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Background/aimsTo investigate the association between longitudinal changes of foveal avascular zone (FAZ) area and the rate of structural and functional progression in glaucoma.MethodsA longitudinal cohort included 115 eyes (46 glaucoma suspect and 66 primary open-angle glaucoma) of 81 patients having ≥2 year follow-up, and ≥4 visits with optical coherence tomography angiography and visual field (VF). Eyes in the longitudinal cohort with a slope greater than that found in 95 percentile of separate healthy test-retest series for FAZ area were categorised into FAZ progressors; all other eyes were defined as FAZ non-progressors. A generalised linear mixed-effect model was used to investigate the association of FAZ progressors with demographic and clinical characteristics.ResultsFaster ganglion cell complex (GCC) thinning and faster VF mean deviation (MD) loss were found in eyes with FAZ progressors compared with FAZ non-progressors (mean difference: -0.7 (95% CI, -1.4 to -0.1) µm/y; p=0.026, -0.3 (-0.5 to -0.1) dB/y; p=0.017, respectively), while whole image vessel density was not associated with FAZ progressors (p=0.929). SD of intraocular pressure (IOP) and IOP range were also associated with FAZ progressors in separate multivariable models (OR: 1.54 (1.02 to 2.32) per 1 mm Hg higher, p=0.041; OR: 1.20 (1.01 to 1.41) per 1 mm Hg higher; p=0.035, respectively).ConclusionsSignificant FAZ increase was weakly associated with moderately faster rates of both GCC thinning and VF MD loss, but not macular vessel density change in glaucoma eyes. Additional studies are needed to elucidate the pathophysiological associations between macula GCC thinning and FAZ area increases in glaucoma.

In primates, high-acuity vision is mediated by the fovea, a small specialized central region of the retina. The fovea, unique to the anthropoid lineage among mammals, undergoes notable neuronal morphological changes during postnatal maturation. However, the extent of cellular similarity across anthropoid foveas and the molecular underpinnings of foveal maturation remain unclear. Here, we used high-throughput single-cell RNA sequencing to profile retinal cells of the common marmoset (Callithrix jacchus), an early divergent in anthropoid evolution from humans, apes, and macaques. We generated atlases of the marmoset fovea and peripheral retina for both neonates and adults. Our comparative analysis revealed that marmosets share almost all their foveal types with both humans and macaques, highlighting a conserved cellular structure among primate foveas. Furthermore, by tracing the developmental trajectory of cell types in the foveal and peripheral retina, we found distinct maturation paths for each. In-depth analysis of gene expression differences demonstrated that cone photoreceptors and Müller glia (MG), among others, show the greatest molecular divergence between these two regions. Utilizing single-cell ATAC-seq and gene-regulatory network inference, we uncovered distinct transcriptional regulations differentiating foveal cones from their peripheral counterparts. Further analysis of predicted ligand-receptor interactions suggested a potential role for MG in supporting the maturation of foveal cones. Together, these results provide valuable insights into foveal development, structure, and evolution.

Prior research has investigated the quality of information a reader can extract from upcoming parafoveal words. However, very few studies have considered parafoveal processing in bilingual readers, who may differ from monolinguals due to slower lexical access and susceptibility to cross-language activation. This eye-tracking experiment, therefore, investigated how bilingual readers process parafoveal semantic information within and across languages. We used the boundary technique to replace a preview word in a sentence with a different target word during the first rightward saccade from the pretarget region. We manipulated both preview language (nonswitch vs. code-switch) and semantic relatedness (synonym/translation vs. unrelated) between previews and targets. Upon fixation, target words always appeared in the same language as the rest of the sentence to create an essentially monolingual language context. Semantic preview benefits emerged for nonswitched synonym previews but not for code-switched translation previews. Furthermore, participants skipped code-switched previews less often than nonswitched previews and no more often than previews that were unfamiliar to them. These data suggest that bilinguals can extract within-language semantic information from the parafovea in both native and nonnative languages, but that cross-language words are not accessible while reading in a monolingual language mode, as per the partial selectivity hypothesis of bilingual language control. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

PurposeTo 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.MethodsWe 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.ResultsInter-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.ConclusionsHigher than normal parafoveal cone densities (presumably dominated by S-cones) confer better than normal S-cone-mediated acuity in ESCS subjects.

SIGNIFICANCE: This case report demonstrates the use of novel imaging techniques and functional tests to longitudinally evaluate retinal structure and function after laser retinal injury. The structural and functional prognosis could be predicted with clinical findings, high-resolution retinal imaging, and functional testing. PURPOSE: We present a laser retinal injury case in which an adaptive optics scanning laser ophthalmoscope and adaptive optics-based psychophysics were used to examine and monitor retinal structure and function after accidental exposure to a 1-W infrared laser beam. CASE REPORT: A 23-year-old patient was unwittingly exposed to a 1-W, 852-nm continuous-wave laser at work as they noticed a small central blurry spot in the right eye. An initial eye examination was done 1 day after exposure, and the right eyes acuity was 20/25 -2 . Posterior segment evaluation revealed disrupted outer retina near the right eyes fovea. Adaptive optics imaging 2 weeks after the exposure revealed a 0.50 × 0.75° elliptical area with irregular borders and abnormal cone reflectivity just below the fovea. Starting at 1-month follow-up, structural recovery was observed on optical coherence tomography (OCT). Subsequent adaptive optics imaging showed significant recovery of cone reflectivity. Importantly, adaptive optics microperimetry showed measurable detection thresholds at all affected retinal locations at 6 months. By 10 months, all sites exhibited normal sensitivities. CONCLUSIONS: Retinal structure and function from laser injury can be visualized and measured with OCT, adaptive optics imaging, and psychophysics. An intact Bruchs membrane on OCT and measurable retinal sensitivity by adaptive optics microperimetry may serve as good biomarkers for retinal recovery.

Background/aimsTo investigate the relationship between the foveal avascular zone (FAZ) parameters assessed by optical coherence tomography angiography (OCTA) and central visual field parameters in glaucoma and healthy subjects.MethodsOne hundred and eighty-eight subjects (248 eyes), including 24 healthy (38 eyes), 37 glaucoma suspect (42 eyes, and 127 primary open angle glaucoma (POAG) patients (168 eyes), underwent imaging using OCTA and standard automated perimetry using the 24-2 and 10-2 Swedish Interactive Thresholding Algorithm. OCTA-based and OCT-based FAZ parameters (superficial FAZ area, FAZ circumference), foveal vessel density (FD300) and foveal thickness were measured. The correlation between FAZ parameters and visual field parameters was assessed using linear mixed model.ResultsAxial length adjusted-FAZ area was not different among the three groups (mean (95% CI)): in healthy 0.31 (0.27 to 0.36) mm2, glaucoma suspect 0.29 (0.26 to 0.31) mm2 and POAG eyes 0.28 (0.27 to 0.30) mm2 (p=0.578). FD300 was lower in glaucoma suspect 49.1% (47.9% to 50.4%) and POAG eyes 48.7% (48.1% to 49.4%) than healthy eyes 50.5% (49.3% to 51.7%) though the difference was not statistically significant (p=0.071). Lower FD300 was associated with worse 24-2 and 10-2 visual field mean deviation and foveal threshold in multivariable linear mixed models (all p

PurposeFoveoschisis involves the pathologic splitting of retinal layers at the fovea, which may occur congenitally in X-linked retinoschisis (XLRS) or as an acquired complication of myopia. XLRS is attributed to functional loss of the retinal adhesion protein retinoschisin 1 (RS1), but the pathophysiology of myopic foveoschisis is unclear due to the lack of animal models. Here, we characterized a novel nonhuman primate model of myopic foveoschisis through clinical examination and multimodal imaging followed by morphologic, cellular, and transcriptional profiling of retinal tissues and genetic analysis.MethodsWe identified a rhesus macaque with behavioral and anatomic features of myopic foveoschisis, and monitored disease progression over 14 months by fundus photography, fluorescein angiography, and optical coherence tomography (OCT). After necropsy, we evaluated anatomic and cellular changes by immunohistochemistry and transcriptomic changes using single-nuclei RNA-sequencing (snRNA-seq). Finally, we performed Sanger and whole exome sequencing with focus on the RS1 gene.ResultsAffected eyes demonstrated posterior hyaloid traction and progressive splitting of the outer plexiform layer on OCT. Immunohistochemistry showed increased GFAP expression in Müller glia and loss of ramified Iba-1+ microglia, suggesting macro- and microglial activation with minimal photoreceptor alterations. SnRNA-seq revealed gene expression changes predominantly in cones and retinal ganglion cells involving chromatin modification, suggestive of cellular stress at the fovea. No defects in the RS1 gene or its expression were detected.ConclusionsThis nonhuman primate model of foveoschisis reveals insights into how acquired myopic traction leads to phenotypically similar morphologic and cellular changes as congenital XLRS without alterations in RS1.

Patients with central vision loss often adopt a location outside their scotoma as the new reference for vision, the preferred retinal locus (PRL). The development of a PRL is important not only for the rehabilitation of patients with central vision loss, but also helps us better understand how the brain adapts to the lack of visual input. Many investigators studied this question using a gaze-contingent display paradigm by imposing an artificial scotoma to simulate central vision loss for normally sighted subjects, with an important assumption that the PRL thus developed is the result of visuomotor adaptation, as is the case for people with a real scotoma. In this study, we tested the validity of this assumption. We used a gaze-contingent display combined with an artificial scotoma to first train normally sighted subjects to develop a PRL for saccade eye movements. Then, we compared the properties of saccades when the artificial scotoma was randomly turned off or on. When the artificial scotoma was absent, subjects automatically reverted to using their fovea, with a shorter saccade latency. Our findings suggest that the development of a PRL in response to an artificial scotoma may represent a strategy, instead of a genuine visuomotor adaptation.

It is well known that crowding, the disruptive influence of flanking items on identification of targets, is the primary limiting factor to object identification in the periphery, while limits in the fovea are more determined by the ability to resolve individual items. Whether this is a dichotomous or merely a quantitative difference, and the transition between these two regimes, has remained unexplained. Here, using an adaptive optics system for optimal control of optical and stimulus factors, we measured threshold acuity for identification of Tumbling Es flanked by bars at a variety of flanker spacings and eight eccentricities in the parafovea. Thresholds at each eccentricity were influenced by resolution, contour interaction, and a saturating pedestal effect. When target-flanker spacing was plotted in terms of cortical distance, a single canonical clipped-line fit unified the resultant curves. The critical spacing for letters flanked by bars was found to be 1.3 to 1.5 cortical millimeters, corresponding to approximately 0.1*E outside the fovea.

PurposeTo characterize the structure and function of patches of dysflective cones in the foveal region of subjects with normal vision and no known pathology. Dysflective cones are cones that have little or no reflective properties in optical coherence tomography (OCT) or adaptive optics scanning laser ophthalmoscope (AOSLO) images yet exhibit measurable function.MethodsAOSLO images were surveyed for the presence of hyporeflective cone patches, and subjects were brought back for imaging to determine the changes in the hyporeflective region. Adaptive optics microperimetry (AOMP) was used to assess the function of hyporeflective patches in four subjects to determine that they did, in fact, contain dysflective cones. AOMP utilized a stimulus size of less than 1 arcmin to measure thresholds inside and outside the hyporeflective region.ResultsNineteen out of 47 individuals retrospectively reviewed had one or more regions with hyporeflective cone patches in one or both eyes. Ten subjects with hyporeflective cone patches were brought back for imaging. Seven of the 10 had resolved at follow up, and in three subjects new hyporeflective patches appeared in a different location. All AOMP-measured subjects had measurable function in the dysflective cone region. Three out of four subjects showed no difference in light sensitivity in the dysflective region compared to adjacent areas, and one subject showed a 3× reduction in sensitivity in the area.ConclusionsPatches of dysflective cone have been identified in subjects with normal vision and no known pathology, and we have observed instances where dysflective cones in these subjects regain normal reflective properties.

Background/aimsTo evaluate quantitative changes in the foveal avascular zone (FAZ) area after glaucoma surgery using swept-source optical coherence tomography angiography (SS-OCTA).MethodsFifty-four consecutive patients with primary open-angle glaucoma (POAG) who met the inclusion criteria and underwent unilateral glaucoma surgery to reduce intraocular pressure (IOP) between April 2018 and July 2019.Eyes underwent IOP-lowering glaucoma surgery and their fellow (non-surgical) eyes were included. OCTA of the macula was performed in both eyes before glaucoma surgery and 3 months postoperatively. Two blinded examiners reviewed the image quality. Within- and between-group comparisons of the FAZ area and correlation of the FAZ area with age, IOP, central sensitivity and clinical variables.ResultsThe mean (±SD) age was 66.7±11.3 years. After surgery, the IOP and FAZ area significantly decreased from 22.1±9.5 mmHg to 10.3±3.5 mmHg and from 0.485±0.193 mm2 to 0.446±0.174 mm2, respectively (both p

Mutations in the Membrane-type frizzled related protein (Mfrp) gene results in an early-onset retinal degeneration associated with retinitis pigmentosa, microphthalmia, optic disc drusen and foveal schisis. In the current study, a previously characterized mouse model of human retinal degeneration carrying homozygous c.498_499insC mutations in Mfrp (MfrpKI/KI) was used. Patients carrying this mutation have retinal degeneration at an early age. The model demonstrates subretinal deposits and develops early-onset photoreceptor degeneration. We observed large subretinal deposits in MfrpKI/KI mice which were strongly CD68 positive and co-localized with autofluorescent spots. Single cell RNA sequencing of MfrpKI/KI mice retinal microglia showed a significantly higher number of pan-macrophage marker Iba-1 and F4/80 positive cells with increased expression of activation marker (CD68) and lowered microglial homeostatic markers (TMEM119, P2ry13, P2ry13, Siglech) compared with wild type mice confirming microglial activation as observed in retinal immunostaining showing microglia activation in subretinal region. Trajectory analysis identified a small cluster of microglial cells with activation transcriptomic signatures that could represent a subretinal microglia population in MfrpKI/KI mice expressing higher levels of APOE. We validated these findings using immunofluorescence staining of retinal cryosections and found a significantly higher number of subretinal Iba-1/ApoE positive microglia in MfrpKI/KI mice with some subretinal microglia also expressing lowered levels of microglial homeostatic marker TMEM119, confirming microglial origin. In summary, we confirm that MfrpKI/KI mice carrying the c.498_499insC mutation had a significantly higher population of activated microglia in their retina with distinct subsets of subretinal microglia. Further, studies are required to confirm whether the association of increased subretinal microglia in MfrpKI/KI mice are causal in degeneration.

The maintenance of stable visual perception across eye movements is hypothesized to be aided by extraretinal information (e.g., corollary discharge [CD]). Previous studies have focused on the benefits of this information for perception at the fovea. However, there is little information on the extent that CD benefits peripheral visual perception. Here we systematically examined the extent that CD supports the ability to perceive transsaccadic changes at the fovea compared to peripheral changes. Human subjects made saccades to targets positioned at different amplitudes (4° or 8°) and directions (rightward or upward). On each trial there was a reference point located either at (fovea) or 4° away (periphery) from the target. During the saccade the target and reference disappeared and, after a blank period, the reference reappeared at a shifted location. Subjects reported the perceived shift direction, and we determined the perceptual threshold for detection and estimate of the reference location. We also simulated the detection and location if subjects solely relied on the visual error of the shifted reference experienced after the saccade. The comparison of the reference location under these two conditions showed that overall the perceptual estimate was approximately 53% more accurate and 30% less variable than estimates based solely on visual information at the fovea. These values for peripheral shifts were consistently lower than that at the fovea: 34% more accurate and 9% less variable. Overall, the results suggest that CD information does support stable visual perception in the periphery, but is consistently less beneficial compared to the fovea.

PURPOSE: Human photoreceptors are sensitive to infrared light (IR). This sensitivity can be used as a novel indicator of retinal function. Diabetic retinopathy patients were assessed using in vivo two-photon excitation and compared their scotopic IR threshold with that of healthy patients. METHODS: Sixty-two participants, 28 healthy and 34 with diabetic retinopathy, underwent a comprehensive eye examination, where visual acuity and contrast sensitivity were assessed. Infrared thresholds were measured in the fovea and parafovea following 30-minute dark adaptation. A two-photon excitation device was used with integrated pulsed laser light (1,045 nm) for sensitivity testing and scanning laser ophthalmoscopy for fundus imaging. RESULTS: The mean Snellen visual acuity of diabetic patients (6/7.7) was worse than that of the healthy patients (6/5.5), which was significantly different (P < 0.001). Disease patients had decreased contrast sensitivity, especially at 6 and 18 cycles/degree. The mean retinal sensitivity to IR light in eyes with diabetic retinopathy (11.6 ± 2.0 dB) was significantly (P < 0.001) lower than that in normal eyes (15.5 ± 1.3 dB). CONCLUSION: Compared with healthy control subjects, the IR light sensitivity of diabetic patients was significantly impaired. Two-photon measurements can be used in the assessment of retinal disease, but further studies are needed to validate IR light stimulation in various stages of diabetic retinopathy.

PurposeTo use visible light optical coherence tomography (OCT) to investigate subcellular reflectivity contributions to the outermost (4th) of the retinal hyperreflective bands visualized by current clinical near-infrared (NIR) OCT.MethodsVisible light OCT, with 1.0 µm axial resolution, was performed in 28 eyes of 19 human subjects (21-57 years old) without history of ocular pathology. Two foveal and three extrafoveal hyperreflective zones were consistently depicted within band 4 in all eyes. The two outermost hyperreflective bands, occasionally visualized by NIR OCT, were presumed to be the retinal pigment epithelium (RPE) and Bruch's membrane (BM). RPE thickness, BM thickness, and RPE interior reflectivity were quantified topographically across the macula.ResultsA method for correcting RPE multiple scattering tails was found to both improve the Gaussian goodness-of-fit for the BM intensity profile and reduce the coefficient of variation of BM thickness in vivo. No major topographical differences in macular BM thickness were noted. RPE thickness decreased with increasing eccentricity. Visible light OCT signal intensity in the RPE was weighted to the apical side and attenuated more across the RPE in the fovea than peripherally.ConclusionsMorphometry of the presumed RPE and BM bands is consistent with known anatomy. Weighting of RPE reflectivity toward the apical side suggests that melanosomes are the predominant contributors to RPE backscattering and signal attenuation in young eyes.Translational relevanceBy enabling morphometric analysis of the RPE and BM, visible light OCT deciphers the main reflectivity contributions to outer retinal band 4, commonly visualized by commercial OCT systems.

PurposeThe purpose of this study was to examine whether racial and ethnic differences in retinal microvasculature are detectable with quantitative measures derived from optical coherence tomography angiography (OCTA).MethodsOCTA scans and fundus photography were obtained in 447 eyes from 271 patients with and without diabetes between April and October 2018. Fundus photos were graded by the hospital reading center for diabetic retinopathy (DR) severity. Eight OCTA parameters relating to the foveal avascular zone (FAZ), superficial vascular perfusion, and deep vascular perfusion were analyzed for significant differences between race and ethnicity groups, self-reported by patients and organized according to National Center for Health Statistics groupings. Multiple regression was then used to adjust estimates for possible confounding by age, gender, hypertension, and last hemoglobin A1c level.ResultsSignificant differences in FAZ area were found between white and non-white patients. After adjustment, the differences between white and all non-white groups were statistically significant (p

PurposeTo analyze the effect of induced astigmatism on en-face spectral-domain optical coherence tomography angiography quantitative metrics.DesignProspective crossover study.MethodsNormal eyes without astigmatism and with 0.75, 1.75, and 2.75 diopters (D) of with-the-rule (WTR) astigmatism were imaged using a 3 × 3-mm scan pattern SD-OCTA CIRRUS 5000 HD-OCT with AngioPlex (Carl Zeiss Meditec, Dublin, CA, USA). Quantitative parameters, including foveal avascular zone metrics, parafoveal vessel length density (VD), and perfusion density (PD) were corrected for magnification secondary to axial length and analyzed. Univariate linear regressions were performed within each eye to correlate quantitative metrics to the level of an induced astigmatic cylinder.ResultsFifteen eyes from 15 patients were imaged. Every 1-D increase in induced WTR astigmatism was associated with a statistically significant decrease in VD and PD within all Early Treatment Diabetic Retinopathy Study inner ring quadrants; however, especially more so nasally (VD: 0.63; P < .001; PD: 0.0089; P = .001). For every 1-D increase in induced astigmatism, the resulting decrease in the inner ring superior quadrant was 12% greater for VD and 16% greater for PD versus that in the inferior quadrant. The resulting decrease in the inner ring nasal quadrant was 40% greater for VD and 48% greater for PD versus that in the temporal quadrant.ConclusionsIncreasing levels of induced WTR astigmatism correlated with globally diminishing VD and PD, was more symmetrical for vertical than horizontal quadrants, and was most pronounced nasally. This may be due to a high prevalence of horizontally oriented vessels nasally and the horizontal optical defocus induced by WTR astigmatism.

We have used recent measurements of mammalian cone light responses and voltage-gated currents to calculate cone ATP utilization and compare it to that of rods. The largest expenditure of ATP results from ion transport, particularly from removal of Na+ entering outer segment light-dependent channels and inner segment hyperpolarization-activated cyclic nucleotide-gated channels, and from ATP-dependent pumping of Ca2+ entering voltage-gated channels at the synaptic terminal. Single cones expend nearly twice as much energy as single rods in darkness, largely because they make more synapses with second-order retinal cells and thus must extrude more Ca2+ In daylight, cone ATP utilization per cell remains high because cones never remain saturated and must continue to export Na+ and synaptic Ca2+ even in bright illumination. In mouse and human retina, rods greatly outnumber cones and consume more energy overall even in background light. In primates, however, the high density of cones in the fovea produces a pronounced peak of ATP utilization, which becomes particularly prominent in daylight and may make this part of the retina especially sensitive to changes in energy availability.

PURPOSE: The eye can see pulsed near-infrared (IR) radiation with the color corresponding to half of the wavelength used. Until recently, the technology required for measuring IR vision was confined to optical laboratories and was not studied clinically. The current investigation sought to determine the values for IR thresholds in a healthy population. METHODS: IR-light threshold was measured in 45 healthy participants, aged from 21 to 70 years. Ten patients with retinal pathology were included for comparison. Ocular media clarity was assessed with a straylight parameter. The sensitivity of dark-adapted eyes (expressed on a 0-26 dB scale) were tested using an IR microperimeter. The device consists of a femtosecond laser that emits 1045 nm light to project a stimulus at the retina. RESULTS: All participants were able to see the IR stimulus, which they perceived as green, and all performed the test. Measurements at seven locations revealed lower sensitivity at the fovea (15.5 dB) than in paracentral regions (18.2 dB). We noted a significant straylight increase with age. Although, in our study population, it was only a slight, -0.18 dB decline per decade of the average IR-sensitivity. The retinal-pathology group demonstrated impaired sensitivity to IR light. CONCLUSIONS: We showed that IR-light sensitivity does not significantly decrease with age despite a straylight increase. A reference level for the IR threshold was proposed. The application of IR-light microperimetry can be extended to the assessment of retinal pathology. TRANSLATIONAL RELEVANCE: IR-light microperimetry could be applied clinically to measure visual function.

BackgroundTo explore the role of foveal and parafoveal Müller cells in the morphology and pathophysiology of tractional macular disorders with a mathematical model of mechanical force transmission.MethodsIn this retrospective observational study, spectral-domain optical coherence tomography images of tractional lamellar macular holes and patients with myopic foveoschisis were reviewed and analysed with a mathematical model of force transmission. Parafoveal z-shaped Müller cells were modelled as a structure composed of three rigid rods, named R1, R2 and R3. The angle formed between the rods was referred to as θ . R1, R2 and R3 lengths as well as the variation of the angle θ were measured and correlated with best corrected visual acuity (BCVA).ResultsIn tractional lamellar macular holes, there was a significant reduction of the angle θ towards the foveal centre (p

PurposeThe purpose of this study was to investigate the characteristics of focal γ-zone parapapillary atrophy (focal γPPA) in patients with primary open-angle glaucoma (POAG) using spectral-domain optical coherence tomography (SD-OCT).MethodsThree groups of POAG eyes (n = 214) were defined according to the circumferential extent of Bruch's membrane (BM) within the β-zone PPA, as follows: (1) no γPPA (intact BM; n = 81), (2) conventional γPPA (γPPA involving the fovea-BM-opening axis; n = 89), and (3) focal γPPA (γPPA not involving the fovea-BM-opening axis; n = 44). Clinical and ocular characteristics, including age, axial length (AXL), and focal lamina cribrosa (LC) defects were compared among the three groups.ResultsThe focal γPPA group was significantly older (60.6 ± 11.0 years) and had shorter AXL (24.10 ± 1.34 mm) than those of the conventional γPPA group (46.2 ± 13.8 years and 26.53 ± 1.61 mm, respectively; P < 0.001). These values of the focal γPPA group were similar to those of the no γPPA group (23.73 ± 0.97 mm for AXL and 64.0 ± 13.0 years for age). The focal γPPA group had a significantly higher prevalence of focal LC defects than did the other two groups (70.5% [31/44] for the focal γPPA group versus 46.1% [41/89] for the conventional γPPA group versus 37.0% [30/81] for the no γPPA group; P = 0.002).ConclusionsFocal γPPA was differentiated from conventional γPPA by older age and shorter AXL. Further, focal γPPA was frequently accompanied by focal LC defects. Longitudinal studies elucidating whether focal LC defects and focal γPPA share common pathogenesis are warranted.

A recent theory posits that ocular drifts of fixational eye movements serve to reformat the visual input of natural images, so that the power of the input image is equalized across a range of spatial frequencies. This "spectral whitening" effect is postulated to improve the processing of high-spatial-frequency information and requires normal fixational eye movements. Given that people with macular disease exhibit abnormal fixational eye movements, do they also exhibit spectral whitening? To answer this question, we computed the power spectral density of movies of natural images translated in space and time according to the fixational eye movements (thus simulating the retinal input) of a group of observers with long-standing bilateral macular disease. Just as for people with normal vision, the power of the retinal input at low spatial frequencies was lower than that based on the 1/f2 relationship, demonstrating spectral whitening. However, the amount of whitening was much less for observers with macular disease when compared with age-matched controls with normal vision. A mediation analysis showed that the eccentricity of the preferred retinal locus adopted by these observers and the characteristics of ocular drifts are important factors limiting the amount of whitening. Finally, we did not find a normal aging effect on spectral whitening. Although these findings alone cannot form a causal link between macular disease and spectral properties of eye movements, they suggest novel potential means of modifying the characteristics of fixational eye movements, which may in turn improve functional vision for people with macular disease.

Most irreversible blindness results from retinal disease. To advance our understanding of the etiology of blinding diseases, we used single-cell RNA-sequencing (scRNA-seq) to analyze the transcriptomes of ~85,000 cells from the fovea and peripheral retina of seven adult human donors. Utilizing computational methods, we identified 58 cell types within 6 classes: photoreceptor, horizontal, bipolar, amacrine, retinal ganglion and non-neuronal cells. Nearly all types are shared between the two retinal regions, but there are notable differences in gene expression and proportions between foveal and peripheral cohorts of shared types. We then used the human retinal atlas to map expression of 636 genes implicated as causes of or risk factors for blinding diseases. Many are expressed in striking cell class-, type-, or region-specific patterns. Finally, we compared gene expression signatures of cell types between human and the cynomolgus macaque monkey, Macaca fascicularis. We show that over 90% of human types correspond transcriptomically to those previously identified in macaque, and that expression of disease-related genes is largely conserved between the two species. These results validate the use of the macaque for modeling blinding disease, and provide a foundation for investigating molecular mechanisms underlying visual processing.

PurposeTo assess the relationship between cone spacing and visual acuity in eyes with rod-cone degeneration (RCD) followed longitudinally.MethodsHigh-resolution images of the retina were obtained using adaptive optics scanning laser ophthalmoscopy from 13 eyes of nine RCD patients and 13 eyes of eight healthy subjects at two sessions separated by 10 or more months (mean 765 days, range 311-1935 days). Cone spacing Z-score measured as close as possible (average

Background/aimsTo better understand the pattern of degeneration progression in cases with choroideremia.MethodsA cohort of genotypically confirmed choroideremia cases who underwent optical coherence tomography (OCT) and fundus autofluorescence (FAF) imaging was studied. Using HEYEX review software, the foveal centre was marked on FAF images under guidance of corresponding OCT images, followed by application of an ETDRS grid. The boundaries of preserved autofluorescence (AF) were manually segmented in each individual ETDRS subfield. The regional distribution of preserved AF was assessed by comparing its area among the various subfields.ResultsA total of 168 eyes from 84 choroideremia cases were enrolled. There was a statistically significant difference in the amount of preserved AF area between inner subfields as determined by one-way analysis of variance (F (3,668)=9.997, p

PurposeMutations in six genes have been associated with achromatopsia (ACHM): CNGA3, CNGB3, PDE6H, PDE6C, GNAT2, and ATF6. ATF6 is the most recent gene to be identified, though thorough phenotyping of this genetic subtype is lacking. Here, we sought to test the hypothesis that ATF6-associated ACHM is a structurally distinct form of congenital ACHM.MethodsSeven genetically confirmed subjects from five nonconsanguineous families were recruited. Foveal hypoplasia and the integrity of the ellipsoid zone (EZ) band (a.k.a., IS/OS) were graded from optical coherence tomography (OCT) images. Images of the photoreceptor mosaic were acquired using confocal and nonconfocal split-detection adaptive optics scanning light ophthalmoscopy (AOSLO). Parafoveal cone and rod density values were calculated and compared to published normative data as well as data from two subjects harboring CNGA3 or CNGB3 mutations who were recruited for comparative purposes. Additionally, nonconfocal dark-field AOSLO images of the retinal pigment epithelium were obtained, with quantitative analysis performed in one subject with ATF6-ACHM.ResultsFoveal hypoplasia was observed in all subjects with ATF6 mutations. Absence of the EZ band within the foveal region (grade 3) or appearance of a hyporeflective zone (grade 4) was seen in all subjects with ATF6 using OCT. There was no evidence of remnant foveal cone structure using confocal AOSLO, although sporadic cone-like structures were seen in nonconfocal split-detection AOSLO. There was a lack of cone structure in the parafovea, in direct contrast to previous reports.ConclusionsOur data demonstrate a near absence of cone structure in subjects harboring ATF6 mutations. This implicates ATF6 as having a major role in cone development and suggests that at least a subset of subjects with ATF6-ACHM have markedly fewer cellular targets for cone-directed gene therapies than do subjects with CNGA3- or CNGB3-ACHM.

PURPOSE: This study measured and correlated degeneration of the junction between the inner and outer segments (IS/OS), the retinal pigment epithelium (RPE), and the choriocapillaris (CC) in Stargardt disease (STGD). DESIGN: Prospective cross-sectional study. METHODS: This study was conducted at the Casey Eye Institute. A total of 23 patients with STGD were enrolled and underwent optical coherence tomography angiography (OCTA). Scans were centered on the fovea. OCT slab projections and en face boundary maps were used to create masks to measure total IS/OS loss or RPE atrophy as well as regions of isolated IS/OS loss, isolated RPE atrophy, and matched IS/OS and RPE degeneration or intact IS/OS junction and RPE. CC vascular density (CCVD) was quantified from the CC angiogram. Outcomes included the area of loss, and the CCVD of degeneration in different areas was quantified and correlated. RESULTS: The total area of IS/OS loss was strongly correlated with the total area of RPE atrophy (r = 0.96; P < 0.0001) by a 1.6:1 ratio (r2 = 0.90). CCVD within regions of matched degeneration (85.6% ± 2.7%; P < 0.0001), isolated IS/OS junction loss (93.6% ± 1.0%; P = 0.0011), and isolated RPE atrophy (94.1% ± 1.1%; P = 0.0065) were all significantly lower than normal (99.0% ± 0.17%). There was a trend for CCVD within intact areas (97.6% ± 0.38%) to decline as the area diminished (r = 0.68). CONCLUSIONS: Photoreceptor and RPE degeneration exhibited a strong relationship wherein the IS/OS loss was 1.6-fold greater than that of RPE atrophy, supporting the theory that photoreceptor degeneration precedes RPE in STGD. Both the photoreceptors and the RPE degeneration contributed synergistically to CCVD attenuation, but extralesional CCVD also tended to be abnormal. The findings and techniques in this study may be of utility in developing endpoints for clinical trials.

High-acuity vision in primates, including humans, is mediated by a small central retinal region called the fovea. As more accessible organisms lack a fovea, its specialized function and its dysfunction in ocular diseases remain poorly understood. We used 165,000 single-cell RNA-seq profiles to generate comprehensive cellular taxonomies of macaque fovea and peripheral retina. More than 80% of >60 cell types match between the two regions but exhibit substantial differences in proportions and gene expression, some of which we relate to functional differences. Comparison of macaque retinal types with those of mice reveals that interneuron types are tightly conserved. In contrast, projection neuron types and programs diverge, despite exhibiting conserved transcription factor codes. Key macaque types are conserved in humans, allowing mapping of cell-type and region-specific expression of >190 genes associated with 7 human retinal diseases. Our work provides a framework for comparative single-cell analysis across tissue regions and species.

High-acuity vision in primates, including humans, is mediated by a small central retinal region called the fovea. As more accessible organisms lack a fovea, its specialized function and its dysfunction in ocular diseases remain poorly understood. We used 165,000 single-cell RNA-seq profiles to generate comprehensive cellular taxonomies of macaque fovea and peripheral retina. More than 80% of >60 cell types match between the two regions but exhibit substantial differences in proportions and gene expression, some of which we relate to functional differences. Comparison of macaque retinal types with those of mice reveals that interneuron types are tightly conserved. In contrast, projection neuron types and programs diverge, despite exhibiting conserved transcription factor codes. Key macaque types are conserved in humans, allowing mapping of cell-type and region-specific expression of >190 genes associated with 7 human retinal diseases. Our work provides a framework for comparative single-cell analysis across tissue regions and species.

PurposeTo describe the functional and anatomical outcomes of pars plana vitrectomy with epiretinal membrane and internal limiting membrane peel in eyes with and without ectopic inner foveal layers (EIFLs).MethodsIn this retrospective multicenter study, patients diagnosed with idiopathic epiretinal membranes who underwent pars plana vitrectomy with epiretinal membrane and internal limiting membrane peel were enrolled, with a minimum follow-up of 12 months. Preoperative and postoperative spectral domain optical coherence tomography scans were qualitatively and quantitatively evaluated. The association of the EIFL and other spectral domain optical coherence tomography parameters with preoperative and postoperative best-corrected visual acuity (BCVA) was analyzed.ResultsOne hundred eleven eyes of 107 patients were included. Preoperatively, the EIFLs were present in 56 of 111 eyes (50.4%). The presence of EIFL was significantly associated with lower preoperative and postoperative BCVA (P < 0.001). Ectopic inner foveal layer thickness was negatively correlated with preoperative BCVA (r = 0.58, P < 0.001). Postoperatively, the EIFL persisted in 51 of 56 eyes (91%) with Stage 3 and 4 epiretinal membranes. Ectopic inner foveal layer thickness decreased significantly after surgery (P < 0.001), but postoperative EIFL thinning had no direct effect on postoperative change in BCVA. At 12 months from surgery, EIFL thickness maintained a significant negative correlation with BCVA (r = 0.55, P < 0.001).ConclusionThe presence of EIFL should be considered a negative prognostic factor for postoperative anatomical and functional recovery.

We provide the first measures of foveal cone density as a function of axial length in living eyes and discuss the physical and visual implications of our findings. We used a new generation Adaptive Optics Scanning Laser Ophthalmoscope to image cones at and near the fovea in 28 eyes of 16 subjects. Cone density and other metrics were computed in units of visual angle and linear retinal units. The foveal cone mosaic in longer eyes is expanded at the fovea, but not in proportion to eye length. Despite retinal stretching (decrease in cones/mm2), myopes generally have a higher angular sampling density (increase in cones/deg2) in and around the fovea compared to emmetropes, offering the potential for better visual acuity. Reports of deficits in best-corrected foveal vision in myopes compared to emmetropes cannot be explained by increased spacing between photoreceptors caused by retinal stretching during myopic progression.

The human retina contains three classes of cone photoreceptors each sensitive to different portions of the visual spectrum: long (L), medium (M) and short (S) wavelengths. Color information is computed by downstream neurons that compare relative activity across the three cone types. How cone signals are combined at a cellular scale has been more difficult to resolve. This is especially true near the fovea, where spectrally-opponent neurons in the parvocellular pathway draw excitatory input from a single cone and thus even the smallest stimulus projected through natural optics will engage multiple color-signaling neurons. We used an adaptive optics microstimulator to target individual and pairs of cones with light. Consistent with prior work, we found that color percepts elicited from individual cones were predicted by their spectral sensitivity, although there was considerable variability even between cones within the same spectral class. The appearance of spots targeted at two cones were predicted by an average of their individual activations. However, two cones of the same subclass elicited percepts that were systematically more saturated than predicted by an average. Together, these observations suggest both spectral opponency and prior experience influence the appearance of small spots.

SignificanceLittle is known about how the preferred retinal locus (PRL) develops in patients with macular disease. We found that acuity is worse at the PRL than at other retinal locations around the scotoma, suggesting that the selection of the PRL location is unlikely to be based on optimizing acuity.PurposeFollowing the onset of bilateral macular disease, most patients adopt a retinal location outside the central scotoma, the PRL, as their new retinal location for visual tasks. Very little information is known about how the location of a PRL is chosen. In this study, we tested the hypothesis that the selection of the location for a PRL is based on optimizing visual acuity, which predicts that acuity is the best at the PRL, compared with other retinal locations.MethodsUsing a scanning laser ophthalmoscope that allowed us to position visual targets at precise retinal locations, we measured acuity psychophysically using a four-orientation Tumbling-E presented at the PRL and at multiple (ranged between 23 and 36 across observers) locations around the scotoma for five observers with bilateral macular disease.ResultsFor all five observers, the acuity at the PRL was never the best among all testing locations. Instead, acuities were better at 15 to 86% of the testing locations other than the PRL, with the best acuity being 17 to 58% better than that at the PRL. The locations with better acuities did not cluster around the PRL and did not necessarily lie at the same distance from the fovea or the PRL.ConclusionsOur finding that acuity is worse at the PRL than at other locations around the scotoma implies that the selection of the PRL location is unlikely to be based on optimizing acuity.

Psychophysical inferences about the neural mechanisms supporting spatial vision can be undermined by uncertainties introduced by optical aberrations and fixational eye movements, particularly in fovea where the neuronal grain of the visual system is fine. We examined the effect of these preneural factors on photopic spatial summation in the human fovea using a custom adaptive optics scanning light ophthalmoscope that provided control over optical aberrations and retinal stimulus motion. Consistent with previous results, Ricco's area of complete summation encompassed multiple photoreceptors when measured with ordinary amounts of ocular aberrations and retinal stimulus motion. When both factors were minimized experimentally, summation areas were essentially unchanged, suggesting that foveal spatial summation is limited by postreceptoral neural pooling. We compared our behavioral data to predictions generated with a physiologically-inspired front-end model of the visual system, and were able to capture the shape of the summation curves obtained with and without pre-retinal factors using a single postreceptoral summing filter of fixed spatial extent. Given our data and modeling, neurons in the magnocellular visual pathway, such as parasol ganglion cells, provide a candidate neural correlate of Ricco's area in the central fovea.

PurposeTo evaluate foveal function in patients with inherited retinal degenerations (IRD) by measuring visual acuity (VA) after correction of higher-order aberrations.MethodsAdaptive optics scanning laser ophthalmoscopy (AOSLO) was used to image cones in 4 healthy subjects and 15 patients with IRD. The 840-nm scanning laser delivered an "E" optotype to measure AOSLO-mediated VA (AOSLO-VA). Cone spacing was measured at the preferred retinal locus by two independent graders and the percentage of cones below the average density of 47 age-similar healthy subjects was computed. Cone spacing was correlated with best-corrected VA measured with the Early Treatment of Diabetic Retinopathy Study protocol (ETDRS-VA), AOSLO-VA, and foveal sensitivity.ResultsETDRS-VA significantly correlated with AOSLO-VA (ρ = 0.79, 95% confidence interval [CI] 0.5-0.9). Cone spacing correlated with AOSLO-VA (ρ = 0.54, 95% CI 0.02-0.7), and negatively correlated with ETDRS letters read (ρ = -0.64, 95% CI -0.8 to -0.2). AOSLO-VA remained ≥20/20 until cones decreased to 40.2% (CI 31.1-45.5) below normal. Similarly, ETDRS-VA remained ≥20/20 until cones were 42.0% (95% CI 36.5-46.1) below normal. Cone spacing z scores negatively correlated with foveal sensitivity (ρ = -0.79, 95% CI -0.9 to -0.4) and foveal sensitivity was ≥35 dB until cones were 43.1% (95% CI 39.3-46.6) below average.ConclusionsVA and foveal cone spacing were weakly correlated until cones were reduced by 40% to 43% below normal. The relationship suggests that VA is an insensitive measure of foveal cone survival; cone spacing may be a more sensitive measure of cone loss.

Crowding is the substantial interference of neighboring items on target identification. Crowding with letter stimuli has been studied primarily in the visual periphery, with conflicting results for foveal stimuli. While a cortical locus for peripheral crowding is well established (with a large spatial extent up to half of the target eccentricity), disentangling the contributing factors in the fovea is more challenging due to optical limitations. Here, we used adaptive optics (AO) to overcome ocular aberrations and employed high-resolution stimuli to precisely characterize foveal lateral interactions with high-contrast letters flanked by letters. Crowding was present, with a maximal edge-to-edge interference zone of 0.75-1.3 minutes at typical unflanked performance levels. In agreement with earlier foveal contour interaction studies, performance was non-monotonic, revealing a recovery effect with proximal flankers. Modeling revealed that the deleterious effects of flankers can be described by a single function across stimulus sizes when the degradation is expressed as a reduction in sensitivity (expressed in Z-score units). The recovery, however, did not follow this pattern, likely reflecting a separate mechanism. Additional analysis reconciles multiple results from the literature, including the observed scale invariance of center-to-center spacing, as well as the size independence of edge-to-edge spacing.

PurposeThe purpose of this study was to investigate the diurnal variation in peripapillary and macular vessel density (VD) measurements using optical coherence tomographic angiography (OCT-A) and its correlation to intraocular pressure (IOP) changes in glaucoma patients.MethodsProspective, observational cross-sectional study including 37 patients (74 eyes; age, 63.8±12.9 y) with open-angle glaucoma. OCT-A imaging and IOP measurements were performed at 08:00, 11:00, 14:00, and 16:00 timepoints on a single day. At each timepoint, 2 scan protocols were used to generate 3-dimensional en face OCT angiograms: 4.5×4.5-mm scan centered on the optic nerve head and 6×6-mm scan centered on the fovea. For each scan mode, the "radial peripapillary capillary" segment, composed of the vasculature of the retinal nerve fiber layer and ganglion cell layer, was calculated. Two trained readers reviewed OCT-A image quality. Only scans with signal strength intensity (SSI) higher than 46 and without image artifacts interfering with measurements were included. Variation in VD measurements assessed using analysis of variance (ANOVA) and the association between VD and IOP changes assessed using linear mixed modeling methods.ResultsThe optic nerve head and peripapillary VD measurements at 14:00 and 16:00 timepoints were greater than the measurements at 08:00 and 11:00 timepoints. The 14:00 and 16:00 VD measurements were statistically significantly greater (P

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Introduction: Fovea plana is indicative of an immature inner retina, yet its association with epimacular membrane (ERM) remains unexplored. This study aims to investigate the prevalence of fovea plana in the contralateral eye of patients diagnosed with ERM., Methods: A retrospective analysis was conducted on consecutive patients in a monocentric tertiary ophthalmic department between January and April 2021. The study included all patients referred for ERM, with dense optical coherence tomography (OCT) B-scans utilized to assess the incidence of fovea plana in the contralateral eye. Patients with bilateral ERM were excluded from the analysis., Results: Out of 181 patients, 26 exhibited fovea plana in the contralateral eye, resulting in an incidence rate of 14.3%. Demographic characteristics, OCT patterns, and indications for surgery did not differ significantly between patients with and without fovea plana., Discussion: The prevalence of fovea plana in patients with ERM did not exhibit a statistically significant increase compared to the reported incidence in patients undergoing preoperative cataract surgery., Conclusion: In our cohort, the incidence of fovea plana in patients with ERM was determined to be 14.3%., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To compare functional and anatomical outcomes between posterior drainage of residual fluid using a 41G cannula, fluid tolerance (residual subretinal fluid), and conventional complete drainage methods, including removal through peripheral retinal breaks, perfluorocarbon liquid, and posterior retinotomy., Methods: In this retrospective, multicenter study, we evaluated cases for visual acuity at 3 months of follow-up. Secondary outcomes included surgical success, postoperative metamorphopsia, shifts, full-thickness folds, optical coherence tomography parameters, and safety. Subgroup analyses were also conducted., Results: Visual acuity did not differ significantly between the three main groups. Subgroup analyses revealed worse visual acuity for posterior retinotomy (20/270 in Snellen conversion, P = 0.002), with significantly more Grade C proliferative vitreoretinopathy (40.0%, P = 0.003). Residual subretinal fluid tended to offer better secondary outcomes, without statistical significance except for postoperative epiretinal membrane (30.8%, P = 0.041). Subgroup analyses found significantly more shifts with PFCL (91.7%, P = 0.036). No cases of postoperative full-thickness folds or macular holes were observed with the 41G., Conclusion: Our study introduced the 41G technique, indicating favorable outcomes for fovea-off retinal detachments. Nevertheless, fluid tolerance appeared to be the best option, offering a cost-effective and faster method, with an optimal microstructural profile and visual acuity comparable with that of complete drainage techniques.

Abnormal early visual development can result in a constellation of neural and visual deficits collectively known as amblyopia. Among the many deficits, a common finding is that both saccadic and manual reaction times to targets presented to the amblyopic eye are substantially delayed when compared to the fellow eye or to normal eyes. Given the well-known deficits in contrast sensitivity in the amblyopic eye, a natural question is whether the prolonged reaction times are simply a consequence of reduced stimulus visibility. To address this question, in Experiment 1 we measure saccadic reaction times (RT) to perifoveal stimuli as a function of effective stimulus contrast (i.e., contrast scaled by the amblyopic eye's contrast threshold). We find that when sensory differences between the eyes are minimized, the asymptotic RTs of our anisometropic amblyopes were similar in the two eyes. However, our results suggest that some strabismic amblyopes have an irreducible delay at the asymptote. That is, even when the sensory differences of the stimulus were accounted for, these observers still had large interocular differences (on average, 77 ms) in saccadic reaction time. In Experiment 2, to assess the role of fixation on saccadic reaction time we compared reaction time with and without a foveal target (the "gap effect"). Our results suggest that, while removing the fixation target does indeed speed up reaction time in the amblyopic eye, the gap effect is similar in the two eyes. Therefore, the gap effect does not eliminate the irreducible delay in the amblyopic eye. Finally, in Experiment 3 we compared the interocular differences in saccadic and manual reaction times in the same observers. This allowed us to determine the relationship between the latencies in the two modalities. We found a strong correlation between the differences in saccadic and manual reaction times; however, the manual RT difference is about half that of saccadic RT, suggesting that there may be two separable effects on saccadic reaction time: (a) a central problem with directing actions to a target, related to disengagement of attention at the fovea, which results in delays in both saccadic and manual reaction times, and (b) a further delay in saccadic reaction times because of the motor refractory period from a previous saccade or microsaccade, made in an attempt to stabilize the amblyopic eye of strabismics.

PurposeTo describe the characteristics of MAK-related retinal degeneration using optical coherence tomography angiography (OCTA) and adaptive optics scanning laser ophthalmoscopy (AOSLO).DesignCross-sectional study.MethodsSix patients with rod-cone degeneration and disease-causing mutations in MAK were evaluated with visual acuity, spectral-domain OCT, confocal AOSLO, and OCTA. Foveal avascular zone (FAZ) area, vessel densities, and perfusion densities of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in the central macula in all 6 patients were compared with 5 normal subjects. Cone spacing was measured in 4 patients from AOSLO images and compared with 37 normal subjects.ResultsPatients ranged from 25 to 81 years of age (mean, 52 years). Visual acuity varied from 20/13 to 20/40+2, except in 1 patient with cystoid macular edema whose vision was 20/60- and 20/70+1. The SCP (P = .012) and DCP (P = .013) vessel density and perfusion density (P =.015 and .013, respectively) were significantly lower in patients compared to normal subjects in the parafoveal region 1.0-3.0 mm from the fovea, but were similar to normal subjects within 1.0 mm of the fovea. The FAZ area was not significantly different from normal (all P ≥ .24). Cone spacing was normal at almost all locations in 2 patients with early disease and increased in 2 patients with advanced disease.ConclusionsAlthough retinal vascular densities are reduced and cone spacing is increased in advanced disease, central foveal structure is maintained until late stages of disease, which may contribute to preservation of foveal vision in eyes with MAK-related retinal degeneration.

PurposeMigraine, particularly with aura, has been associated with ocular and systemic ischemic complications, but there are limited data on the ocular vasculature in migraine. We used optical coherence tomography angiography (OCTA) to assess perfusion of the macula and optic nerve in migraine patients, with (MA) and without (MO) aura, compared to healthy controls (HC).MethodsWe recruited 15 MA (mean age 42 years), 12 MO (mean age 46 years), and 22 HC (mean age 39 years) participants from neurology and neuro-ophthalmology clinics. Participants underwent optical coherence tomography and 3 × 3 mm OCTA of the macula and optic nerve. Foveal avascular zone area was automatically measured using AngioVue software, and vessel density was calculated as blood vessel length divided by scan area (mm-1) after skeletonization of OCTA images.ResultsOn macular OCTA, MA participants had an enlarged foveal avascular zone area when compared with HC (0.300 ± 0.019 vs. 0.220 ± 0.066 mm2, P = 0.006). In addition, superficial foveal vessel density was decreased in MA participants when compared with MO participants (7.8 ± 0.31 vs. 9.3 ± 0.44, P = 0.04) and HC (7.8 ± 0.31 vs. 9.4 ± 0.21 mm-1, P = 0.002). On optic nerve OCTA, the MA participants had reduced superior peripapillary vessel density when compared with the MO participants (12.0 ± 0.45 vs. 14.0 ± 0.38 mm-1, P = 0.031) and HC (12.0 ± 0.45 vs. 14.1 ± 0.53 mm-1, P = 0.035). There were no significant differences between the MO and HC groups.ConclusionsMigraine with, but not without, aura was associated with foveal and peripapillary vascular decrements, which may possibly mediate increased risk of ocular and systemic vascular complications in these patients. OCTA could potentially be useful as a biomarker for migraine with aura.

Copyright of Arquivos Brasileiros de Oftalmologia is the property of Arquivos Brasileiros de Oftalmologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

PurposeHigh-quality optical coherence tomography (OCT) macular scans make it possible to distinguish a range of normal and diseased states by characterising foveal pit shape. Existing mathematical models lack the flexibility to capture all known pit variations and thus characterise the pit with limited accuracy. This study aimed to develop a new model that provides a more robust characterisation of individual foveal pit variations.MethodsA Sloped Piecemeal Gaussian (SPG) model, consisting of a linear combination of a tilted line and a piecemeal Gaussian function (two halves of a Gaussian connected by a separate straight line), was developed to fit retinal thickness data with the flexibility to characterise different degrees of pit asymmetry and pit bottom flatness. It fitted the raw pit data between the two rims of the fovea to improve accuracy. The model was tested on 3488 macular scans from both eyes of 581 young adults (376 myopes and 206 non-myopes, mean (S.D.) age 21.9 (1.4) years). Estimates for retinal thickness, wall height and slope, pit depth and width were derived from the best-fitting model curve. Ten variations of Gaussian and Difference of Gaussian models were fitted to the same scans and compared with the SPG model for goodness of fit (by Root mean square error, RMSE), model complexity (by the Bayesian Information Criteria) and model fidelity.ResultsThe SPG model produced excellent goodness of fit (mean RMSE = 4.25 and 3.89 μm; 95% CI: 4.20, 4.30 and 3.86, 3.93 for fitting horizontal and vertical profiles respectively). The SPG model showed pit asymmetry, with average nasal walls 17.6 (11.6) μm higher and 0.96 (0.61)° steeper than temporal walls and average superior walls 7.0 (12.2) μm higher and 0.41 (0.65)° steeper than the inferior walls. The SPG model also revealed a continuum of human foveal shapes, from round bottoms to extended flat bottoms (up to 563 μm). 49.1% of foveal profiles were best fitted with a flat bottom >30 μm wide. Compared with the other tested models, the SPG was the preferred model overall based on the Bayesian Information Criteria.ConclusionsThe SPG is a new parsimonious mathematical model that improves upon other models by accounting for wall asymmetry and flat pit bottoms, providing an excellent fit and more faithful characterisation of typical foveal pit shapes and their known variations. This new model may be helpful in distinguishing normal foveal shape variations by refractive status as well by other characteristics such as sex, ethnicity and age.

Blur from defocus can be both useful and detrimental for visual perception: It can be useful as a source of depth information and detrimental because it degrades image quality. We examined these aspects of blur by measuring the natural statistics of defocus blur across the visual field. Participants wore an eye-and-scene tracker that measured gaze direction, pupil diameter, and scene distances as they performed everyday tasks. We found that blur magnitude increases with increasing eccentricity. There is a vertical gradient in the distances that generate defocus blur: Blur below the fovea is generally due to scene points nearer than fixation; blur above the fovea is mostly due to points farther than fixation. There is no systematic horizontal gradient. Large blurs are generally caused by points farther rather than nearer than fixation. Consistent with the statistics, participants in a perceptual experiment perceived vertical blur gradients as slanted top-back whereas horizontal gradients were perceived equally as left-back and right-back. The tendency for people to see sharp as near and blurred as far is also consistent with the observed statistics. We calculated how many observations will be perceived as unsharp and found that perceptible blur is rare. Finally, we found that eye shape in ground-dwelling animals conforms to that required to put likely distances in best focus.

Purpose: To understand subfoveal neurosensory detachment flattening and observe (SNF-Ob) strategy and its relationship with visual acuity in the management of centre-involved diabetic macular oedema (Ci-DMO)., Methods: This was a multicentric retrospective observational study. We reviewed data of 188 eyes of 130 patients who presented with Ci-DMO with subfoveal neurosensory detachment (NSD) and treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents or steroids. The primary outcome was best corrected visual acuity (BCVA) measured at the time of the first subfoveal neurosensory detachment flattening (SNF) and at the end of follow-up., Results: Eyes that achieved 20/50 (LogMAR = 0.40) or better at first SNF had mean LogMAR BCVA 0.38 ± 0.21, 0.24 ± 0.11 and 0.21 ± 0.15 at baseline, at the time of first SNF, and at the end of the last follow-up respectively. Mean LogMAR BCVA significantly improved from baseline to first SNF (p < 0.0001; 95% CI 0.115-0.183) and at the end of the last follow-up (p < 0.0001; 95% CI 0.126-0.213) with a change of Early Treatment Diabetic Retinopathy Study (ETDRS) 10 letters. There was no significant difference in improvement in BCVA from the first SNF and at the end of the last follow-up (p = 0.0781; 95% CI -0.002 to 0.046)., Conclusions: Eyes presenting with Ci-DMO and subfoveal NSD are unlikely to improve at SNF with BCVA > 20/50 (LogMAR = 0.40). Further evidence is needed before the combination of good BCVA and SNF may be considered as endpoint of pharmacological therapy for DMO., Competing Interests: Competing interests: AS: consultant: for Novartis, Allergan, Bayer, Lupin, Intas, Biogen. TW: None. CDR- consultant: 4DMT, Adverum, Allergan, Annexon, Apellis, Aviceda, Bausch and Lomb, Boehringer-Ingelheim, Clearside, Eyepoint, Genentech/Roche, Iveric, Janssen, Kodiak, Merck, NGM, Novartis, Ocugen, Opthea, Regenxbio, Stealth, Thea, Zeiss and receives research support from 4DMT, Adverum, Allergan, Annexon, Apellis, Eyepoint, Genentech/Roche, Iveric, Janssen, Kodiak, NGM, Novartis, Ocugen, Opthea, Regenxbio, Regeneron. CMGC: Novartis, Bayer, Roche, Boehringer-Ingelheim, Topcon, Zeiss and Chui Ming Gemmy Cheung is a member of the Eye editorial board. AL reports other from Allergan, other from Novartis, other from Roche, other from Notal Vision, other from Forsightslabs, other from Beyeonics, other from Bayer Health Care. DZ: consultant for Novartis, Abbvie, Bayer and Roche. DG: None. AH: None. SO: consultant for Novartis, Allergan, Bayer, Bauch & Lomb. HBÖ: None. NP: None. NK: None. BDK: CLINICAL RESEARCH: Alcon, Alimera, Allegro, Allergan, Apellis, Clearside, Genentech, GSK, Ionis, jCyte, Novartis, Regeneron, ThromboGenics; consultant: Alimera, Allegro, Allergan, Cell Care, Dose, Eyedaptic, Galimedix, Genentech, Glaukos, Interface Biologics, jCyte, Novartis, Ophthotech, Regeneron, Revana, Theravance Biopharma. FB: consultant: Allergan, Bayer, Boehringer- Ingelheim, FidiaSooft, Hofmann La Roche, Novartis, NTC Pharma, Sifi, Thrombogenics, Zeiss. GQ: consultant: Alimera Sciences, Allegro, Allergan Inc, Amgen, Bayer Shering-Pharma, Baush & Lomb, Boehringer-Ingelheim, CenterVue, Heidelberg, KBH, LEH Pharma, Lumithera, Nevacar, Novartis, Roche, Sandoz, Sifi, Sooft-Fidia, Topcon, Thea, Zeiss., (© 2024. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

We studied which retinal area controls short-term axial eye shortening when human subjects were exposed to + 3.0D monocular defocus. A custom-built infrared eye tracker recorded the point of fixation while subjects watched a movie at a 2 m distance. The eye tracker software accessed each individual movie frame in real-time and covered the points of fixation in the movie with a uniform grey patch. Four patches were programmed: (1) foveal patch (0-3 degrees), (2) annular patch (3-9 deg), (3) foveal patch (0-3 deg) combined with an annular patch (6-9 deg), and (4) full-field patch where only 6-10 deg were exposed to the defocus. Axial eye shortening was elicited similarly with full-field positive defocus and with the foveal patch, indicating that the fovea made only a minor contribution (-11 ± 12 μm vs. -14 ± 17 μm, respectively, n.s.). In contrast, patching a 3-9 degrees annular area or fovea together with an annular area of 6-9 degrees, completely suppressed the effect when compared with full-field defocus (+ 3 ± 1 μm or -2 ± 13 μm vs. -11 ± 12 μm, respectively, p < 0.001). Finally, we found that the near-peripheral retina (6-10 degrees) is a "sweet spot" for positive defocus detection and alone can regulate eye growth control mechanism, and perhaps long-term refractive development (-9 ± 8 μm vs. full-field: -11 ± 12 μm, n.s.)., (© 2024. The Author(s).)