Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intravitreal implantation of dermal connective tissue in rabbits caused a fibroplasia resulting in vitreous retraction, retinal detachment, and traction of nervous tissue from the optic nerve into the vitreous space. Following implantation into eyes with an intact vitreous the incidence of retinal detachment was low (2 eyes of 12). When the hyaluronic acid of the vitreous was degraded by hyaluronidase prior to implantation, 9 eyes of 12 developed a progressive detachment of the retina, usually within one or two months. Intravitreal fibroplasia was found to be an important pathogenic factor causing deteachment of the retina.
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PMID:Experimental fibroplasia in the rabbit vitreous. Effects of hyaluronidase and implantation of autologous dermal tissue. 77 3

The rate of transfer of intravitreally injected tritiated water from the mid vitreous to the choroid is significantly increased after depolymerization of vitreous hyaluronic acid by injected hyaluronidase. The significance of this finding is discussed in relation to such conditions as retinal detachment and reattachment.
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PMID:Effect of intravitreal hyaluronidase on the clearance of tritiated water from the vitreous to the choroid. 401 49

A biochemical analysis of 66 samples of subretinal fluid from patients with primary rhegmatogenous retinal detachment showed that 46 contained hyaluronic acid. Seventeen samples that did not contain hyaluronic acid disclosed hyaluronidase activity. Hyaluronidase activity in the subretinal fluid increased with the duration of the detachment but there was no correlation between enzyme activity and the age of the patient or the extent of the retinal detachment.
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PMID:Lysosomal hyaluronidase in the subretinal fluid of patients with rhegmatogenous retinal detachments. 709 Dec 83

An original model of experimental proliferative vitreoretinopathy consisting of an intravitreal injection of 10(7) human platelets and 1 IU of hyaluronidase was developed in pigmented rabbits. One group of 11 eyes served as non-treated controls. Two other groups of 11 eyes each received Ginkgo Biloba extracts which are known free radical scavengers (EGb761, Ipsen, France), given orally in two doses, 50 mg kg-1 day-1 and 100 mg kg-1 day-1 respectively, from the day after the platelet injection to the end of the first month. The fourth group (11 eyes) was intravenously injected with a unique dose of 15000 U kg-1 of superoxide dismutase the day after platelet injection. All animals were ophthalmoscopically examined in a masked fashion twice a week for 1 month and killed at the end of the experiment for histological analysis. Vitreoretinal proliferation was graded according to a six-stage classification. The non-treated eyes showed a high rate of retinal detachment (11/11 eyes), with a mean final score of 3.91 +/- 0.94. Histologic examinations consistently showed retinal retraction by fibrocellular preretinal membranes spreading to both surfaces of the retina as well as preretinal neovascularization. Many cells positively reacted with anti-cytokeratin or anti-vimentin monoclonal antibodies. All three groups of treated eyes showed significantly lower scores of vitreoretinal proliferation at almost each time point of examination. At the end of the study, five retinal detachments were found in the EGb761 group at 50 mg kg-1 day-1 (mean final score 2.45 +/- 1.37), only one in the group receiving 100 mg kg-1 day-1 (mean score 1.64 +/- 1.03), and one in the SOD treated eyes. The lowest mean score found at day 28 was observed in the group receiving SOD (1.36 +/- 1.43), although this group presented during the first 3 weeks with an intense vitreous and sometimes anterior chamber inflammation. Statistical comparison between treatments did not show significant differences at most time points of the study. These results demonstrate that antioxidants may efficiently prevent preretinal proliferation, in clinicopathological entities where free radicals had not yet been shown to play a direct pathogenetic role. They are also among the first attempts for inhibiting preretinal proliferations with non-cytotoxic agents and using a non-ocular route.
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PMID:Inhibition of preretinal proliferation by free radical scavengers in an experimental model of tractional retinal detachment. 769 62

ISTA Pharmaceuticals (formerly Advanced Corneal Systems) has developed an ophthalmic injectable formulation of highly purified hyaluronidase [ovine hyaluronidase, Vitrase] for the initial treatment of vitreous haemorrhage and diabetic retinopathy. Hyaluronidase is a naturally occurring enzyme that digests certain forms of carbohydrate molecules called proteoglycans. The current medical treatment for vitreous haemorrhage is vitrectomy, an invasive surgical procedure that may result in future cataract formation, retinal detachment or other complications. There are currently no approved drug therapies for vitreous haemorrhage. ISTA believes that an injection of Vitrase causes the vitreous to liquefy, thereby promoting the clearance of vision-distorting blood. The elimination of blood helps to restore vision and provides an ophthalmologist with an unobstructed view of the retina, allowing the doctor to diagnose and treat the underlying cause of the hemorrhage. In mid-1997, Advanced Corneal Systems (now ISTA Pharmaceuticals) formed a Singapore subsidiary called Visionex to develop and market the company's technologies in Southeast Asia and China. In March 2000, ISTA completed the acquisition of Visionex. Also in March 2000, subsidiaries of Allergan obtained marketing, sales and distribution agreements from ISTA for Vitrase worldwide, except Mexico (until April 2004) and Japan. ISTA will split Vitrase profits equally with Allergan and receive royalties on sales in non-US countries. ISTA is responsible for all costs of product development, preclinical studies and clinical trials, of Vitrase and may receive up to 35 million US dollars in milestone payments from Allergan upon the achievement of specified regulatory and development objectives. In December 2001, Otsuka gained exclusive rights to develop, market and commercialise Vitrase in Japan. In July 2002, ISTA announced that it has entered into an agreement with Cardinal Health for the manufacture of commercial quantities of Vitrase. The agreement covers the US, Canada, Japan and the European Union. Cardinal Health will also provide manufacturing-related information for the US New Drug Application (NDA). Sophia Laboratories distribute Vitrase in Mexico. The US FDA designated Vitrase as a fast track product in October 1998, which means the FDA will facilitate the development and expedite the review of the product. Vitrase has being investigated in two multinational, randomised, placebo-controlled, phase III trials in patients with severe vitreous haemorrhage. One was conducted in the US, Mexico and Canada (North American trial) with an enrolment of 750 patients. The second trial was conducted in Europe, Brazil, Australia and South Africa and enrolled 556 patients. In March 2002, ISTA began unmasking the data, revealing that although preliminary efficacy results did not show any statistically significant improvement in the primary endpoint, clinically relevant improvements in visual acuity and a decrease in the density of vitreous haemorrhage were observed in patients treated with a 55IU dose of Vitrase, compared with placebo-treated patients. In December 2002, the FDA accepted the NDA for Vitrase for filing. The FDA's Dermatologic and Ophthalmic Drugs Advisory Committee reviewed the Vitrase NDA on 17 March 2003 and voted 8 to 4 that there was insufficient statistical evidence to support the use of Vitrasefor the treatment of vitreous haemorrhage. However, the Committee did recognise that in certain patient subgroups, the benefits of Vitrase therapy outweighed the potential risks. The FDA has recommended that ISTA provide additional analyses from the two pivotal phase III trials conducted. In April 2003, the FDA issued an approvable letter for Vitrase for the treatment of vitreous haemorrhage. ISTA anticipates that the FDA will complete its review of the Vitrase NDA anete its review of the Vitrase NDA and issue the results during the second half of 2003. In addition, ISTA plans to submit a marketing approval application with the European Medical Evaluation Agency (EMEA) in the first half of 2003. A phase II trial in Singapore was being conducted by Visionex. However, in March 2000, ISTA completed the acquisition of Visionex. In its Securities and Exchange Commission (SEC) filing, as at 31 December 2002, ISTA stated that the continued development of Vitrase for diabetic retinopathy will be dependent upon a number of factors including the FDA's evaluation of Vitrase for the treatment of vitreous hemorrhage, the successful completion of any additional clinical trials for the diabetic retinopathy, and the continuing assessment of the market opportunity for this indication compared with other product opportunities that ISTA may be pursuing at the time. ISTA is also developing hyaluronidase products for the treatment of cataracts (Keratase) and keratoconus (Keraform).
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PMID:Hyaluronidase (Vitrase)--ISTA: hyaluronidase--ISTA pharmaceuticals. 1275 8

The purpose of this study was to evaluate peri-operative outcome after vitreoretinal surgery when peribulbar anaesthesia is combined with general anaesthesia. Sixty adult patients undergoing elective primary retinal detachment surgery with scleral buckling or an encircling procedure received either peribulbar anaesthesia in conjunction with general anaesthesia or general anaesthesia alone. For peribulbar anaesthesia a single percutaneous injection of 5-7 ml of local anaesthetic solution (0.75% ropivacaine with hyaluronidase 15 iu.ml(-1)) was used. The incidence of intra-operative oculocardiac reflex and surgical bleeding interfering with the surgical field, postoperative pain and analgesia requirements, and postoperative nausea and vomiting were recorded. In the block group there was a lower incidence of oculocardiac reflex and surgical bleeding intra-operatively. Patients in the block group also had better postoperative analgesia and a lower incidence of postoperative nausea and vomiting compared with the group without a block. The use of peribulbar anaesthesia in conjunction with general anesthesia was superior to general anaesthesia alone for vitreoretinal surgery with scleral buckling.
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PMID:The effect on outcome of peribulbar anaesthesia in conjunction with general anesthesia for vitreoretinal surgery. 2003 68