Ocular distribution, bactericidal activity and settling characteristics of TobraDex® ST ophthalmic suspension compared with TobraDex® ophthalmic suspension

Introduction

TobraDex® ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.1%; Alcon Laboratories Inc, Fort Worth, Tex) is frequently used for inflammatory ocular conditions where a risk of bacterial ocular infection exists. A new formulation, TobraDex® ST ophthalmic suspension (tobramycin 0.3%, dexamethasone 0.05%, Alcon), utilises a novel suspension technology to reduce viscosity and help prevent settling in the container.

Methods

A rabbit model that closely mimics the human eye and a clinical study with cataract patients was used to compare the pharmacokinetics and tissue permeability of TobraDex ST and TobraDex. An in-vitro model was used to assess the bactericidal activity using the rabbit tear concentrations of tobramycin 10 minutes after a single topical dose.

Results

Concentrations of both tobramycin and dexamethasone were greater in the tear film and ocular tissues of rabbits treated with TobraDex ST. There was an 8.3-fold increase in tobramycin concentration in the rabbit tear film 10 minutes after dosing with TobraDex ST compared with TobraDex. Concentrations of tobramycin and dexamethasone in ocular tissues from rabbits exposed to TobraDex ST were up to 12.5-fold greater relative to TobraDex. The in-vitro bactericidal activity (>99.9% kill, 3-log reduction) of TobraDex ST toward tobramycin-resistant and methicillin-resistant Staphylococcus aureus occurred in 90 minutes. TobraDex ST killed Streptococcus pneumoniae 3-log in 5 minutes. TobraDex had no activity toward tobramycin-resistant, methicillin-resistant S. aureus and required approximately 120 minutes for 3-log reduction of S. pneumoniae. In humans, the mean ratio of dexamethasone levels in the aqueous humour at 1 hour was 1.17 in favour of TobraDex ST.

Conclusion

TobraDex ST demonstrated improved suspension formulation characteristics, enhanced pharmacokinetic distribution and improved bactericidal characteristics, and may provide a useful alternative as compared to TobraDex.     

Reflux of Drug During Intra-vitreal Anti-VEGF Therapies

Purpose: To report reflux of anti-VEGF drug during intravitreal injections.

Method: Review of electronic case notes of patients undergoing intra-vitreal anti-VEGF treatments. Prospective data collection was performed with a specific emphasis on presence or absence of reflux.

Results: 152 records of 102 eyes were available from an 8-month period. 119 Ranibizumab injections and 33 bevazicumab injections were considered.

Reflux was noted in 48 injections (31%). For eyes with first injection of anti-VEGF agent, reflux was noted in 9/23 eyes. Eyes with at least one previous injection were observed to have reflux in 24/79 eyes.

Presence of reflux was statistically tested against posterior vitreous detachment and phakic status and was found to be statistically insignificant.

Conclusion: Intra-vitreal anti-VEGF injections with volumes of 0.05?ml appears to produce displacement of the conjunctiva with a transient fluid-filled bleb immediately after the injection in approximately 1/3 of eyes.     

Long-Term Visual Function and Relative Amblyopia in Posterior Persistent Hyperplastic Primary Vitreous (PHPV)

Background: Favorable results in the management of PHPV, made possible by improved surgical techniques, are described in the literature. However, the functional results are in general in the low-vision sector (rarely better than 0.025–0.1 maximum). Purpose: To introduce long-term acuity results and estimate the relative amblyopia in early operated PHPV. Material and Methods: Six patients suffering from PHPV of varying degrees (posterior polar cataract, posterior lenticonus, traction and malformation of the optic nerve head and macula region, persistent vitreous vessels) underwent pleoptic treatment after surgery (lentectomy in all, additional stalk-cutting in three cases) at the age of 3 to 7 months. The patients were followed up to age 7 to 12 years. Visual acuity was assessed by Landolt ring single and closely interspaced linear optotypes (C-Test developed by Haase/Hohmann). Results: Compliance with the amblyopia treatment was good in five patients. Visual acuity (VA) improvement in the affected eye could be seen up to early school age (6–8 years). Final VA outcome was 0.1 (minimum) to 0.7 (maximum) with single optotypes. VA for crowded optotypes was maximum 1 octave below single optotype VA. The visual development of the phakic eye was not delayed, i.e. not disturbed by long-term patching. Discussion: Compliance with amblyopia treatment and long-term visual acuity in the cases presented here are even more favorable than described in the literature. As the amount of crowding is small, we conclude that there is little relative (additional) amblyopia and that the functional outcome is limited only by the degree of ocular malformation. Surgical treatment in comparable cases is encouraged.     

Risk Factors for Postoperative Hemorrhage after Vitrectomy for Diabetic Retinopathy

Objective: To identify the potential risk factors for postvitrectomy diabetic vitreous hemorrhage (PDVH). Methods: A matched case-control nested into a retrospective follow-up study was done to review the surgical results in 68 consecutive eyes undergoing primary pars plana vitrectomy for vitreous hemorrhage. The eyes were divided into two groups based on the presence of PDVH (19 cases and 49 controls) and were matched on surgeon and the date of surgery. Twenty-three factors related to the preoperative examination and eight factors related to the operative procedure were analyzed. Statistical analysis was based on conditional logistic regression models with PDVH as the dependent variable. The mean follow-up interval was six months. Results: The factors associated with the incidence of PDVH were iris neovascularization (OR = 9.8, P = 0.03), lower extremity amputations (OR = 8.3, P = 0.02) and the use of antihypertensive agents within three months before vitrectomy (OR = 0.2, P = 0.04). Phakic and aphakic eyes of diabetic patients with lower extremity amputations would have a 70% probability of developing PDVH. This probability would have dropped to 30–40% had they been taking antihypertensive treatment. Conclusions: Iris neovascularization and lower extremity amputations increase the risk of PDVH. Antihypertensive treatment before vitrectomy decreases this risk.     

Vitreous Proteomics and Diabetic Retinopathy

Diabetic retinopathy is the major cause of acquired blindness in working-age adults. Studies of the vitreous proteome have provided insights into the etiology of diabetic retinopathy and suggested potential molecular targets for treatments. Further characterization of the protein changes associated with the progression of this disease may suggest additional therapeutic approaches as well as reveal novel factors that may be useful in predicting risk and functional outcomes of interventional therapies. This article provides an overview of the various techniques used for proteomic analysis of the vitreous and details results from various studies evaluating vitreous of diabetic patients using the proteomic approach.     

Unilateral Uveitis with Vitreous Haze Following Zoledronic Acid Therapy for Osteoporosis

ABSTRACT

Zoledronic acid is widely used in the treatment of osteoporosis and other bone diseases. However, patients may experience adverse effects involving the anterior segment of the eye following intravenous infusion. This paper reports a rare case of uveitis involving the vitreous cavity following the intravenous administration of zoledronic acid.     

自拟消瘀汤治疗玻璃体积血的疗效观察

目的观察自拟消瘀汤治疗玻璃体积血的疗效。方法中等量玻璃体积血患者31例（33只眼），随机分为对照组15例（17只眼）和治疗组16例（16只眼）。对照组予以常规西药治疗，治疗组予以自拟消淤汤配合常规西药治疗。结果治疗3个月后，治疗组16只眼中，痊愈12只眼，显效0只眼，有效3只眼，无效1只眼，总有效率93．75％：对照组17只眼中，痊愈7只眼，显效0只眼，有效4只眼，无效6只眼，总有效率64．71％，2组差异有统计学意义（X^2=4．16，P〈0．05）。治疗后1～6个月，治疗组每个月的痊愈眼数分别为2、8、12、14、14、14只眼；对照组每个月的痊愈眼数分别为1、4、7、8、8、8只眼。结论自拟消瘀汤治疗玻璃体积血有较好疗效，且能缩短病程。减轻患者痛苦。     

白内障囊外摘除人工晶体植入术后囊破裂和玻璃体脱出的临床分析

目的：分析现代白内障囊外摘出人工晶体植入术中后囊破裂和玻璃体脱出的原因。方法：对230例白内障实放白内障囊外摘除人工晶体植入术，总结其中后囊破裂及玻璃体脱出的原因。结果：术中后囊破裂19眼（8.2%)，均合并玻璃体脱出。10眼直接植入后房型人工晶体。9眼行后房型人工晶体缝线固定。结论：只要掌握其易发因素。提高手术技巧。后囊破裂及玻璃体脱出绝大多数可以避免。     

Vitreous intercellular adhesion molecule 1 in uveitis complicated by retinal detachment

AIMS—The vitreous levels of soluble intercellular adhesion molecule 1 (sICAM-1) were investigated in uveitic eyes undergoing vitrectomy for retinal detachment (RD) or other complications, and the presence of this molecule was related to disease activity and vitreous levels of the cytokine tumour necrosis factor α (TNFα), known to upregulate ICAM-1 expression on various cells.
METHODS—Vitreous and serum samples from 23 patients with either active or quiescent uveitis undergoing retinal surgery were examined for the levels of immunoreactive sICAM-1 and TNFα by ELISA methods, and for the presence of biologically active TNFα. Vitreous from non-uveitic eyes with rhegmatogenous retinal detachment (RRD), macular holes or cadaveric eyes were used as controls.
RESULTS—As a whole, vitreous from uveitic eyes complicated or uncomplicated by RRD contained significantly higher levels of sICAM-1 than vitreous from non-uveitic eyes with RRD alone (p < 0.0005), eyes with macular holes (p< 0.0001), or normal cadaveric vitreous (p < 0.0001). The proportion of vitreous containing >20 ng/ml sICAM-1 (> four times the normal values) was significantly higher in eyes with uveitis complicated by RRD than in those eyes without RRD (Fisher's test, p= 0.02), and although levels of sICAM-1 were higher in eyes with active uveitis than in those with quiet disease (p < 0.02), this could not be dissociated from the increase caused by RRD. There was a relation between the vitreous levels of sICAM-1 and those of immunoreactive TNFα (Spearman's correlation coefficient; r = 0.601, p = 0.006), but not between the vitreous levels of sICAM-1 and those of biologically active TNFα.
CONCLUSION—Increased vitreous sICAM-1 levels and the association of this molecule with the presence of immunoreactive TNFα in uveitic eyes confirm the operation of cytokine mediated vascular reactions at the blood-retinal barrier during the development of this condition. The persistence of high vitreous levels of sICAM-1 in eyes with uveitis complicated by RRD despite previous immunosuppression may indicate a low rate of clearance of inflammatory molecules from the vitreous cavity and an exacerbation of the existing inflammatory process by the retinal detachment itself.

Keywords: vitreous; retinal detachment; ICAM-1; TNFα; uveitis     

结膜下给药兔眼玻璃体内维拉帕米的药代动力学研究

目的 :研究结膜下给药兔眼玻璃体内维拉帕米 (Verapamil,Ver)的药代动力学参数。方法 :制备外伤性PVR动物模型 ,结膜下注射 1 2 5mg/0 5mlVer,按时抽取玻璃体样品。样品经提取、浓缩处理后 ,采用美国HP10 5 0HPLC系统测定样品中Ver的浓度 ,计算其药代动力学参数。结果 :结膜下注射Ver后 ,吸收半衰期t1/2(Ka) =(0 5 4± 0 16 )h ,达到峰浓度的时间T(peak) =(2 10± 0 84 )h ,峰浓度Cmax =(17 6 5± 4 6 4 ) μg/ml,消除半衰期t1/2 (Ke) =(7 2 9± 1 4 6 )h ,药 时曲线下面积AUC =(2 0 8 0 7± 4 0 2 2 ) μg/(ml·h)。 结论 :结膜下注射Ver可以进入玻璃体并能达到有效治疗浓度 ,为结膜下注射Ver防治PVR提供了理论依据。