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PURPOSE: We assessed the impact of sequential double running suture removal on corneal curvature after penetrating keratoplasty (PK), comparing mechanical and nonmechanical excimer laser trephination. METHODS: PK was performed in 134 patients (mean age 51 ± 18 yrs) using either the excimer laser [excimer, n = 60 (37 keratoconus and 23 Fuchs dystrophy)] or motor trephination [control, n = 74 (44 keratoconus and 30 Fuchs dystrophy)] and a double running cross-stitch suture. Refractometry, Zeiss keratometry, and Tomey corneal topography were performed before removal of the first suture (15.2 ± 4.2 mo) and immediately before and at least 6 weeks after removal of the second suture (21.4 ± 5.6 mo). RESULTS: Keratometry before removal of the first (-1.7 ± 2.3 D vs. -3.1 ± 2.8 D) and second (-2.3 ± 2.6 D vs. -3.8 ± 2.8 D) sutures showed that the change in the corneal base curve was significantly smaller in the excimer group than the control group (P < 0.004). After complete suture removal, astigmatism decreased in 52% and 11%, remained stable (±0.5 D) in 27% and 9%, and increased in 21% and 80% of eyes in the excimer and control groups, respectively, resulting in significantly lower astigmatism in the excimer (3.1 ± 2.1 D) group compared with the control group (6.2 ± 2.9 D) with "all-sutures-out" (P < 0.0001). The change in vector-corrected astigmatism (Jaffe) was significantly smaller in the excimer group (4.3 ± 3.5 D) than in the control group (6.9 ± 4.5 D; P < 0.001). CONCLUSIONS: In conclusion, less change in astigmatism and the base curve after sequential removal of a double running suture indicates better alignment of the graft in the recipient bed after excimer laser trephination. After double running suture removal, astigmatism decreases or remains unchanged in 79% of patients after excimer laser keratoplasty and increases in 80% of patients after conventional motor trephination.
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Enfermedades de la Córnea/cirugía , Queratoplastia Penetrante/métodos , Láseres de Excímeros/uso terapéutico , Técnicas de Sutura , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Astigmatismo/patología , Topografía de la Córnea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
Epithelial invasion after open globe injury is a rare complication. Wrong treatment (laser opening of the cyst) or no treatment can lead to painful blindness. Forty percent (25/62) of patients with block excision with epithelial downgrowth had a history of open globe injury. Four of them were female. Their mean age was 45 ±21 years. A tectonic keratoplasty with block excision was performed on 25 patients. Seven of them had simultaneously undergone cataract surgery. The mean extension of epithelial invasion was 3.0 ± 1.3 clock hours. Laser cystotomy was contraindicated. The diameter of the block excision was 8.2 ± 1.5 mm. Histological examination revealed diffuse epithelial invasion in three eyes and cystic epithelial downgrowth in 22 eyes. Mean pre- and post-operative visual acuity (20/60) did not differ significantly. The intraocular pressure was 16 ± 7 mm Hg before and 14 ± 7 mm Hg after the surgery. Only one eye (4%) developed ocular hypotony after block excision. Epithelial invasion can become manifest many years after an open globe injury. En block excision for cystic epithelial downgrowth with an extension less than 150 degrees is the therapy of choice. Opening of the cyst by laser or surgically is not recommended: It can induce transformation of cystic into diffuse epithelial invasion, and the succeeding secondary glaucoma can be refractory to therapy and lead to blindness. Clin. Anat. 31:68-71, 2018. © 2017 Wiley Periodicals, Inc.
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Extracción de Catarata , Conjuntiva/patología , Quistes/cirugía , Epitelio Corneal/patología , Oftalmopatías/cirugía , Lesiones Oculares Penetrantes/cirugía , Queratoplastia Penetrante , Complicaciones Posoperatorias/cirugía , Adulto , Anciano , Trasplante de Córnea , Quistes/patología , Epitelio/patología , Lesiones Oculares/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenAsunto(s)
Cuerpo Ciliar/patología , Neoplasias del Iris/patología , Vasos Linfáticos/patología , Melanoma/patología , Neoplasias de la Úvea/patología , Anciano , Cuerpo Ciliar/metabolismo , Humanos , Inmunohistoquímica , Neoplasias del Iris/cirugía , Vasos Linfáticos/metabolismo , Masculino , Melanoma/cirugía , Glicoproteínas de Membrana/metabolismo , Neoplasias de la Úvea/cirugía , Proteínas de Transporte Vesicular/metabolismoRESUMEN
PURPOSE: To evaluate whether tumor-associated lymphangiogenesis contributes to prognosis of conjunctival malignant melanomas and to study its association with other tumor characteristics. DESIGN: Nonrandomized, retrospective case series. PARTICIPANTS: A total of 109 consecutive patients with primary conjunctival malignant melanoma. METHODS: Proliferating lymphatic vessels were identified immunohistochemically using lymphatic vascular endothelial hyaluronan receptor-1 and podoplanin as specific lymphatic endothelial markers and Ki-67 as proliferation marker. Baseline tumor characteristics included tumor location, tumor thickness, tumor diameter, tumor origin, and tumor growth pattern. Kaplan-Meier and Cox regression analyses of the risk of local recurrence, lymphatic spread, distant metastasis, and melanoma-related death were performed. MAIN OUTCOME MEASURES: Intratumoral lymphatic vascular density and its association with tumor characteristics and recurrence-free, lymphatic spread-free, distant metastasis-free, and melanoma-specific survival. RESULTS: Intratumoral and peritumoral proliferating lymphatic vessels could be detected in all of the 109 conjunctival melanoma samples. High intratumoral lymphatic density was significantly associated with palpebral tumor location (P<0.001), greater tumor thickness (P<0.001), larger tumor diameter (P = 0.001), tumor origin de novo (P = 0.002), and nodular tumor growth pattern (P = 0.037). Patients with high intratumoral lymphatic density revealed significantly lower recurrence-free, lymphatic spread-free, distant metastasis-free, and melanoma-specific survival rates (P<0.001 for all). By multivariate Cox regression, factors predictive of local recurrence included palpebral tumor location (hazard ratio [HR] 2.66, P = 0.014), large tumor diameter (HR 5.48, P<0.001), and high intratumoral lymphatic density (HR 2.48, P = 0.043); factors predictive of lymphatic spread included palpebral tumor location (HR 4.13, P = 0.009), high tumor thickness (HR 12.17, P<0.001), and high intratumoral lymphatic density (HR 6.79, P = 0.019); factors predictive of distant metastasis included palpebral tumor location (HR 7.63, P<0.001), high tumor thickness (HR 8.60, P<0.001), large tumor diameter (HR 0.30, P = 0.029), and high intratumoral lymphatic density (HR 8.90, P = 0.047); and factors predictive of melanoma-related death included palpebral tumor location (HR 7.74, P<0.001), high tumor thickness (HR 10.88, P<0.001), large tumor diameter (HR 0.28, P = 0.018), and, with borderline significance, high intratumoral lymphatic density (HR 8.46, P = 0.052). CONCLUSIONS: Tumor-associated lymphangiogenesis seems to be associated with an increased risk of local recurrence, lymphatic spread, distant metastasis, and melanoma-related death in patients with conjunctival malignant melanomas. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Neoplasias de la Conjuntiva/patología , Endotelio Linfático/patología , Linfangiogénesis , Vasos Linfáticos/patología , Melanoma/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Neoplasias de la Conjuntiva/metabolismo , Endotelio Linfático/metabolismo , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Metástasis Linfática , Vasos Linfáticos/metabolismo , Masculino , Melanoma/metabolismo , Glicoproteínas de Membrana/metabolismo , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Proteínas de Transporte Vesicular/metabolismoRESUMEN
PURPOSE: To analyze whether tumor-associated lymphangiogenesis is concurrent with the progression of premalignant conjunctival melanocytic intraepithelial neoplasia (C-MIN) into invasive conjunctival melanoma (CM) and to study its association with prognosis. METHODS: Twenty patients with CM were closely matched with 20 patients with C-MIN with atypia and 20 with C-MIN without atypia regarding tumor size, tumor location, tumor extension, and patient's age. All conjunctival specimens were analyzed for the immunohistochemical presence of proliferating lymphatic vessels, with LYVE-1 and podoplanin used as specific lymphatic endothelial markers and Ki-67 as a proliferation marker. Lymphatic vascular density was measured within the mass (intratumoral) and within an area ≤ 500 µm from the tumor border (peritumoral) and was correlated with recurrence, metastasis, and survival rates. RESULTS: Intratumoral and peritumoral proliferating lymphatic vessels were detected in none of the C-MINs without atypia, in 10 of the 20 C-MINs with atypia, and in all 20 CMs. Invasive CM showed a significantly higher intra- and peritumoral density of proliferating lymphatics than did C-MIN with atypia (P ≤ 0.001). Patients with high intratumoral lymphatic density revealed significantly lower recurrence-free survival rates (P = 0.041) in C-MIN with atypia and significantly lower recurrence-free (P = 0.006), lymphatic-spread-free (P = 0.041), distant-metastasis-free (P = 0.029), and melanoma-specific survival rates (P = 0.029) in CM. CONCLUSIONS: Development of CM from premalignant precursors is concurrent with the outgrowth of lymphatic vessels. This active lymphangiogenesis seems to be associated with an increased risk of local recurrence in patients with C-MIN with atypia and with an increased risk of local recurrence, lymphatic spread, distant metastasis, and tumor-related death in patients with invasive CM.
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Carcinoma in Situ/patología , Neoplasias de la Conjuntiva/patología , Linfangiogénesis , Vasos Linfáticos/patología , Melanoma/patología , Lesiones Precancerosas , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma in Situ/metabolismo , Neoplasias de la Conjuntiva/metabolismo , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/metabolismo , Metástasis Linfática , Vasos Linfáticos/metabolismo , Masculino , Melanoma/metabolismo , Glicoproteínas de Membrana/metabolismo , Persona de Mediana Edad , Proteínas de Transporte Vesicular/metabolismoRESUMEN
Pseudoexfoliation (PEX) syndrome, which is an age-related, generalized elastotic matrix process, currently represents the most common identifiable risk factor for open-angle glaucoma. Dysregulated expression of proinflammatory cytokines has been implicated in the initiation of various fibrotic disorders and in the pathophysiology of glaucoma. Here we investigated the presence, expression, regulation, and functional significance of proinflammatory cytokines in eyes with early and late stages of PEX syndrome/glaucoma in comparison with normal and glaucomatous control eyes using multiplex bead analysis, immunoassays, real-time PCR, Western blotting, immunohistochemistry, and cell culture models. Early stages of PEX syndrome were characterized by approximately threefold (P < 0.005) elevated interleukin (IL)-6 and IL-8 levels in the aqueous humor and a concomitant approximately twofold (P < 0.001) increase in mRNA expression levels in anterior segment tissues as compared with controls. In contrast, late stages of PEX syndrome/glaucoma did not differ significantly from controls. IL-6, IL-6 receptor, and phospho-signal transducer and activator of transcription 3 could be mainly localized to walls of iris vessels and to the nonpigmented epithelium of ciliary processes. IL-6 and IL-8 were significantly up-regulated by ciliary epithelial cells in response to hypoxia or oxidative stress in vitro, whereas IL-6, but not IL-8, induced the expression of transforming growth factor-beta1 and elastic fiber proteins. These findings support a role for a stress-induced, spatially, and temporally restricted subclinical inflammation in the onset of the fibrotic matrix process characteristic of PEX syndrome/glaucoma.
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Citocinas/inmunología , Síndrome de Exfoliación , Matriz Extracelular/patología , Glaucoma de Ángulo Abierto , Adulto , Anciano , Anciano de 80 o más Años , Animales , Humor Acuoso/inmunología , Línea Celular , Citocinas/genética , Síndrome de Exfoliación/inmunología , Síndrome de Exfoliación/patología , Síndrome de Exfoliación/fisiopatología , Matriz Extracelular/metabolismo , Ojo/anatomía & histología , Ojo/inmunología , Ojo/patología , Ojo/fisiopatología , Femenino , Glaucoma de Ángulo Abierto/inmunología , Glaucoma de Ángulo Abierto/patología , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Interleucina-6/genética , Interleucina-6/inmunología , Interleucina-8/genética , Interleucina-8/inmunología , Masculino , Persona de Mediana Edad , Datos de Secuencia MolecularRESUMEN
PURPOSE: To analyze whether tumor-associated lymphangiogenesis accompanies the development from premalignant conjunctival intraepithelial neoplasia (CIN) into invasive squamous cell carcinoma (SCC) of the conjunctiva and to study its association with prognosis and other tumor characteristics. DESIGN: Case-controlled, matched-pair cohort study. PARTICIPANTS: Twenty patients with invasive SCC were closely matched with 20 patients with high-grade CIN and 20 patients with low-grade CIN regarding tumor size, tumor location, tumor extension, and patients' age. METHODS: Proliferating lymphatic vessels were identified using lymphatic vascular endothelial hyaluronan receptor-1 and podoplanin as specific lymphatic endothelial markers and Ki-67 as proliferation marker. Baseline tumor characteristics included tumor size, tumor-to-limbus distance, tumor-to-fornix distance, 2009 TNM classification, tumor cell type, mitotic rate, and Ki-67 proliferation index. Kaplan-Meier and Cox regression analyses of recurrence-free survival were performed. MAIN OUTCOME MEASURES: Lymphatic vascular density (LVD) and relative lymphatic vascular area (RLVA) of proliferating lymphatic vessels within the tumor mass (intratumoral) and within an area < or = 500 microm from the tumor border (peritumoral), and its association with tumor characteristics and recurrence-free survival. RESULTS: Intratumoral and peritumoral proliferating lymphatic vessels could be detected in all of the 60 conjunctival tumor samples. Invasive SCC revealed significantly higher values of intratumoral and peritumoral LVD and RLVA of proliferating lymphatics than high-grade or low-grade CIN (P < or = 0.001). Higher intratumoral lymphatic densities were significantly associated with larger tumor size (P=0.001), lower tumor-to-limbus distance (P=0.002), lower tumor-to-fornix distance (P=0.003), and higher TNM categories (P<0.001). Recurrence-free survival rates decreased significantly with higher intratumoral lymphatic densities (P<0.001). By multivariate Cox regression, large tumor size (hazard ratio 1.68, P=0.002) and high intratumoral lymphatic density (hazard ratio 1.10, P=0.046) were significant prognostic predictors of local recurrence. CONCLUSIONS: Development of conjunctival SCC from premalignant lesions is accompanied by the outgrowth of new conjunctival lymphatic vessels. This active tumor-associated lymphangiogenesis seems to be associated with an increased risk of local recurrence in patients with CIN and conjunctival invasive SCC. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Carcinoma in Situ/patología , Carcinoma de Células Escamosas/patología , Neoplasias de la Conjuntiva/patología , Linfangiogénesis , Vasos Linfáticos/patología , Lesiones Precancerosas , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma in Situ/metabolismo , Estudios de Casos y Controles , Neoplasias de la Conjuntiva/metabolismo , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Técnicas para Inmunoenzimas , Antígeno Ki-67/metabolismo , Vasos Linfáticos/metabolismo , Masculino , Análisis por Apareamiento , Glicoproteínas de Membrana/metabolismo , Persona de Mediana Edad , Invasividad Neoplásica , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Proteínas de Transporte Vesicular/metabolismoRESUMEN
PURPOSE: To evaluate whether intraocular tumor-associated lymphangiogenesis contributes to prognosis of ciliary body melanomas with extraocular extension and to study its association with other tumor characteristics. DESIGN: Nonrandomized, retrospective case series. PARTICIPANTS: Twenty consecutive patients enucleated for a malignant melanoma of the ciliary body with extraocular extension. METHODS: Lymphatic vessels were identified using lymphatic vascular endothelial-specific hyaluronic acid receptor-1 (LYVE-1) and podoplanin as specific immunohistochemical markers for lymphatic vascular endothelium. Baseline tumor characteristics included intra- and extraocular tumor size, 2009 tumor, node, metastasis (TNM) classification, route of extraocular spread, tumor cell type, mitotic rate, Ki-67 proliferation-index, microvascular patterns and density, tumor-infiltrating lymphocytes and macrophages, and expression of human leukocyte antigen (HLA) class I and insulin-like growth factor-1 receptor. Kaplan-Meier and Cox regression analyses of melanoma-specific survival were performed. MAIN OUTCOME MEASURES: Prevalence of intraocular LYVE-1(+)/podoplanin(+) lymphatic vessels and association with intraocular tumor characteristics and metastasis-free survival. RESULTS: Intraocular LYVE-1(+) and podoplanin(+) lymphatic vessels could be detected in 12 (60%) of 20 ciliary body melanomas with extraocular extension. Presence of intraocular LYVE-1(+)/podoplanin(+) lymphatic vessels was significantly associated with larger intra- (P = 0.002) and extraocular tumor size (P<0.001), higher TNM categories (P = 0.004), epithelioid cellularity (P = 0.016), higher mitotic rate (P = 0.003), higher Ki-67 proliferation-index (P = 0.049), microvascular networks (P = 0.005), higher microvascular density (P = 0.003), more tumor-infiltrating macrophages (P = 0.002), higher expression of HLA class I (P = 0.046), and insulin-like growth factor-1 receptor (P = 0.033), but not significantly with route of extraocular spread (P = 0.803), and tumor-infiltrating lymphocytes (P = 0.069). Melanoma-specific mortality rates increased significantly with the presence of intraocular LYVE-1(+)/podoplanin(+) lymphatic vessels (P = 0.008). By multivariate Cox regression, tumor size (hazard ratio, 14.40; P = 0.002), and presence of intraocular lymphatic vessels (hazard ratio, 8.09; P = 0.04) were strong prognostic predictors of mortality. CONCLUSIONS: Intraocular peritumoral lymphangiogenesis seems to be associated with an increased mortality risk in patients with ciliary body melanomas and extraocular extension. This association may be primarily because of an association of intraocular lymphangiogenesis with greater tumor size and increased malignancy.
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Cuerpo Ciliar/patología , Linfangiogénesis , Vasos Linfáticos/patología , Melanoma/secundario , Neoplasias de la Úvea/patología , Anciano , Biomarcadores de Tumor/metabolismo , Cuerpo Ciliar/metabolismo , Femenino , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Técnicas para Inmunoenzimas , Antígeno Ki-67/metabolismo , Metástasis Linfática , Vasos Linfáticos/metabolismo , Linfocitos Infiltrantes de Tumor/patología , Masculino , Melanoma/metabolismo , Melanoma/mortalidad , Glicoproteínas de Membrana/metabolismo , Persona de Mediana Edad , Pronóstico , Receptor IGF Tipo 1/metabolismo , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias de la Úvea/metabolismo , Neoplasias de la Úvea/mortalidad , Proteínas de Transporte Vesicular/metabolismoAsunto(s)
Neoplasias de la Coroides/patología , Neoplasias del Ojo/secundario , Melanoma/secundario , Siembra Neoplásica , Tomografía de Coherencia Óptica , Cuerpo Vítreo/patología , Anciano , Biomarcadores de Tumor/metabolismo , Neoplasias de la Coroides/metabolismo , Neoplasias de la Coroides/cirugía , Enucleación del Ojo , Humanos , Inmunohistoquímica , Masculino , Melanoma/metabolismo , Melanoma/cirugíaAsunto(s)
Amantadina/efectos adversos , Analgésicos no Narcóticos/efectos adversos , Edema Corneal/inducido químicamente , Dopaminérgicos/efectos adversos , Trastorno Bipolar/tratamiento farmacológico , Edema Corneal/fisiopatología , Edema Corneal/cirugía , Humanos , Queratoplastia Penetrante , Esclerosis Múltiple/tratamiento farmacológico , Agudeza VisualAsunto(s)
Migración de Cuerpo Extraño/prevención & control , Cápsula del Cristalino/fisiopatología , Lentes Intraoculares , Facoemulsificación , Prótesis e Implantes , Falla de Prótesis , Humanos , Fotograbar , Implantación de Prótesis , Errores de Refracción/fisiopatología , Errores de Refracción/prevención & controlRESUMEN
PURPOSE: The functional long-term outcome after differentiated surgical therapy of solid corneal dermoids and subconjunctival lipodermoids with special regard to determinants for amblyopia will be assessed. METHODS: Forty-six consecutive patients undergoing surgery for solid epibulbar dermoids, subconjunctival lipodermoids, or both were included. Visual acuity, refraction, keratometry, and degree of amblyopia were determined. Surgical therapy for corneal dermoids consisted of lamellar sclerokeratectomy, lamellar keratoplasty, corneoscleroplasty, and lamellar removal with autologous episcleral transplant. Surgical therapy for lipodermoids consisted of excision and reduction of the volume of the tumor. Follow-up examination was performed on average 4.5 years after surgical intervention. RESULTS: A significant correlation between tumor volume and preoperative visual acuity could be observed in patients with solid corneal dermoids not occluding the optical axis. Visual acuity improved significantly from 0.21 +/- 0.4 to 0.35 +/- 0.4 after surgery of corneal dermoids. Most eyes had concomitant hyperopia. Postoperative visual acuity correlated positively with preoperative visual acuity (P = 0.0001). After tumor excision, hyperopia and astigmatism were not reduced significantly on average. Nineteen of 47 patients suffered from amblyopia. Amblyopia was more often observed in patients with preoperative hyperopia > or =2 diopters and astigmatism >2 diopters. Visual acuity, refraction, and astigmatism were not changed significantly by surgery in patients with subconjunctival lipodermoids. CONCLUSIONS: Epibulbar dermoids require differentiated surgical therapy. Amblyopia is a major threat of solid corneal dermoids. The incidence of amblyopia seems to depend on preoperative occlusion of the optical axis and preoperative degree of hyperopia and astigmatism.
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Neoplasias de la Conjuntiva/cirugía , Enfermedades de la Córnea/cirugía , Quiste Dermoide/cirugía , Neoplasias del Ojo/cirugía , Lipoma/cirugía , Procedimientos Quirúrgicos Oftalmológicos/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ambliopía/etiología , Ambliopía/prevención & control , Astigmatismo/etiología , Niño , Preescolar , Neoplasias de la Conjuntiva/complicaciones , Neoplasias de la Conjuntiva/fisiopatología , Enfermedades de la Córnea/complicaciones , Enfermedades de la Córnea/fisiopatología , Quiste Dermoide/complicaciones , Quiste Dermoide/fisiopatología , Neoplasias del Ojo/complicaciones , Neoplasias del Ojo/fisiopatología , Humanos , Hiperopía/etiología , Lactante , Lipoma/complicaciones , Lipoma/fisiopatología , Persona de Mediana Edad , Periodo Posoperatorio , Cuidados Preoperatorios , Factores de Tiempo , Resultado del Tratamiento , Agudeza Visual , Adulto JovenRESUMEN
PURPOSE: To analyze whether lymphatic vessels can invade the normally alymphatic eye (lymphangiogenesis) in patients with malignant melanoma of the ciliary body with extraocular extension and to correlate these findings with metastasis-free survival. METHODS: Ten enucleated globes with the histopathologically and immunohistochemically (S-100, HMB-45, PNL-2, and Melan-A) confirmed diagnosis of malignant melanoma of the ciliary body with extraocular extension were matched with 10 globes with a ciliary body melanoma without extraocular extension regarding tumor size, cell type, melanin content, mitotic count, vascular networks, and patients' age. In all 20 cases, immunohistochemistry was performed to identify lymphatic vessels by using LYVE-1 and podoplanin as specific markers for lymphatic vascular endothelium. RESULTS: Intraocular LYVE-1(+) and podoplanin(+) lymphatic vessels were detected in 7 of 10 malignant melanomas of the ciliary body with extraocular extension (two of these developed a regional lymph node metastasis). Lymphatic vessels were found only at the tumor periphery directly adjacent to the sclera within the eye, more often in tumors of the epithelioid type (P = 0.017, Mann-Whitney test). Ciliary body melanomas without extrascleral extension revealed no intraocular LYVE-1(+) and podoplanin(+) lymphatic vessels. The presence of intraocular LYVE-1(+)/podoplanin(+) lymphatic vessels was significantly associated with lower metastasis-free survival rates (P = 0.038, log-rank test). CONCLUSIONS: Malignant melanomas of the ciliary body with extraocular extension show intraocular lymphatic vessels. This first evidence of lymphangiogenesis into the normally alymphatic eye may explain the increased risk of lymphatic metastasis in ciliary body melanoma with extraocular extension.
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Cuerpo Ciliar/patología , Linfangiogénesis , Vasos Linfáticos/patología , Melanoma/secundario , Neoplasias de la Úvea/patología , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Estudios de Casos y Controles , Cuerpo Ciliar/metabolismo , Supervivencia sin Enfermedad , Endotelio Linfático/metabolismo , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Melanoma/metabolismo , Melanoma/mortalidad , Glicoproteínas de Membrana/metabolismo , Microscopía Confocal , Persona de Mediana Edad , Tasa de Supervivencia , Neoplasias de la Úvea/metabolismo , Neoplasias de la Úvea/mortalidad , Proteínas de Transporte Vesicular/metabolismoRESUMEN
Pseudoexfoliation (PEX) syndrome is a generalized disease of the extracellular matrix and the most common identifiable cause of open-angle glaucoma. Two single nucleotide polymorphisms in the lysyl oxidase-like 1 (LOXL1) gene (rs1048661 and rs3825942) have been recently identified as strong genetic risk factors for both PEX syndrome and PEX glaucoma. Here we investigated the expression and localization of LOXL1, LOXL2, and lysyl oxidase (LOX) in tissues of PEX syndrome/glaucoma patients and controls in correlation with their individual single nucleotide polymorphism genotypes and stages of disease. LOXL1 ocular expression was reduced by approximately 20% per risk allele of rs1048661, whereas risk alleles of rs3825942, which were highly overrepresented in PEX cases, did not affect LOXL1 expression levels. Irrespective of the individual genotype, LOXL1 expression was significantly increased in early PEX stages but was decreased in advanced stages both with and without glaucoma compared with controls, whereas LOX and LOXL2 showed no differences between groups. LOXL1 was also found to be a major component of fibrillar PEX aggregates in both intra- and extraocular locations and to co-localize with various elastic fiber components. These findings provide evidence for LOXL1 involvement in the initial stages of abnormal fibrogenesis in PEX tissues. Alterations of LOXL1 activation, processing, and/or substrate specificity may contribute to the abnormal aggregation of elastic fiber components into characteristic PEX fibrils.
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Aminoácido Oxidorreductasas/metabolismo , Síndrome de Exfoliación/enzimología , Síndrome de Exfoliación/genética , Ojo/enzimología , Glaucoma , Isoenzimas/metabolismo , Proteína-Lisina 6-Oxidasa/metabolismo , Anciano , Anciano de 80 o más Años , Aminoácido Oxidorreductasas/genética , Animales , Síndrome de Exfoliación/patología , Síndrome de Exfoliación/fisiopatología , Proteínas de la Matriz Extracelular/metabolismo , Ojo/patología , Femenino , Fibrilinas , Predisposición Genética a la Enfermedad , Genotipo , Glaucoma/enzimología , Glaucoma/genética , Glaucoma/patología , Humanos , Isoenzimas/genética , Cristalino/metabolismo , Cristalino/ultraestructura , Masculino , Proteínas de Microfilamentos/metabolismo , Polimorfismo de Nucleótido Simple , Proteína-Lisina 6-Oxidasa/genética , Tropoelastina/metabolismoRESUMEN
PURPOSE: Evidence suggests that chronically increased stress conditions in the anterior eye segment constitute major mechanisms involved in the pathobiology of pseudoexfoliation (PEX) syndrome. The expression of stress-related genes in eyes from patients with and without PEX syndrome/glaucoma was investigated to determine whether PEX syndrome is associated with an altered cellular stress response. METHODS: cDNA array hybridization, quantitative real-time PCR, Western blot analysis, and immunohistochemistry were applied to analyze the mRNA and protein expression of stress-related genes in anterior segment tissues of PEX eyes, with and without glaucoma, and to compare them with normal and glaucomatous control eyes. RESULTS: Hybridization of cDNA arrays identified a set of stress-related candidate genes for differential expression in PEX syndrome/glaucoma, of which 10 were confirmed by real-time PCR in ciliary processes and iris tissue. The expression of MAPKp38, heat shock proteins (HSP40, HSP60), and superoxide dismutase (SOD2) was increased up to threefold in PEX specimens. In contrast, a large set of cytoprotective gene products, including antioxidant defense enzymes (glutathione S-transferases mGST1 and GSTT1), ubiquitin-conjugating enzymes (UBE2A, UBE2B), the DNA repair protein MLH1, and the stress-inducible transcription factor GADD153, were found to be consistently downregulated up to threefold in PEX specimens on both the mRNA and protein levels. CONCLUSIONS: The present findings provide evidence of alterations in cytoprotective mechanisms including antioxidant defense, proteasome function, endoplasmic reticulum-related stress response, and DNA repair in anterior segment tissues of PEX eyes. The resultant enhanced sensitivity and vulnerability to cellular stress conditions may therefore be one contributing factor in the pathobiology of PEX syndrome.
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Segmento Anterior del Ojo/metabolismo , Síndrome de Exfoliación/genética , Proteínas del Ojo/genética , Regulación de la Expresión Génica/fisiología , Glaucoma de Ángulo Abierto/genética , Factores de Transcripción/genética , Anciano , Anciano de 80 o más Años , Western Blotting , Síndrome de Exfoliación/metabolismo , Femenino , Glaucoma de Ángulo Abierto/metabolismo , Proteínas de Choque Térmico/genética , Humanos , Inmunohistoquímica , Hibridación in Situ , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
PURPOSE: To assess long-term refractive and visual outcome of elliptical excimer laser penetrating keratoplasty (EELPK). METHODS: Inclusion criteria (17 eyes): (1) Primary central elliptical excimer laser penetrating keratoplasty in phakic eyes; (2) No other simultaneous procedure except cataract surgery in 6 eyes; (3) Interrupted sutures; (4) Complete sequence of follow-ups before EELPK, with all-sutures-in, with all-sutures-out; (5) No active inflammation at the time of EELPK. Best corrected visual acuity (BCVA), refractive and keratometric astigmatism, topographic surface regularity index (SRI), surface asymmetry index (SAI) were determined in 5.9+/-3.3 years follow-up. RESULTS: BCVA improved from 0.2 preoperatively to 0.6 after suture removal (p<0.001). After suture removal, keratometric (4.9D/5.8D, p=0.01) and refractive cylinder (2.8D/4.4D; p<0.001) increased, and SRI and SAI decreased significantly (3.0/1.0; 1.9/0.9; p=0.01) compared to all-suture-in values. CONCLUSIONS: EELPK is effective in improving visual acuity. Despite topographic regularization, an increase of refractive more than keratometric astigmatism may occur after suture removal.
Asunto(s)
Astigmatismo/fisiopatología , Córnea/fisiopatología , Queratoplastia Penetrante/métodos , Láseres de Excímeros , Refracción Ocular/fisiología , Agudeza Visual/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de la Córnea/cirugía , Topografía de la Córnea , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Técnicas de Sutura , Resultado del TratamientoRESUMEN
INTRODUCTION: Corpora amylacea (CAm) occur in the optic nerve and in retinal ageing and degeneration. Cellular expression of L-kynurenine aminotransferases (KAT I and II) in the avian and rodent retina and its changes in retinal development and neurodegeneration have been documented. This study examines KAT I and II immunoreactivity in CAm in the human retina and optic nerve. MATERIAL AND METHODS: Immunohistochemistry was performed using polyclonal antibodies against KAT I and KAT II on sections of 23 human eyes enucleated for malignant uveal melanoma. Occurrence and location of KAT I- or KAT II-stained CAm was compared with PAS-stained sections. RESULTS: KAT I and KAT II expression in CAm has been shown in the retina and optic nerve with similar location to PAS-stained sections. KAT I immunoreactivity was more intense than KAT II and its staining was more pronounced in the retrolaminar part of the optic nerve. Some of the CAm showed only faint KAT II expression and occasionally there was no staining. KAT II revealed no association of staining variability and localisation of CAm. Similarly to animal studies, in the human retina KAT I was observed on Müller cell endfeet while KAT II was expressed in retinal ganglion cells. CONCLUSIONS: Presence of kynurenine aminotransferases in CAm in the human retina and optic nerve suggest that both enzymes may be involved in mechanisms of retinal ageing and neurodegeneration leading to CAm formation.
Asunto(s)
Envejecimiento/fisiología , Nervio Óptico/enzimología , Retina/enzimología , Transaminasas/metabolismo , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: To assess intraoperative complications and long-term outcome of elliptical excimer laser trephination for penetrating keratoplasties (EELPKs) performed at the Friedrich-Alexander University of Erlangen, between 1989 and 2002. METHODS: This was a retrospective, longitudinal, single-center, clinical, interventional case series. Forty-two eyes (14 Fuchs dystrophy, 11 corneal ulcer, 7 aphakic/pseudophakic bullous keratopathy, 9 corneal scars, 1 keratotorus) after EELPK were observed. Trephination was performed with a 193-nm Meditec excimer laser along metal masks with 0-8 orientation teeth/notches. Horizontal/vertical graft diameters ranged from 7.0/6.0 to 8.0/7.0 mm, and 12 to 24 interrupted sutures were used. Simultaneously, 11 eyes (26.2%) underwent cataract surgery, 3 (7.1%) underwent intraocular lens (IOL) exchange, and 1 (2.4%) underwent secondary IOL implantation. The main outcome measures included intraoperative complications, immune reactions, and final astigmatism/visual acuity at the end of follow-up. RESULTS: During surgery, 4 (9.5%) recipients had iris bleedings, and 10 (23.8%) ring-shaped superficial corneal thermal donor damages were detected. One (2.4%) immunologic graft rejection was seen in Fuchs dystrophy, and 3 (7.1%) in corneal ulcers occurred during follow-up (4.7 +/- 3.2 years). At the end of follow-up, corrected visual acuity (0.1/0.4; P < 0.001) and keratometric astigmatism (2.3 D/4.7 D, P = 0.001) increased significantly. CONCLUSIONS: In EELPK, intraoperative disadvantages, such as the need for interrupted sutures and a tendency toward higher and more irregular astigmatism, may be expected. This study does not have the power to statistically confirm the tendency of EELPK toward a lower rate of immunologic graft rejections after normal-risk keratoplasty. However, EELPK may have advantages in deep or perforated elliptically shaped corneal ulcers (such as in acanthamoeba keratitis).
Asunto(s)
Enfermedades de la Córnea/cirugía , Complicaciones Intraoperatorias , Queratoplastia Penetrante/métodos , Terapia por Láser/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Queratoplastia Penetrante/instrumentación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Técnicas de Sutura , Donantes de Tejidos , Resultado del TratamientoRESUMEN
PURPOSE: To assess the intra-individual variability of outcomes after penetrating keratoplasty by comparing mechanical and nonmechanical corneal trephination. METHODS: Fifteen patients (30 eyes, 16 with keratoconus and 14 with Fuchs' dystrophy; median age at penetrating keratoplasty 56.3/53.5 years) were assessed whose trephination was performed using a motor trephine in one eye and the 193-nm excimer laser (MEL 60, Carl Zeiss-Meditec) in the other eye by one experienced surgeon. Subjective refractometry, standard keratometry, and corneal topography were used to assess best spectacle-corrected visual acuity (BSCVA); spherical equivalent refraction; keratometric and topographic central corneal power; refractive, keratometric, and topographic astigmatism; surface regularity index; surface asymmetry index; and potential visual acuity preoperatively, before first suture removal (at 1 year), and at last available follow-up after final suture removal but before additional surgery (1.3 and 1.9 years, respectively). RESULTS: Before first suture removal BSCVA was significantly higher (0.7 vs 0.5; P=.008) after excimer laser trephination. At the end of follow-up, refractive/ keratometric/topographic astigmatism (2.20/2.10/2.40 diopters [D] vs 5.00/6.00/7.10 D) and surface regularity index (0.8 vs 1.1) were significantly lower (P=.02, P=.005, P=.01, and P=.03, respectively) and potential visual acuity was significantly higher (0.9/0.6; P=.02) after excimer laser trephination. CONCLUSIONS: During long-term follow-up, all-sutures-out postkeratoplasty astigmatism and surface regularity are superior in the eye where nonmechanical excimer laser was applied in contrast to the fellow eye with motor trephination in the same individual.