IMI-The Dynamic Choroid: New Insights, Challenges, and Potential Significance for Human Myopia.

The choroid is the richly vascular layer of the eye located between the sclera and Bruch's membrane. Early studies in animals, as well as more recent studies in humans, have demonstrated that the choroid is a dynamic, multifunctional structure, with its thickness directly and indirectly subject to modulation by a variety of physiologic and visual stimuli. In this review, the anatomy and function of the choroid are summarized and links between the choroid, eye growth regulation, and myopia, as demonstrated in animal models, discussed. Methods for quantifying choroidal thickness in the human eye and associated challenges are described, the literature examining choroidal changes in response to various visual stimuli and refractive error-related differences are summarized, and the potential implications of the latter for myopia are considered. This review also allowed for the reexamination of the hypothesis that short-term changes in choroidal thickness induced by pharmacologic, optical, or environmental stimuli are predictive of future long-term changes in axial elongation, and the speculation that short-term choroidal thickening can be used as a biomarker of treatment efficacy for myopia control therapies, with the general conclusion that current evidence is not sufficient.

Lowering Intraocular Pressure: A Potential Approach for Controlling High Myopia Progression.

High myopia is among the most common causes of vision impairment, and it is mainly characterized by abnormal elongation of the axial length, leading to pathologic changes in the ocular structures. Owing to the close relationship between high myopia and glaucoma, the association between intraocular pressure (IOP) and high myopia progression has garnered attention. However, whether lowering IOP can retard the progression of high myopia is unclear. On reviewing previous studies, we suggest that lowering IOP plays a role in progressive axial length elongation in high myopia, particularly in pathologic myopia, wherein the sclera is more remodeled. Based on the responses of the ocular layers, we further proposed the potential mechanisms. For the sclera, lowering the IOP could inhibit the activation of scleral fibroblasts and then reduce scleral remodeling, and a decrease in the scleral distending force would retard the ocular expansion like a balloon. For the choroid, lowering IOP results in an increase in choroidal blood perfusion, thereby reducing scleral hypoxia and slowing down scleral remodeling. The final effect of these pathways is slowing axial elongation and the development of scleral staphyloma. Further animal and clinical studies regarding high myopia with varied degree of IOP and the changes of choroid and sclera during IOP fluctuation in high myopia are needed to verify the role of IOP in the pathogenesis and progression of high myopia. It is hoped that this may lead to the development of a prospective treatment option to prevent and control high myopia progression.

Morphological changes in amblyopic eyes in choriocapillaris and Sattler's layer in comparison to healthy eyes, and in retinal nerve fiber layer in comparison to fellow eyes through quantification of mean reflectivity: A pilot study.

PURPOSE: Establishing the reliability of a new method to check the mean retinal and choroidal reflectivity and using it to find retinal and choroid changes in amblyopia. METHODS: Design: Retrospective case-control. Population: 28 subjects of which 10 were healthy controls (20 eyes): 8 with refractive errors, 1 with strabismus, and 1 with both. 18 patients with unilateral amblyopia included: 7 anisometropic, 6 isoametropic, 1 strabismic, and 4 combined. Mean participants' age: 13.77 years ± 10.28. Observation procedures: SD-OCT and ImageJ. Main outcome measure: mean reflectivity of retinal and choroid layers. Amblyopic, fellow, and healthy eyes were compared. RESULTS: The method of measuring reflectivity is good to excellent reliability for all regions of interest except the fourth. The mean reflectivity of the choriocapillaris and Sattler's layer in amblyopic eyes were significantly lower than in healthy eyes (p = 0.003 and p = 0.008 respectively). The RNFL reflectivity was lower than that of fellow eyes (p = 0.025). Post-hoc pairwise comparisons showed statistically significant differences between amblyopic and healthy eyes for choriocapillaris (p = 0.018) and Sattler's (p = 0.035), and between amblyopic and fellow eyes for RNFL (p = 0.039). CONCLUSION: A decrease in reflectivity of the choriocapillaris and Sattler's in amblyopic compared to healthy eyes, and a decrease in reflectivity of the RNFL in the amblyopic compared to fellow eyes, indicate that the pathophysiology is partly peripheral and might be bilateral.

Correlation of choriocapillaris hemodynamic data from dynamic indocyanine green and optical coherence tomography angiography.

To investigate the correlation between posterior pole choroidal blood flow evaluated with digital subtraction indocyanine green angiography and enface optical coherence tomography angiography (OCTA). Imaging in animal study. The anatomy of 2 cynomogulus monkeys was studied. Each monkey was given a 0.75 mg/kg injection of indocyanine green in the saphenous vein. The dynamic angiographic filling sequence was recorded at 15 frames per second using the Heidelberg Spectralis. After image registration, sequential frame subtraction was used to image the dye front moving through the choroid. The OCTA was obtained by frame averaging nine separate choriocapillaris slab flow images obtained from the Zeiss Plex Elite 9000. Posterior pole choriocapillaris filling pattern in relation to the choriocapillaris anatomy as imaged by OCTA. In the posterior pole, the choriocapillaris fills in the pattern of discrete units with variable sizes and shapes. The cycle of dye filling begins in the peripapillary area and progresses toward the periphery in a wavelike manner. This filling pattern repeats in a cyclical manner, consistent with the cardiac cycle. OCTA shows a uniform mesh of vessels. While OCTA shows a uniform meshwork appearance of the choriocapillaris, the dynamic dye angiography suggests an irregular configuration of functional units partitioned by pressure gradients as opposed to structural boundaries. Disturbance of local perfusion pressure within choroidal vasculature may result in abnormal flow patterns, which could be evaluated in the clinic using commercially available equipment.

Drusen and pigment abnormality predict the development of neovascular age-related macular degeneration in Japanese patients.

Drusen are known to be the important hallmark to predict the development of age-related macular degeneration (AMD). The prevalence of drusen is lower in Asians compared with Caucasians so that the role of signs constituting early AMD is not well established in Asian populations as in Western countries. In this study, we retrospectively investigated clinical characteristics and 5-year incidence of neovascular AMD (nAMD) in the fellow eye of unilateral nAMD patients. Of 296 consecutive unilateral nAMD patients who had been followed up more than 5 years, 170 typical AMD, 119 polypoidal choroidal vasculopathy, and 7 retinal angiomatous proliferation were included. To examine factors associated with nAMD occurrence in the fellow eye, drusen and pigmentary abnormality in the fellow eye were classified into 4 categories; Category 1: no or small drusen < 63 µm (37.2%), Category 2: 63-125 µm medium drusen or pigmentary abnormality (22.2%), Category 3: large drusen > 125 µm (25.0%), Category P: pachydrusen (15.5%). The mean sub-foveal choroidal thickness (SFCT) was Category 1: 276 µm, Category 2: 308 µm, Category 3: 246 µm, and Category P: 302 µm, respectively. Of note, SFCT in Category 2 and Category P was significantly larger than those of Category 3. Finally, the 5-year incidence of nAMD in the fellow eye was 32/296 (10.8%); Category 1: 0/110 (0%), Category 2: 12/66 (18.2%), Category 3: 20/74 (27.0%), and Category P: 0/46 (0%). Thus, signs of intermediate AMD (large drusen) as well as those of early AMD, especially the pigmentary abnormality, may contribute to development of bilateral nAMD in Japanese patients.

Correlation between choroidal structure and smoking in eyes with central serous chorioretinopathy.

PURPOSE: A smoking habit can cause various health problems encompassing retinal diseases including central serous chorioretinopathy (CSC). The aim of the current study was to investigate the effect of smoking on the choroidal structure in patients with CSC. METHODS: The choroidal vascular index (CVI) was calculated using the binarized OCT images. Baseline parameters (age, refractive error [SE], subfoveal choroidal thickness [SFCT] and CVI) were compared between smokers and non-smokers using Wilcoxon rank sum test. Moreover, the associations between SFCT and the baseline parameters were analyzed using a multivariate linear regression followed by the AICc model selection. RESULTS: Among 75 CSC patients, 45 patients were smokers and 30 patients were non-smokers. No significant differences in age and SE were seen between the smoking group and the non-smoking group. A significant difference in the SFCT was seen between two groups (382.0 ± 68.2 µm in the smoking group vs. 339.3 ± 52.3 µm in the non-smoking group, p = 0.0038), while no significant difference was observed in the CVI (p = 0.32). The optimal model for SFCT included the variables of age, SE and past history of smoking among the baseline parameters. Additionally, increased pack years was associated with increased SFCT. CONCLUSION: Cigarette smoking was associated with an increased SFCT in patients with CSC. Thicker choroid in smoking CSC patients may be an important modulator of the disease.

Physiological changes in retinal layers thicknesses measured with swept source optical coherence tomography.

PURPOSE: To evaluate the physiological changes related with age of all retinal layers thickness measurements in macular and peripapillary areas in healthy eyes. METHODS: Wide protocol scan (with a field of view of 12x9 cm) from Triton SS-OCT instrument (Topcon Corporation, Japan) was performed 463 heathy eyes from 463 healthy controls. This protocol allows to measure the thickness of the following layers: Retina, Retinal nerve fiber layer (RNFL), Ganglion cell layer (GCL +), GCL++ and choroid. In those layers, mean thickness was compared in four groups of ages: Group 1 (71 healthy subjects aged between 20 and 34 years); Group 2 (65 individuals aged 35-49 years), Group 3 (230 healthy controls aged 50-64 years) and Group 4 (97 healthy subjects aged 65-79 years). RESULTS: The most significant thinning of all retinal layers occurs particularly in the transition from group 2 to group 3, especially in temporal superior quadrant at RNFL, GCL++ and retinal layers (p≤0.001), and temporal superior, temporal inferior, and temporal half in choroid layer (p<0.001). Curiously group 2 when compared with group 1 presents a significant thickening of RNFL in temporal superior quadrant (p = 0.001), inferior (p<0.001) and temporal (p = 0.001) halves, and also in nasal half in choroid layer (p = 0.001). CONCLUSIONS: Excepting the RNFL, which shows a thickening until the third decade of life, the rest of the layers seem to have a physiological progressive thinning.

Repeatability of binarization thresholding methods for optical coherence tomography angiography image quantification.

Binarization is a critical step in analysis of retinal optical coherence tomography angiography (OCTA) images, but the repeatability of metrics produced from various binarization methods has not been fully assessed. This study set out to examine the repeatability of OCTA quantification metrics produced using different binarization thresholding methods, all of which have been applied in previous studies, across multiple devices and plexuses. Successive 3 × 3 mm foveal OCTA images of 13 healthy eyes were obtained on three different devices. For each image, contrast adjustments, 3 image processing techniques (linear registration, histogram normalization, and contrast-limited adaptive histogram equalization), and 11 binarization thresholding methods were independently applied. Vessel area density (VAD) and vessel length were calculated for retinal vascular images. Choriocapillaris (CC) images were quantified for VAD and flow deficit metrics. Repeatability, measured using the intra-class correlation coefficient, was inconsistent and generally not high (ICC < 0.8) across binarization thresholds, devices, and plexuses. In retinal vascular images, local thresholds tended to incorrectly binarize the foveal avascular zone as white (i.e., wrongly indicating flow). No image processing technique analyzed consistently resulted in highly repeatable metrics. Across contrast changes, retinal vascular images showed the lowest repeatability and CC images showed the highest.

Are choriocapillaris flow void features robust to diurnal variations? A swept-source optical coherence tomography angiography (OCTA) study.

We evaluated the impact of diurnal variation on choroidal and retinal microvasculature and structural measurements using a swept-source optical coherence tomography angiography machine (SS-OCTA; PLEX Elite 9,000, Carl Zeiss Meditec, Inc., Dublin, USA). Fourteen participants who were without ocular diseases underwent SS-OCTA imaging using 3 × 3-mm2 macular scan pattern on two separate days at five time points. Choriocapillaris flow voids were generated to determine its density (percentage), size (µm) and numbers. Perfusion densities of the large superficial vessels, as well as capillaries on superficial and deep vascular plexuses were generated from retinal angiograms. Subfoveal choroidal and retinal thicknesses were manually measured. Repeated-measures ANOVA was used to investigate the impact of diurnal variation on choroidal and retinal measurements. There was no observable diurnal pattern for any of the flow void features, in terms of the density, size and numbers. There was a significant diurnal pattern observed in the choroidal thickness, where it decreased progressively during the day (P < 0.005). As opposed to sub-foveal choroidal thickness, there does not appear to be significant diurnal variation in choriocapillaris flow voids in normal individuals. This suggests that alterations of choriocapillaris flow deficit seen in pathological eyes will not be confounded by the diurnal fluctuation.

Effect of weight loss on the retinochoroidal structural alterations among patients with exogenous obesity.

PURPOSE: To evaluate the changes in the retinochoroidal vasculature in patients with exogenous obesity using swept-source optical coherence tomography (SS-OCT) and OCT angiography (OCTA). METHODS: In this prospective study, 60 patients diagnosed with obesity (47 males) (mean age: 46.47±10.9 years) were included, of which 30 patients underwent bariatric surgery (Group A), and 30 patients underwent conservative management (exercise/diet) (Group B). Parameters including choroidal thickness (CT), choroidal vascularity index (CVI) and retinal capillary density index (CDI) and arteriovenous ratio (AVR) were measured at the baseline and three months follow up. 30 eyes (30 age and gender-matched) of normal participants were included for comparison. RESULTS: Baseline CT was lower in 60 participants with obesity compared to controls. Compared with normal subjects, subjects with obesity had higher mean CVI (0.66±0.02 versus 0.63±0.04; p<0.01), smaller FAZ area (0.26±0.07 versus 0.45±0.32; p<0.01), higher CDI (superficial plexus: 0.7±0.04 versus 0.68±0.06; p = 0.04, deep plexus: 0.38±0.02 versus 0.35±0.06; p = 0.01), and lower AVR (0.68±0.05 versus 0.70±0.03 versus; p<0.01). At 3-month after intervention, CT showed a significant increase in participants from Group A (329.27±79µm; p<0.01) but not in Group B from baseline. No significant change was noted in CVI or CDI at 3-month in either group compared to baseline. AVR significantly increased in Group B (p = 0.03). CONCLUSION: Subclinical changes in retinochoroidal vasculature occurs in participants with exogenous obesity compared to healthy subjects. Surgical intervention (bariatric surgery) may have a favorable outcome on the choroidal thickness in these patients.

[Anatomy of the retina]. / Anatomie de la rétine.

The neuroretina is a functional unit of the central nervous system that converts a light signal into a nerve impulse. Of neuroectodermal origin, derived from the diencephalon, the neuroretina is a layered tissue composed of six types of neuronal cells (two types of photoreceptors: cones and rods, horizontal, bipolar, amacrine and ganglion cells) and three types of glial cells (Müller glial cells, astrocytes and microglial cells). The neuroretina lays on the retinal pigmentary epithelium, that together form the retina. The existence of the internal and external blood-retinal barriers and intra-retinal junctions reflects the fineness of regulation of the retinal exchanges with the circulation and within the retina itself. The central zone of the human retina, which is highly specialized for visual acuity, has anatomical specificities. Recent imaging methods make it possible now to enrich our knowledge of the anatomical and functional characteristics of the retina, which are still imperfectly described.

TITLE: Anatomie de la rétine. ABSTRACT: La neurorétine est une unité fonctionnelle du système nerveux central assurant la conversion d'un signal lumineux en un influx nerveux. D'origine neuroectodermique, dérivée du diencéphale, la neurorétine est un tissu stratifié, composé de six types de cellules neuronales (deux types de photorécepteurs : les cônes et les bâtonnets ; les cellules horizontales, bipolaires, amacrines et ganglionnaires) et de trois types de cellules gliales (les cellules gliales de Müller, les astrocytes et les cellules microgliales). La neurorétine repose sur l'épithélium pigmentaire rétinien, l'ensemble constituant la rétine. L'existence des barrières hémato-rétiniennes interne et externe et des jonctions intra-rétiniennes rend compte de la finesse de la régulation des échanges de la rétine avec la circulation et au sein de la rétine elle-même. La zone centrale de la rétine humaine, la macula, zone hautement spécialisée pour assurer l'acuité visuelle, présente des spécificités anatomiques. Les méthodes d'imagerie récentes permettent d'enrichir nos connaissances sur les caractéristiques anatomiques et fonctionnelles de la rétine, qui restent encore imparfaitement décrites.

Astigmatic Defocus Leads to Short-Term Changes in Human Choroidal Thickness.

Purpose: To examine the choroidal thickness (ChT) response to short-term with-the-rule (WTR) and against-the-rule (ATR) simple myopic astigmatic defocus, with the response to spherical myopic defocus and clear vision used as control conditions. Methods: The left eye of 18 healthy adults aged 28 ± 6 years was exposed to clear vision, +3 D spherical myopic defocus, +3 D × 180 WTR, or +3 D × 90 ATR astigmatic defocus for 60 minutes, over four randomly ordered visits, while their right eye was optimally corrected. The macular ChT was measured with optical coherence tomography along the vertical and horizontal meridians before and after 20, 40, and 60 minutes of defocus. Results: After 60 minutes of defocus, ChT increased by +8 ± 5 µm (P < 0.001) with spherical myopic defocus, but varied with simple myopic astigmatic defocus, depending on the axis of astigmatism (P < 0.001), increasing by +5 ± 6 µm (P = 0.037) with WTR and decreasing by -4 ± 5 µm (P = 0.011) with ATR astigmatic defocus. These changes were similar across the vertical and horizontal meridians (P = 0.22). The ChT changes were greater than the change during the clear vision control condition (-1 ± 4 µm) for WTR (+5 ± 5 µm, P = 0.002) but not ATR (-4 ± 6 µm, P = 0.09) astigmatic defocus. Conclusions: These results provide insights into the human ChT response to short-term astigmatic defocus and highlight a potential difference in the myopiagenic signal associated with the orientation of astigmatic blur.

Comparison of one-year results of photodynamic therapy combined with ranibizumab or aflibercept for treating polypoidal choroidal vasculopathy.

PURPOSE: To compare the 1-year visual outcomes and anatomical responses of patients who received photodynamic therapy (PDT) combined with intravitreal ranibizumab (IVR) injections with those of patients who received PDT combined with intravitreal aflibercept (IVA) injections for treating polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively studied all treatment-naïve patients with PCV who received PDT combined with either IVR or IVA. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), the number of additional injections, and the presence of polypoidal lesions, as indicated by indocyanine green angiography (ICGA), during 1 year were evaluated. RESULTS: Forty-four eyes were assessed at the 1-year follow-up examination. Of these, 23 were treated with PDT combined with IVR (PDT/IVR group), and 21 were treated with PDT combined with IVA (PDT/IVA group). In both groups, BCVA was shown to be significantly improved 1 year after the initial treatment. CMT and CCT were also significantly decreased after 1 year. There were no significant differences in the changes in BCVA or CMT between the two groups. However, the change in CCT in the PDT/IVA group was significantly larger than that of the PDT/IVR group (P < 0.001). The mean number of additional injections was 0.78 ± 0.21 in the PDT/IVR group and 0.57 ± 0.21 in the PDT/IVA group with no significant difference between the two groups (P = 0.45). The polyp regression rate at 12 months was 78.2% in the PDT/IVR group and 78.9% in the PDT/IVA group with no significant difference between the two groups. CONCLUSIONS: PDT combined with either IVR or IVA was well tolerated and appeared to improve both vision and anatomy in patients with PCV. PDT/IVA may have a more pronounced effect on macular choroidal thickness at 1-year follow-up.

Exosomal MiRNA Transfer between Retinal Microglia and RPE.

The retinal pigment epithelium (RPE), the outermost layer of the retina, provides essential support to both the neural retina and choroid. Additionally, the RPE is highly active in modulating functions of immune cells such as microglia, which migrate to the subretinal compartment during aging and age-related degeneration. Recently, studies have highlighted the important roles of microRNA (miRNA) in the coordination of general tissue maintenance as well as in chronic inflammatory conditions. In this study, we analyzed the miRNA profiles in extracellular vesicles (EVs) released by the RPE, and identified and validated miRNA species whose expression levels showed age-dependent changes in the EVs. Using co-culture of RPE and retinal microglia, we further demonstrated that miR-21 was transferred between the two types of cells, and the increased miR-21 in microglia influenced the expression of genes downstream of the p53 pathway. These findings suggest that exosome-mediated miRNA transfer is a signaling mechanism that contributes to the regulation of microglia function in the aging retina.

Short-Term Effects of Dark Chocolate on Retinal and Choriocapillaris Perfusion in Young, Healthy Subjects Using Optical Coherence Tomography Angiography.

(1) Aim: Contrasting results have been published on the effect of dark chocolate on visual function. The aim of this study was to evaluate retinal and choriocapillaris perfusion, using optical coherence tomography angiography (OCT-A), and visual function in healthy subjects following dark chocolate ingestion. (2) Methods: This prospective randomized study was carried out on 18 healthy young subjects at the St. Andrea Hospital, Sapienza, University of Rome. Visual acuity assessment and a complete ophthalmologic examination were carried out at baseline. In session one, each subject was randomized to eat either a 100 g dark chocolate bar or a 100 g white chocolate bar. In session two, the opposite chocolate was given to each participant. OCT-A and best corrected visual acuity (BCVA) were performed before the chocolate was eaten and repeated 1, 2, and 3 h after that. Retinal vessel density and choriocapillaris flow area were assessed. (3) Results: 18 patients with a mean (SD) age of 26.3 (1.5) years were included. No significant differences between dark or white chocolate were found when evaluating foveal density (%), whole density (%), choriocapillaris flow area, and BCVA. (4) Conclusions: Dark chocolate did not result in significant changes in retinal perfusion and choriocapillaris flow area. However, given the results of other studies showing the positive effects of flavonoids on visual function, further studies are warranted using pure chocolate without other components such as caffeine that can potentially affect results. Furthermore, we cannot rule out the possible benefits of higher doses of flavonoids in dietary supplementation over a more extended period and in a larger patient population.

Choroidal thickness estimation from colour fundus photographs by adaptive binarisation and deep learning, according to central serous chorioretinopathy status.

This study was performed to estimate choroidal thickness by fundus photography, based on image processing and deep learning. Colour fundus photography and central choroidal thickness examinations were performed in 200 normal eyes and 200 eyes with central serous chorioretinopathy (CSC). Choroidal thickness under the fovea was measured using optical coherence tomography images. The adaptive binarisation method was used to delineate choroidal vessels within colour fundus photographs. Correlation coefficients were calculated between the choroidal vascular density (defined as the choroidal vasculature appearance index of the binarisation image) and choroidal thickness. The correlations between choroidal vasculature appearance index and choroidal thickness were -0.60 for normal eyes (p < 0.01) and -0.46 for eyes with CSC (p < 0.01). A deep convolutional neural network model was independently created and trained with augmented training data by K-Fold Cross Validation (K = 5). The correlation coefficients between the value predicted from the colour image and the true choroidal thickness were 0.68 for normal eyes (p < 0.01) and 0.48 for eyes with CSC (p < 0.01). Thus, choroidal thickness could be estimated from colour fundus photographs in both normal eyes and eyes with CSC, using imaging analysis and deep learning.

Analysis of Choroidal Vascularity in Children with Unilateral Hyperopic Amblyopia.

This institutional case control study was carried out to compare choroidal vascularity (CV) in amblyopic eyes, fellow eyes, and control eyes in children with unilateral hyperopic amblyopia. Sixty-four eyes of 32 childeren with unilateral anisometropic hyperopic amblyopia and 38 eyes of 19 healthy children (controls), aged 3 to 16 years. Subfoveal choroidal thickness (CT) and CV were measured using spectral domain optical coherence tomography. The mean subfoveal CT of amblyopic eyes (338.9 ± 60.0 µm) was greater than that of fellow eyes (315.3 ± 63.3 µm, P = 0.043) and control eyes (313.0 ± 42.1 µm, P = 0.025). The mean CV of amblyopic eyes (0.715 ± 0.020) was greater than that of control eyes (0.700 ± 0.020, P < 0.001). While a positive correlation between CT and CV was found in normal eyes (r = 0.470, P = 0.004), a strong negative correlation existed in amblyopic eyes (r = -0.684, P < 0.001). In conclusion, although mean CV was higher in amblyopic eyes, the negative correlation between CT and CV may suggests insufficient blood supply to the outer retina and choroid in the affected eyes of patients with unilateral anisometropic hyperopic amblyopia.

Twenty-four hour ocular and systemic diurnal rhythms in children.

PURPOSE: Ocular diurnal rhythms have been implicated in myopia, glaucoma, diabetes, and other ocular pathologies. Ocular rhythms have been well described in adults; however, they have not yet been fully examined in children. The goal of this study was to investigate ocular and systemic diurnal rhythms over 24 h in children. METHODS: Subjects, ages 5 to 14 years (n = 18), wore a light, sleep, and activity monitor for one week to assess habitual sleep/wake patterns, then underwent diurnal measurements every 4 h for 24 h. Measurements included blood pressure, heart rate, body temperature, intraocular pressure (IOP), ocular biometry, and optical coherence tomography imaging. Saliva was collected for melatonin and cortisol analysis. Mean ocular perfusion pressure was calculated from IOP and blood pressure. Central corneal thickness, corneal power, anterior chamber depth, lens thickness, vitreous chamber depth, and axial length were determined from biometry. Total retinal thickness, retinal pigment epithelium (RPE) + photoreceptor outer segment thickness, photoreceptor inner segment thickness, and choroidal thickness were determined for a 1 mm diameter centred on the fovea. Subjects' amplitude and acrophase of diurnal variation for each parameter were determined using Fourier analysis, and mean acrophase was calculated using unit vector averaging. RESULTS: Repeated measures analysis of variance (ANOVA) showed that all parameters except anterior chamber depth exhibited significant variations over 24 h (p ≤ 0.005 for all). Axial length underwent diurnal variation of 45.25 ± 6.30 µm with an acrophase at 12.92 h, and choroidal thickness underwent diurnal variation of 26.25 ± 2.67 µm with an acrophase at 1.90 h. IOP was approximately in phase with axial length, with a diurnal variation of 4.19 ± 0.50 mmHg and acrophase at 11.37 h. Total retinal thickness underwent a significant diurnal variation of 4.09 ± 0.39 µm with an acrophase at 15.04 h. The RPE + outer segment layer was thickest at 3.25 h, while the inner segment layer was thickest at 14.95 h. Melatonin peaked during the dark period at 2.36 h, and cortisol peaked after light onset at 9.22 h. CONCLUSIONS: Ocular and systemic diurnal rhythms were robust in children and similar to those previously reported in adult populations. Axial length and IOP were approximately in phase with each other, and in antiphase to choroidal thickness. These findings may have important implications in myopia development in children.

Optical coherence tomography angiography to assess vascular remodeling of the choriocapillaris after low-fluence photodynamic therapy for chronic central serous chorioretinopathy.

BACKGROUND: To evaluate the efficacy of optical coherence tomography angiography (OCTA) in identifying changes in the choriocapillaris layer after low-fluence verteporfin photodynamic therapy (vPDT) in patients affected by chronic central serous chorioretinopathy (CSCR). METHODS: Low-fluence vPDT was performed on 28 eyes of 27 patients with CSCR. All patients underwent the following tests at baseline and 6 months after treatment: best corrected visual acuity (BCVA), fluorescein angiography, indocyanine green angiography, enhanced depth imaging OCT and OCTA. RESULTS: Subretinal fluid was completely absorbed in 18 of the 28 affected eyes (64.3%) after low-fluence vPDT ("responders"), and incompletely absorbed in 10 eyes (35.7%) ("non responders"). BCVA was significantly improved (p = 0.006) whereas central foveal thickness and choroidal foveal thickness were significantly decreased (p = 0.001 and p = 0.00 respectively) 6 months after treatment in responders. CONCLUSIONS: OCTA revealed a different pattern of vascular remodeling of the choriocapillaris between CSC patients who responded and those who did not respond to low-fluence vPDT.

Beta-catenin signaling regulates barrier-specific gene expression in circumventricular organ and ocular vasculatures.

The brain, spinal cord, and retina are supplied by capillaries that do not permit free diffusion of molecules between serum and parenchyma, a property that defines the blood-brain and blood-retina barriers. Exceptions to this pattern are found in circumventricular organs (CVOs), small midline brain structures that are supplied by high permeability capillaries. In the eye and brain, high permeability capillaries are also present in the choriocapillaris, which supplies the retinal pigment epithelium and photoreceptors, and the ciliary body and choroid plexus, the sources of aqueous humor and cerebrospinal fluid, respectively. We show here that (1) endothelial cells in these high permeability vascular systems have very low beta-catenin signaling compared to barrier-competent endothelial cells, and (2) elevating beta-catenin signaling leads to a partial conversion of permeable endothelial cells to a barrier-type state. In one CVO, the area postrema, high permeability is maintained, in part, by local production of Wnt inhibitory factor-1.