The Characteristic of Optical Coherence Tomography Angiography and Retinal Arteries Angle in Familial Exudative Vitreoretinopathy with Inner Retinal Layer Persistence.

PURPOSE: To compare the angle of retinal arteries and macular vessel density and foveal avascular zone (FAZ) in early stage familial exudative vitreoretinopathy (FEVR) patients with inner retinal layer (IRL) persistence with FEVR patients without IRL persistence and normal people. METHODS: This study enrolled 113 early stage FEVR patients and 55 age-matched normal subjects. FEVR patients were divided into IRL group and non-IRL group based on the presence or absence of IRL in fovea. The angle of superior temporal and inferior temporal branch retinal arteries on ultra-wide-field fundus images were measured. Superficial and deep vessel density of whole image, fovea and parafovea, the area and perimeter of FAZ, A-circularity index (AI, perimeter/standard circle perimeter with equal area) and vessel density around the 300-µm width of the FAZ (FD), central macular thickness (CMT) on 3 mm × 3mm OCTA were measured. RESULTS: 30 FEVR patients in IRL group, 83 FEVR patients in non-IRL group, 55 normal people in control group were evaluated. BCVA were worst in IRL group (p < .001). The angle of retinal arteries was smaller in FEVR groups (p < .001) and were smallest in IRL group (p < .001). Superficial and deep vessel density of whole and parafovea area in FEVR patients were significantly lower than that in normal people (p < .05), AI were biggest (p = .01) and FD were smallest in IRL group (p < .001). CMT in IRL group were thicker than non-IRL group and control group (p < .05). CONCLUSION: Worse BCVA, smaller angle of retinal arteries (more vessels traction), lower macular vessel density, smaller and more irregular FAZ and thicker CMT were observed in FEVR patients with IRL persistence even in early stage.

Clinical characteristics and mutation spectrum in 33 Chinese families with familial exudative vitreoretinopathy.

OBJECTIVE: To explore the clinical manifestations and search for the variants of six related genes (LRP5, FZD4, TSPAN12, NDP, KIF11 and ZNF408) in Chinese patients with familial exudative vitreoretinopathy (FEVR), and investigate the correlation between the genetic variants and the clinical characteristics. PATIENTS AND METHODS: Clinical data, including the retinal artery angle, acquired from wide-field fundus imaging, structural and microvascular features of the retina obtained from optical coherence tomography (OCT) and OCT angiography (OCTA) were collected from 33 pedigrees. Furthermore, mutation screening was performed. Variants filtering, bioinformatics analysis and Sanger sequencing were conducted to verify the variants. RESULTS: Twenty-one variants were successfully detected in 16 of 33 families, of which 10 variants were newly identified. The proportion of variants in LRP5, FZD4, TSPAN12, NDP and KIF11 was 38.1% (8/21), 33.3% (7/21), 19.1% (4/21), 4.8% (1/21) and 4.8% (1/21), respectively. Three new variants were considered to be pathogenic or likely pathogenic. The FEVR group tended to exhibit a smaller retinal artery angle, higher incidence of foveal hypoplasia and lower vascular density compared to the control group. Patients who harboured variants of FZD4 exhibited greater severity of FEVR than those with LRP5 variants. However, those who harboured LRP5 variants tended to possess lower foveal vascular density. CONCLUSIONS: Six known pathogenic genes were screened in 33 pedigrees with FEVR in our study, which revealed 10 novel variants. These findings enrich the clinical features and mutation spectrum in Chinese patients with FEVR, revealing the genotype-phenotype relationship, and contributing to the diagnosis and treatment of the disease.Key messagesWe identified 21 variants in 5 genes (LRP5, FZD4, TSPAN12, NDP and KIF11) associated with FEVR, 10 of which are novel (three were pathogenic or likely pathogenic).The proportion of variants was the highest for the LRP5 gene.FZD4 variants may be responsible for greater FEVR severity than LRP5 variants.

Macular density alterations in myopic choroidal neovascularization and the effect of anti-VEGF on it.

AIM: To analyse macular microvascular alterations in myopic choroidal neovascularization (mCNV) and the efficiency of anti-vascular endothelial growth factor (anti-VEGF) therapy for mCNV by optical coherence tomography angiography (OCTA). METHODS: A total of 123 patients were included in this retrospective study, divided into mCNV group, high myopia (HM) group, and normal group at the Affiliated Eye Hospital of Wenzhou Medical University from January 2017 to January 2019. Superficial vessel density, deep capillary density, foveal avascular zone (FAZ) area, A-circularity index (AI) and vessel density around the 300 µm width of the FAZ region density (FD) and the area of choroidal neovascularization (CNV) lesion (only for mCNV group) were measured on 3×3 mm2 OCTA images. FAZ area was corrected for axial length. Central macular thickness (CMT) was measured on OCT in mCNV group. Compared the parameters on OCTA of 3 groups and pre-anti-VEGF and post-anti-VEGF at 1, 2, 3, and 6mo follow-up in mCNV group. RESULTS: There were significant differences among 3 groups in superficial vessel density, deep capillary density and FD (P<0.05). FAZ area in HM group was smaller than normal group (P<0.05), but there was no significant difference between mCNV group and the other two group. AI increased in mCNV group (P<0.05). The mean CMT, area and flow area of CNV lesion decreased after treatment (P<0.05), while vessel density and FAZ didn't change. The mean CMT, area and flow area of CNV lesion statistically decreased after anti-VEGF treatment in mCNV group (P<0.05), while superficial vessel density, deep capillary density and FAZ area, AI and FD didn't change. The mean reduction ratio of lesions was 50.32% (7.07% to 100%). Lesion regression 100% was observed in 2 cases (4.88%). There was a negative correlation between the CNV lesion area and reduction ratio (r=-0.380, P=0.042) and the flow lesion area and reduction ratio (r=-0.402, P=0.030). CONCLUSION: Macular vessel density decreases, FAZ turns smaller and more irregular in mCNV eyes. Anti-VEGF therapy is efficient for mCNV without affecting vessel density and FAZ, but it is unable to completely eliminate CNV lesions in most cases. The bigger mCNV lesions have lower reduction ratio.

ULTRA-WIDE-FIELD IMAGING AND INTRAVENOUS FUNDUS FLUORESCEIN ANGIOGRAPHY IN INFANTS WITH RETINOPATHY OF PREMATURITY.

PURPOSE: To determine the feasibility of ultra-wide-field imaging and ultra-wide-field intravenous fundus fluorescein angiography (UWF-IV-FFA) in infants with retinopathy of prematurity (ROP) using Optos 200Tx. METHODS: We performed Optos 200Tx capturing on 32 premature infants (14 females) and UWF-IV-FFA with Optos 200Tx on 12 of the 32 infants between April 2017 and July 2018 at the affiliated eye hospital of Wenzhou Medical University and analyzed their fundus images. RESULTS: Ultra-wide-field color images were acquired from 32 infants (64 eyes). UWF-IV-FFA was performed successfully in 12 premature infants (24 eyes). No adverse events were observed. The ultra-wide-field Optos 200Tx color images and UWF-IV-FFA images revealed Stages 1, 2, and 3 ROP and aggressive posterior ROP. CONCLUSION: Ultra-wide-field imaging and intravenous fundus fluorescein angiography using Optos 200Tx are feasible in infants with ROP, which have the potential to screen, diagnose, and follow-up for ROP.

Automated diagnosis and quantitative analysis of plus disease in retinopathy of prematurity based on deep convolutional neural networks.

BACKGROUND: The purpose of this study was to develop an automated diagnosis and quantitative analysis system for plus disease. The system provides a diagnostic decision but also performs quantitative analysis of the typical pathological features of the disease, which helps the physicians to make the best judgement and communicate the decisions. METHODS: The deep learning network provided segmentation of the retinal vessels and the optic disc (OD). Based on the vessel segmentation, plus disease was classified and tortuosity, width, fractal dimension and vessel density were evaluated automatically. RESULTS: The trained network achieved a sensitivity of 95.1% with 97.8% specificity for the diagnosis of plus disease. For detection of preplus or worse, the sensitivity and specificity were 92.4% and 97.4%. The quadratic weighted k was 0.9244. The tortuosities for the normal, preplus and plus groups were 3.61 ± 0.08, 5.95 ± 1.57 and 10.67 ± 0.50 (104  cm-3 ). The widths of the blood vessels were 63.46 ± 0.39, 67.21 ± 0.70 and 68.89 ± 0.75 µm. The fractal dimensions were 1.18 ± 0.01, 1.22 ± 0.01 and 1.26 ± 0.02. The vessel densities were 1.39 ± 0.03, 1.60 ± 0.01 and 1.64 ± 0.09 (%). All values were statistically different among the groups. After treatment for plus disease with ranibizumab injection, quantitative analysis showed significant changes in the pathological features. CONCLUSIONS: Our system achieved high accuracy of diagnosis of plus disease in retinopathy of prematurity. It provided a quantitative analysis of the dynamic features of the disease progression. This automated system can assist physicians by providing a classification decision with auxiliary quantitative evaluation of the typical pathological features of the disease.

New grading criterion for retinal haemorrhages in term newborns based on deep convolutional neural networks.

BACKGROUND: To define a new quantitative grading criterion for retinal haemorrhages in term newborns based on the segmentation results of a deep convolutional neural network. METHODS: We constructed a dataset of 1543 retina images acquired from 847 term newborns, and developed a deep convolutional neural network to segment retinal haemorrhages, blood vessels and optic discs and locate the macular region. Based on the ratio of areas of retinal haemorrhage to optic disc, and the location of retinal haemorrhages relative to the macular region, we defined a new criterion to grade the degree of retinal haemorrhages in term newborns. RESULTS: The F1 scores of the proposed network for segmenting retinal haemorrhages, blood vessels and optic discs were 0.84, 0.73 and 0.94, respectively. Compared with two commonly used retinal haemorrhage grading criteria, this new method is more accurate, objective and quantitative, with the relative location of the retinal haemorrhages to the macula as an important factor. CONCLUSIONS: Based on a deep convolutional neural network, we can segment retinal haemorrhages, blood vessels and optic disc with high accuracy. The proposed grading criterion considers not only the area of the haemorrhages but also the locations relative to the macular region. It provides a more objective and comprehensive evaluation criterion. The developed deep convolutional neural network offers an end-to-end solution that can assist doctors to grade retinal haemorrhages in term newborns.

Factors That Influence Refractive Changes in the First Year of Myopia Development in Premature Infants.

PURPOSE: To study the development of refractive status from 36 weeks to one year of postmenstrual age and to identify factors that contribute to development of myopia, including gender, birth weight, gestational age, and retinopathy of prematurity (ROP). METHODS: Premature infants underwent full cycloplegic retinoscopy at 36 weeks, 38 weeks, 40 weeks, 42 weeks, 44 weeks, 46 weeks, 48 weeks, 3 months, 6 months, 9 months, and 12 months of postmenstrual age. The infants were grouped by gender, birth weight, gestational age, and the severity of ROP to evaluate the correlation with refractive status at each postmenstrual age. RESULTS: A total of 942 infants were recruited in this study. A total of 2716 readings were obtained. Refractive state had a hyperopic shift until 46 weeks of postmenstrual age (r = 0.42, P < 0.0001). After that, the mean spherical equivalent (SE) gradually declined (r = -0.30, P < 0.0001). Boys had lower hyperopia than girls at nine months (t = 3.10, P=0.003) and one year (t = 3.34, P=0.001) of postmenstrual age. Premature infants with ROP had a lower average SE at most of the postmenstrual ages; however, this value did not vary significantly (P > 0.05). Premature infants with severe ROP were less hyperopic than those without it at every postmenstrual age, and the average SE differed significantly at one year of postmenstrual age (t = 2.60, P=0.011). There was no significant difference between each birth weight and gestational age (P > 0.05). CONCLUSIONS: The dioptric value of premature infants within one year was generally hyperopic. Different gender, birth weight, gestational age, and ROP did not affect the overall development of refractive status. Females may have higher hyperopia at nine months of postmenstrual age. Birth weight and gestational age had little effect on change of refractive status. Severe ROP was an important contributing factor in myopia progression, which may be related to the treatment required. Further study may be carried out to understand the mechanism behind myopia progression in premature infants, including changes in refractive system parameters and emmetropization process.

The Efficacy of Intravitreal Conbercept for Chronic Central Serous Chorioretinopathy.

PURPOSE: To evaluate the efficacy and safety of conbercept for patients with chronic central serous chorioretinopathy (CSC). METHODS: A retrospective clinical study. Thirty-one patients (35 eyes) with chronic CSC were given intravitreal injections of conbercept and followed up for at least 6 months. Observed indicators included best-corrected visual acuity (BCVA), central macular thickness (CMT), and resolution of subretinal fluid (SRF). Serial changes in BCVA and CMT were analyzed by using repeated measures analysis of variance. RESULTS: During the 6-month follow-up, the mean number of injections required and performed was 1.77 ± 0.60. The logMAR BCVA was 0.48 ± 0.26 at the baseline, 0.34 ± 0.26, 0.30 ± 0.26, 0.27 ± 0.26, 0.24 ± 0.26, and 0.23 ± 0.26 at 2-week and 1-, 2-, 3-, and 6-month follow-ups, respectively (F = 27.173, P < 0.05). CMT was 313.74 ± 144.51 µm at the baseline and decreased to 263.49 ± 120.44 µm, 225.91 ± 91.98 µm, 195.77 ± 66.69 µm, 189.74 ± 65.41 µm, and 199.49 ± 81.50 µm at 2-week and 1-, 2-, 3-, and 6-month follow-ups, respectively (F = 18.093, P < 0.05). Full resolution of SRF was achieved in 8 (22.9%) eyes at 1 month, 16 (45.7%) eyes at 2 months, 22 (62.9%) eyes at 3 months, and 27 (77.1%) eyes at 6 months after the initial treatment of anti-VEGF injection. No severe adverse event was noted relevant to the therapy. CONCLUSIONS: Intravitreal injection of conbercept may effectively reduce the CMT and improve the BCVA in chronic CSC in a short term of 6 months.