Topical azelastine in perennial allergic conjunctivitis

SUMMARY

Objective: Azelastine is a selective H1-receptor antagonist that inhibits histamine release and interferes with activation of several other mediators of allergic inflammation. Together with demonstrated efficacy in seasonal allergic conjunctivitis, azelastine indicated a therapeutic potential for perennial allergic conjunctivitis (PAC).

The present study aimed to evaluate azelastine eye drops in patients with PAC compared to placebo.

Research design and methods: A multinational trial in 22 centres randomised 139 patients to twice-daily treatment for 6 weeks with masked 0.05% azelastine eye drops, matching masked placebo, or open-label levocabastine. Randomisation required a sum itching and conjunctival redness score of at least 3 (0-6 scale) after 1 week of placebo. The change in sum score was evaluated during treatment.

Results: Azelastine significantly improved itching and conjunctival redness compared to placebo (p?<?0.001) with global tolerability that was not substantially different from placebo. On day 7, the mean symptoms sum score improved with azelastine by 1.9?±?1.1 and with levocabastine by 1.5?±?1.2 compared to placebo (0.6?±?1.1) from baseline values of 3.7-3.8. The sum scores continued to improve up to day 42. Daily patient logs confirmed the clinically assessed scores. Most frequent adverse events following azelastine were bitter taste and application site reaction.

Conclusions: Topical azelastine progressively improved itching and conjunctival redness in PAC patients compared to placebo and was at least as effective as levocabastine. Rapid relief is consistent with H1-receptor antagonist action, while continued improvement up to 6 weeks may be consistent with mechanisms involving other mediators of allergic inflammation.     

Preservative-free versus preserved brimonidine %0.15 preparations in the treatment of glaucoma and ocular hypertension: short term evaluation of efficacy,safety, and potential advantages

Abstract

Purpose: To compare the efficacy, safety, and potential advantages of the preservative-free versus preserved brimonidine %0.15 preparations in patients with primer open-angle glaucoma (POAG) or ocular hypertension (OHT).

Methods: Forty-two eyes of the 21 treatment-naive patients with POAG or OHT were enrolled in this study. Eyes were randomly assigned to receive brimonidine-purite 0.15% or preservative-free brimonidine 0.15% two times daily. Efficacy of the two eye drops was assessed by measuring the intraocular pressure (IOP) at 9–10 am at baseline and week 4. Safety and potential advantages of the drops were evaluated at weeks 4 in terms of ocular symptoms and tear parameters. Ocular symptom values of the patients were evaluated with a scale of 0–4 (0?=?no discomfort and 4?=?severe discomfort).

Results: Both of the brimonidine tartrate formulations resulted in statistically similar IOP reduction (preserved formulation; ?5.2?mmHg [22.9% reduction] preservative-free formulation; ?5.7?mmHg [24.1% reduction], p?=?0.37). It was found that brimonidine tartrate formulations with and without topical preservatives did not produce a statistically significant difference in pain, stinging, and blurred vision at the upon instillation (p?>?0.05). However, the burning sensation was significantly higher in the preservative-free formulation at the first instillation compared to the preserved formulation (p?=?0.01). Also, there was no statistically significant difference between the two formulations in terms of symptoms (itching, burning, tearing, stinging, and photophobia) and tear parameters during the day (p?>?0.05).

Conclusions: Although topical preservative-free brimonidine tartrate treated eyes had a more burning sensation at the first drop, the two formulations were similar in terms of ocular tolerability in the short term period. Also, both formulations were found to reduce IOP at a similar rate.     

Comparison of the efficacy and tolerability of topically administered azelastine,sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis and rhino-conjunctivitis

SUMMARY

Objective and setting: Azelastine (AZE) in a novel, eye drop, formulation, was compared with topically applied sodium cromoglycate (SCG) and placebo (PLA) in the treatment of seasonal allergic conjunctivitis or rhino-conjunctivitis in a multicentre, parallel group study.

Research design: 144 subjects ranging in age from 16 to 65 years participated. All had at least a 2-year history of seasonal allergic conjunctivitis and were symptomatic at the time of inclusion.

Medications were administered topically either twice daily (AZE/PLA) or four times daily (SCG) over a 2-week treatment period.

Method and outcome measures: Azelastine and placebo were compared double-blind; the comparison versus SCG was carried out in an open manner. Itching, redness, flow of tears, eyelid swelling, foreign-body sensation, photophobia, soreness and discharge were scored on a 4-point severity scale.

Results: Results for the decrease of main conjunctivitis symptoms (itching, tearing and conjunctival redness) showed a marked effect for both active treatments on day 3 with a sustained improvement on days 7 and 14. A clear response to treatment (an improvement of sum scores for day 3 of >3 points compared to baseline) occurred in 85.4% of azelastine-treated patients, 83.0% of sodium cromoglycate patients and 56.3% of placebo patients. Response rates for both active treatments were statistically superior to those for placebo (azelastine p?=?0.005; sodium cromoglycate p?=?0.007). Global assessment of efficacy was at least 'satisfactory' for 90.0% of azelastine patients, 81.3% of sodium cromoglycate patients and 66.3% of placebo-treated patients. The most frequent adverse effects were transient application site reactions which tended to disappear with increasing duration of treatment, and, less frequently, taste perversion.

Conclusion: The results of this study indicate that the therapeutic use of azelastine eye drops in patients with seasonal allergic conjunctivitis or rhino-conjunctivitis can be recommended.     

Clinical efficacy of olopatadine vs epinastine ophthalmic solution in the conjunctival allergen challenge model

SUMMARY

Background: Olopatadine hydrochloride 0.1% ophthalmic solution (Patanol*) and epinastine hydrochloride 0.05% ophthalmic solution (Elestat?) are two topical antiallergic agents. Olopatadine is indicated for the treatment of the signs and symptoms of allergic conjunctivitis that include itching, redness, tearing, lid swelling, and chemosis. Epinastine is indicated for the prevention of itching associated with allergic conjunctivitis.

Objective: This study compared the clinical efficacy of olopatadine and epinastine in the prevention of itching and conjunctival redness in the conjunctival allergen challenge (CAC) model.

Research design and methods: This was a prospective, randomized, double-masked, contralaterally-controlled, single center allergen challenge study. Ninety-six subjects with a history of allergic conjunctivitis were screened, and the 66 who responded to conjunctival allergen challenge at visits 1 and 2 were randomized into 1 of 3 treatment groups at visit 3 to receive one drop of study medication in each eye: (1) olopatadine in one eye and epinastine in the fellow eye, (2) olopatadine in one eye and placebo in the fellow eye, and (3) epinastine in one eye and placebo in the fellow eye. Five minutes after study drop instillation, subjects were bilaterally challenged with the allergen concentration that had elicited a positive conjunctival allergic response at Visits 1 and 2. Subjective itching assessments were given at 3?min, 5?min, and 7?min post challenge. Objective redness and chemosis assessments were made at 10?min, 15?min, and 20?min post challenge. Paired sample two-tailed t-tests were performed on the mean scores at each time point to assess statistical significance in the differences between treatments.

Main outcome measures; results: Fifty-three subjects were randomized into the olopatadine/epinastine treatment group, the primary analysis group. Olopatadine treated eyes exhibited significantly lower mean itching and conjunctival redness scores than the contralateral epinastine treated eyes, –0.19 (?p = 0.003) and –0.52 (?p < 0.001), respectively. Olopatadine treated eyes also exhibited significantly less chemosis –0.24 (?p < 0.001), ciliary redness –0.55 (?p < 0.001), and episcleral redness –0.58 (?p < 0.001) than epinastine treated eyes.

Conclusion: Olopatadine is significantly more effective than epinastine in controlling itching, redness and chemosis associated with allergic conjunctivitis in the CAC model.

* Patanol is a registered tradename of Alcon Laboratories Inc, Forth Worth, TX, USA     

Systemic iodine absorption associated with the use of preoperative ophthalmic antiseptics containing iodine

Abstract

Background: Polyvinylpyrrolidone-Iodine (PVP-I) is routinely used as preoperative antiseptic during ophthalmic surgery. Iodine absorption from iodine-containing antiseptics can lead to the development of thyroid disorders. Therefore, a quantitative measurement of iodine absorption from these antiseptics was performed in patients undergoing elective cataract surgery.

Methods: This study enrolled 241 patients to evaluate systemic iodine absorption after exposure to conjunctival and/or periorbital 1.25% and 10% PVP-I compared to an iodine-free antiseptic.

Results: All patients who received the 10% PVP-I regardless of the application site showed a 1.2–1.5-fold increase in urinary iodine excretion after 24?h (p?=?0.01). In 17 out of 110 (15.5%) patients in whom 10% PVP-I was used, the critical threshold of urinary iodine excretion as defined by WHO (>300?µg/L) was exceeded. In contrast, no significant ioduria was observed with the use of 1.25% PVP-I except in patients after 48?h (p?=?0.01) and with a concurrent conjunctival and periorbital application. The proportion of the excreted iodine in urine ranged from 0.24% to 1.77%. No correlation was found between the total applied concentration of iodine and the amount excreted in urine.

Conclusion: Based on our findings, we believe that the use of 10% PVP-I as preoperative ophthalmic antiseptic should undergo further clinical evaluation in regard to its impact on thyroid function. Conjunctival or periorbital application of 1.25% PVP-I does not result in significant ioduria.     

Chloramphenicol/sulfobutyl ether-β-cyclodextrin complexes in an ophthalmic delivery system: prolonged residence time and enhanced bioavailability in the conjunctival sac

Objective: Conventional chloramphenicol (CHL) eye drops are widely used anti-infection formulations for acute bacterial conjunctivitis. However, the therapeutic effects are limited by insufficient concentration in the conjunctival sac. Hence, the objective of this study is to formulate and develop novel CHL eye drops with improved topical concentrations by increasing the solubility and decreasing the transcorneal penetration.

Research design and methods: CHL was included in the sulfobutyl ether-β-cyclodextrin (SBE-β-CD) using the freeze-drying method. Eye drops containing CHL/SBE-β-CD complexes were prepared and evaluated for in vitro and in vivo studies.

Results: The formation of CHL/SBE-β-CD inclusion was confirmed by DSC, XRD, NMR, and SEM. The aqueous solubility of CHL was significantly enhanced, and the drug transcorneal penetration was inhibited after inclusion. The CHL/SBE-β-CD displayed sustained release profiles. The tear fluid elimination kinetic study showed that the CHL/SBE-β-CD eye drops had better ability to prolong the residence time, and significantly increase CHL concentration in the conjunctival sac. Besides, it was shown that CHL/SBE-β-CD eye drops were nonirritating to rabbits’ eyes.

Conclusions: The SBE-β-CD inclusions offer a potential alternative strategy for ocular administration of poorly water-soluble drugs in the conjunctival sac.     

高锰酸钾洗眼液临床适宜浓度探讨

目的:为临床推荐最佳的高锰酸钾洗眼液应用浓度。方法:配制3种不同浓度的高锰酸钾洗眼液,观察其中2种浓度对115例结膜炎患者行结膜囊冲洗的眼局部刺激性和3种浓度对18对正常眼行结膜囊冲洗的舒适度、对角膜上皮的影响及冲洗前、后菌落数变化。结果:115例结膜炎患者中,自述刺激性大者98例,约占85%;因刺激性大无法忍受者8例,约占7%。随着洗眼液浓度的升高,正常眼结膜囊冲洗的舒适度下降,但对各组角膜上皮无影响,且冲洗前、后菌落数无显著变化。结论:推荐临床应用100ml∶1.5mg浓度的高锰酸钾洗眼液行结膜囊冲洗。     

Effectiveness of heparin eye drops in paraquat-induced ocular injury

Purpose: To evaluate the efficacy of heparin eye drops in the treatment of paraquat-induced ocular surface injury.

Design and methods: In this retrospective study, we included 25 patients (31 eyes) with paraquat-induced ocular surface injury, who attended the Affiliated Hospital of Weifang Medical University between October 2008 and October 2013. The patients were split into two groups according to whether or not received heparin eye drops. The clinical data were compared between the two groups, i.e. clinical histories, results of examinations, treatments and outcomes.

Results: Eleven patients (group A, 15 eyes) received prompt irrigation with 0.9% saline every two hours, 0.1% pranoprofen eye drops four times a day, 20% autologous serum every two hours, recombinant bovine basic fibroblast growth factor eye-gel two times a day, oral vitamin C 2.0?g and prednisone 30?mg daily. Fourteen patients (group B, 16 eyes) received additional treatment with heparin eye drops. Ten eyes in group A and seven eyes in group B developed a pseudomembrane on the ocular surface at significantly different rate (mean?±?SD) of 1.20?±?1.01 and 0.43?±?0.51, respectively (t?=?2.66, p?=?0.01). Seven eyes among 10 had a pseudomembrane reoccurred in group A while none had a pseudomembrane reoccurred in group B (Fisher’s exact test, p?=?0.01). No significant differences were seen in the duration of epithelial recovery between the two groups: 15.13?±?5.13 days in group A and 16.81?±?5.56 days in group B (t?=?0.87, p?=?0.39). After the treatment, mild corneal opacity and pannus were observed in five patients of group A and four patients of group B, without any significant difference between the two groups (p?=?0.70).

Conclusions: The paraquat-induced ocular surface injury observed in this case series was characterized by the formation of conjunctival pseudomembrane with good prognosis and mild complications. Heparin eye drops reduce the occurrence, especially the reoccurrence of pseudomembrane. Further studies are warranted.     

Ocular surface effects of repeated application of povidone iodine in patients receiving frequent intravitreal injections

Background: The aim of this study was to investigate the patient reported symptoms and objective signs of tear film and ocular surface abnormalities experienced by patients undergoing repeated exposure to povidone iodine as a consequence of requiring frequent intravitreal injections for wet macular degeneration.

Methods: This was a prospective study of consecutive patients who had received recent povidone 5% solution for sterile preparation of intravitreal injection less than 3?months prior to inclusion with a total of at least 3 intravitreal injections for macular degeneration. Each patient had one study eye which was undergoing regular intravitreal injection and a fellow eye which was not undergoing any injections. Each patient underwent evaluations of various tear film parameters on a single occasion for both eyes. The primary outcome was severity of dry eye symptoms as measured by the Schein dry eye questionnaire. The secondary outcomes were tear film osmolarity and corneal punctate staining using the Oxford Grading Scale.

Results: A total of 90 patients were included in the study. 43.3% n?=?39, were using ocular lubricating medication on a regular basis. A significantly greater proportion of study eyes had a Schein dry eye questionnaire score of 7 or higher; 12.2%, n?=?11 amongst study eyes vs 4.4%, n?=?4 amongst control, fellow eyes (p?p?=?0.087). The study eyes had statistically significantly worse corneal staining as determined by the Oxford grading scale; 0.69 in study eyes vs 0.58 in control, fellow eyes (p?=?0.02).

Conclusion: Our results confirm the detrimental impact of repeated application of povidone iodine for intravitreal injection procedures on symptoms of dry eyes as experienced and reported by patients.     

庆大霉素和活力碘的体外抑菌效应及其对开放性骨折术后感染的预防作用

目的:探讨庆大霉素和活力碘体外抑菌效应及其术中冲洗对开放性骨折术后感染的预防作用。方法:体外抑菌实验检测庆大霉素和活力碘对表皮葡萄球菌和金黄色葡萄球菌的最低抑菌浓度(M IC)和最低杀菌浓度(M BC),药敏实验观察其分别对这两种细菌的抑菌圈大小。体内动物实验将家兔分为3组,均将右侧胫骨近端软组织切开,并不全离断胫骨,局部加入金黄色葡萄球菌菌液100u l后等待3 m in。模型对照组伤口不予冲洗直接关闭。另两组分别以0.1%活力碘和庆大霉素溶液冲洗创面。术后10d通过观察伤口和深部局部炎症表现、脓液性状和细菌培养来判断是否发生感染。结果:庆大霉素和活力碘均有不同程度的体外抑菌和杀菌作用,庆大霉素的M IC和M BC明显低于其他组,其抑菌圈明显大于其他组。体内动物实验模型对照组感染率100%,庆大霉素生理盐水冲洗组感染率明显低于模型对照组和活力碘冲洗组(P<0.01)。结论:庆大霉素溶液冲洗创面能明显降低开放性骨折术后感染率,体外抑菌杀菌作用明显,可较好地预防开放性骨折术后感染。     

聚维酮碘在白内障患者术前结膜囊冲洗中的应用

目的 探讨聚维酮碘在白内障患者术前结膜囊冲洗中的应用方法和临床效果.方法 选择100例白内障手术患者,随机分为实验组和对照组.术前实验组用0.25%聚维酮碘消毒液冲洗结膜囊;对照组用0.08%庆大霉素注射液冲洗结膜囊;然后两组分别取样进行结膜囊细菌培养,比较两组洗眼效果.结果 术前用0.25%聚维酮碘消毒液、庆大霉素注射液洗眼后细菌培养阳性率分别为2.0%、20.0%.两组自觉症状和眼内炎发病率无明显差别（P＆gt;0.05）.结论 术前用0.25%聚维酮碘消毒液冲洗结膜囊可以降低术炎细菌培养阳性率, 使白内障术后眼内炎发病率明显下降,且无严重角膜并发症,是一种有效、安全的预防白内障术后眼内炎的措施之一.     

Comparative efficacy of olopatadine 0.1% ophthalmic solution versus levocabastine 0.05% ophthalmic suspension using the conjunctival allergen challenge model

SUMMARY

Objective: To compare the efficacy of olopatadine and levocabastine in reducing ocular allergic itching and vascular hyperemia (redness) induced by conjunctival allergen challenge.

Research design and methods: The study was a randomized, double-masked, contralateral study using the conjunctival allergen challenge (CAC) model. At Visit 1, subjects with a positive allergen skin test and a history of allergic conjunctivitis were administered increasing concentrations of allergen until at least a moderate grade 2 ocular itching and conjunctival redness response was obtained in both eyes. Allergic signs were graded on standardized 0–4 scales. Subjects who reacted positively were re-challenged at Visit 2 with the pre-determined concentration of allergen. Subjects who again responded with at least a grade 2 bilateral ocular itching and conjunctival redness score at Visit 2 were eligible for drug evaluation. At Visit 3, subjects received olopatadine in one eye and levocabastine in the contralateral eye according to a computer-generated randomization scheme generated prior to commencement of the study. Ocular discomfort was then graded in both eyes. Subjects were bilaterally challenged with the predetermined concentration of allergen 27?min after topical drug administration, such that the first post-challenge assessment was made 30?min post-drug instillation. Allergic signs and symptoms were evaluated at 3?min, 10?min, and 20?min post-challenge and safety and efficacy analyses were performed.

Results: Sixty-eight subjects received study drug and were included in the safety and efficacy analyses. Ocular itching scores for olopatadine were significantly lower than levocabastine at 3?min and 10?min post-challenge (?p < 0.001). Ocular redness scores for olopatadine were significantly lower than levocabastine at all time points post-challenge (?p < 0.0001). Of all subjects, 4.41% reported ocular discomfort in the olopatadine eye and 26.5% in the levocabastine treated eye.

Conclusion: Olopatadine treated eyes had significantly less itching and redness than levocabastine treated eyes after conjunctival allergen challenge. Olopatadine was also associated with less discomfort upon instillation than levocabastine.     

Efficacy and comfort of olopatadine 0.2% versus epinastine 0.05% ophthalmic solution for treating itching and redness induced by conjunctival allergen challenge

ABSTRACT

Background: Olopatadine 0.2% (Pataday, Alcon Laboratories Inc., Fort Worth, Texas, USA) and epinastine 0.05% (Elestat, Inspire Pharmaceuticals, Inc., Durham, NC, USA) are topical ocular anti-allergic agents. Both are H₁ antihistamine/mast cell stabilizers indicated for the treatment of ocular itching associated with allergic conjunctivitis.

Objective: To compare the efficacy and comfort of olopatadine 0.2% with epinastine 0.05%, in the prevention of ocular itching associated with allergic conjunctivitis following conjunctival allergen challenge (CAC).

Research design and methods: This was a 7 week, four visit, double-masked, randomized, placebo-controlled CAC study. Visit 1 screened subjects for positive ocular allergic responses and Visit 2 confirmed those responses. At Visit 3, 92 subjects were randomized into one of four treatment groups to receive one drop of study medication in each eye: (1) olopatadine 0.2%/placebo, (2) epinastine 0.05%/placebo, (3) olopatadine 0.2%/epinastine 0.05%, (4) placebo/placebo. Subjects were challenged 12?h after drop instillation to evaluate duration of action. At Visit 4, subjects were challenged 5?min after drop instillation to evaluate onset of action. Drop comfort was assessed at Visit 4.

Main outcome measures; results: This article focuses on the results of the onset-of-action challenge (Visit 4). At Visit 4, ocular itching was assessed at 3, 5, and 7?min and redness was assessed at 7, 15, and 20?min post-challenge. Drop comfort was assessed upon instillation, at 30?s, and at 1, 2, and 5?min post-instillation. Olopatadine 0.2%-treated eyes exhibited significantly lower mean ocular itching scores versus epinastine 0.05%-treated eyes at 5 (?p = 0.024) and 7?min (?p = 0.003) post-challenge. Olopatadine 0.2%-treated eyes exhibited significantly lower mean redness scores versus epinastine 0.05%-treated eyes at all time points post-challenge (ciliary: p ≤ 0.013, conjunctival: p ≤ 0.015, episcleral: p ≤ 0.006). Olopatadine 0.2% was rated as significantly more comfortable than epinastine 0.05% at 1?min post-drop instillation (?p = 0.003). All adverse events were non-serious and unrelated to study medication. Although the CAC model reproduces allergic responses that are not environmentally-induced, patients experience varying severities of responses as are seen in real-world situations.

Conclusion: Olopatadine 0.2% was superior to epinastine 0.05% in preventing ocular itching and redness at onset when induced by the CAC model.     

Intravitreal anti-VEGF treatment for retinopathy of prematurity in infants with active adenoviral keratoconjunctivitis

Purpose: To evaluate the results of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for retinopathy of prematurity (ROP) in infants with active adenoviral keratoconjunctivitis (AKC).

Material and methods: A retrospective analysis was performed using the medical records of all infants treated with intravitreal injections of anti-VEGF agents during an AKC outbreak previously reported in the literature at a tertiary center for treatment of ROP. The infants were divided into two groups. Group 1 included nine infants (18 eyes) with AKC, while Group 2 included 13 infants (26 eyes) without AKC.

Results: During the AKC outbreak, 22 infants were treated with anti-VEGF agents for treatment-requiring ROP. In all patients in both groups, the ROP and plus disease displayed a significant regression within 2 days after the intravitreal injections. Moreover, no serious complications such as endophthalmitis, retinal detachment, cataract or intravitreal hemorrhage were observed after the treatment and there were no statistically significant differences between the groups in terms of postoperative complications.

Conclusion: Immediate and appropriate intervention is very important in cases of treatment-requiring ROP otherwise it can result in blindness. However, laser treatment for ROP is technically difficult in infants with active AKC. The results of this study showed that favorable outcomes without serious ocular complications could be obtained via intravitreal injections of anti-VEGF agents in infants with active AKC.     

Effects of a new hemostatic agent Ankaferd Blood Stopper® on the intraocular tissues in rat model

Purpose: To investigate the histopathological changes due to administration of Ankaferd Blood Stopper^® (ABS) into intraocular tissues by an anterior chamber and intravitreal injections.

Methods: Twenty Wistar albino rats were divided into four equal groups. Group 1 was injected 0.01?mL ABS into anterior chamber. Group 2 was injected intravitreal 0.02?mL ABS. Groups 3 and 4, which were used as controls, were injected into the anterior chamber and intravitreal 0.01?mL and 0.02?mL balanced salt solution (BSS), respectively. At 2, 5, 10, 15 and 20 days after injection, the eyes were examined under an operating microscope and were subsequently enucleated for histopathological examination.

Results: Ophthalmic examination of the rats prior to enucleation revealed ocular complications ranging from conjunctival hyperemia to corneal perforation in group 1 and increased conjunctival hyperemia and discharge in group 2. No physical and histopathological anomalies were detected in groups 3 and 4. All eyes in group 1 showed mixed type inflammatory cell reaction, foreign-body reaction, stromal congestion, disintegration of the collagen fibers and loss of the epithelium of the posterior wall in the iris and ciliary body were observed histopathologically. All eyes in group 2 showed disintegration and separation of the retina, brown pigment accumulation and mixed type inflammatory cell reaction.

Conclusion: Our results indicate that the commercially available form of ABS solution exerts a toxic effect on intraocular tissues. We consider that the intraocular use of different concentrations, rather than multiple time point of ABS should be investigated.     

A comparison of the fourth-generation fluoroquinolones gatifloxacin 0.3% and moxifloxacin 0.5% in terms of ocular tolerability

SUMMARY

Purpose: To compare the ocular tolerability of the commercially available ophthalmic solutions of the fourth-generation fluoroquinolones, gatifloxacin 0.3% (Zymart, Allergan, Inc., Irvine, CA) with benzalkonium chloride (BAK) and moxifloxacin 0.5% (Vigamoxt) without BAK.

Methods: A baseline evaluation was conducted on 30 healthy volunteers for conjunctival hyperemia, conjunctival vascularity, pupil size, and anterior chamber (AC) cell and flare. Pupils were measured under scotopic conditions with a Colvard pupillometer. Conjunctival hyperemia and vascularity, and AC reaction were measured on a Likert-like scale of 0-3. Subjects then received drops in both eyes from masked bottles of gatifloxacin ophthalmic solution 0.3% with BAK (in one eye determined randomly) and moxifloxacin ophthalmic solution 0.5% without BAK (in the contralateral eye) in a double-masked fashion. Subjects graded pain and ocular irritation in each eye on a scale of 1-10 after 5min with their eyes closed. The examination was then repeated.

Results: The average age of this study population was 34.4years. The groups of eyes receiving moxifloxacin 0.5% demonstrated an increase in mean conjunctival hyperemia (0.21 [range: 0-1] at baseline to 1.52 [range: 0-3] at 5min.)

that was significantly greater (p?=?0.0005) compared with that of the group receiving gatifloxacin 0.3% (0.22 [range: 0-1] at baseline to 0.45 [range: 0-2] at 5min). The group receiving moxifloxacin 0.5% showed an increase in conjunctival vascularity (0.55 [range: 0-1] at baseline to 1.61 [range: 0.5-3] at 5?min.) that was significantly greater (p?=?0.0005) compared with that of the group receiving gatifloxacin 0.3% (0.52 [range: 0-1] at baseline to 0.68 [range: 0-2] at 5?min.). Significantly less pain (1.2 vs. 3.2, p?=?0.001) and irritation (0.64 vs. 3.42, p?=?0.001) occurred with gatifloxacin 0.3% than with moxifloxacin 0.5%. Pupil size was significantly reduced (5.65mm-5.05mm) in eyes receiving moxifloxacin 0.5% (p?=?0.004) and no significant change occurred in pupil size (5.60mm-5.65mm) in eyes that received gatifloxacin 0.3% (p?=?0.878). No AC reaction was noted with either medication.

Conclusions: The group of eyes receiving gatifloxacin 0.3% with BAK demonstrated greater ocular tolerability in comparison to the group receiving moxifloxacin 0.5% without BAK. Moxifloxacin-induced pupillary miosis may be due to prostaglandin release in the anterior chamber. A limitation of this study is the relatively young age of the study population.     

Safety and tolerability of the tafluprost/timolol fixed combination for the treatment of glaucoma

Introduction: The preservative-free (PF) fixed combination (FC) of tafluprost 0.0015%/timolol 0.5% is the newest member of the prostaglandin analogue/timolol FC class.

Areas covered: In this review, we summarize data on safety and tolerability of this FC.

Expert opinion: The intraocular pressure-lowering effect of the tafluprost/timolol FC is approximately 30 – 35%, which is similar to that of the other members of the class. However, in contrast to most similar eye drops the tafluprost/timolol FC is manufactured in a PF, unit-dose pipette formulation. The PF nature eliminates preservative-related ocular surface changes, and improves tolerability. In clinical studies, the tafluprost/timolol FC was well tolerated. The side effects represented the typical side effects of the topical prostaglandin analogue class. The most common side effect, conjunctival hyperemia was mild, and occurred in only 6.4 – 8% of patients during 6 months of treatment. The figures for ocular irritation were also low (7.0 – 12.7%). The other side effects occurred only in very few patients. The frequency and severity of conjunctival hyperemia was lower than those published for most prostaglandin/timolol FCs. Thus, the main clinical advantage of this PF FC is improved tolerability, which may support treatment adherence of glaucoma patients.     

Preservative-free versus preserved latanoprost eye drops in patients with open-angle glaucoma or ocular hypertension

Objective: This study compared the efficacy, safety, and pharmacokinetics of a preservative-free latanoprost formulation to an established, benzalkonium chloride (BAK) containing formulation for the treatment of open-angle glaucoma or ocular hypertension.

Methods: This was a phase II, randomized, cross-over, investigator-masked, multi-center, pilot study (NCT01494753). A total of 30 untreated adult patients (aged ≥18 years) with primary open angle glaucoma, pseudo-exfoliative glaucoma, pigmentary glaucoma, or ocular hypertension received either preservative-free or preserved latanoprost once daily in both eyes for 6 weeks, before crossing over to receive the other treatment. Efficacy (intraocular pressure [IOP] at 8 am, midday, 4?pm and 8?pm, and global efficacy assessment by investigator), safety (adverse events, ocular symptoms and global tolerance, slit lamp examination, funduscopy, visual field examination, visual acuity, and heart rate), and pharmacokinetics were assessed at Days 0, 42, and 84.

Results: Both treatments resulted in a reduction in IOP that was similar for the preservative-free and the preserved formulation at all time points. Similarly, the overall diurnal reduction was similar in both groups (6.3?mmHg [27.9% reduction] and 6.4?mmHg [28.1% reduction] for preserved and preservative-free latanoprost, respectively). There were no differences in global efficacy assessment or in the safety and tolerance of each treatment. Systemic concentrations of latanoprost were very low; AUC_0–30 and C_max were lower and t_max was longer for preservative-free latanoprost.

Conclusions: Preservative-free latanoprost showed similar efficacy at all time points compared to BAK preservative containing formulation, with no difference in tolerance, allowing progression to phase III clinical development.     

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.     

Phase III efficacy and safety study of besifloxacin ophthalmic suspension 0.6% in the treatment of bacterial conjunctivitis

ABSTRACT

Objective: To compare the clinical and antimicrobial efficacy of besifloxacin ophthalmic suspension 0.6% with that of vehicle in the treatment of bacterial conjunctivitis.

Research design and methods: This was a randomized, multicenter, double-masked, vehicle-controlled study. A total of 957 patients aged 1 year and older with bacterial conjunctivitis were randomized to treatment with besifloxacin ophthalmic suspension 0.6% or vehicle applied topically three times daily for 5 days.

Main outcome measures: Primary endpoints were clinical resolution and microbial eradication of baseline bacterial infection at Visit 2 (Day 5?±?1). Secondary endpoints included clinical resolution and microbial eradication at Visit 3 (Day 8 or 9), individual clinical outcomes at follow-up visits, and safety.

Clinical trial registration: NCT number, NCT00347932.

Results: Three hundred and ninety patients had culture-confirmed bacterial conjunctivitis. Clinical resolution and microbial eradication were significantly greater with besifloxacin ophthalmic suspension than with vehicle at Visit 2 (45.2% vs. 33.0%, p?=?0.0084; and 91.5% vs. 59.7%, p?<?0.0001, respectively) and Visit 3 (84.4% vs. 69.1%, p?=?0.0011; and 88.4% vs. 71.7%, p?<?0.0001, respectively). Results for secondary endpoints of individual clinical outcomes were consistent with primary endpoints. Fewer eyes receiving besifloxacin ophthalmic suspension experienced adverse events than those receiving vehicle (9.2% vs. 13.9%; p?=?0.0047).

Conclusions: Besifloxacin ophthalmic suspension produces clinical resolution and microbial eradication rates significantly better than vehicle and is safe for the treatment of bacterial conjunctivitis.

Limitations: A limitation of this study is the lack of a non-treatment control group.