RESUMO
The cornea is a fundamental ocular tissue for the sense of sight. Thanks to it, the refraction of two-thirds of light manages to participate in the visual process and protect against mechanical damage. Because it is transparent, avascular, and innervated, the cornea comprises five main layers: Epithelium, Bowman's layer, stroma, Descemet's membrane, and endothelium. Each layer plays a key role in the functionality and maintenance of ocular tissue, providing unique ultrastructural and biomechanical properties. Bullous Keratopathy (BK) is an endothelial dysfunction that leads to corneal edema, loss of visual acuity, epithelial blisters, and severe pain, among other symptoms. The corneal layers are subject to changes in their biophysical properties promoted by Keratopathy. In this context, the Atomic Force Microscopy (AFM) technique in air was used to investigate the anterior epithelial surface and the posterior endothelial surface, healthy and with BK, using a triangular silicone tip with a nominal spring constant of 0.4 N/m. Six human corneas (n = 6) samples were used for each analyzed group. Roughness data, calculated by third-order polynomial adjustment, adhesion, and Young's modulus, were obtained to serve as a comparison and identification of morphological and biomechanical changes possibly associated with the pathology, such as craters and in the epithelial layer and exposure of a fibrotic layer due to loss of the endothelial cell wall. Endothelial cell membrane area and volume data were calculated, obtaining a relevant comparison between the control and patient. Such results may provide new data on the physical properties of the ocular tissue to understand the physiology of the cornea when it has pathology.
Assuntos
Doenças da Córnea , Edema da Córnea , Humanos , Endotélio Corneano/metabolismo , Lâmina Limitante Posterior/metabolismo , Edema da Córnea/metabolismo , Córnea/patologia , Doenças da Córnea/patologiaRESUMO
PURPOSE: The aim of this study was to report a case of corneal plana-like phenotype with bilateral peripheral scleralization associated with a PITX2 pathogenic variant. METHODS: Clinical findings were obtained by ophthalmologic examination. Molecular diagnosis was performed by whole-exome sequencing in the patient and his parents. RESULTS: A 12-month-old male patient present with bilateral peripheral corneal scleralization, corneal plana-like phenotype, and iris hypoplasia. The genetic analysis revealed a de novo PITX2 pathogenic variant (c.323G>A, p.R108H). CONCLUSIONS: PITX2 c.323G>A (p.R108H) can be associated with a unique corneal plana-like phenotype with peripheral scleralization, and thus, PITX2 should be targeted in genetic testing of this specific phenotype.
Assuntos
Doenças da Córnea , Proteínas de Homeodomínio , Humanos , Masculino , Doenças da Córnea/patologia , Proteínas de Homeodomínio/genética , Mutação , Linhagem , Fenótipo , Fatores de Transcrição/genética , Lactente , Proteína Homeobox PITX2RESUMO
PURPOSE: Corneal pathology can obstruct the visualization required for surgical management of coexisting posterior segment diseases, and use of a temporary keratoprosthesis (TKP) permits combined penetrating keratoplasty (PK) and vitreoretinal surgery. We evaluated graft outcomes after TKP for combined PK and vitreoretinal surgery and analyzed risk factors for graft failure. METHODS: We reviewed the electronic medical records for patients who underwent TKP for PK combined with vitreoretinal surgery at Wills Eye Hospital between May 2007 and April 2021. Overall, 28 variables were analyzed. The main outcome measure was corneal graft failure, defined as irreversible graft edema or opacification. RESULTS: A total of 46 eyes of 46 patients underwent combined surgery and were included in the study. The mean age at surgery was 55.7 ± 18.6 years (range 19-86 years), and the mean follow-up was 31.8 ± 30.5 months (range 1.6-114.0 months). Multivariable analysis revealed 2 factors significantly associated with graft failure: history of trauma (hazard ratio = 5.38; 95% confidence interval, 1.53-18.91; P = 0.009) and intraocular silicone oil after transplant (hazard ratio = 5.67; confidence interval 1.66-19.44; P = 0.006). Corneal graft failure occurred in 60.9% of all cases over the course of follow-up, but the absence of both variables yielded a 33.3% failure rate. CONCLUSIONS: Although outcomes vary, previous ocular trauma and the presence of intraocular silicone oil are risk factors for failure that may facilitate patient selection and improve counseling about long-term graft potential after TKP for combined PK and vitreoretinal surgery.
Assuntos
Doenças da Córnea , Cirurgia Vitreorretiniana , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Córnea/patologia , Ceratoplastia Penetrante , Doenças da Córnea/patologia , Próteses e Implantes , Óleos de Silicone , Acuidade Visual , Vitrectomia , Estudos Retrospectivos , Sobrevivência de Enxerto , Seguimentos , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the impact of corneal and conjunctival tumors on the ocular surface and quality of life of patients before and after surgical treatment. METHODS: This prospective study conducted a preoperative and 30- and 90-day postoperative assessment of patients diagnosed with conjunctival and corneal tumors. Demographic data were collected preoperatively. The 12-Item Short-Form Health Survey (SF-12) and Ocular Surface Disease Index (OSDI) questionnaires were applied to assess patients' quality of life and perception of their vision-related functions. The tear breakup time and Schirmer tests were performed for ocular surface evaluation. The tumor extensions were measured using ImageJ image analysis software. RESULTS: Twenty-three patients were enrolled. The mean age at examination was 52.8 ± 17.3 years (range: 27-9 years). The most common tumor type was squamous cell carcinoma (61.5%). The patients' visual acuity improved significantly at 1 month and 3 months (p=0.018 and p=0.036, respectively). No significant differences were found between tear breakup time and Schirmer tests preoperatively and at 3 months postoperatively (p=0.150 and p=0.490, respectively). The SF-12 scores demonstrated significant differences between the preoperative and 30- and 90-day postoperative mental components (p=0.008 and p=0.026, respectively). Tumor extension was 868.7 ± 344.9 pixels (range, 224.6-1481.6 pixels) and were significantly correlated with the preoperative (p=0.011), 30-day postoperative (p=0.017), and 90-day postoperative (p=0.012) SF-12 mental components, as well as the emotional component at the 30th postoperative day (p=0.016). CONCLUSION: Patients with corneal and conjunctival tumors improved their ocular symptoms, visual acuity, and the emotional component of their quality of life after surgical excision of the tumor.
Assuntos
Neoplasias da Túnica Conjuntiva , Doenças da Córnea , Síndromes do Olho Seco , Humanos , Neoplasias da Túnica Conjuntiva/cirurgia , Neoplasias da Túnica Conjuntiva/patologia , Qualidade de Vida , Estudos Prospectivos , Córnea/patologia , Doenças da Córnea/cirurgia , Doenças da Córnea/patologia , Lágrimas , Síndromes do Olho Seco/patologiaRESUMO
PURPOSE: The goal of this study was to evaluate corneal profiles of patients with osteogenesis imperfecta (OI) due to a collagen I gene mutation. METHODS: This was a cross-sectional comparative study. There were 84 eyes from 42 patients with OI types I, III, and IV who were recruited from the OI Clinic at the Clinical Hospital of Porto Alegre, Brazil. All cases presented either COL1A1 or A2 gene mutations. Controls were matched by sex, age, and refractive error. Corneal Scheimpflug tomography was used to determine curvature and thickness parameters in both groups. RESULTS: Quantitative collagen mutations were found only in OI type I. Qualitative mutations were responsible for all mutations observed in type III and IV patients. Each OI type presented significantly lower pachymetric values at the thinnest point compared with controls (443.7-505.1 vs. 541.9-548.5 µm; P < 0.001). In addition, significantly lower pachymetric values were observed in patients with OI compared with controls in all positions between the central and corneal periphery (581.4-657.0 vs. 704.5-720.7 µm at an 8.0-mm-diameter circle; P < 0.001). Differences in anterior and posterior radii of curvatures, respectively, between patients with OI and controls were not statistically significant (7.64-7.80 vs. 7.65-7.69 mm; P > 0.05) except for a lower anterior radii of curvatures in type III (7.33 vs. 7.72 mm; P < 0.01). CONCLUSIONS: Although patients with OI have homogenously thinner corneas compared with controls, we observed that a collagen I chain mutation was not responsible for corneal curvature alterations in OI.
Assuntos
Colágeno Tipo I/genética , Córnea/metabolismo , Doenças da Córnea/genética , DNA/genética , Mutação , Osteogênese Imperfeita/genética , Adolescente , Adulto , Colágeno Tipo I/metabolismo , Córnea/patologia , Doenças da Córnea/etiologia , Doenças da Córnea/patologia , Topografia da Córnea , Estudos Transversais , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Masculino , Osteogênese Imperfeita/diagnóstico , Osteogênese Imperfeita/metabolismo , Adulto JovemRESUMO
Acute ocular chemical burns are ophthalmic emergencies requiring immediate diagnosis and treatment as they may lead to permanent impairment of vision. The clinical manifestations of such burns are produced by exacerbated innate immune response via the infiltration of inflammatory cells and activation of stromal fibroblasts. New therapies are emerging that are dedicated to repair mechanisms that improve the ocular surface after damage; for example, transplantation of stem cells (SC) has been successfully reported for this purpose. The pursuit of easily accessible, noninvasive procedures to obtain SC has led researchers to focus on human tissues such as amniotic membrane. Human amniotic mesenchymal SC (hAM-MSC) inhibits proinflammatory and fibrotic processes in different diseases. hAM-MSC expresses low levels of classical MHC-I and they do not express MHC-II, making them suitable for regenerative medicine. The aim of this study was to evaluate the effect of intracameral injection of hAM-MSC on the clinical manifestations, the infiltration of inflammatory cells, and the activation of stromal fibroblasts in a corneal alkali-burn model. We also determined the in vitro effect of hAM-MSC conditioned medium (CM) on α-SMA+ human limbal myofibroblast (HLM) frequency and on release of neutrophil extracellular traps (NETs). Our results show that intracameral hAM-MSC injection reduces neovascularization, opacity, stromal inflammatory cell infiltrate, and stromal α-SMA+ cells in our model. Moreover, in in vitro assays, CM from hAM-MSC decreased the quantity of α-SMA+ HLM and the release of NETs. These results suggest that intracameral hAM-MSC injection induces an anti-inflammatory and anti-fibrotic environment that promotes corneal wound healing. Stem Cells Translational Medicine 2018;7:906-917.
Assuntos
Queimaduras Químicas/terapia , Doenças da Córnea/terapia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Âmnio/citologia , Animais , Queimaduras Químicas/patologia , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Córnea/diagnóstico por imagem , Córnea/patologia , Córnea/fisiologia , Doenças da Córnea/patologia , Meios de Cultivo Condicionados/química , Meios de Cultivo Condicionados/farmacologia , Modelos Animais de Doenças , Humanos , Pressão Intraocular , Células-Tronco Mesenquimais/citologia , Microscopia de Fluorescência , Miofibroblastos/citologia , Miofibroblastos/metabolismo , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Coelhos , Tomografia de Coerência ÓpticaRESUMO
The authors used microscopy and synchrotron-based small-angle X-ray scattering analysis (SAXS) to describe lesions macroscopically typical of tropical keratopathy ("Florida spots") from 6 cats on St Kitts. Microscopically, there were varying degrees of epithelial hyperplasia and thinning of the cornea (by 4% to 18%) due to loss of corneal stroma associated with dense accumulations of collagen in the superficial stroma. The collagen fibrils in lesions were wider and had more variable diameters (39.5 ± 5.0 nm, mean ± SD) than in normal corneas (25.9 ± 3.6 nm; P < .01). There were occasional vacuoles (<1 µm) in the corneal epithelial basement membrane but no evidence of inflammation, edema, stromal neovascularization, fibrosis, acid-fast organisms, or structures suggestive of a fungal organism. SAXS analysis showed collagen fibril diameters and variation in size were greater in stroma containing the lesions compared to normal corneas (48.8 ± 4.5 nm vs 35.5 ± 2.6; P < .05). The d-spacing of collagen in the stroma of lesions and normal corneas was the same, but the average orientation index of collagen in lesions was greater (0.428 ± 0.08 vs 0.285 ± 0.03; P < .05). A survey revealed Florida spots lesions were static over time and became less obvious in only 1 of 6 affected cats adopted on St Kitts and taken to areas in the US where lesions are not reported. An anterior stromal collagen disorder with various degrees of epithelial hyperplasia is the pathologic hallmark of lesions clinically identical to Florida spots in cats from St Kitts.
Assuntos
Doenças do Gato/patologia , Doenças da Córnea/veterinária , Animais , Gatos , Doenças da Córnea/patologia , Substância Própria/patologia , Substância Própria/ultraestrutura , Feminino , Masculino , Microscopia Eletrônica de Transmissão/veterinária , São Cristóvão e Névis , Espalhamento a Baixo Ângulo , Pele/patologia , Difração de Raios X/métodos , Difração de Raios X/veterináriaRESUMO
PURPOSE: To evaluate microstructural differences between corneas with and without Kayser-Fleischer rings in age-matched subjects with Wilson's disease with neurological symptoms, using confocal laser scanning microscopy. METHODS: The study included 12 subjects with Wilson's disease with neurological symptoms. Twelve corneas presented clinically with classic Kayser-Fleischer rings, visible on slit lamp examination; the other 12 served as controls. The subjects underwent a comprehensive clinical examination. Microstructural analysis using confocal laser scanning microscopy evaluated increased corneal thickness, decreased number of cells, increased debris or specific deposits, and unusual microstructures. RESULTS: Clinically, the subjects with Kayser-Fleischer rings had similar corneal findings and normal intraocular pressure; two had typical sunflower cataracts and decreased visual acuity. The control eyes all presented normal visual acuity, intraocular pressure, and corneal appearance. The microstructural analysis demonstrated similar findings in all the affected corneas. Compared with the control corneas, there were fewer keratocytes in the anterior stroma (17.380 vs. 22.380/mm3). Round, "hollow" dark areas were observed between the keratocytes; these were universal and similar in appearance in all affected corneas and all cornea layers. In the peripheral posterior stroma, there were dust-like, bright, granular deposits that tended to increase in number and density toward Descemet's membrane, masking the peripheral endothelium. The control corneas presented a normal microstructure apart from dust-like granular deposits in the periphery. CONCLUSIONS: In vivo confocal microscopy is a useful tool for evaluating the corneal microstructure when a Kayser-Fleischer ring is clinically present. The ring consists of granular, bright particles that increase in density toward Descemet's membrane, and is associated with a decreased number of keratocytes and peculiar dark, round areas in all stromal layers, probably a sign of corneal damage. When the ring is not visible in subjects with Wilson's disease, changes to the corneal microstructure are insignificant.
Assuntos
Doenças da Córnea/diagnóstico por imagem , Doenças da Córnea/patologia , Degeneração Hepatolenticular/diagnóstico por imagem , Degeneração Hepatolenticular/patologia , Microscopia Confocal/métodos , Adolescente , Adulto , Criança , Cobre/metabolismo , Paquimetria Corneana , Lâmina Limitante Posterior/diagnóstico por imagem , Lâmina Limitante Posterior/patologia , Lâmina Limitante Posterior/ultraestrutura , Feminino , Humanos , Pressão Intraocular , Masculino , Estudos Prospectivos , Valores de Referência , Adulto JovemAssuntos
Queimaduras Químicas/diagnóstico , Doenças da Córnea/diagnóstico , Queimaduras Oculares/diagnóstico , Tomografia de Coerência Óptica/métodos , Adulto , Álcalis/efeitos adversos , Queimaduras Químicas/patologia , Córnea/diagnóstico por imagem , Córnea/efeitos dos fármacos , Córnea/patologia , Doenças da Córnea/induzido quimicamente , Doenças da Córnea/patologia , Queimaduras Oculares/patologia , Guadalupe , Humanos , MasculinoRESUMO
ABSTRACT Purpose: To evaluate microstructural differences between corneas with and without Kayser-Fleischer rings in age-matched subjects with Wilson's disease with neurological symptoms, using confocal laser scanning microscopy. Methods: The study included 12 subjects with Wilson's disease with neurological symptoms. Twelve corneas presented clinically with classic Kayser-Fleischer rings, visible on slit lamp examination; the other 12 served as controls. The subjects underwent a comprehensive clinical examination. Microstructural analysis using confocal laser scanning microscopy evaluated increased corneal thickness, decreased number of cells, increased debris or specific deposits, and unusual microstructures. Results: Clinically, the subjects with Kayser-Fleischer rings had similar corneal findings and normal intraocular pressure; two had typical sunflower cataracts and decreased visual acuity. The control eyes all presented normal visual acuity, intraocular pressure, and corneal appearance. The microstructural analysis demonstrated similar findings in all the affected corneas. Compared with the control corneas, there were fewer keratocytes in the anterior stroma (17.380 vs. 22.380/mm3). Round, "hollow" dark areas were observed between the keratocytes; these were universal and similar in appearance in all affected corneas and all cornea layers. In the peripheral posterior stroma, there were dust-like, bright, granular deposits that tended to increase in number and density toward Descemet's membrane, masking the peripheral endothelium. The control corneas presented a normal microstructure apart from dust-like granular deposits in the periphery. Conclusions: In vivo confocal microscopy is a useful tool for evaluating the corneal microstructure when a Kayser-Fleischer ring is clinically present. The ring consists of granular, bright particles that increase in density toward Descemet's membrane, and is associated with a decreased number of keratocytes and peculiar dark, round areas in all stromal layers, probably a sign of corneal damage. When the ring is not visible in subjects with Wilson's disease, changes to the corneal microstructure are insignificant.
RESUMO Objetivo: Avaliar, ao nível microestrutural, através de microscopia confocal in vivo a lazer, 12 córneas com anel de Kayser-Fleischer visível ao exame da lâmpada de fenda e compará-las com 12 córneas clinicamente normais de indivíduos com idades correspondentes aos pacientes com doença de Wilson e sintomas neurológicos. Métodos: O estudo incluiu 12 indivíduos com doença de Wilson e sintomas neurológicos (24 córneas). Doze córneas apresentavam clinicamente o anel clássico de Kayser-Fleischer e as outras 12 serviram como controle. Todos os pacientes foram submetidos a um exame clínico abrangente e a uma análise microestrutural subsequente utilizando microscopia confocal in vivo de varredura a laser. Os principais resultados observados foram: aumento da espessura da córnea, diminuição do número de células, aumento de resíduos/depósitos específicos e microestrutura atípica. Resultados: Clinicamente, todos os indivíduos com anel de Kayser-Fleischer (12 olhos) apresentaram achados similares da córnea e pressão intraocular normal. Dois indivíduos também apresentaram uma catarata de girassol típica e diminuição da acuidade visual. Todos os olhos do grupo controle apresentaram acuidade visual, pressão intraocular e aparência corneana normais. A microscopia confocal in vivo com varredura a laser revelou achados semelhantes em todas as córneas afetadas. O número de ceratócitos no estroma anterior era menor, 17.380/mm3 (22.380/mm3 no grupo controle), e entre eles foram identificadas áreas escuras arredondadas "vazias". Essas zonas escuras eram generalizadas e similares em todas as córneas examinadas e em todas as camadas da córnea. No estroma posterior periférico, havia presença de depósitos granulares brilhantes e com aparência de pó que tendiam a aumentar em número e densidade no sentido da membrana de Descemet, mascarando o endotélio periférico. As córneas controle apresentaram estrutura normal, com exceção de depósitos granulares com aparência de pó na periferia. Conclusões: A microscopia confocal in vivo é uma ferramenta útil para a avaliação da microestrutura da córnea quando o anel de Kayser-Fleischer está clinicamente presente. O anel é constituído de partículas granulares brilhantes com densidade aumentada no sentido da membrana de Descemet. Sua presença está associada com uma diminuição do número de ceratócitos e com áreas circulares escuras "peculiares" em todas as camadas estromais, que representam, provavelmente, um sinal de dano da córnea. Quando o anel não está clinicamente visível, a estrutura da córnea in vivo encontra-se insignificantemente alterada.