WO1999040933A1 - Utilisation de hyaluronidase afin de diminuer les hausses de pression intraoculaire associees a la viscoelasticite - Google Patents
Utilisation de hyaluronidase afin de diminuer les hausses de pression intraoculaire associees a la viscoelasticite Download PDFInfo
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- WO1999040933A1 WO1999040933A1 PCT/US1999/003125 US9903125W WO9940933A1 WO 1999040933 A1 WO1999040933 A1 WO 1999040933A1 US 9903125 W US9903125 W US 9903125W WO 9940933 A1 WO9940933 A1 WO 9940933A1
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- hyaluronidase
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
Definitions
- This invention relates to the reduction of postoperative intraocular pressure spiking.
- the eye is divided into two major sections; the anterior segment which encompasses the crystalline lens and all structures in front of it; and the posterior segment which encompasses all structures behind the lens.
- the cornea, conjunctiva, iris, ciliary body, and the lens are all found in the anterior segment.
- the cavity defined by these structures within the anterior segment is sub-divided into anterior and posterior chambers. From front to back, the anterior chamber is the space between the iris, 'and the cornea, while the posterior chamber is the cavity between the iris and the lens. Peripherally, the anterior chamber is defined by the iridocorneal angle while the posterior chamber is circumscribed by the ciliary sulcus.
- This chamber system is filled with aqueous humor which is very similar to plasma (water, NaCl, K * , etc.), is void of cells, and has little protein except in inflammatory or disease processes.
- the aqueous humor provides oxygen and nutrients to the lens, the corneal endothelium, and the trabecular meshwork, and carries metabolites away from many structures. It is secreted intc the posterior chamber bv the ciliary Drocesses - 2 - and then flows into the anterior chamber through the pupillary opening.
- the aqueous humor leaves the eye through the trabecular meshwork in the iridocorneal angle and Schlemm' s canal. Crisscrossed collagen beams covered by endothelial cells form the meshwork.
- the aqueous humor drains through the meshwork and into the Schlemm' s canal which is a small vessel in the sclera.
- the tissue between the inner wall of the Schlemm' s canal and the corneoscleral meshwork is responsible for most of the resistance to outflow of aqueous humor in the outflow pathway.
- Abnormal resistance to outflow of aqueous humor leads to an increase in intraocular pressure, which is believed to be the cause of open angle glaucoma.
- the posterior segment of the eye consists of the retina with the optic nerve, the vitreous, the choroid, and the posterior portion of the sclera.
- the vitreous fills the cavity between the lens and the retina.
- the vitreous humor is a connective tissue composed of a small amount of glycosaminoglycans, collagen and a large amount of water.
- the vitreous consists of the cortical layer, the intermediate zone, and the central zone.
- the closest area to the retina is the cortical vitreous, which consists of collagen and hyaluronic acid and has a gel-like consistency.
- the cells of the vitreous called hyalocytes, are dispersed in the outer parts of the cortical vitreous.
- the water content of the vitreous is as high as 98 to 99.7%.
- As the vitreous is an avascular structure, there is no flow through the vitreous, only diffusion.
- the blood vessels in the retina, the pigment epithelium, and the choroid are also barriers to drug penetration into the retina and the vitreous .
- Hyaluronan also known as hyaluronic acid or sodium hyaluronate, is a naturally occurring viscoelastic compound found in many tissues of the body, including the synovial fluid and vitreous. This material, in different commercial formulations, is often used in anterior and posterior segment - 3 - surgical procedures to prevent damage to tissue surfaces and to allow for more space during surgical manipulation; as a transparent substance, hyaluronan does not interfere with intraoperative visibility. Viscoelastics of several kinds have been used, e.g., in cataract surgery to maintain the shape of the anterior chamber, during lens implantation and phacoemulsification, and to protect the corneal endothelium from mechanical trauma and contact with nearby tissues and surgical instruments. This use has resulted in significant decreases in complication rates and has dramatically increased the safety of surgical procedures.
- viscoelastics have been correlated with significant increases in intraocular pressure postoperatively .
- the viscoelastic can remain in the anterior chamber, in sufficient amount to cause postoperative problems, for up to 6 days and, as a result, inhibit the elimination of anterior-chamber fluid, inflammatory products and inflammatory cells.
- Dangerous post-operative pressure spikes can occur before elimination of viscoelastic is completed.
- These intraocular pressure spikes can be caused by any of the viscoelastics and are apparent as early as 3 hours after the surgery.
- the pressure spikes can last many days, with pressures reaching as high as 60 mm Hg. Such spikes cause severe headaches and nausea and may potentially complicate blood flow, causing vision-threatening ocular ischemia and tissue damage.
- Hyaluronidase e.g., Wydase ®
- Wydase ® is currently used for subcutaneous/retrobulbar injections of local anesthesia to promote the diffusion of anesthetics.
- Hyaluronidase is a highly specific naturally occurring enzyme which cleaves hyaluronan into disaccharide components, thus reducing both its viscosity and molecular weight.
- Calder and Smith Bosh J. Ophthalmol . 20 . : 418-420, 1986
- hyaluronidase in small doses, i.e., less than 15 (and more preferably less than 10) IU per treated eye, hyaluronidase can safely and effectively be employed to blunt the postoperative intraocular pressure spikes normally caused by residual amounts of the viscoelastic hyaluronan used during anterior segment surgical procedures. Furthermore, in very low doses, e.g., less than 5 IU per treated eye, hyaluronidase can be added at the same time as the required hyaluronan, for additional beneficial effects. If the viscoelastic is in sufficient excess over the degredative enzyme, its protective effect will be maintained during the critical surgical time period.
- hyaluronidase administration in small doses either during or subsequent to surgery, can be combined with that of other medication.
- anti-glaucoma medication e.g., acetazolamide
- Diamox during intraocular lens replacement or other procedure, would be appropriate, e.g., if it were known that the patient had glaucoma, if undiagnosed glaucoma were a possibility, if there were damage to the optic nerve or if the patient also had cataracts.
- the appropriate dosage of hyaluronidase can be injected at the end of the surgical procedure, simultaneously with the injection of, e.g., acetylcholine (Miochol) or other agent used to return the pupil to normal size, so that no modification in surgical procedure is necessary.
- hyaluronidase could be added to the infusion fluid (e.g., Balanced Salt Solution) routinely used during surgery to maintain a formed anterior chamber.
- infusion fluid e.g., Balanced Salt Solution
- Fig. 1 shows the average changes of intraocular pressure in eyes treated with various viscoelastic substances (Control Eyes) ;
- Fig. 2 shows the effect of hyaluronidase alone on intraocular pressure
- Figs. 3a and 3b show the effects of the viscoelastic Healon ® on intraocular pressure with and without the addition of 5 IU and 10 IU hyaluronidase, respectively;
- Figs. 4-6 show the effects of the viscoelastics Healon GV ® , Viscoat ® and Ocucoat ® , respectively, on intraocular pressure, with and without the addition of 10 IU hyaluronidase .
- hyaluronidase to prevent increases in intraocular pressure provides for a method of preventing viscoelastic related post operative pressure spikes.
- This enzyme can be instilled in the anterior chamber of the eye of a patient at some point after hyaluronan containing viscoelastic has been used during anterior segment surgery.
- Use of hyaluronidase to degrade the hyaluronan obviates the need to evacuate the viscoelastic completely following surgery.
- a practitioner would begin by calculating the risk of a patient in getting postoperative increases in intraocular pressure following surgery. If a patient has a high risk of ocular damage from such IOP increases (e.g., a glaucoma patient or a patient with retinal vascular disorders, or a very old patient) , then the practitioner may administer the hyaluronidase during the surgery. The surgeon would decide - 7 - either to dilute 5-10 units of hyaluronidase into the infusion bottle to be used throughout the procedure or, alternatively, to give 5-10 units of hyaluronidase as a separate injection (or perhaps combined with Miochol) towards the end of the procedure.
- IOP increases e.g., a glaucoma patient or a patient with retinal vascular disorders, or a very old patient
- the surgeon would decide - 7 - either to dilute 5-10 units of hyaluronidase into the infusion bottle to be used throughout the procedure or, alternatively, to
- One further option may be adding 1-5 units of hyaluronidase to hyaluronan (which may be mixed at the time of hyaluronan' s administration) and then injecting this hyaluronan/hyaluronidase combination. If the surgeon feels that increases in intraocular pressure are not likely or are inconsequential, he/she may omit such injections and use hyaluronidase the next day, should IOP increase post-operatively .
- Rabbits were anesthetized with intramuscular injection of a combination of ketamine (50 g/Kg) and 0.5 ml of chlorpromazine HC1 (100 mg/ml) .
- Proparacaine HCl 0.5%) eye drops were instilled into the conjunctival cul de sac 1 minute prior to injection.
- Preoperative intraocular pressures were measured using a tonopen in each eye.
- the lids were held open using a wire speculum and after the eyes - 9 - were immobilized, a syringe fitted with a 30G needle was inserted at the limbus into the anterior chamber and 0.22 ml of aqueous fluid was removed.
- rabbits were examined by biomicroscopy to evaluate possible ocular trauma caused by the injections.
- Intraocular pressures were measured using tonopen tonometry immediately after injection. Subsequent tonometry was done by using topical anesthesia using proparacaine 0.5%. Tonometry was repeated at 1, 2, 4, 6, 8, 12, 24, and 48 hours after injection.
- Ocular examination was performed using slit lamp biomicroscopy and indirect ophthalmoscopy to evaluate the anterior chamber, lens, vitreous and retina. The data were analyzed statistically using the one and two tailed paired student t-test. At the completion of the study period, all rabbits were killed with a lethal dose of pentobarbital (100 mg/kg given in the marginal ear vein) .
- Intraocular pressure increased within 1 hour after anterior chamber injection of the respective viscoelastic and reached a peak at approximately 4-6 hours post injection.
- Intraocular pressure - 10 - gradually decrease to approximate pre-inj ection levels at about 24 hours post-injection.
- An increase in intraocular pressure occurred with all of the viscoelastics evaluated.
- Healon GV ® appeared to have the most profound increase in intraocular pressure (p ⁇ 0.05 at 2, 4,. and 6 hours post injections) compared to other viscoelastics.
- Fig. 2 shows the intraocular pressures obtained after 10 IU of hyaluronidase were injected in the anterior chamber of the right eye. Compared to control (left eye), hyaluronidase alone appears to have brought about a modest decrease in intraocular pressure in the experimental eye. These results were statistically significant only at 4 and 48 hours post injections (p ⁇ 0.05).
- Figs. 3a-6 summarize the results of intraocular pressure changes when Healon ® , Healon GV ® , Viscoat ® , and Ocucoat ® were used in the presence (treated right eye) and absence (control left eye) of hyaluronidase. Differences in intraocular pressure between the treated and control eyes were assessed by the unequal paired student t-test. Referring to Figs. 3a and 3b, 5 IU of hyaluronidase reduced the Healon ® produced intraocular pressure maximum almost by half, while treatment with 10 IU of hyaluronidase eliminated the IOP spike seen with Healon ® alone. As shown in Figs.
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Abstract
On peut utiliser efficacement et sans danger des doses limitées, inférieures à 15 IU et, de préférence, inférieures à 10 IU par oeil traité, de hyaluronidase afin de diminuer la pression intraoculaire postopératoire provoquée par des quantités résiduelles de hyaluronan utilisé pendant des opérations chirurgicales du segment antérieur. On peut administrer hyaluronidase après l'intervention chirurgicale ou en raison d'une dose égale ou inférieure à 5 IU par oeil traité de façon concomitante. On peut combiner le traitement par hyaluronidase avec des traitements mettant en application d'autres médications.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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AU26772/99A AU2677299A (en) | 1998-02-17 | 1999-02-12 | Use of hyaluronidase to reduce viscoelastic related increases in intraocular pressure |
Applications Claiming Priority (2)
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US7483798P | 1998-02-17 | 1998-02-17 | |
US60/074,837 | 1998-02-17 |
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WO1999040933A1 true WO1999040933A1 (fr) | 1999-08-19 |
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PCT/US1999/003125 WO1999040933A1 (fr) | 1998-02-17 | 1999-02-12 | Utilisation de hyaluronidase afin de diminuer les hausses de pression intraoculaire associees a la viscoelasticite |
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WO (1) | WO1999040933A1 (fr) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000056354A2 (fr) * | 1999-03-22 | 2000-09-28 | Boston Innovative Optics, Inc. | Methodes d'utilisation d'agents agissant sur l'epithelium de l'oeil humain |
EP1589992A2 (fr) * | 2003-02-05 | 2005-11-02 | David B. Soll | Procede de traitement d'une pression intra-oculaire elevee, y compris d'un glaucome |
WO2007064543A1 (fr) * | 2005-12-01 | 2007-06-07 | Advanced Medical Optics, Inc. | L'acide hyaluronique et hyaluronidase dans l'amelioration de la regeneration du cristallin |
US7794697B2 (en) | 2004-06-30 | 2010-09-14 | Abbott Medical Optics Inc. | Enhancement of lens regeneration using materials comprising polysiloxane polymers |
US8475831B2 (en) | 2003-12-19 | 2013-07-02 | Osio Corporation | Treatment of ophthalmic conditions |
US8802651B2 (en) | 2004-06-30 | 2014-08-12 | Abbott Medical Optics Inc. | Hyaluronic acid in the enhancement of lens regeneration |
US9086580B2 (en) | 2012-08-10 | 2015-07-21 | Osio Corporation | Contact lens use in the treatment of an ophthalmologic condition |
-
1999
- 1999-02-12 AU AU26772/99A patent/AU2677299A/en not_active Abandoned
- 1999-02-12 WO PCT/US1999/003125 patent/WO1999040933A1/fr active Application Filing
Non-Patent Citations (4)
Title |
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CALDER I G, SMITH V H: "HYALURONIDASE AND SODIUM HYALURONATE IN CATARACT SURGERY", BRITISH JOURNAL OF OPHTHALMOLOGY, BMJ PUBLISHING GROUP, GB, vol. 70, no. 06, 1 June 1986 (1986-06-01), GB, pages 418 - 420, XP002918693, ISSN: 0007-1161 * |
EQUI R A, ET AL.: "HYALURONAN POLYMER SIZE MODULATES INTRAOCULAR PRESSURE", JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS., MARY ANN LIEBERT, INC., NEW YORK, NY., US, vol. 13, no. 04, 1 August 1997 (1997-08-01), US, pages 289 - 295, XP002918692, ISSN: 1080-7683 * |
LANG E, ET AL.: "SHEAR FLOW CHARACTERISTICS OF SODIUM HYALURONATE RELATIONSHIP TO PERFORMANCE IN ANTERIOR SEGMENT SURGERY", ARCHIVES OF OPHTHALMOLOGY, AMERICAN MEDICAL ASSOCIATION, US, vol. 102, no. 07, 1 July 1984 (1984-07-01), US, pages 1079 - 1082, XP002918695, ISSN: 0003-9950 * |
RANKOVA C B, ET AL.: "APPLICATION OF HYALURONIDASE AFTER UNSUCCESSFUL TRABECULECTOMY", DOCUMENTA OPHTHALMOLOGICA., KLUWER, DORDRECHT., NL, vol. 80, no. 04, 1 January 1992 (1992-01-01), NL, pages 381 - 383, XP002918694, ISSN: 0012-4486, DOI: 10.1007/BF00154388 * |
Cited By (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000056354A3 (fr) * | 1999-03-22 | 2000-12-28 | Boston Innovative Optics Inc | Methodes d'utilisation d'agents agissant sur l'epithelium de l'oeil humain |
US6335006B1 (en) | 1999-03-22 | 2002-01-01 | Boston Innovative Optics, Inc. | Methods of using agents that act on the epithelial sheet of a human eye |
WO2000056354A2 (fr) * | 1999-03-22 | 2000-09-28 | Boston Innovative Optics, Inc. | Methodes d'utilisation d'agents agissant sur l'epithelium de l'oeil humain |
EP1589992A4 (fr) * | 2003-02-05 | 2008-02-20 | David B Soll | Procede de traitement d'une pression intra-oculaire elevee, y compris d'un glaucome |
EP1589992A2 (fr) * | 2003-02-05 | 2005-11-02 | David B. Soll | Procede de traitement d'une pression intra-oculaire elevee, y compris d'un glaucome |
US9241980B2 (en) | 2003-12-19 | 2016-01-26 | Osio Corporation | Treatment of ophthalmic conditions |
US8475831B2 (en) | 2003-12-19 | 2013-07-02 | Osio Corporation | Treatment of ophthalmic conditions |
US8679521B2 (en) | 2003-12-19 | 2014-03-25 | Osio Corporation | Treatment of ophthalmic conditions |
US8877228B2 (en) | 2003-12-19 | 2014-11-04 | Osio Corporation | Treatment of ophthalmic conditions |
US9566317B2 (en) | 2003-12-19 | 2017-02-14 | Osio Corporation | Treatment of ophthalmic conditions |
US9931382B2 (en) | 2003-12-19 | 2018-04-03 | Osio Corporation | Treatment of ophthalmic conditions |
US7794697B2 (en) | 2004-06-30 | 2010-09-14 | Abbott Medical Optics Inc. | Enhancement of lens regeneration using materials comprising polysiloxane polymers |
US8802651B2 (en) | 2004-06-30 | 2014-08-12 | Abbott Medical Optics Inc. | Hyaluronic acid in the enhancement of lens regeneration |
WO2007064543A1 (fr) * | 2005-12-01 | 2007-06-07 | Advanced Medical Optics, Inc. | L'acide hyaluronique et hyaluronidase dans l'amelioration de la regeneration du cristallin |
US9086580B2 (en) | 2012-08-10 | 2015-07-21 | Osio Corporation | Contact lens use in the treatment of an ophthalmologic condition |
US10254564B2 (en) | 2012-08-10 | 2019-04-09 | Osio Corporation | Contact lens use in the treatment of an ophthalmologic condition |
US10969609B2 (en) | 2012-08-10 | 2021-04-06 | Osio Corporation | Contact lens use in the treatment of an ophthalmologic condition |
Also Published As
Publication number | Publication date |
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AU2677299A (en) | 1999-08-30 |
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