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1.
Graefes Arch Clin Exp Ophthalmol ; 262(1): 179-190, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37615697

RESUMEN

PURPOSE   : To compare the efficacy and safety of the fixed-dose combination (FDC) of netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (NET/LAT; Roclanda®) with bimatoprost 0.03%/timolol maleate 0.5% (BIM/TIM; Ganfort®) ophthalmic solution in the treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT). METHODS: MERCURY-3 was a 6-month prospective, double-masked, randomized, multicenter, active-controlled, parallel-group, non-inferiority study. Patients (≥ 18 years) with a diagnosis of OAG or OHT in both eyes that was insufficiently controlled with topical medication (IOP ≥ 17 mmHg in ≥ 1 eye and < 28 mmHg in both eyes) were included. Following washout, patients were randomized to once-daily NET/LAT or BIM/TIM for up to 6 months; efficacy was assessed at Week 2, Week 4, and Month 3; safety was evaluated for 6 months. Comparison of NET/LAT relative to BIM/TIM for mean IOP at 08:00, 10:00, and 16:00 h was assessed at Week 2, Week 6, and Month 3. Non-inferiority of NET/LAT to BIM/TIM was defined as a difference of ≤ 1.5 mmHg at all nine time points through Month 3 and ≤ 1.0 mmHg at five or more of nine time points through Month 3. RESULTS: Overall, 430 patients were randomized (NET/LAT, n = 218; BIM/TIM, n = 212), and all received at least one dose of study medication. Efficacy analyses were performed at Month 3 on 388 patients (NET/LAT, n = 184; BIM/TIM, n = 204). NET/LAT demonstrated non-inferiority to BIM/TIM, with a between-treatment difference in IOP of ≤ 1.5 mmHg achieved at all time points and ≤ 1.0 mmHg at the majority of time points (six of nine) through Month 3. Mean diurnal IOP during the study ranged from 15.4 to 15.6 mmHg and 15.2 to 15.6 mmHg in the NET/LAT and BIM/TIM groups respectively, with no between-group statistically significant difference. No significant differences were observed in key secondary endpoints. No serious, treatment-related adverse events (AEs) were observed, and AEs were typically mild/moderate in severity. The most common treatment-related AEs were conjunctival hyperemia (NET/LAT, 30.7%; BIM/TIM, 9.0%) and cornea verticillata (NET/LAT, 11.0%; BIM/TIM, 0%). CONCLUSIONS: Once-daily NET/LAT was non-inferior to BIM/TIM in IOP reduction in OAG and OHT, with AEs consistent with previous findings. NET/LAT offers a compelling alternative FDC treatment option for OAG and OHT.


Asunto(s)
Benzoatos , Glaucoma de Ángulo Abierto , Hipertensión Ocular , beta-Alanina/análogos & derivados , Humanos , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Timolol/efectos adversos , Bimatoprost/uso terapéutico , Latanoprost/efectos adversos , Estudios Prospectivos , Presión Intraocular , Antihipertensivos/efectos adversos , Tonometría Ocular , Hipertensión Ocular/diagnóstico , Hipertensión Ocular/tratamiento farmacológico , Soluciones Oftálmicas , Resultado del Tratamiento , Método Doble Ciego
2.
Graefes Arch Clin Exp Ophthalmol ; 259(8): 2337-2349, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33929592

RESUMEN

PURPOSE: The aim of the study was to compare the frequency and the level of expression of selected miRNAs in the aqueous humor of patients with various types of glaucoma. METHODS: The studied group consisted of 42 patients with glaucoma: 19 with primary open-angle glaucoma (POAG), 14 with pseudoexfoliation glaucoma (PEXG), 9 with primary angle closure glaucoma (PACG), and the control group of 36 patients with senile cataract without glaucoma. The real-time polymerase chain reaction method was used to analyze the expression of miRNAs. RESULTS: There were no significant differences in the frequency and the level of miRNA expression between various types of glaucoma. There was a tendency for hsa-miR-6722-3p and hsa-miR-184 to be expressed more frequently in PEXG and hsa-miR-1260b in POAG. The expression levels of hsa-miR-1260b and hsa-miR-6515-3p were correlated with age in POAG. Target annotation and functional analyses showed that genes targeted by the most frequently expressed miRNAs (hsa-miR-1202, -1260b, -184, -187-5p, -6515-3p, -6722-3p, and hsa-mir-4634) are involved mainly in response to hypoxia, cardiovascular system development, and apoptosis. CONCLUSION: Hsa-miR-1260b was the most abundantly expressed among studied miRNAs and may be a potential biomarker of clinical status in PEXG and PACG.


Asunto(s)
Síndrome de Exfoliación , Glaucoma de Ángulo Abierto , Glaucoma , MicroARNs , Humor Acuoso , Síndrome de Exfoliación/diagnóstico , Síndrome de Exfoliación/genética , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/genética , Humanos , MicroARNs/genética
3.
Clin Oral Investig ; 25(6): 4107-4114, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33389133

RESUMEN

INTRODUCTION: Oral and ocular dryness are the most common symptoms reported during ophthalmological and dental examinations. It is becoming a serious and growing problem due to the huge variety of affecting factors and with population aging. OBJECTIVES: The purpose was to demonstrate an application of the Schirmer test for xerostomia. Subsequently, to compare and correlate the results achieved from the lacrimal Schirmer test and salivary Schirmer test in non-Sjögren patients. METHODS: Study group consisted of 642 patients with/without subjective or/and objective symptoms of dry eye or mouth who did not fulfill the criteria for diagnosis of Sjögren syndrome. The lacrimal Schirmer test (lST) and the salivary Schirmer tests (sST) were performed (sSTm was put on the floor of the mouth, sSTp in front of the parotid gland duct). The results were recorded after 1 min (sSTm), 3 min (sSTp), and 5 min (lST). RESULTS: The lST and sST test scores were considerably higher in the healthy group than in others, p < 0.001. The results of sST1 and sST2 decreased with the appearance of subjective and objective symptoms, p < 0.001. There were positive correlations between lST and sSTm outcomes between the groups, p < 0.001. CONCLUSIONS: We present the Schirmer test adapted to measure salivary gland hypofunction that is a time-saving tool in our daily practice. Results of this study reveal an excellent correlation between the eye Schirmer test and the salivary Schirmer tests. CLINICAL RELEVANCE: The salivary Schirmer tests seem to be rapid, convenient, and reliable objective screening tools for salivary gland hypofunction in non-Sjögren patients.


Asunto(s)
Síndromes de Ojo Seco , Aparato Lagrimal , Síndrome de Sjögren , Xerostomía , Síndromes de Ojo Seco/diagnóstico , Humanos , Glándulas Salivales , Síndrome de Sjögren/diagnóstico , Xerostomía/diagnóstico
4.
JAMA ; 325(8): 753-764, 2021 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-33620406

RESUMEN

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. Design, Setting, and Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. Main Outcomes and Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses. Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. Conclusions and Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.


Asunto(s)
Síndrome de Exfoliación/genética , Variación Genética , Esteroide Hidroxilasas/genética , Anciano , Anciano de 80 o más Años , Cámara Anterior/patología , Estudios de Casos y Controles , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Femenino , Humanos , Modelos Logísticos , Masculino , Metaanálisis como Asunto , Persona de Mediana Edad , ARN Mensajero/metabolismo , Secuenciación del Exoma
5.
Exp Eye Res ; 178: 186-197, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30312593

RESUMEN

Glaucoma is one of the leading causes of visual impairment and blindness worldwide. However, the cause of retinal ganglion cell loss and damage of the optic nerve in its pathogenesis is largely unknown. The high energy demands of these cells may reflect their strong dependence on mitochondrial function and thus sensitivity to mitochondrial defects. To address this issue, we studied whole mitochondrial genome variation in normal tension glaucoma patients and control individuals from the Polish population using next generation sequencing. Our findings indicate that few features of mitochondrial DNA variation are different for glaucoma patients and control subjects. New insights into normal tension glaucoma development are discussed. We provide also a comprehensive approach for mitochondrial DNA analysis and variant evaluation.


Asunto(s)
ADN Mitocondrial/genética , Variación Genética , Genoma Mitocondrial/genética , Glaucoma de Baja Tensión/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Amplificación de Genes , Perfilación de la Expresión Génica , Gonioscopía , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Presión Intraocular/fisiología , Masculino , Persona de Mediana Edad , Tonometría Ocular
6.
Med Sci Monit ; 24: 200-206, 2018 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-29320472

RESUMEN

BACKGROUND Eye and mouth dryness are the most common symptoms reported during ophthalmological and dental examinations, and their frequency increases with age. In connection with population aging and the huge variety of factors and conditions that can induce this condition, it is becoming a serious and growing problem. The purpose of the present study was to determine whether ocular dryness and concomitant xerostomia is associated with particular systemic diseases. MATERIAL AND METHODS We enrolled 642 non-Sjögren patients referred for examination to the ophthalmology or dental clinic of Lublin region, Poland. The research was conducted using a standardized interview: The Interview and Examination Questionnaire. All patients responded to the survey questions, which concerned systemic diseases, lifestyle, with special emphasis on computer work, spending time in polluted and air-conditioned rooms, and subsequent questions about the subjective symptoms of ocular and mouth dryness. RESULTS There were 424 patients who presented signs and symptoms of both ocular and mouth dryness. Our study showed a statistically significant association between this condition and the age and sex of the patients and systemic diseases such as hypertension (p=0.0000), cardiovascular disease (p=0.057), and stress (p=0.036), and time spent at the computer (p=0.00015). CONCLUSIONS Ocular dryness and concomitant xerostomia may occur in apparently healthy individuals, but is more frequent in patients with systemic disorders. The lack of dry eye and dry mouth symptoms does not exclude insufficient tearing and salivation; thus, the disorders are usually underestimated. Our study indicates that ocular and mouth dryness are the most common conditions seen in out-patients, due to increased use of medications, computers, and air conditioning.


Asunto(s)
Síndromes de Ojo Seco/complicaciones , Síndrome de Sjögren/complicaciones , Xerostomía/complicaciones , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polonia , Adulto Joven
7.
Cell Mol Biol Lett ; 22: 5, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28536636

RESUMEN

BACKGROUND: Human Tenon's fibroblasts (HTFs) play a crucial role in wound healing. They cause postoperative scarring of the filtering bleb and are thus responsible for trabeculectomy failure. This study aimed to find an effective and fast protocol for HTF isolation from trabeculectomy biopsies. The protocol was compared with the commonly recommended HTF isolation procedure, which uses Dulbecco's modified Eagle's medium (DMEM). We used Eagle's minimum essential medium (EMEM) enriched with fibroblast growth factor (FGF), which selectively promoted the proliferation of HTF cells. A secondary goal was to compare HTF morphology, metabolism and growth during parallel cultivation of the isolated cells in FGF-enriched EMEM and DMEM. RESULTS: Standard procedures for HTF isolation from tissue biopsies require a 20- to 30-day culture of the explants to obtain the first monolayer. Our protocol yielded the first monolayer after approx. 15 days. More importantly, the majority of the cells were fibroblasts with only individual epithelium-derived cells present. Using FGF-enriched EMEM allowed 1.3 × 106 vimentin-positive fibroblasts to be obtained from a single biopsy within approx. 25 days. Using DMEM resulted in isolation failure and required exchange to FGF-enriched medium to recover the fibroblast culture. HTFs maintained in FGF-enriched EMEM also showed faster proliferation and a different type I collagen production ability compared to HTFs cultured in DMEM. Thus, FGF-enriched EMEM is recommended for fast propagation of HTFs unless the aim of the study is to assess the effect of a tested agent on proliferation ability or type I collagen production. CONCLUSIONS: Our fast protocol for HTF isolation allows easy setup of cell banks by researchers under laboratory conditions and could be very useful during testing of novel ophthalmologic anti-fibrotic agents in vitro. Molecular analysis of HTFs isolated from patients with known treatment histories may provide valuable information on the effects of some medications taken before glaucoma surgery on the subsequent wound-healing process and potential for trabeculectomy failure.


Asunto(s)
Separación Celular/métodos , Fibroblastos/citología , Anciano , Biopsia , Células Cultivadas , Medios de Cultivo , Humanos , Masculino , Persona de Mediana Edad , Trabeculectomía
8.
Metab Brain Dis ; 32(2): 351-358, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27644408

RESUMEN

Among non-pharmacological treatments, the ketogenic diet (KD) has the strongest demonstrated evidence of clinical success in drug resistant epilepsy. In an attempt to model the anticonvulsant effects of the KD pre-clinically, the present study assessed the effects of the KD against electroshock-induced convulsions in mice. After confirming that exposure to the KD for 2 weeks resulted in stable ketosis and hypoglycemia, mice were exposed to electroshocks of various intensities to establish general seizure susceptibility. When compared to mice fed the standard rodent chow diet (SRCD), we found that mice fed the KD were more sensitive to electroconvulsions as reflected by a significant decrease in seizure threshold (3.86 mA in mice on the KD vs 7.29 mA in mice on the SRCD; P < 0.05) in the maximal electroshock seizure threshold (MEST) test. To examine if this increased seizure sensitivity to electroconvulsions produced by the KD would affect anticonvulsant effects of antiepileptic drugs (AEDs), anticonvulsant potencies of carbamazepine (CBZ), phenobarbital (PB), phenytoin (PHT), and valproate (VPA) against maximal electroshock (MES)-induced convulsions were compared in mice fed the KD and SRCD. We found that potencies of all AEDs studied were decreased in mice fed the KD in comparison to those on the SRCD, with decreases in the anticonvulsant potencies ranging from 1.4 fold (PB) to 1.7 fold (PHT). Finally, the lack of differences in brain exposures of the AEDs studied in mice fed the KD and SRCD ruled out a pharmacokinetic nature of the observed findings. Taken together, exposure to the KD in the present study had an overall pro-convulsant effect. Since electroconvulsions require large metabolic reserves to support their rapid spread throughout the brain and consequent generalized tonic-clonic convulsions, this effect may be explained by a high energy state produced by the KD in regards to increased energy storage and utilization.


Asunto(s)
Dieta Cetogénica/efectos adversos , Electrochoque , Convulsiones/etiología , Animales , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/farmacología , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Desempeño Psicomotor/efectos de los fármacos
9.
Mol Vis ; 22: 1256-1266, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27777505

RESUMEN

PURPOSE: The purpose of this study was to determine whether four single nucleotide polymorphisms (SNPs) of endothelin and endothelin receptor type A genes can constitute a risk factor for normal tension glaucoma (NTG) and high tension glaucoma (HTG). METHODS: The study included 160 patients with NTG, 124 patients with HTG, and 165 healthy controls. To analyze the frequency of polymorphic variants of the endothelin EDN gene (K198N) and the endothelin receptor type A gene EDN RA (C1222T, C70G, G231A), DNA was isolated from peripheral blood, and SNP genotyping was performed using the real-time PCR (RT-PCR) method. Plasma endothelin (ET) concentrations were detected using an enzyme immunoassay. Endothelin levels were compared with genotype and allele distributions, patients' clinical status, and various risk factors for NTG. RESULTS: There was a significant difference between the patients with NTG and HTG and the controls (p = 0.035, p = 0.008) regarding the genotype of the C1222T and C70G polymorphism. Plasma concentrations of ET did not differ between the NTG and HTG groups, and no significant correlation with intraocular pressure (IOP), best-corrected visual acuity (BCVA), and the cup to disc ratio (c/d ratio) was seen in patients with NTG. Plasma endothelin levels showed a noticeably positive correlation with age in the NTG group (R = 0.249, p = 0.042). Higher endothelin levels corresponded to more advanced visual field damage. No statistical difference was observed between variant genotypes of K198N and the ET-1 plasma concentration in patients with NTG, whereas a slightly higher ET level was observed in the patients with HTG with the GT genotype in comparison to those with the GG genotype (p = 0.001). The C1222T polymorphism significantly affected the plasma ET level in patients with NTG. The TT genotype carriers had the highest ET level, and the CC genotype carriers the lowest (p = 0.034). The AA variant genotype of the G231A polymorphism exhibited the highest ET level, while the GG variant genotype represented the lowest level (p = 0.033). No significant differences were observed regarding the endothelin levels and the frequency of notches, peripapillary atrophy, low blood pressure, cold extremities, or migraine in the two groups studied. Slightly lower endothelin plasma levels were observed in patients with optic disc hemorrhages in the NTG group (p = 0.05). CONCLUSIONS: Polymorphic variants of endothelin EDN (K198N) and endothelin receptor type A genes EDN RA (C1222T, C70G, G231A) affected ET plasma concentrations. There was no association between the plasma endothelin levels and the risk factors for NTG. According to these results, plasma endothelin concentrations do not appear to be a marker for NTG.


Asunto(s)
Endotelina-1/sangre , Endotelina-1/genética , Glaucoma de Baja Tensión/genética , Polimorfismo de Nucleótido Simple , Receptor de Endotelina A/genética , Anciano , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnicas de Genotipaje , Humanos , Presión Intraocular , Glaucoma de Baja Tensión/sangre , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de Riesgo , Agudeza Visual
10.
Klin Oczna ; 118(4): 298-300, 2016.
Artículo en Polaco | MEDLINE | ID: mdl-29911363

RESUMEN

Intracameral application of Aprokam (cefuroxime) during cataract surgery is documented to significantly reduce the incidence of endophthalmitis. It is very important to consider its very rare but potentially very dangerous complication, that is anaphylactic reaction of varying severity in patients at risk of such allergy. It is necessary to take a detailed history and check all relevant medical records concerning previous treatment to avoid this complication.


Asunto(s)
Anafilaxia/inducido químicamente , Extracción de Catarata/efectos adversos , Cefuroxima/efectos adversos , Anafilaxia/etiología , Cámara Anterior , Cefuroxima/administración & dosificación , Femenino , Humanos , Complicaciones Posoperatorias/inducido químicamente
11.
Klin Oczna ; 118(3): 208-13, 2016.
Artículo en Polaco | MEDLINE | ID: mdl-30088385

RESUMEN

Aim: To determine differences in visual field abnormalities in primary open angle glaucoma between patients with high and normal baseline intraocular pressure, and to assess whether some risk factors affect the defect pattern. Material and methods: The study group consisted of 170 patients with normal tension glaucoma and 125 patients with high tension glaucoma. The retrospective analysis of visual field, splinter hemorrhages, peripapillary atrophy, disc notches and vascular risk factors (low blood pressure, migraines and cold extremities) was carried out. Results: In patients with high tension glaucoma the most frequently observed scotoma were advanced changes (65.8%), arcuate scotoma (19.7%), paracentral scotoma (7.7%). Advanced changes were observed in 43.5% of patients with normal tension glaucoma, with arcuate scotoma seen in 28.7% and paracentral scotoma in 15.7% of them. The difference in visual field changes between both groups was statistically significant (p=0.003). The prevalence of disc hemorrhages was significantly higher in patients with normal tension glaucoma (16% vs. 4.3%, respectively). In patients with normal tension glaucoma and hemorrhages (DH+) the paracentral scotoma was seen more frequently (DH+ vs. DH-: 22.3% vs.10.2%). The type of scotoma in normal tension glaucoma was linked to the presence of cold distal extremities, which were seen more frequently in this group (p=0.000). Patients with normal tension glaucoma and cold extremities (CE+) typically presented with arcuate scotoma (CE+ vs. CE-: 27.8% vs. 0%). Peripapillary atrophy was more frequent in normal tension glaucoma and in males, and it was not linked to the type of scotoma (p= 0.133). Patient with high tension glaucoma and peripapillary atrophy had more often presented with advanced changes in visual field (p= 0.001). Conclusions: Scotoma morphology in primary open angle glaucoma depends on glaucoma subtype. Additionally, in normal tension glaucoma, it is related to the presence of disc hemorrhages and vascular risk factors.


Asunto(s)
Glaucoma de Ángulo Abierto/fisiopatología , Glaucoma de Baja Tensión/fisiopatología , Hipertensión Ocular/fisiopatología , Campos Visuales , Anciano , Femenino , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Trastornos de la Visión/fisiopatología , Pruebas del Campo Visual
12.
Exp Eye Res ; 132: 91-100, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25625506

RESUMEN

PURPOSE: To evaluate the in vivo biocompatibility of grafts composed of sheets of decellularized human corneal stroma with or without the recellularization of human adipose derived adult stem cells (h-ADASC) into the rabbit cornea. METHODS: Sheets of human corneal stroma of 90 µm thickness were decellularized, and their lack of cytotoxicity was assayed. The recellularization was achieved by the injection of 2 × 10(5) labeled h-ADASC in the graft followed by five days of cell culture. The grafts were implanted in vivo into a stromal pocket at 50% depth. After a triple-masked three-month follow-up, the animals were euthanized and the biointegration of the graft, the viability of the stem cells and the expression of keratocan (human keratocyte-specific protein) were assessed. RESULTS: The decellularized stromal sheets showed an intact extracellular matrix with a decellularization rate of 92.8% and an excellent recellularization capacity in vitro with h-ADASC. A complete and stable graft transparency was observed during the full follow-up, with absence of any clinical sign of rejection. The postmortem analysis demonstrated the survival of the transplanted human stem cells inside the graft and their differentiation into functional keratocytes, as assessed by the expression of human keratocan. CONCLUSIONS: We report a new model of lamellar keratoplasty that requires only a simple and safe procedure of liposuction and a donor allogeneic cornea to provide an optically transparent autologous stromal graft with excellent biocompatibility and integration into the host tissue in a rabbit model.


Asunto(s)
Tejido Adiposo/citología , Enfermedades de la Córnea/cirugía , Sustancia Propia/trasplante , Trasplante de Córnea/métodos , Células Madre Mesenquimatosas , Animales , Sustancia Propia/citología , Modelos Animales de Enfermedad , Matriz Extracelular , Humanos , Conejos , Trasplante de Células Madre , Ingeniería de Tejidos/métodos , Andamios del Tejido , Trasplante Homólogo
13.
Ophthalmic Res ; 53(3): 162-7, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25832811

RESUMEN

OBJECTIVE: This study was conducted to investigate neuroprotective effects of a high fat/low carbohydrate and protein diet (ketogenic diet, KD) in a model of N-methyl D-aspartate (NMDA)-induced retinal ganglion cell (RGC) damage in juvenile and young adult rats. METHODS: Juvenile (30-35 days old) and young adult (56-70 days old) female Brown Norway rats were fed the KD for 21 days; rats exposed to a standard rodent diet (SRD) served as controls. The main constituents of the KD used in the present study were approximately 80% fats, 8% proteins, and less than 1% carbohydrates. On day 14 of exposure to the KD (or the SRD in the control group), each rat received a single intravitreal injection of NMDA; RGCs were then retrogradely labelled by hydroxystilbamidine on day 19 and collected on day 21 to assess the degree of damage induced by NMDA. Blood biomarkers to confirm the expected metabolic response to the KD (i.e. ketosis and hypoglycaemia) were also assessed. RESULTS: Although both the juvenile and young adult rats developed comparable ketosis and hypoglycaemia when fed the KD, NMDA-induced loss in RGCs was significantly attenuated only in juvenile rats exposed to the KD in comparison with those fed the SRD; exposure to the KD had no protective effect in young adult rats. In summary, exposure to the KD had a neuroprotective effect in NMDA-induced RGC damage in juvenile rats, but not in young adult rats. CONCLUSION: These results support further exploration of metabolic interventions to treat optic neuropathies associated with neurodegeneration.


Asunto(s)
Dietoterapia/métodos , Dieta Cetogénica , N-Metilaspartato/toxicidad , Fármacos Neuroprotectores/administración & dosificación , Degeneración Retiniana/dietoterapia , Células Ganglionares de la Retina/citología , Animales , Recuento de Células , Ácido D-Aspártico/metabolismo , Modelos Animales de Enfermedad , Femenino , Ratas , Ratas Endogámicas BN , Degeneración Retiniana/inducido químicamente , Degeneración Retiniana/patología , Células Ganglionares de la Retina/efectos de los fármacos
14.
BMC Ophthalmol ; 14: 56, 2014 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-24885864

RESUMEN

BACKGROUND: The aim of the study was to evaluate the relationship between the area of isopters obtained using semi-automated kinetic perimetry (SKP) and Vigabatrin dosage in epilepsy patients with pretreatment baseline examination during 2-years of the follow-up. METHODS: 29 epilepsy patients were included into the study, but 15 individuals were excluded due to cognitive impairment, intracranial pathologies or eye diseases. Finally, 14 patients were examined with SKP before VGB treatment and after 6, 12, 18, and 24 months. Reaction time (RT)-corrected areas of three isopters (III4e, I4e and I2e) were measured for each of five examinations and compared intra-individually during 2-years period. Additionally, six epilepsy patients on other antiepileptic drugs were examined five times with SKP as a control. RESULTS: There was a significant decrease of I2e, I4e and III4e isopters' area during the follow-up of two years. Correlation was found between the I2e isopter's area and both cumulative dose and mean daily dose of VGB. With increasing RT, there was decreasing of all isopters' area in patients receiving VGB. In epilepsy patients who were not receiving VGB, there were no significance differences in isopters' area during follow-up. CONCLUSION: There was attenuation of area of III4e, I4e and I2e isopters obtained with SKP during a period of 2 years. RT, the cumulative dose and the mean daily dose of VGB influenced isopters' area obtained with SKP.


Asunto(s)
Epilepsia/tratamiento farmacológico , Enfermedades del Nervio Óptico/inducido químicamente , Escotoma/etiología , Vigabatrin/administración & dosificación , Campos Visuales/efectos de los fármacos , Adulto , Anticonvulsivantes/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Enfermedades del Nervio Óptico/complicaciones , Enfermedades del Nervio Óptico/fisiopatología , Polonia/epidemiología , Estudios Prospectivos , Factores de Riesgo , Escotoma/epidemiología , Escotoma/fisiopatología , Factores de Tiempo , Pruebas del Campo Visual , Adulto Joven
15.
Sci Rep ; 14(1): 8279, 2024 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594403

RESUMEN

The aim of the study was to compare the anterior segment parameters after cataract surgery in pseudoexfoliation syndrome (PEX) and control eyes. We conducted a prospective comparative study of 36 eyes (PEX group), 16 eyes (PEXG group) and 46 eyes (control group) of 98 patients after phacoemulsification with intraocular lens implantation. Before surgery, 1 week, 1 month and 3 months postoperatively, anterior chamber parameters were evaluated by swept source anterior segment optical coherence tomography (AS-OCT). Anterior chamber depth (ACD), angle opening distance (AOD500/750), trabecular-iris space area (TISA500/750), trabecular-iris angle (TIA500/750) and lens vault (LV) were assessed at each study visit. Preoperatively, ACD, AOD500/750 and TISA500/750 were significantly smaller, while LV was significantly greater in PEX and PEXG eyes than in controls. 3 months postoperatively all irido-corneal parameters and ACD were significantly greater in all study groups without intergroup differences. ACD and LV significantly increased in PEX group between 1 and 3 months after surgery while being stable in control group. Relative increases in ACD, AOD500, TISA750, TIA500/750 were significantly higher in PEX and PEXG groups than in controls. Our study finds that ACD and iridocorneal parameters in AS-OCT demonstrated significantly greater relative increases 3 months after phacoemulsification in PEX and PEXG groups than in control eyes. Significantly greater deepening of anterior chamber and opening of the irido-corneal angle may be a reason for different refractive outcomes and IOP control in patients with PEX and PEXG after routine cataract surgery.


Asunto(s)
Catarata , Síndrome de Exfoliación , Humanos , Tomografía de Coherencia Óptica/métodos , Síndrome de Exfoliación/diagnóstico por imagen , Estudios Prospectivos , Presión Intraocular , Cámara Anterior , Segmento Anterior del Ojo/diagnóstico por imagen
16.
BMC Ophthalmol ; 13: 17, 2013 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-23617885

RESUMEN

BACKGROUND: Trabeculectomy remains the most efficient method of lowering he IOP applied for the treatment of glaucoma refractory to pharmacological treatment. Cataract is concerned as the most frequent late complication of trabeculectomy. The aim of the study was to analyse the effect of phacoemulsification with posterior chamber lens implantation on the morphology and function of filtering bleb in patients after previous successful trabeculectomy. METHODS: The retrospective study included 122 eyes treated for primary open angle glaucoma, 50 eyes (study group) in which, after a successful trabeculectomy with 5-Fluorouracil, phacoemulsification with posterior chamber lens implantation was performed, and 72 eyes (control group), in which only a successful trabeculectomy was conducted. The surgical success of the trabeculectomy was expressed as IOP < 17 mmHg. RESULTS: In the group of patients subjected to both trabeculectomy and phacoemulsification, mean IOP was significantly higher than in the group of patients who underwent trabeculectomy after 6 months (p = 0.003), 12 months (p = 0.01) and 18 months (p = 0.007) of observation. The filtering blebs after phacoemulsification in the study group were characterized by a greater reduction, compared to those in the control group. Cox regression survival success was 75% (SE = 5.9; 95% CI: 63.4-86.6), 75% (SE = 5.9; 95% CI: 63.4-86.6), 71% (SE = 5.4; 95% CI: 60.4-81.6) in study group and 92% (SE = 1.8; 95% CI: 91.5-98.5), 92% (SE = 1.9; 95% CI: 88.3-95.7), 91% (SE = 2.0; 95% CI: 87.1-94.9) in control group after 6, 12 and 18 months, respectively. CONCLUSIONS: Phacoemulsification causes a significant elevation of IOP in the eyes after previous successful trabeculectomy and deterioration of filtering bleb morphology.


Asunto(s)
Cirugía Filtrante , Glaucoma de Ángulo Abierto/cirugía , Facoemulsificación/métodos , Trabeculectomía/métodos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Presión Intraocular , Masculino , Persona de Mediana Edad , Análisis de Regresión , Estudios Retrospectivos
17.
Klin Oczna ; 115(3): 177-83, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24741920

RESUMEN

PURPOSE: To determine the efficacy and safety of mitomycin C-augmented revision in eyes after failed primary trabeculectomy failure. MATERIAL AND METHODS: Retrospective review of 40 eyes after a single MMC-augmented revision due to primary trabeculectomy failure. MAIN OUTCOME MEASURES: intraocular pressure, best corrected visual acuity, number of antiglaucoma medications, complications. RESULTS: Twelve months after revision the mean intraocular pressure declined from 24.5 +/- 6.7 mmHg to 15.4 +/- 4.4 mmHg (p < 0.05) and remained decreased at 24 months (16.33 +/- 4.2 mmHg) and at 84 months (16.75 +/- 2.8 mmHg). The therapeutic success, defined as intraocular pressure < or = 18 mmHg without medication at 12 months after revision, was achieved in seventeen eyes (42.5%). Fourteen eyes (35.0%) achieved qualified success, defined as intraocular pressure < or = 18 mmHg with antiglaucoma medication, and 9 of 40 eyes (22.5%) were classified as failures. Mean best corrected visual acuity did not change significantly after the surgery (12 month: p = 0.76, 36-48 months: p = 0.25, 72-84 months: p = 0.15). The mean number of medications was reduced from 1.2 +/- 0.8 preoperatively to 0.68 +/- 0.8 postoperatively at 12 months, to 0.78 +/- 0.49 at 24 months and the drop was statistically significantly. Early complications developed in 7 (17.5%) eyes but they resolved spontaneously. CONCLUSIONS: MMC-augmented revision appears to be a safe and useful tool in reducing intraocular pressure after trabeculectomy failure. This simple-technique procedure is successful in 42.5% of eyes for up to 24-36 months and helps protect the eye from other surgical intervention, more destructive for the conjunctiva.


Asunto(s)
Glaucoma/tratamiento farmacológico , Glaucoma/cirugía , Presión Intraocular/efectos de los fármacos , Mitomicina/administración & dosificación , Complicaciones Posoperatorias/tratamiento farmacológico , Trabeculectomía/efectos adversos , Agudeza Visual/efectos de los fármacos , Adulto , Anciano , Anciano de 80 o más Años , Conjuntiva/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Insuficiencia del Tratamiento , Resultado del Tratamiento
19.
Artículo en Inglés | MEDLINE | ID: mdl-36768125

RESUMEN

AIM: The aim of the study was to retrospectively evaluate the efficacy and safety of GATT during a 6-month observation period. MATERIAL AND METHODS: The studied group consisted of 69 open-angle glaucoma patients treated with GATT as the only procedure or in combination with cataract surgery. Patients were assessed 1 day, 10 days, 1 month, 3 months, and 6 months after the surgery via standard ophthalmic examination including VF, IOP, and BCVA. The number of medications taken daily and possible complications were checked. Two criteria of success were established (S1: IOP decrease by 30% and S2: IOP lower than 18 mm Hg). RESULTS: Before the surgery, the mean IOP was 26.94 mmHg and significantly decreased after GATT to 15.59 mmHg at 6M. BCVA did not significantly differ between the visits. The mean MD did not change significantly within the 6-month observation period (-8.20 dB vs. -8.16 dB, p = 0.9824), similar to the mean VFI (64.31% vs. 63.05%, p = 0.8571). A 30% IOP decrease at 6M visit was obtained in 95.6% of patients, and 37.7% needed medications to stabilize IOP. An IOP lower than 18 mmHg at 6M was obtained in 91.3% of studied patients after the GATT procedure, and in 58.0% without additional medications. The mean number of medications received daily decreased significantly at 6M compared to preoperative results (2.59 at inclusion vs. 0.76 at 6M, p = 0.0004). The most frequent complication after surgery was hyphema, which resolved spontaneously within 10 days. CONCLUSION: The 6-month observation showed that GATT is a minimally invasive glaucoma-surgery technique that enables an effective and safe IOP decrease.


Asunto(s)
Glaucoma de Ángulo Abierto , Trabeculectomía , Humanos , Glaucoma de Ángulo Abierto/cirugía , Glaucoma de Ángulo Abierto/diagnóstico , Estudios de Seguimiento , Resultado del Tratamiento , Presión Intraocular , Trabeculectomía/métodos , Estudios Retrospectivos , Gonioscopía
20.
J Glaucoma ; 32(10): 820-825, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37523648

RESUMEN

PRCIS: Subgrouping of angle closure mechanisms based on the swept-source optical coherence tomography images may help to identify the predominant underlying anatomic mechanism, evaluate personal treatment, and improve the better outcomes. PURPOSE: The purpose of this study was to evaluate changes in anterior segment parameters in Caucasian eyes with different angle closure mechanisms before and after laser peripheral iridotomy (LPI). METHODS: Sixty-six subjects underwent swept-source optical coherence tomography (CASIA, Tomey Corporation) angle imaging in the dark before and 7 days after LPI. On the basis of the baseline swept-source optical coherence tomography images, the eyes were categorized into 4 angle closure mechanisms, namely pupillary block (PB), plateau iris configuration (PIC), thick peripheral iris (TPI), and large lens vault (LLV). Sixteen out of 128 cross-sectional images (11.25 degrees apart) per volume scan were selected for analysis. We used a generalized estimating equation to compare quantitative parameters among angle closure mechanisms and between before and after LPI after adjusting the intereye correlation. RESULTS: The mean age of subjects was 67.7±9.2 years, with the majority being female (82.2%). One hundred twenty-nine eyes (67 primary angle closure suspects, 34 primary angle closure, and 28 primary angle closure glaucoma) were categorized into PB (n=71, 55%), PIC (n=40, 31%), TPI (n=14, 10.9%), and LLV (n=4, 3.1%). Anterior chamber depth was the shallowest in the LLV, followed by TPI, PB, and PIC group at baseline. Widening of the angle and reduction of the iris curvature (IC) due to LPI were observed in all groups (all P <0.01). When compared to the PB group, the LPI-induced angle widening in the TPI group was significantly less even though the iris curvature reduction in the TPI group was greater (all P <0.05). CONCLUSIONS: In patients with angle closure, anterior segment morphology and LPI-induced angle widening were different among the various angle closure mechanisms.


Asunto(s)
Glaucoma de Ángulo Cerrado , Terapia por Láser , Láseres de Estado Sólido , Trastornos de la Pupila , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Segmento Anterior del Ojo/diagnóstico por imagen , Iridectomía/métodos , Presión Intraocular , Glaucoma de Ángulo Cerrado/diagnóstico , Glaucoma de Ángulo Cerrado/cirugía , Iris/cirugía , Terapia por Láser/métodos , Tomografía de Coherencia Óptica/métodos , Gonioscopía
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