PDLIM1 inhibits cell migration and invasion in diabetic retinopathy via negatively regulating Wnt3a.

The injury of vascular endothelial cells is a crucial factor in the development of diabetic retinopathy (DR). PDLIM1 (a member of the PDZ and LIM protein family) has been reported to exert an essential function in vascular diseases. This study aimed to elucidate the role of PDLIM1 on retinal vascular endothelial cells in DR. Immunofluorescence staining was used to localize the expression of PDLIM1 in the mouse retina. In some tumor diseases, PDLIM1 has been reported to play a key role in regulating the Wnt pathway. However, no in-depth reports have been found in DR. Retinal capillary endothelial cells (RCECs) were treated with high-glucose and high-lipid (HG/HL) culture medium, and siRNA transfection to investigate the role of PDLIM1 in DR. PDLIM1 and Wnt3a expression was confirmed by qRT-PCR and western blotting. Flow cytometry, Transwell assay, and scratch assay were used to test the ability of cell apoptosis, migration, and invasion. PDLIM1 was mainly expressed in the retinal pigment epithelium (RPE), ganglion cell layer (GCL), inner plexus layer (IPL), and outer plexus layer (OPL). HG/HL increased Wnt3a levels and promoted cell's ability of apoptosis, migration, and invasion, which were reversed by the knockdown of PDLIM1. PDLIM1 was found to play a protective role in diabetic retinopathy by counter-regulating Wnt3a. PDLIM1 ameliorates cell apoptosis, migration, and invasion by negatively regulating Wnt3a in RCECs of DR, which suggests that PDLIM1 might be a promising therapeutic target for DR treatment.

Plexus-specific retinal capillary avascular area in exudative age-related macular degeneration with projection-resolved OCT angiography.

OBJECTIVE: To detect the plexus-specific retinal capillary avascular area in exudative age-related macular degeneration (EAMD) with projection-resolved optical coherence tomography angiography (PR-OCTA). METHODS AND ANALYSIS: In this prospective cross-sectional single centre study, eyes with treatment-naïve EAMD underwent macular 3×3 mm OCTA with AngioVue system. OCTA scans were analysed and processed including three-dimensional projection artefact removal, retinal layer semi-automated segmentation and en face angiogram generation. Automated quantification of extrafoveal (excluding the central 1 mm circle) avascular area (EAA) were calculated on projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP) and deep capillary plexus (DCP), respectively. RESULTS: Nineteen eyes with EAMD and 19 age-matched healthy control eyes were included. There was no significant difference between the EAMD and control eyes in terms of age, sex, axial length and mean ocular perfusion pressure (all p>0.05). Compared with control eyes, EAMD eyes had significantly larger EAA in SVC (median 0.125 vs 0.059 mm2, p=0.006), ICP (0.016 vs 0.000 mm2, p=0.004) and DCP (0.033 vs 0.000 mm2, p＜0.001). CONCLUSION: PR-OCTA showed that EAMD is associated with focal avascular area in all the three retinal vascular plexuses.

Normative intercapillary distance and vessel density data in the temporal retina assessed by wide-field spectral-domain optical coherence tomography angiography.

A limitation of conventional optical coherence tomography angiography (OCTA) is the limited field of view normally used in data acquisition. As the technology improves, larger fields of view that capture information away from the macular are being explored in order to provide an enhanced ability to detect pathology. However, normative measurements for important OCTA metrics like vessel density and intercapillary distance are not currently well-characterized in the peripheral retina. In this prospective study, we measured vessel density and intercapillary distance of the superficial vascular complex, ganglion cell layer plexus, and deep capillary plexus in montaged macular/temporal scans from 53 (33 men) healthy volunteers. Vessel density and intercapillary distance were also compared across different regions of the retina, including along arcs at separate distance from the fovea. Compared to the central macular region, the temporal retina had significantly lower vessel density, decreased thickness, and greater intercapillary distance in the superficial vascular complex, GCLP ganglion cell layer plexus, and deep capillary plexus (Wilcoxon rank sum test P < 0.001), with each of the plexuses examined here showing a general decrease in vessel density and an increase in intercapillary distance towards the temporal region. No significant difference was noted comparing corresponding vessel density and intercapillary distance regions above and below the macula, and multiple linear regression showed that age and intraocular pressure were not associated with vessel density and intercapillary distance in most models. Repeatability analysis reported as intraclass correlation coefficients demonstrated moderate to excellent reliability of vessel density and intercapillary distance in all OCTA layers. These results should help provide an enhanced baseline to help identify vascular pathology in the peripheral retina.

Focal Loss Analysis of Nerve Fiber Layer Reflectance for Glaucoma Diagnosis.

Purpose: To evaluate nerve fiber layer (NFL) reflectance for glaucoma diagnosis. Methods: Participants were imaged with 4.5 × 4.5 mm volumetric disc scans using spectral-domain optical coherence tomography. The normalized NFL reflectance map was processed by an azimuthal filter to reduce directional reflectance bias caused by variation of beam incidence angle. The peripapillary area of the map was divided into 160 superpixels. Average reflectance was the mean of superpixel reflectance. Low-reflectance superpixels were identified as those with NFL reflectance below the fifth percentile normative cutoff. Focal reflectance loss was measured by summing loss in low-reflectance superpixels. Results: Thirty-five normal, 30 preperimetric, and 35 perimetric glaucoma participants were enrolled. Azimuthal filtering improved the repeatability of the normalized NFL reflectance, as measured by the pooled superpixel standard deviation (SD), from 0.73 to 0.57 dB (P < 0.001, paired t-test) and reduced the population SD from 2.14 to 1.78 dB (P < 0.001, t-test). Most glaucomatous reflectance maps showed characteristic patterns of contiguous wedge or diffuse defects. Focal NFL reflectance loss had significantly higher diagnostic sensitivity than the best NFL thickness parameter (from map or profile): 77% versus 55% (P < 0.001) in glaucoma eyes with the specificity fixed at 99%. Conclusions: Azimuthal filtering reduces the variability of NFL reflectance measurements. Focal NFL reflectance loss has excellent glaucoma diagnostic accuracy compared to the standard NFL thickness parameters. The reflectance map may be useful for localizing NFL defects. Translational Relevance: The high diagnostic accuracy of NFL reflectance may make population-based screening feasible.

Cognitive decline in older adults: What can we learn from optical coherence tomography (OCT)-based retinal vascular imaging?

INTRODUCTION: Accumulated vascular damage contributes to the onset and progression of vascular dementia and possibly to Alzheimer's disease. Here we evaluate the feasibility and utility of using retinal imaging of microvascular markers to identify older adults at risk of cognitive disease. METHODS: The "Eye Determinants of Cognition" (EyeDOC) study recruited a biracial, population-based sample of participants from two sites: Jackson, MS, and Washington Co, MD. Optical coherence tomographic angiography (OCTA) was used to capture vessel density (VD) from a 6 × 6 mm scan of the macula in several vascular layers from 2017 to 2019. The foveal avascular zone (FAZ) area was also estimated. Image quality was assessed by trained graders at a reading center. A neurocognitive battery of 10 tests was administered at three time points from 2011 to 2019 and incident mild cognitive impairement (MCI)/dementia cases were ascertained. Linear mixed-effects models were used to evaluate associations of retinal vascular markers with cognitive factor score change over time. RESULTS: Nine-hundred and seventy-six older adults (mean age of 78.7 (± 4.4) years, 44% black) were imaged. Gradable images were obtained in 55% (535/976), with low signal strength (66%) and motion artifact (22%) being the largest contributors to poor quality. Among the 297 participants with both high-quality images and no clinically significant retinal pathology, the average decline in global cognitive function factor score was -0.03 standard deviations per year. In adjusted analyses, no associations of VD or FAZ with longitudinal changes in either global cognitive function or with incident MCI/dementia were found. CONCLUSIONS: In this large biracial community sample of older adults representative of the target population for retinal screening of cognitive risk, we found that obtaining high-quality OCTA scans was infeasible in a nearly half of older adults. Among the select sample of healthier older adults with scans, OCTA markers were not predictive of cognitive impairment.

Quantification of Nonperfusion Area in Montaged Widefield OCT Angiography Using Deep Learning in Diabetic Retinopathy.

Purpose: To examine the efficacy of a deep learning-based algorithm to quantify the nonperfusion area (NPA) on montaged widefield OCT angiography (OCTA) for assessment of diabetic retinopathy (DR) severity. Design: Cross-sectional study. Participants: One hundred thirty-seven participants with a full range of DR severity and 26 healthy participants. Methods: A deep learning-based algorithm was developed for detecting and quantifying NPA in the superficial vascular complex on widefield OCTA comprising 3 horizontally montaged 6 × 6-mm OCTA scans from the nasal, macular, and temporal regions. We trained the algorithm on 978 volumetric OCTA scans from all participants using 5-fold cross-validation. The algorithm can distinguish NPA from shadow artifacts. The F1 score evaluated segmentation accuracy. The area under the receiver operating characteristic curve and sensitivity with specificity fixed at 95% quantified network performance to distinguish patients with diabetes from healthy control participants, referable DR from nonreferable DR (nonproliferative DR [NPDR] less than moderate severity), and severe DR (severe NPDR, proliferative DR, or DR with edema) from nonsevere DR (mild to moderate NPDR). Main Outcome Measures: Widefield OCTA NPA, visual acuity (VA), and DR severities. Results: Automatically segmented NPA showed high agreement with the manually delineated ground truth, with a mean ± standard deviation F1 score of 0.78 ± 0.05 in nasal, 0.82 ± 0.07 in macular, and 0.78 ± 0.05 in temporal scans. The extrafoveal avascular area (EAA) in the macular scan showed the best sensitivity at 54% for differentiating those with diabetes from healthy control participants, whereas montaged widefield OCTA scan showed significantly higher sensitivity than macular scans (P < 0.0001, McNemar's test) for detecting eyes with DR at 66%, referable DR at 63%, and severe DR at 62%. Montaged widefield OCTA showed the highest correlation (Spearman ρ = 0.74; P < 0.0001) between EAA and DR severity. The macular scan showed the strongest negative correlation (Pearson ρ = -0.42; P < 0.0001) between EAA and best-corrected VA. Conclusions: A deep learning-based algorithm for montaged widefield OCTA can detect NPA accurately and can improve the detection of clinically important DR.

DcardNet: Diabetic Retinopathy Classification at Multiple Levels Based on Structural and Angiographic Optical Coherence Tomography.

OBJECTIVE: Optical coherence tomography (OCT) and its angiography (OCTA) have several advantages for the early detection and diagnosis of diabetic retinopathy (DR). However, automated, complete DR classification frameworks based on both OCT and OCTA data have not been proposed. In this study, a convolutional neural network (CNN) based method is proposed to fulfill a DR classification framework using en face OCT and OCTA. METHODS: A densely and continuously connected neural network with adaptive rate dropout (DcardNet) is designed for the DR classification. In addition, adaptive label smoothing was proposed and used to suppress overfitting. Three separate classification levels are generated for each case based on the International Clinical Diabetic Retinopathy scale. At the highest level the network classifies scans as referable or non-referable for DR. The second level classifies the eye as non-DR, non-proliferative DR (NPDR), or proliferative DR (PDR). The last level classifies the case as no DR, mild and moderate NPDR, severe NPDR, and PDR. RESULTS: We used 10-fold cross-validation with 10% of the data to assess the network's performance. The overall classification accuracies of the three levels were 95.7%, 85.0%, and 71.0% respectively. CONCLUSION/SIGNIFICANCE: A reliable, sensitive and specific automated classification framework for referral to an ophthalmologist can be a key technology for reducing vision loss related to DR.

Hole diameter ratio for prediction of anatomical outcomes in stage III or IV idiopathic macular holes.

BACKGROUND: To determine whether preoperative hole diameter ratio (HDR) is a predictive factor for postoperative anatomical outcome for stage III or IV idiopathic macular holes (IMHs). METHODS: One-hundred and one eyes with stage III or IV IMH were included in this retrospective case series study. All cases were treated with vitrectomy combined with internal limiting membrane (ILM) peeling and room air tamponade. The macular hole (MH) minimum and maximum diameter was measured on preoperative optical coherence tomography (OCT) images. The HDR was defined as the minimum to maximum diameter ratio. RESULTS: Eighty-one eyes (80.2%) got a Type I closure after surgery (group A). Postoperative unclosed MHs were found in 20 eyes (19.8%) (group B). The preoperative minimal diameter (703.6 ± 116.1 µm vs. 597.6 ± 120.1 µm, P < 0.01) and HDR (0.6 ± 0.1 vs. 0.5 ± 0.1, P = 0.01) were both significantly smaller in postoperative closed eyes. The closure rate of IMHs with HDR < 0.6 was significantly higher than those with HDR ≥ 0.6 (90.2% vs. 65.0%P = 0.002) . CONCLUSIONS: Preoperative HDR < 0.6 is predictive for a good postoperative anatomical outcome in stage III or IV IMHs.

Evolution and visual outcomes of outer foveolar lucency after surgery for large idiopathic macular hole.

PURPOSE: To explore the evolution of outer foveolar lucency (OFL) after vitrectomy and the correlation between OFL and visual acuity (VA) outcome in eyes with large idiopathic macular hole (IMH). METHODS: In this retrospective study, 244 eyes of 233 subjects with large IMH (diameter > 400 µm), who underwent vitrectomy, were included. Preoperative clinical data, postoperative optical coherence tomography (OCT) images, and VA at 1-, 4-, and 10-month visits were documented. The prevalence, incidence, and width of OFL and their correlation with postoperative VA were analyzed. RESULTS: The prevalence of OFL was 10.4% (24/231) at 1 month and significantly increased to 30.4% (55/181) at 4 months (P < 0.001) and 34.2% (25/73) at 10 months (P < 0.001). The incidence was 26.1% (40/153) and 22.0% (9/41) at 4 and 10 months, respectively. OFL appeared at 1 month while disappeared at 4 or 10 months in 8 eyes (50.0%). The presence of OFL at 1 month was negatively associated with IMH diameter (Nagelkerke R2 = 0.06; P = 0.02). Eyes with OFL at 4 months had better VA at their 4-month visit than eyes without OFL (P = 0.02). Eyes with early-developed OFLs had better VA at 10 months than those with later-developed ones (P = 0.02). Width of OFL was not associated with postoperative VA at any point. CONCLUSIONS: OFL is not rare in eyes with large IMH after surgery. It can occur gradually and remain during the 10-month follow-up. The presence of OFL appears to have no negative impact on the postoperative VA and it may represent the remodeling of foveal photoreceptors.

Effect of internal limiting membrane peeling on normal retinal function evaluated by microperimetry-3.

BACKGROUND: To evaluate the effect of internal limiting membrane (ILM) peeling surrounding macular holes (MH) for the function of retina by microperimetry-3(MP-3). METHODS: This is a prospective, cohort study which included patients with MHs who were treated by 23-gauge 3-port pars plana vitrectomy and ILM peeling with air tamponade. Color fundus photography, retinal optical coherence tomography and MP-3 were performed 1 week before, 1 and 4 months after the operation. In MP-3 examination, a customized follow-up pattern with 45 spots in the central 8° visual field was used. The spots corresponding to the retina surrounding macular holes were selected for comparison of pre- and post-operative function. RESULTS: We incuded 44 eyes of 44 patients with best corrected visual acuity (BCVA) of 1.06 ± 0.40 (logMAR). All eyes achieved an anatomical success at 4 months. BCVA significantly improved at 1 month (0.53 ± 0.30, P < 0.01) and 4 months (0.31 ± 0.24, P < 0.01), respectively. Mean retinal sensitivity (MRS, dB) of the retina surrounding macular hole was 23.46 ± 3.01 dB at baseline, and significantly increased at 1 month (26.25 ± 2.31 dB, u = - 4.88, P < 0.01) and 4 months (27.14 ± 2.45 dB, t = - 6.29, P < 0.01). Patients with increased MRS are significantly younger than those with deceased MRS (59.72 ± 3.22 years vs. 65.60 ± 8.19 years, P < 0.01). After ILM peeling, the increasing extent of MRS was significantly higher in inferior and nasal retina than in superior and temporal retina at 1 and 4 months (P < 0.05). CONCLUSION: ILM peeling in normal retina will not decrease the retinal function in a short-term after surgery.

Prevalence and associations of myopia in Hong Kong primary school students.

PURPOSE: To examine the prevalence of myopia in primary school children in Hong Kong, and the risk factors for myopia development. STUDY DESIGN: A cross-sectional study. METHODS: Subjective refraction and axial length were measured in all participants. Structured questionnaire was completed by the parents to assess risk factors of myopia. RESULTS: A total of 1396 children (491 boys) from Grade 1 to Grade 6 from 4 primary schools in Sham Shui Po district of Hong Kong participated. All participants underwent non-cycloplegic refraction. The overall prevalence of myopia (spherical equivalent, SE ≤ -0.5 diopter [D]) was 37.7%, which significantly increased with age, from 13.3% at grade 1 to 54.7% at grade 6. The prevalence of moderate myopia (-3.0D < SE < -6.0D) increased from 1.6% at grade 1 to 18.2% at grade 6 and the prevalence of high myopia (SE < = -6.0 D and/or AL ≥ 26.5 mm) increased from 0.94% (7/747) in grade 1-3 students to 1.85% (12/649) in grade 4-6 students. Among the students with myopia, only 23.6% of the parents knew their children had refractive errors and only 19.8% of the children wore glasses. Multivariate logistic regression analysis showed myopia development was significantly associated with older age (OR = 1.36, P = 0.008), better academic ranking in class in the preceding semester (OR = 1.01, P = 0.02) and absence of routine eye check (OR = 2.70, P = 0.001). CONCLUSION: The prevalence of myopia in primary school students in Hong Kong is high. There is a low level of awareness of refractive errors among parents, and high proportion of under-correction, resulting in suboptimal vision.

Robust non-perfusion area detection in three retinal plexuses using convolutional neural network in OCT angiography.

Non-perfusion area (NPA) is a quantitative biomarker useful for characterizing ischemia in diabetic retinopathy (DR). Projection-resolved optical coherence tomographic angiography (PR-OCTA) allows visualization of retinal capillaries and quantify NPA in individual plexuses. However, poor scan quality can make current NPA detection algorithms unreliable and inaccurate. In this work, we present a robust NPA detection algorithm using convolutional neural network (CNN). By merging information from OCT angiograms and OCT reflectance images, the CNN could exclude signal reduction and motion artifacts and detect the avascular features from local to global with the resolution preserved. Across a wide range of signal strength indices, and on both healthy and DR eyes, the algorithm achieved high accuracy and repeatability.

Silencing of GAS5 Alleviates Glaucoma in Rat Models by Reducing Retinal Ganglion Cell Apoptosis.

Retinal ganglion cells (RGCs) play a key role in the pathogenesis and development of glaucoma. The present study aims to investigate the underlying mechanism of long noncoding RNA growth arrest-specific transcript 5 (GAS5) in glaucoma development through regulating the apoptosis of RGCs. Rat models of chronic glaucoma were successfully established by translimbal laser photocoagulation. Retinal tissues were collected to determine the density of RGCs through Toluidine blue staining. The overexpression vector or short hairpin RNA for GAS5 or enhancer of zeste homolog 2 (EZH2) was transfected into RGCs after in vitro pressurization culture to examine the function of GAS5 in RGC apoptosis. The involvement of EZH2 and ATP-binding cassette transporter A1 (ABCA1) was further identified. Cell apoptosis after laser treatment and transfection was assessed by flow cytometry. We found abundant GAS5 expression and a reduction in RGC density in the retinal tissues of glaucoma rats. Silencing of GAS5 led to increased EZH2 expression and decreased ABCA1 expression in RGCs. In addition, upregulation of EZH2 promoted trimethylation of lysine 27 on histone H3, thereby suppressing ABCA1 expression and eventually leading to the inhibition of RGC apoptosis. These findings provide further understanding of the function of GAS5 in RGC apoptosis. We conclude that downregulation of GAS5 could help relieve glaucoma symptoms. GAS5 is therefore a promising target for developing novel therapeutic approaches for treating patients with glaucoma.

Detecting and measuring areas of choriocapillaris low perfusion in intermediate, non-neovascular age-related macular degeneration.

Age-related macular degeneration (AMD) is a vision-threatening disease that affects the outer retina and choroid of elderly adults. Because photoreceptors are found in the outer retina and rely primarily on the trophic support of the underlying choriocapillaris, imaging of flow or lack thereof in choriocapillaris by optical coherence tomography angiography (OCTA) has great clinical potential in AMD assessment. We introduce a metric using OCTA, named "focal perfusion loss" (FPL) to describe the effects of age and non-neovascular AMD on choriocapillaris flow. Because OCTA imaging of choriocapillaris is vulnerable to artifacts-namely motion, projections, segmentation errors, and shadows-they are removed by postprocessing software. The shadow detection software is a machine learning algorithm recently developed for the evaluation of the retinal circulation and here adapted for choriocapillaris analysis. It aims to exclude areas with unreliable flow signal due to blocking of the OCT beam by objects anterior to the choriocapillaris (e.g., drusen, retinal vessels, vitreous floaters, and iris). We found that both the FPL and the capillary density were able to detect changes in the choriocapillaris of AMD and healthy age-matched subjects with respect to young controls. The dominant cause of shadowing in AMD is drusen, and the shadow exclusion algorithm helps determine which areas under drusen retain sufficient signal for perfusion evaluation and which areas must be excluded. Such analysis allowed us to determine unambiguously that choriocapillaris density under drusen is indeed reduced.

Genetic factors for idiopathic choroidal neovascularization.

Objective: The aim of this study was to investigate genetic factors associated with idiopathic choroidal neovascularization (ICNV). Methods: We conducted a case-control study including 69 cases with ICNV and 114 controls who underwent cataract surgery. Single nucleotide polymorphisms (SNPs) from genes reported to be related to AMD, CNV and uveitis were selected for this study. Results: In an univariate analysis, the rs669676 SNP located in the COL8A1 gene was associated with the proportion of people who has idiopathic CNV ( X2 = 9.3453, corrected p-value = 0.1). For the rs669676 SNP, minor allele homozygotes, in the dominant model of genotype analysis (GG versus AA-GA), it showed significant differences in the ICNV group vs controls (p = .01, OR = 1.219 (95%CI: 1.04-1.429)). Conclusions: The rs669676 SNP located in the COL8A1 gene may contribute to a genetic susceptibility for ICNV.

COMPARISON OF 3 MM × 3 MM VERSUS 6 MM × 6 MM OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY SCAN SIZES IN THE EVALUATION OF NON-PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: To evaluate the utility of different optical coherence tomography angiography scan protocols in evaluating retinal changes in non-proliferative diabetic retinopathy. METHODS: Patients were imaged with the RTVue XR Avanti OCT 3 mm × 3 mm and 6 mm × 6 mm "Angio Retina" scan protocols. Ability to clearly delineate the foveal avascular zone (FAZ), FAZ remodeling, microaneurysms, capillary nonperfusion, motion, and doubling artifacts were evaluated. RESULTS: Forty-six eyes from 27 patients were enrolled. Eighty-nine percent of 3 mm × 3 mm versus 59% of 6 mm × 6 mm scans clearly delineated the FAZ (P = 0.001). Eighty percent of 3 mm × 3 mm versus 43% of 6 mm × 6 mm scans demonstrated FAZ remodeling (P = 0.0002). Microaneurysms were detected by 57% of 6 mm × 6 mm and 35% of 3 mm × 3 mm scans (P = 0.003). Capillary nonperfusion was detected in 87% of 3 mm × 3 mm scans versus 89% of 6 mm × 6 mm scans (P = 0.99). No significant differences were noted in the incidence of artifacts between the scan sizes (motion artifact P = 0.29 and doubling artifact P = 0.29). CONCLUSION: 3 mm × 3 mm scan delineated FAZ and remodeling better than 6 mm × 6 mm scan, likely because of its higher scan density. 6 mm × 6 mm scans detected microaneurysms more readily than 3 mm × 3 mm, likely because of its larger scan area. There were utility for both 3 mm × 3 mm and 6 mm × 6 mm scans when evaluating these patients.

A novel deletion mutation, c.1296delT in the BCOR gene, is associated with oculo-facio-cardio-dental syndrome.

The purpose of the present study was to analyze the clinical phenotypes of a girl with oculo-facio-cardio-dental (OFCD) syndrome and to identify the potential pathogenic mutation responsible for her disease. The patient underwent detailed clinical examinations and phenotype data were collected over a follow-up period of 9 years. Mutation analysis of the candidate gene BCOR was performed with polymerase chain reaction and Sanger sequencing. BCOR of 60 unrelated normal individuals were also sequenced as a control group. Clinical phenotyping and follow-up study results indicate that this patient had multiple system anomalies including ocular, facial, cardiac, dental, and limb malformations. In addition, papilloma of the choroid plexus was identified, which represents the first report of this phenotype in an OFCD patient. A novel deletion mutation, c.1296delT in exon 4 of the BCOR gene, was identified in this patient and was not found in her parents or in 60 normal unrelated individuals. This deletion was a frameshift mutation and is proposed to encode a premature stop codon, thus producing a truncated protein. Our patient fitted the diagnostic criteria for OFCD syndrome and we report the first papilloma of the choroid plexus in an OFCD patient, expanding the recognized phenotypic spectrum of this disease. Meanwhile, we identified a novel deletion mutation that may cause OFCD syndrome.

Tear film evaluation by scanning laser ophthalmoscopy during retinal imaging.

PURPOSE:: Herein, we describe a novel finding which appears as a reticular pattern on multicolor confocal scanning laser ophthalmoscopy image during routine imaging of retina and we aim to show whether there is an association between this pattern and dry eye findings. MATERIALS AND METHODS:: A total of 162 eyes of 81 patients that were scheduled for a routine retinal imaging by scanning laser ophthalmoscopy at a vitreoretinal practice underwent dry eye evaluation including corneal and conjunctival lissamine green staining, fluorescein staining, tear break-up time, and tear meniscus height measurement before acquiring any images. Then, multicolor images were taken and graded for the severity of reticular pattern. RESULTS:: Among 150 eyes of 81 patients with gradable multicolor imaging, 45 eyes (30%) had some reticular pattern on multicolor image. Severity of reticular pattern on multicolor imaging was significantly correlated with total lissamine score (rho = 0.378, p = 0.007) and tear meniscus height (rho = -0.408, p = 0.011). Furthermore, they were found to be the best set of predictors for the severity pattern on multicolor imaging (odds ratio = 1.30, 95% confidence interval = 1.01-1.37, p = 0.027 and odds ratio = 0.25, 95% confidence interval = 0.128-0.342, p < 0.001, respectively). CONCLUSION:: Reticular pattern seen on multicolor image while acquiring retinal images using scanning laser ophthalmoscopy may be related to tear film instability. Further modulations of the scanning laser ophthalmoscopy instrument will likely improve this indicator of dry eye syndrome.

REDUCED GANGLION CELL VOLUME ON OPTICAL COHERENCE TOMOGRAPHY IN PATIENTS WITH GEOGRAPHIC ATROPHY.

PURPOSE: Geographic atrophy (GA) is the sequelae of macular degeneration. Automated inner retinal analysis using optical coherence tomography is flawed because segmentation software is calibrated for normal eyes. The purpose of this study is to determine whether ganglion cell layer (GCL) volume is reduced in GA using manual analysis. METHODS: Nineteen eyes with subfoveal GA and 22 controls were selected for morphometric analyses. Heidelberg scanning laser ophthalmoscope optical coherence tomography images of the optic nerve and macula were obtained, and the Viewing Module was used to manually calibrate retinal layer segmentation. Retinal layer volumes in the central 3-mm and surrounding 6-mm diameter were measured. Linear mixed models were used for statistics. RESULTS: The GCL volume in the central 3 mm of the macula is less (P = 0.003), and the retinal nerve fiber layer volume is more (P = 0.02) in patients with GA when compared with controls. Ganglion cell layer volume positively correlated with outer nuclear layer volume (P = 0.020). CONCLUSION: The patients with geographic atrophy have a small significant loss of the GCL. Ganglion cell death may precede axonal loss, and increased macular retinal nerve fiber layer volumes are not indicative of GCL volume. Residual ganglion cell stimulation by interneurons may enable vision in patients with GA.