RÉSUMÉ
Purpose: Primary open-angle glaucoma (POAG) is a leading cause of blindness, and its primary risk factor is elevated intraocular pressure (IOP) due to pathologic changes in the trabecular meshwork (TM). We previously showed that there is a cross-inhibition between TGFß and Wnt signaling pathways in the TM. In this study, we determined if activation of the Wnt signaling pathway using small-molecule Wnt activators can inhibit TGFß2-induced TM changes and ocular hypertension (OHT). Methods: Primary human TM (pHTM) cells and transduced SBE-GTM3 cells were treated with or without Wnt and/or TGFß signaling activators and used for luciferase assays; for the extraction of whole-cell lysate, conditioned medium, cytosolic proteins, and nuclear proteins for Western immunoblotting (WB); or for immunofluorescent staining. Human donor eyes were perfusion cultured to study the effect of Wnt activators on IOP. Results: We found that the small-molecule Wnt activators (GSK3ß inhibitors) (BIO, SB216763, and CHIR99021) activated canonical Wnt signaling in pHTM cells without toxicity at tested concentrations. This activation inhibited TGFß signaling as well as TGFß2-induced extracellular matrix deposition and formation of cross-linked actin networks in pHTM cells or SBE-GTM3 cells. We also observed nuclear translocation of both Smad4 and ß-catenin in pHTM cells, which suggested that the cross-inhibition between the TGFß and Wnt signaling pathways may occur in the nucleus. Using our ex vivo model, we found that CHIR99021 inhibited TGFß2-induced OHT in perfusion-cultured human eyes. Conclusions: Our results showed that small-molecule Wnt activators have the potential for treating TGFß signaling-induced OHT in patients with POAG.
Sujet(s)
Glaucome à angle ouvert , Glycogen synthase kinase 3 beta , Pression intraoculaire , Réseau trabéculaire de la sclère , Humains , Réseau trabéculaire de la sclère/métabolisme , Réseau trabéculaire de la sclère/effets des médicaments et des substances chimiques , Pression intraoculaire/physiologie , Pression intraoculaire/effets des médicaments et des substances chimiques , Glaucome à angle ouvert/métabolisme , Glaucome à angle ouvert/traitement médicamenteux , Cellules cultivées , Glycogen synthase kinase 3 beta/métabolisme , Glycogen synthase kinase 3 beta/antagonistes et inhibiteurs , Technique de Western , Voie de signalisation Wnt/effets des médicaments et des substances chimiques , Voie de signalisation Wnt/physiologie , Hypertension oculaire/métabolisme , Hypertension oculaire/traitement médicamenteux , Transduction du signal , Facteur de croissance transformant bêta/métabolisme , Facteur de croissance transformant bêta-2/pharmacologieRÉSUMÉ
BACKGROUND: Primary open-angle glaucoma (POAG), often associated with increased intraocular pressure (IOP), can lead to permanent damage of the optic nerve, concomitant visual field loss, and blindness. Latanoprost, a prostaglandin F2α analogue, reduces IOP and is used to treat glaucoma. In this clinical trial, we evaluated the efficacy of Latanoprost Polpharma, a generic preservative-free latanoprost 0.05 mg/ml eye drops solution, in lowering IOP when compared to the originator Xalatan® (latanoprost 0.005% ophthalmic solution, Pfizer). METHODS: This was a Phase III, multicentre, randomized, investigator-masked, cross-over, comparative, non-inferiority trial carried out in 5 sites in Hungary and Russia. The primary endpoint was to evaluate the non-inferiority of the test product when compared to the reference product with respect to the differences in the mean diurnal IOP on Day 1 (baseline) and Day 29. The secondary endpoints included efficacy, ocular tolerance, safety, and usability. We recruited adult patients (18-75 years) with open-angle glaucoma or ocular hypertension. RESULTS: Forty-nine patients were randomised and received at least one dose of the test or reference product. A virtually identical reduction of the mean diurnal IOP of 7.04 ± 2.14 mmHg or 7.17 ± 2.11 mmHg was found after treatment with test or reference product, respectively (N = 44). In the intention to treat analysis, the reduction was 7.29 ± 2.53 mmHg (95% CI: 6.55-8.04) or 7.43 ± 2.78 mm Hg (95%CI: 6.61-8.24) after treatment with test or reference product, respectively (N = 47). There were no serious adverse events. CONCLUSIONS: Latanoprost Polpharma was shown to be non-inferior to Xalatan®. Both investigational products were equally well tolerated and safe. The data show a trend in favour of the test product with regards to the severity of hyperaemia and to the velocity of remission of ocular discomfort. Latanoprost Polpharma, being preservative-free, also avoids the cytotoxicity of benzalkonium chloride, the side effects of which may affect patient compliance and lower the quality of life. TRIAL REGISTRATION: The study had the ethical and regulatory approval from the National Institute of Pharmacy and Nutrition (OGYEI, OGYEI/41,779- 11/2018) and the Ethics Committee for Clinical Pharmacology (KFEB) of Hungary and from the Ministry of Healthcare of the Russian Federation (MOH of Russia) prior to the beginning of the study (642/25.12.2018) (clinical trial identification number: 848,300,144/0103/1 - POP03; IND number/EudraCT number: 2018-001727-39).
Sujet(s)
Antihypertenseurs , Études croisées , Glaucome à angle ouvert , Pression intraoculaire , Latanoprost , Hypertension oculaire , Solutions ophtalmiques , Humains , Latanoprost/usage thérapeutique , Glaucome à angle ouvert/traitement médicamenteux , Glaucome à angle ouvert/physiopathologie , Mâle , Femelle , Adulte d'âge moyen , Pression intraoculaire/effets des médicaments et des substances chimiques , Hypertension oculaire/traitement médicamenteux , Antihypertenseurs/usage thérapeutique , Antihypertenseurs/effets indésirables , Sujet âgé , Adulte , Médicaments génériques/usage thérapeutique , Médicaments génériques/effets indésirables , Résultat thérapeutique , Conservateurs pharmaceutiques/usage thérapeutique , Méthode en simple aveugle , Tonométrie oculaire , Méthode en double aveugleRÉSUMÉ
Neuroinflammation, characterized by microglial activation and the release of multiple inflammatory mediators, is a key factor in acute glaucomatous injury leading to retinal ganglion cell (RGC) death and ultimately irreversible vision loss. Irisin, a novel exercise-induced myokine, has demonstrated anti-inflammatory activity in ischemia/reperfusion injuries across multiple organs and has displayed a significant neuroprotective role in experimental stroke disease models. This study examined the protective impact of irisin and investigated its potential mechanism involved in this process utilizing an acute ocular hypertension (AOH)-induced retinal injury model in mice and a microglia inflammation model induced by lipopolysaccharide (LPS). There was a transient downregulation of irisin in the retina after AOH injury, with parallel emergence of retinal neuroinflammation and RGC death. Irisin attenuated retinal and optic nerve damage and promotes the phenotypic conversion of microglia from M1 to M2. Mechanistically, irisin significantly upregulated the expression of integrin αVß5, p-AMPK, and autophagy-related markers. Integrin αVß5 was highly expressed on microglia but hardly expressed on RGC. The integrin αVß5 inhibitor cilengitide, the AMPK inhibitor dorsomorphin, and the autophagy inhibitor 3-Methyladenine (3-MA) blocked the neuroprotective effects of irisin. Our results suggest irisin attenuates acute glaucoma-induced neuroinflammation and RGC death by activating integrin αVß5/AMPK in microglia and promoting autophagy. It should be considered a potential neuroprotective therapy for acute glaucoma.
Sujet(s)
AMP-Activated Protein Kinases , Autophagie , Fibronectines , Glaucome , Microglie , Maladies neuro-inflammatoires , Récepteur vitronectine , Animaux , Mâle , Souris , AMP-Activated Protein Kinases/métabolisme , Autophagie/effets des médicaments et des substances chimiques , Modèles animaux de maladie humaine , Fibronectines/métabolisme , Glaucome/traitement médicamenteux , Glaucome/immunologie , Glaucome/métabolisme , Lipopolysaccharides , Souris de lignée C57BL , Microglie/effets des médicaments et des substances chimiques , Microglie/métabolisme , Microglie/immunologie , Maladies neuro-inflammatoires/traitement médicamenteux , Maladies neuro-inflammatoires/immunologie , Maladies neuro-inflammatoires/étiologie , Neuroprotecteurs/pharmacologie , Neuroprotecteurs/usage thérapeutique , Hypertension oculaire/traitement médicamenteux , Hypertension oculaire/métabolisme , Récepteur vitronectine/métabolisme , Cellules ganglionnaires rétiniennes/effets des médicaments et des substances chimiques , Cellules ganglionnaires rétiniennes/anatomopathologie , Cellules ganglionnaires rétiniennes/métabolismeRÉSUMÉ
The aim of this study was to explore the neuroprotective effects of the P2X7 receptor antagonist A740003 on retinal ganglion cells (RGCs) in chronic intraocular hypertension (COH) experimental glaucoma mouse model. Bioinformatics was used to analyze the glaucoma-related genes. Western blot, real-time fluorescence quantitative PCR, and immunofluorescence staining techniques were employed to explore the mechanisms underlying the neuroprotective effects of A740003 on RGCs in COH retinas. Bioinformatic analysis revealed that oxidative stress, neuroinflammation, and cell apoptosis were highly related to the pathogenesis of glaucoma. In COH retinas, intraocular pressure elevation significantly increased the levels of translocator protein, a marker of microglial activation, which could be reversed by intravitreal preinjection of A740003. A740003 also suppressed the increased mRNA levels of proinflammatory cytokines interleukin (IL) 1ß and tumor necrosis factor α in COH retinas. In addition, although the mRNA levels of anti-inflammatory cytokine IL-4 and IL-10 were kept unchanged in COH retinas, administration of A740003 could increase their levels. The mRNA and protein levels of Bax and cleaved caspase-3 were increased in COH retinas, which could be partially reversed by A740003, while the levels of Bcl-2 kept unchanged in COH retinas with or without the injections of A740003. Furthermore, A740003 partially attenuated the reduction in the numbers of Brn-3a-positive RGCs in COH mice. A740003 could provide neuroprotective roles on RGCs by inhibiting the microglia activation, attenuating the retinal inflammatory response, reducing the apoptosis of RGCs, and enhancing the survival of RGCs in COH experimental glaucoma.
Sujet(s)
Glaucome , Souris de lignée C57BL , Neuroprotecteurs , Antagonistes des récepteurs purinergiques P2X , Cellules ganglionnaires rétiniennes , Animaux , Cellules ganglionnaires rétiniennes/effets des médicaments et des substances chimiques , Cellules ganglionnaires rétiniennes/métabolisme , Cellules ganglionnaires rétiniennes/anatomopathologie , Glaucome/traitement médicamenteux , Glaucome/métabolisme , Neuroprotecteurs/pharmacologie , Souris , Antagonistes des récepteurs purinergiques P2X/pharmacologie , Modèles animaux de maladie humaine , Mâle , Benzopyranes/pharmacologie , Neuroprotection/effets des médicaments et des substances chimiques , Apoptose/effets des médicaments et des substances chimiques , Récepteurs purinergiques P2X7/métabolisme , Récepteurs purinergiques P2X7/effets des médicaments et des substances chimiques , Hypertension oculaire/traitement médicamenteux , Hypertension oculaire/métabolisme , Pression intraoculaire/effets des médicaments et des substances chimiques , CarbazolesRÉSUMÉ
To evaluate the protective effect of gallic acid on the optic nerve by studying the inhibitory effect of gallic acid on oxidative stress in retinal ganglion cells. 100 male SD rats were randomly divided into four groups: normal control group, simple high IOP group, 0.5% gallic acid experimental group, and 1% gallic acid experimental group. HE staining, immunofluorescence, DHE staining, Western blot, and q-PCR were used to observe the antioxidant effect of gallic acid on the retina of acute ocular hypertension rats. HE staining of the retina of SD rats confirmed that the nucleus of RGCs was clear, the thickness of the RNFL was regular in the normal control group, and the nucleus of RGCs was ruptured and lysed in the simple high intraocular pressure (IOP) group and the gallic acid group, and the thickness of the RNFL was significantly thickened, but the thickness of the RNFL in the gallic acid group was significantly reduced compared with that in the simple high IOP group (p < 0.05). DHE staining showed that ROS content in the simple high IOP group was significantly increased compared with the normal control group, and ROS content was significantly decreased after the application of gallic acid (p < 0.05). Immunofluorescence staining with Brn-3a antibody confirmed that the number of RGCs was significantly reduced in the simple high IOP group compared with the normal control group, whereas after application of gallic acid, the number of RGCs was significantly more in the gallic acid group than in the simple high IOP group (p < 0.05). Western Blot and q-PCR confirmed that hypoxia-inducing factor 1α (HIF-1α) protein content and transcription level were significantly increased in the retinal tissue of the simple high IOP group, and gallic acid could inhibit HIF-1α protein content (p < 0.05) and reduce transcription factor level (p < 0.05). Gallic acid exerts a protective effect on RGC by inhibiting oxidative stress in rats with acute IOP elevation.
Sujet(s)
Antioxydants , Modèles animaux de maladie humaine , Acide gallique , Glaucome , Stress oxydatif , Rat Sprague-Dawley , Cellules ganglionnaires rétiniennes , Acide gallique/pharmacologie , Animaux , Cellules ganglionnaires rétiniennes/effets des médicaments et des substances chimiques , Cellules ganglionnaires rétiniennes/métabolisme , Cellules ganglionnaires rétiniennes/anatomopathologie , Antioxydants/pharmacologie , Mâle , Rats , Glaucome/métabolisme , Glaucome/traitement médicamenteux , Glaucome/anatomopathologie , Stress oxydatif/effets des médicaments et des substances chimiques , Espèces réactives de l'oxygène/métabolisme , Sous-unité alpha du facteur-1 induit par l'hypoxie/métabolisme , Pression intraoculaire/effets des médicaments et des substances chimiques , Hypertension oculaire/traitement médicamenteux , Hypertension oculaire/métabolisme , Hypertension oculaire/anatomopathologieRÉSUMÉ
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.
Sujet(s)
Antihypertenseurs , Glaucome à angle ouvert , Latanoprost , Hypertension oculaire , Tomographie par cohérence optique , Humains , Latanoprost/usage thérapeutique , Glaucome à angle ouvert/traitement médicamenteux , Femelle , Mâle , Adulte d'âge moyen , Études transversales , Études prospectives , Hypertension oculaire/traitement médicamenteux , Tomographie par cohérence optique/méthodes , Antihypertenseurs/usage thérapeutique , Sujet âgé , Pression intraoculaire/effets des médicaments et des substances chimiques , Papille optique/effets des médicaments et des substances chimiques , Papille optique/anatomopathologie , Papille optique/imagerie diagnostique , Administration par voie topique , Adulte , Prostaglandines F synthétiques/administration et posologie , Prostaglandines F synthétiques/usage thérapeutiqueRÉSUMÉ
The management protocol for patients with neovascular age-related macular degeneration (nAMD) involves multiple intravitreal injections (IVI) of anti-VEGF drugs. The ability to reduce the peak intraocular pressure (IOP) rise is greatly important in clinical practice. PURPOSE: This study evaluates the effect of topical hypotensive drugs on the short-term IOP rise after IVI of anti-VEGF drugs in patients with nAMD. MATERIAL AND METHODS: The prospective study included 80 patients with newly diagnosed nAMD. Before the start of treatment, the patients were divided into 4 groups of 20 people each: 1st - controls, who received no prophylactic drugs, in the 2nd, 3rd and 4th groups local instillations of one drop of hypotensive drugs brinzolamide 1%, brinzolamide-timolol, brimonidine-timolol were performed in the conjunctival sac twice: 1 day before the injection (at 20:00) and on the day of the injection 2 hours before the manipulation (at 08:00), respectively. IOP was measured in each patient using ICare Pro non-contact tonometer before injection, as well as 1 min, 30 and 60 min after injection. RESULTS: Prophylactic use of hypotensive drugs was associated with a significant decrease in IOP immediately after IVI compared to the same parameter in the 1st group (p<0.001), the maximum decrease in IOP values was observed when using a fixed combination of brimonidine-timolol by 12.1 mm Hg compared to the controls (p<0.001), the combination of brinzolamide-timolol reduced IOP by 8.5 mm Hg (p<0.001), brinzolamide 1% led to the smallest decrease in IOP - by 5.1 mm Hg (p<0.001). CONCLUSION: Study patients that received instillations of brimonidine-timolol combination of one drop into the conjunctival sac 1 day before the injection and on the day of the injection showed the maximum decrease in IOP compared to patients of the other groups.
Sujet(s)
Inhibiteurs de l'angiogenèse , Pression intraoculaire , Injections intravitréennes , Hypertension oculaire , Sulfonamides , Humains , Mâle , Femelle , Sujet âgé , Pression intraoculaire/effets des médicaments et des substances chimiques , Hypertension oculaire/prévention et contrôle , Hypertension oculaire/traitement médicamenteux , Hypertension oculaire/physiopathologie , Inhibiteurs de l'angiogenèse/administration et posologie , Études prospectives , Sulfonamides/administration et posologie , Résultat thérapeutique , Antihypertenseurs/administration et posologie , Facteur de croissance endothéliale vasculaire de type A/antagonistes et inhibiteurs , Tonométrie oculaire/méthodes , Adulte d'âge moyen , Timolol/administration et posologie , Tartrate de brimonidine/administration et posologie , Solutions ophtalmiques/administration et posologie , Thiazines/administration et posologie , Dégénérescence maculaire/traitement médicamenteux , Dégénérescence maculaire/diagnosticRÉSUMÉ
Glaucoma, the leading cause of irreversible blindness worldwide, is characterized by neurodegeneration and neuroinflammation with retinal NAD/NADP and GSH decline. Nicotinamide adenine dinucleotide (NAD)/NAD phosphate (NADP) and glutathione (GSH) are two redox reducers in neuronal and glial metabolism. However, therapeutic strategies targeting NAD/NADP or GSH do not exert ideal effects, and the underlying mechanisms are still poorly understood. We assessed morphological changes in retinal ganglion cells (RGCs), the affected neurons in glaucoma, and Müller cells, the major glial cells in the retina, as well as the levels of phosphorylated p38 (p-p38) and Caspase-3 in glaucoma patients. We constructed a modified chronic ocular hypertensive rat model and an oxygen-glucose deprivation (OGD) cell model. After applying NADPH and N-acetylcysteine (NAC), a precursor to cysteine, the rate-limiting substrate in GSH biosynthesis, to cells, apoptosis, axonal damage and peroxidation were reduced in the RGCs of the NAC group and p-p38 levels were decreased in the RGCs of the NADPH group, while in stimulated Müller cells cultured individually or cocultured with RGCs, gliosis and p38/MAPK, rather than JNK/MAPK, activation were inhibited. The results were more synergistic in the rat model, where either NADPH or NAC showed crossover effects on inhibiting peroxidation and p38/MAPK pathway activation. Moreover, the combination of NADPH and NAC ameliorated RGC electrophysiological function and prevented Müller cell gliosis to the greatest extent. These data illustrated conjoined mechanisms in glaucomatous RGC injury and Müller cell gliosis and suggested that NADPH and NAC collaborate as a neuroprotective and anti-inflammatory combination treatment for glaucoma and other underlying human neurodegenerative diseases.
Sujet(s)
Acétylcystéine , NADP , Hypertension oculaire , Rat Sprague-Dawley , Cellules ganglionnaires rétiniennes , p38 Mitogen-Activated Protein Kinases , Animaux , NADP/métabolisme , p38 Mitogen-Activated Protein Kinases/métabolisme , Hypertension oculaire/métabolisme , Hypertension oculaire/traitement médicamenteux , Hypertension oculaire/anatomopathologie , Acétylcystéine/pharmacologie , Rats , Mâle , Cellules ganglionnaires rétiniennes/effets des médicaments et des substances chimiques , Cellules ganglionnaires rétiniennes/métabolisme , Cellules ganglionnaires rétiniennes/anatomopathologie , Glaucome/métabolisme , Glaucome/anatomopathologie , Glaucome/traitement médicamenteux , Maladies neuro-inflammatoires/traitement médicamenteux , Maladies neuro-inflammatoires/métabolisme , Humains , Cellules épendymogliales/effets des médicaments et des substances chimiques , Cellules épendymogliales/métabolisme , Cellules épendymogliales/anatomopathologie , Modèles animaux de maladie humaine , Système de signalisation des MAP kinases/effets des médicaments et des substances chimiques , Apoptose/effets des médicaments et des substances chimiques , Maladie chronique , Neuroprotecteurs/pharmacologie , Cellules cultivées , Peroxydation lipidique/effets des médicaments et des substances chimiquesRÉSUMÉ
Glaucoma is a blinding disease. Reduction of intraocular pressure (IOP) is the mainstay of treatment, but current drugs show side effects or become progressively ineffective, highlighting the need for novel compounds. We have synthesized a family of perhydro-1,4-oxazepine derivatives of digoxin, the selective inhibitor of Na,K-ATPase. The cyclobutyl derivative (DcB) displays strong selectivity for the human α2 isoform and potently reduces IOP in rabbits. These observations appeared consistent with a hypothesis that in ciliary epithelium DcB inhibits the α2 isoform of Na,K-ATPase, which is expressed strongly in nonpigmented cells, reducing aqueous humor (AH) inflow. This paper extends assessment of efficacy and mechanism of action of DcB using an ocular hypertensive nonhuman primate model (OHT-NHP) (Macaca fascicularis). In OHT-NHP, DcB potently lowers IOP, in both acute (24 h) and extended (7-10 days) settings, accompanied by increased aqueous humor flow rate (AFR). By contrast, ocular normotensive animals (ONT-NHP) are poorly responsive to DcB, if at all. The mechanism of action of DcB has been analyzed using isolated porcine ciliary epithelium and perfused enucleated eyes to study AH inflow and AH outflow facility, respectively. 1) DcB significantly stimulates AH inflow although prior addition of 8-Br-cAMP, which raises AH inflow, precludes additional effects of DcB. 2) DcB significantly increases AH outflow facility via the trabecular meshwork (TM). Taken together, the data indicate that the original hypothesis on the mechanism of action must be revised. In the OHT-NHP, and presumably other species, DcB lowers IOP by increasing AH outflow facility rather than by decreasing AH inflow.NEW & NOTEWORTHY When applied topically, a cyclobutyl derivative of digoxin (DcB) potently reduces intraocular pressure in an ocular hypertensive nonhuman primate model (Macaca fascicularis), associated with increased aqueous humor (AH) flow rate (AFR). The mechanism of action of DcB involves increased AH outflow facility as detected in enucleated perfused porcine eyes and, in parallel, increased (AH) inflow as detected in isolated porcine ciliary epithelium. DcB might have potential as a drug for the treatment of open-angle human glaucoma.
Sujet(s)
Humeur aqueuse , Digoxine , Pression intraoculaire , Macaca fascicularis , Hypertension oculaire , Animaux , Pression intraoculaire/effets des médicaments et des substances chimiques , Digoxine/pharmacologie , Humeur aqueuse/métabolisme , Humeur aqueuse/effets des médicaments et des substances chimiques , Hypertension oculaire/traitement médicamenteux , Hypertension oculaire/physiopathologie , Hypertension oculaire/métabolisme , Modèles animaux de maladie humaine , Glaucome/traitement médicamenteux , Glaucome/métabolisme , Glaucome/physiopathologie , Lapins , Humains , Corps ciliaire/effets des médicaments et des substances chimiques , Corps ciliaire/métabolisme , Sodium-Potassium-Exchanging ATPase/métabolisme , Sodium-Potassium-Exchanging ATPase/antagonistes et inhibiteurs , Mâle , Réseau trabéculaire de la sclère/effets des médicaments et des substances chimiques , Réseau trabéculaire de la sclère/métabolismeRÉSUMÉ
PURPOSE: To analyze the medical management of primary open-angle glaucoma (POAG) and ocular hypertension (OHT) and the placement of fixed-drug combination drugs (FDC) in the treatment paradigm at a tertiary eye care center in South India. METHODS: Retrospective study (January 2011-December 2015) of newly diagnosed POAG and OHT patients (≥18 years) with ≥5 years follow-up. Primary outcome included percentage use of different antiglaucoma drugs (at initiation) and FDCs at the first, second, and third progression (sequencing). Secondary outcomes: Percentage discontinuation for different FDCs, efficacy parameters (decrease in intraocular pressure (IOP)/visual field), adverse events, and the median number of antiglaucoma medications (AGMs) after 5 years. RESULTS: Three hundred and seventy eyes (198 patients) were analyzed; 84% of them had POAG. Prostaglandin analogs (PGAs) were the most common (66.2%). FDCs were started in 48 eyes (12.9%), with brimonidine + timolol combination being the most common. FDC usage at subsequent modifications was 10.1%, 24.04%, and 30.0%. Beta-blockers and PGAs were the most frequently prescribed AGMs in our practice pattern, with ß-blockers being the most consistent one. CONCLUSION: This study is a fairly large study with a minimum of a 5-year follow-up of patients with POAG and OHT and gives insights into the treatment patterns, use of FDCs, and the need for multiple medications over time.
Sujet(s)
Antihypertenseurs , Glaucome à angle ouvert , Pression intraoculaire , Centres de soins tertiaires , Humains , Études rétrospectives , Inde/épidémiologie , Pression intraoculaire/effets des médicaments et des substances chimiques , Pression intraoculaire/physiologie , Mâle , Antihypertenseurs/administration et posologie , Femelle , Glaucome à angle ouvert/traitement médicamenteux , Glaucome à angle ouvert/physiopathologie , Adulte d'âge moyen , Centres de soins tertiaires/statistiques et données numériques , Études de suivi , Association médicamenteuse , Hypertension oculaire/traitement médicamenteux , Hypertension oculaire/diagnostic , Sujet âgé , Adulte , Solutions ophtalmiques/administration et posologie , Résultat thérapeutique , Relation dose-effet des médicaments , Champs visuels/physiologie , Association de médicamentsRÉSUMÉ
Purpose: To compare the efficacy of Brinzolamide-Brimonidine (BB) (1%+0.2%) with the gold standard Latanoprost-Timolol (LT) (0.005%+0.5%) in treating primary open-angle glaucoma (POAG) and ocular hypertension (OHT). Methods: A 1-year prospective study, spanning from May 2022 to May 2023, conducted at a tertiary eye-care hospital. Participants, aged 40-60, with a baseline intraocular pressure (IOP) >21 mm Hg, requiring a >30% reduction, were enrolled. Group A (n = 100) received BB, and Group B (n = 100) received LT. Outcomes were assessed at 1 month (IOP difference from baseline), 3 and 6 months (mean diurnal variations). Results: The mean age at presentation was 55.5 ± 4.5 years in Group A and 54.7 ± 4.2 years in Group B. At 1 month, Group A exhibited a mean IOP of 18.7 mm Hg, while Group B had 17.6 mm Hg, with no statistically significant difference (P = 0.53). No significant diurnal variation was observed in either group (P = 0.07). Target pressure was achieved in 88% of patients in Group A and slightly higher at 92% in Group B. Moreover, no serious side effects were reported, and compliance was higher in Group B (98%) compared to Group A (96%). Conclusion: Although LT showed slightly better and sustained IOP reduction, the difference was not statistically significant. Both BB and LT demonstrated comparable outcomes for managing POAG and OHT.
Sujet(s)
Antihypertenseurs , Tartrate de brimonidine , Glaucome à angle ouvert , Pression intraoculaire , Latanoprost , Hypertension oculaire , Sulfonamides , Timolol , Humains , Glaucome à angle ouvert/traitement médicamenteux , Adulte d'âge moyen , Pression intraoculaire/effets des médicaments et des substances chimiques , Hypertension oculaire/traitement médicamenteux , Latanoprost/administration et posologie , Latanoprost/usage thérapeutique , Latanoprost/pharmacologie , Tartrate de brimonidine/administration et posologie , Tartrate de brimonidine/usage thérapeutique , Tartrate de brimonidine/pharmacologie , Tartrate de brimonidine/effets indésirables , Mâle , Femelle , Études prospectives , Timolol/administration et posologie , Timolol/usage thérapeutique , Timolol/effets indésirables , Antihypertenseurs/administration et posologie , Antihypertenseurs/usage thérapeutique , Antihypertenseurs/effets indésirables , Antihypertenseurs/pharmacologie , Adulte , Sulfonamides/administration et posologie , Sulfonamides/usage thérapeutique , Sulfonamides/effets indésirables , Sulfonamides/pharmacologie , Thiazines/administration et posologie , Thiazines/usage thérapeutique , Thiazines/effets indésirables , Association médicamenteuse , Résultat thérapeutique , Solutions ophtalmiques/administration et posologieRÉSUMÉ
Glaucoma is a kind of neurodegenerative disorder characterized by irreversible loss of retinal ganglion cells (RGCs) and permanent visual impairment. It is reported that resveratrol (RES) is a promising drug for neurodegenerative diseases. However, the detailed molecular mechanisms underlying its protective potential have not yet been fully elucidated. The present study sought to investigate whether resveratrol could protect RGCs and retinal function triggered by acute ocular hypertension injury through the SIRT1/NF-κB pathway. An experimental glaucoma model was generated in C57BL/6J mice. Resveratrol was intraperitoneally injected for 5 days. Sirtinol was injected intravitreally on the day of retinal AOH injury. RGC survival was determined using immunostaining. TUNEL staining was conducted to evaluate retinal cell apoptosis. ERG was used to evaluate visual function. The proteins Brn3a, SIRT1, NF-κB, IL-6, Bax, Bcl2, and Cleaved Caspase3 were determined using western blot. The expression and localisation of SIRT1 and NF-κB in the retina were detected by immunofluorescence. Our data indicated that resveratrol treatment significantly increased Brn3a-labelled RGCs and reduced RGC apoptosis caused by AOH injury. Resveratrol administration also remarkably decreased NF-κB, IL-6, Bax, and Cleaved Caspase3 proteins and increased SIRT1 and Bcl2 proteins. Furthermore, resveratrol treatment obviously inhibited the reduction in ERG caused by AOH injury. Importantly, simultaneous administration of resveratrol and sirtinol abrogated the protective effect of resveratrol, decreased NF-κB protein expression, and increased SIRT1 protein levels. These results suggest that resveratrol administration significantly mitigates retinal AOH-induced RGCs loss and retinal dysfunction, and that this neuroprotective effect is partially regulated through the SIRT1/NF-κB pathway.
Sujet(s)
Benzamides , Glaucome , Naphtols , Hypertension oculaire , Souris , Animaux , Resvératrol/pharmacologie , Resvératrol/usage thérapeutique , Facteur de transcription NF-kappa B/métabolisme , Sirtuine-1/métabolisme , Protéine Bax , Interleukine-6 , Souris de lignée C57BL , Hypertension oculaire/traitement médicamenteux , Glaucome/traitement médicamenteuxRÉSUMÉ
Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs), leading to irreversible visual function impairment. Sustained increase in intraocular pressure represents a major risk factor for glaucoma, yet the underlying mechanisms of RGC apoptosis induced by intraocular pressure remains unclear. This study aims to investigate the role of TRPV4 in RGC apoptosis in a rat model of chronic ocular hypertension (COH) and the underlying molecular mechanism. In the COH rat models, we evaluated the visual function, retinal pathological changes and RGC apoptosis. TRPV4 expression and downstream signaling molecules were also detected. We found that RGC density decreased and RGC apoptosis was induced in COH eyes compared with control eyes. TRPV4 expression increased significantly in response to elevated IOP. TRPV4 inhibition by the TRPV4 antagonist HC-067047 (HC-067) suppressed RGC apoptosis and protected visual function. HC-067 treatment upregulated the phosphorylation of CaMKII in both control and COH eyes. Finally, HC-067 treatment suppressed the production of TNF-α induced by ocular hypertension. The TRPV4 antagonist HC-067 might suppress RGC apoptosis by regulating the activation of CaMKII and inhibiting the production of TNF-α in the COH model. This indicated that TRPV4 antagonists may be a potential and novel therapeutic strategy for glaucoma.
Sujet(s)
Apoptose , Calcium-Calmodulin-Dependent Protein Kinase Type 2 , Morpholines , Hypertension oculaire , Pyrroles , Cellules ganglionnaires rétiniennes , Canaux cationiques TRPV , Facteur de nécrose tumorale alpha , Animaux , Rats , Apoptose/effets des médicaments et des substances chimiques , Calcium-Calmodulin-Dependent Protein Kinase Type 2/métabolisme , Modèles animaux de maladie humaine , Glaucome/traitement médicamenteux , Hypertension oculaire/traitement médicamenteux , Cellules ganglionnaires rétiniennes/effets des médicaments et des substances chimiques , Cellules ganglionnaires rétiniennes/anatomopathologie , Canaux cationiques TRPV/antagonistes et inhibiteurs , Facteur de nécrose tumorale alpha/métabolisme , Morpholines/pharmacologie , Morpholines/usage thérapeutique , Pyrroles/pharmacologie , Pyrroles/usage thérapeutiqueRÉSUMÉ
Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice.
Sujet(s)
Glaucome , Maladies neurodégénératives , Hypertension oculaire , Mâle , Souris , Animaux , Maladies neurodégénératives/complications , Glaucome/étiologie , Hypertension oculaire/traitement médicamenteux , Hypertension oculaire/anatomopathologie , Pression intraoculaire , Anti-inflammatoires/pharmacologie , Anti-inflammatoires/usage thérapeutique , Cilastatine/usage thérapeutique , Modèles animaux de maladie humaineRÉSUMÉ
We tested five chemically and metabolically stable prostaglandin (PG) receptor agonists in a mouse model of dexamethasone-induced ocular hypertension (OHT). Whilst all compounds significantly (p < 0.05, ANOVA) lowered intraocular pressure (IOP) after twice-daily bilateral topical ocular dosing (5 µg/dose) over three weeks, the time course and magnitude of the responses varied. The onset of action of NS-304 (IP-PG receptor agonist) and rivenprost (EP4-PG receptor agonist) was slower than that of misoprostol (mixed EP2/EP3/EP4-PG receptor agonist), PF-04217329 (EP2-PG receptor agonist), and butaprost (EP2-PG receptor agonist). The rank order of IOP-lowering efficacies aligned with the onset of actions of these compounds. Peak IOP reductions relative to vehicle controls were as follows: misoprostol (74.52%) = PF-04217329 (74.32%) > butaprost (65.2%) > rivenprost (58.4%) > NS-304 (55.3%). A literature survey indicated that few previously evaluated compounds (e.g., latanoprost, timolol, pilocarpine, brimonidine, dorzolamide, cromakalim analog (CKLP1), losartan, tissue plasminogen activator, trans-resveratrol, sodium 4-phenyl acetic acid, etc.) in various animal models of steroid-induced OHT were able to match the effectiveness of misoprostol, PF-04217329 or butaprost. Since a common feature of the latter compounds is their relatively high affinity and potency at the EP2-PG receptor sub-type, which activates the production of intracellular cAMP in target cells, our studies suggest that drugs selective for the EP2-PG receptor may be suited to treat corticosteroid-induced OHT.
Sujet(s)
Acétamides , Acétates , Misoprostol , Hypertension oculaire , Pyrazines , Sulfonamides , Animaux , Souris , Misoprostol/pharmacologie , Misoprostol/usage thérapeutique , Activateur tissulaire du plasminogène , Hypertension oculaire/induit chimiquement , Hypertension oculaire/traitement médicamenteux , Récepteur prostaglandine , Sous-type EP4 des récepteurs des prostaglandines E , StéroïdesRÉSUMÉ
PURPOSE: To evaluate the long-term efficacy and safety of ripasudil-brimonidine fixed-dose combination (RBFC), a new intraocular pressure (IOP)-lowering medication for glaucoma and ocular hypertension (OHT). METHODS: This prospective, multicentre (23 sites in Japan), open-label study enrolled patients with primary open-angle glaucoma (POAG), OHT or exfoliative glaucoma and assigned them to one of four combination therapy cohorts, based on previous treatment(s) received: prostaglandin (PG) analogue (Cohort 1); PG analogue and beta-adrenoceptor blocker (ß-blocker) (Cohort 2); PG analogue, ß-blocker and carbonic anhydrase inhibitor (Cohort 3); or other/no treatment (Cohort 4). After a ≥ 4-week screening period, eligible patients received twice-daily RBFC for 52 weeks in addition to the treatments they were already receiving. Efficacy was assessed by change in IOP from baseline through week 52. Adverse events and adverse drug reactions (ADRs) were monitored throughout. RESULTS: In total, 179 patients from Cohort 1 (n = 48), Cohort 2 (n = 44), Cohort 3 (n = 41) and Cohort 4 (n = 46) entered the RBFC treatment period. For all cohorts, mean IOP was significantly reduced at 11:00 (2 h after instillation of RBFC) through week 52 with the changes from baseline at week 52 of - 2.7 to - 4.1 mmHg across cohorts; all p < 0.001. Common ADRs were conjunctival hyperaemia (58%), allergic conjunctivitis (18%) and blepharitis (17%), most of which were mild in severity. CONCLUSION: These data demonstrated the long-term efficacy and safety of RBFC, both alone and in combination with other anti-glaucoma agents. RBFC may offer a new treatment option for the long-term management of glaucoma and OHT. TRIAL REGISTRATION: Japan Registry of Clinical Trials Identifier: jRCT2080225063. DATE OF REGISTRATION: 17 February 2020.
Sujet(s)
Antihypertenseurs , Tartrate de brimonidine , Pression intraoculaire , Isoquinoléines , Hypertension oculaire , Sulfonamides , Humains , Pression intraoculaire/effets des médicaments et des substances chimiques , Pression intraoculaire/physiologie , Hypertension oculaire/traitement médicamenteux , Hypertension oculaire/physiopathologie , Hypertension oculaire/diagnostic , Mâle , Femelle , Études prospectives , Sujet âgé , Sulfonamides/administration et posologie , Sulfonamides/effets indésirables , Isoquinoléines/administration et posologie , Isoquinoléines/effets indésirables , Tartrate de brimonidine/administration et posologie , Résultat thérapeutique , Adulte d'âge moyen , Antihypertenseurs/administration et posologie , Antihypertenseurs/effets indésirables , Études de suivi , Solutions ophtalmiques , Facteurs temps , Relation dose-effet des médicaments , Tonométrie oculaire , Association médicamenteuse , Glaucome à angle ouvert/traitement médicamenteux , Glaucome à angle ouvert/physiopathologieRÉSUMÉ
PRCIS: Noninferiority of efficacy was demonstrated for a preservative-free bimatoprost 0.01% compared with BAK-containing bimatoprost 0.01% following a 12-week treatment period in patients with open angle glaucoma or ocular hypertension. Improved tolerability, in particular conjunctival hyperemia, was also observed. PURPOSE: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of a preservative-free bimatoprost 0.01% ophthalmic gel (PFB 0.01% gel) compared with preserved bimatoprost 0.01% (PB 0.01%). DESIGN: Phase III, international, multicenter, randomized, 2-parallel group, investigator-masked, 3-month treatment duration. METHODS: Patients with glaucoma or ocular hypertension were randomized after a 7-week run-in/washout period to receive once-daily PFB 0.01% gel (n=236) or PB 0.01% (n=249) for 3 months. The primary efficacy measure was changed from baseline in IOP at week 12. Safety measures included adverse events (AEs) and assessment of conjunctival hyperemia. RESULTS: The mean changes from baseline in IOP at week 12 in the PFB 0.01% gel and PB 0.01% were -9.72±2.97 and -9.47±3.06 mm Hg, respectively, at 8 am , -9.41±3.03 and -9.19±3.12 mm Hg at 10 am , and -8.99±3.36 and -8.54±3.44 mm Hg at 4 pm . Noninferiority of PFB 0.01% gel to PB 0.01% was demonstrated at week 12 based on predetermined criteria (upper 95% CI margin of 1.5 mmHg at all time points). The most frequently reported AE was conjunctival hyperemia; 13 (5.5%) patients with PFB 0.01% gel and 17 (6.8%) patients with PB 0.01%. The percentage of patients experiencing a worsening from baseline in conjunctival hyperemia score was lower with PFB 0.01% gel compared to PB 0.01% at week 6 (20.1% vs. 29.3%, respectively) and week 12 (18.3% vs. 30.4%, respectively). CONCLUSIONS: PFB 0.01% ophthalmic gel has the same efficacy in lowering IOP as PB 0.01% and demonstrated less aggravation of conjunctival hyperemia at weeks 6 and 12.
Sujet(s)
Antihypertenseurs , Bimatoprost , Gels , Glaucome à angle ouvert , Pression intraoculaire , Hypertension oculaire , Solutions ophtalmiques , Conservateurs pharmaceutiques , Tonométrie oculaire , Humains , Bimatoprost/administration et posologie , Pression intraoculaire/effets des médicaments et des substances chimiques , Pression intraoculaire/physiologie , Femelle , Mâle , Antihypertenseurs/administration et posologie , Antihypertenseurs/effets indésirables , Adulte d'âge moyen , Sujet âgé , Conservateurs pharmaceutiques/administration et posologie , Glaucome à angle ouvert/traitement médicamenteux , Glaucome à angle ouvert/physiopathologie , Hypertension oculaire/traitement médicamenteux , Hypertension oculaire/physiopathologie , Solutions ophtalmiques/administration et posologie , Résultat thérapeutique , Adulte , Méthode en double aveugle , Sujet âgé de 80 ans ou plus , Hyperhémie/induit chimiquementRÉSUMÉ
PURPOSE: To compare intraocular pressure (IOP)-lowering efficacy and safety of NCX 470, a nitric oxide (NO)-donating bimatoprost, to latanoprost in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). DESIGN: Prospective, phase 3, randomized, adaptive dose-selection, double-masked, parallel-group trial. METHODS: 691 subjects with OAG or OHT and unmedicated IOP ≥26 mmHg at 8AM, ≥24 mmHg at 10AM, and ≥22 mmHg at 4PM in the study eye were randomized to NCX 470 0.065%, NCX 470 0.1%, or latanoprost 0.005%. An interim analysis was performed to select the final dose of NCX 470. We evaluated noninferiority of NCX 470 versus latanoprost, based on IOP reduction from baseline at 8AM and 4PM at 2 weeks, 6 weeks, and 3 months. RESULTS: 661 subjects were analyzed; IOP was significantly reduced at all on-treatment time points, with reductions ranging from 8.0 to 9.7 mmHg (P < .0001 at each time point) in the NCX 470 0.1% group. Mean IOP reductions were greater with NCX 470 0.1% than latanoprost 0.005% at all 6 time points and significantly greater (P < .05) at 4 of the 6 time points. The most common adverse event was conjunctival/ocular hyperemia. CONCLUSION: The NO-donating prostaglandin analogue NCX 470 0.1% was well-tolerated and lowered IOP more than latanoprost in subjects with OAG or OHT at all 6 time points. With a dual mechanism of action that enhances both uveoscleral and trabecular outflow, NCX 470 could become an important first-line therapy for IOP reduction in glaucoma.
Sujet(s)
Antihypertenseurs , Bimatoprost , Glaucome à angle ouvert , Pression intraoculaire , Latanoprost , Hypertension oculaire , Solutions ophtalmiques , Prostaglandines F synthétiques , Tonométrie oculaire , Humains , Glaucome à angle ouvert/traitement médicamenteux , Glaucome à angle ouvert/physiopathologie , Latanoprost/usage thérapeutique , Pression intraoculaire/effets des médicaments et des substances chimiques , Pression intraoculaire/physiologie , Hypertension oculaire/traitement médicamenteux , Hypertension oculaire/physiopathologie , Méthode en double aveugle , Bimatoprost/usage thérapeutique , Mâle , Études prospectives , Femelle , Antihypertenseurs/usage thérapeutique , Antihypertenseurs/administration et posologie , Adulte d'âge moyen , Sujet âgé , Prostaglandines F synthétiques/usage thérapeutique , Donneur d'oxyde nitrique/usage thérapeutique , Donneur d'oxyde nitrique/administration et posologie , Résultat thérapeutique , Amides/usage thérapeutique , Amides/effets indésirables , Adulte , Cloprosténol/analogues et dérivés , Cloprosténol/usage thérapeutiqueRÉSUMÉ
PURPOSE: To examine if 12.5 µl timolol maleate 0.5% microdrops dispensed with the Nanodropper Adaptor provide noninferior intraocular pressure (IOP) reduction compared with conventional 28 µl drops in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). DESIGN: Prospective, noninferiority, parallel, multicenter, single-masked, active-controlled, randomized trial. PARTICIPANTS: Treatment-naïve subjects who were recently diagnosed with OAG and OHT at the Aravind Eye Care System. METHODS: Both eyes of subjects received 1 commercially available drop or both eyes of subjects received 1 microdrop of timolol maleate 0.5%. We measured IOP, resting heart rate (HR), and blood pressure (BP) at baseline and 1, 2, 5, and 8 hours after timolol administration. MAIN OUTCOME MEASURES: The IOP was the primary outcome measure. Secondary outcomes were resting HR, systolic BP (sBP), and diastolic BP (dBP). RESULTS: Adaptor-mediated microdrops and conventional drops of timolol significantly decreased IOP compared with baseline at all timepoints. Noninferiority was established at 3 of 4 timepoints. Heart rate decreases with Nanodropper were approximately 3 beats per minute (bpm) less than with conventional drops. CONCLUSIONS: Timolol microdrops appear to be as effective in ocular hypotensive action as conventional drops with a slightly attenuated effect on resting HR and BP. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
Sujet(s)
Antihypertenseurs , Pression sanguine , Glaucome à angle ouvert , Rythme cardiaque , Pression intraoculaire , Hypertension oculaire , Solutions ophtalmiques , Timolol , Tonométrie oculaire , Humains , Timolol/administration et posologie , Pression intraoculaire/effets des médicaments et des substances chimiques , Pression intraoculaire/physiologie , Études prospectives , Glaucome à angle ouvert/traitement médicamenteux , Glaucome à angle ouvert/physiopathologie , Mâle , Femelle , Hypertension oculaire/traitement médicamenteux , Hypertension oculaire/physiopathologie , Adulte d'âge moyen , Solutions ophtalmiques/administration et posologie , Antihypertenseurs/administration et posologie , Méthode en simple aveugle , Pression sanguine/effets des médicaments et des substances chimiques , Pression sanguine/physiologie , Sujet âgé , Rythme cardiaque/effets des médicaments et des substances chimiques , Résultat thérapeutique , Adulte , Systèmes de délivrance de médicamentsRÉSUMÉ
Purpose: The Ocular Hypertension Treatment Study (OHTS) identified risk factors for primary open-angle glaucoma (POAG) in patients with ocular hypertension, including pattern standard deviation (PSD). Archetypal analysis, an unsupervised machine learning method, may offer a more interpretable approach to risk stratification by identifying patterns in baseline visual fields (VFs). Methods: There were 3272 eyes available in the OHTS. Archetypal analysis was applied using 24-2 baseline VFs, and model selection was performed with cross-validation. Decomposition coefficients for archetypes (ATs) were calculated. A penalized Cox proportional hazards model was implemented to select discriminative ATs. The AT model was compared to the OHTS model. Associations were identified between ATs with both POAG onset and VF progression, defined by mean deviation change per year. Results: We selected 8494 baseline VFs. Optimal AT count was 19. The highest prevalence ATs were AT9, AT11, and AT7. The AT-based prediction model had a C-index of 0.75 for POAG onset. Multivariable models demonstrated that a one-interquartile range increase in the AT5 (hazard ratio [HR] = 1.14; 95% confidence interval [CI], 1.04-1.25), AT8 (HR = 1.22; 95% CI, 1.09-1.37), AT15 (HR = 1.26; 95% CI, 1.12-1.41), and AT17 (HR = 1.17; 95% CI, 1.03-1.31) coefficients conferred increased risk of POAG onset. AT5, AT10, and AT14 were significantly associated with rapid VF progression. In a subgroup analysis by high-risk ATs (>95th percentile or <75th percentile coefficients), PSD lost significance as a predictor of POAG in the low-risk group. Conclusions: Baseline VFs, prior to detectable glaucomatous damage, contain occult patterns representing early changes that may increase the risk of POAG onset and VF progression in patients with ocular hypertension. The relationship between PSD and POAG is modified by the presence of high-risk patterns at baseline. An AT-based prediction model for POAG may provide more interpretable glaucoma-specific information in a clinical setting.