Autologous Plasmin Enzyme Research Articles

Invivo generated autologous plasmin enzyme assisted vitrectomy, partial circumferential-oral retinotomy, silicone oil injection in patients with chronic retinal detachment without posterior vitreous detachment

PurposeTo report the results of invivo generated autologous plasmin enzyme(IVAP) assisted vitrectomy, partial circumferential-oral retinotomy and silicone oil injection for surgical treatment of patients with chronic retinal detachment without posterior vitreous detachment(PVD).MethodsStudy was performed in retrospective, comparative manner. A total of 16 consecutive eyes with chronic retinal detachment who had intravitreal injection of 50 µgr of t-PA and 0.1 ml of autologous whole blood, 3 days before surgery, underwent lens extraction with phacoemulsification, IVAP assisted vitrectomy, partial circumferential-oral retinotomy, and silicone oil injection(Study Group) were compared to a similar group of 15 eyes who had undergone vitrectomy, with or without lens extraction and silicone oil injection(Control Group) for the treatment of chronic retinal detachment. Primary outcome measures were initial retinal reattachment and number of operations at postoperative 6 months.ResultsMean age of 16 patients of whom 7 were female, was 39.31 ± 17.76 years in study group and 15 patients of whom 4 were female, was 35.40 ± 11.92 years (p = 0.607). Mean follow-up time was 10.68 ± 7.15 months in study group and 29.13 ± 18.83 months in control group (p = 0.001). Initial retinal reattachment was achieved in 87.50% (14 out of 16 patients) in the study group, whereas it was 46.66% (7 out of 15 patients) in the control group (p = 0.017). The mean number of operations for reattachment in the study group was 1.12 ± 0.34, whereas it was 1.46 ± 0.51 in the control group (p = 0.039) at postoperative 6 months While the preoperative LogMAR visual acuity was 1.25 ± 0.64, it was 0.53 ± 0.37 at postoperative 6 months in study group (p = 0.001). Conversely, in the control group, the preoperative LogMAR visual acuity was 1.22 ± 0.33, it was 1.20 ± 0.89 at postoperative 6 months (p = 0.780). At postoperative 6 months,, epiretinal membrane developed in 2 eyes of the study group, 1 eye in the control group, and phthisis bulbi occurred in 1 eye of control group.ConclusionIVAP assisted vitrectomy, partial circumferential-oral retinotomy and silicone oil injection is effective and safe for the surgical treatment of chronic retinal detachment without PVD.

A Literary Pediatric Retina Fellowship With Michael T. Trese, MD.

Michael T. Trese, MD (1946-2022), a vitreoretinal surgeon, made significant contributions to the field of retina. Although most known for his work in pediatric retina surgery, he was a pioneer in areas such as medical retina, translational research, and telemedicine. This article reviews his major contributions to spread his knowledge more widely to vitreoretinal trainees and specialists. We discuss six areas where Trese made a lasting impact: lens-sparing vitrectomy, familial exudative vitreoretinopathy, congenital X-linked retinoschisis, autologous plasmin enzyme, regenerative medicine, and telemedicine. [Ophthalmic Surg Lasers Imaging Retina 2023;54:701-712.].

Treatment of vitreomacular traction syndrome with autologous plasmin enzyme

PurposeTo determine whether intravitreal injection of autologous plasmin enzyme (APE) is effective in vitreomacular traction syndrome (VMTS) by improving visual acuity and restoring macular morphology. MethodsA prospective study of 11 consecutive patients diagnosed with VMTS in the Ophthalmology Department from January to May 2011. Inclusion criteria: best corrected visual acuity (BCVA) less than 0.5, and vitreomacular attachment in foveal area resulting in macular thickness >250μm diagnosed by optical coherence tomography (Cirrus OCT, Carl Zeiss Meditec, Inc, Oberkochen, Germany). Exclusion criteria: active proliferative diabetic retinopathy, axial myopia >26mm, vitrectomy, glaucoma, previous intravitreal injections and previous rhegmatogenous detachment. One to the 3 monthly intravitreal injections of 0.2ml of APE was applied, interrupting if posterior vitreous detachment was attained. Wilcoxon's test was used for statistical analysis. ResultsA total of 12 eyes of 11 patients were treated. A complete posterior vitreous detachment was achieved in 4 (33%) eyes at the end of the study, 2 of them with one injection, and 2 with 3 monthly injections. Improvement of BCVA was statistically significant (p=0.017) and the decrease in central macular thickness also was statistically significant (p=0.016). There was only one complication: intraocular hypertension after injection that subsided with a new paracentesis. ConclusionsIntravitreal APE injections avoided vitrectomy in VMTS in one in every 3 patients.

Tratamiento del síndrome de tracción vitreomacular con plasmina autógena

PurposeTo determine whether intravitreal injection of autologous plasmin enzyme (APE) is effective in vitreomacular traction syndrome (VMTS) by improving visual acuity and restoring macular morphology. MethodsA prospective study of 11 consecutive patients diagnosed with VMTS in the Ophthalmology Department from January to May, 2011. Inclusion criteria: best corrected visual acuity (BCVA) less than 0.5, and vitreomacular attachment in foveal area resulting in macular thickness>250 microns diagnosed by optical coherence tomography (Cirrus OCT, Carl Zeiss Meditec, Inc, Oberkochen, Germany). Exclusion criteria: active proliferative diabetic retinopathy, axial myopia>26mm, vitrectomy, glaucoma, previous intravitreal injections and previous rhegmatogenous detachment. One to 3 monthly intravitreal injections of 0.2ml of APE were applied, interrupting if posterior vitreous detachment was attained. Wilcoxon's test was used for statistical analysis. ResultsA total of 12 eyes of 11 patients were treated. A complete posterior vitreous detachment was achieved in 4 (33%) eyes at the end of the study, 2 of them with one injection, and 2 with 3 monthly injections. Improvement of BCVA was statistically significant (P=.017) and the decrease in central macular thickness also was statistically significant (P=.016). There was only one complication: intraocular hypertension after injection that subsided with a new paracentesis. ConclusionsIntravitreal APE injections avoided vitrectomy in VMTS in one in every 3 patients.

The role of autologous plasmin enzyme in the therapy of macular edema secondary to RVO

AbstractAbstract not provided

Reply to Matonti et al

Sir, We thank Dr Matonti et al1 for their interest in and comments on our recent article.2 We agree that in our study we should have been waiting longer to definitely assess the effects of autologous plasmin enzyme (APE) in patients with vitreomacular traction syndrome. In fact, although we could not ascertain if a greater time gap could have influenced the rate of posterior vitreous detachment occurrence, as Dr Matonti et al correctly pointed out, we remarked that the single injection appeared as a useful tool in vitreoretinal surgery because of obtaining an easier-to-peel posterior hyaloid.3 However, as per our ethical committee-approved protocol (reported in the Methods section), and due to medico-legal reasons, we were allowed to perform just one single intravitreal injection for each study patient, with a 24-h waiting time before vitrectomy. This, together with the impossibility (per protocol) to re-inject patients with APE, should be acknowledged as the limitation of our study.

Reply to Grzybowski and Ascaso

Sir, We thank Drs Grzybowski and Ascaso1 for their interest in and comments on our recent article.2 We agree that in our paper there is a lack of details concerning the statistical tests used (which were omitted for the sake of brevity). In the study, we proved that each variable group was normally distributed using the Kolmogorov-Smirnov normality test. Then we applied the ANOVA for repeated measures test, which best fitted for our analysis. Please note, the Kruskal-Wallis test is valuable only for a two-group comparison. We also agree that the lack of a control group is crucial, and this was acknowledged as a limitation of our study. We also acknowledged the unmasked design of the study as a limitation of our analysis. Regarding the evaluation of posterior hyaloid peeling, our method to describe the intrasurgical findings has been already published by Azzolini et al3 in a study investigating autologous plasmin enzyme for diabetic macular oedema, and, to our knowledge, no other classification systems are available in the literature. In the conclusion section, we stated that a single intravitreal autologous plasmin enzyme injection seemed to be insufficient to induce a complete posterior vitreous detachment in patients affected by focal vitreomacular traction syndrome, as in our case series, we did not obtain any complete posterior vitreous detachment with a single injection. We thank the authors for the opportunity to clarify this important aspect, which we do not find contradictory. As per our ethical committee approved protocol (reported in the Methods section), we were allowed to perform just one single intravitreal injection for each study patient, with a 24-hour waiting time before vitrectomy. Although we could not ascertain if a greater time gap could have influenced the rate of posterior vitreous detachment occurrence, we remarked that the single injection appeared as a useful tool in vitreoretinal surgery by obtaining an easier-to-peel posterior hyaloid. Finally, during the revision process of our paper, we preferred to exclude the comparison of our results with the MIVI-IIT study,4 as the MIVI-IIT study has a very different study design and uses a different drug. Particularly, we believe that our impossibility (per protocol) to re-inject patients preclude any comparison between the two studies.

MICROPLASMIN (OCRIPLASMIN) IN PEDIATRIC VITREORETINAL SURGERY

To discuss the potential role of microplasmin (ocriplasmin) as a surgical adjunct to vitrectomy in pediatric vitreoretinopathies. Literature review of the laboratory and clinical evidence to date for the use of both autologous plasmin enzyme as an adjunct to vitrectomy and more recently recombinant microplasmin (ocriplasmin) as monotherapy for focal vitreomacular traction in adults. Autologous plasmin enzyme is currently being used as a surgical adjunct to vitrectomy, with supporting Levels 2 and 3 published evidence in a range of pediatric vitreoretinopathies including Stage 5 retinopathy of prematurity and congenital X-linked retinoschisis. The availability of autologous plasmin enzyme is limited. In recent Phase 3 clinical trials, intravitreal ocriplasmin versus sham injection resulted in resolution of focal vitreomacular traction in 27% versus 10% (P < 0.001, n = 652). Ocriplasmin may potentially be used as a surgical adjunct to vitrectomy in place of autologous plasmin enzyme. A Phase 2, randomized, placebo-controlled surgical trial is under way to assess this.

Enzymatic vitrectomy for diabetic retinopathy and diabetic macular edema

The aim of this paper is to determine the role of enzymatic vitrectomy performed by intravitreal injection of autologous plasmin enzyme (APE) in the management of diabetic retinopathy and diabetic macular edema (DME). Diabetic patients with proliferative diabetic retinopathy or DME and evident posterior hyaloid adherence to the retinal surface were included. All cases were treated with an initial intravitreal injection of APE and reevaluated one month later, measuring changes in best-corrected visual acuity (BCVA), macular thickness and the status of the posterior hyaloid. A second APE injection was performed in cases with no evident posterior vitreous detachment (PVD) after the initial treatment. Sixty-three eyes were included in the present review. A complete PVD appeared in 38% of cases (24 eyes) after one injection of plasmin and the total increased to 51% (32 eyes) after the second injection, separated at least by one month. The central macular thickness improved in all cases (100%) and BCVA in 89%. Finally, in 50% of eyes with proliferative diabetic retinopathy, a high reduction of new vessels regression was observed. Enzymatic vitrectomy could be considered a good therapeutic alternative in diabetic retinopathy and macular edema.

Vitreomacular traction syndrome: a comparison of treatment with intravitreal plasmin enzyme vs spontaneous vitreous separation without treatment

To evaluate the effects of intravitreal autologous plasmin enzyme (APE) in patients with focal vitreomacular traction (VMT). APE was obtained by incubation of patient-derived purified plasminogen with streptokinase, and intravitreally injected 5-12 days later. Twenty-four hours after injection, in case of incomplete VMT release, a pars plana vitrectomy was performed. The hyaloid internal limiting membrane adherence and removal of the posterior hyaloid were intraoperatively evaluated. Thirteen patients were recruited. During preparation of APE, five patients had spontaneous release of VMT. Eight patients received APE injection (2 IU). In five patients, spontaneous resolution of VMT occurred before APE administration. Twenty-four hours after injection, persistence of VMT was detected in all the eight treated patients. Best-corrected visual acuity was 0.51±0.37 LogMAR at baseline, improving to 0.23±0.14 LogMAR at 6 months (P=0.002). Foveal thickness was 464±180 μm at baseline, reducing to 246±59 μm at 6 months (P<0.001). Hyaloid was intraoperatively judged 'partially detached' in seven cases and 'totally detached' in one case. Hyaloid peeling was evaluated 'easy' in six eyes and 'very easy' in two eyes. In the current study, there was a large percentage of spontaneous resolution of VMT before an APE administration. A single intravitreal APE injection seems insufficient to induce a complete posterior vitreous detachment in these patients.

Intravitreal Plasmin Without Vitrectomy for Macular Edema Secondary to Branch Retinal Vein Occlusion

To evaluate the effects and safety of intravitreal injections of autologous plasmin enzyme (APE), without vitrectomy, as a treatment for macular edema secondary to branch retinal vein occlusion. Prospective, comparative, interventional case series. Patients were recruited and enrolled consecutively from February 1 through October 31, 2008, at the Retina Unit of the Hospital General Universitario, Valencia, Spain. An eye from 8 patients diagnosed as having macular edema due to branch retinal vein occlusion received an injection, after having received topical anesthesia, of 0.2 mL of APE, which had been obtained using a simplified method. Best-corrected visual acuity and central macular thickness measured by optical coherence tomography constitute the main outcome measures of the study. The mean (SD) central macular thickness decreased from 494.875 (68.82) to 226.375 (28.67) μm 1 month after APE injection and to 228.570 (21.53) μm after 6 months (P < .001). The best-corrected visual acuity (logarithm of the minimal angle of resolution) improved from a preoperative value of 0.552 (0.17) to 0.217 (0.087) (mean, 20/80-20/32, Snellen equivalent) at the end of follow-up (P < .01). No secondary effects were observed during 6 months of follow-up. This pilot study suggests that intravitreal injection of APE as a treatment for macular edema secondary to branch retinal vein occlusion improves central macular thickness and best-corrected visual acuity and may be a safe and effective alternative therapy for this condition if confirmed in controlled trials compared with standard care with longer follow-up.

Pharmacologic Vitreolysis in Diabetic Retinopathy

Diabetic retinopathy remains a major cause of worldwide preventable blindness. The vitreo-retinal interface plays a critical role in the pathogenesis of diabetic retinopathy. The term pharmacologic vitreolysis refers to the use of enzymes to liquefy the vitreous gel, and to induce posterior vitreous detachment (PVD). Intravitreal ovine hyaluronidase injection was effective in clearing vitreous hemorrhage. Several human case series demonstrated that intravitreal injection of autologous plasmin enzyme was a safe and effective adjunct to vitreous surgery for the treatment of diabetic macular edema and proliferative diabetic retinopathy. Recently, it was shown that intravitreal injection of plasmin enzyme without the performance of vitrectomy induced complete PVD and reduced macular thickening due to refractory diabetic macular edema.

Intravitreal Injection of Autologous Plasmin Enzyme for Macular Edema Associated with Branch Retinal Vein Occlusion

To investigate the effects of an intravitreal injection of autologous plasmin enzyme for macular edema associated with a branch retinal vein occlusion (BRVO). Prospective, interventional case studies. Twenty-six eyes of 26 patients (14 men and 12 women) with macular edema resulting from a BRVO were studied. None of the eyes had a posterior vitreous detachment (PVD). The average age at the onset of BRVO was 58.7 ± 6.6 years. The interval between onset of the macular edema and injection of autologous plasmin enzyme was 4.2 months. One international unit of autologous plasmin enzyme in 0.1 mL was injected into each vitreous. The presence of a PVD was evaluated 1 week after the injection, and the visual acuity and macular thickness were measured before and 1 week and 1, 3, 6, and 12 months after the autologous plasmin enzyme injection. After the autologous plasmin enzyme injection, a total PVD was observed in 23 eyes and no PVD was observed in 3 eyes. The visual acuity gradually recovered after the injection, improved by 2 lines or more in 23 eyes, and remained unchanged in the 3 eyes. The retinal thickness also recovered gradually at 1, 3, 6, and 12 months. The mean retinal thickness was reduced from 602.12 to 253.62 μm at 12 months after surgery. It was reduced significantly after 1, 3, 6, and 12 months (P < .0001). Intravitreal autologous plasmin enzyme may lead to an improvement of visual acuity and a reduction of macula edema in eyes with BRVO.

Intravitreal Plasmin Without Associated Vitrectomy as a Treatment for Refractory Diabetic Macular Edema

To determine the effectiveness of a low-dose intravitreal injection of autologous plasmin enzyme (APE), without the performance of a vitrectomy, as a treatment for refractory diffuse diabetic macular edema (DDME). Prospective, comparative, interventional case series. Sixteen patients with bilateral DDME who had not responded to prior laser photocoagulation. All patients received an injection in 1 eye, while the other eye served as a control. Intravitreal 0.2 mL APE injection under topical anesthesia. The APE was obtained using a simplified method. Central macular thickness (CMT) at 1 and 6 months, determined by optical coherence tomography (OCT) and best corrected visual acuity (BCVA). All patients underwent a 1-month follow-up. Prior to injection, CMT in the eye about to receive the injection was 541 +/- 79 microm (mean +/- standard deviation [SD]) versus 535 +/- 76 microm in the control eye. One month after injection, CMT was 241 +/- 47 microm in injected eyes and 530 +/- 85 microm in control eyes (P < 0.001, bilateral Wilcoxon test for paired samples). The macular edema (ME) improved in all injected eyes (100%), with complete resolution in 7 patients (44%). The mean BCVA of treated eyes was 0.618 +/- 0.27 (mean +/- SD) at baseline and 0.45 +/- 0.24 four weeks after injection (paired samples t-test, P < 0.001). No adverse effects were observed in any of the patients. BCVA and CMT were stable when evaluated at 6-month follow-up (0.43 +/- 0.242 and 244 +/- 46 microm, respectively). Intravitreal APE injection effectively reduces macular thickening due to DDME in cases that fail to respond to conventional laser photocoagulation, and improves visual acuity in a short term, and this results remain stable in a medium term what is very important. Further investigation is warranted in order to assess long-term efficacy and safety.

SURGICAL OUTCOMES OF EPIRETINAL MEMBRANES ASSOCIATED WITH COMBINED HAMARTOMA OF THE RETINA AND RETINAL PIGMENT EPITHELIUM

To determine the surgical outcomes of epiretinal membranes associated with combined hamartoma of the retina and retinal pigment epithelium after pars plana vitrectomy and membrane peeling with or without assistance of autologous plasmin enzyme. Retrospective review of 11 pediatric eyes that underwent pars plana vitrectomy with membrane peeling with or without autologous plasmin enzyme. Preoperative and postoperative assessments of visual function and retinal architecture were performed by indirect ophthalmoscopy, optical coherence tomography imaging, fundus photography, and measurement of visual acuity. The mean age of the patients was 4.6 years (range, 1-14). Mean follow-up was 15.6 months (range, 6-42 months). The lesions were located solely in the macula in 8 of 11 (73%) patients and in the macula and posterior pole in 3 of 11 (27%) patients. Of the 11 eyes, 6 were preoperatively injected with autologous plasmin enzyme to assist in removal of the posterior hyaloid. All 11 patients (100%) had complete macular reattachment postoperatively. Eight of 11 (73%) showed improved visual acuity postoperatively, and 3 of 11 showed stabilized vision. Eight eyes required only one surgery. Four eyes (36.6%) had recurrences of epiretinal membrane, and three of these eyes required additional surgery. Of the eyes with preoperative plasmin injection, 4 of 6 (66%) showed an improvement in visual acuity whereas 2 of 6 (33%) showed stabilization of visual acuity. Four of five without plasmin showed visual improvement, and one of five had stabilization of vision. In the pediatric population, pars plana vitrectomy with membrane peeling with or without the use of autologous plasmin enzyme for epiretinal membrane associated with combined hamartomas of the retina and retinal pigment epithelium can result in improved retinal architecture and visual acuity. Visual acuity may improve despite recurrence of the epiretinal membrane.

AUTOLOGOUS PLASMIN FOR PHARMACOLOGIC VITREOLYSIS PREPARED 1 HOUR BEFORE SURGERY

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. 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. 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. 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.

POSTERIOR HYALOID CONTRACTURE IN PEDIATRIC VITREORETINOPATHIES

Retinal detachment in pediatric vasoproliferative disorders such as retinopathy of prematurity (ROP) and familial exudative vitreoretinopathy (FEVR) have an exudative and tractional component. Younger eyes have an especially adherent posterior hyaloid. Contraction of the posterior hyaloid interface may lead to tractional retinal detachment. Retrospective chart review of six eyes (four ROP, two FEVR) with diffuse contraction of the posterior hyaloid resulting in retinal detachment. Fundus photographs and optical coherence tomography findings (one eye) are presented. Diffuse proliferation along the posterior hyaloid required extensive lamellar dissection at times aided by autologous plasmin enzyme. A diffuse, taut posterior hyaloid resulted in marked tractional component to retinal detachment. Recognition of hyaloid contracture will aid in the proper diagnosis and surgical planning and repair of eyes with pediatric vasoproliferative disorders.

Use of Autologous Plasmin during Vitrectomy for Diabetic Maculopathy

To evaluate the efficacy of autologous plasmin enzyme as an adjunct to vitrectomy in diabetic macular edema. Plasmin derived from autologous blood was injected intravitreally into seven eyes 15 min before vitreous surgery. The development and progression of a posterior vitreous detachment (PVD) was followed, and the time required for vitreous removal was measured. Both pre- and postoperative visual acuities and optical coherence tomography (OCT)-determined macular thickness were measured. In the seven eyes in which plasmin was used, a PVD developed approximately 5 min after the injection and was confirmed to extend to the far periphery. In all cases, the removal of the vitreous was completed in a shorter time and no complications were observed. A restoration of the shape of the macula was observed in all cases. The visual acuity improved by two or more lines in four eyes, and remained unchanged in the remaining three eyes. Autologous plasmin alone will create a full PVD, and eliminates the need for a mechanical creation of a PVD. Thus, plasmin is a safe and effective adjunct to vitreous surgery for the treatment of diabetic maculopathy.

Intrasurgical plasmin enzyme in diabetic macular edema

To evaluate in a prospective study the efficacy of intrasurgical autologous plasmin enzyme (APE) in producing posterior vitreous detachment. Consecutive, interventional case series. A group of 12 eyes of 11 patients with diabetic macular edema secondary to posterior vitreous cortex contraction was considered. A quantity of 0.1- to 0.2-ml containing 0.8 to 1.2 IU of APE prepared by our Coagulation Service was injected into the vitreous body 25 minutes before surgery. The efficacy of the APE was subjectively evaluated. A control group of 10 eyes with the same clinical characteristics underwent the same surgery without APE injection. Complete eye examinations, including optical coherence tomography, were performed on all patients before surgery and during the 1-year follow-up period. During surgery in the APE-treated group, the posterior vitreous cortex was judged adherent in three cases, partially detached in six cases, and totally detached in three cases. In two cases a complete collapse of the vitreous body was observed. During surgery in the non-APE-treated group, the posterior vitreous cortex was judged still adherent in nine of 10 eyes and partially detached in 1 eye. Comparing the postoperative results between the APE-treated group and the non-APE-treated group, we found no significant differences in final postoperative retinal thickness (P = .2552), whereas we found a significant difference in final visual acuity (P = .0121). Autologous plasmin enzyme was useful in inducing a pharmacologic posterior vitreous detachment and in facilitating surgery. It did not seem to interfere with the final retinal thickness, and it ameliorates the final visual acuity.

Ultrastructure of internal limiting membrane removed during plasmin-assisted vitrectomy from eyes with diabetic macular edema

Purpose To study the effect of autologous plasmin enzyme (APE) on the adhesion of the vitreous cortex to the internal limiting membrane (ILM) in eyes with diabetic macular edema. Design Nonrandomized, comparative, interventional case series. Participants Ten eyes of 10 patients with diabetic macular edema without a posterior vitreous detachment (PVD), which were treated with APE as an adjunct to conventional pars plana vitrectomy, and 10 eyes of 9 patients without a PVD, which underwent pars plana vitrectomy without APE, were studied. Methods In the APE group, 0.4 IU of APE was injected into the midvitreous cavity in 9 eyes, and 0.8 IU of APE in 1 eye. Thirty minutes after plasmin injection, the eyes underwent pars plana vitrectomy with ILM peeling. All eyes in the control group had conventional vitreous surgery with ILM peeling. The removed ILMs were investigated for the presence of vitreous and for ultrastructural differences by transmission and scanning electron microscopy. Main outcome measures The status of the vitreous and induction of a PVD during surgery, and the presence of vitreous and ultrastructural differences of the removed ILM by transmission and scanning electron microscopy. Results In APE-treated eyes, the degree of liquefaction of the vitreous was graded as high in 4 eyes. Spontaneous PVD occurred in 2 eyes, whereas core vitrectomy with a maximum vacuum of 100 mmHg induced a PVD in 2 additional eyes. In the control group, 8 eyes required suction with a maximum of 200 mmHg to induce the PVD. Scanning electron micrography of the removed ILM in the APE-treated eyes showed a smooth surface on the vitreous side in 8 eyes and only sparse collagen fibers in 2 eyes. Conversely, in the control group, dense vitreous fibers were found in 4 eyes, sparse collagen fibrils in 3 eyes, and a smooth retinal surface in 3 eyes. Conclusions These findings indicate that APE helps separate the vitreous hyaloid from the ILM surface and may be a useful adjunct to conventional vitreous surgery for diabetic macular edema.