Short-term efficacy of latanoprostene bunod for the treatment of open-angle glaucoma and ocular hypertension: a systematic literature review and a network meta-analysis.

BACKGROUND/AIMS: To assess the comparative efficacy of latanoprostene bunod (LBN), a novel prostaglandin analogue (PGA), to other medications for open-angle glaucoma and ocular hypertension on lowering intraocular pressure (IOP). METHODS: A systematic literature review adapted from the Li et al (Ophthalmology, 2016) study was conducted. Medline, Embase and PubMed were searched for randomised controlled trials published between 1 January 2014 and 19 March 2020. Studies had to report IOP reduction after 3 months for at least two different treatments among placebo, PGAs (bimatoprost 0.01%, bimatoprost 0.03%, latanoprost, LBN, tafluprost, unoprostone) or apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide, levobunolol, timolol, travoprost. A Bayesian network meta-analysis was performed to provide the relative effect in terms of mean difference (95% credible interval) of IOP reduction and ranking probabilities. Surface under the cumulative ranking curve (SUCRA) was generated. RESULTS: A total of 106 trials were included with data for 18 523 participants. LBN was significantly more effective than unoprostone (-3.45 (-4.77 to -2.12)). Although relative effect was not significative, compared with other PGAs, LBN numerically outperformed latanoprost (-0.70 (-1.83 to 0.43)) and tafluoprost (-0.41 (-1.87 to 1.07)), was similar to bimatoprost 0.01% (-0.02(-1.59 to 1.55)) and was slightly disadvantaged by bimatoprost 0.03% (-0.17 (-1.42 to 1.07)). LBN was significantly more efficient than the beta-blockers apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide and timolol. According to SUCRA, LBN was ranked second after bimatoprost 0.03%, followed by bimatoprost 0.01%. CONCLUSION: LBN was significantly more effective than the PGA unoprostone and most of the beta-blockers. Compared with the most widely used PGAs, LBN numerically outperformed latanoprost and travoprost and was similar to bimatoprost 0.01%.

Research and correlation analysis on the dripper contamination of carteolol hydrochloride eye drops.

BACKGROUND: Multi-dose eye drops are easily contaminated by microorganisms, and reportedly, the highest contamination rate can reach 96.46%. The use of contaminated eye drops can cause serious eye infections. METHODS: Carteolol hydrochloride eye drops provided by glaucoma patients who visited the ophthalmic clinic of the First Affiliated Hospital of Soochow University from May 2018 to December 2019 were collected. Microbial culture was carried out on the eye drops, and the microbial species were identified by standard procedures. At the same time, the unsealing time, storage method, hand cleaning before dripping, and contact with the eyelid or the surrounding environment during infusion were recorded. Univariate and multivariate logistic regression analyses were used to analyze the risk factors associated with the contamination of carteolol hydrochloride eye drops. RESULTS: A total of 244 bottles of carteolol hydrochloride eye drops were collected, and the positive rate of flora culture was 6.6%. A total of 18 strains of bacteria were isolated. The most common bacteria were Staphylococcus epidermidis and Corynebacterium. Univariate analysis showed that the risk factors associated with contamination were the unsealing time, the frequency of daily use, contact with the eyelid or the surrounding environment during the infusion process, and the use of more than 2 kinds of eye drops at the same time. Multivariate analysis showed that the unsealing time, the frequency of daily use, and contact with the eyelid or the surrounding environment were independent risk factors associated with contamination. CONCLUSIONS: A long unsealing time, frequent use, and non-standard operation can increase the risk of eye drop contamination, which cannot be ignored.

Efficacy of the combination of carteolol hydrochloride + latanoprost in the treatment of glaucoma and ocular hypertension.

INTRODUCTION: The only evidence-based mechanism for prevention and treatment of glaucomatous optic neuropathy is decreasing the intraocular pressure (IOP). Prescribing multiple ocular hypotensive agents, such as the combination of carteolol and latanoprost, may synergistically improve IOP; however, doing so may increase the complexity of a medication regimen, in turn, impairing patient adherence. Fixed-combination glaucoma medications offer convenience and effectiveness. New to this class of glaucoma medication is fixed combination carteolol-latanoprost (FCCL). Area covered: This review intends to give the reader a better understanding of the efficacy of the combination of carteolol and latanoprost separately, and where FCCL fits into the vast medical arsenal of IOP drops. Furthermore, it outlines the particular pharmacologic mechanisms targeted, the pharmacokinetics, effectiveness, the advantages of fixed-combination administration, and tolerability. Expert opinion: The combination of carteolol and latanoprost, separately or in a fixed-combination, is more effective than either drug alone. Given the early stage in development of FCCL, it has yet to be determined how FCCL compares to other fixed-combination medications. However, pending further approval, fixed-combination carteolol-latanoprost may represent a reasonable alternative for a patient whose IOP is inadequately controlled on a prostaglandin analog alone and for whom a simplified combination is preferred.

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.

Individualized Treatment for Infantile Hemangioma.

Infantile hemangioma can grow dramatically or typically locate on the face, which may lead to functional impairment, cosmetically disfiguring and exhibiting complications such as ulceration, bleeding, or infection. Early intervention is necessary. In this study, the authors chose individual treatment for different patients. From January 2012 to December 2016, 185 patients with hemangioma were enrolled into this study. Lesion area ranged from 0.5 cm × 0.5 cm to 9 cm × 12 cm. The initial treatment age ranged from 1 to 7 months with an average age of 3.9 months. Thirty-five children achieved the treatment of Intralesional Compound Betamethasone, 134 children achieved the treatment of oral propranolol, and 16 children achieved the treatment of topical carteolol. In the follow-up, the treatment could be repeated or switched to oral propranolol if the tumor tended to grow again. At the end of follow-up, 89% of the patients' tumors shrinked or involuted completely, 5 patients switched to oral propranolol. The adverse effects included soft tissue atrophy, moon face, diarrhea, heart rate reduction, and liver enzyme abnormalities. All of the patients recovered in a short period. Early treatment for hemangioma can achieve good results and avoid functional impairment. For different patients, the authors suggest individualized treatment according to the tumors' size and location.

Chitosan nanoparticles amplify the ocular hypotensive effect of cateolol in rabbits.

PURPOSE: To assess the potential of chitosan (CS) nanoparticles for ocular drug delivery by investigating their intraocular retention by γ-scintigraphy and intraocular pressure reduction. METHODS: Carteolol (CRT) loaded CS-NPs were prepared by ionotropic gelation method. A four-factor three-level Box-Behnken design was employed to investigate the influence of independent variables on particle size, loading capacity and entrapment efficiency. Characterization was done for particle size, encapsulation efficiency, loading capacity and in vitro drug release and transcorneal permeation, histopathology and confocal microscopy, in vitro ocular tolerance. Intraocular retention was assessed by γ-scintigraphy, and intraocular pressure was measured by tonometer betamethasone induced glaucoma rabbits. RESULTS AND DISCUSSION: The optimized nanoparticles showed a particle size of 243 nm (PDI - 0.304±0.04) and drug loading 49.21±2.73% with entrapment efficiency of 69.57±3.54%. In vitro release studies showed a sustained release for 24h as compared to drug solution. Ex vivo studies showed good permeation with non-significant changes in cornea anatomy indicating its safe nature. γ-Scintigraphy study showed good spread and retention (<0.05) in precorneal area as compared to the aqueous CRT solution and prolonged reduction in intraocular pressure (P<0.001). CONCLUSION: These results indicate that CS nanoparticles are promising vehicles of CRT for ocular drug delivery.

[Effect of 0.004% travoprost and 2% carteolol on intraocular pressure in patients with ocular hypertension after laser peripheral iridotomy or trabeculectomy in primary angle-closure glaucoma].

OBJECTIVE: To compare the intraocular pressure (IOP) lowering effect of 0.004% travoprost and 2% carteolol in patients with ocular hypertension (OHT) after laser peripheral iridotomy (LPI) or trabeculectomy in primary angle-closure glaucoma (PACG). METHODS: Clinical case control trial. 52 consecutive PACG patients (52 eyes) with IOP > 21 mm Hg (1 mm Hg = 0.133 kPa) after LPI or trabeculectomy were enrolled. 24 patients received topical application of 0.004% travoprost (once daily) and 28 received 2% carteolol (twice daily). IOP lowering effect of travoprost and carteolol before and after treatment was measured by Goldmann tonometer and compared using t-test. The relationship of IOP lowering effect and the degree of angle open was performed by gonioscope and analyzed using Spearman rank correlation. RESULTS: Compared with pre-treatment, the IOP was significantly reduced in 24 patients (24 eyes) in 0.004% travoprost group [pre-treatment: (24.67 ± 3.08) mm Hg, post-treatment: (18.58 ± 2.71) mm Hg; t = 6.600, P < 0.05], while significantly reduced in 28 patients (28 eyes) received 2% carteolol [pre-treatment: (23.57 ± 1.60) mm Hg, post-treatment: (19.57 ± 1.60) mm Hg; t = 5.130, P < 0.05]. 0.004% travoprost group is more significant in both quantity and percentage of IOP lowering than 2% carteolol (t = 2.533, 2.532; P < 0.05). There was no correlation between the IOP lowering effect and the degree of angle open in both groups (0.004% travoprost r = 0.145, 0.009; P > 0.05; 2% carteolol r = 0.090, 0.183, P > 0.05). CONCLUSIONS: Both of 0.004% travoprost and 2% carteolol reduce IOP in patients with OHT after LPI or trabeculectomy in PACG. 0.004% travoprost is more effective than 2% carteolol in IOP lowering. However, the decrease of IOP is not acted through the alteration of anterior chamber angle in both study groups.

[Effects of carteolol hydrochloride on experimental choroidal neovascularization].

PURPOSE: To investigate the effects of carteolol hydrochloride on choroidal neovascularization (CNV). METHODS: Laser photocoagulation was performed to induce CNV in C 57 BL/6 mice. The response of CNV was assessed by fluorescein isothiocyanate-isolectin B 4 staining. The expression of intercellular adhesion molecule (ICAM)-1 and monocyte chemotactic protein (MCP)-1 in the retinal pigment epithelium (RPE)-choroid complex and tumor necrosis factor (TNF)-alpha in the RAW 264.7 macrophage culture was evaluated by enzyme-linked immunosorbent assay. RESULTS: Carteolol hydrochloride application led to significant suppression of the generation of CNV, the production of ICAM-1 and MCP-1 in the RPE-choroid, and macrophage expression of TNF-alpha. CONCLUSION: Carteolol hydrochloride prevented CNV development through its anti-inflammatory action.

[The influence of carteolol and pentoxyphylin on the visual field in glaucoma patients--case reports of selected patients]. / Vliv kombinace carteololu a pentoxifylinu na zorné pole u pacientu s glaukomem--kazuistiky vybraných pacientu.

The author follows the influence of combined treatment to the changes in visual field in glaucoma patients. The combined treatment is understood as simultaneous application of eye drops with carteolol as active substance together with systemically applied pentoxyphylin. The paper reports some case reports of patients with already severe changes in the visual field, in who after the beginning of the treatment, the retinal sensitivity, as well as the extent of the visual field improved.

Simultaneous quantification of carteolol and dorzolamide in rabbit aqueous humor and ciliary body by liquid chromatography/atmospheric pressure chemical ionization mass spectrometry.

A rapid, sensitive and selective method for the simultaneous quantification of carteolol and dorzolamide in rabbit aqueous humor (AH) and ciliary body (CB) has been developed and validated using reversed phase-high performance liquid chromatography (RP-HPLC) with isocratic elution coupled with atmospheric pressure chemical ionization mass spectrometry/mass spectrometry (APCI-MS/MS). The analytes and nadolol (used as internal standard, IS) were purified from AH by protein precipitation. The sample preparation from CB was based on a two steps extraction procedure at different pH, utilizing a liquid-liquid extraction with a mixture of ethyl acetate, toluene and isopropanol 50:40:10 (v/v) at pH 8, followed by a second extraction with ethyl acetate at pH 11. The combined organic extracts were then back extracted into 0.1% aqueous trifluoroacetic acid (TFA). The accuracy and precision values, calculated from three different sets of quality control samples analyzed in sestuplicate on three different days, were within the generally accepted criteria for analytical methods (<15%). The assay proved to be accurate and precise when applied to the in vivo study of carteolol and dorzolamide in rabbit AH and CB after single administration of an eye drops containing both drugs.

Designing dendrimers for ocular drug delivery.

New series of phosphorus-containing dendrimers, having one quaternary ammonium salt as core and carboxylic acid terminal groups have been synthesized from generation 0 (3 carboxylic acid terminal groups) to generation 2 (12 carboxylic acid terminal groups). These dendrimers react with the neutral form of carteolol (an ocular anti-hypertensive drug used to treat glaucoma) to afford ion pair (saline) species. The solubility in water of these charged dendrimers depends on the generation considered: generation 0 (3 carteolol) is well soluble, whereas generation 1 (6 carteolol) and generation 2 (12 carteolol) are poorly soluble. These dendrimers have been tested in vivo, as vehicle for ocular drug delivery of carteolol to rabbits.

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.

Additive effect of dorzolamide or carteolol to latanoprost in primary open-angle glaucoma: a prospective randomized crossover trial.

PURPOSE: To compare the additive effect of dorzolamide or carteolol to latanoprost on intraocular pressure (IOP) in glaucoma patients. DESIGN: Prospective open-label randomized crossover clinical study. METHODS: A total of 64 patients with primary open-angle glaucoma were treated with latanoprost 0.005% once daily for 3 months then randomized to receive latanoprost plus dorzolamide 1% 3 times daily (dorzolamide preceding group; n=32) or carteolol hydrochloride 2% twice daily (carteolol preceding group; n=32) for a further 3 months. Then, all patients were crossed over to the opposite treatment arm for a further 3 months. IOP was recorded each month at around the time same as on the baseline day. RESULTS: Sixty-one patients (95%) completed this trial. In the dorzolamide preceding group, mean (+/-SD) IOP was 19.0+/-2.1 mm Hg at baseline and 16.0+/-2.1 mm Hg at the end of latanoprost monotherapy (P<0.01). Addition of dorzolamide reduced IOP to 15.0+/-1.3 mm Hg and this was not changed by switching to carteolol (15.1+/-1.7 mm Hg). In the carteolol preceding group, IOP was 19.1+/-1.9 mm Hg at baseline and 16.2+/-1.2 mm Hg at the end of latanoprost monotherapy (P<0.01). Addition of carteolol reduced IOP to 14.9+/-1.5 mm Hg, and after switching to dorzolamide IOP was 15.2+/-1.5 mm Hg. Mean additional IOP reduction was 0.9+/-1.2 mm Hg (5.6%) for the latanoprost-dorzolamide combination and 1.1+/-1.5 mm Hg (6.8%) for the latanoprost-carteolol combination. Hence, IOP reduction by carteolol and dorzolamide additionally to latanoprost was not different. CONCLUSIONS: Both dorzolamide and carteolol reduce IOP additively when used in combination with latanoprost, and the additive effect of these drugs is equal.

[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.

Ventricular tachycardia in a neonate with prenatally diagnosed cardiac tumors: a case with tuberous sclerosis.

We report a patient with prenatally diagnosed tuberous sclerosis. Fetal ultrasonography demonstrated multiple cardiac tumors and arrhythmia. After birth, because of frequent supraventricular extrasystoles, the infant was admitted to the neonatal intensive care unit. Findings on 24-hour ambulatory electrocardiogram (ECG) showed frequent supraventricular tachycardia and ventricular tachycardia with four beats as the longest run. At the age of 12 days, he developed cardiopulmonary arrest after crying out. A monitored ECG showed ventricular tachycardia. Twenty minutes after onset, a 12-lead ECG showed ventricular fibrillation, which returned to normal sinus rhythm with repeated DC cardioversion. Oral antiarrhythmic therapy with carteolol hydrochloride was effective. The patient showed no further symptoms after oral medication was initiated and the tumors regressed spontaneously.