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1.
BMC Ophthalmol ; 24(1): 281, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992579

RESUMO

BACKGROUND: Glaucoma treatment often involves multi-drug regimens, which can lead to poor adherence and side effects. Fixed-dose combinations aim to improve adherence and reduce side effects compared to traditional therapies. This study aimed to compare the prevalence and clinical characteristics of ocular allergy in glaucoma patients using brinzolamide 1.0%/brimonidine 0.2% fixed combination (BBFC), with and without concurrent ß-blocker. METHODS: Of these, 176 patients used a ß-blocker concurrently, whereas 96 patients did not. Allergy prevalence, allergy type, and allergy occurrence time were compared between the concurrent and non-concurrent ß-blocker-usage groups. Ocular allergies were classified and evaluated using Kaplan-Meier survival analysis. RESULTS: Allergy prevalence was 10.23% and 15.63% (p = 0.193), whereas allergy occurrence time was 15.92 ± 13.80 months and 6.26 ± 6.20 months (p = 0.04) in the concurrent and non-concurrent ß-blocker-usage groups, respectively. Kaplan-Meier survival analysis indicated that half of the allergies in the concurrent ß-blocker-usage group occurred within 12.5 months, with the BBFC discontinuation rate gradually increasing up to 36 months. Contrarily, half of the allergies in the non-concurrent ß-blocker-usage group occurred within 3.3 months, with a rapid increase in BBFC discontinuation rate the first 6 months. Intergroup differences in allergy types were significant (p = 0.015). Among all patients with allergy, the average allergy occurrence time of blepharoconjunctivitis, papillary conjunctivitis, and follicular conjunctivitis was 12.52, 9.53, and 13.23 months, respectively. Follicular conjunctivitis tended to occur later than papillary conjunctivitis (p = 0.042). In the concurrent ß-blocker-usage group, follicular conjunctivitis was the most prevalent allergy type (61.1%), whereas papillary conjunctivitis was the most common (66.7%) in in the non-concurrent ß-blocker-usage group. CONCLUSIONS: Concurrent use of ß-blocker with BBFC decreases allergy prevalence, delays allergy onset, and predominantly results in follicular conjunctivitis, thereby facilitating longer treatment duration. Understanding these characteristics of allergy in BBFC users is useful to manage patients and improve treatment adherence. This study provides insights into the role of ß-blockers in modulating ocular allergy in BBFC-treated glaucoma patients, highlighting implications for clinical practice and patient education.


Assuntos
Antagonistas Adrenérgicos beta , Tartarato de Brimonidina , Combinação de Medicamentos , Glaucoma , Soluções Oftálmicas , Sulfonamidas , Tiazinas , Humanos , Masculino , Feminino , Estudos Retrospectivos , Tartarato de Brimonidina/administração & dosagem , Tartarato de Brimonidina/uso terapêutico , Tartarato de Brimonidina/efeitos adversos , Idoso , Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas Adrenérgicos beta/administração & dosagem , Tiazinas/administração & dosagem , Tiazinas/uso terapêutico , Tiazinas/efeitos adversos , Pessoa de Meia-Idade , Prevalência , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Glaucoma/epidemiologia , Glaucoma/tratamento farmacológico , Hipersensibilidade a Drogas/epidemiologia , Inibidores da Anidrase Carbônica/administração & dosagem , Inibidores da Anidrase Carbônica/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Quimioterapia Combinada , Pressão Intraocular/fisiologia , Pressão Intraocular/efeitos dos fármacos , Idoso de 80 Anos ou mais
2.
Ophthalmic Surg Lasers Imaging Retina ; 55(7): 415-417, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38917399

RESUMO

Morning glory disc anomaly is a rare congenital anomaly affecting the optic disc and is frequently associated with retinal detachment. This report presents a unique case of a 10-year-old boy with morning glory disc anomaly and serous retinal detachment, treated with oral acetazolamide. Remarkably, half of the retina exhibiting bullous detachment was reattached leading to full recovery of vision within a few days after starting acetazol-amide treatment. There was no recurrence after discontinuation of medication. Oral acetazolamide can be considered an alternative treatment option for retinal detachment associated with morning glory disc anomaly of non-rhegmatogenous origin. [Ophthalmic Surg Lasers Imaging Retina 2024;55:415-417.].


Assuntos
Acetazolamida , Inibidores da Anidrase Carbônica , Disco Óptico , Descolamento Retiniano , Tomografia de Coerência Óptica , Humanos , Acetazolamida/uso terapêutico , Acetazolamida/administração & dosagem , Masculino , Criança , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/tratamento farmacológico , Descolamento Retiniano/etiologia , Administração Oral , Disco Óptico/anormalidades , Inibidores da Anidrase Carbônica/uso terapêutico , Inibidores da Anidrase Carbônica/administração & dosagem , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Angiofluoresceinografia/métodos
3.
Int J Pharm ; 661: 124391, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38936444

RESUMO

The complex structure of the eye poses challenges in delivering drugs effectively, which can be circumvented by employing nanotechnologies. The present study aimed to prepareacetazolamide-loadedleciplex (ACZ - LP) using a simple one-step fabrication approach followed byoptimization employing a 32 Full Factorial Design. The ACZ - LP demonstrated high entrapment efficiency (93.25 ± 2.32 %), average diameter was recorded around 171.03 ± 3.32 with monodisperse size distribution and zeta potential of 41.33 ± 2.10 mV. Invitro release and ex vivo permeation studies of prepared formulation demonstrated an initial burst release in 1 h followed by sustained release pattern as compared to plain acetazolamide solution. Moreover, an ex vivo corneal drug retention (27.05 ± 1.20 %) and in vitro mucoadhesive studies with different concentration of mucin indicated strong electrostatic bonding confirming the mucoadhesive characteristics of the formulation. Additionally, the histopathological studies ensured that the formulation was non-irritant and nontoxic while and HET-CAM ensured substantial tolerability of the formulation. The in vivo pharmacodynamic investigation carried out on a rabbit model demonstrated that treatment with ACZ - LP resulted in a significant and prolonged reduction in intraocular pressure as compared to plain acetazolamide solution, acetazolamide oral tablet, and Brinzox®. In summary, the ACZ - LP is anefficient and versatile drug delivery approach which demonstrates significant potential in controlling glaucoma.


Assuntos
Acetazolamida , Inibidores da Anidrase Carbônica , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Pressão Intraocular , Acetazolamida/administração & dosagem , Acetazolamida/farmacocinética , Acetazolamida/química , Acetazolamida/farmacologia , Animais , Coelhos , Inibidores da Anidrase Carbônica/administração & dosagem , Inibidores da Anidrase Carbônica/farmacocinética , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/farmacologia , Pressão Intraocular/efeitos dos fármacos , Córnea/metabolismo , Córnea/efeitos dos fármacos , Masculino , Administração Oftálmica , Tamanho da Partícula , Portadores de Fármacos/química
4.
Indian J Ophthalmol ; 72(7): 976-982, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38905461

RESUMO

PURPOSE: To evaluate the effect of topical carbonic anhydrase inhibitor (brinzolamide) versus placebo on visual function and waveforms in infantile nystagmus syndrome (INS). DESIGN: Prospective, placebo-controlled, double-blind, cross-over study. METHODS: Setting- A tertiary eye care center. Patients- Cases of idiopathic INS with and without abnormal head posture aged ≥10 years who had not received previous treatment for nystagmus. Intervention- Patients were randomized into two groups. Group 1 was given placebo for 3 months, and after a washout period of 7 days started on topical brinzolamide for the next 3 months. In group 2, the order was reversed. The drops were administered topically three times (every 8 hours) in both eyes. Outcome measure- Binocular best corrected visual acuity (BCVA) using the ETDRS chart, eXpanded nystagmus acuity function (NAFX) score and INS waveforms obtained from eye movement recordings, intraocular pressure (IOP) by Goldmann applanation tonometer, near stereopsis by TNO stereo test, and change in abnormal head posture before and after intervention in the null position. RESULTS: A total of 29 cases completed the study (23 with abnormal head posture; 6 without abnormal head posture).A significant improvement was noted in INS waveform characteristics, mean NAFX score (P < 0.001), and mean binocular visual acuity (P < 0.001) with topical brinzolamide in comparison to baseline as well as placebo. No significant change in head position and stereopsis was noted. No side effects were reported with 3 months of brinzolamide therapy. CONCLUSIONS: While brinzolamide shows improvement in visual acuity and NAFX score in idiopathic INS, its clinical significance needs further evidence.


Assuntos
Administração Tópica , Inibidores da Anidrase Carbônica , Estudos Cross-Over , Soluções Oftálmicas , Sulfonamidas , Tiazinas , Acuidade Visual , Humanos , Inibidores da Anidrase Carbônica/administração & dosagem , Inibidores da Anidrase Carbônica/uso terapêutico , Método Duplo-Cego , Masculino , Feminino , Acuidade Visual/fisiologia , Estudos Prospectivos , Tiazinas/administração & dosagem , Sulfonamidas/administração & dosagem , Criança , Adulto , Soluções Oftálmicas/administração & dosagem , Adolescente , Nistagmo Congênito/tratamento farmacológico , Nistagmo Congênito/fisiopatologia , Nistagmo Congênito/diagnóstico , Resultado do Tratamento , Adulto Jovem , Seguimentos , Pessoa de Meia-Idade , Movimentos Oculares/fisiologia , Movimentos Oculares/efeitos dos fármacos , Visão Binocular/fisiologia
5.
Br J Clin Pharmacol ; 90(7): 1751-1755, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38770584

RESUMO

To our knowledge, no prior study has analysed a possible association between acetazolamide and pulmonary oedema. The aim of this study was to use data from the EudraVigilance to detect a safety signal for acetazolamide-induced pulmonary oedema. We performed a disproportionality analysis (case-noncase method), calculating reporting odds ratios (RORs) up to 22 February 2024. Among 11 684 208 spontaneous cases of adverse reactions registered in EudraVigilance, 38 275 were pulmonary oedemas. Acetazolamide was involved in 31 cases. In more than half of those cases, the patients received a single dose of acetazolamide after undergoing cataract surgery: latency was 10-90 min. Remarkably, there were five cases of positive rechallenge and six cases resulted in death. The ROR for acetazolamide was 3.63 (95% CI 2.55-5.17). Disproportionality was also observed in VigiBase®: ROR 4.44 (95% CI 3.34-5.90). Our study confirms a signal that suggests a risk of serious pulmonary oedema associated with acetazolamide.


Assuntos
Acetazolamida , Bases de Dados Factuais , Edema Pulmonar , Humanos , Acetazolamida/efeitos adversos , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Bases de Dados Factuais/estatística & dados numéricos , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Adulto , Inibidores da Anidrase Carbônica/efeitos adversos , Inibidores da Anidrase Carbônica/administração & dosagem , Farmacovigilância , Idoso de 80 Anos ou mais
7.
Klin Monbl Augenheilkd ; 241(4): 554-558, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38653306

RESUMO

We report the case of a 32-year-old male who presented with an acute myopic shift as a result of uveal effusion following a single administration of 250 mg acetazolamide. The drug was discontinued and following cycloplegia and topical steroid therapy, we observed progressive deepening of the anterior chamber, reopening of the iridocorneal angle, and complete resolution of the myopic shift after 5 days. A literature review since 1956 identified 23 cases, including ours, which developed a myopic shift after a median time of 24 h (3 - 24) following a median dose of 500 mg (125 - 1000) acetazolamide, with about a third complicated by angle closure ocular hypertension. This presumed idiosyncratic reaction can occur without prior drug exposure and independent of the phakic status. Treatment options include systematic drug withdrawal associated with cycloplegia, anti-glaucomatous agents, and/or corticosteroids. Full recovery is achieved within about 5 days (2 - 14). Given the widespread use of acetazolamide, awareness of this idiosyncratic reaction is crucial to avoid complications of acute angle-closure glaucoma.


Assuntos
Acetazolamida , Miopia , Humanos , Acetazolamida/uso terapêutico , Acetazolamida/efeitos adversos , Acetazolamida/administração & dosagem , Masculino , Adulto , Miopia/induzido quimicamente , Miopia/tratamento farmacológico , Inibidores da Anidrase Carbônica/efeitos adversos , Inibidores da Anidrase Carbônica/administração & dosagem , Inibidores da Anidrase Carbônica/uso terapêutico , Doença Aguda , Resultado do Tratamento
9.
Int J Pharm ; 657: 124098, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38621614

RESUMO

Glaucoma, the second most common cause of blindness worldwide, requires the development of new and effective treatments. This study introduces a novel controlled-release system utilizing elastin-like recombinamers (ELR) and the Supercritical Antisolvent (SAS) technique with supercritical CO2. Acetazolamide (AZM), a class IV drug with limited solubility and permeability, is successfully encapsulated in an amphiphilic ELR at three different ELR:AZM ratios, yielding up to 62 %. Scanning electron microscopy (SEM) reveals spherical microparticles that disintegrate into monodisperse nanoparticles measuring approximately 42 nm under physiological conditions. The nanoparticles, as observed via Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM), do not exhibit aggregates, a fact confirmed by the zeta potential displaying a value of -33 mV over a period of 30 days. Transcorneal permeation tests demonstrate a 10 % higher permeation level compared to the control solution, which increases to 30 % after 2 h. Ocular irritation tests demonstrate no adverse effects or damage. Intraocular pressure (IOP) tests conducted on hypertensive rabbits indicate greater effectiveness for all three analyzed formulations, suggesting enhanced drug bioavailability during treatment. Consequently, the combination of recombinant biopolymers and high-pressure techniques represents a promising approach for advancing glaucoma therapy, emphasizing its potential clinical significance.


Assuntos
Acetazolamida , Elastina , Glaucoma , Pressão Intraocular , Nanopartículas , Coelhos , Animais , Acetazolamida/administração & dosagem , Acetazolamida/química , Acetazolamida/farmacocinética , Glaucoma/tratamento farmacológico , Elastina/química , Pressão Intraocular/efeitos dos fármacos , Nanopartículas/química , Preparações de Ação Retardada/química , Solventes/química , Solubilidade , Masculino , Inibidores da Anidrase Carbônica/administração & dosagem , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/farmacocinética , Disponibilidade Biológica , Córnea/metabolismo , Córnea/efeitos dos fármacos , Composição de Medicamentos/métodos , Permeabilidade
10.
J Nephrol ; 37(4): 911-922, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38265601

RESUMO

BACKGROUND: Urine alkalization is one of the standard treatments to prevent acute kidney injury in patients receiving high-dose methotrexate. Carbonic anhydrase inhibitors are promising adjuvants/substitutes with advantages such as faster urine alkalization time and prevention of fluid overload. However, there is limited and contradictory evidence on its efficacy and safety. We aimed to compare the efficacy and safety of carbonic anhydrase inhibitors to standard treatments in adult patients receiving high-dose methotrexate. METHODS: The protocol was registered at PROSPERO (CRD42022352802) in August 2021. We evaluated the use of carbonic anhydrase inhibitors in combination with standard treatment compared to standard treatment alone. We excluded articles irrelevant to the efficacy and safety of acetazolamide in patients receiving high dose methotrexate and/or did not provide sufficient data regarding doses, recruitment criteria, and follow-up period. Two authors performed the data extraction independently. RESULTS: Among 198 articles retrieved, six observational studies met all eligibility criteria. Four studies with five datasets (totaling 558 patients/cycles) had enough data to be included in the meta-analysis. We independently report the results from the two remaining studies. The results did not show a significant difference between acetazolamide versus standard treatment in acute kidney injury (AKI) rate (OR = 0.79, 95% CI 0.48-1.29, P = 0.34, I2 = 0%). Regarding the time to urine pH goal, there was no significant time difference between the two groups (Mean Difference = 0.07, 95% CI - 1.9 to 2.04, P = 0.95, I2 = 25%). Furthermore, our meta-analysis showed that acetazolamide did not reduce length of stay (Mean Difference = 0.75, 95% CI - 0.8 to 2.31, P = 0.34, I2 = 0%). In one study, the only reported side effect of acetazolamide was hypokalemia (nearly 50% in the acetazolamide group). CONCLUSIONS: This systematic review showed no significant difference between acetazolamide and standard care treatment regarding urine alkalinization time and AKI rate in adult patients receiving high dose methotrexate. We suggest performing a large blinded, randomized, controlled trial to evaluate the potential benefits of this low-cost medication.


Assuntos
Acetazolamida , Injúria Renal Aguda , Inibidores da Anidrase Carbônica , Metotrexato , Acetazolamida/administração & dosagem , Acetazolamida/uso terapêutico , Acetazolamida/efeitos adversos , Humanos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Metotrexato/administração & dosagem , Inibidores da Anidrase Carbônica/administração & dosagem , Inibidores da Anidrase Carbônica/efeitos adversos , Inibidores da Anidrase Carbônica/uso terapêutico , Resultado do Tratamento
11.
Retina ; 44(5): 852-860, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38166238

RESUMO

PURPOSE: To compare within-subject efficacy and safety of intravitreal dexamethasone implant and topical carbonic anhydrase inhibitors in the treatment of retinitis pigmentosa-related cystoid macular edema. METHODS: Patients with bilateral retinitis pigmentosa-related cystoid macular edema were treated with intravitreal dexamethasone implant in one eye and topical carbonic anhydrase inhibitors in the contralateral eye. The primary endpoint was a change in central macular thickness. Secondary endpoints were changes in best-corrected visual acuity and microperimetric central retinal sensitivity. Intraocular pressure and other ocular complications were evaluated for safety assessment. RESULTS: Nine patients were recruited for this 12-month follow-up study. Central macular thickness was significantly lower in intravitreal dexamethasone implant-treated eyes than in topical carbonic anhydrase inhibitors-treated eyes at Months 1 and 7, whereas mean best-corrected visual acuity was better in eyes treated with topical carbonic anhydrase inhibitors at Month 12 (borderline significant P = 0.0510). There was no difference in microperimetric sensitivity between the two treatments. Three patients developed ocular hypertension after intravitreal dexamethasone implant. Intravitreal dexamethasone implant showed an effect on the contralateral eye in five of nine patients. CONCLUSION: Intravitreal dexamethasone implant was more effective than topical carbonic anhydrase inhibitors in reducing retinitis pigmentosa-related cystoid macular edema 1 month after treatment. Corticosteroids can play a key role in the management of retinitis pigmentosa-related cystoid macular edema; however, their routes, timing, and modes of administration should be further explored.


Assuntos
Inibidores da Anidrase Carbônica , Dexametasona , Implantes de Medicamento , Glucocorticoides , Edema Macular , Retinose Pigmentar , Tomografia de Coerência Óptica , Acuidade Visual , Humanos , Retinose Pigmentar/tratamento farmacológico , Retinose Pigmentar/fisiopatologia , Retinose Pigmentar/complicações , Retinose Pigmentar/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Edema Macular/diagnóstico , Edema Macular/fisiopatologia , Inibidores da Anidrase Carbônica/administração & dosagem , Inibidores da Anidrase Carbônica/uso terapêutico , Dexametasona/administração & dosagem , Estudos Prospectivos , Feminino , Masculino , Projetos Piloto , Glucocorticoides/administração & dosagem , Pessoa de Meia-Idade , Adulto , Seguimentos , Injeções Intravítreas , Idoso , Resultado do Tratamento , Administração Tópica
12.
Ophthalmol Retina ; 8(6): 600-606, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38104928

RESUMO

PURPOSE: To date, there is no standard treatment regimen for carbonic anhydrase inhibitors (CAIs) in X-linked retinoschisis (XLRS) patients. This retrospective study aims to evaluate the efficacy of CAIs on visual acuity and cystoid fluid collections (CFC) in XRLS patients in Dutch and Belgian tertiary referral centers. DESIGN: Retrospective cohort study. PARTICIPANTS: Forty-two patients with XLRS. METHODS: In total, 42 patients were enrolled. To be included, patients had to have previous treatment with an oral CAI (acetazolamide), a topical CAI (brinzolamide/dorzolamide), or a combination of an oral and a topical CAI for at least 4 consecutive weeks. We evaluated the effect of the CAI on best-corrected visual acuity (BCVA) and central foveal thickness (CFT) on OCT. MAIN OUTCOME MEASURES: Central foveal thickness and BCVA. RESULTS: The median age at the baseline visit of the patients in this cohort study was 14.7 (range, 43.6) years, with a median (interquartile range [IQR]) follow-up period of 4.0 (2.2-5.2) years. During the follow-up period, 25 patients were treated once with an oral CAI (60%), 24 patients were treated once with a topical CAI (57%), and 11 patients were treated once with a combination of both topical and oral CAI (26%). We observed a significant reduction of CFT for oral CAI by 14.37 µm per 100 mg per day (P < 0.001; 95% confidence interval [CI], -19.62 to -9.10 µm) and for topical CAI by 7.52 µm per drop per day (P = 0.017; 95% CI, -13.67 to -1.32 µm). The visual acuity changed significantly while on treatment with oral CAI by -0.0059 logMAR per 100 mg (P = 0.008; 95% CI, -0.010 to -0.0013 logMAR). Seven patients (17%) had side effects leading to treatment discontinuation. CONCLUSIONS: Our data indicate that treatment with (oral) CAI may be beneficial for short-term management of CFC in patients with XLRS. Despite a significant reduction in CFT, the change in visual acuity was modest and not of clinical significance. Nonetheless, the anatomic improvement of the central retina in these patients may be of value to create an optimal retinal condition for future potential treatment options such as gene therapy. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.


Assuntos
Inibidores da Anidrase Carbônica , Retinosquise , Tomografia de Coerência Óptica , Acuidade Visual , Humanos , Inibidores da Anidrase Carbônica/administração & dosagem , Retinosquise/tratamento farmacológico , Retinosquise/diagnóstico , Retinosquise/fisiopatologia , Estudos Retrospectivos , Masculino , Tomografia de Coerência Óptica/métodos , Adulto , Adolescente , Feminino , Seguimentos , Adulto Jovem , Resultado do Tratamento , Criança , Líquido Sub-Retiniano , Pessoa de Meia-Idade , Sulfonamidas/administração & dosagem , Administração Oral
13.
Retina ; 42(1): 168-173, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34393209

RESUMO

PURPOSE: To investigate the rate of the recurrence of cystoid macular edema (CME) secondary to retinitis pigmentosa (RP) after the initiation of topical dorzolamide and the recurrence risk factors. METHODS: We retrospectively analyzed the data of RP patients at Kyushu University Hospital. We included patients who showed a treatment response to 1.0% topical dorzolamide. The day of treatment initiation was set as the baseline. Topical dorzolamide treatment was continued during the follow-up. The recurrence of CME (defined as a >20% increase in central subfield thickness compared to previous visit, or a central subfield thickness value that exceed baseline value) was evaluated at each follow-up visit. Risk factors for RP-CME recurrence were analyzed by Cox proportional hazards modeling. A Kaplan-Meier survival analysis was used to evaluate the time to recurrent RP-CME. RESULTS: Forty RP-CME patients showed a treatment response to topical dorzolamide. During the mean 3.9-year follow-up, 14 patients exhibited recurrence; its rate was 15.6%, 34.7%, and 48.7% at 1, 3, and 5 years, respectively. A high baseline central subfield thickness was significantly associated with recurrent (hazard ratio 1.11, 95% CI: 1.05-1.18, P = 0.0004). CONCLUSION: The recurrence rate of RP-CME increased with time. A high baseline central subfield thickness value was a risk factor for recurrence.


Assuntos
Macula Lutea/crescimento & desenvolvimento , Edema Macular/epidemiologia , Retinose Pigmentar/complicações , Medição de Risco/métodos , Sulfonamidas/administração & dosagem , Tiofenos/administração & dosagem , Tomografia de Coerência Óptica/métodos , Acuidade Visual , Administração Tópica , Inibidores da Anidrase Carbônica/administração & dosagem , Feminino , Seguimentos , Humanos , Incidência , Japão/epidemiologia , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Retinose Pigmentar/diagnóstico , Fatores de Risco , Fatores de Tempo
14.
Semin Pediatr Neurol ; 40: 100922, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34749916

RESUMO

Primary intracranial hypertension (PIH) is characterized by clinical signs of increased intracranial pressure, papilledema, elevated opening pressure, and absence of mass lesion, hydrocephalus, or meningeal enhancement on neuroimaging. Visual changes are a common presenting feature and if untreated there is risk of irreversible vision loss. There have been recent proposed changes to the criteria for PIH along with studies looking at the differences in imaging characteristics between adult and pediatric PIH. The presence of transverse sinus stenosis alone was highly sensitive and specific for pediatric PIH. The Idiopathic Intracranial Hypertension Treatment Trial was an adult, multicenter study that examined the use of acetazolamide and weight loss on the course of PIH. The study confirmed many previously held beliefs including the most common presenting symptom in PIH is headache. Most patients present with bilateral papilledema with 58.2% of patients having symmetric Frisen scale grading and within one grade in 92.8%. Although diplopia is a common reported symptom, very few have evidence of cranial nerve palsy. Male gender, high-grade papilledema, and decreased visual acuity at presentation are risk factors for treatment failure. Acetazolamide use is associated with mild metabolic acidosis. During acetazolamide treatment, monitoring for hypokalemia or aplastic anemia is not recommended. Monitoring transaminases in the titration phase of treatment should be considered due to a case of transaminitis and pancreatitis with elevated lipase. Newer case reports have also seen associations of secondary intracranial hypertension with concurrent COVID-19 infection and MIS-C.


Assuntos
Acetazolamida/administração & dosagem , COVID-19/diagnóstico , Inibidores da Anidrase Carbônica/administração & dosagem , Cefaleia/diagnóstico , Hipertensão Intracraniana , Papiledema/diagnóstico , Transtornos da Visão/diagnóstico , Redução de Peso , Acetazolamida/efeitos adversos , Adolescente , Adulto , COVID-19/complicações , Inibidores da Anidrase Carbônica/efeitos adversos , Criança , Terapia Combinada , Diagnóstico Diferencial , Feminino , Cefaleia/etiologia , Humanos , Hipertensão Intracraniana/complicações , Hipertensão Intracraniana/diagnóstico , Hipertensão Intracraniana/terapia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Papiledema/etiologia , Pseudotumor Cerebral/complicações , Pseudotumor Cerebral/diagnóstico , Pseudotumor Cerebral/etiologia , Pseudotumor Cerebral/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome de Resposta Inflamatória Sistêmica/complicações , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Tomografia de Coerência Óptica , Transtornos da Visão/etiologia , Adulto Jovem
15.
Drug Deliv ; 28(1): 2177-2186, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34662264

RESUMO

Acetazolamide is the drug of choice for glaucoma treatment in an emergency. However, it is not available in any topical formulation and it is available only as systemic tablets. Despite its efficiency as a drug in decreasing intraocular pressure, it has negative systemic effects as renal toxicity and metabolic acidosis. Moreover, it suffers from poor aqueous solubility and low corneal permeability limiting its ocular bioavailability and its use topically. Cubosomes have enormous advantages as a drug delivery system, most importantly, high surface area, thermal stability, and ability to encapsulate hydrophobic, amhiphilic, and hydrophilic molecules. Herein, we have exploited the unique properties of cubosomes as a novel nano-delivery system for acetazolamide as eye drops dosage form for glaucoma treatment. Different acetazolamide-loaded cubosomes have been developed and evaluated. The best-optimized formulation (F5), was cubic shaped structure, with an average particle size of 359.5 ± 2.8 nm, surface charge -10.8 ± 3.2 mV, and 59.8% entrapment efficiency. Ex-vivo corneal permeation studies have revealed a 4-fold increase in acetazolamide permeability coefficient compared to that stated in the literature. F5 showed superior therapeutic efficacy represented by a 38.22% maximum decrease in intraocular pressure vs. 31.14 and 21.99% decrease for the commercial Azopt® eye drops and Cidamex® tablets, respectively. It also exhibited higher (AUC0-10) compared to Azopt® eye drops and Cidamex® tablets by 2.3 and 3 times, respectively. F5 showed mean residence time 4.22 h vs. 2.36 and 2.62 h for Azopt® and Cidamex® with no eye irritation observed according to the modified Draize test. To the best of our knowledge, this is the first study for developing acetazolamide-loaded cubosomes as the topical delivery system for glaucoma treatment.


Assuntos
Acetazolamida/farmacologia , Inibidores da Anidrase Carbônica/administração & dosagem , Inibidores da Anidrase Carbônica/farmacologia , Nanopartículas/química , Acetazolamida/farmacocinética , Administração Tópica , Animais , Área Sob a Curva , Inibidores da Anidrase Carbônica/efeitos adversos , Inibidores da Anidrase Carbônica/farmacocinética , Química Farmacêutica , Córnea/efeitos dos fármacos , Portadores de Fármacos/química , Concentração de Íons de Hidrogênio , Pressão Intraocular/efeitos dos fármacos , Soluções Oftálmicas/administração & dosagem , Tamanho da Partícula , Coelhos
17.
Eur J Med Chem ; 225: 113793, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34507012

RESUMO

Platinum-based chemotherapy is widely used for the treatment of different tumors but is associated with serious side effects, among which neuropathic pain. Carbonic anhydrase (CA, EC 4.2.1.1) inhibitors have recently been validated as therapeutic agents in neuropathic pain and as antitumor agents. We report the synthesis of new organochalcogenides bearing the benzensulfonamide moiety acting as potent inhibitors of several human CA isoforms and, in particular, against hCA II and VII endowed with potent neuropathic pain attenuating effects. Moreover, in combination with cisplatin or doxorubicin, some of the new CA inhibitors enhanced the effects of the anticancer drugs capability in counteracting breast cancer MCF7 cell viability. The concomitant anti-neuropathic pain and antiproliferative effects of the new chalcogenide-based CA inhibitors represent an innovative approach for the counteraction and management of side effects associated with clinically platinum drugs as antitumor agents.


Assuntos
Antineoplásicos/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Calcogênios/farmacologia , Cisplatino/farmacologia , Neuralgia/tratamento farmacológico , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Inibidores da Anidrase Carbônica/administração & dosagem , Inibidores da Anidrase Carbônica/química , Proliferação de Células/efeitos dos fármacos , Calcogênios/síntese química , Calcogênios/química , Cisplatino/administração & dosagem , Cisplatino/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Células MCF-7 , Masculino , Camundongos , Estrutura Molecular , Neuralgia/induzido quimicamente , Oxaliplatina , Estresse Oxidativo/efeitos dos fármacos , Medição da Dor , Relação Estrutura-Atividade
18.
Drug Test Anal ; 13(10): 1803-1806, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34463045

RESUMO

The use of specific medicine up to several months before a doping control is not be reported on the doping control form, while the drug could then still be detectable in urine in case of a very slow elimination. It may lead to a positive test result. For example, dorzolamide, a carbonic anhydrase inhibitor for topical ophthalmic application, has a very slow elimination rate via the renal route (half-life > 4 months). This substance can be a source of unintended anti-doping rule violations.


Assuntos
Inibidores da Anidrase Carbônica/administração & dosagem , Dopagem Esportivo/prevenção & controle , Sulfonamidas/administração & dosagem , Tiofenos/administração & dosagem , Administração Oftálmica , Adulto , Inibidores da Anidrase Carbônica/farmacocinética , Feminino , Meia-Vida , Humanos , Sulfonamidas/farmacocinética , Tiofenos/farmacocinética , Fatores de Tempo
19.
Int J Biol Macromol ; 186: 864-872, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34274401

RESUMO

Mucoadhesive formulations capable of situ gelation are promising for improving ocular drug delivery. Here we investigated two types of nanogels based on anionic glycosaminoglycans with grafted thermo-responsive poly(N-isopropylacrylamide) chains. One type of nanogels were formed by thermo-induced gelling of heparin-graft-poly(N-isopropylacrylamide) and chondroitin sulfate-graft-poly(N-isopropylacrylamide) copolymers. Another type of nanogels was based on the same copolymers, but terminal groups of thermosensitive macromolecular chains were modified to form covalent disulfide cross-links. All types of nanogels were studied towards their ability to encapsulate and release model drug - dexamethasone. Mucoadhesivity of both thermo-gelled and covalently cross-linked polymeric systems, as well as their ability to interact with dexamethasone, was assessed by microscale thermophoresis (MST). Mucoadhesion properties were also evaluated by isothermal titration calorimetry (ITC), which were in good correlation with MST data. The presence of disulfide linkages and thiol groups were shown to favor improved binding of cross-linked nanogels to mucin. Moreover, in vivo intraocular pressure studies showed that presence of polymers in solution can alter the ocular absorption of carbonic anhydrase inhibitor from eyedrops. The pharmacological effect was in line with mucoadhesive properties of these copolymers.


Assuntos
Resinas Acrílicas/química , Inibidores da Anidrase Carbônica/química , Dexametasona/análogos & derivados , Glicosaminoglicanos/química , Mucinas/química , Nanogéis , Piperazinas/química , Polímeros Responsivos a Estímulos/química , Temperatura , Adesividade , Administração Oftálmica , Animais , Inibidores da Anidrase Carbônica/administração & dosagem , Dexametasona/química , Composição de Medicamentos , Liberação Controlada de Fármacos , Feminino , Pressão Intraocular/efeitos dos fármacos , Masculino , Nanotecnologia , Soluções Oftálmicas , Piperazinas/administração & dosagem , Coelhos , Ratos
20.
Medicine (Baltimore) ; 100(22): e26232, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087906

RESUMO

RATIONALE: Metastasis of neoplasms to the eye is quite uncommon. In this case report, we describe a patient where primary esophageal cancer was diagnosed by fine needle aspiration biopsy (FNAB) of an iris tumor. PATIENT CONCERNS: A 70-year-old male complained of redness and discomfort in the right eye. DIAGNOSIS AND INTERVENTIONS: The patient's right eye was diagnosed as idiopathic uveitis, and a topical steroid was administered. As vitreous opacities were observed even after topical therapy, oral prednisolone was administered. On slit-lamp examination of the right eye, an iris mass with neovascularization was seen in the anterior chamber. A metastatic tumor was suspected, and FNAB was performed. Histology revealed squamous cell carcinoma. Systemic workup revealed esophageal cancer with several metastases. Best-corrected visual acuity decreased to 20/400, and intraocular pressure was 40 mmHg in the right eye. Two iris tumors with neovascularization were present extending into the anterior chamber with posterior iris synechiae and 360 degree peripheral anterior synechiae. Intraocular pressure in the right eye was medically managed with hypotensive eye drops and oral acetazolamide. Iris metastases were treated with 40 Gray of radiation therapy and concurrent chemotherapy. OUTCOMES: The tumor regressed, but intraocular pressure was refractory to treatment because of 360 degree goniosynechial closure. The right eye lost light perception six months after treatment commenced, and the patient died 9 months after the onset of therapy due to multiple systemic metastases. LESSONS: This is a rare case of masquerade syndrome without systemic symptoms in which FNAB of an iris tumor led to a diagnosis of metastatic esophageal squamous cell carcinoma. Although the patient lost his sight due to uncontrollable ocular hypertension, systemic chemotherapy, and radiation therapy were initially effective in the treatment of the metastatic iris tumor. As the prognosis of patients with metastatic iris tumors is poor, it is important for ophthalmologists to consider such diagnoses and conduct systemic investigations when necessary.


Assuntos
Biópsia por Agulha Fina/métodos , Neoplasias Esofágicas/patologia , Neoplasias da Íris/secundário , Iris/patologia , Hipertensão Ocular/tratamento farmacológico , Acetazolamida/administração & dosagem , Acetazolamida/uso terapêutico , Administração Oral , Idoso , Câmara Anterior/patologia , Inibidores da Anidrase Carbônica/administração & dosagem , Inibidores da Anidrase Carbônica/uso terapêutico , Carcinoma de Células Escamosas/diagnóstico , Quimiorradioterapia/métodos , Evolução Fatal , Humanos , Pressão Intraocular/efeitos dos fármacos , Neoplasias da Íris/diagnóstico , Neoplasias da Íris/terapia , Masculino , Metástase Neoplásica/patologia , Neovascularização Patológica/patologia , Acuidade Visual
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