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1.
PLoS Genet ; 20(5): e1011230, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713708

RESUMO

Fuchs endothelial corneal dystrophy (FECD) is an age-related cause of vision loss, and the most common repeat expansion-mediated disease in humans characterised to date. Up to 80% of European FECD cases have been attributed to expansion of a non-coding CTG repeat element (termed CTG18.1) located within the ubiquitously expressed transcription factor encoding gene, TCF4. The non-coding nature of the repeat and the transcriptomic complexity of TCF4 have made it extremely challenging to experimentally decipher the molecular mechanisms underlying this disease. Here we comprehensively describe CTG18.1 expansion-driven molecular components of disease within primary patient-derived corneal endothelial cells (CECs), generated from a large cohort of individuals with CTG18.1-expanded (Exp+) and CTG 18.1-independent (Exp-) FECD. We employ long-read, short-read, and spatial transcriptomic techniques to interrogate expansion-specific transcriptomic biomarkers. Interrogation of long-read sequencing and alternative splicing analysis of short-read transcriptomic data together reveals the global extent of altered splicing occurring within Exp+ FECD, and unique transcripts associated with CTG18.1-expansions. Similarly, differential gene expression analysis highlights the total transcriptomic consequences of Exp+ FECD within CECs. Furthermore, differential exon usage, pathway enrichment and spatial transcriptomics reveal TCF4 isoform ratio skewing solely in Exp+ FECD with potential downstream functional consequences. Lastly, exome data from 134 Exp- FECD cases identified rare (minor allele frequency <0.005) and potentially deleterious (CADD>15) TCF4 variants in 7/134 FECD Exp- cases, suggesting that TCF4 variants independent of CTG18.1 may increase FECD risk. In summary, our study supports the hypothesis that at least two distinct pathogenic mechanisms, RNA toxicity and TCF4 isoform-specific dysregulation, both underpin the pathophysiology of FECD. We anticipate these data will inform and guide the development of translational interventions for this common triplet-repeat mediated disease.

4.
J Clin Med ; 13(3)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38337570

RESUMO

(1) Background: This study offers a biexponential model to estimate corneal endothelial cell decay (ECD) following preloaded "endothelium-in" Descemet membrane endothelial keratoplasty (DMEK) in Fuchs' endothelial corneal dystrophy (FECD) patients; (2) Methods: A total of 65 eyes undergoing DMEK alone or combined with cataract surgery were evaluated. The follow-up period was divided into an early phase (first 6 months) and a late phase (up to 36 months). Endothelial cell count (ECC) and endothelial cell loss (ECL) were analyzed; (3) Results: The half time of the ECD was 3.03 months for the early phase and 131.50 months for the late phase. The predicted time-lapse interval to reach 500 cells/mm2 was 218 months (18.17 years), while the time-lapse interval to reach 250 cells/mm2 was 349 months (29.08 years). There was no statistically significant difference between the ECL in DMEK combined with cataract extraction and DMEK alone at 24 months (p ≥ 0.20). At the late phase, long-term ECL prediction revealed a lower ECC half time in patients undergoing DMEK combined with cataract surgery (98.05 months) than DMEK alone (250.32 months); (4) Conclusions: Based on the mathematical modeling, a predicted average half-life of a DMEK graft could reach 18 years in FECD. Moreover, combining cataract extraction with DMEK could result in excessive ECL in the long term.

5.
Surv Ophthalmol ; 69(3): 465-482, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38199504

RESUMO

The cornea is the most frequently transplanted human tissue, and corneal transplantation represents the most successful allogeneic transplant worldwide. In order to obtain good surgical outcome and visual rehabilitation and to ensure the safety of the recipient, accurate screening of donors and donor tissues is necessary throughout the process. This mitigates the risks of transmission to the recipient, including infectious diseases and environmental contaminants, and ensures high optical and functional quality of the tissues. The process can be divided into 3 stages: (1) donor evaluation and selection before tissue harvest performed by the retrieval team, (2) tissue analysis during the storage phase conducted by the eye bank technicians after the retrieval, and, (3) tissue quality checks undertaken by the surgeons in the operating room before transplantation. Although process improvements over the years have greatly enhanced safety, quality, and outcome of the corneal transplants, a lack of standardization between centers during certain phases of the process still remains, and may impact on the quality and number of transplanted corneas. Here we detail the donor screening process for the retrieval teams, eye bank operators. and ophthalmic surgeons and examine the limitations associated with each of these stages.


Assuntos
Transplante de Córnea , Bancos de Olhos , Garantia da Qualidade dos Cuidados de Saúde , Doadores de Tecidos , Humanos , Transplante de Córnea/métodos , Transplante de Córnea/normas , Bancos de Olhos/normas , Seleção do Doador/normas , Seleção do Doador/métodos , Córnea , Obtenção de Tecidos e Órgãos/normas , Doenças da Córnea/cirurgia
6.
J Clin Med ; 13(2)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38256667

RESUMO

Peters' anomaly (PA) is a manifestation of complex disorders in the development of the anterior segment of the eye. The most recognizable feature of the disease is a doughnut-shaped central corneal opacity and adhesions between the opacity and underlying iris. Glaucoma is observed in 30-70% of patients, with up to 50% of the patients showing concomitant vision-threatening disorders. Up to 60% of patients have systemic abnormalities or developmental delays. Being a rare malformation, PA is one of the most common congenital indications for corneal transplantation in infants. Penetrating keratoplasty is used as the primary method of treatment in cases with corneal opacification of a degree that forbids visual development in both eyes. The heterogeneity of co-occurring ophthalmic and systemic malformations in the spectrum of PA determines the wide range of success, defined by various endpoints: graft clarity or visual acuity. Although surgical advancement has made corneal grafting possible in younger children, it has a higher graft failure rate and worse visual prognosis than adult keratoplasty. Optical sector iridectomy, pupil dilation, or cornea rotation can alternatively be performed. Satisfying results of pediatric keratoprosthesis in particular cases of PA have been described. Postoperative treatment of PA aims to maintain a clear optical pathway and prevent amblyopia. This article therefore aims at reporting the ophthalmic treatment and need for multidisciplinary management of PA, including pharmacological and surgical treatment.

7.
BMJ Open Ophthalmol ; 9(1)2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38272533

RESUMO

OBJECTIVE: To evaluate the Descemet membrane endothelial keratoplasty (DMEK) preparation performance of trainee surgeons in an ex vivo human donor cornea DMEK wet lab simulation setting. METHODS: Human donor corneoscleral rims unsuitable for transplantation were obtained from Moorfields Lions Eye Bank. At the wet lab, graft stripping was performed by scoring the peripheral endothelium. The trypan blue positive cells (TBPC) and cell density (cells/mm2-reticule count) were counted manually before and after stripping. The procedural time, peripheral and central tears and complete peel-off were also recorded and analysed. RESULTS: Eight trainee surgeons attended the wet lab each attempting three DMEKs. Between the first and last attempts a significant decrease was seen in the procedural time (17.6 min vs 10.6 min (p<0.05)) and the TBPC % (12.9% vs 3.8% (p<0.05)). The percentage of tears peripherally and centrally also reduced between the first and the last trials (50% vs 13% (p=0.2226) and 38% vs 0% (p=0.1327)). A significant correlation was found between longer peeling times and higher TBPC % (p<0.001) with a 0.7% endothelial mortality increase for each additional minute required to complete the peel. CONCLUSIONS: DMEK wet labs provide a controlled risk-free learning opportunity for trainee surgeons to improve confidence and competence. Wet labs improve the success rate of DMEK graft preparation as well as flatten the learning curve. This emphasises the importance of continued support for the expansion of this valuable learning resource, promoting wider uptake of DMEK surgery.


Assuntos
Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Humanos , Córnea/cirurgia , Bancos de Olhos , Doadores de Tecidos , Curva de Aprendizado , Azul Tripano
8.
Acta Ophthalmol ; 102(1): e22-e30, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37155336

RESUMO

To compare the outcomes of Descemet membrane endothelial keratoplasty (DMEK) performed after phacoemulsification and intraocular lens (IOL) implantation (sequential DMEK) and DMEK combined with phacoemulsification and IOL implantation (combined DMEK) in patients with Fuchs endothelial corneal dystrophy (FECD) and cataract. Systematic literature review and meta-analysis performed according to the PRISMA guidelines and registered in PROSPERO. Literature searches were conducted in Medline and Scopus. Comparative studies reporting sequential DMEK and combined DMEK in FECD patients were included. The main outcome measure of the study was the corrected distance visual acuity (CDVA) improvement. Secondary outcomes were postoperative endothelial cell density (ECD), rebubbling rate and primary graft failure rate. Bias risk was assessed and a quality appraisal of the body of evidence was completed using the Cochrane Robin-I tool. A total of 667 eyes (5 studies) were included in this review, 292 eyes (43.77%) underwent a combined DMEK, while 375 (56.22%) eyes underwent a sequential DMEK surgery. We found no evidence of a difference between the two groups (mean difference, 95% CI) regarding: (1) CDVA improvement (-0.06; -0.14, 0.03 LogMAR; 3 studies, I2 : 0%; p = 0.86); (2) postoperative ECD (-62; -190, 67 cells/mm2 ; 4 studies, I2 : 67%; p = 0.35); (3) rebubbling (risks ratio: 1.04; 0.59, 1.85; 4 studies, I2 : 48%; p = 0.89); and primary graft failure rate (risks ratio: 0.91; 0.32, 2.57; 3 studies, I2 : 0%; p = 0.86). Of all the 5 non-randomized studies, all (100%) were graded as low quality. The overall quality of the analysed studies was low. Randomized controlled trials are needed to confirm no difference or superiority of one approach in terms of CDVA, endothelial cell count and postoperative complication rate between the two arms.


Assuntos
Catarata , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Distrofia Endotelial de Fuchs , Humanos , Distrofia Endotelial de Fuchs/cirurgia , Endotélio Corneano/transplante , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/efeitos adversos , Estudos Retrospectivos , Lâmina Limitante Posterior/cirurgia , Catarata/complicações , Contagem de Células
9.
Redox Biol ; 69: 102986, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38091879

RESUMO

Fuchs endothelial corneal dystrophy (FECD) is a genetically complex, age-related, female-predominant disorder characterized by loss of post-mitotic corneal endothelial cells (CEnCs). Ultraviolet-A (UVA) light has been shown to recapitulate the morphological and molecular changes seen in FECD to a greater extent in females than males, by triggering CYP1B1 upregulation in females. Herein, we investigated the mechanism of greater CEnC susceptibility to UVA in females by studying estrogen metabolism in response to UVA in the cornea. Loss of NAD(P)H quinone oxidoreductase 1 (NQO1) resulted in increased production of estrogen metabolites and mitochondrial-DNA adducts, with a higher CEnC loss in Nqo1-/- female compared to wild-type male and female mice. The CYP1B1 inhibitors, trans-2,3',4,5'-tetramethoxystilbene (TMS) and berberine, rescued CEnC loss. Injection of wild-type male mice with estrogen (E2; 17ß-estradiol) increased CEnC loss, followed by increased production of estrogen metabolites and mitochondrial DNA (mtDNA) damage, not seen in E2-treated Cyp1b1-/-male mice. This study demonstrates that the endo-degenerative phenotype is driven by estrogen metabolite-dependent CEnC loss that is exacerbated in the absence of NQO1; thus, explaining the mechanism accounting for the higher incidence of FECD in females. The mitigation of estrogen-adduct production by CYP1B1 inhibitors could serve as a novel therapeutic strategy for FECD.


Assuntos
Distrofia Endotelial de Fuchs , Masculino , Feminino , Camundongos , Animais , Distrofia Endotelial de Fuchs/genética , Células Endoteliais/metabolismo , Estrogênios , Dano ao DNA , Córnea/metabolismo , DNA Mitocondrial/genética
10.
Eur J Ophthalmol ; 34(1): 287-291, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37861107

RESUMO

PURPOSE: To describe a new method for delivering DMEK grafts into the recipient's eye with endothelium inward configuration using a no-forceps injection technique. METHODS: We retrospectively review 11 patients that underwent DMEK surgery at our institution using a no-forceps injection technique. The graft was preloaded into an intraocular lens (IOL) cartridge and connected to an anterior chamber maintainer (ACM). A 5 ml non luer lock syringe was inserted into the other end of the ACM to create a one-flow system. The cartridge was inserted into the posterior end of an injector, and the graft was successfully delivered into the recipient's eye. RESULT: Twelve eyes of 11 patients were included. Mean follow-up was 9.16 ± 1.3 months. At baseline, mean best corrected visual acuity (BCVA) was 0.76 ± 0.13 logMAr and mean endothelial cell density (ECD) was 2619.00 ± 115.89 cells/mm2. At follow-up, BCVA significantly improved to 0.22 ± 0.05 logMAR (p = 0.003). Although we observed a significant reduction in ECD at follow-up (1688 ± 182.20, p = 0.002), our patients lost only 35.69 ± 6.36% of endothelial cells. CONCLUSION: Our technique can help surgeons safely deliver an endothelium-in graft into the recipient's eye. The method doesn't require the use of a forceps, minimizing the risk of endothelial cell loss or graft damage.


Assuntos
Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Distrofia Endotelial de Fuchs , Humanos , Lâmina Limitante Posterior/cirurgia , Distrofia Endotelial de Fuchs/cirurgia , Estudos Retrospectivos , Células Endoteliais , Acuidade Visual , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Endotélio Corneano/transplante , Contagem de Células
11.
Eur J Ophthalmol ; : 11206721231217127, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38099841

RESUMO

PURPOSE: To report the outcomes of standardizing pre-loaded DMEK with endothelium-inwards and its associated learning curve. METHODS: Between 2017 and 2021, a total of 599 tissues were stripped using 'trephine and strip' method and loaded by folding the tissue as a taco-fold with endothelium-inwards. The folded tissues were pulled inside the funnel of a 2.2 mm IOL cartridge and stored for the desired number of days in organ culture media supplemented with dextran. Donor characteristics, endothelial cell loss (ECL) and mortality assessed by trypan blue positivity before and after stripping, and eventful cases during stripping/loading were recorded. RESULTS: The tissues found unsuitable for transplant after stripping (6.7%) were significantly higher compared with loading (0.67%). Central or peripheral tears, fragility of the tissues, and insufficient endothelial cell density mainly attributed towards the discard rate. Mean ECL from pre-stripping to post-stripping was 0.27% with endothelial cell mortality of 0.64% at the end of stripping. Cumulative endothelial mortality fold change (pre-strip to post-strip) was high in the first two years of operation (18.9%), which reduced to 5.1% in the following three years with significant difference (p = 0.0352). Average tissue wastage (3 operators) from first 1-150 tissues was 3%, which significantly reduced to 0.9% after achieving the learning curve (151-250) (p = 0.0492). CONCLUSION: DMEK graft preparation requires a learning curve. However, an operator with DMEK stripping skills can easily adapt to pre-loading a DMEK graft in endothelium-inwards fashion with minimal learning curve.

12.
J Clin Med ; 12(17)2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37685508

RESUMO

OBJECTIVE: We sought to evaluate the clinical outcomes of hemi-UT-DSAEK grafts from the pediatric donor corneas of patients affected by Fuchs Endothelial Corneal Dystrophy (FECD). METHODS: A prospective, interventional case series was conducted at the Ophthalmology Department of Venice Civil Hospital and the Veneto Eye Bank Foundation (Venice, Italy). Six eyes of six patients affected by FECD received large-diameter, semicircular hemi-UT-DSAEK grafts obtained from three pediatric donor corneas using the standard pull-through method. Endothelial cell density (ECD), central corneal thickness (CCT), best-corrected visual acuity (BCVA) and intraoperative and postoperative complications were recorded at different time intervals up to 12 months. RESULTS: The average donor age was 64.6 ± 8.6 years, and the pre-operative ECD was 3266 ± 225 cells/mm2. At 12 months postoperatively, the average ECD was 1376 ± 509 cells/mm2 with a mean decrease of 56.8 ± 19.1% from the preoperative donor count. At 12 months, four out of six eyes had significantly improved and reached a BCVA of ≥20/25 (Snellen equivalent). The mean CCT significantly decreased from 788 ± 138 µm before surgery to 576 ± 30 µm at 12 months postoperatively (p < 0.01). CONCLUSIONS: Hemi-UT-DSAEK grafts using pediatric donor corneas are surgically feasible and can provide similar clinical outcomes compared to conventional UT-DSAEK. Transplanting pediatric donor tissues with high ECD into two patients could potentially increase the donor tissue pool to treat endothelial disease.

13.
BMJ Open Ophthalmol ; 8(1)2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37730252

RESUMO

INTRODUCTION: The success of keratoplasty strongly depends on the health status of the transplanted endothelial cells. Donor corneal tissues are routinely screened for endothelial damage before shipment; however, surgical teams have currently no means of assessing the overall viability of corneal endothelium immediately prior to transplantation. The aim of this study is to validate a preoperative method of evaluating the endothelial health of donor corneal tissues, to assess the proportion of tissues deemed suitable for transplantation by the surgeons and to prospectively record the clinical outcomes of a cohort of patients undergoing keratoplasty in relation to preoperatively defined endothelial viability. METHODS AND ANALYSIS: In this multicentre cohort study, consecutive patients undergoing keratoplasty (perforating keratoplasty, Descemet stripping automated endothelial keratoplasty (DSAEK), ultra-thin DSAEK (UT-DSAEK) or Descemet membrane endothelial keratoplasty) will be enrolled and followed-up for 1 year. Before transplantation, the endothelial viability of the donor corneal tissue will be evaluated preoperatively through trypan blue staining and custom image analysis to estimate the overall percentage of trypan blue-positive areas (TBPAs), a proxy of endothelial damage. Functional and structural outcomes at the end of the follow-up will be correlated with preoperatively assessed TBPA values. ETHICS AND DISSEMINATION: The protocol will be reviewed by the ethical committees of participating centres, with the sponsor centre issuing the final definitive approval. The results will be disseminated on ClinicalTrials.gov, at national and international conferences, by partner patient groups and in open access, peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05847387.


Assuntos
Transplante de Córnea , Cirurgiões , Humanos , Endotélio Corneano/cirurgia , Células Endoteliais , Estudos de Coortes , Azul Tripano , Transplante de Córnea/efeitos adversos , Estudos Multicêntricos como Assunto
14.
Surv Ophthalmol ; 68(6): 1129-1152, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37392969

RESUMO

Descemet membrane endothelial keratoplasty (DMEK) is a partial-thickness corneal transplantation procedure that involves selective transplantation of the Descemet membrane and endothelium. DMEK offers significant advantages over other keratoplasty techniques, such as faster visual rehabilitation, better final visual acuity due to minimal optical interface effects, lower risk of allograft rejection, and less long-term dependence on topical steroids. Despite all its advantages, DMEK has been found to be more challenging than other corneal transplantation techniques, and its steep learning curve appears to be an obstacle to its widespread use and adoption by corneal surgeons worldwide. DMEK surgical training laboratories (wet labs) provide a window of opportunity for surgeons to learn, prepare, manipulate, and deliver these grafts in a risk-free environment. Wet labs are a significant learning tool, especially for those institutions that have limited tissue availability in their local centers. We provide a step-by-step guide for preparing DMEK grafts using different techniques on human and nonhuman models with instructional videos. This article should eventually help the trainees and the educators understand the requirements for performing DMEK and conducting a DMEK wet lab and develop their skills and interests from a wide variety of available techniques.


Assuntos
Doenças da Córnea , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Humanos , Lâmina Limitante Posterior/cirurgia , Laboratórios , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Córnea/cirurgia , Endotélio Corneano/cirurgia , Doenças da Córnea/cirurgia
15.
Int J Mol Sci ; 24(14)2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37511249

RESUMO

Transparency of the human cornea is responsible for clear vision, which is maintained by a monolayer of non-proliferative human corneal endothelial cells (HCEnCs). Dysfunction of these cells can result in irreversible corneal blindness. It is important to identify key factors that limit the proliferation of HCEnCs and thus attempt to reverse them. Extracellular vesicles contain cargo which includes microRNAs (miRNAs) that can modulate a cellular function. In non small cell lung cancer, expression of miR-195-5p has been shown to inhibit proliferation; therefore, we aimed to investigate the inhibitory effect of miR-195-5p in inducing the proliferation of HCEnCs. Human corneal endothelial cell line (HCEC-12) and primary HCEnCs were cultured with miR-195-5p scramble, mimic or inhibitor. Corneal tissues from human cadaveric and FECD donors, and from pigs, mice and rabbits, were used for RT-PCR. miR-195-5p showed an abundance value of 11,363.31 a.u. When normalized against HCEnCs from cadaveric donors, FECD tissues showed a significant upregulation of miR-195-5p (p < 0.05) but was significantly downregulated in pig (p < 0.001), mouse (p < 0.01) and rabbit (p < 0.001) CEnCs, which have known proliferative capacity. Proliferation, cell doubling, and wound healing rates were significantly higher when miR-195-5p was inhibited. Inhibiting miR-195-5p showed a significant improvement in viability (HEC staining), decreased cell apoptosis (TdT-dNTP staining) and expression of ZO-1, NA+/K+-ATPase and Ki-67 markers. Expression of miR-195-5p is found in HCEnCs and FECD cells, which restricts the proliferation of these cells. However, inhibiting miR-195-5p can induce the proliferation of HCEnCs, which opens exciting directions for future research in prolonging FECD pathogenesis by increasing the proliferative capacity of HCEnCs using anti-miR therapy in vivo.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Animais , Camundongos , Coelhos , Suínos , Células Endoteliais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células , Cadáver
16.
Surv Ophthalmol ; 68(5): 940-956, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37146692

RESUMO

Congenital aniridia is a panocular disorder that is typically characterized by iris hypoplasia and aniridia-associated keratopathy (AAK). AAK results in the progressive loss of corneal transparency and thereby loss of vision. Currently, there is no approved therapy to delay or prevent its progression, and clinical management is challenging because of phenotypic variability and high risk of complications after interventions; however, new insights into the molecular pathogenesis of AAK may help improve its management. Here, we review the current understanding about the pathogenesis and management of AAK. We highlight the biological mechanisms involved in AAK development with the aim to develop future treatment options, including surgical, pharmacological, cell therapies, and gene therapies.


Assuntos
Aniridia , Doenças da Córnea , Humanos , Doenças da Córnea/etiologia , Doenças da Córnea/terapia , Aniridia/complicações , Aniridia/terapia , Aniridia/genética , Córnea/patologia , Transtornos da Visão , Previsões
17.
Transl Vis Sci Technol ; 12(5): 14, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37184500

RESUMO

Purpose: To evaluate a novel deep learning algorithm to distinguish between eyes that may or may not have a graft detachment based on pre-Descemet membrane endothelial keratoplasty (DMEK) anterior segment optical coherence tomography (AS-OCT) images. Methods: Retrospective cohort study. A multiple-instance learning artificial intelligence (MIL-AI) model using a ResNet-101 backbone was designed. AS-OCT images were split into training and testing sets. The MIL-AI model was trained and validated on the training set. Model performance and heatmaps were calculated from the testing set. Classification performance metrics included F1 score (harmonic mean of recall and precision), specificity, sensitivity, and area under curve (AUC). Finally, MIL-AI performance was compared to manual classification by an experienced ophthalmologist. Results: In total, 9466 images of 74 eyes (128 images per eye) were included in the study. Images from 50 eyes were used to train and validate the MIL-AI system, while the remaining 24 eyes were used as the test set to determine its performance and generate heatmaps for visualization. The performance metrics on the test set (95% confidence interval) were as follows: F1 score, 0.77 (0.57-0.91); precision, 0.67 (0.44-0.88); specificity, 0.45 (0.15-0.75); sensitivity, 0.92 (0.73-1.00); and AUC, 0.63 (0.52-0.86). MIL-AI performance was more sensitive (92% vs. 31%) but less specific (45% vs. 64%) than the ophthalmologist's performance. Conclusions: The MIL-AI predicts with high sensitivity the eyes that may have post-DMEK graft detachment requiring rebubbling. Larger-scale clinical trials are warranted to validate the model. Translational Relevance: MIL-AI models represent an opportunity for implementation in routine DMEK suitability screening.


Assuntos
Doenças da Córnea , Aprendizado Profundo , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Humanos , Endotélio Corneano/transplante , Tomografia de Coerência Óptica/métodos , Estudos Retrospectivos , Inteligência Artificial , Acuidade Visual , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Doenças da Córnea/cirurgia
18.
Graefes Arch Clin Exp Ophthalmol ; 261(11): 3097-3111, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37103622

RESUMO

PURPOSE: To provide a comprehensive review of the incidence, risk factors, and management of early complications after deep anterior lamellar keratoplasty (DALK), Descemet stripping automated keratoplasty (DSAEK), and Descemet membrane endothelial keratoplasty (DMEK). METHODS: A literature review of complications, that can occur from the time of the transplant up to 1 month after the transplant procedure, was conducted. Case reports and case series were included in the review. RESULTS: Complications in the earliest postoperative days following anterior and posterior lamellar keratoplasty have shown to affect graft survival. These complications include, but are not limited to, double anterior chamber, sclerokeratitis endothelial graft detachment, acute glaucoma, fluid misdirection syndrome, donor-transmitted and recurrent infection, and Uretts-Zavalia syndrome. CONCLUSION: It is essential for surgeons and clinicians to not only be aware of these complications but also know how to manage them to minimize their impact on long-term transplant survival and visual outcomes.

19.
Cornea ; 42(9): 1133-1139, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36538420

RESUMO

PURPOSE: The aim of this study was to compare long-term clinical outcomes of preloaded Descemet membrane endothelial keratoplasty (DMEK) between Fuchs endothelial corneal dystrophy (FECD) and bullous keratopathy (BK). METHODS: In this single-center retrospective clinical case series, 71 eyes of 64 patients indicated with FECD (62%) or BK (38%) (with or without cataract) were treated with preloaded DMEK grafts between March 2018 and February 2020. Standard DMEK peeling, followed by manual folding of the tissue with endothelium-inward orientation and storing in a preloaded fashion inside a 2.2-mm intraocular lens cartridge. All tissues were delivered using a bimanual pull-through technique, followed by air tamponade. Graft unfolding time, endothelial cell loss, corrected distance visual acuity, central corneal thickness, rebubbling rate, and intraoperative and postoperative complications at 1, 3, 6, 12, and 24 months were recorded. RESULTS: The mean intraoperative graft unfolding time in FECD did not differ from the BK group ( P = 0.6061). Cystoid macular edema did not differ in either group ( P = 0.6866). The rebubbling rate was found to be significantly higher in FECD compared with the BK group ( P = 0.0423). Corrected distance visual acuity significantly improved at the first month after surgery ( P = 0.0012), with no differences between FECD and BK at 24 months ( P = 0.2578). Central corneal thickness was stable postoperatively and showed no differences between the groups ( P = 0.3693). Significantly higher endothelial cell counts were observed in the FECD group at 24 months ( P = 0.0002). CONCLUSIONS: Preloaded DMEK with "endothelium-in" offers acceptable intraoperative time, rebubbling rate, and clinical outcomes in both FECD and BK groups. Patients with FECD show better postoperative clinical outcomes even if the rebubbling rate is relatively high.


Assuntos
Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Distrofia Endotelial de Fuchs , Humanos , Distrofia Endotelial de Fuchs/cirurgia , Lâmina Limitante Posterior/cirurgia , Endotélio Corneano/transplante , Estudos Retrospectivos , Perda de Células Endoteliais da Córnea/cirurgia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Contagem de Células
20.
Eur J Ophthalmol ; 33(3): 1480-1483, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36576965

RESUMO

INTRODUCTION: We describe a novel technique for identifying endothelial Descemet membrane (DM) tags remaining after descemetorhexis in patients undergoing Descemet membrane endothelial keratoplasty (DMEK) surgery. METHODS: A surgical goniolens is applied to the corneal surface after descemetorhexis in order to visualize the peripheral inner corneal layer at 360° and identify endothelial-DM tags. RESULTS: A detailed visualization of the peripheral inner corneal layer is possible using goniolens, without using any staining in the anterior chamber. CONCLUSION: The technique may be used to screen the posterior corneal surface for any retained endothelial-DM tags. It may to lower the risk of remaining tags and indirectly lower the incidence of DMEK graft detachment.


Assuntos
Doenças da Córnea , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Distrofia Endotelial de Fuchs , Humanos , Lâmina Limitante Posterior/cirurgia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Acuidade Visual , Doenças da Córnea/cirurgia , Córnea , Estudos Retrospectivos , Endotélio Corneano/transplante , Distrofia Endotelial de Fuchs/cirurgia
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