Nonaxoplasmic transfer of indocyanine green into the optic nerve after intravitreal application

PURPOSE: To investigate whether indocyanine green (ICG) migrates into the optic nerve after intravitreal application in the rabbit eye. METHODS: Gas vitrectomy was performed in one eye of adult Dutch belted rabbits by pars plana injection of 0.4 ml of 100% C3F8 (n = 10). One week later, vitrectomy was performed and 0.2 ml of 0.25% ICG was instilled into the vitreous cavity of these vitrectomized eyes. After 30 seconds of ICG application, the vitreous cavity was rinsed with balanced salt solution plus. Unoperated rabbits served as controls (n = 2). Globes, optic nerves, and the entire brain were removed, and ICG fluorescence of the specimens was examined with a digital fundus camera starting from the first day to the fourth postoperative week. Other rabbit eyes (n = 2) were injected with ICG directly into the vitreous without vitrectomy, and assessed for ICG signal after 1 day of ICG application. In the second part of the experiment, four rabbit eyes were gas vitrectomized and ICG was instilled onto retina after blockage of axonal flow by vinblastine. They were evaluated on the first (n = 2) and seventh postoperative days (n = 2). RESULTS: No fluorescein was detected in the visual pathways and the brains of the control group of rabbits. The optic nerves of the ICG-instilled eyes were stained diffusely with ICG starting from the first day after surgery. ICG injected nonvitrectomized eyes showed similar ICG staining patterns when compared with vitrectomized eyes. ICG staining pattern of the optic nerve did not differ in vinblastine-pretreated eyes. Fluorescence extended along the intraorbital portion of the optic nerve but did not transport more posteriorly in all animals. At the fourth week after vitrectomy, ICG signal was still detectable, but staining was less intense. CONCLUSION: Intravitreal ICG injection results in nonaxoplasmic extension into the optic nerve in the rabbit.     

Morphological and functional damage of the retina caused by intravitreous indocyanine green in rat eyes

BACKGROUND: This study was designed to investigate the influence of intravitreal indocyanine green (ICG) on retinal morphology and function. METHODS: Brown Norway rats eyes ( n=24) were vitrectomized by the injection of 0.05 ml of 100% SF(6) gas. Two weeks later, ICG solution was injected into the vitreous cavity of vitrectomized eyes at a dose of 25 mg/ml, 2.5 mg/ml, 0.25 mg/ml or 0.025 mg/ml (0.05 ml/eye). Retinal toxicity was histologically assessed by light microscopy on day 10. The retinal function was also evaluated by electroretinography (ERG) in the low-dose groups (0.25 mg/ml and 0.025 mg/ml) after 10 days and again after 2 months,. Sham-operated eyes (SF(6) injected followed by 0.05 ml of BSS plus, n=6) were used as controls. RESULTS: In the high-dose group (25 mg/ml ICG), the retinal structure was severely deformed and the retinal pigment epithelium partly disappeared. In eyes with 2.5 mg/ml ICG, the retinal structure was also affected but less strongly so than with 25 mg/ml. No apparent pathologic change was observed in the low-dose groups (0.25 mg/ml or 0.025 mg/ml) by light microscopy. In contrast, 10 days later the amplitude of dark-adapted a- and b-waves of ERGs in the eyes of low-dose group rats were found to have decreased. In addition the light-adapted b-waves did not change significantly. These changes remained for 2 months. CONCLUSION: Even at a low dose (0.025 mg/ml), intravitreous ICG induced functional damage of the retina without any apparent morphological damage. This information should be taken into account when clinically administering ICG into the vitreous cavity.     

Retinal toxicity of intravitreal ganciclovir in rabbit eyes following vitrectomy and insertion of silicone oil

BACKGROUND: Although intravitreal ganciclovir dosages up to 500 microg have been demonstrated to be safe in some studies, other studies have shown toxic retinal effects in rabbit eyes without silicone oil at lower dosages. In current clinical practice, the same dosage of intravitreal antiviral agent is given regardless of whether there has been retinal detachment repair with silicone oil. We performed a study to investigate, in rabbit eyes following vitrectomy and silicone oil insertion, the retinal toxicity of serial intravitreal injections of ganciclovir, using dosages previously found not to produce significant toxic effects in nonvitrectomized eyes. METHODS: Twenty-eight eyes of 14 New Zealand pigmented rabbits underwent pars plana vitrectomy and silicone oil insertion. One eye of each animal received an intravitreal ganciclovir injection twice weekly for 2 weeks.The other eye received 0.1 mL of normal saline as a control. Three dosages of ganciclovir (50, 100 or 200 microg/0.1 mL) were used in three groups of three to six animals. Scotopic electroretinography and histologic examination were performed 2 weeks postoperatively. RESULTS: No differences in scotopic b-wave threshold (p = 0.23, 0.78 and 0.50 for ganciclovir dosages of 50, 100 and 200 microg/0.1 mL respectively, Mann-Whitney U test) or in light microscopy findings were noted between the treatment and control eyes at any dosage of ganciclovir. Surgical complications were observed in eight eyes; the data for these eyes were not used for analysis. INTERPRETATION: Ganciclovir dosages of up to 200 microg/0.1 mL appear to be safe for serial intravitreal injection in rabbit eyes following vitrectomy and silicone oil insertion.     

2,4-Dinitrophenol pharmacologically promotes retinal detachment in rabbits

PURPOSE: The most difficult and unpredictable step of macular translocation surgery is creating the retinal detachment. The authors evaluated the efficacy of 2,4-dinitrophenol (2,4-DNP) to promote retinal detachment in the rabbit. METHODS: A vitrectomy was performed in each eye of a Dutch-belted rabbit. One eye was injected with 0.1 cc of a 5 mmol/L 2,4-DNP, the other eye with 0.1 cc of BSS+. After 30 minutes, the minimum aspiration pressure required to visibly elevate the retina was recorded. Four nonvitrectomized eyes received an intravitreal injection of either 0.1 cc of BSS+ or 5 mmol/L 2,4-DNP, and were enucleated and fixated for histopathologic examination. RESULTS: In the 12 masked eyes, the mean aspiration pressure decreased from 217 +/- 20 mmHg in the six BSS+ eyes to 117 +/- 20 mmHg in the six 2,4-DNP treated eyes (P = 0.0022). A retinal detachment was present in three of six masked and two of two unmasked 2,4-DNP treated eyes and none of eight BSS+ treated eyes. There was no short-term toxicity to the retina at the light microscope level. CONCLUSION: Intravitreal injection of 2,4-DNP reduced the retinal adhesive force by over 50% when compared to the BSS+ treated control eyes, without any short-term retinal toxicity.     

RGD peptide-assisted vitrectomy to facilitate induction of a posterior vitreous detachment: a new principle in pharmacological vitreolysis

PURPOSE: To evaluate a new concept in pharmacological vitreolysis by studying the efficacy of intravitreal RGD peptide-assisted vitrectomy in facilitating the separation of the posterior cortical vitreous from the retinal surface in an animal model. METHODS: Eight rabbits (16 eyes) received an intravitreal injection of 1 or 5 mg of RGD peptide in one eye and either RGE peptide (inactive control) or phosphate buffered saline in the fellow eye. After 24 hours, a pars plana vitrectomy with low aspiration (< or =30 mmHg) was performed in an attempt to create a detachment of the posterior cortical vitreous. A masked observer performed pre- and postoperative indirect ophthalmoscopy and B-scan ultrasonography. Postoperative scanning electron microscopy evaluated the vitreoretinal surface in selected eyes. Two additional rabbits received intravitreal injections of RGD peptide in one eye (1 mg and 5 mg) and 1 mg of RGE peptide in the fellow eye to examine apoptosis of the retinal cells by TUNEL assay. RESULTS: Based on postoperative ultrasound findings, six of the eight rabbits had a greater degree of posterior vitreous detachment in the RGD eye compared to the fellow eye (p = 0.03). The total number and the average number of detached quadrants in the group of RGD peptide eyes was twenty-three and 2.85 respectively compared to seven and 0.85 for the control fellow eyes (p = 0.02). Scanning electron microscopy confirmed the presence of postoperative posterior vitreous detachment. There was no evidence of retinal cell apoptosis in RGD injected eyes. CONCLUSION: RGD peptide-assisted vitrectomy facilitated posterior vitreous detachment in rabbit eyes, suggesting that RGD-containing peptides may prove to be effective adjuncts in producing posterior vitreous separation during vitreous surgery.     

Retinal ganglion cells toxicity caused by photosensitising effects of intravitreal indocyanine green with illumination in rat eyes

AIM: To investigate the effects of indocyanine green (ICG) with or without illumination on rat retinal ganglion cells (RGC) and retinal morphology. METHODS: Intravitreal injections of 1.0 mg/ml ICG solution were performed in rat eyes with or without subsequent illumination for 5 minutes. Eyes in the control group had intravitreal injections of balanced salt solution with illumination. Retrograde labelling of RGC with 6% Fluoro-Gold was performed 1 month later and RGC densities were compared between the three groups. Light microscopy with measurements of outer nuclear layer (ONL) and inner nuclear layer (INL) thicknesses were also performed and compared. RESULTS: Eyes with ICG without illumination showed insignificant reduction in RGC density compared with the control group (p = 0.28), whereas a significant decrease in RGC density was found in eyes that had ICG injection with illumination (p = 0.036). A significant increase in ONL thickness was also observed in the ICG with illumination treated eyes compared with the ICG without illumination and the control groups (p<0.001). No significant difference in INL thickness was observed between the three groups. CONCLUSIONS: Intravitreal injection of 0.1 mg/ml ICG in rat eyes followed by illumination resulted in photosensitising toxicity to RGC. Lower ICG concentration or illumination level should be considered when performing ICG assisted macular surgery.     

Preclinical investigation of fluorometholone acetate as a potential new adjuvant during vitreous surgery.

OBJECTIVE: To examine the effects of intravitreal fluorometholone acetate (FMT) on the morphology and function of the retina and to investigate its possible use for vitreous surgery. METHODS: Brown Norway rat eyes (n = 6, 12 groups) were injected with 0.05 ml of SF6 gas for vitrectomization. Four weeks later, FMT solution was injected into the vitreous cavity/subretinal space of the vitrectomized eyes at doses of 10, 20, and 40 mg/ml (0.05 ml/eye, n = 12 for each group). The retinal function was evaluated by electroretinography (ERG) at 4 and 8 weeks after FMT injection. Retinal toxicity was also assessed histologically by a light microscopy. Sham-operated eyes (0.05 ml of irrigating solution, n = 12) were used as control animals. FMT-assisted pars plana vitrectomy with internal limiting membrane (ILM) peeling was performed in primate eyes (n = 2). Retinal toxicity was assessed by ophthalmoscope, fluorescein angiography and electron microscopy three months after the vitreous surgery. RESULTS: There was no remarkable reduction in any ERG waves at either time interval at 4 and 8 weeks after the intravitreal/subretinal injection of FMT. No obvious histological change was observed in any of the rat eyes either. Using ophthalmoscope, fluorescein angiography and electron microscopy, the appearance of the primate retinas remained to be in a non-pathological condition. CONCLUSION: FMT appears to be a potentially useful tool in assisting vitreous surgery including safe ILM peeling.     

Ocular toxicity of intravitreal indocyanine green.

We report 6 cases of indocyanine green (ICG)-related ocular toxicity after intravitreal ICG usage. Five cases had preoperative diagnosis of macular hole, 1 case had preoperative rhegmatogenous retinal detachment complicated with proliferative vitreoretinopathy. All cases received vitrectomy, ICG-assisted internal limiting membrane (ILM) peeling and air-fluid exchange. All eyes had residual ICG left at the end of surgery. Patients were followed up with indirect ophthalmoscopy, visual acuity, color fundus photography, fluorescein angiography, and ocular coherence tomography. Circular foveal retinal pigment epithelium atrophy larger than the area of macular hole and surrounding cuff was noted in 4 of 5 cases with preoperative macular hole. The other eye with preoperative diagnosis of macular hole had shallow anterior chamber and low intraocular pressure lasting for 1 week postoperatively. Diffuse retinal pigment epithelial atrophy was noted in the eye with preoperative proliferative vitreoretinopathy. Four eyes demonstrated optic atrophy postoperatively. Ocular toxicity caused by ICG may present as pigment epithelial atrophy, which is characteristically larger than the previous area of macular hole and surrounding cuff. Disc atrophy, retinal toxicity, and ocular hypotony were also observed in some cases. To prevent toxicity, residual ICG and ICG-stained ILM must be removed as completely as possible.     

Retinal toxicity of indocyanine green in albino rabbits

PURPOSE: Intravitreal indocyanine green (ICG) is commonly used in vitreoretinal surgery. The purpose of this study was to evaluate possible toxicity of ICG in the retina of albino rabbits. METHODS: Twenty-two albino rabbits were injected intravitreally with 0.1 mL ICG solution in one eye, and three rabbits were studied for the effects of 0.1 mL distilled water. All rabbits were injected intravitreally with 0.1 mL saline into the fellow eye, which served as the control. The electroretinogram (ERG) and visual evoked potential (VEP) were recorded from each rabbit at different time intervals after injection. The rabbits were killed at the termination of the follow-up periods and their retinas prepared for histologic examination at the light microscopic level. RESULTS: Three hours after injection, the ERG responses were reduced in amplitude in all ICG-injected eyes, and the VEPs were of abnormal pattern (reduced amplitude and delayed). Partial dose-dependent recovery was observed during 4 weeks of follow-up. Light microscopy of the retinas of the experimental eyes exhibited considerable damage to all retinal layers in all eyes studied that received the highest ICG dose. CONCLUSIONS: ICG is potentially toxic to all retinal layers of the albino rabbit. Although it is difficult to extrapolate these findings directly to human eyes, caution should be exercised when using ICG intravitreally.     

t-PA对实验性玻璃体渗出的治疗作用

18只兔眼玻璃体腔内注射自体血浆0.2ml制成的玻璃体渗出模型，随机接受玻璃体内注射组织型纤溶酶原激恬酶(t-PA)或生理盐水，其中10眼玻璃体内注入t-PA 12.5μg，结果6眼的纤维蛋白在6h内清除，另4眼在1d内彻底清除．注入生理盐水的7眼需7d才完全清除。两用从时间上比较，差别有显著性(P<0.05)．经裂隙灯、ERG、光镜及电镜检查未见毒性作用．另1只注入10μg t-PA的兔眼虽然6h内见纤维蛋白凝块溶解，但眼底镜和光镜下已显示视网膜的毒性变化。 （中华眼底病杂志，1994，10：14-16）     

Removal of retinal indocyanine green dye by autologous serum irrigation in macular hole surgery

PURPOSE: To investigate the efficacy of autologous serum irrigation for removal of retinal indocyanine green (ICG) dye used to visualize the internal limiting membrane (ILM) in macular hole surgery. METHODS: Eighteen consecutive eyes of 16 patients with macular holes underwent vitrectomy and ILM peeling using ICG solution. Nine of 18 eyes underwent intravitreal autologous serum irrigation before completion of the surgery to remove residual ICG dye in the retina. The main outcome measures were postoperative visual acuity, macular hole status, retinal pigment epithelial changes, and time course of ICG dye fading from the retina with or without intravitreal autologous serum irrigation. RESULTS: No significant difference was noted in the improvement of visual acuity between the two groups. An abnormal pigment epithelial change was seen in one eye without serum application. ICG dye disappeared from the retina within an average of 6.1 months after surgery without serum and 2.4 months after surgery with serum (P < 0.01). CONCLUSIONS: Autologous serum irrigated in the vitreous cavity just before completion of macular hole surgery can help remove ICG dye used in surgery. The application was simple and safe and significantly shortened the period of residual retinal ICG staining.     

更昔洛韦玻璃体腔注药术治疗急性视网膜坏死

目的 探讨更昔洛韦玻璃体腔注药术治疗急性视网膜坏死（ARN）的手术适应证、手术时机及其疗效。方法ARN住院患者14例（14只眼）,均符合美国葡萄膜炎学会ARN诊断标准。患者初诊视力为光感、眼前手动、数指者各1只眼,0．08～0．1者4只眼,0．2～0．4者5只眼,0．5、0．8者各1只眼。角膜后沉着物、房水闪光均阳性。眼底表现为周边部局灶性和（或）片状视网膜坏死、视网膜动脉白线、视网膜出血等。全身分别给予阿昔洛韦或更昔洛韦静脉滴注,患者病情继续发展、恶化,但尚未出现视网膜脱离。再对14只眼行更昔洛韦玻璃体腔注药术。其中2只眼注药后,病情不能控制,出现了增生性玻璃体视网膜病变（PVR）和视网膜脱离,即行玻璃体切除术。术后患者随访4～74个月,平均25个月。结果更昔洛韦玻璃体腔注药术后,12只眼视力显著提高,提高至1．0～1．5者5只眼,0．5～0．9者5只眼,0．3者2只眼。玻璃体切除术后的2只眼,术后视力较术前亦有提高,分别由眼前数指提高至0．4,光感提高至眼前数指。14只眼的眼前节炎性反应和玻璃体混浊消失或明显减轻,视网膜黄白色病变消退,出血吸收,视网膜在位。结论对全身抗病毒药物治疗不能控制病情的ARN患者,在尚未发生PVR或视网膜脱离时,及早给予更昔洛韦玻璃体腔注药术可获得满意疗效,能显著提高患者视力。（中华跟科杂志,2007,43：631-637）     

玻璃体腔注C3F8治疗实验性兔玻璃体出血

目的 研究膨胀性气体Ｃ３Ｆ８对玻璃体出血机化有何影响。方法 新西兰大白兔８只,全麻下双眼抽取前房水０．１ｍｌ,平坦部注射自体抗凝血０．１ｍｌ。４８小时后,抽取眼前房水０．１ｍｌ,随机在各兔右眼或左眼注Ｃ３Ｆ８气体０．３ｍｌ于玻璃体腔内。另眼注０．１ｍｌ。４８小时后,抽双眼前房水０．１ｍｌ,随机在各兔右眼或左眼注Ｃ３Ｆ８气体０．３ｍｌ于玻璃体腔内。另眼注０．１ｍｌ的生理盐水作对照。术后散瞳查眼底及玻璃体。观察玻璃体出血和气体吸收情况。结果 注气眼与对照眼玻璃体出血的消退在时间上有显著性差异,Ｐ〈０．０５。对照眼最终有３只眼发生牵引性视网膜脱离。注气眼出血完全吸收后,均未发生视网膜脱离。未发生视网膜了眼,两组ＥＲＧ均正常,无明显差异。而有网脱的眼,ＥＲＧ明显下降。结论 Ｃ３Ｆ８气体在玻璃体手术和黄斑裂孔视网膜脱离的     

Effects of indocyanine green on the retina and retinal pigment epithelium in a porcine model of retinal hole

PURPOSE: This study was designed to emulate human macular hole surgery and to test the effects of indocyanine green (ICG) on the retina and retinal pigment epithelium (RPE). METHODS: Yorkshire Cross pigs (n = 23) underwent vitrectomy, separation of the posterior cortical vitreous, and creation of a single retinal hole. In three study groups (n = 6, each group), air-fluid exchange was performed, following which balanced salt solution (BSS), 1.0% ICG, or 0.5% ICG was applied over the retinal hole. In one additional group (n = 5), 0.5% ICG was injected into the fluid-filled eye. At 4 weeks, the eyes were examined clinically, and fundus photographs were obtained before enucleation and light microscopic examination. RESULTS: Clinical evaluations documented a statistically significant difference between study groups (P = 0.036). There was a higher rate of moderate or severe RPE atrophy among animals where 1% or 0.5% ICG was applied in air-filled eyes (83% and 67%, respectively) compared with BSS controls (17%) and fluid-filled eyes receiving 0.5% ICG (40%). Histologic evaluation demonstrated a statistically significant difference between groups (P = 0.044), with extensive outer retinal degeneration observed in air-filled eyes receiving 1% or 0.5% ICG (66% and 60%, respectively) compared with BSS controls or fluid-filled eyes receiving 0.5% ICG (none of the eyes in either group). None of the study groups had any changes in the inner retina except at the retinal hole site. CONCLUSIONS: Retina exposed to ICG concentrations used in human vitreoretinal surgery had greater RPE atrophy and outer retinal degeneration than control eyes undergoing the same surgery without ICG. Eyes filled with infusion fluid during ICG injection had less damage to the RPE and outer retina than did air-filled eyes receiving ICG.     

Effects of indocyanine green injection on the retinal surface and into the subretinal space in rabbits

PURPOSE: To evaluate the effects of indocyanine green (ICG) injection on the retinal surface and into the subretinal space of rabbit eyes. METHODS: Twenty-two Dutch-belted rabbits underwent two-port vitrectomy followed by injection of ICG (5 mg/mL) on the retinal surface and into the subretinal space. Balanced salt solution (BSS) was also injected subretinally. The locations where ICG was delivered (both epiretinal and subretinal) were exposed to light from an endoilluminator for 7 minutes. The animals were examined at 1, 7, and 14 days after surgery. The eyes were studied by fluorescein angiography as well as light and electron microscopy. RESULTS: No damage was observed after epiretinal ICG injection, but subretinal ICG injection resulted in damage to the outer nuclear layer, photoreceptor inner and outer segments, and retinal pigment epithelium. This damage was more severe with longer follow-up. Control experiments without ICG, in which balanced salt solution was injected into the subretinal space or light was delivered on the epiretinal surface, demonstrated only damage to the photoreceptor outer segments. CONCLUSION: Subretinal delivery of ICG (5 mg/mL) in rabbits induces retinal pigment epithelium, photoreceptor inner and outer segment, and outer nuclear layer damage. These mechanisms of damage may explain the retinal pigment epithelium changes that are sometimes seen after ICG-assisted internal limiting membrane peeling in humans.     

Retinal toxicity of liposome-incorporated and free ofloxacin after intravitreal injection in rabbit eyes

Background: Ofloxacin (OFLX) is a fluoroquinolone-antibiotic with a broad antimicrobial spectrum that may have a potential role in the treatment of bacterial endophthalmitis. However, its elimination half life after intravitreal injection is short. To prolong the intravitreal antibacterial level OFLX was incorporated into liposomes. This study was performed to investigate the retinal toxicity of liposome-incorporated and free OFLX. Materials and methods: OFLX was incorporated into multilamellar large vesicles. 0,1 ml of this suspension (= 180.2 μg OFLX) was injected into the midvitreous of rabbit eyes (n = 6). Free OFLX in doses of 100 μg, 500 μg and 1,000 μg was injected into the midvitreous of a second group of rabbit eyes (n = 18). The other eye served as a control and received empty liposomes or normal saline solution, respectively. Before injection and at the end of follow-up an ERG was obtained. After a follow-up of 1 day, 14 and 28 days the animals were perfused with glutaraldehyde and the eyes were examined by light- and transmission electron microscopy. Results: The ERG as well as the histologic studies did not reveal any pathological changes after injection of liposome-incorporated OFLX compared to the control eyes. Significant reduction of the ERG was observed after 500 μg free OFLX in 2 out of 6 eyes after 1 and 14 days, respectively, and in 2 eyes 1 day after 1,000 μg free OFLX. Three days after injection of 1,000 μg OFLX the retina showed focal destruction in 1 out of 6 eyes. In another eye with the same dose 14 days after injection the photoreceptor outer segments showed disorganisation. Conclusion: This study shows that liposome-incorporated OFLX did not have any retinal toxicity in this animal model. Free OFLX appears to have no retinal toxicity in rabbit eyes at a dose of 100 μg after intravitreal injection. Injection of higher doses resulted in ERG changes and marked retinal damage. This revised version was published online in July 2006 with corrections to the Cover Date.     

Retinal toxicity of intravitreal tenecteplase in the rabbit

Aim: To investigate the retinal toxicity of intravitreal injection of a novel fibrinolytic tenecteplase in rabbit eyes. METHODS: Tenecteplase (25-350 micro g in 0.1 ml BSS) was injected into the vitreous cavity of normal rabbit eyes. Control (fellow) eyes received 0.1 ml of BSS. One day, 1 week, and 2 months post-injection, the eyes were examined by slit lamp biomicroscopy, indirect ophthalmoscopy, and electroretinography, and then harvested for histopathological examination. RESULTS: No evidence of retinal toxicity was seen with tenecteplase doses up to and including 50 micro g. At a dose of 150 micro g ophthalmoscopy was normal, but histology showed mild retinal damage in the inner nuclear layer and electroretinography showed a temporary reduction in B-wave amplitude. At doses of 200 micro g and above, there was evidence of retinal toxicity on electroretinography, ophthalmoscopy, and histology. Ophthalmoscopic findings included vitreal fibrosis, retinal necrosis and tractional retinal detachment and light microscopy revealed necrosis of retinal pigment epithelium and other retinal layers. Damage was centred around the injection site but was more widespread with the higher doses. CONCLUSION: A dose of 50 micro g tenecteplase appears safe for intravitreal injection in the rabbit. Tenecteplase could have potential applications in the treatment of submacular haemorrhage and retinal vein occlusion.     

Intravitreal toxicity of high-dose etanercept.

PURPOSE: The aim of this study was to evaluate the retinal toxicity of high-dose intravitreal etanercept, a U.S. Food and Drug Administration-approved anti-inflammatory drug, in the rabbit model. METHODS: Twenty (20) New Zealand albino rabbits were divided into 5 groups (n=4); eyes in each group were intravitreally injected with one of the following doses of etanercept: 125 microg, 250 microg, 500 microg, 1 mg, or 2.5 mg. One (1) eye in each animal was used for the study dose; the fellow eye was injected with buffered sterile saline as a control. All animals were examined using indirect ophthalmoscopy and slit-lamp biomicroscopy before and after intravitreal injection and at days 1, 7, and 14. Electroretinography (ERG) was performed on all animals before intravitreal injection and 14 days after injection. The animals were euthanized on day 14. Histological preparations of the enucleated eyes were examined with light microscopy for retinal toxicity. RESULTS: Clinical examination, histological evaluation, and ERG results of all 5 groups demonstrated no signs of retinal toxicity. CONCLUSIONS: Intravitreal doses as high as 2.5 mg of etanercept did not cause retinal toxicity. Intravitreal doses of up to 2.5 mg of etanercept may provide a more potent, prolonged effect than the lower doses previously recommended.     

国产猪源纤维蛋白黏合剂玻璃体腔注射后对兔眼视网膜组织的生物安全性研究

背景 猪源纤维蛋白黏合剂已广泛应用于临床手术中,能够起到止血和闭合伤口的作用.目前眼科学者认为猪源纤维蛋白黏合剂在玻璃体切割术中可替代长效气体或硅油作为填充物,但国产猪源纤维蛋白黏合剂是否对视网膜有毒性作用仍在研究中. 目的 研究国产猪源纤维蛋白黏合剂在眼内应用后对视网膜组织的生物安全性. 方法 15只青紫兰兔任选一眼作为实验眼,对侧眼作为对照眼.兔眼行玻璃体切割术,实验眼术毕于玻璃体腔内注射猪源纤维蛋白胶0.5 ml,对照眼注射等量平衡盐溶液.术后1、3、7、15、30 d用裂隙灯及直接/间接检眼镜检查眼前后节的炎症反应,术后1、3、7d用Schi(o)tz眼压计测量眼压,分别于术前和术后30 d进行视网膜电图(ERG)检查,评估视网膜的功能变化,术后30 d行眼科B型超声检查.玻璃体腔内注射后第30天摘除眼球并制备视网膜切片,光学显微镜下检查视网膜的组织形态学变化,透射电子显微镜下观察视网膜的超微结构变化. 结果 实验组15只兔眼中出现并发症者7只眼,其中晶状体损伤后发生白内障者3只眼,术后增生性玻璃体病变和视网膜脱离者5只眼,眼内炎者1只眼.对照组15只兔眼晶状体损伤后发生白内障者2只眼,术中发生视网膜损伤者2只眼.眼内注射后30d实验组未出现并发症的8只眼及对照组的11只眼均未见明显的眼内炎症反应,术后眼压均正常,2个组间及手术前后各时间点间的眼压变化差异均无统计学意义(F分组=0.008,P=0.929;F时间=3.600,P=0.075).实验组及对照组间兔眼注药前后ERG a波、b波振幅的总体差异均无统计学意义(a波:F分组=0.728,P=0.405;b波:F分组=0.222,P=0.644);各组兔眼手术前后ERG a波、b波振幅的总体差异均无统计学意义(a波:F时间=0.516,P=0.482;b波:F时间=0.057,P=0.814).眼内注射后30 d,实验眼和对照眼视网膜组织层次清晰,无水肿及阳性细胞浸润,各层视网膜的细胞及视网膜光感受器、视网膜色素上皮的色素细胞形态均正常,亚细胞器结构清晰,细胞膜和核膜完整,线粒体嵴排列整齐. 结论 国产猪源纤维蛋白黏合剂玻璃体腔注射后对兔眼视网膜无毒性作用.     

Toxicity of the photosensitizer NPe6 following intravitreal injection

BACKGROUND AND OBJECTIVE: To determine the retinal toxicity of mono-L-aspartyl chlorin e6 (NPe6) following intravitreal injection. METHODS: Twelve Dutch-belted rabbits divided into 5 experimental groups (n=2 each) were injected intravitreally with 6.25, 12.5, 25, 50, or 100 microg of NPe6; one control group (n=2) was injected with intravitreal normal saline. One eye in each rabbit was sutured shut to test the effect of light exposure. Fundus photography and electroretinograms were performed before treatment and 2 days, 1 week, and 2 weeks after injection. Animals were euthanized and the eyes enucleated for histopathologic analysis. RESULTS: After 1 week, 4 uncovered eyes given 50 and 100 microg had central retinal vein occlusion and varying degrees of retinal hemorrhage. RPE proliferation was seen in the covered eyes given 50 or 100 microg. Electroretinograms revealed absent retinal response at 100 microg and mild toxicity at 50 microg, but no change from normal at doses of < or = 25 microg of NPe6. CONCLUSIONS: Intravitreal doses of < or = 25 microg NPe6 caused little or no apparent toxicity; however, toxicity was significant at doses of 50 microg and 100 microg.