Features of Peripapillary Hyperreflective Ovoid Mass-Like Structures in Nonarteritic Anterior Ischemic Optic Neuropathy Patients and Normal Controls.

Purpose: To determine the characteristics of peripapillary hyperreflective ovoid mass-like structures (PHOMS) in patients with nonarteritic anterior ischemic optic neuropathy (NAION) and in normal adults. Methods: A total of 406 included eyes were divided into four groups: acute NAION group, chronic NAION group, unaffected group, and normal eyes group. PHOMS were detected on optical coherence tomography slices from optical coherence tomography angiography scans centered on the optic nerve head (ONH). The differences in age, sex, and ONH parameters were investigated between eyes with PHOMS and eyes without PHOMS among groups. Results: The prevalence of PHOMS in acute eyes (43.48%) and fellow eyes (28.20%) was significantly higher than that in normal eyes (11.76%) (acute vs. normal, P < 0.001; fellow vs. normal, P = 0.014). In the acute group, the PHOMS score of size was negatively correlated with age in acute eyes (r = -0.486, P = 0.03). The size of PHOMS was negatively correlated with age and cup/disc ratio and positively correlated with retinal nerve fiber layer thickness in the nasal and inferior sectors in the normal groups. No differences in age, sex, ONH parameters, or visual field defects were found between eyes with PHOMS and eyes without PHOMS. Conclusions: The prevalence of PHOMS increased significantly in acute nonoptic disc drusen (NODD)-NAION eyes and fellow eyes. PHOMS could also be found among normal adults. PHOMS may be a nonspecific sign secondary to ONH edema and axoplasmic stasis. Translational Relevance: The high prevalence of PHOMS in acute NODD-NAION eyes may indicate axoplasmic stasis secondary to tissue edema.

Quantitative analysis of retinal vasculature in normal eyes using ultra-widefield fluorescein angiography.

AIM: To quantify the area and density of retinal vascularity by ultra-widefield fluorescein angiography (UWFA). METHODS: In a retrospective study, UWFA images were obtained using an ultra-widefield imaging device in 42 normal eyes of 42 patients. Central and peripheral steered images were used to define the edge of retinal vasculature by a certified grader. The length from the center of the optic disc to the edge of retinal vascularity (RVL) in each quadrant and the total retinal vascular perfusion area (RVPA) were determined by the grader using OptosAdvance software. The density of retinal vascularity (RVD) was quantified in different zones of central-steered images using Image J software. RESULTS: Among 42 healthy eyes, the values for mean RVL in each quadrant were 19.007±0.781 mm (superior), 18.467±0.869 mm (inferior), 17.738±0.622 mm (nasal) and 24.241±1.336 mm (temporal). The mean RVPA was 1140.117±73.825 mm2. The mean RVD of the total retina was 4.850%±0.638%. RVD varied significantly between different retina zones (P<0.001), and significant differences existed in the RVD values for total retinal area in patients over 50 years old compared to those under 50 years old (P=0.033). No gender difference was found. CONCLUSION: The UWFA device can be a promising tool for analyzing the overall retinal vasculature and may provide a better understanding of retinal vascular morphology in normal eyes. Aging may be related to lower RVD.

Expression of purinergic receptors on microglia in the animal model of choroidal neovascularisation.

To investigate the effect of P2 receptor on microglia and its inhibitor PPADS on choroidal neovascularization. Forty CX3CR1GFP/+ mice were randomly divided into 8 groups. In addition to the normal group, the rest of groups were receiving laser treatment. The retina and choroid from the second, third, fourth and fifth group of mice were taken in the 1, 4, 7, 14 days after laser treatment. The mice in the sixth and seventh group received intravitreal injection of 2 µl PPADS or PBS respectively immediately after laser treatment. The mice in the eighth group received topical application of PPADS once per day of three days. The mice in sixth, seventh and eighth group received AF and FFA examination on the fourth day after laser treatment. Immunofluorescence histochemical staining and real-time quantitative PCR were used to evaluate P2 expression and its effect on choroidal neovascularization. After laser treatment, activated microglia can express P2 receptors (P2X4, P2X7, P2Y2 and P2Y12). The expression of P2 increased on the first day after laser damage, peaked on the fourth day (tP2X4 = 6.05, tP2X7 = 2.95, tP2Y2 = 3.67, tP2Y12 = 5.98, all P < 0.01), and then decreased. After PPADS inhibition, compared with the PBS injection group, the mRNA of P2X4, P2X7, P2Y2 and P2Y12 were decreased significantly in the PPADS injection group (tP2X4 = 5.54, tP2X7 = 9.82, tP2Y2 = 3.86, tP2Y12 = 7.91, all P < 0.01) and the PPADS topical application group (tP2X4 = 3.24, tP2X7 = 5.89, tP2Y2 = 6.75, tP2Y12 = 4.97, all P < 0.01). Compared with the PBS injection group, not only the activity of microglia cells but also the leakage of CNV decreased significantly (P < 0.01) in the PPADS injection group and the PPADS topical application group. But between two PPADS groups, the leakage of CNV had no difference (P = 0.864). After laser induced CNV, activated microglia can express P2 receptors. The P2 receptor inhibitor, PPADS, can significantly affect the function of microglia and inhibit the formation of choroidal neovascularization.

Observation of the far peripheral retina of normal eyes by ultra-wide field fluorescein angiography.

PURPOSE: The appearance of the far peripheral retina in normal eyes was observed using an Optos ultra-wide field fluorescein angiography imaging system. METHODS: A cross-sectional study of ultra-wide field pseudocolor and angiography images obtained using the Optos 200Tx. Four different non-vascular and six vascular-associated fluorescence features in far peripheral retina were analyzed. RESULTS: A total of 166 eyes in 83 patients met the inclusion criteria. The mean patient age was 40.78 ± 10.94 years (range: 20-65 years) with a female-to-male ratio of 0.98. Slight cataract were present in 64 eyes (38.55%), low to moderate myopia in 50 eyes (30.12%), and unspecified visual disturbances in 52 eyes (31.33%). Far peripheral retinas were found to have mottled florescent band in 42.17% eyes, ground glass hyperfluorescence in 84.34% eyes, granular hyperfluorescence in 12.65% eyes, local mottled fluorescence in 10.84% eyes, vascular anastomosis with a peripheral avascular area in 36.23% eyes, invisible capillary details in 50.67% eyes, vessels passing through the ora serrata in 16.98% eyes, late-phase slight leakage in 32.53% eyes, angiectasis in 18.67% eyes, and microaneurysm in 34.94% eyes. CONCLUSION: Ultra-wide field fluorescein angiography revealed various fluorescence features in the periphery of normal eyes, providing a basis for interpreting normal and pathological changes in peripheral retina and an important reference for clinical work.

Efficacy of Vincamine treatment in a rat model of anterior ischemic optic neuropathy.

Non-arteritic anterior ischemic optic neuropathy (NAION) is characterized by the progressive and irreversible death of retinal ganglion cells (RGCs) which is caused by the insufficient blood supply to the optic nerve (ON) head. At present, hormone therapy is used to reduce optic edema, followed by nerve nutrition therapy to protect the ON. However, no surgical or medical therapy has proven to be beneficial consistently in treating NAION. Vincamine is an alkaloid extracted from the Apocynaceae Vinca plant. Vincamine and its derivatives acting as cerebral vasodilators can easily cross the blood-brain barrier, improve the metabolism of ischemic tissue and protect the neuron. In this study, we aimed to investigate the potential neuroprotection of Vincamine in the photodynamic induced rat model of NAION (rAION), to evaluate its effects and possible mechanisms. We found that Vincamine can rescue RGC death and reduce the number of apoptotic cells. The protection of Vincamine might play through the PI3K/Akt/eNOS signaling pathway. Therefore, Vincamine can be an effective therapy method for NAION.

Correction to: Assessment of choriocapillary blood flow changes in response to half-dose photodynamic therapy in chronic central serous chorioretinopathy using optical coherence tomography angiography.

An amendment to this paper has been published and can be accessed via the original article.

Bioinformatics analysis of multi-omics data identifying molecular biomarker candidates and epigenetically regulatory targets associated with retinoblastoma.

Retinoblastoma (RB) is the commonest malignant tumor of the infant retina. Besides genetic changes, epigenetic events are also considered to implicate the occurrence of RB. This study aimed to identify significantly altered protein-coding genes, DNA methylation, microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and their molecular functions and pathways associated with RB, and investigate the epigenetically regulatory mechanism of DNA methylation modification and non-coding RNAs on key genes of RB via bioinformatics method.We obtained multi-omics data on protein-coding genes, DNA methylation, miRNAs, and lncRNAs from the Gene Expression Omnibus database. We identified differentially expressed genes (DEGs) using the Limma package in R, discerned their biological functions and pathways using enrichment analysis, and conducted the modular analysis based on protein-protein interaction network to identify hub genes of RB. Survival analyses based on The Cancer Genome Atlas clinical database were performed to analyze prognostic values of key genes of RB. Subsequently, we identified the differentially methylated genes, differentially expressed miRNAs (DEMs) and lncRNAs (DELs), and intersected them with key genes to analyze possible targets of the underlying epigenetic regulatory mechanisms. Finally, the ceRNA network of lncRNAs-miRNAs-mRNAs was constructed using Cytoscape.A total of 193 DEGs, 74 differentially methylated-DEGs (DM-DEGs), 45 DEMs, 5 DELs were identified. The molecular pathways of DEGs were enriched in cell cycle, p53 signaling pathway, and DNA replication. A total of 10 key genes were identified and found significantly associated with poor survival outcome based on survival analyses, including CDK1, BUB1, CCNB2, TOP2A, CCNB1, RRM2, KIF11, KIF20A, NDC80, and TTK. We further found that hub genes MCM6 and KIF14 were differentially methylated, key gene RRM2 was targeted by DEMs, and key genes TTK, RRM2, and CDK1 were indirectly regulated by DELs. Additionally, the ceRNA network with 222 regulatory associations was constructed to visualize the correlations between lncRNAs-miRNAs-mRNAs.This study presents an integrated bioinformatics analysis of genetic and epigenetic changes that may be associated with the development of RB. Findings may yield many new insights into the molecular biomarker candidates and epigenetically regulatory targets of RB.

Assessment of choriocapillary blood flow changes in response to half-dose photodynamic therapy in chronic central serous chorioretinopathy using optical coherence tomography angiography.

BACKGROUND: Optical coherence tomography angiography (OCTA) is a newly developed imaging quantitative technique for analysis of choriocapillaris (CC) flow changes, thereby exploring the pathological mechanism of chronic central serous chorioretinopathy (CCSC) and the therapeutic effects of photodynamic therapy (PDT). In this study, we sought to quantify the blood flow changes in CC of CCSC patients receiving half-dose PDT using OCTA. METHODS: A total of 28 affected eyes and 24 unaffected eyes of 26 CCSC patients receiving half-dose PDT, and 40 eyes of 20 healthy gender- and age-matched subjects were retrospectively enrolled in this study. The proportion of total areas of flow signal voids (FSV, %) in CC level of OCTA was assessed in both eyes of the CCSC patients at baseline and repeated in multiple sections at 1-week, 1-month, 3-month and 6-month intervals after PDT. In addition, the CC patterns in response to PDT at early stage and the subsequent morphologic changes were qualitatively documented using OCTA. RESULTS: For affected eyes, FSV at 6-m follow-up was significantly lower than that at 1-m follow-up (p = 0.036). When compared to normal control eyes, FSV in affected eyes was significantly higher at 1-m, 3-m and 6-m follow-up (p < 0.05 for all), and FSV in unaffected eyes was significantly higher at baseline, 1-w, 1-m and 3-m follow-up (p < 0.05 for all). Three CC patterns of early response to PDT were identified, including signs of recovery with more even flow signals, transient appearance of worse ischemia and secondary neovascularization within CC level. CONCLUSION: Abnormal CC flow attenuation remains in completely resolved eyes of CCSC patients treated with half-dose PDT.

Assessment of the Dynamic Alteration of Choriocapillaris Vessel Density after Focal Laser Photocoagulation with OCT Angiography.

PURPOSE: To evaluate the changes of choriocapillaris blood flow beneath laser lesions in noncenter-involved diabetic macular edema patients using optical coherence tomography angiography (OCTA). METHODS: This was a retrospective case-series study. We used OCTA to analyze the characteristics of the choriocapillaris blood flow beneath laser lesions before laser treatment and at several intervals after treatment. The choriocapillaris vessel density (CCVD) beneath the laser lesions was based on the OCTA images and was defined as the proportion of flow pixels in the selected area calculated using FIJI software through automatic binarization processing based on threshold methods. RESULTS: A total of 63 laser lesions in 8 eyes of 5 patients were included in this study. There was a significant decrease in the CCVD at 1 hour and 1 day following laser treatment (24.25% ± 5.04% and 22.00% ± 4.71%, respectively) when compared with the baseline value (39.09% ± 3.71%, all p < 0.001). The CCVD was 31.82% ± 4.53% in 1 week after laser treatment, which was significantly higher than that in 1 day after treatment (p < 0.001). The CCVD was 31.82% ± 4.53% in 1 week after laser treatment, which was significantly higher than that in 1 day after treatment (p < 0.001). The CCVD was 31.82% ± 4.53% in 1 week after laser treatment, which was significantly higher than that in 1 day after treatment (. CONCLUSIONS: OCTA image analysis can reflect changes in the choriocapillaris blood flow beneath laser lesions at different times following laser treatment in vivo. Spot size and laser energy may affect blood flow recovery.

CLINICAL APPLICATION OF MULTICOLOR IMAGING IN CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To characterize features of central serous chorioretinopathy (CSC) using multicolor (MC) imaging and to compare the efficacy of using MC imaging and traditional color fundus photography (CFP) for detecting features of CSC. METHODS: A retrospective review of 75 eyes of 69 participants with CSC from the Eye Center of the Renmin Hospital of Wuhan University. The patients underwent same-day CFP, fundus fluorescein angiography (FFA), spectral domain optical coherence tomography (SD-OCT), and MC imaging (including infrared reflectance (IR), green reflectance (GR), blue reflectance (BR), combined standard MC image, and green-blue-enhanced image). Positive CSC lesions were evaluated using FFA and SD-OCT. Features in images of CFP, standard MC, green-blue-enhanced, IR, GR, and BR were analyzed and calculated. RESULTS: Among the 75 eyes of 69 patients, 75 eyes with subretinal fluid (SRF) and retinal pigment epithelial (RPE) leakage point, and 43 eyes with RPE damage were observed by FFA and SD-OCT. The detection rate of SRF was significantly higher with the standard MC image (92.0%), green-blue-enhanced image (92.0%), IR (88.0%), and GR (88.0%) than that with CFP (66.7%) (P < 0.05). Blue reflectance (45.3%) was associated with lower rate of SRF detection compared to CFP (P < 0.05). The standard MC image (84.0%), green-blue-enhanced image (84.0%), IR (78.7%), and GR (80%) delineated the boundaries of SRF more effectively than CFP (44%). The abnormal areas corresponding to RPE leakage points on FFA were observed with the standard MC image, green-blue-enhanced image, and IR at detection rates of 90.7, 82.7, and 90.7%, respectively, which were significantly higher than with CFP (29.3%) (P < 0.05). However, the detection rates of the abnormalities corresponding to leakage on FFA were lower with GR (5.3%) and BR (1.3%) than those with CFP (P < 0.05). Areas of RPE damage on FFA were observed at the same locations with the standard MC image, green-blue-enhanced image, and IR at detection rates of 97.7, 93.0, and 95.3%, respectively, which were significantly higher than with CFP (41.9%) (P < 0.05). Compared with CFP, the detectable rates of RPE damage on GR (14.0%) and BR (9.3%) were lower (P < 0.05). CONCLUSION: As an adjunct to SD-OCT, the MC image can delineate the extent or boundaries of SRF more effectively than CFP. As an adjunct to FFA, the MC image can identify foci of leakage more effectively than CFP. The MC image, particularly the IR channel, can identify areas of RPE damage more effectively than CFP. Therefore, the MC image may be a useful adjunct to FFA and OCT for detecting or monitoring CSC.

Peripapillary and Macular Flow Changes in Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) by Optical Coherence Tomography Angiography (OCT-A).

BACKGROUND: To analyze the blood flow changes of radial peripapillary capillaries (RPCs) and macula with time procession in patients with nonarteritic anterior ischemic optic neuropathy (NAION) by optical coherence tomography angiography (OCT-A). METHODS: A total of 21 affected eyes and 19 unaffected eyes from 21 NAION patients were included. Assessments of BCVA, CFP, SD-OCT, and OCT-A were performed on NAION patients at enrollment and at 1-2 weeks, 1-2 months, and 3-6 months after enrollment. Measures of the thickness of the peripapillary retinal nerve fiber layer (wRNFL) and macular ganglion cell complex (wGCC) of the whole image in SD-OCT, vessel density of the RPC (wRPC) and superficial and deep vascular complexes (wSVD, wDVD) in the whole image of OCT-A, and their superior- and inferior-hemi values (s/iRNFL, s/iGCC, s/iRPC, and s/iSVD) were assessed. RESULTS: Compared to unaffected control eyes, wRPC (p ≤ 0.001) was significantly lower in affected eyes at baseline, and there was no significant difference in wSVD (p > 0.05). The wRPC and wSVD values of affected eyes were significantly decreased at follow-up time points of 1-2 and 3-6 months compared to baseline (p=0.001, p ≤ 0.001; p ≤ 0.001, p ≤ 0.001). The sRPC values were significantly lower than iRPC at 1-2/3-6 months (p=0.016, p=0.013), and sSVD values were lower than iSVD at 1-2 months (p=0.010). Statistically significant correlations were found between wRPC and wRNFL values at 3-6 months (r = 0.626, p=0.022), between wSVD and wGCC at 1-2 weeks and 1-2 months (r = 0.570, r = 0.436; p=0.007, p=0.048). CONCLUSION: OCT-A revealed a sectorial reduction in vessel density in the RPC and macula with the disease progression of NAION from acute to atrophic stages, a classification associated with structural deficits.