Regular silicone and fluorosilicone oil in the prevention of retinal detachment caused by experimental proliferative vitreoretinopathy

The effect of both regular silicone and fluorosilicone in preventing retinal detachment caused by experimental proliferative vitreoretinopathy was studied in rabbit eyes which received 250,000 fibroblasts after vitrectomy and lensectomy. In the control group, 14 out of 20 eyes which received fibroblasts had retinal detachments with disorganization of internal structures. In eyes receiving fibroblast and regular silicone, 4 out of 20 eyes had shallow retinal detachment. In the eyes receiving fibroblasts and fluorosilicone, 5 of 28 eyes had shallow retinal detachment. Our findings indicate that both regular silicone and fluorosilicone were effective in preventing retinal detachments caused by experimental proliferative vitreoretinopathy. There was no statistical difference between the two silicone oils.Supported in part by Public Health Service Grant EYO 2377, from the National Eye Institute, National Institutes of Health, Bethesda, MD.     

Success and complications of pneumatic retinopexy

Fifty-eight consecutive patients with rhegmatogenous retinal detachment were treated by pneumatic retinopexy using intravitreal perfluoropropane gas. Reattachment was achieved in 29 of 35 eyes (83%) having single retinal breaks (up to 45 degrees in extent), including dialyses (up to 60 degrees), and groups of breaks within one clock hour. The cumulative reattachment rate was 37 of 58 eyes (64%), including eyes with detachments with multiple breaks 30 to 120 degrees apart and vitreous hemorrhage as well as aphakic and pseudophakic eyes. Pneumatic retinopexy was successful in 18 of 22 (82%) myopic eyes (-3 to -11 diopters). Virtually all complications developed in the inferior retinal quadrants, and included preretinal vitreous condensations or membranes in 27 of 58 eyes (47%), new retinal breaks in seven eyes (12%), and rhegmatogenous or tractional detachments in previously attached areas in 14 eyes (24%). Postoperative proliferative vitreoretinopathy occurred in six eyes (10%) and macular pucker in two (3%).     

Naka-Rushton equation parameters in electroretinogram analysis of daunomycin effects on retinal function

Intraocular daunomycin may inhibit intravitreal cellular proliferation in proliferative vitreoretinopathy after rhegmatogenous retinal detachments and retinal reattachment surgery. Doses of 15 nmol or more have shown histological retinal toxicity when injected into the intact vitreous of rabbit eyes. We injected 30, 20, 10 and 0 nmol doses of daunomycin into rabbit eyes with gas-compressed vitreous to better simulate the clinical conditions in which it would be used. We then evaluated effects on retinal function by examining scotopic b-wave amplitudes, measured for a four log unit set of intensities. We used the three independent parameters Rmax, log K, and n of the Naka-Rushton equation to measure changes in retinal function. All three doses of daunomycin failed to measurably depress retinal function (i.e., there were no dose-related losses of Rmax, log K or n) in this experimental model. We used this approach to monitor alterations in retinal function since it can show selective changes in each parameter. This selectivity is an advantage over monitoring retinal function with single intensities or comparisons limited solely to electroretinogram amplitudes.     

The effect of triamcinolone acetonide on a refined experimental model of proliferative vitreoretinopathy

Animal models of proliferative vitreoretinopathy in which the intact vitreous body is injected with large numbers of fibroblasts do not resemble the human situation. Using a refined rabbit model of proliferative vitreoretinopathy in which the vitreous is compressed and partially detached from the retinal surface and small amounts of tissue-cultured homologous fibroblasts (25,000) are scattered over the vascularized part of the retina, we reevaluated the effect of intravitreally injected triamcinolone acetonide. We found that 2 mg of the corticosteroid reduced the incidence of retinal detachments from 90% to 56%. The effect was less than in previous models with intact vitreous. Large doses of the corticosteroid had no additional effect on the reduction of retinal detachments, indicating an optimal dosage of 2 mg. The effect of the corticosteroid on neovascularization was considerable; with 8 mg it could almost be prevented (reduction from 74% to 8%).     

Experimental scar membranes in the rabbit's vitreous. An autoradiographic and quantitative morphological study

A morphological and autoradiographic assessment was made of scar tissue development in an experimental rabbit model of proliferative vitreoretinopathy which involves the intravitreal injection of cultured autologous skin fibroblasts. Within a few hours after injection as many as 40% of the cultured cells had autolysed. However, the remaining cells proliferated and formed membranes. The incorporation of [3H] thymidine was maximal at 1 week. Between 2 and 4 weeks spindle-shaped myofibroblasts were prominent, and this form of fibroblast has been considered to have an important role in scar tissue contraction. At the end of 4 weeks it was noted that all eyes had developed retinal detachments. Subsequently the membranes became progressively more fibrous and lipid-like material accumulated in the cytoplasm of many cells. The findings were discussed in relation to the use of this model to test the effectiveness of various drugs which may be of value in the treatment of proliferative vitreoretinopathy.     

Evaluation of experimental proliferative vitreoretinopathy in rabbits

We established an effective animal experimental model for proliferative vitreoretinopathy (PVR) by intravitreally injecting cultured cells in order to investigate therapies for PVR, including intravitreal drugs, radiation and hyperthermia. After making posterior vitreal separation by injecting SF6 gas into the rabbit's vitreous body, cultured cells were intravitreally injected. Fundus changes were followed up for 4 weeks and PVR stage was recorded according to the classification described by Hida et al. The cultured cells injected were rabbit dermal fibroblasts (5 x 10(4) and 10 x 10(4) and human retinal pigment epithelial (RPE) cells (5 x 10(4]. A total of 37% of animals reached STAGE 5-7 (traction retinal detachment) in 4 weeks in 41 eyes injected with 5 x 10(4) rabbit fibroblasts and were 86% in 14 eyes injected with 10 x 10(4) rabbit fibroblasts. The 10 eyes injected with human RPE cells showed STAGE 2 or less in 4 weeks. Consequently, we selected the experimental PVR model using injecting of 10 x 10(4) rabbit fibroblasts as the most effective method.     

A morphological study of experimental intravitreal proliferative tissues]

Experimental tractional retinal detachments in rabbits' eyes was produced several weeks following aspiration of vitreous gels through a posterior small window of the eye wall. Histological examination showed that intravitreal proliferative tissues contained many fibroblasts, derived from the optic disc a small amount of migrated RPE, macrophages and other cells associated with proliferative tissues, Glial cells also grew especially at the epi-retina, causing shrinkage of the sensory retina. Vitreous neovascularization deriving from the retinal vessels was also found in these proliferative tissues. Our experimental data indicated that the extent of proliferative tissues mainly depend upon the amount of vitreous loss and vitreous hemorrhage, and the duration of retinal detachment. This experiment may be useful as an animal model of vitreous neovascularization.     

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     

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.     

Liposome suppression of proliferative vitreoretinopathy. Rabbit model using antimetabolite encapsulated liposomes

The effects of the antimetabolites, cytarabine (Ara-C) and 5-fluorouridine 5'-monophosphate (FUMP), encapsulated in multivesicular liposomes on formation of vitreous fibroproliferative membranes in New Zealand white (NZW) rabbits were studied. In pharmacokinetic studies, the drug half-life in the vitreous cavity was 124 hr after intravitreal administration of 1.0 mg of FUMP in liposomes. By contrast, the drug half-life after a single injection in nonliposome-treated controls was only 4.5 hr. In a heterologous dermal fibroblast model of proliferative vitreoretinopathy (PVR), there was a 92% decrease in frequency of tractional retinal detachments in rabbits receiving a single intravitreal injection of liposome-encapsulated 0.1 mg of FUMP compared with controls receiving liposomes without drug. A dose of 1 mg of Ara-C in liposome-treated rabbits was associated with only a 46% reduction in tractional detachment compared with controls. Multivesicular liposome-encapsulated FUMP may be useful for inhibiting formation of fibroproliferative membranes in the vitreous after vitreoretinal surgery.     

Vitreon, a new perfluorocarbon.

We evaluated a new liquid perfluorocarbon, perfluorophenanthrene (Vitreon). This material has proven to be non-toxic in vitrectomised rabbit eyes for up to six weeks. Present investigation under FDA guidelines establishes both the safety and efficacy of Vitreon in human eyes. We used Vitreon for intraoperative hydrokinetic retinal manipulation in 15 patients. In cases of proliferative vitreoretinopathy (6), rhegmatogenous retinal detachment (5), giant retinal tear (2), retinal dialysis (1), and tractional retinal detachment (1) the retina was successfully reattached. Postoperatively two patients developed proliferative vitreoretinopathy necessitating further surgery, and one patient developed hypotony. Follow-up showed 100% reattachment rate with a mean duration of 6.3 months. Postoperative visual acuity ranges from light perception to 20/30.     

玻璃体腔注射阿霉素和万古霉素治疗眼球穿孔伤并发症的实验研究

目的观察玻璃体腔注射阿霉素和万古霉素对感染性眼内炎及外伤性增生性玻璃体视网膜病变（PVR）的抑制效果。方法40只新西兰白兔随机分为4组,每组10只。右眼建立外伤性出血性眼球穿孔伤模型,左眼为空白对照眼。4个组中生理盐水组,玻璃体腔注射生理盐水0．1mL;阿霉素组,注射阿霉素2．5μg（0．1mL）;万古霉素组,注射万古霉素1．0mg（0．1mL）;联合用药,注射阿霉素2．5μg（0．1mL）及万古霉素1．0mg（0．1mL）。以裂隙灯显微镜观察眼前段炎症情况,炎症持续超过2周者行玻璃体微生物学培养;直接检眼镜观察外伤性PVR情况。结果联合用药组PVR程度低于生理盐水组（P=0．023）及万古霉素组（P=0．034）;生理盐水组、阿霉素组各发生细菌性眼内炎2例（20．0％）;万古霉素组、联合用药组未见细菌性眼内炎发生。结论在外伤性出血性眼球穿孔伤动物模型中,玻璃体腔注射阿霉素可能降低外伤性PVR程度;而玻璃体腔注射万古霉素可能降低感染性眼内炎症发生率。     

The role of the vitreous in retinal detachment surgery with external buckling

PURPOSE: To prove the role of the vitreous in retinal detachment surgery with scleral buckling procedures, we retrospectively investigated the charts of patients who were operated on for retinal detachment by scleral buckling between January 1995 and June 1997. METHODS: Out of a total of 718 cases, 41 retinal detachments occurred in previously vitrectomized eyes. The buckling procedure consisted of silicone sponge explants in 513 cases (254 radial, 259 circumferential) and of encircling elements in 202 cases. Three eyes received a temporary balloon. The minimal follow-up was 3 months. RESULTS: After primary surgery in the 677 nonvitrectomized eyes, the retina was attached in 482 eyes (71.2%), after reoperation in 627 eyes (92.6%). With up to 3 reoperations (including vitrectomy with gas or silicone oil tamponade in 79 eyes), the final success rate was 98.7%. The corresponding reattachment rates in the 41 vitrectomized eyes were 82.9% after primary surgery and 97.6% after reoperation. Repeated surgery in 6 eyes consisted of successful internal tamponade by silicone oil. The reattachment rates after primary buckle procedure are of most interest to the role of the vitreous: the highest success rate (82.9%) was achieved in the vitrectomized eyes versus 71.2% in the nonvitrectomized eyes. The difference is statistically not significant. CONCLUSIONS: We therefore conclude that the absence of the vitreous has no adverse effect on the results of buckling procedures for retinal detachment. The choice of the surgical technique in treating retinal detachments in vitrectomized eyes should only determined by retinal findings such as the number and extent of breaks or the presence and stage of proliferative vitreoretinopathy.     

Transferrin–Ricin A Chain Toxin Limits the Development of Experimental Proliferative Vitreoretinopathy

This study was designed to determine the safety and efficacy of transferrin–ricin A chain toxin (Tfr-rRA) at preventing retinal detachment in a rabbit model of proliferative vitreoretinopathy (PVR). The toxicity of intravitreal Tfr-rRA (1000–5000ng) was determined by indirect ophthalmoscopy and electroretinography on days 1, 5, 8, 16, 26 and 48 post-injection, and by light and transmission electron microscopy conducted on eyes enucleated 48 days after drug exposure. PVR was created by injecting 25000 homologous fibroblasts into the vitreous cavity of eyes which had previously undergone a gas compression vitrectomy. Eyes then received intravitreal Tfr-rRA (2000ng) or vehicle. Animals were examined on days 1, 4, 7, 10, 14, 21 and 28 post-injection. Intravitreal injection of 1000 and 2000ng Tfr-rRA did not show ophthalmoscopic or electroretinographic toxicity. Injection of 5000ng Tfr-rRA showed mild retinal whitening, retinal arteriolar narrowing, and electroretinographic toxicity, but no morphologic damage, such as photoreceptor loss, nuclear layer vacuolation, or inflammatory cell infiltration, to the retina. Tfr-rRA (2000ng) injected intravitreally 3 days after fibroblast injection prevented traction retinal detachment in 90% of eyes compared to 22% of sham treated eyes (P< 0.001). The data from this study suggest that transferrin-ricin A chain toxin (2000ng) safely and effectively limits retinal detachment in experimental PVR.     

维拉帕米防治外伤增生性玻璃体视网膜病变的实验研究

目的观察维拉帕米(verapamil,Ver)对眼后节穿通伤增生性玻璃体视网膜病变(proliferative Vitreoretinopathy,PVR)的影响。方法64只青紫蓝兔，每只兔任选其中一只眼制备外伤性PVR模型后随机分为两组，治疗组在模型制备后立即每日结膜下注射2.5 mg/ml的Ver0.5ml，对照组则每日结膜下注射生理盐水0.5　ml，共21天。模型制备后7天内每天用裂隙灯显微镜及间接立体检眼镜观察伤口、角膜、前房及眼底情况，此后每周第3，7天各检查1次。伤后第35天时常规摘除模型制备眼作光镜观察。结果在模型制备后第35 天，治疗组18只眼发生牵引性视网膜脱离，占56.3%，对照组26只眼发生，占81.3%(χ²=4.655，P=0.031)；玻璃体视网膜增生程度治疗组较对照组明显减轻( 秩和检验，u=3.5419，P<0.001)；未发现Ver对角膜上皮有明显毒性反应。结论结膜下注射Ver能有效抑制外伤性PVR的发展，减少牵引性视网膜脱离的发生率；Ver在实验所用剂量对角膜上皮无明显毒性反应。(中华眼底病杂志,1999,15:69-71)     

The lack of an effect of intraocular steroids on irradiated fibroblasts in experimental proliferative vitreoretinopathy

Contraction of intraocular membranes is an important event in the development of proliferative vitreoretinopathy (PVR). When sufficient numbers of cells are present in the vitreous cavity, the retina usually detaches as a result of the contractive force generated by these cells. Steroids reduce the occurrence of retinal detachments in rabbit models of PVR by inhibiting the proliferation of injected fibroblasts. In this study, we used non-proliferative, irradiated cells to determine a possible effect of steroids on preretinal membrane contraction in PVR. We found no clinical difference between steroid treated eyes and sham-treated control eyes. Surgical reduction of the contractile tissue and medical therapy to prevent reproliferation are necessary in order to treat PVR effectively. Offprint requests to: R. MachemerThis study was supported by the National Eye Institute, Grant EYO 2903, Research to Prevent Blindness, Alcon Laboratories, and the Helena Rubinstein Foundation     

An intravitreal biodegradable sustained release naproxen and 5-fluorouracil system for the treatment of experimental post-traumatic proliferative vitreoretinopathy

BACKGROUND/AIMS: To determine the potential of an intravitreal sustained release naproxen and 5-fluorouracil (NA/5-FU) codrug for the treatment of experimental proliferative vitreoretinopathy (PVR) in a model for trauma associated tractional retinal detachment (TRD). METHODS: Sustained release pellets were prepared by covalently linking naproxen to 5-fluorouracil. Drug release was tested in vitro and toxic effects were evaluated by electroretinography and light microscopy. Traumatic PVR was induced in pigmented rabbits by performing a scleral laceration, followed by repair and intravitreal injection of 0.4 ml of autologous blood. Thirty six eyes were treated with a sustained release implant containing 1.5 mg NA/5-FU as a codrug and 36 control eyes were submitted to surgery alone. Eyes were evaluated for TRD by serial indirect ophthalmoscope examination at different time points followed by postmortem fundus evaluation of the enucleated eye RESULTS: The NA/5-FU pellets were found to provide linear release of 5-FU and naproxen over the 30 day duration of the in vitro release test. Both the severity of PVR grade and the percentage of eyes with moderate or worse tractional detachment were significantly lower in eyes treated with the codrug pellet. There were no drug related toxic effects evident on histopathological or electroretinograph examination of eyes containing the NA/5-FU pellet. CONCLUSIONS: The results suggest that this NA/5-FU codrug device effectively inhibits the progression of PVR in a rabbit trauma model that closely resembles PVR in humans. Additional studies to add knowledge to these initial findings and to clarify the potential of the codrug device for the treatment of human PVR are warranted.     

The antidepressant hypericin inhibits progression of experimental proliferative vitreoretinopathy.

PURPOSE. Hypericin, a polycyclic dione used as an antidepressant, has been shown to inhibit the protein kinase C (PKC) pathway. Many of the pathologic responses found in proliferative vitreoretinopathy (PVR) are dependent upon PKC. Therefore, we studied the effect of hypericin on the treatment of experimental PVR. METHODS. PVR was induced in pigmented rabbits by intravitreal injection of 50,000 rabbit conjunctival fibroblasts after vitrectomy. Subsequently, the eyes received an intravitreal injection of either balanced salt solution (BSS, 0.1 mL) (group A, control) or hypericin (0.1 mL) in doses of 1 muM (group B), 10 muM (group C), and 100 muM (group D). The eyes were examined ophthalmoscopically on days 1, 3, 7, 14, and 28 after surgery and the stage of PVR was evaluated (0 to V). The effect of hypericin on retinal morphology and function was also determined for the eyes injected with 100 muM hypericin with no fibroblasts by light microscopy and electroretinogram (ERG). RESULTS. In the control eyes, the retina was detached after 5 days, membranes had formed on and beneath it, and the PVR had progressed to higher stages over time. In the eyes injected with hypericin, the PVR also progressed; however, the severity of PVR on each day was lower than that in control eyes on that day. PVR was significantly inhibited in groups C and D as compared with the control eyes after day 5 (P < 0.05). Histological examination of the hypericin-treated control eyes disclosed no morphological change, and ERG analysis revealed no significant functional change. CONCLUSIONS. Intravitreal injection of hypericin is a safe and effective means of reducing experimental PVR.     

药物性玻璃体后脱离对增生性玻璃体视网膜病变影响的实验研究

目的 观察药物性玻璃体后脱离（PVD）对增生性玻璃体视网膜病变（PVR）的影响。方法 24只有色成年家兔,左眼为实验眼。兔自体富含血小板血浆玻璃体腔注射建立兔眼PVR模型,同时随机将实验兔分为A、B组及对照组,每组各8只眼。建模后3 h A组玻璃体腔内注入1 U纤溶酶（0.05 ml）+20 U透明质酸酶（0.05 ml）共0.1 ml、B组玻璃体腔内注入纤溶酶0.1 ml、对照组玻璃体腔内注入等量的平衡盐溶液。给药后1、7、28 d记录实验眼PVR级别,进行各组PVR等级评分,并行闪光视网膜电图（F-ERG）、眼部B型超声检查及视网膜组织病理学检查。结果 PVR模型成功建立,并在注药后7 d,A组发生完全性PVD 5只眼,不完全性PVD3只眼;B组不完全性PVD 5只眼,未见完全性PVD,另3只及对照组无PVD发生。A、B组在注药后28 d PVR等级评分均低于对照组,差异有统计学意义（D=75.6, 98.9;P=0.003,P=0.011）;注药后7、28 d,A、B 两组F-ERG b 波波幅均高于对照组;产生PVD的眼中PVR级别均较无PVD的眼级别低,其中完全性PVD眼中PVR级别仅为0～1级。结论 在兔眼PVR建模后3 h,纤溶酶与透明质酸酶联合玻璃体腔注射诱导的完全性PVD在一定程度上可以阻止兔眼PVR的发生和发展,纤溶酶单独或联合透明质酸酶玻璃体腔注射诱导的不完全 性PVD对PVR的发展有减缓作用。     

Healon in retinal detachment with proliferative vitreoretinopathy

In 73 eyes, retinal detachments complicated by proliferative vitreoretinopathy (PVR) were treated by intravitreal injections of Healon, in addition to scleral buckling procedures. The number of completely reattached retinas three months postoperatively was dependent upon the grade of PVR: 50% were reattached when PVR comprised only one quadrant (Grade C-1); 30% when two to four quadrants were involved (Grade C-2, C-3 and D-1). Reattachment was not achieved in two cases of PVR with funnel-like configurations (D-2). Major complications that could be attributed to Healon did not occur. The results indicate that Healon injections, combined with scleral buckling procedures, are an encouraging approach to retinal detachments with PVR Grades C-2 through D-1.