Evaluation of toxicity of intravitreal ceftazidime, vancomycin, and ganciclovir in a silicone oil-filled eye

PURPOSE: To evaluate the toxicity of intravitreal drugs in an eye filled with silicone oil for prolonged internal retinal tamponade. METHODS: Vitrectomy was performed in 21 rabbit eyes, and the vitreous was replaced with silicone oil. Different concentrations of various drugs (ceftazidime, vancomycin, and ganciclovir) were injected intravitreally. RESULTS: Silicone oil increased the toxicity of these drugs, which were injected in previously determined nontoxic doses, possibly because of a reduction of the preretinal space. Injecting one quarter of the known nontoxic dose failed to show any toxicity. CONCLUSIONS: Nontoxic concentrations of intravitreal drugs can cause toxicity in a silicone-filled eye.     

Rituximab penetrates full-thickness retina in contrast to tissue plasminogen activator control

PURPOSE: To assess whether intravitreal rituximab 1 mg/0.1 cc penetrates the retina of Dutch-belted rabbits. METHODS: Two right eyes of two rabbits were injected with intravitreal rituximab 1 mg/0.1 mL, and one right eye of one rabbit was injected with intravitreal tissue plasminogen activator (tPA) 12.5 microg/0.1 mL, as a protein control. The three left eyes received no intravitreal injections. The rabbits were killed; the eyes were enucleated and immediately frozen at -80 degrees C. Rituximab was detected using rabbit antihuman IgG (whole molecule) peroxidase conjugated antibody. tPA was detected using an antihuman IgG with a sheep antihuman tPA antibody conjugated with peroxidase. RESULTS: There was staining in all retinal layers of the two eyes injected with intravitreal rituximab, and no staining of the retina in the eye injected with intravitreal tPA. The three control eyes showed no staining in any retinal layer. CONCLUSION: Intravitreal rituximab at a dose of 1 mg/0.1 cc penetrates the retina of Dutch-belted rabbits while the control intravitreal tPA at a dose of 12.5 microg/0.1 cc does not.     

Use of Perfluorocarbon Liquids, Silicone Oil, and 5-Fluorouracil in the Management of Experimental PVR

Purpose: To evaluate the toxicity and efficacy of 5-fluorouracil (5-FU) in combination with perfluoroperhydrophenanthrene (Vitreon), silicone oil, or a combination of silicone oil and Vitreon in a ratio of 3:2 in the management of experimental proliferative vitreoretinopathy (PVR). Methods: Toxicity study. Seventy rabbit eyes underwent vitrectomy followed by intravitreal injection of 5-FU in doses of 800, 400, or 200 μg: Group 1, 5-FU alone; Group 2, 5-FU plus 1 mL Vitreon; Group 3, 5-FU plus 1 mL silicone oil; Group 4, 5-FU plus 0.6 mL silicone oil and 0.4 mL Vitreon; Group 5, 0.6 mL silicone oil plus 0.4 mL Vitreon. Electroretinography was performed preoperatively and 8 weeks postoperatively before the animals were sacrificed. Efficacy study. Seventy-two rabbit eyes underwent vitrectomy and were injected intravitreally with 100,000–200,000 retinal pigment epithelial cells to induce PVR. Groups were injected with 200 μg 5-FU alone or with 1 mL silicone oil, 1 mL Vitreon, or a combination of 0.6 mL silicone oil and 0.4 mL Vitreon. Others were given only 1 mL Vitreon or 1 mL silicone oil. The animals were followed for 8–12 weeks; PVR was graded using Fastenberg's system. Results: Toxicity study. Eyes given 200 μg 5-FU, silicone, and Vitreon showed mild inflammation and vitritis which resolved in 1 week; the dose was nontoxic by electroretinography and histopathology. Doses of 400 and 800 μg 5-FU were toxic. Efficacy study. Clinical severity of PVR was less in the groups which received 5-FU plus vitreous substitutes when compared to the control groups at all time points. The lowest incidences were in groups given 5-FU plus Vitreon or 5-FU plus Vitreon and silicone oil: 33.33% and 11.11%, respectively. Conclusions: A dose of 200 μg 5-FU with silicone oil and Vitreon combined was nontoxic to the rabbit retina. The combination of 5-FU, Vitreon, and silicone oil showed significant efficacy in the prevention of experimental PVR. This revised version was published online in July 2006 with corrections to the Cover Date.     

药物辅助下玻璃体切除术治疗增生性糖尿病视网膜病变

目的:探讨曲安奈德联合Bevacizumab(Avastin)辅助玻璃体切除术治疗严重糖尿病视网膜病变的临床应用价值。方法:回顾性分析药物辅助下玻璃体切除治疗的严重增生性糖尿病视网膜病变13例15眼,15眼均于术前3~14d行Bevacizumab(Avastin)1.25mg/0.05mL玻璃体腔注射,常规玻璃体切除术中使用曲安奈德辅助切除残留的玻璃体皮质、视网膜增殖膜,其中9例合并牵拉性视网膜脱离及黄斑水肿者硅油填充并留置4mg/0.1mL曲安奈德,4眼未使用硅油填充眼因合并黄斑水肿大量硬性渗出予曲安奈德留置。2眼单纯玻璃体积血者未注射曲安奈德。结果:除1例玻璃体腔注射Avastin 3d后术中出血较多特别是在剥离纤维新生血管膜过程中,其余病例术中出血很少,并能迅速自凝。联合曲安奈德辅助可清晰地辨别残留皮质、视网膜前膜甚至内界膜,黄斑水肿术后明显减轻,所有病例术后炎症反应轻,眼压控制良好,硅油眼中留置曲安奈德无明显并发症。结论:严重的增生性糖尿病视网膜病变玻璃体切除术前7~14d玻璃体腔注射Bevacizumab(Avastin),明显减少术中出血,术中使用曲安奈德辅助可视性良好。术毕留置4mg曲安奈德可有效减轻黄斑水肿及术后反应。     

The effects of indocyanine green and endoillumination on rabbit retina: an electroretinographic and histological study

AIM: To evaluate the functional and morphological retinal toxicity associated with intravitreal injection of indocyanine green (ICG) dye in rabbit eyes during vitrectomy with endoillumination. METHODS: 20 eyes of 10 New Zealand pigmented rabbits were used in the study. All eyes underwent pars plana vitrectomy and removal of posterior vitreous cortex under endoillumination. In one eye of each rabbit, intravitreal injection of 0.1 ml of 2.5 mg/ml ICG was applied for 30 seconds followed by 10 minutes of endoillumination. The control eye had endoillumination only without ICG injection. Dark adapted and light adapted electroretinograms (ERGs) were performed before the surgery and 1 week after surgery for serial comparisons. Rabbits were killed 1 week after surgery and eyes were enucleated for histological examination. RESULTS: Serial ERG comparisons showed significant reduction in the light adapted a-wave amplitude (p = 0.037) and significant delays in the dark adapted and light adapted b-wave latencies (p = 0.020 and p = 0.038, respectively) in the ICG treated eyes. Histological examinations demonstrated loss of photoreceptor outer segments with focal absence of photoreceptors in some areas in the ICG injected eyes. CONCLUSIONS: Vitrectomy followed by intravitreal injection of 2.5 mg/ml ICG for 30 seconds with endoillumination may result in retinal toxicity causing functional and morphological retinal damages in rabbit eyes. The lowest concentration of ICG should be used if necessary for intraocular use to prevent potential retinal toxicity.     

Intravitreal toxicity of garenoxacin

PURPOSE: To assess the retinal toxicity of varying concentrations of intravitreally injected garenoxacin. METHODS: Twenty eyes of 20 New Zealand albino rabbits were used for this study. The animals were anesthetized with ketamine (35-50 mg/kg) and xylazine (3-5 mg/kg). Garenoxacin was titrated using distilled water to the following concentrations: 4,000, 2,000, 1,000, 400, 200, and 100 microg/0.1 mL. Each concentration was injected intravitreally (0.1 mL) into three rabbit eyes. Three control eyes were injected with 0.1 mL of balanced saline solution. All animals were examined before and after injection by indirect ophthalmoscopy and slit-lamp biomicroscopy. Electroretinography was performed on all animals before intravitreal injection and 14 days after injection. The animals were examined by indirect ophthalmoscopy and slit-lamp biomicroscopy before they were killed; the eyes were enucleated and examined with light microscopy. RESULTS: No electroretinographic changes or signs of retinal toxicity by slit-lamp examination, indirect ophthalmoscopy, or light microscopy were seen in any eyes 14 days after intravitreal injection of garenoxacin (< or =4,000 microg/0.1 mL). CONCLUSIONS: Garenoxacin injected intravitreally appeared safe at concentrations of < or =4,000 microg/0.1 mL.     

曲安奈德玻璃体腔内注射辅助治疗脉络膜脱离型视网膜脱离

目的:评价玻璃体手术前1d玻璃体腔内注射曲安奈德治疗脉络膜脱离型视网膜脱离的疗效和安全性。方法:对28例(28眼)脉络膜脱离型视网膜脱离患者于玻璃体手术前1d玻璃体腔注射曲安奈德混悬液0.1mL(4mg)。手术方式为巩膜环扎联合玻璃体切除,术后C3F8或硅油充填。24眼随访6～17(平均8.9)mo。结果:28眼注射曲安奈德后葡萄膜炎症减轻。24眼单次手术视网膜解剖复位率87.5%(21/24)。结论:在玻璃体手术治疗脉络膜脱离型视网膜脱离前1d玻璃体注射曲安奈德使手术难度降低,提高了视网膜复位率。     

Retinal toxicity of combination antiviral drugs in an animal model

We investigated the retinal toxicity of various combinations of four antiviral agents in intravitreal injection and vitrectomy infusion solutions in the rabbit. The nontoxic concentration of each individual agent for intravitreal injection and for vitrectomy infusion has previously been described. Our results support the concept that concentrations of 200 micrograms/0.1 mL of trifluridine, 400 micrograms/0.1 mL of hydroxyacyclovir, 200 micrograms/0.1 mL of acyclovir and 30 micrograms/0.1 mL of vidarabine can be combined for intravitreal injection without toxic retinal effects. Moreover, 60 micrograms/mL of trifluridine, 20 micrograms/mL of hydroxyacyclovir, 40 micrograms/mL of acyclovir and 8 micrograms/mL of vidarabine can be combined in vitrectomy infusion solutions without retinal damage. Further study is needed to determine the full potential of such combinations.     

Lipophilic substances in intraocular silicone oil

PURPOSE: To examine intravitreal silicone oil samples for lipophilic substances, including cholesterol, fatty acids, and derived methyl esters. DESIGN: Clinical interventional case series study. METHODS: The study included 53 patients (53 eyes; mean age 57.6 years) who underwent removal of intravitreal silicone oil used for intraocular tamponade with pars plana vitrectomy for retinal detachment. The silicone oil was removed 8.3 +/- 5.7 months after pars plana vitrectomy and analyzed using gas chromatography with a flame ionization detector. RESULTS: Cholesterol was present in all samples with a mean concentration of 65 +/- 32.3 microg/ml (95% confidence interval: 56.1 to 73.9 microg/ml). The concentration increased (P < .001) with the time of tamponade, and decreased (P = .003) with the age of the patients. Fatty acids along with derived methyl acids were detected in low concentrations in 49 samples (92.5%). CONCLUSIONS: Cholesterol and lipophilic acids accumulate in intravitreal silicone oil used in intraocular tamponade.     

Changes in rabbit lens epithelial cells after intravitreal silicone oil injection]

Using adult albino rabbits, the clinical course of lens opacity and morphological changes of lens epithelial cells were observed from 2 weeks to 3 months after intravitreal silicone oil injection. Simple vitrectomy was performed in both rabbit eyes. One eye with silicone oil injection served as an experimental eye, while another control eye did not receive any injection. Seven examined eyes showed early posterior subcapsular lens opacity from one month after silicone oil injection by slit-lamp microscopy. Small intracellular vacuoles near to the interdigitation of the lens epithelial cells were observed in the 7 eyes from 2 weeks after the procedure by transmission electron microscopy. These changes were not observed in 7 control eyes. As a result, it is surmised that cataract formation after intravitreal silicone oil injection may be associated with morphological changes of the lens epithelial cells.     

Scanning laser polarimetry via intravitreal silicone oil.

PURPOSE: To investigate whether scanning laser polarimetry, a promising new technique for early detection of glaucomatous nerve fiber loss, is a suitable method to measure retinal nerve fiber layer thickness in eyes with intravitreal silicone oil. PATIENTS AND METHODS: Eleven eyes of 11 consecutive patients two days to 16 months after successful vitrectomy and intravitreal silicone oil injection and 12 eyes of 12 consecutive subjects, who never had any vitreoretinal surgery were examined using the GDx Nerve Fiber Analyzer. Three individual images were computed to a mean image using the software in each case. RESULTS: "Variance", a software-provided parameter, which represents the differences between the individual images used to calculate the mean image was higher in the "silicone oil" group (unpaired t test for different variances, p = 0.02). Good-quality mean images with a "Variance" value similar to that of the control eyes were obtained in seven of the 11 cases. Characteristic artifacts caused by intravitreal silicone oil were observed in five of the 11 cases. CONCLUSION: Successful scanning laser polarimetry is possible after vitrectomy and intravitreal silicone oil injection, and may help to monitor the retinal nerve fiber layer of these eyes in case of silicone oil induced glaucoma.     

兔玻璃体内注射聚N-异丙基丙烯酰胺-聚氧化乙烯纳米粒的眼内毒理学效应

目的:评估玻璃体腔内注射新型缓释给药载体聚N-异丙基丙烯酰胺-聚氧化乙烯(PNIPAAm-PEO)纳米粒的眼内毒理学效应。方法:玻璃体腔注射不同浓度(1mg/0.1mL,2mg/0.1mL,3mg/0.1mL,4mg/0.1mL)的PNIPAAm-PEO纳米稀释液后于不同时间点行裂隙灯、检眼镜、视网膜电图以及组织病理学检测。对照组注射0.1mL无菌生理盐水。将所用不同浓度稀释液局部点眼,观察局部组织的刺激反应。结果:兔眼角结膜对检测浓度范围内的PNIPAAm-PEO有良好耐受性,眼部无刺激症状。玻璃体腔内注射1mg和2mg组未见明显视网膜毒性反应。3mg组眼底检查无异常,ERG-b波1~3d下降幅度>30%,第7~14d略有恢复;第14d光镜下视网膜部分感光细胞外节间隙增宽,外丛状层以内结构空泡变性,细胞排列正常;电镜下各层均有较明显的结构改变,广泛的细胞水肿和空泡变性,细胞间隙增宽,感光细胞膜盘结构基本正常。4mg组ERG-b波波幅下降>30%;第1~14d组织病理学观察均有明显视网膜结构破坏,广泛空泡变性,部分感光细胞的盘膜崩解,层状结构紊乱、模糊不清。结论:PNIPAAm-PEO纳米粒的眼部耐受性良好,具有用作眼部给药载体的潜力,但大剂量使用时应注意眼部安全性问题。     

再次玻璃体手术治疗硅油填充眼视网膜脱离

目的:探讨再次玻璃体手术治疗硅油填充眼视网膜脱离的效果。方法:对12例硅油填充眼视网膜脱离患眼行再次玻璃体手术,其中下方视网膜脱离10例,黄斑裂孔复发2例。结果:12例术后视网膜全部复位,10例3～6mo取出硅油。最佳矫正视力提高4行1例,提高3行4例,提高2行3例,提高1行3例,不提高1例。结论:再次玻璃体手术是治疗硅油填充眼视网膜脱离的有效方法,早期手术有重要意义。     

硅油下视网膜复位术疗效探讨

目的 总结硅油填充术后视网膜再脱离行硅油正视网膜复位术的疗效,探讨该手术的适应证及手术技巧。方法 对１７例（１７只眼）硅油填充术后视网膜再脱离者,在保留硅油的条件下,做睫状体扁平部３切口,在导光纤维的导引下行剥膜、断膜、视网膜切开、内放液、内激光光凝、视网膜下全氟化碳液体取出、补充硅油等使视网膜得位。结果 １７只眼中,术后视网膜重位１４只眼,成功率为８２．４％。术中硅油误入前房１只眼,误入脉络膜上     

Retinal toxicity of triamcinolone acetonide in silicone-filled eyes

OBJECTIVE: To determine the retinal toxicity of triamcinolone acetonide at different doses in vitrectomized, silicone-filled rabbit eyes. MATERIALS AND METHODS: Vitrectomy with silicone oil placement was performed in 32 rabbit eyes. A dosage of 1 mg/0.025 mL, 2 mg/0.05 mL, or 4 mg/0.1 mL of triamcinolone acetonide was injected intravitreally in the study group eyes; the control group received 0.1 mL of sterile saline. Electroretinography and retinal histology were performed to evaluate toxicity. RESULTS: No retinal toxicity was seen in the groups given 1, 2, and 4 mg of triamcinolone acetonide or in the control group. ERG and histologic sections in all groups were normal. No drug was visible in the vitreous cavity at the end of the 140-day period (average) in eyes injected with 4 mg of triamcinolone acetonide. CONCLUSIONS: Up to 4 mg of triamcinolone acetonide can be safely injected in silicone-filled, vitrectomized eyes without any significant retinal toxicity.     

Intravitreal moxifloxacin: retinal safety study with electroretinography and histopathology in animal models

PURPOSE: To determine whether moxifloxacin can be used safely as an intraocular antibiotic, retinal safety of intravitreal moxifloxacin was studied with electroretinography (ERG) and histopathology in animal models. METHODS: Moxifloxacin was injected into mouse eyes at intravitreal concentrations of 5 to 500 microg/mL and into rabbit eyes at 150 microg/mL. As the control, the vehicle was injected into the fellow eyes of each animal. Four weeks after injection, ERG recordings were performed, and animal eyes were processed for histologic examination. RESULTS: ERG studies showed no significant difference between control and moxifloxacin-injected eyes at any dose in either the mouse or rabbit model. Histologic examination revealed no retinal abnormality in mice at 5 to 100 microg/mL or in rabbits at 150 microg/mL intravitreal moxifloxacin. In mice at 500 microg/mL, occasional focal retinal necroses were observed, suggesting isolated retinal toxicity at this concentration of moxifloxacin. CONCLUSIONS: Intravitreal moxifloxacin, up to 100 microg/mL in mice or 150 microg/mL in rabbits, caused no ERG or retinal histologic abnormality. These results indicate that moxifloxacin is a safe intravitreal antibiotic in mouse and rabbit animal models. If proven safe and efficacious by further study in humans, intravitreal injection of moxifloxacin could be considered as an alternative to currently used antibiotics in selected patients with resistance or allergy to the more traditional antibiotics.     

Long-term anatomical and visual outcome of vitreous surgery for retinal detachment with choroidal coloboma

CONTEXT: Vitreous surgery has been advocated as an alternative treatment of selected retinal detachments with choroidal colobomas. AIM: To study the long term anatomical and visual outcome of choroidal coloboma with retinal detachment managed by pars plana vitrectomy with silicone oil tamponade. SETTING AND DESIGN: Retrospective study conducted in a tertiary eye care hospital. MATERIALS AND METHODS: Fourty two eyes of 40 patients with retinal detachments related to coloboma of the choroid without any peripheral breaks were analyzed. All eyes underwent pars plana vitrectomy with internal tamponade using silicone oil. Endolaser was performed along the coloboma border. Silicone oil was removed in 50% of patients. The main outcome measures were retinal reattachment and visual recovery. SPSS (Statistical Package for the Social Science), version 10.0 was used for analysis. RESULTS: The retina in all cases (100%) undergoing vitrectomy were completely reattached intra-operatively. After a mean follow-up of 14 months, 37 (88.1%) eyes had attached retina. The best corrected visual acuity was 10/200 or better in 33 (78.4%) eyes. The best corrected visual acuity improved from a preoperative median of counting fingers (range 20/40 to perception of light) to median best corrected visual acuity of 20/200 (range 20/40 to perception of light) at the end of 6 months. Of the 50% (21) cases that underwent silicone oil removal, two eyes had re-detachment of retina. CONCLUSION: Pars plana vitrectomy along with silicone oil tamponade for retinal detachment related to choroidal coloboma improves the long-term anatomical and visual outcome.     

Intravitreal toxicity of moxifloxacin

PURPOSE: To assess the retinal toxicity of various concentrations of intravitreally administered moxifloxacin, a fourth-generation fluoroquinolone. METHODS: Ten New Zealand albino rabbits were divided into five groups. The initial concentration of moxifloxacin (400 mg/250 mL) was titrated using 5% dextrose solution to concentrations (320 microg/0.1 mL, 160 microg/0.1 mL, 100 microg/0.1 mL, and 50 microg/0.1 mL) that were injected intravitreally into 1 eye of each rabbit. Two control eyes were injected intravitreally with 0.1 mL of 5% dextrose solution. All animals were examined before and after injection by indirect ophthalmoscopy and slit-lamp biomicroscopy; electroretinography (ERG) was performed on all animals. The animals were killed, and their eyes were enucleated and examined with light microscopy. RESULTS: Remarkable decreases in ERG findings were noted in the group injected with moxifloxacin at a concentration of 320 microg/0.1 mL. No meaningful ERG changes were observed in eyes injected with moxifloxacin at other concentrations. There were no signs of retinal toxicity during slit-lamp examination, indirect ophthalmoscopy, or light microscopy in any eyes injected with moxifloxacin concentrations of < or =160 microg/0.1 mL. CONCLUSIONS: Intravitreal injection of moxifloxacin at a concentration of < or =160 microg/0.1 mL appeared nontoxic in the rabbit eye.     

Experimental retinal tolerance to emulsified silicone oil

Vitreous replacement by silicone oil has become increasingly popular in the treatment of severe and complicated retinal detachment. Several studies have suggested that silicone oil may be toxic to the retina or may stimulate periretinal proliferation. To better understand its effects, emulsified or nonemulsified silicone oil was injected into rabbit eyes that had undergone mechanical vitrectomy. Silicone oil was labeled with phthalocyanine blue to aid in histologic localization. Retinal changes were compared by light microscopy at 1, 4, and 12 weeks after intraocular injection. Emulsified silicone oil was found to penetrate the inner retina at 1 week and cause epiretinal membrane formation as early as 4 weeks after injection. Nonemulsified oil produced no histologic changes in the retina. No cytotoxic effects were observed in eyes treated with ether emulsified or nonemulsified silicone oil. It is concluded that emulsified silicone oil can both penetrate the retina and stimulate epiretinal membrane formation in the vitrectomized rabbit eye.     

Absence of histologic retinal toxicity of intravitreal nanogold in a rabbit model

PURPOSE: To evaluate the retinal toxicity of intravitreal nanogold, a novel antiangiogenic and long-term delivery agent. METHODS: One eye of each of 16 Dutch-belted rabbits was injected with intravitreal nanogold; the other eye served as a control. Eight rabbits received a dose of 67 micromol/0.1 mL of nanogold intravitreally into 1 eye; the other 8 rabbits received a dose of 670 micromol/0.1 mL of nanogold intravitreally into 1 eye. Eight rabbits were killed at 1 week, and eight were killed at 1 month; both eyes of each rabbit were enucleated. The eyes were fixed with 2% paraformaldehyde and sectioned for histologic examination. RESULTS: In all injected and control eyes, there was mild vacuolization in the inner plexiform and ganglion cell layers. The retina and retinal pigment epithelium were otherwise histologically normal. CONCLUSION: Intravitreal nanogold at concentrations of 67 micromol/0.1 mL and 670 micromol/0.1 mL showed no signs of retinal or optic nerve toxicity by light microscopy during histologic examination at 1 month.