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1.
Int J Mol Sci ; 25(18)2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39337505

RESUMO

Glaucoma is chronic optic neuropathy whose pathogenesis has been associated with the altered metabolism of Trabecular Meshwork Cells, which is a cell type involved in the synthesis and remodeling of the trabecular meshwork, the main drainage pathway of the aqueous humor. Starting from previous findings supporting altered ubiquitin signaling, in this study, we investigated the ubiquitin-mediated turnover of myocilin (MYOC/TIGR gene), which is a glycoprotein with a recognized role in glaucoma pathogenesis, in a human Trabecular Meshwork strain cultivated in vitro in the presence of dexamethasone. This is a validated experimental model of steroid-induced glaucoma, and myocilin upregulation by glucocorticoids is a phenotypic marker of Trabecular Meshwork strains. Western blotting and native-gel electrophoresis first uncovered that, in the presence of dexamethasone, myocilin turnover by proteasome particles was slower than in the absence of the drug. Thereafter, co-immunoprecipitation, RT-PCR and gene-silencing studies identified STUB1/CHIP as a candidate E3-ligase of myocilin. In this regard, dexamethasone treatment was found to downregulate STUB1/CHIP levels by likely promoting its proteasome-mediated turnover. Hence, to strengthen the working hypothesis about global alterations of ubiquitin-signaling, the first profiling of TMCs ubiquitylome, in the presence and absence of dexamethasone, was here undertaken by diGLY proteomics. Application of this workflow effectively highlighted a robust dysregulation of key pathways (e.g., phospholipid signaling, ß-catenin, cell cycle regulation) in dexamethasone-treated Trabecular Meshwork Cells, providing an ubiquitin-centered perspective around the effect of glucocorticoids on metabolism and glaucoma pathogenesis.


Assuntos
Proteínas do Citoesqueleto , Dexametasona , Proteínas do Olho , Glicoproteínas , Complexo de Endopeptidases do Proteassoma , Malha Trabecular , Ubiquitinação , Malha Trabecular/metabolismo , Malha Trabecular/efeitos dos fármacos , Malha Trabecular/citologia , Humanos , Dexametasona/farmacologia , Glicoproteínas/metabolismo , Glicoproteínas/genética , Proteínas do Olho/metabolismo , Proteínas do Olho/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas do Citoesqueleto/genética , Células Cultivadas , Ubiquitina/metabolismo , Glaucoma/metabolismo , Glaucoma/patologia
2.
Clin Ophthalmol ; 18: 1751-1760, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919404

RESUMO

Purpose: The effectiveness, safety and tolerability of the preservative-free fixed combination of tafluprost and timolol (PF-TTFC) were evaluated over the 24-h in patients with open-angle glaucoma or ocular hypertension showing signs and symptoms of Ocular Surface Disease (OSD) and uncontrolled intraocular pressure (IOP) on prior benzalkonium chloride (BAK) - Latanoprost monotherapy. Methods: In this multi-center, prospective, interventional, non-comparative clinical trial, patients treated with BAK-Latanoprost underwent 24-h IOP measurements (8 am, 11 am, 2 pm, 5 pm, 8 pm, 11 pm, 2 am, 5 am) at baseline and after 3 months from switch to PF-TTFC. Mean 24-h IOP and daytime (8 am-8 pm) vs nighttime (11 pm - 5 am) IOP were compared. Changes in OSD signs and symptoms, quality of life (QoL) and in-vivo corneal confocal microscopy (IVCM) were also evaluated. Results: Thirty-eight patients were analyzed. The mean 24-h IOP significantly decreased after 3 months from 17.8 mmHg (95% CI: 17.1-18.6) to 15.3 mmHg (95% CI: 14.6-16.1, p < 0.001). IOP was significantly reduced both at daytime (p < 0.001) and nighttime (p < 0.001), with better IOP control at night [-2.9 (95% CI: -3.5 to -2.1) mmHg vs -2.3 (95% CI: -2.9 to -1.6) mmHg]. In 20 patients (52.6%), corneal fluorescein staining improved, whereas in 4 patients (10.5%) it worsened. Hyperemia has improved in 24 (63.3%) patients and worsened in 2 (5.3%). Breakup time, Schirmer test and QoL scores showed no changes. At IVCM, the mean corneal wing-cell size was found significantly decreased (p < 0.005). Conclusion: The switch from BAK-Latanoprost to PF-TTFC significantly reduced IOP over the 24-h and improved OSD signs and symptoms.

3.
Int J Mol Sci ; 25(11)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38892100

RESUMO

To analyze in vivo scleral changes induced by MicroPulse transscleral laser therapy (MP-TLT) in refractory glaucoma using anterior segment-optical coherence tomography (AS-OCT). Forty-two candidate patients for MP-TLT were consecutively enrolled and underwent AS-OCT at baseline and after six months. MP-TLT success was defined as an intraocular pressure (IOP) reduction by one-third. The main outcome measures were the mean superior (S-), inferior (I-), and total (T-) intra-scleral hypo-reflective space area (MISHA: mm2) and scleral reflectivity (S-SR, I-SR, T-SR; arbitrary scale) as in vivo biomarkers of uveoscleral aqueous humor (AH) outflow. The IOP was the secondary outcome. The relations between the baseline-to-six months differences (D) of DS-MISHA, DI-MISHA, and DT-MISHA and DS-SR, DI-SR, DT-SR, and DIOP, were investigated. At 6 months, the median IOP reduction was 21% in the failures and 38% in the successes. The baseline S-MISHA, I-MISHA, and T-MISHA did not differ between the groups, while S-SR and T-SR were higher in the successes (p < 0.05). At six months, successful and failed MP-TLTs showed a 50% increase in S-MISHA (p < 0.001; p = 0.037), whereas I-SR and T-SR reduced only in the successes (p = 0.002; p = 0.001). When comparing DS-MISHA, DI-MISHA, and DT-MISHA and DS-SR, DI-SR, and DT-SR, there were no significant differences between the groups. In the successful procedures, DIOP was positively correlated with DT-MISHA and DI-MISHA (ρ = 0.438 and ρ = 0.490; p < 0.05). MP-TLT produced potentially advantageous modifications of the sclera in refractory glaucoma. Given the partial correlation between these modifications and post-treatment IOP reduction, our study confirmed that the activation of the uveoscleral AH outflow route could significantly contribute to the IOP lowering after MP-TLT.


Assuntos
Humor Aquoso , Glaucoma , Pressão Intraocular , Terapia a Laser , Esclera , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Esclera/cirurgia , Esclera/diagnóstico por imagem , Masculino , Feminino , Glaucoma/cirurgia , Glaucoma/diagnóstico por imagem , Pessoa de Meia-Idade , Terapia a Laser/métodos , Idoso , Humor Aquoso/metabolismo , Úvea/diagnóstico por imagem , Úvea/cirurgia , Adulto , Resultado do Tratamento
4.
J Clin Med ; 13(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38592217

RESUMO

Purpose: To investigate the relationship between glaucoma, pseudoexfoliation and hearing loss (HL). Methods: A systematic literature search following PRISMA guidelines was conducted using the PubMed, Embase, Scopus and Cochrane databases from 1995 up to 28 August 2023. Results: Thirty studies out of the 520 records screened met the inclusion criteria and were included. Most articles (n = 20) analysed the association between pseudoexfoliation syndrome (XFS) and HL, showing XFS patients to have higher prevalence of sensorineural hearing loss (SNHL) at both speech frequencies (0.25, 0.5, 1 and 2 kHz), and higher frequencies (4 and 8 kHz) compared to controls in most cases. No significant differences in prevalence or level of HL between XFS and pseudoexfoliative glaucoma (XFG) were detected in most studies. Eight articles analysed the relationship between primary open-angle glaucoma (POAG) and HL. Overall, a positive association between the two conditions was highlighted across all studies except for two cases. Similarly, articles focusing on NTG and HL (n = 4) showed a positive association in most cases. The role of autoimmunity and, in particular, the presence of antiphosphatidylserine antibodies (APSA) in patients with NTG and HL suggested an underlying autoimmune or vascular mechanism contributing to their pathogenesis. Only one study analysed the relationship between angle-closure glaucoma (ACG) and HL, showing higher incidence of ACG in patients with SNHL compared to normal hearing controls. Conclusions: Most studies detected an association between XFS and HL as well as POAG/NTG/ACG and HL, suggesting the presence of a similar pathophysiology of neurodegeneration. However, given the strength of the association of XFS with HL, it remains unclear whether the presence of XFG is further associated with SNHL. Further research specifically targeted to assess the correlation between glaucoma, XFS and HL is warranted to provide a more comprehensive understanding of this association.

5.
J Glaucoma ; 33(3): 162-167, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38245812

RESUMO

PRCIS: Using a Compass (CMP) (CMP, Centervue, Padova, Italy) fundus perimeter, Zippy Estimation by Sequential Testing (ZEST) FAST strategy showed a significant reduction in examination time compared with ZEST, with good agreement in the quantification of perimetric damage. PURPOSE: The aim of this study was to compare the test duration of ZEST strategy with ZEST FAST and to evaluate the test-retest variability of ZEST FAST strategy on patients with glaucoma and ocular hypertension. PATIENTS AND METHODS: This was a multicenter retrospective study. We analyzed 1 eye of 60 subjects: 30 glaucoma patients and 30 patients with ocular hypertension. For each eye we analyzed, 3 visual field examinations were performed with Compass 24-2 grid: 1 test performed with ZEST strategy and 2 tests performed with ZEST FAST. Mean examination time and mean sensitivity between the 2 strategies were computed. ZEST FAST test-retest variability was examined. RESULTS: In the ocular hypertension cohort, test time was 223±29 seconds with ZEST FAST and 362±48 seconds with ZEST (38% reduction, P <0.001). In glaucoma patients, it was respectively 265±62 and 386±78 seconds (31% reduction using ZEST FAST, P <0.001). The difference in mean sensitivity between the 2 strategies was -0.24±1.30 dB for ocular hypertension and -0.14±1.08 dB for glaucoma. The mean difference in mean sensitivity between the first and the second test with ZEST FAST strategy was 0.2±0.8 dB for patients with ocular hypertension and 0.24±0.96 dB for glaucoma patients. CONCLUSIONS: ZEST FAST thresholding provides similar results to ZEST with a significantly reduced examination time.


Assuntos
Glaucoma , Hipertensão Ocular , Humanos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Algoritmos , Pressão Intraocular , Hipertensão Ocular/diagnóstico , Testes de Campo Visual/métodos
6.
Mol Aspects Med ; 94: 101225, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38000334

RESUMO

In the last years, neuroprotective therapies have attracted the researcher interests as modern and challenging approach for the treatment of neurodegenerative diseases, aimed at protecting the nervous system from injuries. Glaucoma is a neurodegenerative disease characterized by progressive excavation of the optic nerve head, retinal axonal injury and corresponding vision loss that affects millions of people on a global scale. The molecular basis of the pathology is largely uncharacterized yet, and the therapeutic approaches available do not change the natural course of the disease. Therefore, in accordance with the therapeutic regimens proposed for other neurodegenerative diseases, a modern strategy to treat glaucoma includes prescription of drugs with neuroprotective activities. With respect to this, several preclinical and clinical investigations on a plethora of different drugs are currently ongoing. In this review, first, the conceptualization of the rationale for the adoption of neuroprotective strategies for retina is summarized. Second, the molecular aspects highlighting glaucoma as a neurodegenerative disease are reported. In conclusion, the molecular and pharmacological properties of most promising direct neuroprotective drugs used to delay glaucoma progression are examined, including: neurotrophic factors, NMDA receptor antagonists, the α2-adrenergic agonist, brimonidine, calcium channel blockers, antioxidant agents, nicotinamide and statins.


Assuntos
Glaucoma , Doenças Neurodegenerativas , Doenças Retinianas , Humanos , Doenças Neurodegenerativas/patologia , Células Ganglionares da Retina/patologia , Células Ganglionares da Retina/fisiologia , Glaucoma/tratamento farmacológico , Glaucoma/patologia , Tartarato de Brimonidina/uso terapêutico , Retina
7.
Invest Ophthalmol Vis Sci ; 64(14): 36, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38010697

RESUMO

Purpose: The purpose of this study was to test whether functional loss in the glaucomatous macula is characterized by an enlargement of Ricco's area (RA) through the application of a computational model linking retinal ganglion cell (RGC) damage to perimetric sensitivity. Methods: One eye from each of 29 visually healthy subjects <40 years old, 30 patients with glaucoma, and 20 age-similar controls was tested with a 10-2 grid with stimuli of 5 different area sizes. Structural estimates of point-wise RGC density were obtained from optical coherence tomography (OCT) scans. Structural and functional data from the young healthy cohort were used to estimate the parameters of a computational spatial summation model to generate a template. The template was fitted with a Bayesian hierarchical model to estimate the latent RGC density in patients with glaucoma and age-matched controls. We tested two alternative hypotheses: fitting the data by translating the template horizontally (H1: change in RA) or vertically (H2: loss of sensitivity without a change in RA). Root mean squared error (RMSE) of the model fits to perimetric sensitivity were compared. Ninety-five percent confidence intervals were bootstrapped. The dynamic range of the functional and structural RGC density estimates was denoted by their 1st and 99th percentiles. Results: The RMSE was 2.09 (95% CI = 1.92-2.26) under H1 and 2.49 (95% CI = 2.24-2.72) under H2 (P < 0.001). The average dynamic range for the structural RGC density estimates was only 11% that of the functional estimates. Conclusions: Macular sensitivity loss in glaucoma is better described by a model in which RA changes with RGC loss. Structural measurements have limited dynamic range.


Assuntos
Glaucoma , Células Ganglionares da Retina , Adulto , Humanos , Teorema de Bayes , Glaucoma/diagnóstico , Tomografia de Coerência Óptica/métodos , Testes de Campo Visual , Campos Visuais , Degeneração Macular/diagnóstico
8.
J Clin Med ; 11(19)2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36233376

RESUMO

Background: To explore the agreement between clinical judgment and Guided Progression Analysis II (GPAII) in the evaluation of visual fields (VF) progression in patients with glaucoma. Methods: Three glaucoma experts and three general ophthalmologists were asked to rate the VF series by classifying them as progressive through the observation of the overview report. The agreement between clinical judgment and GPAII event analysis (EA) and trend analysis (TA) was assessed by Cohen statistic. The sensitivity and specificity of clinical judgment in detecting the presence of progression was evaluated considering the results of GPAII as the reference standard. Results: 66 VF series were included in the study. Glaucoma experts, general ophthalmologists, GPAII EA, and GPAII TA found progression in 39%, 38%, 15%, and 21% of the VF series (p < 0.05). The clinical judgment of glaucoma experts and general ophthalmologists was discordant with GPAII EA in 27.2% and 28.7% (k = 0.35, 95% CI 0.15−0.56 and k = 0.30, 95% CI 0.09−0.52) and with GPAII TA in 21.2% and 25.7% of the VF series examined (k = 0.51, 95% CI 0.31−0.72 and k = 0.41, 95% CI 0.18−0.62). Considering the GPAII EA and TA as reference standard, glaucoma experts showed a sensitivity of 90% and 92.8% and a specificity of 69.6% and 75%, while general ophthalmologists showed a sensitivity of 80% and 78.5% and a specificity of 69.6% and 73%. Conclusions: The agreement between clinical judgment and GPAII ranges from fair to moderate. Glaucoma experts showed better ability than general ophthalmologists in detecting VF progression.

9.
PLoS One ; 16(10): e0259143, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34710167

RESUMO

This study investigated the agreement of intraocular pressure measurements using rebound tonometry and applanation tonometry in response to atmospheric changes in a hyperbaric chamber. Twelve eyes of 12 healthy subjects were included in this prospective, comparative, single-masked study. Intraocular pressure measurements were performed by rebound tonometry followed by applanation tonometry in a multiplace hyperbaric chamber at 1 Bar, followed by 2, 3 and 4 Bar during compression and again at 3 and 2 Bar during decompression. Mean differences between rebound and applanation intraocular pressure measurements were 1.6, 1.7, and 2.1 mmHg at 2, 3, and 4 Bar respectively during compression and 2.6 and 2.2 mmHg at 3 and 2 Bar during decompression. Lower limits of agreement ranged from -3.7 to -5.9 mmHg and upper limits ranged from -0.3 to 1.9 mmHg. Multivariate analysis showed that the differences between rebound and applanation intraocular pressure measurements were independent of atmospheric pressure changes (p = 0.79). Intraocular pressure measured by rebound tonometry shows a systematic difference compared to intraocular measured by applanation tonometry, but this difference is not influenced by changes of atmospheric pressure up to 4 Bar in a hyperbaric chamber. Agreement in magnitude of change between devices suggests rebound tonometry is viable for assessing intraocular pressure during atmospheric changes. Future studies should be designed in consideration of expected differences in IOP values provided by the two devices.


Assuntos
Pressão Atmosférica , Pressão Intraocular/fisiologia , Fenômenos Fisiológicos Oculares , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Método Simples-Cego , Tonometria Ocular
10.
Front Aging Neurosci ; 13: 697425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34408643

RESUMO

Purpose: This study was conducted in order to evaluate retinal ganglion cell (RCG) function and the neural conduction along the postretinal large and small axons and its correlation with retinal nerve fiber layer thickness (RNFL-T) in open-angle glaucoma (OAG) eyes. Methods: Thirty-seven OAG patients (mean age: 51.68 ± 9.83 years) with 24-2 Humphrey mean deviation (MD) between -2.5 and -20 dB and IOP <21 mmHg on pharmacological treatment (OAG group) and 20 age-matched controls (control group) were enrolled. In both groups, simultaneous pattern electroretinograms (PERG) and visual evoked potentials (VEP), in response to checks stimulating macular or extramacular areas (the check edge subtended 15' and 60' of visual arc, respectively), and RNFL-T (measured in superior, inferior, nasal, and temporal quadrants) were assessed. Results: In the OAG group, a significant (ANOVA, p < 0.01) reduction of 60' and 15' PERG P50-N95 and VEP N75-P100 amplitudes and of RNFL-T [overall (average of all quadrants) or temporal] with respect to controls was found; the values of 60' and 15' PERG P50 and VEP P100 implicit times and of retinocortical time (RCT; difference between VEP P100 and PERG P50 implicit times) were significantly (p < 0.01) increased with respect to control ones. The observed increased RCTs were significantly linearly correlated (Pearson's test, p < 0.01) with the reduced PERG amplitude and MD values, whereas no significant linear correlation (p < 0.01) with RNFL-T (overall or temporal) values was detected. Conclusions: In OAG, there is an impaired postretinal neural conduction along both large and small axons (increased 60' and 15' RCTs) that is related to RGC dysfunction, but independent from the RNFL morphology. This implies that, in OAG, the impairment of postretinal neural structures can be electrophysiologically identified and may contribute to the visual field defects, as suggested by the linear correlation between the increase of RCT and MD reduction.

11.
Pharmaceuticals (Basel) ; 14(6)2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34207162

RESUMO

Glaucoma patients often suffer from ocular surface disease (OSD) caused by the chronic administration of topical anti-glaucoma medications, especially in cases of long-term therapy with preserved or multiple drugs. Additionally, glaucoma surgery may determine ocular surface changes related to the formation and location of the filtering bleb, the application of anti-mitotic agents, and the post-operative wound-healing processes within the conjunctiva. Recently, several studies have evaluated the role of advanced diagnostic imaging technologies such as in vivo confocal microscopy (IVCM) and anterior segment-optical coherence tomography (AS-OCT) in detecting microscopic and macroscopic features of glaucoma therapy-related OSD. Their clinical applications are still being explored, with recent particular attention paid to analyzing the effects of new drug formulations and of minimally invasive surgical procedures on the ocular surface status. In this review, we summarize the current knowledge about the main changes of the ocular surface identified at IVCM and AS-OCT in glaucoma patients under medical therapy, or after surgical treatment.

12.
Adv Ther ; 37(8): 3643-3644, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32567020

RESUMO

In the original article, the The VISIONARY Study Group Principal Investigator Jose Javier Garcia-Medina.

13.
Graefes Arch Clin Exp Ophthalmol ; 258(6): 1237-1251, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32221692

RESUMO

BACKGROUND/AIMS: To evaluate diurnal variations in optic nerve head (ONH) vessel density assessed by optical coherence tomography angiography (OCT-A) in healthy subjects, ocular hypertension (OHT), and open-angle glaucoma (OAG) patients. METHODS: Forty subjects (OAG, 21; OHT, 6; healthy, 13) were assessed for vessel density percentage (VD%) and flow index in the ONH (NH VD%, NH index), and in the radial peripapillary capillary layer (RPC VD%, RPC index) at 9:00, 11:00, 14:00, 16:00, and 18:00 on a single day. Repeated measures ANOVAs were used to test for changes in the parameters measured at multiple time points. RESULTS: All OCT-A parameters analyzed at the different time points were statistically lower in the OAG patients compared to both the OHT and healthy groups (p < 0.05). In the OAG group, the NH index, RPC index, NH VD%, and RPC VD% were statistically lower at 18:00 compared to 14:00, and the RPC VD% was statistically lower at 9:00 than 14:00. In the OHT group, the RPC index was statistically lower at 9:00 than 11:00. In the healthy group, the NH VD% and RPC VD% were statistically lower at 16:00 than 18:00, and the RPC index was statistically lower at 9:00 than 11:00. No other statistically significant difference was found in none of the three groups comparing any other time point (p > 0.05). CONCLUSION: In healthy subjects, OHT and OAG patients, the variations in the OCT-A derived parameters were relatively small. These results suggest that in the clinical practice the OCT-A assessment can be performed independently of the time of the day, contrasting IOP evaluation.


Assuntos
Ritmo Circadiano/fisiologia , Glaucoma de Ângulo Aberto/fisiopatologia , Disco Óptico/irrigação sanguínea , Vasos Retinianos/fisiopatologia , Adulto , Idoso , Feminino , Angiofluoresceinografia , Glaucoma de Ângulo Aberto/diagnóstico , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/fisiopatologia , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica , Tonometria Ocular , Campos Visuais
14.
Adv Ther ; 37(4): 1436-1451, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32072493

RESUMO

INTRODUCTION: A non-interventional, multicenter, European, prospective evaluation of the effectiveness, tolerability, and safety of a topical preservative-free tafluprost (0.0015%) and timolol (0.5%) fixed-dose combination (PF tafluprost/timolol FC) in adults with open-angle glaucoma (OAG) and ocular hypertension (OHT) demonstrating insufficient response to topical beta-receptor blockers or prostaglandin analogue (PGA) monotherapy. METHODS: Mean intraocular pressure (IOP) change from baseline was measured at study visits following a switch to PF tafluprost/timolol FC. Primary endpoint was absolute mean IOP change at month 6. Change from baseline concerning ocular signs and symptoms was also explored. RESULTS: Analyses included 577 patients (59.6% female). Mean age (SD) was 67.8 (11.67) years. Mean (SD) IOP reduction from baseline was significant at all study visits; 5.4 (3.76) mmHg (23.7%) at week 4, 5.9 (3.90) mmHg (25.6%) at week 12, and 5.7 (4.11) mmHg (24.9%) at month 6 (p < 0.0001 for all visits). At month 6, 69.2%, 53.6%, 40.0%, and 25.8% were responders based on ≥ 20%, ≥ 25%, ≥ 30%, and ≥ 35% cutoff values for mean IOP, respectively. Significant reductions were observed concerning corneal fluorescein staining (p < 0.0001), dry eye symptoms, irritation, itching, and foreign body sensation (p < 0.001 for each parameter). Conjunctival hyperemia was significantly reduced at all study visits (p < 0.0001 at each visit). Overall, 69 treatment-related adverse events (AEs) were reported, one of which was serious (status asthmaticus). Most AEs were mild to moderate in severity, and the majority had resolved or were resolving at the end of the study period. CONCLUSION: In clinical practice, PF tafluprost/timolol FC provided statistically and clinically significant IOP reductions in patients with OAG and OHT insufficiently controlled on or intolerant to PGA or beta-receptor blocker monotherapy. The full IOP reduction appeared at week 4 and was maintained over the 6-month study period. Key symptoms of ocular surface health improved. TRIAL REGISTRATION: European Union electronic Register of Post-Authorisation Studies (EU PAS) register number, EUPAS22204.


Assuntos
Anti-Hipertensivos/uso terapêutico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Hipertensão Ocular/tratamento farmacológico , Prostaglandinas F/uso terapêutico , Prostaglandinas Sintéticas/uso terapêutico , Timolol/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Pressão Intraocular , Masculino , Pessoa de Meia-Idade , Conservantes Farmacêuticos , Estudos Prospectivos , Prostaglandinas F/administração & dosagem , Prostaglandinas F/efeitos adversos , Prostaglandinas Sintéticas/administração & dosagem , Prostaglandinas Sintéticas/efeitos adversos , Timolol/administração & dosagem , Timolol/efeitos adversos , Tonometria Ocular
15.
Surv Ophthalmol ; 65(4): 458-472, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32057761

RESUMO

Glucocorticoids are a class of anti-inflammatory drugs commonly used to treat various ocular and systemic conditions. Although the role of glucocorticoids in the treatment of numerous serious inflammatory diseases is pivotal, their prolonged use may increase intraocular pressure resulting in steroid-induced glaucoma. We provide a detailed update on steroid-induced glaucoma as a preventable cause of blindness in the adult and pediatric population and describe its epidemiology, social impact, and risk factors. Furthermore, we explore the propensity of different steroids to increase the intraocular pressure, the role of different routes of steroid administration, dosage and duration of treatment, as well as the clinical features, genetics, and management of steroid-induced glaucoma.


Assuntos
Glaucoma/induzido quimicamente , Glucocorticoides/efeitos adversos , Pressão Intraocular/efeitos dos fármacos , Acuidade Visual , Glaucoma/epidemiologia , Glaucoma/terapia , Saúde Global , Humanos , Incidência , Fatores de Risco
16.
PLoS One ; 14(11): e0224982, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31725734

RESUMO

PURPOSE: To evaluate the presence and concentration of citicoline and its metabolites (choline, cytidine and uridine) in the vitreous body in human eyes after topical application of an ophthalmic solution of citicoline 2%, in vivo. METHODS: Twenty-one subjects affected by epiretinal membrane with surgical indication for pars-plana vitrectomy underwent treatment with 1 drop 3 times/day of a solution of citicoline 2%, 0.2% high molecular weight hyaluronic acid and 0.01% benzalkonium chloride (OMK1, Omikron Italia s.r.l., Rome, Italy) 14 days before surgery and 2 hours prior to surgery. Five additional patients served as controls and received an OMK1 vehicle solution without citicoline. The vitreous samples were taken at the beginning of the pars-plana vitrectomy and analyzed for qualitative/quantitative determination of vitreous concentration of citicoline and its metabolites by means of high performance liquid chromatography. RESULTS: The overall mean concentration of citicoline in patients treated with citicoline 2% solution was 406.72 ± 52.99 µg/mL, while the mean concentration of choline, cytidine and uridine was 180.88 ± 41.49 µg/mL, 44.45 ± 10.19 µg/mL and 330.41 ± 75.8 µg/mL, respectively. The concentration of citicoline in phakic eyes (n = 13, 366.61 ± 129.61 µg/mL) was lower compared to that found in pseudophakic eyes (n = 8, 435.89 ± 131.42 µg/mL) and the difference was not statistically significant. The concentration of citicoline in the control eyes was 45.66 ± 26.36 µg/mL, while the concentration of choline, cytidine and uridine were 17.21 ± 9.93 µg/mL, 6.24 ± 3.6 µg/mL and 172.80 ± 99.76 µg/mL, respectively. CONCLUSION: Citicoline can reach the human vitreous in high concentration when administered in ophthalmic solution. This evidence contributes to the build-up of the pyramid of the evidences required for determining the role of citicoline administered in ophthalmic formulation in retinal and optic nerve neurodegenerative diseases.


Assuntos
Citidina Difosfato Colina/administração & dosagem , Soluções Oftálmicas/administração & dosagem , Idoso , Cromatografia Líquida de Alta Pressão , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas/química
17.
Curr Med Chem ; 26(22): 4253-4261, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31099319

RESUMO

Ocular surface disease is characterized by tear film instability and histopathologic and clinical changes of the ocular surface. Glaucoma patients often suffer from ocular surface disease caused by the chronic use of preserved medical treatment to reduce intraocular pressure. Benzalkonium chloride is the preservative most frequently used in glaucoma medications. Its effect on tear film, conjunctiva and cornea and the consequences in glaucoma management are discussed in this mini-review.


Assuntos
Anti-Hipertensivos/farmacologia , Túnica Conjuntiva/efeitos dos fármacos , Córnea/efeitos dos fármacos , Glaucoma/tratamento farmacológico , Conservantes Farmacêuticos/farmacologia , Lágrimas/efeitos dos fármacos , Animais , Anti-Hipertensivos/química , Compostos de Benzalcônio/química , Compostos de Benzalcônio/farmacologia , Humanos , Conservantes Farmacêuticos/química
18.
Adv Ther ; 36(4): 987-996, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30790180

RESUMO

INTRODUCTION: To evaluate the retinal function and the relative neural conduction along the visual pathway after treatment with citicoline in liposomal formulation (CLF) eye drops in patients with open angle glaucoma (OAG). METHODS: Twelve OAG patients (mean age ± standard deviation 52.58 ± 11.39 years, intraocular pressure < 18 mmHg under topical hypotensive treatment, Humphrey field analyzer mean deviation - 4.49 ± 2.46 dB) were enrolled. Only one eye of studied patients was treated with CLF eye drops (OMK1-LF®, Omikron Italia, 3 drops/day) (CLF group, 12 eyes) over a period of 4 months. In CLF eyes, pattern electroretinogram (PERG), visual evoked potentials (VEP), and visual field test were assessed at baseline and at the end of treatment (month 4). RESULTS: After treatment with CLF eye drops, a significant increase of PERG P50-N95 amplitude and a significant shortening of VEP P100 implicit time were found. In CLF eyes, the shortening of VEP P100 implicit time was significantly correlated with the increase of PERG P50-N95 amplitude. CONCLUSION: Data from this pilot study suggest that treatment with CLF eye drops induces an enhancement of the retinal bioelectrical responses (increase of PERG amplitude) with a consequent improvement of the bioelectrical activity of the visual cortex (shortening of VEP implicit time). FUNDING: Omikron Italia S.r.l. and Opko Health Europe.


Assuntos
Citidina Difosfato Colina , Potenciais Evocados Visuais , Glaucoma de Ângulo Aberto , Disponibilidade Biológica , Citidina Difosfato Colina/administração & dosagem , Citidina Difosfato Colina/farmacocinética , Monitoramento de Medicamentos , Eletrorretinografia/métodos , Feminino , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/tratamento farmacológico , Humanos , Lipossomos , Masculino , Pessoa de Meia-Idade , Condução Nervosa/efeitos dos fármacos , Soluções Oftálmicas/administração & dosagem , Soluções Oftálmicas/farmacocinética , Projetos Piloto , Retina/efeitos dos fármacos , Retina/fisiopatologia , Tonometria Ocular/métodos , Testes de Campo Visual/métodos , Vias Visuais/efeitos dos fármacos
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