Comparison of the efficacy of latanoprost versus dorzolamide/timolol fixed combination therapy in patients with pseudoexfoliative glaucoma according to glaucoma stage / Comparação da eficácia da terapia de combinação fixa latanoprosta versus dorzolamida/timolol em pacientes com glaucoma pseudoesfoliativo de acordo com o estágio de glaucoma

ABSTRACT Purpose: Only a few trials have compared the intraocular pressure-lowering effects of prostaglandin analogs to carbonic anhydrase inhibitor plus beta-blocker fixed-dose combination therapy in patients with pseudoexfoliative glaucoma. Furthermore, the influence of the glaucoma stage on the intraocular pressure-lowering effects of these drug types has not been studied. The purpose of this study was to compare the IOP-lowering efficacy of latanoprost, a prostaglandin analog versus dorzolamide/timolol fixed combination, a carbonic anhydrase inhibitor plus beta-blocker fixed-dose combination therapy, in patients with pseudoexfoliative glaucoma based on glaucoma stage. Methods: The data of 32 eyes (32 patients) diagnosed with uniocular pseudoexfoliative glaucoma and treated with topical latanoprost (Group 1) or dorzolamide/timolol fixed combination (Group 2) were retrospectively assessed. The groups were subdivided into early and moderate-advanced stages. Patients' demographics, baseline intraocular pressure, final intraocular pressure, and intraocular pressure difference (the difference between the baseline and final intraocular pressure) were determined from medical records and compared between groups and according to glaucoma stage. Results: The mean drug use duration was 17.7 ± 13.5 months. No significant differences in mean baseline intraocular pressure, mean final intraocular pressure and mean intraocular pressure difference between Groups 1 and 2. In Group 2, the mean intraocular pressure difference was significantly greater in patients with early versus moderate-advanced stage glaucoma (p=0.015). The difference, however, was not detected in Group 1. The mean intraocular pressure difference in early-stage glaucoma was significantly greater in Group 2 versus 1 (p=0.033). Conclusions: Latanoprost and dorzolamide/timolol fixed combination are effective treatments for newly diagnosed pseudoexfoliative glaucoma. In early-stage pseudoexfoliative glaucoma, greater intraocular pressure reduction was noted with dorzolamide/timolol fixed combination than with latanoprost; thus, dorzolamide/timolol fixed combination should be considered when a significant decrease in intraocular pressure is desired in early-stage glaucoma.

RESUMO Objetivo: Estudos limitados examinaram os efeitos de redução de pressão intraocular de análogos de prostaglandina versus inibidor de anidrase carbônica mais terapia de combinação de dose fixa beta-bloqueador em pacientes com glaucoma pseudoesfoliativo. Além disso, a influência do estágio de glaucoma nos efeitos de redução da pressão intraocular desses tipos de drogas não foi avaliada. Este estudo teve como objetivo comparar a eficácia de redução do IOP do latanoprosta, uma combinação fixa análoga de prostaglandina versus dorzolamida/timolol, um inibidor de anidrase carbônica mais terapia de combinação de dose fixa beta-bloqueador, em pacientes com glaucoma pseudoesfoliativo de acordo com o estágio de glaucoma. Métodos: Os dados de 32 olhos (32 pacientes) diagnosticados com glaucoma pseudoesfoliativo monocular e tratados com latanoprosta tópica (Grupo 1) ou combinação fixa de dorzolamida/timolol (Grupo 2) foram avaliados retrospectivamente. Os grupos foram subdivididos em estágios inicial e moderado-avançado. A demografia dos pacientes, a pressão intraocular da linha de base, a pressão intraocular final e a diferença de pressão intraocular (a diferença entre a pressão intraocular da linha de base e a pressão intraocular final) foram determinadas a partir dos prontuários médicos e comparadas entre os dois grupos e de acordo com o estágio de glaucoma. Resultados: A duração média do uso de drogas foi de 17,7 ± 13,5 meses. Nenhuma diferença significativa foi observada entre os grupos 1 e 2 para a média da pressão intraocularda linha de base, média da pressão intraocular final e média da diferença da pressão intraocular. No Grupo 2, a média da diferença da pressão intraocular foi significativamente maior em pacientes com glaucoma de estágio precoce versus moderado-avançado (p=0,015). No entanto, essa diferença não foi observada no Grupo 1. A média da diferença da pressão intraocular em glaucoma de estágio inicial foi significativamente maior no Grupo 2 versus 1 (p=0,033). Conclusões: Terapias com Latanoprosta e dorzolamida/timolol são tratamentos eficazes para glaucoma pseudoesfoliativo recém-diagnosticado. Observou-se em glaucoma pseudoesfoliativo de estágio inicial, uma maior redução da pressão intraocular com combinação fixa de dorzolamida/timolol do que com latanoprosta; assim, a combinação fixa de dorzolamida/timolol deve ser considerada quando uma diminuição significativa da pressão intraocular é almejada em glaucoma de estágio inicial.

Efficacy of selective laser trabeculoplasty versus latanoprost as initial management in glaucoma / Eficácia da trabeculoplastia seletiva a laser versus latanoprosta como tratamento inicial no glaucoma

ABSTRACT Objective: To compare the hypotensive effect of SLT vs the use of latanoprost in the initial management of patients with suspected glaucoma and diagnosis of glaucoma. To evaluate the patients' quality of life using the Glaucoma Quality of Life questionnaire. Methods: Randomized controlled clinical trial conducted in the city of Cartagena, Colombia, between October 2021 to June 2023. Assignment to the SLT or latanoprost group with follow-up at days 7, 30, 90, 180, and 365 in patients diagnosed with suspected glaucoma, mild and moderate glaucoma. Results: 31 patients (60 eyes), of which 17 were men. Group SLT were 31 eyes and the latanoprost group included 29 eyes. The mean baseline IOP of the SLT group was 18.9mmHg and in the latanoprost group, it was 19.6mmHg. The mean IOP at the end of the follow-up group SLT was 13.9mmHg and for latanoprost 14.5mmHg. The IOP reduction percentage at one year of follow-up in the SLT group was 23.4% and that of the latanoprost group was 23.6% Conclusions: Selective laser trabeculoplasty with Nd-YAG laser is as effective as the use of prostaglandin analogues as initial treatment in the early stages of glaucoma. Regarding the quality of life scale, although there were no statistically significant differences in both groups, the SLT showed an increase in the difficulty perceived by the patient for activities that involve peripheral vision, which is the most affected in patients with glaucoma.

RESUMO Objetivo: Comparar o efeito hipotensor da trabeculoplastia seletiva a laser versus o uso de latanoprosta no tratamento inicial de pacientes com suspeita de glaucoma e diagnóstico de glaucoma; avaliar a qualidade de vida dos pacientes por meio do Glaucoma Quality of Life Survey. Métodos: Ensaio clínico randomizado controlado realizado na cidade de Cartagena, Colômbia, entre outubro de 2021 e junho de 2023. Atribuição ao grupo trabeculoplastia seletiva a laser ou latanoprosta com acompanhamento nos dias 7, 30, 90, 180 e 365 em pacientes diagnosticados com suspeita de glaucoma, glaucoma leve e moderado. Resultados: Foram incluídos 31 pacientes (60 olhos), sendo 17 homens. No Grupo Trabeculoplastia Seletiva a Laser, foram 31 olhos, e, no Grupo Latanoprosta, 29 olhos. A pressão intraocular basal média do Grupo Trabeculoplastia Seletiva a Laser foi de 18,9mmHg e, no Grupo Latanoprosta, foi de 19,6mmHg. A pressão intraocular média no fim do grupo de acompanhamento trabeculoplastia seletiva a laser foi de 13,9mmHg e para latanoprosta de 14,5mmHg. A percentagem de redução da pressão intraocular em 1 ano de acompanhamento no Grupo Trabeculoplastia Seletiva a Laser foi de 23,4% e a do Grupo Latanoprosta foi de 23,6%. Conclusões: A trabeculoplastia seletiva a laser com Nd-YAG é tão eficaz quanto o uso de análogos de prostaglandinas como tratamento nas fases iniciais do glaucoma. Em relação à escala de qualidade de vida, embora não tenha havido diferenças estatisticamente significativas em ambos os grupos, a A trabeculoplastia seletiva a laser mostrou aumento na dificuldade percebida pelo paciente para atividades que envolvem a visão periférica, que é a mais afetada em pacientes com glaucoma.

Use Pattern of Ophthalmic Antiglaucoma Agents with and without Preservatives: A Cross-Sectional Study.

BACKGROUND: Different drugs have been approved to reduce the intraocular pressure. However, most of them contain preservatives to maintain sterility and these can be toxic to the ocular surface. The aim was to determine the patterns of use of antiglaucoma agents and ophthalmic preservatives in a group of patients from Colombia. METHODS: A cross-sectional study that identified ophthalmic antiglaucoma agents from a population database of 9.2 million. Sociodemographic and pharmacological variables were considered. Descriptive and bivariate analyses were performed. RESULTS: A total of 38,262 patients were identified, with a mean age of 69.2 ± 13.3 years, and 58.6% were women. A total of 98.8% were prescribed antiglaucoma drugs in multidose containers. The most widely used were prostaglandin analogs (59.9%), especially latanoprost (51.6%) and ß-blockers (59.2%). A total of 54.7% of patients received combined management, especially with fixed-dose combination (FDC) drugs (41.3%). A total of 94.1% used antiglaucoma drugs with preservatives (benzalkonium chloride, 68.4%). CONCLUSIONS: The pharmacological treatment of glaucoma was very heterogeneous, but the most commonly used therapeutic groups were in accordance with the recommendations of clinical practice guidelines but with differences by sex and age. Most of the patients were exposed to preservatives, especially benzalkonium chloride, but the wide use of FDC drugs can minimize toxicity on the ocular surface.

Comparación de Latanoprostene bunod 0,024 % y Latanoprost 0,005 % en glaucoma de ángulo abierto e hipertensión ocular

Introducción: El glaucoma es la principal causa de ceguera irreversible en el mundo. La prevalencia mundial de glaucoma en personas de 40 a 80 años se estima en un 3,5 %. Objetivo: Comparar el efecto reductor de la PIO de Latanoprostene bunod (LBN) al 0,024% con Latanoprost al 0,005 % en sujetos con glaucoma de ángulo abierto (GAA) o hipertensión ocular (HTO). Metodología: Ensayo observacional de estudio de cohorte prospectivo. Resultados: Fue realizado en 28 pacientes (56 ojos) quienes fueron aleatorizados en 2 grupos paralelos (28 ojos por grupo), el grupo Latanoprost y el grupo LBN. En el grupo LBN la media de la PIO antes del tratamiento fue de 25,3 ± 6,6 mmHg y la media de la PIO luego de 1 mes de tratamiento fue de 16,5 ± 4,9 mmHg (p<0,05). En el grupo Latanoprost la media de la PIO antes del tratamiento fue de 23,6 ± 3,6 mmHg y la media de la PIO luego de 1 mes de tratamiento con Latanoprost al 0,005% fue de 15,3 ± 2,4 mmHg (p<0,05). Sin embargo, al comparar las PIOs luego de 1 mes de tratamiento con LBN 0,024% y Latanoprost 0,005% se objetiva que la diferencia en reducción de la presión intraocular entre estos dos fármacos no fue significativa (p= 0,238). Discusión: Las prostaglandinas tópicas, con su potente efecto hipotensor ocular son una importante opción de tratamiento para el glaucoma. La reducción de la PIO es la esperada con ambos medicamentos, sin embargo, no existen diferencias significativas entre ambas luego de 1 mes de uso. Con respecto a los efectos secundarios, en el grupo LBN se encontró más efectos adversos oculares.

Introduction: Glaucoma is the main cause of irreversible blindness worldwide. The global prevalence of glaucoma in people aged 40 to 80 years is estimated at 3.5%. Objective: To compare the intraocular pressure (IOP) lowering effect of 0.024% Latanoprostene bunod (LBN) with 0.005% Latanoprost in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods: Observational trial of prospective cohort study. Results: It was performed in 28 patients (56 eyes) who were randomized into 2 parallel groups (28 eyes per group), the Latanoprost group and the Latanoprostene bunod (LBN) group. In the LBN group, the mean intraocular pressure before treatment was 25.3 ± 6.6 mmHg and the mean intraocular pressure after 1 month of treatment was 16.5 ± 4.9 mmHg (p<0,05). In the Latanoprost group, the mean intraocular pressure before treatment was 23.6 ± 3.6 mmHg and the mean intraocular pressure after 1 month of treatment with 0.005% Latanoprost was 15.3 ± 2.4 mmHg (p<0,05). However, when comparing the IOPs to the 1-month treatment with Latanoprostene bunod 0.024% and Latanoprost 0.005%, it is observed, through ANOVA, that the difference in intraocular pressure reduction between these two drugs is not significant (p= 0,238). Discussion: Topical prostaglandins, with their potent ocular hypotensive effect (resulting from increased uveoscleral outflow), are an important treatment option for glaucoma. The IOP reduction is as expected with both drugs, however, there are no significant differences between the two. In the LBN group, more drug-related ocular adverse effects were found after 1 month of use.

Ocular Surface Evaluation after Switch from Latanoprost 0.005% to Latanoprostene Bunod 0.024.

Aim and background: To evaluate the ocular surface of patients treated with latanoprost (LT) 0.005% who switched to latanoprostene bunod (LBN) 0.024%. Materials and methods: A prospective and nonrandomized clinical study of a case series was performed, including patients with chronic open-angle glaucoma who were on previous LT-only treatment and, after a washout period, switched to LBN, with a 3-month follow-up. The main parameter to be evaluated was the ocular surface disease index (OSDI) test. In addition, best-corrected visual acuity (BCVA), intraocular pressure (IOP), biomicroscopic aspect of the ocular surface, measuring tear breakup time, fluorescein staining (grading performed on Oxford scale) and Schirmer I test were evaluated. Results: A total of 36 patients (72 eyes) were included, 21 women (58.3%) and 15 men (41.7%, with a mean age of 65.6 ± 10.9 years (37-86). The initial OSDI score was 17.8 ± 12.1 and improved to 11.1 ± 10.5 (p < 0.01). From the data evaluated at biomicroscopy, an improvement was observed in the Oxford scale from 0.6 ± 0.7 to 0.2 ± 0.8 (p: 0.01), but no statistically significant changes were observed in the break-up time (BUT) and Schirmer. BCVA remained stable, as did IOP, which was initially 13.4 ± 2.1 mm Hg and, after performing the LBN treatment change, went to 13.1 ± 1.7 mm Hg. Conclusion: After the change of treatment from LT 0.005% to LBN 0.024%, the patients had an improvement in the ocular surface, maintaining control of their IOP. The need to investigate possible beneficial mechanisms on the ocular surface in glaucoma patients treated with LBN, potentially related to nitric oxide, is raised. Clinical significance: Patients treated with LT 0.005% who switched to LBN 0.024% had an improvement in ocular surface symptoms and signs, keeping IOP under control.Latanoprostene bunod (LBN) 0.024% may have beneficial effects on the ocular surface, which should be further studied. How to cite this article: Zanutigh V, Galetto L, Valvecchia F, et al. Ocular Surface Evaluation after Switch from Latanoprost 0.005% to Latanoprostene Bunod 0.024%. J Curr Glaucoma Pract 2023;17(4):205-209.

Nanostructured lipid carriers loaded with an association of minoxidil and latanoprost for targeted topical therapy of alopecia.

Alopecia is a condition associated with different etiologies, ranging from hormonal changes to chemotherapy, that affects over 80 million people in the USA. Nevertheless, there are currently few FDA-approved drugs for topical treatment, and existing formulations still present skin irritation issues, compromising treatment adherence. This work aimed to develop a safe formulation based on nanostructured lipid carriers (NLC) that entrap an association of minoxidil and latanoprost and target drug delivery to the hair follicles. To do so, thermal techniques combined with FTIR were used to assess the chemical compatibility of the proposed drug association. Then, NLC with 393.5 ± 36.0 nm (PdI < 0.4) and +22.5 ± 0.2 mV zeta potential were produced and shown to entrap 86.9% of minoxidil and 99.9% of latanoprost efficiently. In vitro, the free drug combination was indicated to exert positive effects over human primary epidermal keratinocytes, supporting cell proliferation, migration and inducing the mRNA expression of MKI67 proliferation marker and VEGF - a possible effector for minoxidil-mediated hair growth. Interestingly, such a favorable drug combination profile was optimized when delivered using our NLC. Furthermore, according to the HET-CAM and reconstructed human epidermis assays, the nanoformulation was well tolerated. Finally, drug penetration was evaluated in vitro using porcine skin. Such experiments indicated that the NLC could be deposited preferentially into the hair follicles, causing a considerable increase in the penetration of the two drugs in such structures, compared to the control (composed of the free compounds) and generating a target-effect of approximately 50% for both drugs. In summary, present results suggest that hair follicle-targeted delivery of the minoxidil and latanoprost combination is a promising alternative to treat alopecia.

A novel ophthalmic latanoprost 0.005% nanoemulsion: a cytotoxicity study.

BACKGROUND: Benzalkonium chloride (BAK), the most commonly used preservative in anti-glaucoma eye drops, inflicts damage to the ocular surface. A novel anti-glaucoma formulation that avoids the use of BAK has been developed. The aim of this study was to evaluate the cytotoxicity of this formulation and to compare it with an ophthalmic solution containing BAK. METHODS: Two different latanoprost eye drops were used: one ophthalmic solution (LSc) containing BAK 0.02% and one ophthalmic nanoemulsion (LNe) with a soft preservative (potassium sorbate 0.18%). Human epithelial conjunctival cells were incubated for 15, 30, and 60 min with either LSc or LNe. The cytotoxicity was determined by MTT assay. Cell death was measured by flow cytometry using annexin V-FITC and propidium iodide. RESULTS: The values of cell viability and proliferation obtained from cells exposed to LNe were between 80 and 90% relative to the control group, whereas values obtained from cells exposed to LSc were around 30% at all study times (p < 0.05 at 15 and 30 min; p < 0.01 at 60 min). The percentage of viable cells decreased significantly when cells were incubated with LSc compared with cells incubated with LNe at all the study times, while the percentage of cells in late apoptosis/necrosis increased significantly in cells exposed to LSc compared to LNe. CONCLUSIONS: The new latanoprost nanoemulsion is significantly less cytotoxic on human conjunctival cells than LSc. These results suggest that the new formulation might be gentler on the eye surface than currently available BAK-preserved latanoprost solutions.

Comparison of the hypotensor effect between latanoprost versus selective laser trabeculoplasty obtained with the water drinking test / Comparação do efeito hipotensor entre latanoprosta versus trabeculoplastia seletiva a laser obtida com teste de sobrecarga hídrica

ABSTRACT Purpose: Glaucoma is the main cause of irreversible blindness worldwide. Peak intraocular pressure is one of the main risk factors for glaucoma progression, and intraocular pressure reduction remains the only therapeutic strategy for all types of glaucoma. The main purpose of our study was to compare the baseline and peak intraocular pressure reduction obtained with the water drinking test between the two eyes of the same patients using 0.005% latanoprost in one eye and selective laser trabeculoplasty application in the contralateral eye. Methods: This was a prospective, interventional, longitudinal, and randomized clinical trial, in which 30 consecutive glaucomatous patients, medically controlled using latanoprost monotherapy, were recruited from a single ophthalmological center. The patients' eyes were randomized, and one eye was selected for SLT treatment and topical 0.005% latanoprost was introduced in the contralateral eye. The baseline intraocular pressure and peak intraocular pressure were evaluated 1 month (water drinking test 2) and 6 months (water drinking test 3) after treatment. Results: There was no significant difference between the mean pre-washout intraocular pressure in the randomized eyes for selective laser trabeculoplasty and latanoprost (13.6 ± 2.1 and 13.3 ± 1.8 mmHg, respectively; p=0.182). Regarding baseline intraocular pressure, there was no significant difference in the water drinking test 2 (p=0.689) and water drinking test 3 (p=0.06) between the groups. There was no significant difference in the intraocular pressure peak between the SLT and latanoprost groups at water drinking test 2 (p=0.771) or water drinking test 3 (p=0.774). Conclusions: The intraocular pressure reduction efficacy is similar between latanoprost and selective laser trabeculoplasty. Glaucomatous patients who are medically controlled with latanoprost and switch treatment to selective laser trabeculoplasty maintain control of intraocular pressure.

RESUMO Objetivo: Glaucoma é a principal causa de cegueira irreversível no mundo. O pico da pressão intraocular é um dos principais fatores de risco para progressão do glaucoma, e o controle pressórico ainda é o único tratamento efetivo para todas as formas de glaucoma. O objetivo principal deste estudo é comparar a redução basal e do pico da pressão intraocular, obtidas através do Teste de Sobrecarga Hídrica, entre os dois olhos dos mesmos pacientes utilizando latanoprosta 0,005% em um olho e submetidos à aplicação de trabeculoplastia a laser seletiva no olho contralateral. Métodos: Este é um estudo prospectivo, intervencionista, longitudinal e randomizado. Trinta pacientes consecutivos, glaucomatosos, com pressão intraocular controlada em uso de monoterapia com latanoprosta, foram recrutados de um único centro oftalmológico. Os olhos dos pacientes foram randomizados e um olho foi selecionado para tratamento com trabeculoplastia a laser seletiva e olho contralateral tratado com colírio de latanoprosta 0,005%. Foram avaliados a pressão intraocular basal e pico de pressão intraocular um mês (Teste de Sobrecarga Hídrica 2) e seis meses (Teste de Sobrecarga Hídrica 3) após tratamento. Resultados: Não houve diferença estatística entre a pressão intraocular pré washout entre os olhos randomizados para trabeculoplastia a laser seletiva e latanoprosta, 13,6 ± 2,1 e 13,3 ± 1,8 mmHg, respectivamente (p=0,182). Em relação à pressão intraocular basal, não houve diferença estatística entre os grupos, tanto no Teste de Sobrecarga Hídrica 2 (p=0,689) e Teste de Sobrecarga Hídrica 3 (p=0,06). Não houve diferença estatística em relação ao pico de pressão intraocular entre os grupos trabeculoplastia a laser seletiva e latanoprosta, no Teste de Sobrecarga Hídrica 2 (p=0,771) e Teste de Sobrecarga Hídrica 3 (p=0,774). Conclusões: Em resumo, nosso estudo demonsrou que a eficácia da redução pressórica é similar entre latanoprosta e trabeculoplastia a laser seletiva, e pacientes glaucomatosos que estão com a pressão intraocular clinicamente controlados com latanoprosta e trocam de tratamento para trabeculoplastia a laser seletiva mantém sua pressão intraocular controlada.

Latanoprost-loaded phytantriol cubosomes for the treatment of glaucoma.

Glaucoma is a degenerative optic neuropathy characterized by increased intraocular pressure that if untreated can result in blindness. Ophthalmological drug therapy is a challenge of great clinical importance due to the diversity of ocular biological barriers which commonly causes limited or no effectiveness for drugs delivered through the eye. In this work, we proposed the development of nanosized cubic liquid crystals (cubosomes) as a new drug carrier system for latanoprost, an anti-glaucoma drug. Latanoprost-loaded phytantriol cubosomes (CubLnp) were prepared using a top-down method. Latanoprost concentration in the formulations ranged from 0.00125% to 0.02% w/v. All cubosomes displayed an average size around 200 nm, a low polydispersity index of 0.1 and zeta potential values around -25 mV, with an encapsulation efficiency of about 90%. Structural studies revealed that cubosomes displayed a double-diamond surface, Pn3m cubic-phase structure, and was not affected by drug loading. Calorimetric studies revealed a fast and exothermic interaction between latanoprost and cubosomes. According to in vitro essays, latanoprost release from cubosomes was slow in time, evidencing a sustained release profile. Based on this behavior, the in vivo hypotensive intraocular effect was evaluated by means of the subconjunctival administration of CubLnp in normotensive rabbits. We obtained promising results in comparison with a marketed latanoprost formulation (0.005% w/v).

LC-MS bioanalytical method for simultaneous determination of latanoprost and minoxidil in the skin.

The association of minoxidil sulphate and latanoprost is currently emerging as a promising strategy for the treatment of androgenic alopecia, which is the most common type of scalp hair loss. In order to support the development of new pharmaceutical products containing such drugs combination, this study proposes a simple and efficient LC-MS bioanalytical method to simultaneously quantify minoxidil sulphate and latanoprost in different skin layers. Compounds separation was performed by liquid chromatography using a C18 column with gradient elution of a mobile phase composed of 0.1 % formic acid in acetonitrile and water at a flow rate of 0.5 mL min-1. Determinations were executed using mass spectrometry equipped with an ESI interface operating in a positive ionization mode. Quantification was performed using selective ion mode monitoring of m/z 210.1 for minoxidil sulphate and 433.3 for latanoprost. The matrix effect was very pronounced in samples containing some skin layers or electrolyte solution. Accordingly, a calibration curve for each contaminant group was built, leading to correlation coefficient values higher than 0.99. Additionally, lower limits of detection and quantification were obtained, and precision (repeatability and intermediate precision) achieved results with a coefficient of variation less than 15 %. Drug recovery from skin samples was higher than 70 %, fulfilling the recommendations. Also, the bioanalytical method was successfully tested in in vitro skin penetration studies proving its effectiveness in the development of topical formulations containing both drugs.

Clinical Evaluation of a Novel Electromechanical Topical Ocular Drug Delivery System: Two Phase 1 Proof of Concept Studies.

PURPOSE: Self-administration of topical ophthalmic therapies remains challenging for many patients as errors due to improper technique are common. The aim of the current studies was to evaluate a novel electromechanical topical ocular drug delivery device designed to facilitate precise dosing and accurate delivery with substantially lower drug exposure than conventional eye drops. PATIENTS AND METHODS: Two randomized Phase 1 studies were performed to evaluate the efficacy and safety of a single dose of a topical ophthalmic solution administered as a ~9 µL microfluid stream via the test device compared with a ~30-40 µL drop delivered via conventional dropper in healthy subjects (Trial 1) and glaucoma patients (Trial 2). In Trial 1, a 1% tropicamide/2.5% phenylephrine solution was administered via the test device in one eye and by conventional dropper in the contralateral eye. Pupil dilation was measured at 30 min intervals post-instillation and subject comfort was assessed using a visual analogue scale (range, 0-100). In Trial 2, patients were randomized to receive latanoprost 0.005% via the test device or conventional dropper. Intraocular pressure was measured at baseline and 4-8 hrs post-instillation. RESULTS: In Trial 1 (N=20), mean (SD) pupil diameter 30 mins post-instillation increased by 3.4 (0.9) and 3.5 (1.0) mm in the test and control eyes, respectively. The mean comfort score was 81.7 for the test device versus 57.3 for conventional dropper delivery. In Trial 2 (N=18), the mean change in intraocular pressure following administration of latanoprost was -5.0 (1.8) and -4.3 (3.3) mm Hg in the test and control groups, respectively. No serious adverse events were observed in either study. CONCLUSION: Administration of a single dose of topical ophthalmic therapy via an electromechanical drug delivery device resulted in comparable effects on pupil dilation and intraocular pressure with lower drug exposure and increased patient comfort compared with conventional dropper delivery.

Comparative evaluation of Latanoprostene Bunod, Timolol Maleate, and latanoprost Ophthalmic Solutions to assess their safety and efficacy in lowering intraocular pressure for the management of Open-Angle Glaucoma

OBJECTIVES: Timolol maleate has been reported to be a safer intraocular pressure (IOP) lowering treatment than latanoprost. The United States Food and Drug Administration approved latanoprostene bunod, a nitric oxide-donating prodrug of latanoprost, for lowering IOP. This study compared the safety and efficacy of latanoprost, latanoprostene bunod, and timolol maleate in patients with open-angle glaucoma. METHODS: Patients who received latanoprost eye drops once daily in the evening were included in the latanoprost Ophthalmic Solutions (LP) cohort (n=104). Those who received latanoprostene bunod eye drops once daily in the evening were included in the Latanoprostene Bunod (LB) cohort (n=94). Those who received timolol eye drops twice daily were included in the Timolol Maleate (TM) cohort (n=115). All treatments were administered to the affected eye(s) for 3 months. Informed Consent has been taken from each participant before the trial. RESULTS: At the end of 3 months of treatment, latanoprost, latanoprostene bunod, and timolol were all successful in reducing IOP. The LB cohort had the highest reduction in IOP, compared to the LP and TM cohorts. All treatments had some common adverse ocular effects. CONCLUSION: Latanoprostene bunod was superior to latanoprost and timolol for the treatment of open-angle glaucoma.

Comparison of clinical effects of two latanoprost 0.005% solutions (Xalatan® and Arulatan®) in primary open-angle glaucoma or ocular hypertensive patients: a randomized clinical trial.

Purpose: To evaluate the therapeutic non-inferiority between two ophthalmic latanoprost 0.005% solutions (Arulatan® [ALT] versus the reference drug Xalatan® [XLT]) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). Patients and methods: This was a 12-week Phase IV, experimental, randomized, parallel-group, double-masked clinical trial. Consecutive patients with POAG or OH from the Glaucoma Service of Instituto Paulista de Estudos e Pesquisas em Oftalmologia (São Paulo, Brazil) were enrolled between July and December 2017. The primary outcome of the study was an analysis of therapeutic non-inferiority between ALT versus XLT at 12 weeks, while secondary outcomes were mean intraocular pressure (IOP) change from baseline at 2, 6 and 12 weeks, mean IOP at 2, 6 and 12 weeks, and topical and systemic side effects. Statistical significance was set at P<0.05. Computerized analysis was performed using the R software, version 3.4.4. Results: A total of 45 patients were randomized to the two treatment groups: ALT (22) and XLT (23). A statistically significant reduction in IOP from baseline was observed in both treatment groups at all timepoints, while no statistically significant difference between groups was detected. By week 12, observed IOP reduction was -7.95 and -7.89 mmHg in the ALT and in the XLT groups, respectively (P=0.60). Treatment difference between the ALT and the XLT groups was -0.06 mm Hg (95% CI: -0.97, 0.85) and fell within the interval set for therapeutic non-inferiority. There was no statistically significant difference between the two groups in terms of safety profiles. The most commonly reported side effect was mild conjunctival/palpebral hyperemia. Conclusion: ALT was considered non-inferior to XLT in achieving a statistically significant reduction in IOP at 12 weeks in POAG and OH patients. No significant difference in the occurrence of side effects was found between both groups.

Desarrollo tecnológico de una solución oftálmica de latanoprost para el tratamiento del glaucoma / Technological development of latanoprost eye solution for treatment of glaucoma

Introducción: el latanoprost, análogo de la prostaglandina F2α, es un agonista selectivo del receptor FP prostanoide que reduce la presión intraocular por incremento del flujo del humor acuoso, se clasifica como un antiglaucomoso y se indica en el tratamiento del glaucoma de ángulo abierto y la hipertensión ocular. Objetivo: se diseñó una formulación de uso oftálmico conteniendo latanoprost como sustancia activa, a una concentración de 500 µg/mL, que cumpla con los índices de control de calidad para esta forma farmacéutica y proporcione el efecto terapéutico deseado. Métodos: se realizaron los estudios de formulación y se ensayaron nueve variantes tecnológicas, seleccionándose la composición y procedimiento tecnológico más adecuados para su posterior escalado en la industria. Se ajustó el pH empleando la trometamina y la isotonicidad, con manitol, según las exigencias de una formulación oftálmica. Se desarrolló y validó una técnica analítica por Cromatografía Líquida de Alta Resolución para estudiar la estabilidad, determinar su fecha de vencimiento y para efectuar el control de la calidad de la formulación. Resultados: el desarrollo tecnológico, resultó satisfactorio, se obtiene una formulación que cumple con todas las especificaciones descritas en la técnica desarrollada por el fabricante, para el control de la calidad del producto. Se comprobó que la preparación mantiene sus propiedades físicas, químicas y microbiológicas inalterables por un período de 24 meses, almacenada a una temperatura controlada entre 2 y 8 °C y protegido de la luz. El escalado a nivel piloto no reveló problemas tecnológicos y resultó no irritante, según el criterio establecido por la Unión Europea para la irritabilidad oftálmica. Conclusiones: se obtuvo una formulación de colirio de latanoprost, útil en el tratamiento del glaucoma, con todas las especificaciones de calidad para este tipo de forma farmacéutica, con lo que pudiera aumentarse el arsenal terapéutico de Cuba(AU)

Introduction: latanoprost, F2α prostaglandine analogue, is a selective FP receptor Prostanoide agonist that reduces the intraocular pressure due to increase of aqueous humor; it is classified as an anti-glaucoma drug and indicated for the treatment of open angle glaucoma and eye hypertension. Objective: aformula for ophthalmic uses was designed, which contains latanoprost as active ingredient at concentration of 500 µg/mL and complies with the quality control indexes for this pharmaceutical form and provides the desired therapeutic effect. Methods: the formulation studies were conducted and nine technological variants were tested; the most adequate composicion and technological procedure was selected for further industry scaling. The pH index and isotonicity were then adjusted using trometamin and manitol, respectively according to the demands of the eye formulation. A high resolution liquid chromatography-based analytical technique was developed and validated to study the stability, to determine the expiry date and to make the quality control of the formulation. Results: the technological development proved to satisfactory since this formulation complies with all the specifications described in the manufacturer's technique for the quality control of the product. It was confirmed that this preparation keeps its physical, chemical and microbiological properties unchanged for 24 months if stored at 2-8 ºC and protected from light. Pilot scale-up did not show either technological problem or irritating effect according to the European Union criteria for eye irritability. Conclusions: there was attained a latanoprost eye drop formulation for the treatment of glaucoma, which complies with all the quality specifications for this type of pharmaceutical form and could increase the therapeutic arsenal in Cuba(AU)

Validación de un método cromatográfico para la cuantificación de latanoprost 50 µg/mL en el colirio de producción nacional / Validation of a chromatographic method for quantitation of 50 µg/mL Latanoprost in a Cuban eye drops

Introducción: el latanoprost está indicado para el tratamiento de la presión intraocular elevada en pacientes con hipertensión ocular o glaucoma de ángulo abierto.Objetivo: desarrollar y validar un método analítico por cromatografía líquida de alta resolución, aplicable al control de la calidad del latanoprost 50 µg/mL, colirio.Métodos: para cuantificar el principio activo en el producto terminado, la separación se realizó a través de una columna cromatográfica Altima C-18 (10 µm) (250 × 4 mm), con detección ultravioleta a 205 nm, empleando una fase móvil compuesta por acetonitrilo-buffer fosfato pH 4,5 (650:350) y la cuantificación de este frente a una muestra de referencia con el método del estándar externo.Resultados: los resultados de los parámetros evaluados en la validación del método se encontraron dentro de los límites establecidos.Conclusiones: el método analítico desarrollado y validado por cromatografía líquida de alta resolución para el control de la calidad del colirio de latanoprost 50 µg/mL, resultó específico, lineal, exacto y preciso en el rango de concentraciones estudiadas, por lo que puede emplearse de manera confiable y segura(AU)

Validación de un método cromatográfico para la cuantificación de latanoprost 50 µg/mL en el colirio de producción nacional / Validation of a chromatographic method for quantitation of 50 µg/mL Latanoprost in a Cuban eye drops

Introducción: el latanoprost está indicado para el tratamiento de la presión intraocular elevada en pacientes con hipertensión ocular o glaucoma de ángulo abierto.Objetivo: desarrollar y validar un método analítico por cromatografía líquida de alta resolución, aplicable al control de la calidad del latanoprost 50 µg/mL, colirio.Métodos: para cuantificar el principio activo en el producto terminado, la separación se realizó a través de una columna cromatográfica Altima C-18 (10 µm) (250 × 4 mm), con detección ultravioleta a 205 nm, empleando una fase móvil compuesta por acetonitrilo-buffer fosfato pH 4,5 (650:350) y la cuantificación de este frente a una muestra de referencia con el método del estándar externo.Resultados: los resultados de los parámetros evaluados en la validación del método se encontraron dentro de los límites establecidos.Conclusiones: el método analítico desarrollado y validado por cromatografía líquida de alta resolución para el control de la calidad del colirio de latanoprost 50 µg/mL, resultó específico, lineal, exacto y preciso en el rango de concentraciones estudiadas, por lo que puede emplearse de manera confiable y segura