Comparison of posterior capsule opacification in rabbit eyes receiving different administrations of rapamycin

Background

Posterior capsule opacification (PCO) is a common complication after cataract surgery. The purpose of this study was to determine the effects of three administering ways of rapamycin (RAPA) on the formation of PCO in rabbit eyes for 12 weeks.

Methods

Eighty rabbits were divided into four groups, according to the different administrations of RAPA which they received. These were: (1) the control group, (2) the irrigation-treated group — 5 ng/ml intraoperative RAPA irrigation solution, (3) the eye-drop-treated group — 2 mg/ml RAPA eye drops, and (4) the IOL-treated group — RAPA–poly(lactic-co-glycolic) acid (PLGA) loaded on the surface of intraocular lens (IOLs) (RAPA-PLGA-IOLs). All right eyes were treated with lens extraction plus IOL implantation, receiving relative administrations of RAPA. RAPA concentrations in the aqueous humour were determined by high performance of liquid chromatography (HPLC). The anterior chamber (AC) response was observed through slit-lamp biomicroscopy. After 12 weeks, the degree of PCO was determined by clinical evaluation. The histological sections, immunohistochemistry expression of proliferating cell nuclear antigen (PCNA) in the lens capsule were conducted.

Results

In the early period, AC response for both experimental and control eyes were similar. In the IOL-treated group, RAPA reached its peak at 25.68?±?0.74 μg/ml on the 4th day, and it was detectable until 8 weeks afterwards. However, in the other groups, RAPA could not be detected all the time. Compared with other groups, in the IOL-treated group, PCO was greatly alleviated; only a few layers of the lens epithelial cells (LECs) and a little proliferative material around the posterior capsules, and a significantly weak expression of PCNA in the nuclei of LECs. By contrast, there was no significant statistical difference in eye-drop-treated or irrigation-treated eyes and control eyes respectively.

Conclusions

Intraocular RAPA-PLGA-IOL was a promising, effective, and safe administration to prevent PCO compared with other methods in the rabbit PCO model.     

Selenium functionalized intraocular lenses inhibit posterior capsule opacification in an ex vivo canine lens capsular bag assay

The purpose of this study was to determine the inhibitory effect of selenocystamine coated intraocular lenses (IOLs) on the formation of posterior capsule opacification (PCO) in an ex vivo canine lens capsular bag assay. Selenocystamine was covalently bound to the surface of poly(2-hydroxyethyl methacrylate) (poly(HEMA)) discs. Three groups of canine lens capsules (6 coated IOLs (SeIOLs), 7 non-coated control IOLs and 8 empty capsules) were cultured for 10 days. During the culture period PCO was scored based on visual inspection of the capsules using phase contrast microscopy. On day 10 all the capsules were prepared for light microscopic examination and lens epithelial cells (LECs) were quantified. Proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (α-SMA) and cleaved caspase-3 were examined by immunohistochemistry. Additionally, cell viability assays were performed on LECs cultured in tissue culture medium pre-incubated with either a SeIOL or control IOL. The viability assays demonstrated that no detectable cytotoxic leachables were associated with the functionalized IOLs. The central posterior capsule was free of cells underneath all SeIOLs, although large numbers of LECs populated the capsular periphery. Apoptotic cells were observed underneath the periphery of some SeIOLs. Both the PCO scores and LEC counts of SeIOL containing capsules were significantly lower than those of control group capsules (p < 0.01 and p = 0.0004, respectively).The use of selenium functionalized IOLs resulted in a significant reduction of PCO in this ex vivo model. Binding of selenocystamine to a foldable IOL may provide an effective method to prevent population of the central posterior capsule with LECs.     

Uveal and capsular biocompatibility of two foldable acrylic intraocular lenses in patients with endogenous uveitis — a prospective randomized study

Background  To compare a hydrophobic and a hydrophilic acrylic single-piece intraocular lens (IOL) in uveitis patients with respect to biocompatibility and visual outcome. Methods  Prospective, randomized study in patients with noninfectious uveitis after phacoemulsification and implantation of either a hydrophobic AcrySof™ (group 1, n = 30) or a hydrophilic Akreos adapt™ (group 2, n = 30), sharp-edged acrylic IOL. The primary outcome was uveal biocompatibility, detected by giant-cell deposition, anterior chamber cell count and laserflare photometry over a 6-month follow-up period. Secondary outcome measures were capsular biocompatibility, as detected by posterior capsule opacification (PCO), lens epithelial cell outgrowth and Nd:YAG capsulotomies, and visual outcome. Results  The groups did not differ with respect to anatomic type of uveitis, immunosuppressive treatment, associated systemic disease, and intraoperative manipulation. The number of giant cells on the anterior IOL surface was higher in group 1 than in group 2 (p = 0.03). The number of anterior chamber cells, laser flare photometry levels, and uveitis reactivations after surgery did not differ between the groups. After 6 months, the number of patients with PCO development (p = 1.0) and Nd:YAG capsulotomies (p = 0.21), lens epithelial cell outgrowth, visual outcome and uveitis complications were comparable in both groups. Conclusions  Both of the acrylic IOLs used had good uveal and capsular biocompatibility, leading to significant improvement in BCVA in patients with noninfectious uveitis. No obvious differences were detected at 6 months with respect to uveal and capsular biocompatibility and visual outcome. The authors have no financial interest in any of the materials used in this study.     

兔晶状体上皮细胞和人成纤维细胞在雷帕霉素涂层人工晶状体表面的生长

目的:研究兔晶状体上皮细胞和人胚肺成纤维细胞在雷帕霉素联合可降解高分子材料PLGA涂层的人工晶状体表面的生长分布状况,为将雷帕霉素涂层人工晶状体植入体内抑制后发性白内障奠定基础。方法:采用专利技术将雷帕霉素联合PLGA或单独PLGA作为对照组喷涂至人工晶状体光学区的外围,制备出药物涂层人工晶状体。将兔晶状体上皮细胞和人胚肺成纤维细胞悬液(3×105)分别接种于人工晶状体的表面,雷帕霉素+PLGA涂层人工晶状体组(与兔晶状体上皮细胞同培养的为A组,与人胚肺成纤维细胞共培养的为a组),高分子材料PLGA组(B和b),普通人工晶状体组(C和c),对人工晶状体表面不同区域细胞的分布疏密程度进行分级,应用MTT法对人工晶状体表面的细胞数量进行间接计数。结果:雷帕霉素+PLGA或PLGA能够均匀地喷涂在人工晶状体的外周,无涂层的开裂。无论是直接通过相差显微镜下对细胞分布疏密进行分级还是MTT法间接计数活细胞数量,两种细胞在6组人工晶状体表面分布不同,A和a组细胞数量明显减少,与其它组相比具有统计学意义(P<0.05),B、b、C和c组相比细胞数量无统计学差异。各涂层人工晶状体表面涂层区和非涂层区域细胞分布无明显差别,差异无统计学意义(P>0.05)。结论:将高分子缓释材料PLGA联合抗增殖药物雷帕霉素涂层至人工晶状体的外周制备出生物相容性佳的涂层人工晶状体,起到抑制兔晶状体上皮细胞和人胚肺成纤维细胞生长的作用,有望成为能够抑制后发性白内障发生的新型人工晶状体。     

Retinal toxicity of triamcinolone’s vehicle (benzyl alcohol): an electrophysiologic and electron microscopic study

Purpose To assess retinal toxicity of the vehicle of triamcinolone, benzyl alcohol (BA), when injected into the vitreous cavity of rabbits. Methods This prospective comparative experimental study included 24 pigmented rabbits assigned into two groups: group 1 (experimental, n = 12) received intravitreal 0.1 ml of BA, and group 2 (control, n = 12) received intravitreal 0.1 ml of balanced salt solution (BSS); all injections were done in the right eyes. Clinical examinations [slit lamp biomicroscopy, indirect ophthalmoloscopy, and three intraocular pressure (IOP) measurements] were done on both eyes before injection, at 1 and 3 h post injection, together with electroretinograms (ERGs) at 3 days, 1, 2, 4, and 6 weeks following injections. Three rabbits from each group were euthanased at 1, 2, 4, or 6 weeks and eyes were sent for light and electron microscopic examination for quantitative morphometric measurements. Results The mean amplitudes of the a and b waves of the BA-injected eyes were 6.42 ± 9.02 μv and 11.18 ± 15.18 μv at 3 days, respectively, which were significantly reduced compared with the BSS-injected eyes (30.87 ± 8.22 μv and 57.90 ± 13.38 μv, respectively; P < 0.01 t-test) and the non-injected contralateral eyes (36.20 ± 7.85 μv and 64.10 ± 9.36 μv, respectively; P < 0.01 t-test). These ERG responses continued to be significantly reduced in the BA-injected eyes (P < 0.01 t-test) throughout the study period. The mean ganglion cell count was significantly reduced (P < 0.005 t-test) in the BA-injected eyes (8.42 ± 2.4) compared with the BSS- and non-injected eyes (16.42 ± 3.9 and 16.5 ± 4.2, respectively). The mean thicknesses of the inner nuclear layer (INL) and outer nuclear layer (ONL) were significantly reduced (P < 0.005 t-test) in the BA-injected eyes (3.78 ± 0.96 μm and 11.77 ± 1.29 μm, respectively) compared with the BSS- (6.1 ± 0.92 μm and 21.82 ± 0.95 μm, respectively) and non-injected eyes (7.05 ± 1.9 μm and 22.49 ± 1.01 μm, respectively). Electron microscopy showed moderate to severe intracellular changes in the ganglion cell layer, INL, ONL, and photoreceptor layer at 6 weeks in BA-injected eyes, with no significant changes in BSS-injected eye. There was no significant rise in the IOP or clinical evidence of increased lens density during the study period in any of the eyes. Conclusions Triamcinolone acetonide’s vehicle, BA, produced severe ERG and structural damage to the retina when injected intravitreally.     

Ocular penetration of caspofungin in a rabbit uveitis model

Background Little is known about the ocular penetration of echinocandin antifungals. We studied the ocular distribution of systemically administered caspofungin in a rabbit uveitis model. Methods Caspofungin (1 mg/kg per day) was given intravenously to rabbits as a single dose or as repeated daily doses on 7 days starting 24 h after induction of unilateral uveitis by intravitreal endotoxin injection. Caspofungin concentrations were determined by high-performance liquid chromatography in the cornea, aqueous humor, vitreous humor, and serum 4, 8, 16, and 24 h after administration of a single dose and 24 h after the last of seven doses. Results The mean caspofungin concentration in the aqueous of the inflamed eye 4 and 8 h after single-dose administration was 1.30 ± 0.39 μg/ml and 1.12 ± 0.34 μg/ml, respectively. Drug concentrations decreased to 0.24 ± 0.09 μg/ml at 16 h and 0.26 ± 0.14 μg/ml at 24 h. In the vitreous of inflamed eyes drug levels were undetectable at all time points. No drug was found in the aqueous of inflamed eyes 24 h after the last of seven repeated doses, and the vitreous only contained trace amounts. In the corneas of inflamed eyes concentrations reached 1.64 ± 0.48 μg/g at 4 h, peaked at 2.16 ± 1.14 μg/g at 8 h, and declined to 1.87 ± 0.52 μg/g and 1.49 ± 0.48 μg/g at 16 and 24 h, respectively. After repeated dosing, corneal concentrations of caspofungin were 0.8 and 1.0 μg/g and below the limit of detection in two of four animals. In non-inflamed eyes no drug was detectable in the aqueous and vitreous humor, and the corneas at any time point. Conclusions In our model, caspofungin reached therapeutically relevant levels in the aqueous and cornea but not in the vitreous humor of inflamed eyes. Intraocular drug deposition was critically dependent on a disrupted blood-eye barrier. These findings suggest a limited role for caspofungin in the treatment of fungal endophthalmitis. This study was supported in part by an independent research grant from Merck & Co., Inc., Switzerland. S.Z. has received additional independent research grants and drugs from the same organisation which had no influence on the design of the present study, the data analysis and the interpretation of results. We the authors have full control of all primary data and we agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review our data upon request.     

Correction of high myopia with different phakic anterior chamber intraocular lenses: ICARE angle-supported lens and Verisyse iris-claw lens

Purpose To evaluate the efficacy, predictability and safety of implanting two models of anterior chamber IOLs for high myopia. Comparison of the refractive results between two groups of patients implanted with different IOLs.Materials and methods Forty eyes were implanted with phakic IOLs. The ICARE myopia lens was implanted in 20 eyes of 12 patients with preoperative myopia that ranged from −21.875 to −10.0. The mean patients‘ age was 30 years. The Verisyse IOL was implanted in 20 eyes of 12 patients with spherical equivalent of the refractive error from −21.625 to −10.375D, and the mean patients’ age was 32.25 years. The dioptric power of the intraocular lens was calculated by considering refraction, keratometry, and anterior chamber depth. The follow-up period was 12 months.Results Twelve months after surgery, the mean refractive error (SE) was −0.19D (100% of eyes were within ±1.0D of the target refraction) in the ICARE group, and −0.86D (95% of eyes were within ±1.0D of the target refraction) in the Verisyse group. The postoperative refraction remained stable during the entire follow-up period. The mean uncorrected visual acuity was 0.7 in the ICARE group, and 0.69 in the Verisyse group 1 year postoperatively. There was no loss in visual acuity 1 year after surgery in the ICARE implanted eyes, one patient in the Verisyse group lost 1 line of BCVA as compared to the preoperative state. Mean endothelial cell density loss was 6.12% and 6.79% in the ICARE and Verisyse groups, respectively. There were no statistically significant differences regarding the analyzed outcome parameters between the two study groups.Conclusion The implantation of both anterior chamber phakic intraocular lenses to correct high myopia resulted in a stable and predictable refractive outcome. Efficacy and safety of surgery for both implanted lens models are very high.This material was previously presented at the American Academy of Ophthalmology Annual Meeting in New Orleans, October 2004.The authors have no financial interest in this study. This was prospective randomized clinical trial.     

The effect of contact lens-induced corneal edema on Goldmann applanation tonometry and dynamic contour tonometry

Purpose  To evaluate the effect of contact lens-induced corneal edema on intraocular pressure (IOP) measurements using Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT) in Asian subjects. Participants  The study included 40 eyes of 20 normal volunteers with no evidence of ocular disease. Methods  Forty eyes of 20 healthy volunteers were required to wear soft contact lenses for 2 hours to induce corneal swelling. Central corneal thickness (CCT) and IOP were measured before and immediately after contact lens wear using specular microscope, GAT, and DCT. The IOP measurements by GAT and DCT were compared. The changes in the CCT and the IOP measurements after wearing contact lenses were assessed. Results  The mean CCT of the 40 eyes evaluated was 532.6 ± 31.6 μm. The mean IOP was 11.78 ± 2.04 mmHg for the GAT and 14.46 ± 1.89 mmHg for the DCT, and the difference was statistically significant (P < 0.001). After wearing contact lenses, the mean CCT was 553.2 ± 34.3 μm, which was 20.6 ± 12.9 μm greater than before wearing them (P < 0.001). The mean IOP measurements of the GAT and DCT were decreased after wearing the contact lenses. The mean decrease of the GAT values was 0.43 ± 1.95 mmHg, which was not statistically significant (P = 0.175). However, the mean decrease of the DCT readings, which was 0.75 ± 1.74 mm Hg, was statistically significant (P = 0.010). Conclusion  The IOP measurements with DCT were significantly higher than those with GAT in healthy Asian eyes. Although the mean IOP measurements of both the GAT and the DCT were decreased in the edematous cornea, IOP measurements of the DCT were more affected by corneal edema than were the GAT. The authors have no proprietary, commercial, or financial interests in any of the products described in this study.     

Intravitreal bevacizumab for refractory choroidal neovascularization (CNV) secondary to uveitis

Purpose  To assess the short-term efficacy and safety of intravitreal bevacizumab injections (IVB) for refractory choroidal neovascularization (CNV) secondary to uveitis. Methods  Ten patients affected by choroidal neovascularization secondary to uveitis unresponsive to immunosuppression associated or not with photodynamic therapy (PDT) were consecutively included. All patients underwent a complete ophthalmic examination including best-corrected visual acuity (BCVA), fluorescein (FA) and indocyanine green angiographies (ICG), optical coherence tomography (OCT) at baseline, and after IVB injection (1.25 mg/0.05 ml). Results  CNV was subfoveal in eight cases and juxtafoveal in two cases. Mean follow-up was 7.5 months. After treatment, the logMAR BCVA improved from 0.62 ± 0.4 (Snellen equivalent of 20/55) to 0.45 ± 0.35 (Snellen equivalent of 20/40) at 1 month (p = 0.01), then remained stable during the follow-up. Mean central macular thickness (CMT) was reduced from 326 ± 95 μm before treatment to 267 ± 28 μm (p = 0.03) at last visit. Mean number of IVB was 2.5. Leakage from inflammatory CNV was stopped in three eyes and decreased in seven eyes. No systemic or ocular adverse events were recorded. Conclusions  Intravitreal bevacizumab improves BCVA and reduces central macular thickness in eyes with inflammatory CNV refractory to immunosuppression associated or not with PDT. Further study is necessary to assess the efficacy and safety in the long term. None of the authors has any financial interest in this study. The authors have full control of all primary data and agree to allow Graefe’s Archive for Clinical and Experimental Opthalmology to review the data if requested.     

5-Fu纳米粒涂层人工晶状体抑制兔晶状体后囊膜混浊的实验研究

目的 制备5-Fu纳米粒涂层人工晶状体(IOL)并探讨其对兔晶状体后囊膜混浊的抑制作用的有效性和可行性.方法 通过低能离子束表面氟离子注入技术使5-Fu纳米粒与IOL表面交联黏附形成涂层.取新西兰大白兔40只,随机分为A、B两组,每组20只,对左眼行超声乳化透明晶状体吸出术,对照组为A组,植入普通IOL;实验组为B组,植入5-Fu纳米粒涂层IOL.术后行裂隙灯显微镜、组织病理学及电镜检查.所有数据用SAS统计软件处理,前房闪光和晶状体后囊膜中央视区混浊程度均用Kruskal-Wallis秩和检验进行分析.结果 前房炎性反应:B组的前房闪光轻于A组,差异有统计学意义(x~2=11.245,P=0.024).两组兔眼的前房反应均在术后3 d至1周内缓解.晶状体后囊膜混浊:B组晶状体后囊膜的混浊程度轻于A组,差异有统计学意义(x~2=10.304,P=0.016).光学显微镜行组织病理学检查:A组眼内炎性反应较轻,B组无明显眼内炎性反应表现,A、B两组角巩缘结构及组织均无病理损害.扫描电子显微镜检查:A组见晶状体上皮细胞增生现象,B组未见明显晶状体上皮细胞增生.结论 兔眼透明晶状体超声乳化吸出术后植入5-Fu纳米粒涂层IOL,可有效抑制晶状体后囊膜混浊的发生,眼内毒性较小.