Genome-wide RNA sequencing of ocular fibroblasts from glaucomatous and normal eyes: Implications for glaucoma management.

Primary open angle glaucoma is a leading cause of visual impairment and blindness which is commonly treated with drugs or laser but may require surgery. Tenon's ocular fibroblasts are involved in wound-healing after glaucoma filtration surgery and may compromise a favourable outcome of glaucoma surgery by contributing to fibrosis. To investigate changes in gene expression and key pathways contributing to the glaucomatous state we performed genome-wide RNA sequencing. Human Tenon's ocular fibroblasts were cultured from normal and glaucomatous human donors undergoing eye surgery (n = 12). mRNA was extracted and RNA-Seq performed on the Illumina platform. Differentially expressed genes were identified using a bioinformatics pipeline consisting of FastQC, STAR, FeatureCounts and edgeR. Changes in biological functions and pathways were determined using Enrichr and clustered using Cytoscape. A total of 5817 genes were differentially expressed between Tenon's ocular fibroblasts from normal versus glaucomatous eyes. Enrichment analysis showed 787 significantly different biological functions and pathways which were clustered into 176 clusters. Tenon's ocular fibroblasts from glaucomatous eyes showed signs of fibrosis with fibroblast to myofibroblast transdifferentiation and associated changes in mitochondrial fission, remodeling of the extracellular matrix, proliferation, unfolded protein response, inflammation and apoptosis which may relate to the pathogenesis of glaucoma or the detrimental effects of topical glaucoma therapies. Altered gene expression in glaucomatous Tenon's ocular fibroblasts may contribute to an unfavourable outcome of glaucoma filtration surgery. This work presents a genome-wide transcriptome of glaucomatous versus normal Tenon's ocular fibroblasts which may identify genes or pathways of therapeutic value to improve surgical outcomes.

MiR-146a reduces fibrosis after glaucoma filtration surgery in rats.

PURPOSE: To explore the impact of microRNA 146a (miR-146a) and the underlying mechanisms in profibrotic changes following glaucoma filtering surgery (GFS) in rats and stimulation by transforming growth factor (TGF)-ß1 in rat Tenon's capsule fibroblasts. METHODS: Cultured rat Tenon's capsule fibroblasts were treated with TGF-ß1 and analyzed with microarrays for mRNA profiling to validate miR-146a as the target. The Tenon's capsule fibroblasts were then respectively treated with lentivirus-mediated transfection of miR-146a mimic or inhibitor following TGF-ß1 stimulation in vitro, while GFS was performed in rat eyes with respective intraoperative administration of miR-146a, mitomycin C (MMC), or 5-fluorouracil (5-FU) in vivo. Profibrotic genes expression levels (fibronectin, collagen Iα, NF-KB, IL-1ß, TNF-α, SMAD4, and α-smooth muscle actin) were determined through qPCR, Western blotting, immunofluorescence staining and/or histochemical analysis in vitro and in vivo. SMAD4 targeting siRNA was further used to treat the fibroblasts in combination with miR-146a intervention to confirm its role in underlying mechanisms. RESULTS: Upregulation of miR-146a reduced the proliferation rate and profibrotic changes of rat Tenon's capsule fibroblasts induced by TGF-ß1 in vitro, and mitigated subconjunctival fibrosis to extend filtering blebs survival after GFS in vivo, where miR-146a decreased expression levels of NF-KB-SMAD4-related genes, such as fibronectin, collagen Iα, NF-KB, IL-1ß, TNF-α, SMAD4, and α-smooth muscle actin(α-SMA). Additionally, SMAD4 is a key target gene in the process of miR-146a inhibiting fibrosis. CONCLUSIONS: MiR-146a effectively reduced TGF-ß1-induced fibrosis in rat Tenon's capsule fibroblasts in vitro and in vivo, potentially through the NF-KB-SMAD4 signaling pathway. MiR-146a shows promise as a novel therapeutic target for preventing fibrosis and improving the success rate of GFS.

Incidence of glaucoma filtration surgery from disease onset of open-angle glaucoma.

AIMS: To investigate the rate and risk factors of undergoing glaucoma filtration surgery (GFS) in patients with newly diagnosed open-angle glaucoma (OAG). METHODS: This is a population-based historic cohort study, consisting of 9420 patients older than 45 years diagnosed with OAG during 1997-2010. Follow-up spanned from 1997 to 2017. We obtained data for trabeculectomy (TRE), deep sclerectomy (DS), and glaucoma drainage implant (GDI) surgeries from national administrative healthcare registers by hospital billing data. We plotted the cumulative incidence of GFS and carried out a multivariate Poisson regression analysis adjusted for age, sex, hospital district, systemic comorbidities, and the number of IOP-lowering drugs. We reported incidence rate ratios (IRR) with 95% confidence intervals (CI) for GFS after the onset of OAG. RESULTS: The cumulative incidence of GFS at 5 years from OAG onset was 3.1% and at 10 years 5.4%. Age over 80 years at baseline was associated with lower GFS incidence (IRR 0.51, CI 0.31-0.84). The number of IOP-lowering drugs in the first 2 years of treatment correlated with the risk of GFS increasing from (IRR 3.23, CI 2.32-4.50) for two drugs, (IRR 7.44, CI 5.28-10.47) for three and to (IRR 14.95, CI 10.38-21.52) for four drugs. CONCLUSION: This study characterized the treatment path of OAG from diagnosis to surgical intervention refining the role of GFS among glaucoma therapies.

Evaluación cualitativa de la ampolla de filtración / Qualitative evaluation of filtering blebs

Se realizó una búsqueda sobre la evaluación cualitativa de la ampolla de filtración. La ampolla conjuntival es la parte visible de la cirugía filtrante, y su morfología es un indicador de factores que pueden determinar el resultado hipotensor de la cirugía y las posibles complicaciones posoperatorias. Se han desarrollado diversos estudios que relacionan la evaluación clínica de su morfología y el control de la presión intraocular, y se han establecido varios sistemas de puntuación, entre ellas: Wuerzburg Bleb Classification Score, Moorfields Bleb Grading System, Indiana Bleb Appearance Grading Scale y métodos de imagen para evaluar el segmento anterior (biomicroscopia ultrasónica, Tomografía retinal de Heidenberg y tomografía de coherencia óptica). Estos métodos proporcionan una herramienta útil para el seguimiento de la cirugía filtrante y su documentación(AU)

A review was conducted on the qualitative evaluation of the filtering bleb. The conjunctival bleb is the visible part of filtration surgery, and its morphology is an indicator of factors which may determine the hypotensive result of surgery and the possible postoperative complications. Various studies have been conducted which relate the clinical evaluation of its morphology and intraocular pressure control. Several grading systems have thus been established: Wuerzburg Bleb Classification Score, Moorfields Bleb Grading System, Indiana Bleb Appearance Grading Scale and imaging methods to evaluate the anterior segment (ultrasound biomicroscopy, Heidenberg retinal tomography and optical coherence tomography). These methods are a useful tool for the follow-up of filtration surgery and its documentation(AU)

Implante Ex-PRESS mediante la técnica de Richard Hoffman / Ex-PRESS implantation by Richard Hoffman's technique

La cirugía filtrante es una opción de tratamiento encaminada a disminuir la presión intraocular una vez que no hay respuesta a las alternativas no quirúrgicas. En los últimos años ha experimentado una evolución sorprendente. Aparecen nuevos dispositivos que buscan obtener un control tensional con las mínimas complicaciones; entre estos, el implante Ex-PRESS ha demostrado una efectividad similar a la trabeculectomía, mientras que la variante técnica para su implantación, descrita por Richard Hoffmann, posibilita excelentes resultados con menos dificultades. Se presenta un paciente masculino de 51 años de edad, de raza blanca, con antecedente de glaucoma, con agudeza visual mejor corregida de 100 VAR y presión intraocular de 32 mmHg. Se realizó implante de dispositivo Ex-PRESS (modelo P-50) mediante la técnica modificada de Richard Hoffmann, asociada al uso de mitomicina C al 0,2 por ciento en el transoperatorio. A los dos años se lograron tensiones oculares de 17 mmHg y agudeza visual mejor corregida de 100 VAR(AU)

Filtration surgery is a therapeutic option aimed at reducing intraocular pressure when there is no response to non-surgical alternatives. Filtration surgery has developed remarkably in recent years. New devices have emerged geared to achieving pressure control with minimum complications. Among them, Ex-PRESS implantation has shown to be as effective as trabeculectomy, and the technique described by Richard Hoffman provides excellent results with fewer difficulties. A case is presented of a male white 51-year-old patient with a history of glaucoma, best corrected visual acuity 100 VAR, and intraocular pressure 32 mmHg. Implantation was performed of an Ex-PRESS (model P-50) device by modified Richard Hoffman's technique associated to 0.2 percent mitomycin C in the perioperative period. Two years after surgery, ocular tensions of 17 mmHg and a best corrected visual acuity of 100 VAR had been achieved(AU)

Retinosquise peripapilar e descolamento seroso de retina neuro-sensorial após esclerectomia profunda não penetrante / Peripapillary retinoschisis and serous detachment of neurosensory retina after a non-penetrating deep sclerectomy

Resumo Relato de caso de um paciente de 46 anos com glaucoma juvenil de controle clínico insatisfatório, portador de retinosquise peripapilar que, após ser submetido à esclerectomia profunda não penetrante, evoluiu com descolamento seroso da retina neuro-sensorial. A associação entre retinosquise peripapilar e o descolamento seroso pós cirurgia filtrante é de ocorrência rara, tendo sido descrito apenas um caso na literatura. A partir deste relato temos por objetivo, além de enfatizar a raridade da associação, mostrar a importância de investigar retinosquise peripapilar em pacientes glaucomatosos, em especial se associada a camada de fibras nervosas, e a importância da explanação adequada aos pacientes de um possível descolamento seroso de retina no pós-operatório de cirurgia filtrante.

Abstract Case report of a 46-year-old patient with unsatisfactory clinical controlled juvenile glaucoma and peripapillary retinoschisis who, after being submitted to non-penetrating deep sclerectomy, evolved with serous detachment of the neurosensory retina. The association between peripapillary retinoschisis and serous detachment after filtering surgery is rare and only one case has been described in the literature. The purpose of this report is, besides to emphasize the rarity of the association, to show the importance of investigating peripapillary retinoschisis in glaucomatous patients, especially if associated with retinal nerve fiber layer, and the importance of adequate explanation to patients of possible serous detachment of retina in the postoperative of filtering surgery.

Use of compressive suture in the prevention and management of perioperative complications of glaucoma surgery / Uso da sutura compressiva na prevenção e manejo das complicações peroperatórias da cirurgia antiglaucomatosa

Abstract Purpose: To describe the use of compressive suture (CS) in the prevention and management of adverse events associated with glaucoma surgery. Methods: This was a descriptive, retrospective study based on information retrieved from the records of patients submitted to glaucoma surgery between 1999 and 2012 at a regional main public hospital and at a private ophthalmology clinic belonging to one of the authors. Only cases with adverse events treated with CS were eligible. Results: Compressive suture was successfully used to improve the closure of the anterior and/or lateral edge of the conjunctival flap, to limit the downward extension of filtering blebs, to prevent excessive filtration from the scleral flap edge in cases of difficult closure with conventional suture, and in patients submitted to trabeculotomy-trabeculectomy. Conclusion: Safe, low-cost and easy to perform, compressive suture is a useful tool for the prevention and management of adverse events associated with glaucoma surgery.

Resumo Objetivo: Descrever o uso de sutura compressiva (SC) na prevenção e no manejo de complicações associadas à cirurgia antiglaucomatosa. Métodos: Trata-se de um estudo descritivo, retrospectivo, baseado em informações obtidas dos registros de pacientes submetidos à cirurgia de glaucoma entre 1999 e 2012 em um hospital público de referência regional e em uma clínica oftalmológica privada de um dos autores. Somente casos com eventos adversos tratados com SC foram selecionados. Resultados: A SC foi usada com sucesso para proporcionar melhor vedação nas bordas anterior e/ou lateral do retalho conjuntival, para limitar a extensão descendente das bolhas filtrantes, para evitar a filtração excessiva da borda do retalho escleral em casos de fechamento difícil pela sutura convencional, e em pacientes submetidos à trabeculotomia - trabeculectomia. Conclusão: Trata-se de um procedimento de fácil realização, seguro e de baixo custo, bastante útil na abordagem de intercorrências e complicações durante a cirurgia antiglaucomatosa.

Bolsa encapsulada em cirurgias filtrantes com retalho conjuntival base fórnice - estudo retrospectivo / Encapsulated bleds in filtering surgeries with fornix based conjuntival flap: prospective study

Analisamos o papel do retalho conjuntival na incidência de bolsa filtrante encapsulada em pacientes portadores de glaucoma primário de ângulo aberto. Em 22 trabeculectomias foi utilizado o retalho conjuntival de base fórnice; estes resultados foram comparados com 23 olhos submetidos à trabeculectomia utilizando o retalho conjuntival de base límbica. Foi encontrada maior incidência de bolsa encapsulada nos casos com retalho conjuntival de base límbica: 7/23 (30,4 por cento), quando comparados com os de base fórnice: 1/22 (4,5 por cento) (p<0,02).