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1.
Vestn Oftalmol ; 140(2. Vyp. 2): 73-79, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38739134

RESUMO

The management protocol for patients with neovascular age-related macular degeneration (nAMD) involves multiple intravitreal injections (IVI) of anti-VEGF drugs. The ability to reduce the peak intraocular pressure (IOP) rise is greatly important in clinical practice. PURPOSE: This study evaluates the effect of topical hypotensive drugs on the short-term IOP rise after IVI of anti-VEGF drugs in patients with nAMD. MATERIAL AND METHODS: The prospective study included 80 patients with newly diagnosed nAMD. Before the start of treatment, the patients were divided into 4 groups of 20 people each: 1st - controls, who received no prophylactic drugs, in the 2nd, 3rd and 4th groups local instillations of one drop of hypotensive drugs brinzolamide 1%, brinzolamide-timolol, brimonidine-timolol were performed in the conjunctival sac twice: 1 day before the injection (at 20:00) and on the day of the injection 2 hours before the manipulation (at 08:00), respectively. IOP was measured in each patient using ICare Pro non-contact tonometer before injection, as well as 1 min, 30 and 60 min after injection. RESULTS: Prophylactic use of hypotensive drugs was associated with a significant decrease in IOP immediately after IVI compared to the same parameter in the 1st group (p<0.001), the maximum decrease in IOP values was observed when using a fixed combination of brimonidine-timolol by 12.1 mm Hg compared to the controls (p<0.001), the combination of brinzolamide-timolol reduced IOP by 8.5 mm Hg (p<0.001), brinzolamide 1% led to the smallest decrease in IOP - by 5.1 mm Hg (p<0.001). CONCLUSION: Study patients that received instillations of brimonidine-timolol combination of one drop into the conjunctival sac 1 day before the injection and on the day of the injection showed the maximum decrease in IOP compared to patients of the other groups.


Assuntos
Inibidores da Angiogênese , Pressão Intraocular , Injeções Intravítreas , Hipertensão Ocular , Sulfonamidas , Humanos , Masculino , Feminino , Idoso , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/prevenção & controle , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/fisiopatologia , Inibidores da Angiogênese/administração & dosagem , Estudos Prospectivos , Sulfonamidas/administração & dosagem , Resultado do Tratamento , Anti-Hipertensivos/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Tonometria Ocular/métodos , Pessoa de Meia-Idade , Timolol/administração & dosagem , Tartarato de Brimonidina/administração & dosagem , Soluções Oftálmicas/administração & dosagem , Tiazinas/administração & dosagem , Degeneração Macular/tratamento farmacológico , Degeneração Macular/diagnóstico
2.
Am J Physiol Cell Physiol ; 326(5): C1505-C1519, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557355

RESUMO

Glaucoma is a blinding disease. Reduction of intraocular pressure (IOP) is the mainstay of treatment, but current drugs show side effects or become progressively ineffective, highlighting the need for novel compounds. We have synthesized a family of perhydro-1,4-oxazepine derivatives of digoxin, the selective inhibitor of Na,K-ATPase. The cyclobutyl derivative (DcB) displays strong selectivity for the human α2 isoform and potently reduces IOP in rabbits. These observations appeared consistent with a hypothesis that in ciliary epithelium DcB inhibits the α2 isoform of Na,K-ATPase, which is expressed strongly in nonpigmented cells, reducing aqueous humor (AH) inflow. This paper extends assessment of efficacy and mechanism of action of DcB using an ocular hypertensive nonhuman primate model (OHT-NHP) (Macaca fascicularis). In OHT-NHP, DcB potently lowers IOP, in both acute (24 h) and extended (7-10 days) settings, accompanied by increased aqueous humor flow rate (AFR). By contrast, ocular normotensive animals (ONT-NHP) are poorly responsive to DcB, if at all. The mechanism of action of DcB has been analyzed using isolated porcine ciliary epithelium and perfused enucleated eyes to study AH inflow and AH outflow facility, respectively. 1) DcB significantly stimulates AH inflow although prior addition of 8-Br-cAMP, which raises AH inflow, precludes additional effects of DcB. 2) DcB significantly increases AH outflow facility via the trabecular meshwork (TM). Taken together, the data indicate that the original hypothesis on the mechanism of action must be revised. In the OHT-NHP, and presumably other species, DcB lowers IOP by increasing AH outflow facility rather than by decreasing AH inflow.NEW & NOTEWORTHY When applied topically, a cyclobutyl derivative of digoxin (DcB) potently reduces intraocular pressure in an ocular hypertensive nonhuman primate model (Macaca fascicularis), associated with increased aqueous humor (AH) flow rate (AFR). The mechanism of action of DcB involves increased AH outflow facility as detected in enucleated perfused porcine eyes and, in parallel, increased (AH) inflow as detected in isolated porcine ciliary epithelium. DcB might have potential as a drug for the treatment of open-angle human glaucoma.


Assuntos
Humor Aquoso , Digoxina , Pressão Intraocular , Macaca fascicularis , Hipertensão Ocular , Animais , Pressão Intraocular/efeitos dos fármacos , Digoxina/farmacologia , Humor Aquoso/metabolismo , Humor Aquoso/efeitos dos fármacos , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/fisiopatologia , Hipertensão Ocular/metabolismo , Modelos Animais de Doenças , Glaucoma/tratamento farmacológico , Glaucoma/metabolismo , Glaucoma/fisiopatologia , Coelhos , Humanos , Corpo Ciliar/efeitos dos fármacos , Corpo Ciliar/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Masculino , Malha Trabecular/efeitos dos fármacos , Malha Trabecular/metabolismo
3.
J Glaucoma ; 33(5): 375-380, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38129940

RESUMO

PRCIS: This study showed that the XEN patency should be verified by OCT imaging in cases of encapsulated blebs. Although fibrosis plays the principal role, humor aqueous flow reduction could affect the "spacer" effect that inhibits the fibroblast attachments. PURPOSE: To evaluate the application of the anterior segment optical coherence tomography (AS-OCT) imaging in studying the relationship between a low flow rate through the XEN63 and the development of a cystic bleb. METHODS: Retrospective case series of 3 eyes presenting a cystic bleb after an XEN63 implantation for uncontrolled intraocular pressure (IOP). Demographic and clinical data were obtained from medical records. The imaging findings, complications, and managements following the surgery were evaluated. RESULTS: Three patients, with an average age of 67.3 years, initially showed a patent stent lumen and a functional bleb after surgery. The IOP of all eyes increased on average at 28.3 days from the surgery, with a mean value of 39.66 mm Hg. The slit lamp examination showed a cystic bleb. The AS-OCT imaging confirmed the previous finding and revealed either a partial or total occlusion of the stent internal ostium. A Nd:YAG laser, in proximity to the ostium, was performed to resolve the obstruction. Although the AS-OCT imaging showed the device patency and the IOP immediately decreased, the latter became elevated again. Consequently, in all the cases, a further needling procedure was needed to achieve an adequate IOP reduction. Six months after the two-step procedure, the IOP averaged 13.33 mm Hg, the XEN63 lumens appeared cleared, and the blebs showed a functional morphology. No adverse events were observed. CONCLUSION: The development of a cystic bleb may result from an altered balance between the flow rate through the XEN63 and the fibrosis development in the postoperative healing process. A proper follow-up based on slit lamp biomicroscopy, IOP measurement, and AS-OCT imaging is advisable to estimate and manage a cystic bleb following XEN63 implantation.


Assuntos
Segmento Anterior do Olho , Implantes para Drenagem de Glaucoma , Pressão Intraocular , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Segmento Anterior do Olho/diagnóstico por imagem , Glaucoma/cirurgia , Glaucoma/fisiopatologia , Glaucoma/diagnóstico , Pressão Intraocular/fisiologia , Hipertensão Ocular/fisiopatologia , Hipertensão Ocular/diagnóstico , Complicações Pós-Operatórias , Estudos Retrospectivos , Stents , Tomografia de Coerência Óptica/métodos , Tonometria Ocular
5.
Cornea ; 41(2): 243-248, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35037906

RESUMO

ABSTRACT: The Rho kinase inhibitor netarsudil is a recently approved therapeutic option for the management of increased intraocular pressure in the United States. Although phase 3 clinical trials noted corneal changes related to the medication-namely, nonvisually-significant corneal verticillata-descriptions of a unique form of cystic epithelial edema began to surface as netarsudil (and its sister drug ripasudil, approved in Japan) gained widespread use. This series adds 3 new cases and reviews the current literature on this unique side effect.


Assuntos
Benzoatos/efeitos adversos , Edema da Córnea/induzido quimicamente , Epitélio Corneano/patologia , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/tratamento farmacológico , beta-Alanina/análogos & derivados , Quinases Associadas a rho/antagonistas & inibidores , Benzoatos/uso terapêutico , Edema da Córnea/diagnóstico , Epitélio Corneano/efeitos dos fármacos , Humanos , Hipertensão Ocular/enzimologia , Hipertensão Ocular/fisiopatologia , Estudos Retrospectivos , beta-Alanina/efeitos adversos , beta-Alanina/uso terapêutico
6.
Curr Eye Res ; 47(1): 91-101, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34165383

RESUMO

PURPOSE: To assess the neuroprotective effects of methylene blue (MB) in a rat model of acute ocular hypertension (AOH) and explore its possible mechanisms. METHODS: Our AOH rat model was obtained with anterior chamber perfusion for 60 min. After that, 100 µM MB was injected into the vitreous cavity immediately after injury. Electroretinogram, fundus photography, optical coherence tomography (OCT) and retina morphology examination were utilized to quantify retinal damage before surgery, as well as 7, 14 and 28 days after. The average number of surviving retinal ganglion cells (RGCs) was counted after fluorescent retrograde labelling with 4% DiI. And TUNEL assay was used to investigate retinal cell apoptosis at 24 hours after AOH. Nrf2 and BACE1 in the retina were determined by RT-qPCR analysis. RESULTS: AOH did produce a severe degeneration effect on the whole retinal layer. Intravitreally injected MB maintained certain retinal thickness after AOH, reduced the destruction of electroretinograms, and enhanced RGCs survival. The average number of TUNEL-labelled cells statistically reduced in the MB-treated retina tissue compared with retina treated with normal saline. The relative mRNA level of Nrf2 was also much higher in the MB-treated retinas after AOH, and the expression of BACE1 had a decline in the AOH + MB group. CONCLUSIONS: MB can protect the retina from AOH injury and the possible mechanism might involve the inhibition of BACE1 expression and the activation of Nrf2 antioxidant pathway.


Assuntos
Pressão Intraocular/fisiologia , Azul de Metileno/administração & dosagem , Hipertensão Ocular/prevenção & controle , Retina/efeitos dos fármacos , Tomografia de Coerência Óptica/métodos , Doença Aguda , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eletrorretinografia , Inibidores Enzimáticos/administração & dosagem , Injeções Intravítreas , Masculino , Hipertensão Ocular/fisiopatologia , Ratos , Retina/diagnóstico por imagem
7.
Cornea ; 41(1): 83-88, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074893

RESUMO

PURPOSE: The purpose of this study was to investigate the impact of transient elevations in postoperative intraocular pressure (IOP) on the clinical outcome of Descemet membrane endothelial keratoplasty (DMEK) surgery in non-glaucoma patients. METHODS: Retrospective analysis from a prospective database of eyes without preexisting glaucoma that underwent DMEK with 90% anterior chamber and 20% sulfur hexafluoride endotamponade. Group A included eyes without postoperative IOP increase (IOP <30 mm Hg and a relative increase from preoperative value <10 mm Hg). Group B included eyes with IOP elevation (postoperative IOP ≥30 mm Hg or a relative increase from preoperative value ≥10 mm Hg) handled according to a standardized protocol. The impact of elevated IOP within 3 days after DMEK surgery was evaluated regarding best-corrected visual acuity (BCVA), central corneal thickness (CCT), and endothelial cell count (ECC) at 1, 3, and 6 months. RESULTS: One hundred seventy-six eyes from 164 patients were included. An IOP increase after DMEK occurred in 20 eyes (11.3%; 19 patients, group B), and the mean peak IOP was 48 ± 12 mm Hg (range 32-69 mm Hg). There were no significant postoperative differences in BCVA, CCT, and ECC on comparing both groups. The BCVA increased significantly (P < 0.001, respectively), whereas CCT (P < 0.001, respectively) and ECC (P < 0.001, respectively) decreased significantly from preoperative values. The rebubbling rate tended to be higher in group B without statistical significance (6.4% vs. 10%, P = 0.648). CONCLUSIONS: Temporary IOP elevation after DMEK may not affect functional and morphological outcomes in non-glaucoma patients. However, careful postoperative IOP monitoring and appropriate management are crucial to avoid irreversible ocular damage.


Assuntos
Perda de Células Endoteliais da Córnea/cirurgia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/efeitos adversos , Endotélio Corneano/patologia , Pressão Intraocular/fisiologia , Hipertensão Ocular/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Idoso , Contagem de Células , Perda de Células Endoteliais da Córnea/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Hipertensão Ocular/etiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Estudos Retrospectivos , Fatores de Tempo
8.
Br J Haematol ; 196(5): 1248-1256, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34862597

RESUMO

Most childhood acute lymphoblastic leukaemia (ALL) protocols include high-dose steroid therapy. However, the known potential of high-dose steroids to significantly elevate intraocular pressure (IOP) and lead to glaucomatous optic neuropathy has not been intensively investigated in children with ALL. Moreover, as children with ALL do not routinely undergo IOP measurements, the need for IOP monitoring and therapy is unknown. We prospectively measured IOP in 90 children with newly diagnosed ALL attending a tertiary paediatric haematology/oncology centre, at diagnosis and at the middle and end of induction therapy. Ocular hypertension (IOP > 21 mm Hg) at any time point was documented in 64 children (71%), and the prevalence increased during induction. Thirty-six children (40%) had elevated IOP at ALL diagnosis before therapy initiation, and stratification to non-standard ALL was a risk factor. IOP reduction therapy was administered to 13 children (14%); none required surgery. Values normalised in all cases. On multivariate logistic regression analysis, dexamethasone therapy was a significant risk factor for ocular hypertension. High body mass index was an additional risk factor in children with elevated IOP at ALL diagnosis. Routine evaluation of IOP during steroid therapy is very important in children with ALL to ensure early intervention which may prevent permanent ocular damage.


Assuntos
Antineoplásicos Hormonais/efeitos adversos , Dexametasona/efeitos adversos , Pressão Intraocular , Hipertensão Ocular/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Antineoplásicos Hormonais/uso terapêutico , Índice de Massa Corporal , Criança , Pré-Escolar , Dexametasona/uso terapêutico , Feminino , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Lactente , Pressão Intraocular/efeitos dos fármacos , Masculino , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Estudos Prospectivos , Fatores de Risco
9.
Rev. bras. oftalmol ; 81: e0036, 2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1376779

RESUMO

ABSTRACT The purpose of this study was to highlight the impact of biomechanical corneal response in available in vivo tonometry methods for glaucoma management. Systematic review of non-contact air-puff tonometers that analyzes the corneal deformation response, with special focus on the investigation of the correlation of derived parameters with intraocular pressure measurements. The two actual and commercially available in vivo corneal tonometers provide promising information about biomechanical characteristics of the cornea and its relation to glaucoma, allowing the development of new protocols to evaluate, diagnose, and manage this disease.


RESUMO O objetivo deste estudo é destacar o impacto da resposta biomecânica corneana em métodos de tonometria in vivo disponíveis para o manejo do glaucoma. Trata-se de revisão sistemática de tonômetros de ar que analisa a resposta à deformação corneana, com foco especial na investigação da correlação dos parâmetros derivados com as medições da pressão intraocular. Os dois tonômetros mais recentes e comercialmente disponíveis fornecem informações promissoras sobre as características biomecânicas da córnea e sua relação com o glaucoma, permitindo o desenvolvimento de novos protocolos para avaliar, diagnosticar e controlar a doença.


Assuntos
Humanos , Tonometria Ocular/instrumentação , Tonometria Ocular/métodos , Fenômenos Biomecânicos , Córnea/anatomia & histologia , Córnea/fisiologia , Pressão Intraocular/fisiologia , Glaucoma/fisiopatologia , Hipertensão Ocular/fisiopatologia , Técnicas de Diagnóstico Oftalmológico/instrumentação , Elasticidade/fisiologia , Modelos Teóricos
11.
Exp Eye Res ; 213: 108806, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34715090

RESUMO

Glaucoma is the second leading cause of blindness worldwide. This multifactorial, neurodegenerative group of diseases is characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons, leading to irreversible visual impairment and blindness. There is a huge unmet and urging need for the development of new and translatable strategies and treatment options to prevent this progressive loss of RGC. Accumulating evidence points towards a critical role of neuroinflammation, in particular microglial cells, in the pathogenesis of glaucoma. Leukotrienes are mediators of neuroinflammation and are involved in many neurodegenerative diseases. Therefore, we tested the leukotriene receptors CysLT1R/GPR17-selective antagonist Montelukast (MTK) for its efficacy to modulate the reactive state of microglia in order to ameliorate RGCs loss in experimental glaucoma. Ocular hypertension (OHT) was induced unilaterally by injection of 8 µm magnetic microbead (MB) into the anterior chamber of female Brown Norway rats. The contralateral, untreated eye served as control. Successful induction of OHT was verified by daily IOP measurement using a TonoLab rebound tonometer. Simultaneously to OHT induction, one group received daily MTK treatment and the control group vehicle solution by oral gavage. Animals were sacrificed 13-15 days after MB injection. Retina and optic nerves (ON) of OHT and contralateral eyes were analyzed by immunofluorescence with specific markers for RGCs (Brn3a), microglial cells/macrophages (Iba1 and CD68), and cysteinyl leukotriene pathway receptors (CysLT1R and GPR17). Protein labeling was documented by confocal microscopy and analyzed with ImageJ plugins. Further, mRNA expression of genes of the inflammatory and leukotriene pathway was analyzed in retinal tissue. MTK treatment resulted in a short-term IOP reduction at day 2, which dissipated by day 5 of OHT induction in MTK treated animals. Furthermore, MTK treatment resulted in a decreased activation of Iba1+ microglial cells in the retina and ON, and in a significantly increased RGC survival in OHT eyes. Within the retina, GPR17 and CysLT1R expression was demonstrated in single RCGs and in microglial cells respectively. Further, increased mRNA expression of pro-inflammatory genes was detected in OHT induced retinas. In the ON, OHT induction increased the number of GPR17+ cells, showing a trend of reduction following MTK treatment. This study shows for the first time a significantly increased RGC survival in an acute OHT model following treatment with the leukotriene receptor antagonist MTK. These results strongly suggest a neuroprotective effect of MTK and a potential new therapeutic strategy for glaucoma treatment.


Assuntos
Antagonistas de Leucotrienos/uso terapêutico , Microglia/metabolismo , Hipertensão Ocular/metabolismo , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Receptores de Leucotrienos/metabolismo , Células Ganglionares da Retina/fisiologia , Acetatos/uso terapêutico , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Sobrevivência Celular/fisiologia , Ciclopropanos/uso terapêutico , Modelos Animais de Doenças , Eletrorretinografia , Feminino , Regulação da Expressão Gênica/fisiologia , Pressão Intraocular/fisiologia , Proteínas dos Microfilamentos/metabolismo , Microscopia Confocal , Microscopia de Fluorescência , Hipertensão Ocular/fisiopatologia , Quinolinas/uso terapêutico , RNA Mensageiro/genética , Ratos , Ratos Endogâmicos BN , Reação em Cadeia da Polimerase em Tempo Real , Retina/metabolismo , Retina/fisiopatologia , Sulfetos/uso terapêutico , Tonometria Ocular , Fator de Transcrição Brn-3B/metabolismo
12.
Sci Rep ; 11(1): 9052, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33907301

RESUMO

Recently, we established silicone oil-induced ocular hypertension (SOHU) mouse model with significant glaucomatous neurodegeneration. Here we characterize two additional variations of this model that simulate two distinct glaucoma types. The first is a chronic model produced by high frequency (HF) pupillary dilation after SO-induced pupillary block, which shows sustained moderate IOP elevation and corresponding slow, mild glaucomatous neurodegeneration. We also demonstrate that although SO removal quickly returns IOP to normal, the glaucomatous neurodegeneration continues to advance to a similar degree as in the HF group without SO removal. The second, an acute model created by no pupillary dilation (ND), shows a greatly elevated IOP and severe inner retina degeneration at an early time point. Therefore, by a straightforward dilation scheme, we extend our original SOHU model to recapitulate phenotypes of two major glaucoma forms, which will be invaluable for selecting neuroprotectants and elucidating their molecular mechanisms.


Assuntos
Modelos Animais de Doenças , Glaucoma/patologia , Hipertensão Ocular/fisiopatologia , Degeneração Retiniana/patologia , Células Ganglionares da Retina/patologia , Óleos de Silicone/toxicidade , Doença Aguda , Animais , Feminino , Glaucoma/induzido quimicamente , Pressão Intraocular , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hipertensão Ocular/induzido quimicamente , Degeneração Retiniana/induzido quimicamente , Células Ganglionares da Retina/efeitos dos fármacos , Óleos de Silicone/administração & dosagem
13.
Proc Natl Acad Sci U S A ; 118(13)2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33753495

RESUMO

Activation of autophagy is one of the responses elicited by high intraocular pressure (IOP) and mechanical stretch in trabecular meshwork (TM) cells. However, the mechanosensor and the molecular mechanisms by which autophagy is induced by mechanical stretch in these or other cell types is largely unknown. Here, we have investigated the mechanosensor and downstream signaling pathway that regulate cyclic mechanical stretch (CMS)-induced autophagy in TM cells. We report that primary cilia act as a mechanosensor for CMS-induced autophagy and identified a cross-regulatory talk between AKT1 and noncanonical SMAD2/3 signaling as critical components of primary cilia-mediated activation of autophagy by mechanical stretch. Furthermore, we demonstrated the physiological significance of our findings in ex vivo perfused eyes. Removal of primary cilia disrupted the homeostatic IOP compensatory response and prevented the increase in LC3-II protein levels in response to elevated pressure challenge, strongly supporting a role of primary cilia-mediated autophagy in regulating IOP homeostasis.


Assuntos
Cílios/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Malha Trabecular/metabolismo , Autofagia , Células Cultivadas , Cílios/patologia , Técnicas de Silenciamento de Genes , Humanos , Pressão Intraocular/fisiologia , Microscopia Intravital , Mecanotransdução Celular/genética , Hipertensão Ocular/patologia , Hipertensão Ocular/fisiopatologia , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/genética , Proteína Smad2/genética , Proteína Smad3/genética , Estresse Mecânico , Imagem com Lapso de Tempo , Malha Trabecular/citologia , Malha Trabecular/patologia
14.
Invest Ophthalmol Vis Sci ; 62(1): 5, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33393971

RESUMO

Purpose: Loss of ganglion cell inner plexiform layer (GCIPL) and visual sensitivity in the macula region are known to occur at all stages of glaucoma. While both are dependent on the underlying retinal ganglion cells (RGCs), the relationship between structure and function is modest. We hypothesize that the imprecise relationship is due to a lack of direct correspondence between in vivo measures and RGC counts, as well as the relatively large stimulus size used by standard perimetry, which exceeds spatial summation. Methods: The relationship between optical coherence tomography (OCT)-derived GCIPL thickness and corresponding inner cell density from retinal flat mounts was determined for four nonhuman primates with varying stages of neuropathy. Normative data for 10-2 threshold using Goldman size I to V stimuli were established for 10 animals, 4 of which were then followed longitudinally with OCT and perimetry. The relationship between GCIPL volume, which incorporated stimulus size after removal of residual thickness, and differential light sensitivity was determined for both experimental glaucoma and healthy eyes. Results: Peak inner retinal cell density was 63,052 ± 9238 cells/mm2 in the healthy eye. Cell density was related to both GCIPL thickness and eccentricity (R2 = 0.74, P < .01). For all 10-2 eccentricities, size III stimuli were greater than the critical area (P < 0.01). Based on the structural and histologic relationship, the critical area corresponds to approximately 156 RGCs. Conclusions: The relationship between cell density and GCIPL thickness is dependent on retinal eccentricity. For 10-2 perimetry, perimetric loss, especially at earlier stages of neuropathy, may best be detected using size II or smaller stimuli.


Assuntos
Modelos Animais de Doenças , Glaucoma/fisiopatologia , Macula Lutea/patologia , Doenças do Nervo Óptico/fisiopatologia , Células Ganglionares da Retina/patologia , Acuidade Visual/fisiologia , Campos Visuais/fisiologia , Animais , Contagem de Células , Estudos Transversais , Glaucoma/diagnóstico por imagem , Pressão Intraocular/fisiologia , Terapia a Laser , Macaca mulatta , Macula Lutea/diagnóstico por imagem , Microscopia Confocal , Hipertensão Ocular/fisiopatologia , Disco Óptico/diagnóstico por imagem , Disco Óptico/patologia , Doenças do Nervo Óptico/diagnóstico por imagem , Tomografia de Coerência Óptica , Malha Trabecular/cirurgia , Testes de Campo Visual
15.
Curr Opin Ophthalmol ; 32(2): 141-147, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33470670

RESUMO

PURPOSE OF REVIEW: For decades, laser trabeculoplasty has been a well-proven therapeutic option in glaucoma management, and more recently, it has only gained in popularity. One reason for such popularity is that selective laser trabeculoplasty (SLT) is a therapy independent of patient adherence, which is typically low among glaucoma patients. Consequently, the number of studies on SLT has multiplied throughout the past years. This review provides an overview of studies on SLT from the last 12 months. RECENT FINDINGS: The studies on treatment outcome show a wide range of success rates of SLT reaching between 18 and 88%; however, study designs differ and many studies are not directly comparable. The prospective laser trabeculoplasty for open-angle glaucoma and ocular hypertension (LiGHT) trial has demonstrated good efficacy of SLT - 75% of the eyes achieved their target pressure without drops and 58% after a single SLT. SUMMARY: SLT has proven to be effective in lowering IOP with satisfactory success rates even after single SLT. SLT is repeatable independent of patient's adherence.


Assuntos
Glaucoma de Ângulo Aberto/cirurgia , Terapia a Laser/métodos , Lasers de Estado Sólido/uso terapêutico , Malha Trabecular/cirurgia , Trabeculectomia/métodos , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular/fisiologia , Hipertensão Ocular/fisiopatologia , Hipertensão Ocular/cirurgia
16.
Am J Ophthalmol ; 223: 149-158, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33049242

RESUMO

PURPOSE: We examined patients in a large clinical registry to assess factors associated with laser trabeculoplasty (LTP) responses. DESIGN: Retrospective cohort study. METHODS: StudyPopulation: LTP patients in the Intelligent Research in Sight (IRIS) Registry, 2013-2018. OBSERVATION: IRIS Registry data were extracted if the eye had a procedural code for LTP and a glaucoma diagnosis. Eyes were excluded if LTP laterality or baseline intraocular pressure (IOP) could not be determined. Following LTP, "nonresponders" were those with <20% IOP reduction after 8 weeks, while "responders" were those with ≥20% IOP reduction. MainOutcomeMeasures: Proportion of responders, odds ratios (OR) of pre-LTP factors associated with being a nonresponder. RESULTS: A total of 263,480 eyes were included, with mean age 71.4 ± 11.7 years. Mean baseline IOP was 19.1 ± 5.0 mm Hg, mean number of pre-LTP medications was 2.1 ± 1.5. Response rate was 36.9% overall and 68.8% for those with baseline IOP >24 mm Hg. Higher baseline IOP was associated with reduced odds of nonresponse (OR = 0.60, P < .0001 for a 3 mm Hg increase). Angle recession, uveitis, and aphakia increased the odds of a nonresponse (ORs 2.46, 1.50 (both P < .0001), and 1.55 (P = .0259), respectively). In nonresponders with at least 1 medication at baseline, 76.3% of eyes had fewer medications postoperatively. CONCLUSIONS: Lower baseline IOP, angle recession, uveitis, and aphakia were associated with increased odds of nonresponse. Future studies that analyze LTP responder survival and implementation lag would facilitate resource optimization in glaucoma therapy.


Assuntos
Glaucoma de Ângulo Aberto/cirurgia , Terapia a Laser/métodos , Malha Trabecular/cirurgia , Trabeculectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/fisiopatologia , Hipertensão Ocular/cirurgia , Sistema de Registros , Estudos Retrospectivos , Tonometria Ocular , Resultado do Tratamento
17.
Curr Eye Res ; 46(5): 689-693, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32985270

RESUMO

PURPOSE: To evaluate the effect of anterior migration of triamcinolone acetonide on intraocular pressure (IOP) elevation after posterior subtenon injection of triamcinolone acetonide (PSTA) for macular edema. METHODS: One hundred and ten eyes from 89 patients who received PSTA for macular edema were prospectively enrolled. The extent of anterior migration of triamcinolone acetonide was recorded immediately after the injection. If TA particles were visible in the subtenon space (or subconjunctival space), it was recorded as "anterior subtenon migration" (or "anterior subconjunctival migration"). The correlation between anterior migration of triamcinolone acetonide and severe IOP elevation, which was defined as an increase of 8 mm Hg or more in IOP, was evaluated. RESULTS: A total of 159 PSTAs were given to 110 eyes. After PSTA, anterior subtenon migration occurred in 70.4% and anterior subconjunctival migration occurred in 12.0% of injection. Severe IOP elevation occurred in 7.1% of those without anterior migration, in 25.9% of those with anterior subtenon migration, and in 31.6% of those with anterior subconjunctival migration after PSTA (P = .052). Compared to those without anterior migration of triamcinolone acetonide, the hazard ratio for severe IOP elevation was 3.307 in those with anterior subtenon migration (P = .12) and 5.289 in those with anterior subconjunctival migration (P = .042). CONCLUSIONS: Anterior migration of triamcinolone acetonide after PSTA predisposes eyes to severe IOP elevation. Careful injection to restrict the triamcinolone particle within the subtenon space and behind the equator may lower the rate of IOP elevation after PSTA.


Assuntos
Segmento Anterior do Olho/efeitos dos fármacos , Glucocorticoides/efeitos adversos , Pressão Intraocular/efeitos dos fármacos , Edema Macular/tratamento farmacológico , Hipertensão Ocular/induzido quimicamente , Triancinolona Acetonida/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Injeções Intraoculares , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/fisiopatologia , Estudos Prospectivos , Cápsula de Tenon/efeitos dos fármacos , Tonometria Ocular
18.
Curr Eye Res ; 46(5): 704-709, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33026255

RESUMO

PURPOSE: To evaluate the associations between medical check-up items (MCI) for fundus and intraocular pressure abnormality (FIPA) diseases in the Department of Health Management Centre, the Fifth Affiliated Hospital of Sun Yat-sen University (DHMC-FHS). PATIENTS AND METHODS: Individuals who visited DHMC-FHS and underwent MCI between June 2017 to May 2019 were included, 3237 subjects. A total of 356 participants were diagnosed as FIPA and enrolled. The general clinical characteristics were collected. Diseases for FIPA diagnosed included five cohort, high intraocular pressure, diabetic retinopathy, hypertension fundus arteriosclerosis, large eye cup, and high myopia fundus changes. Possible impact factors of MCI included blood routine, B-ultrasound, heart rate, hypertension, hyperlipidemia, standard vision, cerebral arteriosclerosis, body mass, arterial/carotid arteriosclerosis, etc. Further, the Pearson's correlation coefficients and logistic regression analyses were used to examine associations between MCI and FIPA. RESULTS: The weighted study population who belonged to FIPA included 356 subjects. There were significant differences in age, IOP, habitual exercise, smoking, sleep duration (P˂0.05) between FIPA and without FIPA. And RBC, Hemoglobin, B-ultrasound abnormal event, heart rate, systolic pressure, diastolic pressure, TC, LDL-C, standard vision, cerebral arteriosclerosis, body mass index, carotid arteriosclerosis were positively correlated with high intraocular pressure, hypertension fundus arteriosclerosis and high myopia fundus changes (P < .05). Possible prognosis risk factors, higher IOP, habitual exercise and more frequent smoking affect FIPA prognosis significantly [Odds ratio (OR) = 0.53, P = .01; OR = 0.13, P = .03; OR = 0.83; P = .04, respectively]. CONCLUSION: Of FIPA participants, high intraocular pressure, hypertension fundus arteriosclerosis and high myopia fundus changes were shown a positive relationship with MCI. Control IOP, habitual exercise and less frequent smoking were regarded as positive associations with decreased FIPA. These findings could help us prevent and diagnose FIPA diseases in time via MCI.


Assuntos
Arteriosclerose/diagnóstico , Retinopatia Diabética/diagnóstico , Fundo de Olho , Hipertensão/diagnóstico , Pressão Intraocular/fisiologia , Miopia Degenerativa/diagnóstico , Hipertensão Ocular/diagnóstico , Adulto , Idoso , Pressão Sanguínea/fisiologia , Colesterol/sangue , Estudos de Coortes , Estudos Transversais , Feminino , Frequência Cardíaca/fisiologia , Testes Hematológicos , Humanos , Hiperlipidemias/diagnóstico , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/fisiopatologia , Exame Físico , Fatores de Risco
19.
Br J Ophthalmol ; 105(2): 205-209, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32277009

RESUMO

BACKGROUND: To review the changes in intraocular pressure (IOP) following topical hypotensive medications washout in patients with primary open angle glaucoma (POAG), ocular hypertension (OHT) and uveitic glaucoma (UG)/OHT. METHODS: The study included 120 patients with POAG, OHT and UG recruited from prospective clinical trials between February 2013 and July 2017. We excluded 20 eyes with IOP of ≤21 mm Hg, 11 eyes with previous incisional surgery and 17 eyes with incomplete data. UG eyes with active inflammation and on steroid treatment were excluded. Participants underwent a 1-month washout period from topical ocular hypotensive medications before IOP phasing. Comparisons were made between pre/post-washout IOP, and highest-recorded (peak) and post-washout IOP. RESULTS: A total of 110 eyes with POAG, 33 eyes with OHT and 43 eyes with UG were included for analysis. The mean pre-washout IOP was 18.1±3.3 mm Hg in POAG, 18.8±3.3 mm Hg in OHT and 17.9±8.8 mm Hg in UG; the mean post-washout IOP was 26.6±4.8 mm Hg, 26.4±3.9 mm Hg, 23.1±10.1 mm Hg in POAG, OHT and UG, respectively. The mean increase in IOP after washout was significantly lower in UG compared with POAG and OHT eyes (p=0.01). The percentage of eyes with post-washout IOP <22 mm Hg was 12.7% in POAG, 6.1% in OHT and 51.2% in UG. CONCLUSION: Active inflammation and steroid treatment contributes to elevated IOP in uveitis. Therefore, IOP may revert to normal once inflammation subsides. We recommend ocular hypotensive treatment washout to be considered in UG eyes that have IOP under control in the absence of recurrence of uveitis.


Assuntos
Anti-Hipertensivos/uso terapêutico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Pressão Intraocular/fisiologia , Administração Oftálmica , Adulto , Idoso , Feminino , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/fisiopatologia , Soluções Oftálmicas , Estudos Prospectivos , Tonometria Ocular , Resultado do Tratamento , Uveíte/tratamento farmacológico , Uveíte/fisiopatologia , Acuidade Visual/fisiologia , Testes de Campo Visual , Campos Visuais/fisiologia , Suspensão de Tratamento
20.
Retina ; 41(7): 1438-1445, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33315814

RESUMO

PURPOSE: To analyze the incidence, risk factors, and time to onset of ocular hypertension (OHT) after intravitreal injections (IVI) of dexamethasone implant and to evaluate the long-term cumulative probability of intraocular pressure elevation. METHODS: Eyes of patients having received at least one dexamethasone implant IVI between October 2010 and February 2015 were included in the present study. Ocular hypertension was defined as intraocular pressure > 25 mmHg and/or an increase of 10 mmHg over the follow-up period compared with baseline intraocular pressure. RESULTS: Four hundred ninety-four eyes were studied in 410 patients. For a total of 1,371 IVI, the incidence of OHT was 32.6% in the study eyes with a mean follow-up period of 30 months (3-62.5) and a median follow-up of 29 months. Pressure-lowering treatment was introduced for 36.9% of eyes. Topical treatment alone was sufficient to manage OHT in 97%. Young age, male sex, uveitis and retinal vein occlusion, and glaucoma treated with a double- or triple-combination topical pressure-lowering medication were found to be risk factors for OHT. The incidence of OHT did not change with an increase in the number of IVI, and there was no cumulative effect, defining by an increase of the incidence of OHT in patients after repeated IVI (P = 0.248). CONCLUSION: This study confirmed that OHT is of moderate incidence, transient, controlled by topical treatment and provides data on the long-term cumulative probability of intraocular pressure elevation in a large cohort of eyes treated with dexamethasone implant IVI. Repeat injections of dexamethasone implant neither increase nor decrease the risk of OHT.


Assuntos
Dexametasona/efeitos adversos , Implantes de Medicamento/efeitos adversos , Pressão Intraocular/fisiologia , Hipertensão Ocular/epidemiologia , Medição de Risco/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Dexametasona/administração & dosagem , Feminino , Seguimentos , França/epidemiologia , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Incidência , Pressão Intraocular/efeitos dos fármacos , Injeções Intravítreas , Edema Macular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/induzido quimicamente , Hipertensão Ocular/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Adulto Jovem
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