron or exon junctions of the PAX6 gene. High-resolution retinal images were acquired with OCT and adaptive optics scanning light ophthalmoscopy. Cone density (CD; in cones per square millimeter) and mosaic regularity were estimated along nasal-temporal meridians within the central 0° to 5° eccentricity. Horizontal spectral-domain OCT line scans were segmented to analyze the severity of foveal hypoplasia (FH) and to measure retinal layer thicknesses. Within-family variability in macular retinal layer thicknesses, cone photoreceptor density, and mosaic regularity in aniridia compared with normal control participants. DNA sequencing revealed a known PAX6 mutation (IV2-2delA). Those with aniridia showed variable iris phenotype ranging from almost normal appearance to no iris. Four participants with aniridia demonstrated FH grade 2, 2 demonstrated grade 3 FH, and 1 demonstrated grade 4 FH. Visual acuity ranged from 0.20 to 0.86 logarithm of the minimum angle of resolution. Adaptive optics scanning light ophthalmoscopy images were acquired from 5 family members with aniridia. Foveal CD varied between 19 899 and 55 128 cones/mm2 with overlap between the foveal hypoplasia grades. Cone density was 3 standard deviations (SDs) or more less than the normal mean within 0.5°, 2 SDs less than the normal mean at 0.5° to 4°, and more than 1 SD less than the normal mean at 5° retinal eccentricity. The results showed considerable variability in foveal development within a family carrying the same PAX6 mutation. This, together with the structural and functional variability within each grade of foveal hypoplasia, underlines the importance of advancing knowledge about retinal cellular phenotype in aniridia.

High-Resolution Retinal Imaging Reveals Preserved Cone Photoreceptor Density and Choroidal Thickness in Female Carriers of Choroideremia.

To characterize the photoreceptors and choroidal morphology of heterozygous female carriers of choroideremia who typically do not have any visual defects but can have severe funduscopic changes. This was a clinical case series study. Detailed ophthalmic examinations were performed on six female carriers from four families with choroideremia. The subfoveal choroidal thickness (SFCT) was determined by spectral-domain optical coherence tomography (SD-OCT) and the cone photoreceptor density by adaptive optics (AO) retinal imaging. SFCT and cone densities of the carriers were compared to that of normal eyes of healthy subjects. The mean age of the carriers was 42.5 years. Fundus photographs showed diffuse, patchy depigmentation; however, the SFCT was within the normal limits. AO retinal imaging revealed preserved cone densities at temporal eccentricities from 2 to 8 angular degrees. The findings indicate that despite the presence of distinctive depigmentation of the retinal pigment epithelium in female carriers of choroideremia, their cone photoreceptor densities and SFCT are well-preserved. These observations may account for the good visual acuity and lack of an awareness of visual disturbances. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:76-85.].

Distribution of mid-peripheral cones in emmetropic and myopic subjects using adaptive optics flood illumination camera.

We measured invivo cone photoreceptors up to 24° of eccentricity along the horizontal meridian of healthy human retina. We also investigated the impact on cone densities of axial eye length elongation occurring with myopia. Using a flood illumination device coupled with an adaptive optics system, rtx1™, ( www.imagine-eyes.com), 55 right healthy retinas were imaged along the horizontal (i.e. nasal and temporal) meridian over a 48° field (i.e. from 3° to 24° each 3°). Then, cones were manually detected within 80×80 pixel regions of interest. Cone density and packing geometry (i.e. number of neighbours) were calculated (AOdetect software™). Subjects were divided into three groups: a group of 36 emmetropic (i.e. refractive error from -0.25D to +0.50D) subjects; a group of 10 low myopic subjects (i.e. refractive error from -0.50D to -2.50D); and a group of nine high myopic subjects (i.e. >-2.50D). Cone density decreased with eccentricity in both semi-meridians. The decrease in cone photoreceptors occurred mainly in the first 9°. The difference of cone density between the nasal and temporal semi-meridian increased with eccentricity from 0.6% at 3° to 26% at 24°. Average cone density of emmetropes (850conesdeg-2 or 11087conesmm-2 ), low myopes (830conesdeg-2 or 9731conesmm-2 ), and high myopes (912conesdeg-2 or 9744conesmm-2 ), suggested that the retinas of the high myopic subjects were more stretched than the low myopic subjects retinas and even more stretched than that of the emmetropes. The axial eyeball elongation (square of the ratio of the axial eye length of 9%) seems to explain the cone density (11%) difference between emmetropes and low myopes. However, while the eyeball elongation between low and high myopes is still important (i.e. 11%), cone density difference between both populations was negligible (i.e. 3%). The ratio of cone density varied from -17% to 22% as a function of eccentricity involving that the retinal stretching is not uniform along the horizontal meridian. The difference of cone density (i.e. conemm-2 ) between groups supports the hypothesis that the retina is stretched with the eyeball elongation. However, this elongation does not seem to be uniform along the horizontal meridian favouring the hypothesis of a local elongation of the retina.

Adaptive Optics Retinal Imaging in CNGA3-Associated Achromatopsia: Retinal Characterization, Interocular Symmetry, and Intrafamilial Variability.

PurposeTo investigate retinal structure in subjects with CNGA3-associated achromatopsia and evaluate disease symmetry and intrafamilial variability.MethodsThirty-eight molecularly confirmed subjects underwent ocular examination, optical coherence tomography (OCT), and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). OCT scans were used for evaluating foveal hypoplasia, grading foveal ellipsoid zone (EZ) disruption, and measuring outer nuclear layer (ONL) thickness. AOSLO images were used to quantify peak foveal cone density, intercell distance (ICD), and the coefficient of variation (CV) of ICD.ResultsMean (±SD) age was 25.9 (±13.1) years. Mean (± SD) best corrected visual acuity (BCVA) was 0.87 (±0.14) logarithm of the minimum angle of resolution. Examination with OCT showed variable disruption or loss of the EZ. Seven subjects were evaluated for disease symmetry, with peak foveal cone density, ICD, CV, ONL thickness, and BCVA not differing significantly between eyes. A cross-sectional evaluation of AOSLO imaging showed a mean (±SD) peak foveal cone density of 19,844 (±13,046) cones/mm2. There was a weak negative association between age and peak foveal cone density (r = −0.397, P = 0.102), as well as between EZ grade and age (P = 0.086).ConclusionsThe remnant cone mosaics were irregular and variably disrupted, with significantly lower peak foveal cone density than unaffected individuals. Variability was also seen among subjects with identical mutations. Therefore, subjects should be considered on an individual basis for stratification in clinical trials. Interocular symmetry suggests that both eyes have comparable therapeutic potential and the fellow eye can serve as a valid control. Longitudinal studies are needed, to further examine the weak negative association between age and foveal cone structure observed here.

Cone-to-Müller cell ratio in the mammalian retina: A survey of seven mammals with different lifestyle

Mammalian retinal glial (Müller) cells are known to guide light through the inner retina to photoreceptors (Franze et al., 2007; Proc Natl Acad Sci U S A 104:8287–8292). It was shown that Müller cells transmit predominantly red-green and less violet-blue light (Labin et al., 2014; Nat Commun 5:4319). It is not known whether this optical function is reflected in the cone-to-Müller cell ratio. To determine this ratio in the retinas of mammals with different lifestyle, we evaluated the local densities of cones and Müller cells in the retinas of guinea pigs, rabbits, sheep, red deer, roe deer, domestic pigs, and wild boars. Retinal wholemounts were labeled with peanut agglutinin to mark cones and anti-vimentin antibodies to identify Müller cells. Wholemounts of guinea pig and rabbit retinas were also labeled with anti-S-opsin-antibodies. With the exceptions of guinea pig and pig retinas that had cone-to-Müller cell ratios of above one, the local densities of cones and Müller cells in the retinas of the species investigated were roughly equal. Because the proportion of S-cones is usually low (for example, 5.3% of all cones in the dorsal guinea pig retina expressed S-opsin), it is suggested that Müller cells are mainly coupled to M-cones. Exceptions are the ventral peripheries of guinea pig and rabbit retinas which are specialized areas with high S-cone densities. Here, up to 50% of Müller cells may be coupled to S-cones, and 40% of S-cones may be not coupled to Müller cells. Among the species investigated, the density of Müller cells in the central retina was inversely correlated with the axial length of the eyes. It is suggested that (with the exception of specialized S-cone areas) Müller cells support high acuity vision by predominant guidance of red-green light to M-opsin expressing cones.

Nanopipet and truncated cone pores; influence of the cone size and density on fluid structure and adsorption: DFT approach

The modified fundamental measure theory, MFMT is employed to investigate the hard sphere structure inside and around nanopipet pores. Our findings show that fluid molecules have a strong tendency to accumulate at the conical part of the nanopipet. This allows the fluid to have a greater layering in its structure in the cone region in comparison to the cylindrical part. For the cone region, contact density at the concave wall decreases with the radius of the cross section. Also, a pronounced maximum peak observed for contact density of fluids in the pore in the junction of the two parts of a nanopipet. A reverse behavior is, however, observed for fluid density at the convex outer wall. Comparison of fluid adsorption in nano-cylindrical with nanotruncated cone pores of identical volumes reveals that the first kind of pore record higher adsorption values for reduced integer values of tip radius.

Metipranolol promotes structure and function of retinal photoreceptors in the rd10 mouse model of human retinitis pigmentosa.

Metipranolol is a β-adrenergic receptor antagonist that is given orally for the treatment of hypertension and also applied topically to the cornea for treating glaucoma. It also inhibits nitrosative stress which has previously been shown to be the cause of cone photoreceptor death in retinitis pigmentosa. In this study, we tested the hypothesis that metipranolol protects photoreceptor structure and function in the mouse model rd10. At P35, compared with vehicle-treated rd10 mice in which rod degeneration was nearly complete, rd10 mice given daily subcutaneous injections of 40mg/kg of metipranolol had reduction in markers of nitrosative stress, fewer TUNEL-positive cells, increased outer nuclear layer thickness, and substantially more staining for rhodopsin. This was accompanied by significantly higher mean scotopic and photopic electroretinogram b-wave amplitudes indicating improved photoreceptor function. At P50, metipranolol-treated rd10 mice had decreased 3-nitrotyrosine staining in the retina, increased immunostaining for cone arrestin, a marker for cone photoreceptors, and significantly higher scotopic and photopic b-wave amplitudes at the highest stimulus intensity compared with vehicle-treated mice. At P65, cone density was significantly higher in metipranolol-treated versus vehicle-injected rd10 mice. Metipranolol applied as eye drops promoted cone photoreceptor function in retinas of rd10 mice greater than subcutaneously injected metipranolol. The reduced nitrosative damage and rescue of functional loss of photoreceptors in rd10 mice suggests that metipranolol, a drug with established ocular safety and tolerability, may have potential for treating patients with retinitis pigmentosa.

Functional architecture of the foveola revealed in the living primate.

The primate foveola, with its high cone density and magnified cortical representation, is exquisitely specialized for high-resolution spatial vision. However, uncovering the wiring of retinal circuitry responsible for this performance has been challenging due to the difficulty in recording receptive fields of foveal retinal ganglion cells (RGCs) in vivo. In this study, we use adaptive optics scanning laser ophthalmoscopy (AOSLO) to image the calcium responses of RGCs in the living primate, with a stable, high precision visual stimulus that allowed us to localize the receptive fields of hundreds of foveal ganglion cells. This approach revealed a precisely radial organization of foveal RGCs, despite the many distortions possible during the extended developmental migration of foveal cells. By back projecting the line connecting RGC somas to their receptive fields, we have been able to define the ‘physiological center’ of the foveola, locating the vertical meridian separating left and right hemifields in vivo.

Automated identification of cone photoreceptors in adaptive optics optical coherence tomography images using transfer learning

Automated measurements of the human cone mosaic requires the identification of individual cone photoreceptors. The current gold standard, manual labeling, is a tedious process and can not be done in a clinically useful timeframe. As such, we present an automated algorithm for identifying cone photoreceptors in adaptive optics optical coherence tomography (AO-OCT) images. Our approach fine-tunes a pre-trained convolutional neural network originally trained on AO scanning laser ophthalmoscope (AO-SLO) images, to work on previously unseen data from a different imaging modality. On average, the automated method correctly identified 94% of manually labeled cones when compared to manual raters, from twenty different AO-OCT images acquired from five normal subjects. Voronoi analysis confirmed the general hexagonal-packing structure of the cone mosaic as well as the general cone density variability across portions of the retina. The consistency of our measurements demonstrates the high reliability and practical utility of having an automated solution to this problem.

Cone Photoreceptor Cell Segmentation and Diameter Measurement on Adaptive Optics Images Using Circularly Constrained Active Contour Model.

PurposeCone photoreceptor cells can be noninvasively imaged in the living human eye by using nonconfocal adaptive optics scanning ophthalmoscopy split detection. Existing metrics, such as cone density and spacing, are based on simplifying cone photoreceptors to single points. The purposes of this study were to introduce a computer-aided approach for segmentation of cone photoreceptors, to apply this technique to create a normal database of cone diameters, and to demonstrate its use in the context of existing metrics.MethodsCone photoreceptor segmentation is achieved through a circularly constrained active contour model (CCACM). Circular templates and image gradients attract active contours toward cone photoreceptor boundaries. Automated segmentation from in vivo human subject data was compared to ground truth established by manual segmentation. Cone diameters computed from curated data (automated segmentation followed by manual removal of errors) were compared with histology and published data.ResultsOverall, there was good agreement between automated and manual segmentations and between diameter measurements (n = 5191 cones) and published histologic data across retinal eccentricities ranging from 1.35 to 6.35 mm (temporal). Interestingly, cone diameter was correlated to both cone density and cone spacing (negatively and positively, respectively; P < 0.01 for both). Application of the proposed automated segmentation to images from a patient with late-onset retinal degeneration revealed the presence of enlarged cones above individual reticular pseudodrusen (average 23.0% increase, P < 0.05).ConclusionsCCACM can accurately segment cone photoreceptors on split detection images across a range of eccentricities. Metrics derived from this automated segmentation of adaptive optics retinal images can provide new insights into retinal diseases.

Sintering and collapse of synthetic coal ash and slag cones as observed through constant heating rate optical dilatometry

Ash agglomeration and slagging are responsible for costly maintenance problems in coal-fired boilers. Boiler design and operation rely on critical ash fusion temperatures defined by geometric criteria that explicitly ignore shrinkage or warping. Reproducibility of ash fusion test (AFT) results is known to be a major problem, given the subjective nature of some criteria used in critical temperature reporting. Decades of faulty predictions based on AFT data underscore the need for an objective measure of the likelihood for agglomeration and slagging as a function of coal ash composition and temperature. Heating microscopes and ash fusibility determinators are AFT instruments that are widely available and readily adapted for optical dilatometry of ash cones through digital image analysis. Optical dilatometry enables the continuous measurement of cone height and face area, and the calculation of changes in cone volume and density as a function of temperature during constant heating. A strong correlation was found between the sintering onset temperatures of two synthetic ash compositions measured through optical dilatometry and their corresponding solidus temperatures predicted through thermophysical modeling. The sintering onset temperatures of synthetic slag cones appears consistent with glass transition temperatures estimated using the Kauzmann-Beaman rule. Cone collapse is highly correlated with softening, hemispherical, and fluid temperatures for ash cones. Rapid changes in solid, liquid, and gas volume fractions near the collapse temperature suggest that a transition from capillary to slurry state may play an important role in triggering collapse. Slag cone collapse is better explained by a decrease in viscosity as a function of temperature in the glass working range. The sintering onset temperature and cone collapse temperature are readily understood through thermophysical modeling based on ash composition and provide two additional critical temperatures in the modeling of coal ash agglomeration and slagging.

The topography of rods, cones and intrinsically photosensitive retinal ganglion cells in the retinas of a nocturnal (Micaelamys namaquensis) and a diurnal (Rhabdomys pumilio) rodent.

We used immunocytochemistry to determine the presence and topographical density distributions of rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) in the four-striped field mouse (Rhabdomys pumilio) and the Namaqua rock mouse (Micaelamys namaquensis). Both species possessed duplex retinas that were rod dominated. In R. pumilio, the density of both cones and rods were high (cone to rod ratio: 1:1.23) and reflected the species’ fundamentally diurnal, but largely crepuscular lifestyle. Similarly, the ratio of cones to rods in M. namaquensis (1:12.4) reflected its nocturnal lifestyle. Similar rod density peaks were observed (R. pumilio: ~84467/mm2; M. namaquensis: ~81088/mm2), but a density gradient yielded higher values in the central (~56618/mm2) rather than in the peripheral retinal region (~32689/mm2) in R. pumilio. Two separate cone types (S-cones and M/L-cones) were identified implying dichromatic color vision in the study species. In M. namaquensis, both cone populations showed a centro-peripheral density gradient and a consistent S- to M/L-cone ratio (~1:7.8). In R. pumilio, S cones showed a centro-peripheral gradient (S- to M/L-cone ratio; central: 1:7.8; peripheral: 1:6.8) which appeared to form a visual streak, and a specialized area of M/L-cones (S- to M/L-cone ratio: 1:15) was observed inferior to the optic nerve. The number of photoreceptors per linear degree of visual angle, estimated from peak photoreceptor densities and eye size, were four cones and 15 rods per degree in M. namaquensis and 11 cones and 12 rods per degree in R. pumilio. Thus, in nocturnal M. namaquensis rods provide much finer image sampling than cones, whereas in diurnal/crepuscular R. pumilio both photoreceptor types provide fine image sampling. IpRGCs were comparably sparse in R. pumilio (total = 1012) and M. namaquensis (total = 862), but were homogeneously distributed in M. namaquensis and densest in the dorso-nasal quadrant in R. pumilio. The adaptive significance of the latter needs further investigation.

Central Retina Functional Damage in Usher Syndrome Type 2: 22 Years of Focal Macular ERG Analysis in a Patient Population From Central and Southern Italy

Recent studies show that patients with Usher syndrome type 2 (USH2) have abnormal cone structure and density in the central retina. This occurs in the presence of normal acuity, opening the quest for additional sensitive functional measures of central cone function in USH. We tested here whether focal macular cone electroretinogram (fERG) could be such a tool. This retrospective study of central cone function loss was based on data from 47 patients with USH2 from the Ophthalmology Department of the Policlinico Gemelli/Catholic University in Rome. The analysis focused on the decrease of the fERG, obtained in response to a 41-Hz sinusoidal modulation of a uniform field presented to the central 18°, generated by red light-emitting diodes (LEDs) and superimposed on an equiluminant steady adapting background. fERG decrease was compared with the decrease of best-corrected visual acuity and Goldmann kinetic perimetry V4E field. fERG follow-up data document a severe and precocious loss of central cone function in USH2 patients, preceding losses in other measures of cone function. fERG is already reduced to 40% of control at the beginning of the second decade of life, and by 25 years of age, all USH2 patients have fERGs less than 30% of control values. fERG represents a sensitive tool to evaluate central cone function in USH2, anticipating the decline of other central cone function measures, such as visual acuity and Goldmann perimetry.