Elevated concentrations of amyloid-ß oligomers and their proapoptotic effects on age-related cataract.

Recently, amyloid-ß oligomers (AßOs) have been studied as the primary pathogenic substances in Alzheimer's disease (AD). Our previous study revealed that the Aß expression level is closely related to ARC progression. Here, we demonstrated that the accumulation of AßOs in the lens epithelium of age-related cataract (ARC) patients increased during ARC progression and that this alteration was consistent with the changes in mitochondrial function, oxidative stress, and cellular apoptosis. In vitro, human lens epithelial cells (HLECs) treated with AßOs exhibited Ca2+ dyshomeostasis, impaired mitochondrial function, elevated oxidative stress levels, and increased apoptosis. Moreover, the proapoptotic effect of AßOs was alleviated after the uptake of mitochondrial Ca2+ was inhibited. These results establish that AßOs may promote HLEC apoptosis by inducing mitochondrial Ca2+ overload, thus preliminarily revealing the possible association between the accumulation of AßOs and other pathological processes in ARC.

Mutations in ADAMTSL4 cause a unique form of autosomal-recessive congenital ectopia lentis.

Several unique mutations of ADAMTSL4 leading to congenital ectopia lentis (CEL) have been previously reported by our team. The purpose of this study is to find out the possible mechanism of a recurrent novel intronic variant in ADAMTSL4 led to CEL. Twelve novel ADAMTSL4 mutations with a unique form congenital ectopic lentis were detected previously by panel-based NGS. Genetic analysis verified a novel heterozygous ADAMTSL4 variation c.2177+4A > G on Intron 11 in two unrelated patients with iris and lens abnormalities. MINI-Gene assay showed two splicing modes of mRNA that process two different bands A and B, and mutant-type shows replacement with the splicing mode of Exon 11 skipping. Construction of wild-type and mutant ADAMTSL4 vector showed the appearance of premature termination codons (PTC). In vitro expression detection showed significant down-regulated expression level of ADAMTSL4 mRNAs and proteins in cells transfected with mutant vectors compared with in wild-type group. On the contrary, translation inhibitor CHX and small interfering RNA of UPF1 (si-UPF1) significantly increased mRNA or protein expression of ADAMTSL4 in cells transfected with the mutant vectors. 12 novel mutations in ADAMTSL4 gene have been previously reported by our team in 6 CEL patients with a unique series of ocular abnormalities. The recurrent novel ADAMTSL4 mutation c.2177+4A > G triggering the splicing mode of Exon 11 skipping and NMD would cause the decrease of ADAMTSL4 proteins that participate in biosynthesis and assembly of microfibers, which might lead to CEL, and suggest that sequencing of certain intronic splicing varition might be a vital tool for genetic counseling and prenatal diagnoses.

Application of sutureless corneal incision for patients with congenital ectopia lentis - Is it feasible, effective and safe?

Purpose: To compare the clinical outcomes, feasibility, and safety between groups with sutured and sutureless wound closure in congenital ectopia lentis (CEL) patients. Methods: Patients with CEL who received phacoemulsification combined with intrascleral fixation of capsular hook (CH) and implantation of capsular tension ring (CTR) and in-the-bag intraocular lens (IOL) were included in this study. Results: A total of 68 eyes of 34 patients aged 18 years or younger were enrolled in this study. Incisions of 21 patients (34 eyes) did not require sutures while sutures were applied in 21 patients (34 eyes). Postoperative uncorrected distance visual acuity, best corrected distance visual acuity and intraocular pressure measurements were comparable on follow-up visits (P > 0.05). The magnitude of surgically induced astigmatism was significantly greater (P = 0.001) in the suture group (Median: 0.47; IQ: 1.63, 2.97) than in the sutureless group (Median: 0.88; IQ: 0.63, 1.35). No cases of endophthalmitis and retinal detachment were found postoperatively in either group, while suture-related complications were observed in the sutured group, including loose suture with discomfort in 5 (14.71%) eyes, loose suture with mucus infiltration in 3 (8.82%) eyes. In total, 22 sutures (64.71%) of 34 eyes required removal. Conclusions: Sutureless clear corneal incision in CEL patients can achieve satisfactory clinical results comparable to sutured wound closure in terms of the efficacy and safety. Advantages of this approach are the reduced risk of suture-related complications, no need for additional surgery under general anesthesia for suture removal, and less cost.

Incidence and mechanism of conjunctival chemosis during phacoemulsification.

BACKGROUND: This study aims to determine the incidence of conjunctival chemosis during phacoemulsification and to explore the possible mechanism and treatments. METHODS: Patients with or without chemosis during phacoemulsification by the same operator within two years were included. The initial site of chemosis, the chemosis originated time, and the degree of chemosis at the end of the surgery were recorded. The differences in phacoemulsification energy/time and irrigation volume were compared between two groups. Meanwhile, the distance between the clear corneal incision (CCI) and the end of the Bowman's layer, surgically induced astigmatism (SIA), intraocular pressure and central corneal thickness were also compared between the two groups. RESULTS: The incidence of intraoperative chemosis was 9.17% (66/720). The distance between CCI and the end of the Bowman's layer in the chemosis group was significantly longer than that in the non-chemosis group postoperatively (P < 0.0001). The initial sites of chemosis were located on both sides of the external opening of the CCI. The average time from the phacoemulsification probe introducing into the anterior chamber to the originating of chemosis was 30.23 ± 49.23s. CONCLUSION: Intraoperative chemosis is related to the distance from CCI to the end of Bowmen's layer. The residual conjunctiva around the incision wraps the phacoemulsification probe sleeve to form a passage, the leakage fluid enters the subconjunctiva through this passage, forming chemosis. Conjunctival incision on both sides of CCI can effectively prevent the development of chemosis.

Lens subluxation combined with parry-romberg syndrome: case report.

BACKGROUND: Parry-Romberg syndrome (PRS) is a rare progressive degenerative disorder of unknown etiology. Here we report a rare case of PRS combined with lens subluxation in Eye and ENT hospital of Fudan University, Shanghai. To our knowledge, it is the first reported case of PRS combined with lens subluxation that has been managed surgically with phacoemulsification and CTR placement and IOL implantation in Shanghai. CASE PRESENTATION: A 60-year-old woman was referred for "right visual blur for 2 years" and had persistent right facial paralysis of unknown etiology since the age 12. She had right facial muscle atrophy and paralysis. Eye examination also showed the right eyelid pseudoptosis, enophthalmos, age-related cataract combined with lens subluxation existed in the right eye. The patient was diagnosed as age-related cataract and lens subluxation in the right eye and progressive hemifacial atrophy (Parry-Romberg syndrome). We conducted a combined phacoemulsification, IOL and CTR implantation and pupilloplasty surgery for the patient under general anesthesia and the postoperative UCVA was 20/30 and remained for 1 year's follow up. CONCLUSIONS: Here we reported a rare case of PHA combined with lens subluxation in China. After appropriate eye surgery, the patient achieved satisfying vision result in the right eye.

Biallelic ADAMTSL4 variants in a Chinese cohort of congenital ectopia lentis: Implications for genotype-phenotype relationships.

ADAMTSL4 variants are one of the common causes of congenital ectopia lentis (EL), reported ocular comorbidities of which include iris anomalies, cataract, and glaucoma. However, a genotype-phenotype correlation has not been established. Potentially pathogenic ADAMTSL4 variants were screened from a Chinese cohort of congenital EL using panel-based next-generation sequencing followed by multiple bioinformatics analyses. The genotype-phenotype correlation was assessed via a systematic review of ADAMTSL4 variants within our data and those from the literature. A total of 12 variants of ADAMTSL4, including seven frameshift variants, one nonsense variant, two splicing variants, and two missense variants, were found in nine probands. Combing genetic and clinical information from 72 probands in the literature revealed 37 ADAMTSL4 variants known to cause EL, and the ethnic difference was prominent. The lens was inclined to dislocate inferior temporally (22, 27.16%), while the pupil was always located oppositely (9, 81.82%). Several anterior segments anomalies were identified, including ectopia pupillae (15, 18.52%), persistent pupillary membrane (9, 11.10%), poor pupil dilation (4, 30.8%), cataract (13, 24.10%), and glaucoma (8, 13.33%). Genotype-phenotype analysis revealed that truncation variants had higher risks of combined iris anomalies, including either ectopia pupillae or a persistent pupillary membrane (p = 0.007). The data from this study not only extend our knowledge of the ADAMTSL4 variant spectrum but also suggest that deleterious variants of ADAMTSL4 might be associated with severe ocular phenotypes.

Structural and functional analysis of SNP rs76740365 G>A in exon-3 of the alpha A-crystallin gene in lens epithelial cells.

Purpose: To clarify the effect of a previously identified single nucleotide polymorphism (SNP; rs76740365 G>A) in the exon-3 of the alpha A-crystallin (CRYAA) gene on the properties of CRYAA and to investigate its function in human lens epithelial cells (HLECs). Methods: The human recombinant wild-type and mutant CRYAA (E156K) were constructed, and the molecular weight was measured by mass spectrometry. The structural changes induced by E156K mutation were analyzed by UV circular dichroism spectra and intrinsic tryptophan fluorescence and were predicted using Schrödinger software. The chaperone-like ability of wild-type and E156K mutant CRYAA was invested against the heat-induced aggregation of ßL-crystallin and the DTT-induced aggregation of insulin. HLECs expressing wild-type and mutated CRYAA were subjected to quantitative PCR (qPCR) and western blot. Cell apoptosis was determined using flow cytometry analysis, and the expression of apoptosis-related proteins were determined using western blot. Results: The mass spectrometric detection revealed that E156K mutation had no significant effect on the apparent molecular mass of the CRYAA oligomeric complex. Evaluation of the structures of the CRYAA indicated that E156K mutation did not significantly affect the secondary structures, while causing perturbations of the tertiary structure. The mutant CRYAA displayed an increase in chaperone-like activity, which might be related to the increase of the surface hydrophobicity. We also predicted that E156K mutation would induce a change from negatively charged surface to positively charged, which was the possible reason for the disturbance to the surface hydrophobicity. Transfection studies of HLECs revealed that the E156K mutant induced anti-apoptotic function in HLECs, which was possibly associated with the activation of the p-AKT signal pathway and downregulation of Casepase3. Conclusions: Taken together, our results for the first time showed that E156K mutation in CRYAA associated with ARC resulted in enhanced chaperone-like function by inducing its surface hydrophobicity, which was directly related to the activation of its anti-apoptotic function.

Protective effect of Glutaredoxin 1 against oxidative stress in lens epithelial cells of age-related nuclear cataracts.

Purpose: Glutaredoxin 1 (Grx1) is a key antioxidant protein that catalyzes disulfide redox reactions. In this study, we investigated the expression and protective effect of Grx1 against oxidative stress in nuclear cataracts. Methods: Human anterior capsule membrane samples were obtained from the eyes of cataract patients (experimental group) and non-cataractous (control group) donors. The levels of Grx1 protein and mRNA expression were investigated. The human lens epithelial (HLE) cell line SRA 01/04 was transfected with Grx1-containing plasmid or Grx1 small interfering RNA, and cultured under H2O2 treatment, mimicking oxidative stress conditions. Cell counts, clone formation, cell apoptosis, cell cycle, and levels of oxidized glutathione disulfide and cellular reactive oxygen species (ROS) were evaluated and quantified. Results: Protein and mRNA transcript levels of Grx1 were significantly lower in the human anterior capsule membrane of the age-related nuclear (ARN) cataract group than in the control group. Grx1 overexpression protected HLE cells from H2O2-induced oxidative damage, including alleviating G1 phase arrest, promoting cell proliferation, reducing cell apoptosis, and decreasing intracellular ROS generation. Furthermore, extracellular-signal-regulated kinase (ERK) phosphorylation in the human anterior capsule membrane of ARN patients was higher in the experimental group than in the control group. Grx1 overexpression reduced the levels of oxidized glutathione disulfide and the phosphorylation of ERK. The administration of an ERK phosphorylation inhibitor, PD98059, induced antioxidant effects in Grx1-silenced cells. Conclusions: Grx1 expression is downregulated in the human anterior capsule membrane of ARN patients, accompanied by an increase in ERK phosphorylation. Thus, Grx1 can protect HLE cells against oxidative stress.

Changes in Vector Astigmatism After Superotemporal Versus Temporal Clear Corneal Incision Cataract Surgery.

PURPOSE: To investigate vector and refractive astigmatism changes after superotemporal versus temporal clear corneal incision cataract surgery. METHODS: Patients were diagnosed with age-related cataract with corneal astigmatism < 1.5 diopters (D) and were divided into two groups: superotemporal incision (R group) and temporal incision (L group). Uncorrected visual acuity, manifest refraction, corneal topography, anterior segment optical coherence tomography was performed pre- and six months postoperatively. Total ocular astigmatism, corneal astigmatism, vector of surgically induced corneal astigmatism (SICA), non-corneal ocular residual astigmatism (N-CORA), postoperative intraocular lens decentration and tilt were analyzed.  Results: Thirty-eight subjects were included: 21, R group; 17, L group. After surgery, the N-CORA decreased significantly from 1.17±0.72 D to 0.73±0.47 D in all patients (P=0.001), 1.03±0.52 D to 0.70±0.40 D in the R group (P=0.005) and 1.35±0.90 D to 0.78±0.55 D in the L group (P=0.033). Significant differences between t:he R and L groups were found in the postoperative meridian of anterior corneal astigmatism (75.95±52.50 vs 116.79±47.29; P=0.017), total corneal astigmatism (51.65±42.75 vs 95.20±57.32; P=0.011), J45 change vector of SICA in the anterior cornea (-0.10±0.18 vs 0.00±0.11; P=0.048) and total cornea surface (-0.14±0.17 vs 0.03±0.12; P=0.001).  Conclusion: The N-CORA decreased significantly after cataract surgery. Superotemporal and temporal incisions caused differences in the meridian components of oblique astigmatism in some patients but did not have a significant effect on the magnitude of corneal astigmatism.

Comparison of Accuracy in Keratometries Measured by Different Camera Devices for Predicting the Intraocular Lens Power in Lens-Dislocated Patients.

INTRODUCTION: This is a cross-sectional cohort study focused on assessing the influence of ocular biometric parameters of different camera devices for accurately predicting the intraocular lens (IOL) power in the congenital ectopia lentis (EL) patients. METHODS: This study includes a total of 91 eyes of 60 patients with congenital EL from June 2018 to April 2021. All patients underwent lens subluxation surgery with Cionni modified capsular tension rings (MCTR) implantation. Ocular parameters measured by partial coherence interferometry (IOLMaster 700, Carl Zeiss Meditec AG, Jena, Germany) and rotating Scheimpflug camera (Pentacam HR system, Oculus Optikgeräte GmbH, Wetzlar, Germany) were acquired from the database. The authenticity of the different keratometries (K) were analyzed by comparing the prediction error in spherical equivalent under controlled formula SRK/T, Haigis, and after Wang-Koch (WK) adjustment. RESULTS: We observed significant greater K values were obtained in IOLMaster than Pentacam, resulting in more significant hyperopia error while calculating SRK/T. The IOL power calculated with the total corneal refractive power (TCRP) from Pentacam revealed the highest prediction accuracy, indicating that TCRP is the closest to the actual refractive power of the cornea. However, in an exceptional case for long eye patients, total keratometry from IOLMaster was better recommended when using formula Haigis with WK adjustment. CONCLUSIONS: For most instances, TCRP is the best-recommended source of K value while calculating IOL power for EL patients. However, the total keratometry from IOLMaster preferably fits for long eye patients, who require WK adjustment for Haigis formula.

Zonular defects in loxl1-deficient zebrafish.

BACKGROUND: To investigate the roles of the lysyl oxidase-like 1 (loxl1) gene in zebrafish eye development and the potency of loxl1 deficiency in mimicking the ocular manifestations of exfoliation syndrome (XFS). METHODS: CRISPR/Cas9 technology was used to generate a frameshift coding deletion in zebrafish loxl1. Expression profiles and ocular manifestations of the wildtype, heterozygous mutant (loxl1+/- ) and homozygous mutant (loxl1-/- ) zebrafish were analysed in a range of developmental stages from zebrafish larvae to dissected adult zebrafish eyes. RESULTS: The loxl1 deficiency caused zonular bundling disorders in juvenile zebrafish and accumulation of pearl-like particles adhering to the adult zebrafish zonule. The bundles appeared to lack form and were thinner in both loxl1+/- and loxl1-/- zebrafish compared with the wildtype (p < 0.01 for all Bonferroni post-hoc analyses). The zonule of loxl1-/- zebrafish appeared stretched, ragged and torn, with isolated fibres also detected. The particles in loxl1-/- zebrafish were more numerous (counts: 92.33 ± 10.02/100 µm2 vs. 58.33 ± 5.03/100 µm2 , p = 0.006), but smaller in size (diameter: 0.21 ± 0.03 µm vs. 0.43 ± 0.04 µm, p = 0.002) compared with those in loxl1+/- . Transmission electron microscopy revealed thinning or even loss of elastic lamina in loxl1+/- Bruch's membrane (BM) (thickness of elastic lamina: 92.94 ± 18.19 nm in the wildtype vs 35.65 ± 14.76 nm in loxl1+/- , p = 0.003). The breakage of BM was observed in loxl1-/- . CONCLUSIONS: The loxl1-/- zebrafish is a promising animal model of XFS zonular pathology.

Correlation between FBN1 mutations and ocular features with ectopia lentis in the setting of Marfan syndrome and related fibrillinopathies.

Mutations of fibrillin-1 (FBN1) have been associated with Marfan syndrome and pleiotropic connective tissue disorders, collectively termed as "type I fibrillinopathy". However, few genotype-phenotype correlations are known in the ocular system. Patients with congenital ectopia lentis (EL) received panel-based next-generation sequencing, complemented with multiplex ligation-dependent probe amplification. In a total of 125 probands, the ocular phenotypes were compared for different types of FBN1 mutations. Premature termination codons were associated with less severe EL and a thinner central corneal thickness (CCT) than the inframe mutations. The eyes of patients with mutations in the C-terminal region had a higher incidence of posterior staphyloma than those in the middle and N-terminal regions. Mutations in the TGF-ß-regulating sequence had larger horizontal corneal diameters (white-to-white [WTW]), higher incidence of posterior staphyloma, but less severe EL than those with mutations in other regions. Mutations in the neonatal region were associated with thinner CCT. Longer axial length (AL) was associated with mutations in the C-terminal region or TGF-ß regulating sequence after adjusting for age, EL severity, and corneal curvature radius. FBN1 genotype-phenotype correlations were established for some ocular features, including EL severity, AL, WTW, CCT, and so forth, providing novel perspectives and directions for further mechanistic studies.

Effectiveness comparisons of drug therapies for postoperative aneurysmal subarachnoid hemorrhage patients: network meta­analysis and systematic review.

OBJECTIVE: To compare the effectiveness of various drug interventions in improving the clinical outcome of postoperative patients after aneurysmal subarachnoid hemorrhage (aSAH) and assist in determining the drugs of definite curative effect in improving clinical prognosis. METHODS: Eligible Randomized Controlled Trials (RCTs) were searched in databases of PubMed, EMBASE, and Cochrane Library (inception to Sep 2020). Glasgow Outcome Scale (GOS) score, Extended Glasgow Outcome Scale (GOSE) score or modified Rankin Scale (mRS) score was used as the main outcome measurements to evaluate the efficacy of various drugs in improving the clinical outcomes of postoperative patients with aSAH. The network meta-analysis (NMA) was conducted based on a random-effects model, dichotomous variables were determined by using odds ratio (OR) with 95% confidence interval (CI), and a surface under the cumulative ranking curve (SUCRA) was generated to estimate the ranking probability of comparative effectiveness among different drug therapies. RESULTS: From the 493 of initial citation screening, forty-four RCTs (n = 10,626 participants) were eventually included in our analysis. Our NMA results showed that cilostazol (OR = 3.35,95%CI = 1.50,7.51) was the best intervention to improve the clinical outcome of patients (SUCRA = 87.29%, 95%CrI 0.07-0.46). Compared with the placebo group, only two drug interventions [nimodipine (OR = 1.61, 95%CI 1.01,2.57) and cilostazol (OR = 3.35, 95%CI 1.50, 7.51)] achieved significant statistical significance in improving the clinical outcome of patients. CONCLUSIONS: Both nimodipine and cilostazol have exact curative effect to improve the outcome of postoperative patients with aSAH, and cilostazol may be the best drug to improve the outcome of patients after aSAH operation. Our study provides implications for future studies that, the combination of two or more drugs with relative safety and potential benefits (e.g., nimodipine and cilostazol) may improve the clinical outcome of patients more effectively.

Modified colonic transit test in healthy subjects and constipated patients: A triple-phase, two-center prospective study.

BACKGROUND AND AIM: Classic daily-ingestion single-film protocol using radiopaque markers for colonic transit time (CTT) is unsuitable for Chinese patients because of rapid colonic motility. A new modified method needs to be established. METHODS: The triple-phase study was performed. In Phase I, the classic protocol was assessed to evaluate its feasibility for Chinese subjects. In Phase II, a modified protocol was performed in two centers on 180 healthy subjects and 90 constipated patients to determine optimal conditions. In Phase III, the simplified protocol was validated on 90 constipated patients. RESULTS: All the subjects of the Phase I expelled more than 95% of the markers during the examination period, which means that the classic protocol is unsuitable for Chinese patients. The 20.9-h mean total CTT for healthy Chinese subjects was much faster than that seen in Western countries. As shown by Phase II, the numbers of subjects went beyond the upper limit were 22 in P1TCTT and 10 in P2TCTT (8.14% vs 3.70%, P = 0.029). The percentage of values fall outside of the measurement range of excretion ratio was around half of our study subjects (45-70%), whereas this percentage was only 3.70% using P2TCTT. The simplified protocol had a diagnostic accuracy for constipation of 0.81, with a sensitivity and specificity of 0.46 and 0.97, respectively. CONCLUSIONS: Colon movement in Chinese individuals is significantly faster than that of Western populations. The modified protocol generated in this study is appropriate for diagnosis of constipation in population with rapid colon motility.

Evaluation of the B/F Ratio Distribution of Cataract Patients Without Corneal Abnormalities and Its Effect on Ocular Parameters.

PURPOSE: To evaluate the distribution of the posterior-anterior corneal radius ratio (B/F ratio; posterior corneal radius/anterior corneal radius) in patients without corneal abnormalities, and to investigate which parameters affect this ratio. METHODS: Five thousand eyes from 5,000 patients who underwent cataract surgery were recruited to this study. We explored the linear relationship between B/F ratio and 13 variables using Principal Component-Multivariate Linear Regression Analysis. RESULTS: The B/F ratio was negatively correlated with the difference between simulated keratometry (SimK) and true net power (TNP), central corneal thickness, spherical aberration (SA), and posterior corneal astigmatism and positively correlated with posterior corneal radius, corneal posterior surface, axial length (AL) and anterior corneal radius. Several variables (central corneal thickness, difference between SimK and TNP and asphericity coefficient (Q-value) of the posterior corneal surface) had the highest loading on the final score. B/F ratio reflects the refractive state and anatomical structure of the cornea: thus, higher B/F ratios were associated with larger posterior corneal surface curvature radius, longer axial length, thinner central corneal thickness, lower high order aberrations of the cornea and SA, and the numerical difference between simK and TNP gradually reduced. In clinical practice, for patients with lower B/F ratio, special care should be taken in the choice of system used for intraocular lens (IOL) measurements.

Primary scleral-fixated posterior chamber intraocular lenses in patients with congenital lens subluxation.

OBJECTIVE: We investigated the long-term visual outcomes and ocular complications of primary scleral-fixated posterior chamber intraocular lenses (SF-PC-IOLs) in patients with congenital lens subluxation. METHODS: We enrolled 53 patients (77 eyes) with congenital lens subluxation caused by ectopia lentis, Marfan syndrome, and Weill-Marchesani syndrome who underwent primary implantation of a SF-PC-IOL. All patients underwent a complete ophthalmic examination include visual acuity (VA), intraocular pressure (IOP), intraocular lenses (IOL) position, intraoperative complications and postoperative complications. Cox regression analysis and survival analysis were used to evaluate the risk factors for postoperative complications. RESULTS: Seventy seven eyes from 53 patients were included. Mean age at surgery was 23 ± 20 years (5 to 67 years), with a mean follow-up of 39 ± 27 months (12 to 130 months). The best-corrected VA improved from 0.84 ± 0.55 to 0.26 ± 0.43 logarithms of the minimum angle of resolution (p < 0.001). Best-corrected VA improved postoperatively in 73 eyes (94%). The main causes of reduced vision after surgery were retinal pathologies and amblyopia. Complications included transient intraocular haemorrhage (2 eyes, 2.6%), early vitreous incarceration (2 eyes, 2.6%), retinal detachment (6 eyes, 7.8%) and IOL dislocation (3 eyes, 3.9%). Cox regression showed that postoperative eye trauma was a risk factor for long-term postoperative complications. CONCLUSION: SF-PC-IOLs provide good visual outcomes in patients with congenital lens subluxation. The SF-PC-IOLs showed good stability, except in patients suffering from postsurgical eye trauma.

Analysis of Axial Length in Young Patients with Marfan Syndrome and Bilateral Ectopia Lentis by Z-Scores.

INTRODUCTION: Marfan syndrome (MFS) is characterized by ectopia lentis (EL) and elongated axial length (AL). The characteristics of AL in young patients with MFS and bilateral EL before the lens surgery are not fully understood. METHODS: This study reviewed MFS patients under 20 years old with bilateral EL from January 2015 to October 2020. The Z-scores were introduced in terms of the number of standard deviations from the mean of age-matched normative data. Using Z-scores, the distribution of AL and influence factors were evaluated. The correlations between AL and other biometrics were analyzed. RESULTS: We reviewed 183 patients and enrolled both eyes. The mean age was 8.44 ± 4.69 years. About 36% of the patients were children under 6 years old. The median AL increased from 23.16 mm under 5 years old to 26.20 mm in the 16-20 age group, and when plotted, the trend presented a logarithmic curvature (R2 = 0.145, p < 0.001). The median Z-AL score was 1.24. One-third of eyes had Z-score <0. About 20% of the patients had AL difference over 1 mm between the right and left eyes, and the right one had longer Z-AL scores (p = 0.013). The eye complicated with megalocornea (10, 7.04%) had larger Z-AL scores (4.72 ± 3.51 vs. 1.10 ± 2.25, p = 0.002). A positive correlation was found between Z-AL and Z-corneal curvature radius (r = 0.265, p < 0.001). CONCLUSION: Young patients with bilateral EL but small AL should not be excluded from MFS without systematic examination. The age-adjusted Z-score will facilitate further study of the individual variations in AL across different ages.

Down-regulation of CRTAC1 attenuates UVB-induced pyroptosis in HLECs through inhibiting ROS production.

Pyroptosis has been found to be related to diverse ocular diseases, including cataract. Abnormal CRTAC1 expression has been reported to involve in cataract formation by affecting cell apoptosis. Whether CRTAC1 regulates pyroptosis in the formation progress of cataract is completely unknown. Here, we aimed to investigate the regulatory effects of CRTAC1 on pyroptosis and the potential mechanism in the UVB-induced cell damage model. The results showed that the levels of the established pyroptosis markers (NLRP3, active Caspase-1, pro Caspase-1, GSDMD-N, IL-1ß and IL-18) were significantly increased in cataract patients. The above pyroptosis markers could be obviously induced by UVB-irradiation in human lens epithelial cells (HLECs), while down-regulation of CRTAC1 significantly reversed the UVB-induced pyroptosis. Up-regulation of CRTAC1 promoted HLECs pyroptosis, while the ROS inhibitor N-acetyl-l-cysteine blocked the effects of CRTAC1 overexpression. In conclusion, our findings further suggested that the prominent role of CRTAC1 in cataract formation.

HMGB1 aggravates lipopolysaccharide-induced acute lung injury through suppressing the activity and function of Tregs.

BACKGROUND: CD4+CD25+FoxP3+ T helper cells (Tregs), a subgroup of CD4+ T helper cells, are critical effectors that protect against acute lung injury (ALI) by contact-dependent suppression or releasing anti-inflammatory cytokines including interleukin-10 (IL-10), and transforming growth factor (TGF-ß). HMGB1 (High mobility group box 1 protein) was identified as a nuclear non-histone DNA-binding chromosomal protein, which participates in the regulation of lung inflammatory response and pathological processes in ALI. Previous studies have suggested that Tregs overexpresses the HMGB1-recognizing receptor. However, the interaction of HMGB1 with Tregs in ALI is still unclear. OBJECTIVE: To investigate whether HMGB1 aggravates ALI by suppressing immunosuppressive function of Tregs. METHODS: Anti-HMGB1 antibody and recombinant mouse HMGB1 (rHMGB1) were administered in lipopolysaccharide (LPS)-induced ALI mice and polarized LPS-primed Tregs in vitro. The Tregs pre-stimulated with or without rHMGB1 were adoptively transferred to ALI mice and depleted by Diphtheria toxin (DT). For coculture experiment, isolated Tregs were first pre-stimulated with or without rHMGB1 or anti-HMGB1 antibody, then they were cocultured with bone marrow-derived macrophages (BMMs) under LPS stimulation. RESULTS: Tregs protected against acute lung pathological injury. HMGB1 modulated the suppressive function of Tregs as follows: reduction in the number of the cells and the activity of Tregs, the secretion of anti-inflammatory cytokines (IL-10, TGF-ß) from Tregs, the production of IL-2 from CD4+ T cells and CD11c+ DCs, and the M2 polarization of macrophages, as well as inducing proinflammatory response of macrophages. CONCLUSIONS: HMGB1 could aggravate LPS induced-ALI through suppressing the activity and function of Tregs.

The safety and outcomes of acutely ruptured intracranial aneurysms with incomplete occlusion after coiling: a case-control study.

BACKGROUND: Incomplete aneurysmal occlusion is a common feature of immediate posttreatment angiography. The safety and outcomes of acutely ruptured intracranial aneurysms (RIAs) with incomplete occlusion after stent-assisted coiling (SAC) and no-stent coiling (NSC) have not been well clarified. Progressive occlusion of stents can promote the complete occlusion of intracranial aneurysms (IAs), but it remains to be determined if progressive occlusion in acutely RIAs with incomplete occlusion after coiling may be enhanced by protective stenting. This study aimed to evaluate the safety and outcomes of those aneurysms after SAC and NSC; And to discover whether the stents can promote progressive aneurysm occlusion in such lesions or not. METHODS: We reviewed 199 patients with acutely RIAs underwent endovascular coiling and developed incomplete occlusion in the past seven years. The patients' clinical and imaging information were recorded and analyzed. Univariate and multivariate analyses were performed to determine the association of recurrence rate with potential risk factors. RESULTS: SAC group had wider aneurysms neck (3.471 mm vs 2.830 mm, P = 0.009) and smaller dome-to-neck ratio (1.536 vs 2.111, P = 0.001) than in NSC group. There was no significant difference between the two groups in total procedure-related complications rate (31.7% vs 23.5%, P = 0.195), procedure-related mortality (6.9% vs 2.0%, P = 0.170) and modified Rankin Scale (mRS) score at 6-month follow-up (P > 0.05). However, SAC group had significantly higher ischemic complications rate (21.8% vs 8.2%, P = 0.007) and complete occlusion rate (65.6% vs 48.3%, P = 0.020), and lower recurrence rate (15.6% vs 28.1%, P = 0.042) than NSC group based on 6-month follow-up angiograms. Additionally, Multivariable analysis showed NSC was an independent risk factor for aneurysm recurrence (Odds Ratio [OR]: 4.061; P = 0.018). CONCLUSIONS: Acutely RIAs with incomplete occlusion after SAC is associated with higher complications rate and mortality, but has an acceptable safety profile and similar clinical outcome compared to NSC, as well as gives patients superior angiography outcome by progressive occlusion of stents.