AIM:

To compare the 24-h intraocular pressure (IOP) control obtained with the bimatoprost-timolol fixed combination (BTFC) versus latanoprost in newly diagnosed, previously untreated exfoliation syndrome (XFS) or exfoliative glaucoma (XFG) patients with baseline morning IOP greater than 29 mm Hg.

METHODS:

One eye of 41 XFS/XFG patients who met inclusion criteria was included in this prospective, observer-masked, crossover, comparison protocol. All subjects underwent a 24-h untreated curve and were then randomised to either evening administered BTFC or latanoprost for 3 months and then switched to the opposite therapy. At the end of each treatment period, patients underwent a treated 24-h IOP assessment.

RESULTS:

37 patients completed the trial. At baseline, mean untreated 24-h IOP was 31.1 mm Hg. Mean 24-h IOP with BTFC was significantly lower than with latanoprost (18.9 vs 21.2 mm Hg; p<0.001). Furthermore, BTFC reduced IOP significantly more than latanoprost at every time point, for the mean peak and trough 24-h IOP (p<0.001). There was no difference, however, in mean 24-h IOP fluctuation between the two medications (3.8 with BTFC vs 4.2 with latanoprost; p=0.161). Both treatments were well tolerated and there was no statistically significant difference for any adverse event between them.

CONCLUSIONS:

As first choice therapy in high-pressure, at-risk exfoliation patients, BTFC controlled mean 24-h IOP significantly better than latanoprost monotherapy.

There has been widespread interest surrounding the use of beta-blockers (i.e. propranolol, timolol, nadolol, acebutolol) in the treatment of infantile hemangiomas (IH).To review literature evaluating treatment of IH with propranolol.We conducted a literature search on PubMed and investigated for case reports, case series, and controlled trials by using search terms including hemangioma and propranolol. RESUltS: Data suggest that beta-blockers are efficacious in cutaneous, orbital, subglottic, and hepatic hemangiomas and assist in the resolution of ulcerated hemangiomas. Improvement has also been documented in children with PHACE syndrome. Propranolol produces favorable results in children who do not respond to steroids and with no long-term adverse effects. Propranolol should be administered with caution due to rare but serious side effects including hypoglycemia, wheezing, hypotension, and bradycardia. Additionally, recurrence of lesions following the cessation of treatment has been documented.Although large-scale randomized controlled trials must be conducted in order to further evaluate the safety and the possible role of propranolol in the treatment of IH, the reviewed literature suggests that propranolol carries promise as a potential replacement for corticosteroids as first-line therapy or as a part of a multimodal approach.

Propranolol (PPL) imprinted microspheres (MIP) were successfully prepared via oil/water polymerization using a methyl methacrylate (MMA) monomer, PLL template, and divinylbenzene (DVB) cross-linker and favorably incorporated in a Eudragit-RS100 nanofiber membrane. A non-PPL imprinted polymer (NIP), without a template, was used as a control. The morphology and particle size of the beads were investigated using scanning electron microscopy. The results revealed that both MIP and NIP had a spherical shape with a micron size of approximately 50-100 μm depending on the amounts of DVB and PPL used. NIP2 (MMA/DVB, 75:2.5) and MIP8 (PPL/MMA/DVB, 0.8:75:2.5) were selected for reloading of PPL, and the result indicated that increasing the ratio of PPL to polymer beads resulted in increase PPL reloading (>80%). A total of 10-50% NIP2 or MIP8 was incorporated into a 40% (w/v) Eudragit-RS100 fiber membrane using an electrospinning technique. PPL could be bound to the 50% MIP8 composite fiber membrane with a higher extent and at a higher rate than the control (NIP2). Furthermore, the MIP8 composite fiber membrane showed higher selectivity to PPL than the other β-blockers (atenolol, metoprolol, and timolol). Thus, the MIP8 composite fiber membrane can be further developed for various applications in pharmaceutical and other affinity separation fields.

OBJECTIVE:

Timolol maleate 0.5% gel is a safe and effective medication for treating superficial infantile hemangiomas (IHs) in infants with a median age of 9 weeks.

METHODS:

Forty-one infants who had superficial IHs without ulceration and not near mucosal surfaces were recruited and randomly assigned to placebo and treatment (timolol maleate 0.5% gel) groups. Efficacy was assessed by performing blinded volume measurements at weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, and 24 and blinded investigator photograph scoring at weeks 0, 12, and 24. Safety was assessed by measuring heart rate and systolic and diastolic blood pressure at weeks 0, 1, 2, 3, 4, 8, 12, 16, 20, and 24.

RESULTS:

Fifteen of the 19 infants receiving treatment and 17 of the 22 infants receiving placebo completed the study. Significant color change on the blinded photographic scores was noted at week 24 of the study (P = .003). There was a significantly higher proportion of treated IHs that reduced in size by >5% at weeks 20 and 24 (P < .02). The predicted proportion of IH volume change was also significantly less for treated IHs from week 16 onward when compared with placebo (P < .05). There was no significant variation in blood pressure and heart rate between the groups.

CONCLUSIONS:

Topical timolol maleate 0.5% gel with a maximum dose of 0.5 mg per day is a safe and effective option for small superficial IHs that have not ulcerated and are not on mucosal surfaces.

Macular edema constitutes a serious pathologic entity of ophthalmology resulting in vision loss with a remarkable impact on the quality of life of patients. It is the final common pathway of various systemic diseases and underlying intraocular conditions, with diabetes mellitus being the most frequent cause. Other causes include venous occlusive disease, intraocular surgery, and inflammatory conditions of the posterior segment of the eye. Macular edema is a recognized side effect of various systemic and local medications and requires special consideration among ophthalmologists and other clinicians. Recently, antidiabetic thiazolidinediones have been implicated in the development of macular edema, and a review of the English literature revealed that other systemically administered drugs like fingolimod, recently approved for relapsing forms of multiple sclerosis, the anticancer agents tamoxifen and the taxanes, as well as niacin and interferons have been reported to cause macular edema. Ophthalmologic pharmaceutical agents, like prostaglandin analogs, epinephrine, timolol, and ophthalmic preparation preservatives have also been reported to cause macular edema as an adverse event. The purpose of this article is to provide a short, balanced overview of the available evidence in this regard. The available data and the possible pathophysiologic mechanisms leading to the development of macular edema are discussed. Possible therapeutic strategies for drug-induced macular edema are also proposed.

Purpose:

To investigate the intraocular pressure (IOP) reduction with prostaglandin analogs (PGAs)-timolol fixed combinations versus the unfixed combination of the same PGAs and timolol 0.1% in gel-forming carbomer. 


Methods:

Patients with primary open-angle glaucoma (POAG) receiving for at least 4 weeks the fixed combinations of PGA-timolol, administered once a day in the evening (0.005% latanoprost with 0.5% timolol, 0.004% travoprost with 0.5% timolol, 0.03% bimatoprost with 0.5% timolol) were switched to an unfixed combination of the same PGA (once a day in the evening) with timolol 0.1% in gel-forming carbomer (once a day in the morning) for at least 4 weeks. The primary endpoint was to compare efficacy of fixed vs unfixed combinations in lowering IOP. The effects of both regimens on short-term IOP fluctuations were also assessed. 


Results:

A total of 32 patients (64 eyes) fulfilled inclusion criteria: 17 patients received latanoprost-timolol fixed combination, 9 travoprost-timolol fixed combination, 6 bimatoprost-timolol fixed combination. For all considered time periods each unfixed combination induced an IOP reduction significantly higher than the corresponding fixed combination (paired t test: p<0.05 in all measurements). The diurnal IOP reduction was significantly higher during the unfixed combinations (p<0.001). Unfixed combinations significantly decreased IOP diurnal fluctuations and increased the percentage of patients with daily IOP fluctuation ≤2 mm Hg.


Conclusion:

In this pilot study, PGA and timolol seems to be more effective in POAG treatment when administered as unfixed combinations, reducing both IOP and daily fluctuations. The once a day timolol 0.1% gel-forming carbomer may be a valuable option in PGA-timolol unfixed combination regimen.

To evaluate 5-year effectiveness and cost between latanoprost or timolol monotherapy in a pilot trial.A retrospective, multi-center trial performed at 6 sites in Germany of patients who had a diagnosis of primary open-angle or pigmentary glaucoma, in at least one eye, initiated on monotherapy with latanoprost or timolol maleate. Qualified consecutive charts were reviewed in which 5-year efficacy, safety and cost data was abstracted.Seventy-seoen latanoprost and 49 timolol patients were included, at the final visit no difference existed between the two groups in disc parameters including: rim area, rim area/disc area ratio, cup volume or vertical cup/disc ratio (P>0.05). There was no difference in intraocular pressure (IOP) between the initial latanoprost (17.4±2.6) and timolol (16.3±2.8mmHg) groups. There was less change in medicines over the follow-up period (0.1 vs 0.8) and fewer medications at the final visit (1.2 vs 1.8) with latanoprost compared to timolol. No patient treated with latanoprost discontinued therapy during follow-up, while 12% discontinued timolol mostly due to inadequate IOP control. Cost/year was less with initial timolol ($458±236) as compared to latanoprost ($552±202).Patients begun on latanoprost or timolol and followed over 5 years may have similar clinical outcomes. However, timolol patients may require more medicines and medicine changes to control IOP for long-term, but at a lower cost.

Postpartum blood pressure (BP) is highest three to six days after birth when most women have been discharged home. A significant rise in BP may be dangerous (e.g., can lead to stroke), but there is little information about how to prevent or treat postpartum hypertension.To assess the relative benefits and risks of interventions to: (1) prevent postpartum hypertension, by assessing whether 'routine' postpartum medical therapy is better than placebo/no treatment; and (2) treat postpartum hypertension, by assessing whether (i) one antihypertensive therapy is better than placebo/no therapy for mild-moderate postpartum hypertension; and (ii) one antihypertensive agent offers advantages over another for mild-moderate or severe postpartum hypertension.We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2013), bibliographies of retrieved papers, and personal files.For women with antenatal hypertension, trials comparing a medical intervention with placebo/no therapy. For women with postpartum hypertension, trials comparing one antihypertensive with either another or placebo/no therapy.We extracted the data independently and were not blinded to trial characteristics or outcomes. We contacted authors for missing data when possible.Nine trials are included.Prevention: Four trials (358 women) compared furosemide, nifedipine capsules, or L-arginine with placebo/no therapy. For women with antenatal pre-eclampsia, postnatal furosemide is associated with a strong trend towards reduced use of antihypertensive therapy in hospital.Treatment: For treatment of mild-moderate postpartum hypertension, three trials (189 women) compared timolol, oral hydralazine, or oral nifedipine with methyldopa. Use of additional antihypertensive therapy did not differ between groups (risk ratio (RR) 0.92, 95% confidence interval (CI) 0.20 to 4.20; three trials), but the trials were not consistent in their effects. The drugs were well tolerated.For treatment of severe postpartum hypertension, two trials (120 women) compared intravenous hydralazine with either sublingual nifedipine or intravenous labetalol. There were no maternal deaths or hypotension. Use of additional antihypertensive therapy did not differ between groups (RR 0.58, 95% CI 0.04 to 9.07; two trials), but the trials were not consistent in their effects.For women with pre-eclampsia, postnatal furosemide may decrease the need for postnatal antihypertensive therapy in hospital, but more data are needed on substantive outcomes before this practice can be recommended. There are no reliable data to guide management of women who are hypertensive postpartum. Any antihypertensive agent used should be based on a clinician's familiarity with the drug. Future studies should include data on postpartum analgesics, severe maternal hypertension, breastfeeding, hospital length of stay, and maternal satisfaction with care.

BACKGROUND:

Infantile haemangiomas (IHs) are the most common vascular tumours of infancy. Topical therapies are a possible treatment for superficial IHs.

AIM:

To determine the efficacy and safety of topical therapy in the treatment of superficial proliferating IHs.

METHODS:

The medical records of all the patients with proliferating superficial IHs were reviewed. All lesions had been treated either with imiquimod 5% cream or timolol 0.5% ophthalmic solution. Lesions were classified into pairs, with one of each treatment in each pair, matched by anatomical location, colour and size. A visual analogue scale (VAS) and the Haemangioma Activity Score (HAS) were used to evaluate the efficacy of the two drugs. The paired Student t-test was used to test for differences in recovery with these two treatments.

RESULTS:

In total, 51 patients treated with timolol and 94 treated with imiquimod met the inclusion criteria, and 20 lesions treated with timolol were successfully matched to a lesion treated with imiquimod. The paired t-test indicated that there was no significant difference in either VAS score (P = 0.11) or HAS (P = 0.49). For the imiquimod-treated patients, crusting was the most common reaction (65.0%, 13/20). This did not cause any superficial scarring or skin pigmentation in the matched pairs; however, superficial scars (14.9%, 14/94) and skin pigmentation disorders (28.7%, 27/94) were reported for some of the unmatched cases. There were no adverse events (AEs) during the treatment with timolol.

CONCLUSIONS:

Both imiquimod 5% cream or timolol 0.5% ophthalmic solution showed equivalent clinical efficacy after 4 months of treatment. Timolol appeared to have fewer AEs than imiquimod in the management of superficial IHs. Larger, prospective controlled trials with long-term treatment are needed to confirm these results.

A transient percutaneous drug absorption model was solved in two dimensions. Clearance of the topically-applied pharmaceutical occured at the skin-capillary boundary. Timolol penetration profiles in the dermal tissue were produced revealing concentration gradients in the directions normal and parallel to the skin surface. Ninety-eight percent of the steady-state flux was reached after 85h or four time constants. The analytical solution procedure agreed with published results. As the clearance rate increased relative to diffusion, the delivery rate and amount of drug absorbed into the bloodstream increased while the time to reach the equilibrium flux decreased. Researchers can apply the closed-form expressions to simulate the process, estimate key parameters and design devices that meet specific performance requirements.