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PURPOSE OF REVIEW: While effective for treating endothelial dysfunction, keratoplasty has shortcomings including limited access to donor tissue for much of the world. Thus, alternative strategies are under development. This review explores the main advancements achieved in this field during 2022-2023. RECENT FINDINGS: Recent publications further support the validity of intracameral cultivated allogeneic endothelial cell injection and Descemet stripping only, while emphasizing the benefits of adjunctive Rho-associated kinase inhibitor (ROCKi) therapy. New donor-independent artificial implants, such as EndoArt, show favorable results. Multiple pharmacologic agents, especially ROCKi, show promise as monotherapies, yet none are currently approved for human treatment. Multiple regenerative and genetic therapies are being investigated but all are still in preclinical stages. SUMMARY: A plethora of innovative alternatives to keratoplasty for endothelial disease is in development. Among these, surgical methods are still the mainstay of treatment and closest to clinical application, though further studies to establish their benefits over keratoplasty are needed. Albeit promising, pharmacologic, regenerative, and genetic approaches require validation and are farther from clinical application.
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Endotélio Corneano , Humanos , Doenças da Córnea/cirurgia , Transplante de Córnea/métodos , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodosRESUMO
PURPOSE: To assess the refractive accuracy of eight intraocular lens (IOL) formulas in eyes that underwent combined phacovitrectomy. METHODS: A retrospective chart review of 59 eyes that underwent uncomplicated phacovitrectomy between 2017 and 2020 at the Johns Hopkins Wilmer Eye Institute. Inclusion criteria were postoperative best corrected visual acuity of 20/40 or better within 6 months of surgery and IOL implantation in the capsular bag. The Barrett Universal II (BUII), Emmetropia Verifying Optical (EVOv2.0), Hill-Radial Basis Function (Hill-RBFv3.0), Hoffer Q, Holladay I, Kane, Ladas Super Formula (LSF), and SRK/T formulas were compared for accuracy in predicting postoperative spherical equivalents (SE) using Wilcoxon rank sum tests. Pearson's correlation coefficients were used to assess correlations between biometric parameters and errors for all formulas. RESULTS: Prediction errors of SE ranged from - 1.69 to 1.43 diopters (D), mean absolute errors (MAE) ranged from 0.39 to 0.47 D, and median absolute errors (MedAE) ranged from 0.23 to 0.37 D among all formulas. The BUII had the lowest mean error (- 0.043), MAE (0.39) and MedAE (0.23). The BUII also had the highest percentage of eyes with predicted error within ± 0.25 D (51%) and ± 0.50 D (83%). Based on MedAE however, no pairwise comparisons resulted in statistically significant differences. Axial length (AL) was positively correlated with the error from the Hoffer Q and Holladay I formulas (correlation coefficients = 0.34, 0.30, p values < 0.01, 0.02 respectively). CONCLUSION: While all eight IOL formulas had comparable accuracy in predicting refractive outcomes in eyes undergoing combined phacovitrectomy, the BUII and Kane formulas had a tendency to greater accuracy.
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Olho Artificial , Lentes Intraoculares , Humanos , Estudos Retrospectivos , Olho , Refração OcularRESUMO
PURPOSE: Corneal biomechanical failure is the hallmark of keratoconus (KC); however, the cause of this failure remains elusive. Collagen type XII (COL12A1), which localises to Bowman's layer (BL), is thought to function in stress-bearing areas, such as BL. Given the putative protective role of COL12A1 in biomechanical stability, this study aims to characterise COL12A1 expression in all corneal layers involved in KC. METHODS: TaqMan quantitative PCR was performed on 31 corneal epithelium samples of progressive KC and myopic control eyes. Tissue microarrays were constructed using full-thickness corneas from 61 KC cases during keratoplasty and 18 non-KC autopsy eyes and stained with an antibody specific to COL12A1. Additionally, COL12A1 was knocked out in vitro in immortalised HEK293 cells. RESULTS: COL12A1 expression was reduced at transcript levels in KC epithelium compared with controls (ratio: 0.58, p<0.03). Immunohistochemical studies demonstrated that COL12A1 protein expression in BL was undetectable, with reduced expression in KC epithelium, basement membrane and stroma. CONCLUSIONS: The apparent absence of COL12A1 in KC BL, together with the functional importance that COL12A1 is thought to have in stress bearing areas, suggests that COL12A1 may play a role in the pathogenesis of KC. Further studies are necessary to investigate the mechanisms that lead to COL12A1 dysregulation in KC.
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Epitélio Corneano , Ceratocone , Humanos , Ceratocone/metabolismo , Colágeno Tipo XII/genética , Colágeno Tipo XII/metabolismo , Células HEK293 , Córnea/patologia , Epitélio Corneano/patologiaRESUMO
PURPOSE: This study aimed to compare outcomes and early complications using an endothelium-in pull-through Descemet membrane endothelial keratoplasty (DMEK) technique with preloaded versus surgeon-loaded donor tissue. METHODS: Data from 163 eyes of 125 patients at the Wilmer Eye Institute diagnosed with Fuchs endothelial corneal dystrophy who underwent DMEK with or without cataract extraction using surgeon-loaded tissue (n = 83) or preloaded tissue (n = 80) were reviewed. Best-corrected visual acuity and early postoperative complications including small graft detachment (less than one third of the graft area), large graft detachment (more than one third), graft failure, and rebubbling were compared. RESULTS: Baseline characteristics including age, sex, and visual acuity were not statistically different between the groups. Small graft detachment was observed in 18.1% of the surgeon-loaded and 22.5% of the preloaded group ( P = 0.48), whereas large detachment occurred in 12.0% and 5.0%, respectively ( P = 0.11). Among these, rebubbling was performed in 18 (21.7%) in the surgeon-loaded compared with 12 (15.0%) in the preloaded group ( P = 0.27). The rebubbling rate of the combined procedure (cataract surgery and DMEK) was 21.8% and of DMEK alone was 7.7% ( P = 0.048). Primary graft failure occurred in 2 surgeon-loaded cases (2.4%) and 1 preloaded case (1.3%) ( P = 0.58). There was no difference in postoperative best-corrected visual acuity at 1 year (logarithm of the minimum angle of resolution 0.21 ± 0.25 for the surgeon-loaded vs. 0.16 ± 0.16 for the preloaded group, P = 0.23). CONCLUSIONS: DMEK surgery using preloaded endothelium-in tissue has comparable outcomes with surgeon-loaded endothelium-in tissue. However, there was a trend toward the lower rebubbling rate in DMEK alone compared with combined procedures.
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Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Distrofia Endotelial de Fuchs , Cirurgiões , Humanos , Lâmina Limitante Posterior/cirurgia , Endotélio Corneano/transplante , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Distrofia Endotelial de Fuchs/cirurgia , Estudos Retrospectivos , Contagem de CélulasRESUMO
ABSTRACT Purpose: This study aimed to report an experiment designed to determine anatomical changes in porcine corneas following placement of a novel polymer implant into the cornea. Methods: An ex vivo porcine eye model was used. A novel type I collagen-based vitrigel implant (6 mm in diameter) was shaped with an excimer laser on the posterior surface to create three planoconcave shapes. Implants were inserted into a manually dissected stromal pocket at a depth of approximately 200 μm. Three treatment groups were defined: group A (n=3), maximal ablation depth 70 μm; Group B (n=3), maximal ablation depth 64 μm; and group C (n=3), maximal ablation depth 104 μm, with a central hole. A control group (D, n=3) was included, in which a stromal pocket was created but biomaterial was not inserted. Eyes were evaluated by optical coherence tomography (OCT) and corneal tomography. Results: Corneal tomography showed a trend for a decreased mean keratometry in all four groups. Optical coherence tomography showed corneas with implants placed within the anterior stroma and visible flattening, whereas the corneas in the control group did not qualitatively change shape. Conclusions: The novel planoconcave biomaterial implant described herein could reshape the cornea in an ex vivo model, resulting in the flattening of the cornea. Further studies are needed using in vivo animal models to confirm such findings.
RESUMO Objetivo: Relatar um experimento projetado para determinar alterações anatômicas em córneas porcinas após a colocação de um novo implante de polímero na córnea. Métodos: Foi utilizado olho de porco ex vivo. Um novo agente modelador biocompatível, de colágeno tipo 1, com 6mm de diâmetro foi moldado com excimer laser em sua face posterior, para criar três formatos planocôncavos. Os implantes foram inseridos dentro de um bolsão, dissecado manualmente, a 200 micrômetros (μm). Foram definidos três grupos de tratamento: grupo A (n=3), teve a profundidade máxima de ablação de 70 μm; o grupo B (n=3), profundidade máxima de ablação de 64 μm; e o grupo C (n=3), profundidade máxima de ablação de 104 μm, com buraco central. O grupo controle, D (n=3), foi incluído, com a criação do bolsão estromal, porém sem inserir o material. A avaliação desses olhos foi realizada por tomografia de coerência óptica (OCT) e por tomografia corneana. Resultados: A tomografia corneana mostrou uma tendência para diminuição da ceratometria média em todos os 4 grupos. A tomografia de coerência óptica mostrou córneas com implantes localizados no estroma anterior e aplanamento visível, enquanto as córneas não mudaram qualitativamente o formato no grupo controle. Conclusões: O novo implante de biomaterial planocôncavo descrito aqui foi capaz de remodelar a córnea em modelo de animal ex vivo, resultando no aplanamento corneano. Novos estudos são necessários usando modelos animais in vivo para confirmar tais achados.
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PRCIS: Cataract, glaucoma, and glaucoma suspect patients report differing visual symptoms. Asking patients about their visual symptoms may provide useful diagnostic information and inform decision-making in patients with comorbid conditions. PURPOSE: To compare visual symptoms in glaucoma, glaucoma suspect (controls), and cataract patients. METHODS: Glaucoma, cataract, and glaucoma suspect patients at Wilmer Eye Institute responded to a questionnaire rating the frequency and severity of 28 symptoms. Univariate and multivariable logistic regression determined the symptoms that best differentiate each disease pair. RESULTS: In all, 257 patients (mean age: 67.4 ± 13.4 y; 57.2% female; 41.2% employed), including 79 glaucoma, 84 cataract, and 94 glaucoma suspect patients, participated. Compared with glaucoma suspects, glaucoma patients were more likely to report poor peripheral vision (OR 11.29, 95% CI: 3.73-34.16), better vision in 1 eye (OR 5.48, 95% CI: 1.33-22.64), and light sensitivity (OR 4.85, 95% CI: 1.78-13.24), explaining 40% of the variance in diagnosis (ie, glaucoma vs. glaucoma suspect). Compared with controls, cataract patients were more likely to report light sensitivity (OR 3.33, 95% CI: 1.56-7.10) and worsening vision (OR 12.20, 95% CI: 5.33-27.89), explaining 26% of the variance in diagnosis (ie, cataract vs. glaucoma suspect). Compared with cataract patients, glaucoma patients were more likely to report poor peripheral vision (OR 7.24, 95% CI: 2.53-20.72) and missing patches (OR 4.91, 95% CI: 1.52-15.84), but less likely to report worsening vision (OR 0.08, 95% CI 0.03-0.22), explaining 33% of the variance in diagnosis (ie, glaucoma vs. cataract). CONCLUSIONS: Visual symptoms distinguish disease state to a moderate degree in glaucoma, cataract, and glaucoma suspect patients. Asking about visual symptoms may serve as a useful diagnostic adjunct and inform decision-making, for example, in glaucoma patients considering cataract surgery.
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Extração de Catarata , Catarata , Glaucoma , Hipertensão Ocular , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Fotofobia , Pressão Intraocular , Acuidade Visual , Glaucoma/complicações , Glaucoma/diagnóstico , Hipertensão Ocular/diagnóstico , Catarata/complicações , Catarata/diagnósticoRESUMO
PURPOSE OF REVIEW: With limited access of more than half the world's population to corneal transplantation, regenerative medicine may represent a promising alternative. This review explores the main advancements achieved in cell-based therapies for corneal epithelium, stroma, and endothelium during 2021-2022. RECENT FINDINGS: Multiple surgical techniques have been developed for epithelial limbal stem cell replacement. Recent studies aimed to gain greater understanding and characterization of these techniques. Though no clear superiority could be demonstrated, simple limbal epithelial transplantation seems to have the most clinical and cost effectiveness. For stromal disease, autologous adipose-derived stem cells have shown favorable results. For endothelial dysfunction, the validity of intracameral cultivated allogeneic endothelial cell injection and Descemetorrhexis without endothelial keratoplasty, as well as the benefits of adjunctive rho-associated kinase inhibitors, were emphasized. SUMMARY: A plethora of innovative cell-based regenerative therapies for corneal diseases have been developed in past years. While recent literature solidifies our knowledge, most studies are still in preliminary or preclinical stages. Though showing great promise, these approaches will require larger studies with better-defined endpoints to establish their benefits over currently available treatments.
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Doenças da Córnea , Transplante de Córnea , Epitélio Corneano , Limbo da Córnea , Humanos , Doenças da Córnea/cirurgia , Transplante de Córnea/métodos , Terapia Baseada em Transplante de Células e Tecidos , Medicina Regenerativa , Transplante de Células-Tronco/métodos , Transplante AutólogoRESUMO
PURPOSE: The objective of this study is to perform a histological analysis of Bowman layer (BL) grafts. METHODS: BL grafts were procured from 13 human cadaver corneal tissues using 3 different donor preparation techniques. Subsequently, the grafts were fixed in 10% buffered formalin phosphate and embedded in paraffin. Hematoxylin and eosin sections of BL grafts were obtained and analyzed under a light microscope. BL and full graft thickness were measured using an image-processing software. RESULTS: All 13 BL grafts contained residual anterior stromal tissue. BL stripping using Kelman-McPherson and Moorfield forceps (technique 3) achieved the thinnest graft thickness with a mean full graft thickness of 18.7 µm (95% confidence interval [CI], -9.8 to 47.2) at the thinnest point of the graft, whereas BL procurement using the Melles lamellar dissector (technique 2) led to the highest mean full graft thickness of 279.9 µm (95% CI, 251.4-308.5) even at the thinnest area of the graft. By contrast, BL dissection using a blunt dissector (technique 1) provided a mean full graft thickness of 70.2 µm (95% CI, 40.4-100.1) at the graft's thinnest point. Although peripheral graft tears occurred in 50%, 50%, and 100% of techniques 1, 2, and 3, respectively, intact 6.25-mm diameter BL grafts could be secured in 50%, 100%, and 80% of techniques 1, 2, and 3, respectively. CONCLUSIONS: None of the techniques used led to the procurement of pure BL grafts devoid of the anterior stroma. Peripheral scoring with a thin needle and tissue manipulation with Kelman-McPherson and Moorfield forceps led to the thinnest grafts in this study.
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Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Endotélio Corneano , Humanos , Endotélio Corneano/patologia , Lâmina Limitante Posterior , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Doadores de Tecidos , Coleta de Tecidos e ÓrgãosRESUMO
PURPOSE: This study aimed to report an experiment designed to determine anatomical changes in porcine corneas following placement of a novel polymer implant into the cornea. METHODS: An ex vivo porcine eye model was used. A novel type I collagen-based vitrigel implant (6 mm in diameter) was shaped with an excimer laser on the posterior surface to create three planoconcave shapes. Implants were inserted into a manually dissected stromal pocket at a depth of approximately 200 µm. Three treatment groups were defined: group A (n=3), maximal ablation depth 70 µm; Group B (n=3), maximal ablation depth 64 µm; and group C (n=3), maximal ablation depth 104 µm, with a central hole. A control group (D, n=3) was included, in which a stromal pocket was created but biomaterial was not inserted. Eyes were evaluated by optical coherence tomography (OCT) and corneal tomography. RESULTS: Corneal tomography showed a trend for a decreased mean keratometry in all four groups. Optical coherence tomography showed corneas with implants placed within the anterior stroma and visible flattening, whereas the corneas in the control group did not qualitatively change shape. CONCLUSIONS: The novel planoconcave biomaterial implant described herein could reshape the cornea in an ex vivo model, resulting in the flattening of the cornea. Further studies are needed using in vivo animal models to confirm such findings.
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PURPOSE: The aim of this study was to describe a case of temporary pupilloplasty during Descemet stripping endothelial keratoplasty to prevent opacification of a hydrophilic acrylic intraocular lens (IOL). METHODS: A 60-year-old man presented with corneal edema in the left eye after a traumatic cataract removal and scleral suture fixation of a hydrophilic acrylic IOL (Akreos, Bausch + Lomb, Bridgewater, NJ). Descemet stripping endothelial keratoplasty with temporary pupilloplasty was performed. The pupilloplasty was lysed with neodymium:YAG laser on postoperative day 5 after the air bubble was no longer present. RESULTS: At 1 year after surgery, the patient did not develop IOL opacification despite the intracameral air used during the surgery. CONCLUSIONS: Opacification of hydrophilic acrylic lenses is a visually significant complication of intracameral gas from endothelial keratoplasty. Our case demonstrates the potential to prevent IOL opacification in a patient with a hydrophilic acrylic IOL by using temporary pupilloplasty.
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Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Lentes Intraoculares , Facoemulsificação , Masculino , Humanos , Pessoa de Meia-Idade , Falha de Prótese , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/efeitos adversos , Acuidade Visual , Lentes Intraoculares/efeitos adversos , Complicações Pós-Operatórias , Transtornos da Visão/etiologia , Facoemulsificação/efeitos adversosRESUMO
PURPOSE: The aim of the current research was to measure the thickness of the residual central corneal bed after performing the manual "Groove and Peel" deep anterior lamellar keratoplasty (GP-DALK) technique on human cadaveric eyes. METHODS: The manual GP-DALK technique was performed on 6 human cadaver eyes by an experienced corneal surgeon. After surgery, the eye globes were fixed in 10% buffered formalin and embedded in paraffin. For each eye, 4-µm-thick hematoxylin and eosin sections involving the pupillary axis were obtained and examined. Using an image-processing software, 2 observers measured the corneal thickness of the residual central corneal bed and the peripheral corneal rims. RESULTS: The overall mean central corneal bed thickness was 35.5 ± 12.9 µm, whereas the mean right and left peripheral rim thicknesses were 993.0 ± 141.1 and 989.3 ± 147.1 µm, respectively ( P = 0.0006 ). In most corneas, the level of dissection reached almost to the pre-Descemetic collagen (Dua) layer. CONCLUSIONS: The GP-DALK technique is effective in removing most of the corneal stroma and may be non-inferior to "big-bubble" deep anterior lamellar keratoplasty in some cases.
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Substância Própria , Transplante de Córnea , Humanos , Substância Própria/cirurgia , Cadáver , Córnea , Membrana Celular , Progressão da DoençaRESUMO
This study aimed to evaluate the efficacy of in situ adeno-associated virus (AAV)-mediated gene delivery into the human corneal limbal region via targeted sub-limbal injection technique. Human cadaveric corneal tissues were fixed on an artificial anterior chamber. Feasibility of sub-limbal injection technique was tested using trypan blue and black India ink. An enhanced green fluorescent protein (eGFP) encoding AAV DJ was injected into sub-limbal region. After AAV injection, corneal tissues were incubated in air-lift culture and prepared for immunohistochemical analysis. Cell survivial and expression of eGFP, stem cell markers (p63α and cytokeratin 19 (KRT19)), and differentiation marker cytokeratin 3 (KRT3) were evaluated using confocal microscopy. Both trypan blue and black India ink stained and were retained sub-limbally establishing specificity of the injection technique. Immunohistochemical analysis of corneas injected with AAV DJ-eGFP indicated that AAV-transduced cells in the limbal region co-express eGFP, p63α, and KRT19 and that these transduced cells were capable of differentiating to KRT3 postitive corneal epithelial cells. Our sub-limbal injection technique can target cells in the human limbus in a reproducible and efficient manner. Thus, we demonstrate that in situ injection of corneal limbus may provide a feasible mode of genetic therapy for corneal disorders with an epithelial etiology.
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Epitélio Corneano , Limbo da Córnea , Humanos , Dependovirus/genética , Azul Tripano , Córnea/metabolismoRESUMO
Purpose: To describe the occurrence of corneal thinning in a patient following intrastromal injection of bevacizumab to treat lipid keratopathy. Observations: A 36-year-old female presented with decreased vision in her right eye with central posterior corneal haze and underwent a treatment regimen including artificial tears, cyclosporine 0.05% drops, prednisolone 1% and oral Valacyclovir 1g with no improvement. Neovascularization was noted at 18 months follow up and treated with intrastromal bevacizumab injections at 24 months. The feeder vessel was attenuated at 3- and 6-months post-injection, but tomography indicated sustained thinning and flattening of the cornea at the injection site contributing to the development of irregular astigmatism. Conclusions and Importance: Corneal thinning is an uncommon potential side effect of intrastromal bevacizumab injection that may affect postoperative visual acuity.
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Purpose: To investigate the effect of an active integrated stress response (ISR) on human corneal epithelial cell motility and cytokine production. Methods: ISR agonists tunicamycin (TUN) and SAL003 (SAL) were used to stimulate the ISR in immortalized corneal epithelial cell lines, primary human limbal epithelial stem cells, and ex vivo human corneas. Reporter lines for ISR-associated transcription factors activating transcription factor 4 (ATF4) and XBP1 activity were generated to visualize pathway activity in response to kinase-specific agonists. Scratch assays and multiplex magnetic bead arrays were used to investigate the effects of an active ISR on scratch wounds and cytokine production. A C/EBP homologous protein (CHOP) knockout cell line was generated to investigate the effects of ISR ablation. Finally, an ISR antagonist was assayed for its ability to rescue negative phenotypic changes associated with an active ISR. Results: ISR stimulation, mediated through CHOP, inhibited cell motility in both immortalized and primary human limbal epithelial cells. Scratch wounding of ex vivo corneas elicited an increase in the ISR mediators phosphorylated-eIF2α and ATF4. ISR stimulation also increased the production of vascular endothelial growth factor (VEGF) and proinflammatory cytokines. ISR ablation, through CHOP knockout or inhibition with integrated stress response inhibitor (ISRIB) rescued epithelia migration ability and reduced VEGF secretion. Conclusions: We demonstrate that the ISR has dramatic effects on the ability of corneal epithelial cells to respond to wounding models and increases the production of proinflammatory and angiogenic factors. Inhibition of the ISR may provide a new therapeutic option for corneal diseases in which the ISR is implicated.
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Estresse Fisiológico , Fator A de Crescimento do Endotélio Vascular , Fator 4 Ativador da Transcrição/metabolismo , Fator 4 Ativador da Transcrição/farmacologia , Citocinas/metabolismo , Células Epiteliais/metabolismo , Humanos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
A missense mutation of collagen type VIII alpha 2 chain (COL8A2) gene leads to early-onset Fuchs' endothelial corneal dystrophy (FECD), which progressively impairs vision through the loss of corneal endothelial cells. We demonstrate that CRISPR/Cas9-based postnatal gene editing achieves structural and functional rescue in a mouse model of FECD. A single intraocular injection of an adenovirus encoding both the Cas9 gene and guide RNA (Ad-Cas9-Col8a2gRNA) efficiently knocked down mutant COL8A2 expression in corneal endothelial cells, prevented endothelial cell loss, and rescued corneal endothelium pumping function in adult Col8a2 mutant mice. There were no adverse sequelae on histology or electroretinography. Col8a2 start codon disruption represents a non-surgical strategy to prevent vision loss in early-onset FECD. As this demonstrates the ability of Ad-Cas9-gRNA to restore the phenotype in adult post-mitotic cells, this method may be widely applicable to adult-onset diseases, even in tissues affected with disorders of non-reproducing cells.
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Sistemas CRISPR-Cas/genética , Códon de Iniciação/genética , Distrofia Endotelial de Fuchs , Edição de Genes/métodos , Animais , Colágeno Tipo VIII/genética , Modelos Animais de Doenças , Distrofia Endotelial de Fuchs/genética , Distrofia Endotelial de Fuchs/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA Guia de Cinetoplastídeos/genéticaRESUMO
Purpose: Cataract surgery is the most common eye surgery. Appropriate optimization of intraocular lens (IOL) calculation formulae can result in improved patient outcomes. The purpose of this article is to describe a methodology of optimizing existing IOL formulae and develop hybrid formulae based on artificial intelligence (AI). Methods: Preoperative biometric and postoperative outcomes data were obtained from medical records at a single institution. A numeric computing environment was used to analyze these data and refine IOL formulae using supervised learning AI. The mean absolute error of each IOL formulae with and without AI enhancement was determined, as well as the number of eyes within 0.5 diopter of the predicted refraction. Results: AI algorithms improved the mean absolute error as well as number of eyes within 0.5 diopters of predicted refraction for each of the formulae tested (P < 0.05). Conclusions: A novel methodology is described that uses AI to improve existing IOL formulae. This methodology has the potential to improve clinical outcomes for cataract surgery patients. Translational Relevance: Artificial intelligence can be used to improve existing IOL formulae.
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Inteligência Artificial , Lentes Intraoculares , Humanos , Implante de Lente Intraocular , Óptica e Fotônica , Refração OcularRESUMO
Purpose: To identify global gene expression changes in the corneal epithelium of keratoconus (KC) patients compared to non-KC myopic controls. Methods: RNA-sequencing was performed on corneal epithelium samples of five progressive KC and five myopic control patients. Selected results were validated using TaqMan quantitative PCR (qPCR) on 31 additional independent samples, and protein level validation was conducted using western blot analysis on a subset. Immunohistochemistry was performed on tissue microarrays containing cores from over 100 KC and control cases. WNT10A transcript levels in corneal epithelium were correlated with tomographic indicators of KC disease severity in 15 eyes. Additionally, WNT10A was overexpressed in vitro in immortalized corneal epithelial cells. Results: WNT10A was found to be underexpressed in KC epithelium at the transcript (ratio KC/control = 0.59, P = 0.02 per RNA-sequencing study; ratio = 0.66, P = 0.03 per qPCR) and protein (ratio = 0.07, P = 0.06) levels. Immunohistochemical analysis also indicated WNT10A protein was decreased in Bowman's layer of KC patients. In contrast, WNT10A transcript level positively correlated with increased keratometry (Kmax ρ = 0.57, P = 0.02). Finally, WNT10A positively regulated COL1A1 expression in corneal epithelial cells. Conclusions: A specific Wnt ligand, WNT10A, is reduced at the mRNA and protein level in KC epithelium and Bowman's layer. This ligand positively regulates collagen type I expression in corneal epithelial cells. The results suggest that WNT10A expression in the corneal epithelium may play a role in progressive KC.