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1.
Rom J Ophthalmol ; 68(3): 219-224, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39464766

RESUMO

Objective: To describe ocular hypertension cases after using a new aflibercept prefilled syringe and to assess the main characteristics of these eyes and their possible association with intraocular pressure (IOP) changes. Methods: Case series. We reported all the cases of ocular hypertension following aflibercept prefilled syringes (PFS) treatment in our department between April 2021 and December 2023. Results: A total of 4183 eyes were treated with aflibercept PSF. Thirteen transitory IOP elevations were observed immediately after injection (0.3%). Two eyes had an IOP between 30-35 mmHg, five eyes had an IOP between 36-55 mmHg and three eyes had an IOP > 56 mmHg. The mean IOP was 45.5 mmHg±11.33. Only six eyes needed anterior chamber paracentesis (37.5%). The other patients were treated conservatively (ocular massage and/or IOP-lowering drops). The mean IOP after treatment was 15.71 mmHg±7.20. Visual acuity improved after treatment in all the patients. Discussion: Compared with other injectors, reports have indicated a higher incidence of moderate and severe IOP spikes with aflibercept PSF. The European Medicine Agency (EMA) has associated this significant increase with incorrect syringe handling, leading to higher injection volumes. Although plunger misalignment seems to play a role in the IOP spikes, some other characteristics of this new injector could play a role. Factors such as syringe diameter, plunger alignment, and injection force may contribute to this issue. The reason some authors found no significant differences in IOP elevation after IVI, with aflibercept PFS, could be due to variations in patient characteristics, which may also play an important role in post-IVI pressure changes. Conclusions: Intraocular pressure spikes after aflibercept PFS can be explained by injector characteristics. The PFS of aflibercept has a domed plunger. Incorrect alignment between the base of the plunger and the black dosing line could cause an increase in the injected volume. Furthermore, the wider syringe diameter of aflibercept PFS could imply a larger injection force, increasing the risk of IOP elevation. Patient characteristics, such as previous VPP, axial length, or glaucoma history, may also play a role. Further studies are required to develop an ideal intravitreal syringe.


Assuntos
Inibidores da Angiogênese , Pressão Intraocular , Injeções Intravítreas , Hipertensão Ocular , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão , Seringas , Humanos , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Pressão Intraocular/fisiologia , Pressão Intraocular/efeitos dos fármacos , Masculino , Feminino , Hipertensão Ocular/fisiopatologia , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/induzido quimicamente , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Idoso , Pessoa de Meia-Idade , Acuidade Visual , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Desenho de Equipamento , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Tonometria Ocular
2.
Vestn Oftalmol ; 140(2. Vyp. 2): 90-93, 2024.
Artigo em Russo | MEDLINE | ID: mdl-38739136

RESUMO

This article presents a case of a 31-year-old male patient who presented to the outpatient department of the Krasnov Research Institute of Eye Diseases with complaints of diplopia and increased intraocular pressure (IOP) up to 30 mm Hg. The patient had been using minoxidil topically for androgenic alopecia for 8 years. On examination, mild swelling of the bulbar conjunctiva in the upper fornix was revealed; optical coherence tomography showed thinning of the ganglion cell layer, most likely due to moderate myopia. The patient responded well to discontinuation of minoxidil and topical therapy with prostaglandin analogues. After 4 months, an attempt was made to replace topical hypotensive therapy with carbonic anhydrase inhibitors, but the previous hypotensive regimen had to be resumed due to an increase in IOP. During 10 months of observation, no signs of progression were detected according to optical coherence tomography and static perimetry.


Assuntos
Minoxidil , Hipertensão Ocular , Tomografia de Coerência Óptica , Humanos , Masculino , Adulto , Hipertensão Ocular/etiologia , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/induzido quimicamente , Hipertensão Ocular/fisiopatologia , Tomografia de Coerência Óptica/métodos , Minoxidil/administração & dosagem , Minoxidil/efeitos adversos , Pressão Intraocular/efeitos dos fármacos , Alopecia/etiologia , Alopecia/diagnóstico , Resultado do Tratamento
3.
Int J Mol Sci ; 25(6)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38542305

RESUMO

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.


Assuntos
Acetamidas , Acetatos , Misoprostol , Hipertensão Ocular , Pirazinas , Sulfonamidas , Animais , Camundongos , Misoprostol/farmacologia , Misoprostol/uso terapêutico , Ativador de Plasminogênio Tecidual , Hipertensão Ocular/induzido quimicamente , Hipertensão Ocular/tratamento farmacológico , Receptores de Prostaglandina , Receptores de Prostaglandina E Subtipo EP4 , Esteroides
4.
Curr Opin Pharmacol ; 74: 102426, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38168596

RESUMO

More than 75 million people worldwide suffer from ocular hypertension (OHT)-associated retinal and optic nerve degenerative diseases that cause visual impairment and can lead to blindness. In an effort to find novel pharmaceutical therapeutics to combat OHT with reduced side-effect potential, several emerging drug candidates have advanced to human proof-of-concept in recent years. One such compound is a nonprostaglandin (non-PG) EP2-receptor-selective agonist (omidenepag isopropyl ester). Omidenepag (OMD; free acid form) is a novel non-PG that selectively binds to and activates the human EP2-prostglandin receptor (EP2R) with a high affinity (Ki = 3.6 nM) and which potently generates intracellular cAMP in living cells (EC50 = 3.9-8.3 nM). OMD significantly downregulated COL12A1 and COL13A1 mRNAs in human trabecular meshwork (TM) cells, a tissue involved in the pathogenesis of OHT. Omidenepag isopropyl (OMDI) potently and efficaciously lowered intraocular pressure (IOP) in ocular normotensive rabbits, dogs, and monkeys, and also in ocular hypertension (OHT) Cynomolgus monkeys, after a single topical ocular (t.o.) instillation at doses of 0.0001-0.01%. No reduction in IOP-lowering response to OMDI was observed after repeated t.o. dosing with OMDI in dogs and monkeys. Additive IOP reduction to OMDI was noted with brinzolamide, timolol, and brimonidine in rabbits and monkeys. OMDI 0.002% t.o. decreased IOP by stimulating the conventional (TM) and uveoscleral (UVSC) outflow of aqueous humor (AQH) in OHT monkeys. In a Phase-III clinical investigation, 0.002% OMDI (once daily t.o.) reduced IOP by 5-6 mmHg in OHT/primary open-angle glaucoma (POAG) patients (22-34 mmHg baseline IOPs) that was maintained over 12-months. In an additional month-long clinical study, 0.002% OMDI induced IOP-lowering equivalent to that of latanoprost (0.005%), a prostanoid FP-receptor agonist, thus OMDI was noninferior to latanoprost. Additive IOPreduction was also noted in OHT/OAG patients when OMDI (0.002%, once daily t.o.) and timolol (0.05%, twice daily t.o.) were administered. Patients with OHT/POAG who were low responders or nonresponders to latanoprost (0.005%, q.d.; t.o.) experienced significant IOP-lowering (additional approximately 3 mmHg) when they were switched over to OMDI 0.002% (q.d.; t.o.). No systemic or ocular adverse reactions (e.g. iris color changes/deepening of the upper eyelid sulcus/abnormal eyelash growth) were noted after a year-long, once-daily t.o. dosing with 0.002 % OMDI in OHT/POAG patients. However, OMDI caused transient conjunctival hyperemia. These characteristics of OMDI render it a suitable new medication for treating OHT and various types of glaucoma, especially where elevated IOP is implicated.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Glicina/análogos & derivados , Hipertensão Ocular , Pirazóis , Piridinas , Humanos , Coelhos , Animais , Cães , Latanoprosta/uso terapêutico , Glaucoma de Ângulo Aberto/induzido quimicamente , Glaucoma de Ângulo Aberto/tratamento farmacológico , Pressão Intraocular , Timolol/uso terapêutico , Glaucoma/tratamento farmacológico , Glaucoma/induzido quimicamente , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/induzido quimicamente , Macaca fascicularis , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico
5.
Graefes Arch Clin Exp Ophthalmol ; 262(4): 1231-1243, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37930443

RESUMO

PURPOSE: To evaluate the baseline intraocular pressure (IOP)-related risk of severe steroid-induced ocular hypertension (SIOH). We hypothesized that the incidence and severity of SIOH may differ according to baseline IOP in patients who received intravitreal dexamethasone implants. METHODS: A total of 889 eyes treated with intravitreal dexamethasone implants and a baseline IOP of ≤ 23 mmHg were enrolled. Enrolled patients were divided into two groups: the steroid-responders (127 eyes) and the non-steroid-responders (762 eyes). The steroid-responders group was subdivided into post-injection IOP of ≥ 25, > 30, or > 35 mmHg or IOP elevation of ≥ 10 mmHg over the baseline value. The odds ratio of SIOH was calculated using univariable logistic regression analysis, and significant variables were analyzed with a multivariable model. IOP was measured before (baseline IOP) and after dexamethasone implant injection at 1 week and 1, 2, 3, 6, and 12 months. RESULTS: Although baseline IOP was significantly associated with the development of SIOH in logistic regression analysis, the results from the subgroup analysis differed. In the group with IOP elevation of ≥ 10 mmHg over the baseline, SIOH was not significantly associated with baseline IOP, but it was significantly related to higher baseline IOP in the severe SIOH group (IOP > 30 and > 35 mmHg). CONCLUSIONS: Higher baseline IOP is a risk factor for severe SIOH. Clinicians should be aware of the risk of SIOH when administering steroids intravitreally to patients with high baseline IOP (IOP > 19 mmHg).


Assuntos
Glaucoma , Edema Macular , Hipertensão Ocular , Humanos , Pressão Intraocular , Dexametasona , Edema Macular/etiologia , Hipertensão Ocular/induzido quimicamente , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/tratamento farmacológico , Glaucoma/complicações , Fatores de Risco , Injeções Intravítreas , Glucocorticoides , Estudos Retrospectivos
6.
Cornea ; 43(3): 323-326, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37155339

RESUMO

PURPOSE: The aim of this study was to assess the long-term risk of steroid-induced ocular hypertension and the need for glaucoma treatment with long-term use of topical prednisolone acetate 1% in patients without preexisting glaucoma. METHODS: We retrospectively reviewed the charts of 211 patients without previous glaucoma, who underwent Descemet stripping endothelial keratoplasty (DSEK) and used topical prednisolone acetate long-term to prevent graft rejection. Dosing was 4 times daily for 4 months and tapered to once daily. The main outcomes were ocular hypertension (defined as intraocular pressure ≥24 mm Hg, or increase of ≥10 mm Hg over baseline) and initiation of glaucoma treatment. RESULTS: The median patient age was 70 years (range: 34-94 years). The indications for DSEK were Fuchs dystrophy (88%), pseudophakic corneal edema (7%), failed DSEK (3%), and failed penetrating keratoplasty (2%). The median follow-up period was 7 years (range, 1-17 years). At 1, 5, and 10 years, the cumulative risks of steroid-induced ocular hypertension were 29%, 41%, and 49%, respectively, and the risks of requiring glaucoma treatment were 11%, 17%, and 25%, respectively. Among 35 eyes treated for glaucoma, 28 (80%) were managed medically and 7 (20%) had filtration surgery. CONCLUSIONS: Long-term use of potent topical corticosteroids, such as prednisolone acetate 1%, entails substantial risk of developing steroid-induced ocular hypertension, so frequent monitoring of intraocular pressure is required. With corneal transplantation, the risk can be mitigated by using techniques with a low inherent risk of rejection, such as Descemet membrane endothelial keratoplasty, whenever possible, to allow earlier reduction of steroid potency.


Assuntos
Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Glaucoma , Hipertensão Ocular , Prednisolona/análogos & derivados , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/efeitos adversos , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Glaucoma/induzido quimicamente , Glaucoma/cirurgia , Hipertensão Ocular/induzido quimicamente , Hipertensão Ocular/cirurgia , Pressão Intraocular , Ceratoplastia Penetrante/métodos
7.
Curr Opin Pharmacol ; 74: 102424, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38160646

RESUMO

Recent advancements in prostaglandin analogs (PGAs) have reinforced their role in managing intraocular pressure (IOP). Latanoprost excels in 24-h IOP control, while various PGAs offer similar effectiveness and side effects, generic PGAs perform as well as branded ones, and a notable IOP rise observed upon PGA discontinuation. Formulations with or without preservatives show comparable IOP reduction and adherence, often surpassing benzalkonium chloride (BAK)-preserved options. Emergent PGAs, such as latanoprostene bunod, fixed-dose netarsudil combined with latanoprost, and omidenepag Isopropyl, offer enhanced or non-inferior IOP reduction. The bimatoprost implant introduces a novel administration method with effective IOP reduction. These developments underscore ongoing progress in PGA-focused ophthalmological research. This article offers a comprehensive review of available prostanoid analogs and explores new developments.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Hipertensão Ocular , Humanos , Latanoprosta/uso terapêutico , Glaucoma de Ângulo Aberto/induzido quimicamente , Glaucoma de Ângulo Aberto/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Soluções Oftálmicas/uso terapêutico , Glaucoma/tratamento farmacológico , Glaucoma/induzido quimicamente , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/induzido quimicamente , Pressão Intraocular , Prostaglandinas Sintéticas/uso terapêutico , Resultado do Tratamento
8.
BMJ Open Ophthalmol ; 8(1)2023 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-38135349

RESUMO

BACKGROUND/AIMS: This study aims to determine the incidence and risk of open-angle glaucoma or ocular hypertension (OHT) following ocular steroid injections using healthcare claims data. METHODS: We retrospectively reviewed deidentified insurance claims data from the IBM MarketScan Database to identify 19 156 adult patients with no prior history of glaucoma who received ocular steroid injections between 2011 and 2020. Patient demographics and steroid treatment characteristics were collected. Postinjection glaucoma/OHT development was defined as a new diagnosis of glaucoma/OHT, initiation of glaucoma drops, and/or surgical or laser glaucoma treatment. Cox proportional hazards models were used to determine the risk of glaucoma/OHT development within 5 years after first steroid injection. RESULTS: Overall, 3932 (20.5%) patients were diagnosed with new glaucoma/OHT, 3345 (17.5%) started glaucoma drops and 435 (2.27%) required a laser or surgical glaucoma procedure within 5 years of first steroid injection. Triamcinolone subconjunctival injections were associated with a lower risk of glaucoma/OHT development than retrobulbar or intravitreal steroid injections (p<0.001, HR 0.68, 95% CI 0.59 to 0.79), whereas the 0.59 mg fluocinolone acetonide intravitreal implant had the highest risk of glaucoma/OHT development (p=0.001, HR 2.01, 95% CI 1.34 to 3.02). The risk of glaucoma/OHT development was also higher for patients receiving multiple steroid injections (p<0.001), with the largest increase in risk occurring after three total steroid injections. CONCLUSION: Patients receiving ocular steroid injections are at risk of developing glaucoma/OHT, even with no prior glaucoma/OHT diagnosis or treatment. Patients should be closely monitored for the development of glaucoma following ocular steroid injections, particularly in the setting of intravitreal and/or repeated steroid administration.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Hipertensão Ocular , Adulto , Humanos , Pressão Intraocular , Glaucoma de Ângulo Aberto/tratamento farmacológico , Estudos Retrospectivos , Injeções Intravítreas , Hipertensão Ocular/induzido quimicamente , Glaucoma/tratamento farmacológico , Corpo Vítreo , Esteroides/efeitos adversos
9.
Genes (Basel) ; 14(11)2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-38002955

RESUMO

Glucocorticoids (GCs) are known to regulate several physiological processes and are the mainstay in the management of inflammatory eye diseases. The long-term use of GC causes raised intraocular pressure (IOP) or ocular hypertension (OHT) in about 30-50% of the susceptible individuals depending on the route of administration, and can lead to steroid-induced secondary glaucoma. The present study aims to understand the role of microRNAs (miRNAs) in differential glucocorticoid (GC) responsiveness in human trabecular meshwork (HTM) cells using small RNA sequencing. The human organ-cultured anterior segment (HOCAS) model was used to identify whether donor eyes were from GC-responders (GC-R; n = 4) or GC-non-responders (GC-NR; n = 4) following treatment with either 100 nM dexamethasone (DEX) or ethanol (ETH) for 7 days. The total RNA was extracted from cultured HTM cells with known GC responsiveness, and the differentially expressed miRNAs (DEMIRs) were compared among the following five groups: Group #1: ETH vs. DEX-treated GC-R; #2: ETH vs. DEX-treated GC-NR; #3: overlapping DEGs between Group #1 and #2; #4: Unique DEMIRs of GC-R; #5: Unique DEMIRs of GC-NR; and validated by RT-qPCR. There were 13 and 21 DEMIRs identified in Group #1 and Group #2, respectively. Seven miRNAs were common miRNAs dysregulated in both GC-R and GC-NR (Group #3). This analysis allowed the identification of DEMIRs that were unique to GC-R (6 miRNAs) and GC-NR (14 miRNAs) HTM cells, respectively. Ingenuity Pathway Analysis identified enriched pathways and biological processes associated with differential GC responsiveness in HTM cells. This is the first study to reveal a unique miRNA signature between GC-R and GC-NR HTM cells, which raises the possibility of developing new molecular targets for the management of steroid-OHT/glaucoma.


Assuntos
Glaucoma , MicroRNAs , Hipertensão Ocular , Humanos , Glucocorticoides/farmacologia , Malha Trabecular/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Hipertensão Ocular/induzido quimicamente , Hipertensão Ocular/metabolismo , Glaucoma/genética , Dexametasona/farmacologia , Análise de Sequência de RNA , Esteroides/metabolismo
10.
Georgian Med News ; (342): 30-35, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37991953

RESUMO

To determine risk factors and the overall incidence of ocular surface disorders in a cohort of long-term glaucoma patients. Utilizing simple clinical tools, cross-sectional observational research were constructed to evaluate ocular surface problems and indicators. Using a four-grade scale, ten queries regarding symptoms and indications on the cornea's surface were used to create an OSD severity score. The patients were divided into three groups: A, B, and C, depending on the result. The variables that increase the incidence of surface sickness were identified using a multinomial logistic regression. Five hundred and twenty patients made up the total population. According to the multivariate analysis, the patient's age, the number of daily eyedrops, any previous changes in topical treatment for ocular intolerance, intraocular pressure, and degree of glaucoma were all connected with the severity of ocular surface illness. Ocular surface disorders are frequently developed by patients getting treatment for primary open-angle glaucoma or ocular hypotension. which are less prevalent and serious in geriatric patients because their use greater drugs and have greater advanced glaucoma.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Hipertensão Ocular , Humanos , Idoso , Glaucoma de Ângulo Aberto/tratamento farmacológico , Endotélio Corneano , Hipertensão Ocular/induzido quimicamente , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/tratamento farmacológico , Estudos Transversais , Anti-Hipertensivos/uso terapêutico , Glaucoma/induzido quimicamente , Glaucoma/diagnóstico , Glaucoma/tratamento farmacológico , Pressão Intraocular
11.
Methods Mol Biol ; 2708: 57-69, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37558960

RESUMO

In this chapter, we describe a clinically relevant inducible and reversible ocular hypertension glaucoma model, which mimics the secondary glaucoma that can be a postoperative complication when silicone oil (SO) is used as a tamponade agent in human vitreoretinal surgery. First, we detail the procedures for generating SO-induced ocular hypertension (SOHU) in mouse and describe the two variations of this model that simulate common but distinct glaucoma types. We also describe separately the related procedures for measuring IOP and removing SO to return IOP to normal. Lastly, we describe the extension of the SOHU model in nonhuman primate (NHP), which recapitulates the severe neurodegeneration of acute human glaucoma but with unique dynamic changes of IOP due to the tolerance of the NHP ciliary body. The SOHU glaucoma model is, therefore, suitable for assessing experimental therapies for neuroprotection and regeneration, with or without treatment to lower IOP (SO removal), and consequently for translating relevant findings into novel and effective clinical treatments for glaucoma and other neurodegenerations. This model is straightforward, does not require special equipment or repetitive procedures, closely simulates clinical situations, and may be applicable to diverse animal species although minor modifications may be required.


Assuntos
Glaucoma , Hipertensão Ocular , Humanos , Animais , Camundongos , Óleos de Silicone/efeitos adversos , Pressão Intraocular , Roedores , Glaucoma/induzido quimicamente , Hipertensão Ocular/induzido quimicamente , Hipertensão Ocular/complicações , Primatas
12.
Methods Mol Biol ; 2708: 71-76, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37558961

RESUMO

Glaucoma is an irreversible blinding disease characterized by the loss of retinal ganglion cells. Development of therapeutics relies on suitable models and, given its complex nature, these are typically in vivo models. A widely used model, owing to its relative simplicity, is the microbead model. This model involves the injections of beads into the anterior chamber, which are suitably sized to block the aqueous outflow pathway, leading to an elevation in intraocular pressure and ultimately, retinal ganglion cell death. In this chapter, we describe in detail the materials and methods for modelling glaucoma using microbeads (both magnetic and nonmagnetic).


Assuntos
Glaucoma , Hipertensão Ocular , Animais , Microesferas , Roedores , Hipertensão Ocular/induzido quimicamente , Glaucoma/etiologia , Pressão Intraocular , Modelos Animais de Doenças
13.
Graefes Arch Clin Exp Ophthalmol ; 261(12): 3569-3579, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37432451

RESUMO

PURPOSE: For the treatment of macular edema, in addition to the use of antivascular endothelial growth factors, steroids are also used intravitreally and sub-Tenon. Side effects include among others cataract formation and elevation of intraocular pressure (IOP). The aim of this retrospective study was to elicit the IOP elevation after administration of various steroidal medication, the time of onset, and the efficacy of the administered IOP-lowering therapies. METHODS: We included 428 eyes with a postoperative (n = 136), diabetic (n = 148), uveitic macular edema (n = 61), and macular edema after retinal vein occlusion (n = 83). These patients were treated with one or more diverse steroidal agents once or multiple times. These drugs included: triamcinolone acetonide (TMC) as intravitreal injection (TMC IVI) or sub-Tenon (TMC ST), as well as dexamethasone (DXM) and fluocinolone acetonide (FA) intravitreally. An increase of IOP of ≥ 25 mmHg was designated as pathological. A steroid response in anamnesis, the time of onset of IOP rise from the first administration, and the therapy administered were documented. RESULTS: Of 428 eyes, 168 eyes (39.3%) had IOP elevation up to a mean of 29.7 (SD ± 5.6) mmHg, which occurred at a median of 5.5 months. Steroids most frequently leading to rise of IOP included DXM (39.1% of all eyes receiving that drug), TMC IVI (47.6%), TMC ST combined with DXM (51.5%), DXM with FA (56.8%), and TMC IVI with DXM (57.4%). A Kaplan-Meier analysis and the Log Rank test showed a significant difference (p < 0.001). IOP rise was treated as follows: 119 conservatively (70.8%), and 21 surgically (12.5%, cyclophotocoagulation 8.3%, filtering surgery 1.8%, in 4 the steroidal drug implant was removed 2.4%), and 28 eyes received no therapy (16.7%). Sufficient IOP regulation was achieved in 82 eyes (68.9%) with topical therapy. In 37 eyes (31.1%) with persistently elevated intraocular pressure, topical therapy had to be continued over the follow-up of 20 ± 7 months. CONCLUSIONS: IOP increases after any type of steroid application are not rare. Results of our study let us suspect that especially therapy with intravitreal dexamethasone, either as a monotherapy or in combination with another steroid, tends to increase IOP more than other steroids. Regular IOP checks are necessary after each steroid administration, with possible initiation of long-term conservative and/or surgical therapy if necessary.


Assuntos
Glaucoma , Edema Macular , Hipertensão Ocular , Doenças Retinianas , Humanos , Pressão Intraocular , Glucocorticoides , Edema Macular/tratamento farmacológico , Edema Macular/epidemiologia , Edema Macular/etiologia , Incidência , Estudos Retrospectivos , Hipertensão Ocular/induzido quimicamente , Hipertensão Ocular/tratamento farmacológico , Triancinolona Acetonida/efeitos adversos , Doenças Retinianas/tratamento farmacológico , Glaucoma/complicações , Fluocinolona Acetonida , Injeções Intravítreas , Dexametasona
14.
Jpn J Ophthalmol ; 67(4): 396-401, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37310574

RESUMO

PURPOSE: To report the characteristics of the steroid-induced ocular hypertensive response in pediatric patients with acute lymphoblastic leukemia (ALL) treated with prednisolone (PSL) during induction therapy and with dexamethasone (DEX) during reinduction therapy. STUDY DESIGN: Retrospective. PATIENTS AND METHODS: This study included pediatric patients diagnosed with B-cell precursor ALL and treated with systemic corticosteroids sometime during the period from 2016 to 2018 at Shizuoka Children's Hospital. Data were extracted from the hematology/oncology records related to the type, dose, and duration of systemic corticosteroids as well as to the ophthalmologic examination findings, intraocular pressure (IOP) data, symptoms of high IOP, and antiglaucoma medications obtained during corticosteroid administration. The maximal IOPs of the PSL and DEX groups were compared. RESULTS: Twenty-eight patients (18 boys and 10 girls; mean age 5.5 years) were treated with systemic corticosteroids. Twelve of the 22 courses of PSL and 33 of the 44 courses of DEX were found to be associated with high IOP. The maximal IOP was higher with the use of DEX than with the use of PSL, including in those who received prophylactic therapy (PSL 25.2 mmHg, DEX 33.6 mmHg; P = 0.02). Antiglaucoma medication was given to 21 patients; 6 patients had symptoms of ocular hypertension. The maximal IOPs were 52.8 mmHg and 70.8 mmHg in the PSL and DEX groups, respectively. Both groups of patients reported severe headache. CONCLUSION: Increased IOP was frequently observed during systemic corticosteroid therapy in pediatric patients with ALL. Although most patients were asymptomatic, they occasionally presented with severe systemic symptoms. Regular ophthalmologic examinations should be included in the treatment guidelines for ALL.


Assuntos
Glaucoma , Hipertensão Ocular , Leucemia-Linfoma Linfoblástico de Células Precursoras , Masculino , Feminino , Humanos , Criança , Pré-Escolar , Glucocorticoides/uso terapêutico , Estudos Retrospectivos , Hipertensão Ocular/induzido quimicamente , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/tratamento farmacológico , Pressão Intraocular , Prednisolona/efeitos adversos , Glaucoma/tratamento farmacológico , Corticosteroides/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/induzido quimicamente
15.
J Fr Ophtalmol ; 46(8): e249-e256, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37302867

RESUMO

These guidelines are a consensus of French glaucoma and retina experts on the management of ocular hypertension (OHT) observed in a third of the cases after corticosteroid implant intravitreal injections. They update the first guidelines published in 2017. Two implants are marketed in France: the dexamethasone implant (DEXi) and the fluocinolone acetonide implant (FAci). It is essential to assess the pressure status before injecting a patient with a corticosteroid implant. A molecule-specific monitoring of the intraocular pressure is needed throughout the follow-up and at the time of reinjections. Real-life studies have allowed optimizing the management algorithm by significantly increasing the safety of these implants. Corticosteroid testing with DEXi should be performed before switching to FAci to optimize pressure tolerance of FAci. Beyond topical hypotensive treatments, selective laser trabeculoplasty may be considered in the therapeutic arsenal for the management of steroid-induced OHT and subsequent injections.


Assuntos
Glaucoma , Hipertensão Ocular , Oftalmologia , Humanos , Dexametasona , Hipertensão Ocular/induzido quimicamente , Glaucoma/tratamento farmacológico , Glucocorticoides/uso terapêutico , Pressão Intraocular , Corticosteroides/efeitos adversos , Injeções Intravítreas , Esteroides/uso terapêutico , Retina , Implantes de Medicamento/efeitos adversos
16.
Sci Rep ; 13(1): 9143, 2023 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-37277443

RESUMO

It is important to identify at-risk patients prior to administering steroid injections to prevent avoidable irreversible blindness inducted by steroid-induced ocular hypertension (SIOH). We aimed to investigate the association of SIOH following intravitreal dexamethasone implantation (OZURDEX) using anterior segment optical coherence tomography (AS-OCT). We conducted a retrospective case control study to assess the association between trabecular meshwork and SIOH. A total of 102 eyes that underwent both AS-OCT and intravitreal dexamethasone implant injection were divided into the post-steroid ocular hypertension and normal intraocular pressure groups. Ocular parameters that can contribute to intraocular pressure were measured using AS-OCT. Univariable logistic regression analysis was used to calculate the odds ratio of the SIOH and significant variables were further analyzed using a multivariable model. Trabecular meshwork (TM) height was significantly shorter in the ocular hypertension group (716.13 ± 80.55 µm) than that in the normal intraocular pressure group (784.27 ± 82.33 µm) (p < 0.001). The receiver operating characteristic curve technique analysis showed that the optimal cut-off of ≥ 802.13 µm for TM height specificity was 96.2%, and TM height with < 646.75 µm had a sensitivity of 94.70%. The odds ratio of the association was 0.990 (p = 0.001). TM height was identified as a newly observed association with SIOH. TM height can be assessed using AS-OCT, with acceptable sensitivity and specificity. Caution must be exercised while injecting steroids in patients with short TM height (especially < 646.75 µm) as it may cause SIOH and irreversible blindness.


Assuntos
Glaucoma , Hipertensão Ocular , Humanos , Malha Trabecular , Estudos Retrospectivos , Estudos de Casos e Controles , Hipertensão Ocular/induzido quimicamente , Pressão Intraocular , Dexametasona/efeitos adversos , Cegueira
17.
Harefuah ; 162(3): 160-164, 2023 03.
Artigo em Hebraico | MEDLINE | ID: mdl-36966373

RESUMO

INTRODUCTION: Netarsudil ophthalmic solution 0.02% is a new treatment for open-angle glaucoma and ocular hypertension, which was approved for treatment in the United States and in the European Commission. The drug is a rho- kinase inhibitor (ROCK) that lowers intraocular pressure by enhancing the outflow at the trabecular meshwork and decreasing both aqueous humor production and episcleral venous pressure. This literature review aims to present this new treatment, characterize its specific mechanism of action, and discuss its effect and adverse events profile. The efficacy and safety of the drug were studied in the ROCKET and MERCURY clinical trials, in which Netarsudil was compared to other common drugs, including Timolol (Beta-blocker), Latanoprost (Prostaglandin analog), and a combination drop containing Netarsudil and Latanoprost. These trials showed a reduction of 16%-21% in the intraocular pressure (IOP) when using Netarsudil. Moreover, it was found that when using a combination of Netarsudil and Latanoprost, 64.5% of these patients achieved ≥30% reduction in mean diurnal IOP versus 28.8% of patients treated only with Netarsudil and 37.2% of patients treated only with Latanoprost (P<0.0001). The most common adverse event reported was conjunctival hyperemia, which was more frequent in patients using Netarsudil. However, this did not significantly affect the drug tolerance.


Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Hipertensão Ocular , Humanos , Estados Unidos , Glaucoma de Ângulo Aberto/tratamento farmacológico , Glaucoma de Ângulo Aberto/induzido quimicamente , Latanoprosta/efeitos adversos , Quinases Associadas a rho/uso terapêutico , Soluções Oftálmicas/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Hipertensão Ocular/tratamento farmacológico , Hipertensão Ocular/induzido quimicamente , Pressão Intraocular , Timolol/uso terapêutico , Resultado do Tratamento
18.
Invest Ophthalmol Vis Sci ; 64(2): 7, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36734964

RESUMO

Purpose: We investigated mechanisms of reduction of intraocular pressure (IOP) by Rho kinase inhibitor AR-12286 in steroid-induced ocular hypertension (SIOH). Methods: C57BL/6 mice (N = 56) were randomly divided into Saline, dexamethasone (DEX), DEX + AR-12286, and DEX-discontinuation (DEX-DC) groups. IOP was measured weekly during the first four weeks in all groups. Beginning at week 5, the DEX-DC group was followed without treatment until IOP returned to normal, and the other groups were treated as assigned with IOP measured every other day for another week. Fluorescent tracer was injected into the anterior chamber to visualize the outflow pattern in the trabecular meshwork (TM) and TM effective filtration area (EFA) was determined. Radial sections from both high- and low-tracer regions were processed for electron microscopy. Results: AR-12286 reduced IOP in SIOH mouse eyes in one day (P < 0.01). At the end of week 5, mean IOP in the DEX + AR-12286 group was ∼4 mm Hg lower than DEX group (P < 0.001) and ∼2 mm Hg lower than DEX-DC group (P < 0.05). After one-week AR-12286 treatment (P < 0.05) or five-week DC of DEX (P < 0.01), DEX-induced reduction of EFA was rescued and DEX-induced morphological changes in the TM were partially reversed. Conclusions: AR-12286 reversed steroid-induced morphological changes in the TM and reduced EFA, which correlated with reduced IOP in SIOH eyes. AR-12286 reduced IOP elevation in SIOH eyes more effectively than discontinuing DEX treatment even when accompanied by continuous DEX treatment. Therefore Rho kinase inhibitors may lower SIOH in patients who rely on steroid treatment.


Assuntos
Glaucoma , Hipertensão Ocular , Animais , Camundongos , Pressão Intraocular , Camundongos Endogâmicos C57BL , Hipertensão Ocular/induzido quimicamente , Hipertensão Ocular/tratamento farmacológico , Quinases Associadas a rho/farmacologia , Malha Trabecular
19.
Ophthalmol Retina ; 7(6): 480-488, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36572383

RESUMO

OBJECTIVE: To compare the rates of complications in eyes that received a dexamethasone (DEX) implant (0.7 mg) or intravitreal triamcinolone (IVT) (2 mg) to treat postvitrectomy macular edema (ME). DESIGN: Retrospective, comparative, case series. SUBJECTS: A total of 148 eyes (147 patients); 75 eyes (75 patients) in the DEX group and 73 eyes (72 patients) in the IVT group. METHODS: The medical records of patients who received an intravitreal DEX 0.7 mg (Ozurdex) or triamcinolone (2 mg) (Triesence) for postvitrectomy ME between July 2014 and December 2021 with a minimum follow-up of 3 months were reviewed. Ocular hypotony and ocular hypertension were defined as intraocular pressure of < 6 mmHg and > 24 mmHg, respectively. MAIN OUTCOME MEASURES: The rates of complications. RESULTS: The follow-up duration was 2.5 ± 1.6 years, with no significant difference between the groups (P = 0.398). The rate of transient ocular hypotony per eye and per injection was significantly higher in the DEX group (10 eyes [13%], 30 of 443 injections [7%]) compared with the IVT group (2 eyes [3%], 2 of 262 injections [0.8%]) (P = 0.039 and < 0.001, respectively). Mean visual acuity significantly decreased at the time of ocular hypotony (P = 0.031), but returned to preinjection level after resolution of the hypotony after a median of 12 days. The incidence of ocular hypertension was higher in the DEX group (23 eyes [31%]) than the IVT group (16 eyes [22%]), but this was not statistically significant (P = 0.307). Ocular hypertension was controlled with observation or topical medication. There were no between-group differences in the incidence of vitreous hemorrhage (DEX, 3 eyes [4%]; IVT, 1 eye [1%]; P = 0.632) or rhegmatogenous retinal detachment (DEX, 3 eyes [4%]; IVT, 0 eyes [0%]; P = 0.253). Four eyes (5%) experienced migration of the DEX implant into the anterior chamber. No eye developed endophthalmitis. CONCLUSION: The incidence of ocular hypotony, which causes transient visual impairment, was significantly higher in vitrectomized eyes treated with DEX compared with eyes treated with IVT. Injections other than the inferotemporal quadrant or rotating injection sites may be recommended. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.


Assuntos
Edema Macular , Hipertensão Ocular , Hipotensão Ocular , Humanos , Glucocorticoides , Triancinolona , Estudos Retrospectivos , Dexametasona , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Hipertensão Ocular/induzido quimicamente , Hipertensão Ocular/complicações
20.
Intern Med ; 62(17): 2513-2516, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36476545

RESUMO

Vasospastic angina (VSA) can be worsened by oral nonselective beta-blockers. Ophthalmic carteolol eye drops are nonselective beta-blockers and effective against glaucoma and ocular hypertension. Systemic effects of ophthalmic beta-blockers on VSA have not yet been reported. We herein report a case of VSA that developed after a patient started carteolol eye drops for ocular hypertension. Even though benidipine, a calcium channel blocker, was started, a VSA attack with incessant non-sustained ventricular tachycardia occurred. Once the carteolol eyedrops were discontinued, the VSA resolved. This case demonstrates that carteolol eye drops can induce life-threatening VSA.


Assuntos
Angina Pectoris Variante , Carteolol , Vasoespasmo Coronário , Glaucoma , Hipertensão Ocular , Humanos , Carteolol/efeitos adversos , Vasoespasmo Coronário/induzido quimicamente , Vasoespasmo Coronário/tratamento farmacológico , Soluções Oftálmicas/efeitos adversos , Antagonistas Adrenérgicos beta/efeitos adversos , Hipertensão Ocular/induzido quimicamente , Hipertensão Ocular/tratamento farmacológico
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