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BACKGROUND: Ultrasound cycloplasty is a noninvasive surgery used to reduce intraocular pressure in patients with glaucoma, with fewer severe complications. This report presents several cases of iris neovascularization and neurotrophic keratopathy following ultrasound cycloplasty. CASE PRESENTATION: Six patients diagnosed with refractory glaucoma underwent ultrasound cycloplasty at our clinic. Three cases developed iris neovascularization at postoperative day 3, week 2 and week 4 respectively, with intraocular pressure ranging from 12 to 24 mmHg. The other three cases developed neurotrophic keratopathy at postoperative week 3, week 6 and week 8 which completely healed within 60 days. CONCLUSIONS: Iris neovascularization and neurotrophic keratopathy can be triggered after ultrasound cycloplasty, which are uncommon and self-limited but potentially vision-threatening. Preoperative risk assessment and regular postoperative follow-up are recommended to manage complications effectively.
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Glaucoma , Pressão Intraocular , Iris , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Córnea/cirurgia , Doenças da Córnea/etiologia , Glaucoma/cirurgia , Pressão Intraocular/fisiologia , Iris/cirurgia , Iris/irrigação sanguínea , Iris/diagnóstico por imagem , Neovascularização Patológica , Complicações Pós-OperatóriasRESUMO
Purpose: Trabecular meshwork (TM) fibrosis is a crucial pathophysiological process in the development of primary open-angle glaucoma. Pirfenidone (PFD) is a new, broad-spectrum antifibrotic agent approved for the treatment of idiopathic pulmonary fibrosis. This study investigated the inhibitory effect of PFD on TM fibrosis and evaluated its efficacy in lowering intraocular pressure (IOP). Methods: Human TM cells were isolated, cultured, and characterized. Cell Counting Kit-8 was used to evaluate the proliferation and toxicity of different concentrations of PFD on normal or fibrotic TM cells. TM cells were treated with transforming growth factor beta-2 (TGF-ß2) in the absence or presence of PFD. Western blotting and immunofluorescence analyses were used to analyze changes in the TM cell cytoskeleton and extracellular matrix (ECM) proteins, including alpha-smooth muscle actin (α-SMA), F-actin, collagen IV (COL IV), and fibronectin (FN). An ocular hypertension (OHT) mouse model was induced with Ad-TGF-ß2C226/228S and then treated with PFD or latanoprost (LT) eye drops to confirm the efficacy of PFD in lowering IOP. Results: PFD inhibited the proliferation of fibrotic TM cells in a dose-dependent manner and inhibited TGF-ß2-induced overexpression of α-SMA, COL IV, and FN in TM cells. PFD stabilized F-actin. In vivo, PFD eye drops reduced the IOP of the OHT models and showed no significant difference compared with LT eye drops. Conclusions: PFD inhibited TGF-ß2-induced TM cell fibrosis by rearranging the disordered cytoskeleton and decreasing ECM deposition, thereby enhancing the aqueous outflow from the TM outflow pathway and lowering IOP, which provides a potential new approach to treating glaucoma. Translational Relevance: Our work with pirfenidone provides a new approach to treat glaucoma.
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Glaucoma de Ângulo Aberto , Glaucoma , Hipertensão Ocular , Animais , Humanos , Camundongos , Actinas/metabolismo , Células Cultivadas , Fibrose , Glaucoma de Ângulo Aberto/tratamento farmacológico , Soluções Oftálmicas/farmacologia , Malha Trabecular/metabolismo , Malha Trabecular/patologia , Fator de Crescimento Transformador beta2/farmacologiaRESUMO
Purpose: To measure visual crowding, an essential bottleneck on object recognition and reliable psychophysical index of cortex organization, in older children and adults with horizontal concomitant strabismus before and after strabismus surgery. Methods: Using real-time eye tracking to ensure gaze-contingent display, we examined the peripheral visual crowding effects in older children and adults with horizontal concomitant strabismus but without amblyopia before and after strabismus surgery. Patients were asked to discriminate the orientation of the central tumbling E target letter with flankers arranged along the radial or tangential axis in the nasal or temporal hemifield at different eccentricities (5° or 10°). The critical spacing value, which is the minimum space between the target and the flankers required for correct discrimination, was obtained for comparisons before and after strabismus surgery. Results: Twelve individuals with exotropia (6 males, 21.75 ± 7.29 years, mean ± SD) and 15 individuals with esotropia (6 males, 24.13 ± 5.96 years) participated in this study. We found that strabismic individuals showed significantly larger critical spacing with nasotemporal asymmetry along the radial axis that related to the strabismus pattern, with exotropes exhibiting stronger temporal field crowding and esotropes exhibiting stronger nasal field crowding before surgical alignment. After surgery, the critical spacing was reduced and rebalanced between the nasal and temporal hemifields. Furthermore, the postoperative recovery of stereopsis was associated with the extent of nasotemporal balance of critical spacing. Conclusions: We find that optical realignment (i.e., strabismus surgery) can normalize the enlarged visual crowding effects, a reliable psychophysical index of cortical organization, in the peripheral visual field of older children and adults with strabismus and rebalance the nasotemporal asymmetry of crowding, promoting the recovery of postoperative stereopsis. Our results indicated a potential of experience-dependent cortical organization after axial alignment even for individuals who are out of the critical period of visual development, illuminating the capacity and limitations of optics on sensory plasticity and emphasizing the importance of ocular correction for clinical practice.
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Ambliopia , Esotropia , Estrabismo , Adulto , Masculino , Criança , Humanos , Adolescente , Acuidade Visual , Estrabismo/cirurgia , Percepção Visual , SulfadiazinaRESUMO
Background: The ocular features of phacomatosis pigmentovascularis (PPV) have rarely been reported, and glaucoma is the leading cause of blindness in patients with this condition. To protect vision in these patients, it is important to identify glaucoma as early as possible. Objectives: To systematically report the systemic and ocular manifestations of phacomatosis cesioflammea and phacomatosis cesioflammeo-marmorata, and to investigate a glaucoma risk scoring system. Materials & Methods: In this prospective study, patients with PPV from 2014 to 2021 were included. Clinical information was collected, and associations with glaucoma were evaluated. The suitability of the scoring system was assessed. A systematic literature review and analysis of reported cases of PPV was performed. Results: A total of 28 participants with PPV were included. Their ocular findings were similar, ranging from episcleral hyperpigmentation (78.5%), glaucoma (75%), choroid haemangioma (38%), and retinal vascular abnormalities (48%), to hyperpigmentation of the cornea, iris, lens and fundus. Glaucoma was associated with multiple factors, especially a thick choroid (odds ratio: 2.61; p = 0.008) and a diffuse mass-type of episcleral hyperpigmentation (odds ratio: 41.3; p = 0.027). The risk scoring system was characterized by high sensitivity (84%) and specificity (80%; AUC = 0.91) in predicting glaucoma. Conclusion: In addition to involving the systemic system, phacomatosis cesioflammea and phacomatosis cesioflammeo-marmorata also represent a specific spectrum of ophthalmic vascular malformations and hyperpigmentation. Early and periodic detailed ocular examination are recommended. The novel scoring system will help to tailor follow-up for visual protection.
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Glaucoma , Hiperpigmentação , Síndromes Neurocutâneas , Esclerose Tuberosa , Humanos , Síndromes Neurocutâneas/complicações , Estudos Prospectivos , Glaucoma/complicaçõesRESUMO
PURPOSE: To describe the baseline characteristics of a trial to evaluate whether selective laser trabeculoplasty (SLT), as a first-line treatment, provides superior economic and health-related quality of life outcomes to medical treatment in China. DESIGN: The LiGHT China trial is an unmasked, single-center, pragmatic, randomized controlled trial. METHODS: A total of 771 previously undiagnosed patients with primary open angle glaucoma (POAG, 622 patients) or ocular hypertension (OHT, 149 patients) at Zhongshan Ophthalmic Center were recruited from March 2015 to January 2019. Subjects were randomized to SLT-1st (followed by medication then surgery when required) or Medicine-1st (medication followed by surgery when required). The primary outcome was health-related quality of life (HRQL). The secondary outcomes were clinical outcomes, cost, cost-effectiveness, Glaucoma Utility Index, Glaucoma Symptom Scale, visual function, and safety. RESULTS: The mean age of POAG patients was 49.8 years and 38.8 years for OHT. The median intraocular pressure was 20 mm Hg for the 1,105 POAG eyes and 24 mm Hg for the 271 OHT eyes. POAG eyes had thinner central cornea thickness (CCT, 536 µm) than OHT eyes (545 µm). Median mean deviation of the visual field in POAG eyes was -4.2 dB. Median refractive error was -1.5 D for OHT eyes and -1.25 D for POAG eyes. There was no difference between POAG and OHT patients on baseline scores of GUI, GSS and VF-14. The difference between OHT and POAG on the EQ-5D-5L was 0.024. CONCLUSIONS: Compared with participants in the LiGHT UK trial, participants in this trial were younger, more myopic and had more severe visual field defects.
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Glaucoma de Ângulo Aberto , Glaucoma , Hipertensão Ocular , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/cirurgia , Humanos , Pressão Intraocular , Lasers , Pessoa de Meia-Idade , Hipertensão Ocular/tratamento farmacológico , Qualidade de VidaRESUMO
BACKGROUND: To investigate dynamic stereopsis in intermittent exotropia [X(T)] patients using a novel dynamic random-dot stereopsis assessment method. METHODS: A novel dynamic random-dot stereopsis test was performed using novel self-programmed software, which consisted of red and green dots and four blocks on the screen. The test included motion + disparity (MD), motion (M), and disparity (D), where the D cues ranged from 200 to 1,200 arc-seconds. The characteristics of preoperative dynamic stereopsis in 83 X(T) patients and associations with clinical features were analysed, and the prognosis was followed up on the 1st day and at the 2nd, 6th and 12th months postoperatively. RESULTS: Preoperatively, the mean reciprocal values of near and far stereopsis were 0.013±0.0016 and 0.0011±0.0005 arc-seconds in static stereopsis patients, respectively, and the MD, M, and D values were 0.002±0.0002, 0.0018±0.0001, and 0.0012±0.0002 arc-seconds in dynamic stereopsis, respectively. The MD value was negatively correlated with the Newcastle control score, disease course, and prism deviations (P<0.05), M was correlated with disease course and the Newcastle control score (P<0.05), and D was not correlated with any clinical features. Postoperative dynamic stereopsis improved from the 1st day and gradually peaked at the 6th month, while static stereopsis showed a decreased tendency in near but not far stereopsis. CONCLUSIONS: The dynamic stereopsis quantitative evaluation method based on random dots is a feasible test and shows that destruction of X(T) patients' dynamic stereopsis is affected by age at surgery, disease course, strabismus controllability and the strabismus degree.
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To increase the amount of pirfenidone (PFD) loaded in polyvinyl alcohol (PVA) film embedded soft contact lens (SCL), and evaluate its function of sustaining delivery of drug in vitro and in vivo. Drug loading efficiency within PVA film and SCLs, drug release from SCLs in vitro, and the effects of parameters of SCLs and external environment on drug release in vitro were evaluated by ultraviolet-visible spectrophotometer at 312 nm. Safety of SCLs was evaluated in vitro by transformed human corneal epithelial cell. Safety in vivo was determined by optical coherence tomography and histology of anterior segment of rabbits. Drug release study in tear fluid and aqueous humor were measured by ultra-performance liquid chromatography. SCLs had smooth surface and were fit for experimental rabbits. Amount of PFD in PVA film and SCLs were 153.515 µg ± 12.508 and 127.438 µg ± 19.674, respectively, PFD in PVA film was significantly higher than SCLs (p=.006) and closed to 150 µg (targeting amount of PFD to be loaded). Thickness of SCLs, molecular weight of PVA, and amount of PVA used in SCLs affected drug release in vitro significantly. Thickness of PVA film and amount of drug in SCLs had no effect on drug release rate in vitro. SCLs were safe in vitro and in vivo, PFD released from SCLs could be detected around 12 hours in tears and aqueous humor, and the concentration of drug was higher than eye drop at all detected time points while amount of PFD in SCLs was lower than eye drop. Drug loaded PVA film embedded SCLs may be a promising ocular drug delivery system.
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Anti-Inflamatórios não Esteroides/administração & dosagem , Lentes de Contato Hidrofílicas , Sistemas de Liberação de Medicamentos/métodos , Álcool de Polivinil/química , Piridonas/administração & dosagem , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Química Farmacêutica , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Células Epiteliais , Humanos , Hidrogéis/química , Piridonas/farmacologia , Coelhos , Lágrimas/químicaRESUMO
Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 1 (lingo-1) is selectively expressed on neurons and oligodendrocytes in the central nervous system and acts as a negative regulator in neural repair, implying a potential role in optic neuropathy. The aim of the present study was to determine whether adeno-associated virus serotype 2 (AAV2) vector-mediated transfer of lingo-1 short hairpin RNA could reduce nerve crush-induced axonal degeneration and enhance axonal regeneration following optic nerve (ON) injury in vivo. The expression of lingo-1 was knocked down in vivo using a green fluorescent protein (GFP)-tagged AAV2 encoding lingo-1 shRNA via intravitreal injection in adult Sprague-Dawley rats. Silencing effects of AAV2-lingo-1-shRNA were confirmed by detecting GFP labelling of RGCs, and by quantifying lingo-1 expression levels with reverse transcription-quantitative polymerase chain reaction and western blotting. Rats received an intravitreal injection of AAV2-lingo-1-shRNA or negative control shRNA. The ON crush (ONC) injury was performed 2 weeks after the intravitreal injection. RGC density, lesion volume of the injured ON and the visual electrophysiology [flash visual evoked potential (F-VEP)] at different time points post-injury were determined. Transduction with lingo-1-shRNA decreased lingo-1 expression levels and promoted RGC survival following ONC. Lingo-1-shRNA promoted ON tissue repair and functional recovery. The mechanism underlying the effect of AAV2-lingo-1-shRNA on RGCs may be the phosphorylation of protein kinase B (Akt) at Ser473 and activation of the Akt signaling pathway acting downstream of lingo-1. The results of the current study indicate that the inhibition of lingo-1 may enhance RGC survival and facilitate functional recovery following ON injury, representing a promising potential strategy for the repair of optic neuropathy.
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PRECIS: Biomechanically corrected intraocular pressure (bIOP) measurements provided by the new Corvis ST (CST) were higher than measurements obtained with Goldman applanation tonometry (GAT) in eyes with ocular hypertension (OHT) or open-angle glaucoma (OAG). PURPOSE: To compare bIOP obtained with a new version of CST with GAT measurements in patients with OAG and OHT, and to identify factors affecting IOP measurement differences between these methods. METHODS: A total of 122 eyes with OAG or OHT were enrolled. Sixty eyes were treated with prostaglandin analogs (PGA) and 62 eyes with selective laser trabeculoplasty (SLT). IOP was measured with CST, followed by GAT. Central corneal thickness (CCT) was measured with ultrasound pachymetry. Measurements obtained with these 2 approaches were compared. RESULTS: The overall mean IOP was 15.2±3.0 mm Hg and 14.1±3.2 mm Hg with the CST and GAT, respectively (r=0.74; P<0.0001). There was a 1.17 mm Hg bias between tonometers, with 95% limits of agreement of -2.66 to 5.01 mm Hg. According to multivariate regression analysis, differences between bIOP and GAT-IOP were associated with CCT (P=0.001) and age (P=0.007) in the PGA group, but only with CCT in the SLT group (P=0.002). bIOP and GAT-IOP values were influenced by age (PGA: P=0.014; SLT: P=0.006) and CCT (PGA: P=0.007; SLT: P=0.032), respectively. CONCLUSIONS: BIOP values were higher and less affected by CCT than GAT-IOP values in eyes with OAG and OHT. However, these measurements may not be interchangeable in the clinic.
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Córnea/fisiopatologia , Glaucoma de Ângulo Aberto/fisiopatologia , Pressão Intraocular/fisiologia , Tonometria Ocular , Adulto , Idoso , Idoso de 80 Anos ou mais , Instituições de Assistência Ambulatorial , Anti-Hipertensivos/uso terapêutico , Fenômenos Biomecânicos/fisiologia , Paquimetria Corneana , Estudos Transversais , Feminino , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/terapia , Humanos , Terapia a Laser , Pessoa de Meia-Idade , Análise Multivariada , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/fisiopatologia , Hipertensão Ocular/terapia , Trabeculectomia , Adulto JovemRESUMO
Purpose: Lysophosphatidic acid (LPA) is a growth factor-like phospholipid that has been recognized as a profibrotic mediator in numerous tissues, yet, whether it plays a role in subconjunctival fibrosis remains to be investigated. Therefore, this study was designed to examine the effect of LPA1-3 signaling inhibitor, Ki16425 on the conversion of human Tenon's fibroblasts (HTFs) into myofibroblasts. Methods: Primary cultured HTFs were incubated with transforming growth factor-ß1 (TGF-ß1) alone or combined with Ki16425, the cell proliferation and migration were measured by Cell Counting Kit-8 and the scratch wound assay, respectively. HTFs contractility was evaluated with 3-dimensional (3D) Collagen Contraction assay. The mRNA and protein levels of α-smooth muscle actin (α-SMA), Snail and the phosphorylation levels of Smad2/3, p38MAPK, and ERK1/2 were determined by real-time quantitative polymerase chain reaction (RT-qPCR), western blot, and immunofluorescence staining. Results: Ki16425 significantly prevent the proliferation and migration of Tenon's fibroblasts (HTFs) in a dose-dependent manner. Furthermore, Ki16425 blocked HTFs myofibroblast differentiation via downregulation of mRNA and protein expression of α-SMA. 3D collagen gel contraction assay demonstrated that Ki16425 effectively inhibits myofibroblast contraction induced by TGF-ß1. Mechanistically, we revealed that Ki16425 reduces Smad2/3 but not p38MAPK or ERK1/2 phosphorylation by TGF-ß1. By using an LPA1-specific inhibitor, AM095, we confirmed that LPA1 signaling but not LPA2 or LPA3 is involved in TGF-ß1 induced HTFs activation. Conclusions: Our results show that inhibition of LPA1 signaling presents potent antifibrotic effect in HTFs, which may serve as a promising intervention strategy for preventing subconjunctival fibrosis caused by glaucoma filtration surgery.
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Fibroblastos/citologia , Isoxazóis/farmacologia , Lisofosfolipídeos/metabolismo , Miofibroblastos/citologia , Propionatos/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Glaucoma/cirurgia , Humanos , Isoxazóis/administração & dosagem , Propionatos/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
Subconjunctival fibrosis represents the primary cause of postoperative failure of trabeculectomy, and at present there is a lack of effective intervention strategies. The present study aimed to investigate the effect of the mitogenactivated protein kinase kinase (MEK) inhibitor U0126 on human tenon fibroblast (HTF) myofibrosis transdifferentiation, and to illuminate the underlying molecular mechanisms involved. It was demonstrated that U0126 significantly inhibited the proliferation, migration and collagen contraction of HTFs stimulated with TGFß1. In addition, U0126 largely attenuated the TGFß1induced conversion of HTFs into myofibroblasts, as indicated by a downregulation of the mRNA and protein expression of αsmooth muscle actin and zinc finger protein SNAI1, and by ameliorating the 3Dcollagen contraction response. Mechanistically, U0126 suppressed the TGFß1stimulated phosphorylation of mothers against decapentaplegic homolog 2/3, P38 mitogenactivated protein kinase and extracellular signalregulated kinase 1/2, indicating that U0126 may inhibit HTF activation through the canonical and noncanonical signaling pathways of TGFß1. Therefore, U0126 exhibits a potent antifibrotic effect among HTFs, and the inhibition of MEK signaling may serve as an alternative intervention strategy for the treatment of trabeculectomyassociated fibrosis.
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Transdiferenciação Celular/fisiologia , Fibroblastos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Miofibroblastos/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Actinas/metabolismo , Butadienos/farmacologia , Diferenciação Celular/fisiologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Transdiferenciação Celular/efeitos dos fármacos , Células Cultivadas , Colágeno/metabolismo , Regulação para Baixo/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibrose/tratamento farmacológico , Fibrose/metabolismo , Humanos , Miofibroblastos/efeitos dos fármacos , Nitrilas/farmacologia , Fosforilação/efeitos dos fármacos , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Fatores de Transcrição da Família Snail/metabolismoRESUMO
AIM: To evaluate the effectiveness of autologous conjunctival flap surgery for repairing the late-onset filtering bleb leakage after trabeculectomy. METHODS: This study retrospectively reviewed 106 eyes from 106 patients with late-onset filtering bleb leakage after trabeculectomy who received autologous conjunctival flap surgery at the Zhongshan Ophthalmic Centre from 2005 to 2015. The basic information was recorded, and the interval time between trabeculectomy and autologous conjunctival flap surgery as well as related risk factors, intraocular pressure (IOP), anterior chamber depth (ACD) and best corrected visual acuity (BCVA) were analysed. Moreover, 41 patients who completed the 1-year follow up were analysed to determine the IOP and BCVA changes and long-term success rates. RESULTS: The 50 male and 56 female subjects (average age 39.13±17.96y) included 47 (44.34%) and 33 (31.13%) cases of primary open angle and primary angle-closure glaucoma. The mean interval between trabeculectomy and repair surgery was 60.60±56.92 (3-264)mo. The mean mitomycin (MMC) concentration during trabeculectomy was 0.27±0.04 (0.12-0.4) mg/mL in the fornix-based conjunctival flap group (68 patients) and 0.28±0.04 (0.20-0.33) mg/mL in the limbal-based conjunctival flap group (11 patients). After bleb leakage, the patients' vision remained stable while the IOP decreased from 10.25±4.76 (3-20.86) to 9.44±4.33 (2-21) mm Hg (P<0.01). In the 41 analysed patients, the IOP was controlled at 15.68±5.11 (7-40) mm Hg in the 1st year after autologous conjunctival flap surgery and recurrence was not observed, for a long-term success rate of 100%. CONCLUSION: Autologous conjunctival flap repairing surgery is an effective technique for sealing filtering bleb leakages and controlling IOP postoperatively.
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Abstracts Purpose: Pirfenidone is mostly used in antifibrotic and anti-inflammatory therapies. We have previously demonstrated that pirfenidone had antifibrotic and anti-inflammatory effects on the wound healing process after glaucoma filtration surgery in vitro and in vivo. Since the wound healing and reactive scarring process simultaneously involves inflammation, fibrosis, and angiogenesis, and angiogenesis plays a more important role in chronic or prolonged wound healing, we tried to explore the antiangiogenesis effect in pirfenidone and its potential multitarget function in regulating excessive scarring. The aim of the present study was to investigate the antiangiogenesis effect of pirfenidone. METHODS: The proliferation of human umbilical vein endothelial cells (HUVECs) and human Tenon's fibroblasts (HTFs) were detected by WST-1 assay. The cell viability of HUVECs was measured by Trypan Blue together with lactate dehydrogenase, Annexin 5 experiment, and Ki-67 immunofluorescence assay. The functions of HUVECs and HTFs were demonstrated using cell migration assay, transwell invasion assay, and tube formation assay. The expression levels of vascular endothelial growth factor-A (VEGF-A), VEGF receptor-2 (VEGFR-2), neuropilin-1(NRP-1), and their downstream signaling proteins p-PI3K, PI3K, p-AKT, AKT, p-mTOR, and mechanistic target of rapamycin (mTOR) were indicated by western blot assay. The secretion of VEGF-A was detected by enzyme-linked immunosorbent assay. RESULTS: Pirfenidone inhibited proliferation, migration, invasion, and tube formation of HUVECs in vitro, and had an equivalent antiangiogenesis effect when compared with Ranibizumab in HUVECs and HTFs. Pirfenidone downregulated VEGF-A/VEGFR-2, VEGF-A/NRP-1, and its downstream signaling pathway protein expression. CONCLUSIONS: Pirfenidone has an antiangiogenesis effect in the wound healing process and may become an ideal multitarget antiscarring agent after glaucoma filtration surgery.
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Inibidores da Angiogênese/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Piridonas/farmacologia , Cicatrização/efeitos dos fármacos , Anexina A5/metabolismo , Western Blotting , Movimento Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Fibroblastos/efeitos dos fármacos , Citometria de Fluxo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Antígeno Ki-67/metabolismo , L-Lactato Desidrogenase/metabolismo , Neurofisinas/metabolismo , Cápsula de Tenon/citologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
PURPOSE: To investigate the underlying mechanism by which pirfenidone blocks the transition from the G1 to S phase in primary human Tenon's fibroblasts. METHODS: Primary human Tenon's fibroblasts were characterized by immunocytofluorescence staining with vimentin, fibroblast surface protein, and cytokeratin. After treating Tenon's fibroblasts with pirfenidone under proliferation conditions (10% fetal bovine serum), cell proliferation was measured using a WST-1 assay. Progression through the cell cycle was analyzed by flow cytometry. The expression of CDK2, CDK6, cyclinD1, cyclinD3, and cyclinE and the phosphorylation of AKT, ERK1/2/MAPK, JNK/MAPK, and p38 MAPK were estimated using western blot analysis. RESULTS: Under proliferative conditions, pirfenidone inhibited Tenon's fibroblasts proliferation and arrested the cell cycle at the G1 phase; decreased the phosphorylation of AKT, GSK3ß, ERK1/2/MAPK, and JNK/MAPK; increased the phosphorylation of p38 MAPK; and inhibited CDK2, CDK6, cyclin D1, cyclin D3, and cyclin E in a dose-dependent manner. Inhibitors of AKT (LY294002), ERK1/2 (U0126), and JNK (SP600125) arrested the G1/S transition, similar to the effect of pirfenidone. The p38 inhibitor (SB202190) decreased the G1-blocking effect of pirfenidone. The expression of CDK2, CDK6, cyclin D1, and cyclin D3 were inhibited by LY294002, U0126, and SP600125. SB202190 attenuated the pirfenidone-induced reduction of CDK2, CDK6, cyclin D1, cyclin D3, and cyclin E. CONCLUSIONS: Pirfenidone inhibited HTFs proliferation and induced G1 arrest by downregulating CDKs and cyclins involving the AKT/GSK3ß and MAPK signaling pathways.
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Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridonas/farmacologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Fibroblastos/metabolismo , Humanos , Relação Estrutura-AtividadeRESUMO
PURPOSE: To investigate the relationship between preoperative expectations and actual postoperative outcomes of visual function (VF) among patients undergoing first eye cataract surgery. METHODS: A longitudinal study of 182 patients from hospitals in urban Southern China were surveyed prior to surgery and 3 month after cataract surgery regarding their preoperative, expected postoperative and actual postoperative VF for each of the items on the Catquest-9SF and their satisfaction with cataract surgery. In addition, detailed clinical data were collected preoperatively and postoperatively. RESULTS: The majority of cataract patients in urban Southern China had high expectations for VF outcomes after cataract surgery and in most cases postoperative outcomes achieved the expected level of improvement. The mean (standard deviation, SD) preoperative Catquest-9SF score was 15.7 (5.86) and the mean (SD) expected postoperative score was 26.3 (2.93). The discrepancy between actual and expected improvement was significantly correlated with patients' health literacy, presence of systemic and ocular comorbidity, preoperative visual acuity of the surgery eye, LOCS III nuclear opalescence and cortical cataract grading. CONCLUSION: Cataract patients in urban Southern China had high expectations for surgery outcomes. Patients with low level of health literacy and the presence of systemic and ocular comorbidity may need a comprehensive counseling to decrease the discrepancy regarding expected and actual outcomes.
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Catarata/epidemiologia , Catarata/terapia , Satisfação do Paciente , População Urbana , Visão Ocular , Adulto , Idoso , Idoso de 80 Anos ou mais , Catarata/diagnóstico , Catarata/fisiopatologia , Extração de Catarata , China/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Período Pré-Operatório , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento , Testes Visuais , Acuidade Visual , Adulto JovemRESUMO
AIM: To assess the outcomes of posterior chamber implantable collamer lens (ICL) implantation in Chinese pediatric patients with unilateral high myopic amblyopia. METHODS: Eleven eyes of 11 amblyopic patients aged 11.02±3.34y underwent ICL (model V4, Staar Surgical Inc.) implantation to treat unilateral anisometropia were studied. Visual acuity, cycloplegic refraction, contrast sensitivity, stereopsis, intraocular pressure (IOP), vaulting, corneal endothelial cell count and complications were evaluated. Patients completed follow-up at 3d, 1, 3mo and the last follow-up time (mean 8.18±2.82mo) after surgery. RESULTS: The mean myopic anisometropia was -13.70±3.25 D preoperatively and +0.69±2.63 D at 8mo postoperatively. The logMAR corrected distance visual acuity (CDVA) of the amblyopic eye was 1.51±0.72 preoperatively and 0.75±0.40 at 8mo postoperatively. The logMAR CDVA at 3d, 1, 3 and 8mo postoperatively improved by a mean of 0.64, 1.55, 1.82 and 2.64 lines and gained more than 2 lines accounted for 18%, 45%, 45%, 64%, respectively. The contrast sensitivity of 0.5, 1 and 2 cpd in amblyopic eyes was significantly increased after surgery. No patient had near stereopsis recovery. The vaulting at 3 and 8mo was significantly lower than that at 1mo postoperatively. No other intraoperative or postoperative complications were observed, except an acute pupillary block glaucoma happened in a patient at two weeks postoperatively. CONCLUSION: This short-term results indicate that ICL implantation can be a promising alternative therapy for high myopic anisometropic amblyopia in pediatric patients who have failed with conventional treatments and not suitable to corneal refraction surgery.
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PURPOSE: To investigate the pharmacologic effect of tetramethylpyrazine (TMP) on human Tenon's fibroblasts (HTFs), the cells implicated in scarring after filtration surgery. METHODS: Transforming growth factor-ß2 (TGF-ß2) was used to stimulate a fibrotic phenotype in primary HTFs, and the influence of TMP on the fibrotic phenotype was assessed. Cell proliferation and cell cycle regulation were profiled. Immunofluorescence staining tracked proliferating cell nuclear antigen (PCNA) expression. Transwell assays monitored cell migration. Flow cytometry measured TMP toxicity. In addition, in TGF-ß2-treated HTFs, Western blot and immunofluorescence were employed to assess the expression of α-smooth muscle actin (α-SMA). The TMP-mediated activity on cytoskeletal arrangements and extracellular matrix (ECM) accumulation in HTFs was evaluated using actin polymerization and Western blot assays. Moreover, TGF-ß-dependent activation of Smad3 and p38 was examined by Western blot analysis. RESULTS: In TGF-ß2-treated HTFs, TMP reduced proliferation and migration but did not induce apoptosis. Moreover, TMP attenuated expression of α-SMA and suppressed stress fiber formation stimulated by profibrotic cytokine; it also counteracted TGF-ß2-induced cytoskeletal rearrangements, morphologic changes, and ECM accumulation. Smad3 and p38 mitogen-activated protein kinase (MAPK) signaling were downstream of the TMP-sensitive effect. CONCLUSIONS: Tetramethylpyrazine counteracts TGF-ß2-mediated myofibroblast transdifferentiation and attenuates ECM component deposition and cell proliferation in HTFs, implicating TMP as a potential antifibrosis agent in glaucoma filtration surgery.
Assuntos
Pirazinas/farmacologia , Cápsula de Tenon/patologia , Fator de Crescimento Transformador beta2/farmacologia , Western Blotting , Proliferação de Células , Transdiferenciação Celular/efeitos dos fármacos , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Cirurgia Filtrante , Citometria de Fluxo , Glaucoma/cirurgia , Humanos , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/metabolismo , Complicações Pós-Operatórias/patologia , Cápsula de Tenon/efeitos dos fármacos , Vasodilatadores/farmacologiaRESUMO
The aim of this study was to investigate the safety and efficacy of selective laser trabeculoplasty (SLT) treatment of patients with primary open-angle glaucoma (POAG) who could not obtain target intraocular pressure (IOP) through post-trabeculectomy medication. Sixteen patients with POAG (18 eyes), who could not obtain target IOP following medication and surgery, were treated with 360° SLT. The IOP, anterior chamber inflammation, and daytime and long-term IOP fluctuations before and 2 h, 1 day, 7 days, 1 month, 3 months, 6 months and 9 months after SLT were documented. SLT treatment success was defined as >20% IOP reduction compared with the baseline IOP at 6 and 9 months after the laser treatment date. Prior to SLT, the patients were administered different types (average, 2.8±0.8) of anti-glaucoma drugs and had an average IOP of 21.3±3.4 mmHg. Following SLT, the average IOP decreased to 16.2±3.0 mmHg and the success rate was 77.7%. The pre-SLT daytime IOP fluctuation was 4.1±1.4 mmHg, which decreased to 2.6±1.1 mmHg following the laser treatment (P<0.05). In conclusion, this study demonstrated that SLT could reduce the IOP in post-trabeculectomy patients with POAG, and reduce the daytime IOP fluctuations.
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Phakomatosis pigmentovascularis (PPV) is a rare congenital malformation syndrome that is characterized by a combination of capillary abnormalities and dermal melanocytosis.We describe 3 cases of PPV combined with bilateral Sturge-Weber syndrome (SWS), Ota nevus, and congenital glaucoma.Case 1 was a 2-year-old boy. Facial port-wine stains distributed along the 3 branches of his trigeminal nerves, which suggested the existence of SWS. Gray-blue patches were spread over the frontal and temporal areas of bilateral face, waist, buttocks, and thigh. Bilateral triangular alopecia was found on the temporal scalp. The diagnosis of Ota nevus was made by the bilateral scleral malanocystosis. Increased intraocular pressure, enlarged cornea, and pathologic optic disc cupping supported the diagnoses of infantile bilateral glaucoma. Case 2 was a 4-year-old boy. Port-wine stains were found on the face along the 3 branches of the trigeminal nerve and distributed along the trunk, arms, and legs. Mongolian spots spread over his frontal and temporal areas of the bilateral face, waist, buttocks, thigh, abdomen, and back. Infantile glaucoma was found in both eyes. Ota nevus were found in the both eyes. Optic coherent tomography (OCT) scans revealed increased thickness of choroid. Case 3 was a 5-year-old boy. Besides Ota nevus and infantile glaucoma in both eyes, color Doppler ultrasonography showed choroidal hemagioma. OCT scan showed increased choroidal thickness. The bilateral triangular alopecia on the child's temporal scalp was similar to that of Case 1. Cases 1 and 2 presented with port-wine stain patches that were consistent with the characteristic manifestation of PPV type IIb. However, the CMTC of Case 3 met the diagnostic criteria for PPV type Vb.Case 1 was treated with trabeculotomies in both eyes. For Cases 2 and 3, surgical interventions were not considered due to the high risks of antiglaucomatous operation complications. We prescribed them antiglaucoma indications.The simultaneously coexistence of PPV with SWS, Ota nevus, and congenital glaucoma is rare. In the clinic, additional detailed examinations and tests of PPV patients to exclude other ocular abnormalities or extraocular involvements are necessary.
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Glaucoma/congênito , Nevo de Ota/complicações , Síndrome de Sturge-Weber/complicações , Pré-Escolar , Glaucoma/complicações , Glaucoma/terapia , Humanos , MasculinoRESUMO
OBJECTIVE: To evaluate the efficacy and safety of selective laser trabeculoplasty (SLT) as a replacement for medical therapy in primary open-angle glaucoma (POAG). METHODS: A prospective, randomized, controlled study.SLT treatment with SOLO SLT Nd: YAG laser was provided to 45 participants with advanced POAG (67 eyes, IOP ≤ 21 mmHg, 1 mmHg = 0.133 kPa) under anti-glaucomatous medications control). A table of random numbers was created by simple randomization method. Participants were randomly divided into two groups: the standard-energy group (34 eyes), which received a 270° standard-energy SLT treatment and the sub-threshold energy group (33 eyes), which received a 360° sub-threshold energy treatment. The intraocular pressure (IOP) before and after SLT, daytime IOP curve, dosage of anti-glaucoma drugs and treatment complications were observed, which were be followed up for 6-9 months (average 6.4 months). Two-tailed t-test or paired t test was used when the continuous variables were normal distribution, such as the basic data, daily fluctuations of IOP, laser energy. Non-parametric Mann-Whitney U test or Wilcoxon rank test was used when data was not distributed normally, such as drug category. Chi-square or Fisher's exact test was used when count variables such as success rate and complications were analyzed. RESULTS: The number of anti-glaucomatous drugs used in the standard-energy group and the sub-threshold energy group before SLT was (2.3 ± 0.5) and (2.1 ± 0.4), respectively; whereas, after the last treatment, it reduced to (1.3 ± 0.5) and (1.1 ± 0.3), respectively (Z = -5.477, -5.396; P < 0.05). The success rate of the standard-energy group and the sub-threshold energy group was 91.1%, and 87.9%, respectively, which was not significant different (P = 0.70). Laser treatment was found to reduce the IOP fluctuation during the daytime.IOP fluctuation decreased from (3.6 ± 1.0) mmHg to (2.3 ± 1.0) mmHg in the standard-energy group, and decreased from (3.9 ± 1.4) mmHg to (2.4 ± 0.9) mmHg in the sub-threshold energy group, which was significant different (t = 4.911, 4.679; P < 0.05). The total laser energy of the standard-energy group (47.8 ± 6.0) mJ was higher than the sub-threshold energy group (43.2 ± 5.1) mJ (t = 12.006, 3.233; P < 0.05). However, there was no significant difference in the daily IOP fluctuations, success rate, reduction of medication categories, preoperative and postoperative IOP, and adverse reactions between the two groups. CONCLUSIONS: SLT is a safe and effective replacement for medical therapy in primary open-angle glaucoma treatment. SLT could reduce the applications of anti-glaucoma drugs. There was no significant difference between therapeutic effects of which eyes received 360° sub-threshold energy and 270° standard-energy.