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1.
Cell Mol Life Sci ; 80(7): 194, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37392222

RESUMO

Apolipoprotein J (APOJ) is a multifunctional protein with genetic evidence suggesting an association between APOJ polymorphisms and Alzheimer's disease as well as exfoliation glaucoma. Herein we conducted ocular characterizations of Apoj-/- mice and found that their retinal cholesterol levels were decreased and that this genotype had several risk factors for glaucoma: increased intraocular pressure and cup-to-disk ratio and impaired retinal ganglion cell (RGC) function. The latter was not due to RGC degeneration or activation of retinal Muller cells and microglia/macrophages. There was also a decrease in retinal levels of 24-hydroxycholesterol, a suggested neuroprotectant under glaucomatous conditions and a positive allosteric modulator of N-methyl-D-aspartate receptors mediating the light-evoked response of the RGC. Therefore, Apoj-/- mice were treated with low-dose efavirenz, an allosteric activator of CYP46A1 which converts cholesterol into 24-hydroxycholesterol. Efavirenz treatment increased retinal cholesterol and 24-hydroxycholesterol levels, normalized intraocular pressure and cup-to-disk ratio, and rescued in part RGC function. Retinal expression of Abcg1 (a cholesterol efflux transporter), Apoa1 (a constituent of lipoprotein particles), and Scarb1 (a lipoprotein particle receptor) was increased in EVF-treated Apoj-/- mice, indicating increased retinal cholesterol transport on lipoprotein particles. Ocular characterizations of Cyp46a1-/- mice supported the beneficial efavirenz treatment effects via CYP46A1 activation. The data obtained demonstrate an important APOJ role in retinal cholesterol homeostasis and link this apolipoprotein to the glaucoma risk factors and retinal 24-hydroxycholesterol production by CYP46A1. As the CYP46A1 activator efavirenz is an FDA-approved anti-HIV drug, our studies suggest a new therapeutic approach for treatment of glaucomatous conditions.


Assuntos
Glaucoma , Esteróis , Animais , Camundongos , Clusterina , Colesterol 24-Hidroxilase , Glaucoma/tratamento farmacológico , Glaucoma/genética
2.
Exp Eye Res ; 226: 109351, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36539052

RESUMO

α-Synuclein (α-Syn) is implicated in Parkinson's disease (PD), a neuromotor disorder with prominent visual symptoms. The underlying cause of motor dysfunction has been studied extensively, and is attributed to the death of dopaminergic neurons mediated in part by intracellular aggregation of α-Syn. The cause of visual symptoms, however, is less clear. Neuroretinal degeneration due to the presence of aggregated α-Syn has been reported, but the evidence is controversial. Other symptoms including those arising from primary open angle glaucoma (POAG) are believed to be the side-effects of medications prescribed for PD. Here, we explored the alternative hypothesis that dysfunction of α-Syn in the anterior eye alters the interaction between the actin cytoskeleton of trabecular meshwork (TM) cells with the extracellular matrix (ECM), impairing their ability to respond to physiological changes in intraocular pressure (IOP). A similar dysfunction in neurons is responsible for impaired neuritogenesis, a characteristic feature of PD. Using cadaveric human and bovine TM tissue and primary human TM cells as models, we report two main observations: 1) α-Syn is expressed in human and bovine TM cells, and significant amounts of monomeric and oligomeric α-Syn are present in the AH, and 2) primary human TM cells and human and bovine TM tissue endocytose extracellular recombinant monomeric and oligomeric α-Syn via the prion protein (PrPC), and upregulate fibronectin (FN) and α-smooth muscle actin (α-SMA), fibrogenic proteins implicated in POAG. Transforming growth factor ß2 (TGFß2), a fibrogenic cytokine implicated in ∼50% cases of POAG, is also increased, and so is RhoA-associated coiled-coil-containing protein kinase 1 (ROCK-1). However, silencing of α-Syn in primary human TM cells reduces FN, α-SMA, and ROCK-1 in the absence or presence of over-expressed active TGFß2, suggesting modulation of FN and ROCK-1 independent of, or upstream of TGFß2. These observations suggest that extracellular α-Syn modulates ECM proteins in the TM independently or via PrPC by activating the RhoA-ROCK pathway. These observations reveal a novel function of α-Syn in the anterior eye, and offer new therapeutic options.


Assuntos
Fibronectinas , Glaucoma de Ângulo Aberto , Animais , Bovinos , Humanos , alfa-Sinucleína/metabolismo , alfa-Sinucleína/farmacologia , Células Cultivadas , Fibronectinas/metabolismo , Glaucoma de Ângulo Aberto/genética , Glaucoma de Ângulo Aberto/metabolismo , Pressão Intraocular , Malha Trabecular/metabolismo , Fator de Crescimento Transformador beta2/farmacologia , Fator de Crescimento Transformador beta2/metabolismo
3.
Ophthalmology ; 129(7): 742-751, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35218867

RESUMO

PURPOSE: To present the 5-year results of the HORIZON trial comparing cataract surgery (CS) combined with an intracanalicular microstent with CS alone. DESIGN: Prospective, multicenter, controlled randomized clinical trial. PARTICIPANTS: Patients with cataract and primary open-angle glaucoma treated with 1 or more glaucoma medications, washed-out diurnal intraocular pressure (DIOP) of 22 to 34 mmHg, and no prior incisional glaucoma surgery. METHODS: Eyes were randomized 2:1 to receive a Hydrus Microstent (HMS; Ivantis, Inc) or no stent after successful CS. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), glaucoma medication use, repeat glaucoma surgery, visual acuity, visual field, procedure-related adverse events, and corneal endothelial cell counts. RESULTS: Three hundred sixty-nine eyes were randomized to HMS treatment, and 187 eyes were randomized to CS only. Study groups were well matched for preoperative IOP, medication use, washed-out DIOP, and glaucoma severity. Five-year follow-up was completed in 80% of patients. At 5 years, the HMS group included a higher proportion of eyes with IOP of 18 mmHg or less without medications than the CS group (49.5% vs. 33.8%; P = 0.003), as well as a greater likelihood of IOP reduction of 20% or more without medications than the CS group (54.2% vs. 32.8%; P < 0.001). The number of glaucoma medications was 0.5 ± 0.9 in the HMS group and 0.9 ± 0.9 in the CS group (P < 0.001), and 66% of eyes in the HMS group were medication free compared with 46% in the CS group (P < 0.001). The cumulative risk of incisional glaucoma surgery was lower in the HMS group (2.4% vs. 6.2%; P = 0.027, log-rank test). No clinical or statistically significant differences were found in the rate of endothelial cell loss from 3 to 60 months between the HMS and CS alone groups (P = 0.261). CONCLUSIONS: The addition of a Schlemm's canal microstent in conjunction with CS was safe, resulted in lowered IOP and medication use, and reduced the need for postoperative incisional glaucoma filtration surgery compared with CS after 5 years. Long-term presence of the implant did not affect the corneal endothelium adversely.


Assuntos
Catarata , Glaucoma de Ângulo Aberto , Glaucoma , Facoemulsificação , Catarata/complicações , Glaucoma/cirurgia , Glaucoma de Ângulo Aberto/cirurgia , Humanos , Pressão Intraocular , Facoemulsificação/métodos , Estudos Prospectivos , Stents
4.
Curr Opin Ophthalmol ; 33(2): 112-118, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35137708

RESUMO

PURPOSE OF REVIEW: This review discusses recent findings in surgical management of glaucoma, focusing on trabeculectomy and minimally invasive glaucoma surgery (MIGS). We discuss how the role these procedures play in conjunction with phacoemulsification. RECENT FINDINGS: New findings of the Primary Trab Vs Tube study and findings regarding the Hydrus, Xen 45, Kahook dual blade, Ab-interno Canaloplasty and head-to-head MIGS studies are summarized. SUMMARY: Patients with glaucoma greatly benefit from combining cataract surgery with a MIGS procedure that can be tailored to disease severity and medication use. Certain MIGS combined with phacoemulsification in severe and refractory glaucoma can potentially delay incisional glaucoma, although trabeculectomy- mitomycin C (MMC) still remains the best option in certain patient populations. We provide an update in the MIGS treatment paradigm based on newer, stronger evidence.


Assuntos
Extração de Catarata , Glaucoma , Facoemulsificação , Trabeculectomia , Glaucoma/cirurgia , Humanos , Pressão Intraocular , Procedimentos Cirúrgicos Minimamente Invasivos , Resultado do Tratamento
5.
Ophthalmology ; 128(6): 857-865, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33166551

RESUMO

PURPOSE: To report 3-year outcomes of the HORIZON study comparing cataract surgery (CS) with Hydrus Microstent (Ivantis, Inc) implantation versus CS alone. DESIGN: Multicenter randomized clinical trial. PARTICIPANTS: Five hundred fifty-six eyes from 556 patients with cataract and primary open-angle glaucoma (POAG) treated with 1 or more glaucoma medication, washed out diurnal intraocular pressure (IOP) of 22 to 34 mmHg, and no prior incisional glaucoma surgery. METHODS: After phacoemulsification, eyes were randomized 2:1 to receive a Hydrus Microstent or no stent. Follow-up included comprehensive eye examinations through 3 years. MAIN OUTCOME MEASURES: Outcome measures included IOP, medical therapy, reoperation rates, visual acuity, adverse events, and changes in corneal endothelial cell counts. RESULTS: Three hundred sixty-nine eyes were randomized to microstent treatment and 187 to CS only. Preoperative IOP, medication use, washed-out diurnal IOP, and glaucoma severity did not differ between the two treatment groups. At 3 years, IOP was 16.7 ± 3.1 mmHg in the microstent group and 17.0 ± 3.4 mmHg in the CS group (P = 0.85). The number of glaucoma medications was 0.4 ± 0.8 in the microstent group and 0.8 ± 1.0 in the CS group (P < 0.001), and 73% of microstent group eyes were medication free compared with 48% in the CS group (P < 0.001). The microstent group included a higher proportion of eyes with IOP of 18 mmHg or less without medications compared with the CS group (56.2% vs. 34.6%; P < 0.001), as well as IOP reduction of at least 20%, 30%, or 40% compared with CS alone. The cumulative probability of incisional glaucoma surgery was lower in the microstent group (0.6% vs. 3.9%; hazard ratio, 0.156; 95% confidence interval, 0.031-0.773; P = 0.020). No difference was found in postoperative corneal endothelial cell loss between groups. No procedure- or device-related serious adverse events resulting in vision loss occurred in either group. CONCLUSIONS: Combined CS and microstent placement for mild to moderate POAG is safe, more effective in lowering IOP with fewer medications, and less likely to result in further incisional glaucoma filtration surgery than CS alone at 3 years.


Assuntos
Catarata/complicações , Cirurgia Filtrante/métodos , Glaucoma de Ângulo Aberto/cirurgia , Pressão Intraocular/fisiologia , Facoemulsificação/métodos , Stents , Acuidade Visual , Seguimentos , Glaucoma de Ângulo Aberto/complicações , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Estudos Prospectivos , Desenho de Prótese , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do Tratamento
6.
Curr Opin Ophthalmol ; 32(2): 129-133, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395110

RESUMO

PURPOSE OF REVIEW: To discuss a new class of medication that has recently become available for the treatment of glaucoma; as well as share insights into developments in glaucoma medicine administration which has the potential to revolutionize medical therapy for glaucoma. RECENT FINDINGS: Newly available eye drops, netarsudil 0.02% and latanoprostene bunod 0.024%, are improving aqueous outflow through the conventional outflow tract. Other new developments in medical glaucoma are focused on alternative methods for sustained glaucoma medication delivery. SUMMARY: Newer medications may be able to extend the duration of medically controlled glaucoma, delaying or possibly eliminating the need of glaucoma surgery for some patients. Alternative methods of delivery for glaucoma medications may be a key factor in improving outcomes with currently available medications.


Assuntos
Anti-Hipertensivos/uso terapêutico , Benzoatos/uso terapêutico , Glaucoma/tratamento farmacológico , Pressão Intraocular/efeitos dos fármacos , Prostaglandinas F Sintéticas/uso terapêutico , beta-Alanina/análogos & derivados , Administração Oftálmica , Humanos , Soluções Oftálmicas , beta-Alanina/uso terapêutico , Quinases Associadas a rho/antagonistas & inibidores
7.
Ophthalmology ; 127(1): 52-61, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31034856

RESUMO

PURPOSE: To compare the efficacy of different microinvasive glaucoma surgery (MIGS) devices for reducing intraocular pressure (IOP) and medications in open-angle glaucoma (OAG). DESIGN: Prospective, multicenter, randomized clinical trial. PARTICIPANTS: One hundred fifty-two eyes from 152 patients aged 45 to 84 years with OAG, Shaffer angle grade III-IV, best-corrected visual acuity (BCVA) 20/30 or better, and IOP 23 to 39 mmHg after washout of all hypotensive medications. Eyes with secondary glaucoma other than pseudoexfoliative or pigmentary glaucoma, angle closure, previous incisional glaucoma surgery, or any significant ocular pathology other than glaucoma were excluded. INTERVENTION: Study eyes were randomized 1:1 to standalone MIGS consisting of either 1 Hydrus Microstent (Ivantis, Inc, Irvine, CA) or 2 iStent Trabecular Micro Bypass devices (Glaukos Inc, San Clemente, CA). Follow-up was performed 1 day, 1 week, and 1, 3, 6, and 12 months postoperatively. MAIN OUTCOME MEASURES: Within-group and between-group differences in IOP and medications at 12 months and complete surgical success defined as freedom from repeat glaucoma surgery, IOP 18 mmHg or less, and no glaucoma medications. Safety measures included the frequency of surgical complications, changes in visual acuity, slit-lamp findings, and adverse events. RESULTS: Study groups were well matched for baseline demographics, glaucoma status, medication use, and baseline IOP. Twelve-month follow-up was completed in 148 of 152 randomized subjects (97.3%). At 12 months, the Hydrus had a greater rate of complete surgical success (P < 0.001) and reduced medication use (difference = -0.6 medications, P = 0.004). More Hydrus subjects were medication free at 12 months (difference = 22.6% P = 0.0057). Secondary glaucoma surgery was performed in 2 eyes in the 2-iStent group (3.9%) and in none of the Hydrus eyes. Two eyes in the Hydrus group and 1 in the 2-iStent group had BCVA loss of ≥2 lines. CONCLUSION: Standalone MIGS in OAG with the Hydrus resulted in a higher surgical success rate and fewer medications compared with the 2-iStent procedure. The 2 MIGS devices have similar safety profiles.


Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma de Ângulo Aberto/cirurgia , Implantação de Prótese , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-Cego , Stents , Tonometria Ocular , Resultado do Tratamento , Acuidade Visual/fisiologia
8.
Exp Eye Res ; 194: 108019, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32222455

RESUMO

Bimatoprost, latanoprost, and unoprostone are prostaglandin F2α analogs (PGAs) and are used to lower intraocular pressure. We investigated the free acid effects of these three prostaglandin analogs: bimatoprost, latanoprost, and unoprostone on human matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP) in the trabecular meshwork (TM) cells. Immunoblot results show that all three PGAs generally increased MMPs-1,9 and TIMPs-4. Additionally, bimatoprost and latanoprost both increased MMP-3 and TIMP-2, while unoprostone had an indeterminate effect on both. Zymography results show that all three PGAs except unoprostone increased intermediate MMP-1 activity while bimatoprost and latanoprost increased MMP-9 activity. Together, these data suggest that the balance between MMPs and TIMPs correlate to the relative intraocular pressure lowering effectiveness observed in clinical studies of these PGAs.


Assuntos
Bimatoprost/farmacologia , Glaucoma de Ângulo Aberto/tratamento farmacológico , Latanoprosta/farmacologia , Inibidores de Metaloproteinases de Matriz/metabolismo , Metaloproteinases da Matriz/biossíntese , Compostos de Amônio Quaternário/farmacologia , Malha Trabecular/patologia , Adulto , Idoso , Anti-Hipertensivos/farmacologia , Células Cultivadas , Feminino , Glaucoma de Ângulo Aberto/metabolismo , Glaucoma de Ângulo Aberto/patologia , Humanos , Immunoblotting , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/farmacologia , Prostaglandinas A Sintéticas/farmacologia , Malha Trabecular/efeitos dos fármacos , Malha Trabecular/metabolismo , Adulto Jovem
10.
Exp Eye Res ; 171: 164-173, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29526795

RESUMO

Cultured trabecular meshwork (TM) cells are a valuable model system to study the cellular mechanisms involved in the regulation of conventional outflow resistance and thus intraocular pressure; and their dysfunction resulting in ocular hypertension. In this review, we describe the standard procedures used for the isolation of TM cells from several animal species including humans, and the methods used to validate their identity. Having a set of standard practices for TM cells will increase the scientific rigor when used as a model, and enable other researchers to replicate and build upon previous findings.


Assuntos
Técnicas de Cultura de Células , Separação Celular/métodos , Guias como Assunto , Malha Trabecular/citologia , Fatores Etários , Animais , Biomarcadores/metabolismo , Consenso , Feto , Humanos , Doadores de Tecidos , Preservação de Tecido , Coleta de Tecidos e Órgãos , Malha Trabecular/metabolismo
11.
Curr Opin Ophthalmol ; 29(1): 88-95, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29064837

RESUMO

PURPOSE OF REVIEW: This review discusses the options available to be used in conjunction with phacoemulsification cataract surgery to control intraocular pressure. We present a strategy for planning which surgery should be performed based on goals of care. RECENT FINDINGS: New clinical evidence for using the CyPass, Kahook and Xen45 devices has been published recently and is summarized. SUMMARY: Cataract and glaucoma frequently exist together. Because the field of glaucoma surgical care is expanding and cataract surgery is becoming progressively safer, it is important to frequently re-evaluate our treatment paradigms. We review and evaluate current studies and treatment options.


Assuntos
Extração de Catarata/métodos , Catarata/complicações , Cirurgia Filtrante/métodos , Glaucoma/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Glaucoma/complicações , Humanos
12.
Ophthalmology ; 127(4): e24-e25, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32200849
13.
Clin Ophthalmol ; 18: 1789-1795, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919403

RESUMO

To review the latest surgical advances and evolving clinical use of scleral bio-tissue for reinforcement in the eye and review the published literature on novel surgical applications of scleral allograft bio-tissue. Conventional surgical procedures for scleral reinforcement using homologous scleral allograft have been traditionally ab-externo interventions comprising of anterior or posterior reinforcement of the sclera for clinical indications such as trauma, scleromalacia, glaucoma drainage device coverage, scleral perforation, buckle repair as well as posterior reinforcement for pathologic myopia and staphyloma. There have been a few novel ab-interno uses of scleral bio-tissue for reinforcement in both retina and glaucoma. Over the last decade, there has been an increase in peer-reviewed publications on scleral reinforcement, reflecting more interest in its clinical applications. With favorable biological and biomechanical properties, scleral allograft may be an ideal substrate for an array of new applications and surgical uses.

14.
J Glaucoma ; 33(9): 671-678, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38874528

RESUMO

PRCIS: About one-fourth of survey respondents from an ASCRS database initiate treatment for primary open angle glaucoma (POAG) with laser trabeculoplasty. Factors impacting physicians' choice of laser versus topical treatment for POAG were explored. PURPOSE: To characterize primary treatment preferences (topical medication versus laser trabeculoplasty or intracameral sustained release implants) in primary open angle glaucoma (POAG) patients and determine factors related to primary intervention selection. METHODS: A 33-question survey was distributed to an American Society of Cataract and Refractive Surgery database on treatment choices made by ophthalmologists for POAG. Data collected included country of practice, years of practice, completion of glaucoma fellowship training, type of practice, and preference for the first line of treatment for POAG. Multiple logit regression was used to compare the effect of covariates on physicians' choice of either topical medication or laser trabeculoplasty for POAG. RESULTS: A total of 252 of 19,246 (1.3%) surveys were returned. Almost three-quarters of respondents used topical medication as the first line of treatment for POAG (73.6%), whereas 26.4% preferred to start with laser treatment. Significant variables associated with the selection of laser (vs. drops) are practicing in the United States (odds ratio [OR] 2.85; 95% CI, 1.33-6.10), the more recent completion of ophthalmology residency (OR 1.95; 95% CI, 1.00-3.77), the greater volume of minimally invasive glaucoma surgeries (MIGS) (OR 1.68; 95% CI, 1.18-2.40), and a glaucoma patient base greater than 25% (OR 2.21; 95% CI, 1.09-4.48). CONCLUSIONS: For the first-line treatment of POAG, laser trabeculoplasty is more likely to be preferred, over topical drops, by U.S. physicians who are relatively new in practice, who have a larger glaucoma patient base, and who perform more MIGS.


Assuntos
Anti-Hipertensivos , Glaucoma de Ângulo Aberto , Terapia a Laser , Oftalmologia , Padrões de Prática Médica , Trabeculectomia , Humanos , Glaucoma de Ângulo Aberto/cirurgia , Glaucoma de Ângulo Aberto/terapia , Padrões de Prática Médica/estatística & dados numéricos , Anti-Hipertensivos/uso terapêutico , Terapia a Laser/métodos , Inquéritos e Questionários , Estados Unidos , Pressão Intraocular/fisiologia , Implantes para Drenagem de Glaucoma , Feminino , Oftalmologistas/estatística & dados numéricos , Masculino , Soluções Oftálmicas
15.
Exp Eye Res ; 115: 106-12, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23806329

RESUMO

Accurate and reliable measurement of intraocular pressure (IOP) is crucial in the study of glaucoma using the mouse model. The purpose of this study was to determine the relationship between TonoLab-measured IOP and central corneal thickness (CCT) in mouse strains with single gene mutations of matricellular proteins. Wild-type (WT) and transgenic mouse strains with single gene mutations (KO) of thrombospondin-1 (TSP-1), thrombospondin-2 (TSP-2), osteopontin (OPN), hevin, and secreted protein acidic rich in cysteine (SPARC) were imaged at six weeks using optical coherence tomography (Stratus, Zeiss) to determine CCT. IOP was measured between 11am and 3pm using TonoLab, one week later. For all measurements, mice were anesthetized using intraperitoneal injection ketamine:xylazine. CCT and IOP were measured in 583 mice (TSP-1 n = 71 and 41, TSP-2 n = 60 and 32, OPN n = 81 and 50, hevin n = 59 and 76, SPARC n = 54 and 59, WT and KO, respectively). Mean CCT was 5-6% lower in three KO strains-TSP-1, OPN, and SPARC-compared to their corresponding WT (p = 1.55 × 10(-7), 1.63 × 10(-11), and 1.91 × 10(-7), respectively). The mean IOP was 8.3%, 6.6%, and 15.1% lower in three KO strains-TSP-1, TSP-2, and SPARC-compared to corresponding WT (p = 2.11 × 10(-5), 2.93 × 10(-3), and 3.76 × 10(-9), respectively. Linear regression of IOP versus CCT yielded no statistically significant within-strain correlations for TSP-1 (p = 0.12 and 0.073), TSP-2 (p = 0.473 and 0.92), OPN (p = 0.212 and 0.916), Hevin (p = 0.746 and 0.257), and SPARC (p = 0.080 and 0.056), reported as p-values considering a null hypothesis of zero slope (WT and KO, respectively). Neither C57-derived strains (TSP-1 and OPN) nor 129-derived strains (TSP-2, hevin, SPARC) demonstrated a correlation between mean IOP and mean CCT across different strains (p = 0.75 and p = 0.53, respectively). Taken together, these results indicate that CCT is not required to interpret TonoLab IOP readings in the mice when CCT varies 10% about the mean. This does not exclude the possibility of an IOP-CCT correlation for CCT values outside this range or for inter-strain comparisons where the mean CCT differs more than 10%.


Assuntos
Córnea/patologia , Proteínas do Olho/genética , Pressão Intraocular/fisiologia , Mutação , Tonometria Ocular/instrumentação , Animais , Proteínas de Ligação ao Cálcio/genética , Proteínas da Matriz Extracelular/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Osteonectina/genética , Osteopontina/genética , Trombospondina 1/genética , Trombospondinas/genética , Tomografia de Coerência Óptica
16.
Ophthalmol Glaucoma ; 6(6): 657-667, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37321374

RESUMO

PURPOSE: To examine the generalizability, discuss limitations, and critically appraise recommendations on the management of primary angle-closure suspects (PACSs) that emerged as a result of recent randomized clinical trials challenging the widely accepted clinical practice of offering laser peripheral iridotomy (LPI) to PACS patients. To synthetize findings from these and other studies. DESIGN: Narrative review. SUBJECTS: Patients classified as PACS. METHODS: The Zhongshan Angle-Closure Prevention (ZAP)-Trial and the Singapore Asymptomatic Narrow Angle Laser Iridotomy Study (ANA-LIS) along with accompanying publications were reviewed. Epidemiologic studies reporting on the prevalence of primary angle-closure glaucoma and other precursor forms of the disease were also analyzed along with publications reporting on the natural course of the disease or studies reporting on outcomes after prophylactic LPI. MAIN OUTCOME MEASURES: Incidence of progression to more severe forms of angle closure. RESULTS: Patients recruited in recent randomized clinical trials are asymptomatic, do not have cataracts, may be younger, and have, on average, deeper anterior chambers depth compared with patients treated with LPI in clinics. CONCLUSIONS: The ZAP-Trial and ANA-LIS clearly represent the best available data on PACS management, additional parameters however may need to be considered when physicians face patients in clinic. PACS patients encountered at tertiary referral centers may represent more advanced cases with respect to ocular biometric parameters and may be at higher risk for disease progression compared with those recruited through population-based screening. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Assuntos
Glaucoma de Ângulo Fechado , Iris , Humanos , Iris/cirurgia , Pressão Intraocular , Glaucoma de Ângulo Fechado/cirurgia , Glaucoma de Ângulo Fechado/diagnóstico , Procedimentos Cirúrgicos Oftalmológicos , Lasers
17.
Invest Ophthalmol Vis Sci ; 64(3): 15, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36877514

RESUMO

Purpose: The purpose of this study was to evaluate the effects of pharmacologically relevant bimatoprost and bimatoprost free acid (BFA) concentrations on matrix metalloproteinase (MMP) gene expression in cells from human aqueous outflow tissues. Methods: MMP gene expression by human trabecular meshwork (TM), scleral fibroblast (SF), and ciliary muscle (CM) cells exposed to 10 to 1000 µM bimatoprost or 0.1 to 10 µM BFA (intraocular concentrations after intracameral bimatoprost implant and topical bimatoprost dosing, respectively) was measured by polymerase chain reaction array. Results: Bimatoprost dose-dependently upregulated MMP1 and MMP14 mRNA in all cell types and MMP10 and MMP11 mRNA in TM and CM cells; in TM cells from normal eyes, mean MMP1 mRNA levels were 62.9-fold control levels at 1000 µM bimatoprost. BFA upregulated MMP1 mRNA only in TM and SF cells, to two- to three-fold control levels. The largest changes in extracellular matrix (ECM)-related gene expression by TM cells derived from normal (n = 6) or primary open-angle glaucoma (n = 3) eyes occurred with 1000 µM bimatoprost (statistically significant, ≥50% change for 9-11 of 84 genes on the array, versus 1 gene with 10 µM BFA). Conclusions: Bimatoprost and BFA had differential effects on MMP/ECM gene expression. Dramatic upregulation in MMP1 and downregulation of fibronectin, which occurred only with bimatoprost at high concentrations observed in bimatoprost implant-treated eyes, may promote sustained outflow tissue remodeling and long-term intraocular pressure reduction beyond the duration of intraocular drug bioavailability. Variability in bimatoprost-stimulated MMP upregulation among cell strains from different donors may help explain differential long-term responses of patients to bimatoprost implant.


Assuntos
Glaucoma de Ângulo Aberto , Pressão Intraocular , Humanos , Metaloproteinase 1 da Matriz/genética , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/cirurgia , Tonometria Ocular , Esclera , Bimatoprost/farmacologia
18.
Ophthalmology ; 119(1): 36-42, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21982416

RESUMO

PURPOSE: To compare the effect of ab interno trabeculectomy with trabeculectomy. DESIGN: Retrospective, cohort study. PARTICIPANTS: A total of 115 patients who underwent ab interno trabeculectomy (study group) compared with 102 patients who underwent trabeculectomy with intraoperative mitomycin as an initial surgical procedure (trabeculectomy group). Inclusion criteria were open-angle glaucoma, age ≥ 40 years, and uncontrolled on maximally tolerated medical therapy. Exclusion criterion was concurrent surgery. METHODS: Clinical variables were collected from patient medical records. MAIN OUTCOME MEASURES: Intraocular pressure (IOP) and Cox proportional hazard ratio (HR) and Kaplan-Meier survival analyses with failure defined as IOP >21 mmHg or less than 20% reduction below baseline on 2 consecutive follow-up visits after 1 month; IOP ≤ 5 mmHg on 2 consecutive follow-up visits after 1 month; additional glaucoma surgery; or loss of light perception vision. Secondary outcome measures include number of glaucoma medications and occurrence of complications. RESULTS: Mean follow-up was 27.3 and 25.5 months for the study and trabeculectomy groups, respectively. Intraocular pressure decreased from 28.1 ± 8.6 mmHg at baseline to 15.9 ± 4.5 mmHg (43.5% reduction) at month 24 in the study group, and from 26.3 ± 10.9 mmHg at baseline to 10.2 ± 4.1 mmHg (61.3% reduction) at month 24 in the trabeculectomy group. The success rates at 2 years were 22.4% and 76.1% in the study and trabeculectomy groups, respectively (P<0.001). Younger age (P = 0.037; adjusted HR, 0.98 per year; 95% confidence interval [CI], 0.97-0.99) and lower baseline IOP (P = 0.016; adjusted HR, 0.96 per 1 mmHg; 95% CI, 0.92-0.99) were significant risk factors for failure in the multivariate analysis of the study group. With the exception of hyphema, the occurrence of postoperative complications was more frequent in the trabeculectomy group (P<0.001). More additional glaucoma procedures were performed after ab interno trabeculectomy (43.5%) than after trabeculectomy (10.8%, P<0.001). CONCLUSIONS: Ab interno trabeculectomy has a lower success rate than trabeculectomy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.


Assuntos
Glaucoma de Ângulo Aberto/cirurgia , Malha Trabecular/cirurgia , Trabeculectomia/métodos , Adulto , Anti-Hipertensivos/administração & dosagem , Feminino , Seguimentos , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular/fisiologia , Masculino , Mitomicina/administração & dosagem , Complicações Pós-Operatórias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual/fisiologia
19.
Ophthalmology ; 119(3): 468-73, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22137043

RESUMO

PURPOSE: To compare the results of Glaucoma Progression Analysis (GPA, Carl Zeiss Meditec, Dublin, CA) to subjective expert consensus in the detection of glaucomatous visual field progression. DESIGN: Retrospective, observational case series. PARTICIPANTS: We included 100 eyes of 83 glaucoma patients. METHODS: Five serial Humphrey visual fields from 100 eyes of 83 glaucoma patients were evaluated by 5 masked glaucoma subspecialists for determination of progression. Four months later, with a randomly reordered patient sequence, the same visual field series were reevaluated by the same graders, at which time they had access to the Glaucoma Progression Analysis (GPA) printout. MAIN OUTCOME MEASURES: The level of agreement between majority expert consensus and GPA, both before and after access to GPA data, was assessed using kappa statistics. RESULTS: On initial review and on reevaluation with access to the GPA printout, the level of agreement between majority expert consensus and GPA was fair (kappa = 0.52, 95% confidence interval [CI], 0.35-0.69 and kappa = 0.62; 95% CI, 0.46-0.78, respectively). Expert consensus was more likely to classify a series of fields as showing progression than was GPA (P ≤ 0.002). There was good agreement between expert consensus on initial review and reevaluation 4 months later (kappa = 0.77; 95% CI, 0.65-0.90). CONCLUSIONS: The level of agreement between majority expert consensus of subjective determination of visual field progression and GPA is fair. In cases of disagreement with GPA, the expert consensus classification was usually progression. Access to the results of GPA did not significantly change the level of agreement between expert consensus and the GPA result; however, expert consensus did change in 11 of 100 cases.


Assuntos
Sistemas Inteligentes , Glaucoma de Ângulo Aberto/diagnóstico , Oftalmologia , Transtornos da Visão/diagnóstico , Campos Visuais , Progressão da Doença , Glaucoma de Ângulo Aberto/fisiopatologia , Humanos , Pressão Intraocular , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/fisiopatologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Software , Tonometria Ocular , Transtornos da Visão/fisiopatologia , Testes de Campo Visual
20.
J Cataract Refract Surg ; 48(1): 3-7, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34282070

RESUMO

In an online survey of >1200 global cataract surgeons, 66% were using intracameral (IC) antibiotic prophylaxis. This compared with 50% and 30% in the 2014 and 2007 surveys, respectively. Irrigation bottle infusion and intravitreal injection was each used by only 5% of respondents. For IC antibiotics, vancomycin was used by 6% in the United States (52% in 2014), compared with 83% for moxifloxacin (31% in 2014). Equal numbers used compounded moxifloxacin or the Vigamox bottle as the source. There was a decrease in respondents using preoperative (73% from 85%) and postoperative (86% from 97%) topical antibiotic prophylaxis; the latter was not used by 24% of surgeons injecting IC antibiotics. Reasons cited by those not using IC antibiotics include mixing/compounding risk (66%) and being unconvinced of the need (48%). However, 80% believe having a commercially approved IC antibiotic is important; if reasonably priced, this would increase adoption of IC prophylaxis to 93%.


Assuntos
Extração de Catarata , Catarata , Endoftalmite , Infecções Oculares Bacterianas , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Endoftalmite/tratamento farmacológico , Endoftalmite/prevenção & controle , Infecções Oculares Bacterianas/tratamento farmacológico , Infecções Oculares Bacterianas/prevenção & controle , Humanos , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/prevenção & controle , Inquéritos e Questionários
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