Alterations of large-scale functional network connectivity in patients with infantile esotropia before and after surgery.

BACKGROUND: Growing evidences have indicated neurodevelopmental disorders in infantile esotropia (IE). However, few studies have analyzed the characteristics of large-scale functional networks of IE patients or their postoperative network-level alterations. METHODS: Here, individuals with IE (n = 32) and healthy subjects (n = 30) accomplished the baseline clinical examinations and resting-state MRI scans. A total of 17 IE patients also underwent corrective surgeries and completed the longitudinal clinical assessments and resting-state MRI scans. Linear mixed effects models were applied for cross-sectional and longitudinal network-level analyses. Correlation analysis was performed to assess the relationship between longitudinal functional connectivity (FC) alterations and baseline clinical variables. RESULTS: In cross-sectional analyses, network-level FC were apparently aberrant in IE patients compared to controls. In longitudinal analyses, intra- and internetwork connectivity were observed with significant alterations in postoperative IE patients compared to the preoperative counterparts. Longitudinal FC changes are negatively correlated to the age at surgery in IE. CONCLUSIONS: Obviously, altered network-level FC benefiting from the corrective surgery serves as the neurobiological substrate of the observed improvement of stereovision, visuomotor coordination, and emotional management in postoperative IE patients. Corrective surgery should be performed as early as possible to obtain more benefits for IE in brain function recovery.

Abnormal developmental trends of functional connectivity in young children with infantile esotropia.

Previous studies have shown that functional networks are present at birth and change dynamically throughout infancy and early childhood. However, the status of functional connectivity is still poorly understood in patients with infantile esotropia (IE). The aim of this study is to investigate the developmental trends of functional connectivity in patients with IE during a critical period of growth and development. A total of 17 patients with IE (9 males and 8 females; mean age: 3.36 ± 2.03 years, age range: 0.67-6.36 years) and 20 healthy subjects matched for age and gender were recruited and underwent resting-state functional magnetic resonance imaging. The whole-brain functional network connectivity was analyzed for the IE group and healthy control group. A general linear model was applied to assess the group-age interaction in terms of the functional connectivity. The discrepancy between the two groups in functional connectivity trajectories was also quantified across age and exhibited by the quadratic parabolic model. There were significant group-age interactions between the visual network and the default mode network, the visual network and the sensorimotor network, the limbic network and the default mode network, and within the limbic network in the functional connectivity. A U-shaped tendency across age, with an "inflection point" ranging from 3.1 to 4.0 years of age was exhibited in the difference between functional connectivity trajectories of the IE patients and normal controls. Abnormality in functional network connectivity could present in IE patients at birth, exhibiting aberrant developmental patterns over time. An abnormal functional network could reduce the ability of the cortex in visual information processing, further reactivating the subcortical visual information processing system, which is probably the pathogenesis of IE. Three to four years after birth is the critical time window for children with IE to establish normal network connections in the brain. Early surgery during this period may be helpful for affected children to have an opportunity to approach the normal development trajectory as early as possible.

Differences in gene expression between the primary and secondary inferior oblique overaction.

Background: This study sought to define different adaptive changes in the molecular levels of the overacting inferior oblique muscle in primary and secondary inferior oblique overaction. Methods: The inferior oblique muscles of patients with congenital superior oblique palsy (SOP) and those of patients with congenital esotropia were collected during surgery. RNA-seq technology was performed to detect the differentially expressed genes (DEGs) between the two groups. A comprehensive analysis of the gene expression profiles was then conducted, including the identification of DEGs, a Gene Ontology (GO) analysis, and a gene set enrichment analysis (GSEA). Finally, a protein-protein interaction (PPI) network was constructed with Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape software. Results: We identified 221 DEGs, of which 104 were significantly upregulated and 117 were downregulated in the SOP group. Additionally, several isoforms of the myosin heavy chain (MyHC) gene were found to be significantly and differentially expressed in the SOP group, including 3 upregulated fast-twitch MyHC isoforms (i.e., MYH1, MYH4, and MYH13) and 1 downregulated slow-twitch MyHC isoform (i.e., MYH3). The GO analysis indicated that the upregulated DEGs were mainly enriched in the muscle system process and muscle contraction. The GSEA analysis revealed that the upregulated pathways of ribosome, proteasome, oxidative phosphorylation, fatty acid metabolism, viral myocarditis, and cardiac muscle contraction were enriched. Conclusions: Our findings provide insights into the different molecular changes of inferior oblique muscle overaction secondary to SOP and suggest the potential pathological mechanisms of inferior oblique overaction (IOOA) in SOP. The results suggest that upregulated fast-twitch MyHC isoforms and downregulated slow-twitch MyHC isoform in SOP may contribute to the increased force of its inferior oblique muscle.

Nasal Transposition of the Split Lateral Rectus Muscle for Strabismus Associated With Bilateral 3rd-Nerve Palsy.

PURPOSE: To determine the success rate and complications associated with nasal transposition of the split lateral rectus muscle (NTSLR) for treating bilateral 3rd-nerve palsy. DESIGN: Retrospective, interventional case series. METHODS: An international, multicenter registry was used for the study. The study population was all patients with bilateral 3rd-nerve palsy treated with NTSLR. Sensorimotor evaluations were conducted before and 6 months after unilateral or bilateral NTSLR. Outcome measures were postoperative horizontal alignment ≤15 prism diopters (PD), intraoperative technical difficulties, and vision-threatening complications. The association of patient demographics and surgical technique with each outcome was analyzed using multivariable logistic regression. RESULTS: A total of 34 patients were included, with a median age of 46 years (interquartile range [IQR] = 25-54 years) at surgery. The most common etiologies were ischemic (29%), neoplastic (15%), and congenital (12%). NTSLR performed unilaterally with alternative surgery on the opposite eye (65%) resulted in a median postoperative exotropia of 18 PD (IQR = 7-35 PD), and when performed bilaterally (35%) resulted in postoperative exotropia of 14 PD (IQR = 5-35 PD). Success was achieved in 50% of cases, intraoperative technical difficulties were reported in 18%, and vision-threatening complications occurred in 21%. Attachment of the lateral rectus muscle ≥10 mm posterior to the medial rectus insertion was associated with increased vision-threatening complications (odds ratio = 9.0; 95% CI = 1.3-99). CONCLUSIONS: NTSLR can address the large-angle exotropia associated with bilateral 3rd-nerve palsy. Surgeons should be aware that posterior placement of the lateral rectus muscle may increase the risk of vision-threatening complications, particularly serous choroidal effusion.

Mutations of TOPORS identified in families with retinitis pigmentosa.

PURPOSE: To identify TOPORS mutations in patients with retinitis pigmentosa (RP) from our cohort and summarize the genotypes and phenotypes of TOPORS reported previously. METHOD: Probands with RP phenotypes were recruited from our genetic retinopathy screening work. DNA was extracted from the peripheral venous blood, and exome sequencing was performed. We further examined the clinical data and family history in detail in these patients. TOPORS mutations associated with RP were searched and summarized from the previous reports, and the results were combined with the data presented in our study. The mutation spectrum of TOPORS was systematically analyzed, and the phenotypes of truncated mutations and missense mutations were compared and described. RESULT: Mutations in TOPORS were detected in three families, including two novel mutations (c.2017C>T, p.Arg673Cys, c.2371A>T, p.Lys791Term) and a known frameshift mutation (c.2554_2557delGAGA, p. Glu852fsTer13). A comprehensive analysis showed that 64.1% (25/39) of the mutant alleles are truncated mutations, and 34.3% (12/39) are missense mutations. About 89.7% (35/39) of the mutations are located in the terminal half of exon 3, which affected the C-terminal of the TOPORS protein. Night blindness was a common onset symptom, and TOPORS-related ERG changes can be observed in early stage. In addition, patients with missense mutations retained better central vision in older age compared to the patients with truncated mutations. CONCLUSION: We expand the mutation spectrum and assess the possible genotype-phenotype correlations of TOPORS, which can provide a valuable reference for exploring the pathogenesis of adRP caused by TOPORS mutations.

A single inferior rectus muscle surgery for treatment of congenital superior oblique palsy with small deviation in primary position.

PURPOSE: To evaluate outcomes of one muscle surgery for treatment of congenital superior oblique palsy (SOP) with Knapp Class V. METHODS: Medical records were retrospectively reviewed for the patients with the congenital SOP type V who underwent surgical treatment through one muscle surgery between July 2015 and September 2020. The surgical procedure was resection-recession on the contralateral inferior rectus muscle of the hypertrophic or paretic eye. Vertical alignment at nine cardinal gaze positions, and resolution of the abnormal head posture were evaluated pre- and postoperatively. The follow-up was scheduled regularly at postoperative day 1, 1 week, 1 month, and followed by 2-month intervals until 18 months. RESULTS: Twelve patients were included in this study, with a mean age of 6.4 years (range from 3 to 10 years). The mean follow-up period was 10.5 months after surgery (range from 6 to 18 months). The average vertical deviation at primary position was 6.33△ ± 2.93△ preoperatively and 0.75△ ± 1.14△ postoperatively (p < 0.05). The average vertical deviation at downgaze was 23.33△ ± 4.75△ preoperatively and 1.92△ ± 1.62△ postoperatively (p < 0.05). All patients had an abnormal head position preoperatively. Postoperative results indicated that the patients' abnormal head position had been improved significantly. CONCLUSIONS: The surgical procedure of resection-recession on a single inferior rectus muscle is a successful intervention for the correction of superior oblique palsy (SOP) with Knapp Class V.

A modified Fox pentagon technique performed using a polytetrafluoroethylene sling in frontalis suspension to treat blepharophimosis syndrome.

The purpose of this study was to evaluate the functional and cosmetic outcomes of a new modified Fox pentagon technique performed using polytetrafluoroethylene in frontalis suspension surgery for blepharophimosis syndrome. This retrospective study enrolled 40 patients diagnosed with blepharophimosis syndrome from March 2016 to October 2018. All patients underwent frontalis suspension using a new modified Fox pentagon technique. The functional and cosmetic outcomes were evaluated. After the operation, the mean palpebral fissure height increased from 2.68 to 6.93 in right eyes and from 2.73 to 6.98 in left eyes. The mean MRD1 increased from 0.53 to 3.76 in right eyes and from 0.50 to 3.78 in left eyes. While preoperative to postoperative differences were statistically significant (p < 0.01), there were no significant differences between right and left eyes either before or after the surgery (p > 0.01). All patients achieved good cosmetic results with an average score of 0.6. We have experimentally created a modified Fox pentagon technique performed using a polytetrafluoroethylene sling in a frontalis suspension to treat BPES; this approach yielded favorable cosmetic and functional outcomes.

TGFBI gene mutations analysis in Chinese families with corneal dystrophies.

The aim of the present study was to examine the clinical features of three Chinese families with autosomal dominant corneal dystrophy (CD) and examine transforming growth factor­ß­induced (TGFBI) gene mutations in these families. The TGFBI gene mutations were detected using direct sequencing of the whole coding regions and exon-intron boundaries of the TGFBI gene in the affected members from the three families with CD. The phenotypes of all affected individuals in the three families were observed via slit lamp examination. Sections of the cornea were used for biopsy following keratoplasty. Three types of TGFBI gene mutations, R124C, H626R and R124H, were detected in the patients from these three families. One family, with the R124C mutation, was diagnosed with lattice corneal dystrophy type 1, and the family with the H626R mutation was diagnosed with lattice corneal dystrophy type IIIB. The family with the R124H mutation was diagnosed with granular corneal dystrophy type 2. The TGFBI gene mutations were considered underlying factors in the molecular mechanism underlying the pathogenesis of cornea dystrophy. Therefore, the detection of TGFBI gene mutations may be useful in the differential diagnosis of CD.

Bilateral lateral rectus muscle recession for the convergence insufficiency type of intermittent exotropia.

PURPOSE: To evaluate the surgical efficacy of bilateral lateral rectus recession (BLRR) for intermittent exotropia with convergence insufficiency (CI-type X[T]). METHODS: The medical records of patients with CI-type X(T) who underwent BLRR on adjustable suture from January 2011 to March 2014 were retrospectively reviewed. Ocular alignment and sensory status were evaluated pre- and postoperatively for each patient. The mean distance and mean near deviation, before and after surgery, as well as the mean near-distance difference, were compared. Success was defined as postoperative alignment of esophoria/tropia of ≤5(Δ) and exophoria/tropia of ≤8(Δ) at distance. RESULTS: A total of 25 patients were included. The mean exodeviation was significantly reduced, from 32.5(Δ) preoperatively to 0.08(Δ) postoperatively (P < 0.001) at distance and from 45(Δ) preoperatively to 2.4(Δ) (P < 0.001) postoperatively at near. The mean near-distance difference was reduced from 16(Δ) preoperatively to 2(Δ) postoperatively (P < 0.01). Of the 25 patients, 21 (84%) obtained successful motor alignment, 2 had recurrent exodeviation of ≥10(Δ) at distance, and 2 had overcorrected esotropia with deviation angles of >8(Δ). CONCLUSIONS: In this cohort of patients, bilateral lateral rectus recession using an adjustable suture technique successfully treated CI-type X(T).

[Recession of both horizontal rectus muscles in Duane Retraction Syndrome with significant globe retraction].

OBJECTIVE: To evaluate the effect of Recession of both horizontal rectus muscles in Duane Retraction Syndrome with significant globe retraction. METHODS: Sixteen cases with DRS were summarized retrospectively. All patients had undergone surgery with recession of both horizontal rectus muscles. All clinical records, including sex, age, types of DRS, clinical features, surgical methods and clinical outcomes were analyzed. All patients were followed up for 3 months to 1 year. RESULTS: Fifteen cases had only monocular involvement while one had both eyes. The number of type I DRS was 3 cases, 1 case was esotropia while others were orthotropic in primary position. Type III DRS was observed 13 cases. Esotropia was seen in 6 cases (7 eyes), exotropia of 1 cases and orthotropic in primary position of 6 cases. 10 cases exhibited marked face turn. An upshoot or downshoot and variable severity of retraction of globe were found in all patients on attempt adduction of the affected eye. All patients had undergone surgery with recession of both horizontal rectus muscles. The medical rectus muscles were recessed from 5 mm to 7 mm and lateral rectus muscles 3 mm to 9 mm simultaneously, which was based on the amount of primary position deviation. Among these 2 cases were combined with Y-splitting of lateral rectus muscle. After surgery, all patients were orthotropic in primary position. Their symptom of unacceptable abnormal head position, significant globe retraction, noticeable narrowing of the palpebral fissure and significant upshoot or downshoot were ameliorated or disappeared. Especially the recession of lateral rectus muscle in addition to Y-splitting combining with the simultaneous medial rectus recession resulted in further amelioration of globe retraction in addition to upshoot and downshoot. CONCLUSION: Recession of both horizontal rectus muscles is effective in the treatment of significant globe retraction in Duane syndrome. Type III DRS with significant globe retraction but has no marked deviation and face turn can adopt this method to ameliorate their aspect. The method of lateral rectus muscle in addition to Y-splitting plays an important role in the treatment of upshoot and downshoot.

[Screening of FBN1 gene mutations in a family with Marfan syndrome].

OBJECTIVE: To identify FBN1 gene mutations in a Chinese family with Marfan syndrome. METHODS: Four affected and two unaffected individuals in the family were recruited after informed consent. Five ml blood samples were drawn from each family member and genomic DNA was extracted. Mutations were detected by directly sequencing to the whole coding region and exon-intron boundaries of FBN1 gene. Polyphen program was used to predict the functional and structural changes of the mutant protein. RESULTS: We found all four affected individuals carried FBN1gene mutations, c.2261A > G (p.Y754C), in exon18 by sequence analysis, while two unaffected family members and 100 normal controls did not have this mutation. A PSIC score of 2.6 was acquired by Polyphen program analysis. CONCLUSION: Our study supports that FBN1 gene mutation, c.2261A > G (p.Y754C), is the underlying molecular pathogenesis of this family with Marfan syndrome. This mutation is identified for the first time in Chinese population.

Correlation of the expression of telomerase RNA with risk factors for recurrence of sebaceous gland carcinoma.

AIMS: To investigate the expression of human telomerase gene RNA (hTR) and human telomerase reverse transcriptase (hTRT) in eyelid sebaceous gland carcinoma and to evaluate risk factors for sebaceous carcinoma recurrence. METHODS: The expression patterns of hTR and hTRT were detected by in situ hybridization (ISH) in paraffin-embedded samples of 55 eyelid sebaceous gland carcinoma, 12 chalazia, and four sebaceous adenoma. The proliferation index (PI) of sebaceous gland carcinoma was determined by Ki-67 immunolabeling and the results were compared with the expression of hTR and hTRT. Several factors for recurrence of sebaceous gland carcinoma were evaluated by statistical analysis. RESULTS: Expression of hTR and hTRT was present mainly in the sebaceous gland carcinoma tissues and not in adjacent tissues of carcinoma, chalazia, and sebaceous adenoma. The prevalence of hTR, hTRT, and Ki-67 expression in 55 sebaceous carcinoma samples were 84.45%, 58.1%, and 78.18%, respectively. hTR expression was highly associated with the degree of carcinoma differentiation (P<0.001) and hTRT expression was correlated with the proliferation index as determined by Ki-67 staining (P<0.005). There was a correlation between the recurrence of sebaceous gland carcinoma and the patient's onset age (OR=0.914, P<0.05), as well as the time to first treatment (OR=1.163, P<0.01). CONCLUSIONS: Telomerase may play an important role in the carcinogenesis of sebaceous gland carcinoma, and expression of hTR and hTRT combined with other features of sebaceous gland carcinoma may be helpful for the diagnosis and evaluation of clinical prognosis. Risk factors for recurrence of sebaceous gland carcinoma are patients' onset age and the time to first treatment.

Telomerase expression in sebaceous carcinoma of the eyelid.

BACKGROUND: In humans telomerase is expressed in most cancers and immortal cell lines, and activation of telomerase may play important roles in tumorigenesis and immortalization. This study was to investigate the roles of telomerase activity (TA) and human telomerase RNA (hTR) in sebaceous carcinoma of the eyelid. METHODS: The telomerase repeated amplification protocol (TRAP) was used to demonstrate telomerase activity in 12 cases of sebaceous carcinoma of the eyelid. In situ hybridization (ISH) was used to demonstrate the expression of hTR in 55 cases of paraffin-embedded sebaceous carcinoma of the eyelid, and the results were compared with the proliferative index determined by Mib-1 immuno-labeling, histological patterns and recurrence of the tumor. RESULTS: Different telomerase activity was shown in the 12 cases of sebaceous carcinoma of the eyelid. The positive expression of hTR was 85.5% (47/55) in tumor cells, but not in the adjacent tissues. The positive expression of hTR was correlated with the proliferative activity (as assessed by Mib-1 immunolabelling, r = 0.942, P < 0.001) and the differentiation of sebaceous carcinoma of the eyelid (chi(2) = 17.621, P < 0.001), but not significantly related to tumor recurrence. The level of hTR expression increased with the decrease of differentiation of sebaceous carcinoma of the eyelid. CONCLUSIONS: The results suggest that the up-regulation of telomerase expression plays some roles in tarsal gland carcinogenesis, and the expression of hTR is a useful marker for malignant degree of sebaceous carcinoma of the eyelid.

[Telomerase expression in tarsal gland carcinoma].

OBJECTIVE: To investigate the roles of telomerase activity (TA) and human telomerase RNA (hTR) in tarsal gland carcinoma. METHODS: The telomerase repeated amplification protocol (TRAP) was used to demonstrate telomerase activity in 12 tarsal gland carcinomas. In situ hybridization (ISH) was used to demonstrate the expression of hTR in 55 cases of paraffin-embedded tarsal gland carcinoma, and the results were compared with the proliferative index determined by Mib-1 immunolabeling, histological patterns and recurrence of the tumor. RESULTS: The telomerase activity was revealed in 12 tarsal gland carcinomas with different degrees. The positive expression of hTR was 85.5% (47/55) and observed in tumor cells, but not in the adjacent tissues. The expression of hTR was correlated with the proliferative activity (as assessed by Mib-1 immunolabelling, r = 0.942, P < 0.001) and the differentiation of tarsal gland carcinoma (chi(2) = 17.621, P < 0.001), but no significant relationship with tumor recurrence. The level of hTR expression had a gradually raised tendency along with the decrease of differentiation of tarsal gland carcinoma. CONCLUSION: The results suggest that up-regulation of telomerase expression play some roles in tarsal gland carcinogenesis, and the expression of hTR be a useful marker for malignant degree of tarsal gland carcinoma.