ErbB4 deficiency exacerbates olfactory dysfunction in an early-stage Alzheimer's disease mouse model.

Olfactory dysfunction is increasingly recognized as an early indicator of Alzheimer's disease (AD). Aberrations in GABAergic function and the excitatory/inhibitory (E/I) balance within the olfactory bulb (OB) have been implicated in olfactory impairment during the initial stages of AD. While the neuregulin 1 (NRG1)/ErbB4 signaling pathway is known to regulate GABAergic transmission in the brain and is associated with various neuropsychiatric disorders, its specific role in early AD-related olfactory impairment remains incompletely understood. This study demonstrated that olfactory dysfunction preceded cognitive decline in young adult APP/PS1 mice and was characterized by reduced levels of NRG1 and ErbB4 in the OB. Further investigation revealed that deletion of ErbB4 in parvalbumin interneurons reduced GABAergic transmission and increased hyperexcitability in mitral and tufted cells (M/Ts) in the OB, thereby accelerating olfactory dysfunction in young adult APP/PS1 mice. Additionally, ErbB4 deficiency was associated with increased accumulation of Aß and BACE1-mediated cleavage of APP, along with enhanced CDK5 signaling in the OB. NRG1 infusion into the OB was found to enhance GABAergic transmission in M/Ts and alleviate olfactory dysfunction in young adult APP/PS1 mice. These findings underscore the critical role of NRG1/ErbB4 signaling in regulating GABAergic transmission and E/I balance within the OB, contributing to olfactory impairment in young adult APP/PS1 mice, and provide novel insights for early intervention strategies in AD. This work has shown that ErbB4 deficiency increased the burden of Aß, impaired GABAergic transmission, and disrupted the E/I balance of mitral and tufted cells (M/Ts) in the OB, ultimately resulting in olfactory dysfunction in young adult APP/PS1 mice. NRG1 could enhance GABAergic transmission, rescue E/I imbalance in M/Ts, and alleviate olfactory dysfunction in young adult APP/PS1 mice. OB: olfactory bulb, E/I: excitation/inhibition, Pr: probability of release, PV: parvalbumin interneurons, Aß: ß-amyloid, GABA: gamma-aminobutyric acid.

Genotype-phenotype profile of global ASPH-associated ectopia lentis and clinical findings from a Chinese cohort.

BACKGROUND: Traboulsi syndrome is an under-recognized syndromic form of ectopia lentis (EL) caused by the aspartate beta-Hydroxylase (ASPH) variant. The genotype-phenotype profile of ASPH-associated disease is poorly understood due to the rarity of the condition. METHODS: We conducted targeted next-generation sequencing and bioinformatics analysis to identify potentially pathogenic ASPH variants in the cohort. Furthermore, we characterized the expression pattern of ASPH and major components of the zonules using single-cell RNA-sequencing (scRNA-seq) and evaluated the genotype-phenotype correlations by combining our data and those from the literature. RESULTS: We identified a novel missense variant c.2075G > A (p.G692D) and a recurrent nonsense variant c.1126C > G (p.R376*) of ASPH in two pedigrees from a Chinese cohort of EL. Both probands were 5-year-old boys with canonical facial dysmorphisms and bilateral anteriorly-dislocated lenses. Other ocular comorbidities included microspherophakia, shallow anterior chamber, and narrow chamber angel. No cardiac involvements or filtering blebs were identified. The single-cell expression atlas of ciliary epithelium demonstrated the coexpression of ASPH with FBN1, FBN2, and LTBP2 in the non-pigmented ciliary epithelium cells. Furthermore, molecular modeling simulation of p.G692D revealed increased affinity to the cb EGF-like domain and a subsequent destabilized calcium-binding motif. The genotype-phenotype analysis demonstrated that patients with cardiac involvements all harbored biallelic truncation variants. CONCLUSIONS: The data from this study provide new insights into the genotype-phenotype profile of ASPH-associated disease and implicate the potential role of ASPH in the pathogenesis of EL.

Time-bin phase-encoding quantum key distribution using Sagnac-based optics and compatible electronics.

In this work, we present a new time-bin phase-encoding quantum key distribution (QKD), where the transmitter utilizes an inherently stable Sagnac-type interferometer, and has comparable electrical requirements to existing polarization or phase encoding schemes. This approach does not require intensity calibration and is insensitive to environmental disturbances, making it both flexible and high-performing. We conducted experiments with a compact QKD system to demonstrate the stability and secure key rate performance of the presented scheme. The results show a typical secure key rate of 6.2 kbps@20 dB and 0.4 kbps@30 dB with channel loss emulated by variable optical attenuators. A continuous test of 120-km fiber spool shows a stable quantum bit error rate of the time-bin basis within 0.4%∼0.6% over a consecutive 9-day period without any adjustment. This intrinsically stable and compatible scheme of time-bin phase encoding is extensively applicable in various QKD experiments, including BB84 and measurement-device-independent QKD.

Genotype Impacts Axial Length Growth in Pseudophakic Eyes of Marfan Syndrome.

Purpose: The purpose of this study was to investigate the relationship between axial length (AL) growth and FBN1 genotype in patients with Marfan syndrome (MFS) after lens surgery and customize the selection of intraocular lens (IOL) power. Methods: Patients with MFS who had lens surgery and primary IOL implantation received panel-based next-generation sequencing (NGS). The rate of axial length growth (RALG) was calculated using pre- and postoperative AL measurements and corrected log10-transformed age. A multivariable regression model of RALG was developed after analyzing the effect of FBN1 genotypes and confounding factors. Results: A total of 139 probands of MFS with a median age at lens surgery of 6.25 years (interquartile range [IQR] = 4.67, 12.50 years) were followed up for a median duration of 2.08 years (IQR = 1.16, 3.00 years). The AL growth curve between the age of 3 and 15 years old was logarithmic. Dominant-negative (DN) variants affecting the disulfide-bridge forming cysteines and the conserved residues for calcium-binding had significantly higher RALG than DN variants affecting other structures (P = 0.001) but comparable to that of haplo-insufficiency variants (P = 1.000). Pre-operative AL (b = 0.563, P = 0.011) and genotype constant (b = 2.603, P = 0.011) were significantly associated with RALG in the final model. A Python-based calculator, Marfan IOL Calculator version 2.0, was programmed using the RALG to predict postoperative AL and customize IOL selection based on the ocular biometric parameters and FBN1 genotype. Conclusions: FBN1 genotype impacted the growth of AL in patients with MFS after IOL implantation. Knowing the FBN1 genotype could help cataract surgeons to customize IOL selection.

A retrospective study of the accuracy of Invisalign Progress Assessment with clear aligners.

The objective of this study was to detective the accuracy of model superimposition and automatic analysis for upper and lower dentition width in Invisalign Progress Assessment during the process of clear aligners. 19 cases were included in this study. Pre-treatment dental cast (T0) and post-treatment dental cast after staged treatment (T1) were available for three-dimensional model superimposition. Subsequently, movements of maxillary teeth in the horizontal plane (cross-section) after staged treatment and width of upper and lower dentition were measured by three-dimensional model superimposition in the real world and Invisalign Progress Assessment separately. Consequently, the data collected from these two methods were compared. In Invisalign Progress Assessment, movements of maxillary teeth in the horizontal plane after staged treatment was 2.31 (1.59,3.22) [median (upper quartile, lower quartile)] millimeter (mm), while in three-dimensional model superimposition, the result was 1.79 (1.21,3.03) mm. The difference between the two groups is significant (P < 0.05). Intercanine width upper, intermolar width upper, intercanine width lower, and intermolar width lower were 36.55 ± 2.76 mm, 56.98 ± 2.62 mm, 28.16 ± 1.85 mm, 53.21 ± 2.72 mm separately in Invisalign Progress Assessment and were 36.48 ± 2.78 mm, 56.89 ± 2.58 mm, 28.05 ± 1.85 mm, 53.16 ± 2.64 mm separately in three-dimensional model analysis, which was no significant difference among these groups (P > 0.05). The data from Invisalign Progress Assessment was not in parallel with what was achieved from model superimposition with palate as a reference completely. The accuracy of model superimposition in Invisalign Progress Assessment needs further investigation, whereas the accuracy of model analysis in Invisalign Progress Assessment was accurate. Thereby, results from Invisalign Progress Assessment should be interpreted with caution by the orthodontist in the clinic.

Amelioration of olfactory dysfunction in a mouse model of Parkinson's disease via enhancing GABAergic signaling.

BACKGROUND: Olfactory dysfunction is among the earliest non-motor symptoms of Parkinson's disease (PD). As the foremost pathological hallmark, α-synuclein initiates the pathology in the olfactory pathway at the early stage of PD, particularly in the olfactory epithelium (OE) and olfactory bulb (OB). However, the local neural microcircuit mechanisms underlying olfactory dysfunction between OE and OB in early PD remain unknown. RESULTS: We observed that odor detection and discrimination were impaired in 6-month-old SNCA-A53T mice, while their motor ability remained unaffected. It was confirmed that α-synuclein increased and accumulated in OB but not in OE. Notably, the hyperactivity of mitral/tufted cells and the excitation/inhibition imbalance in OB were found in 6-month-old SNCA-A53T mice, which was attributed to the impaired GABAergic transmission and aberrant expression of GABA transporter 1 and vesicular GABA transporter in OB. We further showed that tiagabine, a potent and selective GABA reuptake inhibitor, could reverse the impaired olfactory function and GABAergic signaling in OB of SNCA-A53T mice. CONCLUSIONS: Taken together, our findings demonstrate potential synaptic mechanisms of local neural microcircuit underlying olfactory dysfunction at the early stage of PD. These results highlight the critical role of aberrant GABAergic signaling of OB in early diagnosis and provide a potential therapeutic strategy for early-stage PD.

Morphometric Assessment of the Ciliary Body in Patients With Marfan Syndrome and Ectopia Lentis: A Quantitative Study Using Ultrasound Biomicroscopy.

PURPOSE: To explore the biometric characteristics of the ciliary body in patients with Marfan syndrome (MFS) and ectopia lentis (EL). DESIGN: Cross-sectional study. METHODS: Seventy-two consecutive patients with MFS and EL and 72 nondiseased control subjects were recruited. Ciliary body biometric parameters such as ciliary muscle cross-sectional area at 2000 µm from the scleral spur (CMA2000), ciliary muscle thickness at 1000 µm from the scleral spur (CMT1000), and maximum ciliary body thickness (CBTmax) were measured from multiple directions with ultrasound biomicroscopy (UBM). The relationship between ciliary body parameters and other ocular characteristics was also evaluated. RESULTS: Average CMA2000, CMT1000, and CBTmax were 0.692 ± 0.015 mm2, 0.405 ± 0.010 mm, and 0.855 ± 0.023 mm in eyes of patients with MFS, respectively, and were significantly smaller than these values in control subjects (all P < .001). The prevalence of ciliary body thinning was 22.2% in the MFS group vs 0 in the control group (P < .001); eyes with more severe EL had smaller CMA2000 (P = .050), thinner CMT1000 (P = .022), and shorter CBTmax (P = .015). Patients with microspherophakia (MSP) had even smaller CMA2000 (P = .033) and CMT1000 (P = .044) than those without MSP. The most common subluxation direction was in the superonasal quadrant (n = 25; 39.7%), which probably correlates with the thinnest CMT1000 in the inferotemporal quadrant (P = .005). CONCLUSIONS: Patients with MFS and EL had thinner ciliary muscles, shorter ciliary processes, and a higher prevalence of ciliary body thinning, especially those with MSP. Both the extent and direction of subluxation were associated with ciliary body biometry..

Predicting axial length in patients with Marfan syndrome and ectopia lentis after modified capsular tension ring and intraocular lens implantation.

PURPOSE: To predict the growth of axial length (AL) in patients with Marfan syndrome (MFS) and ectopia lentis (EL). SETTING: Eye and ENT Hospital of Fudan University, Shanghai, China. DESIGN: Consecutive retrospective case series. METHODS: Eyes were evaluated that had modified capsular tension ring and intraocular lens (IOL) implantation. The rate of AL growth (RALG) was calculated using AL divided by log10-transformed age. A multivariate linear regression model of RALG was developed after validation. RESULTS: 128 patients with MFS and EL were enrolled with a median follow-up duration of about 3 years. RALG was independent of age between 3 years and 15 years old ( P = .799) and decreased to 0 thereafter ( P = .878). Preoperative AL was associated with RALG in patients under 15 years old ( P = .003). Beta values for the final model of RALG were as below: intercept (-9.794) and preoperative AL (0.664). The postoperative AL was predicted as: postAL = preAL + RALG × log 10 ([postAge + 0.6]/[preAge + 0.6]). The mean prediction error was -0.003 (95% CI, -0.386 to 0.3791) mm and the mean absolute percentage error was 1.93% (95% CI, 0.73% to 3.14%). A Python-based calculator was developed to use the predicted AL in selecting IOL power and setting undercorrection. CONCLUSIONS: The AL growth of patients with MFS followed a logarithmic pattern and ceased at about age 15. A prediction model of postoperative AL was established for individual MFS patients between 3 and 15 years old, which could potentially optimize the IOL power selection.

Supracapsular scleral sutured intraocular lens implantation in anterior segment dysgenesis patients with ectopia lentis.

OBJECTIVE: To describe a new strategy to manage ectopia lentis in ASD patients assessing the visual outcomes and safety of supracapsular scleral sutured intraocular lens implantation and analyzing the accuracy of different intraocular lens (IOL) power calculation formulae. METHODS: Eight patients with ASD (13 eyes) were underwent supracapsular scleral suture fixation of posterior chamber (PC) IOL without capsular extirpation. The preoperative and postoperative clinical features were compared. The prediction error values from four formulae (SRK/T, Holladay 1, Hoffer Q, Haigis), with or without Wang-Koch (WK) adjustment, were calculated for the cases. RESULTS: Zonulodialysis and premature cataracts could be the main reason for the decreased vision in patients with ASD. There was a significant improvement in best corrected visual acuity on 3-month follow-up after applying supracapsular scleral suture fixation of PC IOL. The prediction errors of the different formulae showed a slight tendency towards postoperative myopia. The Haigis formula with WK adjustment showed the best performance. CONCLUSIONS: Supracapsular scleral suture fixation of IOLs for retaining the capsule-zonule barrier is a good option for ASD patients. The Haigis formula is recommended for ASD patients treated with supracapsular scleral suture fixation of IOLs. The predicted IOL power should be reduced based on the effect of the new anatomic position of the IOL to achieve a satisfactory visual outcome.

SVF-GEL Cryopreserved for Different Times Exhibits Varied Preservation and Regeneration Potential After Transplantation in a Mouse Model.

BACKGROUND: Matrix vascular component (SVF) gels derived from fat preserve tissue integrity and cell viability under cryopreserved conditions, making them easy to inject again for later use. Here, we compared the preservation power and regeneration potential of SVF-gel under different cryopreservation times. METHODS: The SVF-gel stored under - 20 °C, without cryoprotectant cryopreservation for 5, 15, and 45 days, with fresh SVF-gel as control. We evaluated the rate of volume retention after thawing the SVF-gel and the apoptosis rate of adipose-derived stem cells. Next, we analyzed retention rated, adipogenesis, angiogenesis, and connective tissue hyperplasia of the grafts, one month after subcutaneously transplanting the specimen into immunodeficient mice. RESULTS: SVF-gel cryopreserved for 5 and 15 days exhibited no significant different in apoptosis rates relative to the control group. Extending the cryopreservation time to 45 days resulted in significantly increased and decreased apoptosis and volume retention rates of SVF-gel, respectively. SVF-gel grafts cryopreserved for 5 and 15 days exhibited no significant differences from those in the control group, although their weights and volumes still fluctuated. Extending the cryopreservation time to 45 days resulted in significantly decreased retention rates of the grafts. Histologically, extending freezing time resulted in a gradual decline in the graft's health adipose tissue, as well as decreased angiogenesis, and connective tissue hyperplasia. CONCLUSION: Simple freezing of SVF-gel at - 20 °C conferred them with sufficient cell viability. Notably, short-term cryopreservation did not significantly increase the apoptosis rate, and it still had a certain regeneration after transplantation. However, prolonging freezing time to 45 days resulted in increased apoptosis rate and worsened transplantation effect. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Treatment with injectable platelet-rich fibrin in a rat model of melasma.

The management of melasma is challenging. Platelet-rich plasma (PRP) therapy has been shown to be beneficial, however, the use of anticoagulants for PRP is dangerous. To evaluate the efficacy of recently developed blood-derived biomaterials (injectable platelet-rich fibrin [I-PRF]) in a rat model of melasma. Sprague Dawley (SD) rats were used to replicate an experimental animal model of melasma. SD rats exhibiting melasma were randomly divided into experimental and control groups. The experimental group was administered weekly intradermal injections of I-PRF, whereas the control group received an equivalent amount of saline. After four weeks, back skin was removed and evaluated based on (1) gross observation, (2) pathological examination and imaging analysis, and (3) biochemical detection. Data were analysed using SAS9.4 software. I-PRF, a safe blood product without anticoagulants, inhibited melanin production in the epidermis and reduced oxidative stress damage in the cortex, improving melasma. I-PRF is a safe and cost-effective blood-derived biomaterial which is useful for the treatment of melasma.

Three-dimensional analysis of maxillary dentition during molar distalization with clear aligners under different movement designs: an in vitro experiment / 中华口腔医学杂志

Objective: To investigate the three-dimensional force in the maxillary dentition under different movement designs for molar distalization with clear aligners Methods: Three groups were designed: simultaneous movement group (simultaneous distalization of maxillary first and second molars), second molar movement group (distalization of maxillary second molars) and first molar movement group (distalization of maxillary first molars). Ten clear aligners were made in each group, and the displacement was designed to be 0.2 mm. A force sensing device was established to measure the three-dimensional force on the upper dentition with the clear aligner. The device contained a model of the maxillary dentition consisting of 14 teeth, each tooth connected to an individual sensor. After the clear aligner was fitted, the data of 14 sensors were collected and analyzed using computer analysis software. The moving teeth were taken as the target teeth, and the rest of the teeth were anchorage. The data of the three-dimensional force in the three groups in each tooth position were measured and compared. Results: The sagittal forces on the first and second molars in the simultaneous movement group were (5.61±0.94) and (5.81±1.08) N, respectively, which were significantly smaller than those of the target teeth in the same position in other groups (P<0.05). The second molars in the first molar movement group received a sagittal reaction force, which was (-6.73±1.99) N. The anterior teeth in the three groups were all subjected to sagittal reaction force, and the force value was in a range of (-3.33 to 0.46) N. In the coronal direction, the second premolars of the simultaneous movement group received the reaction force in the palatal direction, and the force value was (-2.17±1.06) N. The first molars in the second molar movement group were also subjected to palatal reaction force of (-1.99±0.70) N. The second molars and second premolars in the first molar movement group were also subjected to palatal reaction force, which were (-2.85±0.57) and (-1.85±0.74) N, respectively. Compared with the sagittal and coronal forces, the target teeth and anchorage teeth in the three groups were less stressed in the vertical direction. Conclusions: The first and second molars distalized simultaneously, the correction force in the sagittal direction was relatively small. When first molar was moved distally alone, a greater reaction force in the sagittal direction was exerted on the second molar. Buccal displacement of the adjacent anchorage teeth should be designed to counteract the palatal reaction force on the anchorage teeth as the molars moved distally.

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.

Mutation analysis of SUOX in isolated sulfite oxidase deficiency with ectopia lentis as the presenting feature: insights into genotype-phenotype correlation.

BACKGROUND: Isolated sulfite oxidase deficiency (ISOD) caused by sulfite oxidase gene (SUOX) mutations is a rare neurometabolic disease associated with ectopia lentis (EL). However, few genotype-phenotype correlations have been established yet. METHODS: Potentially pathogenic SUOX mutations were screened from a Chinese cohort of congenital EL using panel-based next-generation sequencing and analyzed with multiple bioinformatics tools. The genotype-phenotype correlations were evaluated via a systematic review of SUOX mutations within our data and from the literature. RESULTS: A novel paternal missense mutation, c.205G > C (p.A69P), and a recurrent maternal nonsense mutation, c.1200 C > G (p.Y400*), of SUOX were identified in a 4-year-old boy from 312 probands. The biochemical assays manifested elevated urine sulfite and S-sulfocysteine accompanied by decreased homocysteine in the blood. The patient had bilateral EL and normal fundus, yet minimal neurological involvement and normal brain structure. Molecular modeling simulation revealed the p.A69P mutant had an unstable structure but an unchanged affinity for sulfite, while the truncated p.Y400* mutant showed decreased binding capacity. Genotype-phenotype analysis demonstrated patients with biallelic missense mutations had milder symptoms (P = 0.023), later age of onset (P < 0.001), and a higher incidence of regression (P = 0.017) than other genotypes. No correlations were found regarding EL and other neurological symptoms. CONCLUSION: The data from this study not only enrich the known mutation spectrum of SUOX but also suggest that missense mutations are associated with mild and atypical symptoms.

Genotype-phenotype correlations of marfan syndrome and related fibrillinopathies: Phenomenon and molecular relevance.

Marfan syndrome (MFS, OMIM: 154700) is a heritable multisystemic disease characterized by a wide range of clinical manifestations. The underlying molecular defect is caused by variants in the FBN1. Meanwhile, FBN1 variants are also detected in a spectrum of connective tissue disorders collectively termed as 'type I fibrillinopathies'. A multitude of FBN1 variants is reported and most of them are unique in each pedigree. Although MFS is being considered a monogenic disorder, it is speculated that the allelic heterogeneity of FBN1 variants contributes to various manifestations, distinct prognoses, and differential responses to the therapies in affected patients. Significant progress in the genotype-phenotype correlations of MFS have emerged in the last 20 years, though, some of the associations were still in debate. This review aims to update the recent advances in the genotype-phenotype correlations of MFS and related fibrillinopathies. The molecular bases and pathological mechanisms are summarized for better support of the observed correlations. Other factors contributing to the phenotype heterogeneity and future research directions were also discussed. Dissecting the genotype-phenotype correlation of FBN1 variants and related disorders will provide valuable information in risk stratification, prognosis, and choice of therapy.

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.

Biometric and Structural Ocular Manifestations of Anterior Megalophthalmos.

Objective: The aim of this study was to examine the biometric ocular manifestations and structural ocular features of anterior megalophthalmos (AM). Methods: Fifteen patients with AM (30 eyes) from the Eye & ENT Hospital of Fudan University were included. The age-matched control group consisted of 30 participants (30 eyes) who underwent Pentacam HR and IOLMaster 700 measurements for one normal eye. Data on demographics, biometric manifestations, and genotypes were carefully compared. Results: A total of 15 patients with AM and 30 control patients were enrolled. There were no differences in age (37.27 ± 19.1 vs. 31.43 ± 19.69 years, P = 0.249) between these two groups. AM eyes were characterized by premature cataracts (11/30, 36.67%) and zonular weakness with lens subluxation (22/30, 73.33%) compared with the control group. Notably, 20 of the 30 AM eyes (66.67%) had significant posterior iris bowing, and 16 of the 30 AM eyes (53.33%) showed an enlarged ciliary ring on ultrasound biomicroscopy (UBM). Mean corneal curvature was lower in the AM eyes (42.01 ± 2.06 D vs. 43.14 ± 1.38 D, P = 0.023). There was no significant difference in corneal pachymetry and central endothelial cell count between the AM and control groups. Significant differences were found in terms of the anterior chamber and white-to-white (WTW) among the Pentacam HR and IOLMaster 700 in patients with AM (P < 0.05). The difference was 0.53 ± 0.48 mm and 0.36 ± 0.14 mm, respectively (P < 0.001). Conclusion: The results of this cohort study conclude the biometric and structural ocular manifestations in Chinese cohorts. Posterior iris bowing (66.67%) and lens subluxation (73.33%) are the most characteristic findings in patients with AM with anatomical abnormalities of megalocornea and a deep anterior chamber, although corneal biometric manifestations of AM included flatter cornea and lower total corneal astigmatism. The knowledge of ocular manifestations of AM is important for diagnosis and preparation for the operation in advance to avoid intraoperative and postoperative complications. Significant differences were found in the anterior chamber and WTW values between the Pentacam HR and IOLMaster 700. Thus, we suggest that various examinations should be carefully considered before determining an AM diagnosis.

Phacoemulsification Combined With Supra-Capsular and Scleral-Fixated Intraocular Lens Implantation in Microspherophakia: A Retrospective Comparative Study.

Background: Microspherophakia (MSP) is a rare ocular condition, the lens surgery of which is complicated by both insufficient zonules and undersized capsule. Methods: This study included MSP eyes managed with phacoemulsification combined with supra-capsular and scleral-fixated intraocular lens implantation (SCSF-IOL) and made the comparison with those treated by transscleral-fixated modified capsular tension ring and in-the-bag intraocular lens implantation (MCTR-IOL). Results: A total of 20 MSP patients underwent SCSF-IOL, and 17 patients received MCTR-IOL. The postoperative best corrected visual acuity was significantly improved in both groups (P < 0.001), but no difference was found between the groups (P = 0.326). The IOL tilt was also comparable (P = 0.216). Prophylactic Nd:YAG laser posterior capsulotomy was performed 1 week to 1 month after the SCSF-IOL procedure. In the SCSF-IOL group, two eyes (10.00%) needed repeated laser treatment and one eye (5.00%) had a decentered capsule opening. Posterior capsule opacification was the most common complication (6, 35.29%) in the MCTR group. No IOL dislocation, secondary glaucoma, or retinal detachment was observed during follow-up. Conclusions: SCSF-IOL is a viable option for managing MSP and is comparable with the MCTR-IOL. Nd:YAG laser posterior capsulotomy was necessary to prevent residual capsule complications after the SCSF-IOL procedure.

Combination of Panel-based Next-Generation Sequencing and Clinical Findings in Congenital Ectopia Lentis Diagnosed in Chinese Patients.

PURPOSE: To evaluate the diagnostic yield of congenital ectopia lentis (EL) in a Chinese cohort by combining panel-based next-generation sequencing with clinical findings. DESIGN: A cohort study. METHODS: In total, 175 patients with congenital EL and their available family members (n = 338) were enrolled. All patients with congenital EL underwent genetic testing. Genotype-phenotype analyses were conducted to assess the biometric and structural ocular manifestations of congenital EL. RESULTS: In total, 175 patients with congenital EL and 338 of their relatives were included in this study. In these patients, 92.57% (162 of 175) of disease-related variants were detected in FBN1 (83.43%), CPAMD8 (1.71%), COL4A5 (0.57%), ADAMTSL4 (3.43%), LTBP2 (1.71%), and CBS (2.29%). Based on genetic and clinical findings, the primary diagnostic rate was increased to 40.57% from 19.43% with the exception of the 91 diagnoses of potential Marfan syndrome, with a new diagnostic strategy for congenital EL, thus having been developed. Within this group of patients harboring FBN1 mutations, 16.44% (19 of 141) probands were diagnosed with EL syndrome and 2.13% (3 of 141) were diagnosed with Marfan syndrome. CONCLUSIONS: The results of this cohort study expand the genomic landscape associated with congenital EL in Chinese cohorts. FBN1 mutations represent the most common cause of congenital EL in this population, and we have developed a new diagnostic strategy for congenital EL subtypes via the use of a well-designed panel-based next-generation sequencing that can be used to efficiently and precisely diagnose patients with congenital EL in a cost-effective manner.

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.