RESUMEN
Fuchs Endothelial Corneal Dystrophy (FECD), a late-onset oxidative stress disorder, is the most common cause of corneal endothelial degeneration and is genetically associated with CTG repeat expansion in Transcription Factor 4 (TCF4). We previously reported accumulation of nuclear (nDNA) and mitochondrial (mtDNA) damage in FECD. Specifically, mtDNA damage was a prominent finding in development of disease in the ultraviolet-A (UVA) induced FECD mouse model. We hypothesize that an aberrant DNA repair may contribute to the increased DNA damage seen in FECD. We analyzed differential expression profiles of 84 DNA repair genes by real-time PCR arrays using Human DNA Repair RT-Profiler plates using cDNA extracted from Descemet's membrane-corneal endothelium (DM-CE) obtained from FECD patients with expanded (>40) or non-expanded (<40) intronic CTG repeats in TCF4 gene and from age-matched normal donors. Change in mRNA expression of <0.5- or >2.0-fold in FECD relative to normal was set as cutoff for down- or upregulation. Downregulated mitochondrial genes were further validated using the UVA-based mouse model of FECD. FECD specimens exhibited downregulation of 9 genes and upregulation of 8 genes belonging to the four major DNA repair pathways, namely, base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), and double strand break (DSB) repair, compared to normal donors. MMR gene MSH2 and BER gene POLB were preferentially upregulated in expanded FECD. BER genes LIG3 and NEIL2, DSB repair genes PARP3 and TOP3A, NER gene XPC, and unclassified pathway gene TREX1, were downregulated in both expanded and non-expanded FECD. MtDNA repair genes, Lig3, Neil2, and Top3a, were also downregulated in the UVA-based mouse model of FECD. Our findings identify impaired DNA repair pathways that may play an important role in DNA damage due to oxidative stress as well as genetic predisposition noted in FECD.
Asunto(s)
ADN Glicosilasas , Distrofia Endotelial de Fuchs , Animales , Ratones , Humanos , Distrofia Endotelial de Fuchs/genética , Distrofia Endotelial de Fuchs/metabolismo , Endotelio Corneal/metabolismo , Predisposición Genética a la Enfermedad , Reparación del ADN/genética , ADN Mitocondrial/genética , ADN Glicosilasas/genética , ADN Glicosilasas/metabolismoRESUMEN
PURPOSE: To evaluate safety and efficacy of a custom-manufactured artificial iris device (CustomFlex Artificial Iris; HumanOptics AG) for the treatment of congenital and acquired iris defects. DESIGN: Multicenter, prospective, unmasked, nonrandomized, interventional clinical trial. PARTICIPANTS: Patients with photophobia, sensitivity secondary to partial or complete congenital or acquired iris defects, or both. METHODS: Eyes were implanted from November 26, 2013, to December 1, 2017, with a custom, foldable artificial iris by 1 of 4 different surgical techniques. Patients were evaluated 1 day, 1 week, and 1, 3, 6, and 12 months after surgery. At each examination, slit-lamp findings, intraocular pressure, implant position, subjective visual symptoms, and complications were recorded. Corrected distance visual acuity (CDVA) and endothelial cell density (ECD) were measured at 3, 6, or 12 months as additional safety evaluations. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was used to assess health-related quality of life affected by vision. The Global Aesthetic Improvement Scale was used to assess cosmetic results. MAIN OUTCOME MEASURES: Photosensitivity, glare, visual symptoms, NEI VFQ-25 score, Global Aesthetic Improvement Scale rating, prosthesis-related adverse events, intraocular lens (IOL)-related adverse events, and surgery-related adverse events 12 months after surgery. RESULTS: At the 12-month postoperative examination, a 59.7% reduction in marked to severe daytime light sensitivity (P < 0.0001), a 41.5% reduction in marked to severe nighttime light sensitivity (P < 0.0001), a 53.1% reduction in marked to severe daytime glare (P < 0.0001), and a 48.5% reduction in severe nighttime glare (P < 0.0001) were found. A 15.4-point improvement (P < 0.0001) in the NEI VFQ-25 total score was found, and 93.8% of patients reported an improvement in cosmesis as measured by the Global Aesthetic Improvement Scale 12 months after surgery. No loss of CDVA of > 2 lines related to the device was found. Median ECD loss was 5.3% at 6 months after surgery and 7.2% at 12 months after surgery. CONCLUSIONS: The artificial iris surpassed all key safety end points for adverse events related to the device, IOL, or implant surgery and met all key efficacy end points, including decreased light and glare sensitivity, improved health-related quality of life, and satisfaction with cosmesis. The device is safe and effective for the treatment of symptoms and an unacceptable cosmetic appearance created by congenital or acquired iris defects.
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Iris , Implantación de Lentes Intraoculares , Humanos , Iris/anomalías , Iris/cirugía , Implantación de Lentes Intraoculares/métodos , Lentes Intraoculares , Fotofobia/cirugía , Estudios Prospectivos , Calidad de Vida , Estados Unidos , United States Food and Drug AdministrationRESUMEN
Corneal endothelium (CE) is a monolayer of mitochondria-rich cells, critical for maintaining corneal transparency compatible with clear vision. Fuchs endothelial corneal dystrophy (FECD) is a heterogeneous, genetically complex disorder, where oxidative stress plays a key role in the rosette formation during the degenerative loss of CE. Increased mitochondrial fragmentation along with excessive mitophagy activation has been detected in FECD; however, the mechanism of aberrant mitochondrial dynamics in CE cell loss is poorly understood. Here, the role of oxidative stress in mitophagy activation in FECD is investigated. Immunoblotting of FECD ex vivo specimens revealed an accumulation of PINK1 and phospho-Parkin (Ser65) along with loss of total Parkin and total Drp1. Similarly, modeling of rosette formation with menadione (MN), led to phospho-Parkin accumulation in fragmented mitochondria resulting in mitophagy-induced mitochondrial clearance, albeit possibly in a PINK1-independent manner. Loss of PINK1, phospho-Drp1, and total Drp1 was prominent after MN-induced oxidative stress, but not after mitochondrial depolarization by carbonyl cyanide m-chlorophenyl hydrazone. Moreover, MN-induced mitophagy led to degradation of Parkin along with sequestration of Drp1 and PINK1 that was rescued by mitophagy inhibition. This study shows that in FECD, intracellular oxidative stress induces Parkin-mediated mitochondrial fragmentation where endogenous Drp1 and PINK1 are sequestered and degraded by mitophagy during degenerative loss of post-mitotic cells of ocular tissue.
Asunto(s)
Endotelio Corneal/patología , Distrofia Endotelial de Fuchs/patología , Mitocondrias/patología , Proteínas Mitocondriales/metabolismo , Mitofagia , Proteínas Quinasas/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Antifibrinolíticos/farmacología , Endotelio Corneal/efectos de los fármacos , Endotelio Corneal/metabolismo , Distrofia Endotelial de Fuchs/genética , Distrofia Endotelial de Fuchs/metabolismo , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Proteínas Mitocondriales/genética , Estrés Oxidativo , Proteínas Quinasas/genética , Transducción de Señal , Ubiquitina-Proteína Ligasas/genética , Vitamina K 3/farmacologíaRESUMEN
PURPOSE: To investigate whether the riboflavin dosing frequency affects corneal cross-linking efficacy or safety, given that isotonic riboflavin solution is viscous and each installation coats the corneal surface with a film that absorbs some of the incident ultraviolet A light. DESIGN: Prospective, randomized, single-center equivalence trial. PARTICIPANTS: Patients with progressive keratoconus or ectasia after refractive surgery (n = 510). METHODS: One eye per patient was prospectively randomized to 2-minute or 5-minute riboflavin dosing intervals with standard corneal cross-linking (epithelial removal and 30-minute irradiation with 3 mW/cm2 ultraviolet A light). Block randomization resulted in comparable representation of keratoconus and ectasia after refractive surgery in the 2 treatment arms. Treatment equivalence was assessed using the 2 one-sided test. Fellow eyes (n = 207) were treated with 5-minute dosing and considered in the safety analysis. MAIN OUTCOME MEASURES: The primary hypothesis was equivalent change in the topography-derived maximum keratometry value from baseline to 6 months with 2-minute vs. 5-minute dosing. A ±0.75-diopter margin of equivalence for the treatment difference between dosing regimens was considered clinically relevant. Adverse events and changes from baseline to 6 months in corrected distance visual acuity (CDVA), uncorrected distance visual acuity, and minimum corneal thickness were assessed. RESULTS: The mean reduction in maximum keratometry from baseline was equivalent with 2-minute and 5-minute riboflavin dosing intervals at 6 months (0.97 and 0.76 diopters, respectively; 90% confidence interval for treatment difference, -0.23 to 0.66; per-protocol population). With both dosing intervals, the mean improvement in CDVA was 0.07 logarithm of the minimum angle of resolution or 3.5 letters at 6 months. Of the 635 study and fellow eyes examined at 6 months, 134 (21%) gained and 32 (5%) lost 2 or more lines of CDVA. Three eyes (0.4%) developed sterile infiltrates, 1 (0.1%) had delayed epithelial healing with dendrites, and 3 (0.4%) had recurrent epithelial defects. Three eyes (0.4%) were re-treated. CONCLUSIONS: The 2 riboflavin dosing regimens produced equivalent reduction in the maximum keratometry value, with a favorable safety profile.
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Colágeno/metabolismo , Sustancia Propia/metabolismo , Reactivos de Enlaces Cruzados , Queratocono/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/administración & dosificación , Riboflavina/administración & dosificación , Adolescente , Adulto , Anciano , Niño , Paquimetría Corneal , Topografía de la Córnea , Dilatación Patológica/tratamiento farmacológico , Dilatación Patológica/metabolismo , Dilatación Patológica/fisiopatología , Método Doble Ciego , Femenino , Humanos , Queratocono/metabolismo , Queratocono/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Refracción Ocular/fisiología , Equivalencia Terapéutica , Factores de Tiempo , Rayos Ultravioleta , Agudeza Visual/fisiologíaRESUMEN
PURPOSE: To determine whether the reduced risk of immunologic rejection with Descemet membrane endothelial keratoplasty (DMEK) results in a 5-year survival advantage relative to Descemet stripping endothelial keratoplasty (DSEK) and to determine whether matching the donor and recipient sex affects the rejection episode and graft survival rates. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with Fuchs' endothelial corneal dystrophy treated with DSEK or DMEK. METHODS: This study reviewed 2017 consecutive cases (1312 DSEK and 705 DMEK) performed by 13 surgeons between 2003 and 2012 and included the surgeons' first cases. Survival rates were calculated by Kaplan-Meier analysis. MAIN OUTCOME MEASURES: Immunologic rejection episodes, graft failure or replacement for any reason, and endothelial cell loss. RESULTS: The 5-year rejection episode rate was lower with DMEK (2.6% vs. 7.9% with DSEK, relative risk, 0.29; 95% confidence interval, 0.16-0.53) despite early reduction of topical corticosteroids in 25% of the DMEK cases. African Americans (n = 46) had a higher risk of rejection episodes than other races (relative risk, 4.4; 95% confidence interval, 2.0-9.6). The cumulative 5-year survival rate was 93% with DSEK and DMEK (P = 0.86). Forty-four DMEK and 69 DSEK grafts failed or were replaced within 5 years, but only 1 DMEK and 4 DSEK failures followed a rejection episode. Rejection episodes increased endothelial cell loss (P = 0.004) but were not a significant risk factor for graft failure within 5 years (P = 0.90). The mean 5-year endothelial cell loss was similar between DMEK (48%±19%) and DSEK (47%±19%) (P = 0.22). Graft rejection episode and survival rates were not significantly influenced by whether the sex of the donor matched that of the recipient (rejection episodes: P = 0.07 for female recipients and P = 0.33 for male recipients; graft survival: P = 0.67 for female recipients and P = 0.17 for male recipients). CONCLUSIONS: Five-year graft survival was similar between DMEK and DSEK. Although DMEK had a significantly lower risk of immunologic rejection, rejection episodes rarely resulted in graft failure within 5 years with either procedure. Sex matching the donor and recipient provided no survival advantage with DSEK or DMEK.
Asunto(s)
Queratoplastia Endotelial de la Lámina Limitante Posterior/métodos , Endotelio Corneal/patología , Distrofia Endotelial de Fuchs/cirugía , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Agudeza Visual , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Distrofia Endotelial de Fuchs/diagnóstico , Rechazo de Injerto/diagnóstico , Humanos , Incidencia , Indiana/epidemiología , Masculino , Microscopía Confocal , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Donantes de Tejidos , Adulto JovenRESUMEN
Human corneal endothelial cells are derived from neural crest and because of postmitotic arrest lack competence to repair cell loss from trauma, aging, and degenerative disorders such as Fuchs endothelial corneal dystrophy (FECD). Herein, we identified a rapidly proliferating subpopulation of cells from the corneal endothelium of adult normal and FECD donors that exhibited features of neural crest-derived progenitor (NCDP) cells by showing absence of senescence with passaging, propensity to form spheres, and increased colony forming efficacy compared with the primary cells. The collective expression of stem cell-related genes SOX2, OCT4, LGR5, TP63 (p63), as well as neural crest marker genes PSIP1 (p75(NTR)), PAX3, SOX9, AP2B1 (AP-2ß), and NES, generated a phenotypic footprint of endothelial NCDPs. NCDPs displayed multipotency by differentiating into microtubule-associated protein 2, ß-III tubulin, and glial fibrillary acidic protein positive neurons and into p75(NTR)-positive human corneal endothelial cells that exhibited transendothelial resistance of functional endothelium. In conclusion, we found that mitotically incompetent ocular tissue cells contain adult NCDPs that exhibit a profile of transcription factors regulating multipotency and neural crest progenitor characteristics. Identification of normal NCDPs in FECD-affected endothelium holds promise for potential autologous cell therapies.
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Células Progenitoras Endoteliales/metabolismo , Endotelio Corneal/patología , Distrofia Endotelial de Fuchs/patología , Adulto , Anciano , Biomarcadores/metabolismo , Células Progenitoras Endoteliales/patología , Endotelio Corneal/metabolismo , Femenino , Distrofia Endotelial de Fuchs/metabolismo , Humanos , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Cresta Neural/metabolismo , Cresta Neural/patología , Fenotipo , Tubulina (Proteína)RESUMEN
PURPOSE: To assess the risk of immunologic rejection episodes if topical corticosteroids are discontinued 1 year after Descemet's membrane endothelial keratoplasty (DMEK) compared with continued once-per-day use. DESIGN: Prospective, longitudinal, parallel-group study. PARTICIPANTS: A total of 400 eyes of 259 DMEK recipients, aged 23 to 90 years. METHODS: Patients were enrolled 1 year after DMEK and allowed to choose whether to stop or continue once-daily topical corticosteroids to maximize compliance. Fellow eyes were eligible for enrollment because the donor grafts were independent. Participants were examined at 1, 3, 6, and 12 months during the second year after DMEK. Results were assessed using Kaplan-Meier survival analysis. MAIN OUTCOME MEASURES: Incidence of immunologic rejection episodes. RESULTS: Steroids were discontinued in 277 eyes (no steroid group) and continued once per day in 123 eyes (steroid group). The subject demographics were well balanced across groups; 99% of the subjects were white, and 95% of the grafts were performed to treat Fuchs' dystrophy. The cumulative incidence of rejection episodes was significantly greater in the no steroid group (6% vs. 0% in the steroid group; P = 0.013). Thirteen of 14 rejection episodes (all in the no steroid group) resolved with resumption of topical corticosteroids. Overall, 1 of 277 grafts (0.4%) failed in the no steroid group, and none failed in the steroid group during the second year after DMEK (P = 0.49). The endothelial cell loss between 1 and 2 years was comparable in the no steroid and steroid groups (6.4%±12% vs. 5.6%±14%, respectively; P = 0.67). CONCLUSIONS: Continued once-per-day use of a topical corticosteroid, even a weak one, was protective against rejection episodes during the second year after DMEK, whereas 6% experienced a rejection episode when steroids were discontinued. Among the 364 eyes that completed 12 months' follow-up, only 1 graft (0.27%) failed.
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Queratoplastia Endotelial de la Lámina Limitante Posterior , Glucocorticoides/administración & dosificación , Rechazo de Injerto/epidemiología , Privación de Tratamiento , Administración Tópica , Adulto , Anciano , Anciano de 80 o más Años , Recuento de Células , Pérdida de Celulas Endoteliales de la Córnea/diagnóstico , Endotelio Corneal/patología , Femenino , Fluorometolona/administración & dosificación , Distrofia Endotelial de Fuchs/cirugía , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Humanos , Estudios Longitudinales , Etabonato de Loteprednol/administración & dosificación , Masculino , Persona de Mediana Edad , Soluciones Oftálmicas , Prednisolona/administración & dosificación , Prednisolona/análogos & derivados , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
PURPOSE: To assess endothelial cell density (ECD) and model 10-year cell loss after Descemet stripping endothelial keratoplasty (DSEK), and to compare with results after penetrating keratoplasty (PK) performed for the same indications in the Cornea Donor Study (CDS). DESIGN: Retrospective, longitudinal study. PARTICIPANTS: Five hundred ninety DSEK recipients, 21 to 96 years of age, treated for Fuchs' dystrophy (n = 498; 84%), pseudophakic or aphakic corneal edema (n = 89; 15%), or other endothelial dysfunction (n = 3; <1%). METHODS: Review of 1005 consecutive primary DSEK procedures by 6 surgeons identified 752 grafts (75%) in 590 recipients with ECD measurements at 1 or more postoperative examinations between 6 months and 10 years. Four statistical models applied previously to the CDS PK data were considered. The preferred model (Bayesian Markov chain Monte Carlo) accounted for missing data, selective dropout from graft failure, correlations between fellow eyes, and correlations between longitudinal repeated measures. MAIN OUTCOME MEASURES: Central corneal ECD. RESULTS: The median donor corneal ECD (25th-75th percentiles) was 3005 cells/mm(2) (2852-3203 cells/mm(2)) at baseline, 2077 cells/mm(2) (1660-2411 cells/mm(2)) at 6 months, and 926 cells/mm(2) (617-1433 cells/mm(2)), with a range from 408 to 2538 cells/mm(2) at 10 years. After median cell loss of 32% in the perioperative period, ECD declined at a linear rate of approximately 110 cells/mm(2) per year between 6 months and 10 years after DSEK. At 10 years, the median cell loss was 71% (53%-80%) relative to the baseline donor ECD, comparable with the 76% (70%-82%) median cell loss after PK by 68 surgeons in the CDS. The 10-year ECD correlated with the 6-month postoperative ECD (r = 0.56; P < 0.001), but not with the baseline donor ECD (r = -0.04; P = 0.78). Selective dropout from graft failure did not affect the cell loss model significantly. CONCLUSIONS: The linear decline in ECD after DSEK was consistent with shorter-term endothelial keratoplasty studies and was distinct from the biexponential cell loss trend characteristic of PK. By 10 years, cell loss was comparable in surviving clear grafts for both DSEK and PK.
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Pérdida de Celulas Endoteliales de la Córnea/patología , Queratoplastia Endotelial de la Lámina Limitante Posterior/efectos adversos , Endotelio Corneal/patología , Queratoplastia Penetrante/efectos adversos , Complicaciones Posoperatorias/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Teóricos , Adulto JovenRESUMEN
PURPOSE: To assess patient satisfaction and perceived outcomes with different methods of refractive error correction through annual surveys administered over a 3-year period. DESIGN: Prospective, longitudinal, parallel-group, multicenter survey. PARTICIPANTS: A total of 1800 subjects, aged 18 to 60 years, who had LASIK or continued using contact lenses. METHODS: Twenty sites across the United States enrolled subjects who completed a study-specific baseline survey during a contact lens examination or while being evaluated as a candidate for LASIK. Links to follow-up surveys were emailed annually for 3 years. Between-group differences were assessed by analysis of variance, and associations were assessed by logistic multivariate regression. MAIN OUTCOME MEASURES: Visual satisfaction. RESULTS: Of 1800 subjects, 694 (39%) comprised the control group who continued contact lens wear, 819 (45%) wore contacts at baseline and had LASIK, and 287 (16%) wore glasses at baseline and had LASIK. Most contact lens users had worn them successfully ≥5 years. The proportion expressing strong satisfaction with their current vision correction method decreased from 63% at baseline to 54% at year 3 in the contact lens control group, whereas 88% of former contact lens wearers and 77% of former glasses wearers were strongly satisfied with LASIK at year 3. Patients 40 years of age or younger when they had LASIK were somewhat more likely to be strongly satisfied than older patients. LASIK significantly reduced difficulties with night driving and nighttime visual disturbances among former contact lens users and former glasses users. The proportion with dry eye symptoms at 1, 2, or 3 years after LASIK was not significantly increased relative to baseline contact lens wear but was significantly increased relative to baseline glasses use, consistent with many glasses users having tried and abandoned contact lenses because of latent dry eye problems. Compared with continued contact lens wear, LASIK significantly reduced the self-reported rates of eye infections, ulcers, and abrasions each year. CONCLUSIONS: Compared with contact lens wear, current LASIK technology improved ease of night driving, did not significantly increase dry eye symptoms, and resulted in higher levels of satisfaction at 1, 2, and 3 years follow-up.
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Lentes de Contacto , Hiperopía/terapia , Queratomileusis por Láser In Situ , Miopía/terapia , Satisfacción del Paciente/estadística & datos numéricos , Trastornos de la Visión/terapia , Agudeza Visual/fisiología , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Encuestas Epidemiológicas , Humanos , Hiperopía/fisiopatología , Masculino , Persona de Mediana Edad , Miopía/fisiopatología , Estudios Prospectivos , Trastornos de la Visión/fisiopatologíaRESUMEN
PURPOSE OF REVIEW: New treatments for corneal ulcers are needed to address challenges with antibiotic resistance, cost, and specificity requiring timely pathogen identification. This review assesses the evidence regarding safety and efficacy of corneal cross-linking (CXL) as an adjunct or stand-alone treatment. RECENT FINDINGS: To date approximately 200 clinical cases of CXL used with various types of infectious keratitis have been reported in about 30 publications. Most employed the CXL protocol developed for keratoconus as an adjunct to antibiotics for resistant ulcers, and a number of cases resolved after this intervention. However, a few studies raised concerns about resurgence and perforation when CXL was utilized with deep fungal infections. The infiltrate depth is an important consideration, because the standard CXL treatment is cytotoxic (to keratocytes) to a depth of approximately 200-300âµm and 50% of the energy is absorbed within the first 100âµm. CXL was used successfully as a monotherapy in approximately 16 eyes with early bacterial or shallow fungal infections. SUMMARY: Further work is needed to develop optimized CXL protocols for treatment of corneal ulcers, define the appropriate conditions for use, and determine the safety and efficacy relative to standard antibiotic treatments.
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Úlcera de la Córnea/tratamiento farmacológico , Antibacterianos/uso terapéutico , Úlcera de la Córnea/complicaciones , Úlcera de la Córnea/microbiología , Humanos , Queratitis/complicaciones , Queratocono/tratamiento farmacológicoRESUMEN
PURPOSE: To investigate whether specific glaucoma surgeries are associated with differences in aqueous humor protein concentrations compared to eyes without filters. METHODS: In this cross-sectional study, aqueous humor samples were prospectively collected from control subjects who underwent routine cataract surgery (n=14) and from patients who had different glaucoma filters: Baerveldt aqueous shunt (n=6), Ahmed aqueous shunt (n=6), trabeculectomy (n=5), and Ex-Press trabeculectomy (n=3). Total protein concentrations were determined with Bradford assay. Tryptic digests were analyzed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Proteins were identified with high confidence using stringent criteria and were quantitatively compared with a label-free platform. Relative protein quantities were compared across groups with ANOVA. Post hoc pair-wise comparisons were adjusted for multiple comparisons. RESULTS: Compared to the control eyes, the aqueous humor protein concentration was increased approximately tenfold in the Ahmed and Baerveldt eyes and fivefold in the trabeculectomy and Ex-Press eyes. Overall, 718 unique proteins, splice variants, or isoforms were identified. No differences in the protein concentrations were detected between the Baerveldt and Ahmed groups. Likewise, the trabeculectomy and Ex-Press groups were remarkably similar. Therefore, the aqueous shunt groups were pooled, and the trabeculectomy groups were pooled for a three-way comparison with the controls. More than 500 proteins differed significantly in relative abundance (ANOVA p<0.01) among the control, aqueous shunt, and trabeculectomy groups. Functional analyses suggested these alterations in relative protein abundance affected dozens of signaling pathways. CONCLUSIONS: Different glaucoma surgical procedures were associated with marked increases in the aqueous humor protein concentration and distinctive changes in the relative abundance of numerous proteins involved in multiple signaling pathways.
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Humor Acuoso/metabolismo , Proteínas del Ojo/metabolismo , Cirugía Filtrante/métodos , Glaucoma/metabolismo , Glaucoma/cirugía , Estudios de Casos y Controles , Pérdida de Celulas Endoteliales de la Córnea/etiología , Estudios Transversales , Cirugía Filtrante/efectos adversos , Implantes de Drenaje de Glaucoma/efectos adversos , Humanos , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Proteoma/metabolismo , Transducción de Señal , Espectrometría de Masas en Tándem , Trabeculectomía/efectos adversos , Trabeculectomía/métodosRESUMEN
PURPOSE: To evaluate the outcomes of secondary Descemet membrane endothelial keratoplasty (DMEK) after failed primary DMEK. DESIGN: Retrospective, interventional case series. PARTICIPANTS: Fifty-five DMEK recipients 42 to 89 years of age. METHODS: An initial consecutive series of 1655 DMEK surgeries was reviewed to identify cases of secondary DMEK after failed primary DMEK (n = 55). A paired fellow-eye analysis was performed with a subgroup of 29 patients who underwent secondary DMEK in 1 eye and successful primary DMEK in the fellow eye. MAIN OUTCOME MEASURES: Corrected distance visual acuity (CDVA), central corneal thickness, and 1-year endothelial cell loss. RESULTS: The median follow-up after DMEK regraft was 18 months (range, 3-61 months). All 55 regrafts cleared, 8 (15%) had air reinjected to promote attachment, 1 eye (2%) with trabeculectomy and progressive synechiae demonstrated late endothelial failure, and no rejection episodes occurred (0%). In the paired analysis, the median duration of endothelial decompensation before the regraft was 21 days (range, 2-133 days). At 1, 3, 6, or 12 months, CDVA did not differ between the primary and secondary grafts in fellow eyes (mean difference, ≤2 Snellen letters; P > 0.05 at all examinations). At 1 year, the visual acuity was ≥20/20 in 61%, ≥20/25 in 81%, and ≥20/40 in 100% of the secondary grafts in the paired analysis, excluding 1 eye with retinal problems. Vision differed by ≤1 line between fellow eyes in all but the 1 patient with the longest time to regraft (133 days), who demonstrated central haze and irregular astigmatism from anterior stromal scarring during that period. At 1 year, CDVA associated with the scarring was 20/40 versus 20/20 for the fellow-eye primary graft. The central corneal thickness was comparable between fellow-eye primary and secondary grafts at 3, 6, and 12 months (mean difference at 1 year, 2 µm; P = 0.57). The 1-year endothelial cell loss was comparable in primary and secondary grafts (27% vs. 31%, respectively; P = 0.58). CONCLUSIONS: In patients who received prompt intervention to minimize the duration of central corneal decompensation, the visual outcomes with secondary DMEK matched the fellow-eye visual outcomes with primary DMEK.
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Córnea/fisiopatología , Queratoplastia Endotelial de la Lámina Limitante Posterior , Agudeza Visual/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de la Córnea/cirugía , Pérdida de Celulas Endoteliales de la Córnea/diagnóstico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Insuficiencia del Tratamiento , Resultado del TratamientoRESUMEN
OBJECTIVE: To examine the long-term effect of donor diabetes history on graft failure and endothelial cell density (ECD) after penetrating keratoplasty (PK) in the Cornea Donor Study. DESIGN: Multicenter, prospective, double-masked, controlled clinical trial. PARTICIPANTS: One thousand ninety subjects undergoing PK for a moderate risk condition, principally Fuchs' dystrophy or pseudophakic or aphakic corneal edema, were enrolled by 105 surgeons from 80 clinical sites in the United States. METHODS: Corneas from donors 12 to 75 years of age were assigned by 43 eye banks to participants without respect to recipient factors. Donor and recipient diabetes status was determined from existing medical records. Images of the central endothelium were obtained before surgery (baseline) and at intervals for 10 years after surgery and were analyzed by a central image analysis reading center to determine ECD. MAIN OUTCOME MEASURES: Time to graft failure (regraft or cloudy cornea for 3 consecutive months) and ECD. RESULTS: There was no statistically significant association of donor diabetes history with 10-year graft failure, baseline ECD, 10-year ECD, or ECD values longitudinally over time in unadjusted analyses, nor after adjusting for donor age and other significant covariates. The 10-year graft failure rate was 23% in the 199 patients receiving a cornea from a donor with diabetes versus 26% in the 891 patients receiving a cornea from a donor without diabetes (95% confidence interval for the difference, -10% to 6%; unadjusted P=0.60). Baseline ECD (P=0.71), 10-year ECD (P>0.99), and changes in ECD over 10 years (P=0.86) were similar comparing donor groups with and without diabetes. CONCLUSIONS: The study results do not suggest an association between donor diabetes and PK outcome. However, the assessment of donor diabetes was imprecise and based on historical data only. The increasing frequency of diabetes in the aging population in the United States affects the donor pool. Thus, the impact of donor diabetes on long-term endothelial health after PK or endothelial keratoplasty, or both, warrants further study with more precise measures of diabetes and its complications.
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Pérdida de Celulas Endoteliales de la Córnea/etiología , Complicaciones de la Diabetes , Endotelio Corneal/patología , Rechazo de Injerto/etiología , Queratoplastia Penetrante , Donantes de Tejidos/estadística & datos numéricos , Adolescente , Adulto , Anciano , Recuento de Células , Niño , Enfermedades de la Córnea/cirugía , Pérdida de Celulas Endoteliales de la Córnea/diagnóstico , Método Doble Ciego , Bancos de Ojos , Femenino , Rechazo de Injerto/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de TiempoRESUMEN
PURPOSE: To determine glare-induced change during visual acuity testing in patients with and without cataract using the controlled point source light-emitting diode (LED) glare tester (EpiGlare Tester; Epico, LLC, Columbus, OH), a new medical device for identification of glare disability. METHODS: This prospective, multicenter study enrolled 40 patients (80 eyes with cataracts) and 49 control subjects (98 eyes without cataracts). Corrected distance visual acuity (CDVA) was measured with and without glare using the EpiGlare Tester as a glare source. Functional visual ability was evaluated using driving and glare subscales from the Refractive Status Vision Profile questionnaire. The primary efficacy measure was change in CDVA measurement with and without glare in patients with senile cataract compared to participants without cataract. Secondary efficacy measures included correlation of the CDVA change caused by functional glare disability and subjective patient and investigator assessments. RESULTS: CDVA reduction was greater for patients with cataract, with a mean reduction of -0.49 ± 0.3 logMAR, than for participants without cataracts at -0.13 ± 0.2 logMAR (P < .001). This equates to a 5-line Snellen reduction (0.49 logMAR) in patients with cataracts and a 1-line reduction (-0.13 logMAR) in patients without cataracts. Among patients with cataracts, 83% stated the device accurately represented the difficulty experienced while driving at night (P < .001); among participants without cataracts, 71% reported being minimally affected by glare from the device (P = .003). CONCLUSIONS: A new controlled point source LED glare tester demonstrated the adverse effect on visual acuity due to glare in patients with cataract, accurately simulated night driving glare issues for patients with cataracts, and was rated as easy to use and useful by investigators.
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Catarata/complicaciones , Evaluación de la Discapacidad , Deslumbramiento , Trastornos de la Visión/diagnóstico , Pruebas de Visión/instrumentación , Agudeza Visual/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
PURPOSE: To compare the outcomes of triple Descemet's membrane endothelial keratoplasty (DMEK) versus DMEK alone in pseudophakic eyes. DESIGN: Retrospective, comparative, interventional case series. PARTICIPANTS: Patients with Fuchs' endothelial dystrophy, secondary corneal edema, and prior failed endothelial keratoplasty with or without prior cataract extraction. METHODS: Outcomes of 492 DMEK procedures performed between April 2010 and August 2012 were reviewed; 292 pseudophakic eyes underwent DMEK (group 1) and 200 eyes had concurrent cataract surgery with DMEK (group 2). MAIN OUTCOME MEASURES: Corrected distance visual acuity, endothelial cell loss, immediate and early postoperative complications. RESULTS: The mean age at the time of surgery was 70 years (range, 47-94 years) in group 1 and 64 years (range, 46-90 years) in group 2 (P <0.0001). At 6 months, the median corrected distance visual acuity was 20/25 (range, 20/16-20/80; n = 164) in group 1 and 20/20 (range, 20/16-20/100; n = 121) in group 2 (P <0.0001), excluding 21 eyes with retinal or optic nerve problems. The DMEK graft failed to clear in 9 eyes (3.1%) in group 1 and 7 eyes (3.5%) in group 2 (P = 0.34); all were regrafted successfully with DMEK. No further graft failures occurred during the follow-up period. The air reinjection rate was 30% in group 1 and 29% in group 2 (P = 0.69). The air reinjection rate dropped significantly in both groups, from 45% to 16%, after use of viscoelastic was eliminated during the tissue insertion step. The median endothelial cell loss at 3 to 6 months did not differ significantly between groups (26% in both). CONCLUSIONS: Triple DMEK was not associated with any higher risk of complications than DMEK alone. Compared with sequential management of patients with concomitant cataract and endothelial dysfunction, triple DMEK is an effective strategy in rapid visual rehabilitation and offers the advantage of a 1-stage procedure, with reduced risks and costs.
Asunto(s)
Edema Corneal/cirugía , Queratoplastia Endotelial de la Lámina Limitante Posterior , Distrofia Endotelial de Fuchs/cirugía , Implantación de Lentes Intraoculares , Facoemulsificación , Seudofaquia/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Catarata/complicaciones , Recuento de Células , Pérdida de Celulas Endoteliales de la Córnea/diagnóstico , Endotelio Corneal/patología , Femenino , Rechazo de Injerto , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento , Trastornos de la Visión/rehabilitación , Agudeza Visual/fisiologíaRESUMEN
PURPOSE: The purpose of this study was to document, to our knowledge, the first reported case of keratoconus progression accompanied with newly diagnosed pellucid marginal degeneration after corneal cross-linking (CXL). METHODS: A novel case of further keratoconus progression plus development of pellucid marginal degeneration in the same eye after CXL was documented with supporting evidence from Scheimpflug and optical coherence tomography imaging. RESULTS: A male patient was diagnosed with progressive keratoconus in the left eye and treated with CXL when aged 25 years. Although strongly cautioned not to rub his eyes, he admitted that he continued eye rubbing in association with atopic disease. At a follow-up examination 3.5 years after CXL, progressive keratoconus was detected and pellucid marginal degeneration was newly diagnosed in the left eye. The eye was retreated with CXL. CONCLUSIONS: This case illustrates that progressive keratoconus and pellucid marginal degeneration can occur in the same eye after CXL and demonstrates the deleterious effects that can develop with continued eye rubbing.