Transfer RNA derived fragment, tRF-Glu-CTC, aggravates the development of neovascular age-related macular degeneration.

Rationale: Angiogenesis expedites tissue impairment in many diseases, including age-related macular degeneration (AMD), a leading cause of irreversible blindness in elderly. A substantial proportion of neovascular AMD patients, characterized by aberrant choroidal neovascularization (CNV), exhibit poor responses or adverse reactions to anti-VEGF therapy. Herein, we aimed to unveil the function of newly identified transfer RNA-derived small RNA, tRF-Glu-CTC, in the pathology of CNV and determine its potential in inhibiting angiogenesis. Methods: Small non-coding RNA sequencing and quantitative polymerase chain reaction were conducted to detect expression pattern of tRF-Glu-CTC in CNV development. Immunofluorescence staining, fundus fluorescein angiography and ex vivo choroidal sprouting assays were employed for the evaluation of tRF-Glu-CTC's function in CNV development. The role of tRF-Glu-CTC in endothelial cells were determined by in vitro endothelial cell proliferation, migration and tube formation assays. Transcriptome sequencing, dual-luciferase reporter assay and in vitro experiments were conducted to investigate downstream mechanism of tRF-Glu-CTC mediated pathology. Results: tRF-Glu-CTC exhibited substantial up-regulation in AMD patients, laser-induced CNV model, and endothelial cells under hypoxia condition, which is a hallmark of CNV. Inhibiting tRF-Glu-CTC reduced angiogenesis and hypoxia stress in the neovascular region without neuroretina toxicity in laser-induced CNV model, showing an anti-angiogenic effect comparable to bevacizumab, while overexpression of tRF-Glu-CTC significantly augmented CNV. Mechanically, under hypoxia condition, angiogenin was involved in the production of tRF-Glu-CTC, which in turn triggered endothelial cell tubulogenesis, migration and promoted the secretion of inflammatory factors via the suppression of vasohibin 1 (VASH1). When downregulating VASH1 expression, the inhibition of tRF-Glu-CTC showed minimal suppression on angiogenesis. Conclusions: This study demonstrated the important role of tRF-Glu-CTC in the progression of angiogenesis. Targeting of tRF-Glu-CTC may be an alternative to current anti-VEGF therapy for CNV in AMD and other conditions with angiogenesis.

Identification and characterization of differentially expressed circular RNAs in extraocular muscle of oculomotor nerve palsy.

BACKGROUND: Oculomotor nerve palsy (ONP) is a neuroparalytic disorder resulting in dysfunction of innervating extraocular muscles (EOMs), of which the pathological characteristics remain underexplored. METHODS: In this study, medial rectus muscle tissue samples from four ONP patients and four constant exotropia (CXT) patients were collected for RNA sequencing. Differentially expressed circular RNAs (circRNAs) were identified and included in functional enrichment analysis, followed by interaction analysis with microRNAs and mRNAs as well as RNA binding proteins. Furthermore, RT-qPCR was used to validate the expression level of the differentially expressed circRNAs. RESULTS: A total of 84 differentially expressed circRNAs were identified from 10,504 predicted circRNAs. Functional enrichment analysis indicated that the differentially expressed circRNAs significantly correlated with skeletal muscle contraction. In addition, interaction analyses showed that up-regulated circRNA_03628 was significantly interacted with RNA binding protein AGO2 and EIF4A3 as well as microRNA hsa-miR-188-5p and hsa-miR-4529-5p. The up-regulation of circRNA_03628 was validated by RT-qPCR, followed by further elaboration of the expression, location and clinical significance of circRNA_03628 in EOMs of ONP. CONCLUSIONS: Our study may shed light on the role of differentially expressed circRNAs, especially circRNA_03628, in the pathological changes of EOMs in ONP.

Deficits of Visual Cortex Function in Acute Acquired Concomitant Esotropia Patients.

Purpose: The purpose of this study was to explore the cortical deficits of patients with acquired concomitant esotropia (AACE) using the resting-state functional magnetic resonance imaging (rs-fMRI) technique. Methods: Rs-fMRI signals from 25 patients with AACE and 25 matched controls were collected. The repeated-measures analysis of variance (RM-ANOVA) test and two-sample t-test were used to investigate statistical differences of the amplitudes of low-frequency fluctuation (ALFF) signals and correlation analysis was performed to validate the relationship of signal change and clinical features. Results: The AACE group showed decreased ALFF in both hemispheres symmetrically (t = 0.38, P = 0.71), with peak t in both middle occipital gyrus. The ALFF signal from the upper left inferior frontal gyrus was negatively correlated with the age of onset (r = 0.62, P = 0.0008), and the ALFF signal from the right superior temporal gyrus was negatively correlated with the near work hours (r = 0.63, P = 0.0008). The ALFF signal in the left fusiform gyrus was positively correlated with both near (r = 0.48, P = 0.01) and far (r = 0.44, P = 0.03) deviation, whereas it was only positively correlated with far deviation (r = 0.44, P = 0.03) in the right. Besides, the age of onset and the near work hour were independent factors of signal changes. Conclusions: Using the ALFF signal of rs-fMRI, we found functional deficits in the primary visual cortex and dorsal pathway in patients with AACE. There were functional changes in the fusiform gyrus, and the greater the deviation angle, the higher the changing level. These findings reveal the association of AACE and the visual center, giving us more clues about the treatment of AACE.

Three-muscle surgery for large-angle esotropia in chronic sixth nerve palsy: comparison of two approaches.

AIMS: To report the effect of two three-muscle surgeries, inferior rectus belly transposition plus augmented superior rectus transposition plus medial rectus recession (ISM) and modified vertical rectus belly transposition plus medial rectus recession (VM), in the management of large-angle esotropia in Chinese patients with chronic sixth nerve palsy. METHODS: Twenty-eight consecutive patients with large-angle esotropia ≥50Δ were prospectively enrolled and underwent either ISM or VM. Main outcomes included preoperative and postoperative deviation in primary position, abduction limitation and complications. Follow-up was at least 6 months. RESULTS: Of the included patients, 13 underwent ISM and 15 underwent VM. Preoperatively, ISM group displayed larger esotropia and more severe abduction limitation. 27 patients completed the follow-up. The postoperative horizontal deviation and abduction limitation were similar in both groups. At the last follow-up, ISM group demonstrated greater improvement of abduction limitation than VM group in both grading (group difference -2.1, p<0.001) and quantitation (group difference 2.6 mm, p=0.001). However, eight (30%) patients revealed an induced adduction limitation ≤-1. Of the 22 patients with unilateral palsy, more esotropia of 14.8Δ was corrected in ISM group, compared with VM group (p=0.003). Three patients (14%) developed vertical diplopia and three (14%) developed torsional diplopia. Unexpectedly, keratitis was observed in 4 of 27 (15%) patients, all with concurrent fifth and/or seventh nerve palsy. Three patients aggravated to corneal ulceration. CONCLUSIONS: Two three-muscle surgeries, ISM and VM were both effective for large-angle esotropia in Chinese patients with chronic sixth nerve palsy. However, attention should be paid to potential complications.

The profiles and clinical significance of extraocular muscle-expressed lncRNAs and mRNAs in oculomotor nerve palsy.

Introduction: Oculomotor nerve palsy (ONP) arises from primary abnormalities in the central neural pathways that control the extraocular muscles (EOMs). Long non-coding RNAs (lncRNAs) have been found to be involved in the pathogenesis of various neuroparalytic diseases. However, little is known about the role of lncRNAs in ONP. Methods: We collected medial rectus muscle tissue from ONP and constant exotropia (CXT) patients during strabismus surgeries for RNA sequencing analysis. Differentially expressed mRNAs and lncRNAs were revealed and included in the functional enrichment analysis. Co-expression analysis was conducted between these differentially expressed mRNAs and lncRNAs, followed by target gene prediction of differentially expressed lncRNAs. In addition, lncRNA-microRNA and lncRNA-transcription factor-mRNA interaction networks were constructed to further elaborate the pathological changes in medial rectus muscle of ONP. Furthermore, RT-qPCR was applied to further validate the expression levels of important lncRNAs and mRNAs, whose clinical significance was examined by receiver operating characteristic (ROC) curve analysis. Results: A total of 618 differentially expressed lncRNAs and 322 differentially expressed mRNAs were identified. The up-regulated mRNAs were significantly related to cholinergic synaptic transmission (such as CHRM3 and CHRND) and the components and metabolism of extracellular matrix (such as CHI3L1 and COL19A1), while the down-regulated mRNAs were significantly correlated with the composition (such as MYH7 and MYL3) and contraction force (such as MYH7 and TNNT1) of muscle fibers. Co-expression analysis and target gene prediction revealed the strong correlation between MYH7 and NR_126491.1 as well as MYOD1 and ENST00000524479. Moreover, the differential expressions of lncRNAs (XR_001739409.1, NR_024160.1 and XR_001738373.1) and mRNAs (CDKN1A, MYOG, MYOD1, MYBPH, TMEM64, STATH, and MYL3) were validated by RT-qPCR. ROC curve analysis showed that lncRNAs (XR_001739409.1, NR_024160.1, and NR_002766.2) and mRNAs (CDKN1A, MYOG, MYOD1, MYBPH, TMEM64, and STATH) might be promising biomarkers of ONP. Conclusions: These results may shed light on the molecular biology of EOMs of ONP, as well as the possible correlation of lncRNAs and mRNAs with clinical practice.

Corrigendum: Integrative metabolic analysis of orbital adipose/connective tissue in patients with thyroid-associated ophthalmopathy.

[This corrects the article DOI: 10.3389/fendo.2022.1001349.].

Integrative metabolic analysis of orbital adipose/connective tissue in patients with thyroid-associated ophthalmopathy.

Objective: Thyroid-associated ophthalmopathy (TAO) is a disfiguring autoimmune disease, which destroys the structure of orbital tissues and even threatens vision. Metabolic reprograming is critical in autoimmune diseases; however, the metabolic basis of TAO remains to be clarified. Our study aimed to reveal the metabolic profile of TAO. Methods: Orbital adipose/connective tissues from eleven TAO patients and twelve control subjects were collected during surgeries and analyzed with liquid chromatograph-mass spectrometer. Orthogonal partial least-squares discrimination analysis (OPLS-DA), variable importance in projection (VIP), heat map, and volcano plot were used to reveal metabolic profile in TAO. Pathway analysis and metabolites-gene analysis were utilized to explore potential metabolic metabolism in TAO. Results: 3038 metabolites were detected in samples from the TAO patients and the controls. OPLS-DA analysis of the metabolomics results showed two distinguished groups, demonstrating that TAO has a unique metabolome. Univariate tests identified 593 dysregulated metabolites (P < 0.05), including 367 increased metabolites and 226 decreased metabolites. Pathway analysis showed that changed metabolites were enriched in cholesterol metabolism, choline metabolism in cancer, fat digestion and absorption, regulation of lipolysis in adipocytes, and insulin resistance. In addition, metabolites-gene analysis illustrated that cholesterol metabolism was involved in the pathogenesis of TAO. Endoplasmic reticulum stress-related genes (ATF6, PERK, and IRE1α) expressions were higher in TAO orbital tissues than in control orbital tissues verified by western blot. Additionally, the expression level of diacylglycerol acyltransferase 1 (DGAT1), a key metabolic protein for triacylglycerol synthesis, was increased in orbital tissues of TAO detected by qRT-PCR, indicating disrupted cholesterol metabolism in TAO. Conclusion: The present study demonstrated different metabolite profiles and potential metabolic mechanisms in TAO.

Congenital Fibrosis of the Extraocular Muscles: An Overview from Genetics to Management.

Congenital fibrosis of the extraocular muscles (CFEOM) is a genetic disorder belonging to the congenital cranial dysinnervation disorders and is characterized by nonprogressive restrictive ophthalmoplegia. It is phenotypically and genotypically heterogeneous. At least seven causative genes and one locus are responsible for the five subtypes, named CFEOM-1 to CFEOM-5. This review summarizes the currently available molecular genetic findings and genotype-phenotype correlations, as well as the advances in the management of CFEOM. We propose that the classification of the disorder could be optimized to provide better guidance for clinical interventions. Finally, we discuss the future of genetic-diagnosis-directed studies to better understand such axon guidance disorders.

E2F1/CKS2/PTEN signaling axis regulates malignant phenotypes in pediatric retinoblastoma.

Retinoblastoma (RB) is the most common pediatric intraocular malignancy and is a serious vision- and life-threatening disease. The biallelic mutation of the retinoblastoma gene RB1 is the initial event in the malignant transformation of RB, but the exact molecular mechanism is still unclear. E2F transcription factors can be activated by RB1 loss of function and lead to uncontrolled cell division. Among E2F family numbers, E2F1 has higher expression abundance than E2F2 and E2F3 in RB clinical samples. By integrating E2F1 ChIP-seq data, RNA-seq profiling from RB samples and RNA-seq profiling upon E2F1 knockdown, together with pathway analysis, literature searching and experimental validation, we identified Cyclin-dependent kinases regulatory subunit 2 (CKS2) as a novel regulator in regulating tumor-associated phenotypes in RB. CKS2 exhibited aberrantly higher expression in RB. Depletion of CKS2 in Y79 retinoblastoma cell line led to reduced cell proliferation, delayed DNA replication and decreased clonogenic growth. Downregulation of CKS2 also slowed tumor xenograft growth in nude mice. Importantly, reversed expression of CKS2 rescued cancer-associated phenotypes. Mechanistically, transcription factor E2F1 enhanced CKS2 expression through binding to its promoter and CKS2 regulated the cancer-associated PI3K-AKT pathway. This study discovered E2F1/CKS2/PTEN signaling axis regulates malignant phenotypes in pediatric retinoblastoma, and CKS2 may serve as a potential therapeutic target for this disease.

Effect of Modified Vertical Rectus Belly Transposition vs Augmented Superior Rectus Transposition Plus Medial Rectus Recession for Chronic Sixth Nerve Palsy: A Randomized Clinical Trial.

Importance: Both vertical rectus belly transposition (VRBT) and superior rectus transposition (SRT) can be performed simultaneously with ipsilateral medial rectus recession (MRc) and have been shown to be effective for chronic sixth nerve palsy. However, it is unclear whether VRBT is superior to SRT in correcting esotropia. Objective: To compare the effectiveness of modified VRBT plus MRc (mVRBT-MRc) vs augmented SRT plus MRc (aSRT-MRc) in Chinese patients with chronic sixth nerve palsy. Design, Setting, and Participants: This parallel-design, double-masked, single-center, randomized clinical trial was conducted from January 15, 2018, to May 24, 2021. The follow-up visits were scheduled at 1 month and 6 months. Eligible Chinese participants with unilateral chronic sixth nerve palsy were randomly assigned to receive either mVRBT-MRc (VRBT group) or aSRT-MRc (SRT group). Interventions: mVRBT-MRc or aSRT-MRc. Main Outcomes and Measures: Change of horizontal deviation in primary position from baseline to 6 months. Results: Of the total 25 eligible participants, the mean (SD) age was 45.4 (12.6) years, with 10 male participants (40%) and 15 female participants (60%). Thirteen participants (52%) were randomly assigned to the VRBT group, and 12 (48%) were randomly assigned to the SRT group. At baseline, the mean (SD) horizontal deviation was 65.7 (10.8) prism diopters (Δ) in the VRBT group and 60.5Δ(14.1Δ) in the SRT group. Similar amounts of MRc were performed in both groups. At 6 months, the horizontal deviation changed from baseline by 66.3Δ in the VRBT group and by 51.5Δ in the SRT group. The adjusted group difference was 10.9Δ (95% CI, 5.3Δ-16.6Δ), favoring the VRBT group (P = .001). Four times as many participants corrected more than 60Δ with mVRBT-MRc compared with aSRT-MRc. The group difference of the improvement of abduction limitation was -0.2 (95% CI, -0.8 to 0.5; P = .64). Although there was a higher proportion of undercorrection in the SRT group (difference, 45%; 95% CI, 16%-75%; P = .01), no differences were identified for other suboptimal outcomes between groups. Conclusions and Relevance: Compared with aSRT-MRc, mVRBT-MRc showed better effect in correcting esotropia with no differences detected for other suboptimal outcomes. mVRBT-MRc may be a promising alternative surgical procedure for chronic sixth nerve palsy, particularly for large esotropia of more than 60Δ, if these results are confirmed in larger, diverse cohorts with longer follow-up. Trial Registration: ChiCTR Identifier: ChiCTR-INR-17013705.

Outcomes of a Simple Lateral Rectus Belly Transposition Procedure Combined With Ipsilateral Antagonist Recession for Vertical Rectus Palsy.

PURPOSE: To report the surgical effects of a combination treatment comprising the lateral rectus belly transposition (LRBT) procedure, without muscle splitting or disinsertion, and ipsilateral antagonist recession for vertical rectus palsy. METHODS: The medical records of consecutive patients who underwent the LRBT procedure between 2017 and 2020 were reviewed. Preoperative and postoperative deviation in primary position, preoperative and postoperative scale of duction of the palsied muscle, any induced horizontal or torsional deviation, and other complications were collected. RESULTS: Thirteen patients were identified: 10 with inferior rectus palsy and 3 with superior rectus palsy. The mean postoperative follow-up time was 20.4 ± 8.0 months. Eleven patients (84.6%) underwent simultaneous recession of the ipsilateral antagonist muscle of the palsied vertical rectus. After surgery, the mean vertical deviation improved from 31.4 ± 16.4 to 1.9 ± 3.6 prism diopters (PD) (P < .001). The mean vertical duction limitation of the palsied muscle improved from -2.7 ± 0.6 to -0.6 ± 0.5 (P = .001). In one patient, the scleral fixation suture was removed due to continuous reverse vertical diplopia. The total success rate was 76.9%. No induced horizontal deviation was noted. Anterior segment ischemia or other severe surgical complications did not occur. CONCLUSIONS: The LRBT procedure can be effective, safe, and reversible in patients with vertical rectus palsy. It allows for the option of simultaneous ipsilateral antagonist recession, and it is especially valuable in patients whose vertical duction deficiency is worse in abduction but mild in adduction. [J Pediatr Ophthalmol Strabismus. 2022;59(6):396-404.].

[History of Superior Oblique Muscle Surgery].

The superior oblique muscle has the longest tendon among the six extraocular muscles and serves complex functions. Surgery on the superior oblique muscle is considered the most complicated and difficult procedure in the field of strabismus. This article focuses on the history of superior oblique muscle surgeries, including superior oblique weakening procedure and superior oblique strengthening procedure. We discussed the advantages, disadvantages, and indications of each type of surgery, providing colleagues in the field of ophthalmology with a comprehensive understanding of superior oblique muscle surgery and facilitating the carefully weighed decision to choose and perform the procedure.

The Potential Role of Osteopontin in the Pathogenesis of Graves' Ophthalmopathy.

Purpose: The aim of this study is to evaluate the expression of osteopontin (OPN) and its relationship with relative cytokines in patients with Graves' ophthalmopathy (GO), and to observe the effect of OPN on orbital fibroblasts (OFs) proliferation, migration, and the expression of relative cytokines, as well as the signaling pathways involved in its effect. Methods: The orbital adipose connective tissue was obtained from 24 patients with GO (12 cases of active GO, and 12 cases of inactive GO) and 12 healthy controls. OFs were isolated from orbital tissues obtained from patients with active GO who were undergoing orbital decompression surgery. Quantitative PCR and Western blot were performed to detect RNA and protein expression. The proliferation and cell migration rates of OFs were measured by methylthiazol tetrazolium (MTT) and the cell scratch test. Signaling pathway inhibitors, such as OPN monoclonal antibody 1A12, ERK1/2 inhibitor PD98059, and PI3K inhibitor LY294002, were applied to determine the involved pathways. Results: The mRNA and protein levels of OPN were increased in orbital adipose connective tissue from patients with active GO than those from patients with inactive GO (2.83-fold increase, P < 0.001; 1.91-fold increase, P < 0.05). The OPN mRNA level was positively correlated with CD40 ligand (CD40L) and hyaluronan synthases 2 (HAS2) mRNA in patients with GO. OPN promoted proliferation and migration rate of OFs and induced vascular endothelial growth factor (VEGF) and collagen I mRNA expression, and the effects were inhibited by 1A12 or LY294002. Conclusions: OPN in orbital adipose connective tissues were significantly increase in active GO, and there were significant correlations of OPN with CD40L and HAS2 mRNA levels in patients with GO. OPN promoted proliferation and migration of OFs and induced VEGF and collagen I mRNA expression in OFs through PI3K/Akt signaling pathway. This suggested a role for OPN in the pathogenesis of GO through the activation of OFs.

Adipose/Connective Tissue From Thyroid-Associated Ophthalmopathy Uncovers Interdependence Between Methylation and Disease Pathogenesis: A Genome-Wide Methylation Analysis.

In response to pathological stimulation, methylation status conversion of the genome drives changes of cell feature and is able to promote disease development. Yet the role of methylation in the development of thyroid-associated ophthalmopathy (TAO) remains to be evaluated. Overexpansion of orbital tissue is the key feature of TAO. In this study, the methylation profile of orbital adipose/connective tissue from TAO patients and normal individuals were compared. After screening 3,739 differentially methylated probes, the distribution and properties of these probes were analyzed. Furthermore, enriched biological functions of these genes associated with differential methylation and the relationship between their methylation status and expression profile were also identified, including PTPRU and VCAM-1. According to our results, methylation was involved in disregulated immune response and inflammation in TAO and might contribute to activation of fibroblast and adipogenesis, leading to the expansion of orbital tissue. Neuropathy and neurobehavioral symptoms were also potentially associated with methylation. These results may help to extend the understanding of methylation in TAO and provide more insights into diagnosis and treatment of patients.

Effect of inferior oblique muscle belly transposition on versions and vertical alignment in primary position.

PURPOSE: To evaluate the effect of inferior oblique muscle belly transposition (IOBT) on vertical deviation (VD) in primary position and inferior oblique overaction (IOOA). METHODS: Twenty-eight patients who underwent unilateral IOBT for mild hypertropia (≤ 10△) due to unilateral IOOA were included. Surgical results regarding the correction of hypertropia, IOOA, and fovea disc angle (FDA) were analyzed and compared between groups A (VD ≤ 5△) and B (5△ < VD ≤ 10△). RESULTS: IOBT showed an overall reduction of 5.86△ (± 2.24△) of primary position VD, a mean correction of 1.00 (± 0.27) of IOOA, and an average change of 1.83° (± 3.02°) of FDA. The surgical success rate of IOBT for VD correction and IOOA elimination in all patients was 68% and 71%, respectively. The correction of VD was correlated with preoperative VD significantly (r = 0.86, p < 0.001). Consistently, IOBT demonstrated comparable efficacy in reduction of VD between group A and group B (p = 0.507). Furthermore, the two groups were comparable in the success rates for correcting VD and IOOA (both p > 0.05). None of the patients developed consecutive hypotropia, postoperative contralateral IOOA, or anti-elevation syndrome postoperatively. CONCLUSIONS: IOBT achieved satisfactory outcomes in patients with mild primary position VD (≤ 10△) that is associated with unilateral IOOA, without any risk of overcorrection of VD and contralateral IOOA for a follow-up period of up to 12 months. This procedure is considered effective and safe alternative for weakening the IO in patients with appropriate surgical indications.

Differential expression and alternative splicing of transcripts in orbital adipose/connective tissue of thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy is a typical autoimmune disease of orbital tissues. Alternative splicing significantly influences many diseases progression, including cancer, age-related macular degeneration, and multiple sclerosis, by modulating the expression of transcripts. However, its role in thyroid-associated ophthalmopathy is still unclear. In this study, differential expression transcripts and differential alternative splicing genes in orbital adipose/connective tissues of thyroid-associated ophthalmopathy patients were detected using RNA sequencing, Cuffdiff, and replicate multivariate analysis of transcript splicing. Three thousand ninety six differential expression transcripts and 2355 differential alternative splicing genes were screened out, while functional enrichment analysis indicated that differential expression transcript and differential alternative splicing genes were associated with immune modulation, extracellular matrix remodeling, and adipogenesis. The expression of the SORBS1, SEPT2, COL12A1, and VCAN gene transcripts was verified by qRT-PCR. In conclusion, prevalent alternative splicing is involved in the disease development in thyroid-associated ophthalmopathy. More attention should be paid to the mechanism of alternative splicing to explore more potential therapeutic targets in thyroid-associated ophthalmopathy.

Outcomes of modified vertical rectus belly transposition versus augmented superior rectus transposition for chronic abducens nerve palsy.

PURPOSE: To compare the surgical outcomes of modified vertical rectus belly transposition (mVRBT) and medial rectus recession (MRc) versus augmented superior rectus transposition (aSRT) and MRc in Chinese patients with chronic abducens nerve palsy. METHODS: The medical records of patients with chronic abducens nerve palsy who underwent mVRBT/MRc or aSRT/MRc were retrospectively reviewed. Pre- and postoperative deviation in primary position, pre- and postoperative abduction limitation, and complications were recorded. Follow-up was at least 6 months. RESULTS: A total of 26 patients (mean age, 37.9 ± 19.6 years; 16 males [62%]) were included. Fourteen patients underwent mVRBT/MRc (mVRBT group) and 12 underwent aSRT/MRc (aSRT group). Both groups had similar amounts of recession (t = 0.27; P = 0.79). After surgery, statistically significant changes of abduction limitation and esotropia were observed (both P < 0.05). However, the difference in abduction improvement between groups was not statistically significant (mVRBT vs aSRT, 2.3 ± 0.91 vs 2.3 ± 0.97; t = 0.10, P = 0.92). Of the 19 patients who underwent unilateral surgery, preoperative esotropia was similar in both groups (t = 1.3; P = 0.21), but more esotropia was corrected in the mVRBT group than in the aSRT group (mVRBT vs aSRT, 57.8Δ ± 14.3Δ vs 44.6Δ ± 9.8Δ; t = 2.1; P = 0.047). There was no symptomatic vertical or torsional deviation. CONCLUSIONS: In our patient cohort, mVRBT/MRc showed a better effect in correcting esotropia and a similar effect in improving abduction limitation compared with aSRT/MRc.

Graded superior oblique tendon suture lengthening: A novel procedure.

PURPOSE: Literature regarding different superior oblique (SO) weakening procedures showed variable results. Here, we aim to evaluate the effect of a novel superior oblique tendon suture lengthening (SOSL) procedure on weakening of SO in patients with A-pattern exotropia associated with dissociated vertical deviation and SO overaction (triad exotropia). METHODS: The medical records of triad exotropia patients who underwent SOSL or SO tenotomy were reviewed. Surgical results of SOSL procedure mainly regarding the correction of A pattern, SO overaction, and fundus intorsion were analyzed and compared with those of SO tenotomy procedure. RESULTS: SOSL demonstrated comparable efficacy in correction of A pattern (20.2△ ± 10.7△ vs 29.2△ ± 16.1△, p = 0.172), normalization of SO overaction (1.9 ± 0.9 vs 2.4 ± 1.5, p = 0.349), and conversion of fundus intorsion (11.1° ± 7.0° vs 11.3° ± 4.4°, p = 0.691) as SO tenotomy. Moreover, the success rate of A pattern collapse was significantly higher in the SOSL group than in the SO tenotomy group (86% vs 40%, p = 0.028). None of the patients in the SOSL group, but two in the SO tenotomy group, presented SO palsy postoperatively. In the SOSL group, the corrected magnitude of SO overaction strongly correlated with the dosage of suture lengthening (p < 0.001). CONCLUSION: SOSL procedure could effectively eliminate the clinical manifestations associated with SO overaction. The graded dosage of SOSL leads to more controllable and predictable results compared to SO tenotomy, which makes SOSL a good alternative choice for SO weakening.

Identification of differentially expressed long non-coding RNAs and mRNAs in orbital adipose/connective tissue of thyroid-associated ophthalmopathy.

Extracellular matrix remodeling and orbital adipose/connective tissue expansion are two key features of thyroid-associated ophthalmopathy (TAO). Recent studies have indicated the critical role of long non-coding RNAs (lncRNAs) in the pathogenesis of ocular disorders. However, little is known about the roles of lncRNAs in orbital adipose/connective tissue of TAO. In this study, the profiles of lncRNAs and mRNAs in the orbital adipose/connective tissue of TAO were identified by RNA sequencing. A total of 809 differential lncRNAs and 607 differential mRNAs were identified, among which 52 genes were found to be significantly related to the extracellular matrix. Co-expression network analysis suggested that lncRNAs might regulate extracellular matrix remodeling in orbital adipose/connective tissue of TAO. Additionally, the target genes of lncRNAs involved in the lipid metabolism and cytokine-cytokine receptor interaction were also identified. These results may provide potential regulatory mechanisms of lncRNAs in the orbital adipose/connective tissue of TAO.

Disrupted neural signals in patients with concomitant exotropia.

PURPOSE: Decreased binocular and oculomotor function in strabismics has recently been considered as cortical in origin. This study aimed to investigate functional abnormalities using a frequency-specific neuroimaging method in patients with concomitant exotropia (XT), and to demonstrate the clinical implications. METHODS: Resting-state functional magnetic resonance imaging data were collected in 26 XT patients and 26 matched controls. To evaluate the local spontaneous neural activity, the amplitude of low frequency fluctuations (ALFF) was calculated in the typical frequency band (0.01-0.08 Hz) as well as five narrowly-defined frequency bands (slow-6: 0-0.01 Hz, slow-5: 0.01-0.027 Hz, slow-4: 0.027-0.073 Hz, slow-3: 0.073-0.167 Hz, and slow-2: 0.167-0.25 Hz), respectively. RESULTS: Patients with XT showed decreased ALFF in the bilateral parieto-occipital sulcus (POS), and increased ALFF in the bilateral thalamus within the typical frequency band. Frequency-dependent ALFF alterations were found in the higher visual areas such as the right lateral occipital complex (LOC). Furthermore, ALFF in the right LOC in the slow-5 band was positively correlated with fusion control score (r = 0.70, p < 0.0001) and binocular function score (r = 0.67, p = 0.0002). Regression analyses showed that early age of onset remained the only significant explanatory factor for ALFF reduction in the right POS in the typically-measured frequency band (also referred to as the typical frequency band) (Odds ratio, 0.038; 95% confidence interval, 0.001 to 0.075). CONCLUSIONS: Our findings provide spatial information regarding the functionally disrupted regions in XT. Moreover, the frequency-dependent ALLF alteration in the right LOC might reflect a potential plastic capacity in binocular function, which could be a potential objective index for evaluating disease severity.