Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2001-05-01
2002-08-13
Fay, Zohreh (Department: 1614)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S458000, C514S912000
Reexamination Certificate
active
06433007
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention is directed to methods for the prevention, reduction or amelioration of surgery-induced formation of cataract or posterior capsular opacification.
Various ocular surgeries are performed in an effort to improve vision. Some ocular surgeries. however, such as vitrectomy (posterior-segment surgery), cataract surgery or refractive surgery. may result in the development of post-surgical complications involving the formation of posterior subcapsular cataract (“PSC”) and posterior capsule opacification
Refractive surgery typically involves the modification of the cornea in myopic patients to correct the focus of light on the retina. Examples of such surgeries include radial keratotomy (radial slices in the cornea), photorefractive keratotomy (laser ablation of the epitheilial and stromal layers of the cornea), LASIK (slicing a cornea flap and removing part of the stromal layer followed by the replacement of the flap), as well as procedures involving the insertion of corneal rings or phakic intraocular lens (“IOL”). During these and other corneal surgeries the cornea is typically bathed with a surgical irrigating solution. Due to the traumatic insult of such procedures, however. various inflammatory events or other tissue or cellular complications may arise. See. e.g., Lipner. Phakic dwellings: Redecorating the ocular interior with vision-bosting designs, www.eyeworld.org, volume 3, number 11, pages 40-43 (1998).
Cataract surgery involves the removal of the cataractous lens and replacement with an IOL. In such surgeries the entire lens is removed in one piece, or the lens is broken down into smaller pieces and suctioned out of the lens capsule by phacoemulsification techniques. In some cases following surgery, however, opacification of the posterior capsule forms, inhibiting clear vision and potentially necessitating further surgery.
Vitrectomylposterior segment surgery procedures are performed for a variety of reasons to correct visual acuity deprivation arising from age-related degenerative processes and other disease processes including diabetes, proliferative vitreoretinopathy (PVR), and trauma-induced retinal hemorrhage.
Vitrectomy involves the removal of the vitreous of the eye, and replacement with another fluid. Vitrectomies are typically performed with the SERIES TEN THOUSAND® OCUTOME® or ACCURUS® posterior-segment surgical systems (Alcon Laboratories, Inc.), or similar instrument, wherein an aspirating, cutting and irrigation probe is inserted through the side of the globe. The instrument cuts and aspirates the vitreous while concurrently replacing the vitreous fluid with a surgical irrigation solution (e.g., BSS PLUS® Surgical Irrigation Solution). Following vitrectomy, the fluid of the posterior segment may be replaced by silicone oil (Foulds WS. Is your vitreous really necessary? The role of vitreous in the eye with particular reference to retinal attachment, detachment, and the mode of action of vitreous substitutes.
Eye
, volume 1, pages 641-664 (1987) or gas tamponade (Phelps-Brown N A, et al., Aetiological classification of cataract: ocular, toxic, nutritional and physical factors, and senile cataract In: Phelps-Brown N A, Bron A J, eds. Lens Disorders:
A Clinical Manual of Cataract Diagnosis
. Oxford: Butterworth-Herine,amm Ltd. pages 190-211, 1996; Ruellan et al., Cataract and Implantation in the Vitrectomized Eyes,
J. Fr. Ophtalmol
., volume 16, issue 5, pages 315-319 (1993); and Koch et al., Development of Lens Opacities in a Period of 6 Months After Pneumatic Relinopexy,
Fortschr. Ophthalmol
., volume 88, No. 3, pages 216-218 (1991)) in order to achieve/maintain retinal attachment.
Vitrectomy can induce a variety of post-surgical complications. Many of these complications are further potentiated in diabetic patients who are at risk for many ocular pathologies. Due to the severity of the surgical procedure, the posterior segment surgery process can cause tissue damage at both the acute and chronic phases of the recovery. Tissue edema generally occurs during the post-surgical acute phase. This is caused by breakdown of the blood aqueous and blood retinal barrier functions resulting in sustained vascular permeability and accumulation of plasma constituents in the ocular compartments following the surgical trauma. Slitlamp clinical examinations at 24 hours have indicated extensive anterior chamber flare and cell influx, conjunctival congestion and swelling (with discharge), iritis, corneal haze and cataract formation. See for example, Kreiger, A. E., Wound Complications In Pars Plana Vitrectomy
Retina
, volume 13, No. 4, pages 335-344 (1993); Cherfan et al., Nuclear sclerotic cataract after vitrectomy for idiopathic epiretinal membranes causing macular pucker,
Am. J. Ophthalmol
., volume 111, pages 434-438 (1991); Thompson, J. T., et al., Progression of Nuclear Sclerosis and Long-term Visual Results of Vitrectomy With Transforming Growth Factor Beta-2 for Macular Holes,
Am. J. Ophthalmol
., volume 119, pages 48-54 (1995) and Dobbs, R. E., et al., Evaluation Of Lens Changes In Idiopathic Epiretinal Membrane, volume 5, Nos. 1 & 2, pages 143-148 (1988).
A disruption of the blood-ocular barriers and influx/or local release of growth factors occurs during inflammatory ocular pathology/or surgical trauma. Such fluid disruption and inflow of growth factors is suspected to play a key role in the development of cataract. (See generally, Beebe, et al., Control of lens cell differentiation and ion fluxes by growth factors.
Prog. Clin. Biol. Res
., volume 217A, pages 365-9 (1986); Chamberlain, et al., Evidence that fibroblast growth factor promotes lens fibre differentiation.
Curr. Eye Res
., volume 6, pages 1165-9 (1987); Hales, et al., Cataract induction in lenses cultured with transforming growth factor-beta.
Invest. Ophthalmol. Vis. Sci
., volume 36, pages 1709-13 (1995); Peek, et al., Rise and fall of crystallin gene messenger levels during fibroblast growth factor induced terminal differentiation of lens cells.
Dev. Biol
., volume 52, pages 152-60 (1992); and Wickström, et al., The effect of transforming growth factor-alpha (TGF alpha) on rabbit and primate lens epithelial cells in vitro.
Curr. Eye Res
., volume 12, pages 1123-9 (1993).)
In fact, there is a high incidence (approximately 80%) of post-vitrectomy cataract formation and loss of visual acuity in patients reviewed over a period of 6 to 99 months post-vitrectomy (Cherfan, et al.,
Am. J. Ophthalmol
., volume 111, pages 434-438 (1991)). It is now recognized that this PSC is the consequence of abnormal, post-surgical lens fiber growth resulting in a distortion and branching of line sutures (Kuszak et al., Lens optical quality is a direct function of lens sutural architecture.
Invest. Ophtalmol. Vis. Sci
., volume 32, pages 2119-2129 (1991). Continued abnormal lens fiber cell growth leads to a progressive decay of lens optical properties due to localized suture defects in newly formed lens fiber layers.
U.S. Pat. No. 5,607,966 (Hellberg et al.), U.S. Pat. No. 5,643,943 (Gamache et al.), U.S. Pat. No. 20 5,811,438 (Hellberg et al.) and U.S. Pat. No. 5,811,453 (Yanni et al.) disclose bifunctional compounds, compositions and methods of use for the treatment of ocular inflammation. The compounds disclosed in these patents are useful in the methods of the present invention. However, these patents do not disclose specific methods of preventing surgery-induced formation of PCO or PSC, using systemic, topical or surgical irrigating solutions of the present invention. The inventors of the present invention have surprisingly found that methods involving the administration of compositions containing compounds disclosed in the preceding patents prevent or reduce the incidence of post-surgical cataract formation.
SUMMARY OF INVENTION
The present invention provides methods of preventing or ameliorating post-surgical formation of PCO or PSC. The methods involve the administration of compositions comprising bifunctional compounds. The compositions may be administ
Garner Wiliam H.
Graff Gustav
Alcon Manufacturing Ltd.
Brown Gregg C.
Fay Zohreh
LandOfFree
Methods for the prevention and treatment of post-surgical... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Methods for the prevention and treatment of post-surgical..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods for the prevention and treatment of post-surgical... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2949958