Postoperative anterior uveitis in a patient submitted to combined treatment with cataract surgery and iStent inject®. How to manage? / Uveíte anterior no pós-operatório de facectomia combinada com implante de iStent inject®. Como manejar?

ABSTRACT Minimally invasive glaucoma surgeries are surgical treatment alternatives for glaucoma aimed at reducing intraocular pressure with a better safety profile compared to traditional trabeculectomy. However, in spite of less invasive techniques, complications may develop in any surgical procedure. To the best of our knowledge, this is the first case report of anterior uveitis following combined treatment with cataract surgery and iStent inject® which addresses the management of postoperative inflammation.

RESUMO As cirurgias minimamente invasivas para glaucoma consistem em uma opção de tratamento cirúrgico para glaucoma, a qual promove redução da pressão intraocular com melhor perfil de segurança do que a trabeculectomia. Todavia, complicações são inerentes à realização de procedimentos cirúrgicos, apesar do uso de técnicas menos invasivas. Este é o primeiro relato que apresenta um caso de uveíte anterior após cirurgia combinada de catarata e iStent inject®, além de orientações quanto ao manejo do quadro inflamatório.

Glaucoma e óleo de silicone / Glaucoma and silicone oils

RESUMO O óleo de silicone é um importante tampão utilizado na retinopexia cirúrgica de casos graves de descolamento de retina. O aumento da pressão intraocular e o desenvolvimento de glaucoma secundário são frequentes complicações da sua utilização. A depender do período de aparecimento, diversos mecanismos justificam a ocorrência de tais complicações. Compreender os fatores de riscos e a patogênese do aumento da pressão intraocular associada a aplicação de óleo de silicone em cirurgia retiniana ajuda a orientar o tratamento adequado para cada paciente. O objetivo deste artigo é revisar a literatura sobre a patogenia, a incidência, os fatores de risco e o tratamento desta condição clínica.

ABSTRACT Silicone oil has been an important intraocular tamponade in retinopexy in cases of complicated retinal detachment surgery. The increase of intraocular pressure and development of secondary glaucoma are a known complication of its use. A variety of mechanisms have been proposed for the pathogenesis, depending on the onset. This article aims to review the literature about pathogenesis, the incidence and risk factors, as well as the treatment of this pathology.

Procedimentos Minimamente Invasivos para Glaucoma: uma revisão atualizada da literatura / Minimally Invasive Glaucoma Surgery (MIGS): an updated literature review

RESUMO O glaucoma é considerado a maior causa de cegueira irreversível no mundo, e o aumento da pressão intraocular constitui seu principal fator de risco. Usualmente, a terapia inicial do glaucoma consiste na redução da pressão intraocular a partir da instilação de drogas hipotensoras tópicas, estando as cirurgias antiglaucomatosas reservadas, na maioria das vezes, para casos em que o controle da doença não é atingido clinicamente. Classicamente, o tratamento cirúrgico do glaucoma é realizado a partir dos procedimentos filtrantes: trabeculectomia e implante de dispositivos de drenagem. O acrônimo MIGS (do inglês minimally invasive glaucoma surgery, procedimentos minimamente invasivos para glaucoma) corresponde a um grupo de procedimentos cirúrgicos pouco invasivos, que propõem a redução pressórica de maneira mais segura e previsível, quando comparada às técnicas cirúrgicas antiglaucomatosas convencionais.

ABSTRACT Glaucoma is considered the biggest cause of irreversible blindness in the world and the increase in intraocular pressure is its main risk factor. Usually, the initial therapy for glaucoma consists of reducing IOP through the instillation of topical hypotensive drugs, with antiglaucoma surgeries being normally reserved for cases in which disease control is not clinically achieved. Classically, the surgical treatment of glaucoma is performed using filtering procedures: trabeculectomy; non-penetrating sclerotomy and glaucoma drainage devices. The acronym MIGS (Minimally Invasive Glaucoma Surgery) corresponds to a group of minimally invasive surgical procedures that provide a safer and more predictable pressure reduction when compared to conventional antiglaucoma surgical techniques.

Preventing glaucoma progression using the trabecular micro-bypass implant iStent inject®. A cost-effectiveness analysis / Prevenindo a progressão do glaucoma por meio do implante de by-pass trabecular iStent inject®. Uma análise de custo-efetividade

ABSTRACT Objective To assess the economic impact of reducing glaucoma progression by using the trabecular micro-bypass implant, iStent inject®, in the Reference Centers for glaucoma treatment within the Brazilian Public Unified Health System (SUS). Methods In a cost-effectiveness analysis, a Markov model was developed, and the costs were obtained from the SUS perspective (medical direct costs). Effectiveness was measured in progression-free life-years. The time horizon was the mean life expectancy of the Brazilian population. The model parameters were obtained through a review and a critical analysis of the literature. The base case comprised a hypothetical cohort of patients with open-angle glaucoma, using anti-glaucoma eye drops and followed up at Reference Centers of SUS. We tested whether the incorporation of iStent inject® as an alternative second-line therapy would be cost-effective. The outcome measure was the incremental cost-effectiveness ratio (R$/progression-free life-years). We tested the robustness of the model by univariate and probabilistic sensitivity analyses. Results The use of iStent inject® led to decreased progression rate of glaucoma, evidenced by the amount of progression-free life-years obtained with each treatment strategy (7.82 progression-free life-years with iStent inject® versus 6.33 progression-free life-years with medical treatment), thereby improving glaucoma control. There was also a reduction in future costs associated with eye drops, filtering surgeries, and treatment complications. Incremental cost-effectiveness ratio ranged from R$ 6,429.30 to R$ 7,550.97/progression-free life-years. The model proved to be robust in the sensitivity analyses. Conclusion This analysis showed that iStent inject®, when used after the failure of the first-line therapy, is able to reduce the rate of glaucoma progression at an acceptable cost.

RESUMO Objetivo Avaliar o impacto econômico da redução da progressão do glaucoma pelo uso do implante de by-pass trabecular iStent inject® no ambiente dos Centros de Referência para tratamento do Sistema Único de Saúde (SUS). Métodos Em uma análise de custo-efetividade, elaborou-se um modelo de Markov, cujos custos foram obtidos a partir da perspectiva do SUS financiador (custos médicos diretos). A efetividade foi medida em anos de vida livres de progressão. O horizonte temporal foi a expectativa de vida média da população brasileira. Os parâmetros do modelo foram obtidos pela revisão e pela análise crítica da literatura. O caso base foi composto de uma coorte hipotética de portadores de glaucoma de ângulo aberto em uso de colírios antiglaucomatosos e em acompanhamento nos Centros de Referência do SUS. Testou-se se a incorporação do iStent inject® como alternativa à segunda linha de tratamento seria custo-efetiva. A medida de desfecho foi a razão de custo-efetividade incremental (R$/anos de vida livres de progressão). A robustez do modelo foi testada por meio de análises de sensibilidade univariada e probabilística. Resultados A utilização do iStent inject® proporcionou uma diminuição da velocidade de progressão do glaucoma, evidenciada pela quantidade de anos de vida livres de progressão obtida com cada estratégia de tratamento (7,82 anos de vida livres de progressão com iStent inject® versus 6,33 anos de vida livres de progressão com tratamento com colírios), melhorando, dessa forma, o controle do glaucoma. Houve ainda redução nos custos futuros associados aos colírios, às cirurgias filtrantes e às complicações do tratamento. A razão de custo-efetividade incremental variou de R$6.429,30 a R$7.550,97/anos de vida livres de progressão. O modelo mostrou-se robusto nas análises de sensibilidade. Conclusão O iStent inject®, quando usado após a falha do primeiro medicamento, é capaz de reduzir a taxa de progressão do glaucoma a um custo aceitável.

A influência do oxido nítrico na fisiopatologia da neuropatia glaucomatosa / The influence of nitric oxide on the pathophysiology of glaucomatous neuropathy

Resumo O oxido nitrico (NO) é um fator relaxante derivado do endotélio e um potente vasodilatador que impacta em vários sistemas em todo o corpo. Estudos comprovam que o fluxo sanguíneo ocular basal é regulado pelo NO, sendo um importante regulador da homeostase, especialmente dentro dos tecidos uveais. A disfunção da produção de NO seria associado ao glaucoma através da alteração da perfusão da cabeça do nervo óptico associado ao aumento da pressão intraocular devido um sistema de drenagem trabecular deficiente. O NO tornou-se uma molécula atraente para o tratamento do glaucoma devido a possibilidade de modulação da drenagem trabecular, abaixando a pressão intraocular e ação neuroprotetora melhorando a perfusão sanguínea na cabeça do nervo óptico.

Abstract Nitric Oxide (NO) is a relaxing endothelium-derived factor and a potent vasodilator that impacts various systems throughout the body. Proven studies of basal ocular blood flow are regulated by NO, being an important regulator of homeostasis, especially within the uveal tissues. The dysfunction of the production associated with glaucoma due to alteration of the optic nerve head associated to the increase of the intraocular pressure by a deficient trabecular meshwork. NO became an attractive molecule for the treatment of glaucoma due to a modulation of the trabecular meshwork, lowering the neuroprotective intra and ocular pressure for a blood surgery in the head of the optic nerve.

New classes of glaucoma medical treatment

Glaucoma is a progressive degenerative disease of the optic nerve head, characterized by a specific pattern of axonal loss and visual field deterioration. This review aims at introducing the different novel pharmacologic agents for its treatment, as well as their mechanisms. Most glaucoma patients require lifelong care and individualized treatment. Intraocular pressure (IOP), which is regulated by aqueous humor production, outflow via the trabecular meshwork (parasympathomimetics only) and uveoscleral outflow pathways, is currently the only treatable target for glaucoma treatment. Conventional glaucoma medications are categorized as β blockers, α agonists, carbonic anhydrase inhibitors, parasympathomimetics, and prostaglandin analogues. The development of basic research-derived novel classes of pharmacologic agents features novel action mechanisms, which are different from those of conventional medications. New classes of recently approved or clinical trial-tested medications include Rho-kinase inhibitors, nitric oxide donors, adenosine agonists, and prostaglandin analogs targeting E-type prostanoid receptors, etc. Their integration and future development will facilitate the expansion and customization of therapeutic options.

Goniodysgenesis-associated glaucoma in a Jindo dog / 대한수의학회지

A 10-year-old intact female Jindo dog was presented with a 1-week history of conjunctival redness and ocular discharge in the left eye. There was an absence of menace response, dazzle reflex, and direct pupillary light reflex. Slit-lamp biomicroscopy revealed corneal edema, ciliary flush, and aqueous flare. Intraocular pressure was 68 mmHg. Based on the information available, a diagnosis of glaucoma and uveitis was made. Subsequent histopathologic examination showed the glaucoma was produced by the effects of goniodysgenesis, posterior synechia, and pigment dispersion in the trabecular meshwork. This is the first report of primary glaucoma caused by goniodysgenesis in Jindo dogs.

Effect and Mechanism of Phosphodiesterase Inhibitors on Trabecular Outflow

PURPOSE: Phosphodiesterase (PDE) inhibitors increase matrix metalloproteinase (MMP) production by inhibiting re-uptake of adenosine and may potentiate nitric oxide (NO) activity. This study was performed to investigate the effects and mechanisms of PDE inhibitors on trabecular outflow in cultured human trabecular meshwork cells (HTMCs). METHODS: Primary HTMC cultures were exposed to 0, 20, and 50 µM dipyridamole (DPD) or theophylline (TPN). Permeability through the HTMC monolayer was assessed using carboxyfluorescein. The production of NO was assessed using the Griess assay and MMP-2 levels were measured via Western blotting. RESULTS: DPD significantly increased permeability accompanied with increased nitrite concentration and MMP-2 levels (all p 0.05). When treated with DPD and TPN together, both permeability and nitrite production were increased; however, MMP-2 levels showed no difference compared to DPD exposure alone (p > 0.05). CONCLUSIONS: DPD increased trabecular permeability accompanied with increased nitrite production and MMP-2 levels. PDE inhibitors may increase trabecular outflow by increasing MMP-2 levels and by potentiating NO activity through cyclic GMP in HTMC.

Effect of Chronic Benzalkonium Chloride Exposure on Senescence in Trabecular Meshwork Cells

PURPOSE: To determine the possible effects of chronic exposure of low dose benzalkonium chloride (BAK) on trabecular meshwork cells, and to characterize the pathways involved in the effects. METHODS: Trabecular meshwork cells were treated with 0.0005%, 0.00075%, 0.001%, and 0.0025% BAK for 10 minutes; then, the cells were transferred to a new medium for 24 hours. This process was repeated three times. Cell survival was assessed using the MTT assay to determine the non-apoptotic BAK concentration. Senescence-associated (SA)-β-gal staining was performed to compare quantitatively the cellular senescence of BAK-treated cells with the control group. Cells treated with BAK were analyzed by western blot to determine whether the expressions of cell cycle regulators were affected. RESULTS: Two concentrations (0.0005% and 0.00075%) showed persistent cell viability and were chosen for further experiments. After SA-β-gal staining, cells treated with 0.0005% and 0.00075% BAK showed 28% (± 2.08), 37% (± 2.08) increases in cellular senescence expression, respectively, when compared with control cells (p < 0.05). To identify the molecular pathways involved in cell cycle arrest via BAK, western blot analysis was performed on trabecular meshwork cells, resulting in decreased expressions of cyclin E/CDK2, and increased expressions of the upper stream control molecules, p53 and p21. CONCLUSIONS: Chronic exposure to low dose BAK accelerated cell senescence through cell cycle arrest. Because senescent cells of the trabecular meshwork can inhibit its outflow pathway function and ultimately worsen the glaucomatous process, long-term usage of topical glaucoma medications containing BAK should be conducted with caution.

Bone mineral density and trabecular bone score in patients with non-radiographic axial spondyloarthropathy

Background: spondyloarthropathies (SpA) are a group of chronic inflammatory rheumatic conditions that share multiple clinical features including axial and/or peripheral arthritis, enthesitis, absence of serum rheumatoid factor and presence of common extra articular manifestations. Objective: the aim of this work is to study bone mineral density and trabecular bone score at patients with non-radiographic axial spondyloarthropathy. Patients and Methods: this study is a cross sectional study in which 200 patients having chronic back pain selected from those attending the outpatient clinic and inpatient of Al-Azhar University Hospitals, Damietta and were divided into two groups: 1- (Group A, study group): (160) patients had inflammatory low back pain fulfilling Calin criteria for inflammatory low back pain. 2- (Group B, control group): (40) patients had mechanical low back pain not fulfilling criteria of inflammatory back pain. Results: regarding results of clinical examination, there was significant increase of arthritis, dactylitis, enthesitis and psoriasis in Group A when compared to Group B (43.3%, 16.7%, 30.0%, 20.0% vs 3.3%, 0.0%, 3.3% and 3.3% respectively). In addition, there was significant increase of arthritis plus dactylitis and arthritis plus enthesitis in Group A when compared to Group B (16.7%, 30.0% vs 3.3% and 0.0% respectively). Conclusion: results of the present study proved that, both bone mineral density and trabecular bone scores showed early changes in patients with non-radiographic axial spondylo-arthropathy. In addition, both correlated with each other and with results of axial magnetic resonance imaging. Thus, they are advocated in diagnosis of nr. SPA

Effect of Valproic Acid on Nitric Oxide and Nitric Oxide Synthase in Trabecular Meshwork Cell

PURPOSE: To investigate the effects of valproic acid on the production of nitric oxide (NO) and expression of endothelial nitric oxide synthase (eNOS) in cultured human trabecular meshwork cells (HTMC). METHODS: Primarily cultured HTMC were exposed to 0.25, 0.5, and 1.0 mM valproic acid for 6, 12, and 24 hours. Expression of eNOS mRNA was assessed with Reverse transcription-polymerase chain reaction, and production of NO was assessed with Griess assay. Cellular survival was assessed with the 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. RESULTS: Valproic acid at concentrations of 0.25, 0.5, 1.0 mM did not affect the cellular survival of HTMC significantly after exposure for 24 hours. Valproic acid increased NO production in a dose- and time-dependent manner. Also, valproic acid increased the degree of eNOS mRNA expression in a dose-dependent manner in HTMC. CONCLUSIONS: Valproic acid increases production of NO and expression of eNOS mRNA in HTMC. Thus, valproic acid might increase aqueous outflow through the trabecular meshwork.

Effects of High Glucose and Dexamethasone on the Permeability in Trabecular Meshwork Cells

PURPOSE: To investigate the effects of high glucose (HG) and dexamethasone (DEX) on the survival and permeability of trabecular meshwork cells (HTMC), and associated changes in tight junctions. METHODS: Primary cultured HTMC were exposed to 5 mM low glucose (LG) or 25 mM HG with or without 1.0 µM DEX for 3 days. The permeability of the HTMC monolayer was assessed using carboxyfluorescein or transendothelial electrical resistance (TEER). Gene and protein expressions of claudin-5 and occludin were assessed with reverse transcription polymerase chain reaction (RT-PCR) and Western blot, respectively. RESULTS: HG was significantly associated with greater HTMC monolayer permeability compared to LG by both the carboxyfluorescein permeability test and TEER (p = 0.022, 0.028). HG also decreased claudin-5 and occludin mRNA expression, respectively (7.5%, 12.9%). DEX abolished HG-induced increased permeability, and increased the protein expression of claudin-5 and occludin, respectively (p = 0.015, 0.012). CONCLUSIONS: In HTMCs, DEX reversed HG-induced permeability increase. DEX increased tight junction molecules claudin-5 and occludin. Thus, DEX-induced changes in junctional proteins could be another mechanism of increased resistance through the trabecular meshwork and may result in steroid-induced glaucoma.

Regulation of Matrix Metalloproteinase 2 Expression by an Adenosine A1 Agonist in Trabecular Meshwork Cells

PURPOSE: We investigated the extent of adenosine A1 agonist-induced expression and regulation of matrix metalloproteinase 2 (MMP-2) synthesis in human trabecular meshwork cells (HTMC). METHODS: Primary HTMC cultures were exposed to 0.1 or 1.0 µM N6-cyclohexyladenosine (CHA) for 2 h in the presence or absence of an inhibitor thereof, 8-cyclopentyl-1,3-dimethylxanthine (CPT). The expression level of mRNA encoding MMP-2 was assessed via reverse transcription-polymerase chain reaction, and the levels of tissue inhibitor of metalloproteinase 2 (TIMP2) and membrane-type-1 MMP (MT1-MMP) measured by Western blotting. The permeability of the HTMC monolayer was assessed with the aid of carboxyfluorescein. RESULTS: CHA at 1.0 µM increased the permeability of the HTMC monolayer (p = 0.003) and CHA at both 0.1 and 1.0 µM significantly increased MMP-2 mRNA expression, which was inhibited by co-exposure to CPT (all p < 0.05). CHA increased MMP-2 activity, decreased that of TIMP2, and increased that of MT1-MMP (all p < 0.05). CONCLUSIONS: CHA increased the permeability of the HTMC monolayer and increased MMP-2 activity, decreased TIMP2 activity, and increased MT1-MMP activity. Thus, regulation of TIMP2 and MT1-MMP expression may be involved in the adenosine A1 agonist-induced increase in MMP-2 activity.

Secondary glaucoma induced by bilateral acute depigmentation of the iris / Glaucoma secundário à despigmentação bilateral aguda da íris

Abstract We report a case of a middle-aged woman who developed acute, bilateral, symmetrical, slightly transilluminating depigmentation of the iris and pigment discharge into the anterior chamber following the use of oral moxifloxacin for bacterial sinusitis. She had been misdiagnosed as having autoimmune uveitis, treated with steroids and tropicamide, and underwent severe ocular hypertension and glaucoma despite posterior correct diagnosis.

Resumo Relato de um caso de uma paciente do sexo feminino de meia idade que desenvolveu despigmentação bilateral simultânea aguda com dispersão de pigmentos na câmara anterior e discreta transiluminação após o uso de moxifloxacino oral para tratamento de sinusite bacteriana. Ela Havia sido diagnosticada com uveite autoimune e tratada com corticosteroide tópico e tropicamida e evoluiu com hipertensão ocular grave e glaucoma apesar de ,posteriormente, o diagnóstico ter sido correto.

Effect of Tetrahydrozoline on the Permeability of Trabecular Meshwork Cell Monolayer

PURPOSE: To investigate the effects of tetrahydrozoline (THZ) on the survival of cultured human trabecular meshwork cells (HTMC) and the permeability of HTMC monolayer. METHODS: Primary cultured HTMC were exposed to an adrenergic agonist (0.01, 0.1, 1.0 or 10 µM THZ) for 1 day and 3 days. Carboxyfluorescein permeability through the HTMC monolayer was measured using Transwell. Cellular viability and nitric oxide (NO) production were assessed using MTT and Griess assays, respectively. RESULTS: THZ did not affect the cellular survival (p > 0.05) or NO production (p > 0.05). THZ significantly increased the carboxyfluorescein permeability through the HTMC monolayer in a dose-dependent manner compared with non-exposed control (p < 0.05) after exposure for 1 and 3 days. CONCLUSIONS: THZ does not affect the survival of HTMC but decreases the permeability of HTMC monolayer in a dose-dependent manner. Thus, THZ may possibly decrease trabecular outflow.

Comparative Study of the Effects of Trabecular Meshwork Outflow Drugs on the Permeability and Nitric Oxide Production in Trabecular Meshwork Cells

PURPOSE: To compare the effects of the barrier function in human trabecular meshwork (TM) cells monolayer and the production of nitric oxide (NO) between trabecular outflow drugs, Rho-associated kinase (ROCK) inhibitors, adenosine, and statin. METHODS: Primary cultured TM cells were exposed to 10 or 25 µM Y-27632, 0.1 or 1 µM N6-cyclohexyladenosine (CHA), or 15 or 30 µM simvastatin for 24 hours. NO production and expression of endothelial nitric oxide synthase mRNA were measured by Griess assay and reverse transcription polymerase chain reaction, respectively. Barrier functions of the TM cell monolayer were measured by carboxyfluorescein and trans-endothelial electrical resistance. The expression of matrix metalloproteinase-2 mRNA was assessed with reverse transcription polymerase chain reaction. RESULTS: In TM cells, treatment with each drug increased endothelial nitric oxide synthase mRNA expression. Treatment with 25 µM Y-27632 and 1.0 µM CHA increased NO production significantly (p = 0.035 and p = 0.043, respectively). Treatment with each drug increased the permeability (all p = 0.001) and decreased the trans-endothelial electron resistance of the TM cell monolayer. Treatment with 0.1 µM and 1.0 µM CHA significantly increased matrix metalloproteinase-2 mRNA expression, but simvastatin inhibited its expression. CONCLUSIONS: Since treatment with ROCK inhibitor more greatly increased NO production and permeability than did adenosine or statin, ROCK inhibitor seems to be more effective for lowering intraocular pressure.