Big data in corneal diseases and cataract: Current applications and future directions

Frontiers in Big Data, Journal Year: 2023, Volume and Issue: 6

Published: Feb. 1, 2023

The accelerated growth in electronic health records (EHR), Internet-of-Things, mHealth, telemedicine, and artificial intelligence (AI) the recent years have significantly fuelled interest development big data research. Big refer to complex datasets that are characterized by attributes of “5 Vs”—variety, volume, velocity, veracity, value. analytics research has so far benefitted many fields medicine, including ophthalmology. availability these not only allow for comprehensive timely examinations epidemiology, trends, characteristics, outcomes, prognostic factors diseases, but also enable highly accurate AI algorithms diagnosing a wide range medical diseases as well discovering new patterns or associations previously unknown clinicians researchers. Within field ophthalmology, there is rapidly expanding pool large clinical registries, epidemiological studies, omics biobanks through which can be accessed. National corneal transplant genome-wide association national cataract databases, ophthalmology-related EHR-based registries (e.g., AAO IRIS Registry) some key resources. In this review, we aim provide succinct overview applicability particularly from perspective cataract, synergistic potential data, technologies, internet things, wearable smart devices, barriers realizing field.

Language: Английский

---

A multi-ancestry GWAS of Fuchs corneal dystrophy highlights the contributions of laminins, collagen, and endothelial cell regulation

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: April 6, 2024

Fuchs endothelial corneal dystrophy (FECD) is a leading indication for transplantation, but its molecular etiology remains poorly understood. We performed genome-wide association studies (GWAS) of FECD in the Million Veteran Program followed by multi-ancestry meta-analysis with previous largest GWAS, total 3970 cases and 333,794 controls. confirm four loci, identify eight novel loci: SSBP3, THSD7A, LAMB1, PIDD1, RORA, HS3ST3B1, LAMA5, COL18A1. further TCF4 locus GWAS admixed African Hispanic/Latino ancestries show an enrichment European-ancestry haplotypes at cases. Among associations are low frequency missense variants laminin genes LAMA5 LAMB1 which, together previously reported LAMC1, form laminin-511 (LM511). AlphaFold 2 protein modeling, validated through homology, suggests that mutations may destabilize LM511 altering inter-domain interactions or extracellular matrix binding. Finally, phenome-wide scans colocalization analyses suggest CTG18.1 trinucleotide repeat expansion leads to dysregulation ion transport endothelium has pleiotropic effects on renal function.

Language: Английский

---

Vernal keratoconjunctivitis and keratoconus

Current Opinion in Allergy and Clinical Immunology, Journal Year: 2021, Volume and Issue: 21(5), P. 507 - 514

Published: July 15, 2021

Vernal keratoconjunctivitis (VKC) is a severe allergic inflammatory disease affecting the conjunctiva in children and young adults. Keratoconus (KC) progressive corneal characterized by thinning of stroma, increased asymmetric curvature, with potential for significant visual deterioration one most common complications VKC. We aimed to review association these two diseases, focus on mechanisms, prevalence, natural history treatment strategies KC associated VKC.KC complication prevalence can be as high 26.8% among VKC patients, whereas abnormal topography may appear up 71% them. It more progresses faster setting (P < 0.05), remarkable an need keratoplasty. Crosslinking transplantation effective patients compared without However, postoperative are higher demand close monitoring, tight control local inflammation prompt awareness consequent restrain eye rubbing.Patients should closely monitored KC. Prompt recognition allows pathogenesis timely management progression preservation vision quality life patients.

Language: Английский

---

Machine Learning Algorithms to Detect Subclinical Keratoconus: Systematic Review

JMIR Medical Informatics, Journal Year: 2021, Volume and Issue: 9(12), P. e27363 - e27363

Published: Oct. 14, 2021

Background Keratoconus is a disorder characterized by progressive thinning and distortion of the cornea. If detected at an early stage, corneal collagen cross-linking can prevent disease progression further visual loss. Although advanced forms are easily detected, reliable identification subclinical be problematic. Several different machine learning algorithms have been used to improve detection keratoconus based on analysis multiple types clinical measures, such as imaging, aberrometry, or biomechanical measurements. Objective The aim this study survey critically evaluate literature algorithmic equivalent definitions. Methods For systematic review, we performed structured search following databases: MEDLINE, Embase, Web Science Cochrane Library from January 1, 2010, October 31, 2020. We included all full-text studies that for excluded did not perform validation. This review followed PRISMA (Preferred Reporting Items Systematic Reviews Meta-Analyses) recommendations. Results compared measured parameters design reported in 26 papers met inclusion criteria. All salient information required detailed comparison, including diagnostic criteria, demographic data, sample size, acquisition system, validation details, parameter inputs, algorithm, key results study. Conclusions Machine has potential routine ophthalmic practice. Currently, there no consensus regarding should assessment optimal algorithm. identified avenues research stratification patients treatment progression.

Language: Английский

---

Association of Novel Loci With Keratoconus Susceptibility in a Multitrait Genome-Wide Association Study of the UK Biobank Database and Canadian Longitudinal Study on Aging

JAMA Ophthalmology, Journal Year: 2022, Volume and Issue: 140(6), P. 568 - 568

Published: April 21, 2022

Importance

Keratoconus can be a debilitating corneal ectasia in which the cornea thins, bulges, and steepens into conical shape. Early features of keratoconus include myopia irregular astigmatism, affect vision treated with contact lenses, collagen cross-linking, or, advanced cases, transplant. Recent estimates prevalence based on results Scheimpflug imaging young adults are as high 1.2%. However, obtaining very large data sets for genome-wide association study (GWAS) is problematic because few population studies severe relatively rare.

Objective

To identify novel loci using resistance factor (CRF) central thickness (CCT).

Design, Setting, Participants

This multitrait GWAS used European ancestry CRF from UK Biobank (UKB) (n = 105 427) Canadian Longitudinal Study Aging (CLSA) 18 307) CCT International Glaucoma Genetics Consortium (IGGC) 17 803). The variants published (4669 cases 116 547 controls) were compared. set UKB was compiled March 24, 2020; released CLSA July IGGC available May 1, 2018.

Main Outcomes Measures

Association risk.

Results

included 4 cohorts: 427 (56 134 women [53.2%] 49 293 men [46.7%]; mean [SD] age, 57 [8] years), 5029 South Asian (2368 [47.1%] 2661 [52.9%]; 54 902 East (622 [68.9%] 280 [31.0%]; 53 307 (9260 [50.6%] 9047 [49.4%]; 63 [10] years) participants. A total 369 233 identified, including 36 114 loci. Twenty-nine 24 associated keratoconus. Polygenic risk scores (PRS) constructed CRF- CCT-associated variants. PRS result showed that adding or CCT-based to previously improved prediction area under receiver operating characteristic curve (from 0.705 0.756 0.715 0.755 CCT).

Conclusions Relevance

These findings support use modeling parameters new enhance polygenic score models.

Language: Английский

---

Genome-Wide Association Study Identifies Two Common Loci Associated with Pigment Dispersion Syndrome/Pigmentary Glaucoma and Implicates Myopia in its Development

Ophthalmology, Journal Year: 2022, Volume and Issue: 129(6), P. 626 - 636

Published: Jan. 11, 2022

PurposeTo identify genetic variants associated with pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) in unrelated patients to further understand the potentially causal relationships between PDS risk factors.DesignA 2-stage genome-wide association meta-analysis replication subsequent silico analyses including Mendelian randomization.ParticipantsA total of 574 cases PG or 52 627 controls European descent.MethodsGenome-wide were performed 4 cohorts meta-analyzed 3 stages: (1) a discovery was cohorts, (2) fourth cohort, (3) all increase statistical power. Two-sample randomization used determine whether refractive error intraocular pressure exert effects over PDS.Main Outcome MeasuresThe myopia exerts PDS.ResultsSignificant present at 2 novel loci for PDS/PG. These follow-up implicate genes gamma secretase activator protein (GSAP) (lead single nucleotide polymorphism [SNP]: rs9641220, P = 6.0×10-10) glutamate metabotropic receptor 5 (GRM5)/TYR SNP: rs661177, 3.9×10-9) as important factors disease risk. showed significant evidence that negative (myopia) direct effect (P 8.86×10-7).ConclusionsCommon SNPs relating GSAP GRM5/TYR are development PG. Although is known factor, this study uses data demonstrate is, part, cause To factors. A randomization. descent. Genome-wide PDS. The Significant 8.86×10-7). Common

Language: Английский

---

Identification of the regulatory circuit governing corneal epithelial fate determination and disease

PLoS Biology, Journal Year: 2023, Volume and Issue: 21(10), P. e3002336 - e3002336

Published: Oct. 19, 2023

The transparent corneal epithelium in the eye is maintained through homeostasis regulated by limbal stem cells (LSCs), while nontransparent epidermis relies on epidermal keratinocytes for renewal. Despite their cellular similarities, precise cell fates of these two types epithelial cells, which give rise to functionally distinct epithelia, remain unknown. We performed a multi-omics analysis human LSCs from cornea and characterized molecular signatures, highlighting similarities differences. Through gene regulatory network analyses, we identified shared type-specific transcription factors (TFs) that define specific established hierarchy. Single-cell RNA-seq (scRNA-seq) analyses confirmed TFs. Notably, LSC-specific TFs can cooperatively target genes associated with opacity. Importantly, discovered FOSL2, direct PAX6 gene, novel candidate opacity, it regulates implicated diseases. By characterizing our study unveils circuitry governing LSC fate its association

Language: Английский

---

Whole-genome sequencing identifies novel loci for keratoconus and facilitates risk stratification in a Han Chinese population

Eye and Vision, Journal Year: 2025, Volume and Issue: 12(1)

Published: Jan. 6, 2025

Abstract Background Keratoconus (KC) is a prevalent corneal condition with modest genetic basis. Recent studies have reported significant associations in multi-ethnic cohorts. However, the situation Chinese population remains unknown. This study was conducted to identify novel variants linked KC and evaluate potential applicability of polygenic risk model Han population. Methods A total 830 individuals diagnosed 779 controls from cohort were enrolled genotyped by whole-genome sequencing (WGS). Common rare respectively subjected single variant association analysis gene-based burden analysis. Polygenic score (PRS) models developed using top single-nucleotide polymorphisms (SNPs) identified meta-analysis then evaluated cohort. Results The characterization germline entailed correction for stratification validation East Asian ancestry included samples via principal component For protein-truncating (PTVs) minor allele frequency (MAF) < 5%, ZC3H11B emerged as prioritized gene, albeit failing reach significance threshold. We detected three common reaching genome-wide ( P ≤ 5 × 10 −8 ), all which are KC. Our validated well known predisposition loci, COL5A1 , EIF3A FNDC3B . Additionally, correlation allelic effects observed suggestive SNPs between largest meta-genome-wide (GWAS) our study. PRS model, generated meta-GWAS, stratified upper quartile, revealing up 2.16-fold increased Conclusions comprehensive WGS-based GWAS large enhances efficiency array-based studies, highlighting refining clinical decision-making early prevention strategies.

Language: Английский

---

Evaluation of Scleral Thickness in Patients With Keratoconus

Eye & Contact Lens Science & Clinical Practice, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

To evaluate scleral thickness of patients with keratoconus by anterior segment optical coherence tomography (AS-OCT). Fifty-two eyes 42 (group 1) and right healthy individuals 2) were included. Scleral measurements taken AS-OCT 6, 4, 2 mm behind the spur in four gaze positions: superior, inferior, temporal, nasal. The data including central corneal (CCT) Pentacam from was also analyzed its relationship evaluated. In group 1, mean 6 posterior to nasal quadrants 397±35.3 (320-482), 408±29.5 (341-467), 393±40.8 (297-469), 403±35.8 (310-482) μm, respectively. 2, 440±42.2 (346-552), 461±33.9 (390-563), 451±46.6 (340-549) 448±34.3 (350-521) 1 significantly lower all compared (P<0.001). CCT 478.22±87.55 (306-632) μm. Positive correlation found between at 4 (ϱ=0.312, P=0.037) (ϱ=0.308, P=0.039) inferior quadrant CCT. keratoconus. positively correlated quadrant. Even though it is not yet known whether changes are progressive or not, measurement may find a place diagnosis follow-up future.

Language: Английский

---

Looking to the Future of Viral Vectors in Ocular Gene Therapy: Clinical Review

Biomedicines, Journal Year: 2025, Volume and Issue: 13(2), P. 365 - 365

Published: Feb. 5, 2025

Eye diseases can significantly affect the quality of life patients due to decreased visual acuity. Although modern ophthalmological diagnostic methods exist, some system are asymptomatic in early stages. Most seek advice from an ophthalmologist as a result rapidly progressive manifestation symptoms. A number inherited and acquired eye have only supportive treatment without eliminating etiologic factor. promising solution this problem may be gene therapy, which has proven efficacy safety shown clinical studies. By directly altering or replacing defective genes, therapeutic approach will stop well reverse progression diseases. This review examines concept therapy its application field ocular pathologies, emphasizing most recent scientific advances their potential impacts on function status.

Language: Английский

---