Fixed combination of latanoprost and timolol vs the individual components for primary open angle glaucoma and ocular hypertension:a systematic review and meta-analysis

AIM:To assess the effects of the fixed combination of 0.005% latanoprost and 0.5% timolol (FCLT) vs their individual components for primary open angle glaucoma (POAG) and ocular hypertension (OHT).METHODS:After searched PubMed, EMBASE, the Cochrane Library and SCI, all randomized controlled clinical trials (RCTs) and cross-over studies were included. The control groups were the mono therapy or the concomitant therapy of latanoprost and timolol. The outcomes were visual field defect, optic atrophy, mean intraocular pressure (IOP) and IOP fluctuation. The analysis was carried out in RevMan version 5.1 software.RESULTS:The post-intervention mean IOP of FCLT was significantly lower compared to timolol [mean difference (MD) -2.92, 95%CI -3.28 to -2.55, P<0.00001] and latanoprost (MD -1.11, 95%CI -1.51 to -0.72, P＜0.00001). The post-intervention IOP fluctuation was also significantly lower compared to timolol (MD -0.88, 95%CI -1.23 to -0.53, P<0.00001) and latanoprost (MD -0.63, 95%CI -1.04 to -0.22, P=0.002). The mean IOP was higher in FCLT morning dose group than the one in unfixed combination of 0.005% latanoprost and 0.5% timolol (UFCLT) (MD 1.10, 95%CI 0.81 to 1.39, P<0.00001). Otherwise, there was no difference between FCLT evening dose group and UFCLT (MD 0.34, 95% CI -0.01 to 0.69, P=0.06). There was no statistical difference for the incidence of visual field defect and optic atrophy between FCLT and the monotherapy of components.CONCLUSION:A better IOP lowering effect has been demonstrated for FCLT compared to the mono therapy of components. The IOP lowering effect was worse for FCLT morning dose and almost same for FCLT evening dose compared to the UFCLT. We need more long-term high quality RCTs to demonstrate the outcomes of visual field defect and optic atrophy.     

卢美根与噻吗心安治疗高眼压疗效对比的Meta分析

目的研究卢美根与噻吗心安在青光眼与高眼压症患者中降压的有效性,并观察不良反应。方法检索PubMed、EMBASE、The Cochrane Library Controlled Trials Register及中国生物医学文献数据库收录的有关卢美根与噻吗心安治疗青光眼与高眼压症的对照研究,并辅以手工检索、因特网搜索。对纳入的6项随机对照试验,针对眼压下降比例、达到目标眼压人数、药物不良反应3项内容进行综合分析。结果卢美根降眼压效果优于噻吗心安,差异有统计学意义（P〈0.01）[合并的加权均数差（WMD）=-2.04%,95%CI（-2.44,-1.64）]。3篇文献报道随访3个月时达到目标眼压的患者人数,卢美根组与噻吗心安组比较差异有统计学意义（P〈0.01）[合并危险比（RR）=1.87,95%CI（1.45,2.41）];2篇文献报道随访〉6个月时达到目标眼压患者人数,卢美根组与噻吗心安组比较差异有统计学意义（P〈0.01）[合并RR=1.60,95%CI（1.36,1.90）]。结膜充血及睫毛变长为拟前列腺素类抗青光眼药物2种较为常见的不良反应,其发生率卢美根组与噻吗心安组比较,差异均有统计学意义（P〈0.01）[合并RR=4.18,95%CI（2.89,6.05）、RR=9.40,95%CI（5.62,15.71）]。结论卢美根在降低眼压的程度和随访不同时期达到目标眼压的人数方面均优于噻吗心安。除结膜充血及睫毛变长的发生率卢美根组高于噻吗心安组外,2种药物均未发现有严重的药物相关不良反应。     

High-dose ruthenium-106 plaque therapy for circumscribed choroidal hemangioma: a retrospective study of 25 Chinese patients

AIM: To evaluate the efficacy and safety of ruthenium-106 (106Ru) plaque radiotherapy at a dose (>50 Gy) higher than recommended (29-50 Gy) for treatment of circumscribed choroidal hemangioma (CCH) in Chinese patients. METHODS: This retrospective study included 25 symptomatic CCH patients undergoing 106Ru plaque brachytherapy involving 25 eyes between January 2005 and August 2016. Ophthalmic examination was performed at the baseline and at each post-treatment follow-up visit, using best-corrected visual acuity (BCVA), dilated fundus examination, and B-scan ultrasonography. The primary efficacy outcome measures included the changes in BCVA and hemangioma dimensions at the last followup visit from the baseline. RESULTS: The mean follow-up duration was 28.0±26.6 (range, 12-110)mo. All the hemangiomas were located in the posterior pole except for two involving the fovea. The mean apex dose of 106Ru plaque radiotherapy was 84.4±19.7 Gy. The mean BCVA improved from 41.4±29.3 (0-97) at the baseline to 53.0±33.8 (0-97) ETDRS letters at the last visit (P=0.01). The mean hemangioma height declined from 3.98±0.88 (2.40-5.50) mm to 0.84±1.63 (0-6.47) mm (P≤0.001), and the greatest linear diameter (GLD) reduced from 9.36±2.23 (6.80-15.00) to 7.40±2.45 (0-13.00) mm (P≤0.001). Hemangioma size increased in one (4%) eye with a worsened vision, and subretinal fluid completely resolved in all but one patient (4%). Radiation-related retinopathy was observed in two patients at post-treatment 9 and 11mo, respectively. CONCLUSION: 106Ru plaque brachytherapy at a dose (>50 Gy) higher than recommended (29-50 Gy) is an effective treatment regimen for symptomatic CCH associated with significantly improved visual acuity and a favorable safety profile in Chinese patients.     

拉坦前列素与噻吗心安治疗国人开角型青光眼和高眼压症有效性安全性 Meta 分析

目的：系统评价拉坦前列素（ Latanoprost ）滴眼液与噻吗心安（Timolol）滴眼液降眼压的有效性和安全性。 方法：计算机检索PubMed,Medline,CNKI及中国生物医学文献数据库收录的,并辅以手工检索、因特网搜索的有关拉坦前列素与噻吗心安治疗原发性开角型青光眼和高眼压症的随机对照试验（ RCT ）。按照纳入和排除标准限定研究对象,通过Jadad 评分量表进行文献质量评估后,针对眼压下降比例、药物不良反应2项内容,使用Cochrane协作网提供的RevMan 5．0软件进行Meta分析。 结果：共纳入9项RCT,合计555例患者。 Meta分析结果显示：（1）拉坦前列素滴眼液与噻吗心安滴眼液降眼压效果,在2,6,12wk时差异均有统计学意义（ P＜0．01）,加权平均差（WMD）分别为：在2wk[WMD＝-0．76,95％CI（-1．32,-0．20）],在6wk[WMD＝-1．15,95％CI（-1．68,0．63）]和12wk[WMD＝-1．01,95％CI（-1．42,-0．61）]。（2）随访结束时,结膜充血、异物感为拉坦前列素的两种较为常见的不良反应,但其发生率拉坦前列素组与噻吗心安组比较,结膜充血的发生率[OR＝2．25,95％CI（0．99,5．08）],异物感的发生率[OR＝2．48,95％CI（1．02,6．03）],显示二者差异均无统计学意义。 结论：治疗原发性开角型青光眼和高眼压症,拉坦前列素降眼压效果在用药12 wk内较噻吗心安好;两者在12 wk内引起结膜充血、异物感、虹膜色素加深、视野损害等的不良反应方面,差异不明显。由于纳入研究的样本量偏小,且方法学质量中等,致使本系统评价结果论证强度不高,因此还需要开展更多的高质量的临床随机对照研究,以便更客观、准确、全面地评价其疗效和安全性。     

Efficiency and safety of laser photocoagulation with or without intravitreal ranibizumab for treatment of diabetic macular edema: a systematic review and Meta-analysis

AIM: To compare the therapeutic effect and safety of laser photocoagulation along with intravitreal ranibizumab (IVR) versus laser therapy in treatment of diabetic macular edema (DME). METHODS: Pertinent publications were identified through comprehensive searches of PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov to identify randomized clinical trials (RCTs) comparing IVR+laser to laser monotherapy in patients with DME. Therapeutic effect estimates were determined by weighted mean differences (WMD) of change from baseline in best corrected visual acuity (BCVA) and central retinal thickness (CRT) at 6, 12, or 24mo after initial treatment, and the risk ratios (RR) for the proportions of patients with at least 10 letters of improvement or reduction at 12mo. Data regarding major ocular and nonocular adverse events (AEs) were collected and analyzed. The Review Manager 5.3.5 was used. RESULTS: Six RCTs involving 2069 patients with DME were selected for this Meta-analysis. The results showed that IVR+laser significantly improved BCVA compared with laser at 6mo (WMD: 6.57; 95% CI: 4.37-8.77; P<0.00001), 12mo (WMD: 5.46; 95% CI: 4.35-6.58; P<0.00001), and 24mo (WMD: 3.42; 95% CI: 0.84-5.99; P=0.009) in patients with DME. IVR+laser was superior to laser in reducing CRT at 12mo from baseline with statistical significance (WMD: -63.46; 95% CI: -101.19 to -25.73; P=0.001). The pooled RR results showed that the proportions of patients with at least 10 letters of improvement or reduction were in favor of IVR+laser arms compared with laser (RR: 2.13; 95% CI: 1.77-2.57; P<0.00001 and RR: 0.37; 95% CI: 0.22-0.62; P=0.0002, respectively). As for AEs, the pooled results showed that a significantly higher proportion of patients suffering from conjunctival hemorrhage (study eye) and diabetic retinal edema (fellow eye) in IVR+laser group compared to laser group (RR: 3.29; 95% CI: 1.53-7.09; P=0.002 and RR: 3.02; 95% CI: 1.24-7.32; P=0.01, respectively). The incidence of other ocular and nonocular AEs considered in this Meta-analysis had no statistical difference between IVR+laser and laser alone. CONCLUSION: The results of our analysis show that IVR+laser has better availability in functional (improving BCVA) and anatomic (reducing CRT) outcomes than laser monotherapy for the treatment of DME. However, the patients who received the treatment of IVR+laser may get a higher risk of suffering from conjunctival hemorrhage (study eye) and diabetic retinal edema (fellow eye).     

Meta-analysis of randomized controlled trials comparing timolol with brimonidine in the treatment of glaucoma

This paper aims to compare the efficacy and tolerability of timolol versus brimonidine in the treatment of glaucoma. Comprehensive searches were performed using Medline, Embase and the Cochrane Controlled Trials Register for randomized controlled trials comparing timolol and brimonidine. Two reviewers independently assessed trials for eligibility and quality and extracted data. A random effects model was used to combine studies. Outcome was defined as the absolute mean intraocular pressure (IOP) reduction from baseline to end-point for efficacy, and relative risk (RR) for adverse events. Subgroup analysis and meta-regression were used to explore heterogeneity according to trial design and quality. Ten publications reporting on eight trials with 2387 participants were included in the meta-analysis. Two further trials were commented on qualitatively. IOP reduction was not significantly different between timolol and brimonidine. Weighted mean difference (WMD) of IOP reduction was 0.24 mmHg (favouring brimonidine) with a 95% confidence interval of -0.57 to 1.04 mmHg. There was significant heterogeneity between studies (chi(2) (13) = 73.75, P < 0.00001, I(2) = 91%). Subgroup analysis showed no significant WMD for studies where data were analysed from end-points >/=6 months or <6 months. Meta-regression analysis showed increased WMD IOP reduction in favour of brimonidine with increased trial quality (t(3) = -4.58, P = 0.01), but no significant association with trial duration (t(3) = 0.73, P = 0.51) or size (t(3) = -0.59, P = 0.57). The RR of ocular allergy was much lower with timolol than brimonidine (RR = 0.08, 95% confidence interval 0.01 to 0.47). Publication bias was not evident on a funnel plot, although the number of studies was small. The conclusion is that both drugs are equally effective in lowering IOP. Brimonidine is associated with a higher rate of allergy.     

拉坦噻吗滴眼液治疗青光眼临床疗效观察

目的:评价拉坦噻吗滴眼液(适利加)降眼压治疗的有效性和安全性。方法:选取30例52眼原发性开角型/闭角型青光眼患者单用拉坦噻吗滴眼液,每晚1次,随访16wk,观察眼压、视野、平均视神经纤维层厚度及不良反应。结果:拉坦噻吗滴眼液能显著降低眼压(P=0.000),16wk后降眼压幅度的95%可信区间为10.31～13.92mmHg,但对视野及平均视神经纤维层厚度无改善(P>0.05),不良反应主要为眼睛轻度充血。结论:拉坦噻吗滴眼液能显著降低原发性开角型/闭角型青光眼患者的眼压,而且用药安全,依从性好。但短期随访并未发现其对视野及平均视神经纤维层厚度有改善。     

[In Press] Changes in intraocular pressure and central corneal thickness during pregnancy: a systematic review and Meta-analysis

AIM: To conduct a Meta-analysis for investigating the variations in intraocular pressure (IOP) and central corneal thickness (CCT) during normal pregnancy. METHODS: We searched for clinical trials published up to November 2015 without language or region restrictions in PubMed, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, Ovid, EBSCO, Elsevier, the Chinese Biomedicine Database, WanFang, CNKI, CQVIP and Google Scholar. Studies of the ocular changes observed in pregnant women were selected. The main outcomes were assessed by changes in IOP and CCT. RESULTS: Fifteen studies were included. In subgroup analyses, IOP was significantly decreased during the second (MD=-1.53, 95% CI [-2.19, -0.87]; P<0.00001) and third (MD=-2.91, 95% CI [-3.74, -2.08]; P<0.00001) trimesters of pregnancy. CCT was increased during the second (MD=10.12, 95% CI [2.01, 18.22]; P=0.01) trimester of pregnancy; moreover, during the third trimester of pregnancy, the CCT displayed an increasing trend, but the difference was not significant (MD=5.98, 95% CI [-1.11, 13.07]; P=0.1). CONCLUSION: A decrease in IOP was accompanied by an increase in CCT in the second and third trimesters of a normal pregnancy in women.     

Naturalistic, prospective study of glaucoma and ocular hypertension treatment in France: Strategies, clinical outcomes, and costs at 2 years

PURPOSE: To prospectively observe second-line treatment strategies, their clinical outcomes, and treatment costs in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH) in France. METHODS: Second-line patients were recruited from September 14, 1998, to December 20, 2000, in 37 centers and were followed for up to 2 years. Outcomes were numbers of and reasons for treatment changes, changes in clinical parameters (intraocular pressure (IOP) levels, visual field defects, and optic nerve excavation), and direct medical costs associated with glaucoma management. This article reports results of the final analysis of 2-year follow-up data for patients with at least two contacts with a study ophthalmologist. RESULTS: Data were analyzed for 346 patients and 672 treated eyes. Monotherapy was used as first-line therapy in 92.0% of eyes. Second-line treatment was initiated an average of 2.8+/-0.2 years after diagnosis, primarily due to insufficient IOP control (60.3%) and adverse drug reactions (18.3%). Relative risk (RR) (95% CI) for adverse drug reactions (ADR) under monotherapy was 1.00 (1.00-1.00) under beta blockers (n = 116) versus 0.40 (0.16-0.64) under latanoprost (n = 21), 2.30 under carbonic anhydrase inhibitors (n = 29), and 2.90 under adrenergics (n = 38); RR for ADR under combination therapy was 1.00 (1.00-1.00) for unfixed combinations without latanoprost (n = 66) versus 0.11 (0.00-0.22) for unfixed combinations of latanoprost + timolol (n = 3). Cardiac or pulmonary problems have been reported in 26.9% of patients. Persistency on initial therapy was 62.5% (95% CI 53.0-72.0) for latanoprost monotherapy versus 41.1% (34.8-47.4) for beta-blocker monotherapy and 43.6% (26.6-60.6) for the latanoprost + timolol combination versus 29.8% (15.2-44.4) for combination therapies that did not include latanoprost. Average daily cost for latanoprost monotherapy was similar to that for patients who failed beta-blocker monotherapy: latanoprost + timolol did not cost more than therapeutic combinations without latanoprost. CONCLUSIONS: Insufficient IOP control and adverse drug reactions are the two main reasons for changing first-line treatment in patients with POAG or OH. After 2 years, second-line treatment with latanoprost, as monotherapy or combined with timolol, provides superior safety and persistency to treatment at an acceptable cost.     

降眼压药物治疗LASIK术后屈光回退的效果评估和机制探讨

目的:评估降眼压药物—2.5g/L马来酸噻吗洛尔眼液治疗LASIK术后屈光回退的疗效,并初步探讨其作用机制。方法:选取使用2.5g/L马来酸噻吗洛尔眼液治疗的LASIK术后屈光回退患者25例(46眼),收集治疗前和治疗1mo后的UCVA、BSCVA、屈光度、角膜前表面曲率、眼压、屈光度与角膜前表面曲率的变化值,进行配对t检验。结果:治疗1mo后的UCVA由治疗前的0.63±0.27上升为0.95±0.33(t=9.07,P<0.01),其中提高1行的14眼(30%),提高2行以上的27眼(59%),不变的5眼(11%),有效率达89%;BSCVA治疗前为1.19±0.27,治疗1mo后为1.29±0.28,二者差异有统计学意义(t=3.81,P=0.01);屈光度治疗前(-1.39±0.69)D,治疗1mo后为(-0.57±0.62)D,平均下降(0.82±0.50)D(t=11.15,P<0.01);角膜前表面曲率治疗前为(37.64±1.68)D,治疗1mo后为(37.14±1.81),下降为(0.50±0.34)D(t=10.02,P<0.01);眼压治疗前平均为(11.84±1.91)mmHg,治疗1mo后为(11.14±1.60)mmHg,二者差异有统计学意义(t=4.02,P<0.01)。结论:降眼压药物—2.5g/L马来酸噻吗洛尔眼液对LASIK术后屈光回退具有显著疗效,其机制可能是通过降低眼压,使前膨的全角膜(包括角膜前、后表面曲率)得到回复而发挥其治疗作用。     

Predicting intraocular pressure change before initiating therapy: timolol versus latanoprost

Purpose: To study intraocular pressure (IOP) reductions with timolol and latanoprost reached in clinical practice, taking into account data that are routinely collected by the ophthalmologist; to predict IOP reduction from these variables. Methods: A cohort of patients with primary open‐angle glaucoma (suspect) or ocular hypertension was recruited from nine Dutch centres. Mean absolute and relative IOP reduction was calculated in order to compare timolol to latanoprost. IOP reduction was calculated by comparing patients with certain characteristics to those who had none. Results: One hundred and fifty‐six persons started on timolol and 76 started on latanoprost monotherapy. Mean [95% confidence interval (CI)] absolute reduction was 7.2 mmHg (7.9; 6.5) for timolol and 6.9 mmHg (8.0; 5.8) for latanoprost. Mean relative reduction (95% CI) was 27.2% (29.3; 25.1) for timolol and 26.6% (30.2; 22.9) for latanoprost. No significant difference in IOP reduction between timolol and latanoprost was found when adjusting for data that are routinely collected by the ophthalmologist. At the time of starting treatment, none of these items normally used for the management of glaucoma, except IOP at baseline, could predict change in IOP. Conclusion: In clinical practice, timolol and latanoprost achieve similar IOP reductions that are comparable to those achieved in randomized trials. No clinically relevant information for glaucoma management can be used to predict IOP reduction accurately.     

Intraocular pressure-lowering effects of commonly used fixed combination drugs with timolol in the management of primary open angle glaucoma

AIM:To evaluate intraocular pressure (IOP)-lowering effect and ocular tolerability of brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies in the management of primary open angle glaucoma.METHODS:Each drug was administered for two months, after which a circadian tonometric curve was recorded using a Goldmann applanation tonometer. Ocular discomfort (conjunctival hyperemia, burning or stinging, foreign body sensation, itching, ocular pain) of each eye was assessed by the subject on a standardized ocular discomfort scale.RESULTS:Among the three study groups, there were no significant differences in the mean baseline IOP measurements, mean 2^nd mo IOP measurements, and mean (%) change of IOPs from baseline. Among the three study groups, there were no significant differences in the mean IOP measurements obtained at circadian tonometric curves at baseline and at two months controls. In sum brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar effects on IOP levels.CONCLUSION:Brimonidine/timolol, dorzolamide/timolol and latanoprost/timolol fixed combination therapies showed similar lowering efficaties on IOP levels whereas there was no any difference between each other.     

Phacoemulsification versus combined phacotrabeculectomy in the treatment of primary angle-closure glaucoma with cataract: a Meta-analysis

AIM: To compare the efficacy and safety of phacoemulsification (Phaco) against combined phacotrabeculectomy (Phacotrabe) in primary angle-closure glaucoma (PACG) with coexisting cataract. METHODS: By searching electronically the PubMed, EMBASE, Scientific Citation Index and Cochrane Library published up from inception to January 2014, all randomized controlled trials that matched the predefined criteria were included. The quality of included trials was evaluated according to the guidelines developed by the cochrane collaboration. And the outcomes estimating efficacy and safety of two different surgical treatments were measured and synthesised by RevMan 5.0. RESULTS: Five randomized controlled trials were selected and included in Meta-analysis with a total of 468 patients (468 eyes) with both PACG and cataract. We found that Phacotrabe had a greater intraocular pressure (IOP) lowing effect [preoperative IOP: weighted mean difference (WMD)=0.58, 95% confidence intervals (95% CI, -0.53 to 1.69), P=0.31; postoperative IOP: WMD=1.37, 95% CI (0.45 to 2.28), P=0.003], a lower number of anti-glaucoma medications [ risk ratio (RR) =0.05, 95% CI (0.02 to 0.18), P<0.00001] needed postoperatively and less serious damage of optic nerve [risk ratio (RR)=0.48, 95% CI (0.21 to 1.07), P=0.07], but a higher risk of complications [odds ratio (OR) =0.04, 95% CI (0.01 to 0.16), P<0.00001] compared with Phaco. The rest studies indicated that there had no significantly difference between the two surgical methods for postoperative best-corrected visual acuity (BCVA) [WMD=-0.05, 95% CI (-0.14 to 0.05), P=0.32] and loss of visual field [OR=1.06, 95% CI (0.61 to 1.83), P=0.83]. CONCLUSION: Phaco alone compared with Phacotrabe had a better effect in IOP reduction, whereas the security decline. Considering the number of sample size, our results remains to be further studied.     

0.5%马来酸噻吗洛尔滴眼液对LASIK术后屈光回退的疗效分析

目的 评估降眼压药物0.5%马来酸噻吗洛尔滴眼液对近视准分子激光原位角膜磨镶术（LASIK）后屈光回退的疗效.方法 回顾性病例系列研究.2001年7月至2009年11月期间,近视LASIK术后不同时期出现屈光回退、局部应用0.5%马来酸噻吗洛尔滴眼液治疗、随访资料完整的患者16例（30眼）.收集用药前、用药后及停药后的裸眼视力（UCVA）、最佳矫正视力（BCVA）、显然验光屈光度数、Pentacam眼前节分析参数、Goldmann压平眼压值.将用药前后测量数据以及停药前后测量数据分别进行自身对照研究,采用Wilcoxon配对秩和检验进行分析.结果 用药后与用药前相比,眼压明显下降,前后差异具有统计学意义（Z=-3.17,P=0.002） 显然验光屈光度数、角膜屈光力及UCVA明显下降,前后差异具有统计学意义（Z=-4.70、-3.36、-4.57 P=0.000、0.001、0.000） 中央角膜厚度在用药前后差异无统计学意义（Z=-0.16,P=0.876）.所有眼在用药前后的BCVA均达到1.0及以上.停药后与用药后相比,眼压明显上升,差异具有统计学意义（Z=-3.06,P=0.002） 角膜屈光力、显然验光度数及UCVA明显升高,差异具有统计学意义（Z=-2.12、-2.52、-1.98 P=0.034、0.012、0.047） 停药后中央角膜厚度无显著改变（Z=0.59,P=0.556）.结论 0.5%马来酸噻吗洛尔滴眼液通过降眼压作用,对近视LASIK术后出现的屈光回退有显著的疗效,但停药后屈光回退仍可再次发生,故需长期维持用药.     

Sub-threshold micro-pulse diode laser treatment in diabetic macular edema: A Meta-analysis of randomized controlled trials

AIM: To examine possible differences in clinical outcomes between sub-threshold micro-pulse diode laser photocoagulation (SDM) and traditional modified Early Treatment Diabetic Retinopathy Study (mETDRS) treatment protocol in diabetic macular edema (DME). METHODS: A comprehensive literature search using the Cochrane Collaboration methodology to identify RCTs comparing SDM with mETDRS for DME. The participants were type I or type II diabetes mellitus with clinically significant macular edema treated by SDM from previously reported randomized controlled trials (RCTs). The primary outcome measures were the changes in the best corrected visual acuity (BCVA) and the central macular thickness (CMT) as measured by optical coherence tomography (OCT). The secondary outcomes were the contrast sensitivity and the damages of the retina. RESULTS: Seven studies were identified and analyzed for comparing SDM (215 eyes) with mETDRS (210 eyes) for DME. There were no statistical differences in the BCVA after treatment between the SDM and mETDRS based on the follow-up: 3mo (MD, -0.02; 95% CI, -0.12 to 0.09; P=0.77), 6mo (MD, -0.02; 95% CI, -0.12 to 0.09; P=0.75), 12mo (MD, -0.05; 95% CI, -0.17 to 0.07; P=0.40). Likewise, there were no statistical differences in the CMT after treatment between the SDM and mETDRS in 3mo (MD, -9.92; 95% CI, -28.69 to 8.85; P=0.30), 6mo (MD, -11.37; 95% CI, -29.65 to 6.91; P=0.22), 12mo (MD, 8.44; 95% CI, -29.89 to 46.77; P=0.67). Three RCTs suggested that SDM laser results in good preservation of contrast sensitivity as mETDRS, in two different follow-up evaluations: 3mo (MD, 0.05; 95% CI, 0 to 0.09; P=0.04) and 6mo (MD, 0.02; 95% CI, -0.10 to 0.14; P=0.78). Two RCTs showed that the SDM laser treatment did less retinal damage than that mETDRS did (OR, 0.05; 95% CI, 0.02 to 0.13; P<0.01). CONCLUSION: SDM laser photocoagulation shows an equally good effect on visual acuity, contrast sensitivity, and reduction of DME as compared to conventional mETDRS protocol with less retinal damage.     

Latanoprost versus timolol gel-forming solution once daily in primary open-angle glaucoma or ocular hypertension

BACKGROUND: To compare the efficacy and safety of latanoprost and timolol gel-forming solution (GFS). METHODS: This was a randomized, crossover, investigator-masked, active-control study of patients with primary open-angle glaucoma and ocular hypertension. Patients received either once-daily 0.5% timolol GFS (n=40) or once-daily 0.005% latanoprost (n=35) for 8 weeks (period 1). Patients were then crossed over to the other medication and treated for another 8 weeks (period 2). Intraocular pressure (IOP) was determined every 2 hours from 8:00 to 20:00 at baseline and weeks 8 and 16. Safety was assessed by visual acuity, slit-lamp biomicroscopy, and adverse event reports. RESULTS: During period 1, reduction in mean (SD) diurnal IOP was significantly greater in latanoprost-treated patients (-6.9 [3.0] mm Hg) than in timolol GFS-treated patients (-5.5 [2.4] mm Hg), p=0.034. There was also a significant reduction in IOP from baseline after switching from timolol GFS to latanoprost (p<0.001), not observed when patients were switched from latanoprost to timolol GFS. After results from each drug's treatment periods were combined between treatment arms, latanoprost reduced IOP more (-6.9 [2.9] mm Hg) than did timolol GFS (-6.2 [2.7] mm Hg), p=0.018. Hyperemia was the most common adverse event in both treatment groups, with 5 incidences in timolol GFS-treated patients, and 10 in latanoprost. INTERPRETATION: Latanoprost is more effective than timolol GFS in reducing IOP, and patients switched from timolol GFS to latanoprost have a further significant reduction in IOP.     

Clinical efficacy of topical nipradilol and timolol on visual field performance in normal-tension glaucoma: a multicenter,randomized, double-masked comparative study

Purpose  To compare the effects of topical nipradilol and timolol on the visual field in Japanese normaltension glaucoma (NTG) patients. Methods  We enrolled 146 NTG patients. At baseline, age, intraocular pressure (IOP), and mean deviation (MD) by the Humphrey field analyzer were 47.6 (SD 8.5), 14.2 (1.7) mmHg, and −4.5 (3.0) dB. Seventy-two patients were randomly assigned to the 0.25% nipradilol group and 74 patients to the 0.5% timolol ophthalmic solution group twice daily for the 3-year study period. The Humphrey full-threshold 30-2 visual field test was performed every 6 months. The primary end point was the nonparametric O’Brien summary score (sum of the ranks of six slopes calculated from the average of the total deviation in each cluster) in each patient. The secondary analyses were differences in the MD slope, average of the total deviation in each cluster, the corrected pattern standard deviation (CPSD), and the time course of IOP. Results  No significant intergroup differences were found in baseline characteristics, or in the parameters of the primary and secondary analyses. In both groups, central superior clusters showed negative slopes and IOP decreased by about 1 mmHg from baseline. Conclusion  No significant difference in visual field performance or IOP reduction was seen between the nipradilol and timolol groups.     

Travoprost 0.004%/timolol 0.5%-fixed combination with and without benzalkonium chloride: a prospective, randomized, doubled-masked comparison of safety and efficacy

Purpose

The purpose of this study is to compare the safety and intraocular pressure (IOP)-lowering efficacy of travoprost/timolol in a benzalkonium chloride (BAK)-free fixed combination preserved with polyquaternium-1 (TRA/TIM BAK-free), with travoprost/timolol-fixed combination preserved with BAK (TRA/TIM), in patients with open-angle glaucoma or ocular hypertension.

Methods

In this prospective randomized controlled trial, subjects with IOP of at least 22 mm Hg in one or both eyes at 0900 h, and IOP of at least 21 mm Hg in one or both eyes at 1100 h and 1600 h at two eligibility visits were randomly assigned to receive either TRA/TIM BAK-free (n=195) or TRA/TIM (n=193), dosed once daily in the morning (0900 h) for 6 weeks. IOP was assessed at 0900 h, 1100 h, and 1600 h at each scheduled visit (baseline, 2 and 6 weeks after randomization).

Results

Mean IOP reduction across all visits and time points was 8.0 mm Hg in the TRA/TIM BAK-free group and 8.4 mm Hg in the TRA/TIM group (P=0.0943). The difference in mean IOP between groups ranged from 0.2 to 0.7 mm Hg across visits and time points, with a mean pooled difference of 0.4 mm Hg (95% CI: −0.1 to 0.8), demonstrating equivalence of the two formulations. The most common drug-related adverse event was hyperemia of the eye (ocular hyperemia and conjunctival hyperemia combined), occurring in 11.8% of the TRA/TIM BAK-free group and 13.0% of the TRA/TIM group.

Conclusion

Travoprost/timolol BAK-free demonstrated equivalence to travoprost/timolol preserved with BAK in efficacy. No clinically relevant differences in the safety profiles of travoprost/timolol BAK-free and travoprost/timolol preserved with BAK were identified.     

The effects on the intraocular pressure and visual field resulting from a switch in the treatment from timolol to betaxolol.

Patients with primary open-angle glaucoma (POAG) were dosed twice-daily with 0.5% timolol maleate for 2 years, followed by 2 years of twice-daily dosing with 0.5% betaxolol hydrochloride. The changes in intraocular pressure (IOP) and effects on visual field by each treatment were monitored over this 4-year period. Both the timolol and betaxolol treatments controlled IOP. The mean MD (mean deviation in visual field) values at 24 months of the timolol treatment were -6.18 dB (decibels) and -5.32 dB. Mean MD baseline values following 24 months of the timolol treatment produced 2.31 dB and 0.95 dB reductions in sensitivity in the right and left eyes, and the reduction in the right eye was statistically significant (p < 0.01). The mean MD values after 24 months of the betaxolol treatment were -3.82 dB in the right eyes, an increase of 2.36 dB, and -4.05 dB in the left eyes, up by 1.28 dB. The results from this clinical trial demonstrated that betaxolol was superior over timolol in improving mean retinal sensitivity.     

Success rates for switching to dorzolamide/timolol fixed combination in timolol responders who are insufficiently controlled by latanoprost monotherapy

Purpose: We aimed to investigate the safety and efficacy of dorzolamide/timolol fixed combination (DTFC) in timolol responders with ocular hypertension or open‐angle glaucoma who switched to DTFC because of insufficient control on latanoprost. Methods: We carried out a prospective, open‐label cohort study with an active‐historical control in which qualifying patients must have been treated with latanoprost monotherapy for at least 4 weeks, must have demonstrated insufficiently controlled intraocular pressure (IOP) (≥ 19 mmHg at 08.00 hours), and must have shown a decrease in IOP at 2 hours after timolol instillation of ≥ 3 mmHg or ≥ 15%. Patients then began DTFC dosed at 08.00 hours and 20.00 hours and discontinued latanoprost. Patients were evaluated again after 4 and 12 weeks. Results: In 57 patients IOP was further reduced by 2.4 ± 3.3 mmHg at 08.00 hours (p < 0.0001) and by 3.5 ± 3.3 mmHg at 10.00 hours (p < 0.0001) after switching to DTFC. Responses to the Comparison of Ophthalmic Medications for Tolerability (COMTol) questionnaire showed no difference between DTFC and latanoprost for in terms of overall preference, typical daily activities, limitation of activities, compliance, satisfaction or quality of life (p > 0.05). However, greater frequency in burning and/or stinging (p < 0.0001) and bitter taste (p < 0.0001) were observed with DTFC, whereas unusual taste (p = 0.02) and itchy eyes (p = 0.05) were associated with latanoprost. Conclusions: This study suggests that patients who are insufficiently controlled on latanoprost monotherapy, and who are timolol responders, can generally achieve further IOP reduction and similar tolerance levels when changed to DTFC.