Drug – bio-affecting and body treating compositions – Topical body preparation containing solid synthetic organic... – Ophthalmic preparation
Reexamination Certificate
2001-12-17
2004-09-07
Azpuru, Carlos A. (Department: 1615)
Drug, bio-affecting and body treating compositions
Topical body preparation containing solid synthetic organic...
Ophthalmic preparation
C424S427000, C424S429000
Reexamination Certificate
active
06787131
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to the prevention of damage to the cornea in mammals resulting from discontinuities in the epithelial layer.
BACKGROUND OF THE INVENTION
Ophthalmic lenses have been investigated for a number of years. Such materials can generally be subdivided into two major classes, namely hydrogels and non-hydrogels. Non-hydrogels do not absorb appreciable amounts of water, whereas hydrogels can absorb and retain water in an equilibrium state.
Those skilled in the art have long recognized that the surface characteristics of contact lenses play a major role in their ocular compatibility. For example, it is known that increasing the hydrophilicity of the contact lens surface improves the wettability of the contact lenses. This in turn is associated with improved wear comfort of contact lenses. Additionally, the surface of the lens can affect the lens's susceptibility to deposition, particularly the deposition of proteins and lipids from the tear fluid during lens wear. Accumulated deposits can cause eye discomfort or even inflammation. In the case of extended wear lenses (i.e. lenses used without daily removal of the lens before sleep), the surface is especially important, since extended wear lenses must be designed for high standards of comfort and biocompatibility over an extended period of time.
The degree of ocular compatibility is more specifically the compatibility of the superior corneal epithelium with the posterior surface of the contact lens. Because the radius of curvature of the posterior surface of the contact lens is usually slightly smaller than radius of curvature of the convex anterior surface of the cornmeal epithelium, the thinnest portion of the tear film separating the corneal epithelium and the contact lens is usually at the outer perimeter of the contact lens.
One can envision this area by striking an imaginary circle on the cornea that is concentric with the pupil and that has a radius equal to that of the contact lens. Allowing for the normal movement of the contact lens on the cornea, one would broaden the width of the imaginary circle. This circle or its arcuate portions are then of principal interest in the present invention.
Since the introduction of soft daily wear contact lenses in the late 1960's and extended wear soft contact lenses in the 1980's, the number of people wearing contact lenses for vision correction has increased dramatically. It is estimated that the number of contact lenses wears in the United States alone is in excess of 25 million
1
. Contact lenses are prescribed by optometrists and ophthalmologists, and most contact lens wearers follow their health care provider's instructions on the use and care of the contact lenses. Thus the vast majority of contact lens wearers enjoy the benefits of their contact lenses with no adverse side effects.
Although the relative numbers of problems arising from contact lens wear are quite small, the absolute number of incidents has risen with the increasing number of contact lens wearers. Thus the increasing popularity of contact lenses has yielded a concomitant increase in the incidence of complications related to contact lens wear. Corneal infiltrates and superior epithelial arcuate lesions (SEALs) are of particular interest since neither are completely described with respect to either causative factors or predisposing conditions. The SEALs appear principally in arcuate sections of the circular region defined by the outer posterior edge of the contact lens as discussed above.
Corneal infiltrates account for a small percentage of all contact lens-related problems and are more commonly found in extended wear versus daily wear patients. Corneal infiltrates arise in the cornmeal epithelium and are characterized by an inflammatory response, such that there is a visible (1 to 2 mm) accumulation of polymorphonucleocytes (PMNs) to the localized area. Infiltrates have been observed to be sterile and non-sterile, symptomatic and asymptomatic. Corneal infiltrates are most commonly found on the superior cornea, although are also found elsewhere. Most patients present with a single infiltrate, however multiple infiltrates are not uncommon. Generally, there is minimal disruption to the overlying epithelium and epithelial edema or superficial punctate keratitis is found in approximately half of the cases. Anterior chamber inflammation is absent or minimal in affected patients. A number of causative agents have been proposed, ranging from hypersensitivity/toxicity to contact lens care product preservatives
2
, to bacteria
3
/blepharitis
4
, to protein lens deposits
5
. However, given the range and degree of symptoms it seems most probable that these infiltrates are more likely the result of a general immunological response, since PMNs are relatively non-specific components of the immune system, which respond to a variety of chemotactic and other signals.
Superior epithelial arcuate lesions are primarily the result of mechanical damage of the corneal epithelium, typically due to contact lens wear. Characteristic arcuate epithelial staining is observed where micro-abrasions readily take up fluorescein at the site of the arc of contact between the edge of the lens and the cornea.
The similarity between these two conditions, aside from contact lens wear, is the involvement or proximity to the corneal epithelium. Thus it would be desirable to provide a method of preventing these conditions or mitigating their severity.
SUMMARY OF THE INVENTION
The invention provides a method for improving the integrity of the corneal epithelium in an eye wearing a contact lens comprising introducing an ophthalmically compatible form of a retinoid into the eye in an amount sufficient to enhance the integrity of the corneal epithelium. The method of the invention may optionally include examining for the presence of retinoid deficiency (clinical and sub-clinical). Suitable methods for determining the level of available retinoic acids include measuring the level of retinoic acids in the serum or tear film.
DETAILED DESCRIPTION
In accordance with the invention, it has been found that certain individuals in the contact lens wearing population may be predisposed to developing superior epithelial arcuate lesions and/or corneal infiltrates. While not to limit the scope of the invention by a recitation of theory, it is believed that insufficient levels of retinoid (alone or in combination with other factors) or other nutritional deficiencies may increase the surface roughness of the epithelium. This increased surface roughness can be accompanied by local retinoid deficiencies. When the roughness of the epithelium increases, it may minimally cause the epithelium to become “leaky” or functionally ineffective at completely protecting the underlying layers of the corneal epithelium. As a result of the lack of cellular differentiation, the epithelium is more susceptible to invasion by microorganisms and/or to chemotactic substances, which can recruit the leukocytes observed in non-sterile and sterile infiltrates alike. Exposure of the underlying epithelial layers to chemotactic substances and microbial invaders/metabolites will cause the accumulation of PMNs or other leukocytes characteristic of the corneal infiltrate phenomenon.
In addition (again, not to limit the invention by a recitation of theory) it is believed that insufficient levels of retinoid (alone or in combination with other factors) or other nutritional deficiencies which can result in local retinoid deficiencies, minimally cause the epithelium to be more susceptible or prone to SEALs. It has been found that the epithelium appears to be less resistant to mechanical abrasion due to the reduction of cellular differentiation as a direct result of retinoid deficiency.
Retinoids are known to have a profound influence on many aspects of ocular health. Vitamin A deficiency is well documented as a cause of childhood blindness, xerophthalmia, throughout the world. Sub-clinical vitamin A deficiency, without overt symptoms, has been observed i
Lever Andrea M.
Lever, Jr. O. William
Salamone Joseph C.
Smerbeck Richard V.
Azpuru Carlos A.
Bausch & Lomb Incorporated
Furr, Jr. Robert B.
Polyn Denis A.
Vacca Rita D.
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