PURPOSE:A prospective, randomised, masked study comparing three different intraocular infusion solutions used during vitrectomy on postoperative electroretinography (ERG) and retinal histology of rabbit eyes. METHODS MATERIALS AND ANIMALS:Twelve rabbit eyes were used with each group of three intraocular infusion solutions: Lactated Ringers (LR), balanced salt solution (BSS) and balanced salt solution-plus (BSS-Plus). RESULTS:At 24 hours postoperatively, the ERG values were 36%, 68% and 75% of the normal values for LR, BSS and BSS-Plus, respectively. At 72 hours postoperatively, the ERG values were 50%, 84% and 100% of the normal values for LR, BSS and BSS-Plus, respectively. At 72 hours postoperatively, 3/12, 10/12 and 12/12 of the vitrectomised eyes had regained normal-value ERGs for LR, BSS, and BSS-Plus eyes, respectively. At 1 week postoperatively, 4/12 and 12/12 of LR and BSS eyes, respectively, had normal ERGs. The number of LR eyes regaining normal ERG values was 4/12, 6/12 and 9/12, measured at 1, 4 and 15 weeks postoperatively, respectively. RETINA HISTOLOGY:At 15 weeks follow-up, histopathology was performed on several rabbit eyes. Histological examination of LR-irrigated eyes showed 2/7 normal retinas, whereas 5/7 showed changes that ranged from vacuoles in the inner retina to numerous vacuoles in both the outer and inner retina with disruption of the inner nuclear layer. The histology of BSS-infused and BSS-Plus-infused rabbit eyes was normal. CONCLUSION:LR solution, when used during vitrectomy, has a more prolonged negative effect on ERG than BSS and BSS-Plus. Histological changes seen in LR eyes may explain the ERG results.

The generation of an atraumatic posterior vitreous detachment (PVD), a common goal in vitreoretinal surgery, is a challenge particularly in children and young trauma patients. Plasmin has been proposed as a surgical adjunct to enzymatically generate a PVD. This study assesses the performance and safety of a new system for rapid purification of plasmin as an adjunct to vitrectomy.

Intravitreal plasmin creates a posterior vitreous detachment, but may also liquefy the vitreous. This study measures the rate of vitreous removal from rabbit eyes after plasmin injection in vivo.

PURPOSE:To describe the finding of tenascin C and cystatin-C in the intraschisis cavities of pediatric patients with intraretinal schisis cavities. METHODS:Three patients with congenital X-linked retinoschisis (CXLRS) and one girl with clinical retinoschisis underwent vitrectomy for vision-threatening schisis cavities. At the time of surgery undiluted samples of intraschisis fluid and vitreous fluid from four eyes (three male and one female) were obtained and analyzed by gel electrophoresis and protein sequencing for the presence of tenascin C and cystatin-C. RESULTS:Tenascin C and cystatin-C were found in all four samples of fluid from the intraschisis cavities, including a girl with a clinical presentation of CXLRS. The vitreous samples did not have detectable levels of either protein as determined by gel electrophoresis. CONCLUSIONS:Tenascin C and cystatin-C levels are elevated in intraschisis cavity fluid. Interestingly, this was also found in a girl not carrying a mutation in the retinoschisin gene, indicating that elevated concentrations of tenascin C and cystatin-C result from pathologic changes in the retina and not from the presence of aberrant retinoschisin.

Purpose: To describe the intraschisis cavity protein composition in congenital X-linked retinoschisis (CXLRS) from two eyes of one child.Methods: The authors present a child with complex, Type 3 CXLRS who underwent bilateral surgical repair with autologous plasmin enzyme-assisted lens-sparing vitrectomy. Undiluted samples of intraschisis fluid and vitreous fluid from two eyes (one child) were obtained and used for protein analysis.Results: The patient underwent successful schisis repair with plasmin-assisted lens-sparing vitrectomy and silicone oil. Two unique protein bands were identified in the intraschisis cavity sample of each eye by gel electrophoresis. The proteins were identified as tenascin-C, an extracellular matrix protein involved in wound healing, and cystatin C, a ubiquitous cysteine protease inhibitor implicated in inflammation.Conclusions: Tenascin-C has previously been described in its complex relationship with decorin and fibronectin in normal wound healing. Tenascin's upregulation in sites of inflammation and tenascin's role as an antiadhesive molecule may contribute to the pathogenesis of CXLRS. To the authors' knowledge, this is the first description of intraschisis cavity fluid.

BACKGROUND:The generation of an atraumatic posterior vitreous detachment (PVD), a common goal in vitreoretinal surgery, is a challenge, particularly in children and young trauma patients. Plasmin has been proposed as an adjunct to vitrectomy to enzymatically generate a PVD. Low doses of streptokinase-activated plasmin were tested in human pilot studies. This dose-escalation study assesses the safety range of intravitreal human streptokinase-plasmin in rabbits.METHODS:Plasminogen was isolated from human plasma by affinity chromatography, followed by activation with streptokinase (1:1), to generate the streptokinase-plasmin complex. Enzyme doses from 0.1-7 activity units (AU, in 0.1 ml) were injected into the mid-vitreous of 35 eyes; six control eyes were injected with balanced salt solution (BSS, 0.1 ml). Thirty minutes after injection, a two-port vitrectomy was performed. Fundus and slit lamp examinations were performed on days 1 and 7. On days 2 and 7, bright flash electroretinography was performed and compared with preoperative recordings. Some animals receiving higher doses of streptokinase-plasmin (1-7 AU) were followed clinically and with electroretinography for up to 9 months.RESULTS:A mild-to-moderate inflammatory response was seen in both control and plasmin-treated eyes on day 1, but had disappeared completely by day 7 in most eyes. In the 7 AU group, inflammation was stronger and more protracted. Two of three eyes from this group developed wrinkling of the medullary rays; one of them showed discoloration and traction at the medullary rays in the late follow-up. Electroretinograms (ERGs) of vitrectomized control eyes showed the following changes from preoperative values: 48 h, a-wave -11.10% [no significant (n.s.)], b-wave -14.62% (P=0.046); 7 days, a-wave +9.18% (n.s.), b wave +11.69% (n.s.). For the enzyme-treated eyes: 48 h: a-wave -20.43% (P<0.001), b-wave -9.57% (p<0.001); 7 days: a wave -14.21% (P<0.001), b-wave +2.48% (P<0.001). There was no evidence of dose-dependent ERG changes in enzyme-treated eyes at doses up to 5 AU. Groups of up to 3 AU were investigated by light and transmission electron microscopy, without evidence of toxicity.CONCLUSION:Streptokinase-plasmin doses up to 3 AU were found to be safe when injected into rabbit eyes followed by vitrectomy.

Purpose: To describe treatment of a child with recalcitrant ligneous conjunctivitis secondary to a systemic plasminogen deficiency.Design: Interventional case report.Methods: A seven-year-old boy developed severe unilateral membranous conjunctivitis recalcitrant to surgical debridement and treatment with topical prednisone, topical cyclosporine, and oral prednisone. Systemic evaluation revealed a severe plasminogen deficiency.Results: Treatment with surgical debridement and topical plasmin was ineffective and resulted in prompt recurrence of dense conjunctival membranes. Treatment with topical plasminogen resulted in dramatic improvement and complete resolution of the membranes.Conclusions: Ligneous conjunctivitis is secondary to a systemic plasminogen deficiency. Treatment with topical plasminogen resulted in prompt resolution of the membranes. Treatment with topical plasmin was ineffective.