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1.
Int Ophthalmol ; 44(1): 311, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963456

RESUMO

PURPOSE: To study the effect of brimonidine on vascular density and flow index of optic nerve head (ONH) and macula in primary open angle glaucoma (POAG) using optical coherence tomography angiography (OCTA). METHODS: Twenty-three brimonidine-naïve POAG patients were started on brimonidine. They underwent OCTA ONH and macula before commencing brimonidine and one month thereafter. Systemic arterial blood pressure (SABP) and intraocular pressure (IOP) were measured at each visit to calculate mean ocular perfusion pressure (MOPP). The OCT angiograms were analyzed using ImageJ software to calculate ONH and macular flow indices. RESULTS: Thirty-seven eyes (23 patients) with a mean age of 56.7 ± 12.49 years were included of whom 60.8% were males. Brimonidine was associated with an increase in the superficial flow index (SFI) (P-value = 0.02) and optic nerve head flow index (ONHFI) (P-value = 0.01). Also, superficial vascular density (SVD) for whole image, superior-hemi and fovea increased (P-value = 0.03, 0.02, 0.03 respectively). ONH inferior-hemi vascular density decreased (P-value = 0.01) despite an increase in inferior quadrant retinal nerve fiber layer thickness (RNFLT) (P-value = 0.03). There was no statistically significant correlation between flow indices and MOPP at baseline and follow-up. A moderate negative correlation was found between SVD and DVD at the fovea and MOPP at baseline and follow-up (P-value = 0.03, 0.05) (P-value = 0.02, 0.01) respectively. CONCLUSIONS: Brimonidine was associated with an increase in SFI, ONHFI and SVD indicating improved GCC and RNFL perfusion in POAG. Despite the increase in inferior quadrant RNFLT, the concomitant decrease in inferior-hemi ONHVD precluded a conclusion of hemodynamically-mediated improvement of RNFLT.


Assuntos
Tartarato de Brimonidina , Angiofluoresceinografia , Glaucoma de Ângulo Aberto , Pressão Intraocular , Macula Lutea , Disco Óptico , Vasos Retinianos , Tomografia de Coerência Óptica , Humanos , Glaucoma de Ângulo Aberto/fisiopatologia , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/diagnóstico , Masculino , Disco Óptico/irrigação sanguínea , Tartarato de Brimonidina/administração & dosagem , Tartarato de Brimonidina/farmacologia , Tartarato de Brimonidina/uso terapêutico , Pessoa de Meia-Idade , Feminino , Tomografia de Coerência Óptica/métodos , Macula Lutea/irrigação sanguínea , Macula Lutea/diagnóstico por imagem , Pressão Intraocular/fisiologia , Pressão Intraocular/efeitos dos fármacos , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/fisiopatologia , Vasos Retinianos/efeitos dos fármacos , Angiofluoresceinografia/métodos , Fluxo Sanguíneo Regional/fisiologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Idoso , Fundo de Olho , Estudos Prospectivos , Campos Visuais/fisiologia , Células Ganglionares da Retina/patologia , Células Ganglionares da Retina/efeitos dos fármacos , Anti-Hipertensivos/uso terapêutico , Fibras Nervosas/patologia , Fibras Nervosas/efeitos dos fármacos , Adulto , Seguimentos
2.
Exp Eye Res ; : 110000, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38992852

RESUMO

Glaucoma is the leading cause of irreversible blindness worldwide. Previous observational studies have suggested a relationship between central corneal thickness (CCT) and glaucoma; however, the results are inconsistent. This study aimed to investigate whether CCT is associated with a risk for developing open-angle glaucoma (OAG). We employed two-sample Mendelian randomization to assess the relationship between CCT and OAG, namely, primary open-angle glaucoma (POAG) and suspected glaucoma. Genetic instruments composed of variants associated with CCT at genome-wide significance (P <5×10-8) were obtained from published genome-wide association studies from Iglesias et al. for discovery and Bonnemaijer et al. for replication. Summary-level statistics for these instruments for the OAG were obtained from the FinnGen Project (Release 10). Inverse-variance-weighted regression of genetic susceptibility predicted that increased CCT was positively associated with an increased risk for POAG (odds ratio [OR], 1.005; 95% confidence interval [CI], 1.002-1.008; P=0.001) and suspected glaucoma (OR, 1.006; 95% CI, 1.003-1.009; P<0.001). In the replication sample of CCT, increased CCT was also positively associated with an increased risk for POAG (OR, 1.004; 95% CI, 1.000-1.008; P=0.029) and suspected glaucoma (OR, 1.005; 95% CI, 1.001-1.008; P=0.013). We found genetic evidence supporting a potential causal association between increased CCT and the risk of POAG and suspected glaucoma in the European population. This findings indicates the clinical significance of CCT in the diagnosis and treatment of glaucoma. Further studies are needed to elucidate the underlying mechanisms of this causal relationship.

3.
Int Ophthalmol ; 44(1): 317, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38972018

RESUMO

PURPOSE: To evaluate and compare the long-term outcomes of canaloplasty and phaco-canaloplasty in the treatment of open angle glaucoma and assess the prognostic factors associated with surgical outcome. METHODS: A 48-month retrospective analysis was performed on n = 133 open angle glaucoma eyes treated with canaloplasty and n = 57 open angle glaucoma eyes treated with phaco-canaloplasty by a single surgeon. Surgical success was defined according to six criteria, achieving a target intraocular pressure (IOP) ≤ 21, 18 or 15 mmHg on glaucoma medications (qualified success) or without any further treatment (complete success), including laser therapy or surgery. Kaplan-Meier survival analysis and Cox regression analysis were performed to evaluate surgical success and preoperative factors associated with surgical outcome. Surgical complications in the early postoperative period were compared between canaloplasty and phaco-canaloplasty. RESULTS: Canaloplasty and phaco-canaloplasty significantly reduced postoperative IOP and number of glaucoma medications (p = 0.001 for both). Phaco-canaloplasty showed higher rates of cumulative surgical success over canaloplasty, but only for target IOP ≤ 21 and ≤ 18 (p = 0.018 and p = 0.011, respectively). A preoperative number of > 4 glaucoma medications predicted surgical failure. Phaco-canaloplasty was associated with a higher rate of IOP peaks in the first month compared with canaloplasty (40.4% vs 12.7%, p = 0.000). CONCLUSION: Canaloplasty and phaco-canaloplasty demonstrated long-term efficacy in the treatment of open angle glaucoma, with phaco-canaloplasty showing higher rates of surgical success compared to canaloplasty, but not for target IOPs lower than 16 mmHg. Patients on more than 4 preoperative glaucoma medications may not be good candidates for canaloplasty and may benefit from other surgical options.


Assuntos
Cirurgia Filtrante , Glaucoma de Ângulo Aberto , Pressão Intraocular , Humanos , Glaucoma de Ângulo Aberto/cirurgia , Glaucoma de Ângulo Aberto/fisiopatologia , Estudos Retrospectivos , Feminino , Masculino , Pressão Intraocular/fisiologia , Idoso , Pessoa de Meia-Idade , Cirurgia Filtrante/métodos , Seguimentos , Resultado do Tratamento , Acuidade Visual , Facoemulsificação/métodos , Idoso de 80 Anos ou mais , Fatores de Tempo
4.
Methods Mol Biol ; 2816: 175-191, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38977599

RESUMO

The trabecular meshwork (TM) from primary open-angle glaucoma (POAG) cases has been found to contain decreased levels of intracellular plasmalogens. Plasmalogens are a subset of lipids involved in diverse cellular processes such as intracellular signaling, membrane asymmetry, and protein regulation. Proper plasmalogen biosynthesis is regulated by rate-limiting enzyme fatty acyl-CoA reductase (Far1). ATPase phospholipid transporting 8B2 (ATP8B2) is a type IV P-type ATPase responsible for the asymmetric distribution of plasmalogens between the intracellular and extracellular leaflets of the plasma membranes. Here we describe the methodology for extraction and culturing of TM cells from corneal tissue and subsequent downregulation of ATP8B2 using siRNA transfection. Further quantification and downstream effects of ATP8B2 gene knockdown will be analyzed utilizing immunoblotting techniques.


Assuntos
Glaucoma de Ângulo Aberto , Plasmalogênios , Malha Trabecular , Malha Trabecular/metabolismo , Malha Trabecular/citologia , Humanos , Plasmalogênios/metabolismo , Glaucoma de Ângulo Aberto/metabolismo , Glaucoma de Ângulo Aberto/genética , Glaucoma de Ângulo Aberto/patologia , Adenosina Trifosfatases/metabolismo , Adenosina Trifosfatases/genética , RNA Interferente Pequeno/genética , Regulação para Baixo , Células Cultivadas , Técnicas de Silenciamento de Genes
5.
Int Ophthalmol ; 44(1): 320, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977648

RESUMO

PURPOSE: To evaluate the effects of a water drinking test (WDT) on the intraocular pressure (IOP) and vascular density of the optic nerve head and macula in healthy individuals and those with primary open glaucoma using optical coherence tomography angiography. METHODS: In this prospective comparative study, 30 healthy patients and 44 POAG subjects were divided into two groups. The study's outcome measures were the IOP and vessel density of the optic nerve and macular area. After ingesting 1000 ml of water in 5 min, the effect of the WDT on the IOP and the vascular density of the macular area and optic nerve head were measured at baseline and then 20, 40, and 60 min later at intervals of 20 min. RESULTS: The initial IOP in the healthy and glaucomatous eye groups was comparable (15.94 ± 2.6 and 16.87 ± 4.21 mmHg, respectively, P = 0.506). The IOP of both groups peaked at 40' measurements. POAG eyes had significantly higher IOP elevation (4.34 ± 0.30 vs. 2.24 ± 0.30 mmHg, P < 0.001). The glaucomatous eyes had lower radial peripapillary capillary (RPC) and whole macular superficial capillary plexus (SCP) densities at baseline (48.55 ± 5.99 vs. 51.33 ± 3.75) and (48.92 ± 3.41 vs. 45.29 ± 5.29), respectively (P < 0.001). After the WDT, the change in vessel density between groups in the RPC, whole superficial, and deep capillary plexuses was insignificant (SCP and DCP of 0.66 and 0.70, respectively, P = 0.16). CONCLUSION: The WDT caused a significant IOP jump in both glaucomatous and healthy eyes, but generally, the alterations in the glaucomatous eyes were more pronounced. The changes in vascular density in the macula and optic nerve head were similar between the groups.


Assuntos
Angiofluoresceinografia , Glaucoma de Ângulo Aberto , Pressão Intraocular , Macula Lutea , Disco Óptico , Vasos Retinianos , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Masculino , Feminino , Estudos Prospectivos , Disco Óptico/irrigação sanguínea , Disco Óptico/diagnóstico por imagem , Pressão Intraocular/fisiologia , Pessoa de Meia-Idade , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Macula Lutea/irrigação sanguínea , Macula Lutea/diagnóstico por imagem , Glaucoma de Ângulo Aberto/fisiopatologia , Glaucoma de Ângulo Aberto/diagnóstico , Angiofluoresceinografia/métodos , Adulto , Ingestão de Líquidos/fisiologia , Fundo de Olho , Idoso , Células Ganglionares da Retina/patologia
6.
Vestn Oftalmol ; 140(3): 88-94, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38962984

RESUMO

The current primary approach to the therapeutic and surgical management of glaucoma is limited to lowering intraocular pressure (IOP). While normalization of IOP stabilizes some functional parameters, there is still potential for further restoration of lost visual function in the post-operative period while maintaining the "therapeutic window". Neuroprotection refers to the modification of retinal ganglion cells and the neuronal microenvironment to promote their survival and function. Numerous studies have identified effective neuroprotective methods for glaucoma; however, their implementation into clinical practice remains a significant challenge. This review presents the most clinically significant treatment strategies, as well as the latest therapeutic advances in physiotherapy.


Assuntos
Glaucoma , Doenças do Nervo Óptico , Modalidades de Fisioterapia , Humanos , Glaucoma/cirurgia , Glaucoma/fisiopatologia , Glaucoma/etiologia , Doenças do Nervo Óptico/etiologia , Doenças do Nervo Óptico/diagnóstico , Doenças do Nervo Óptico/terapia , Pressão Intraocular/fisiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/terapia , Células Ganglionares da Retina/patologia
7.
Int Ophthalmol ; 44(1): 310, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38960998

RESUMO

BACKGROUND: To investigate the long-term effectiveness and safety of XEN45 implant, either alone or in combination with phacoemulsification, in eyes with open-angle glaucoma (OAG). METHODS: Retrospective and single center study conducted on consecutive OAG patients who underwent a XEN45 implant between February-2017 and December-2021. The primary endpoint was the mean intraocular pressure (IOP) lowering from preoperative values. Surgical success was defined as an IOP-lowering from preoperative values ≥ 20% and an IOP absolute value between 6 and 13 mm Hg, without (Complete-success) or with (Qualified-success) antiglaucoma medications. RESULTS: A total of 158 eyes (34 (21.5%) eyes XEN-solo and 124 (78.5%) XEN + Phaco) were included. The median follow-up time was 28.5 months. In the overall study population, the mean preoperative IOP was significantly lowered from 19.4 ± 6.5 mm Hg to 12.4 ± 5.0 mm Hg. The mean preoperative (95% confidence interval) IOP was significantly lowered from 21.3 (19.3-23.2) mm Hg and 18.8 (17.7-20.0) mm Hg to 12.0 (10.4-13.6) mm Hg and 12.5 (11.6-13.5) mm Hg in the XEN-Solo and XEN + Phaco groups, respectively (p < 0.0001 each, respectively). The mean number of ocular-hypotensive medications was significantly reduced in the overall study sample (from 3.4 ± 0.9 to 0.9 ± 1.3, p < 0.0001), XEN-Solo (from 3.5 ± 1.1 to 0.6 ± 1.0, p < 0.0001, and XEN + Phaco (from 3.4 ± 1.1 to 0.9 ± 1.3, p < 0.0001) groups. Eighty-four (53.2%) eyes were categorized as success, with 49 (58.3%) classified as complete success. Eighty-one (51.3%) eyes underwent needling and 15 (9.5%) eyes required an additional surgical procedure. One (0.6%) eye had endophthalmitis. CONCLUSION: XEN implant, either alone or in combination with phacoemulsification significantly lowered IOP and reduced the need of ocular-hypotensive medication, while maintaining a good safety profile.


Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma de Ângulo Aberto , Pressão Intraocular , Acuidade Visual , Humanos , Glaucoma de Ângulo Aberto/cirurgia , Glaucoma de Ângulo Aberto/fisiopatologia , Estudos Retrospectivos , Feminino , Pressão Intraocular/fisiologia , Masculino , Idoso , Seguimentos , Pessoa de Meia-Idade , Resultado do Tratamento , Facoemulsificação/métodos , Desenho de Prótese , Fatores de Tempo , Idoso de 80 Anos ou mais
8.
Am J Ophthalmol ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906208

RESUMO

PURPOSE: Polygenic risk scores (PRSs) likely predict risk and prognosis of glaucoma. We compared the PRS performance for primary open-angle glaucoma (POAG), defined using International Classification of Diseases (ICD) codes versus manual medical record review. DESIGN: Retrospective cohort study METHODS: We identified POAG cases in Mount Sinai BioMe and Mass General Brigham (MGB) biobank using ICD codes. We confirmed POAG based on optical coherence tomograms and visual fields. In a separate 5% sample, the absence of POAG was confirmed with intraocular pressure and cup-disc ratio criteria. We used genotype data and either self-reported glaucoma diagnoses or ICD-10 codes for glaucoma diagnoses from the UK Biobank and the lassosum method to compute a genome-wide POAG PRS. We compared the area under the curve (AUC) for POAG prediction based on ICD codes versus medical records. RESULTS: We reviewed 804 of 996 BioMe and 367 of 1,006 MGB ICD-identified cases. In BioMe and MGB, respectively: positive predictive value was 53% and 55%; negative predictive value was 96% and 97%; sensitivity was 97% and 97%; and specificity was 44% and 53%. Adjusted PRS AUCs for POAG using ICD codes vs. manual record review in BioMe were not statistically different (p≥0.21) by ancestry: 0.77 vs. 0.75 for African, 0.80 vs. 0.80 for Hispanic, and 0.81 vs. 0.81 for European. Results were similar in MGB (p≥0.18): 0.72 vs. 0.80 for African, 0.83 vs. 0.86 for Hispanic, and 0.74 vs. 0.73 for European. CONCLUSIONS: A POAG PRS performed similarly using either manual review or ICD codes in two EHR-linked biobanks; manual assessment of glaucoma status might be unnecessary for some PRS studies. However, caution should be exercised with using ICD codes for glaucoma diagnosis given their low specificity (44-53%) for manually confirmed cases of glaucoma.

9.
Eur J Ophthalmol ; : 11206721241261236, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847127

RESUMO

Idiopathic elevated episcleral venous pressure (IEEVP), also known as Radius-Maumenee syndrome, is a rare condition which can pose a diagnostic and management challenge for clinicians. Filtration surgery is often required due to medical treatment proving ineffective. We describe to our knowledge the first case of familial Radius-Maumenee syndrome in a father and son duo. Primary management using a glaucoma drainage device is an effective option in addition to being a safer alternative when compared to trabeculectomy. Patients will require rigorous monitoring in the post-operative period to reduce the risk of complications.

10.
Am J Ophthalmol ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38876313

RESUMO

PURPOSE: To investigate glaucoma progression based on Optical Coherence Tomography (OCT) Guided Progression Analysis (GPA) according to baseline ß-zone parapapillary atrophy (PPA) morphology in glaucoma patients. DESIGN: Retrospective cohort study. METHODS: Patients over 20 years of age who had been diagnosed with primary open-angle glaucoma (POAG) at Seoul National University Hospital, Seoul, Korea between 2010 and 2020. This study included POAG patients with a minimum of 5 years of follow-up. We quantitatively measured the baseline ß-zone PPA parameters, classified ß-zone PPA morphology according to new classification standard we created and analyzed the corresponding GPA progression of the retinal nerve fiber layer (RNFL). RESULTS: A total of 210 patients with POAG (mean age: 53.8 years) were enrolled in the study. The mean follow-up period was 9.8 years. The average value of the baseline mean deviation in visual field perimetry was -2.48 dB. Longer radial extent and larger angular extent of ß-zone PPA were significantly associated with progression on GPA, as was the presence of disc hemorrhage. Among the 4 classified ß-zone PPA morphologies (Crescent type 1 & 2, Solar-eclipse type 1 & 2), the Solar-eclipse type 2 group showed the highest progression. A Kaplan-Meier survival analysis demonstrated significant differences among the 4 types. CONCLUSIONS: The larger the radial and angular extents of ß-zone PPA, the more progression that was shown on OCT GPA. Furthermore, significant differences in progression were noted based on the morphological type of ß-zone PPA. Our findings indicate that baseline ß-zone PPA parameters and morphology are valuable predictors of future glaucoma progression.

11.
Exp Eye Res ; 245: 109973, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880377

RESUMO

Glaucoma is a neurodegenerative disease characterized by visual field loss associated with optic nerve damage and ocular hypertension. The biological basis for the elevated intraocular pressure (IOP) is largely unknown, such that lowering the IOP is currently the only established treatment. Several animal models have been developed to elucidate the mechanism underlying the increased IOP and for use in drug discovery research, but their utility is often limited by the occurrence of severe intraocular inflammation and by technical challenges. In this study, we developed a rabbit glaucoma model that does not require experimental disease induction. Rabbits were chosen as the model because their eyeballs are similar in size to those of humans, and they are easy to breed. By crossing rabbit strains with inherited glaucoma, as indicated by obvious buphthalmos, we produced a strain that exhibits ocular hypertension. The IOP of the Ocular Hypertension (OH) rabbits was significantly higher than that of the wild type (WT; normal New Zealand white rabbits) from the age of 3 weeks to at least 22 weeks. The significantly larger corneal diameter of the OH rabbits indicated ocular enlargement, whereas there was no significant difference in corneal thickness compared with WT rabbits. Anterior segment ocular coherence tomography and gonioscopic observations revealed an open angle in the OH rabbits. Hematoxylin and eosin (HE) staining together with Masson's trichrome staining showed abnormal collagen accumulation in the angle of the OH rabbit's eyes. Furthermore, aqueous humor (AH) outflow imaging following an intravitreal injection of a fluorescent probe into the anterior chamber for tissue-section analysis revealed retention of the probe in the area of collagen deposition in the OH eyes. The OH rabbits also had a time-dependent increase in the cup/disc ratio. In conclusion, investigations using our newly developed rabbit model of open-angle ocular hypertension showed that abnormal accumulation of extracellular matrix at the angle increased AH outflow resistance in the conventional outflow pathway, leading to a high IOP. Furthermore, the OH rabbits exhibited glaucomatous optic disc cupping over time. These findings suggest the utility of the OH rabbits as a model for open-angle glaucoma (OAG).

13.
Int Ophthalmol ; 44(1): 243, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38904834

RESUMO

PURPOSE: To describe the outcomes of double implantation of Xen 45 Gel Stent (Xen) using an ab externo approach with closed conjunctiva. METHODS: Retrospective single-centre case series of primary open-angle glaucoma patients with at least six months of follow-up after implantation of a second Xen in the same eye via ab externo technique without conjunctival opening. RESULTS: Eight pseudophakic eyes of 8 patients were included. Intraocular pressure (IOP) dropped from 30 ± 2.6 mmHg pre-operatively to 22.4 ± 2.3 mmHg one month after the first Xen implant (mean difference: -7.6 mmHg [95% confidence interval: -9.4, -5.9 mmHg], p = 0.0092). A second Xen was then implanted to achieve the target IOP. The procedure showed no significant intraoperative or postoperative complications. The IOP dropped to 16.1 ± 2.7 mmHg six months following this second implant (mean difference: -6.3 mmHg [95% confidence interval: -7.2, -5.3 mmHg], p = 0.0183); however, 3 patients needed medical therapy to further reduce the IOP towards the target value. CONCLUSION: Sequential implantation of two Xen 45 Gel Stents using an ab externo approach with closed conjunctiva appears a promising procedure that showed a favorable safety and efficacy profile in this small case series. This pilot data might pave the way for further studies to evaluate the safety and efficacy of the procedure.


Assuntos
Implantes para Drenagem de Glaucoma , Glaucoma de Ângulo Aberto , Pressão Intraocular , Desenho de Prótese , Stents , Humanos , Glaucoma de Ângulo Aberto/cirurgia , Glaucoma de Ângulo Aberto/fisiopatologia , Projetos Piloto , Masculino , Feminino , Estudos Retrospectivos , Pressão Intraocular/fisiologia , Idoso , Pessoa de Meia-Idade , Seguimentos , Resultado do Tratamento , Implantação de Prótese/métodos , Idoso de 80 Anos ou mais , Acuidade Visual
14.
Am J Ophthalmol ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38909742

RESUMO

PURPOSE: To assess the effect of an intensive initial IOP lowering treatment strategy on the progression of visual field damage. DESIGN: A randomized, controlled, open-labelled two-center clinical trial. METHODS: A total of 242 patients with newly detected early or moderate untreated open-angle glaucoma were enrolled at two university hospitals in Sweden. Participants were randomly allocated (1:1) to either initial treatment with intensive IOP-lowering medications followed by 360° laser trabeculoplasty (LTP), or to traditional mono-therapy, which was increased when deemed necessary. The primary study outcome of interest was the predicted remaining visual field, as measured by the visual field index (VFI) at projected end of life. RESULTS: The median untreated IOP was 24 mmHg in both treatment groups. During follow-up, median and mode IOP was 17 mmHg in the mono- and 14 mmHg in the multi-treated group. In the mono-treated group the median VFI at projected end of life was 79.3%, and in the multi-treated group 87.1%, p=0.15. Annual rate of progression of visual field damage was faster in mono-treated than in multi-treated participants; median losses per year were 0.65 and 0.25 percentage units respectively, p=0.09. Progression events occurred in 21% of the mono- and in 11% of the multi-treated participants, p=0.03. Adverse events, mostly mild, were reported in 25% of the mono-, and in 36% of the multi-treated participants. Differences in visual field outcomes between treatment groups were more pronounced in participants having higher baseline IOP defined by median split of untreated IOP values. CONCLUSION: In the overall analysis the visual field outcomes were not overwhelming better in the multi-treated group, but post-hoc analysis showed definite benefit in patients with higher untreated IOP. Based upon the results of this study, initial intensive treatment may be considered in glaucoma patients with high untreated IOP at diagnosis, while we found no evidence that multi-therapy should be given routinely to all glaucoma patients.

15.
Cells ; 13(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38920689

RESUMO

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous humour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side effects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor ß (TGFß) in the anterior segment of the eye. Understanding how TGFß affects both the structural and functional changes in the outflow pathway and IOP is required to develop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study, we evaluated the effects of TGF-ß1 and -ß2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are presented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in networks to control cellular pathways and processes, a pathway-centric view of miRNA action is also reported. Evaluating TGFß-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.


Assuntos
MicroRNAs , Malha Trabecular , Malha Trabecular/metabolismo , Malha Trabecular/efeitos dos fármacos , Malha Trabecular/patologia , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Glaucoma de Ângulo Aberto/genética , Glaucoma de Ângulo Aberto/metabolismo , Glaucoma de Ângulo Aberto/patologia , Fator de Crescimento Transformador beta2/metabolismo , Fator de Crescimento Transformador beta2/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Células Cultivadas , Regulação da Expressão Gênica/efeitos dos fármacos , Pressão Intraocular/efeitos dos fármacos
16.
In Vivo ; 38(4): 1875-1881, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38936903

RESUMO

BACKGROUND/AIM: The purpose of the current study was to compare the vascular endothelial growth factor-A (VEGF-A) levels in the aqueous humor of patients with primary open angle glaucoma (POAG) and non-glaucomatous eyes and reveal any potential statistically significant correlations. PATIENTS AND METHODS: This was an observational cross-sectional study. Aqueous humor samples (50-100 µl) were collected under aseptic conditions, from the anterior chamber at the start of glaucoma or cataract surgery. The levels of VEGF-A were measured using a multiplex bead-based immunoassay. RESULTS: Aqueous humor samples were obtained from 76 participants: 39 with POAG and 36 with age-related cataracts as controls. VEGF-A levels were significantly elevated in the POAG group (166.37±110.04 pg/ml, p=0.011) compared to the control group (119.02±49.09 pg/ml). The receiver operating characteristic (ROC) analysis showed that VEGF-A had significant prognostic ability for POAG (AUC=0.67; p=0.006). An optimal cut-off for VEGF-A was found to be 148.5 pg/ml with a sensitivity of 54%, specificity of 81.1%, positive prognostic value (PPV) of 75% and negative prognostic value (NPV) of 62.5%. Logistic regression analysis showed that after adjusting for sex and age, patients with VEGF-A higher than 148.5 pg/ml had almost 10 times greater likelihood for POAG. CONCLUSION: VEGF-A is elevated in patients with POAG and can potentially have a prognostic ability for these patients.


Assuntos
Humor Aquoso , Glaucoma de Ângulo Aberto , Curva ROC , Fator A de Crescimento do Endotélio Vascular , Humanos , Glaucoma de Ângulo Aberto/metabolismo , Humor Aquoso/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Estudos Transversais , Prognóstico , Biomarcadores
17.
Sci Total Environ ; 946: 173935, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880145

RESUMO

BACKGROUND: Air pollutants are important exogenous stimulants to eye diseases, but knowledge of associations between long-term exposure to air pollutants and the risk of primary open-angle glaucoma (POAG) is limited. This study aimed to determine whether long-term exposure to air pollutants, genetic susceptibility, and their joint effects lead to an elevated risk of incident POAG. METHODS: This is a population-based prospective cohort study from UK Biobank participants with complete measures of air pollution exposure and polygenetic risk scores. Cox proportional hazard models were fitted to assess the individual and joint effects of long-term exposure to air pollutants and genetics on the risk of POAG. In addition, the effect modification of genetic susceptibility was examined on an additive or multiplicative scale. RESULTS: Among 434,290 participants with a mean (SD) age of 56.5 (8.1) years, 6651 (1.53 %) were diagnosed with POAG during a median follow-up of 13.7 years. Long-term exposure to air pollutants was associated with an increased risk of POAG. The hazard ratios associated with per interquartile range increase in PM2.5, PM2.5 absorbance, PM10, NO2, and NOX individually ranged from 1.027 (95 % CI: 1.001-1.054) to 1.067 (95 % CI: 1.035-1.099). Compared with individuals residing in low-pollution areas and having low polygenic risk scores, the risk of incident POAG increased by 105.5 % (95 % CI: 78.3 %-136.9 %), 79.7 % (95 % CI: 56.5 %-106.5 %), 103.2 % (95 % CI: 76.9 %-133.4 %), 89.4 % (95 % CI: 63.9 %-118.9 %), and 90.2 % (95 % CI: 64.8 %-119.5 %) among those simultaneously exposed to high air pollutants levels and high genetic risk, respectively. Genetic susceptibility interacted with PM2.5 absorbance and NO2 in an additive manner, while no evidence of multiplicative interaction was found in this study. Stratification analyses revealed stronger effects in Black people and the elderly. CONCLUSION: Long-term air pollutant exposure was associated with an increased risk of POAG incidence, particularly in the population with high genetic predisposition.

18.
Photodiagnosis Photodyn Ther ; 48: 104257, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38914184

RESUMO

PURPOSE: To investigate that the changes of lamina cribrosa (LC) thickness and depth after latanoprost therapy in primary open-angle glaucoma (POAG) and ocular hypertension (OHT) patients. METHODS: In this single-center prospective cross-sectional study, 35 eyes from 35 patients with POAG or OHT (study group) and 26 age- and gender- matched healthy individuals (control group) were included. All participants were examined by spectral domain optical coherence tomography (SD-OCT) with enhanced depth imaging (EDI) mode for LC thickness and depth measurements at the first visit before latanoprost therapy and at visits after 1 (second visit) and 3 (third visit) months of latanoprost therapy. RESULTS: The mean LC thickness in both horizontal and vertical scans of the study group were thinner than the control group (p < 0.001, for both). During latanoprost therapy in the study group, the LC thickness values in horizontal scans significantly differed over the three visits, gradually increased (p < 0.05). There was significantly decrease in LC depth in horizontal scans between the first and third visits, and the second and third visits (p = 0.003 and p = 0.008, respectively). The gradual decrease in LC depth in vertical scans was observed at all visits, but the statistically significant difference was between the first and third visits only (p = 0.048). CONCLUSION: POAG/OHT patients showed more LC thinning compared with healthy individuals. The significant increase in LC thickness and the significant decrease in LC depth were detected after IOP reduction therapy with latanoprost in ocular hypertensive/ glaucomatous eyes.

19.
Ophthalmol Glaucoma ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38901799

RESUMO

PURPOSE: To evaluate the association between the systemic use of calcium channel blockers (CCBs) and primary open-angle glaucoma (POAG) using a diverse nationwide dataset. DESIGN: Retrospective cohort study SUBJECTS: 213,424 individuals aged 40 years and older in the National Institutes of Health (NIH) All of Us dataset, notable for its demographic, geographic and medical diversity and inclusion of historically underrepresented populations. Patients with a diagnosis of POAG prior to use of any kind of anti-hypertensive medication were excluded. METHODS: Bivariate and multivariable regression analyses were performed to evaluate associations between CCB use and POAG. CCB use was further divided into exposure to dihydropyridine CCBs and non-dihydropyridine CCBs, and subgroup analyses were performed using Chi-square and Fisher's tests. MAIN OUTCOME MEASURES: Diagnosis of POAG RESULTS: Within our cohort, 2,772 participants (1.3%) acquired a diagnosis of POAG, while 210,652 (98.7%) did not. Among patients who developed POAG, the mean age was 73.3 years, 52.5% were female, and 48.2% identified as White. Among POAG patients, 32.6% used one or more CCB, 28.2% used a dihydropyridine CCB, and 2.2% used a non-dihydropyridine CCB. In bivariate analysis, use of any CCBs was associated with an increased risk of POAG (OR: 1.29, 95% CI: 1.27-1.31, p<0.001). In multivariable analysis adjusting for age, gender, race, ethnicity, and comorbidities such as diabetes, hyperlipidemia, and hypertension, use of any CCBs remained associated with an increased risk of developing POAG (OR: 1.52, 95% CI: 1.33-1.74, p<0.001). When stratified by type of CCB, the use of dihydropyridine CCBs (OR: 1.31, 95% CI: 1.14-1.50, p<0.001) was associated with increased POAG risk. CONCLUSIONS: Use of dihydropyridine calcium channel blockers was associated with a significantly higher risk of developing POAG, both before and while adjusting for demographic factors and comorbid medical conditions.

20.
Cureus ; 16(5): e60905, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38910641

RESUMO

Minimally invasive glaucoma surgery (MIGS) is a cutting-edge approach to treating glaucoma that provides a range of techniques and technology to reduce intraocular pressure (IOP). An 80-year-old man with visually significant cataracts and primary open-angle glaucoma (POAG) underwent combined cataract surgery and TrabEx+ (MicroSurgical Technology, Washington, United States) in his left eye, a unique type of MIGS, as we described in this study. Over the one-year follow-up, this patient showed improved visual function with well-controlled IOP without anti-glaucoma medications.

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