Intraocular pressure control and persistence on treatment in glaucoma and ocular hypertension

BACKGROUND: The purpose of this study was to characterize current patterns of treatment of glaucoma and ocular hypertension and to examine the effect of those patterns on intraocular pressure (IOP) control and persistence on therapy. METHODS: A retrospective chart review was conducted at 3 ophthalmology practices in Alberta. Data were collected for patients who had begun therapy for newly diagnosed primary open-angle glaucoma or ocular hypertension between May 1, 1998, and Sept. 30, 1999 (phase 1), and for patients who had begun second-line therapy after initial therapy with a beta-blocker had failed (phase 2). Data were collected for a minimum of 24 months for phase 1 and a minimum of 18 months for phase 2. RESULTS: We included 115 patient charts in phase 1 and 93 in phase 2. In each phase, the patients for whom latanoprost had been prescribed in unfixed combination with a beta-blocker had the greatest mean percentage reduction in IOP at month 24, and the patients for whom latanoprost had been prescribed alone or in combination with a beta-blocker were more likely to still be on initial therapy at month 24; the difference in persistence on therapy was statistically significant only in phase 1 (p = 0.001). The mean number of switches in therapy was smaller in phase 1 than in phase 2 in all therapy groups. INTERPRETATION: Compared with other first- and second-line forms of therapy, treatment with latanoprost, alone or in combination with a beta-blocker, was associated with greater reductions in IOP, better therapeutic persistence, fewer therapy switches and fewer ophthalmologist visits over a 2-year period.     

New drugs under investigation for the treatment of alopecias

Introduction: Alopecia is a very common complaint in medical practice, which usually has a large psychological impact in patients. Treatment of alopecia is often difficult and frustrating for patients and clinicians owing to the slow growth rate of the hair, long treatment terms, limited efficacy, and possible adverse side effects.

Areas covered: This paper reviews the new and emerging treatments for two of the most common forms of alopecia, known as androgenetic alopecia and alopecia areata. A literature search of PubMed/MEDLINE and ClinicalTrial.gov was performed to gather information about active research on new treatments for alopecias. Websites of companies sponsoring clinical trials were also searched for interim result data.

Expert opinion: Many new therapies in two of the most common forms of hair loss have been developed and are currently being studied with encouraging results. In alopecia areata, JAK inhibitors are promising. The discovery of JAK inhibitors has prompted the research and identification of new molecules. In androgenetic alopecia, we are still looking for a topical treatment that is superior to topical minoxidil. However, stem-cell research is advancing and the goal to create new follicles or refresh dormant follicles may be realized in the near future.     

Assessing the cost-effectiveness of switching from a β-blocker to latanoprost in the treatment of ocular hypertension

Glaucoma is a pathological condition whose most important risk factor is increased intraocular pressure (IOP). The medical treatment of glaucoma essentially consists of compounds that are able to decrease the IOP. The compounds discussed in this review act in a different way, β-blockers mainly inhibit the production of aqueous humor, whereas latanoprost decreases the resistance in the outflow channels. β-Blockers are compounds with a well-known efficacy and safety profile and they are fairly inexpensive. Their systemic and local side effects are mainly cardiovascular and pulmonary adverse events, dry eye and keratopathy. Latanoprost, which has recently been introduced into the market, has been shown to be equally as effective, or better in lowering IOP in patients than timolol, although it is more expensive. Systemic reported side effects are anecdotal; local hyperaemia, keratopathy, hypertrichosis, increased pigmentation of eyelashes and iris, uveitis and cystoid macular oedema have been reported. A comparison of costs reveals that a 1-year therapy with timolol ophthalmic solution starts from €11.00 and can reach €146.00 for the most expensive preservative-free 1-day dispenser packages (～ 13.5 times higher). For latanoprost once-daily administration, the cost for 1years therapy is €98.55, approximately six times higher than generic or brand 0.5% timolol applied twice-daily. What are the factors influencing a change in therapy from β-blockers to latanoprost? The only good reason is represented by a further deterioration in the visual field. This may occur, despite a significant reduction in IOP, because the reached IOP is not sufficient enough to avoid further deterioration because the patient’s work or social activities do not allow a correct daily dosage of the compound (bad compliance); or as a result of treatment suspension, because of the development of systemic and/or local side effects. Changes in therapy must always be related to a failing control of the disease, as any therapeutic modification leading to an increase in the number of visits and additional examinations, consequently enhances the costs.     

拉坦前列腺素眼液预防LASIK术后屈光回退的临床观察

目的:观察准分子激光原位角膜磨镶术后早期应用拉坦前列腺素眼液预防屈光回退的临床效果。方法:将患者采用双盲法随机分为试验组、阳性对照组和空白对照组三组,每组50例100眼。试验组患者术后第1d开始使用拉坦前列腺素滴眼液1次,3mo后停用。阳性对照组早晚点噻吗洛尔眼液2次,3mo后停用。空白对照组不点任何降眼压类药物。观察术前、术后1wk;1,3,6,12,24mo裸眼视力(UCVA)、主觉验光、角膜前表面曲率、角膜后表面曲率、眼压、BUT测定、Schirmer试验等方面的变化。结果:试验组与阳性对照组未出现1例屈光回退病例,试验组48例能够坚持3mo内每天用一次拉坦前列腺素眼液,阳性对照组仅有41例能坚持3mo内每天用2次噻吗洛尔眼液,有统计学差异。空白对照组出现4例屈光回退病例,与试验组有统计学差异,三组患者BUT、Schirmer试验无明显差异。结论:拉坦前列腺素眼液可有效预防准分子激光原位角膜磨镶术后屈光回退,副作用小,患者依从性更好。     

Long-term cost and efficacy analysis of latanoprost versus timolol in glaucoma patients in Germany

AIM: To evaluate 5-year effectiveness and cost between latanoprost or timolol monotherapy in a pilot trial.RESULTS: 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).CONCLUSION: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.     

青光眼的最大耐受药物治疗

青光眼的最大耐受药物治疗 (maxim al tolerated medicaltherapy,MTMT)通常意味着使用 β-受体阻滞剂、拟胆碱能药物 (通常为 pilocarpine)和口服碳酸酐酶抑制剂 (carbonicanhydrase inhibitor,CAI) (通常为 diam ox)。有时将肾上腺素或地匹福林加到这一治疗方案中。某一患者的 MTMT方案依赖于其是否能耐受所有这些药物或部分药物的副作用。由于药物的副作用 (特别是拟胆碱能药物和 CAI)和较复杂的药物剂量安排 ,MTMT的实施总是值得怀疑的。药物治疗的目的是降低眼压 ,当眼压得不到控制时 ,常加强药物治疗(增加药物种类或增加用药次…     

Original and generic latanoprost for the treatment of glaucoma and ocular hypertension: Are they really the same?

We compared the intraocular pressure (IOP)‐lowering effect and safety profile of latanoprost (Xalatan) with its generic variant, Glautan (Unipharm, Tel Aviv, Israel). After 1 and 4 weeks of treatment, a randomized, prospective, cross‐over comparison was carried out that included patients with open‐angle glaucoma or ocular hypertension, either naïve or treated and well‐controlled, who were attending the Department of Ophthalmology, Tel Aviv Medical Centre, Tel Aviv, Israel, between May 2010 and November 2012. After a 3‐week washout period for the medicated subjects, the participants were randomized to 4 weeks of treatment with either Xalatan or Glautan once every evening and then, after a 3‐week washout period, crossed‐over to the other treatment for an additional 4 weeks. Efficacy was expressed by a change in intraocular pressure at three designated hours of the day after 1 week and 1 month of treatment, and tolerability was determined by ocular side‐effects as reported by the patient in a questionnaire. A total of 19 patients (mean age at initial diagnosis 66 ± 9 years, 14 females) were enrolled, of whom 17 had bilateral open‐angle glaucoma and two had unilateral disease. Both drugs lowered intraocular pressure after 1 week and 1 month (P = 0.06 and P = 0.04, respectively) of treatment. Xalatan had a tendency of greater efficacy than Glautan both after 1 week and 1 month, but the difference was not statistically significant (P =0.69 and P = 0.34, respectively). Drug safety was similar for Xalatan or Glautan, but more ocular side‐effects were reported after treatment with Glautan (21 vs 12 for Xalatan, P = 0.06).     

Efficacy and safety of newly developed preservative-free latanoprost 0.005% eye drops versus preserved latanoprost 0.005% in open angle glaucoma and ocular hypertension: 12-week results of a randomized, multicenter, controlled phase III trial

AIM: To evaluate the therapeutic efficacy, safety and tolerability of newly developed preservative-free (PF) latanoprost generic [TJO-002] and compare it with benzalkonium chloride (BAK)-preserved latanoprost [Xalatan®] in patients with primary open angle glaucoma (POAG) and ocular hypertension (OHT). METHODS: Included patients were aged ≥19y with POAG/OHT. After a washout period, patients with IOP 21-35 mm Hg at 9 a.m. were enrolled. After a full ophthalmic and glaucoma examination, 144 patients with POAG and OHT participated in this study. Subjects were randomly assigned either PF latanoprost (74 eyes) or BAK-preserved latanoprost (70 eyes). All subjects were examined at 4, 8, and 12wk after first administration. At each follow-up visit, IOP was measured at 9 a.m. and 5 p.m. and compliance was assessed. Throughout the study, all adverse events were recorded and monitored by the masked investigators who measured IOP. RESULTS: Both groups showed a statistically significant decrease of average diurnal IOP at 12wk compared to baseline (-7.21±3.10 mm Hg in the PF latanoprost group and -7.02±3.17 mm Hg in the BAK latanoprost group, both P<0.0001). There was no statistically significant diurnal IOP variation between the groups. In terms of tolerability, pruritus, burning/stinging, and sticky eye sensation, severity was significantly lower in the PF latanoprost group than in the BAK latanoprost group (P<0.05). CONCLUSION: PF latanoprost has at least similar efficacy in terms of IOP reduction and better tolerability compared with BAK latanoprost.     

Corneal damage and its recovery after instillation of preservative-free versus preserved latanoprost eye drops

Abstract

Purpose: Latanoprost ophthalmic solution is highly effective as a therapeutic agent for glaucoma and is applied worldwide. However, harmful effects on the corneal surface have been reported regarding the commercially available latanoprost ophthalmic solution. Corneal surface toxicity may be caused by the added preservative of the ophthalmic solution. In order to ascertain whether latanoprost itself can damage the cornea or if this is solely due to the added preservatives, this study attempted to determine the corneal changes that occur at different time periods following usage of preservative-free versus preserved latanoprost eye drops.

Materials and methods: Preservative-free latanoprost eye drops (Monoprost^®) or preserved latanoprost eye drops (Xalatan^®) containing 0.02% benzalkonium chloride (BAC) were instilled in the corneas of rabbits. For each of the two different eye drop solutions, the rabbits used in this experiment were divided into three exposure groups: 1?minute, 24?hour, and 1?week groups. Corneal transepithelial electrical resistance (TER) and scanning electron microscopy (SEM) were examined immediately (1?minute) after instillation, at 24?hours after instillation, and at 24?hours after 1?week of daily instillations of latanoprost. Hank’s balanced salt solution was used in the control group.

Results: The mean corneal TER of the control group was 933.8?±?279.0 Ω cm². In preservative-free latanoprost instilled corneas, there was no significant decrease in the TER or morphological changes at any of the time points, with the relative TER values of 117?±?38%, 100?±?34%, and 93?±?21% for 1?minute, 1?day, and 1?week time points, respectively. In preserved latanoprost instilled corneas, SEM showed that only the immediate group exhibited superficial cell damage and a significant decrease in the corneal TER compared to the controls and other time points and to the immediate preservative-free latanoprost corneas. In the preserved latanoprost groups, the relative TER values were 18?±?5%, 110?±?28%, and 92?±?10%, for the three respective observation time points.

Conclusions: Preservative-free latanoprost can be safely instilled to the corneal epithelium. Latanoprost with 0.02% BAC has an immediate deleterious impact on the corneal epithelium; however, it disappears within 24?hours after instillation.     

拉坦、曲伏及比马前列素治疗青光眼的成本效用分析(英文)

目的:评估拉坦前列素,曲伏前列素和比马前列素在挪威,瑞典及丹麦(斯堪的纳维亚)治疗开角型青光眼的成本效用。方法:建立马尔可夫卫生经济学决策分析模型,评估比较前列腺素类似物的成本效用。健康状态为稳定及进展期青光眼。原发性开角型青光眼和表皮剥脱性青光眼的转换概率均由发表的医学文献数据计算所得。通过对分散遍及于各国家的45位眼科医生进行调查获得临床医疗模式。各国家的具体单位成本包括药费,就诊费,诊断及治疗费。生命质量权重值指定为视力0.50 ～0.84,时间范围为5a。所有分析均为付款人观点成本效益分析,成本结果每年降低3%。结果:在挪威和瑞典,拉坦前列素较曲伏前列素和比马前列素费用低而效益高,拉坦前列素比其他药物费用低达4%。在丹麦,所有三种药物的费用在彼此的1.5%之内,比马前列素与曲伏前列素费用相当,而较拉坦前列素费用略低,但是拉坦前列素较曲伏前列素和比马前列素效益高。各国家所有药物的效用在一个窄范围内。结论:在斯堪的纳维亚,拉坦前列素为其他可买到的前列腺素类似物提供了经济有效的替代物。