Assessment of retinal and choroidal microvasculature in night shift medical workers by OCT angiography.

This study evaluated retinal and choroidal microvascular changes in night shift medical workers and its correlation with melatonin level. Night shift medical workers (group A, 25 workers) and non-night shift workers (group B, 25 workers) were recruited. The images of macula and optic nerve head were obtained by swept-source OCT-angiography. Vessel density of retina, choriocapillaris (CC), choriocapillaris flow deficit (CC FD), choroidal thickness (CT) and choroidal vascularity index (CVI) were measured. 6-sulfatoxymelatonin concentration was analyzed from the morning urine. CC FD and CVI were significantly decreased and CT was significantly increased in group A (all P < 0.05). 6-sulfatoxymelatonin concentration was significantly lower in group A (P < 0.05), which was significantly positively correlated with CC FD size (r = 0.318, P = 0.024) and CVI of the most regions (maximum r-value was 0.482, P < 0.001), and was significantly negatively associated with CT of all regions (maximum r-value was - 0.477, P < 0.001). In night shift medical workers, the reduction of melatonin was significantly correlated with CT thickening, CVI reduction and CC FD reduction, which suggested that they might have a higher risk of eye diseases. CC FD could be a sensitive and accurate indicator to reflect CC perfusion.

Assessment of retinal and choroidal microcirculation after unilateral recession-resection surgery for horizontal strabismus by swept-source optical coherence tomography angiography.

This study explored the possible hemodynamic changes of the retina and choroid after horizontal strabismus surgery using swept-source optical coherence tomography angiography (SS-OCTA). 32 eyes of 32 patients who underwent unilateral horizontal rectus muscle recession-resection surgery were included. SS-OCTA examinations were performed preoperatively and one week postoperatively. Several OCTA measurements were used, including vessel density (VD) of the superficial vascular complex (SVC), VD of the deep vascular complex (DVC), VD of the choriocapillaris (CC), choroidal vascular index (CVI) and choroidal thickness (CT). No significant change in VD of SVC, DVC, and CC was observed whereas CT increased significantly with CVI unchanged. Recession-resection surgery for horizontal strabismus seemed not to significantly influence the microcirculation of the retina and CC in the early postoperative period. However, choroidal thickening happened with a constant CVI probably due to the postoperative inflammation. Further studies are needed to investigate the long-term effects of unilateral recession-resection surgery for horizontal strabismus on the microcirculation of the retina and choroid.

Changes in retinal and choroidal blood flow after one or two horizontal rectus muscle surgeries by optical coherence tomography angiography.

PURPOSE: To evaluate the retinal and choroidal microvasculature after one or two horizontal rectus muscle surgeries in strabismus patients using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: 30 eyes of 26 patients who underwent horizontal rectus muscle surgery were included in this study. Group A, A' and Group B , B' respectively consisted preoperative and postoperative measurements of patients who underwent one or two horizontal rectus muscle surgeries. We analyzed the vessel density (VD) of the superficial vascular complex (SVC), the deep vascular complex (DVC), the choriocapillary layer (CC), choroidal vascular index (CVI), choroidal thickness (T-Ch) and retinal nerve fiber layer thickness (T-RNFL) preoperatively, and one week postoperatively. RESULTS: Only in the nasal sector of the perifoveal zone, the VD in SVC demonstrated a significant increase in Group A' (p = 0.027). There was a statistically significant difference in the VD changes of SVC between Group A and Group B (p = 0.043). The VD in DVC did not change significantly in the whole macular compared with the preoperative. Moreover, in both Group A' and Group B', the VD in CC showed a reduction in a single sector of the parafoveal area (p < 0.05). Group A' have increased CVI in the nasal sector of the perifoveal region (p = 0.008). In addition, the T-Ch increase in the perifoveal region was more significant in Group B' than in Group A' (p < 0.05). Group A' showed statistically significant decreases in T-RNFL in the foveal and parafoveal regions (p < 0.05). CONCLUSION: This study revealed that the increase in choroidal thickness was more significant after two rectus muscle surgery. In addition, there were microvascular changes in sectional macular regions after strabismus surgery. OCTA is an excellent way to study the impact of strabismus surgery on the macular structure and blood flow.

We used SS-OCTA, which provided more objective and accurate measurements, to assess macular vessel density and thickness of retinal and choroid after one or two horizontal rectus muscle surgeries.

Role of artesunate in autoimmune diseases and signaling pathways.

Artesunate (ART) is a derivative of artemisinin. Compared with artemisinin, ART has excellent water solubility, high stability and oral bioavailability. In this review, the application of ART in classic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and ulcerative colitis is summarized. ART exhibited similar or even better efficacy than other highly effective immunosuppressive agents, such as methotrexate and cyclophosphamide. In addition, ART exerts its pharmacological effects mainly by inhibiting the production of inflammatory factors, reactive oxygen species, autoantibodies and the migration of cells to reduce damage to tissues or organs. Moreover, ART widely affected the NF-κB, PI3K/Akt, JAK/STAT and MAPK pathways to exert pharmacological effects.

A medicine called artesunate (ART), which comes from a plant, is sometimes used to treat malaria. It was first introduced by Chinese scientist Tu Youyou, who won the Nobel Prize in medicine. Autoimmune diseases (ADs) occur when the body's immune system attacks its own cells. ART has shown promise in treating ADs. ART works as well as, or even better than, other normal medicines used for ADs. ART can act in many ways and could be a promising medicine for the treatment of ADs.

Inhibition of Heat Shock Protein B8 Alleviates Retinal Dysfunction and Ganglion Cells Loss Via Autophagy Suppression in Mouse Axonal Damage.

Purpose: Heat shock protein B8 (HspB8) can be upregulated rapidly in many pathologic processes, but its role in traumatic optic neuropathy remains unclear. In this study, we investigated the involvement of autophagy in the effects of HspB8 by using the optic nerve crush (ONC) model. Methods: Male C57BL/6J mice were intravitreally injected with recombinant adeno-associated virus type 2 (AAV2-shHspB8 or AAV2-GFP) and subsequently received ONC by a self-closing tweezers. Western blot and immunohistochemistry staining were used to evaluate the expression of HspB8. We conducted retinal flat-mount immunofluorescence to measure the quantities of retinal ganglion cells (RGCs), and full-field flash electroretinogram (ff-ERG) and optomotor response (OMR) were used to evaluate retinal function. The autophagy level was reflected by western blot, immunohistochemistry staining, and transmission electron microscope (TEM) images. We also applied 3-methyladenine (3MA) and rapamycin (Rapa) to regulate autophagy level in optic nerve injury. Results: ONC stimulated the expression of HspB8. Declines of RGCs and ff-ERG b-wave amplitudes resulting from ONC can be alleviated by HspB8 downregulation. Increased autophagy activity after ONC was observed; however, this change can be reversed by intravitreal injection of AAV2-shHspB8. Furthermore, application of autophagy inhibitor 3MA had the same neuroprotective effects as AAV2-shHspB8, as illustrated by ff-ERG and quantities of RGCs. Also, protection of AAV2-shHspB8 was compromised by the autophagy activator Rapa. Conclusions: Inhibition of HspB8 in mice optic nerve injury had neuroprotective effects, which may be derived from its downregulation of autophagy.

Enhanced Visualization of Retinal Microvasculature via Deep Learning on OCTA Image Quality.

PURPOSE: To investigate the impact of denoising on the qualitative and quantitative parameters of optical coherence tomography angiography (OCTA) images of the optic nerve and macular area. METHODS: OCTA images of the optic nerve and macular area were obtained using a Canon-HS100 OCT device for 48 participants (48 eyes). Multiple image averaging (MIA) and denoising techniques were used to improve the quality of the OCTA images. The peak signal-to-noise ratio (PSNR) as an image quality parameter and vessel density (VD) as a quantitative parameter were obtained from single-scan, MIA, and denoised OCTA images. The parameters were compared, and the correlation was analyzed between different imaging protocols. RESULTS: In the optic nerve area, there were significant differences in the PSNR and VD in all measured regions between the three groups (P < 0.0001). The PSNR of the denoised group was significantly higher than that of the other two groups (P < 0.0001). The VD in the denoised group was significantly lower than that in the single-scan group in all measured regions (P < 0.0001). In the macular area, there were significant differences in the PSNR and VD in all measured regions among the three groups. The PSNR of the denoised group was significantly higher than that of the other two groups (P < 0.0001). The VD in the denoised group was significantly lower than that in the single-scan group in all measured regions. The VD around the optic nerve in the denoised group was correlated with that in the single-scan group (R = 0.9403, P < 0.0001), but the VD in the MIA group was not correlated with that in the single-scan group (R = 0.2505, P = 0.2076). The VD around the fovea in the denoised and MIA images was correlated with that in the single-scan group (R = 0.7377, P < 0.0001; R = 0.7005, P = 0.0004, respectively). CONCLUSION: Denoising could provide an easy and quick way to improve image quality parameters, such as PSNR. It shows great potential in improving the sensitivity of OCTA images as retinal disease markers.

Retina Vascular Perfusion Dynamics During Exercise With and Without Face Masks in Healthy Young Adults: An OCT Angiography Study.

Purpose: To determine possible impacts on retinal microvasculature in healthy young adults during exercise with a face mask, using optical coherence tomography angiography (OCTA). Methods: Twenty-three healthy participants (23 eyes, 17 women and 6 men) performed the incremental continuous running test (ICRT) with different masks. OCTA of the macula and optic nerve head were performed before and after ICRT to detect changes in retinal vessel density (VD). All participants were in groups A, B, and C (before ICRT) and groups A', B', and C' (after ICRT), which comprised data from volunteers without a mask, with a surgical mask, and with an N95 mask, respectively. Results: Before ICRT, group C showed significantly reduced VD in the superficial plexus (SP), except foveal VD, compared with group A (P < 0.05). After ICRT, groups B' and C' showed significantly shorter maximum running time, lower oxygen saturation, and lower perifoveal VD of SP compared with group A' (P < 0.05). Conclusions: Use of an N95 mask reduced VD in SP even under quiescent conditions, which might have clinical implications for protecting healthy workers and indoor manual labor workers from potential risks of retinal damage due to long-term mask use. Moreover, mask use while exercising might lead to attenuated exercise ability and lower VD in SP, which should be investigated in additional studies. Translational Relevance: Retina vascular perfusion dynamics could be monitored in vivo by OCTA, which would be valuable to study physiologic retinal blood flow redistribution and potential impacts on retinal vascular perfusion during exercise with face masks.

Krüppel-like factor 7 protects retinal ganglion cells and promotes functional preservation via activating the Akt pathway after retinal ischemia-reperfusion injury.

OBJECTIVE: The purpose of this study is to investigate the effects of Krüppel-like factor 7 (KLF7) on retinal ganglion cells (RGCs) and retinal function after retinal ischemia-reperfusion (RIR) injury in mice. METHODS: Male C57BL/6J mice were intravitreally injected with recombinant adeno-associated vectors (rAAV-KLF7-EGFP or rAAV-EGFP), and subsequently used to induce RIR injury. Retinal cryosections were used to access the efficacy of virus transfection, 1, 2, 3, and 4 weeks after rAAV-KLF7-EGFP transfer. RGCs survival rate was observed and quantified by immunofluorescent staining, 7 days after RIR injury. Meanwhile, electroretinogram (ERG) and optomotor response were used to evaluate the electrophysiological functions and visual acuity. Apoptosis was evaluated by TUNEL staining 1 day after RIR injury. Expression of KLF7, Akt, phospho-Akt, Bcl-2, and Bax were further detected by western blot to excavate the underlying mechanism. RESULTS: The transfection efficiency of rAAV-KLF7-EGFP was increased in a time-dependent manner, and the number of EGFP-positive cells was increased significantly 3 weeks after rAAV-KLF7-EGFP transfer. RGCs survival rates, amplitudes of ERG a-, b-wave, Ops, PhNR, and visual acuity of mice were decreased after RIR injury. With the increase of light intensity, the amplitudes of scotopic ERG a- and b-wave were gradually increased while the incubation period was gradually shortened. RGCs survival rates, amplitudes of ERG a-, b-wave, Ops, PhNR, and visual acuity of mice were increased after rAAV-KLF7-EGFP transfer. The protein level of KLF7 was up-regulated after rAAV-KLF7-EGFP transfer. Up-regulation of KLF7 significantly inhibited cells apoptosis, increased phospho-Akt and Bcl-2 expression, and decreased Bax expression. There were no significant changes in Akt expression. CONCLUSION: Overexpression of KLF7 can not only prevent the loss of RGCs, but also preserve the electrophysiological function. In addition, overexpression of KLF7 can ameliorate the retinal dysfunction after RIR injury, and ultimately improve the visual acuity of mice. The activation of Akt pathway and the suppression of the mitochondrial apoptotic pathway contribute to the neuroprotection of KLF7.

Retinal Microvascular Changes in Hypertensive Patients with Different Levels of Blood Pressure Control and without Hypertensive Retinopathy.

PURPOSE: To determine possible correlations between different levels of blood pressure (BP) control and retinal microvascular changes in the macula and optic nerve head, using coherence tomography angiography (OCTA) in hypertensive patients without hypertensive retinopathy. METHODS: This was an observational, cross-sectional study. Seventy-three patients and 40 healthy volunteers were included in this study. The patients and volunteers were divided into four groups and from each participant one eye was selected randomly: Group A comprised 32 hypertensive patients with intensive BP control; Group B comprised 26 hypertensive patients with standard BP control; Group C comprised 15 hypertensive patients with poor BP control; Group D comprised 40 control subjects. 6 × 6 mm macula scan and 4.5 × 4.5 mm optic nerve head scan were obtained using OCTA. RESULTS: In macula scans, most measured regions of retinal VD showed significant reduction in group C, compared to groups A, B, and D (all P < .05). Partial measured regions of retinal VD were significantly lower in group B than groups A and D (all P < .05). In ONH scans, RNFL thickness and inside disc capillary density were significantly thinner and lower in groups B and C than in group D (all P < .05). SBP was significantly correlated with RNFL thickness (R = 0.430, 95% CI -0.583 to -0.201, P ≤ 0.001). CONCLUSIONS: We demonstrated that the frequency of OCTA follow-up may improve detection of reduced retinal VD, thus avoiding further retinal damage in hypertensive patients; however, the clinical implications of this finding deserve further study. Moreover, further exploration is needed regarding the implication that reduced SBP may be beneficial for lowering the risk of glaucoma.

Use of optical coherence tomography angiography for assessment of microvascular changes in the macula and optic nerve head in hypertensive patients without hypertensive retinopathy.

PURPOSE: To compare optical coherence tomography angiography (OCTA) screening parameters of the macula and optic nerve head (ONH) between healthy volunteers and chronic hypertensive patients without hypertensive retinopathy. METHODS: This was an observational, cross-sectional study. Fifty-seven chronic hypertensive patients without hypertensive retinopathy (22 men and 35 women) and 40 healthy volunteers (17 men and 23 women), ranging in age from 60 to 70 years, were included in this study. Patients and volunteers were divided into three groups and one eye was selected randomly from each participant. Group A comprised patients who had a history of hypertension for >10 years (n = 35); Group B comprised patients who had a history of hypertension for 5-10 years (n = 22); and Group C comprised 40 healthy volunteers who had no history of hypertension. A 3 × 3-mm macula scan and a 4.5 × 4.5-mm ONH scan were performed in each group by OCTA using prototype AngioVue software within the AngioVue device. Vessel density (VD), foveal avascular zone (FAZ) area, choriocapillaris flow area, ONH capillary density, retinal nerve fiber layer (RNFL) thickness, and demographic information were compared among the groups. RESULTS: Macula scans showed that superficial plexus VD was significantly lower in groups A and B than in group C (P < 0.05). In addition, FAZ area was significantly larger in group A than in group C (P < 0.05). Inner retinal layer thickness was significantly thinner in groups A and B than in group C (P < 0.05). In ONH scans, RNFL thickness was significantly thinner in group A than in groups B and C (P < 0.05); it was significantly thinner in group B than in group C (P < 0.05). Inside disc capillary density and peripapillary capillary density were significantly lower (P < 0.05) and greater (P < 0.05), respectively, in groups A and B than in group C. CONCLUSIONS: Superficial plexus VD, FAZ area, capillary density, and inner retinal thickness changed significantly in hypertensive patients without hypertensive retinopathy. However, only RNFL thickness was significantly thinner in patients who had >10 years of hypertension, compared to patients who had 5-10 years of hypertension. In addition, OCTA provided a method to prospectively assess changes in retinal microvasculature and thickness, thereby avoiding further long-term retinal damage in hypertensive patients.

Vagal Nerve Stimulation Attenuates Ischemia-Reperfusion Induced Retina Dysfunction in Acute Ocular Hypertension.

Purpose: The present study aimed to investigate whether cervical vagal nerve stimulation (VNS) could prevent retinal ganglion cell (RGC) loss and retinal dysfunction after ischemia/reperfusion (I/R) injury. Methods: First, rats were randomly divided into sham group (n = 4) and VNS group (n = 12). Activation of the nodose ganglia (NOG), nucleus of the solitary tract (NTS), superior salivatory nucleus (SSN), and pterygopalatine ganglion (PPG) neural circuit were evaluated by c-fos expression at 0 h after sham VNS and at 0 h (n = 4), 6 h (n = 4), 72 h (n = 4) after VNS. Secondly, rats were randomly assigned to I/R group (pressure-induced retinal ischemia for 1 h and reperfusion for 1 h in the right eye, n = 16) and I/R+VNS group (right cervical VNS for 2 h during the I/R period, n = 16). The left eye of each rat served as a control. Electroretinogram (ERG), RGC numbers, tumor necrosis factor-α (TNF-α) and vasoactive intestinal polypeptide (VIP) levels in retina were determined. Additionally, the level of VIP in PPG was evaluated. Results: In the first part of the study, compared with the sham group, the VNS group exhibited significantly increased expression of c-fos in NOG, NTS, SSN, and PPG tissues at 0, 6, and 72 h. In the second part of the study, compared with left eyes, retinal function in right eyes (as assessed by the a-wave, b-wave and the oscillatory potential amplitudes of ERG and RGC data) was significantly decreased by I/R. The decreased retinal function was attenuated by VNS. In addition, I/R induced an increase in inflammation, which was reflected by elevated TNF-α expression in the retina. VNS significantly attenuated the increase in I/R-induced inflammation. Moreover, VIP expression in the retina and PPG, which may contribute to the inhibition of the inflammatory response, was significantly increased after VNS. Conclusion: VNS could protect against retinal I/R injury by downregulating TNF-α. Upregulation of VIP expression due to activation of the NOG-NTS-SSN-PPG neural circuit may underlie to the protective effects of VNS.