Parallel comparison of ocular metrics in non-human primates with high myopia by LS900, ultrasonography and MRI-based 3D reconstruction.

We investigate the ocular dimensions and shape by using Lenstar900 (LS900), A-scan ultrasonography, and Magnetic Resonance Imaging (MRI) in highly myopic Macaca fascicularis. The ocular dimensions data of LS900, A-scan ultrasonography and MRI was assessed from 8 eyes (4 adult male cynomolgus macaque) with extremely high myopia (≤-1000DS) and compared by means of coefficients of concordance and 95% limits of agreement. Multiple regression analysis was performed to explore the associations between ocular biometry, volume, refraction and inter-instrument discrepancies. Test-retest reliability of three measurements of ocular parameters at two time points was almost equal (intraclass correlation = 0.831 to 1.000). The parallel-forms reliability of three measurements was strong for vitreous chamber depth (VCD) (coefficient of concordance = 0.919 to 0.981), moderate for axial length (AL) (coefficient of concordance = 0.486 to 0.981), and weak for anterior chamber depth (ACD) (coefficient of concordance = 0.267 to 0.621) and lens thickness (LT) (coefficient of concordance = 0.035 to 0.631). The LS900 and MRI systematically underestimated the ACD and LT comparing to A-scan ultrasonography (P < 0.05). Notably, the average AL on LS900 displayed a significant correlation with those on MRI (r = 0.978, P < 0.001) and A-scan ultrasonography (r = 0.990, P < 0.001). Almost 4/5 eyeballs were prolate. The mean eyeball volume positively correlated with AL (r = 0.782, P = 0.022), the width (r = 0.945, P = 0.000), and the length (r = 0.782, P = 0.022) of eyeball, while negatively correlated with SER (r = -0.901, P = 0.000). In conclusion, there was a high inter-instrument concordance for VCD with LS900, A-scan ultrasonography and MRI, while ACD and LT were underestimated with LS900 compared to A-scan ultrasonography, and the LS900 and A-scan ultrasonography could reliably measure the AL. MRI further revealed an equatorial globe shape in extremely myopic non-human primates.

Characteristics of the fundus and optical coherence tomography angiography metrics in myopic patients with myelinated retinal nerve fibers.

AIMS: To investigate the fundus characteristics and macular optical coherence tomography angiography (OCTA) metrics in patients with myelinated retinal nerve fibers (MRNF) and to identify the associations among myopic parameters, fundus metrics, and OCTA metrics. METHODS: The single-center case-control study included 15 patients with monocular MRNF and 15 patients without MRNF, matched for age, affected eyes' spherical equivalent error (SER), and axial length (AL) between May 2021 and December 2021. Fundus features, including the entire MRNF area (Area1), the denser MRNF area (Area2), and the shortest distance from the fovea to the MRNF border (Df-m), along with ocular parameters, including SER, AL, best corrected visual acuity (BCVA), and OCTA metrics at the fovea, including choroidal (ChT) and retinal (ReT) thicknesses at the fovea, the foveal avascular zone area (FAZ), foveal avascular zone perimeter (FAZP), FAZ-circularity index (FAZ-CI), and foveal vessel density in a 300-µm wide region (FD-300), were assessed. RESULTS: The SER, AL, and BCVA were significantly different, and the ChT was thinner in the affected eyes than in the contralateral eyes. Compared with matched eyes, affected eyes had reduced BCVA and thinner ReT. In the affected eyes, both Area1 and Area2 were negatively correlated with SER (r1 = -0.84, r2 = -0.65), △SER (r1 = -0.86, r2 = -0.61), ReT at the vertical superior 3 mm (VS) (r1 = -0.78, r2 = -0.67), and ChT_VS (r1 = -0.64, r2 = -0.62), and positively correlated with AL (r1 = 0.82, r2 = 0.52) and BCVA (r1 = 0.54, r2 = 0.59). Df-m was negatively correlated with BCVA (r = -0.57). CONCLUSION: The presence of MRNF affects BCVA and ReT at the fovea. The area of the MRNF, as well as the distance from the MRNF to the fovea, are closely associated with the affected eyes' BCVA, SER, AL, and the degree of anisometropia.

Altered time-varying local spontaneous brain activity pattern in patients with high myopia: a dynamic amplitude of low-frequency fluctuations study.

PURPOSE: To investigate the abnormal time-varying local spontaneous brain activity in patients with high myopia (HM) on the basis of the dynamic amplitude of low-frequency fluctuations (dALFF) approach. METHODS: Age and gender matching were performed based on resting-state functional magnetic resonance imaging data from 86 HM patients and 87 healthy controls (HCs). Local spontaneous brain activities were evaluated using the time-varying dALFF method. Support vector machine combined with the radial basis function kernel was used for pattern classification analysis. RESULTS: Inter-group comparison between HCs and HM patients has demonstrated that dALFF variability in the left inferior frontal gyrus (orbital part), left lingual gyrus, right anterior cingulate and paracingulate gyri, and right calcarine fissure and surrounding cortex was decreased in HM patients, while increased in the left thalamus, left paracentral lobule, and left inferior parietal (except supramarginal and angular gyri). Pattern classification between HM patients and HCs displayed a classification accuracy of 85.5%. CONCLUSION: In this study, the findings mentioned above have suggested the association between local brain activities of HM patients and abnormal variability in brain regions performing visual sensorimotor and attentional control functions. Several useful information has been provided to elucidate the mechanism-related alterations of the myopic nervous system. In addition, the significant role of abnormal dALFF variability has been highlighted to achieve an in-depth comprehension of the pathological alterations and neuroimaging mechanisms in the field of HM.

Poster Session: Optical coherence elastography for In situ measurement of stiffness increase in posterior sclera after crosslinking.

During eye growth, scleral development critically determine eye size and thus the refractive status of the eye. Scleral remodeling in myopia includes scleral thinning, loss of scleral tissue, and weakening of the mechanical properties. Therefore, an intervention aiming at stiffening scleral tissues (crosslinking, SCXL) may provide a way to prevent or treat myopia. The development of SCXL requires tools to evaluate the effects of crosslinking on the mechanical properties of tissues, particularly in sclera where the mechanical properties are more spatially heterogeneous than in the cornea, anisotropic, and varying locally from the anterior to posterior regions. Here, we apply the high-frequency OCE technique to measure the heterogeneous mechanical properties of posterior scleral tissues and, evaluate the changes in shear moduli after SCXL. As a model system, we use ex vivo in porcine eyes and riboflavin-assisted UV crosslinking. From measured elastic wave speeds (6-16kHz), the average out-of-plane shear modulus was 0.71±0.12MPa (n=20) for normal scleras. After treatment, the shear modulus increased to 1.50±0.39MPa. This 2-fold change was consistent with the increase of static Young's modulus from 5.5±.1 to 9.3±1.9MPa after crosslinking, using conventional uniaxial extensometry. OCE revealed regional stiffness differences across the temporal, nasal, and deeper posterior sclera, demonstrating its potential as a noninvasive tool to test the effect of scleral crosslinking.

Poster Session: Experimental assessment of scleral anisotropy using multi-meridian air-coupled ultrasonic optical coherence elastography.

Scleral biomechanics plays a key role in the understanding of myopia progression. In this study, we characterized the elastic properties of sclera using an air-coupled ultrasonic (ACUS) optical coherence elastography (OCE) system. New Zealand rabbit eyes (n=7) were measured (<24hr postmortem) in four scleral locations: superior/inferior temporal (ST, IT), and superior/inferior nasal (SN, IN) maintaining an intraocular pressure of 15 mmHg. Elastic waves were induced in the sclera, and wave propagation velocity and shear modulus were measured along two directions: circumferential (superior-inferior) and meridional (nasal-temporal). Wave velocity in scleral tissue ranged from 6 to 24 m/s and shear modulus from 11 to 150 kPa. Velocity was significantly higher (p<.001) in the circumferential vs. meridional directions in the following locations: ST:15.83±2.85 vs 9.43±1.68 m/s, IT:15.00±3.98 vs 8.93±1.53 m/s; SN:16.79±4.30 vs 9.27±1.47 m/s; and IN:13.92±3.85 vs 8.57±1.46 m/s. The average shear modulus in the circumferential was also significantly higher (p<.001) than in the meridional direction for all locations: 65.37±6.04 vs 22.55±1.36 kPa. These results show that the rabbit sclera is mechanically anisotropic with higher rigidity in the circumferential direction compared to the meridional direction. ACUS-OCE is a promising non-invasive method to quantify the biomechanical changes in scleral tissue for future studies involving myopia treatments.

Poster Session: Estimation of scleral biomechanical properties from air-puff-coupled optical coherence tomography.

Progression of myopia is usually accompanied by axial overgrowth of the eyeball, which affects scleral biomechanics (BM). To study scleral biomechanics, we propose the use of air-puff deformation swept-source OCT imaging. Air-puff deformation imaging was performed at different sites of ex vivo porcine (n=5) and rabbit (n=3) eyes, (<24hr postmortem): Nasal/temporal equatorial and posterior sclera (NE, NP, TE, TP), superior (S) and inferior (I) sclera, and cornea (C). Intraocular pressure was kept at 15mmHg. Deformation data were used as input to inverse finite element model (FEM) algorithms to reconstruct BM properties. Experimental deformation amplitudes showed dependence on the animal model, with porcine scleras exhibiting greater inter-site variation (displacement of S, I was up to four times greater than that of N, T), while rabbit scleras exhibited at most 40% of displacement differences between all sites. Both models showed significant (p<.001) differences in the temporal deformation profile between sclera and (C), but similarities in all scleral locations, suggesting that the scleral temporal profile is independent of scleral thickness variations. The FEM estimated an elastic modulus of 1.84 ± 0.30 MPa (I) to 6.04 ± 2.11 MPa (TE) for the porcine sclera. The use of scleral air-puff imaging is promising for noninvasive investigation of structural changes in the sclera associated with myopia and for monitoring possible modulation of scleral stiffness with myopia treatment.

Choriocapillary Flow Correlation with Axial Length in High Myopia - An Angiography Study with Optical Coherence Tomography.

PURPOSE: To investigate parameters of retinal and choroidal microcirculation quantitatively with optical coherence tomography angiography (OCTA) in high myopic children, and to explore potential correlations with age, axial length (AL), spherical equivalent (SE), and central retinal thickness (CRT). METHODS: En face angiograms were generated with an OCTA device and evaluated with automated density and flow analyzer algorithms. Perfusion parameters were correlated with age, AL, SE, and CRT using Spearman's rank correlation analysis. Repeatability and reproducibility of perfusion parameter measurements were calculated in a high myopic cohort. RESULTS: Repeatability and reproducibility of OCTA measurements were good, ranging from 3.6 - 6.5%. Strong positive correlation was identified between age and CRT (rho = 0.673, p = 0.00) as well as between AL and SE (rho = 0.844, p = 0.00). There was a strong negative correlation between AL and choriocapillary flow density (CCFD) (rho = - 0.612, p = 0.00), and a moderate negative correlation between age and superficial parafoveal retinal vessel density (SPRVD) as well as CCFD (rho = - 0.497, p = 0.013 and rho = - 0.483, p = 0.023, respectively). CONCLUSION: OCTA appears to be a reliable tool for the quantitative investigation of retinal and choroidal microcirculation in a high myopic pediatric cohort. CCFD reduction was associated with increasing AL in this cohort.

Use of multimodal dataset in AI for detecting glaucoma based on fundus photographs assessed with OCT: focus group study on high prevalence of myopia.

BACKGROUND: Glaucoma is one of the major causes of blindness; it is estimated that over 110 million people will be affected by glaucoma worldwide by 2040. Research on glaucoma detection using deep learning technology has been increasing, but the diagnosis of glaucoma in a large population with high incidence of myopia remains a challenge. This study aimed to provide a decision support system for the automatic detection of glaucoma using fundus images, which can be applied for general screening, especially in areas of high incidence of myopia. METHODS: A total of 1,155 fundus images were acquired from 667 individuals with a mean axial length of 25.60 ± 2.0 mm at the National Taiwan University Hospital, Hsinchu Br. These images were graded based on the findings of complete ophthalmology examinations, visual field test, and optical coherence tomography into three groups: normal (N, n = 596), pre-perimetric glaucoma (PPG, n = 66), and glaucoma (G, n = 493), and divided into a training-validation (N: 476, PPG: 55, G: 373) and test (N: 120, PPG: 11, G: 120) sets. A multimodal model with the Xception model as image feature extraction and machine learning algorithms [random forest (RF), support vector machine (SVM), dense neural network (DNN), and others] was applied. RESULTS: The Xception model classified the N, PPG, and G groups with 93.9% of the micro-average area under the receiver operating characteristic curve (AUROC) with tenfold cross-validation. Although normal and glaucoma sensitivity can reach 93.51% and 86.13% respectively, the PPG sensitivity was only 30.27%. The AUROC increased to 96.4% in the N + PPG and G groups. The multimodal model with the N + PPG and G groups showed that the AUROCs of RF, SVM, and DNN were 99.56%, 99.59%, and 99.10%, respectively; The N and PPG + G groups had less than 1% difference. The test set showed an overall 3%-5% less AUROC than the validation results. CONCLUSION: The multimodal model had good AUROC while detecting glaucoma in a population with high incidence of myopia. The model shows the potential for general automatic screening and telemedicine, especially in Asia. TRIAL REGISTRATION: The study was approved by the Institutional Review Board of the National Taiwan University Hospital, Hsinchu Branch (no. NTUHHCB 108-025-E).

Development and Testing of a Compact Autorefractor Based on Double-Pass Imaging.

Autorefraction is an objective way to determine the refractive error of the eye, without the need for feedback by the patient or a well-educated practitioner. To make refractive measurements more accessible in the background of the growing prevalence of myopia, a compact autorefractor was built, containing only few optical components and relying on double-pass imaging and the physical properties of the point-spread function and digital image processing instead. A method was developed to analyze spherical defocus as well as the defocus and angle of astigmatism. The device was tested using calibrator eye models in a range of ± 15 D spherical defocus and -3 D astigmatic defocus. Reliable results could be achieved across the whole measurement range, with only a small increase in deviation toward high values of refractive errors, showing the feasibility of a PSF-based approach for a compact and low-cost solution for objective measurements of refractive error.

Automatic Segmentation and Measurement of Choroid Layer in High Myopia for OCT Imaging Using Deep Learning.

Automatic segmentation and measurement of the choroid layer is useful in studying of related fundus diseases, such as diabetic retinopathy and high myopia. However, most algorithms are not helpful for choroid layer segmentation due to its blurred boundaries and complex gradients. Therefore, this paper aimed to propose a novel choroid segmentation method that combines image enhancement and attention-based dense (AD) U-Net network. The choroidal images obtained from optical coherence tomography (OCT) are pre-enhanced by algorithms that include flattening, filtering, and exponential and linear enhancement to reduce choroid-independent information. Experimental results obtained from 800 OCT B-scans of the choroid layers from both normal eyes and high myopia showed that image enhancement significantly increased the performance of ADU-Net, with an AUC of 99.51% and a DSC of 97.91%. The accuracy of segmentation using the ADU-Net method with image enhancement is superior to that of the existing networks. In addition, we describe some algorithms that can measure automatically choroidal foveal thickness and the volume of adjacent areas. Statistical analyses of the choroidal parameters variation indicated that compared with normal eyes, high myopia has a reduction of 86.3% of the choroidal foveal thickness and 90% of the adjacent volume. It proved that high myopia is likely to cause choroid layer attenuation. These algorithms would have wide application in the diagnosis and precaution of related fundus lesions caused by choroid thinning from high myopia in future studies.

Corneal Collagen Crosslinking (CXL) for Corneal Ectasia after Small Incision Lenticule Extraction (SMILE). / Korneales Kollagen-Crosslinking (CXL) bei Hornhautektasie nach SMILE (Small Incision Lenticule Extraction).

With an estimated incidence of 0.011%, the SMILE procedure seems to have the lowest risk of postoperative keratectasia among contemporary keratorefractive procedures. Nevertheless, due to the novelty of the procedure as well as the lack of data, no clear superiority over femto-LASIK or PRK can be stated at this time. In this respect, application of the identical tomographic screening criteria previously developed for excimer-based procedures is of paramount importance to minimize the risk of corneal ectasia. As an adjunct to conventional corneal tomography, newer imaging modalities such as OCT-based epithelial mapping should be used for preoperative screening before keratorefractive surgery. Corneal crosslinking is an established treatment modality for post-SMILE keratectasia, which promises high success rates especially in early stages. The present case report illustrates these diagnostic and therapeutic considerations.

ANATOMIC AND TOPOGRAPHIC CHANGES OF ANTERIOR SEGMENT STRUCTURES IN EHLERS-DANLOS SYNDROME PATIENTS WITH MYOPIA.

OBJECTIVE: The aim: Determination of anatomical and topographical relationships of the eyeball anterior segment structures to assess possible glaucoma development risk factors in SED patients with myopic refraction. PATIENTS AND METHODS: Materials and methods: Patients, aged from 10 to 34, have been examined since 2009. All the patients have undergone required medic and genetic examination as well as generally accepted ophthalmological one. Ultrasound biomicroscopy (UBM) has been performed using the VuMax II apparatus (Sonomed, USA) with a sensor frequency of 50 MHz. RESULTS: Results: Biomicroscopy found no symptoms such as pigment dispersion on the iris stroma, in the chamber anterior angle, iris transillumination and "Krukenberg's Spindle", which are characteristic for the ultrasound picture in pigment dispersion syndrome. CONCLUSION: Conclusions: 1. Clinical and functional study with the eyeballs mandatory ultrasound biomicroscopy have revealed functional space limitations for the structures of the iridociliary zone in patients with myopic type of eye structure in SED. 2. Detected congenital changes in the anterior segment structures (iridociliary cystic formations and residual mesodermal tissue) can lead to the emergence of intraocular blocks. 3. The research has identified conducive anatomical and topographic changes, which are likely to induce pigment dispersion syndrome or lead to the development of pigmentary glaucoma. 4. In our opinion, the UBM role in the early diagnosing and monitoring patients with SED syndrome is quite significant in terms of assessing the stability or dynamics of the changes received and possible complications. Ultrasound biomicroscopic scanning should be added to the list of necessary early diagnostic examinations to determine the markers and features of structures in SED.

Thickness, vessel density of retina and choroid on OCTA in young adults (18-24 years old).

PURPOSE: The purpose of this study was to quantify thickness, vessel density (VD) of retina and choroid in young adults (18-24 years old) using OCTA. METHODS: This observational, cross-sectional study included 154 eyes from 77 young myopic adults. En-face angiogram OCTA was performed on a 3.00 × 3.00 mm region centered on the macula. Automated thickness calculations and macular maps were measured. Spherical equivalent refraction (SER) and AL were examined to determine associations with thickness, vessel density (VD) of retina and choroid. RESULTS: A total of 148 healthy eyes from 77 young myopic adults (29 males and 48 females) with a mean age of 21.80 ± 1.32 years (range: 18-24 years) were included. The mean SER and AL were - 4.06 ± 2.26D and 25.25 ± 1.28 mm, respectively. The mean retinal thickness (RT, ILM-RPE layer) was 240.91 ± 13.36 µm, the retinal superficial (SVD) and deep vessel density (DVD) in fovea region were 18.35 ± 4.77% and 32.99 ± 6.01%, respectively. The foveal avascular zone (FAZ) area was 0.31 ± 0.10 mm2. The mean subfoveal choroidal thickness (SFCT) and choriocapillaris (CC) perfusion area were 232.16 ± 56.65 µm and 2.17 ± 0.10 mm2, respectively. By Pearson's correlation analysis, SER was revealed to be negatively correlated with RT (r = -0.180, p = 0.028) and DVD (r = -0.185, p = 0.025) in fovea region. SER was revealed to be positively correlated with RT in nasal (r = 0.224, p = 0.006) and inferior (r = 0.217, p = 0.008) regions. AL was revealed to be positively correlated with RT (r = 0.250, p = 0.002) and DVD (r = 0.284, p < 0.001) in fovea region. SER was revealed to be positively correlated with SFCT (r = 0.486, p < 0.001). AL was revealed to be negatively correlated with FAZ area (r = -0.232, p = 0.005) and SFCT (r = -0.407). RT was revealed to be negatively correlated with FAZ area (r = -0.645, p < 0.001). SER (r = -0.079), AL (r = 0.071) and SFCT (r = 0.089) did not correlate significantly with the CC perfusion area (all p > 0.05). CONCLUSION: Myopic eyes present increased RT, DVD and thinned SFCT in fovea, while no significant correlation could be found between SER, AL, SFCT and CC perfusion area. It may indicate that the SFCT thinning may be secondary to ocular elongation, while the CC perfusion area may be a factor independent of AL growth.

Choroidal changes in lens-induced myopia in guinea pigs.

INTRODUCTION: This study aimed to determine the role of the choroid in lens-induced myopia (LIM) in guinea pigs. METHODS: Guinea pigs were randomly divided into two groups: a normal control (NC) group and a LIM group. Refraction and axial length (AL) were measured by streak retinoscopy and A-scan ultrasonography. The choroidal thickness (ChT), vessel density of the choriocapillaris (VDCC) and vessel density of the choroidal layer (VDCL) were assessed by Spectral-domain Optical Coherence Tomography Angiography (SD-OCT). In addition, the choroidal expression of nitric oxide synthase (NOS) enzymes at the mRNA and protein levels was analyzed by real-time fluorescence quantitative PCR, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. RESULTS: In the LIM group, refraction and AL were increased significantly compared with those in the NC group at 2 weeks (refraction: LIM vs. NC, -4.23 ± 0.43 D vs. 2.20 ± 0.48 D; AL: LIM vs. NC, 8.36 ± 0.05 mm vs. 8.22 ± 0.03 mm) and 4 weeks (refraction: LIM vs. NC, -5.88 ± 0.49 D vs. 1.63 ± 0.41 D; AL: 8.57 ± 0.06 mm vs. 8.40 ± 0.04 mm). The ChT and VDCC were decreased significantly compared with those in the NC group at 2 weeks (ChT: LIM vs. NC, 60.92 ± 8.15 µm vs. 79.11 ± 7.47 µm; VDCC: LIM vs. NC, 23.43 ± 3.85% vs. 28.74 ± 4.11%) and 4 weeks (ChT: LIM vs. NC, 48.43 ± 6.85 µm vs. 76.38 ± 7.84 µm; VDCC: LIM vs. NC, 21.29 ± 2.17% vs. 27.64 ± 2.91%). The VDCL was also decreased compared with that in the NC group at 2 weeks and 4 weeks (NC vs. LIM, 24.87 ± 5.16% vs. 22.45 ± 3.26%; 23.37 ± 5.85% vs. 21.39 ± 2.62%; all P > 0.05). Moreover, the ChT was positively correlated with the VDCC and VDCL. The mRNA and protein expression of NOS enzymes (eNOS and nNOS) was increased. CONCLUSIONS: During the development of myopia, the ChT, VDCC and VDCL were decreased, while NOS expression in the choroid was increased. The expression of NOS was negatively correlated with the ChT, VDCC and VDCL. NO may play an important role in regulating the choroid during myopia development.

Effect of Laser-assisted Subepithelial Keratectomy with Mitomycin C on Corneal Optical Density Measured with Confocal Microscopy.

SIGNIFICANCE: The development of confocal microscopy allows one to obtain high-resolution corneal images like its optical density. Some studies have evaluated the optical density with Scheimpflug cameras in the early post-operative period after photorefractive keratectomy, but no studies have evaluated the long-term evolution of optical density after surface ablation when mitomycin C is used. PURPOSE: This work aimed to study the changes in corneal optical density measured with confocal microscopy in eyes treated with laser-assisted subepithelial keratectomy (LASEK) and intraoperative mitomycin C (MMC) to correct myopia. METHODS: A study of 24 consecutive myopic eyes that underwent LASEK with 0.02% MMC and a control group of 24 healthy nontreated eyes was performed. Optical density was measured using the images by the confocal microscopy of the Heidelberg Retina Tomograph II with the Rostock Cornea Module. An analysis of confocal microscopy images was performed using the ImageJ software to obtain the optical density, in gray-scale units (GSU). The optical density of the stromal bed was evaluated 3 months, 15 months, and 3 years after surgery and was compared with the optical density at the equivalent depth of the stroma in controls. RESULTS: The mean values of optical density for the LASEK group were 81.7 ± 9.7, 78.6 ± 11.7, and 73.6 ± 18.7 GSU at 3 months, 15 months, and 3 years, respectively, and it was 61.8 ± 8.2 GSU for the control group. A statistically higher optical density 3 and 15 months after LASEK with MMC was found compared with controls (P < .001). No significant difference was found in optical density at 3 years post-operatively. CONCLUSIONS: Our study suggests that, after LASEK with MMC, the anterior corneal stroma has a higher optical density at 3 and 15 months post-operatively, which gradually returns to normal values 3 years after surgery.

A novel homozygous nonsense mutation of VPS13B associated with previously unreported features of Cohen syndrome.

Cohen syndrome (CS) is a rare autosomal recessive disorder associated with mutations in the vacuolar protein sorting 13 homolog B (VPS13B; formerly COH1) gene. The core clinical phenotype comprises a characteristic facial gestalt, marked developmental delay, and myopia. Additional, nonobligatory features include obesity, microcephaly, short stature, muscular hypotonia, scoliosis, narrow hands and feet, progressive retinopathy, as well as neutropenia. Here we report a novel homozygous nonsense mutation in the VPS13B gene and previously undescribed clinical features in a 19-year-old woman with developmental delay, intellectual disability, and a particular facial appearance. The patient showed several features consistent with CS. In addition, the parents observed congenital alacrima and anhidrosis persisting until onset of puberty. The diagnosis was not established based on the clinical phenotype. We performed whole-genome sequencing and identified a novel homozygous nonsense mutation c.62T>G (NM_152564.4), p.(Leu21*) in the VPS13B gene. Our findings extended the previously reported phenotype of CS. We conclude that transient, prepubertal alacrima and anhidrosis are part of the phenotypic spectrum of CS associated with a novel homozygous nonsense mutation in the VPS13B gene.

A prenatally diagnosed case of Donnai-Barrow syndrome: Highlighting the importance of whole exome sequencing in cases of consanguinity.

Donnai-Barrow syndrome (DBS) is an autosomal recessive disorder characterized by typical craniofacial features, vision and hearing loss, intellectual disability, agenesis of the corpus callosum (ACC), congenital diaphragmatic hernia (CDH), and omphalocele. This condition is associated with loss-of-function mutations in the LRP2 gene. Few cases have been described in the literature. In our case, CDH and ACC were prenatally diagnosed by ultrasound, and the fetus was the product of a first-degree union. Single-nucleotide polymorphism-microarray showed large regions of homozygosity. Whole exome sequencing (WES) was performed and revealed a homozygous frameshift pathogenic variant in LRP2 (c.6978dupG). Here, we present a case of DBS, which diagnosed prenatally via WES in a fetus with CDH and ACC.

Inferior rectus displacement in heavy eye syndrome and sagging eye syndrome.

PURPOSE: To evaluate if there is a nasal displacement of the vertical rectus muscles in heavy eye syndrome (HES) and/or sagging eye syndrome (SES) compared with age-matched controls. METHODS: We reviewed the charts of all patients with the diagnosis of HES or SES who were seen at the University of California San Diego (UCSD) between the years 2008-2016 who underwent magnetic resonance imaging (MRI) of the brain and orbits. The control group included patients who had brain and orbital MRIs at UCSD in the absence of known pathology in the orbits or globes. Measurements were taken by 3 separate examiners for all groups. RESULTS: Twenty-four patients (16 with SES and 8 with HES) and 24 age-matched controls were retrospectively reviewed. The superior rectus (SR) of patients with HES and SES was more nasally displaced from the midline compared with that of age-matched controls (p = 0.04, p = 0.03, respectively). The inferior rectus (IR) of patients with HES but not with SES was more nasally displaced from the midline compared with that of age-matched controls (p = 0.04, p = 0.62, respectively). In all groups, the IR nasal displacement from the midline was approximately double compared with the SR. CONCLUSIONS: There is a significant nasal displacement of the SR in HES and SES and IR in HES. The observed IR nasal displacement in HES is a new finding and may explain the residual hypotropia and/or esotropia following surgical interventions for HES not involving the IR.

SURGICAL OUTCOMES OF MYOPIC TRACTION MACULOPATHY ACCORDING TO THE INTERNATIONAL PHOTOGRAPHIC CLASSIFICATION FOR MYOPIC MACULOPATHY.

PURPOSE: To compare treatment results of myopic traction maculopathy according to the international photographic classification for myopic maculopathy. METHODS: This was a retrospective, single-surgeon-based, observational case series of 35 consecutive eyes that underwent vitrectomy for myopic traction maculopathy. Eyes were classified into nonpathologic myopia (PM) (n = 15) and PM (n = 20) groups. Main outcome measures constituted best-corrected visual acuity (BCVA) and anatomical change. RESULTS: The mean follow-up was 32.03 ± 6.85 months. Axial length correlated with myopic maculopathy category (rho = 0.6836, P < 0.001). In the total group, BCVA improved from 20/61 to 20/36 (P = 0.001). In the subgroup, BCVA improved from 20/41 to 20/22 in the non-PM group (P = 0.002), whereas from 20/82 to 20/52 in the PM group (P = 0.048). Postoperative BCVA of the PM group was inferior to that of the non-PM group (P = 0.002) and the PM group was more likely to have postoperative BCVA <20/30 (odds ratio, 17.3; 95% CI, 2.6-325.0; P = 0.012). Two cases of macular hole retinal detachment occurred after surgery in the PM group. CONCLUSION: Because there are limited benefits of vitrectomy in myopic traction maculopathy accompanied by PM, careful consideration would be necessary when determining surgery. Optical coherence tomography should not be used alone in determining vitrectomy because myopic traction maculopathy can also have PM defined mainly by fundus photographs.

Cerebral Blood Flow Alterations in High Myopia: An Arterial Spin Labeling Study.

Objective: The aim of this study was to explore cerebral blood flow (CBF) alterations in subjects with high myopia (HM) using three-dimensional pseudocontinuous arterial spin labeling (3D-pcASL). Methods: A total of sixteen patients with bilateral HM and sixteen age- and sex-matched healthy controls (HCs) were recruited. All subjects were right-handed. Image data preprocessing was performed using SPM8 and the DPABI toolbox. Clinical parameters were acquired in the HM group. Two-sample t-tests and Pearson correlation analysis were applied in this study. Results: Compared to HCs, patients with HM exhibited significantly increased CBF in the bilateral cerebellum, and no decreases in CBF were detected in the brain. However, no relationship was found between the mean CBF values in the different brain areas and the disease duration (P > 0.05). Conclusions: Using ASL analysis, we detected aberrant blood perfusion in the cerebellum in HM patients, contributing to a better understanding of brain abnormalities and brain plasticity through a different perspective.