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 dorzolamide in improving ocular blood flow in patients with open-angle glaucoma: The Indian carbonic anhydrase inhibitor trial

Purpose: Impaired ocular blood flow is an important risk factor in the pathogenesis of open?angle glaucoma (OAG). Studies have reported that dorzolamide 2% may be effective in improving ocular blood flow (OBF) in OAG patients. The objective of this study was to determine the efficacy of dorzolamide 2% (DORZOX, Cipla Ltd.) in improving retrobulbar blood flow in an Indian setting. Methods: The study was conducted as an interventional pilot project in 24 healthy subjects and 19 OAG patients. Baseline OBF measurements were done for all glaucoma patients with color Doppler imaging (CDI). Baseline ocular perfusion pressure (OPP) was calculated for all participants. Glaucoma patients were given dorzolamide 2% thrice daily for 12 weeks. The primary efficacy endpoints were mean changes in the CDI parameters of the retrobulbar vessels and OPP posttreatment. The secondary endpoint was mean change in the intraocular pressure (IOP) and adverse events, if any. Results: In comparison to healthy subjects, glaucoma patients displayed significantly reduced baseline OPP (P = 0.002). Treatment with dorzolamide 2% for 12 weeks led to a significant increase in OPP (P < 0.001) and a significant increase in end diastolic velocity (EDV) in all major ophthalmic arteries like ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary artery (SPCA) (P < 0.001, P = 0.04, and P = 0.0075, respectively). A significant reduction in the intraocular pressure (IOP; P = 0.007) was observed posttreatment, with no adverse events reported. Conclusion: Dorzolamide 2% significantly improved parameters such as the EDV and OPP in major ophthalmic arteries. This pilot study shows promising results on using dorzolamide for treating Indian patients with OAG

Efectividad de la dorzolamida en el tratamiento del edema quístico macular poscirugía de catarata / Effectiveness of dorzolamide in the treatment of cystoid macular edema after cataract surgery

Objetivo: Evaluar la efectividad del tratamiento combinado con dorzolamida tópica en pacientes con edema quístico macular poscirugía de catarata. Métodos: Se realizó un estudio experimental en pacientes atendidos en el Servicio de Vítreo-Retina del Instituto Cubano de Oftalmología "Ramón Pando Ferrer", en el año 2018. Se definió el grupo de casos (dorzolamida y tratamiento convencional) y el grupo control (tratamiento convencional), los cuales se evaluaron en la consulta inicial y al mes de tratamiento. Resultados: La edad media fue de 60,73 ± 11,25 años. Predominó el sexo femenino (53,33 por ciento), el ojo afectado derecho (60,00 por ciento), el tiempo posquirúrgico ≤ 3 meses (63,33 por ciento), sin factores de riesgo asociados (56,67 por ciento). El edema sin alteraciones asociadas fue más frecuente (80,00 por ciento). La media del grosor macular disminuyó en ambos grupos (de 529,27 ± 183,58 a 349,93 ± 221,35 en los casos y de 498,87 ± 213,26 a 373,53 ± 215,51 en los controles). Resultó mayor la variación en el grupo de casos (179,33 p= 0,008). La agudeza visual aumentó en ambos grupos. Se observó un porcentaje mayor de ojos que mejoraron la visión en el grupo de casos (52,38 por ciento). La mejoría de la agudeza visual se relacionó con la recuperación del grosor macular. Conclusiones: En los casos con edema quístico macular poscirugía de catarata, en los que está indicado el tratamiento tópico con antinflamatorios, la combinación con dorzolamida resulta efectiva para la reducción del grosor macular y la mejoría de la agudeza visual corregida(AU)

ABSTRACT Objective: Evaluate the effectiveness of a treatment combined with topical dorzolamide in patients with cystoid macular edema after cataract surgery. Methods: An experimental study was conducted of patients attending the Vitreous-Retina Service at Ramón Pando Ferrer Cuban Institute of Ophthalmology in the year 2018. The sample was divided into a case group (dorzolamide and conventional treatment) and a control group (conventional treatment), and evaluated at the initial consultation and after one month of treatment. Results: Mean age was 60.73 ± 11.25 years. A predominance was found of the female sex (53.33 percent), affected right eye (60.00 percent), postsurgical time ≤ 3 months (63.33 percent), and no associated risk factors (56.67 percent). Edema without associated alterations was more common (80.00 percent). Mean macular thickness decreased in both groups (from 529.27 ± 183.58 to 349.93 ± 221.35 in cases and from 498.87 ± 213.26 to 373.53 ± 215.51 in controls). Variation was greater in the case group (179.33 p= 0.008). Visual acuity increased in both groups. A higher percentage of eyes with improved vision was found in the case group (52.38 percent). Visual acuity improvement was related to macular thickness recovery. Conclusions: In cases of cystoid macular edema after cataract surgery with indication of topical treatment with anti-inflammatories, the combination with dorzolamide is effective to reduce macular thickness and improve corrected visual acuity(AU)

Molecular characterization of a rare phenotype of X-linked retinoschisis with angle-closure glaucoma

A 11-year-old boy presented with complaints of blurred vision and on evaluation was found to have X-linked retinoschisis (XLRS) with angle-closure glaucoma. Clinical and genetic evaluation of first-degree family members was done. His brother had a milder form of XLRS with shallow anterior chamber. Topical dorzolamide 2% and timolol 0.5% were used to control intraocular pressure. Genetic analysis revealed a novel three base pair deleterious mutation (c. 375_377 del AGA) in exon-5 of the RS1 gene in three members of the family.

Study of prescription pattern of antiglaucoma drugs used in treatment of primary open angle glaucoma in ophthalmology outpatient department of a tertiary care hospital

Background: In view of the high prevalence rates and the fact that medication is the primary line of treatment in POAG, an understanding of prescribing patterns can provide an insight into rational use of antiglaucoma drugs.Methods: This prospective, cross-sectional study was conducted in the glaucoma clinic of a tertiary care teaching hospital over a period of 12 months. Data from prescriptions of patients with POAG was recorded to study the prescribing pattern of antiglaucoma medications, completeness of the prescription and analysis of the prescriber’s influence.Results: Total of 103 prescriptions were included in which all the 141 anti-glaucoma drugs were prescribed as eye drops. Average number of drugs prescribed in present study was 1.36. ? blockers, particularly Timolol (58%) was the most frequently prescribed drug. Timolol with dorzolamide (15%) was the only prescribed fixed dose combination. Prostaglandin analogues (5%) were least commonly prescribed. 53% drugs were prescribed by generic names and 43% were prescribed from hospital formulary. Instructions regarding the route and frequency of drug administration with duration of treatment were present in all prescriptions; however, instructions regarding method of instillation of eye drops were missing. Authors observed prescriber’s influence in present study.Conclusions: Overall prescribing pattern in our set up is satisfactory. There is a need to sensitize the prescribers regarding the importance of writing method of instillation in prescription as this could improve efficacy reduce side effects, prevent drug wastage and reduce cost. To encourage the physicians for rational prescribing such type of studies should be done more often for periodic auditing of prescriptions.

Efficacy and safety of topical 2% dorzolamide and 0.5% timolol in cases of open angle glaucoma in a tertiary care hospital of East Singhbhum: an observational, prospective and comparative study

Background: Present study was undertaken to evaluate and compare the efficacy and side effects of 2% dorzolamide and 0.5% timolol in patients with open angle glaucoma.Methods: There were 60 randomly selected patients were equally divided into Group I (n=30) and Group II (n=30). Further both groups were divided into IA (n=10), IB (n=20), IIA (n=10) and IIB (n=20). 2% Dorzolamide hydrochloride in Group IA and IIA and 0.5% Timolol maleate in Group IB and IIB was administered for 24 weeks. Patients were evaluated for general and ocular examinations on day of enrolment and then at the end of 1st, 4th, 8th and 24th week. Adverse effects of the drug during study period were also noted. Mean±SD, t value, p value and comparison between groups were analysed by graph pad software.Results: At the end of 24 weeks difference in mean reduction of IOP was not significant with 6.2±1.85mm Hg (Right eye) and 5.55±1.68mm Hg (left eye) and 4.72±2.97mm Hg (Right eye) and 5.37±1.24mm Hg (left eye) in Group IA and Group IIA respectively. At the end of 24 weeks difference in mean reduction of IOP was not significant with 5.06±1.62mm Hg (Right eye) and 4.40±1.96mm Hg (left eye) and 4.30±1.41mm Hg (Right eye) and 4.12±2.08mm Hg (left eye) in Group IB and Group IIB respectively. Fall in both systolic and diastolic blood pressure in both the groups were significant. Both drug regimens were well-tolerated, and no serious drug-related adverse effects were reported.Conclusions: Dorzolamide was more efficacious for reduction of intra ocular pressure, well-tolerated, had low allergic response and had a favourable ocular, cardiovascular and respiratory safety profile than Timolol.

Dorzolamida en el tratamiento del edema quístico macular poscirugía de catarata / Dorzolamide for the treatment of cystoid macular edema after cataract surgery

El edema quístico macular es, actualmente, una de las complicaciones posoperatorias más prevalentes después de la cirugía de cataratas. En no pocos casos acarrea una disminución en la agudeza visual posquirúrgica de los pacientes. Por la heterogeneidad de criterios diagnósticos, su incidencia ha sido reportada entre el 1 y el 30 por ciento. Con el objetivo de mostrar los resultados del uso de la dorzolamida en el edema quístico macular poscirugía de catarata se realizó la presente revisión de la literatura, mediante búsquedas en diferentes publicaciones relacionadas con la especialidad, en la que fueron utilizadas bases de datos de revistas líderes de Oftalmología de los últimos 10 años. Como la complicación posoperatoria más frecuente de la cirugía de catarata, puede traducirse con pérdida de la visión posoperatoria y cobra importancia el abordaje de aspectos relacionados con el tratamiento, específicamente los resultados de investigaciones que promueven en la actualidad el uso de inhibidores de la anhidrasa carbónica tópicos. En tal sentido, se muestra que la dorzolamida ha cobrado importancia como una opción de tratamiento, con resultados tangibles y pocos efectos adversos en comparación con el empleo sistémico de este grupo de medicamentos(AU)

Macular cystic edema is one of the most prevalent postoperative complications after cataract surgery, leading in many cases to a decrease of postsurgical visual acuity in the patients. Due to the heterogeneity of diagnostic criteria, its incidence has been reported between 1 percent and 30 percent. With the objetive to show the results of the use of dorzolamide in the macular cystic edema after cataract surgery, we was carried out through searches in different publications related to the specialty, using data from leading ophthalmology journals, from the last 10 years. As the most frequent postoperative complication of cataract surgery, that can be translated with loss of postoperative vision, it is important to address aspects related to treatment and specifically the results of research that currently promote the use of topical carbonic anhydrase inhibitors. In this regard, dorzolamide has become important as a treatment option, with tangible results and few adverse effects compared with the systemic use of this group of drugs(AU)

Brinzolamide/timolol versus dorzolamide/timolol fixed combinations: A hospital‑based, prospective, randomized study.

Purpose: To compare the efficacy and tolerability of brinzolamide/timolol (BT) and dorzolamide/ timolol (DT) fixed combinations on intraocular pressure (IOP) reduction. Methods: Patients with primary open angle glaucoma or normal tension glaucoma were randomized to receive either BT or DT. IOPs were measured at baseline, 2 weeks, and 1, 2, and 3 months. The primary outcome measures were the mean change in IOP from baseline at each visit. Secondary outcome measures included the tolerability of each fixed combination. Results: Seventy‑three patients (73 eyes) were included; 37 eyes in BT group and 36 eyes in DT group. Baseline mean IOP were 24.14 ± 4.5 and 29.53 ± 6 mmHg for BT and DT, respectively (P < 0.001). Both BT and DT provided statistically significant mean IOP reductions from baseline values within each group at all study visits (P < 0.001). DT provided greater mean IOP reductions from baseline than BT at each visit which was statistically significant at 2 weeks (P = 0.037). Mean percentage of IOP reduction was 24.35% and 46.33% at 2 weeks (P < 0.001), and 24.65% and 47% at 3 months (P < 0.001) for BT and DT, respectively. Patients’ tolerability appeared to be better for DT than for BT with complete ocular comfort without any ocular adverse effects in 31 patients (81.1%) in DT group and 11 patients (29.7%) in BT group (P < 0.001). Conclusion: Both drops provide effective IOP reduction which was greater, and patients were more likely to achieve lower target pressures with DT than with BT.

Long-term Results of Selective Laser Trabeculoplasty versus Latanoprost or Dorzolamide/Timolol Fixed Combination

PURPOSE: To compare the efficacy of selective laser trabeculoplasty (SLT) in patients treated with either latanoprost or dorzolamide/timolol fixed combination (DTFC) for primary open-angle glaucoma. METHODS: This retrospective study included 92 consecutive patients who underwent a 180-degree SLT for the first time. The subjects divided into two groups:patients who received latanoprost (n = 63) or DTFC (n = 29) before and after SLT. The main outcome measure was intraocular pressure (IOP) decrease over five years after SLT. The mean IOP change, mean percentage of IOP reduction, and success rates were compared between the patients treated with latanoprost and the patients treated with DTFC. Success was defined as an IOP decrease ≥ 3 mm Hg or IOP reduction ≥ 20% without additional medications, laser surgery, or glaucoma surgery. RESULTS: At the postoperative one-year follow-up, the mean IOP was 15.7 ± 2.2 mm Hg in the latanoprost group and, 16.2 ± 2.4 mm Hg in the DTFC group. At the postoperative five-year follow-up, the mean IOP was 15.1 ± 2.5 mm Hg in the latanoprost group and, 14.6 ± 1.7 mm Hg in the DTFC group. There were no statistically significant differences in IOP change, percentage IOP reduction, or success rate between the groups at each time point after the SLT (p > 0.05). CONCLUSIONS: Selective laser trabeculoplasty showed a reasonable efficacy in lowering the IOP over a five-year follow-up period. There were no significant differences in IOP lowering effect or success rate between the patients treated with latanoprost or DTFC.

Adherence to Preservative-Free Dorzolamide/Timolol Fixed Combination Assessed by Counting the Unused Single-Dose Units

PURPOSE: To investigate the actual adherence to treatment with preservative-free dorzolamide-timolol fixed combination (DTFC) eyedrops of primary open-angle glaucoma (POAG) patients by counting the number of unused single-dose units of DTFC. METHODS: This study included 34 POAG patients newly prescribed with preservative-free DTFC eyedrops (formulated in single-dose units). The enrolled patients were asked to bring the unused DTFC units on their next visit after 2 weeks of treatment with DTFC. On their second visit, they were asked to complete a questionnaire regarding the self-reported adherence and the number of unused DTFC single-dose units was counted. The actual adherence (%) was calculated by dividing the expected number of used DTFC units by the actual number of used DTFC units. The correlation between the self-reported adherence and the measured adherence was assessed. RESULTS: Twenty-nine (93.5%) patients answered they adhered to the medication by more than 90% and 2 (6.5%) answered they instilled the eyedrops at 80-90% of the dosing schedule. However, after counting the unused DTFC single-dose units, 9 (29.0%) patients showed an actual adherence of <90%. Moreover, the actual adherence of 3 (9.7%) patients was <60%. Unexpectedly, 4 (12.9%) patients showed the actual adherence exceeding 100% (196%, 1 patient; 107-132%, 3 patients). CONCLUSIONS: We demonstrated a large difference between the self-reported and the actual adherence to treatment by counting the unused single-dose units of eyedrops. Preservative-free topical anti-glaucoma medications (formulated in single-dose units) provide clinicians an opportunity to assess the actual adherence of glaucoma patients by counting the unused units of eyedrops.

Desarrollo tecnológico de dorzolamida 2 % más timolol 0, 5 % solución oftálmica / Techological development of 2 % dorzolamide plus 0. 5 % timolol as eye solution

OBJETIVO: desarrollar una solución oftálmica de dorzolamida 2 % más timolol 0,5 % que cumpla con todos los requerimientos de calidad para proporcionar el efecto terapéutico deseado sin efectos adversos al paciente. MÉTODOS: se prepararon tres ensayos preliminares en los que se utilizaron clorhidrato de dorzolamida y maleato de timolol, una solución tampón que consistió en ácido cítrico monohidratado/citrato trisódico dihidratado, cuyo pH estuviese en el rango de 5 y 6, cloruro de benzalconio, y HPMC F4M (hidroxipropilmetilcelulosa) al 10 %. Se usaron estos componentes en sustitución de los recomendados en la literatura. Se estudió la estabilidad química y física de la formulación durante 3 meses en cuanto a las características organolépticas, concentración del ingrediente activo, el pH, así como las propiedades fluidimétricas, irritabilidad oftálmica y efectividad del preservo. Con la formulación de estudio se desarrolló y se validó la técnica analítica en el Centro de Investigación y Desarrollo de Medicamentos. Se determinó la linealidad, precisión, especificidad y exactitud de método. Se elaboraron tres lotes pilotos de 5 L cada uno. Se utilizó como material de envase frascos plásticos de polietileno de baja densidad con Master Batch de 5 mL de capacidad. RESULTADOS: los ingredientes activos, clorhidrato de dorzolamida y maleato de timolol, y los excipientes de calidad farmacéutica y el material de envase utilizado cumplieron con las especificaciones de calidad informados en la USP 33. Los análisis fisicoquímicos realizados a los tres lotes del escalado piloto e industrial cumplieron con las especificaciones de calidad de la técnica analítica desarrollada por el Departamento de Estabilidad del Centro de Investigación y Desarrollo de Medicamentos y con los análisis microbiológicos informados en la USP 33. CONCLUSIONES: los resultados obtenidos permiten la introducción industrial y sustituir la importación del referido medicamento.

OBJECTIVE: to develop a 2 % dorzolamide plus 0.5 % timolol eye drop solution with all the quality requirements to provide adequate therapeutic effect without adverse reactions for the patients. METHODS: three preliminary trials were prepared with dorzolamide chlorhydrate and timolol maleate, a buffer solution based on monohydrated citric acid/dehydrated trisodic citrate with pH range 5-6, benzalkonium chloride and 10 % HPMC F4M (hydroxypropilmetylcellulose). These components replaced those recommended in the literature review. The chemical and physical stability of this formulation was studied for three months in terms of organoleptic characteristics, active ingredient concentration, pH, fluidmetric properties, eye irritability and effectiveness of preserver. The study formulation allowed developing and validating the analytical technique of the Center for the Drug Research and Development. Linearity, precision, specificity and accuracy of the method were determined. Three 5 L pilot batches were prepared. Master Batch 5 mL low-density polyethylene plastic bottles were used for packing. RESULTS: active ingredients, dorzolamide chlorhydrate and timolol maleate, the pharmaceutical quality excipients and the packing material met the quality specifications according to USP 33. The physical and chemical analysis of the three batches at pilot and industrial scales met the quality specifications of the analytical technique devised by the Department of Stability of the Center for Drug Research and Development and the microbiological analysis reported in USP 33. CONCLUSIONS: the achieved results allowed introducing the formulation at industrial scale and replacing the imported drug.

The Effects of Topical Carbonic Anhydrase Inhibitors on Nitric Oxide Production in Trabecular Meshwork Cells

PURPOSE: To investigate and compare the effects of topical carbonic anhydrase inhibitors on the production and expression of nitric oxide in cultured human trabecular meshwork cells (HTMC). METHODS: Primarily cultured HTMC were exposed to 0, 10, and 100 microM dorzolamide and brinzolamide using serum-deprived media for 3 days. Production of nitric oxide was assessed with Griess assay. Expressions of eNOS mRNA were assessed with RT-PCR. RESULTS: Both dorzolamide and brinzolamide increased the production of nitric oxide eNOS activity (p < 0.05). Dorzolamide had a more potent effect than brinzolamide on the production of nitric oxide and the expression of eNOS mRNA. CONCLUSIONS: Topical carbonic anhydrase inhibitors increased the production of nitric oxide, which was accompanied by increased eNOS activity. Dorzolamide had a more potent effect than brinzolamide on the production of nitric oxide and expression of eNOS mRNA in HTMC. The increased production of nitric oxide by topical carbonic anhydrase inhibitors involves mechanisms other than carbonic anhydrase inhibition.

Comparison of Dorzolamide-Timolol Fixed Combination and Latanoprost, Effects on Intraocular Pressure and Ocular Pulse Amplitude

PURPOSE: To compare dorzolamide-timolol fixed combination (DTFC) and latanoprost with regard to their effects on intraocular pressure (IOP) and ocular pulse amplitude (OPA). METHODS: Sixty eyes of 60 patients with open angle glaucoma or glaucoma suspect were included in the present study. Patients were divided into 2 groups, DTFC-treated (n = 30) and latanoprost-treated (n = 30). IOP and OPA were measured with dynamic contour tonometer (DCT) and Goldmann applanation tonometer (GAT), before and at least 1 month after treatment. RESULTS: GAT IOP, DCT IOP and OPA decreased by 2.25 +/- 2.23 mm Hg, 1.97 +/- 2.06 mm Hg, and 0.14 +/- 0.88 mm Hg, respectively in the DTFC-treated group. In the latanoprost-treated group, GAT IOP, DCT IOP and OPA was reduced by 2.74 +/- 2.96 mm Hg, 2.06 +/- 3.50 mm Hg, and 0.69 +/- 1.07 mm Hg, respectively. There was no significant difference (p = 0.311) in the decline of IOP between the 2 groups, but OPA of the DTFC-treated group decreased less than the latanoprost-treated group (p = 0.032). CONCLUSIONS: No significant differences were observed in the short-term decline of IOP between the 2 medications. However, the influence of DTFC on OPA appeared negligible in the latanoprost-treated group.

A comparison of the efficacy and safety of timolol in combination with dorzolamide, brimonidine or latanoprost in patients of primary open angle glaucoma.

The present study was undertaken to compare the efficacy and safety of timolol with dorzolamide, brimonidine or latanoprost in patients of primary open angle glaucoma. This prospective, observational study was conducted over one and a half year at the Regional Eye Institute, in patients of primary open angle glaucoma who were prescribed dorzolamide (2%) and timolol (0.5%) (DT), brimonidine (0.1%) and timolol (0.5%) (BT) or latanoprost (0.005%) and timolol (0.5%) (LT). Measurement of intraocular pressure (IOP) and indirect ophthalmoscopy was done at baseline and after 1, 3 and 6 months of treatment. Efficacy was assessed by the degree of reduction in intraocular pressure and change in cup-disc ratio. Adverse drug reactions (ADRs), if any, were recorded. The data was analysed using Student’s ‘t’ test and one-way ANOVA test. P value < 0.05 was considered to be statistically significant. Total number of 35 patients in DT group, 34 in BT group and 32 in LT group completed the study. At the end of 6 months, average reduction in IOP levels was 7.83, 9.39 and 9.73mmHg in DT, BT and LT groups respectively. Thus, a percent reduction of 29.4, 35.6 and 36.2 from baseline was observed in these groups respectively. While the reduction was maximum in LT group, there was no statistically significant difference between any of the groups at 1, 3 or 6 months. A total of 47 ADRs were reported, none of which required discontinuation. All three combinations are effective in reducing the IOP level in patients of primary open angle glaucoma and none appear to be superior to the others.

Determinación simultánea de clorhidrato de dorzolamida y maleato de timolol en el colirio / Simultaneous determination of Dorzolamide Chlorhydrate and Timolol Maleate

Objetivo: desarrollar y validar un método analítico por cromatografía líquida de alta resolución, aplicable al control de la calidad y estudio de estabilidad de dorzolamida 2 % y timolol 0,5 % en el colirio. Métodos: para cuantificar simultáneamente los dos principios activos en el producto terminado, la separación se realizó a través de una columna cromatográfica Luna RP-18 (5 µm) (250 x 4 mm), con un detector de arreglo de fotodiodos a 254 y 295 nm, empleando un gradiente con fase móvil A compuesta por acetonitrilo: buffer fosfato pH 2,5: metanol (5:85:10) y fase móvil B: metanol, y la cuantificación de este frente a una muestra de referencia con el método del estándar externo. Resultados: en el estudio de linealidad, los coeficientes de correlación y de determinación obtenidos estuvieron por encima de 0,99 y 0,98 respectivamente. Los porcentajes de recobrado fueron de 99,57 para la dorzolamida y 99,93 para el timolol, con un coeficiente de variación para ambos principios activos inferior al 2 %. En el estudio de repetibilidad realizado, las medias obtenidas fueron de 99,1 % para la dorzolamida y 100,4 % para el timolol, y los coeficientes de variación se encontraron dentro de los límites. En el estudio de precisión intermedia, los valores de p resultaron ser mayores que 0,05, para cada uno de los niveles estudiados Conclusiones: el método analítico desarrollado resulta lineal, preciso, específico y exacto en el rango de concentraciones estudiadas, el cual se establece para el control de la calidad y el estudio de estabilidad del producto terminado ya que no existen métodos analíticos informados para estos fines.

Objective: to develop and validate an analytical high-performance liquid chromatography method applicable to quality control and to stability study of 2 % Dorzolamide plus 0.5 % Timolol eye drops. Methods: to simultaneously quantify both active principles in the finished product, separation was made through a Luna RP-18 (5 µm) (250 x 4 mm) column chromatography, with photodiode array detector at 254 nm an 295nm using a gradient with mobile phase A composed of acetonitrile: phosphate buffer pH 2.5: methanol (5:85:10) and mobile phase B: methanol and the quantification of this front to a reference sample using the external standard method. Results: in the linearity study, the correlation and determination coefficients were above 0.99 and 0.98 respectively. The percentages of having recovered were 99.57 for Dorzolamide and 99.93 for Timolol, with a variation coefficient for both active principles under 2 %. In the repeatability study, the means were 99.1 for Dorzolamide and 100.4 % for Timolol and the variation coefficients were within the set limits. In the study of intermediate precision, p values were higher than 0.05 for each of the studied levels. Conclusions: the developed analytical method was linear, precise, specific and accurate in the range of study concentrations; it is established for the quality control and stability study of the finished product since there were not analytical methods designed for these aims.

Desarrollo de dorzolamida al 2 por ciento solución oftálmica para el tratamiento de la presión intraocular / Desarrollo de dorzolamida al 2 percent solución oftálmica para el tratamiento de la presión intraocular

El desarrollo de una solución oftálmica de dorzolamida al 2 por ciento para el tratamiento de pacientes con hipertensión ocular: glaucoma de ángulo abierto, glaucoma seudoexfoliativo y otros glaucomas secundarios de ángulo abierto, se inició con el estudio de los componentes de la formulación sustituyendo algunos excipientes en el medicamento de los declarados en la literatura revisada, y se estudiaron las propiedades físicas, químicas, biológicas, microbiológicas y reológicas durante los estudios de preformulación. Se desarrolló una técnica analítica para el producto terminado. Se elaboraron 3 lotes de la formulación y se almacenaron en frascos plásticos de polietileno de baja densidad con Master Batch de 5 mL de capacidad, producidos in situ por una llenadora Bottle Pack, los cuales para el estudio de la estabilidad de la dorzolamida, se expusieron durante 24 meses a temperatura ambiente 30 ± 2 °C y 6 meses a temperatura acelerada de 40 ± 2 ºC con 75 por ciento de humedad relativa, según los requerimientos establecidos por el Centro Estatal para el Control de Medicamentos. Al inicio y final del estudio microbiológico se comprobó la esterilidad en cada uno de los lotes; se obtuvieron resultados satisfactorios. El medicamento al cumplir con todos los parámetros de calidad descritos está registrado en el órgano regulador cubano para ser utilizado con seguridad en el tratamiento de las enfermedades al cual está destinado. Este medicamento está siendo producido a nivel industrial y comercializado.

The development of a 2 percent dorzolamide eye solution to treat patients with ocular hypertension, having open angle glaucoma, pseudoexfoliative glaucoma and other secondary open-angle glaucoma began with the study of the formulation components by replacing some excipients stated in the reviewed literature, and the physical, chemical, biological, microbiological and rheological properties were analyzed during the pre-formulation studies. An analytical technique was devised for the finished product. Three batches of formulation were prepared and then stored in low density polyethylene flasks with Master Batch of 5 ml capacity, manufactured in situ by the Bottle Pack filler. These reservoirs were exposed at 30 ± 2 °C room temperature for 24 months and at 40 ± 2 ºC accelerated temperature for 6 months and relative humidity of 75 percent, according to the requirements set by the State Center for Drug Control. At the beginning and at the end of the microbiological study, there was proved the sterility of each batch, the achieved results were satisfactory. After complying with all described quality parameters, the drug was registered in the Cuban regulatory body for its safe use in the treatment of the above-mentioned diseases. This drug is being manufactured at industrial level and thus marketed.

Clinical effectiveness and safety of brimonidine (0.2%) versus Dorzolamide (2.0%) in primary open angle.

A Comparison of efficacy & tolerability of brimonidine (0.2%) versus dorzolamide (2.0%) in primary open angle glaucoma or ocular hypertension. In this open, randomized, cross over comparative study, 30 subjects of primary open angle glaucoma with IOP > 22 mmHg were taken. The patients fulfilling the inclusion criteria and after verifying the exclusion criteria were included in the study after a written informed consent. These subjects were randomized to receive brimonidine (0.2%) TDS or dorzolamide (2.0%) TDS for 4 weeks. After a wash out period of 4 weeks the subjects were crossed over to other therapy .The IOP was measured at 8.00 am before dosing and at 10.00 am i.e. 2 hours after dosing at each baseline and at the end of each treatment period. Monotherapy with brimonidine (0.2%) TDS and dorzolamide (2.0%) TDS given for 4 weeks had caused overall reduction in IOP of 5.833+2.102mmHg (23.48%) and 5.433+ 2.582mmHg (22.42%) respectively at peak levels. The difference is statistically insignificant (p>0.05). Overall monotherapy with brimonidine and dorzolamide appear to produce equivalent IOP lowering efficacy and have well tolerated adverse effect profile, although a trend was observed at 10.00 a.m. of greater brimonidine efficacy compared with dorzolamide.

Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome Caused by Topical Ophthalmic Use of Dorzolamide / 대한피부과학회지

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are the potentially life-threatening, acute hypersensitivity reaction to inciting drugs. These diseases have been often associated with systemic carbonic anhydrase inhibitor such as acetazolamide or methazolamide in Korean and Japanese patients. Dorzolamide is a recently developed topical carbonic anhydrase inhibitor with few significant systemic adverse effects. To the best of our knowledge, there have been only a few reports of SJS or TEN caused by topical dorzolamide in the literature. We herein present two cases of TEN and one case of SJS related with topical use of dorzolamide. It should be emphasized that although rarely, topical dorzolamide may cause serious sulfonamide hypersensitivity such as SJS or TEN in the susceptible patient through the systemic absorption.

The Effect of Dorzolamide-Timolol and Latanoprost on Redox Cycle in Aqueous Humor of Rabbit

PURPOSE: To evaluate the effect of dorzolamide-timolol and latanoprost on redox cycle of superoxide dismutase (SOD) and ascorbic acid in the aqueous humor of the rabbit. METHODS: Group 1 (20 eyes of 10 rabbits) was instilled with dorzolamide-timolol in the right eye and Group 2 (20 eyes of 10 rabbits) was instilled with latanoprost in the same manner. Four weeks after instillation, SOD activity and ascorbic acid concentration were analyzed. RESULTS: In Group 1, SOD activity and ascorbic acid concentration of the right eye and left eye were 15.7% and 19.3% (p=0.27), 2.7 pM and 2.6 pM (p=0.47), respectively. In Group 2, SOD activity and ascorbic acid concentration of the right and left eye were 22.3% and 27.6% (p=0.14), 2.3 pM and 2.1 pM (p=0.89), respectively. CONCLUSIONS: There was no significant difference of SOD activity and ascorbic acid concentration between both eyes in Group 1 and 2.

Toxic Epidermal Necrolysis Induced by the Topical Carbonic Anhydrase Inhibitors Brinzolamide and Dorzolamide

Brinzolamide and dorzolamide are highly specific topical carbonic anhydrase inhibitors (CAIs). They lower intraocular pressure (IOP) by reducing the rate of aqueous humour formation without serious side effects. Although systemic CAIs are the most potent medications for lowering intraocular pressure for conditions with ocular hypertension, many cases with adverse systemic reactions have been reported, including Stevens-Johnson syndrome (SJS) and Toxic epidermal necrolysis (TEN). Here, we report 2 cases of TEN that were associated with topical CAIs rather than systemic CAIs.