Biocompatibility of materials implanted into the subretinal space of Yucatan pigs

PURPOSE: To assess the biocompatibility of materials for possible use in subretinal prostheses. METHODS: Strips (0.5 x 5 mm; 10-microm thick) of either plain poly(imide) or poly(imide) coated with amorphous aluminum oxide (AAO), amorphous carbon (AC), parylene, poly(vinyl pyrrolidone) (PVP), or poly(ethylene glycol) (PEG) were each implanted into the subretinal space of four Yucatan miniature pigs. Two types of control surgery without implantation were performed in four other animals. Electroretinograms (ERGs) were performed before and after surgery. All animals were euthanatized 3 months after surgery, and histologic slides of the retina were assessed for 15 criteria. Paired, two-tailed Student's t-tests were used for statistical analyses. RESULTS: Across all animals, the mean amplitude of the ERG b-wave did not differ from baseline after 3 months. In implanted animals, the histologic analyses revealed that (1) all the implanted materials produced abnormalities that were significantly greater than in the control subjects; (2) overall, PEG, parylene, and PVP produced less histologic disruption than the other three materials; (3) parylene and PEG did not differ significantly from the control in disturbing retinal anatomy; (4) only PI and AAO produced RPE alterations that were significantly greater than in control subjects; and (5) AAO and PI produced a significantly greater degree of peri-implant cellular responses than did the other materials. CONCLUSIONS: All implants produced some alteration of the retina, but there were clear differences among the materials in the degree to which their presence disturbed the normal anatomy of the retina or RPE or incited tissue reactions around the implant.     

Migration of intravitreal silicone oil through a Baerveldt tube into the subconjunctival space

A 28-year-old patient developed proliferative diabetic retinopathy with florid rubeosis iridis and ultimately required the placement of a Baerveldt tube to control his secondary glaucoma. Eighteen months later, he underwent a pars plana vitrectomy, scleral buckle, lensectomy, and membrane peeling to reattach a severe diabetic retinal detachment. Ultimately, some of the 5000 cs silicone oil migrated through the tube to the episcleral region under the plate of the Baerveldt device. The oil intermittently blocked the shunt, causing elevated intraocular pressure. Despite ultimate surgical removal of the oil from around the tube and plate, a substantial amount remained encapsulated in the subconjunctival space. Prevention of this complication includes placement of a short tube well anterior to the iris in the inferior portion of the anterior chamber.     

Migration of intravitreal silicone oil through a Baerveldt tube into the subconjunctival space

A 28-year-old patient developed proliferative diabetic retinopathy with florid rubeosis iridis and ultimately required the placement of a Baerveldt tube to control his secondary glaucoma. Eighteen months later, he underwent a pars plana vitrectomy, scleral buckle, lensectomy, and membrane peeling to reattach a severe diabetic retinal detachment. Ultimately, some of the 5000 cs silicone oil migrated through the tube to the episcleral region under the plate of the Baerveldt device. The oil intermittently blocked the shunt, causing elevated intraocular pressure. Despite ultimate surgical removal of the oil from around the tube and plate, a substantial amount remained encapsulated in the subconjunctival space. Prevention of this complication includes placement of a short tube well anterior to the iris in the inferior portion of the anterior chamber.     

Injection of cultured autologous fibroblasts into the subconjunctival space of rabbits treated with mitomycin C

PURPOSE: To investigate whether cultured autologous fibroblasts injected into the subconjunctival space of rabbit may be used as a new treatment modality for conjunctival and subconjunctival atrophy caused by mitomycin C (MMC). DESIGN: Animal study. METHODS: Thirty New Zealand White rabbits were divided into three groups of 10 animals. A situation similar to bleb leakage after trabeculectomy with MMC was created by injecting 0.1 ml of MMC 0.05% weekly for three weeks into the subconjunctival space of 30 eyes of these 30 rabbits. The animals were then divided into control, autologous blood injection, and cultured autologous fibroblast injection groups. Conjunctiva changes were then observed, and eyes were enucleated for histopathologic study at one, two, four, six, and eight weeks after surgery in each of the three groups. RESULTS: In the control group, the conjunctiva was thin and transparent, and subconjunctival fibroblasts were hardly visible, with coarsely arranged collagen fibers. In contrast, the autologous fibroblast injection group showed a thickened and less transparent conjunctiva along with packed fibroblasts and collagen fibers. In the autologous blood injection group, the transparency of the conjunctiva and the density of fibroblast and collagen fiber arrangement lay between those of the control and autologous fibroblast injection groups. CONCLUSIONS: Cultured autologous fibroblast injection may be a feasible and effective treatment modality for conjunctival and subconjunctival atrophy caused by MMC.     

Immune privilege of allogeneic neuroretinal transplants in the subconjunctival space

Background  The extent of site and tissue-associated immune privilege is of great interest in transplantation experiments involving the CNS. In the present paper we have explored neuroretinal immune privilege by transplantation to a non-immune privileged site. Methods  Fetal and adult full-thickness rabbit neuroretinal grafts were placed in the subconjunctival space of immunocompetent rabbit hosts. Morphological examination was performed after 2–31 days (fetal grafts, n = 46), and after 8 days (adult grafts, n = 4). Results  Hematoxylin and eosin-stained sections and immunohistochemistry directed against microtubule-associated protein 2 (MAP2) revealed surviving grafts containing retinal neurons in the majority of eyes with fetal grafts. In all specimens, a mild inflammatory reaction was evident as seen with major histocompatibility complex class II (MHC-II) labeling. Short-term grafts survived well and displayed lamination and rosette formation whereas older grafts appeared more disorganized and were more often rejected. Müller cell fibers labeled with glial fibrillary acidic protein (GFAP) were present in grafts from 15 days and onwards. Adult grafts were destroyed after 8 days. Conclusions  Allogeneic fetal full-thickness neuroretinal transplants can survive for several weeks in a non-immune privileged environment in which adult grafts are rapidly rejected. Fetal grafts gradually shrink, lose their architecture and go through a glial transformation accompanied by low-grade inflammation. The rabbit neuroretina thus appears to enjoy partial immune privilege, the extent of which depends on the development state of the tissue. The characterization of neuroretinal immune privilege will hopefully influence future clinical trials of retinal transplantation. Supported by the Faculty of Medicine, Lund University, the Crown Princess Margaret Committee for the Blind, the Swedish Research Council. The authors have no financial relationship with the sponsoring organizations. The authors have full control of all primary data and agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review the data if requested.     

Migration of intraocular silicone oil into the subconjunctival space and orbit through an ahmed glaucoma valve

PURPOSE: To report a patient with intraocular silicone oil migration into the subconjunctival space and orbit through an Ahmed glaucoma valve implant. METHODS: Observational case report. A 29-year-old female with diabetes mellitus and proliferative diabetic retinopathy underwent three left eye pars plana vitrectomies and ultimately intraocular silicone oil placement for tractional retinal detachment. Subsequently, she developed neovascular glaucoma and underwent an inferotemporal Ahmed glaucoma tube implant, left eye. RESULTS: Intraocular silicone oil migrated through the Ahmed glaucoma valve into the subconjunctival space and orbit. Left eye evisceration with silicone oil removal was performed for a blind painful left eye and improvement of appearance. CONCLUSION: Silicone oil migration through an Ahmed valve may be observed after retinal detachment repair with intraocular silicone oil. An Ahmed valve may be contraindicated in eyes of patients with intraocular silicone oil.     

Lewis鼠结膜下注射雷帕霉素的眼毒性研究

目的 探讨Lewis鼠结膜下注射雷帕霉素的眼毒性.方法 将20只Lewis鼠随机分为A、B、C、D、E 5组,每组4只.A组Lewis鼠结膜下注射4 μg·kg-1雷帕霉素,B组为20 μg·kg-1,C组为40 μg·kg-1,D组为100 μg·kg-1,E组为200 μg·kg-1.左眼注射5 μL平衡盐溶液(BSS)作为对照,通过裂隙灯、直接检眼镜、视网膜电流图及组织病理切片观察结膜、角膜、前房、虹膜、晶状体、玻璃体和视网膜的变化.结果 A、B、C、D、E和对照组裂隙灯及检眼镜检查均未见结膜充血、水肿及坏死,晶状体透明,玻璃体无混浊,视网膜血管未见缩窄;视网膜电流图检查所有Lewis鼠眼差异未见统计学意义(P>0.05);病理学检查所有鼠角膜结构清晰,虹膜基质及虹膜上皮未见异常,视网膜各层结构清晰,形态规整,未见细胞水肿.4 μg·kg-1、20 μg·kg-1、40 μg·kg-1、100 μg·kg-1 、200 μg·kg-1雷帕霉素剂量组在结膜下注射前和注射后进行裂隙灯、直接眼底镜、视网膜电流图和组织病理学检查均未见明显的异常改变.结论 Lewis鼠结膜下注射200 μg·kg-1及以下剂量雷帕霉素不会引起眼部组织结构及视网膜功能的异常.     

3种几丁聚糖生物膜眼部生物相容性的实验研究

目的 评价合成的3种不同的几丁聚糖生物膜(壳聚糖生物膜、琥珀酰几丁聚糖生物膜、羧甲基几丁聚糖生物膜)眼内植入的生物相容性.方法 健康新西兰白兔9只,随机分为3组,每组3只,分别将壳聚糖生物膜、琥珀酰几丁聚糖生物膜、羧甲基几丁聚糖生物膜(编号分别为1号膜、2号膜、3号膜)植入到不同组别兔的右眼前房内和左眼结膜下,使用裂隙灯显微镜观察并记录植入后不同时间实验兔双眼反应.生物膜植入到前房内第15天时,每组选1只兔处死后将右眼角膜组织送扫描电镜观察.结果 3种不同的几丁聚糖生物膜植入到结膜下,均未造成严重的结膜充血和水肿.1号膜、2号膜植入到结膜下,术后第30天时打开植入处结膜,发现生物膜已经降解;3号膜植入到结膜下,观察至术后2.5个月时结膜下仍可见植入膜的轮廓.1号膜、2号膜植入到前房中,随着材料的降解,出现了前房渗出、角膜水肿、前房积脓等严重炎性反应,它们在前房内的完全降解时间为10～13 d;3号膜植入到前房中未引起明显的炎性反应,在前房内的降解时间大约为60 d.扫描电镜结果显示1号膜、2号膜植入兔的角膜内皮表面有大量降解为小颗粒状的植入材料;3号膜植入兔的角膜内皮细胞六边形形态完整,表面无降解颗粒附着,结论合成的羧甲基几丁聚糖生物膜在免眼结膜下和前房内均具有较好的生物相容性.     

不同壳聚糖膜片兔眼前房生物相容性的实验研究

目的观察不同壳聚糖膜片在兔眼前房的相容性,评价其用作角膜内皮细胞移植载体的可行性。设计实验研究。研究对象新西兰大白兔33只。方法33只兔中30只随机分为三组,分别将脱乙酰度为63％（A组）、74％（B组）、95％（C组）的壳聚糖生物膜植入到兔的左眼前房内,右眼不做操作作为空白组;另3只兔左眼仅做前房穿刺作为对照组。使用裂隙灯显微镜观察并记录植入后3、5、7、10、14天各组兔眼前房反应。1、2,4、8周测量角膜厚度。2、4周行术眼角膜内皮镜观察。1、3个月时病理切片,苏木精一伊红染色,观察术眼的炎症反应情况。主要指标角膜厚度、内皮细胞密度、六角形细胞率、平均细胞大小。结果术后1周内,三组兔眼均出现不同程度的角膜水肿、前房渗出、虹膜充血;术后第2周,A、B组出现前房积脓、虹膜新生血管,且膜片透明度下降,至术后2个月前房积脓、虹膜新生血管基本消失。C组第2周后未出现前房积脓及虹膜新生血管,且膜透明性好。角膜测厚显示,仅术后2周时c组角膜厚度较A、B两组的角膜厚度薄（F=13．425,P=0．000）,其余时间点均未见角膜厚度的差异。术后2周各膜片组术眼内皮细胞密度、六角形细胞率和细胞大小与空白组正常兔眼问均无显著性差异（P均〉0．05）;术后1个月,A、B组HE染色示膜片周围大量炎性细胞聚集,术后3个月形成炎性肉芽肿,膜片被包裹。C组术后1个月,膜片周围未发现炎症细胞的包绕,只在膜片与角膜或虹膜组织接触点上有少量的炎性细胞,3个月后膜片周围无炎症反映。结论脱乙酰度为95％的壳聚糖生物膜较脱乙酰度63％、74％者具有更好的前房生物相容性。     

Effect of long-term subconjunctival administration of Diamox (acetazolamide) on the ocular tension in rabbit

Summary In eight normal rabbits, sodium acetazolamide (5.5 mg per kg of body weight) in 11% solution was injected subconjunctivally daily for about four weeks in the left eye of each rabbit, with the right eye serving as a control. Ocular tension in both eyes was measured by the Perkins hand-held applanation tonometer. Five of the eight rabbits showed a significant difference (P < 0.05) in ocular tension between treated and untreated eyes, with a decrease in the treated left eye. The ocular tension decrease in the treated left eye began about one week after the beginning of the injections and lasted for about two weeks. Thereafter, ocular tension in the treated left eye returned to base-line levels, despite continued subconjunctival injection of sodium acetazolamide.

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Zusammenfassung Bei 8 Kaninchen wurden Sodium Acetazolamide (5,5 mg pro Kilogramm Körpergewicht) in einer 11%igen Lösung subconjunctival unter die Bindehaut des linken Auges von jedem Kaninchen injiziert, während das rechte Auge zur Kontrolle diente. Der intraoculare Druck wurde in beiden Augen mit dem Handapplanationstonometer nach Perkins gemessen. Fünf der acht Kaninchen zeigten einen signifikanten Unterschied (P < 0,05) im intraocularen Druck zwischen dem behandelten und unbehandelten Auge mit einem Abfall im behanddelten Auge. Der Abfall des intraocularen Druckes in dem behandelten Auge begann ungefähr eine Woche nach dem Einsetzen der Injektionen und hielt für ungefähr 2 Wochen an. Danach kehrte der intraoculare Druck in den behandelten Augen zu den Ausgangswerten zurück trotz Fortsetzung der subconjunctivalen Injektionen von Sodium Acetazolamiden.

     

Studies on the lymph drainage of the eye 5. Quantitative registration of the lymph drainage from the subconjunctival space with a radioactive tracer (author's transl)

In 7 rabbits the drainage from the subconjunctival space to the cervical lymph nodes was observed after subconjunctival injection of 99mTc-micro-colloid. Measurements of the activity distribution were made in vivo with an Anger type camera (pho-Gamma-IV Hp, Searle Nuclear Chicago) and in vitro after dissection with a sodium iodine crystal well counter (Clinimat-200, Picker). 6 hours after the injection into the subconjunctival space of the right eye an average of 53.7% of the applied activity had drained off. A significant accumulation of activity could constantly be registrated in the cervical lymph nodes. Its amount was generally up to 2.08% of the applied total activity per animal, with a large individual spreading. In detail, activity was found in all 7 cases in the right superficial cervical lymph node, in 5 cases moreover in the right mandibular lymph node, additionally in 2 animals in the right or left deep cervical lymph node respectively and in one animal as well in the right as in the left deep cervical lymph node. Besides, in all cases high activity was registered in the right retrobulbar and subconjunctival spaces just as in the right eye. A small activity in the right optic nerve could be pointed out in three of our seven cases.     

Effect of subconjunctival bevacizumab (Avastin) on experimental corneal neovascularization in guinea pigs

PURPOSE: To evaluate the effect of subconjunctival bevacizumab (Avastin) on experimental corneal neovascularization in guinea pigs. METHODS: Forty eyes of 40 guinea pigs were chemically cauterized with 75% silver nitrate and 25% potassium nitrate sticks. Fifteen eyes (group 1) received 2 subconjunctival injections of bevacizumab (0.1 mL, 1.25 mg) simultaneously with cauterization and 3 days later. Fifteen eyes (group 2) received 2 subconjunctival injections of bevacizumab (0.1 mL, 1.25 mg) 3 and 5 days after cauterization. Ten eyes (group 3, control group) received 2 subconjunctival injections of 0.1 mL of balanced salt solution 3 and 5 days after cauterization. After we determined the burn and neovascularization scores for all groups, the animals were killed on the 10th day. The percentages of neovascularization on the surface of the cornea were measured in terms of pixels on digital photographs. The average number of vessels at maximally vascularized areas was determined for each specimen. RESULTS: Neovascularization score was 1.1 +/- 0.3 in group 1, 2.46 +/- 1.3 in group 2, and 3.5 +/- 0.5 in the control group. The difference was statistically significant (P < 0.001). The area of neovascularization at the cornea surface was 15.6% +/- 10.1% in group 1, 19.74% +/- 11.2% in group 2, and 23.5% +/- 7.4% in the control group (P = 0.194). The average number of neovascular vessels at group 1 was significantly reduced in comparison with group 2 and the control group (P < 0.001). CONCLUSIONS: Subconjunctival injection of bevacizumab decreases the extent of chemically induced corneal neovascularization in guinea pigs. The antineovascular effect of bevacizumab is higher if the injection is performed simultaneously with the chemical cauterization.     

Aqueous flare induced by heparin-surface-modified poly(methyl methacrylate) and acrylic lenses implanted through the same-size incision in patients with diabetes.

PURPOSE: To compare the degree of blood-aqueous barrier (BAB) breakdown in eyes of diabetic patients after phacoemulsification and implantation of heparin-surface-modified poly(methyl methacrylate) (PMMA) or soft hydrophobic acrylic intraocular lenses (IOLs) performed using the same technique with the same incision size to determine the influence of the IOLs on postoperative inflammation independent of other surgical factors. SETTING: Department of Ophthalmology, University of Paris XIII, Bobigny, France. METHODS: In a prospective study, 44 eyes of 31 diabetic patients with or without mild to moderate diabetic retinopathy were randomly assigned to receive an HSM PMMA IOL (22 eyes) or a soft hydrophobic acrylic IOL (22 eyes) after standardized phacoemulsification surgery. Both types of IOLs had a 6.0 mm optic, were inserted unfolded, and were placed in the bag through a calibrated 6.0 mm superior scleral incision. Anterior chamber flare was measured preoperatively and 1, 7, 30, and 240 days postoperatively using the Kowa 500 laser flare meter. RESULTS: The mean flare value was higher on the first postoperative day in both groups. There were no statistically significant between-group differences in flare scores or clinical parameters preoperatively or at any postoperative visit. CONCLUSIONS: No significant difference was observed in inflammation between eyes having HSM PMMA IOL implantation or those having soft hydrophobic acrylic IOL implantation through the same-size incision. This indicates that hydrophobic acrylic and HSM PMMA materials induce the same degree of BAB breakdown after phacoemulsification in eyes of diabetic patients.