OBJECTIVETo dicuss the clinical efficacy of Timolol Maleate Eye Drops in the treatment of superficial infantile hemangiomas. Methods From April 2012 to May 2014, 210 patients with superficial infantile hemangiomas were included. According to the parents' choice, a total of 176 cases were treated with Timolol Maleate Eye Drops as the treatment group, and the 34 cases who received the treatment of "wait and see" was included in the control group. In the treatment group, the gauzes were dipped into the eye drops and putted evenly on the surface of the hemangioma, 3-4 times daily and lasted for more than 20 minutes. The gauze should completely cover the surface of the tumor. The follow-up periods were 3 weeks and 6 months after treatment with the pictures to record the treatment effect. The therapeutic effect was graded as: grade I (unable to control the growth of the hemangioma), II (the growth of the hemangioma stagnated), III (hemangioma significantly subsided), IV (the hemangioma completely disappeared). The effective rate included the cases with grade II and above grade II . The cure cases included the cases with grade IV. The data was analyzed with the statistical software SPSS 17.0 and the Chi-square test (P < 0.05).

RESULTS3 cases in the treatment group showed eczema action. Tumor ulcer happened in 1 case in treatment group. The side effect rate was 2.3% . The results at 3 weeks following in the treatment group showed that the growth of the hemangioma were stagnated in 154 cases. The color of hemangioma became darker in different degrees than before, and the texture of the hemangioma became soft in majority of children, and the thickness of hemangioma became thinner in some cases. However, only 4 cases showed the hemangiomas were subsided, 18 cases showed the color of the part of the hemangiomas were brighter than before, and 12 cases of the hemangiomas remained original state in the control group. The results of 6 weeks following the treatment showed that 18 patients in the treatment group reached the standard of the grade IV, 84 patients reached the standard of the grade III, 60 patients achieved in the standard of grade II, and only 14 patients showed the volume of hemangiomas were increased as grade I. The effective rate was 58. 0% , and the cure rate was 10. 2% in treatment group. In control group, no children reached the standard of the grade IV, 4 cases reached the standard of grade III, 13 cases who remained original state reached the standard of grade II, and 17 cases showed the volume of hemangiomas continued to increase as grade I . The effective rate was 11. 8% , and the cure rate was 0. By comparison, the effective rate and the cure rate in the control group were relatively lower than those in the treatment group (P < 0.05).

CONCLUSIONSThe efficacy of Timolol Maleate Eye Drops in the treatment of superficial infantile hemangioma is exact, especially in the proliferative phase of the infantile hemangioma. It is safe and easy to perform with mild side effect. It should be selected as first-line treatment.

Administration, Topical ; Adrenergic beta-Antagonists ; administration & dosage ; Child ; Hemangioma ; drug therapy ; Humans ; Ophthalmic Solutions ; administration & dosage ; Skin Neoplasms ; drug therapy ; Timolol ; administration & dosage ; adverse effects ; Treatment Outcome ; Watchful Waiting

PURPOSE: To evaluate and compare the toxic effects of eyedrops containing a fixed combination of 2.0% dorzolamide and 0.5% maleate timolol with or without preservatives on rabbit corneal endothelium. METHODS: This study was performed with 22 eyes of New Zealand white rabbits. Dorzolamide/timolol eyedrops with preservative (Cosopt group) or without preservative (Cosopt-S group) were diluted with a balanced salt solution at a 1 : 1 ratio. We injected 0.1 mL of diluted Cosopt into the anterior chamber of left eyes and an equal volume of diluted Cosopt-S into the anterior chamber of right eyes. Corneal thickness, corneal haze, and conjunctival injection were measured before and 24 hours after treatment. Endothelial damage was compared between both eyes by vital staining (alizarin red/trypan blue staining), live/dead cell assay, TUNEL assay, and scanning electron microscopy. RESULTS: Corneal endothelial damage was severe in the Cosopt group. Cosopt-treated eyes exhibited remarkable corneal edema and prominent apoptosis of endothelial cells. In addition, the live/dead cell assay revealed many dead cells in the endothelium, and scanning electron microscopy analysis showed that corneal endothelial cells exhibited a partial loss of microvilli on the surface as well as extensive destruction of intercellular junctions. However, in the Cosopt-S group, corneal edema was mild and the damage to the corneal endothelium was minimal. CONCLUSIONS: The main cause of corneal endothelial toxicity was due to the preservative in the dorzolamide/timolol fixed combination eyedrops, and not the active ingredient. Thus, it appears to be safer to use preservative-free eyedrops during the early postoperative period.
Animals ; Anterior Chamber/drug effects ; Apoptosis ; Corneal Edema/chemically induced/*pathology ; Disease Models, Animal ; Drug Combinations ; Endothelium, Corneal/drug effects/*pathology ; In Situ Nick-End Labeling ; Ophthalmic Solutions ; Rabbits ; Sulfonamides/administration & dosage/*toxicity ; Thiophenes/administration & dosage/*toxicity ; Timolol/administration & dosage/*toxicity

AIMTo study the diffusion behaviors of drugs in thermosensitive in situ gels, and provide valuable information for designing such delivery systems.

METHODSA free diffusion model was used to evaluate the effects of concentration, the property of drugs, as well as the gel compositions on the diffusivity of drugs.

RESULTSDrug transport through the aqueous channels of the gel followed Fickian mechanism, and no significant influence on the diffusivity was observed when the drug concentration was lowered from 5% to 0.25%. The diffusion coefficients of propranolol, timolol maleate, and salbutamol sulfate were 0.91, 1.32, and 3.30 x 10(-6) cm2 x s(-1), respectively. The flux of hydrophilic drug was 3.6 fold faster than that of the lipophilic one implied the latter partitioned into the hydrophobic micellar core, and consequently the diffusion was retarded. The diffusivity was decreased with increased poloxamer and sodium hyaluronate concentration, due to the distorted aqueous channels and higher microviscosity.

CONCLUSIONThe result suggested that sustained release could be achieved for the thermosensitive in situ gel by incorporating lipophilic drug or increasing polymer concentration.

Albuterol ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Diffusion ; Drug Carriers ; chemistry ; Drug Delivery Systems ; Gels ; Poloxamer ; chemistry ; Propranolol ; administration & dosage ; chemistry ; Surface-Active Agents ; chemistry ; Timolol ; administration & dosage ; chemistry

OBJECTIVETo investigate the efficacy and side effect of topical beta-blocker (Timolol Maleate) in the treatment of periocular hemangioma in a prospective study.

METHODS432 outpatients with infantile hemangioma visited our special clinic service in Shanghai Ninth People's Hospital from July 2010 to December 2011. Among them, 12 superficial periocular lesions were selected in the study. Timolol was used topically on the lesion in every 12 hours. Two independent special doctors evaluated the results according to the pictures before and after four-week application of timolol.

RESULTSWere categorized into four levels: continuous growth (the lesion continues to grow), stable (no visible change), moderate (0-50% of regression) , perfect (more than 50% of improvement). Result of the 12 outpatients, 4 showed perfect result, 2 moderate, 4 stable and 2 continuous growth. No side effect was observed.

CONCLUSIONSTopical timolol is effective and safe in the treatment of superficial periocular infantile hemangioma. It could be considered as the first line treatment of proliferative superficial hemangioma.

Administration, Topical ; Angiogenesis Inhibitors ; therapeutic use ; China ; Facial Neoplasms ; drug therapy ; pathology ; Hemangioma ; drug therapy ; pathology ; Hemangioma, Capillary ; drug therapy ; pathology ; Humans ; Infant ; Prospective Studies ; Skin Neoplasms ; drug therapy ; pathology ; Timolol ; therapeutic use ; Treatment Outcome

PURPOSE: To evaluate the effects of a bimatoprost/timolol fixed combination (BTFC) and a latanoprost/timolol fixed combination (LTFC) on diurnal intraocular pressure (IOP) and anterior ocular parameters in healthy subjects. METHODS: We enrolled 58 healthy subjects in this prospective clinical study. Thirty subjects were treated with BTFC and 28 subjects were treated with LTFC. IOP was measured every 2 hours except from 01:00 and 05:00. Axial length, corneal curvature, and anterior chamber depth were obtained using the IOL master at baseline and 24 hours later. Adverse events were assessed by patient interview and by slit lamp examination. RESULTS: The largest difference in IOP between treated and untreated eyes 8 hours after instillation was 1.67 mmHg in the BTFC group (p < 0.001). The largest difference in IOP between treated and untreated eyes 10 hours after instillation was 1.93 mmHg in the LTFC group (p < 0.001). For anterior ocular parameters such as axial length, corneal curvature, anterior chamber depth at baseline and 24 hours after instillation, there were no significant differences between the baseline and 24-hour values in either the BTFC or LTFC group. The most frequently occurring adverse event was conjunctival hyperemia, which was found in 33.3% (n = 10) of the BTFC group and 25.0% (n = 7) of the LTFC group (p = 0.486). CONCLUSIONS: BTFC and LTFC provided a significant reduction in IOP from baseline without changing any anterior ocular parameters. Our results provide a reference for monocular trials to assess the effect of eye drops in a clinical condition.
Adult ; Aged ; Aged, 80 and over ; Amides/*administration & dosage ; Antihypertensive Agents/administration & dosage ; Circadian Rhythm/*physiology ; Cloprostenol/administration & dosage/*analogs & derivatives ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Glaucoma, Open-Angle/drug therapy/*physiopathology ; Healthy Volunteers ; Humans ; Intraocular Pressure/drug effects/*physiology ; Male ; Middle Aged ; Ophthalmic Solutions ; Prospective Studies ; Prostaglandins F, Synthetic/*administration & dosage ; Timolol/*administration & dosage ; Tonometry, Ocular ; Treatment Outcome

PURPOSE: To evaluate the effects of a bimatoprost/timolol fixed combination (BTFC) and a latanoprost/timolol fixed combination (LTFC) on diurnal intraocular pressure (IOP) and anterior ocular parameters in healthy subjects. METHODS: We enrolled 58 healthy subjects in this prospective clinical study. Thirty subjects were treated with BTFC and 28 subjects were treated with LTFC. IOP was measured every 2 hours except from 01:00 and 05:00. Axial length, corneal curvature, and anterior chamber depth were obtained using the IOL master at baseline and 24 hours later. Adverse events were assessed by patient interview and by slit lamp examination. RESULTS: The largest difference in IOP between treated and untreated eyes 8 hours after instillation was 1.67 mmHg in the BTFC group (p < 0.001). The largest difference in IOP between treated and untreated eyes 10 hours after instillation was 1.93 mmHg in the LTFC group (p < 0.001). For anterior ocular parameters such as axial length, corneal curvature, anterior chamber depth at baseline and 24 hours after instillation, there were no significant differences between the baseline and 24-hour values in either the BTFC or LTFC group. The most frequently occurring adverse event was conjunctival hyperemia, which was found in 33.3% (n = 10) of the BTFC group and 25.0% (n = 7) of the LTFC group (p = 0.486). CONCLUSIONS: BTFC and LTFC provided a significant reduction in IOP from baseline without changing any anterior ocular parameters. Our results provide a reference for monocular trials to assess the effect of eye drops in a clinical condition.
Adult ; Aged ; Aged, 80 and over ; Amides/*administration & dosage ; Antihypertensive Agents/administration & dosage ; Circadian Rhythm/*physiology ; Cloprostenol/administration & dosage/*analogs & derivatives ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Glaucoma, Open-Angle/drug therapy/*physiopathology ; Healthy Volunteers ; Humans ; Intraocular Pressure/drug effects/*physiology ; Male ; Middle Aged ; Ophthalmic Solutions ; Prospective Studies ; Prostaglandins F, Synthetic/*administration & dosage ; Timolol/*administration & dosage ; Tonometry, Ocular ; Treatment Outcome

BACKGROUNDLowering intraocular pressure (IOP) is currently the only therapeutic approach in primary open-angle glaucoma. and the fixed-combination medications are needed to achieve sufficiently low target IOP. A multicenter prospective study in the Chinese population was needed to confirm the safety and efficacy of Bimatoprost/Timolol Fixed Combination Eye Drop in China. In this study, we evaluated the safety and efficacy of Bimatoprost/Timolol Fixed Combination with concurrent administration of its components in Chinese patients with open-angle glaucoma or ocular hypertension.

METHODSIn this multicenter, randomized, double-masked, parallel controlled study, patients with open-angle glaucoma or ocular hypertension who were insufficiently responsive to monotherapy with either topical β-blockers or prostaglandin analogues were randomized to one of two active treatment groups in a 1:1 ratio at 11 Chinese ophthalmic departments. Bimatoprost/timolol fixed combination treatment was a fixed combination of 0.03% bimatoprost and 0.5% timolol (followed by vehicle for masking) once daily at 19:00 P.M. and concurrent treatment was 0.03% bimatoprost followed by 0.5% timolol once daily at 19:00 P.M. The primary efficacy variable was change from baseline in mean diurnal intraocular pressure (IOP) at week 4 visit in the intent-to-treat (ITT) population. Primary analysis evaluated the non-inferiority of bimatoprost/ timolol fixed combination to concurrent with respect to the primary variable using a confidence interval (CI) approach. Bimatoprost/timolol fixed combination was to be considered non-inferior to concurrent if the upper limit of the 95% CI for the between-treatment (bimatoprost/timolol fixed combination minus concurrent) difference was ≤ 1.5 mmHg. Adverse events were collected and slit-lamp examinations were performed to assess safety. Between-group comparisons of the incidence of adverse events were performed using the Pearson chi-square test or Fisher's exact test.

RESULTSOf the enrolled 235 patients, 121 patients were randomized to receive bimatoprost/timolol fixed combination and, 114 patients were randomized to receive concurrent treatment. At baseline the mean value of mean diurnal IOP was (25.20 ± 3.06) mmHg in the bimatoprost/timolol fixed combination group and (24.87 ± 3.88) mmHg in the concurrent group. The difference between the treatment groups was not statistically significant. The mean change from baseline in mean diurnal IOP (± standard deviation) in the bimatoprost/timolol fixed combination group was (-9.38 ± 4.66) mmHg and it was (-8.93 ± 4.25) mmHg in the concurrent group (P < 0.01). The difference between the two treatment groups (bimatoprost/timolol fixed combination minus concurrent) in the change from baseline of mean diurnal IOP was -0.556 mmHg (95% CI: -1.68, 0.57, P = 0.330). The upper limit of the 95% CI was less than 1.5 mmHg, the predefined margin of non-inferiority. Adverse events occurred in 26.4% (32/121) of the bimatoprost/timolol fixed combination patients and 30.7% (35/114) of the concurrent patients. The most frequent adverse event was conjunctival hyperemia, which was reported as treatment related in 16.5% (20/121) in the bimatoprost/timolol fixed combination group and 18.4% (21/114) in the concurrent group (P > 0.05).

CONCLUSIONSBimatoprost/Timolol Fixed Combination administered in Chinese patients with open-angle glaucoma or ocular hypertension was not inferior to concurrent dosing with the individual components. Safety profiles were similar between the treatment groups.

Adolescent ; Adult ; Aged ; Amides ; administration & dosage ; adverse effects ; therapeutic use ; Bimatoprost ; Cloprostenol ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Female ; Glaucoma, Open-Angle ; drug therapy ; Humans ; Male ; Middle Aged ; Ocular Hypertension ; drug therapy ; Timolol ; administration & dosage ; adverse effects ; therapeutic use ; Young Adult