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Purpose: To describe the management and multimodal imaging of lattice corneal dystrophy type II (LCD-II) complicated by an infectious keratitis due to a bandage contact lens and to review current literature., Observation: A 50-year-old female was diagnosed with Meretoja's Syndrome by the triad of facial palsy, loose skin (cutix laxa), and stromal corneal dystrophy. At slit lamp, bilateral lattice corneal dystrophy (LCD) was characterized by multiple linear refractile lines and subepithelial fibrosis along with Neurotrophic keratitis Mackie grade I. Findings of anterior segment optical coherence tomography (AS-OCT) were epithelial irregularity, subepithelial fibrosis, hyperreflectivity on anterior stromal layer, lobulated stromal surface. In vivo confocal microscopy (IVCM) showed hyperreflected deposits on the basal and Bowman layers, visible keratocytes; fine lines and streaks between corneal lamella. The sub-basal nerve plexus and the stromal nerves were no longer visible. She presented in emergency with a left red eye. A severe bacterial keratitis was diagnosed as a complication of a bandage contact lens used to treat recurrent epithelial erosion. Corneal anesthesia was complete. Corneal neovascularization was evident 10 weeks later and topical bevacizumab (5 mg/ml) was introduced twice daily. Partial regression of deep stromal vessels was noticed at 3 months., Conclusion: In Meretoja's syndrome, neurotrophic keratopathy secondary to polyneuropathy due to systemic amyloid deposits is present in the advanced stages, promotes recurrent corneal erosions. Corneal sensitivity test, AS-OCT and IVCM are crucial in the diagnosis behind any recurrent corneal erosion. The use of bandage contact lens should be avoided in Meretoja's syndrome to prevent a possible infectious keratitis.

Background: Map-dot-fingerprint (MDF) is a corneal epithelial dystrophy affecting the basement membrane that presents bilaterally or in an asymmetric manner. Clinically, it appears as opacities or fingerprint lines and histopathologically, microcystic structures, dot-like patterns, or basement membrane thickening are commonly described features. Materials and Methods: We conducted a retrospective study on 10 cases of MDF obtained from 9 patients between 2017 to 2018 from the MUHC-McGill Ocular Pathology & Translational Research Laboratory. Results: Following histopathological evaluation with hematoxylin and eosin, periodic acid–Schiff (PAS), and in one case Alcian Blue, a final diagnosis of MDF was reached in all cases. Conclusion: This case series aims to document MDFs histopathological characteristics. To the best of our knowledge, this is the largest case series with histopathological diagnosis published, filling an important gap in the literature. [ABSTRACT FROM AUTHOR]

Objective: To analyze graft survival and the outcome of the corneal endothelium after corneal transplantation in a single model to predict the long-term prognosis of these grafts., Design: Cohort study. Data were recorded prospectively and then analyzed retrospectively., Participants: One thousand one hundred forty-four consecutive eyes of 1144 patients who underwent corneal transplantation between 1992 and 2006., Interventions: Penetrating keratoplasty and deep anterior lamellar keratoplasty., Main Outcome Measures: Slit-lamp examination and wide-field specular microscopy results. A joint analysis of endothelial cell loss and time to graft failure was undertaken. From midterm simultaneous analysis of graft survival and endothelial cell loss, long-term graft survival was predicted., Results: The observed 5- and 10-year graft survival estimates were, respectively, 74% and 64%. The average endothelial cell density (cell loss) was 2270 cells/mm(2) before surgery, 1058 cells/mm(2) (-53%) during the sixth postoperative year, and 865 cells/mm(2) (-61%) during the 10th postoperative year. Overall, the predicted graft survival estimate was 27% at 20 years and 2% at 30 years. Both observed and predicted graft survival were higher in patients who had undergone lamellar keratoplasty than in patients who had undergone penetrating keratoplasty and had normal recipient endothelium and higher in patients who had undergone penetrating keratoplasty and had normal recipient endothelium than in patients who had undergone penetrating keratoplasty and had impaired recipient endothelium., Conclusions: For corneal diseases involving the endothelium, penetrating keratoplasty seems to be a good therapeutic approach in elderly patients because the graft life-span may be similar to the patient life expectancy. Conversely, for younger patients, penetrating keratoplasty is only a midterm therapeutic approach. For corneal diseases not involving the endothelium, deep anterior lamellar keratoplasty seems to be a promising therapeutic approach with higher long-term expected survival.

After uneventful phacoemulsification and in-the-bag implantation of an AcrySof SA60AT (Alcon) intraocular lens (IOL), a 52-year-old black man developed pigmentary glaucoma. Slitlamp examination, anterior segment optical coherence tomography, and ultrasound biomicroscopy showed that the posterior surface of the iris was being rubbed by the inferior haptic of the IOL, which was in the bag but deformed. Filtering surgery was needed to control the intraocular pressure. This type of IOL can cause IOL-induced pigmentary glaucoma.

Objective: To compare 3 techniques used for removing the recipient stroma during anterior lamellar keratoplasty (ALK): the "big-bubble" technique, manual dissection using a crescent blade and slitlamp operating microscope, and microkeratome lamellar cut., Design: Retrospective comparative cohort study of 69 consecutive ALKs and 69 consecutive penetrating keratoplasties (PKs). Manifest refraction, slitlamp examination, Goldmann tonometry, ultrasound pachymetry, specular microscopy, and confocal microscopy findings were recorded., Results: The 12-month graft survival estimate was 98.5% in the ALK group and 94.1% in the PK group (P = .19). Higher endothelial cell density was found after ALK (P < .001). At 12 months (before suture removal), 53% of eyes that underwent ALK and 44% of eyes that underwent PK had 20/40 or better spectacle-corrected visual acuity (P = .24). In keratoconic eyes, these values were 83% and 69%, respectively (P = .18). Significant differences in visual acuity, corneal central thickness, and keratocyte density among ALK subgroups were found, with the best results obtained using the big-bubble technique and the worst results obtained using the microkeratome. In eyes that underwent ALK, visual acuity increased with keratocyte density., Conclusions: Better results were obtained after ALK vs PK, and the big-bubble technique seemed to provide the best results.

Synopsis: Corneal epithelial wavefront error and epithelial thickness variance qualify as highly sensitive and specific biomarkers for epithelial basement membrane dystrophy (EBMD). The biomarkers show a normalization after treatment of EBMD with phototherapeutic keratectomy. Purpose: To gauge the diagnostic value of epithelial basement membrane dystrophy (EBMD), a novel spectral-domain optical coherence tomography (SD-OCT)-based imaging modality for simultaneous morphological (thickness profile) and refractive (optical wavefront) assessment of the corneal epithelial layer in one of the most common but often underdiagnosed corneal dystrophies. Methods: In this prospective observational study, a total of 32 eyes of 32 patients diagnosed with EBMD and 32 eyes of 32 healthy control subjects were examined with high-resolution anterior segment SD-OCT (MS-39; CSO, Florence, Italy). Various epithelial thickness and epithelial wavefront-derived terms were compared between groups and receiver operating characteristic (ROC) curves were computed to analyze the diagnostic capacity of the respective parameters. A total of 17 of 32 EBMD patients underwent treatment with phototherapeutic keratectomy (PTK) and were followed up for 3 months. Results: Epithelial thickness variance (60.4 ± 56.7 µm versus 7.6 ± 6.1 µm) and interquartile range (11.0 ± 6.9 versus 3.3 ± 1.9 µm) were markedly elevated in EBMD patients as compared with healthy controls (both with p < 0.001). Epithelial wavefront analysis showed a highly statistically significant excess in all examined aberration terms in EBMD patients (all with p < 0.001). Significantly greater areas under the curve (AUCs) were yielded by the epithelial wavefront-derived parameters (e.g., total epithelial wavefront error: AUC = 0.966; 95% confidence interval (CI) 0.932–1) than by the epithelial thickness-derived parameters (e.g., variance: AUC = 0.919; 95% CI 0.848–0.990). Conclusions: Corneal epithelial wavefront aberrometry proved valuable as an objective biomarker for EBMD, with high sensitivity and specificity. PTK resulted in a reduction of morphological and refractive epithelial irregularities in EBMD. [ABSTRACT FROM AUTHOR]

Objective: Unknown etiology Background: This case report illustrates the incidental detection of atypical hyporeflective bleb-like structures in an otherwise asymptomatic human cornea, highlighting the effectiveness of non-invasive biophotonic imaging techniques such as optical coherence tomography (OCT) and large-area confocal laser scanning microscopy (CLSM). Case Report: A 57-year-old man underwent a comprehensive ophthalmological examination, including slit-lamp biomicroscopy, corneal topography, and densitometry, as part of a clinical study. The patient presented with a clear cornea, a deep and optically empty anterior chamber, and a clear crystalline lens in both eyes. Best-corrected distance visual acuity was -0.1 logMAR. He denied ocular pain, tearing, or photophobia. There was no history of ocular trauma, infectious or genetic diseases, or ocular surgery. Further, OCT and large-area CLSM were employed for a more in-depth analysis of the corneal structure. Standard ophthalmological assessments indicated normal ocular health with no apparent corneal abnormalities. High-resolution OCT and large-area CLSM imaging revealed atypical hyporeflective bleb-like structures within the corneal epithelium and sub-basal nerve plexus but not in the stroma. Conclusions: The authors hypothesize that the observed findings may indicate an early stage of epithelial basement membrane dystrophy, potentially preceding the manifestation of clinical symptoms, detectable solely through advanced biophotonic imaging methods. It is important to emphasize that these observations do not represent a definitive diagnosis. Nevertheless, the discovery of these atypical structures via advanced imaging underscores the importance of incorporating non-invasive biophotonic techniques into preoperative eye examinations in certain situations. This approach could significantly improve the early detection and management of corneal diseases, leading to improved patient outcomes. [ABSTRACT FROM AUTHOR]

Background: 22q11.2 deletion syndrome (22q11.2DS) is a genetic disorder caused by the deletion of the q11.2 band of chromosome 22. It may affect various systems, including the cardiovascular, immunological, gastrointestinal, endocrine, and neurocognitive systems. Additionally, several ocular manifestations have been described. Results: We report a case of a 34-year-old female diagnosed with 22q11.2DS who presented with visual discomfort and foreign body sensation in both eyes. She had no history of recurrent ocular pain. A comprehensive ophthalmological examination was performed, including anterior segment optical coherence tomography and in vivo confocal microscopy. Overall, the exams revealed bilateral corneal map-like lines, dots, and fingerprint patterns, consistent with a diagnosis of epithelial basement membrane dystrophy (EBMD). In addition to presenting with this novel corneal manifestation for 22q11.2 DS, we review the ocular clinical features of 22q11.2DS in the context of our case. Conclusions: The EBMD may represent a new corneal manifestation associated with 22q11.2 syndrome, although the link between these conditions is unknown. Further research is warranted to investigate potentially shared genetic or molecular pathways to the understanding of the phenotypic variety observed among this rare syndrome. [ABSTRACT FROM AUTHOR]

Purpose: Axenfeld Rieger syndrome (ARS) is an autosomal dominant inherited disorder affecting development of the ocular anterior chamber, abdomen, teeth and facial structures. The PITX2 gene is a major gene encoding a major transcription factor associated with ARS., Methods: ARS patients were collected from six unrelated families. Patients and their families were ophthalmologically phenotyped and their blood was collected for DNA extraction. We screened the coding region of human PITX2 gene by direct sequencing. The consequences of the mutations described were investigated by generating crystallographic representations of the amino acid changes. In order to better understand the occurrence of glaucoma in ARS patients, we studied the PITX2 gene expression in human embryonic and fetal ocular tissue sections., Results: We identified four novel PITX2 genetic alterations in four unrelated families with ARS. These mutations included two nonsense mutations (E55X and Y121X), an eight nucleotides insertion (1251 ins CGACTCCT) and a substitution (F58L), in familial and sporadic cases of ARS. We also showed for the first time that PITX2 is expressed at early stages of the human embryonic and fetal periocular mesenchyme, as well as at later stages of human development in the fetal ciliary body, ciliary processes, irido corneal angle and corneal endothelium. The human fetal eye PITX2 gene expression pattern reported here for the first time provides a strong basis for explaining the frequent occurrence of glaucoma in patients affected by PITX2 gene mutations., Conclusions: Two mutations identified affect the homeodomain (E55X and F58L). The E55X nonsense mutation is likely to alter dramatically the DNA-binding capabilities of the PITX2 homeodomain. Furthermore, there is a complete loss of the carboxy-terminal part of the PITX2 protein beyond the site of the mutation. The phenylalanine F58 is known to contribute to the hydrophobic network of the homeodomain. The crystallographic representations of the mutation F58L show that this mutation may change the conformation of the helical core. The F58L mutation is very likely to modify the homeodomain conformation and probably alters the DNA binding properties of PITX2. The other mutations (Y121X and the eight-nucleotide insertion (1251 ins CGA CTC CT) CGA CTC CT, at position 224 in PITX2A) result in partial loss of the C-terminal domain of PITX2. Pitx2 synergistically transactivates the prolactin promoter in the presence of the POU homeodomain protein Pit-1. Pitx2 activity is regulated by its own C-terminal tail. This region contains a highly conserved 14-amino-acid element involved in protein-protein interactions. The C-terminal 39-amino-acid tail represses DNA binding activity and is required for Pitx2 interactions with other transcription factors, for Pitx2-Pit-1 interaction and Pit-1synergism. Pit-1 interaction with the Pitx2 C terminus masks the inhibitory effect and promotes increased DNA binding activity. Thus, the partial or complete loss of the C terminus tail can lead to decreased or absent DNA binding activity and trigger severe ARS phenotypes. Our in situ hybridization results obtained on human embryonic and fetal ocular tissue sections constitute the first molecular histological data providing an explanation for the occurrence of precocious glaucoma in human patients affected by ARS caused by PITX2 mutations. Further structural and biochemical studies are needed for understanding the wide spectrum of clinical phenotypes caused by the increasing number of new PITX2 mutations found in ARS affected patients.

Epithelial basement membrane corneal dystrophy (EBMD), also known as Cogan microcystic epithelial dystrophy or map-dot-fingerprint dystrophy, is a common bilateral epithelial dystrophy. Usually, this disease is not considered to be inherited although several families with autosomal dominant inheritance have been described. We report the analysis of two families with an autosomal dominant pattern of inheritance as well as the analysis of single affected individuals; we identified two different point mutations in the TGFBI/BIGH3 genes, genes known to be associated with other corneal dystrophies. This is the first report of a molecular mutation in individuals with EBMD and it increases the spectrum of mutations in the TGFBI/BIGH3 gene. Based on our screening, up to 10% of EBMD patients could have a mutation in this gene., (Copyright 2006 Wiley-Liss, Inc.)

A 70-year-old man was referred to us with a 2-year, progressive, painless decrease in visual acuity in the right eye. Ocular history included extraction of a traumatic cataract with a transclerally fixated posterior chamber intraocular lens. Slitlamp examination showed a raised, white, vascularized mass covering the cornea. The lesion was removed by superficial lamellar keratectomy. Light microscopy examination confirmed the diagnosis of corneal keloid. These uncommon lesions usually develop in adults after corneal traumas, surgery, or inflammatory processes. They have also been described in children with Lowe's syndrome, Rubinstein-Taybi syndrome, and other ocular developmental disorders.

Ocular albinism type 1 (OA1) is an X-linked disorder, mainly characterized by a severe reduction in visual acuity, foveal hypoplasia, nystagmus, hypopigmentation of the retina, the presence of macromelanosomes in the skin and eyes, and the misrouting of optic pathways, resulting in the loss of stereoscopic vision. We screened the OA1 gene for mutations in three unrelated Canadian and French families and in two isolated patients with OA1. We found three different missense mutations and two different nonsense mutations, three of which were novel. To date, 41 mutations (including missense mutations, insertions, and deletions) have been reported in the OA1 gene. Mutation and polymorphism data for this gene are available from the international albinism center albinism database website: http://www.cbc.umn.edu/tad/oa1map.htm.

Type I oculocutaneous albinism (OCA) is an autosomal recessive disorder caused by the reduction or the absence of tyrosinase (TYR) activity in melanocytes of the skin, hair and eyes. Here we report an analysis of 45 patients with OCA. We found five novel mutations in the tyrosinase gene involved in the pathogenesis of oculocutaneous albinism type IA or type IB (OCA-1A/B) in five unrelated patients. Three mutations are missense mutations (G109R, P205T and H256Y) and two are nucleotide deletions (336-337delCA and 678-680delAGG). One patient is homozygous for the previously known V275F mutation but has an extremely mild OCA phenotype and has no eye features typical of OCA. In several patients we discovered only one or even no mutation in the coding sequence of the TYR gene. Thus, this disease may also result from mutations in non coding regions of the gene or in another gene involved in the biosynthesis of melanin. Hum Mutat 17:352, 2001., (Copyright 2001 Wiley-Liss, Inc.)

Purpose: To provide a genotype and phenotype characterization of the BEST1 mutation in Chinese patients with autosomal recessive bestrophinopathy (ARB) through multimodal imaging and next-generation sequencing (NGS). Methods: Seventeen patients from 17 unrelated families of Chinese origin with ARB were included in a retrospective cohort study. Phenotypic characteristics, including anterior segment features, were assessed by multimodal imaging. Multigene panel testing, involving 586 ophthalmic disease-associated genes, and Sanger sequencing were performed to identify disease-causing variants. Results: Among 17 ARB patients, the mean follow-up was 15.65 months and average onset age was 30.53 years (range: 9–68). Best corrected visual acuity ranged from light perception to 0.8. EOG recordings showed a typically decreased Arden ratio in 12 patients, and a normal or slightly decreased Arden ratio in two patients. Anterior features included shallow anterior chambers (16/17), ciliary pronation (16/17), iris bombe (13/17), iridoschisis (2/17), iris plateau (1/17), narrow angles (16/17) and reduced axial lengths (16/17). Sixteen patients had multiple bilateral small, round, yellow vitelliform deposits distributed throughout the posterior pole, surrounding the optic disc. Initial diagnoses included angle-closure glaucoma (four patients), Best disease (three patients), and central serous chorioretinopathy secondary to choroidal neovascularization (CNV) (one patient), with the remainder diagnosed with ARB. Fourteen patients underwent preventive laser peripheral iridotomy, four of whom also received combined trabeculectomy and iridotomy in both eyes for uncontrolled intraocular pressure. One patient received intravitreal conbercept for CNV. Overall, 15 distinct disease-causing variants of BEST1 were identified, with 14 (82.35%) patients having missense mutations. Common mutations included p. Arg255-256 and p. Ala195Val (both 23.68%), with the most frequent sites in exons 7 and 5. Conclusions: This study provides a comprehensive characterization of anterior segment and genetic features in ARB, with a wide array of morphological abnormalities. Findings are relevant for refining clinical practices and genetic counseling and advancing pathogenesis research. [ABSTRACT FROM AUTHOR]

We show here that yttrium is immiscible and precipitates with various sizes in the body centered cubic V 0.6 Ti 0.4 alloy superconductor. The number and size of the precipitates are found to depend on the amount of yttrium added. Precipitates with various sizes up to 30 μ m are found in the V 0.6 Ti 0.4 alloy containing 5 at. % yttrium. The large amount of line disorders generated by the addition of yttrium in this alloy is found to be effective in pinning the magnetic flux lines. While the superconducting transition temperature increases with the increasing amount of yttrium in the V 0.6 Ti 0.4 alloy, the critical current density is maximum for the alloy containing 2 at. % yttrium, where it is more than 7.5 times the parent alloy in fields higher than 1 T. We found that the effectiveness of each type of defect in pinning the flux lines is dependent on the temperature and the applied magnetic filed. [ABSTRACT FROM AUTHOR]

Mutations in the gene encoding the zinc-finger transcription factor Ikaros (IKZF1) are found in patients with immunodeficiency, leukemia, and autoimmunity. Although Ikaros has a well-established function in modulating gene expression programs important for hematopoietic development, its role in other cell types is less well defined. Here, we uncover functions for Ikaros in thymic epithelial lineage development in mice and show that Ikzf1 expression in medullary thymic epithelial cells (mTECs) is required for both autoimmune regulator–positive (Aire+) mTEC development and tissue-specific antigen (TSA) gene expression. Accordingly, TEC-specific deletion of Ikzf1 in mice results in a profound decrease in Aire+ mTECs, a global loss of TSA gene expression, and the development of autoimmunity. Moreover, Ikaros shapes thymic mimetic cell diversity, and its deletion results in a marked expansion of thymic tuft cells and muscle-like mTECs and a loss of other Aire-dependent mimetic populations. Single-cell analysis reveals that Ikaros modulates core transcriptional programs in TECs that correlate with the observed cellular changes. Our findings highlight a previously undescribed role for Ikaros in regulating epithelial lineage development and function and suggest that failed thymic central tolerance could contribute to the autoimmunity seen in humans with IKZF1 mutations. Editor's summary: Within the thymus, a heterogeneous population of epithelial cells make proteins normally restricted to cell types found in other organs. By presenting antigens derived from these proteins, the epithelial cells contribute to the process of deleting T cells within the thymus, avoiding the release of autoreactive immune cells into the rest of the body. Sin et al. investigated what transcription factors, beyond those currently known, may control the development and function of thymic epithelial cells. Deletion of Ikaros in mice changed the development of specific subsets of thymic epithelial cells and decreased expression of tissue-specific antigens, resulting in the presence of autoreactive T cells within tissues. This function in central tolerance might, therefore, contribute to mutations in Ikaros in humans being associated with autoimmunity. —Sarah H. Ross [ABSTRACT FROM AUTHOR]

Sclerochoroidal calcification (SCC) is a rare disease which is characterized by calcium deposition in the sclera. The choroid is secondarily involved. Typical localization is in the midperipheral region, outside the vascular arcades. SCC is mostly located in the superotemporal quadrant. Often times, the patients are referred with the diagnosis of an amelanotic tumor. SCC may be dystrophic or metastatic. Metastatic SCC lesions are associated with conditions altering calcium and phosphate metabolism including primary and secondary hyperparathyroidism, vitamin D intoxication, renal failure, hyperphosphatemia, and destructive bony lesions. SCC lesions have a characteristic appearance and appear as distinct, ill-defined, yellow-white, elevated scleral/choroidal masses funduscopically. The purpose of this literature review is to review the current knowledge on SCC, highlight the imaging features, and discuss the differential diagnosis as well as management options. [ABSTRACT FROM AUTHOR]

Background: Reduced or absence of melanin poses physical, social, and psychological challenges to individuals with albinism. Mobile health (mHealth) applications have the potential to improve the accessibility of information and services while reducing time and costs. This study aimed to develop and evaluate a mHealth application for self-management of albinism. Methods: This applied study was conducted in two stages (development and evaluation) in 2022. Initially, the functional requirements were determined, and the conceptual model of the application was then developed using Microsoft Visio 2021. In the second phase, the application was evaluated using the Mobile Application Usability Questionnaire (MAUQ) involving patients with albinism to reflect their views on the usability of the application. Results: The key capabilities of the application included: reminders, alerts, educational content, useful links, storage and exchange of images of skin lesions, specialist finder, and notifications for albinism-relevant events. Twenty-one users with albinism participated in the usability testing of the application. The users were predominantly satisfied with the application (5.53 ± 1.10; Max: 7.00). Conclusions: The findings of this study suggest that the developed mobile application could assist individuals with albinism to effectively manage their condition by considering the users' requirements and services that the application should deliver. [ABSTRACT FROM AUTHOR]

Paired homologous domain transcription factor 2 (PITX2) is critically involved in ocular and cardiac development. Mutations in PITX2 are consistently reported in association with Axenfeld-Rieger syndrome, an autosomal dominant genetic disorder and atrial fibrillation, a common cardiac arrhythmia. In this study, we have mined missense mutations in PITX2 gene from NCBI-dbSNP and Ensembl databases, evaluated the pathogenicity of the missense variants in the homeodomain and C-terminal region using five in silico prediction tools SIFT, PolyPhen2, GERP, Mutation Assessor and CADD. Fifteen homeodomain mutations G42V, G42R, R45W, S49Y, R53W, E53D, E55V, R62H, P65S, R69H, G75R, R84G, R86K, R87W, R91P were found to be highly pathogenic by both SIFT, PolyPhen2 were further functionally characterized using I-Mutant 2.0, Consurf, MutPred and Project Hope. The findings of the study can be used for prioritizing mutations in the context of genetic studies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We report here the structural, electrical, thermal, and magnetic properties of the as-cast V 1 − x Zr x alloys (x = 0 –0.4) at low temperatures. We observe that all the alloys undergo successive peritectic and eutectic reactions during cooling from the melt, which leads to the formation of five phases, namely, a body centered cubic β -V phase, two phases with slightly different compositions having a face centered cubic ZrV 2 structure, a hexagonal closed packed α -Zr phase, and the β -Zr precipitates. The amount of each phase is found to be dependent on the concentration of zirconium in vanadium. The β -V and ZrV 2 phases show superconductivity below 5.2 K and 8.5 K, respectively. We show that the critical current density is large for the V-rich V 1 − x Zr x alloys with x > --> 0.1. The grain boundaries generated from the eutectic reaction and the point defects formed due to the variation in the composition are found to be responsible for the pinning of flux lines in low and high magnetic fields, respectively. Our studies reveal that the choice of the composition and the heat treatment, which leads to eutectic reactions are important in improving the critical current density in this alloy system. [ABSTRACT FROM AUTHOR]

A patient in his sixth decade presented to us with redness, pain and a deterioration of vision in his left eye. He had previously been diagnosed with lattice corneal dystrophy (LCD). He was diagnosed with microbial keratitis, and mixed infection was confirmed on culture (bacteria and fungus) with a protracted healing period before resolution of keratitis. He presented 2 years later with similar issues in the same eye and was noted to have a second episode of microbial keratitis, with microsporidia spores noted on gram, potassium hydroxide and calcofluor white stains. He was diagnosed with microsporidial stromal keratitis and underwent therapeutic penetrating keratoplasty. Unfortunately, he suffered a recurrence of microsporidial keratitis following surgery with eventual transplant failure. Microsporidia as an infection in LCD has, to our knowledge, not been previously reported. We aim to discuss microsporidial infection and recurrent microbial keratitis in the setting of LCD. [ABSTRACT FROM AUTHOR]

Background: Best vitelliform macular dystrophy (BVMD), caused by pathogenic variants of the BEST1 gene, has not been reported in association with cataracts and ocular malformations. We reported a case with a complex ocular phenotype comprising microphthalmia, microcornea, cataract, and vitelliform macular dystrophy. Case presentation: A six-year-old girl manifested photophobia and a poor visual behavior. A thorough ophthalmic examination revealed the patient to have bilateral microphthalmia, microcornea, congenital cataract, and Best vitelliform macular dystrophy (BVMD). Whole exome sequencing (WES) identified one variant in the BEST1 and one variant in CRYBB2 genes: c.218 T > G p.(Ile73Arg) and c.479G > C p.(Arg160Pro). The first variant was inherited from the proband's father, who was diagnosed with subclinical BVMD, while the second was a de novo variant. A minigene assay showed that c.218 T > G in BEST1 did not affect pre-mRNA splicing. Conclusions: This case suggests that the complex ocular phenotype comprising BVMD and congenital cataract with microphthalmia cannot be explained by variation in one gene but is caused by variants in BEST1 and CRYBB2. This case highlights the importance of general clinical evaluation and comprehensive genetic testing for diagnosing complex eye diseases. [ABSTRACT FROM AUTHOR]

Indeed, a recent analysis of the therapeutic value of drugs marketed through accelerated approval pathways by EMA and FDA found that fewer than a third of such drugs were adjudicated as being of significant value [[15]]. One significant hurdle encountered in the development of topical medications used in the treatment of anterior segment eye conditions is the physiological barrier present in the cornea that can decrease the efficacy of medications significantly. Keywords: Corneal dystrophy; drug repurposing; orphan drugs; rare disease; transforming growth factor beta induced EN Corneal dystrophy drug repurposing orphan drugs rare disease transforming growth factor beta induced 275 278 4 04/25/23 20230401 NES 230401 1. [Extracted from the article]

Background Axenfeld-Rieger syndrome (ARS) is characterised by typical anterior segment anomalies, with or without systemic features. The discovery of causative genes identified ARS subtypes with distinct phenotypes, but our understanding is incomplete, complicated by the rarity of the condition. Methods Genetic and phenotypic characterisation of the largest reported ARS cohort through comprehensive genetic and clinical data analyses. Results 128 individuals with causative variants in PITX2 or FOXC1, including 81 new cases, were investigated. Ocular anomalies showed significant overlap but with broader variability and earlier onset of glaucoma for FOXC1-related ARS. Systemic anomalies were seen in all individuals with PITX2-related ARS and the majority of those with FOXC1-related ARS. PITX2-related ARS demonstrated typical umbilical anomalies and dental microdontia/hypodontia/oligodontia, along with a novel high rate of Meckel diverticulum. FOXC1-related ARS exhibited characteristic hearing loss and congenital heart defects as well as previously unrecognised phenotypes of dental enamel hypoplasia and/or crowding, a range of skeletal and joint anomalies, hypotonia/early delay and feeding disorders with structural oesophageal anomalies in some. Brain imaging revealed highly penetrant white matter hyperintensities, colpocephaly/ventriculomegaly and frequent arachnoid cysts. The expanded phenotype of FOXC1-related ARS identified here was found to fully overlap features of De Hauwere syndrome. The results were used to generate gene-specific management plans for the two types of ARS. Conclusion Since clinical features of ARS vary significantly based on the affected gene, it is critical that families are provided with a gene-specific diagnosis, PITX2-related ARS or FOXC1-related ARS. De Hauwere syndrome is proposed to be a FOXC1opathy. [ABSTRACT FROM AUTHOR]

Background: Tooth agenesis (TA) is a congenital abnormality that may present as syndromic or nonsyndromic. Considering its complex genetic aetiology, the aim of this study was to uncover the pathogenic mutants in patients with nonsyndromic TA and analyse the characteristics of these mutants. Methods: Exome sequencing was performed to detect pathogenic variants in 72 patients from 43 unrelated families with nonsyndromic TA. All candidate variants were validated using Sanger sequencing. Bioinformatics and conformational analyses were performed to determine the pathogenic mechanisms of the mutants. Results: The following eight mutations (six novel and two known) in six genes were identified in eight families: WNT10A [c.742C > T (p.R248*)], LRP6 [c.1518G > A (p.W506*), c.2791 + 1G > T], AXIN2 [c.133_134insGCCAGG (p.44_45insGQ)], PAX9 [c.439C > T (p.Q147*), c.453_454insCCAGC (p.L154QfsTer60)], MSX1 [c.603_604del (p.A203GfsTer10)] and PITX2 [c.522C > G (p.Y174*)]. Bioinformatics and conformational analyses showed that the protein structures were severely altered in these mutants, and indicated that these structural abnormalities may cause functional disabilities. Conclusions: Our study extends the mutation spectrum in patients with nonsyndromic TA and provides valuable data for genetic counselling. The pathogenic mechanisms of TA in patients/families with unknown causative variants need to be explored further. [ABSTRACT FROM AUTHOR]

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to study the clinical features of uveitis-glaucoma-hyphema (UGH) syndrome, particularly those useful for a differential diagnosis from unilateral hypertensive acute anterior uveitis. A retrospective chart review was conducted on the clinical features of 9 patients with UGH syndrome. These features were then compared with those detected in 50 patients with unilateral hypertensive acute anterior uveitis. Fine and pigmented keratic precipitates (p =.0002 and p =.00004, respectively), iris atrophy (p =.0122), hyphema and vitreous opacities > 2+ (p =.0003), and cystoid macular edema (p =.009) were statistically associated with UGH syndrome. These clinical signs show a high specificity, ranging from 58 to 100%; the presence of pigmented keratic precipitates in the setting of a unilateral acute hypertensive anterior uveitis has a sensitivity and specificity of 89% and 84%, respectively. In patients operated on for cataract, UGH syndrome can be differentiated from unilateral hypertensive acute anterior uveitis considering specific clinical signs. [ABSTRACT FROM AUTHOR]