Enzymatically induced posterior vitreous detachment in proliferative diabetic vitreoretinopathy

BACKGROUND: Complete detachment of the posterior vitreous cortex is an important aim in the treatment of proliferative diabetic vitreoretinopathy (PDVR). Today a posterior vitreous detachment (PVD) can only be achieved during vitrectomy. A randomized pilot study was started to evaluate wether intravitreally injected TPA is sufficient to induce a PVD in diabetic eyes. PATIENTS AND METHODS: Eight weeks prior to vitrectomy because of proliferative diabetic vitreoretinopathy (non-clearing haemorrhage, fibrovascular proliferations) 20 eyes which had an attached vitreous received a cryopexy of the peripheral retina. In 11 eyes that had been selected at random 10 micrograms of recombinant tissue plasminogen activator were injected midvitreally 24 hrs later. A newly formed PVD was assessed by means of biomicroscopy or ultrasound. RESULTS: A newly formed partial (n = 3) or complete (n = 7) PVD was found in 10 of 11 TPA-treated eyes versus one partial detached vitreous in the control group. In 3 younger patients PVD developed exclusively after TPA-injection. We did not observe severe changes of the ERG, decrease of visual acuity, severe new vitreous haemorrhages or opacities of the lens. In 3 eyes (2 eyes of the control group) a circumscribed retinal detachment developed during the follow-up period. CONCLUSIONS: The described technique can be used in diabetics without severe side effects. It facilitates the removal of the vitreous cortex and may be a valuable adjunct to the surgical management of PDVR. Unlike other proteases TPA is available for clinical use through recombinant DNA technology which allows standardized enzymatic activities, steril and non-infectious conditions.     

周边视网膜冷冻联合tPA和C3F8玻璃体腔注射诱导玻璃体后脱离的动物实验研究

目的探讨周边视网膜冷冻后玻璃体腔注射酶或/和膨胀气体诱导玻璃体后脱离（Posterior vitreous detachment,PVD）的效果、机制并观察其对视网膜的毒性作用。方法选用新西兰白兔48只,随机分为实验组和对照组。实验组I行周边视网膜冷冻及玻璃体腔内注射纤维蛋白溶解酶原激活剂（tissue plasminogen activator,tPA）,实验组Ⅱ玻璃体腔单纯注射C3F80.3ml,实验组Ⅲ行周边视网膜冷冻,24小时后注射tPA25μg和C3F80.3ml。记录各实验组产生玻璃体后脱离的时间并观察眼内的反应性变化,最后行光镜和扫描电镜检查,观察各实验组用药后的组织形态学变化。结果三组均有效诱导PVD,组间两两比较差异有显著性（〈0.05）,实验组Ⅰ和Ⅱ眼内反应较轻,实验组Ⅲ反应最重,并有视网膜结构及功能损害。结论周边视网膜冷冻后tPA注射是诱导玻璃体后脱离安全有效的方法。单纯膨胀气体注射并非真正意义的玻璃体后脱离。酶与气体联合用药可缩短玻璃体后脱离产生时间,但容易造成视网膜药物毒性变化。     

Einsatz von Enzymen im hinteren Augenabschnitt Derzeitiger Stand und zukünftige Möglichkeiten

The first investigations to treat diseases of the posterior segment enzymatically started 40 years ago. To treat acute subretinal hemorrhage a pneumatic displacement through intravitreally injected gas after enzymatically induced subretinal fibrinolysis (TPA) is recommended. Recent morphometric analysis clearly demonstrated a subretinal fibrinolytic effect after intravitreal injection of TPA. Obviously TPA crosses the retina through microlesions that develop through elevation of the retina during acute bleeding. For the first time pars plana vitrectomy was superseded by a simple and gentle enzymatic therapy combined with pneumatic displacement by intravitreally injected gas. Increasing experience with pars plana vitrectomy demonstrated that a complete removal of the vitreous body has beneficial effects on the course of vasoproliferative vitreoretinal diseases. Therefore enzymes were tested to either liquify the vitreous body (collagenase or hyaluronidase) or to cleave the posterior vitreous cortex and the retina (dispase, plasmin, tissue plasminogen-activator or chondroitinase). At present only tissue-plasminogen activator (TPA), plasmin and hyaluronidase were used in small clinical studies. Recent developments in the understanding of vasoproliferative vitreoretinal disorders offers new therapeutical approaches like enzymatical destruction of growth factors (VEGF) or extracellular adhesive proteins (fibronectin). From this point of view future therapies may include enzymatic cleaning of the vitreous body to prevent proliferative diabetic vitreoretinopathy.     

兔眼玻璃体腔内注射纤维蛋白溶酶诱导产生玻璃体后脱离

目的 观察兔眼玻璃体腔内注射1U纤维蛋白溶酶（后诱导产生玻璃体后脱离（PVD）的情况。方法 以16只新西兰兔作为实验动物，所有右眼内注入1U纤溶酶，按设定的4个观察时间点随机分为4组。通过临床肉眼观察，视网膜电图（ERG）和组织病理学检查，考察药物注入后诱导形成PVD的情况以及药物应用的安全性。结果 玻璃体腔内注入1U纤溶酶后15min-3d，药物对视网膜结构和功能没有任何不良影响；第1d组开始有PVD发生。第3d组效果更佳。结论 1U纤溶酶可以用作玻璃体切割手术的辅助用药。     

Posterior vitreous detachment induced by injection of plasmin and sulfur hexafluoride in the rabbit vitreous

PURPOSE: To investigate whether an injection of plasmin and sulfur hexafluoride (SF6) can induce posterior vitreous detachment (PVD) without vitrectomy. METHODS: One eye each of 15 New Zealand white rabbits was assigned to one of three groups. Eyes in group 1 received a vitreous injection of 1 unit of human plasmin (0.1 mL reconstituted in balanced salt solution) and 0.5 mL of SF6; eyes in group 2 received a vitreous injection of plasmin alone; eyes in group 3 received a vitreous injection of SF6 alone. Seven days after injection, all animals were monitored electroretinographically and killed, and the eyes were enucleated. After fixation, scanning electron microscopy was performed. RESULTS: In group 1 eyes, the retinal surface was smooth except for the vitreous base, which showed complete separation of the vitreous cortex from the retina, indicating PVD. In group 2 and 3 eyes, sparse collagen fibers remained on the retinal surface. CONCLUSION: Vitreous injection of plasmin combined with SF6 can induce PVD without vitrectomy.     

Management of postvitrectomy diabetic vitreous hemorrhage with tissue plasminogen activator (t-PA) and volume homeostatic fluid-fluid exchanger.

The incidence of recurrent vitreous hemorrhage of proliferative diabetic retinopathy following posterior vitrectomy ranges from 29% to 75% in reported series. Fluid-gas exchange and vitreous cavity lavage are the popular methods of treating this kind of recurrent hemorrhage. The fluid-gas exchange cannot offer clear vision immediately after the procedure. To improve the function of the classic vitreous cavity lavage, we designed a volume homeostatic fluid-fluid exchanger - Chen's I/A device. Tissue plasminogen activator (t-PA) is a protease that preferentially converts fibrin-bound plasminogen to the active proteolytic enzyme, plasmin. It has been clinically and experimentally proven effective in lysis of postvitrectomy blood clot and fibrin formation. When the blood clot is formed in the vitreous cavity, intravitreal injection of t-PA can convert plasminogen to plasmin and remove the clot. From July 1999 to January 2000, ten eyes of postvitrectomy diabetic vitreous hemorrhage (PDVH) were collected. In each case, 4 days after intravitreal injection (IVI) of t-PA (30 microg), vitreous cavity lavage was performed with Chen's I/A device. Of these cases, 8 eyes (80%) experienced an immediate clearing of the vitreous cavity. Early complications included anterior hyaloid fibrovascular proliferation (2 eyes) and postoperative intraocular pressure elevation (3 eyes). On the basis of the results of this study, our conclusion is that volume homeostatic vitreous cavity lavage, combined with intravitreal injection of t-PA, is an excellent method for treatment of postvitrectomy diabetic vitreous hemorrhage but, in cases of PDVH with iris rubeosis, the advantage of this procedure is uncertain.     

Cerclage of the eyeball with silicone sponge as a successive procedure in severe retinal detachment

Examined were eighty nine eyes operated for recurrent retinal detachment which were subjected--as an ultimate intervention--to cerclage by means of a silicone sponge with diathermocoagulation of the sclera and with evacuation of the subretinal fluid. In part of the patients one performed additionally a laser coagulation of the retina, scleral cryopexy, intravitreal injection of SF6 gas as well as a posterior vitrectomy. Reattachment of the retina followed in 65 eyes (73%).     

Efficacy of autologous plasmin for idiopathic macular hole surgery

PURPOSE: To determine whether a single intravitreal injection of autologous plasmin or a combination of plasmin and intraocular gas without peeling the internal limiting membrane (ILM) will close idiopathic macular holes. METHODS: Eight eyes of seven patients with an idiopathic macular hole were studied. The degree of posterior vitreous detachment (PVD), vitreal liquefaction, closure of the macular hole, visual acuity, and complications following intravitreal plasmin or plasmin with gas were investigated. The removed ILM was examined by electron microscopy. RESULTS: A PVD was created in seven out of eight eyes exposed to plasmin or plasmin with gas, however, the macular hole was not closed by either. Closure occurred in two eyes using conventional vitrectomy after the plasmin with gas injection, but peeling the ILM was required in the remaining six eyes. Vitreal fibers and glial cells were not observed on the vitreal surface of the extracted ILM. CONCLUSIONS: A PVD was created safely and reliably although closure of the macular hole did not occur with either plasmin or with plasmin and gas injection. However, vitreous surgery became easier, and it required a shorter time to close the macular hole with intravitreal plasmin.     

The role of recombinant lysine-plasminogen and recombinant urokinase and sulfur hexafluoride combination in inducing posterior vitreous detachment

PURPOSE: To determine the optimal method of generating plasmin in vitreous using recombinant lysine-plasminogen and recombinant urokinase and to determine its efficacy in inducing posterior vitreous detachment when combined with sulfur hexafluoride. METHODS: Plasmin concentration of the rabbit vitreous after separate and combined intravitreal administrations of recombinant lysine-plasminogen and recombinant urokinase was tested in 78 rabbits to determine the optimal method of administration. The safety and efficacy of these agents and sulfur hexafluoride in inducing complete posterior vitreous detachment (total separation of the vitreous apart from vitreous base) were also evaluated. RESULTS: The highest plasmin concentration in vitreous was measured 10 minutes after injection. Intravitreal administration of recombinant lysine-plasminogen and recombinant urokinase did not cause any toxicity findings up to concentrations of 100 microg and 200 IU, respectively, on funduscopy, electroretinography, and histopathologic studies. When combined with sulfur hexafluoride injection, separate intravitreal administrations of 75 microg/0.1 mL of recombinant lysine-plasminogen and 15 IU/0.1 mL of recombinant urokinase induced complete posterior vitreous detachment in 75% of the eyes compared with 13% in eyes that received sulfur hexafluoride injection combined with balanced salt solution, recombinant lysine-plasminogen, or recombinant urokinase. CONCLUSIONS: Plasmin was effectively generated in the vitreous after separate intravitreal administrations of recombinant lysine-plasminogen and recombinant urokinase. When combined with intravitreal gas injection, this method of plasmin production induced complete posterior vitreous detachment in 75% of the eyes.     

TPA-assisted vitrectomy for proliferative diabetic retinopathy: results of a double-masked, multicenter trial.

OBJECTIVE: Some complications of vitrectomy are related to adherence of the vitreous body to the retina. We studied whether these complications could be decreased by injecting a proteolytic enzyme, tissue plasminogen activator (TPA), at the beginning of surgery to aid separation of the vitreous from the retina. METHODS: Fifty-six patients receiving surgery for complications of proliferative diabetic retinopathy were divided into two groups in this prospective, randomized, double-blind study. Group I patients received 25 microg of intravitreal TPA in buffered salt solution (BSS) 15 minutes before vitrectomy. Group II received BSS alone. Postoperative follow-up lasted up to 3 months. The major criteria for comparison were the number of perioperative iatrogenic tears, the gain in visual acuity, and the reattachment rate of tractional retinal detachments. RESULTS: No difference was found between the two groups for the principal indicators or for complications. CONCLUSION: In proliferative diabetic retinopathy, the use of 25 microg of TPA by intravitreal injection 15 minutes before vitrectomy does not improve the results. No specific complications of the method were noted. The failure can be attributed to a too-short delay between TPA injection and beginning of surgery, an insufficient dose, or an insufficient quantity of plasminogen in the vitreous at the beginning of the intervention.     

Intravitreale Injektionen

Since 1996 acute subretinal hemorrhages have been treated by intravitreal injections. Large proteins injected into the vitreous cavity can cross the retina as well as the underlying retinal pigment epithelium. After intravitreal injection of tissue plasminogen activator (TPA), plasminogen, which is part of a subretinal clot, is converted to plasmin in the presence of fibrin. Plasmin is a relatively unspecific protease that liquefies a formed fibrin clot. Simultaneous intravitreal injection causes an inferior displacement of the liquefied hemorrhage. Beside mechanical effects on subretinal clots plasmin inhibits choroidal neovascularization by hydrolysis of the extracellular matrix as well as growth factors. After successful displacement of a subretinal hemorrhage an additional anti-VEGF (vascular endothelial growth factor) therapy is required.     

Dispase facilitates posterior vitreous detachment during vitrectomy in young pigs

PURPOSE: To evaluate the role of intravitreal dispase in conjunction with pars plana vitrectomy to facilitate the creation of a posterior vitreous detachment (PVD) in young pig eyes. METHODS: Twenty-four eyes of 24 animals were randomized to receive an intravitreal injection of dispase (50 microg/0.05 mL) or phosphate buffered saline (PBS) immediately after core vitrectomy and before attempted creation of a posterior cortical vitreous detachment. Following a 15-minute waiting period, surgical creation of a posterior vitreous separation was attempted by aspiration of the posterior vitreous immediately adjacent to the optic disk. Eyes were evaluated postoperatively by clinical examination (1, 4, and 8 weeks) and electroretinography (4 and 8 weeks), after which they were enucleated for light, scanning, and transmission electron microscopy. RESULTS: Based on intraoperative findings and postoperative scanning electron microscopy, eyes receiving intravitreal dispase exhibited a higher incidence of PVD compared to eyes receiving PBS (P = 0.029). Electroretinographic responses recorded at postoperative weeks 4 and 8 were similar in both dispase and PBS eyes compared to the unoperated fellow eyes. Clinical examinations, including indirect ophthalmoscopy, were indistinguishable between the PBS eyes and 11 of 12 eyes in the dispase group. Light and transmission electron microscopy demonstrated no differences in the retina between the dispase eyes and the PBS operated controls. CONCLUSION: Dispase is a useful adjunct in facilitating surgical creation of a PVDin young pig eyes.     

人脐带血浆纤维蛋白溶解酶原的纯化及其诱导玻璃体后脱离的研究

背景近年来关于药物性玻璃体溶解的研究已陆续开展，主要包括软骨素酶、透明质酸酶、分散酶和纤维蛋白溶解酶等几大酶类，有些已应用于临床试验。然而对源于人脐带血浆的纤维蛋白溶解酶用于实验性诱导动物眼玻璃体后脱离（PVD）的研究尚未见报道。目的从人脐带血血浆中实现有活性的纤维蛋白溶解酶原的提取及纯化，并探讨其在诱导PVD方面的初步作用。方法利用低温醇沉液相分离法从人脐带血血浆中获得较纯的纤维蛋白溶解酶原（Pig）并进行活性测定。取新鲜离体猪眼25只，分为5组。第一组作为正常对照，第二组每只眼玻璃体腔注入0．1ml平衡盐溶液（BSS），第三组每只眼注入0．1ml含1000Ixmol／（min·L）的重组链激酶（r-sK），第四组每只眼注入0．1ml含1000tzmol／（min·L）的r—sK联合0．1ml含3μmol／（min·L）的Plg（r—SK＋Plg），第五组每只眼注入0．1ml1000μmol／（min·L）的r—sK联合0．1ml3~mol／（min·L）的人纤维蛋白溶解酶原标准品（r—SK＋Plg标准品），各组药物均经睫状体平坦部注射，37℃孵育60min后常规固定，在光学显微镜、扫描电子显微镜和透射电子显微镜下进行视网膜形态学和超微结构观察。结果成功从人脐带血血浆中获得了纤维蛋白溶解酶原的分离及提取，初步纯化后获得有潜在纤溶活性的纤维蛋白溶解酶原。动物实验发现正常对照组、BSS组及r—SK组均未见PVD。除r—SK＋Pig标准品组外，r—SK＋PIg组的猪眼后极部发生PVD，视网膜内界膜表面较光滑，光学显微镜及电镜下视网膜的组织结构和细胞结构均未见异常。结论纤维蛋白溶解酶原能够通过低温醇沉联合液相分离方法从人脐带血血浆中获得并且具有潜在纤维蛋白溶解活性。1000μmol／（min·L）r—SK与3μmol／（min·L）Plg联合注入离体猪眼玻璃体腔60min可以诱发后极部PVD，对视网膜未见毒性作用。     

Triamcinolone acetonide facilitates removal of the epiretinal membrane and separation of the residual vitreous cortex in highly myopic eyes with retinal detachment due to a macular hole

PURPOSE: To study the usefulness of intravitreal triamcinolone acetonide injection during vitrectomy in highly myopic eyes with retinal detachment due to a macular hole. METHODS: Pars plana vitrectomy was performed in 6 patients with retinal detachment resulting from a highly myopic eye with a macular hole. After separation of the posterior hyaloid and removal of any visible epiretinal membrane, triamcinolone acetonide was injected over the posterior pole. Excised specimens were evaluated by transmission electron microscopy. RESULTS: Upon injection of triamcinolone acetonide, the entire epiretinal membrane and residual vitreous cortex could be visualized in all patients. The epiretinal membrane and residual posterior vitreous cortex were completely removed. Successful reattachment was performed without retinal damage in all cases. Electron microscopy revealed a cellular epiretinal membrane within a collagenous matrix lining the smooth internal surface of the internal limiting membrane. No complications related to the use of triamcinolone acetonide were encountered. CONCLUSION: Intraoperative visualization of the epiretinal membrane and residual posterior vitreous cortex with triamcinolone acetonide was found to be a useful adjunct to vitrectomy. Using triamcinolone acetonide during vitrectomy may facilitate both removal of the epiretinal membrane around the macular hole and separation of the residual vitreous cortex from the retina in highly myopic eyes with retinal detachment.     

酶学诱发PVD对视网膜细胞安全性的研究

目的 了解纤溶酶和透明质酸酶诱发玻璃体后脱离（PVD）对视网膜细胞的安全性.方法 新西兰白兔16只分4组,采用玻璃体腔内注药.A组：纤溶酶1 U＋透明质酸酶20 U;B组：纤溶酶2 U＋透明质酸酶20 U;C组：纤溶酶4 U＋透明质酸酶20 U;D组：BSS正常对照组.术后7 d摘除眼球,TUNEL法检测细胞凋亡、RT-PCR检测视网膜内c-fos基因.结果 TUNEL法检测A组视网膜标本内未发现凋亡细胞,B、C组及正常对照组视网膜内各发现1个凋亡细胞.RT-PCR检测A、B、C组及对照组视网膜内均未见c-fos基因mRNA的表达.结论 兔眼内注射纤溶酶1～4 U＋透明质酸酶20 U,在细胞和分子水平上没有加速视网膜细胞凋亡,进一步证实了该联合酶制剂眼内注射的安全性.     

Autologous plasmin for pharmacologic vitreolysis prepared 1 hour before surgery

PURPOSE: To evaluate the safety and efficacy of intravitreal injection of autologous plasmin enzyme (APE) in inducing a posterior vitreous detachment (PVD). APE was obtained by a modified method 1 hour before surgery. METHODS: APE was obtained by centrifugation of autologous whole blood from the patients 1 hour before surgery and by incubation with streptokinase. APE was injected in the vitreous cavity 20 minutes before surgery. This procedure was applied for 20 patients who underwent vitrectomy for macular pucker, macular hole, and macular edema due to vitreoretinal traction. The status of PVD was graded intraoperatively. The plasmin concentration obtained by this method and the plasminogen titer of the plasma from each patient were compared. Activated partial thromboplastin time was controlled before surgery and 1, 6, 12, and 24 hours after surgery to evaluate alteration of the coagulation due to systemic absorption of the plasmin. RESULTS: Preparation of APE was easy and took on average 45 minutes for all patients. A PVD with an evident Weiss ring was observed during surgery in 17 eyes (85%). The average plasmin activity was 0.26 IU/0.2 mL activated plasma. The partial thromboplastin time did not show any alteration in any of the patients with respect to preoperative values. CONCLUSION: APE obtained by this method can lead to a PVD and facilitate the complete remotion of vitreous cortex. The intravitreal injection does not lead to alteration of systemic blood coagulation.     

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.     

纤维蛋白溶解酶和Dispase蛋白酶诱导兔眼玻璃体后脱离的实验研究

目的研究纤维蛋白溶解酶和dispase蛋白酶诱导玻璃体后脱离(PVD)的作用。方法24只健康成年的青紫兰兔随机分为4组,右眼均为实验眼,左眼为对照眼。A组实验眼玻璃体腔内注射纤溶酶1U,B组纤溶酶2 U,C组dispase蛋白酶0.0125U和D组dispase蛋白酶0.025U,对照眼均为眼用平衡盐BSS液0.1 ml。注药前后行眼底镜、裂隙灯和VOLK 90D前置镜以及B超和视网膜电图(ERG)检查,最后取眼球进行光镜、扫描电镜和透射电镜观察。结果电镜结果A组2只实验眼后极部发生不完全性PVD,发生率为33.3%;B、C两组实验眼中各有4只眼发生完全性PVD。发生率为66.7%;D组实验眼有5只眼发生完全性PVD,发生率为83.3%。纤溶酶各组实验眼注药后ERG振幅与术前及对照眼比较无显著性差异(P>0.05),光镜和透射电镜观察视网膜组织结构正常,均未发现明显异常改变。而Dispase蛋白酶各组透射电镜观察视网膜细胞和细胞器出现水肿和变性。ERG检测Dispase两组实验眼术后b波振幅较术前明显降低(P<0.01)。结论玻璃体腔注射纤溶酶2U较注射1U更能有效的诱导PVD且对视网膜无明显的毒性作用。而Dispase蛋白酶虽然可迅速有效的诱导PVD,但对视网膜有明显的毒性作用。     

Efficacy of plasmin enzymes and chondroitinase ABC in creating posterior vitreous separation in the pig: a masked,placebo-controlled in vivo study

Background Induction of posterior vitreous detachment (PVD) during vitrectomy helps to prevent proliferative complications, but can be traumatic to the retina, particularly in young patients. Adjunct enzymes have been proposed to facilitate PVD. We investigated the efficacy of enzymes in creating PVD as an adjunct to vitrectomy in the pig. Methods Five groups of 8 pigs received a masked intravitreal injection of chondroitinase (1 IU), human (0.4 or 1.3 activity units [AU]) or porcine plasmin (0.18 AU or 0.47 AU) into one eye, and osmolarity adjusted control into the other. After incubation, a core vitrectomy was performed on each eye at low suction, without vitreous peeling. The occurrence of spontaneous PVD and its extent were graded. Eyes were investigated using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Vitreous remnants on the retina were quantified in SEM. Data were analyzed using McNemar’s test for paired observations and Wilcoxon paired signed rank test. Results Spontaneous PVD occurred more frequently in human plasmin-treated eyes (p<0.025) and all plasmin eyes (p<0.025) than in placebo controls. The extent of PVD appeared larger in human plasmin (p<0.025) and all plasmin-treated eyes (p<0.025). In plasmin-treated eyes, SEM morphometry showed a significant reduction in the vitreous-covered retina areas. Chondroitinase failed to produce an effect. Conclusions Plasmin may prove a useful adjunct to conventional vitrectomy. The results were presented in part at the ARVO Annual Meeting, 2001.     

The effect of tissue plasminogen activator on premacular hemorrhage

BACKGROUND AND OBJECTIVE: Early vitrectomy is recommended for eyes with premacular hemorrhage, which causes fibrovascular proliferation and macular traction. The purpose of this study was to investigate the therapeutic effects of tissue plasminogen activator (tPA) on premacular hemorrhage, and the clearing of hemorrhage from the macula. PATIENTS AND METHODS: The authors injected tPA (25-37.5 microg) into the vitreous cavity of 13 eyes with premacular hemorrhage. The causes of premacular hemorrhage were diabetic retinopathy in 11 eyes and traumatic injuries in 2 eyes. Prior to tPA injection, 4 eyes had complete posterior vitreous detachment (PVD) and 9 eyes had no PVD. RESULTS: After tPA injection, the hemorrhages in 10 eyes were completely absorbed. They were absorbed partially in 2 eyes and were not absorbed at all in 1 eye. Absorption of hemorrhage in the 4 eyes with complete PVD took an average of 5.5 days, and in the 6 eyes with no PVD, it took an average of 12.7 days (P=0.002). After tPA injection, visual acuity improved in 9 eyes, remained stable in 3 eyes, and worsened in 1 eye. In 5 eyes, pars plana vitrectomy (PPV) was required after tPA injection because of recurrent vitreous hemorrhage, macular traction or nonabsorbed premacular hemorrhage. CONCLUSION: TPA seems to be a good alternative method of treatment for premacular hemorrhage, especially in eyes with complete PVD. It appears to improve vision and defer the need for PPV.