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1.
BMC Ophthalmol ; 22(1): 158, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35382777

RESUMO

BACKGROUND: Eyes with a short axial length or anterior chamber depth often develop narrowed anterior chamber angles in association with an enlarging crystalline lens. We report a case of a patient who presented in angle closure, with a distant history of prior intervention for congenital cataracts and was presumed to be aphakic. CASE PRESENTATION: A 78-year-old male presented with acute onset unilateral eye pain and blurred vision. He was found to have increased intraocular pressure, anteriorly bowed iris, and angle closure. Despite prior documentation of aphakia after treatment for congenital cataracts, detailed workup revealed residual crystalline lens material pushing the peripheral iris anteriorly. Further history confirmed that the patient underwent a procedure in the 1940's to remove lens material centrally but was not truly aphakic. The patient was treated with anterior chamber paracentesis and intraocular pressure lowering drops. His intraocular pressure remains controlled with medical therapy alone. CONCLUSIONS: Patients that appear to be aphakic centrally may still present with angle closure secondary to residual peripheral lens material. This case highlights the importance of keeping this etiology on the differential in a patient with presumed aphakia.


Assuntos
Afacia , Cristalino , Lentes Intraoculares , Idoso , Câmara Anterior , Humanos , Pressão Intraocular , Iris , Masculino
2.
J Neuroophthalmol ; 42(4): 470-475, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35916300

RESUMO

BACKGROUND: The identification of glaucomatous optic neuropathy in the setting of optic disc drusen (ODD) is a challenge, and the decision of whether to offer treatment in the form of intraocular pressure (IOP) reduction is controversial. Here, we present a series of patients with coexisting ocular hypertension and ODD to evaluate clinical features, treatment options, and progression of optic neuropathy. In addition, a review of the literature on ODD with elevated IOP is provided. METHODS: Six patients with ODD and a history of ocular hypertension are presented. Components of the examination and imaging modalities used to establish the diagnosis of ODD were recorded and a description of ocular hypertension history, glaucoma testing, and the potential treatment of IOP were also provided. RESULTS: In this series, 4 of 6 patients with concurrent ocular hypertension and ODD showed progression of optic neuropathy as assessed by visual field or retinal nerve fiber layer thickness. Of the 2 patients who did not show evidence of progression, 1 was treated with IOP-lowering medications and 1 was observed off treatment. Of the 4 patients who showed evidence of progression, all 4 were initially treated with IOP-lowering medications and 2 ultimately went on to have trabeculectomy surgery. In the patients with progressive optic neuropathy, lowering the IOP seemed to halt the progression suggesting there was a pressure-sensitive component. CONCLUSIONS: Distinguishing changes to the optic nerve, particularly the structural changes at the lamina cribrosa of true glaucomatous optic neuropathy in the setting of ODD, is a challenge. Careful consideration of risk factors including age, presenting features, progression indicators, and management goals is to be accounted for in the decision to offer treatment. We see the presence ODD in the patients with ocular hypertension as an additional risk for progressive changes to the nerve fiber layer and visual field that needs to be considered when determining whether to initiate therapy. Our data suggest that treatment of IOP in the patients with ocular hypertension with ODD and evidence of progression reduces the risk of further progression. Further work is needed to determine whether progression of optic neuropathy in the setting of coexisting ODD and ocular hypertension is related mechanistically to predominantly an ODD-type process, a glaucomatous process, or a combination thereof.


Assuntos
Glaucoma , Hipertensão Ocular , Drusas do Disco Óptico , Doenças do Nervo Óptico , Humanos , Drusas do Disco Óptico/complicações , Drusas do Disco Óptico/diagnóstico , Pressão Intraocular , Hipertensão Ocular/complicações , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/terapia , Glaucoma/complicações , Glaucoma/diagnóstico , Doenças do Nervo Óptico/complicações , Doenças do Nervo Óptico/diagnóstico , Doenças do Nervo Óptico/terapia
3.
J Neuroophthalmol ; 42(1): e159-e172, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34812759

RESUMO

BACKGROUND: To determine risk factors for postradiation optic atrophy (PROA) after plaque radiotherapy for uveal melanoma. METHODS: A single center, retrospective cohort study of patients diagnosed with uveal melanoma involving choroid and/or ciliary body treated with plaque between January 1, 2008, and December 31, 2016. Outcomes included development of PROA with pallor alone or with concomitant neuroretinal rim thinning (NRT). Cox regression analysis was performed to identify risk factors for PROA. RESULTS: Of 78 plaque-irradiated patients, PROA developed in 41 (53%), with concomitant NRT in 15 (19%). Risk factors for PROA of any type included presentation with worse visual acuity (odds ratio [95% confidence interval] 5.6 [2.3-14.1], P < 0.001), higher baseline intraocular pressure (IOP; 14 vs 16 mm Hg) (1.1 [1.0-1.2], P = 0.03), shorter tumor distance to optic disc (1.3 [1.2-1.5], P < 0.001) and foveola (1.2 [1.1-1.3], P < 0.001), subfoveal subretinal fluid (3.8 [2.0-7.1], P < 0.001), greater radiation prescription depth (1.3 [1.1-1.6], P = 0.002), dose to fovea (point dose) (1.01 [1.01-1.02], P < 0.001), and mean (1.02 [1.02-1.03], P < 0.001) and maximum dose to optic disc per 1 Gy increase (1.02 [1.01-1.03], P < 0.001). On multivariate modeling, dose to disc, baseline IOP, and subfoveal fluid remained significant. Subanalysis revealed risk factors for pallor with NRT of greater mean radiation dose to disc (1.03 [1.01-1.05], P = 0.003), higher maximum IOP (17 vs 20 mm Hg) (1.4 [1.2-1.7], P < 0.001), and subfoveal fluid (12 [2-63], P = 0.004). CONCLUSION: PROA may result in NRT in addition to optic disc pallor. Risk factors for PROA included higher radiation dose to optic disc, higher baseline IOP, and subfoveal fluid. Higher maximum IOP contributed to concomitant NRT.


Assuntos
Atrofia Óptica , Disco Óptico , Humanos , Pressão Intraocular , Melanoma , Disco Óptico/patologia , Palidez/patologia , Estudos Retrospectivos , Neoplasias Uveais
4.
Curr Opin Ophthalmol ; 32(3): 280-287, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33630786

RESUMO

PURPOSE OF REVIEW: This review explores metabolic syndrome (MetS) as a risk factor that accelerates aging in retinal neurons and may contribute to the neurodegeneration seen in glaucomatous optic neuropathy (GON) and age-related macular degeneration (AMD). RECENT FINDINGS: Both animal model experiments and epidemiologic studies suggest that metabolic stress may lead to aberrant regulation of a number of cellular pathways that ultimately lead to premature aging of the cell, including those of a neuronal lineage. SUMMARY: GON and AMD are each leading causes of irreversible blindness worldwide. Aging is a significant risk factor in the specific retinal neuron loss that is seen with each condition. Though aging at a cellular level is difficult to define, there are many mechanistic modifiers of aging. Metabolic-related stresses induce inflammation, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, alterations to the unfolded protein response, defects in autophagy, alterations to the microbiome, and deposition of advanced glycation end products that can all hasten the aging process. Due to the number of variables related to metabolic health, defining criteria to enable the study of risk factors at a population level is challenging. MetS is a definable constellation of related metabolic risk factors that includes enlarged waist circumference, dyslipidemia, systemic hypertension, and hyperglycemia. MetS has been associated with both GON and AMD and may contribute to disease onset and/or progression in each disease.


Assuntos
Senescência Celular/fisiologia , Síndrome Metabólica/metabolismo , Retina/metabolismo , Animais , Glaucoma/metabolismo , Humanos , Degeneração Macular/metabolismo , Doenças do Nervo Óptico/metabolismo , Estresse Oxidativo
5.
Graefes Arch Clin Exp Ophthalmol ; 258(7): 1533-1541, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32103333

RESUMO

PURPOSE: To determine the degree and rate of ptosis in patients undergoing glaucoma and cataract surgery. METHODS: Patients undergoing cataract extraction (CE), trabeculectomy, or glaucoma drainage device (GDD) placement, or a combination, were consecutively enrolled by a sole surgeon. Eyelid measurements, including margin reflex distance 1 (MRD1) and levator function, were obtained preoperatively and at 1 and 3 months postoperatively. Primary outcome measures were the change in MRD1 pre- vs postoperatively; percentage of patients with ptosis (defined as MRD1 < 2 mm pre- vs postoperatively). Secondary measures were the absolute change in MRD1 between groups, decrease in MRD1 of ≥ 2 mm, and change in levator function. RESULTS: In total, 104 eyes of 73 patients underwent CE, trabeculectomy, or GDD placement and completed at least 1-month follow-up; 93 eyes of 65 patients completed 3-month follow-up. MRD1 decreased significantly in trabeculectomy and GDD groups at 1 and 3 months postoperatively, while it did not change in the CE group. The GDD group had a significant increase in percentage of patients with ptosis at 3 months postoperatively. CONCLUSION: Patients who underwent glaucoma surgery, especially those who underwent GDD placement, were more likely to have postoperative ptosis than patients undergoing CE alone. High ptosis rates in patients undergoing glaucoma surgery may warrant preoperative counseling and post-operative referral to oculoplastic surgeons.


Assuntos
Segmento Anterior do Olho/cirurgia , Blefaroptose/epidemiologia , Pálpebras/diagnóstico por imagem , Glaucoma/cirurgia , Complicações Pós-Operatórias , Idoso , Blefaroptose/etiologia , China/epidemiologia , Pálpebras/cirurgia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Estudos Prospectivos , Fatores de Tempo
6.
Exp Eye Res ; 165: 175-181, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28974356

RESUMO

Retinal degenerations, including age-related macular degeneration and the retinitis pigmentosa family of diseases, are among the leading causes of legal blindness in the United States. We previously found that Stanniocalcin-1 (STC-1) reduced photoreceptor loss in the S334ter-3 and Royal College of Surgeons rat models of retinal degeneration. The results were attributed in part to a reduction in oxidative stress. Herein, we tested the hypothesis that long-term delivery of STC-1 would provide therapeutic rescue in more chronic models of retinal degeneration. To achieve sustained delivery, we produced an adeno-associated virus (AAV) construct to express STC-1 (AAV-STC-1) under the control of a retinal ganglion cell targeting promoter human synapsin 1 (hSYN1). AAV-STC-1 was injected intravitreally into the P23H-1 and S334ter-4 rhodopsin transgenic rats at postnatal day 10. Tissues were collected at postnatal day 120 for confirmation of STC-1 overexpression and histologic and molecular analysis. Electroretinography (ERG) was performed in a cohort of animals at that time. Overexpression of STC-1 resulted in a significant preservation of photoreceptors as assessed by outer nuclear thickness in the P23H-1 (P < 0.05) and the S334ter-4 (P < 0.005) models compared to controls. Additionally, retinal function was significantly improved in the P23H-1 model with overexpressed STC-1 as assessed by ERG analysis (scotopic b-wave P < 0.005 and photopic b-wave P < 0.05). Microarray analysis identified common downstream gene expression changes that occurred in both models. Genes of interest based on their function were selected for validation by quantitative real-time PCR and were significantly increased in the S334ter-4 model.


Assuntos
Dependovirus , Glicoproteínas/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Retinose Pigmentar/tratamento farmacológico , Animais , Modelos Animais de Doenças , Eletrorretinografia , Glicoproteínas/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Células Fotorreceptoras de Vertebrados/patologia , Ratos , Ratos Transgênicos , Retinose Pigmentar/patologia
7.
J Glaucoma ; 33(8): e64-e75, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39141409

RESUMO

Intraocular pressure is currently the only known reliable, modifiable risk factor for the development and progression of glaucoma. Other risk factors for glaucoma include increasing age, myopia, decreased central corneal thickness, and low corneal hysteresis (CH) measurements. Photoablative keratorefractive surgery including laser assisted in situ keratomileusis (LASIK) has become a common way to treat refractive error, with over 25 million procedures performed in the United States alone. Though myopic LASIK has been associated with a decrease in CH measurements, relatively little is known about the risk of LASIK on glaucoma onset and progression. Here we present an observational study of 4 consecutive relatively young and otherwise healthy glaucoma patients with a history of myopic LASIK who showed progression of paracentral visual field deficits at intraocular pressures of 12 mm Hg or less while being carefully monitored. Therefore, these patients required lower targets of intraocular pressure, in the single-digit range, to slow or halt progression. In this cohort, the average corneal hysteresis was more than 2 standard deviations below normal values. This series suggests that additional study into the association of LASIK and glaucoma is warranted, including the potential risk contribution of diminished CH. These studies may be particularly relevant as patients who underwent LASIK procedures in the early 2000s may now be at increased risk of glaucoma due to the risk factor of age.


Assuntos
Progressão da Doença , Pressão Intraocular , Ceratomileuse Assistida por Excimer Laser In Situ , Miopia , Tonometria Ocular , Campos Visuais , Humanos , Ceratomileuse Assistida por Excimer Laser In Situ/efeitos adversos , Pressão Intraocular/fisiologia , Campos Visuais/fisiologia , Miopia/cirurgia , Miopia/fisiopatologia , Masculino , Feminino , Adulto , Córnea/fisiopatologia , Transtornos da Visão/fisiopatologia , Transtornos da Visão/etiologia , Transtornos da Visão/diagnóstico , Testes de Campo Visual , Pessoa de Meia-Idade , Acuidade Visual/fisiologia , Fatores de Risco , Lasers de Excimer/uso terapêutico , Adulto Jovem
8.
Am J Ophthalmol Case Rep ; 34: 102003, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38384737

RESUMO

Purpose: Trabeculectomy surgery is a commonly performed procedure for treatment of glaucoma. While the goal is to lower intraocular pressure, over-filtration may cause hypotony with ocular structural changes and vision loss. Observations: A 53-year-old woman with primary open-angle glaucoma was referred to our service for further evaluation. The patient previously underwent trabeculectomy 9 years prior and was found to have a cataract and hypotony maculopathy in the right eye. Treatment options included cataract surgery alone, bleb revision alone, or combined cataract extraction and bleb revision. Biometry revealed corneal astigmatism in the right eye, and significant disparity in axial length between the two eyes. Since the axial length and corneal astigmatic changes were presumed to be at least partially reversible, measurements from the non-operative left eye influenced the lens selection for the hypotonous right eye. The patient underwent combined phacoemulsification and bleb revision. While IOP increased and hypotony was partly reversed, there was hyperopic and astigmatic refractive surprise after surgery.The patient subsequently underwent intraocular lens exchange using biometric values of the previously hypotonous eye and met the target post-operative refractive goal. Conclusions and importance: This case demonstrates changes to the axial length and ocular structure following longstanding hypotony maculopathy may be permanent, even after restoration of normotensive intraocular pressure.

9.
J Glaucoma ; 33(5): 370-374, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38129939

RESUMO

PRCIS: Damage to disposable selective laser trabeculoplasty (SLT) lenses correlated with the amount of total laser energy. Furthermore, greater lens damage was associated with diminished patient treatment response. PURPOSE: Disposable SLT lenses have been observed to be damaged during use by laser, potentially affecting therapeutic response. This study sought to identify factors associated with the magnitude of lens damage and its effect on treatment outcomes. PATIENT AND METHODS: We analyzed 113 eyes from 82 patients who underwent SLT between 2020 and 2021 at an American academic medical center. For each procedure, we recorded baseline patient characteristics, procedure settings, physician age (as a possible factor causing laser defocus due to accommodation), and area of lens damage. Treatment response was calculated as the difference between preoperative and postoperative intraocular pressure (IOP). RESULTS: Area of lens damage was associated with greater total laser energy ( r =0.34, P <0.001) and greater mean energy per application ( r =0.37, P <0.001). IOP reduction decreased with increasing lens damage ( r =-0.19, P =0.022). Lens damage was not associated with patient characteristics indicative of glaucoma severity or user settings (physician age and slit lamp used). Greater IOP reduction was associated with higher preop IOP ( r =0.46, P <0.001) and a smaller cup-to-disc ratio ( r =0.22, P =0.036). IOP reduction was not associated with retinal nerve fiber layer thickness, patient age, or the number of glaucoma medications. CONCLUSIONS: Increased laser damage to disposable SLT lenses was associated with diminished treatment effect. The amount of damage was correlated with total and average laser energy, but not patient or physician factors. Overall, these findings call for reconsideration of using disposable SLT lenses as part of routine practice.


Assuntos
Pressão Intraocular , Terapia a Laser , Trabeculectomia , Humanos , Trabeculectomia/métodos , Trabeculectomia/efeitos adversos , Pressão Intraocular/fisiologia , Feminino , Masculino , Terapia a Laser/métodos , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Glaucoma de Ângulo Aberto/cirurgia , Glaucoma de Ângulo Aberto/fisiopatologia , Equipamentos Descartáveis , Cristalino/cirurgia , Acuidade Visual/fisiologia , Glaucoma/cirurgia , Glaucoma/fisiopatologia , Tonometria Ocular
10.
Mayo Clin Proc Digit Health ; 2(1): 119-128, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38577703

RESUMO

Objective: To determine the appropriateness of ophthalmology recommendations from an online chat-based artificial intelligence model to ophthalmology questions. Patients and Methods: Cross-sectional qualitative study from April 1, 2023, to April 30, 2023. A total of 192 questions were generated spanning all ophthalmic subspecialties. Each question was posed to a large language model (LLM) 3 times. The responses were graded by appropriate subspecialists as appropriate, inappropriate, or unreliable in 2 grading contexts. The first grading context was if the information was presented on a patient information site. The second was an LLM-generated draft response to patient queries sent by the electronic medical record (EMR). Appropriate was defined as accurate and specific enough to serve as a surrogate for physician-approved information. Main outcome measure was percentage of appropriate responses per subspecialty. Results: For patient information site-related questions, the LLM provided an overall average of 79% appropriate responses. Variable rates of average appropriateness were observed across ophthalmic subspecialties for patient information site information ranging from 56% to 100%: cataract or refractive (92%), cornea (56%), glaucoma (72%), neuro-ophthalmology (67%), oculoplastic or orbital surgery (80%), ocular oncology (100%), pediatrics (89%), vitreoretinal diseases (86%), and uveitis (65%). For draft responses to patient questions via EMR, the LLM provided an overall average of 74% appropriate responses and varied by subspecialty: cataract or refractive (85%), cornea (54%), glaucoma (77%), neuro-ophthalmology (63%), oculoplastic or orbital surgery (62%), ocular oncology (90%), pediatrics (94%), vitreoretinal diseases (88%), and uveitis (55%). Stratifying grades across health information categories (disease and condition, risk and prevention, surgery-related, and treatment and management) showed notable but insignificant variations, with disease and condition often rated highest (72% and 69%) for appropriateness and surgery-related (55% and 51%) lowest, in both contexts. Conclusion: This LLM reported mostly appropriate responses across multiple ophthalmology subspecialties in the context of both patient information sites and EMR-related responses to patient questions. Current LLM offerings require optimization and improvement before widespread clinical use.

12.
Mol Ther ; 20(11): 2143-52, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22929658

RESUMO

Mesenchymal stem/progenitor cells (MSCs) were reported to enhance the survival of cellular and organ transplants. However, their mode of action was not established. We here used a mouse model of corneal allotransplantation and demonstrated that peri-transplant intravenous (i.v.) infusion of human MSCs (hMSCs) decreased the early surgically induced inflammation and reduced the activation of antigen-presenting cells (APCs) in the cornea and draining lymph nodes (DLNs). Subsequently, immune rejection was decreased, and allograft survival was prolonged. Quantitative assays for human GAPDH revealed that <10 hMSCs out of 1 × 10(6) injected cells were recovered in the cornea 10 hours to 28 days after i.v. infusion. Most of hMSCs were trapped in lungs where they were activated to increase expression of the gene for a multifunctional anti-inflammatory protein tumor necrosis factor-α stimulated gene/protein 6 (TSG-6). i.v. hMSCs with a knockdown of TSG-6 did not suppress the early inflammation and failed to prolong the allograft survival. Also, i.v. infusion of recombinant TSG-6 reproduced the effects of hMSCs. Results suggest that hMSCs improve the survival of corneal allografts without engraftment and primarily by secreting TSG-6 that acts by aborting early inflammatory responses. The same mechanism may explain previous reports that MSCs decrease rejection of other organ transplants.


Assuntos
Transplante de Córnea/métodos , Rejeição de Enxerto/prevenção & controle , Transplante de Células-Tronco Mesenquimais , Administração Intravenosa , Animais , Anti-Inflamatórios/administração & dosagem , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/fisiologia , Moléculas de Adesão Celular/administração & dosagem , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Células Cultivadas , Córnea/imunologia , Córnea/metabolismo , Córnea/patologia , Feminino , Técnicas de Silenciamento de Genes , Rejeição de Enxerto/imunologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Pulmão/imunologia , Pulmão/patologia , Linfonodos/imunologia , Linfonodos/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , RNA Interferente Pequeno/genética , Transdução de Sinais , Transcriptoma , Transplante Homólogo
13.
Mol Ther ; 20(4): 788-97, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22294148

RESUMO

Oxidative stress and photoreceptor apoptosis are prominent features of many forms of retinal degeneration (RD) for which there are currently no effective therapies. We previously observed that mesenchymal stem/stromal cells reduce apoptosis by being activated to secrete stanniocalcin-1 (STC-1), a multifunctional protein that reduces oxidative stress by upregulating mitochondrial uncoupling protein-2 (UCP-2). Therefore, we tested the hypothesis that intravitreal injection of STC-1 can rescue photoreceptors. We first tested STC-1 in the rhodopsin transgenic rat characterized by rapid photoreceptor loss. Intravitreal STC-1 decreased the loss of photoreceptor nuclei and transcripts and resulted in measurable retinal function when none is otherwise present in this rapid degeneration. We then tested STC-1 in the Royal College of Surgeons (RCS) rat characterized by a slower photoreceptor degeneration. Intravitreal STC-1 reduced the number of pyknotic nuclei in photoreceptors, delayed the loss of photoreceptor transcripts, and improved function of rod photoreceptors. Additionally, STC-1 upregulated UCP-2 and decreased levels of two protein adducts generated by reactive oxygen species (ROS). Microarrays from the two models demonstrated that STC-1 upregulated expression of a similar profile of genes for retinal development and function. The results suggested that intravitreal STC-1 is a promising therapy for various forms of RD including retinitis pigmentosa and atrophic age-related macular degeneration (AMD).


Assuntos
Glicoproteínas/farmacologia , Degeneração Retiniana/tratamento farmacológico , Animais , Eletrorretinografia , Ensaio de Imunoadsorção Enzimática , Humanos , Canais Iônicos/genética , Canais Iônicos/metabolismo , Degeneração Macular/tratamento farmacológico , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Degeneração Retiniana/metabolismo , Células Fotorreceptoras Retinianas Bastonetes/efeitos dos fármacos , Células Fotorreceptoras Retinianas Bastonetes/metabolismo , Retinose Pigmentar/tratamento farmacológico , Proteína Desacopladora 2
14.
Proc Natl Acad Sci U S A ; 107(39): 16875-80, 2010 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-20837529

RESUMO

Previous reports demonstrated that adult stem/progenitor cells from bone marrow (multipotent mesenchymal stem cells; MSCs) can repair injured tissues with little evidence of engraftment or differentiation. In exploring this phenomenon, our group has recently discovered that the therapeutic benefits of MSCs are in part explained by the cells being activated by signals from injured tissues to express an anti-inflammatory protein TNF-α-stimulated gene/protein 6 (TSG-6). Therefore, we elected to test the hypothesis that TSG-6 would have therapeutic effects in inflammatory but noninfectious diseases of the corneal surface. We produced a chemical and mechanical injury of the cornea in rats by brief application of 100% ethanol followed by mechanical debridement of corneal and limbal epithelium. Recombinant human TSG-6 or PBS solution was then injected into the anterior chamber of the eye. TSG-6 markedly decreased corneal opacity, neovascularization, and neutrophil infiltration. The levels of proinflammatory cytokines, chemokines, and matrix metalloproteinases were also decreased. The data indicated that TSG-6, a therapeutic protein produced by MSCs in response to injury signals, can protect the corneal surface from the excessive inflammatory response following injury.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Moléculas de Adesão Celular/uso terapêutico , Córnea/efeitos dos fármacos , Neovascularização da Córnea/tratamento farmacológico , Ceratite/tratamento farmacológico , Animais , Câmara Anterior/efeitos dos fármacos , Câmara Anterior/patologia , Córnea/patologia , Lesões da Córnea , Neovascularização da Córnea/patologia , Ceratite/induzido quimicamente , Ceratite/patologia , Masculino , Ratos , Ratos Endogâmicos Lew
15.
J Glaucoma ; 32(9): 762-768, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37406302

RESUMO

PRCIS: When comparing patients on systemic immunosuppressive therapy to those without, there was no difference in intraocular pressure (IOP) early after SLT; however, at 1 year following SLT, IOP was higher in the immunosuppression group compared with controls. PURPOSE: To determine whether patients taking systemic immunosuppressive medications have a different IOP-lowering response to selective laser trabeculoplasty (SLT) compared with a control group of patients. METHODS: All patients who underwent SLT at Mayo Clinic 2017-2021 were identified. Patients on systemic immunosuppressive medications at the time of SLT were compared with control patients not receiving systemic immunosuppressive medications. The primary endpoints of this study were the percentage IOP reduction at 1 to 2, 3 to 6, and 12 months. Additional analyses included the percentage of patients who did not require additional therapy at each time point. RESULTS: There were 108 eyes of 72 patients that underwent SLT in the immunosuppressed group and 1997 eyes of 1417 patients in the control group. There was no significant difference in age-adjusted change in IOP between groups at the first postoperative visit 1 to 2 months following SLT (-18.8±20.7% vs. -16.0±16.5%, P =0.256) or 3-6 months following SLT (-15.2±21.6% vs. -18.3±23.2%, P =0.062). However, at 12 months following SLT, the IOP reduction in the immunosuppressive therapy group was significantly less compared with the control group (-15.1±21.2% vs. -20.3±22.9%, P =0.045). There was no difference between groups in the number of additional treatments during the study intervals. CONCLUSION: Patients in the systemic immunosuppressive therapy group showed equivalent early IOP-lowering after SLT compared with a control group, but the treatment response was diminished at 1 year. Further studies investigating IOP regulation after SLT in immunosuppressed patients are needed.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Hipotensão Ocular , Trabeculectomia , Humanos , Lactente , Pressão Intraocular , Anti-Hipertensivos/uso terapêutico , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Hipotensão Ocular/tratamento farmacológico , Lasers de Estado Sólido/uso terapêutico , Resultado do Tratamento
17.
Stem Cells ; 29(10): 1572-9, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21837654

RESUMO

Previous reports demonstrated that the deleterious effects of chemical injury to the cornea were ameliorated by local or systemic administration of adult stem/progenitor cells from bone marrow referred to as mesenchymal stem or stromal cells (MSCs). However, the mechanisms for the beneficial effects of MSCs on the injured cornea were not clarified. Herein, we demonstrated that human MSCs (hMSCs) were effective in reducing corneal opacity and inflammation without engraftment after either intraperitoneal (i.p.) or intravenous (i.v.) administration following chemical injury to the rat cornea. A quantitative assay for human mRNA for glyceraldehyde 3-phosphate dehydrogenase (GAPDH) demonstrated that less than 10 hMSCs were present in the corneas of rats 1-day and 3 days after i.v. or i.p. administration of 1 × 10(7) hMSCs. In vitro experiments using a transwell coculture system demonstrated that chemical injury to corneal epithelial cells activated hMSCs to secrete the multipotent anti-inflammatory protein TNF-α stimulated gene/protein 6 (TSG-6). In vivo, the effects of i.v. injection of hMSCs were largely abrogated by knockdown of TSG-6. Also, the effects of hMSCs were essentially duplicated by either i.v. or topical administration of TSG-6. Therefore, the results demonstrated that systemically administered hMSCs reduce inflammatory damage to the cornea without engraftment and primarily by secretion of the anti-inflammatory protein TSG-6 in response to injury signals from the cornea.


Assuntos
Moléculas de Adesão Celular/metabolismo , Córnea/imunologia , Opacidade da Córnea/terapia , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Células-Tronco Mesenquimais/imunologia , Animais , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/imunologia , Técnicas de Cocultura , Lesões da Córnea , Ensaio de Imunoadsorção Enzimática , Epitélio Corneano/imunologia , Epitélio Corneano/lesões , Técnicas de Silenciamento de Genes , Humanos , Injeções Intraperitoneais , Injeções Intravenosas , Masculino , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , RNA Interferente Pequeno , Ratos , Ratos Endogâmicos Lew , Transfecção
18.
J Glaucoma ; 31(6): e32-e36, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35649259

RESUMO

Trabeculectomy surgery remains the gold standard incisional glaucoma surgical procedure in many practices, particularly for patients requiring intraocular pressure (IOP) in the low teens or below. However, trabeculectomy surgery is associated with complications including leakage, over filtration, or fibrosis of the surgical bleb. Morphology of the surgical bleb is an important predictor of surgical success defined as long-term IOP reduction with minimal to no complications. There have been many, often subtle, variations in the surgical technique in hopes of improving long-term IOP reduction. However, fewer changes have been implemented specifically to modify bleb morphology. In our surgical practice, we began performing a thorough dissection and advancement of Tenon's layer with incorporation into the conjunctival closure in a 2-layered manner. This technique allowed flow of aqueous to a delineated potential space between sclera and Tenon's layer. Our clinical observations were improved bleb morphology characterized by diffuse, low-lying blebs with nonischemic overlying conjunctiva compared with those performed with a more traditional trabeculectomy technique. Since we incorporated this change into our practice at a defined time, we have a small number of patients in our practice that had a more traditional trabeculectomy technique in the fellow eye. Therefore, in our surgical practice, a small number of patients had trabeculectomy in 1 eye before implementation of this new technique, and then had trabeculectomy in the fellow eye after this technique was adopted, providing opportunity for comparison of bleb morphology with and without Tenon advancement. In series we present two representative, index cases and describe our surgical technique.


Assuntos
Glaucoma , Hipotensão Ocular , Trabeculectomia , Adolescente , Humanos , Glaucoma/complicações , Glaucoma/cirurgia , Pressão Intraocular , Hipotensão Ocular/cirurgia , Reoperação/métodos , Estudos Retrospectivos , Esclera/cirurgia , Trabeculectomia/efeitos adversos
19.
J Glaucoma ; 31(1): 15-22, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34731871

RESUMO

PRCIS: Multiple systemic vascular-associated conditions including systemic hypertension and hypotension, diabetes mellitus, migraine headache, peripheral vascular disease, Raynaud syndrome, and anemia were associated with low-tension glaucoma. PURPOSE: The purpose of this study was to identify systemic risk factors associated with low-tension glaucoma. PATIENTS AND METHODS: A retrospective case-control study design was employed to identify patients seen at the Mayo Clinic Department of Ophthalmology between 2005 and 2015 with low-tension glaucoma and an age-matched and sex-matched control group, each containing 277 patients. RESULTS: The low-tension glaucoma group had more myopic refractive errors (-1.6 vs. -1.0 D, P<0.001), lower intraocular pressure (14.2 vs. 15.2 mm Hg, P<0.001), and a higher cup-to-disc ratio (0.7 vs. 0.3, P<0.001). The low-tension glaucoma group was significantly less likely to be obese (body mass index >30, P=0.03). This group had a significantly higher prevalence of systemic hypertension [odds ratio (OR): 1.64, P=0.004], diabetes mellitus (OR: 3.01, P<0.001), peripheral vascular disease (OR: 2.61, P=0.009), migraine headache (OR: 2.12, P=0.02), anemia (OR: 2.18, P=0.003), systemic hypotension (OR: 4.43, P<0.001), Raynaud syndrome (OR: 3.09, P=0.05), and angiotensin-converting enzyme inhibitor (OR: 1.64, P=0.01) or calcium channel blocker use (OR: 1.98, P=0.004). After adjusting for systemic hypertension, calcium channel blocker use remained significant (OR: 1.70, P=0.03). No significant difference was found between groups with respect to hyperlipidemia, obstructive sleep apnea, coronary artery disease, carotid stenosis, stroke, or statin, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, beta-blocker, or metformin use. CONCLUSIONS: Multiple vascular-associated conditions were associated with low-tension glaucoma including systemic hypertension, diabetes mellitus, peripheral vascular disease, migraine headache, Raynaud syndrome, anemia, systemic hypotension, and calcium channel blocker use. This study strengthens the evidence for the vascular hypothesis of low-tension glaucoma.


Assuntos
Pressão Intraocular , Glaucoma de Baixa Tensão , Estudos de Casos e Controles , Humanos , Glaucoma de Baixa Tensão/epidemiologia , Estudos Retrospectivos , Fatores de Risco
20.
J Glaucoma ; 31(6): e18-e31, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34860182

RESUMO

PRCIS: For patients with glaucoma, metabolic syndrome was associated with higher intraocular pressure and greater central corneal thickness. Patients with metabolic syndrome were more likely to have ocular hypertension. PURPOSE: The purpose of this study was to determine whether glaucomatous optic neuropathy, also known as glaucoma, and ocular hypertension are more likely to occur in patients with metabolic syndrome. PATIENTS AND METHODS: Patients in Olmsted County, MN, were identified as having metabolic syndrome based on diagnosis codes, laboratory values, and/or medication use to meet 3 or more of the 5 standard criteria for diagnosing metabolic syndrome: systemic hypertension, hyperglycemia, hypertriglyceridemia, reduced high-density lipoprotein cholesterol, and central adiposity defined by increased body mass index. Patients with glaucoma, including primary open angle, low tension, pigment dispersion, and pseudoexfoliation, were identified using diagnostic codes. The charts of patients with glaucoma were individually reviewed to collect visual acuity, intraocular pressure, cup to disc ratio, central corneal thickness, visual field mean deviation, retinal nerve fiber layer thickness, and treatment of intraocular pressure. Patients with ocular hypertension were separately identified and similarly evaluated. RESULTS: For patients with glaucoma, those with metabolic syndrome had higher intraocular pressure and greater central corneal thickness compared with those without metabolic syndrome. After adjustment for central corneal thickness, there was no longer a significant difference in intraocular pressure between groups. Metabolic syndrome was also associated with the diagnosis of ocular hypertension, and although central corneal thickness trended higher in patients with metabolic syndrome, it did not attain statistical significance. CONCLUSION: In Olmsted County, though metabolic syndrome was associated with ocular hypertension and higher intraocular pressure in patients with glaucoma, the results were likely related to a thicker central corneal in this patient population.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Síndrome Metabólica , Hipertensão Ocular , Córnea , Glaucoma/complicações , Glaucoma/diagnóstico , Glaucoma/epidemiologia , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/epidemiologia , Humanos , Pressão Intraocular , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/epidemiologia , Estados Unidos/epidemiologia
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