ES2688599T3 - Treatment of ophthalmic conditions - Google Patents

Abstract

A pharmaceutical composition comprising hyaluronidase and collagenase for use in the treatment of an ophthalmic condition with a contact lens; wherein the contact lens is adapted to be applied to an eye of a patient suffering from an ophthalmological condition; wherein the pharmaceutical composition is adapted to be applied to the patient's eye; where the ophthalmological condition is presbyopia.

Description

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DESCRIPTION

Treatment of ophthalmic conditions Field of the invention

The present invention provides a system for treating presbyopia, myopia, farsightedness, astigmatism and other ophthalmic conditions by inducing changes in the cornea, including the dioptric power of the cornea.

Background of the invention

Of the four refractive contact surfaces of the eye, the anterior surface of the cornea provides the majority of the refractive power of the eye. Therefore, various techniques that change the curvature of the cornea have been developed in order to treat ophthalmic conditions that involve refractive errors such as myopia and farsightedness. These techniques include keratotomy, keratomileusis by a freezing procedure, automated laminar keratomileusis (aLk), photoreactive keratomileusis (PRK), laser-assisted in situ keratomileusis (LASIK), laser intrastromatic keratomileusis, laser conductive epithelial keratomileusis (LASE) (CK) and sclerotomy (see U.S. Patent Application published 2003/0139737; U.S. Patent 5,144,630; US documents

5,520,679, 5,484,432, 5,489,299, 5,722,952, 5,465,737, 5,354,331, 5,529,076, 6,258,082, 6,263,879). All of these techniques work using various techniques to change the curvature of the cornea, but are limited by the amount of refractive error that can be corrected and the type of patients that can be treated using these techniques (e.g., in some patients, the cornea is too thin to safely use techniques that could further thin the cornea). Some of the techniques involve making incisions in the cornea with a diamond scalpel and / or removing areas of the cornea thereby increasing the risk of infection or other complications. These techniques also depend largely on the skill of the surgeon performing the intervention, his surgical experience and his experience performing laser excisions (e.g., with an Er: YAG laser (at 2.94 microns), Ho: YAg (at approximately 2 microns); solid state laser with Raman shift (at 2.7-3.2 microns) or optical parametric oscillation laser (OPO) (at 2.7-3.2 microns).

Even the most modern techniques are limited by their ability to cut corneal or sclera tissue with the desired accuracy by making a small, or even moderate, amount of refractive error after the intervention and not allowing the desired vision of near and far in a single surgical intervention. The remaining refractive error can also be irregular, making it more difficult to correct in the future. When the visual demands that the patient requires cannot be met, the ophthalmologist must resort to additional methods to correct the remaining refractive error. This is usually done by prescribing glasses, prescribing contact lenses or performing a second surgical intervention (commonly known as "touch up"). Therefore, the limitations on the correction of refractive error using these techniques are significant and the risk of having an uncorrectable vision even with a secondary measure is considerable.

In addition, attempts to treat presbyopia using these techniques have also had very limited success. Presbyopia, also known as short arm disease, is a lack of accommodation of the lens, which prevents the eye from changing its focus. This phenomenon finally occurs in all individuals over forty years old. The accommodation allows an individual to see nearby objects by having both eyes converge on a nearby focal point, the pupil contracts (myosis) and the lens increases its dioptric power, thereby increasing its curvature in order to focus the image of objects close on the retina. Typically, young children have a total accommodation of 14 diopters. As a person ages, the lens becomes larger, thicker and less elastic. These changes in the lens are due in large part to the progressive denaturation of the lens proteins. As the ability of the lens to change conformation decreases, the accommodation power decreases from approximately 14 diopters in young children to less than 2 diopters at 45 to 50 years and around zero at 70 years. Once a person reaches the state of presbyopia, the eye is permanently focused at an almost constant distance, which is largely determined by the physical characteristics of the individual's eye. The eye can no longer accommodate to see both near and far, requiring older people to wear bifocals with the upper segment to see from afar and the lower segment to see closely.

This general picture of accommodation and presbyopia does not take into account other aspects of the visual system. For example, this scenario does not take into account the higher cognitive functions necessary to coordinate the eyes, the muscular system and the brain including the visual cortex in the accommodation process. The monovision techniques described above (e.g., one eye myopia, LASIK monovision), the different techniques that cause positive areas in the central area of the cornea by making changes in peripheral curvature and sclerotomy or implants to change the stiffness of the sclera, ciliary muscle and zonula, and increasing the accommodation power of the lens among other more invasive techniques have had very limited success in treating presbyopia. These disappointing results may come from a variety of sources including the lack of full understanding of the physiological behavior of the eye and its connections with the brain, nervous system and

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muscular system, the inaccurate measurement of the refractive power of the cornea and lens and the lack of precision in surgical techniques performed by human surgeons.

Ophthalmologists have begun using sophisticated equipment to measure various eye parameters to treat presbyopia. However, even the most sophisticated measures are only approximations due to the fact that the cornea and other parts of the eye are similar to a fingerprint in which there are numerous variations that cannot be adequately described by a finite group of parameters. In addition, it is impossible to know precisely how the cornea, lens, retina and other parts of the visual system will react after surgery under different conditions (e.g., near and far visual stimuli). On the other hand, it is impossible to know how the cornea will heal after refractive surgery (e.g., the final radius of curvature).

The limitations of existing presbyopia treatments come from the fact that these techniques consider only an anatomical region of the eye (i.e., the cornea or lens). Any correction of near vision in turn decreases the vision of the subject far away. In addition, these current techniques model the eye using, among others, the Gullstrand model of the eye that reflects the individuality and uniqueness of the eyes of each subject. For example, the eyeball is not a perfect sphere. Although there are many mathematical models of the eye and its components used to calculate the corneal power and the power of the globe (e.g., ray tracking), the Gullstrand model is probably the most popular.

Therefore, there remains a need for satisfactory non-invasive treatment of presbyopia. Presumably, this treatment could also be used to treat other ophthalmic conditions that involve refractive errors including myopia, farsightedness and astigmatism.

Summary of the invention

The invention provides a pharmaceutical composition comprising hyaluronidase and collagenase for use in the treatment of an ophthalmologic condition with a contact lens; wherein the contact lens is adapted to be applied to an eye of a patient suffering from an ophthalmological condition; wherein the pharmaceutical composition is adapted to be applied ocularly to the patient; where the ophthalmological condition is presbyopia.

The composition may be for use in the treatment of the ophthalmological condition by inducing changes in the physiology and anatomy of the cornea with molding contact lenses, where a change in corneal power is induced by changing the radius of curvature of the anterior surface of both eyes or where a change in corneal power is induced by changing the radius of curvature of the anterior surface in a single eye.

The contact lens may be commercially available. The contact lens may not be custom made. The contact lens may not be specially designed for orthokeratology. The contact lens may be a prolonged use contact lens.

The composition may further comprise a polymer. The polymer can be selected from the group consisting of methyl cellulose, cellulose, polyvinyl alcohol and polyethylene glycol.

The pharmaceutical composition may be a liquid or a gel. The pharmaceutical composition may be a liquid. The composition may be in the form of an aerosol or in the form of eye drops. The pharmaceutical composition may be a gel. The composition may be in the form of a semi-solid gel.

The composition for use in the treatment of the ophthalmologic condition may result in the correction of the ophthalmic condition for at least 7 days. The composition for use in the treatment of the ophthalmological condition may result in the correction of the ophthalmological condition for at least 6 months. The composition for use in the treatment of the ophthalmologic condition may result in the correction of the ophthalmic condition for at least 1 year.

The composition for use in the treatment of the ophthalmological condition may result in the correction of up to 3 diopters of refractive error without surgery. The composition for use in the treatment of the ophthalmological condition may result in the correction of up to 4 diopters of refractive error without surgery.

The pharmaceutical composition may comprise:

hyaluronidase in the range of 0.1% to 5%;

collagenase in the range of 0.1% to 6%; and optionally

a polymer selected from the group consisting of cellulose, methylcellulose, polyvinyl alcohol and polyethylene glycol.

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The composition can be hypertonic. The composition can be hypotonic.

The composition may further comprise at least one agent selected from the group consisting of other enzymes, anesthetics, vitamins, zinc, antibiotics, antiallergic agents, carbamide, cytokinase, vasoconstrictors, antiviral agents, antifungal agents, anti-inflammatory agents and lubricants.

The invention also provides a case comprising contact lenses and a pharmaceutical composition as described above. The case may further comprise instructional material or cleaning supplies for contact lenses.

The present disclosure provides a system for treating ophthalmic conditions such as presbyopia, myopia, farsightedness, astigmatism and other conditions that involve errors in the refraction of the eye. The system alters corneal physiology, including the dioptric power of the cornea, through a dynamic and interactive technique that alters the conformation of the cornea, thereby altering its refractive power. The patient being treated guides the treatment with respect to their visual needs, and the doctor or optometrist uses this patient response as well as information regarding the patient's age, the patient's visual needs (e.g., work habits , daily life), the patient's visual acuity, eye measurements, etc., to design the appropriate treatment regimen. In this way, the individuality of each person being treated and their eyes are taken into account during the treatment procedure. Treatment involves using a group of prescribed contact lenses to reshape the cornea and administer a pharmaceutical composition (eg, eye drops) formulated so that the patient allows the cornea to be reshaped.

One of the many advantages of this system is that changes in the cornea are made without using any type of surgery. Another advantage over current treatments is that the present system is dynamic, gradual and interactive; therefore, it can be adjusted or repeated as many times as necessary to meet the patient's visual needs. In addition, induced changes in the cornea are reversible. For example, the technique may need to be repeated due to disease progression, changes in visual acuity, aging, changes in work habits, changes in reading habits, etc. Preferably, the patient's visual needs are covered with the first treatment.

First, to achieve fine adjustments in the curvature of the cornea, instruments are used to measure the refractive power of the cornea, the curvature of the cornea, the thickness of the cornea and the conformation of the eyeball (i.e. total power of the eye). After these initial measurements are made and the change in the curvature of the cornea to be induced is determined, a group of contact lenses is prescribed for use by the patient. Contact lenses are chosen based on their different base curves at the radius of posterior and anterior curvature as well as their optical diameter and multiple peripheral areas to induce changes in corneal physiology and anatomy. In certain embodiments, the contact lens exerts pressure on the central area of the cornea, thereby flattening the cornea and subtracting dioptric power. In other embodiments, the contact lens exerts pressure on the periphery of the cornea, thereby bulging the cornea and adding dioptric power. The contact lenses constantly, gradually and uniformly change the conformation of the cornea to achieve the desired conformation and thus the refractive power needed by the patient. The contact lenses used in the present system are preferably standard rigid or soft contact lenses that already exist commercially. Preferably, the contact lenses are not specifically designed for orthokeratology. The contact lenses may be made especially for the patient in question, or the contact lenses may be made especially for orthokeratology. The use of contact lenses will be determined by various factors including the desired change in the cornea, the patient's visual memory, the patient's age, the patient's tolerance of the lens, the duration of the treatment, the prescribed pharmaceutical composition, etc. . In certain embodiments, contact lenses are worn several hours a day (e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 hours a day) or all day during several weeks (2, 3, 4, 5, 6, 7, 8, 9, 10 weeks) until the desired changes have been made. In certain embodiments, contact lenses are worn overnight. The contact lenses used in the treatment can be changed throughout the course of treatment as determined by the ophthalmologist with patient consultation. The present system can change the dioptric power of the cornea by up to 5 diopters, preferably up to 4 diopters.

In addition to wearing contact lenses, the patient should also use a pharmaceutical composition, preferably eye drops, suitable for the eye supply that allows the cornea to mold more easily. The pharmaceutical composition can also stabilize, improve, increase the change in corneal curvature or reduce the incidence of unwanted side effects. In certain embodiments, the composition enhances the mechanical stress on the eye exerted by the contact lens on the surface of the cornea. These eye drops typically contain enzymes such as hyaluronase and / or collagenase, and / or other agents such as carbamide (urea). In certain embodiments, the pharmaceutical composition also contains a vehicle such as methyl cellulose or polyvinyl alcohol. The formulation of the eye drops is adjusted depending on various factors such as the patient's age, the degree of change that is made in the cornea, the physiology of the patient's cornea, the disease being treated, the duration of treatment, etc. . Eye drops can also

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Contain other ingredients such as lubricants, vitamins, antibiotics, anti-inflammatory agents, antiallergics, immunosuppressants, vasoconstrictors and anesthetics. The eye drops may be in a liquid spray or gel form. Typically, eye drops are administered at least once a day. In certain embodiments, eye drops are administered once, twice, three times, four times or five times a day. In other embodiments, the eye drops are administered every five minutes, every fifteen minutes, every half hour, every hour, every two hours or every three hours. The use of eye drops is continued for as long as the patient wears contact lenses. The present system provides pharmaceutical compositions for use as eye drops in the treatment method. Pharmaceutical compositions may also be useful in combination with refractive surgery, in the treatment of patients with low or moderate refractive error and in the prevention of presbyopia.

In certain embodiments, the pharmaceutical agents found in the eye drops are included in the contact lenses. For example, the contact lenses are impregnated or coated with the agents so that the use of the contact lenses provides a continuous input of the agents. Any of the agents described herein such as hyaluronidase, collagenase, vehicle, anti-inflammatory, lubricants, antibiotics, etc. It can be added to the contact lens for the release of the agent or agents over time. This mode of agent delivery is particularly useful when contact lenses are worn at night while the patient is sleeping.

The present treatment system is useful for treating ophthalmic conditions such as presbyopia, myopia, farsightedness and astigmatism. The treatment system can also be used to treat other diseases that involve refractive error. Preferably, the present system is the first line of treatment for these conditions. In other embodiments, the patient may have already undergone a more traditional treatment such as LASIK or PRK, and the present system can be used to further correct any residual refractive error remaining after the first intervention. This allows the correction of any remaining error without additional surgery. The residual refractive error is commonly due to the lack of an exact measure of the refractive defect before surgery but may be due to other causes as described above. Therefore, the best way to correct the residual error is to use a dynamic and interactive technique such as the present method in order to gradually change the curvature of the cornea until the patient finds that their visual needs are met (i.e. Corneal power is sufficient for the patient's visual needs based on the patient's visual memory and brain accommodation) for near and far vision. In certain embodiments, the corneal power is not corrected perfectly because this can hamper near or far vision. Instead, the patient can rely on other compensatory measures to achieve perfect vision under various circumstances, such as low light, fatigue, far vision, very close vision, reading, etc.

The present disclosure also provides a kit containing articles useful for treating ophthalmic conditions such as presbyopia using the present method. The case may contain all or some of the following: reservoir for contact lenses, solutions for cleaning and disinfecting contact lenses, at least one pair of contact lenses, replacement contact lenses, eye drops as described above, lubricants , eye charts, a mirror and instructions for the patient. Preferably, the items in the case are packed in an ergonomic box that is preferably portable.

Useful software for the ophthalmologist, optometrist, nurse or other responsible healthcare professional is also disclosed. Certain information about the patient is entered into the program run on a computer. This information may include name, age, sex, profession, description of visual needs, visual acuity, keratometry, retinoscopy, etc. The user of the software can then ask a series of questions (eg, rigid or soft contact lenses. From the data entered in the program, the software can determine the type of contact lens to be used (e.g., hard or soft), diopter power, back base curve, posterior peripheral curvature, anterior curve, anterior peripheral curve, center zone diameter and peripheral zone diameter The software can also be used to determine the composition of the pharmaceutical composition to be prescribed to the patient and / or the dosage regimen.

Definitions

"Animal": The term "animal", as used herein, refers to humans as well as non-human animals, including, for example, mammals, birds, reptiles, amphibians and fish. Preferably, the non-human animal is a mammal (e.g., a rodent, a mouse, a rat, a rabbit, a monkey, a dog, a cat, a primate or a pig). In certain embodiments, the animal is a human being.

"Cerebral accommodation": Cerebral accommodation refers to any functions that control the movements of the muscles involved in the optic-cerebral-motor system. Brain accommodation is necessary to focus the image in order to see objects both near and far. In certain cases, cerebral accommodation refers to reflex arcs and muscle and nerve stimuli that are necessary to achieve the appropriate movements of the body (e.g., head, neck) and eyes in order to see closely and from far.

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"Corneal power": Corneal power refers to the mathematical value expressed in diopters of the corneal refractive power or in millimeters when referring to the radius of curvature. Corneal power refers to the mathematical value of the refractive power that is necessary to meet the demands of the visual system including visual memory and brain accommodation. To measure the corneal power, it is necessary to determine the anterior radius of curvature, the corneal thickness and the posterior corneal curvature radius. In most cases, corneal power cannot be measured exactly because not all the different anatomical areas that contribute to corneal power can be measured. Corneal potency may also change during the day (e.g., due to fatigue) and from day to day.

"Induction of change in corneal power" refers to the mathematical change in diopters or millimeters of the radius of curvature, of the value of the radius of the anterior corneal curvature to be induced to reach the dioptric power necessary to change the refractive power corneal and thereby achieve the near and far vision required by the patient in each eye.

"Effective amount": In general, the "effective amount" of an active agent or a pharmaceutical composition refers to the amount necessary to elicit the desired biological response. As will be appreciated by normal experts in this specialty, the effective amount of an agent will vary depending on factors such as the desired biological assessment criteria, the agent that is contributed, the disease being treated, the subject being treated, etc. The effective amount of hyaluronase in the pharmaceutical composition is the amount necessary to degrade enough hyaluronic acid molecule to allow corneal molding. The effective amount of collagenase in the pharmaceutical composition is the amount necessary to degrade enough collagen to allow corneal molding. The effective amount of carbamide in the pharmaceutical composition is the amount necessary to allow corneal molding.

"Shaping contact lenses": Shaping contact lenses are any contact lenses that are used with the method and system present. The lenses may be particularly designed to mold the cornea to a conformation in some embodiments. However, in other embodiments, the molding contact lenses are not specially designed for the present system but instead are standard contact lenses typically used by a patient to correct vision. The molding contact lenses can be rigid or soft, permeable or impervious. Typically molding contact lenses are made of a plastic, polymer or glass. In some embodiments, the molding contact lenses include pharmaceutical agents useful for molding the cornea to a particular conformation.

"Optical-cerebral-motor system": The optical-cerebral-motor system refers to the anatomical structures of the body that interact through interconnections (eg, nerves) to carry out the muscular adjustments of the body and the eyeball to reach a suitable position and be able to activate the reflexes, voluntary and involuntary movements necessary to see objects from near and far. The system may include the visual cortex, the motor cortex, the head and neck muscles, the eye muscles, the optic nerves, the cranial nerves and the eyes.

"Dispersion point": The dispersion point is the point at which divergent rays would intersect if they were drawn backwards. The scattering point can also refer to an image of an object or a visual stimulus that characterizes an optical system.

"Stromatic slippage": Stromatic slippage is the displacement of the corneal stroma after any refractive surgery performed on the cornea. The stromatic sliding is due to the separation of the lamellae during the cutting or removal of the corneal tissue. This allows the corneal wound to slide by flattening the corneal curvature in this way during the healing process. Stromatic slip is also an important part of the present technique.

"Visual acuity": Visual acuity refers to the clarity of vision, a measure of how well a person sees. In certain embodiments, it refers to Snellen acuity (e.g., 20/20).

"Visual memory": Visual memory refers to the accumulation of images in the brain that are received through the brain-motor-optic system during a lifetime. Visual memory begins to form when the first images reach the brain during childhood. The brain recognizes and perceives the wavelengths of light as images. The brain organizes all the images that this information accumulates and uses to react to visual stimuli and recognize objects (eg, letters of the alphabet). Visual memory develops depending on how often certain types of stimuli are in front of the eyes. The development of visual memory may depend on the sharpness of the images that reach the retina or brain, physical and mental development, environmental influences, inheritance, etc. Visual memory is formed from images transmitted to the brain with or without correction (e.g., glasses or contact lenses). Normally, visual memory will tolerate small discrepancies such as, for example, due to ailment, stress, fatigue, etc. Visual memory allows the patient to compensate and carry out normal activities such as driving, reading, writing, drawing, sports, etc. Visual memory is important in the development of visual acuity and is used to coordinate all mechanisms

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compensatory body, such as cerebral accommodation. For example, when the eye cannot transmit good quality images to the brain for a close stimulus, visual memory reacts and begins to demand the visual quality it has come to expect. Visual memory can activate certain compensatory mechanisms such as cerebral accommodation. When the cerebral accommodation cannot be adequately compensated, the patient may need to resort to other compensatory mechanisms such as squinting, raising light levels, moving the eyes further or closer, wearing glasses, etc. For example, when reading a book, if the patient is fatigued, he may need to hold the book closer or raise the level of light to read. The corneal power is preferably adjusted so that the visual images transmitted to the brains are accepted by the visual memory. The patient's own satisfaction and acceptance of the new images is preferably the way in which the corneal power has been corrected by the present system to the extent needed by visual memory.

Brief description of the drawing

Figure 1 is an illustration of the Gullstrand model of the eye. This model is used to calculate the refractive power of the cornea as well as other parts of the eye. This scheme is useful for determining the adjustments in the cornea necessary to correct the patient's vision.

Figure 2 is an illustration of the Sturm cone used to show the formation of an image by a spherocylindrical lens.

Figure 3 is a photograph showing the differences that exist in the thickness and radius of curvature of the anatomical regions of the eye.

Figure 4 is a schematic view showing the stromatic slip.

Figure 5 represents a mathematical model of the eye. The drawing shows the theoretical measures necessary to calculate the corneal power and the dioptric power of the eyeball. Note that this traditional model of the eye uses a sphere to present the eyeball and mathematical constants in the cornea.

Figure 6 shows a normal eye. In fact, the normal eye is not a sphere. It has various irregularities and anatomical differences and the optical axis is offset from the geometric axis.

Figure 7 shows a small contact lens centered on the cornea. Using this contact lens, pressure is applied to the central area of the cornea. The peripheral zone is not touched by the contact lens. The pressure on the central area of the cornea will flatten the central cornea and decrease the dioptric power of the cornea.

Figure 8 shows a small contact lens centered on the cornea. The contact lens is exerting pressure on the peripheral area of the cornea. The central area of the cornea is not touched by the contact lens. The pressure on the periphery will bulge the central cornea, thereby adding dioptric power to the cornea.

Figure 9 shows a larger centered contact lens on the cornea. The contact lens is applying pressure to the peripheral area of the cornea. This peripheral pressure will cause the central portion of the cornea to bulge, thereby adding dioptric power to the cornea.

Figure 10 shows a larger centered contact lens on the cornea. In this figure, the contact lens is exerting pressure on the central area of the cornea. This pressure on the central area will flatten the cornea and subtract dioptric power from the cornea.

Detailed description of the disclosure

The present treatment system is based on inducing a change in the curvature of the cornea (eg, the anterior radius of the cornea). The change allows the patient to see better near and far without the need for glasses, contact lenses or other visual aids. The functional system by inducing a myopic astigmatism compound with a vertical axis (horizontal or oblique) according to the visual needs of the patient in question. The system is interactive and depends on the patient's contribution on how the treatment will proceed. This is one of the differences between the present system and those already known in the art that rely essentially on detailed measurements of aspects of the eye by an ophthalmologist.

Methods used to induce changes in the anterior radius of the cornea include using molded contact lenses after refractive surgical techniques such as LASIK, LASEK, PRK, CK or other surgical interventions that alter the anterior layers of the cornea or the sclera or any change or alteration in the refractive power of the eye; wear molded contact lenses and a pharmaceutical composition suitable for ocular administration when the refractive error is low to moderate, when the patient has been operated and the healing process is almost complete, or when the patient has not had surgery but suffers presbyopia, myopia,

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hyperopia, astigmatism or other ophthalmic condition. The method is a dynamic and interactive technique since the normal physiology of the cornea is altered at the same time as the patient's visual memory and brain accommodation are altered to reach the refractive power of the cornea necessary to achieve near and near vision. desired away from the patient. The present method alters the cornea in a gradual, continuous, programmed and controlled manner without producing irreversible changes or unwanted complications. In certain embodiments, the method alters the cornea in a uniform manner. In other embodiments, the induced change is not uniform (eg, when treating astigmatism). The patient represents an important role in guiding the treatment to achieve the desired vision in much the same way as a photographer focuses on the lens of a camera.

Any patient with a refractive error can be treated using the present system. Treatable ophthalmic conditions using the present system include presbyopia, farsightedness, myopia, astigmatism and other ophthalmic condition that can be treated by changing the conformation of the cornea. In certain embodiments, the patient suffers or is at risk of presbyopia. Certain patients have had good visions for near and far vision, have never needed glasses or contact lenses, but may develop presbyopia with increasing age resulting in a decrease in near vision. In other embodiments, the patient was born with a refractive defect (eg, a genetic refractive defect) and the patient wishes to correct the defect at any one of the different distances - near, intermediate or far. In yet other embodiments, the patient has undergone surgery to correct a refractive error but there is a residual defect in refraction in near, far and / or intermediate vision. In certain embodiments, the patient below 18 years of age is a refractive defect so that when he reaches 40 years of age and symptoms of presbyopia begin, changes in the refractive power of the cornea can be minimized and by therefore, they are better accepted by the patient (eg, visual memory, cerebral accommodation) without discomfort or discomfort.

Brain accommodation is a natural process. The cerebral accommodation is based on a function of the brain, specifically the function that allows images to form through the visual organ and execute the muscular actions used to initiate and complete the reflexes that interconnect the optical and motor systems. Once the images are captured by the eye, they are sent to the brain (visual cortex) and stored in the visual memory. Visual stimuli during the normal development of each individual vary and this is why brain accommodation represents a key role in carrying out actions that the individual apparently performs unconsciously. Therefore, the present system takes into account cerebral accommodation in the treatment of the patient. The transmission of blurry blurred images becomes very difficult to associate and interpret with the other images of visual memory at the beginning of presbyopia when the eye and the nervous system are not synchronized. As a result, the patient requires the use of glasses. The present technique shapes the cornea to achieve the near and far vision that the patient requires to meet the demands of the visual system including the visual cortex and visual memory.

the disclosure is better understood when considering the Gullstrand model of the eye (Figure 1) and the Sturm cone (Figure 2). As will be appreciated by other experts in the art, other models of the eye can also be used to mathematically model the visual system. The Gullstrand model shows the elements for the calculation of the refractive power of the cornea according to the present disclosure using ancient and traditional mathematical concepts. This calculation of the refractive power of the cornea is based on the radius of curvature of the anterior surface of the cornea, the corneal thickness and the curvature ratio of the posterior surface of the cornea.

The initial measurement of the radius of curvature of the anterior surface of the cornea is obtained by measurements with the keratometer. The measurement is performed directly in diopters if the refractive index determined by the keratometer is the same as that used in the calculation by the responsible physician. Preferably, the measurement is performed in the same units that are used by the responsible physician. In addition, it is preferable that all instruments used in the disclosure are calibrated together. In certain embodiments, the measurement of the initial radius (Ri) is made in millimeters and then converted to diopters using the following formula:

D = [(n-n ') x 1,000] / R

where D = diopters, n = index of refraction of the air, n '= index of refraction of the cornea, R = radius of curvature of the anterior surface of the cornea, Ri = initial radius and Di = initial diopter.

Refraction Defect Estimation

The amount of the refractive defect in the eye is measured at the corneal vertex with the following formula:

Dv = Dc / [1- (xDc / 1,000)]

where Dv = diopters to the vertex and Dc = correction diopters.

Then the final diopters are calculated using the following formula:

Df = Di + Dv = 332 / Ri + Dv

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where Df = final diopter, Di = initial diopter, Ri = initial diopter and Dv = diopter to the apex.

Final radius

The final radius of curvature of the anterior surface of the molded cornea is calculated in millimeters, instead of diopters, to facilitate use with different measuring equipment. The final radius is calculated using the following formula:

Rf = 332 / [(332 / Ri) + Dv]

where Rf = final radius, Ri = initial radius and Dv = diopters to the vertex.

Corneal thickness

The corneal thickness is calculated based on the difference between the radius of curvature of the anterior surface and the radius of curvature of the contact surface (the removal obtained in the anterior stroma).

Radius of the posterior surface

The radius of curvature of the posterior surface is equal to the final radius minus the post-surgical stromal thickness (Rsp = Rf-Ed).

The calibration of the optical equipment is based on the Gullstrand model of the eye. When there is a large change in any of the parts of the eye that is measured (e.g., the radius of curvature, the thickness of the cornea, the index of refraction), it is no longer possible to precisely measure the refractive power of the cornea in most automatic optical equipment (eg, autokeratometer refractometer). Therefore, in order to carry out the exact mathematical calculations, it is necessary to use equipment that actually measures the radius of curvature of the anterior surface, the corneal thickness and the radius of curvature of the posterior surface (e.g., ORBSCAN II , commercially available from Bausch & Lomb Surgical). This type of equipment, in general, measures the refractive power of the cornea in very large increments (e.g., 0.25 D), which causes errors for the correct measurement of the patient's vision and therefore to obtain the Mathematical formula for calculating the refractive power of the cornea that is required to achieve the near and far vision desired for the patient.

In the present disclosure, the induced refractive power of the cornea is considered similar to a sphere (myopia) and a myopic cylinder (astigmatism) from 0.100 diopters to 0.999 diopters, that is, the recommended interval to correct near vision without significantly decreasing distance vision. Myopic astigmatism is sphere -0,100 to -0,999 D. Hypermetropic astigmatism is sphere +0,100 to +0,999 D. The cylinder in the

astigmatism is from -0,100 to -0,999. The axis of astigmatism can be from 0 ° to 360 °. As will be appreciated by a

Expert in this specialty, visual quality and visual ability will also be related to the diameter of the pupil.

The entire visual system, including the lens, the zonula, the ciliary muscle, the ciliary body, the sclera, the brain, the visual cortex and the visual memory, is considered in the dynamic and interactive system of the present disclosure. Each part of the eye plays an important role in vision, and the modifications of each of these parts either iatrogenicly or by aging causes changes in the patient's vision.

Once the previous measurements and calculations have been measured, the patient is consulted to determine his visual needs for vision both near and far. This is based on the fact that the patient is the one who really measures, feels and relies on his refractive power of the cornea. The person administering the treatment

You can use this information below in the approach to the mathematical formulas described above.

This combined approach guides the patient's treatment by determining the bulge or plain to be induced in the patient's cornea

To carry out the remodeling of the patient's cornea, the present system combines the use of molding contact lenses and a pharmaceutical agent suitable for ocular administration (eg, eye drops). In certain embodiments, computer software is used to determine the most suitable contact lenses for the patient and / or determine the formulation of the pharmaceutical agent.

The disclosure software asks the healthcare professional (eg, ophthalmologist, optometrist, nurse, etc.) to enter certain information about the patient. This information may include name; age; sex; profession; close working distance; tolerance to contact lenses (if the patient has used them before), optometric data; visual acuity (eg, near, far, with both eyes, each eye separately, corrected or uncorrected); keratometry; topography; pachymetry (corneal thickness); wave front; lightning tracking measures; retinoscopy with normal pupil; refraction with normal pupil; the best corrected visual acuity (eg, near or far, both eyes or each eye separately); retinoscopy with mydriasis; refraction with mydriasis; better near vision for vision at 45 to 55 cm, for Jaeger 3, for Jaeger 4 or for Jaeger 5; etc. Any of the data entered above can be included or excluded from the program determination of the lenses of

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contact or pharmaceutical composition are going to be used by the patient. The software can also allow the conversion of diopter keratometry to millimeters. The user can be asked to choose a flatter, more bulky or medium keratometry. The user may be asked to choose between soft or hard contact lenses for the patient. The user may be asked to enter the curve of the posterior base, the peripheral posterior curve, the anterior curve and / or the anterior peripheral curve. You can also ask the user to choose the power. In certain embodiments, the software uses the data entered to determine the contact lenses to be used by the patient. The software can determine soft to hard contact lenses, diopter power, back base curve, back peripheral curve, anterior curve, anterior peripheral curve, center zone diameter and / or diameter of the peripheral zone. In certain embodiments, the software will determine the composition of the pharmaceutical composition and / or the dosage regimen for the pharmaceutical composition.

In a certain embodiment, the software begins to ask the user for the following patient data: name, age, keratometry of the right eye, pachymetry (thickness of the cornea) of the right eye, ocular defect of the right eye, keratometry of the left eye, pachymetry (thickness of the cornea) of the left eye, ocular defect of the left eye and if the patient has previously used contact lenses. If the patient has previously used contact lenses, the user is asked to enter information regarding what type of contact lenses he was and if they were comfortable. For the patient who has never worn contact lenses, the user is asked to select the patient's level of sensitivity (eg, high, low, null). After the information is entered, the software confirms that all data has been entered and that the information is within certain intervals. For example, the patient's age must be between 1 and 100 years. The keratometry of the right and left eyes should be between 34.09 and 55.32 D. The pachymetry of both eyes should be between 450 and 650 microns. The user is asked to confirm all the data entered to reduce the possibility of error. After all data has been entered, the software then calculates the results using the formula described herein. The software determines the type or contact lenses recommended for the patient and the base curve expressed in millimeters. When the defect is greater than 2 D, the message "Define the lens power depending on the patient". When the keratometric value of any eye is less than 40 or greater than 48 D, the following message "Define the peripheral base curve" appears. Appendix A shows various screenshots of a computer running this software.

The present method of treating a patient suffering from a disorder that involves refractive error such as presbyopia includes assessing the patient (eg, age, patient's work needs, eye disease, etc.), prescribing the use of contact lenses. shapers to induce the necessary changes in the radius of curvature of the anterior surface of the cornea and prescribe the use of a pharmaceutical composition to be used together with the contact lenses.

The present system can be used to induce a change in the refractive power of the cornea by inducing a change in the radius of curvature of the anterior surface of the cornea with a myopic interval (sphere) of -0.25 D to -0, 75 D or with a myopic astigmatism (cylinder) from -0.25 D to -0.75 D. By inducing a change in the refractive power of the cornea with myopia (sphere) greater than 1.00 D or greater than 1, 00 D in astigmatism (cylinder), near vision is improved but distance vision decreases. In certain preferred embodiments, the range for correcting near vision without diminishing distance vision substantially is from 0.100 D to 0.999 D. To determine the best astigmatism axis that the patient requires for near vision, each eye is evaluated separately. .

In other embodiments, the change is induced in the refractive power of the cornea with a vertical axis of myopic astigmatism (eg, in the case of vertical astigmatism with less than 45 ° with respect to the vertical (90 °)).

The present method is particularly useful because it allows the treatment of any eye of each patient to be completely personal. The responsible physician is not limited to the measuring equipment or the glasses or contact lenses available to treat the patient's visual error. Therefore, the accuracy of the correction is not limited to 0.100 D but instead can be performed with a higher degree of accuracy (e.g., 0.01 D, 0.005 D, 0.001 D, 0.0005 D or 0.0001 D). The patient guides the treatment according to his visual needs. The responsible doctor can stop or alter the treatment as necessary.

As described above, currently existing instruments used to measure the degree of myopia or astigmatism do not measure the value of the radius of curvature of the anterior surface of the cornea, the corneal thickness or the radius of curvature of the posterior surface of the cornea. Cornea with the required accuracy.

The molding contact lenses that are prescribed and worn by the patient exert a mechanical force on the anterior surface of the cornea thereby inducing a change in the refractive power of the cornea. In certain embodiments, the molding contact lenses are hard or rigid molding contact lenses. In other embodiments, the molding contact lenses are soft contact lenses.

Once the molding contact lens is placed in the patient's eye, a pharmaceutical composition (e.g., eye drops) that allows corneal molding is ocularly administered eye and / or reduces the connections between the corneal lamellae. Contact lenses and the pharmaceutical composition together produce the change in the refractive power of the cornea. The more frequently the pharmaceutical composition is administered, the more

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quickly corneal lamellae will adopt the desired conformation change. In certain embodiments, the composition is administered at least every 8 hours. In other embodiments, the composition is administered every 6 hours. In certain other embodiments, the composition is administered approximately every 3 hours. In yet other embodiments, the composition is administered approximately every two hours. In other embodiments, the composition is administered every hour. The composition may be hypertonic (5% to 40%, preferably approximately 10, 20, 30 or 40%) or hypotonic (0% to 5%, preferably approximately 1, 2, 3 or 4%) depending on the needs of the patient ( e.g. work needs, rest hours, sleep, etc.). A hypertonic pharmaceutical composition (e.g., 40%) is typically used when a faster result is desired.

Without wishing to limit itself to any particular theory, it is believed that the present system works through the following mechanism. After any refractive surgical technique that causes spaces between the stromatic lamellae either by cutting, either by resection or by means of excisions, a stromatic slide will cause the stroma to slide towards the periphery to correct a more myopic defect or slide towards the center of the cornea to correct farsightedness or presbyopia (see Figure 4). When molding contact lenses are used together with a pharmaceutical composition that improves the mechanical strength of the contact lenses, the corneal stroma is altered along with its anatomical and histological structures. Contact lenses and pharmaceutical composition induce changes in the mechanical strength of the molecular structure (e.g., lamellae) and induce changes in cells and proteins such as collagen and hyaluronic acid found in the corneal stroma. The surface of the cornea becomes more uniform by molding the corneal stroma. All healthy corneas have some irregularities on the surface as seen by isometric tomography and ultrasound. In the present system, the quality and clarity of all images (i.e. visual acuity) is improved by making the surface of the cornea more uniform.

For the calculation of the molding contact lenses, the flattest keratometry is taken. A person skilled in the art could also use bulging keratometry or a mean of both and, based on this corneal curvature, make the necessary calculations to flatten or bulge the radius of curvature of the anterior surface of the cornea and thus correct the refractive defect Of the eye. The base curve of the molding contact lenses is calculated based on the change in refractive power for each eye separately. The base curve of the molding contact lenses is calculated starting from one to four flattest or more domed diopters, more preferably from one to three flattest or more domed diopters, even more preferably from one to two flatter or more diopters. bulging, depending on the refractive error required. The curve of the peripheral base depends on the adaptation of the molding contact lenses and is estimated to be 0.5 mm in radius greater than the central area but may vary depending on the design. The diameter of the molding contact lenses used in the present system is approximately 8.0 mm to 18.0 mm. These diameters are commercially available. In certain embodiments, the molding contact lens is a hard contact lens with a diameter ranging from 8.0 mm to 12.0 mm. In other embodiments, the molding contact lens is a soft contact lens with a diameter ranging from 13.0 mm to 15.0 mm. The soft contact lens can cover the entire cornea and go from sclera to sclera. In certain embodiments, the molding contact lens is a combination of hard and soft materials. It can be hard in the middle up to approximately 12.0 mm, 13.0 mm, 14.0 mm or 15.0 mm, and then soft on the periphery up to 16.0 mm, 17.0 mm and 18.0 mm. A larger contact lens, preferably a soft contact lens, can be used at night as a molding contact lens. The power of the molding contact lens is determined to the closest possible refractive power that the patient requires to see comfortably. During the adaptation process with the molding contact lens, if the vision is not suitable for the patient's needs, glasses are prescribed to the patient while the patient is undergoing treatment.

When the cornea is adapting or adapting, various eye measures are optionally repeated to confirm that the treatment is progressing as planned and appropriate. These measures may include visual acuity for near and far vision, distance to see a small type (J-3 to J-4) (e.g., the type of a newspaper or magazine) satisfactorily, orthotics, keratometry measurements, objective and subjective retinoscopy, diagram of the adaptation of the molding contact lenses, movement of the molding contact lenses and comfort of the molding contact lenses. After the measures are taken, changes in the treatment program are made based on these measures. Changes can be made to the molding contact lenses and / or pharmaceutical compositions to induce the desired refractive power in the cornea over the following weeks. In certain preferred embodiments, weekly periodic reviews are performed during the first 8 weeks after starting treatment. In certain embodiments, if the patient has not undergone refractive surgery, then the pharmaceutical composition should be prescribed for ocular administration.

The molding contact lenses used in the present system can be hard or soft. If it is a soft molding contact lens, a more positive or negative curvature in the cornea is induced, and the discomfort in the patient's eyes will decrease as it adapts to the contact lens. If a hard molding contact lens is used, more mechanical pressure will be exerted on the cornea. In certain embodiments, the contact lenses are gas permeable.

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The pharmaceutical composition used in the present system includes agents that help induce changes in corneal lamellae, collagen fibers, hyaluronic acid and the percentage of corneal hydration. Other aspects of the anatomy, histology and physiology of the cornea may also be affected by agents of the pharmaceutical composition. In certain embodiments, the composition may be hypertonic or hypotonic to induce changes in the percentage of corneal hydration. In other embodiments, the composition is used to change the supporting forces of the molecular structure of the cornea (eg, lamellae) and thereby mold the stroma to the desired curvature. In certain embodiments, the agents used in the pharmaceutical composition have been approved for use in humans by a regulatory agency such as the U.S. Food and Drug Administration (FDA) or a similar foreign regulatory entity. Preferably, the agents are approved for ocular use.

In certain embodiments, the composition contains the enzyme hyaluronidase that is known to break down hyaluronic acid, which functions as a cement between the corneal lamellae. Hyaluronidase is an enzyme that degraded mucopolysaccharides by catalyzing the hydrolysis of one to four bonds in hyaluronic acid, chondroitin, and chondroitin sulfates 4 A and C. Mucopolysaccharide is one of the intracellular ground substances (cement or glue) of the stroma, connective tissue of the middle layer of the cornea. The conformation of the cornea depends largely on the arrangement of the collagen fibrils in the stromal layers of the cornea and the arrangement of the mucopolysaccharide layers between these fibrils. Hyaluronidase breaks down mucopolysaccharide chains when released to the cornea. In this way, the stroma of the cornea softens making it more sensitive to remodeling through a molding contact lens.

Hyaluronidase can be obtained from a variety of natural sources from which the enzyme can be purified to at least 90% purity, at least 95% purity, at least 96% purity, at least 97% purity, at least 98% purity or at least 99% purity. Natural sources include bovine testes (bull), sheep testes (ram) and bacteria (Streptomyces). In certain embodiments, hyaluronidase is commercially available. For example, a form of haluronidase is available under the trade name WYDASE® (Wyeth Laboratories, Inc., Philadelphia, PA). WYDASE® hyaluronidase is a preparation of highly purified bovine testicular hyaluronidase. The hyaluronidase enzyme can be supplied as a lyophilized powder. The powder can be reconstituted using phosphate-saline buffer. Typical proportions include approximately 150 USP units of hyaluronidase per 1 milliliter. In certain embodiments, hyaluronidase is prepared using recombinant DNA technology. Hyaluronidase can be a modified version, e.g. eg, a cleaved, chemically modified or genetically modified form.

In certain embodiments, the concentration (weight percentage) of hyaluronidase in the pharmaceutical composition ranges from 0.01% to 10%, or 0.1% to 7%, or 0.1% to 5%, or 1 % to 5%. Increasing the concentration of hyaluronidase increases the ability of the contact lens to mold the cornea. In addition, the use of a vehicle such as a polymer (eg, methyl cellulose, polyvinyl alcohol, cellulose, etc.) in the composition allows the hyaluronidase to work on the cornea longer than without a vehicle.

An effective amount of hyaluronidase to soften a cornea in a mammal has been found to be between about 50 units of enzyme per milligram of substrate (i.e., the corneal mucopolysaccharide) and approximately 5,000 units per milligram of substrate. Preferably, the effective amount is between 100 and 1,500 units per milligram of substrate. Higher doses may be administered to reduce the number of administrations needed.

Other enzymes that can be included in the corneal softening composition include ABC chondroitinase, BC chondroitinase, queratanse and stromelysin, which have been shown to work on various components of cornea proteoglycan.

In certain embodiments, the composition contains the collagenase enzyme that is known to break down collagen, which functions as an extracellular matrix protein. In certain embodiments, collagenase is prepared using recombinant DNA technology. In other embodiments, collagenase is purified from a natural source. Collagenase may be a modified version, e.g. eg, a cleaved, chemically modified or genetically modified form. Other enzymes that break down the collagen components of the cornea include matrix 1 metalloproteinase (interstitial collagenase) and matrix 2 metalloproteinase (gelatinase). These enzymes can be used individually or in combination with other enzymes such as those that break down the proteoglycan component of the cornea. See US Patents. UU. 5,626,865 and 6,132,735, filed on May 6, 1997 and October 17, 2000, respectively. In certain embodiments, the pharmaceutical composition contains a combination of hyaluronidase and collagenase.

In certain embodiments, the concentration (weight percentage) of collagenase in the pharmaceutical composition ranges from 0.01% to 10%, or 0.1% to 7%, or 0.1% to 6%, or 1 % to 5%. Increasing the concentration of collagenase increases the ability of the contact lens to mold the cornea. In addition, the use of a vehicle such as a polymer (e.g., methyl cellulose, polyvinyl alcohol, cellulose, etc.) in the composition allows the collagenase to work on the cornea longer than without a vehicle.

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In another embodiment, enzymes endogenous to the eye are used to soften the cornea. These endogenous enzymes are activated to begin the softening process. The metalloproteinzases are activated by the administration of interleukin-1a, tumor necrosis factor, monosodium urate monohydrate, 4- aminophenylmercuric acetate, human serum amyloid A, human microglobin B2 and copper chloride. See US Patents. UU. 5,626,865 and 6,132,735, filed on May 6, 1997 and October 17, 2000, respectively.

In certain embodiments, the composition contains carbamide (urea). In certain embodiments, carbamide is obtained from commercial sources. In other embodiments, carbamide is purified from a natural source. The carbamide can be a carbamide derivative or a carbamide salt.

The pharmaceutical composition may also contain enzymes that degrade other sugars or proteins found in the cornea. In certain embodiments, enzymes act at the level of the corneal lamella junctions. In other embodiments, the pharmaceutical composition alters stromal hydration of the cornea or corneal thickness. In other embodiments, an agent that is known to change the supporting forces of the molecular structure of the cornea (e.g., corneal lamellae) is included in the pharmaceutical composition.

The pharmaceutical composition may contain other agents useful in the present process. In certain embodiments, the pharmaceutical composition contains an anesthetic used to reduce irritation of the molding contact lens on the cornea. Examples of anesthetics include benzocaine, bupivacaine, cocaine, etidocaine, lidocaine, mepivacaine, pramoxine, prilocaine, chloroprocaine, procaine, proparacaine, ropicaine and tetracaine. In other embodiments, the pharmaceutical composition includes an anti-inflammatory agent such as a steroid or a steroidal or non-steroidal anti-inflammatory agent. Example antiinflammatory agents include aspirin, acetaminophen, indomethacin, sulfasalazine, olsalazine, sodium salicylate, trisalicylate choline magnesium, salsalate, diflunisal, salicylsalicylic acid, sulindac, etodolac, tolmetin, diclofenac, ketorolac, ibuprofen, naproxen, flurbiprofen, ketoprofen, fenoprofen , suprofen, oxaproxin, mefenamic acid, meclofenamic acid, oxicams, piroxicam, tenoxicam, pyrazolydinediones, phenylbutazone, oxifentatrazone, phenyramine, antazoline, nabumetone, COX-2 inhibitors (Celebrex), apazone, nimesulide and zile. Glucocorticoids such as hydrocortisone, prednisolone, fluorometolone and dexamethasone can also be used as anti-inflammatory agents. In yet other embodiments, the pharmaceutical composition includes a lubricant. These agents are included to improve patient comfort during treatment. An expert in this specialty, based on the individual patient, determines the composition of the eye drops that are prescribed for the patient.

In certain other embodiments, the pharmaceutical composition includes antimicrobial agents such as antibacterial, antiviral and / or antifungal agents. Exemplary antimicrobial agents include bacitracin-zinc, chloramphenicol, chlorotetracycline, ciprofloxacin, erythromycin, gentamicin, norfloxacin, sulfacetamide, sulfisoxazole, polymyxin B, tetracycline, tobramycin, idoxuridine, trifluridine, gancrylamine, acycloiminevir, naphyrimicrovir, naphyrimicrovir, naphyrimicrovir, naphyrimicrovir, naphthinol, naphyrimicrovir, naphyrimicrovir, naphyrimicrovir, naphthinol, naphyrimicrovir, naphthinol, acyclovirine, naphyrimicroviric acid, naphthinolimic, antimicrobial agents. Econazol, fluconazole, ketoconazole, miconazole, flucytosine, clindamycin, pyrimethamine, folinic acid, sulfadiazine and trimethoprim-sulfamethoxazole.

The pharmaceutical composition may also include vasoconstrictors. Vasoconstrictors may include dipivephrine (gratuity), epinephrine, phenylephrine, apraclonidine, cocaine, hydroxyanfetamine, napazoline, tetrahydrozoline, dapiprazole, betaxolol, carteolol, levobunolol, metipranolol and timolol.

The pharmaceutical composition may also include vitamins or other nutrients such as vitamin A, vitamin B1, vitamin B6, vitamin B12, vitamin C (ascorbic acid), vitamin E, vitamin Ky and zinc.

The pharmaceutical composition can be provided in any form suitable for ocular administration. For example, the pharmaceutical composition may be in the form of eye drops, a semi-solid gel or an aerosol. In certain embodiments, the molding contact lenses are impregnated with the agents necessary to mold the stroma. In this way, agents can be delivered to the cornea continuously and in a release mode over time as the patient is wearing contact lenses.

An exemplary pharmaceutical composition of the disclosure may include 5-10% anesthetic, 10-20% antibiotic, 10-20% anti-inflammatory agent, 20-30% antiallergic agent, 20-30% vitamin A, 2-6 % hyaluronidase, 3- 5% carbamide (urea), 2-5% cytokinase and 10-20% vasoconstrictor. These agents can be combined in a hyper- or hypotonic solution. The composition may also include a carrier such as a polymer (eg, methyl cellulose, cellulose, polyvinyl alcohol, polyethylene glycol, etc.). The agents can be administered in combination or separately. As will be appreciated by an expert in this specialty, one or more of the agents can be removed from the pharmaceutical composition as determined by the responsible physician. In addition, as will be appreciated by an expert in this specialty, various substitutions of the agents of the pharmaceutical composition can be made. For example, different broad-spectrum antibiotics may be used depending on factors such as patient allergies, costs, probable organisms, etc. In addition, various anesthetic, anti-inflammatory agents, vasoconstrictors, antiallergic agent and cytokinase can be used.

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In certain embodiments, the molding contact lenses and the pharmaceutical composition are provided in a case. The case may optionally include lubricating eye drops, contact lens cleaning solutions, a container for carrying the contact lenses, a pair of additional contact lenses and instructions for using the contact lenses and using the pharmaceutical composition.

With all the elements considered above, the mathematical formulas for correcting presbyopia with the present method are as follows:

Rf - [332 / (332 / Ri + Dv)] + R (sphere

and visual memory cylinder)

Df - Di + Dv - (332 / Ri) + Dv + D (sphere and cylinder of visual memory)

Where Rf, Ri, Df, Di and Dv are as previously defined. It should be borne in mind that the calculations for the prescription of the molding contact lenses can be performed by a computer programmed with the formula described herein.

In patients with presbyopia and who require refractive surgery, it is necessary to induce the changes in the cornea suggested by the mathematical formula of myopic astigmatism composed with a vertical (or horizontal or oblique) axis so that the patient's visual system (including visual memory ) Start accepting the new images and together with the brain accommodation, train and educate the patient to change their habits for near and far vision.

Once the desired titration criteria has been reached using the present system, the use of the molding contact lenses and the pharmaceutical composition is interrupted. The treatment can be repeated his vision or the patient's visual needs change over time. For example, if presbyopia increases, a new treatment may be necessary. Or if the patient changes their work habits, a new treatment may be necessary. Aging can also cause vision changes that require a new treatment. As already mentioned, the patient guides the treatment to achieve the desired vision. Therefore, based on the information provided by the patient and the results obtained by measuring the refractive power of the cornea, if the patient wants, if the distance vision is better than the near vision, then the radius of curvature of the surface Anterior corneal (both in sphere and in cylinder) needs to bulge. If the patient has better near vision than far vision, the radius of curvature of the anterior corneal surface needs to flatten. If the image is distorted, a change in the axis of astigmatism (cylinder) is induced until the vision improves.

With each evaluation, the decision is made as to whether to continue with the same molding contact lenses or if a new contact lens should be worn. In addition, the same decision must be made regarding the pharmaceutical composition that is used with the molding contact lenses.

Another important aspect of the present method is that it can be used to change the refractive power of the cornea to improve the result of any refractive surgery or other technique to correct refractive errors. In patients who have recently undergone refractive surgery, the refractive power of the cornea can be refined or improved. As described above, in almost all refractive surgeries there is a residual refractive error that can be corrected or improved to achieve the vision required by the patient. During the first four weeks after refractive surgery (which is the approximate time it takes for the corneal wound to heal completely), changes in the refractive power of the cornea can be induced. In certain embodiments, the present treatment is started 24 hours, 48 hours, 73 hours or one week after surgery. External pressure on the cornea caused by a molding contact lens can change the radius of curvature of the anterior surface of the cornea to improve patient vision and fix or reduce any refractive errors that remain after refractive surgery. Since any residual defects in refraction can be corrected using the present technique, refractive surgeries are complemented by the present technique. In certain circumstances the present technique becomes a mandatory complement to refractive surgery.

In Figure 2, the Sturm cone is shown, showing mathematically speaking the circle of least confusion produced by a spherocylindrical lens (e.g., the cornea in the human eye), which is the point at which all the beams of light The Sturm cone considers the spherocylindrical lens as a smooth and uniform surface as if it were made of glass or plastic.

Ophthalmologists continue to refer to myopic compound astigmatism as an incorrect solution for the correction of presbyopia because they think that two images will be produced at the level of the retina and therefore the patient cannot see well with myopia and astigmatism. That is going to be induced. The ophthalmologist and optometrist also perform the measurements at the base of the two planes of the Sturm cone and in the circle of least confusion. However, this interpretation must be done in a different way that implies one of the advantages of the present system. The light beams that form any image at the level of the retina can be interpreted for a paraaxial optics that consists in considering the measurement of a small central area of the cornea and at the apex or axial axis, which includes only the nearby light beams to the central beam, the so-called power axis, and cannot predict aberrations in the images except astigmatism and refractive errors such as myopia. The calculations of the

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Paraaxial optics are relatively easy to perform and can be performed by hand, with a calculator or with a computer. In addition, calculations are made based on geometric optics, which has the limitation that it does not consider light as a wave but instead considers the propagation of light as a beam (that is, a straight line in a uniform medium with a constant refractive index). The method for calculating optical geometry is to trace the beams and typically involves using a computer programmed to perform these calculations. The most important, useful and fundamental theory is that which incorporates optics and physics. This theory takes into account the fact that light is a wave. This theory predicts wave interference and diffraction (when the wave crosses surfaces of different radii, thicknesses and / or refractive indices such as the cornea, the lens and other elements of the eye). Optics calculations using this approach are more difficult. However, this approach does not yet contemplate the irregularities of the retina and the differences in the radius and thickness of each element involved and the differences in refractive indices in each eye separately. Therefore, this calculation is not perfect either.

With the present technique, the disadvantages described above can be minimized or eliminated because this present system takes into account the visual memory and cerebral accommodation of the particular patient and the point dispersion function (PSF) in the retina. As shown in the isometric topographic maps of Figure 3 (Rabinowitz et al., Color Atlas of Corneal Topography, Interpreting Videokeratography, Igaku-Shoin Medical Publishers, Inc., p. 65), both the anterior and posterior surfaces of the cornea they have irregular surfaces for which it is only possible to use the less confusing circle approach to the sharpest possible. The anterior surface of the cornea becomes more uniform throughout the present system. By making the anterior surface of the cornea more uniform and inducing changes in the refractive power of the cornea, the present system is guided by the visual needs and visual memory of the patient for near and far vision.

As described above, all surfaces of the cornea are different in their radii of curvature and thickness. The circle of least confusion and the scattering function of the point in the retina is more blurred than those typically calculated. The reason why certain individuals do not need glasses or contact lenses before is simply because their refractive error is very low, e.g. eg, myopia of 0.690 diopters and astigmatism of 0.712 diopters (the actual measurements would be myopia of 0.50 D and astigmatism of 0.75 D). The brain with visual memory and cerebral accommodation that includes the optic-cerebral-motor system can compensate for these small refractive defects with the muscles of the eye areas that allow adequate focus or accommodation of the refractive defect.

The circle of least confusion found in the retina of the human eye does not correspond to a completely uniform circle and is not spherical in its circumference. In addition, the anatomical irregularities of the cornea produce an infinite number of very small but different focal points that are impossible to calculate. As seen by an ophthalmologist and optometrists, this is complicated even when it is understood that these small irregularities are found in each anatomical structure of the eye.

It should be noted that during a typical LASIK surgery, the corneal disc is raised and the laser beam is applied to produce an excision. In other surgical techniques that involve stomatic cuts or excisions such as the LASIK technique, the corneal disc is allowed to slide into the resected stromal space. The present technique makes use of stromal sliding. The ocularly administered pharmaceutical composition allows or preferably improves stromal sliding, which allows the cornea to bulge or flatten by the pressure exerted by the molding contact lens. Only when the present technique is used after refractive surgery can stromal slippage be observed. Stromatic slippage occurs on all surfaces of the keratectomy and when only one tenth of microns or microns is necessary to correct the residual refractive defect left by surgery. The present system allows the vision to reach the optimum for both eyes, e.g. For example, in the myopic sphere of 0.567 D and in the myopic astigmatism 0.682 D, with an axis of 122.5 °.

The corneal disc travels to the periphery to correct more nearsightedness by flattening the radius of curvature of the anterior surface of the cornea or moves towards the center of the cornea to improve farsightedness or presbyopia by bulging the radius of curvature of the surface anterior cornea (see "Refractive Surgery of the Cornea", Barraquer Institute of America, Bogotá, Colombia, 1999, p. 171), The formula for stromal sliding is already developed in "Refractive Surgery of the Cornea", Barraquer Institute of America, Bogotá, Colombia, 1999, p. 171.

Appendix A

Contact lens specification User manual

Window to capture patient data. (see figure 1).

image 1

Figure 1. Window to capture generic patient data

If the patient has previously used contact lenses, the following window will capture tolerance and other information. (See figure 2)

image2

10

Figure 2. Patients who have worn contact lenses before treatment.

5

If the patient has not used contact lenses before, then additional information is needed such as: sensitivity.

image3

Figure 3. Patients who have not worn contact lenses.

5 When the doctor presses the Review data button, the information is validated following these conditions:

• All data needs to be captured.

• Age needs to be between 1 and 100 years.

• Keratometry of the right and left eye needs to have a value between 34.09 and 55.32 D.

• The pachymetry of both eyes needs to have a value between (both eyes) 450 and 650 microns.

10 Once the information has been captured and validated, a confirmation window appears (see Figure 4). In this window, the doctor has the opportunity to check all the data in case of any error.

When all the data has been reviewed and confirmed, the doctor will press the Process button. Figure 5 shows the results of the captured information.

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Contact Lenses Specification

Paclent Data Confirmatlon

Yam: Alejandra Barrera Rlght Eye

Keratometiy 41.5 dlopters

F'íc jiritTy 500.0 miera

Deferred: -3.5 dlopters

Age: 32

Left eye

41.5 diopters 500.0 miera -2.5 diopters

Figure 4. Confirmation window

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 Contact Lenses Specification

 Pacient Data Confirmation

 Yam: Alejandra Barrera Age: 32

 Right Eye Left Eye

 Keratomet-ry:

 41.5 dlopters 41.5 diopters

 Paquimetry

 500.0 miera 500.0 miera

 Derect:

 -3.5 diopters -2.5 diopters

 Recommendation

 Lens type:

 Soft soft

 Base curve.

 9.054325955734408 mm 9.054325955734408 mm

Define lens power depending on the paclent

Figure 5. Results window.

5

As seen in Figure 5, each eye reads the appropriate recommended contact lens, and the base curvature value is expressed in millimeters. In addition, when the defect is greater than 2 D, the following message "Define lens power depending on the pecient" will appear, and when the keratometric value of any eye is less than 40 or greater than 48 D, the following message "Define peripherical base curve ".

Claims (20)

5 10 fifteen twenty 25 30 35 40 Four. Five fifty 55 60 65 1. A pharmaceutical composition comprising hyaluronidase and collagenase for use in the treatment of an ophthalmic condition with a contact lens; wherein the contact lens is adapted to be applied to an eye of a patient suffering from an ophthalmological condition; wherein the pharmaceutical composition is adapted to be applied to the patient's eye; where the ophthalmological condition is presbyopia. 2. The composition according to claim 1, for use in the treatment of the ophthalmological condition by inducing changes in the physiology and anatomy of the cornea with modifying contact lenses, where a change in corneal power is induced by changing the radius of curvature of the anterior surface of both eyes. 3. The composition according to claim 1, for use in the treatment of the ophthalmological condition by inducing changes in the physiology and anatomy of the cornea with modifying contact lenses, where a change in corneal power is induced by changing the radius of curvature of the anterior surface in one eye. 4. The composition for use according to claim 1, 2 or 3, wherein the contact lenses are commercially available, or where the contact lens is not custom-made, or where the contact lens is not specially designed for orthokeratology, or where the contact lens is a long-term contact lens. 5. The composition for use according to claim 1, 2 or 3, further comprising a polymer. 6. The composition for use according to claim 5, wherein the polymer is selected from the group consisting of methyl cellulose, cellulose, polyvinyl alcohol and polyethylene glycol. 7. The composition for use according to claim 1, 2 or 3, wherein the pharmaceutical composition is a liquid or a gel. 8. The composition for use according to claim 7, wherein the pharmaceutical composition is liquid. 9. The composition for use according to claim 8, wherein the composition is in the form of an aerosol or in the form of eye drops. 10. The composition for use according to claim 7, wherein the pharmaceutical composition is a gel. 11. The composition for use according to claim 10, wherein the composition is in the form of a semi-solid gel. 12. The composition for use according to claim 1, 2 or 3, wherein the treatment results in the correction of the ophthalmological condition for at least 7 days. 13. The composition for use according to claim 1, 2 or 3, wherein the treatment results in the correction of the ophthalmological condition for at least 6 months. 14. The composition for use according to claim 1, 2 or 3, wherein the treatment results in the correction of the ophthalmological condition for at least 1 year. 15. The composition for use according to claim 1, 2 or 3, wherein the treatment results in the correction of up to 3 diopters of refractive error without surgery. 16. The composition for use according to claim 1, 2 or 3, wherein the treatment results in the correction of up to 4 diopters of refractive error without surgery. 17. The pharmaceutical composition for use according to claim 1, 2 or 3, comprising: hyaluronidase in the range of 0.1 to 5%; collagenase in the range of 0.1% to 6%; and optionally a polymer selected from the group consisting of cellulose, methylcellulose, polyvinyl alcohol and polyethylene glycol. 18. The composition for use according to claim 1,2, 3 or 17, wherein the composition is hypertonic. 19. The composition for use according to claim 1,2, 3 or 17, wherein the composition is hypotonic. The composition for use according to claim 1, 2, 3 or 17, further comprising at least one agent selected from the group consisting of other enzymes, anesthetics, vitamins, zinc, antibiotics, antiallergic agents, carbamide, cytokineses, vasoconstrictors, antiviral agents, before antifungals, anti-inflammatory agents and lubricants. 10 21. A case comprising contact lenses and a pharmaceutical composition according to any one of the preceding claims. 22. The case according to claim 21, further comprising instructional material or contact lens cleaning supplies. fifteen