糖尿病视网膜病变患者围手术期散瞳策略

目的：探讨糖尿病视网膜病变患者围手术期最佳散瞳方法,以利于玻璃体切割手术顺利进行。方法：回顾性分析我院2007年6月-2011年6月所有糖尿病视网膜病变患者的手术资料,选取术前常规应用复方托吡卡胺滴眼液、术中瞳孔直径≥7mm的患者手术时散瞳药的应用记录,共189例,204眼。术前点复方托吡卡胺滴眼液,每5min1次,共6次。点滴眼液后,0.5h内瞳孔散大（直径≥7mm）者为A组（78眼）;超过0.5h,但瞳孔散大时间在1h以内者为B组（75眼）;瞳孔散大时间大于1h者为C组（51眼）。B、C组于术前一天随机应用硫酸阿托品眼用凝胶或盐酸环喷托酯滴眼液,术前1h频点复方托吡卡胺滴眼液。结果：术中瞳孔直径能维持≥7mm的眼数比例,B、C组应用硫酸阿托品眼用凝胶者与应用盐酸环喷托酯滴眼液者差异均无统计学意义（P〉0.5）。术中有134眼因白内障同时行超声乳化白内障摘除术,其术中瞳孔直径能维持≥7mm的眼数比例,B组应用盐酸环喷托酯滴眼液者瞳孔维持的比例较用硫酸阿托品眼用凝胶者高（P〈0.5）,C组中二者比较差异无统计学意义（P〉0.5）。结论：对于术前单用复方托吡卡胺滴眼液散瞳时间超过0.5h者,术前点硫酸阿托品眼用凝胶或盐酸环喷托酯滴眼液有利于维持术中瞳孔大小,且二者效果差异无统计学意义。     

Visual recovery using small dilating eye drops.

It is well established that reduced size dilating eye drops of 1% tropicamide and 10% phenylephrine (micro drops) are effective for clinical purposes. Excellent pupil dilatation (mydriasis) is achieved and pupil constriction does not occur in response to light. In this study, the effect of micro drops of 1% tropicamide on distance and near visual recovery was compared with standard drops in a group of 20 healthy volunteers. For each person studied, one eye was selected at random to be tested first with the standard drop size, and then after a minimum of one week, the same eye was again tested using a drop of the same drug one fifth standard size. An iris photograph, Snellen visual acuity at 6 m, and reading visual acuity was obtained for each test procedure: before drop instillation and at 30 min, 1, 2 and 4 h after drug instillation. Use of the micro drops caused a small but statistically significant improvement in the rate of recovery of distance and near visual acuity. These findings, allied to the known beneficial effects of reduced systemic absorption using micro drops, lend further weight to the argument that mydriasis may be achieved more safely, with fewer side effects, and with earlier return of normal vision when reduced size drops are used. It is hoped that practical micro drop dispensers will be developed.     

复方托吡卡胺滴眼液致突发性耳聋

1名60岁女性糖尿病患者，行眼底检查前用复方托吡卡胺滴眼液散瞳，随后出现听力明显下降伴耳呜，检查提示双耳感音神经性耳聋。经高压氧、葛根素治疗后，听力明显恢复。因眼科检查需要，再次用复方托吡卡胺滴眼液，用药后患者又出现听力明显下降，经对症治疗后好转。当患者第4次使用该药后出现耳聋，治疗1月余，听力仍未恢复。     

Reversal of tropicamide-induced mydriasis by thymoxamine eye drops

In a study in 12 healthy volunteers, local instillation of thymoxamine eye drops (0.5%), completely reversed the mydriasis produced by tropicamide (0.5%), but only incompletely that by tropicamide (1.0%). The difference between these effects was statistically significant (p less than 0.025). The thymoxamine eye drops were well tolerated.     

Aqueous carboxymethyl gum kondagogu as vehicle for ocular delivery

Aqueous solutions of carboxymethyl gum kondagogu (CMGK), an anionic bioadhesive polymer were evaluated as vehicles for ophthalmic delivery using tropicamide as a model drug. Aqueous ophthalmic solution of tropicamide (1 %, w/v) in CMGK (5 %, w/v) dispersions were formulated. The aqueous CMGK vehicle, formulated tropicamide eye drops and commercial tropicamide formulations were assessed comparatively for ex vivo ocular tolerance using hen’s egg chorioallantoic membrane assay. The results indicated ocular tolerability of aqueous CMGK vehicle. The results of comparative ex vivo corneal permeation study of tropicamide from the aqueous CMGK vehicle (5 %, w/v) conducted across isolated goat cornea revealed a no significant difference in the corneal permeation of tropicamide from the CMGK vehicle based formulation as compared to the commercial formulation. Further, the results of in vivo mydriatic response study conducted in rabbits revealed a non significant difference in the mydriatic response of tropicamide from the aqueous CMGK vehicle and commercial formulations. In conclusion, CMGK can be used as an ocularly tolerable polymer for formulating ophthalmic dosage forms.     

复方托吡卡胺滴眼液含量测定方法的改进

目的:建立同时测定复方托吡卡胺滴眼液中两组分含量的方法.方法:C18柱,以甲醇-0.03 mol·L-1辛烷磺酸钠溶液(1∶1)为流动相(用磷酸调节pH为3.0),检测波长263nm;柱温30℃;流速1.0 mL·min-1.结果:盐酸去氧肾上腺素在0.054 0～0.504 0 mg·mL-1范围内呈良好的线性关系(r=0.999 9);托吡卡胺在0.05021 ～0.502 1 mg· mL-1范围内呈良好的线性关系(r =0.999 8).盐酸去氧肾上腺素的平均回收率为99.58％,RSD值为1.6％(n=9);托吡卡胺的平均回收率为100.5％,RSD值为1.1％(n=9).结论:方法简便,分离度符合要求,结果准确可靠,可以用于复方托吡卡胺滴眼液的含量测定.     

不同浓度托吡卡胺治疗学龄儿童假性近视的临床观察

目的评价0．5％托吡卡胺滴眼液治疗学龄儿童假性近视的临床效果和用药后的不良反应情况,指导临床应用。方法应用0．5％托吡卡胺滴眼液,隔晚给药;0．25％托吡卡胺滴眼液每晚给药,对假性近视的学龄儿童（每组100例,200眼）进行治疗。治疗前后,记录裸眼远视力,散瞳后的静态屈光度。结果两组假性近视的学龄儿童,治疗后裸眼远视力均有提高,差异有统计学意义（P〈0．01）;治疗后静态屈光状态呈大部分近视度数降低,差异有统计学意义（P〈0．01）。两组间用药后的不良反应出现的频率,差异有统计学意义（P〈0．01）。结论0．5％托吡卡胺滴眼液,隔晚使用,防治青少年假性近视疗效确切。可减少用药后的不良反应,增加用药顺应性。     

The local vasoconstriction of infant’s skin following instillation of mydriatic eye drops

Background  

Systemic absorption of eye drops is known to occur via the nasal mucosa, cornea, and conjunctiva. Diffusion of eye drops through the skin is previously unrecognized. Here, two cases are presented in which we observed skin pallor around the eyes after instillation of phenylephrine 2.5% drops. Case 1 A 32-week gestational age premature infant had mydriatic eye drops instilled as part of retinopathy of prematurity screening. Case 2 A term newborn dysmorphic infant underwent fundus examination to rule out ocular pathology. In both cases, discoloration of periorbital skin was observed 45 min following administration of drops.     

RP-HPLC法测定复方托吡卡胺滴眼液中盐酸去氧肾上腺素与托吡卡胺两组分含量

目的测定复方托吡卡胺滴眼液中盐酸去氧肾上腺素和托吡卡胺两组分的含量。方法用RP HPLC法,色谱柱:Inertsil C8柱(150 mm×4.6 mm,5μm);流动相:甲醇0.01 mol.L-1辛基磺酸钠溶液(体积比为1∶1,用磷酸调pH=3.00);检测波长:263 nm;柱温:30℃;流速:1 mL.min-1。结果盐酸去氧肾上腺素和托吡卡胺的线性范围分别为50.4~504.0 mg.L-1、48.8~487.6 mg.L-1;r值分别为0.999 7、0.999 8;盐酸去氧肾上腺素平均回收率为100.1%,RSD为0.45%;托吡卡胺平均回收率为99.74%,RSD为0.20%。结论该方法与国家标准相比简单、快捷,回收率和重复性良好,其线性、重复性、回收率均符合《中华人民共和国药典》的有关规定,可作为复方托吡卡胺滴眼液质量评价的方法。     

早产儿用复方托吡卡胺眼水散瞳的研究

目的研究复方托吡卡胺眼水在不同胎龄早产儿散瞳效果,加强其在早产儿眼底病筛查的管理。方法在低胎龄和高胎龄早产儿的左右眼分别滴用2次和3次复方托吡卡胺眼水。按距双眼第一次点眼散瞳时间长短将其随机平均分成A、B、C三组。A组距双眼第一次点眼散瞳时间45min行双眼瞳孔直径测量及眼底检查;B组为60min;C组是90min。结果 A、B组中左、右眼散瞳直径无差异(P>0.05),C组左眼散瞳直径比右眼小(P<0.05)。无论散瞳时间的长短,低胎龄和高胎龄早产儿组的平均瞳孔直径比较无差异(P>0.05)。结论滴2次复方托吡卡胺眼水60min后行眼底检查更安全有效,并且复发托吡卡胺眼水对不同胎龄的早产儿散瞳效果无差异。     

Consensual pupillary responses to mydriatic and miotic drugs.

1. Three experiments were conducted to examine whether mydriatic or miotic drugs instilled into one eye have any effect on the diameter of the pupil of the untreated fellow eye, in healthy volunteers. 2. In Experiment 1, the effects of four subjects, using photography in an illuminated room to assess pupil diameter. The drug evoked a dose-dependent mydriasis in the index eye which was accompanied by a simultaneous dose-dependent miosis in the fellow eye. 3. In Experiment 2, the same method was used to assess pupil diameter as in Experiment 1. The effects of mydriatic (methoxamine and tyramine) and of miotic (pilocarpine) drugs instilled into the fellow eye, were studied on the sizes of pupillary responses to the same drugs instilled into the index eye. The presence of a mydriatic drug in the fellow eye resulted in a decrease in the size of the mydriatic responses in the index eye. 4. In Experiment 3, the effects of three concentrations of phenylephrine hydrochloride (0.15-0.60 M) and of three concentrations of pilocarpine hydrochloride (0.002-0.008 M), were studied in darkness using an infra-red binocular television pupillometer, in seven subjects. Phenylephrine evoked dose-dependent mydriasis and pilocarpine evoked dose-dependent miosis. The pupillary responses of the index eye were not accompanied by any changes in the diameter of the pupil of the fellow eye. 5. It is concluded that drug-induced mydriasis in the index eye is accompanied by a consensual miosis in the fellow eye.(ABSTRACT TRUNCATED AT 250 WORDS)     

眼用制剂致不良反应208例文献分析

目的：探讨眼用制剂致不良反应（ADR）的特点及一般规律,为临床合理用药提供参考。方法：检索1995年1月-2013年6月国内医药期刊发表的文献,获得眼用制剂致ADR文献137篇,合计208例患者,就其ADR相关情况进行统计分析。结果：临床上眼用制剂致ADR以阿托品滴眼液、复方托吡卡胺滴眼液、氯霉素滴眼液、盐酸丁卡因滴眼液最为常见,妥布霉素地塞米松滴眼液和噻吗洛尔滴眼液致ADR也较多见;在儿童和老年人中发生率较高;多发生在给药后24h内;其临床表现以过敏反应、变态反应和心血管系统反应居多。结论：临床医师、药师应重视眼用制剂致ADR的规律和特点,加强其合理使用和监测,确保用药安全。     

Epileptic seizures induced by cycloplegic eye drops

Objective: To assess the incidence of seizures induced by cycloplegic ophthalmic drops.

Materials and methods: A survey among members of the American Association for Pediatric Ophthalmology and Strabismus yielded five patients who received cycloplegic eye drops between 1998 and 2010 and who consequently developed a seizure.

Results: The median age of the patients was 5 years (range 3 months to 12 years). Cyclopentolate hydrochloride 1% was the only causative agent. The seizure happened on average 12?min after the instillation of dilating eye drops. Three were generalized convulsions, and two patients had a focal seizure. Past medical history was unremarkable in four cases. In total, 16 previous cases of seizures induced by cycloplegic drugs were identified in reports published between 1890 and 2004, implicating atropine in nine reports, tropicamide and phenylephrine eye drops in one and cyclopentolate in six.

Discussion: A small amount of cyclopentolate drops could induce convulsions in young children after only minutes to less than an hour, while a larger dosage of atropine over the span of several hours could cause this rare and unpredictable complication. Predisposing factors were rare and those developing the seizures were healthy subjects. Generalized seizures were much more frequent than focal convulsions.

Conclusions: Seizures after instillation of cycloplegic drops are extremely rare.     

Safety and tolerability of naproxen ophthalmic solution in comparison to placebo

BACKGROUND: Naproxen is a classic non-steroidal anti-inflammatory drug (NSAID) with established analgesic and anti-inflammatory potency. Its action is related to cyclooxygenase inhibition and consequent decrease in prostaglandin concentration in various fluids and tissues. Since prostaglandin release is involved in several ocular alterations, various NSAID eye drops have come into use in the clinical setting during the last decade. SUBJECTS, MATERIAL AND METHODS: A randomized, double-blind, placebo-controlled, three-way crossover design phase I was performed in 12 healthy volunteers to determine both tolerance and safety of a new NSAID ophthalmic solution containing sodium naproxen (0.1% and 0.2%). Both single dose and repeated dose (TID for 6 days) instillation were performed. Evaluation was entirely based upon tolerance criteria. Subjective and objective signs of ocular irritation and subject comfort preference were evaluated. Also medical examination, hematology, blood chemistry and urine analysis were also assessed to evaluate any possible effect of the test drugs and control. RESULTS: Neither ophthalmic tolerance parameters nor vital signs or laboratory parameters were influenced by treatments. A slight hyperemia of the conjunctiva was the only change observed in the eye during the study, whereas the only symptom mentioned was burning. CONCLUSION: It is concluded that both tolerability and safety of 0.1% and 0.2% naproxen solution are acceptable after single and repeated conjunctival administration.     

2'-Nor-2'-deoxyguanosine is an effective therapeutic agent for treatment of experimental herpes keratitis

2'-Nor-2'-deoxyguanosine (2'NDG), previously reported by us to effectively treat acute herpes simplex infections in mice, was used therapeutically to significantly enhance healing of established herpetic corneal lesions and prevent stromal disease in rabbits. Treatment using 0.06% 2'NDG drops (5 times daily) starting 3 days after infection resulted in more rapid healing of corneal epithelial lesions, rapid resolution of conjunctival inflammation, and prevention of stromal clouding compared to placebo-treated animals. In comparative dose-response titrations, the relative potency of 2'NDG to acyclovir was 6.4, which was significant. In addition, soluble ophthalmic inserts were developed for delivery of 2'NDG. Once a day treatment using ophthalmic inserts which released 100 micrograms 2'NDG significantly enhanced corneal and conjunctival healing and prevented stromal disease; 2'NDG eye drops (100 micrograms) delivered once a day were also effective in inhibiting the progression of corneal lesions. These results indicate that 2'NDG may be therapeutically effective in treatment of herpes keratitis, and further suggest that for use as eye drops or in an ophthalmic insert, 2'NDG may be effective even if applied once per day.     

Review of ocular drug delivery

Successful treatment of eye diseases requires effective concentration of drug at the eye for sufficient period of time. Conventional ocular drug delivery including eye drops, systemic administration, ophthalmic ointments, is no longer sufficient to combat ocular diseases. This article reviews the constraints with conventional ocular therapy, and explores various novel approaches, to improve the ocular bioavailability of drugs to the anterior chamber of the eye.     

托吡卡胺滴眼液防治青少年假性近视效果分析

目的 观察托吡卡胺滴眼液防治青少年假性近视的效果,探讨其临床价值.方法 回顾性分析68例(136只眼)青少年假性近视患者资料,观察应用托吡卡胺滴眼液的验光情况及治疗前后裸眼视力变化.结果 托吡卡胺滴眼液不同滴眼间隔(间隔1 min或间隔5min)散瞳效果差异无统计学意义(P＞0.05),且滴眼间隔不同的假性近视青少年第一次复光的屈光度检查差异无统计学意义(P＞0.05);治疗前、治疗后1周散瞳验光裸眼远视力差异有统计学意义(x2=16.3308,P=0.000969964);治疗1周、治疗4周散瞳光情况差异有统计学意义(x2=50.2750,P=6.98115 × 10-11).结论 0.25％托吡卡胺滴眼液间隔1 min、5 min滴眼散瞳效果满意.托吡卡胺短期内使用能够有效解除青少年假性近视的调节痉挛和调节麻痹现象,而且无明显药物不良反应,具有临床使用价值.     

Formulation and in vivo evaluation of ocular insert containing phenylephrine and tropicamide.

A Gelfoam based ocular device containing 1.7 mg of phenylephrine and 0.6 mg of tropicamide was formulated and evaluated for pupillary dilation in rabbits. The manufacturing procedure is fairly simple and the required excipients are inexpensive. The in vivo results show that the mydriatic response produced by the proposed device is larger and longer lasting than that produced by eyedrops with an equivalent amount of phenylephrine and tropicamide. The results reported in this study, along with those of previous studies, imply that Gelfoam(R) is a versatile drug carrier for either local or systemic drug delivery via the ophthalmic route. Copyright     

Ion-activated, Gelrite-based in situ ophthalmic gels of pefloxacin mesylate: comparison with conventional eye drops

The purpose of our work was to develop an ophthalmic delivery system of a flouroquinolone antibiotic, pefloxacin mesylate, based on the concept of ion-activated in situ gelation. Gelrite gellan gum, a novel ophthalmic vehicle, that gels in the presence of mono- or divalent-cations present in the lacrimal fluid, was used as the gelling agent. The developed formulation was compared with marketed eye drops in efficacy of treatment of bacterial conjunctivitis that was induced artificially in rabbits. The formulations were evaluated for rheological characteristics, in vitro release behavior, antimicrobial efficacy, and efficacy against bacterial conjunctivitis.We found that in situ gelling formulations passed the test for sterility. The formulations exhibited a first-order release pattern over 12 hr in in vitro release studies. The developed formulation was effective against selected micro-organisms in antimicrobial efficacy studies. The shelf lives of formulation was >2 years. The formulation demonstrated better therapeutic efficacy compared with standard eye drops because it improved the clinical parameters monitored for prolonged periods. The developed formulations can be considered as a viable alternative to conventional eye drops.     

A review of implantable intravitreal drug delivery technologies for the treatment of posterior segment eye diseases

Intravitreal implantable device technology utilizes engineered materials or devices that could revolutionize the treatment of posterior segment eye diseases by affording localized drug delivery, responding to and interacting with target sites to induce physiological responses while minimizing side‐effects. Conventional ophthalmic drug delivery systems such as topical eye‐drops, systemic drug administration or direct intravitreal injections do not provide adequate therapeutic drug concentrations that are essential for efficient recovery in posterior segment eye disease, due to limitations posed by the restrictive blood‐ocular barriers. This review focuses on various aspects of intravitreal drug delivery such as the impediment of the blood‐ocular barriers, the potential sites or intraocular drug delivery device implantation, the various approaches employed for ophthalmic drug delivery and includes a concise critical incursion into specialized intravitreal implantable technologies for the treatment of anterior and posterior segment eye disease. In addition, pertinent future challenges and opportunities in the development of intravitreal implantable devices is discussed and explores their application in clinical ophthalmic science to develop innovative therapeutic modalities for the treatment of various posterior segment eye diseases. The inherent structural and functional properties, the potential for providing rate‐modulated drug delivery to the posterior segment of the eye and specific development issues relating to various intravitreal implantable drug delivery devices are also expressed in this review. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2219–2239, 2010