Persistence of the carteolol hydrochloride/latanoprost fixed-combination ophthalmic solution, compared with the other ß-blocker/prostanoid FP receptor agonist fixed-combination ophthalmic solutions.

PURPOSE: To investigate the treatment persistence of carteolol hydrochloride/latanoprost fixed-combination ophthalmic solution (CAR/LAT) and other ß-blocker/prostanoid FP receptor agonist fixed-combination ophthalmic solutions (BB/FP) in the treatment of glaucoma. STUDY DESIGN: Retrospective observational cohort study. METHODS: A retrospective observational cohort study using JMDC Claims Database. Patients aged 20 years or older diagnosed with glaucoma between February 1, 2017, and March 31, 2020, and prescribed CAR/LAT or another BB/FP were included. RESULTS: A total of 16,612 patients (7423 in the CAR/LAT group and 9189 in the other BB/FP group) were included. The cumulative treatment persistence rate at the end of follow-up was 42.0% (64.9% at 1 year, 53.4% at 2 years, 45.0% at 3 years, and 42.0% at 4 years) in the CAR/LAT group and 34.7% (54.8% at 1 year, 43.6% at 2 years, 37.1% at 3 years, and 34.7% at 4 years) in the other BB/FP group. Treatment persistence was significantly longer in the CAR/LAT group compared to that in the other BB/FP group (hazard ratio 0.747, p < 0.0001). Over the treatment period, the number of patients who discontinued treatment was 3281 (44.2%) in the CAR/LAT group and 4926 (53.6%) in the other BB/FP group; the median duration of treatment was 135 days and 97 days, respectively. CONCLUSION: The study results suggest that persistence rates vary depending on the BB/FP and CAR/LAT appears to be more persistent than other BB/FP.

Urinary excretion patterns and potential risks of beta-blocker ophthalmic drops in sports.

Beta-blockers have been prohibited by the World Anti-Doping Agency (WADA) in certain sports, but insufficient research data make it difficult to distinguish between therapeutic uses or misuses. This study aimed at investigating the urinary excretion pattern following beta-blocker ophthalmic drops and the potential risk of constituting an adverse analytical finding (AAF) in sports. Prescribed timolol and carteolol ophthalmic drops were used in healthy participants and glaucoma patients. The urine samples were then collected to investigate the urinary excretion pattern following acute and chronic administration of the above beta-blocker ophthalmic drops. The liquid chromatograph-tandem mass spectrometry method was applied for measuring urinary beta-blockers. Our results demonstrated that the levels of both urinary timolol and carteolol exceeded the minimum reporting levels (MRL) following acute and chronic administration. The highest levels of urinary timolol and carteolol observed in the present study were 255.7 and 923.8 ng/ml, respectively. Regarding the acute administration of timolol ophthalmic drop, 26.19 (11/42) of urine samples were detected with timolol higher than the MRL in timed and random sampling. In contrast, the acute administration of carteolol ophthalmic drops made the carteolol levels higher than the MRL among most urine samples. On the other hand, 36.36% (4/11) of urine samples were detected with beta-blockers higher than the MRL during the chronic administration of timolol and carteolol ophthalmic drops. In the context of receiving ophthalmic beta-blocker medications, the present study has highlighted the potential risk of constituting an AAF in specific sports and suggests strengthening athletes' awareness of therapeutic use exemptions.

Life-threatening Vasospastic Angina Induced by Carteolol Eye Drops.

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

Efficacy and safety of the fixed combinations of tafluprost/timolol and latanoprost/carteolol.

In this study, we made a comparative efficacy and safety assessment of two different fixed combinations of drugs, viz., tafluprost/timolol (TAF/TIM) and latanoprost/carteolol (LAT/CAR), by determining their effects on intraocular pressure (IOP) in ocular normotensive monkeys and examining their toxic effects on ocular surface using human corneal epithelial cells. TAF/TIM was found to be more effective in lowering IOP for a longer duration compared to LAT/CAR. We found that the difference in the intensity of IOP-lowering effect was because of the differences in the strength of timolol compared with that of carteolol as a beta-adrenergic antagonist and strength of tafluprost compared with that of latanoprost as a prostaglandin analogue. In addition, TAF/TIM showed much less cytotoxic effects compared to LAT/CAR on the human corneal epithelial cells. Our findings showed that TAF/TIM is better than LAT/CAR with regard to the IOP-lowering effect in monkeys and toxicity on ocular surface.

Insidious-onset, non-wheezing carteolol-induced asthma in an atopic patient without asthma history.

Carteolol, a non-selective beta-antagonist with a potential risk of severe bronchial constriction in patients with asthma, is one of the most commonly prescribed medication for managing ocular pressure in glaucoma. We present a case of a 24-year-old woman with a history of atopy but no known asthma who presented an insidious onset of clinical manifestations compatible with drug-induced asthma after the initiation of carteolol for ocular hypertension control. The patient developed progressive chest tightness and dyspnoea for 2 months before the pulmonary function test revealed a positive bronchoprovocation response. She reported significant improvement of respiratory symptoms within 2 weeks after the discontinuation of carteolol, and a negative provocation response was later confirmed by repeat pulmonary function test. In conclusion, eye drops with non-selective beta-antagonising effect can induce asthmatic symptoms in patients without a previous diagnosis of asthma and should be administered with caution in patients with associated risk factors.

Short-term Efficacy and Safety of a Latanoprost/Carteolol Fixed Combination Switched From Concomitant Therapy to in Patients With Primary Open-angle Glaucoma or Ocular Hypertension.

PURPOSE: We prospectively investigated the efficacy and safety of switching from concomitant latanoprost and carteolol hydrochloride (CH) to a latanoprost/carteolol fixed combination (LCFC) in patients with primary open-angle glaucoma or ocular hypertension. PATIENTS AND METHODS: A total of 43 patients (43 eyes) who were using latanoprost (once daily in the evening) and CH (once daily in the morning) concomitantly were switched to LCFC (once daily in the morning) with no washout interval. The primary efficacy endpoint was change in intraocular pressure (IOP) between baseline (before switching) and 1 and 3 months after switching. Systemic blood pressure and pulse rate, corneal epithelial defects, and tear film break-up time (TBUT) were also compared before and 1 and 3 months after switching. A questionnaire was administered 1 month after switching to investigate ocular comfort and treatment preferences. Adverse reactions and dropouts were recorded. RESULTS: There was no significant difference in IOP after switching to LCFC (15.0±2.6, 15.1±2.4, and 15.0±2.4 mm Hg at baseline and at 1 and 3 months, respectively). There was a significant decrease in corneal epithelial defects and significant increase in TBUT, without significant changes in systemic blood pressure or pulse rate. Three patients (7.3%) preferred concomitant latanoprost and CH; 33 (80.5%) preferred the LCFC. One patient each (9.3%) discontinued treatment because of foreign body sensation, blepharitis, increased IOP, or loss to follow-up. CONCLUSIONS: Switching from concomitant latanoprost and CH to LCFC led to similar IOP control with good safety and patient acceptance, at least in the short term.

Time course of changes in ocular aberrations after instillation of carteolol long-acting solution and timolol gel-forming solution.

PURPOSE: To investigate the influence of 2% carteolol long-acting solution (long-acting carteolol) and 0.5% timolol gel-forming solution (timolol gel) on ocular wavefront aberrations. METHODS: Ocular aberrations were assessed in the right eye of 24 healthy volunteers at baseline and at 2, 5, 10, and 15 min after instillation of long-acting carteolol, timolol gel or physiological saline using the Hartmann-Shack aberrometer. Ten serial measurements were taken over 10 s at each time point, and the root mean square (RMS) of second-, third-, fourth-, and total higher-order aberrations were calculated. The stability index and fluctuation index were also determined. RESULTS: Second-order aberrations did not change significantly after instillation of study eye-drops. Higher-order aberrations increased significantly after instillation of long-acting carteolol and timolol gel. Timolol gel induced significantly larger changes than long-acting carteolol in third-order RMS at 2 min (P = 0.001), fourth-order RMS at 2 (P < 0.001) and 5 (P = 0.013) min, and total higher-order RMS at 2 (P < 0.001) and 5 (P = 0.016) min after instillation, but not at 10 and 15 min after administration. Fluctuation index increased significantly after instillation of each eye-drop (P < 0.001), with significantly larger increases after timolol gel than long-acting carteolol at 2 min (P = 0.005) and 5 min (P = 0.011). No significant changes were observed in stability index. CONCLUSIONS: Both topical ß blockers with a once-daily dosing regimen temporarily deteriorate optical quality of the eye by increasing higher-order aberrations, and the increases are much larger after instillation of timolol gel than long-acting carteolol.

[The deleterious effect of certain surface active agents on the ocular surface]. / Les effets délétères de certains collyres sur la surface oculaire.

Most ocular solutions enter the eye through the corneal epithelial barrier. In order to pass through this barrier, these hydrosoluble drugs require to be associated with a detergent agent to increase topical efficiency. Although these agents have a preservative action, it was recently demonstrated that, after short or long term use, toxic side effects on the ocular surface will occur.

Ocular carteolol: a review of its use in the management of glaucoma and ocular hypertension.

Ocular carteolol (Mikelan), Teoptic, Ocupress) is a nonselective beta-adrenoceptor antagonist with intrinsic sympathomimetic activity (ISA). Ocular carteolol effectively reduces intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OH). Twice-daily administration of standard carteolol has generally similar IOP-lowering efficacy to other ocular beta-adrenoceptor antagonists such as timolol, betaxolol and metipranolol in patients with OAG or OH. In addition, long-term treatment with carteolol has similar efficacy to timolol and betaxolol in terms of reducing IOP and maintaining visual fields in patients with newly diagnosed primary OAG (POAG). The new long-acting formulation of once-daily carteolol has equivalent efficacy to the standard formulation of carteolol administered twice daily in patients with OAG or OH. Both the standard and long-acting formulations of ocular carteolol are generally well tolerated in terms of topical adverse effects involving the eyes or systemic adverse effects involving the cardiovascular system. Thus, twice-daily carteolol is a well established option in the treatment of glaucoma and OH, and the new once-daily formulation of long-acting carteolol offers similar efficacy and tolerability with a potential for improved patient adherence.

[A case of severe glaucoma with pseudopemphigoid successfully treated by filtration surgery using amniotic membrane].

BACKGROUND: It is necessary to decrease topical anti-glaucoma medication for severe glaucoma with pseudopemphigoid caused by anti-glaucoma eye drops. Glaucoma filtrating surgery is often needed instead of medication, but the prognosis is poor because it induces scar fomation and makes the filtrating bleb vanish. CASE: An 85-year-old male patient with exfoliation syndrome had twice undergone glaucoma surgery about ten years previously. His intra-ocular pressure (IOP) was high despite topical anti-glaucoma medication. At the first examination in our hospital, he had severe superficial punctate keratopathy, blephariticshortening and symblepharon, and we therefore diagnosed severe pseudopemphigoid induced by anti-glaucoma eye drops. Because his IOP could not be controlled by topical and general medication, we conducted a glaucoma filtrating operation using amniotic membrane. CONCLUSION: The administration of oral anti-inflammatory drugs before and after surgery and the use of amniotic membrane prevented post-operative scar formation and the progress of symblepharon, resulting in the successful control of IOP after surgery.

Comparison of the additive effects of nipradilol and carteolol to latanoprost in open-angle glaucoma.

PURPOSE: To compare the effects of nipradilol and carteolol on intraocular pressure (IOP) when added to latanoprost treatment for glaucoma patients. METHODS: Fifty patients with primary open-angle glaucoma were treated with latanoprost 0.005% once daily for 3 months. Then they were assigned to one of two groups randomly. One group received nipradilol 0.25% twice daily (nipradilol preceding group; n = 25), and the other carteolol hydrochloride 2% twice daily (carteolol preceding group; n = 25), for 3 months in addition to latanoprost. Then, nipradilol and carteolol were switched, and the subjects were treated for 3 more months. One eye was selected randomly for analysis. RESULTS: In the nipradilol preceding group, IOP was 21.4 +/- 2.3 mmHg (mean +/- SD) at baseline, and 16.8 +/- 1.9 mmHg at the end of latanoprost monotherapy (P < 0.01). The addition of nipradilol decreased IOP to 15.8 +/- 1.7 mmHg, and the change to carteolol, to 15.3 +/- 2.0 mmHg. In the carteolol preceding group, IOP was 21.2 +/- 2.0 mmHg at baseline, and 17.0 +/- 2.1 mmHg at the end of latanoprost monotherapy (P < 0.01). The addition of carteolol decreased IOP to 15.4 +/- 1.8 mmHg, and the change to nipradilol, to 16.3 +/- 1.9 mmHg. Additional IOP reduction was greater with carteolol than with nipradilol (cross-over analysis of variance; P = 0.0005). CONCLUSIONS: Both nipradilol and carteolol have additive effects when used in combination with latanoprost. Carteolol, however, may have a more potent effect than nipradilol.

Ocular factors relevant to anti-glaucomatous eyedrop-related keratoepitheliopathy.

PURPOSE: To evaluate the ocular factors contributing to keratoepitheliopathy in glaucoma patients treated with or without anti-glaucomatous eyedrops, and the influences of each anti-glaucomatous eyedrop to keratoepitheliopathy. METHODS: The presence and severity of keratoepitheliopathy was investigated in 193 eyes of 110 glaucoma patients. The ocular factors examined were the status of the lipid layer of the tear fluid as assessed by a specular reflection video-recording system, tear volume assessed by Schirmer's test, and tear film stability assessed by tear break-up time. The influences of combined anti-glaucomatous eyedrops and each anti-glaucomatous eyedrops to keratoepitheliopathy were investigated. RESULTS: The overall occurrence of superficial punctate keratitis was 29.0%. Superficial punctate keratitis was more frequently observed in patients who used more than two anti-glaucomatous eyedrops (35.9%) than in those who used without (19.7%) and one (30.9%). Results of Schirmer's test and break-up time were worse in patients who used combined medication. The occurrence of superficial punctate keratitis in patients who used timolol (46.2%) was significantly more frequent than in those who used carteolol (4.2%). Severity of superficial punctate keratitis and break-up time in patients who used timolol were significantly worse than in those who used carteolol. There were no differences of keratoepitheliopathy and ocular factors between patients who used latanoprost and unoprostone. CONCLUSION: The usage of multiple anti-glaucomatous eyedrops induces keratoepitheliopathy by reducing the tear volume and the tear film stability. Carteolol may be used more safely for corneal epithelium.

A new method using pulmonary gas-exchange kinetics to evaluate efficacy of beta-blocking agents in patients with dilated cardiomyopathy.

BACKGROUND AND OBJECTIVES: The effects of beta-blocking agents on exercise tolerance in cardiopulmonary exercise testing (CPX) have not been fully identified. Because the negative chronotropic effects of these agents produce a sluggish increase in heart rate (HR) during CPX, exercise capacity is actually underestimated by methods that depend on HR-related variables such as peak oxygen uptake (O(2)) and anaerobic threshold (AT). The aim of this study was to clarify the efficacy of beta-blocking agents by means of O(2) kinetics, a parameter independent of HR, in patients with dilated cardiomyopathy (DCM). DESIGN AND PATIENTS: The exercise capacity of 12 patients (9 men and 3 women; mean +/- SD age, 54 +/- 12 years; New York Heart Association class I [n = 1], NYHA class 2 [n = 4], and NYHA class III [n = 6]) with DCM, who were treated with beta-blocking agents, was evaluated by CPX. O(2) was calculated from respiratory gas analysis on a breath-by-breath basis. Nine patients were treated with metoprolol (30 mg or 60 mg), two with carteolol (10 mg or 20 mg), and one patient with atenolol (25 mg). RESULTS: All patients showed a significantly favorable results (ie, improvement in symptoms of congestive heart failure). Peak O(2) (20.4 +/- 5.1 to 18.8 +/- 5.8 mL/min/kg), AT (12.7 +/- 3.5 to 12.1 +/- 2.1 mL/min/kg), and exercise time (4.8 +/- 2.2 to 4.5 +/- 2.1 s) were unchanged. The time constant of O(2) kinetics (tau) on response to constant low-dose work loading (warm up) decreased significantly (64 +/- 30 to 44 +/- 24 s; p < 0.01) and ejection fraction increased (30 +/- 14 to 44 +/- 15%, p < 0.01) significantly following treatment with beta-blocking agents. In spite of excluding two NYHA I patients, these changes were also statistically correlated. CONCLUSION: In the low level of exercise, tau was prolonged in patients with DCM. Although indexes of total exercise time and AT were not useful markers for clinical improvement in cardiac performance as assessed by echocardiography, measuring can validly assess the beneficial effects in heart failure treated with beta-blocking agents.

Comparison of the intraocular pressure lowering effect of latanoprost and carteolol-pilocarpine combination in newly diagnosed glaucoma.

PURPOSE: To evaluate the comparative efficacy of latanoprost monotherapy versus combined carteolol and pilocarpine therapy in patients with newly diagnosed glaucoma. METHODS: Masked randomized prospective trial. This study included 51 patients (64 eyes) with newly diagnosed glaucoma or ocular hypertension. The cases were randomly divided into two treatment groups for administration of latanoprost 0.005% once daily, or of carteolol 2% twice daily and pilocarpine 2% twice daily. Mean diurnal intraocular pressure (IOP) was measured at baseline, week 2, week 4, and month 3 after the beginning of treatment. Changes in mean IOP from baseline to the 3-month visit were determined by an analysis of variance. RESULTS: Mean diurnal IOP values were 25.1 +/- 3.1 mm Hg and 25.5 +/- 2.5 mm Hg at baseline in the latanoprost monotherapy group and in the carteolol-plus-pilocarpine group, respectively. Diurnal IOP was significantly decreased from baseline to 3 months in both groups (P <.001). At this time point, latanoprost monotherapy had reduced mean diurnal IOP by 7.2 +/- 2.5 mm Hg (28.7%) and carteolol plus pilocarpine had reduced mean diurnal IOP by 7.4 +/- 2.7 mm Hg (29%). There was no difference between the groups in terms of their IOP reduction effect (P =.51). Decreased visual acuity and twilight vision, blurred vision, and headache were more frequent in the carteolol-plus-pilocarpine group than in the latanoprost group (P <.05). CONCLUSIONS: We concluded that latanoprost monotherapy was at least as effective as the carteolol-pilocarpine combination therapy in reducing mean diurnal IOP in newly diagnosed glaucoma or ocular hypertension.

Assessment of systemic adverse reactions induced by ophthalmic beta-adrenergic receptor antagonists.

To assess quantitatively the risks of ophthalmic beta-blocking agents for cardiovascular and respiratory adverse reactions, we analyzed the binding kinetics of beta-blocking agents to the beta-1 and beta-2 adrenoceptors. The relationship between the occupancies for beta-1 and beta-2 adrenoceptors and the effects on the exercise pulse rate or the forced expiratory volume in one second (FEV1) after topical administration of carteolol, befunolol, timolol and betaxolol was analyzed using a ternary complex model. The beta-1 and beta-2 receptor occupancies after ophthalmic administration were calculated to be quite high as well as those after oral administration. The maximum occupancies for beta-1 and beta-2 receptors after ordinary ophthalmic administration were 52% and 88% for carteolol, 52% and 61% for befunolol, 62% and 82% for timolol, and 44% and 3% for betaxolol, respectively. Concave relationships were obtained between a decrease in exercise pulse rate and the beta-1 receptor occupancy and between a decrease in FEV1 and beta-2 receptor occupancy, respectively. Nasolacrimal occlusion was estimated to decrease the exercise pulse rate and FEV1 by 65% and 50%, respectively. The beta-1 and beta-2 adrenoceptor occupancies were proved to be the most appropriate indicators for cardiac and pulmonary adverse reactions evoked by ophthalmic beta-blocking agents.