Viscoelastic composition for ophthalmic surgery

Abstract

The present invention relates to a viscoelastic composition for use in an ophthalmic surgery method, which is transparent and at the same time colored, which allow the surgeon to easily identify the composition during the ophthalmic surgery which facilitates viscoelastic removal at the end of the operation. The present invention also concerns an ophthalmic viscoelastic device comprising the viscoelastic composition of the present invention.

Description

[0001]SIB BW1347R VISCOELASTIC COMPOSITION FOR OPHTHALMIC SURGERY TECHNICAL FIELD OF THE INVENTION The present invention relates to a viscoelastic composition for use in an ophthalmic surgery method, which is transparent and at the same time colored, which allow the surgeon to easily identify the composition during the ophthalmic surgery which facilitates viscoelastic removal at the end of the operation. The present invention also concerns an ophthalmic viscoelastic device comprising the viscoelastic composition of the present invention. BACKGROUND OF THE INVENTION Ophthalmic Viscosurgical (or viscoelastic) Devices (OVD) are non-active, transparent (those currently known in the art) and gelatinous compositions, with viscous and elastic properties, used in ophthalmic surgery for the execution of mechanical surgical maneuvers in order to create and maintain spaces necessary during the surgical maneuvers. In particular, OVD are used to maintain adequate anterior chamber depth, to prevent mechanical damage to ocular tissues, and to act as buffering agents or vitreous substitutes. The typical individual characteristics of the various compositions on the market are the result of the length of the chains and the intra- and intermolecular interactions of the compounds constituting the viscoelastic substance. All viscoelastic materials have the potential to produce a dramatic increase in intraocular pressure if they are not adequately removed from the anterior chamber after surgery. The mechanism of action is essentially mechanical. It is important to take into account the viscoelasticity of the preparation in relation to the type of operation to be performed. No pharmacological, metabolic or immunological mechanism is involved in the action of the OVD. US 2003 / 088233 A1 and US 2020 / 093941 A1 disclose a viscoelastic composition for use in an ophthalmic surgery comprising hyaluronic acid (HA) and trypan blue as a dye. Currently all viscoelastic compositions used in ophthalmic surgery available on the market are transparent. Due to their transparency, it is difficult for the surgeon to identify the viscoelastic, which represents a problem of considerable importance since, once the operation is finished, the viscoelastic must be completely removed; leaving residues can cause increased eye pressure, resulting in serious eye problems. SUMMARY OF THE INVENTION SIB BW1347R In order to solve the problems of the prior art, the Authors of the present invention have developed a viscoelastic composition for use in a method of treatment of ophthalmic surgery, which maintains an adequate depth of the anterior chamber to prevent mechanical damage to the ocular tissues and is colored, which facilitates viscoelastic removal at the end of the operation. The viscoelastic composition developed by the authors of the present invention is advantageously indicated for: - Cataract operations with or without intraocular lens implantation; - Glaucoma surgery; - Corneal surgery; - Surgical interventions for retinal detachment. Thanks to its visibility, the viscoelastic composition of the present invention makes the removal phase of the viscoelastic extremely easy and allows the surgeon to visually explore all the spaces without the risk of leaving viscoelastic residues inside the operated bulb, which are dangerous for the hypertonic damage. Furthermore, the physic-chemical characteristics of the composition for use of the present invention allow the viscoelastic to guarantee the absorption of artificial wavelengths (such as UV and blue light between 400-450 nm), produced by the light of the surgical ocular microscope. This prevents these radiations from causing photooxidative damage to the macula during surgical maneuvers. It also acts as a deactivator, neutralizing free radicals formed during cataract surgery through the use of ultrasound. The viscoelastic composition of the present invention remains, during cataract surgery, within the eye, thereby creating and maintaining a deep anterior chamber and a clear field of vision during surgery and allows for safe and controlled manipulation at interior of the eye, minimizing any trauma to the corneal endothelium and other tissue organs, and is also used to maneuver, control and separate tissues in an atraumatic way, protecting them from mechanical impacts. Therefore, object of the present invention is: a viscoelastic composition for use in an ophthalmic surgery method comprising a viscoelastic polymer and a dye, wherein said viscoelastic composition is transparent and colored, an ophthalmic viscoelastic device comprising the viscoelastic composition for use according to the present invention, wherein said viscoelastic composition is in a syringe. DETAILED DESCRIPTION OF THE FIGURES SIB BW1347R Fig.1. Photograph of a syringe comprising the viscoelastic composition for use of the present invention, showing that the composition is transparent and colored (yellow). GLOSSARY Unless otherwise defined herein, scientific, and technical terms used in connection with the present invention shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. In any point of the present specification or of the claims, the expression “comprising” or “comprise(s)” can be replaced by “consisting of” or “consist(s) of”. DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a viscoelastic composition for use in an ophthalmic surgery method comprising a viscoelastic polymer and a dye, wherein said viscoelastic composition is transparent and colored. The terms "transparent and colored" refer to specific desirable properties of the viscoelastic composition for use according to the present invention. Being transparent, the viscoelastic composition must be clear and allow light to pass through without significant scattering or absorption. This transparency is crucial during ophthalmic surgery to ensure that the surgeon has an unobstructed view of the surgical field, including the structures within the eye. Clear viscoelastic materials help maintain visibility, which is essential for precision and safety during delicate procedures like cataract removal and lens implantation. The viscoelastic composition for use according to the present invention is intentionally colored by addition of the dye, and according to a preferred embodiment of the present invention the color is yellow. The purpose of coloring is to enhance the surgeon's ability to see the material within the eye. A slight tint can help the surgeon differentiate the viscoelastic material from the eye's natural tissues and other substances used during surgery. This can be especially useful in ensuring that the material is completely removed from the eye at the end of the procedure to avoid post-operative complications. Furthermore, the color provided by the dye allows the viscoelastic to guarantee the absorption of artificial wavelengths (such as UV and blue light between 400-450 nm), produced by the light of the surgical ocular microscope. This prevents these radiations from causing photooxidative damage to the macula during surgical maneuvers. It also acts as a deactivator, neutralizing free radicals formed during cataract surgery through the use of ultrasound. In summary, a viscoelastic composition for use in ophthalmic surgery being "transparent and colored" implies that SIB BW1347R the material should be mostly transparent to allow clear visibility while also potentially having a slight tint to aid the surgeon in visualizing the material during the procedure. In one embodiment, the dye in the viscoelastic composition comprises riboflavin. As well known by the person skilled in the art, Riboflavin, also known as vitamin B2, is a water- soluble vitamin. In one embodiment, said viscoelastic polymer is hyaluronic acid or sodium hyaluronate and / or a mixture thereof. Hyaluronic acid is a naturally occurring polysaccharide found extensively in the extracellular matrix of connective tissues. It is a glycosaminoglycan with a high molecular weight, notable for its ability to retain water, providing significant hydration and lubrication. Hyaluronic acid is clear, viscous, and biocompatible, making it essential for maintaining the structural integrity and functional performance of tissues without eliciting an immune response. Sodium hyaluronate is a specific fraction of sodium hyaluronate widely distributed in the extracellular matrix of connective tissue. It is a compound with a high molecular weight, high viscosity, transparent and without antigenicity. In one embodiment, the dye consists of riboflavin conjugated to a second viscoelastic polymer. Preferably, said second viscoelastic polymer is hyaluronic acid or sodium hyaluronate and hyaluronic acid or sodium hyaluronate. In one preferred embodiment, the second viscoelastic polymer is hyaluronic acid or sodium hyaluronate and hyaluronic acid or sodium hyaluronate and is conjugated to riboflavin. Hyaluronic acid or sodium hyaluronate conjugated with a riboflavin is disclosed in European patent EP3419590B1 herein incorporated by reference. It is a biopolymer belonging to the class of glycosaminoglycans with high molecular weight. Conjugated hyaluronic acid or sodium hyaluronate are biological and biocompatible substances. According to EP3419590B1, the conjugation between hyaluronic acid or sodium hyaluronate and riboflavin is by a covalent bond, in particular is an ester bond between the carboxylic group of hyaluronic acid and the C20 carbon of riboflavin according to the structure formula (I): SIB BW1347R Moreover, the molecular weight of said hyaluronic acid or sodium hyaluronate conjugated to riboflavin is comprised between 200.000 and 5.000.000 of Dalton, in particular between 200.000 and 800.000 Dalton, wherein said molecular weight is the average molecular weight of hyaluronic acid without considering the contribution of the weight of riboflavin. The degree of substitution of riboflavin in the esters in the hyaluronic acid or sodium hyaluronate conjugated to riboflavin is between 2 and 7%. The composition contains hyaluronic acid or sodium hyaluronate conjugated to riboflavin or vitamin B2, has a characteristic transparent straw yellow color that improves contrast. Thus, it ensures excellent visualization and safe capsulorhexis. Hyaluronic acid or sodium hyaluronate conjugated with a riboflavin boasts the benefits of both. In particular, the light-screening action of Riboflavin allows the disappearance or reduction of photophobia observed as early as two hours after instillation of the eye drop, while the longer residence time in the tear film allows the patients to reduce the frequency of instillation while using the hyaluronic acid or sodium hyaluronate conjugated with a riboflavin. The hyaluronic acid or sodium hyaluronate creates a stable protective layer over the tear film, counteracting the premature evaporation of the tear itself, it lubricates the cornea and conjunctiva, and it has moisturizing properties. The Riboflavin on the other hand gives absorbing power on UV radiation and on the spectrum of harmful blue light. In one embodiment the viscoelastic polymer has a molecular weight from 200.000 to 5.000.000 Da, preferably from 200.000 to 800.000 Da. SIB BW1347R In one embodiment the viscoelastic polymer is present in an amount from 1.2 to 1.4% w / w. In one embodiment the dye comprising riboflavin is present in an amount from 0.3 to 0.5% w / w. In one embodiment, the viscoelastic composition for use according to the present invention further comprises at least one solvent and at least one excipient. The person skilled in the art know which solvents and excipient are suitable for the intended use of ophthalmic surgery. Preferably, the solvent is water, and said excipient is a buffering agent, an isotonic agent or mixtures thereof. In one preferred embodiment, the buffering agent is selected from monobasic sodium phosphate or dibasic sodium phosphate, and the isotonic agent is selected from sodium chloride. In one embodiment, the buffering agent is present in an amount from 0.2 to 1.4% w / w, preferably from 1.20 to 1.35% w / w, and / or the isotonic agent is present in an amount from 0.60 to 0.90% w / w. In one embodiment, the viscoelastic composition for use according to the present invention has a pH from 5 to 8, preferably from 6.8 to 7.6. In one embodiment, the viscoelastic composition for use according to the present invention has an osmolality from 200 to 400 mOsm / Kg. In one embodiment, the viscoelastic composition for use according to the present invention has a dynamic viscosity from 60000 to 250000 mPa.s. In one embodiment, the viscoelastic composition for use according to the present invention has a color and transparency. In one preferred embodiment, the viscoelastic composition for use according to the present invention comprises sodium hyaluronate in an amount ranging from 0.5 to 3% w / w, preferably from 1 to 2.5% w / w, still more preferably from 1.2 to 1.9% w / w and hyaluronic acid or sodium hyaluronate conjugated to riboflavin in an amount ranging from 0.05 to 1%, preferably from 0.1 to 0.8%, still more preferably from 0.3 to 0.5% w / w. In one embodiment, the viscoelastic composition for use according to the present invention comprises sodium hyaluronate, and hyaluronic acid or sodium hyaluronate conjugated to riboflavin in an amount ranging from: SIB BW1347R Substance Composition Function % p / p HYALURONIC ACID 0.3-0.5 FUNCTIONAL OR SODIUM INGREDIENT HYALURONATE CONJUGATED WITH RIBOFLAVIN SODIUM 1.2-1.9 * THICKENING HYALURONATE * Quantities refers to an away of Sodium Hyaluronate equal to 100% In one embodiment the ophthalmic surgery method for which the viscoelastic composition herein disclosed is used is a cataract surgery with or without intraocular lens implantation, Glaucoma surgery, Corneal surgery, Surgical interventions for retinal detachment. In the ophthalmic surgery, the composition for use according to the invention can be used for filling up the vitreous body as well as for stabilizing the anterior chamber and for protection of the highly sensible endothelial cell layer of the cornea during surgery on the anterior eye portions, especially the surgery of the cataract. During the phacoemulsification, the anterior chamber of the eye is filled with the ophthalmologic composition comprising the coloured viscoelastic solution. The viscoelastic composition for use according to the present invention is used as a surgical aid to protect intraocular tissues, for example the corneal endothelium, during the phacoemulsification, as a space maintainer to maintain the anterior chamber of the eye, and to facilitate intraocular maneuvers, for example to make a controlled capsulorhexis. In the preferred embodiment wherein the composition comprises sodium hyaluronate or hyaluronic acid and riboflavin conjugated with a second viscoelastic polymer (i.e. sodium hyaluronate or hyaluronic acid), as the dye is covalently bound to the second viscoelastic polymer, the dye do not diffuse out of the solution and therefore do not negatively affect or stain the surrounding tissues. Object of the present invention is also an ophthalmic viscoelastic device comprising the viscoelastic composition for use according to the present invention, wherein said viscoelastic composition is in a syringe. The viscoelastic composition for use according to the present invention, after sterilization can be furnished as a medical device, allocated inside a class syringe, such as a 25 ml syringe with polycarbonate luer lock. The syringe can be closed with an elastomeric rubber luer tip and an external polypropylene cap and a rubber stopper. The syringe can be equipped with a polypropylene piston and polypropylene back stop. The syringe is sterile and can be designed for single use. The SIB BW1347R syringes, preassembled with rubber luer tip and external polypropylene cap, can be packaged in a plastic nest. In one preferred embodiment, the dye consists of riboflavin, preferably riboflavin phosphate, and is in an aqueous solution with the viscoelastic polymer. Preferably, said viscoelastic polymer is a glycosaminoglycan, preferably hyaluronic acid or sodium hyaluronate. In certain embodiments, the present invention relates to a composition in the form of a solution, preferably aqueous, comprising, or consisting essentially of, a glycosaminoglycan; preferably, the glycosaminoglycan is selected from the group consisting of hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratin sulfate, hepanin sulfate and heparin; more preferably, the glycosaminoglycan is hyaluronic acid. This composition is preferably a cohesive and / or dispersive viscosurgical aqueous solution. In certain embodiments, the present invention relates to an aqueous solution, preferably a cohesive and / or dispersive viscosurgical aqueous solution, comprising, or consisting essentially of, hyaluronic acid; preferably, low molecular weight hyaluronic acid; more preferably, hyaluronic acid having a molecular weight not exceeding 3500kDa; more preferably, having a molecular weight not exceeding 650kDa; still more preferably, having a molecular weight in the range 1000kDa-3500kDa. In one embodiment, said hyaluronic acid is present in an amount in the range of 1-20 mg per 1 mL of composition, preferably 1-10 mg per 1 mL of composition, in which solution the molecular weight of hyaluronic acid is less than or equal to 1000 kDa, in other words not more than 1000 kDa; preferably less than or equal to 650 kDa, more preferably less than or equal to 400 kDa, still more preferably in the range of 3-10 kDa. In one embodiment, the aqueous composition may comprise hyaluronic acid, in acid or salt form, preferably in sodium salt form (sodium hyaluronate), in quantities in the range of 1-20 mg per 1 mL of composition. In one embodiment the composition of the present invention comprise any hyaluronic acid with a molecular weight lower than 3500, 3000, 2500, 2000, 1500, 1000, 950, 900, 850, 10, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 250, 200, 150, 100, 90, 80, 70, 60, 50, 40, 30, 20, 10, 9, 8, 7, 6, 5, 4, 3, 2 and 1 kDa or included in the ranges SIB BW1347R having said values at the extremes. In one embodiment, the hyaluronic acid has a molecular weight in the range of 3500-650 kDa. In one embodiment, the hyaluronic acid has a molecular weight in the range of 650-450 kDa, preferably 250-400 kDa. In one embodiment, the hyaluronic acid has a molecular weight not exceeding 250 kDa. In one embodiment, the hyaluronic acid has a molecular weight in the range of 20-500 kDa. In one embodiment, the hyaluronic acid has a molecular weight in the range of 30-80 kDa. In one embodiment, the hyaluronic acid has a molecular weight in the range of 20-30 kDa. In one embodiment, the hyaluronic acid has a molecular weight in the range of 3- 10 kDa. In one embodiment, the molecular weight of hyaluronic acid is determined by gel permeation chromatography (GPC). In one embodiment the composition of the present invention comprises any low molecular weight hyaluronic acid, as defined above, known and commercially available; for example, the hyaluronic acid may be a hyaluronic acid produced by bacterial fermentation, extracted from animal tissues, preferably from rabbits, from cattle, from rooster combs, or from plant tissues and their mixtures. By way of example and not limitation, the hyaluronic acid included in the above aqueous composition is a hyaluronic acid with a molecular weight between 20 and 30 kDa, having an even acid content in the range of 1.75 and 3.75 mmol / g by titration with NaOH (soda), such as product 935166 marketed by Sigma-Aldrich®. The hyaluronic acid included in the aqueous solution above may also be a hyaluronic acid with a molecular weight between 200 and 400 kDa, having one or more of the following characteristics: a glucuronic acid content ≥35%, a hyaluronic acid content ≥95%, a film-like cream ≤20 mm2 / s and a pH between 5.0 and 7.0, such as the product 5394 marketed by Farmalabor™. The hyaluronic acid included in the aqueous composition above may also be a hyaluronic acid with a molecular weight between 3100KDa and 3800KDa, having one or more of the following characteristics: a glucuronic acid titre ≥35%, a cinematographic film ≤20 mm2 / s, a hyaluronic acid titre ≥95% to 105%, an intrinsic skin 3.00 to 3.39 m3 / Kg, and a pH between 5.0 and 8.5, such as product 240076 marketed by HTL Biotechnology. In one embodiment the composition comprises at least one solvent selected from the group consisting of water, isotonic aqueous solutions (e.g. comprising sodium chloride, potassium chloride, magnesium chloride, sodium acetate and / or sodium citrate or solutions having a pH in the range 6.7-7.6, also called balanced salt solutions or BSS®), physiological solutions (e.g. isotonic aqueous solutions comprising 0.9% sodium SIB BW1347R chloride), phosphate buffer solution, or similar sterile aqueous saline solutions, e.g. used for eye irrigation or during ophthalmic surgery or treatment. In one embodiment the composition comprises an additional viscoelastic moisturizing agent, in addition to hyaluronic acid, selected from the group consisting of carboxymethylcellulose, hydroxypropylmethylcellulose, glycerin, povidone, polyethylene glycol, sorbitol, xanthan gum, agarose, and sodium chondroitin sulfate. The aqueous composition may further comprise one or more additional ingredients such as, for example, vitamins and / or antioxidants; preferably, the vitamins are selected from the group consisting of vitamin B2, also called riboflavin, riboflavin phosphate, vitamin C, also called ascorbic acid, vitamin E, also called tocopherol, vitamin A, also called retinol, riboflavin phosphate, vitamin B3, also called niacin, vitamin B6, also called pyridoxine, vitamin B9, also called folic acid, and vitamin B12, also called cobalamin, and concentrations thereof; preferably, vitamin B2, also called riboflavin phosphate and / or basic. In one embodiment, the amount of riboflavin phosphate and / or basic is in the range of 0.0001-0.5 mg per 1 mL of composition; preferably, 0.0005-0.05 mg per 1 mL of composition. The presence of vitamin B2, preferably in the form of riboflavin phosphate, is particularly advantageous: in addition to giving the typical straw-yellow color, it also represents a powerful antioxidant; vitamin B2, preferably in the form of riboflavin phosphate, contributes to the color of the solution of the present invention and, furthermore, to the reduction of free radicals through scavenger action and protects the retina from the oxidative effect of light. In one embodiment, the composition is for parenteral or topical use and formulated in liquid form; such solution may also include any additional ingredients such as vehicles, excipients, additives, physiologically acceptable preservatives. In one embodiment, the additional ingredients may be, by way of example and not limitation, sodium dihydrogen phosphate dihydrate, disodium hydrogen phosphate decahydrate, sodium chloride. In any embodiment, the amount of sodium dihydrogen phosphate dihydrate is in the range of 2 - 2.2 mg per 1 mL of composition. In one embodiment, the amount of disodium hydrogen phosphate decahydrate is in the range of 10-11 mg per 1 mL of composition. In one embodiment, the amount of sodium chloride is in the range of 6--9 mg per 1 mL of composition. In one embodiment, the dynamic viscosity of the composition is in the range of 1000- 300000 mPas. For clarity, Pas stands for pascal-second, which is the SI unit of dynamic sensitivity. One pascal-second (Pa s) is equivalent to one kilogram per meter second SIB BW1347R (kg / (m s)). The prefix m indicates that we are talking about thousandths of a pascal- second, so 1 mPas = 0.001 Pa s. In one embodiment, the composition is a sterile solution. The pH of the composition according to one embodiment of the invention may have any value compatible with the pH of the eye, for example the pH of the solution may be in the range 5.0-8.5 preferably 6.7-7.6; preferably, the pH of the is in the range 7.2-7.5. The composition according to one embodiment of the invention may be comprised, for example, in a device, in a medical device, in a cosmetic composition, in a medicament or in a pharmaceutical composition. The present invention therefore also relates to a pre-filled syringe comprising the composition according to any embodiment of the invention. The volume of composition in such a pre-filled syringe is in the range of 0.3-1 mL, preferably, it is equal to 0.5-1.0 mL. Typically, the device or the medical device comprising the compositions are sterile devices. The present invention also relates to eye drops, gels, ointments, salves, sprays. The present invention further relates to a kit of parts comprising a container containing the composition according to any embodiment of the invention or, alternatively, a kit of parts comprising (i) a first container containing a solvent, (ii) a second container containing a hyaluronic acid having a molecular weight lower than 3800 kDa, and optionally, (iii) a third container containing an additional ingredient, preferably a vitamin and / or an antioxidant preferably, riboflavin phosphate. According to one embodiment, the kit of parts may comprise (i) a first container containing a solvent, as defined above, preferably in an amount of 0.3-1 mL, more preferably in an amount of 0.5 - 1 mL, (ii) a second container containing a hyaluronic acid having a molecular weight lower than 3000 kDa, as defined above, and where present, (iii) a third container containing an additional ingredient, preferably a vitamin and / or an antioxidant as defined above, preferably riboflavin phosphate, preferably in an amount of 0.0001-0.05 mg for every 1 mL of solvent present in the container (ii), and optionally (iv) a third container containing an additional ingredient, preferably a vitamin and / or an antioxidant as defined above, preferably riboflavin phosphate, preferably in an amount of 0.0001 -0.03 mg for every 1 mL of solvent present in the container (ii). SIB BW1347R Where present, the kit may include additional separate compartments containing one or more of the following ingredients: riboflavin phosphate, sodium dihydrogen phosphate dihydrate, disodium hydrogen phosphate decahydrate, sodium chloride. The container containing the solution according to any embodiment of the invention, or the individual ingredients that make up the composition, can be chosen from a syringe, a pre-filled syringe, a vial, a phial, a disposable dispenser, a bottle, preferably in transparent glass or amber glass or opaque glass or plastic, a tube, preferably in aluminum or laminated plastic, a sachet, preferably in laminated material or aluminum, a graduated dispenser, a single-dose capsule, a blister, a zip-lock sachet, a resealable ampoule; obviously, in the case in which the kit contains two or more containers, they can be the same or different from each other. Typically, the pre-filled syringe or the one in the above kit is equipped with a 22-33 gauge needle cannula with a tapered and flattened tip on the horizontal plane or preferably with a rounded tip and a length of 4-mm from the tip and with a 35° angle; preferably, 27-31 gauge with a tapered and flattened tip on the horizontal plane or preferably with a rounded tip and a length of 4-mm from the tip and with a 35° angle. In any embodiment, the needle is a Luer-Lock needle. In certain embodiments, the present invention relates to a composition according to any embodiment of the invention for use as a colored ophthalmic viscosurgical device to be used in ocular surgery and due to its visibility and transparency, due to the typical straw- yellow color, for various intraoperative functions: obtaining and maintaining spaces in a visible manner for the surgeon, protection of the endocular structures and tissues in a visible manner, to create the conditions that the surgeon needs for delicate intraocular maneuvers in a visible manner, all in modern cataract surgery as well as in other intraocular surgeries. The use of a solution according to any embodiment of the invention as a colored ophthalmic viscosurgical device is associated with some advantages, once injected in the dynamic phase of cataract surgery: 1. Fill the front camera (AC) The insertion of a colored OVD is desirable so that the ocular inflation pressure can be visible, assessed and modulated not only by the tactile sensitivity of the surgeon but above all by the visibility of the injected OVD. 2. Capsulorhexis SIB BW1347R During capsulorhexis, the colored OVD will allow for better viewing of the corneal dome and the depth of the anterior camera and will provide visibility of the surgical maneuver boundaries without the risk that the instruments used such as forceps and / or cannulas may hit the ocular tissues. 3. Removal of the core In phacoemulsification during nucleus emulsification, the AC depth will be maintained by the infusion pressure as well as the OVD. The cornea is vulnerable to damage from ultrasonic energy and fluid turbulence. The ideal OVD at this stage is a colored OVD that allows the surgeon to verify during this stage to highlight the presence of the endothelial recoil measure (to protect the endothelium itself. 4. Irrigation / Suction (I / A) In phacoemulsification during nucleus emulsification, the AC depth will be maintained by the infusion pressure as well as by the OVD. The cornea is vulnerable to damage caused by ultrasonic energy that forms free radicals and by fluid turbulence. The ideal OVD in this phase is a riboflavin-colored OVD that in addition to giving the typical straw-yellow color allowing the surgeon to verify during this phase the presence of the measure of endothelial coverability by the viscoelastic to mechanically protect the endothelium from vibrations, but also to play the role of reducing the presence of free radicals formed, by means of a scavenger mechanism and at the same time absorbing the wavelengths emitted by the optical microscope that are harmful to the macula in the spectrum between 350-450 nanometers. 5. IOL implant In this step, the OVD has two main roles: to protect the corneal endothelium from compression that could occur if the lens gets too close to the endothelium and to keep the capsule inflated to facilitate the introduction of the IOL and reduce the risk of touching the capsule with an instrument. A colored OVD allows the surgeon to verify the accuracy of these maneuvers by its visibility, which is not possible when using OVDs currently on the market, which are only transparent and not visible. 6. OVD Removal The last step in both techniques (ECCE and phacoemulsification) is the removal of the OVD. This will be facilitated by a colored OVD presenting no risk of leaving viscoelastic residues and avoiding post-operative intraocular pressure peaks. In certain embodiments, the present invention relates to a solution according to any embodiment of the invention for use in the treatment and / or prevention of post-surgical complication pathologies, preferably in the prevention of hypertonicity after cataract SIB BW1347R surgery. The release of viscoelastic residues at the end of surgery causes an obstruction of the Schlemm canal through which excess aqueous humor is drained. This condition inevitably produces an imbalance between the aqueous humor produced and that to be disposed of, thus determining an increase in ocular tone which translates into subjective symptoms such as pain and corneal edema and objective symptoms such as irreversible damage to the optic nerve. Disclosed herein is a method of performing an ophthalmic surgery on the eye of a subject, comprising a step of administering to said eye an effective amount of the viscoelastic composition according to the present invention. In one embodiment, the method herein disclosed comprises a step of filling up an anterior chamber of said eye of the patient. In one embodiment, the method of herein disclosed comprises a step of removing said viscoelastic composition from said eye of the subject. Thanks to its colouring and hence visibility, the composition for use according to the present invention, as discussed above, allows the surgeon to better visualize the composition and to remove in a more efficient way. In one embodiment, said ophthalmic surgery is a cataract surgery with or without intraocular lens implantation, Glaucoma surgery, Corneal surgery, Surgical interventions for retinal detachment. EXAMPLES During the development phase of the colored ophthalmic viscoelastic, particular attention was paid to obtaining a color that ensured both the transparency necessary for effective and safe use in surgical procedures and optimal visibility for surgeons. The development team's main goal was to create a viscoelastic solution that could be easily visualized during surgery without compromising its transparent and viscoelastic properties. This balance is critical to improving the precision and safety of ophthalmic procedures. In the most preferred embodiment, the choice of riboflavin (vitamin B2) as a coloring agent was strategic and based on numerous tests and analyses. Riboflavin was selected for the following reasons: • Biological Safety: Riboflavin is a biocompatible and safe component for intraocular use, as demonstrated by scientific literature and our internal tests. SIB BW1347R • Visual Effectiveness: The yellow color obtained with riboflavin provides sufficient contrast to improve the visibility of the viscoelastic within the operating field, without being too intense to obscure the surgeon's vision. • Maintenance of Transparency: Despite the coloration, riboflavin maintains the transparency of the viscoelastic, allowing clear visualization of the intraocular structures and facilitating surgical maneuvers. During the development of the colored viscoelastic, numerous tests were conducted to ensure that the solution met the highest quality and safety standards: • Transparency Tests: Optical tests were carried out to ensure that the solution maintained a high degree of transparency, essential for viewing ocular structures during surgery. • Visibility Test: The color has been calibrated to ensure optimal visibility under different lighting conditions, typical of operating theatres. • Stability Test: The stability of the color has been verified through long-term stability studies to ensure that the viscoelastic maintains its properties throughout the shelf life. The results obtained confirm that the colored viscoelastic offers an ideal combination of transparency and visibility, significantly improving the surgical experience and increasing the safety of the procedures. The yellow coloration does not interfere with visual clarity but, instead, provides useful contrast that helps surgeons precisely monitor and control viscoelastic application. The combination of transparency and visibility obtained represents a significant technological advancement that will improve surgical outcomes and patient safety. EXAMPLE OF COMPOSITION #1 Substance Composition Function % p / p HYALURONIC ACID 0.3-0.5 FUNCTIONAL CONJUGATED INGREDIENT WITH RIBOFLAVIN SODIUM 1.2-1.4 * THICKENING HYALURONATE SODIUM 0.2-0.22 BUFFERING AGENT DIHYDROGEN PHOSPHATE DIHYDRATE DISODIUM 1.00-1.10 BUFFERING AGENT HYDROGEN SIB BW1347R PHOSPHATE DODECAHYDRATE SODIUM 0.60-0.90 ISOTONIC AGENT CHLORIDE WATER FOR ENOUGH TO SOLVENT INJECTION 100 * Quantities refers to an away of Sodium Hyaluronate equal to 100% EXAMPLE OF COMPOSITION #2 Substance Composition Function % p / p HYALURONIC ACID 0.3-0.5 FUNCTIONAL CONJUGATED INGREDIENT WITH RIBOFLAVIN SODIUM 1.7-1.9* THICKENING HYALURONATE SODIUM 0.20-0.22 BUFFERING AGENT DIHYDROGEN PHOSPHATE DIHYDRATE DISODIUM 1.00-1.10 BUFFERING AGENT HYDROGEN PHOSPHATE DODECAHYDRATE SODIUM 0.60-0.90 ISOTONIC AGENT CHLORIDE WATER FOR ENOUGH TO SOLVENT INJECTION 100 * Quantities refers to an away of Sodium Hyaluronate equal to 100% EXAMPLE OF COMPOSITION #3 Substance Composition Function mg / mL SODIUM 1-20 THICKENING HYALURONATE RIBOFLAVIN (OR 0,0001-0,05 FUNCTIONAL RIBOFLAVIN INGREDIENT – DYE PHOSPHATE) SODIUM 2-2,2 BUFFERING AGENT DIHYDROGEN PHOSPHATE DIHYDRATE SODIUM 10-11 BUFFERING AGENT DIHYDROGEN PHOSPHATE DECAHYDRATE SODIUM 6-9 ISOTONIC AGENT CHLORIDE WATER FOR ENOUGH TO SOLVENT INJECTION 100 SIB BW1347R * Quantities refers to an away of Sodium Hyaluronate equal to 100% CHEMICAL-PHYSICAL PROPERTIES OF EXAMPLE COMPOSITION #1 CONTROLS SPECIFIC Solution appearance Clear, transparent with slight yellow reflections CHEMICAL- pH 6.8 – 7.6 PHYSICAL osmolality 200-400 mOsm / kg Dinamic viscosity 60’000 – 120’000 mPa.s CHEMICAL-PHYSICAL PROPERTIES OF EXAMPLE COMPOSITION #2 CONTROLS SPECIFIC Solution appearance Clear, transparent with slight yellow reflections CHEMICAL- pH 6.8 – 7.6 PHYSICAL osmolality 200-400 mOsm / kg Dinamic viscosity 130’000 – 250’000 mPa.s

Claims

SIB BW1347R CLAIMS 1. A viscoelastic composition for use in an ophthalmic surgery method comprising a viscoelastic polymer and a dye, wherein said viscoelastic composition is transparent and colored, wherein said dye consists of riboflavin, and wherein said composition has a pH from 5 to 8, wherein said viscoelastic polymer is hyaluronic acid or sodium hyaluronate and / or a mixture thereof.

2. The viscoelastic composition for use according to claim 1, wherein said riboflavin is riboflavin phosphate.

3. The viscoelastic composition for use according to any one of claims 1 or 2, wherein said dye is in a range from 0.0001 to 0.5 mg / mL of viscoelastic composition.

4. The viscoelastic composition for use according to any one of claims 1 to 3, wherein said viscoelastic polymer is in a range from 1 to 20 mg / mL of viscoelastic composition.

5. The viscoelastic composition for use according to any one of claims 1 to 4, wherein said composition is in the form of an aqueous solution.

6. The viscoelastic composition for use according to any one of claims 1 to 5, having an osmolality from 200 to 400 mOsm / Kg and / or a dynamic viscosity from 1000 to 300000 mPa.s.

7. The viscoelastic composition for use according to any one of claims 1 to 6, wherein said viscoelastic composition has a pH from 6.8 to 7.

6.

8. The viscoelastic composition for use according to any one of claims 1 to 7, wherein said hyaluronic acid has a molecular weight lower than 3500 kDa.

9. The viscoelastic composition for use according to any one of claims 1 to 7, wherein said ophthalmic surgery method is a cataract surgery with or without intraocular lens implantation, Glaucoma surgery, Corneal surgery, Surgical interventions for retinal detachment.SIB BW1347R 10. The viscoelastic composition for use according to any one of claims 1 to 9, wherein said viscoelastic composition absorbs light at a wavelength from 400 to 450 nm, thereby protecting the eye from photo-oxidative damages.

11. The viscoelastic composition for use according to any one of claims 1 to 10, wherein said viscoelastic composition has a radical scavenger activity with respect to free radicals formed during the turbulences caused by ultrasounds during the phacoemulsification in cataract surgery.

12. The viscoelastic composition for use according to any one of claims 1 to 11, wherein said cataract surgery method comprises a step of filling the ocular anterior chamber (AC) of a patient with the viscoelastic composition according to any one of claims 1 to 11.

13. The viscoelastic composition for use according to any one of claims 1 to 12, which in a cataract surgery method: - in a capsulorhexis step allows better viewing of the corneal dome and the depth of the anterior chamber and provides visibility of the surgical maneuver borders without the risk that the instruments used such as forceps and / or cannulas may impact the ocular tissues; and / or - in a phacoemulsification step, during nucleus emulsification, allows the AC depth to be maintained and protects the cornea from damage caused by ultrasonic energy and fluid turbulence, and allows the surgeon to verify the presence of endothelial cover measure to protect the endothelium itself; and / or - in an irrigation and aspiration step, allows to avoid the risk of trauma from ultrasound energy or free radicals and assure the surgeon of the confirmation that the endothelial layer is protected and covered by the viscoelastic composition; and / or - in an intraocular lens (IOL) implantation step, allows to protect the corneal endothelium from compression that could occur if the lens gets too close to the endothelium, and allows to keep the capsule inflated to facilitate the introduction of the IOL and reduce the risk of touching the capsule with an instrument; and / or - in a step of removal of the viscoelastic composition, allows a easier removal of the composition avoiding risk of leaving viscoelastic residues and avoids post-operative intraocular pressure peaks.SIB BW1347R 14. An ophthalmic viscoelastic device comprising the viscoelastic composition for use according to any one of claims 1 to 13, wherein said viscoelastic composition is in a syringe.

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