RESUMO
The training of artificial intelligence (AI) is becoming increasingly popular. More and more studies on lamellar keratoplasty are also being published. In particular, the possibility of non-invasive and high-resolution imaging technology of optical coherence tomography predestines lamellar keratoplasty for the application of AI. Although it is technically easy to perform, there are only a few studies on the use of AI to optimise lamellar keratoplasty. The existing studies focus primarily on the prediction probability of rebubbling in DMEK and DSAEK and on their graft adherence, as well as on the formation of a big bubble in DALK. In addition, the automated recording of routine parameters such as corneal oedema, endothelial cell density or the size of the graft detachment is now possible using AI. The optimisation of lamellar keratoplasty using AI holds great potential. Nevertheless, there are limitations to the published algorithms, in that they can only be transferred between centres, surgeons and different device manufacturers to a limited extent.
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Inteligência Artificial , Transplante de Córnea , Tomografia de Coerência Óptica , Humanos , Transplante de Córnea/métodos , Tomografia de Coerência Óptica/métodos , Cirurgia Assistida por Computador/métodos , Doenças da Córnea/cirurgiaRESUMO
BACKGROUND: Patients undergoing corneal abrasion as part of Descemet membrane endothelial keratoplasty (DMEK) under general anesthesia suffer from early burning pain postoperatively. This pain appears to be poorly treatable with systemic analgesics. This study aims to evaluate postoperative pain management using topical lidocaine gel after DMEK with iatrogenic corneal abrasion. METHODS: Retrospective analysis of 28 consecutive patients undergoing DMEK with corneal abrasion from October 19, 2021, to November 12, 2021, at a German university hospital. Patients during week 1 and 2 received peri-operative standard pain treatment (cohort S) and additional local lidocaine gel during week 3 and 4 immediately postoperatively (cohort L). RESULTS: 13 patients were included in cohort S and 15 patients in cohort L. At awakening all patients (100%) in cohort S reported burning pain, and six of 15 patients (40%) in cohort L reported burning pain. Burning pain scores were significantly lower in cohort L (p < 0.001 at awakening, p < 0.001 at 10 min, p < 0.001 at 20 min, p < 0.001 at 30 min, p = 0.007 at 40 min after awakening, and p < 0.001 at leaving recovery room). No significant differences between cohort S and cohort L were detected concerning surgical outcome during 1-month-follow-up (p = 0.901 for best corrected visual acuity). CONCLUSION: Patients undergoing DMEK with corneal abrasion suffer significant pain in the recovery room. A single dose of topic lidocaine gel reduces the early postoperative burning pain sufficiently and does not affect the surgical outcome.
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Lesões da Córnea , Transplante de Córnea , Humanos , Dor Ocular , Lâmina Limitante Posterior , Estudos Retrospectivos , Lidocaína , Anestesia Geral , Lesões da Córnea/complicações , Lesões da Córnea/cirurgia , Dor Pós-Operatória/tratamento farmacológicoRESUMO
Acute hydrops refers to sudden corneal edema caused by rupture of Descemet's membrane (DM) - often in progressive keratectasia. It leads to a sudden decrease in visual acuity, pain, and foreign body sensation as well as an increased glare sensation. Acute hydrops usually heals with scarring within months, but complications such as corneal perforation, infectious keratitis, and corneal vascularization may occur. The prevalence in keratoconus patients is 2.6 to 2.8%. Risk factors include keratoconjunctivitis vernalis, atopic dermatitis, high keratometry, male gender, and eye rubbing. Keratoplasty should be avoided in the acute phase. The prognosis of the graft is reduced, and after scar healing of the hydrops, wearing contact lenses or glasses may be possible again. Conservative therapy alone with lubricants and hyperosmolar eye drops, prophylactic antibiotic eye drops to prevent superinfection, and topical steroids was long considered the only possible form of treatment. However, healing under conservative therapy takes an average of over 100 days. In the meantime, there are different surgical strategies that rapidly shorten the healing and thus the recovery phase of the patients to a few days. If the DM is detached without tension, a simple injection of gas into the anterior chamber can already lead to reattachment and thus to almost immediate deswelling of the cornea. If the DM is under tension, predescemetal sutures combined with a gas injection into the anterior chamber can flatten the cornea and reattach the DM. Mini-Descemet membrane endothelial keratoplasty (mini-DMEK) allows for sutureless closure of the DM defect by transplantation of a small (< 5 mm) graft. In cases of particularly large DM tears and very pronounced hydrops, suture loosening and relapse may occur after the placement of predescemetal sutures. Mini-DMEK can then lead to permanent healing, but in contrast to simple corneal sutures, it is usually performed under general anesthesia and by aid of intraoperative optical coherence tomography. The very good results with regard to the rapid healing prove that surgical therapy makes sense in the vast majority of patients with acute hydrops and should be initiated quickly.
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Edema da Córnea , Transplante de Córnea , Ceratocone , Humanos , Masculino , Edema da Córnea/diagnóstico , Edema da Córnea/etiologia , Edema da Córnea/terapia , Lâmina Limitante Posterior/cirurgia , Ceratocone/cirurgia , Transplante de Córnea/efeitos adversos , Edema/complicações , Edema/cirurgiaRESUMO
BACKGROUND: The blood-aqueous barrier (BAB) separates immunoprivileged tissue of the eye from the blood circulation. Disruption of the BAB is therefore a risk factor for rejection after keratoplasty. PURPOSE: The present work provides a review of the work of our group and others on BAB disruption in penetrating and posterior lamellar keratoplasty and its implications for clinical outcome. METHODS: A PubMed literature search was performed to generate a review paper. RESULTS: Laser flare photometry provides an objective and reproducible method to assess the integrity of the BAB. Studies of the flare after penetrating and posterior lamellar keratoplasty demonstrate a mostly regressive disruption of the BAB in the postoperative course, which is influenced in extent and duration by multiple factors. Persistently elevated flare values or an increase in flare after initial postoperative regeneration may indicate an increased risk of rejection. DISCUSSION: In case of persistent or recurrent elevated flare values after keratoplasty, intensified (local) immunosuppression may potentially be useful. This could become important in the future, especially for the monitoring of patients after high-risk keratoplasty. Whether an increase of the laser flare is a reliable early indicator of an impending immune reaction after penetrating or posterior lamellar keratoplasty has to be shown in prospective studies.
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Barreira Hematoaquosa , Transplante de Córnea , Humanos , Estudos Prospectivos , Transplante de Córnea/efeitos adversos , Transplante de Córnea/métodos , Fatores de Risco , Lasers , Ceratoplastia Penetrante/métodosRESUMO
BACKGROUND: Posterior lamellar keratoplasty and especially Descemet membrane endothelial keratoplasty (DMEK) are gaining interest worldwide. Little is known about the influence of donor factors on DMEK outcome. Here we provide an overview of the existing peer-reviewed literature on this topic and present the design of the upcoming cooperation study COMEDOS (Cologne-Mecklenburg-Vorpommern DMEK Donor Study). METHODS: A literature search of PubMed and MEDLINE was conducted to retrieve articles published between September 2013 and May 2021. Seventeen peer-reviewed articles were selected. Design and concept of the prospective COMEDOS are outlined. RESULTS: Main interest parameters were the donor diabetes mellitus status, age, and lens status. There is a large heterogeneity regarding the sample size, study design, and investigated parameters. There seems to be a consensus that younger donors are associated with tighter rolls, a more difficult preparation, and unfolding setting. Diabetic donors seem to increase the risk of tissue tearing due to adherences and result more frequently in preparation failure. The COMEDOS aims not only to analyze the diabetes status of the donor, but also to correlate all donor systemic comorbidities and their ophthalmologic history to the DMEK clinical outcome. Furthermore, a correlation of Descemet membrane lamella preparation and surgery outcome is planned. CONCLUSION: Currently, there is a lack of knowledge regarding the effect and impact of donor tissue characteristics on DMEK outcome and complications. An in-depth investigation is planned by the upcoming COMEDOS to close this knowledge gap.
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Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Diabetes Mellitus , Lâmina Limitante Posterior/cirurgia , Endotélio Corneano , Humanos , Estudos Prospectivos , Doadores de TecidosRESUMO
PURPOSE: The study aims to compare outcomes after deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK) in keratoconic eyes with or without previous hydrops. METHODS: Retrospective analysis of 211 eyes who received PK (group 1, n = 74 [history of hydrops: n = 33]) or DALK (group 2, n = 137 [history of hydrops: n = 9]) from 2012 to 2019 at the Department of Ophthalmology, University of Cologne, Germany. Analysis included best spectacle-corrected visual acuity (BSCVA), complications, immune reactions, graft survival and keratometry, and subgroup analyses for subjects with or without previous hydrops. RESULTS: Follow-up was 34.0 ± 23.6 months in group 1 and 30.7 ± 22.5 months in group 2. No significant difference was found in the course of BSCVA between groups 1 and 2 (p = 0.182) and in postoperative BSCVA between eyes with and without previous hydrops, regardless of the surgical method (p = 0.768). Endothelial immune reactions occurred exclusively in group 1 and did not occur more frequently in eyes with previous hydrops (p = 0.377). A higher risk of complications for eyes with previous hydrops was observed (p = 0.022). There was no difference in astigmatism and maximum keratometry (Kmax) preoperatively and postoperatively between eyes with and without history of hydrops. CONCLUSION: The prognosis for visual outcome after keratoplasty including visual acuity, astigmatism, and Kmax for keratoconic eyes with previous hydrops is as good as for keratoconic eyes without previous hydrops, irrespective of the surgical method. However, eyes after hydrops seem to have an increased risk of complications.
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Astigmatismo , Transplante de Córnea , Ceratocone , Edema , Seguimentos , Humanos , Ceratoplastia Penetrante , Estudos Retrospectivos , Resultado do TratamentoRESUMO
To discuss and evaluate new technologies for a better diagnosis of corneal diseases and limbal stem cell deficiency, the outcomes of a consensus process within the European Vision Institute (and of a workshop at the University of Cologne) are outlined. Various technologies are presented and analyzed for their potential clinical use also in defining new end points in clinical trials. The disease areas which are discussed comprise dry eye and ocular surface inflammation, imaging, and corneal neovascularization and corneal grafting/stem cell and cell transplantation. The unmet needs in the abovementioned disease areas are discussed, and realistically achievable new technologies for better diagnosis and use in clinical trials are outlined. To sum up, it can be said that there are several new technologies that can improve current diagnostics in the field of ophthalmology in the near future and will have impact on clinical trial end point design.
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Ensaios Clínicos como Assunto , Doenças da Córnea/cirurgia , Epitélio Corneano/patologia , Limbo da Córnea/citologia , Transplante de Células-Tronco/métodos , Células-Tronco/citologia , Congressos como Assunto , Doenças da Córnea/metabolismo , Doenças da Córnea/patologia , Epitélio Corneano/metabolismo , Europa (Continente) , HumanosRESUMO
BACKGROUND: The reduced availability of corneal donor tissue in Ukraine requires the most effective use of the available grafts. The present work describes and evaluates a method to obtain several small diameter corneal grafts from a single donor cornea ("multimodal donor tissue splitting"). MATERIAL AND METHODS: This retrospective cohort study includes keratoplasty procedures performed at the Department of Corneal Pathology, State Institution, "The Filatov Institute of Eye Diseases and Tissue Therapy of the National Academy of Medical Sciences of Ukraine", Odessa, Ukraine. The method of graft preparation includes either lamellar dissection of the entire graft or partial lamellar dissection to obtain two lamellar and/or full-thickness grafts. Grafts were not only cut in a circular manner, but the individual shape was also adjusted to match the shape of non-circular corneal defects. RESULTS: A total of 324 keratoplasties between January 2016 and December 2017, using 270 grafts, were included. In 54 cases (including 34 emergency situations), one transplant was used for two recipients. Of these, 43 were therapeutic keratoplasties and 11 peripheral lamellar keratoplasties due to grade IIIâ-âIV recurrent pterygia. In two cases, two grafts for one patient were dissected from a single donor cornea. Out of 43 patients with curative keratoplasty, visual acuity improved in 28 eyes (65.1%) or remained unchanged in 15 eyes (34.9%). Postoperative visual acuity was dependent on the initial state of the eye, the localisation, the depth and the area of the corneal defect. In eyes with peripheral corneal localisation of ulcerations, even in the presence of corneal perforation, good functional results were obtained. CONCLUSION: If two or more grafts are obtained from a single donor cornea for different kinds of keratoplasty procedures, this reduces the need for corneal graft tissue and, consequently, the cost of preservation. Especially in regions with a high shortage of donor tissue, this provides additional tissue capacities for emergency situations.
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Doenças da Córnea , Transplante de Córnea , Córnea/cirurgia , Doenças da Córnea/cirurgia , Humanos , Estudos Retrospectivos , Doadores de TecidosRESUMO
PURPOSE: Excimer laser phototherapeutic keratectomy (PTK) is a safe treatment for superficial corneal opacities, e.g., in corneal dystrophies or degenerations. Nevertheless, no standardized treatment protocols are available and intraoperative monitoring was not possible, so far. Here we evaluate the potential benefits of the intraoperative assessment by microscope-integrated intraoperative optical coherence tomography (MI-OCT) of corneal optical properties during PTK. METHODS: Retrospective study of eight patients (one male, seven females; age range, 43-80 years, mean = 66.1 years) using an 840-nm microscope-integrated spectral-domain OCT (iOCT; OptoMedical Technologies, Luebeck, Germany adapted to HS Hi-R Neo 900A, Haag Streit Surgical, Wedel, Germany). Images were acquired before and after corneal abrasion and after PTK. For PTK, a SCHWIND Amaris 750S excimer laser (SCHWIND eye-tech-solutions GmbH und KO. KG) was used. Parameters assessed were the central corneal thickness (CCT), changes in central depth-dependent corneal tissue intensity (TI), and corneal surface roughness (SR) in cross-sectional images of the cornea. RESULTS: Intraoperative monitoring using microscope-integrated OCT was possible in all patients at all time points. TI of the anterior corneal stroma decreased significantly (p = 0.037) after PTK (T1 = 15.1 ± 3.6, T2 = 15.0 ± 3.84, T3 = 13.7 ± 3.38), but not after corneal abrasion alone, indicating increased transparency caused by excimer laser PTK. CCT was significantly lower after corneal abrasion (p = 0.017), but not after PTK (T1 = 630.4 ± 70 µm, T2 = 544.1 ± 59.4 µm, T3 = 558.3 ± 52.5 µm. SR significantly decreased (p = 0.043) after PTK (T1 = 614.4 ± 37.5 pixels, T2 = 634.4 ± 35.6 pixels, T3 = 611.0 ± 40.3 pixels). CONCLUSIONS: Intraoperative OCT allows real-time imaging during PTK and the assessment of corneal optical transparency and its surface roughness. It has to be clarified in larger studies if these parameters correlate with later postoperative visual outcomes.
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Córnea/diagnóstico por imagem , Opacidade da Córnea/cirurgia , Paquimetria Corneana/métodos , Ceratectomia/métodos , Lasers de Excimer/uso terapêutico , Monitorização Intraoperatória/métodos , Tomografia de Coerência Óptica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Córnea/cirurgia , Opacidade da Córnea/diagnóstico , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: The surgical treatment of corneal dystrophies develops rapidly as the use of lamellar corneal grafting techniques continue. While penetrating keratoplasty was the gold standard for treating a variety of dystrophies a few years ago, the affected layers of the cornea can, nowadays, be selectively replaced or ablated using laser technology. Of particular importance for these methods is optical coherence tomography, which has recently been integrated into surgical microscopes (MI-OCT). METHODS: Literature overview from PubMed and Google.scholar.de supplemented with own imaging data. RESULTS: The MI-OCT enables the intraoperative real-time monitoring of different ophthalmic surgical procedures, such as deep anterior lamellar keratoplasty, Descemet's membrane endothelial keratoplasty, as well as minimally-invasive procedures, such as phototherapeutic keratectomy. In addition, it enables an evaluation of the cornea, but also of structures of the anterior chamber, in situations in which the cornea, for example, is clouded by an edema. CONCLUSION: Microscope-integrated, intraoperative optical coherence tomography (MI-OCT) represents a useful supplement to the normal surgical microscope. It is superior to the sole surgical microscope, especially in already severely clouded corneas, and represents a sensible supplement, especially for novel lamellar transplantation procedures. Prospective randomized trials are necessary to increase safety and efficacy when using MI-OCT for different indications.
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Distrofias Hereditárias da Córnea , Transplante de Córnea , Tomografia de Coerência Óptica/métodos , Córnea , Distrofias Hereditárias da Córnea/cirurgia , Distrofias Hereditárias da Córnea/terapia , Humanos , Estudos ProspectivosRESUMO
Descemet membrane endothelial keratoplasty (DMEK) has evolved into a routine surgical procedure for posterior lamellar keratoplasty. After its introduction more than 10 years ago, several modifications in grafting technique and postoperative treatment regimen helped to improve its safety and reproducibility. Although DMEK offers faster and better improvements in visual acuity, as well as less graft rejections when compared to Descemet's stripping (automated) endothelial keratoplasty (DS[A]EK), difficulties when implementing this technique hamper the widespread use in many areas. However, different strategies help to reduce the rate of intra- and postoperative complications, making DMEK the method of choice for most patients with corneal endothelial diseases. Certain techniques help to reduce the endothelial damage during graft preparation; correct matching of donor age and recipient's anterior chamber depth eases intracameral unfolding of the DMEK graft, the use of SF6 gas for anterior chamber tamponade reduces the need for additional rebubblings, and the correct frequency and duration of postoperative topical steroid treatment helps to reduce the development of cystoid macular edema and graft rejections. Further standardization, but also individualization, of DMEK helps to offer this treatment option to patients with more complex anterior segment situations like anterior synechia, larger iris defects and glaucoma drainage devices.
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Doenças da Córnea/cirurgia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/efeitos adversos , Endotélio Corneano , Complicações Pós-Operatórias/etiologia , Endotélio Corneano/cirurgia , Distrofia Endotelial de Fuchs/cirurgia , Humanos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/terapia , Fatores de Risco , Acuidade Visual/fisiologiaRESUMO
Fuchs endothelial corneal dystrophy (FECD) is a leading indication for corneal transplantation. FECD is characterized by progressive alterations in endothelial cell morphology, excrescences (guttae) and thickening of the endothelial basement membrane and cell death. Ultimately, these changes lead to corneal edema and vision loss. Due to the lack of vision loss in early disease stages and the decades long disease course, early pathophysiology in FECD is virtually unknown as studies of pathologic tissues have been limited to end-stage tissues obtained at transplant. The first genetic defect shown to cause FECD was a point mutation causing a glutamine to lysine substitution at amino acid position 455 (Q455K) in the alpha 2 collagen 8 gene (COL8A2) which results in an early onset form of the disease. Homozygous mutant knock-in mice with this mutation (Col8a2(Q455K/Q455K)) show features strikingly similar to human disease, including progressive alterations in endothelial cell morphology, cell loss and basement membrane guttae. Ultrastructural analysis shows the predominant defect as dilated endoplasmic reticulum (ER), suggesting ER stress and unfolded protein response (UPR) activation. Immunohistochemistry, western blotting, quantitative reverse transcriptase polymerase chain reaction and terminal deoxynucleotidyl transferase 2-deoxyuridine, 5-triphosphate nick end-labeling analyses support UPR activation and UPR-associated apoptosis in the Col8a2(Q455K/Q455K) mutant corneal endothelium. This study confirms the Q455K substitution in the COL8A2 gene as being sufficient to cause FECD in the first mouse model of this disease and supports the role of the UPR and UPR-associated apoptosis in the pathogenesis of FECD caused by COL8A2 mutations.
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Apoptose , Colágeno Tipo VIII/genética , Modelos Animais de Doenças , Endotélio Corneano/metabolismo , Distrofia Endotelial de Fuchs/patologia , Animais , Endotélio Corneano/patologia , Distrofia Endotelial de Fuchs/genética , Distrofia Endotelial de Fuchs/metabolismo , Camundongos , Camundongos Transgênicos , Microscopia Eletrônica , Mutação , Desnaturação ProteicaRESUMO
PURPOSE: To test whether subconjunctival cyclosporine A (CsA) implants affect the incidence and the degree of corneal neovascularization occurring after penetrating keratoplasty. DESIGN: Prospective, randomized, multicenter, controlled phase 2/3 clinical trial. The study comprised 43 trial sites in Germany, India, and the United States. PARTICIPANTS: Enrolled patients (n = 97) were randomized to 1 of 3 groups: treatment group A (n = 36), treatment group B (n = 40), and the control group (n = 21). METHODS: Patients from each group received either of 2 doses of subconjunctival CsA (group A, low-dose CsA; group B, high-dose CsA) or placebo (carrier only) implants at the time of high-risk penetrating keratoplasty. MAIN OUTCOME MEASURES: The incidence and degree of corneal neovascularization occurring after penetrating keratoplasty were evaluated in a substudy (LX201-01 study: NCT00447187). A web-based image upload system was developed. Standardized digital slit-lamp pictures were quantitatively and objectively evaluated using CellËF morphometry software. RESULTS: No statistically significant difference in incidence and degree of corneal neovascularization developing after penetrating keratoplasty was found between treatment groups and placebo group. Mean corneal neovascularization area at week 52 (visit 12) was 2.32±1.79% in treatment group A versus placebo (2.79±2.11%; P = 0.45) and 2.74±2.22% in treatment group B versus placebo (2.79±2.11%; P = 0.94). CONCLUSIONS: High-dose subconjunctival CsA implants do not significantly affect corneal neovascularization after high-risk penetrating keratoplasty. This suggests that local CsA has negligible antiangiogenic effects in the human cornea, at least in the transplant setting.
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Neovascularização da Córnea/tratamento farmacológico , Ciclosporina/administração & dosagem , Imunossupressores/administração & dosagem , Ceratoplastia Penetrante/efeitos adversos , Neovascularização da Córnea/epidemiologia , Implantes de Medicamento , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estados Unidos/epidemiologiaRESUMO
Fuchs endothelial corneal dystrophy (FECD) is a genetically heterogeneous disease. Hypothesizing that cellular senescence may be relevant in FECD pathogenesis, genetically undifferentiated late-onset FECD endothelial samples were analyzed to identify common changes of specific senescence-related transcripts. Total RNA was extracted from 21 FECD endothelial samples retrieved from patients undergoing lamellar keratoplasty due to clinically diagnosed end-stage FECD and from 12 endothelial samples retrieved from normal autopsy eyes. Taqman low density array (TLDA) cards were used to analyze differential expression of 89 cellular senescence-related transcripts. Result validation was performed using individual real-time PCR assays. TLDA-analysis demonstrated differential expression of 31 transcripts (fold-change >1.5; p < 0.05). Thereof, 27 showed significant up-regulation and 4 significant down-regulation. Markedly elevated mRNA-levels of the constitutively active and reactive oxygen species-generating enzyme NOX4 were found in all evaluable FECD samples. In addition, increased expression of CDKN2A and its transcriptional activators ETS1 and ARHGAP18 (SENEX) along with decreased expression of CDKN2A inhibitor ID1 were detected in FECD samples. Consistent over-expression of NOX4 in FECD endothelial samples suggests a role as pathogenic factor and as a potential new treatment target in FECD. Transcriptional up-regulation of the CDKN2A-pathway provides further evidence for increased cellular senescence in FECD endothelium.
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Apoptose , Senescência Celular , Endotélio Corneano/metabolismo , Proteínas do Olho/genética , Distrofia Endotelial de Fuchs , Regulação da Expressão Gênica , RNA Mensageiro/genética , Endotélio Corneano/patologia , Proteínas do Olho/biossíntese , Distrofia Endotelial de Fuchs/genética , Distrofia Endotelial de Fuchs/metabolismo , Distrofia Endotelial de Fuchs/patologia , Humanos , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo RealAssuntos
Colágeno Tipo IV/genética , Proteínas da Matriz Extracelular/genética , Fibronectinas/genética , Distrofia Endotelial de Fuchs/genética , Expressão Gênica/fisiologia , Laminina/genética , Idoso , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I , Colágeno Tipo III/genética , Edema da Córnea/diagnóstico , Edema da Córnea/genética , Edema da Córnea/cirurgia , Topografia da Córnea , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Matriz Extracelular/metabolismo , Feminino , Distrofia Endotelial de Fuchs/diagnóstico , Distrofia Endotelial de Fuchs/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Microscopia com Lâmpada de FendaRESUMO
Purpose: To determine which donor characteristics, like previous diseases and surgeries, influence the severity of the DM/endothelial lamella preparation prior to DMEK-surgery. Patients and Methods: Retrospective cross-sectional single-center study is presented. Eight hundred and forty-six eyes with DMEK-surgery between 01/2018 and 01/2021 performed at the University Hospital Cologne, Germany, were included. Information regarding the donors' previous diseases and surgeries were provided by a large database of a cornea bank (Multi Tissue Bank Mecklenburg-Vorpommern) and merged with the Cologne DMEK database, which contains information regarding preparation characteristics of the surgeon-prepared graft directly preoperatively. Three preparation groups (easy, difficult and very difficult) were correlated to the donors' previous diseases and surgeries. The following characteristics were used for the assignment in one of the three groups: stripping difficulty, rolling and staining behavior, central and peripheral adherences, tissue fragility and DM-splitting. Results: Significant risk factors for DM-splitting were diabetes mellitus (DMel) type II, heart failure, chronic kidney disease and previous cataract surgery (p=0.022, p=0.012; p=0.047 and p<0.001 respectively). Previous DMel (especially type 2) was significantly associated with the occurrence of central adherences (p=0.009). Several cardiovascular diseases (p-values between <0.001 and p=0.038), DMel type II, chronic kidney disease and previous cataract-surgery were associated with peripheral adherences (p=0.004; p=0.020 and p<0.001 respectively). Furthermore, pseudophakic donor eyes presented a higher degree of fragility of the graft (p<0.001). Age was a significant risk factor for difficult preparation (p<0.001). The staining of the graft was poorer in donors with chronic kidney disease (p=0.037). Conclusion: Donor diabetes mellitus type 2, heart failure, previous cataract surgery, chronic kidney disease and age are associated with a difficult DMEK graft preparation. For every one-year increment in donor age, the odds of having very difficult preparation were increased by 3%. Also, chronic kidney disease predisposes to a poor tissue staining with trypan blue during preparation.
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PURPOSE: To present ocular clinical, histological, systemic, and genetic findings of a patient with familial lecithin-cholesterol acyltransferase (LCAT) deficiency caused by a novel genetic variant of the LCAT gene associated with secondary corneal amyloidosis. METHODS: Case report. RESULTS: A 74-year-old woman presented with decreased visual acuity (VA), sensitivity to light, and progressive whitening of both corneas for approximately 20 years. The patient had undergone penetrating keratoplasty (PKP) on the right eye 6 years ago. Ophthalmologic examination revealed decreased VA in both eyes (OD: 0.05, OS: 0.3), and even further reduced glare VA (OD: 0.05, OS: 0.1), diffuse whitish corneal opacity involving the total thickness of the corneal stroma without crystalline deposits, and a marked peripheral diffuse arcus. Systemic examination revealed severely reduced plasma high-density lipoprotein cholesterol levels, target cells in blood smear, and chronic normochromic anemia. Clinically, LCAT deficiency was the most likely diagnosis. Further genetic analysis confirmed the diagnosis. The patient is homozygous for the novel variant c.943T>C (p.Trp315Arg) in the LCAT gene. Histologic examination of the cornea removed during the first keratoplasty revealed amyloid deposits. The cornea removed at the second keratoplasty had small vacuoles in the anterior stroma, indicating recurrence of lipid deposition. CONCLUSIONS: LCAT deficiency is a rare genetic disorder that can cause corneal opacities because of lipid deposition in the cornea. Systemic manifestations may help in the differential diagnosis to other diseases associated with severe high-density lipoprotein cholesterol reduction. Genetic analysis is employed to confirm the diagnosis. Some mutations in the LCAT gene seem to be associated with secondary corneal amyloidosis. Further investigation of this association is warranted. A recurrence of corneal opacity after PKP seems to occur mainly in the anterior corneal stroma.
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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.
Assuntos
Epitélio Corneano , Ceratocone , Humanos , Ceratocone/metabolismo , Colágeno Tipo XII/genética , Colágeno Tipo XII/metabolismo , Células HEK293 , Córnea/patologia , Epitélio Corneano/patologiaRESUMO
PURPOSE: To describe a novel corneal surgical technique combining Deep Anterior Lamellar Keratoplasty (DALK) with grafting of allogeneic limbus (Limbo-DALK) for the treatment of eyes with corneal stromal pathology and limbal stem cell deficiency (LSCD). METHODS: Clinical records of six Limbo-DALKs performed in five patients diagnosed with LSCD and corneal stromal pathology requiring keratoplasty were retrospectively reviewed. All patients were diagnosed with LSCD due to various pathologies including thermal and chemical burns, congenital aniridia or chronic inflammatory ocular surface disease. Parameters analysed included demographics, diagnoses, clinical history, thickness measurements using anterior segment OCT, visual acuity, and epithelial status. Regular follow-up visits were scheduled at 6 weeks as well as 3, 6, 9, and 12 and 18 months postoperatively. Main outcome measures were time to graft epithelialisation and the occurrence of corneal endothelial decompensation. RESULTS: Two grafts showed complete epithelial closure at 2 days, two at 14 days. In one eye, complete epithelial closure was not achieved after the first Limbo-DALK, but was achieved one month after the second Limbo-DALK. No endothelial decompensation occurred except in one patient with silicone oil associated keratopathy. Endothelial graft rejection was not observed in any of the grafts. CONCLUSION: Based on the data from this pilot series, limbo-DALK appears to be a viable surgical approach for eyes with severe LSCD and corneal stromal pathology, suitable for emergency situations (e.g. corneal ulceration with impending corneal perforation), while minimising the risk of corneal endothelial decompensation.