Chronic restraint stress-induced hyperalgesia is modulated by the periaqueductal gray neurons projecting to the rostral ventromedial medulla in mice.

Stress-induced hyperalgesia (SIH) is induced by repeated or chronic exposure to stressful or uncomfortable environments. However, the neural mechanisms involved in the modulatory effects of the periaqueductal gray (PAG) and its associated loops on SIH development hav e not been elucidated. In the present study, we used chronic restraint stress (CRS)-induced hyperalgesia as a SIH model and manipulated neuronal activity via a pharmacogenetic approach to investigate the neural mechanism underlying the effects of descending pain-modulatory pathways on SIH. We found that activation of PAG neurons alleviates CRS-induced hyperalgesia; on the other hand, PAG neurons inhibition facilitates CRS-induced hyperalgesia. Moreover, this modulatory effect is achieved by the neurons which projecting to the rostral ventromedial medulla (RVM). Our data thus reveal the functional role of the PAG-RVM circuit in SIH and provide analgesic targets in the brain for clinical SIH treatment.

Knockdown of EIF2AK2-OAS1 axis reduces ATP production inducing AMPK phosphorylation to inhibit the malignant behavior of gastric cancer cells.

Energy metabolism has always been a hot topic in cancer progression and targeted therapy, and exploring the role of genes in energy metabolic pathways in cancer cells has become key to address this issue. Eukaryotic translation initiation factor 2α kinase 2 (EIF2AK2) plays regulatory roles in cancer and disorders of energy metabolism. Indeed, the role of EIF2AK2 in energy metabolism has been underestimated. The aim of this study is to reveal the expression specificity of EIF2AK2 in gastric cancer (GC) progression and metastasis, and to demonstrate the role of EIF2AK2 in energy metabolism, cytoskeleton, proliferation, death and metastasis pathways in GC cells. Mechanistically, EIF2AK2 overexpression promoted cytoskeleton remodeling and ATP production, mediated cell proliferation and metastasis, upregulated OAS1 expression, decreases p-AMPK expression and inhibited apoptosis in GC cells. Conversely, knockdown of EIF2AK2 resulted in the opposite effect. However, overexpression of OAS1 mediated the upregulation of mitochondrial membrane potential and promoted ATP production and NAD+/NADH ratio, but knockdown of OAS1 inhibited the above effects. In addition, knockdown of OAS1 had no effect on EIF2AK2 expression, but inhibited AMPK and upregulated p-AMPK expression. In conclusion, our study identified EIF2AK2 and OAS1 as previously undescribed regulators of energy metabolism in GC cells. We hypothesized that EIF2AK2-OAS1 axis may regulate energy metabolism and inhibit cellular malignant behavior in cancer cells by affecting ATP production to induce AMPK phosphorylation, suggesting EIF2AK2 as a potential therapeutic target for cancer cell progression.

Development of Novel Silicon Quantum Dots and Their Potential in Improving the Enhanced Oil Recovery of HPAM.

Hydrolyzed polyacrylamide (HPAM) is commonly used in polymer flooding, however, it is prone to viscosity reduction at high temperatures and high salinities, weakening its ability to improve oil recovery. In this work, sulfonated modified silicon quantum dots (S-SiQDs) were synthesized and then added to HPAM to study the improvement of rheological properties and enhanced oil recovery performance of HPAM at high temperatures and salinities. It is found that the S-SiQDs with a concentration of only 0.1 wt % can significantly increase the viscosity of HPAM from 28.5 to 39.6 mPa·s at 60 °C and 10,000 mg/L NaCl. Meanwhile, the HPAM/S-SiQDs hybrid solution always possessed higher viscosity and viscoelastic moduli than HPAM, attributed to the hydrogen bonding between HPAM and S-SiQDs. Notably, HPAM/S-SiQDs still maintained elastic behavior at harsh conditions, indicating that they formed a strong network structure. Through oil displacement experiments, it was found that the oil recovery of HPAM/S-SiQDs was higher (28.3%), while that of HPAM was only 17.2%. Thereafter, the utilization sequence of oil during the displacement process was studied with nuclear magnetic resonance experiments. Ultimately, the oil displacement mechanism of HPAM/S-SiQDs was deeply analyzed, including viscosity thickening and wetting reversal.

Conditional loss of Ube3d in the retinal pigment epithelium accelerates age-associated alterations in the retina of mice.

Several studies have suggested a correlation between the ubiquitin-proteasome system (UPS) and age-related macular degeneration (AMD), with its phenotypic severity ranging from mild visual impairment to blindness, but the mechanism for UPS dysfunction contributing to disease progression is unclear. In this study, we investigated the role of ubiquitin protein ligase E3D (UBE3D) in aging and degeneration in mouse retina. Conditional knockout of Ube3d in the retinal pigment epithelium (RPE) of mice led to progressive and irregular fundus lesions, attenuation of the retinal vascular system, and age-associated deterioration of rod and cone responses. Simultaneously, RPE-specific Ube3d knockout mice also presented morphological changes similar to the histopathological characteristics of human AMD, in which a defective UPS led to RPE abnormalities such as phagocytosis or degradation of metabolites, the interaction with photoreceptor outer segment, and the transport of nutrients or waste products with choroidal capillaries via Bruch's membrane. Moreover, conditional loss of Ube3d resulted in aberrant molecular characterizations associated with the autophagy-lysosomal pathway, oxidative stress damage, and cell-cycle regulation, which are implicated in AMD pathology. Thus, our findings strengthen and expand the impact of UPS dysfunction on retinal pathophysiology during aging, indicating that genetic Ube3d deficiency in the RPE could lead to the abnormal formation of pigment deposits and secondary fundus alterations. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Efficacy comparison of anti-vascular endothelial growth factor drugs for the treatment of type 1 retinopathy of prematurity: A network meta-analysis of randomised controlled trials.

PURPOSE: To compare the efficacy of different anti-vascular endothelial growth factor (VEGF) agents for the treatment of retinopathy of prematurity (ROP) in preterm infants. METHODS: Seven databases were searched for eligible literature up to February 22, 2023. Studies were included if they were randomised controlled trials (RCTs) investigating the efficacy of anti-VEGF agents for ROP in infants. A network meta-analysis (NMA) was performed. We also conducted subgroup analyses to determine the efficacy ranking of regimens used in different regions. The odds ratio (OR), standardised mean difference (SMD), and surface under the cumulative ranking curve (SUCRA) were calculated for each outcome. RESULTS: Thirteen RCTs of 10 different regimens, involving 1196 infants (2388 eyes), were identified. Bevacizumab (0.625 mg; OR = 0.16, 95% confidence interval [CI] 0.06-0.40, SUCRA = 80.6%) and conbercept (0.15 mg; OR = 0.08, 95% CI 0.02-0.30, SUCRA = 96.0%) were the most effective regimens in reducing the risk of ROP recurrence requiring retreatment in Western countries and China, respectively. Compared with laser therapy, bevacizumab (0.625 mg; SMD = 1.54, 95% CI 0.06-3.02) achieved significantly longer intervals between treatment and recurrence. No significant difference in the risk of retinal detachment was detected between any anti-VEGF agent and laser (p > 0.05). CONCLUSIONS: Bevacizumab (0.625 mg) and conbercept (0.15 mg) appeared to be the most effective therapies for ROP in Western countries and China, respectively. More high-quality RCTs are warranted to evaluate the efficacy and long-term safety of anti-VEGF drugs for the management of ROP.

More light components and less light damage on rats' eyes: evidence for the photobiomodulation and spectral opponency.

The blue-light hazard (BLH) has raised concerns with the increasing applications of white light-emitting diodes (LEDs). Many researchers believed that the shorter wavelength or more light components generally resulted in more severe retinal damage. In this study, based on the conventional phosphor-coated white LED, we added azure (484 nm), cyan (511 nm), and red (664 nm) light to fabricate the low-hazard light source. The low-hazard light sources and conventional white LED illuminated 68 Sprague-Dawley (SD) rats for 7 days. Before and after light exposure, we measured the retinal function, thickness of retinal layers, and fundus photographs. The expression levels of autophagy-related proteins and the activities of oxidation-related biochemical indicators were also measured to investigate the mechanisms of damaging or protecting the retina. With the same correlated color temperature (CCT), the low-hazard light source results in significantly less damage on the retinal function and photoreceptors, even if it has two times illuminance and blue-light hazard-weighted irradiance ([Formula: see text]) than conventional white LED. The results illustrated that [Formula: see text] proposed by IEC 62471 could not exactly evaluate the light damage on rats' retinas. We also figured out that more light components could result in less light damage, which provided evidence for the photobiomodulation (PBM) and spectral opponency on light damage.

Spinal infection caused by Coxiella burnetii.

BACKGROUND: Spinal infection caused by Coxiella burnetii is rare and difficult to diagnose. Here we reported a case of spinal infection from Coxiella burnetii detected by the metagenomic next-generation sequencing (mNGS). CASE PRESENTATION: A 66-year-old male farmer with no medical history reported severe sharp low back pain, numbness and lower limb weakness for three years. Magnetic resonance imaging (MRI) revealed bone destruction and spinal cord compression within L1 and L2. mNGS testing showed that the inspected specimen collected from spinal lesion was detected positively for Coxiella burnetii. After receiving the combined treatment of antibiotic therapy and surgical intervention, the patient recovered well, and the sagittal MRI showed that vertebral edema signals disappeared and the graft of bone fused 16 months after surgery. CONCLUSION: The mNGS may be benefit for early diagnosis and intervention of non-specific spinal infection, and future studies should validate its effectiveness for clinical use in spinal infections. Additionally, antibiotic therapy combined with surgical intervention plays an important role on the treatment of spinal infection caused by Coxiella burnetii.

Nanocomposite Hydrogel Engineered Janus Membrane for Membrane Distillation with Robust Fouling, Wetting, and Scaling Resistance.

Membrane distillation (MD) is considered to be rather promising for high-salinity wastewater reclamation. However, its practical viability is seriously challenged by membrane wetting, fouling, and scaling issues arising from the complex components of hypersaline wastewater. It remains extremely difficult to overcome all three challenges at the same time. Herein, a nanocomposite hydrogel engineered Janus membrane has been facilely constructed for desired wetting/fouling/scaling-free properties, where a cellulose nanocrystal (CNC) composite hydrogel layer is formed in situ atop a microporous hydrophobic polytetrafluoroethylene (PTFE) substrate intermediated by an adhesive layer. By the synergies of the elevated membrane liquid entry pressure, inhibited surfactant diffusion, and highly hydratable surface imparted by the hydrogel/CNC (HC) layer, the resultant HC-PTFE membrane exhibits robust resistance to surfactant-induced wetting and oil fouling during 120 h of MD operation. Meanwhile, owing to the dense and hydroxyl-abundant surface, it is capable of mitigating gypsum scaling and scaling-induced wetting, resulting in a high normalized flux and low distillate conductivity at a concentration factor of 5.2. Importantly, the HC-PTFE membrane enables direct desalination of real hypersaline wastewater containing broad-spectrum foulants with stable vapor flux and robust salt rejection (99.90%) during long-term operation, demonstrating its great potential for wastewater management in industrial scenarios.

Optical coherence tomography angiography-guided vs indocyanine green angiography-guided half-dose photodynamic therapy for acute central serous chorioretinopathy: 6-month randomized trial results.

PURPOSE: This study aimed to compare the anatomic and functional results of optical coherence tomography angiography (OCTA)-guided half-dose photodynamic therapy (PDT) versus indocyanine green angiography (ICGA)-guided PDT in eyes with acute central serous chorioretinopathy (CSC). METHODS: One hundred and thirty-one eyes of 131 patients with acute central serous chorioretinopathy (CSC) were recruited, and randomly assigned to the OCTA-guided group and ICGA-guided group. The primary outcome measures were the rates of complete subretinal fluid (SRF) resolution at 1 month, 3 months, and 6 months. The secondary outcomes included best-corrected visual acuity (BCVA), central retinal thickness (CRT), choroidal capillary flow deficit density at each scheduled visit, and recurrence rate of SRF at 3 months and 6 months. RESULTS: There were 110 eyes that finished the follow-up, with 56 eyes in the OCTA-guided group and 54 eyes in the ICGA guided group. OCTA-guided PDT was demonstrated to be noninferior to ICGA-guided PDT for SRF resolution rate at 1 months and 6 months (P = 0.021 and P = 0.037), but not at 3 months for acute CSC (P = 0.247). The average CRT of the ICGA-guided group was significantly lower than that of the OCTA-guided group at 3-month visit (P = 0.046), but no significant difference was found between them at the 1-month and 6-month visits (P = 0.891 and 0.527). There was no significant difference between the two groups for BCVA (P = 0.359, 0.700, and 0.143, respectively) and the deficit area on CC (P = 0.537, 0.744,and 0.604, respectively) at 1, 3, and 6 months. CONCLUSION: OCTA may replace ICGA to guide PDT for the treatment of acute CSC and their follow-up.

Comparing myopic error in patients with basic and convergence insufficiency intermittent exotropia in China.

PURPOSE: To compare the degree of myopia between the dominant and non-dominant eyes in teenagers with intermittent exotropia (IXT) in China. METHODS: A total of 199 IXT patients with myopia were included in this retrospective study and were divided into two groups according to the difference between near and distance exodeviation: basic IXT and convergence insufficiency (CI) IXT. Refractive errors were analyzed by spherical equivalent (SE) values. Patients were further stratified into anisometropia group and non-anisometropia group based on binocular SE values difference greater than 1.0D or not. RESULTS: There were 127 patients in the CI IXT group, with a near deviation of 46.94 ± 20.53 prism diopters (PD) and a distance deviation of 28.36 ± 14.34 PD, and there were 72 (36.2%) patients in the basic IXT group, with a near deviation of 37.68 ± 22.21 PD and a distance deviation angle of 33.21 ± 23.96 PD. The near exodeviation was significantly larger in the CI group than in the basic IXT group(P < 0.001). In the CI IXT group, the mean SE was - 2.09 ± 1.45 diopters (D) in the dominant eye and - 2.53 ± 1.44D in the non-dominant eye, while in the basic IXT group, the mean SE was - 2.46 ± 1.56D in the dominant eye and - 2.89 ± 1.37D in the non-dominant eye. The anisometropia group included 43 patients, while non-anisometropia group included 156 patients. The near and distance exodeviation in the anisometropia group were 45.26 ± 24.41 PD and 33.53 ± 23.31 PD, respectively, and those in the non-anisometropia group were 43.42 ± 20.69 PD and 29.07 ± 16.84 PD, respectively. There were no significant differences in near and distance deviation (P = 0.78 and P = 0.73 respectively) between the two groups. The SE of the dominant eye was less myopic than of the non-dominant eyes in both the CI and anisometropia groups (P = 0.002 and P < 0.001, respectively). CONCLUSIONS: Our study revealed that convergence insufficiency IXT is more common than the basic type in pediatric myopic population and is characterized by higher inter-eye differences of myopia. The dominant eye was found to be less myopic in IXT patients, particularly in those with convergence insufficiency and anisometropia.

Vitrectomy with sulfur hexafluoride versus air tamponade for idiopathic macular hole: a retrospective study.

BACKGROUND: To evaluate the effect of room air and sulfur hexafluoride (SF6) gas in idiopathic macular hole(MH)surgery. METHODS: Retrospective, interventional, and comparative study. 238 eyes with the idiopathic macular hole that underwent pars plana vitrectomy, internal limiting membrane peeling, fluid-air exchange, and 20% SF6 (SF6 group:125 eyes) or room air tamponade (air group: 113 eyes) were reviewed. The primary outcome measure was the closure rate of primary surgery. RESULTS: The baseline characteristics of the SF6 group and air group were comparable except for the hole size (479.90 ± 204.48 vs. 429.38 ± 174.63 µm, P = 0.043). The anatomical closure rate was 92.8% (116 / 125) with the SF6 group and 76.1% (86 / 113) with the air group (P < 0.001). A cut-off value of MH size to predict primary anatomical closure was 520 µm, which is based on the lower limit of 95% confidential interval of the MH size among the unclosed patients in the air group. There was no significant difference in anatomical closure rates between SF6 and air group (98.7% vs. 91.9%, P = 0.051) for MH ≤ 520 µm, whereas a significantly lower anatomical closure rate was shown in the air group than SF6 group (46.2% vs. 84.0%, P < 0.001) for MH > 520 µm. CONCLUSION: SF6 exhibited more effectiveness than air to achieve a good anatomical outcome for its longer tamponade when MH > 520 µm.

The Landscape of Accessible Chromatin and Developmental Transcriptome Maps Reveal a Genetic Mechanism of Skeletal Muscle Development in Pigs.

The epigenetic regulation mechanism of porcine skeletal muscle development relies on the openness of chromatin and is also precisely regulated by transcriptional machinery. However, fewer studies have exploited the temporal changes in gene expression and the landscape of accessible chromatin to reveal the underlying molecular mechanisms controlling muscle development. To address this, skeletal muscle biopsy samples were taken from Landrace pigs at days 0 (D0), 60 (D60), 120 (D120), and 180 (D180) after birth and were then analyzed using RNA-seq and ATAC-seq. The RNA-seq analysis identified 8554 effective differential genes, among which ACBD7, TMEM220, and ATP1A2 were identified as key genes related to the development of porcine skeletal muscle. Some potential cis-regulatory elements identified by ATAC-seq analysis contain binding sites for many transcription factors, including SP1 and EGR1, which are also the predicted transcription factors regulating the expression of ACBD7 genes. Moreover, the omics analyses revealed regulatory regions that become ectopically active after birth during porcine skeletal muscle development after birth and identified 151,245, 53,435, 30,494, and 40,911 peaks. The enriched functional elements are related to the cell cycle, muscle development, and lipid metabolism. In summary, comprehensive high-resolution gene expression maps were developed for the transcriptome and accessible chromatin during postnatal skeletal muscle development in pigs.

Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022).

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Postsynaptic glutamate response downregulates within presynaptic exaggerated glutamate release by activating TRPV1 in the spinal dorsal horn.

Activating primary afferent TRPV1-positive (TRPV1+) fibers in the spinal dorsal horn triggers exaggerated glutamate release and induces acute pain. However, whether the glutamate postsynaptic responses on dorsal horn neurons are regulated by excessive glutamate is unknown, largely due to intrinsic technical difficulties. In the present study, capsaicin, a specific TRPV1 agonist, was used to activate TRPV1+ fibers in the spinal dorsal horn. Combining three-dimensional (3-D) holographic photostimulation and whole-cell recordings on acute spinal cord slices from adult rodents, we found that postsynaptic glutamate responses were attenuated when activating TRPV1+ fibers with capsaicin. Electron microscopy and Western blot studies found that postsynaptic GluA1 (a subtype of ionotropic glutamate receptors) on the postsynaptic membrane was decreased by acute capsaicin treatment. Therefore, postsynaptic glutamate receptor occupancy and/or downmodulation may underlie this postsynaptic attenuation. Our data thus clarify a scenario in which postsynaptic glutamate responses are largely downregulated upon TRPV1+ activation, and this change may contribute to homeostasis in the dorsal horn circuit when "acute pain" occurs.

Human RGR Gene and Associated Features of Age-Related Macular Degeneration in Models of Retina-Choriocapillaris Atrophy.

Age-related macular degeneration (AMD) is a progressive eye disease and the most common cause of blindness among the elderly. AMD is characterized by early atrophy of the choriocapillaris and retinal pigment epithelium (RPE). Although AMD is a multifactorial disease with many environmental and genetic risk factors, a hallmark of the disease is the origination of extracellular deposits, or drusen, between the RPE and Bruch membrane. Human retinal G-protein-coupled receptor (RGR) gene generates an exon-skipping splice variant of RGR-opsin (RGR-d; NP_001012740) that is a persistent component of small and large drusen. Herein, the findings show that abnormal RGR proteins, including RGR-d, are pathogenic in an animal retina with degeneration of the choriocapillaris, RPE, and photoreceptors. A frameshift truncating mutation resulted in severe retinal degeneration with a continuous band of basal deposits along the Bruch membrane. RGR-d produced less severe disease with choriocapillaris and RPE atrophy, including focal accumulation of abnormal RGR-d protein at the basal boundary of the RPE. Degeneration of the choriocapillaris was marked by a decrease in endothelial CD31 protein and choriocapillaris breakdown at the ultrastructural level. Fundus lesions with patchy depigmentation were characteristic of old RGR-d mice. RGR-d was mislocalized in cultured cells and caused a strong cell growth defect. These results uphold the notion of a potential hidden link between AMD and a high-frequency RGR allele.

Corneal morphology correlates with choriocapillaris perfusion in myopic children.

AIMS: The present study investigated the difference in choriocapillaris (CC) perfusion between different AL/K ratio groups with similar spherical equivalent refraction (SER) and analyzed factors affecting CC perfusion. METHODS: This cross-sectional study included 129 children with low-to-moderate myopia. Axial length (AL), average K-reading (Ave-K), and SER were measured. Choroidal vascularity, including the total choroidal area (TA), choroidal luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), CC flow voids (FVs), and FVs%, was obtained using optical coherence tomography angiography. RESULTS: Participants with similar SER were divided into two groups (high AL/K ratio, n = 57; low AL/K ratio, n = 72). The high AL/K group had lower LA, TA, and CVI (P < 0.01) and lower FVs (inner ring and fovea, P < 0.05) and FVs% (outer ring, inner ring, and fovea, P < 0.05). The AL/K ratio and FVs% were negatively correlated in the outer ring (r = - 0.174, P < 0.05) and inner ring (r = - 0.174, P < 0.05). The Ave-K and inner FVs (r = 0.178, P < 0.05), outer FVs% (r = 0.175, P < 0.05), and inner FVs% (r = 0.196, P < 0.05) were positively correlated. In stepwise multiple regression for the outer ring, the horizontal CVI was related to FVs (ß = 0.175, P < 0.05), and the vertical CVI was related to FVs% (ß = 0.232, P < 0.01). Independent risk factors associated with inner FVs area were vertical CVI (ß = 0.329; P < 0.001) and SER (ß = - 0.196, P < 0.05); FVs% was also associated with vertical CVI (ß = 0.360, P < 0.01) and SER (ß = - 0.196, P < 0.05). CONCLUSION: With a similar SER, myopic eyes with a higher AL/K ratio maintained more CC perfusion and lower CVI, which may indicate rapid myopic progression. Low K-reading eyes had more CC perfusion and less CVI, which may explain the relatively poor myopia control efficacy in the clinic.

Risk factors of persistent subretinal fluid after half-dose photodynamic therapy for treatment-naïve central serous chorioretinopathy.

PURPOSE: To investigate the prognostic factors on spectral domain optical coherence tomography (SD-OCT) associated with incomplete subretinal fluid (SRF) absorption in treated-naïve eyes with central serous chorioretinopathy (CSC) after the half-dose verteporfin photodynamic therapy (vPDT). METHODS: Patients with CSC who underwent half-dose vPDT with a follow-up period of more than 3 months were included in this retrospective study. Logistic regression was performed to determine the risk factors associated with the SRF persistence at 3 months after the treatment. RESULTS: A total of 143 patients with 150 eyes were enrolled in this study (102 male and 41 female patients). The rate of complete SRF resolution was 82.7% at 3 months for all cases. The duration of symptoms > 6 months (odds ratio [OR] = 3.135, 95% confidence interval [95% CI] (1.147-8.573), p = 0.026), larger SRF area with base diameter > 3 mm (odds ratio (OR) = 4.051, 95% CI: 1.336-12.284, p = 0.013), and larger flat irregular pigment epithelium detachment (FI-PED) area with base diameter > 1 mm (OR = 3.311, 95% CI: 1.249-8.780, p = 0.016) on OCT B-scans were risk factors for incomplete SRF absorption after half-dose vPDT, while outer nuclear layer (ONL) thickness was not significantly associated with the anatomical outcome (OR = 1.015, 95% CI: 0.995-1.036, p = 0.145). CONCLUSION: The duration of symptoms, baseline SRF, and FI-PED base diameter on SD-OCT were important predictors for the anatomical outcome at 3 months after half-dose vPDT. Further studies are needed to establish a better therapeutic strategy for patients with poor response to half-dose vPDT.

Comparison of swept-source OCTA and indocyanine green angiography in central serous chorioretinopathy.

BACKGROUND: To compare swept-source optical coherence tomography angiography (SS-OCTA) and indocyanine green angiography (ICGA) in patients with central serous chorioretinopathy (CSC). METHODS: SS-OCTA and ICGA images of 39 eyes with symptomatic CSC were collected and aligned. Spatial overlap of the annotations of the coarse granulated high reflective area on choriocapillary OCTA and the hyperfluorescence area on mid-phase ICGA was calculated according to the Jaccard index (JI). SS-OCTA findings of fellow eyes and changes in SS-OCTA abnormalities during the follow-up were also analyzed. RESULTS: Three main types of abnormalities in choriocapillaris SS-OCTA images were found: type A, coarse granulated high reflective area (39 eyes [100%]); type B, roundish dark halo around Type A (32 eyes [82.1%]); and type C, coarse granulated low reflective area (39 eyes [100%]). The mean JI of type A on SS-OCTA and the hyperfluorescence area on ICGA were 0.55 ± 0.15 for grader 1 and 0.49 ± 0.15 for grader 2. The mean area of type A abnormalities on SS-OCTA and hyperfluorescence on ICGA was 3.976 (IQR, 2.139-8.168) and 3.043 (IQR, 1.408-4.909) mm2 (P = 0.199). The areas of type A, B and C abnormalities on SS-OCTA after laser treatment or observation were 3.36mm2 (IQR, 2.399-9.312), 2.9mm2 (IQR, 2.15-3.7), and 0.19mm2 (IQR, 0.08-0.23), respectively, which was smaller than those in the baseline (7.311mm2 (IQR 3.788-11.209), P < 0.001; 4.3mm2 (IQR, 2.8-9.8), P = 0.002;0.33mm2 (IQR, 0.23-0.38), P < 0.001). The change in the type A, B or C area was not significantly different between the two groups (P = 0.679, 0.732, and 0.892). CONCLUSION: The coarse granulated high reflective area in SS-OCTA corresponded well with the hyperpermeability area in ICGA. SS-OCTA promotes noninvasive visualization and follow-up quantifications of the choroidal vasculature in CSC patients.

Case series: pachychoroid pigment epitheliopathy transformed to polypoidal choroidal vasculopathy after long-term follow-up.

BACKGROUND: Pachychoroid pigment epitheliopathy (PPE), a retinal disorder that falls into the pachychoroid spectrum, is characterized by retinal pigment epithelium changes in pachychoroid eyes without existing or previous subretinal fluid or soft drusen. Previous reports have indicated that PPE may share some pathophysiologic component with other pachychoroid spectrum diseases and could transform into central serous chorioretinopathy (CSC) during follow-up. CSC transformation to PNV and PCV has also been reported, but PPE transformation to PCV has not been reported.  CASE PRESENTATION: Seven eyes of seven patients (four male three female, aged 62.7 ± 8.4 years) who presented with PPE at baseline transformed to PCV during follow-up. All study eyes had baseline contralateral eye diagnoses of PCV. All PPE eyes reported no symptoms at baseline and were followed up regularly for the treatment of their contralateral eyes. All PPE presented as pigment epithelium detachment (PED) at baseline. The mean central macular thickness (CMT) was 217.6 ± 14.6 µm, the mean subfoveal choroidal thickness (SFCT) was 354.9 ± 94.9 µm, and the mean sub-PPE choroidal thickness was 332.3 ± 84.6 µm. The mean PPE width and height were 1326.4 ± 791.4 µm and 58.7 ± 23.6 µm, respectively, at baseline. Disruption of the ellipsoid zone (EZ) was noted in 3 eyes, while choroidal vascular hyperpermeability (CVH) was noted in 5 eyes at baseline. The follow-up period was 75.0 ± 41.1 months, and the mean transformation time was 49.6 ± 24.8 months. All study eyes received no intervention before transformation. CONCLUSIONS: PPE could transform to PCV after a long follow-up period. Regular follow-ups for a long time should be recommended for patients with PPE.

7-Methylxanthine Influences the Behavior of ADORA2A-DRD2 Heterodimers in Human Retinal Pigment Epithelial Cells.

INTRODUCTION: The goal of this study was to investigate the presence of ADORA2A-DRD2 heterodimers in human retinal pigment epithelial (RPE) cells; determine if 7-methylxanthine (7-MX), a nonselective adenosine receptor antagonist which was used to control myopia progression, can influence the behavior of RPE cells through the ADORA2A-DRD2 receptor pathway; and assess the changes in the expression of signaling molecules during cellular signal transduction. METHODS: Human RPE cells were cultured in vitro in the presence or absence of 7-MX. Cell proliferation was evaluated with the CCK-8 assay. Apoptosis and necrosis rates were determined by annexin V-FITC/propidium iodide staining and flow cytometry. Immunofluorescence and coimmunoprecipitation were used to examine the protein expression and colocalization of ADORA2A and DRD2 in RPE cells. ADORA2A and DRD2 were knocked down with small interfering RNAs (siRNAs). Changes in the protein expression of ERK1/2 and phospho-ERK1/2 (pERK 1/2), which are signaling molecules downstream of dopamine receptors, were evaluated by Western blot analysis. RESULTS: Immunofluorescence and coimmunoprecipitation showed that ADORA2A and DRD2 were colocalized in RPE cells. The expression of ADORA2A in RPE cells was inhibited by treatment with 50 µmol/L 7-MX for 48 h, and the expression of DRD2, ERK1/2, and pERK1/2 was increased after treatment with 50 µmol/L 7-MX for 48 h. After siRNA-mediated knockdown of DRD2 in RPE cells and further treatment with 50 µmol/L 7-MX for 48 h, the expression of DRD2 was nearly restored to the level observed in the native control. At the experimental concentrations, 7-MX and siRNAs did not affect the proliferation or apoptosis of human RPE cells. CONCLUSIONS: ADORA2A and DRD2 heterodimers were present in RPE cells. 7-MX may affect the behaviors of RPE cells through the ADORA2A-DRD2 receptor pathway. 7-MX is an inhibitor of ADORA2A receptors that can prevent inhibition of the DRD2 receptor pathway and increase DRD2 receptor pathway activity. This phenomenon may explain the mechanism of action through which 7-MX can control myopia progression.