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3D bioprinting is a major area of interest in health sciences for customized manufacturing, but lacks specific bioinks to enhance the shape fidelity of 3D bioprinting and efficiency of tissue repair for particular clinical purposes. A naringin derived bioink, which contains 1.5 mM methylacryloyl naringin and 0.15 mM methylacryloyl gelatin, improves the fidelity of 3D bioprinting due to 405 nm light absorption of methylacryloyl naringin. The naringin derived bioink promotes the growth of chondrocytes due to preserving bioactivities of naringin and functions as a medical ingredient from which it has been described as a medical bioink in this study. It facilitates cartilage regeneration by upregulating the transcription of chondrogenesis-related genes like

Purpose To apply propensity score matching to evaluate the impact of peripapillary staphylomas (PPS) on vascular and structural characteristics in the myopic eyes. Methods This was a prospective, cross-sectional study. Forty-one control eyes and 41 eyes with PPS were analyzed. The eyes were selected using propensity score matching analysis based on the age and axial length. All subjects underwent ophthalmologic examinations for assessing vessel and structure parameters using swept-source optical coherence tomography (SS-OCT), OCT angiography, color fundus photography, and ocular biometry. Results As compared with control eyes, the eyes with PPS had shallower anterior chamber depth (3.61 ± 0.24 mm vs 3.77 ± 0.24 mm, P = 0.004), higher intraocular pressure (IOP) (16.59 ± 2.88 mmHg vs 14.53 ± 2.45 mmHg, P = 0.002), and higher myopic spherical equivalent (− 11.52 ± 3.22D vs − 9.88 ± 2.20D, P = 0.009). while corneal curvature and lens thickness between the two groups were not statistically different. Compared with control eyes, increased macular deep vessel density, reduced macular choriocapillaris and radial peripapillary capillary, and thinning retinal layer, ganglion cell complex, choroidal layer as well as the superior and inferior peripapillary retinal nerve fiber layer were observed in eyes with PPS, apart from larger disc area, parapapillary atrophy area, and degree of disc rotation. Logistic regression analysis revealed that the IOP (P = 0.046), disc rotation (P = 0.003), and average peripapillary choroidal thickness (P = 0.009) were associated with the presence of PPS. Conclusion Close association of PPS with exacerbation of myopia and anatomical alterations was observed which not only affected the eye posterior segment but also the anterior segments. We further identified significant reductions in the radial peripapillary capillary and macular choroidal perfusion with the increase in macular deep retinal flow blood of myopic eyes with PPS. Higher IOP, thinner peripapillary choroidal thickness, and rotated optic disc were risk factors for the presence of PPS.

High myopia is of worldwide concern due to its high prevalence, and myopia is an independent risk factor for glaucoma. The purpose of this paper is to review the mechanism and clinical manifestations of optic disc tilt and rotation in high myopia and its relationship with glaucoma, to provide clues for monitoring fundus changes in high myopia and the early diagnosis of high myopia with glaucoma.

Objective To analyze the rates of blindness with the demographics and clinical characteristics of patients with primary angle-closure disease (PACD) to provide a comprehensive epidemiologic reference in China. Methods A retrospective analysis was conducted in the Chinese Glaucoma Study Consortium database, which is a national multicenter glaucoma research alliance of 111 hospitals participating between December 21, 2015 and September 9, 2018. The diagnosis of PACD was made by qualified physicians through examination. Comparison of sex, age, family history, subtypes of PACD, and blindness were analyzed. Results A total of 5762 glaucoma patients were included, of which 4588 (79.6%) had PACD. Of PACD patients, 72.1% were female with the sex ratio (F/M) of 2.6, and the average age of patients was 63.8±9.3 years with the majority between 60 and 70 years. Additionally, 30% of these patients had low vision in one eye, 8.8% had low vision in both eyes, 1.7% had blindness in one eye, and 0.3% had blindness in both eyes. There were statistical differences with regards to age between male and female patients with PACD, with male patients being older on average. Primary angle-closure glaucoma was more commonly diagnosed in males (60%) compared to females (35.9%), whereas acute primary angle closure (APAC) was more commonly diagnosed in females (54.3%) compared to males (37.7%). The visual acuity in APAC patients was lower and the rate of low vision and blindness was higher than other subtypes. Conclusion PACD was the major type of glaucoma in Chinese hospitals. There were more female patients with PACD, mostly between 60 and 70 years old, with higher rates of APAC in women. APAC resulted in the worst visual outcomes of all PACD subtypes.

Purpose To identify the potential genes in human trabecular meshwork (TM) related to primary open-angle glaucoma (POAG). Methods First, long noncoding RNA (LncRNA) and mRNA expression profiles in TM samples from 4 control subjects and 4 POAG patients were accessed by microarray analyses. Then, twenty lncRNAs were validated by real-time quantitative PCR in the same samples from microarray analyses. Finally, eight highly expressed lncRNAs were further tested by real-time quantitative PCR in TM from 8 normal controls and 19 POAG patients. Expression data were normalized and analyzed using the R software. Pathway analyses were performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Results A total of 2179 lncRNAs and 923 mRNAs in the TM of POAG patients were significantly upregulated, and 3111 lncRNAs and 887 mRNAs were significantly downregulated. ENST00000552367, ENST00000582505, ENST00000609130, NR_029395, NR_038379, and ENST00000586949 expression levels were significantly higher in the TM from a different cohort of POAG patient than normal controls. Conclusion ENST00000552367, ENST00000582505, ENST000006091- 30, NR_029395, NR_038379, and ENST00000586949 may play essential roles in the development of POAG.

The study is aimed to investigate that the IL-22/IL-22RA1 signaling pathway regulates scar formation. A total of 31 glaucoma patients who had been previously treated with trabeculectomy surgery and the intraocular pressure was uncontrollable because of scarring and 19 strabismus patients as control patient group. ELISA showed that the IL-22 content of serum from glaucoma patients was 29.80±5.1 ng/μl which is higher than that 5.21±0.9 ng/μl from healthy group significantly. Serum from patients was used to incubate human Tenon’s capsule fibroblasts (HTFs) cells and IL-22 antibody rescued the effect of IL-22 on the biological functions. qPCR and western blot result showed that IL-22 mediates the biological function of HTFs cells via binding IL-22RA1 directly. When transfection of siR-IL-22RA1 or IL-22RA1 gene, the HTFs cells shown significantly anti-fibrosis or pro-fibrosis separately. By using STAT3 inhibitor BAY in IL-22RA1 overexpression group, IL-22-induced proliferation were reduced in HTFS cells. IL-22 promoted fibroblasts cell proliferation and α-SMA via IL-22/IL-22RA1/STAT3 signaling pathway, thereby potentially regulating glaucoma filtration trace fibrosis. This results also show the novel factor in process of postoperative scarring.Summary StatementThe present study suggested that IL-22 expression in glaucoma patient after surgery. IL-22/IL-22RA1 signaling pathway promoted fibroblasts cell proliferation and α-SMA by activating the STAT3 signaling pathway, thereby potentially regulating glaucoma filtration trace fibrosis.

Increasing evidence indicates that improving ocular blood flow (OBF) can be a therapeutic direction for glaucoma therapy. Tafluprost, a prostaglandin analogue which lowers the intraocular pressure (IOP), has been shown to improve OBF in animals and humans. Several animal experiments showed that topical tafluprost significantly increased optic nerve head and retinal blood flow. Clinical trials also showed a beneficial effect of tafluprost on optic nerve head and macula blood flow, and a good ocular pulse amplitude-lowering effect. But, there are still a few conflicting results. Overall, tafluprost seems to have a beneficial effect on OBF, and the positive effect is probably independent from its IOP-lowering effect, which also is expected to improve OBF. Moreover, reducing the intracellular free Ca

Objective Retinal vessel morphological parameters are vital indicator for early diagnosis of ophthalmological diseases and cardiovascular events. However, segmentation performance is highly influenced by elusive vessels, especially in low-contrast background and lesion regions. In this work, we present an end-to-end synthetic neural network to strengthen elusive vessels segmentation capability, containing a symmetric equilibrium generative adversarial network (SEGAN), multi-scale features refine blocks (MSFRB), and attention mechanism (AM). Method The proposed network is superior in detail information extraction by maximizing multi-scale features representation. First, SEGAN constructs a symmetric adversarial architecture in which generator is forced to produce more realistic images with local details. Second, MSFRB are devised to optimize the feature merging process, thereby maximally maintaining high resolution information. Finally, the AM is employed to encourage the network to concentrate on discriminative features. Results On public dataset DRIVE, STARE, CHASEDB1, and HRF, we evaluate our network quantitatively and compare it with state-of-the-art works. The ablation experiment shows that SEGAN, MSFRB, and AM both contribute to the desirable performance. Conclusion: The proposed network outperforms the existing methods and effectively functions in elusive vessels segmentation, achieving highest scores in Sensitivity, G-Mean, Precision, and F1-Score while maintaining the top level in other metrics. Significance: The satisfactory performance and computational efficiency offer great potential in clinical retinal vessel segmentation application. Meanwhile, the network could be utilized to extract detail information in other biomedical image computing.

Objective To investigate the microvasculature and structural characteristics of the eyes of myopic patients and their association with posterior staphyloma (PS). Methods This was a retrospective, case-control study comprising of 106 eyes from 72 individuals. Using 1:1 matching of axial length (AL) of their eyes, patients were allocated into a PS group or no posterior staphyloma (NPS) group. All patients were examined using ultra-widefield fundus imaging, optical coherence tomography angiography, and ocular biometry to acquire microvasculature and microstructure parameters. Results The anterior chamber depth (ACD) of the PS group was significantly different from that of the NPS group (3.56 mm vs 3.76 mm, P < 0.001), as was 1ens thickness (3.72 mm vs 3.57 mm, P = 0.005) and spherical equivalent (SE)(-10.11D vs -8.80D, P = 0.014). The PS group had reduced choriocapillaris flow, subfoveal choroidal thickness (SFCT), and a thinner retinal layer compared with the NPS group. No difference in retinal blood flow between the two groups was observed. The PS group exhibited a smaller disc area (15082.89 vs 17,043.32, P = 0.003) and angle α between temporal retinal arterial vascular arcades (113.29°vs 128.39°, P = 0.003), a larger disc tilt ratio (1.41 vs 1.24, P < 0.001) and parapapillary atrophy (PPA) area (13840.98 vs 8753.86, P = 0.020), compared with the NPS group. Multivariate regression analysis indicated that disc tilt ratio (P = 0.031) and SFCT (P = 0.015) were significant predictors of PS. In addition, PS (P = 0.049), AL (P = 0.003), corneal refractive power (P < 0.001), ACD (P = 0.022), relative lens position (P = 0.045), and disc area (P = 0.011) were significant predictors of SE. Conclusions PS was found to be closely linked to a reduction in choriocapillaris perfusion and anatomical abnormalities including posterior and anterior segments. Furthermore, PS exacerbated the progression of myopia.

Objective. Elevated intraocular pressure (IOP) has significant impacts on different stages in the progression of chronic glaucoma. In this study, we investigated changes in the material properties of sclera and lamina cribrosa (LC) in a nonhuman primate model with elevated IOP. Methods. Normal adult Tibetan macaques were selected for the construction of elevated IOP model. After 40 days of stable maintenance on the ocular hypertension, the binocular eyeballs were obtained for the measurement of macroscopic parameters of the eyeballs. Posterior scleral tissue strips were obtained in circumferential and axial directions, and thickness was measured, respectively. Biomechanical parameters were obtained with stress relaxation, creep, and tensile test. The nanoindentation test was performed on the LC and scleral tissue around optic nerve head (ONH) to obtain compressive modulus. Results. In the presence of elevated IOP, variations of the axial diameter of the eyeball were greater than those of the transverse diameter, and the mean scleral thickness around ONH was smaller in the experimental group than control group. The elastic modulus and stress relaxation modulus of sclera were larger, and the creep rate was lower in the experimental group than control group. In the control group, the elastic modulus and stress relaxation modulus of the circumferential sclera were larger in the axial direction, and creep rate was smaller. In the experimental group, there was no significant difference in biomechanical characteristics between the two directions. Compared to the control group, the compression modulus of the LC was smaller, and the compression modulus of sclera around ONH was larger in the experimental group. Conclusion. Elevated IOP alters the viscoelasticity and anisotropy of sclera and LC. These may contribute to reduction of the organizational resistance to external forces and decline in the ability of self-recovery.

Purpose: Using optical coherence tomography (OCTA) and flash electroretinography (F-ERG), we investigated changes to the retinal micromorphology and the overall function of the retina in eyes with different degrees of high myopia. Design: Case-control study. Participants: A total of 64 cases of 118 eyes with axial high myopia with diopters ranging from -−6.0 D to −15.0D were included in the study. The individuals were 18-40 years old.Methods: Subjects were divided into three groups according to the axial length (AL) of the eye and the spherical equivalent (SE)of the lens: the high myopia group (AL: ≤26 mm and SE: −6.0D to −9.0D) with 32 eyes, the ultra-high myopia group (AL: 26-28 mm and SE: -9.25D to -12.0D) with 43 eyes, and the extremely high myopia group (AL: ≥28 mm and SE: −12.25D to −15.0D) with 43 eyes. We used the OCTA measurements macular foveal retinal thickness (MRT), foveal avascular zone (FAZ), and superficial macular and deep retinal microvascular density, and the F-ERG measurements retinal dark-adaptation a-wave and b-wave, oscillation potential (OP) wave, light adaptation a-wave and b-wave, and 30-Hz flicker light amplitudes, which represent the functional state of the retina.Results: The differences in retinal thickness in the macular area between the three groups were only statistically significant within 1 mm of the fovea (P = 0.006). MRT was positively correlated with AL (r = 0.278, P = 0.002) and negatively correlated with SE (R = −0.200, P = 0.031). The difference in the FAZ area between the three groups was also statistically significant (P = 0.036), and FAZ was negatively correlated with AL (r = −0.377, p < 0.001) and positively correlated with SE (r = 0.192, P < 0.5). Both the superficial and deep blood flow density of the macular fovea were positively correlated with AL (p < 0.001). The superficial parafoveal blood flow density was negatively correlated with AL (r = −0.280, P = 0.002) but positively correlated with SE (R = 0.254, P = 0.006). The overall blood flow density of the deep retina, the parafoveal blood flow density, and the blood flow density around the fovea were negatively correlated with AL (p < 0.001) and positively correlated with myopic SE (p < 0.001). The dark-adaptation b-wave, maximum comprehensive response a-wave and b-wave, OP wave, bright-adaptation a-wave and b-wave, and 30-Hz flicker amplitudes of the retina were negatively correlated with AL and positively correlated with SE. The amplitudes of light adaptation a-wave and b-wave were[1] negatively correlated with the foveal avascular density (p < 0.001), and the average amplitude of the OP wave was positively correlated with the superficial retinal avascular density (p < 0.001).Conclusions: Before obvious pathological changes or central vision damage, the morphology and function of the macular area show subtle changes in patients with high myopia. As the degree of myopia increases and the axis of the eye increases, the activity of the cone cells in high myopia eyes decreases and the microvascular circulation in the inner retina and function of inner layer cells, such as non-proa cells, are affected. The changes of retinal dark adaptation are more sensitive than those of bright adaptation, which indicates that retinal rod cell damage may be earlier than cone cell damage in high myopia. Therefore, we believe that the combined use of OCTA and F-ERG can help in the early diagnosis and monitoring of patients at a high risk of myopia and to guide their clinical treatment.Because the p-value is clearly provided, the term “significantly” is not necessary (removed to reduce wordiness).

This study explored morphology and microcirculation changes of optic nerve head (ONH) in simple high myopia(SHM) and pathologic myopia(PM), in order to evaluate and identify ONH changes in the development of PM. We divided 193 right eyes of 193 patients into SHM and PM according to the retinopathy. We found that ONH is one of the earliest pathological changes in myopia, and its morphology changes were also the most obvious. PM is closely linked to the reduction of choroidal perfusion and structural changes of ONH. Microcirculation showed a significant priority changes in myopia. Further research should address whether these fndings are associated with future disease development in highly myopic eyes.

Background: Glaucoma is a group of eye diseases that can damage the optic nerve and cause vision loss. A novel technology micropulse laser trabecular plasty (MLT) can use duty-circle subvisible laser pulses to treat glaucoma. The aim of this study is to evaluate the efficacy of 360° MLT to alleviate intraocular pressure (IOP) in patients with glaucoma.Methods: This was a single-center prospective study on patients treated with 360° MLT using a Diode True-Yellow 577-nm Laser with MicroPulse technology. All the patients were recruited from the Department of Ophthalmology. Follow-up visits were carried out at 1 day, 1 week, 1 month, 3 months, 6 months, 18 months, and 36 months after the procedure. Best-corrected visual acuity (BCVA), Intraocular pressure (IOP), and vertical cup-to-disc ratio (C/D ratio) were measured during the follow-up. Repeated-measures analysis of variance (ANOVA) and Kaplan–Meier analysis were performed to evaluate the outcomes.Results: A total of 39 eyes from 26 patients were included in this study (10 men/15 women). The average age of patients was 41.47±14.39 years old, and the baseline IOP was 21.13 ± 7.75 mmHg. MLT significantly reduced the IOP at 1 day (range 15.61–19.01, P=0.0218), 3 months (range 16.47–19.22, P=0.0390), and 6 months (range 15.38–18.56, P=0.0332) compared with the baseline. However, by the end of the study, only 21.88% of patients demonstrated a ≥ 20% IOP reduction, while seven eyes needed further laser or surgical treatment. Conclusions: Micropulse laser trabeculoplasty could reduce IOP in patients with glaucoma or ocular hypertension for a short period, but its lowering efficiency was limited up to 6 months of the follow-up period.

Background Glaucoma is a group of eye diseases that can damage the optic nerve and cause vision loss. A novel technology micropulse laser trabeculoplasty (MLT) can use duty-circle subvisible laser pulses to treat glaucoma. The aim of this study is to evaluate the efficacy of 360° MLT to alleviate intraocular pressure (IOP) in patients with glaucoma. Methods This was a single-center prospective study on patients treated with 360° MLT using a Diode True-Yellow 577-nm Laser with MicroPulse technology. All the patients were recruited from the Department of Ophthalmology. Follow-up visits were carried out at 1 day, 1 week, 1 month, 3 months, 6 months, 18 months, and 36 months after the procedure. Best-corrected visual acuity (BCVA), Intraocular pressure (IOP), and vertical cup-to-disc ratio (C/D ratio) were measured during the follow-up. Repeated-measures analysis of variance (ANOVA) and Kaplan–Meier analysis were performed to evaluate the outcomes. Results A total of 39 eyes from 25 patients were included in this study (10 men/15 women). The average age of patients was 41.47 ± 14.39 years old, and the baseline IOP was 21.13 ± 7.75 mmHg. MLT significantly reduced the IOP at 1 day (range 15.61–19.01, P = 0.0218), 3 months (range 16.47–19.22, P = 0.0390), and 6 months (range 15.38–18.56, P = 0.0332) compared with the baseline. However, by the end of the study, only 21.88% of patients demonstrated a ≥ 20% IOP reduction, while seven eyes needed further laser or surgical treatment. The IOP of glaucoma patients was significantly lower than the ocular hypertension patients at 1 month (P = 0.0124), 3 months (P = 0.0004), 18 months (P = 0.0061) and 36 months (P = 0.0119). Conclusions Micropulse laser trabeculoplasty reduce IOP in patients with glaucoma or ocular hypertension for a short period, but its lowering efficiency is limited up to 6 months of the follow-up period.

Purpose: To explore the relationship between ocular position control ability and stereopsis recovery in children with intermittent exotropia, and to analyze the influencing factors of distance stereopsis recovery. Methods: In this retrospective study, 78 children with small angle intermittent exotropia received vision training for 3 months. All patients were examined for distance stereopsis with the synoptophore and for near stereopsis with the Titmus stereogram before and after the training. The patients were divided into low and high Newcastle Control Score (NCS) groups. The stereopsis of the two groups was compared. Logistic regression analysis was used to analyze the influencing factors of distance stereopsis recovery. Results: Among 78 children with intermittent exotropia, 33 had near stereopsis (42.3%) and 22 had distance stereopsis (28.2%); the difference was significant ( P < .05). After 3 months of training, there were statistically significant differences between distance and near stereopsis in the low NCS group and the high NCS group (chi-square = 7.127, P = .008; chi-square = 13.005, P < .001). The number of children with distance and near stereopsis in the low NCS group increased significantly compared with before training (chi-square = 13.471, P < .001; chi-square = 22.244, P < .001). Multivariate logistic regression analysis showed that age of onset (odds ratio [OR] = 3.768, P = .001), near point of convergence (OR = 0.347, P = .002), and NCS (OR = 0.142, P = .002) were risk factors that affected stereopsis recovery in children with small angle intermittent exotropia. Conclusions: Control ability is one of the important indicators to assess the severity of intermittent exotropia. The worse the control ability, the more difficult the recovery of stereopsis. Age of onset, near point of convergence, and NCS are risk factors that affect the recovery of distance stereopsis. [ J Pediatr Ophthalmol Strabismus . 2021;58(6):350–354.]

Glaucoma refers to a chronic disease of the eye that leads to vision loss that is irreversible, which is called ‘silent theft of sight’. Thus, an automatic glaucoma screening pipeline from optic disc (OD) localisation to glaucoma risk prediction is proposed in this study. The proposed pipeline consists of three main phases. Firstly, the OD is localised by morphological processing and sliding window methods. Secondly, a novel neural network which is in U-shape and convolutional introduces concatenating path and fusion loss function is developed to split OD and optic cup (OC) at the same time. Thirdly, both clinical measurements including optic cup-to-disc ratio (CDR), neuroretinal rim related features, and hidden features including statistical moments, entropy and energy are combined to train glaucoma classifiers. According to the results of the experiment, the proposed segmentation network achieves the best performance on both OD and OC segmentation and the proposed CDR calculation method is capable of achieving the performance similar to that of ophthalmologist on CDR measurement. Besides, the authors’ glaucoma classification model can obtain the best performance on sensitivity and area under the curve score in comparison with the existing methods.

Background:Aniridia is a congenital, panocular disease which could affect cornea, anterior chamber angle, iris, lens, retina and optic nerve. PAX6 loss-of-function mutations were the most common cause of aniridia. Mutations throughout the PAX6 gene have been linked to a range of ophthalmic abnormalities. Distinct mutations at a given site in PAX6 lead to distinctive phenotypic findings. This study aimed to characterize genetic mutations associated with congenital aniridia in a Chinese family.Methods:The proband and family underwent ophthalmologic examinations as well as exome sequencing. Results have been confirmed by Next Generation Sequencing.Results:A novel mutation(c.114_119delinsAATTTCC:p.Pro39llefsTer17)in the PAX6 gene was identified in subjectsⅡ-1, III-1 and III-2 in these family who exhibited complete aniridia and cataract. Proband and the proband’s brother also exhibited glaucoma, high myopia, and foveal hypoplasia.Conclusions：We identified a novel PAX6 frameshift heterozygous deletion mutation in a Chinese family and infered this mutation a probable cause of various eye abnormalities in carriers. Trial registration：We did not do any health-related interventions on the participants.

Background β-Zone parapapillary atrophy (β-PPA) is a common sign in patients with open-angle glaucoma (OAG). Some studies have suggested that β-PPA can aid in the diagnosis of OAG. We performed a systematic review and meta-analysis of the prevalence and diagnostic ability of β-PPA in OAG. Methods We performed a literature search in PubMed, Web of Science, Embase and Google Scholar from inception to 1st November, 2021. Both hospital-based and population-based studies that reported details of β-PPA in OAG were included. Results We screened 1404 articles from these databases and ultimately included 24 articles in our meta-analysis. The prevalence of β-PPA in OAG was 0.73 (95% CI 0.67 to 0.78). The results of subgroup analysis by country revealed prevalence rates of 0.83 (95% CI 0.78 to 0.88) in Japan, 0.85 (95% CI 0.64 to 0.97) in Korea, 0.64 (95% CI 0.55 to 0.73) in the USA, 0.61 (95% CI 0.58 to 0.63) in Germany and 0.57 (95% CI 0.39 to 0.74) in China. Fundus photography, Heidelberg retina tomography (HRT), Heidelberg retina angiography (HRA) + indocyanine green angiography (ICGA), Spectral domain optical coherence tomography (SD-OCT)and Swept source optical coherence tomography(SS-OCT) values were 0.65 (95% CI 0.58 to 0.71), 0.70 (95% CI 0.50 to 0.86), 0.78 (95% CI 0.61 to 0.91), 0.77 (95% CI 0.65 to 0.88) and 0.99(95% CI 0.87 to 1.00) respectively. The sensitivity and specificity of β-PPA as a diagnostic marker were 0.78 (95% CI 0.68 to 0.85) and 0.63 (95% CI 0.51 to 0.73), respectively. Conclusions β-PPA is a potential diagnostic marker for OAG. However, a more detailed understanding of β-PPA characteristics is needed to improve the ability to predict OAG.

Background Glaucoma is an irreversible eye disease caused by the optic nerve injury. Therefore, it usually changes the structure of the optic nerve head (ONH). Clinically, ONH assessment based on fundus image is one of the most useful way for glaucoma detection. However, the effective representation for ONH assessment is a challenging task because its structural changes result in the complex and mixed visual patterns. Method We proposed a novel feature representation based on Radon and Wavelet transform to capture these visual patterns. Firstly, Radon transform (RT) is used to map the fundus image into Radon domain, in which the spatial radial variations of ONH are converted to a discrete signal for the description of image structural features. Secondly, the discrete wavelet transform (DWT) is utilized to capture differences and get quantitative representation. Finally, principal component analysis (PCA) and support vector machine (SVM) are used for dimensionality reduction and glaucoma detection. Results The proposed method achieves the state-of-the-art detection performance on RIMONE-r2 dataset with the accuracy and area under the curve (AUC) at 0.861 and 0.906, respectively. Conclusion In conclusion, we showed that the proposed method has the capacity as an effective tool for large-scale glaucoma screening, and it can provide a reference for the clinical diagnosis on glaucoma.

Optic disc (OD) localization plays an important role in the automatic screening of ocular fundus diseases. However, it is still a challenge at present to balance the accuracy and efficiency of the OD localization for various of retinal fundus images. In this paper, we propose a new framework to integrate two classes methods based on image intensity and vascular information to obtain the OD location. The classification algorithm within the framework is based on a verification model. Firstly, an OD candidate region is obtained by image intensity. Secondly, the candidate region is validated by verification model. If the verification is passed, the corresponding position of the region is determined as the OD center. Otherwise, the OD is located by the parabola fitting of the main blood vessels and the relocation. The proposed method was evaluated on four public databases STARE, DRIVE, DIARETDB0 and DIARETDB1, and the accuracy rate was 96.3%, 100%, 100% and 100%, respectively. The running time is 0.05 s, 0.03 s, 0.13 s and 0.12 s per image through the validation in each database, while the time spent on images failed in verification is about 0.49 s, 0.38 s, 2.21 s and 2.15 s, individually.

The aim of the present study was to compare the ocular pulse amplitude (OPA) in patients with different types of glaucoma using dynamic contour tonometry (DCT), to evaluate ocular and systemic factors associated with the OPA and to verify whether OPA measured by DCT is an independent predictor for glaucoma diagnosis. A total of 217 eyes of 217 participants in the following five groups were included in this cross-sectional study: Chronic angle closure glaucoma (CACG), primary open angle glaucoma, normal tension glaucoma (NTG), suspected open angle glaucoma (SOAG) and normal control (NC). The following tests were simultaneously performed during a single visit: Intra-ocular pressure (IOP), OPA, cup-to-disk (C/D) ratio, mean damage (MD) and loss variance (LV). OPAs were compared in each group. The association between OPA and IOP, age, C/D ratio, MD and LV was detected. OPA analysis prior to and after trabeculectomy was also performed to assess its prognostic value. Among the 217 individuals, the OPA was consistent with the IOP, both measured by DCT, along with the MD and LV. Patients with CACG and SOAG had higher OPA values than those with NTG and normal controls. Compared with patients aged >30 years, the OPA was significantly lower in younger patients, while they may not have been affected by different C/D ratios. After trabeculectomy, the OPA had significantly decreased compared with the values prior to surgery. In conclusion, the present study showed that the OPA is correlated with the IOP determined by DCT. CACG and SOAG patients had higher OPA values than patients with other types of glaucoma. OPA measured by DCT may be a predictor for glaucoma diagnosis and prognosis.

Attributes of the retinal vessel play important role in systemic conditions and ophthalmic diagnosis. In this paper, a supervised method based on Extreme Learning Machine (ELM) is proposed to segment retinal vessel. Firstly, a set of 39-D discriminative feature vectors, consisting of local features, morphological features, phase congruency, Hessian and divergence of vector fields, is extracted for each pixel of the fundus image. Then a matrix is constructed for pixel of the training set based on the feature vector and the manual labels, and acts as the input of the ELM classifier. The output of classifier is the binary retinal vascular segmentation. Finally, an optimization processing is implemented to remove the region less than 30 pixels which is isolated from the retinal vascilar. The experimental results testing on the public Digital Retinal Images for Vessel Extraction (DRIVE) database demonstrate that the proposed method is much faster than the other methods in segmenting the retinal vessels. Meanwhile the average accuracy, sensitivity, and specificity are 0.9607, 0.7140 and 0.9868, respectively. Moreover the proposed method exhibits high speed and robustness on a new Retinal Images for Screening (RIS) database. Therefore it has potential applications for real-time computer-aided diagnosis and disease screening.

Noncoding RNAs (ncRNAs), including long ncRNAs (lncRNA) have manifested an important role in the pathophysiology of many diseases. Glaucoma is a primary cause of irreversible blindness worldwide. However, the involvement of lncRNAs in glaucoma remains largely unknown. Here, we performed the lncRNA expression assay based on clinical tissues and identified a specific functional lncRNA, NR_003923, and investigated its potential role in glaucoma. Knockdown of NR_003923 in human Tenon’s capsule fibroblast cells (HTFs) inhibited TGF-β-induced cell migration, proliferation, fibrosis, and autophagy. The dual luciferase reporter assay confirmed that miR-760 and miR-215-3p interacted with NR_003923. miR-760 and miR-215-3p inhibitor reversed the effects of NR_003923 and TGF-β-induced cell apoptosis. Moreover, the expression of miR-760 and miR-215-3p was decreased in glaucoma comparing with control. Furthermore, through microarray we found IL22RA1 was increased in glaucoma and both of miR-760 and miR-215-3p bound to the 3′ UTR of IL22RA1. Overexpression of IL22RA1 enhanced HTFs migration and proliferation, while miR-760 and miR-215-3p mimics reversed these promotive biological roles induced by IL22RA1. In conclusion, NR_003923 and IL22RA1 might contribute to glaucoma progression and be a novel and potential biomarkers and therapeutic targets for glaucoma.

Purpose To evaluate the potential antifibrotic effect of rosiglitazone (RSG), a peroxisome proliferator-activated receptor γ (PPARγ)-selective agonist, on subconjunctival fibrosis in a rabbit model of glaucoma filtration surgery (GFS) in vivo, and to investigate the underlying mechanisms in human Tenon's fibroblasts (HTFs) in vitro. Methods GFS were performed on adult male New Zealand white rabbits with chronic ocular hypertension previously established by injections of 2% methylcellulose into the anterior chamber. Rabbits were treated by RSG, mitomycin C (MMC) or 5-fluorouracil (5-FU) intraoperatively. The morphology of filtering blebs was evaluated by Indiana Bleb Appearance Grading Scale (IBAGS) scoring. Expression of profibrotic genes was determined by quantitative PCR, immunoblot, and/or histochemical analysis. In vitro studies were performed in a transforming growth factor (TGF)-β1-based cell model of fibrosis. Autophagy was evaluated by the formation of autophagosomes and autolysosomes using fluorescent and transmission electron microscopy and by expression of key mediators in the autophagic pathway. Results RSG treatment ameliorated a rebound intraocular pressure (IOP) elevation, prolonged the survival of filtering blebs, and attenuated subconjunctival fibrosis in rabbits following trabeculectomy. Pretreatment of HTFs with RSG inhibited TGF-β1-induced expression of profibrotic genes encoding specificity protein 1, connective tissue growth factor, and α smooth muscle actin. RSG augmented TGF-β1-induced autophagy in HTFs via a beclin1/VPS34-dependent mechanism. Augmentation of autophagy is associated with inhibition of TGF-β1-induced profibrotic gene expression by RSG. Conclusions RSG treatment prevents subconjunctival fibrosis after GFS by inhibition of profibrotic gene expression through a mechanism involved in promoting autophagy in local fibroblasts. RSG represents a novel antifibrotic drug with the potential to improve the success rate of GFS.

Purpose. This study aimed to evaluate the effects of excision on dry eye and meibomian gland dysfunction (MGD) in individuals with pterygium, before and after surgery. It also aimed to investigate how these effects correlate with the size and thickness of the pterygium. Subjects and Methods. 63 eyes from 63 patients with primary nasal pterygium and 45 eyes from 45 healthy volunteers without ocular pathologies were enrolled in this study. 63 eyes from 63 patients underwent pterygium surgery. ImageJ software was used to calculate the pterygium size based on images of the anterior segments. Anterior segment spectral domain optical coherence tomography (SD-OCT) was performed preoperatively to measure the thickness of the pterygium 1 mm anterior to the nasal scleral spur. The ocular surface disease index (OSDI), Schirmer I Test (SIT), and MGD grade were used to evaluate the eyes, and the eyes were imaged using the noninvasive keratograph average tear film breakup time (NIBUTav), tear meniscus height (TMH), meiboscore, and lipid layer grading tools of the Oculus® Keratograph 5M, preoperatively and at 1, 3, and 6 months postoperatively. Results. The OSDI, NIBUTav, lid margin abnormality, meiboscore, and lipid layer grading values differed significantly in the pterygium patients in comparison with the controls (p<0.01 for all scores). However, the SIT and TMH values were unchanged between the two groups (all p>0.05). Multivariate regression analysis demonstrated that the NIBUTav, meiboscore, and lipid layer grading score was significantly correlated with the pterygium parameters, such as size and thickness. The postoperative OSDI, NIBUTav, lid margin abnormality, and lipid layer grading values improved significantly (p<0.05 for all scores). The SIT, TMH, and meiboscore results did not differ significantly between the pre- and postoperative values (p>0.05). Among the conventional and automated indexes, at 1 month postoperatively, SIT and TMH were significantly correlated with the pterygium parameters, but no correlation was observed at 3 and 6 months postoperatively. The OSDI, NIBUTav, meiboscore, and lipid layer grading values at 1, 3, and 6 months postoperatively were significantly correlated with the pterygium parameters. Conclusion. Abnormal tear film and meibomian gland (MG) function improved following pterygium excision in the patients with primary pterygium, which was associated with uncomfortable ocular symptoms. Pterygium parameters, such as size and thickness, correlated with the dry eye and MGD indexes in patients pre- and postoperatively, potentially offering a novel strategy for clinical implementation of pterygium excision surgery.

Bruch's membrane opening (BMO) is an important biomarker in the progression of glaucoma. Bruch's membrane opening minimum rim width (BMO-MRW), cup-to-disc ratio in spectral domain optical coherence tomography (SD-OCT) and lamina cribrosa depth based on BMO are important measurable parameters for glaucoma diagnosis. The accuracy of measuring these parameters is significantly affected by BMO detection. In this paper, we propose a method for automatically detecting BMO in SD-OCT volumes accurately to reduce the impact of the border tissue and vessel shadows. The method includes three stages: a coarse detection stage composed by retinal pigment epithelium layer segmentation, optic disc segmentation, and multi-modal registration; a fixed detection stage based on the U-net in which BMO detection is transformed into a region segmentation problem and an area bias component is proposed in the loss function; and a post-processing stage based on the consistency of results to remove outliers. Experimental results show that the proposed method outperforms previous methods and achieves a mean error of 42.38 μm.