Promoting effect of AGTR1 blocker olmesartan on the apoptosis of HTF and its mechanism / 中华实验眼科杂志

Objective:To study the effect and mechanism of angiotensin type 1 receptor (AGTR1) blocker olmesartan (OMS) on the apoptosis of human Tenon capsule fibroblasts (HTF).Methods:Tenon capsule tissues were obtained from patients during strabismus surgery in the Second Affiliated Hospital of Xi'an Jiaotong University.Primary HTF were cultured by explant culture.Primary cells were identified by vimentin immunofluorescence staining and flow cytometry.The fibrosis model of HTF was established using 10 ng/ml transforming growth factor-β2 (TGF-β2). The cells were divided into normal control group cultured in culture medium, TGF-β2 group in culture medium containing TGF-β2, TGF-β2+ OMS group in culture medium containing TGF-β2 and OMS, and OMS group in culture medium containing OMS, and were cultured for 48 hours.Cell apoptosis was detected by flow cytometry with annexin V/PI staining.The early apoptosis, late apoptosis, and total apoptosis rates were analyzed.The protein expression of procaspase-9, cleaved caspase-9, bax and bcl-2 in the mitochondrial apoptosis pathway was detected by Western blot.The activity of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) was detected by colorimetry.The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Xi'an Jiaotong University (No.2019-014).Results:Primary HTF were successfully isolated and cultured.The cultured cells were long spindle-shaped and positive for vimentin.The expression rate of vimentin in the primary cells was greater than 99%.A statistically statistical difference was found in the early apoptosis rate, late apoptosis rate, and total apoptosis rate among the four groups ( F=24.92, 3.96, 41.82; all at P<0.05). The early and total apoptosis rates were significantly higher in TGF-β2+ OMS group than normal control group and TGF-β2 group, and the late apoptosis rate in TGF-β2+ OMS group was significantly higher than that of normal control group (all at P<0.05). There were statistically significant differences in cleaved caspase-9/procaspase-9, bax, and bax/bcl-2 among the four groups ( F=4.40, 7.98, 4.61; all at P<0.05). The bax/bcl-2 expression was significantly increased in TGF-β2+ OMS group in comparison with normal control group, and the expressions of cleaved caspase-9/procaspase-9, bax, and bax/bcl-2 were significantly elevated in TGF-β2+ OMS group compared with TGF-β2 group (all at P<0.05). LDH activity in the normal control group, TGF-β2 group, TGF-β2+ OMS group and OMS group was (783.99±79.97), (913.16±196.86), (2 529.06±240.21), and (2 134.29±138.96) μmol/(min·L), respectively, showing a statistically significant difference ( F=24.95, P<0.05). Compared with normal control group and TGF-β2 group, LDH activity in TGF-β2+ OMS group was increased, and the differences were statistically significant (both at P<0.05). SOD activity in the normal control group, TGF-β2 group, TGF-β2+ OMS group and OMS group was (50.35±0.97), (41.61±4.56), (28.88±3.26), and (37.61±4.83) μmol/(min·L), respectively, showing a statistically significant difference ( F=5.71, P<0.05). SOD activity was reduced in TGF-β2+ OMS group compared with normal control group and TGF-β2 group, reduced in OMS group compared with normal control group, and the differences were statistically significant (all at P<0.05). Conclusions:AGTR1 blocker OMS can promote the apoptosis of HTF effectively.Mitochondrial apoptosis pathway mediated by bax/bcl-2/caspase-9 and oxidative stress pathway are the potential mechanisms that OMS regulates the apoptosis of HTF.

Prospective evaluation of wipe-out after glaucoma filtration surgery in eyes with split fixation

Purpose: To assess the incidence and cause of idiopathic, irreversible loss of vision (“wipe?out”) in the early post?operative period after glaucoma?filtration surgery in advanced glaucoma. Methods: It was a prospective, interventional cohort study. Patients with advanced glaucoma and macular split fixation underwent either only trabeculectomy (group A) or combined phaco?emulsification with trabeculectomy (group B). The incidence and cause of visual loss, changes in intra?ocular pressure, visual acuity, and visual field indices during 2 months post surgery were assessed. Results: Thirty patients (30 eyes) were divided in two groups. No significant difference was noted between the pre?operative and post?operative mean deviations in both groups (P = 0.41, P = 0.65). Two eyes in group A and one eye in group B had visual loss of two lines or more at the end of 2 months because of cataract and choroidal detachment. None of the eyes showed “wipe?out”. Conclusion: “Wipe?out” is a rare phenomenon after surgery in advanced glaucoma

A modified model of glaucoma filtering surgery in Sprague-Dawley rats

Animal models are useful in glaucoma research to study tissue response to wound healing. Smaller animals such as rats offer additional advantages in terms of availability of detection antibodies and microarrays with cheaper maintenance costs. In this study, we describe a glaucoma filtering surgery (GFS) model in adult Sprague–Dawley rats by performing a sclerostomy using a 26?G needle and additionally placing a silicone tube (27 G) connecting the anterior chamber to the subconjunctival space to maintain a patent fistula for the flow of aqueous humor, thus providing a more definitive bleb. This technique will be useful in identifying and modifying newer targets in the wound healing process in order to improve surgical outcomes following GFS

Inhibitory effect of ILK-siRNA-AAV on scar formation after glaucoma filtering surgery in rats / 中华实验眼科杂志

Objective:To investigate the role of integrin-linked kinase (ILK)-small interfering RNA (siRNA)-adeno-associated virus (AAV) in scar formation after glaucoma filtering surgery in rat eyes.Methods:Forty-eight Sprague Dawley rats of SPF grade, aged 8 to 9 weeks old, were selected and divided into blank control group, ILK-siRNA-AAV group, NC-siRNA-AAV group and mitomycin C (MMC) group by random number table method, with 12 rats in each group.Left eyes of the rats were taken as experimental eyes, and no intervention was administered to fellow eyes.The bulbar conjunctival filtering bleb after glaucoma filtration surgery in rats was established by anterior chamber drainage tube implantation.One day after operation, phosphate buffer solution, ILK-siRNA-AAV, and NC-siRNA-AAV were injected into the filtering bleb of blank control group, ILK-siRNA-AAV group and NC-siRNA-AAV group, 5 μl each group, respectively.Cotton tablets containing 0.4 mg/ml MMC were placed under conjunctival flap for 5 minutes during operation in MMC group.Intraocular pressure (IOP) was measured with a handheld tonometer before surgery and at 1, 2, 3, 7, 14, 21, 28 days after surgery.Formation of filtering blebs in rats was observed with a surgical microscope at 1, 2, 3, 7, 14, 21, 28 days after operation, and the bleb survival time was calculated by Kaplan-Meier survival analysis.The mRNA and protein expression levels of ILK in conjunctival and subconjunctival tissues at the surgical sites were detected by reverse transcription PCR and Western blot, respectively, on the 28th day after operation.Silencing of ILK gene was identified.Effect of ILK gene silencing on the morphology of drainage pathway was observed by hematoxylin-eosin staining.Effect of ILK gene silencing on collagen fiber deposition in the bulbar conjunctiva at filtration area was examined by Masson staining, and the percentage of positive area of collagen fiber staining in the total tissue visual field was calculated.The use and care of the animals complied with the ARVO Statement.This research protocol was approved by an Ethics Committee of Xi'an Jiaotong University (No.2013-772). Results:There were statistically significant differences in IOP at different time points between before and after surgery among four groups ( Fgroup=76.84, P<0.001; Ftime=114.49, P<0.001). The IOP of ILK-siRNA-AAV group on the 1st, 7th, 14th and 28th day after operation and the IOP of MMC group on the 2nd, 3rd, 7th, 14th and 28th day after operation were lower than those of blank control group, and the differences were statistically significant (all at P<0.05). The IOP of ILK-siRNA-AAV group was lower on 7th, 14th, 21st and 28th day after operation than those of NC-siRNA-AAV group, with statistically significant differences (all at P<0.05). The bleb survival time of blank control group, NC-siRNA-AAV group, ILK-siRNA-AAV group and MMC group was (3.50±1.51), (5.00±3.41), (31.50±3.15) and (31.33±2.46) days, respectively, with a significant difference among them ( F=395.83, P<0.05). The bleb survival time of ILK-siRNA-AAV group and MMC group was higher than that of blank control group and NC-siRNA-AAV group, and the differences were statistically significant (all at P<0.05). There were statistically significant differences in the relative expression levels of ILK mRNA and protein among four groups ( F=222.32, 752.69; both at P<0.05), and the relative expression levels of ILK mRNA and protein were significantly lower in ILK-siRNA-AAV group than blank control group and NC-siRNA-AAV group, and the differences were statistically significant (all at P<0.05). Proliferative fibrous connective tissue and a large number of cells at surgical sites were found in blank control group and NC-siRNA-AAV group, and the fibroblasts were of a high density and grew in clumps.In ILK-siRNA-AAV group, the bulbar conjunctiva was thin, and the arrangement of fibrous connective tissue was loose, and a few proliferative fibroblasts were found.In MMC group, the conjunctival fibrous layer was loose and thin, forming cavities, and scarce cells were found.There was statistically significant difference in the percentage of collagen fiber positive staining area among four groups ( F=741.66, P<0.05). The positive staining percentage of ILK-siRNA-AAV group and MMC group was significantly lower than that of blank control group, among which there was lower positive staining percentage in ILK-siRNA-AAV group than NC-siRNA-AAV group, and the differences were statistically significant (all at P<0.05). Conclusions:Silencing of ILK can inhibit the scar formation after glaucoma filtering surgery and maintain low IOP in rats.

Inhibitory effect of CLC-2 chloride channel targeted blocking on fibrosis of human conjunctival fibroblasts / 中华实验眼科杂志

Objective:To investigate the inhibitory effect of CLC-2 chloride channel targeted blocking on fibrosis of human conjunctival fibroblasts (HConF).Methods:HConF were divided into blank control group, lipofectamine 2000 (Lipo2000) group, nonsense small interfering RNA (siRNA) group, and CLC-2 siRNA transfected group.The HConF were cultured in medium containing the corresponding transfection reagents according to grouping.No intervention was given to blank control group.The expression level of CLC-2 mRNA of HConF was detected by real-time fluorescence quantitative PCR; absorbance ( A) value indicating the proliferative ability of HConF was determined by CCK-8 kit; the apoptosis ratio of HConF was tested by flow cytometry; the migration ability of HConF was identified by cell scratch test and Transwell migration assay; the contraction rate of HConF was assayed by collagen contraction test; the expression levels of collagenⅠ, collagen Ⅲ, PI3K, Akt, p-PI3K and p-Akt proteins were measured by Western blot. Results:Significant differences were found in relative expression levels of CLC-2 mRNA and A value among four groups ( F=90.110, 198.680; both at P<0.001). The relative expression level of CLC-2 mRNA and A value were significantly lower in CLC-2 siRNA transfected group than nonsense siRNA group, showing statistically significant differences (both at P<0.001). The proportion of apoptotic HConF in blank control group, Lipo2000 group, nonsense siRNA group, and CLC-2 siRNA transfected group was (4.78±1.10)%, (4.54±1.51)%, (4.82±0.88)% and (28.90±0.91)%, respectively, and a statistically significant difference was found ( F=363.260, P<0.001). The proportion of apoptotic HConF was significantly higher in CLC-2 siRNA transfected group than nonsense siRNA group, with a statistically significant difference ( P<0.001). Statistically significant differences were found in cell migration rate and the number of migrating cells among four groups ( F=74.493, 1 625.431; both at P<0.01). The cell migration rate of HConF in CLC-2 siRNA transfected group was significantly lower and the number of migrating cells was significantly smaller than those of nonsense siRNA group, with statistically significant differences (both at P<0.001). A statistically significant difference in contraction rate was found among four groups ( F=104.692, P<0.001). The contraction rate of HConF was significantly lower in CLC-2 siRNA transfected group than nonsense siRNA group, and the difference was statistically significant ( P<0.001). Statistically significant differences were found in relative expression levels of collagen Ⅰ and collagen Ⅲ proteins, p-PI3K/PI3K ratio, and p-Akt/Akt ratio among four groups ( F=112.073, 456.931, 340.889, 43.021; all at P<0.001). The relative expression levels of collagen Ⅰ and collagen Ⅲ proteins, p-PI3K/PI3K ratio and p-Akt/Akt ratio in CLC-2 siRNA transfected group were significantly lower than those of nonsense siRNA group, showing statistically significant differences (all at P<0.05). Conclusions:Targeted blocking of CLC-2 chloride channel gene expression can inhibit fibrosis of HConF by promoting apoptosis of HConF through PI3K/Akt signaling pathway and inhibit fibrotic processes such as cell migration, collagen synthesis and collagen contraction.

Effect of integrin ανβ3 on conjunctival scar formation after glaucoma filtration surgery in rats / 中华实验眼科杂志

Objective:To investigate the expression of integrin ανβ3 in conjunctival scar after glaucoma filtration surgery and to explore its role in the formation of filtering scar in rats.Methods:Fifty-five SPF male SD rats aged 6-8 weeks were selected to establish the model of glaucoma filtration surgery, and 15 unsuccessful modeling rats were excluded.The remaining rats were divided into control group, transforming growth factor (TGF) group, integrin ανβ3 receptor antagonist LM609 group and TGF+ LM609 group, with 10 rats in each group.The conjunctival flap of different groups was treated with cotton piece containing 0.9% sodium chloride, TGF-β2 (2 mg/ml), LM609 (40 μg/ml), TGF-β2 (2 mg/ml)+ LM609 (40 μg/ml) solution for two minutes, respectively, according to grouping.The intraocular pressure (IOP) was monitored with an iCARE tonometer before operation and at 3 days, 1 week, 2 weeks after operation, and the average IOP ratio ([postoperative IOP/preoperative IOP]×100%) was calculated.At 3 days, 1 week and 2 weeks after operation, slit lamp microscopy was used to observe the morphological changes of filtering blebs and calculate the survival rate of filtering blebs.Two weeks after operation, the operative eyeball tissues were removed and made into paraffin section.The inflammatory changes, fibrosis and collagen deposition of bulbar conjunctiva in the operation area were observed by hematoxylin-eosin staining and picric acid-sirius red staining, respectively.Western blot was used to detect the expression of integrin αν and β3.Immunohistochemical staining was used to detect the expression of integrin ανβ3 in the conjunctival tissue of operation area.The use and care of the rats complied with the Instruction Notions with Respect to Care for Laboratory by State Ministry of Science and Technology.The study protocol was approved by an Ethics Committee of The Daping Hospital, Army Medical University (No.2017-06).Results:The IOP of rats in each group was significantly decreased on the third day after operation compared with before operation, and gradually recovered to the preoperative level in the first to second week after operation.The mean IOP ratios of the control group, TGF group, LM609 group and TGF+ LM609 group were (101.80±4.44)%, (103.90±5.65)%, (94.10±7.45)% and (100.60±4.61)%, respectively, showing a statistically significant difference among them ( F=4.571, P=0.010). The mean IOP ratio of LM609 group was lower than that of the control group, TGF group and TGF+ LM609 group (all at P<0.05). Two weeks after operation, the filter blebs became flat and the bulbar conjunctival tissue was slightly thickened in the control group and TGF+ LM609 group, and bulbar conjunctival tissue was significantly thickened with a large number of blood vessels growing in the TGF group, and localized small filter blebs as well as less vascularization were seen in the LM609 group.The survival rate of filtering bleb in the TGF group was significantly lower than that in the control group, LM609 group and TGF+ LM609 group, and the survival rate of filtering bleb in the LM609 group was significantly higher than that in the control group and TGF+ LM609 group (all at P<0.05). Two weeks after operation, there were fewer infiltrated inflammatory cells and looser collagen fiber deposition in the conjunctival tissue in the LM609 group and TGF+ LM609 group compared with the TGF group.The relative expression levels of integrin αν and β3 under conjunctival tissue in the TGF group were significantly higher than those in the control group, LM609 group and TGF+ LM609 group (all at P<0.05). Immunohistochemical staining showed that integrin ανβ3-positive cells were mainly in the conjunctival tissue around the operation area and microtubules.The number of integrin ανβ3-positive cells in the conjunctival tissue of the operation area in the TGF group were significantly greater than those of other groups. Conclusions:Integrin ανβ3 is highly expressed in the scar of conjunctival tissue after filtering surgery in rats.The inhibition of integrin ανβ3 can reduce the deposition of fibers and prolong the survival of filtering blebs, suggesting that integrin ανβ3 may be involved in the formation of conjunctival scar.

Evolução atípica de cisto de tenon após implante de válvula de Ahmed / Atypical evolution of tenon cyst after Ahmed valve implantation

Resumo Descrevemos o caso de um paciente portador de glaucoma secundário que evoluiu com cisto de tenon após implante de válvula de Ahmed. A despeito da conduta expectante inicial e das intervenções cirúrgicas posteriores, apenas com a utilização da ciclofotocoagulação transescleral com laser micropulsado a pressão intraocular atingiu valores aceitáveis.

Abstract We describe the case of a patient with secondary glaucoma who developed tenon cyst after Ahmed valve implantation. Despite the initial expectant management and subsequent surgical interventions, only with the micropulse transecleral cyclophotocoagulation did the intraocular pressure reach acceptable values.

Impacto financeiro no tratamento cirúrgico do glaucoma / Financial impact on glaucoma surgical treatment

Resumo Objetivo: Segunda maior causa de cegueira mundial, o glaucoma, ocasionalmente necessita de procedimento cirúrgico para controle. Tendo o Brasil um Sistema Único de Saúde (SUS), e crise político-econômica em 2016, objetiva-se avaliar o impacto financeiro na decisão terapêutica do glaucoma nos últimos 6 anos no Brasil, e considerar atual discussão sobre indicação de procedimentos intervencionistas precocemente no seu algoritmo terapêutico. Métodos: Estudo ecológico da população brasileira, com base no Sistema de Informações Hospitalares do SUS, avaliando comportamento temporal dos procedimentos cirúrgicos do SUS para tratamento do glaucoma, e variação do dólar como influenciador da tendência temporal sobre os procedimentos. Realizada a análise de Regressão Linear Simples, com significância estatística de P<0.05. Resultados: Entre 2013 e 2018 foram internados 24888 indivíduos por glaucoma, prevalência do sexo masculino (51.68%), brancos (32,57%) e idosos (57.84%). Regiões Sudeste (45.61%) e Nordeste (26.36%) com maior número de internações, sendo a Trabeculectomia (84,18%) principal procedimento realizado. Houve associação da Trabeculectomia e Implante de Válvula, individualmente e atrelados, com os valores do dólar nas regiões Centro-Oeste (β= 1,103 com P= 0,007 para Trabeculectomias e β= 1,105 com P=0,012 para ambos os procedimentos) e Sul (β= 16,727 e P= 0,006 para os Implantes), e associação entre aumento de Implantes na região Sul e maior cobertura na atenção básica (β= 0.64 e P= 0.009). Conclusão: Observou-se não interferência do dólar, e aumento dos procedimentos na região Sul e Centro-Oeste. Os resultados corroboram tendência intervencionista, podendo ser representada pelo possível uso dos procedimentos disponibilizados pelo SUS de forma precoce.

Abstract Objective: The second leading cause of blindness worldwide, glaucoma, occasionally requires surgical procedure for control. Given that Brazil has an Unified Health System (SUS) and a political-economic crisis in 2016, we aim to evaluate the financial impact on the therapeutic decision of glaucoma in the last 6 years in Brazil, and to consider the current discussion about early interventionist indication in its therapeutic algorithm. Methods: Ecological study of the Brazilian population, based on the SUS Hospital Information System, evaluating the temporal behavior of SUS surgical procedures on glaucoma treatment, and dollar variation as influencing the temporal trend on the procedures. Simple Linear Regression analysis was performed, with statistical significance of P <0.05. Results: Between 2013 and 2018, 24888 individuals were hospitalized for glaucoma, male prevalence (51.68%), whites (32.57%) and elderly (57.84%). Southeast (45.61%) and Northeast (26.36%) Regions with the largest number of hospitalizations, and Trabeculectomy (84.18%) being the main procedure performed. There was an association of trabeculectomy and valve implantation, individually and linked, with dollar values in the Midwest (β = 1.103 with P = 0.007 for Trabeculectomies and β = 1.105 with P = 0.012 for both procedures) and South (β). = 16,727 and P = 0,006 for Implants), and association between increased Implants in the South region and greater coverage in primary care (β = 0.64 and P = 0.009). Conclusion: Non-dollar interference was observed, and increased procedures in the South and Midwest. The results corroborate an interventionist tendency and may be represented, possible, by the use of procedures provided by the SUS in an early manner.

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.

Complication of micro-bypass stenting: the anterior chamber displacement of a Xen implant / Complicação de stent micro-bypass: o deslocamento da câmara anterior de um implante de Xen

ABSTRACT Although minimally invasive glaucoma surgery using different types of implants is a promising strategy for treating glaucoma, potential long-term complications require further evaluation. Here, we report a case of the anterior chamber displacement of a Xen implant due to a maneuver aimed at correcting a dysfunctional and bent subconjunctival implant.

RESUMO Embora a cirurgia de glaucoma minimamente in vasiva, que usa diferentes tipos de implantes, seja uma estratégia promissora para o tratamento do glaucoma, as possíveis complicações a longo prazo exigem uma avaliação mais aprofundada. Aqui, relatamos um caso de deslocamento da câmara anterior de um implante Xen devido a uma manobra que visa corrigir um implante subconjuntival disfuncional e dobrado.

Antiscarring effect of intraoperative bevacizumab in experimental glaucoma filtration surgery / Efeito antifibrótico do uso intraoperatório de bevacizumab em cirurgia filtrante experimental

ABSTRACT Purpose: To determine the effects of bevacizumab and mitomycin C alone and in combination on intraocular pressure and the scarring process after modified glaucoma filtration surgery in rabbits. Methods: The rabbits underwent modified glaucoma filtration surgery and were allocated into three groups to receive intraoperative treatment with subconjunctival bevacizumab (group A), mitomycin C and subconjunctival bevacizumab (group B), or mitomycin C (group C). Intraocular pressure was measured immediately preoperatively and on postoperative days 8, 14, 17, 21, 26, and 30. The scarring process was assessed 30 days after surgery by tissue section using hematoxylin and eosin, Masson's trichrome, and picrosirius. Expression of vascular endothelial growth factor (VEGF) was assessed by immunohistochemical analyses. All analyses were performed by a masked observer. Results: Animals in group A had higher intraocular pressure than those in groups B and C (p<0.01). Intraocular pressure did not differ significantly between groups B and C. The amount of fibrosis was similar with all stains used: group A had the highest level of fibrosis compared with groups B and C (p>0.05). There was less VEGF expression in group A than in groups B and C (p<0.01). Groups B and C did not differ in VEGF expression. Conclusion: Mean intraocular pressure and fibrosis were lower in animals receiving bevacizumab in combination with mitomycin C but did not differ from values in animals receiving mitomycin C alone. Inhibition of VEGF was greater when bevacizumab was used alone than when bevacizumab was combined with mitomycin C.

RESUMO Objetivo: Determinar os efeitos do bevacizumab, combinados ou não à mitomicina C (MMC), na pressão intraocular e processo cicatricial pós-cirurgia filtrante anti-glaucomatosa modificada em coelhos. Métodos: Os coelhos foram submetidos à cirurgia filtrante anti-glaucomatosa modificada e alocados em três grupos de acordo com o tratamento instituído - Grupo A: bevacizumab subconjuntival; Grupo B: bevacizumab subconjuntival e à mitomicina C ; Grupo C: à mitomicina C. A pressão intraocular foi aferida no período pré-operatório imediato e nos dias 8, 14, 17, 21, 26 e 30. O processo cicatricial foi avaliado no trigésimo dia de pós-operatório por meio de análise histopatológica utilizando-se hematoxilina eosina, tricrômio de Masson e picrosirius. A expressão do fator de crescimento do Endotélio Vascular (VEGF) foi avaliada por meio de análise imuno-histoquímica. Todas as análises foram feitas por um observador mascarado. Resultados: O Grupo A apresentou maior pressão intraocular que os grupos B e C (p<0.01). Não foram encontradas alterações significativas entre os grupos B e C. A quantidade de fibrose encontrada nos grupos foi similar com os 3 corantes utilizados: o Grupo A apresentou maior nível de fibrose em relação aos grupos B e C (p>0,05). Houve menor expressão de Fator de Crescimento do Endotélio Vascular no Grupo A em relação aos grupos B e C (p<0,01). Não houve diferença estatisticamente significante na expressão de Fator de Crescimento do Endotélio Vascular entre os grupos B e C. Conclusão: O bevacizumab associado à MMC apresentou pressões intraoculares mais baixas e menos fibrose, mas estes não foram estatisticamente significantes quando comparados ao uso da mitomicina C isolada. Uma maior inibição do fator de crescimento do endotélio vascular foi encontrada quando o bevacizumab foi usado isoladamente, em detrimento do seu uso associado à mitomicina C.

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.

Research progress on pathobiology of myofibroblast in wound healing after glaucoma filtering surgery / 国际眼科杂志(Guoji Yanke Zazhi)

@#Glaucoma filtering surgery is the main treatment for the glaucomatous patients. Typically, surgery failed mary due to wound fibrosis and contracture at the post-surgical site.Myofibroblasts transdifferentiated from other cells via a process known as epithelial-mesenchymal transition(EMT)is a common feature of the fibrotic filtering channel, which can produce excessive amounts of the extracellular matrix(ECM), and then exert tractional forces, resulting in the disruption of tissue architecture and obstruction of filtering channel. In this review, we explain the pathological function of myofibroblast in the wound healing process after glaucoma filtering surgery.

Case series of children with steroid-Induced glaucoma

@#Steroid-induced glaucoma is the most serious complication of the injudicious use of steroids, particularly among children affected by allergic conjunctivitis. This condition is steroid-dependent, and children are commonly being prescribed topical anti-inflammatories, including topical steroids, by general practitioners. Furthermore, topical steroids are also available over the counter, and this availability contributes to overuse without proper monitoring by an ophthalmologist. We present a series of five cases illustrating the devastating effect of unmonitored, long-term use of steroids among children for vernal keratoconjunctivitis. The medications were prescribed initially by general ophthalmologists and were continually bought over the counter by parents. At the presentation to our center, these patients were already compromised visually, exhibiting glaucomatous optic disc changes and high intraocular pressure. The series highlights the optic nerve damage resulting in irreversible visual compromises among children on long-term, topical steroids and the importance of regular monitoring with a low threshold for ophthalmologist referral.

Clinical analysis of 17 patients with corneal invasion of filtering blebafter anti-glaucomatous filtering surgery / 眼科新进展

Objective To report a postoperative complication of corneal invasion of filtering bleb (CIFB) and the analysis of its diagnosis and treatment.Methods A retrospective analysis was conducted in 17 patients with CIFB collected from March 2006 to April 2017.They were treated according to the classification standards.Patients suffering the mild type with no obvious conjunctival post-adhesion received conservative observation;but patients with obvious adhesion were given acupuncture separation combined with 5-Fluorouracil filter follicular subconjunctival injection and eye massage.The moderate type with no progress was treated with the mild and mediumpartial filtration and amniotic membrane transplantation.For the severe ones,the conjunctiva filtering bleb was excised with lamellar keratoplasty and filtering bleb reconstruction.Finally,the clinical features,classification standards and the follow-up results were summarized.Results As for the clinical features,17 patients were treated with domeas the basement of the conjunctival incision,and received intraoperative mitomycin administration.For the patients with CIFB growing rapidly,the posterior synechiae of their filtering blebs had occurred and timely actions could slow down or stop its development.As for the classification standards,according to the degree of corneal invasion,there were 11 patients being mild type,5 patients being moderate types,and only 1 patients being severe type.After treatment,the progress stopped in all mild patients,while the moderate and severe types were not relapsed after treatment.Conclusion CIFB is different from overhanging filtering bleb.As a less common kind of filtering bleb complication,timely identification and appropriate treatments can effectively delay or even stop the progress of corneal damage to maintain the filtering surgery effects.

The auxiliary effect of suramin application in acute angle closure glaucoma surgery patients / 中国医师杂志

Objective To investigate the effects of suramin application in acute angle closure glaucoma surgery patients.Methods A prospective study method was used.From February 2012 to January 2016,178 acute angle closure glaucoma surgeries in our hospital for treatment were selected,and were equally divided into observation and control groups (89 cases in each group) according to the order of admission,and two groups were given filtration surgery.The observation group was treated with suramin adjuvant therapy after surgery.The duration were 1 ～ 14 d after operation.The prognosis of two groups was observed.Results All patients were successfully completed surgery.The intraoperative and postoperative complications were no seriously occurred;the postoperative intraocular pressure in the observation group and the control group were (11.52 ± 3.24) mmHg and (16.98 ± 5.33) mmHg that compared preoperative [(31.98 ± 5.22) mmHg,(31.87 ± 5.11) mmHg] with significantly different (P ＜ 0.05),while the observation group was significantly lower than that of the control group (P ＜ 0.05).The postoperative peak systolic velocity (PSV) and end diastolic velocity (EDV) values of the central retinal artery of the observation group and the control group were significantly higher than that of preoperation (P ＜ 0.05),and the postoperative PSV and EDV values of the central retinal artery of the observation group were significantly higher than that in the control group (P ＜ 0.05).The postoperative ratios of functional filtering bleb in the observation group and control group were 80.9％ and 60.7％,respectively.The observation group was significantly higher than that of the control group (P ＜ 0.05).Conclusions The application of suramin in acute close angle glaucoma filtration surgery can promote the function of filtering bleb and intraocular pressure reduction,and improve the ocular blood flow speed that has good application effects.

Quarter-Shifted Microincisional Sutureless Vitrectomy in Patients with a Glaucoma Drainage Implant or Filtering Bleb

When vitrectomy is performed in eyes that have undergone glaucoma surgery, the site of sclerotomy often overlaps with the previous glaucoma operation site. It can lead to serious complications such as postoperative hypotony, leakage, and/or infection. Our technique involves modification of surgeon's position and two sclerotomy sites 45° away from the original position, with an infusion cannula inserted infranasally to avoid damage to the glaucoma drainage implant or filtering bleb. The modified approach was applied to seven eyes with various indications. Vitrectomy was successfully completed, and there were no sclerotomy site complications, leakage, or hypotony in any case. Good intraocular pressure control was maintained throughout the postoperative course in all cases.

Induction of transforming growth facor-β2 to the expression of lysyl oxidases in human Tenon capsule fibroblasts in vitro / 中华实验眼科杂志

Background Researches showed that transforming growth factor-β2 (TGF-β2) promotes the activity of human Tenon capsular fibroblasts (TFs),which plays a role in the scarring of filtering blebs after antiglaucoma surgery.However,its mechanism is not fully clear.Lysyl oxidases (LOXs) are important extracellular matrix proteases which can catalyze the cross-linking of collagen and elastin.Investigating the impact of TGF-β2 on the expression of LOXs has a great significance for the understanding of the pathogenesis of filtering bleb scarring and its prevention.Objective This study was to investigate the effect of TGF-β2 on the expression of LOXs in cultured human TFs.Methods The TFs at 4-8 generations were divided into normal control group and different concentrations of TGF-β2 treated-groups,and 100,200,400,800 μ1 of TGF-β2 with the final concentration of 2,4,8 and 16 ng/ml was added into the medium to treat human TFs respectively for 24 hours.The LOXs in the cells were detected by Western blot to determine the optimal dose of TGF-β2.The 4 ng/ml TGF-β2(200 μ1) was used to treat human TFs for 6,12,24 and 48 hours respectively,and the change of LOXs expression in the cells over time was assayed by Western blot.The expression and distribution of LOX protein in the normal cells and TGF-β2-treated cells was detected by using immunofluorescence technique.This study was approved by Daping Hospital of Third Military Medical University Ethic Commission.The guardians of the patients who offered the specimen knew the purpose of the study and signed informed consent.Results Western blot assay showed that the expressions of LOX,LOXL1,LOXL2,LOXL3 and LOXL4 in the cells were gradually elevated from the normal control group and 2,4,8,16 ng/ml TGF-β2-treated groups,showing significant differences among the groups (F =37.338,13.438,31.067,11.767,15.167,all at P＜0.01).The expression of LOXL2 protein in the cells was 0.68±0.07,1.09±0.10,1.32±0.07,1.50± 0.06 and 1.89±0.12 in the normal control group and 6-,12-,24-and 48-hour groups respectively after 4 ng/ml TGF-β2 treatment,with a significant increase over time (F =82.832,P=0.000).The expression of LOX was weak in the normal cultured TFs,while the fluorescence intensity of LOX expression was evidently enhanced in the cytoplasm of the cells in the TGF-β2-treated group.Conclusions TGF-β2 upregulates the expressions of LOXs in human TFs in a dose-and time-dependent manner,which probably offers a basis for the further study on the prevention of filtering bleb scarring after glaucoma surgery.

Oculo-peritoneal shunt: draining aqueous humor to the peritoneum / Derivação óculo-peritoneal: drenagem do humor aquoso para o peritônio

In 2010, there were estimated to be approximately 60.5 million people with glaucoma. This number is expected to increase to 79.6 million by 2020. In 2010, there were 8.4 million people with bilateral blindness caused by glaucoma, and this number is expected in increase to 11.2 million by 2020. Filtering implants are special devices that have been developed to reduce intraocular pressure in patients with refractory glaucoma. The success rate of these implants is relatively low, and they continue to fail over time. To avoid failure caused by the formation of scar tissue around the implants, attempts have been made to drain the aqueous humor to various sites, including the venous system, lacrimal sac, sinuses, and conjunctival fornix. Recently, a system to shunt aqueous humor from the anterior chamber to the peritoneum has been developed. The surgical technique involved in this system is a modification of the technique currently used by neurosurgeons for the treatment of hydrocephalus. We present the first case operated using this technique.

Calcula-se que em 2010 havia provavelmente 60,5 milhões de pessoas com glaucoma, com aumento previsto para 79,6 milhões em 2020; a cegueira bilateral por glaucoma era detectada em 8,4 milhões de pessoas, em 2010, e com aumento estimado para 11,2 milhões em 2020. Dispositivos especiais foram desenvolvidos para reduzir a pressão intraocular em pacientes com glaucoma refratário, chamados implantes de filtragem. A taxa de sucesso destes implantes é relativamente baixa, e sabe-se que elas continuam a diminuir ao longo do tempo. Para evitar as falhas produzidas pela cicatrização de tecido em torno dos implantes, foram feitas tentativas de drenagem do humor aquoso para diferentes locais, tais como o sistema venoso, saco lacrimal, os seios paranasais e fórnice conjuntival. Revendo o tratamento atual da hidrocefalia, uma técnica de derivação a partir da câmara anterior para o peritônio foi desenvolvida. A técnica cirúrgica desenvolvida é uma modificação da técnica atualmente utilizada por neurocirurgiões para o tratamento de hidrocefalia. Apresentamos o primeiro caso operado com esta técnica.