Methods of administering ophthalmic drugs. Injections into the eyes: types and preparations for injections into the eyeball. Instillation into the eye
Brian C. GilgerDVM, MS, Dipl. ACVO, Dipl. ABT, Professor, Ophthalmology, North Carolina State University College of Veterinary Medicine. Email: [email protected]
Introduction
Traditionally, there are three main routes of drug administration into the eye: using local agents, systemic drugs or injections, intraocular or periocular. Each of these methods has significant drawbacks. Ophthalmic solutions and ointments for external use provide less than 1% penetration into tissues, are subject to rapid dilution and washout with tears, and their use requires the animal owner to strictly follow the instructions for administering the drug. Systemically administered drugs generally have limited ability to penetrate ocular tissue and may therefore require higher and potentially toxic drug concentrations in the periphery. Ocular and periocular injections of the drug are traumatic and invasive, are subject to rapid dilution and may require repeated administration to achieve the required drug concentrations. These disadvantages, especially in cases of chronic intraocular disease in large animals, led the author to study methods of drug delivery into the eye using continuous drug release devices.
Ophthalmology in practice can be reduced to a simple task: delivering the correct pharmacological agent in an appropriate therapeutic dose to the target ocular tissue using a method that does not injure healthy tissue. However, in the case of eye diseases, this simple task is complicated due to the high sensitivity of ocular tissues (such as the uveal tract and retina) and the presence of tissue barriers to the penetration of drugs, namely the lipophilic corneal epithelium, hydrophilic corneal stroma and sclera, lymphatic system of the conjunctiva, choroidal vessels and blood-ocular barriers.
When choosing a method of drug administration for eye therapy, three important aspects must be taken into account:
- duration of administration;
- the target tissue for which the drug is intended;
- the owner's consent to carry out the assignments.
The duration of administration of the drug varies from minutes - in the case of external eye drops, to several years, for some eye implants. The route of drug administration may influence the drug's ability to reach target tissues. For example, topical ophthalmic drugs at therapeutic concentrations are likely to reach the cornea and conjunctiva but are unlikely to reach the retina and choroid.
Finally, the issue of compliance must be taken into account. For example, when treating a chronic disease, in order to achieve therapeutic concentrations of the drug in tissues, it must be administered every hour for a year. It is unlikely that the pet owner will follow the prescription systematically, if at all. Therefore, the method of administration of an ophthalmic drug must be appropriate to the disease in terms of drug target location and duration of effect to ensure pet owner compliance (Figure 1).
The issue of compliance is especially important in veterinary medicine because of the difficulty of consistently treating a sick animal, which often falls on the untrained owner. In this regard, the development of a technology for the continuous administration of an ophthalmic drug has begun, which can eliminate or alleviate the problem of compliance with prescriptions by owners.
Main features of drug administration into the eye
Depending on the location of the target tissue, the main issues to be addressed when administering drugs ocularly are localizing the drug's action to a specific site and maintaining therapeutic concentrations while minimizing systemic effects. Penetration of the drug through the cornea is the main route of entry of the local drug into the anterior chamber of the eye. Most drugs require 20-60 minutes to reach peak concentrations in the intraocular fluid. The interval between the local administration of the drug and its appearance in the intraocular fluid is called the lag time of the drug. The lag time depends on the rate of diffusion of the drug through the cornea. The amount of drug that penetrates the cornea depends linearly on the concentration of the drug in the tear; with the exception of drugs that have other physicochemical properties that affect their penetrating ability (such as interaction with other molecules, binding to proteins, limited solubility of the drug, metabolism by tear enzymes). The decrease in drug concentration in tears (and therefore the amount that penetrates the cornea) follows the rules of first-order reaction kinetics, and the rate of decrease in concentration depends on the rate of dilution of the drug into fresh tears. In rabbits and humans, the half-life of a single 20 µL drop of ophthalmic preparation varies from 2 to 20 minutes. As a result, only 1-10% of the topical dose can reach the anterior chamber of the eye. The residue is excreted with tears through the nasolacrimal system, deposited on the eyelids, or subjected to breakdown by enzymes in tears or integumentary tissues. Systemic absorption of some drugs can be significant. Infusion of a drug at a constant rate or delivery from solid implants containing the drug generally follows the rules of zero-order reaction kinetics.
Anatomical and physiological barriers to the penetration of drugs into the eye
Local ophthalmic administration of drugs is complicated by the fact that the eye has unique functional and structural protective mechanisms, such as blinking, constant production and drainage of tears, which are necessary to maintain visual acuity, but at the same time favor the rapid elimination of locally administered ophthalmic drugs. For drugs administered periocularly or systemically, the main obstacles to penetration into the internal tissues of the eye are the sclera and blood-ocular barriers. The cornea is essentially a multilayer sandwich: fat (epithelium) - water (stroma) - fat (endothelium). The epithelium is the main barrier to absorption, especially of hydrophilic drugs, while the corneal stroma is the main barrier to lipophilic drugs. Thus, a drug with an optimal ratio of hydrophilicity and lipophilicity provides the best transfer through the cornea.
Ocular drug administration
The complex division of the eye into sections creates unique locations for placement of drug administration systems. This review examines both non-invasive local delivery strategies and more invasive implant technologies.
Non-invasive administration strategies
While standard topical ophthalmic solutions are usually sufficient to produce an effective response for most disorders of the superficial structures and anterior chamber of the eye, there are factors that limit the ability of eye drops to achieve concentrations above the minimum effective for the treatment of the posterior segment of the eye. These factors include, but are not limited to, the distribution and diffusion coefficients of the drug in tissues, the hydraulic conductivity of ocular tissues, the solubility limits of the drug, conjunctival clearance, as well as intraocular and episcleral venous blood pressures. There are two approaches to increasing the concentration of the drug in the posterior parts of the eye: increasing the time the drug remains in the eye and increasing the ability of the drug to penetrate the tissue. The local residence time of the drug can be increased with the help of gels and the implantation of solid implants. The penetration ability of drugs can be improved by using prodrugs, solubilizers, and iontophoresis techniques.
Using implants to administer drugs
Collapsed implants
Ocular implants have many advantages, including the ability to deliver sustained therapeutic concentrations of drug directly to the site of ocular disease while reducing systemic side effects. These devices for controlled continuous release of the drug are divided into biodegradable (destructible) and non-biodegradable. The advantage of biodegradable implants is that they can be molded into any shape and do not require removal. The advantage of biodegradable implants is that they release the drug gradually and in a controlled manner over a long period of time (several years), but the disadvantage is that they need to be removed and/or replaced when the drug is depleted.
Non-destructive implants based on diffusion
Non-destructive implants release the drug from a non-biodegradable device that contains either a central reservoir or a dense central device coated with the drug. When the drug is depleted, either type of device can be removed from the eye and replaced. Typical reservoir implants consist of a granular core surrounded by a non-reactive substance such as silicone, ethylene vinyl acetate (EVA) or polyvinyl alcohol (PVA). The main advantage of these implants is their ability to deliver constant doses of the drug over several years.
Non-destructive implant pumps
Historically, studies examining the effects of continuous drug infusion using small pumps have been limited to evaluating the use of Alza osmotic pumps. These commercially available pumps deliver predetermined drug concentrations, are typically placed under the skin, and provide drug delivery over a period of a month. Their use for ocular infusions has been studied in horses (Herring).
Intraocular lenses (IOLs)
Intraocular lenses have also been explored to deliver drugs to ocular tissue after cataract surgery. The drug can be placed inside the lens itself or on its surface, or a separate reservoir with the drug is attached to the VGL. The most commonly used VGLs have a higher water content, such as hydrogels or soft acrylic plastic, which allow the VGL to be filled with the drug using a simple “impregnation” method. The use of VGL reduces the risk of postoperative endophthalmitis through the administration of antibiotics, suppresses inflammation through the administration of dexamethasone or NSAIDs, and/or prevents the development of fibrosis of the posterior capsule of the lens. In our study, acrylic VGLs incubated in celecoxib solution demonstrated the ability to release celecoxib in concentrations sufficient to reduce inflammation and prevent posterior lens capsule opacification for 7 days in vitro. Although there are currently no data from studies in veterinary patients, this method appears to be of practical importance and further development is warranted.
Suprachoroidal administration of drugs
The suprachoroidal (perichoroidal) space is normally almost unexpressed, which is why it is often called “potential” - a narrow gap located between the sclera and the choroid of the eye. Injection into it leads to rapid infiltration of the drug into the ciliary body and choroid. A single injection of the drug into the suprachoroidal space of the eyes of dog and pig corpses ensured the distribution of the drug in more than 50% of the tissues of the posterior segment of the eye. Chronic cyclosporine-releasing implants placed in the suprachoroidal space provided long-term control of uveitis in horses. The use of special microneedles to gain access to the suprachoroidal space will allow this technique to be used with a wide range of drugs and provide access to the macula, optic nerve and posterior pole of the eye.
Results and conclusions
In the last ten years, the development of ophthalmic devices and products designed to improve compliance, selectivity, and duration of ophthalmic drug delivery has accelerated significantly. This is a consequence of a better understanding of ocular fluid dynamics and drug distribution, experimentation using new ocular drug delivery sites, and improved technology leading to better biomaterials and drug release mechanisms. Moreover, the development of new classes of drugs for diseases such as glaucoma, uveitis and retinopathy has initiated the development of unique systems aimed at overcoming the shortcomings observed in the classical therapy of these new complex diseases. The coming wave of new devices undergoing clinical evaluation will offer patients and practitioners a variety of much-needed and more effective treatments.
Literature
1. Wiener AL, Gilger BC. Advancements in Ocular Drug Delivery. Vet Ophthalmol 2010;13(6):395-406.
2. Davis JL, Gilger BC, Robinson MR. Novel approaches to ocular drug delivery. Curr Opin Mol Ther 2004;6:195-205.
3. Gilger BC, Salmon JH, Wilkie DA, et al. A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis. Invest Ophthalmol Vis Sci 2006;47:2596-2605.
4. Blair MJ, Gionfriddo JR, Polazzi LM, et al. Subconjunctivally implanted micro-osmotic pumps for continuous ocular treatment in horses. Am J Vet Res 1999;60:1102-1105.
5. Davis DL, Yi NY, Salmon JH, Charlton AN, Colitz CMH, Gilger BC. Sustained-release celecoxib from incubated acrylic intraocular lenses suppress lens epithelial cell growth in an ex vivo model of posterior capsule opacity (PCO). J Ophthalmol Pharm Therapeutics.
6. Seiler GS, Salmon JH, Mantua R, Feingold S, Dayton PA, Gilger BC. Distribution of contrast after injection into the anterior suprachoroidal space using 2D and 3D ultrasound in pig eyes. Invest Ophthalmol Vis Sci 2011 52(8):5730-5736
7. Gilger BC, Wilkie DA, Clode AB, McMullen RJ, Utter M, Komaromy A, Brooks DE, Salmon JH. Long-term outcome after implantation of a suprachoroidal cyclosporine drug delivery device in horses with recurrent uveitis. Vet Ophthalmol 2010;13(5):294-300.
8. Jiang J, Moore JS, Edelhauser HF, et al. Intrascleral drug delivery to the eye using hollow microneedles. Pharm Res 2009;26:395-403.
The lecture was provided by the organizers of the III Moscow Veterinary Congress of Ophthalmology, translation and publication are carried out with the kind permission of Dr. Brian Gilger.
SVM No. 2/2016
19-01-2013, 00:40
Description
Most often, for the treatment of various eye diseases, medications are administered locally into the conjunctival sac in the form of eye drops or ointments.Eye drops (solutions, suspensions, sprays) and ointments (gels), ophthalmic medicinal films (OMFs) are forms of medicines specially developed for use in ophthalmology.
Their composition, in addition to the active substance that has a therapeutic effect, includes various auxiliary (inactive) components that are necessary to maintain the stability of the dosage form. However, it should be remembered that excipients can act as allergens and have a negative effect on the tissue of the eyeball and its appendages.
Preservatives are used to inhibit the growth of microflora when the drug is contaminated. All preservatives have varying degrees of toxic effects on the epithelium of the cornea and conjunctiva.
The risk of toxic effects of preservatives on eye tissue increases when instilling more than 12 drops during the day of any drug containing a preservative.
In patients with dystrophic and allergic diseases of the cornea, conjunctiva and in children, it is better to use drugs that do not contain preservatives (for example: Santen Oy, Finland, produces sodium cromoglycate solution [INN] in 0.25 ml dropper tubes intended for single use under the trade name "Lecrolin").
As preservatives the most commonly used substances are: benzalkonium chloride (0.005-0.01%), phenylethyl alcohol (0.5%), benzethonium chloride, chlorhexidine (0.005-0.01%), cetylpyridinum chloride, benzoate, chlorobutanol (0.5% ), propionate, boric acid (up to 2%), mercury preservatives - phenylmercury nitrate (acetate, borate) 0.001-0.004%, thiomersal - 0.002%.
It should be noted that in modern pharmaceuticals, mercury preservatives, boric acid and borates are used less and less. The most convenient and safe preservatives at the moment are benzalkopium chloride, chlorobutanol and chlorhexidine. Not only the range of preservatives used changes, but also their concentrations. In recent years, lower concentrations have been used. A reduction in concentration is achieved through the combined use of several preservatives.
To reduce the rate of drug removal from the conjunctival sac, viscosity-increasing agents(prolongators). For this purpose, the following substances are used: carboxymethylcellulose, dextran 70, hydroxyethylcellulose, methylcellulose, hydroxypropylmethylcellulose, gelatin, glycerin, propylene glycol, polyvinyl alcohol, povidone.
Depending on the excipients or carriers used The duration of action of 1 drop varies. The shortest effect is for aqueous solutions, longer when using solutions of viscoactive substances, the maximum is for helium solutions. For example, a single instillation of an aqueous solution of pilocarpine [INN] lasts 4-6 hours, a prolonged solution on methyl cellulose - 8 hours, a helium solution - about 12 hours.
To prevent the disintegration of the active substance included in the drug under the influence of atmospheric oxygen, use antioxidants(bisulfite, EDTA, metabisulfite, thiosulfate).
Acidity of tears a person normally ranges from 7.14 to 7.82. The ability of substances to penetrate through the cornea into the anterior chamber largely depends on the degree of their ionization, which is determined by the pH of the solution. The acidity of the solution affects not only the kinetics of the drug, but also its tolerability. If the pH of the injected solution differs significantly from the pH of the tear, the person experiences a feeling of discomfort (burning, itching, etc.). Therefore, to maintain the pH of the dosage form within 6-8, various buffer systems are used. For this purpose, the following substances are used: boric acid, borate, tetraborate, citrate, carbonate.
The ocular kinetics of drugs is influenced by tonicity of the administered drop of solution in relation to the tear. Hypotonic or isotonic drugs have better absorption. Like acidity, the tonicity of the solution affects the tolerability of the drug. A significant deviation of the osmotic pressure in the calla solution from its level in the tear will cause a feeling of discomfort (dryness or, conversely, lacrimation, etc.). To ensure that the drug is isotonic with the tear film and maintain osmotic pressure within 305 mOsm/l, various osmotic agents are used: dextran 40 and 70, dextrose, glycerin, propylene glycol.
Thus, the effectiveness of treatment depends not only on the active substance, but also on other ingredients included in the drug and determining its individual tolerance. Each company has its own drug formula. If a pronounced burning sensation occurs when the drug is instilled, it is accompanied by lacrimation and an increase in the frequency of blinking, which will lead to accelerated leaching of the drug from the tear and a decrease in its effectiveness.
The effectiveness of therapy depends on volume of the instilled drop of the drug. Studies conducted by various authors (Patton, 1977, Sugaya and Nagataki, 1978) have shown that the therapeutic effect of a 5 μl drop corresponds to 1/2 of the maximum effectiveness. The full therapeutic effect develops when using a drop whose volume ranges from 10 to 20 µl. However, increasing the drop volume to more than 20 µl does not lead to increased efficiency. Thus, the most justified drop volume is within 20 µl. Therefore, it is rational to use special dropper bottles that accurately dose the volume of the administered drop of the drug (for example, Pharmacia, Sweden, produces the drug “Xalatan” in such bottles),
When using ophthalmic dosage forms, it is possible to develop general side effects, which are associated with the reabsorption of the active substance into the systemic bloodstream through the conjunctival vessels, vessels of the iris, and nasal mucosa. The severity of systemic side effects can vary significantly depending on the individual sensitivity of the patient and his age.
For example, instillation of 1 drop of a 1% solution of atropine sulfate [INN] in children will cause not only mydriasis and cycloplegia, but can also lead to hyperthermia, tachycardia, and dry mouth.
Most eye drops and ointments are contraindicated for use while wearing soft contact lenses (SCLs) due to the risk of accumulation of both the active component and the preservatives included in the drug.
If the patient continues to use SCL, he should be warned that he must remove the contact lens before instillation of the drug and can put them on again no earlier than after 20-30 minutes. In this case, eye ointments should be used only at night during the night break from wearing contact lenses.
When prescribing two or more different types of drops, you should remember that when instilling the second drug 30 seconds after the first, its therapeutic effect is reduced by 45%. Therefore, to prevent dilution and washout of pre-administered drops, the interval between instillations should be at least 10-15 minutes. The optimal break between instillations is 30 minutes.
The doctor is obliged not only to prescribe the drug, but also to teach the patient how to use eye drops and ointments correctly, and to monitor the implementation of prescriptions.
In recent years, both in domestic and foreign literature, terms such as compliance(complace) and non-compliance(non complace) of the patient. Compliance is the patient’s compliance with all doctor’s recommendations regarding the regimen of medications, rules for their use and restrictions (nutritional and physical) associated with the disease. With some diseases, at first the person does not experience any discomfort associated with the disease. He is not bothered by pain or blurred vision. At the same time, the prescribed treatment and the need to regularly visit a doctor changes his usual routine of life. In order to increase patient compliance, the doctor needs to explain the seriousness of the disease, as well as teach the patient how to properly instill eye drops and put eye ointments behind the lower eyelid.
Rules for instilling eye drops
Rules for applying eye ointments
Rules for laying eye medicinal films
The frequency of use of eye medications varies. In case of acute infectious diseases of the eye (bacterial conjunctivitis), the frequency of instillation can reach up to 8-12 times a day; in case of chronic processes (glaucoma), the maximum regimen should not exceed 2-3 instillations per day.
Eye ointments are usually applied 1-2 times a day. It is not recommended to use eye ointment in the early postoperative period during intracavitary interventions and for penetrating wounds of the eyeball.
The general shelf life requirements for factory-made drops are 2-3 years if stored at room temperature out of direct sunlight. After opening the bottle for the first time, the period of use of the drug should not exceed 1 month.
Eye ointments have a shelf life of about 3 years on average under the same storage conditions.
In order to increase the amount of drug entering the eye, use forced instillation technique. To do this, eye drops are instilled six times with an interval of 10 minutes for an hour. The effectiveness of forced instillations corresponds to subconjunctival injection.
You can increase the penetration of the drug into the eye by placing a cotton wool soaked in the drug or a soft contact lens saturated with the drug in the conjunctival sac.
Rules for placing cotton wool with a medicinal product
Studies conducted by E. G. Rybakova (1999) revealed that the rate of sorption of drugs from solution into the SCL substance and its desorption from the CL depends on its molecular weight. Low molecular weight compounds accumulate well in both highly hydrophilic and low hydrophilic lenses. Substances with high molecular weight do not accumulate well in low-hydrophilic lenses. The rate of desorption of substances is directly dependent on the hydrophilicity of SCL. The higher it is, the faster substances are removed from the SCL. High-molecular substances are characterized by faster elimination, which is associated with the surface saturation of SCL with these drugs. E. G. Rybakova believes that the most rational is to use SCL with a moisture content of 38% and a thickness of 0.7 mm to prolong the action of low-molecular medicinal substances. The pharmacokinetic parameters of the adsorption of high molecular weight substances differ slightly from drip administration.
An example of changes in pharmacokinetic and pharmacodynamic parameters is the study of Podos S. (1972). When determining the concentration of pilocarpine in the moisture of the anterior chamber after instillation of a 1% solution and the use of SCL soaked in this solution, it was revealed that pilocarpine accumulates in the moisture of the anterior chamber in a larger volume and remains in it longer in concentrations sufficient to maintain the therapeutic effect (diagram. 1).
Diagram 1. Change in the concentration of pilocarpine in the moisture of the anterior chamber after instillation of a 1% solution and the use of SCL saturated with a 1% solution of pilocarpine (submitted by Podos S., 1972).
A study of the relationship between the hypotensive effect and the method of administration of pilocarpine showed that the maximum reduction in IOP was noted in the group of patients who used SCLs saturated with a 0.5% solution of pilocarpine (diagram 2).
Diagram 2. Dependence of the degree of IOP reduction on the method of application of a 0.5% pilocarpine solution (submitted by Podos S., 1972).
In group I, patients used a 0.5% solution of pilocarpine 3 times a day; in group II, patients used SCLs and instilled a 0.5% solution of pilocarpine (without preservative) while wearing the lenses; in group III, patients used SCLs pre-impregnated with 0. 5% pilocarpine solution for 30 minutes.
An additional route of administration is the use of periocular injections. There are subconjunctival, parabulbar and retrobulbar injections.
Rules for subconjunctival injection
Rules for parabulbar injection (1st method)
Rules for parabulbar injection (2nd method)
The rules for retrobulbar injection are the same as for parabulbar injection, however, the needle is inserted to a depth of 3-3.5 cm and is first oriented parallel to the orbital wall, and then obliquely upward behind the eyeball (Fig. 8).
Rice. 8. The position of the needle during retrobulbar injection (1 - at the beginning of the injection, 2 - final position of the needle).
Before administering the drug, pull the syringe plunger towards you to make sure that the needle is not in the vessel. If resistance to the needle moves, it is immediately pulled back. Before injection, the tip of the needle should be slightly blunted.
In special cases, medications are administered directly into the eye cavity(into the anterior chamber or into the vitreous body). The administration is carried out in an operating room during abdominal surgery or as an independent intervention. As a rule, the volume of the administered drug does not exceed 0.2-0.3 ml. The drug solution is injected into the anterior chamber through paracentesis.
Rules for intravitreal injection
When using the injection method of administering the drug, its therapeutic concentration in the eye cavity increases sharply compared to the installation route.
For the treatment of retinal and optic nerve diseases implantation of an infusion system into the sub-Tenon's space is used. This technique was developed by Nesterov A.P. and Basinsky S.N. The infusion system consists of a folded strip of collagen sponge (30x6 mm) and a silicone tube (Fig. 10, a).
Rice. 10. Method of implantation of an infusion system and sub-Tenon's space (according to Nesterov A.P., 1995).
After an incision is made in the conjunctiva and Tenon's membrane in the superior temporal segment of the eye, the collagen sponge is passed into Tenon's fissure to the posterior pole of the eyeball. The conjunctival incision is sutured with a continuous suture. The free end of the silicone tube is brought out onto the forehead and fixed with an adhesive tape (Fig. 10, b). In the postoperative period, a drug is administered through a tube. The course of treatment lasts 7-10 days, after which the tube is removed. In some cases, a silicone sponge is introduced according to the method described above, having previously soaked it with a drug. The introduction of an infusion system can be combined with direct electrical stimulation of the optic nerve. For this purpose, during the introduction of the infusion system, an electrode is inserted into this area through a special conductor, with the help of which electrical stimulation of the optic nerve is carried out. As a result of exposure to electric current, the direction of ion flow changes, which can significantly increase the penetration of drugs into the eye tissue.
For the treatment of diseases of the retina, optic nerve and orbit, long-term intracarotid administration of drugs through a catheter, introduced into the superficial temporal artery before the bifurcation of the common carotid artery. The infusion is carried out around the clock at a rate of 10-16 drops per minute for 5-7 days. This method of administration is based on the research of M. M. Krasnov, who showed that the concentration of the drug in the tissues of the eye after intravenous injection and administration into a. carotis and a. supraorbitalis increases with intra-arterial administration and is in the following proportion: 1:5:17.
Drugs can also be administered using phono- or electrophoresis.
With electrophoresis medicinal substances are introduced into the body through the intact surface of the skin or mucous membrane using direct current. The amount of injected substance is dosed by changing the size of the electrodes, the concentration of the solution, the current strength and the duration of the procedure. Substances are administered from the positive or negative electrodes (sometimes from both electrodes) depending on the charge of the drug molecule.
Electrophoresis is carried out daily; if necessary, several procedures can be performed during the day with an interval of 2-3 hours. The course of treatment includes 10-25 procedures. A second course of treatment should be carried out after 2-3 months, for children - after 1.5-2 months. Electrophoresis can be combined with phonophoresis, UHF therapy and diadynamic therapy.
Electrophoresis used for treatment inflammatory, ischemic and dystrophic processes in the tissues of the eye, hemorrhages and injuries to the organ of vision.
Electrophoresis should not be carried out in patients with neoplasms, regardless of their location, high blood pressure and a history of hypertensive crises, a tendency to thrombus formation, atherosclerosis, with severe eye hypotension or a significant increase in 13GD, intraocular foreign body, extensive ulcerative process, severe purulent discharge, increased sensitivity to direct current .
Several methods are used to administer drugs continuously.
Electrophoresis through an eye bath
Methodology: 5 ml eye bath. Through the bottom or side wall of which a carbon or platinum rod with terminals is passed, it is filled with a solution of a medicinal product heated to 28-30 ° C (antibiotic solutions are not heated). The edges of the bath are lubricated with thick Vaseline. The patient's position is sitting, head tilted back on the chair. The patient presses the tray to the edge of the eye socket, keeping the eye open. The bath is fixed with a rubber bandage. An indifferent electrode with a wet pad measuring 8x12 cm is placed on the back of the neck: the anode in the area of the upper cervical vertebrae, the cathode in the lower cervical vertebrae. The current strength is gradually increased from 0.3 mA to 0.5 (0.8) - 1.5 mA, the duration of the procedure is 3-15 minutes. During the procedure, the patient should feel a slight, uniform tingling in the area of the eyelids and eyes.
The concentrations of drugs administered using electrophoresis through a bath are indicated in Table. 1.
Table 1. Medicines used for electrophoresis through an eye bath (according to I. N. Sosin, A. G. Buyavikh, 1998)
You can administer not only simple solutions, but also mixtures of medications. When preparing a mixture, it is necessary to take into account the possibility of drug interactions and their polarity. The most commonly used mixtures are:
- a mixture of streptomycin and calcium chloride - 2.5 ml of a 2% calcium chloride solution is poured into the bath, then 0.5 ml of streptomycin is added (at the rate of 50,000 units/0.5 ml) and another 2.0 ml of calcium chloride solution is added.
- a mixture of streptomycin, calcium chloride, atropine and adrenaline: 0.5 ml of streptomycin (at the rate of 50,000 units/0.5 ml), 1.5-2.0 ml of a 0.1% atropine solution and the same amount of 2 % calcium chloride solution, last add 0.3-1.0 ml of 0.1% atropine solution.
- a mixture of atropine, adrenaline, novocaine - 2.0-2.2 ml of a 0.1% atropine solution and the same amount of a 2% novocaine solution are poured into the bath, 0.3-1.0 ml of a 0.1% atropine solution is added last.
Electrophoresis through the eyelids
Methodology: position of the patient lying on his back. Before the procedure, to enhance the effect of treatment, you can drop 1 drop of the drug into the conjunctival sac. Place 2 layers of filter paper moistened with a solution of the drug on the eyelids. A wet gauze pad (10-12 layers) of an oval shape measuring 4-5 cm is placed on top of the layer of paper. An electrode measuring 2-3 cm is inserted into the pocket of the gauze pad. The indifferent electrode is positioned in the same way as when using an eye bath. The current strength is increased from 0.5 mA to 1.5-2.0 mA - when treating one eye and to 2-4 mA - when treating both eyes at once. The duration of the procedure is from 3 to 10-15-20 minutes. The first 6-10 procedures are carried out daily, the remaining ones every other day. The course of treatment is 10-25 procedures. A repeat course can be carried out after 1-2 months.
Endonasal electrophoresis
Methodology: after rinsing the nasal cavity with water, a cotton swab 10-15 cm long, moistened with a medicinal substance, is inserted into the lower nasal passage. The ends of the turunda are placed on an oilcloth located on the upper lip and covered with a damp gauze pad measuring 1x3 cm with an electrode. The second electrode with an 8x12 cm spacer is located in the back of the head. The current strength is gradually increased from 0.3 mA to 1 mA, duration 8-15 minutes.
Endonasal electrophoresis contraindicated for rhinitis, adenoids, tendency to nosebleeds, children in puberty.
In addition to the methods described above, ophthalmology uses electrophoresis from reflex segmental zones - the collar zone and cervical sympathetic nodes.
The rate of penetration of medicinal substances into various tissues of the eye can be increased with the help of ultrasound, since under the influence of ultrasound the permeability of cell membranes and the blood-ophthalmic barrier increases, and the diffusion rate increases. For phonophoresis, drugs are used in the same concentrations as for electrophoresis through an eye bath (see Table 1).
Phonophoresis is carried out for the same eye diseases as electrophoresis.
Contraindications: hypotony of the eye, PCRD with a high risk of developing retinal detachment, history of retinal detachment, gross changes in the vitreous, recurrent intraocular hemorrhages, neoplasms of the organ of vision. Phonophoresis should not be performed in patients with severe cardiovascular, endocrine, mental and neurological diseases, with neoplasms of any location, acute infectious diseases and active tuberculosis, in the third trimester of pregnancy.
Phonophoresis technique: to carry out phonophoresis, use an eye tray-dilator. The patient's position is lying on his back. 1 drop of anesthetic is instilled into the conjunctival sac twice with an interval of 5-10 minutes. 1-3 minutes after repeated instillation, a dilator tray is inserted under the eyelids and, using a pipette with a bulb, it is filled with a warm solution of the drug in a volume of 5 ml. A tripod with an attachment is installed at a distance of 2-3 cm from the crown of the patient. The water nozzle with the vibrator is lowered into the bath, not reaching the cornea by 1 - 2 mm. Generation mode is continuous or pulsed, dose 0.2-0.4 W/cm2, procedure duration 5-7 minutes. During the procedure, the patient may feel a slight tingling and warmth. After the procedure, a 10-20% sodium sulfacyl solution is instilled. Before the procedure, the bath is treated with a 1% solution of chloramine and a 70% solution of ethyl alcohol, then washed with saline. Procedures are carried out daily or every other day. The course of treatment is 8-20 procedures. A repeat course can be carried out after 1.5-2 months.
To treat eye diseases, intramuscular and intravenous injections and infusions are used, as well as oral administration of drugs (thus, antibiotics, corticosteroids, plasma replacement solutions, vasoactive drugs, etc. are administered).
Article from the book:
Many ophthalmologists agree that one of the most effective procedures for treating eye diseases is an injection into the eye. This procedure allows the medicine to directly enter the affected area and act in a targeted manner. There are several types of eye injections. The choice of one method or another is determined by the attending physician depending on the disease, the area of the lesion and the individual characteristics of the patient.
Injections into the eyeball differ in the method of administration:
Injections of drugs into the eyeball can only be performed by an experienced ophthalmologist under sterile conditions using disposable instruments. Before making an injection into the eye, a pain relief procedure is performed with Dicaine or Novocaine in the form of eye drops. After 5 minutes you can begin the procedure. If the procedure is performed using a subconjunctival, retrobulbar or parabulbar method, it is necessary to treat the needle insertion area with 70% ethyl alcohol. After the procedure, press a cotton swab with an antibacterial solution for several minutes.
Preparations for injections into the eyes
For some diseases, the only treatment is injections into the eyes. The drugs used for this procedure are varied: hormonal, enzymatic, vitamin, antibiotics, etc.
Antiangiogenic therapy using Avastin and Lucentis
Avastin is an antitumor drug used in a complex of antiangiogenic therapy aimed at suppressing the growth of new blood vessels. Diseases that can provoke this phenomenon: wet form of macular degeneration in older patients, diabetic retinopathy and others.
The main active ingredient is bevacizumab. By penetrating the protein, it blocks the appearance of new blood vessels and also suppresses tumor growth. The drug is injected into, while the needle is directed towards the central sections. Avastin can only be administered to one eye at a time. During the next procedure, which is carried out a month later, the drug is injected into the other eye. As a rule, treatment lasts 3 months and is resumed in case of loss of visual acuity. During treatment, you should refrain from driving and work that requires quick reactions.
Avastin has a number of contraindications:
- individual intolerance;
- pregnancy and breastfeeding;
- not recommended for persons under 18 years of age;
- with special caution in case of existing liver and kidney diseases.
An analogue of the drug "Avastina" is called "Lucentis". They differ in the active substance: in Avastin - bevacizumab, in Lucentis - ranibizumab. The pharmacological action of the drugs is the same: suppression of the growth of new blood vessels. The indications and contraindications for the drugs are identical.
Treatment with Avastin and Lucentis shows very positive dynamics: in 90% of patients who used these drugs, their vision was preserved, and in 70% it became sharper. A study of the effectiveness of these drugs showed that bevacizumab was more effective - vision improvement was +1.89 letters.
"Pheebs"
The drug belongs to the class of biogenic stimulants that have a beneficial effect on the rate of regeneration and metabolic processes. It is used in the treatment of various types of conjunctivitis, inflammation of the cornea and eyelid margins, vitreous opacities, trachoma, eye diseases associated with loss of vision, etc. Main active ingredients: distillation of estuary mud, cinnamic acid and coumarin.
The drug is administered once a day, treatment continues for 30−40 days. A repeat course is prescribed no earlier than two months later. Contraindications for eye injections with the drug "Phibs" are the following: individual intolerance, acute diseases associated with the cardiovascular system and gastrointestinal tract, late pregnancy, should be used with caution in the presence of kidney disease.
"Ozurdex"
It is produced in the form of an implant and contains the hormone dexamethasone (0.7 mg), as well as excipients: a copolymer of lactic and glycolic acid. Dexamethasone belongs to the group of potent corticosteroids and has a pronounced anti-inflammatory and anti-edematous effect, inhibits the growth of new blood vessels, reduces capillary permeability and fibroblast activity, actively fights retinal vein occlusion, and restores blood flow through the capillaries.
The Ozurdex implant is effective in the treatment of macular edema (swelling of the central zone of the retina) due to occlusion of the central retinal vein. The implant is used once in the affected eye. If necessary, a repeat procedure may be performed. If there is no positive response or vision preservation is achieved, re-administration of the drug is not required.
Introduction of the Ozurdex implant shows positive dynamics: in a significant number of patients, the thickness of the retina has decreased by more than half (the indicators have become close to normal) and visual acuity has increased from 5% to 65%. This drug has a number of contraindications, including individual intolerance, glaucoma, purulent, viral and bacterial infections, trachoma.
"Reaferon EU"
The drug has a pronounced immunomodulatory and antitumor effect, fights viruses, suppressing the division of viruses in infected cells. In ophthalmology it is used to treat viral conjunctivitis, uevitis, as well as inflammation of the outer membrane and cornea of the eye.
The main active ingredient of the drug is interferon alpha 2a, containing 165 amino acids. "Reaferon EC" is injected under the conjunctiva daily, the duration of the course is prescribed by the doctor, but on average 15-25 injections under the eyes are sufficient. The drug can also be used as drops. "Reaferon EC" after administration by the subconjunctival route reaches its maximum concentration after 7.5 hours and is excreted by the kidneys.
The drug is contraindicated in persons with severe dysfunction of the liver, kidneys, central nervous system, cardiovascular system, intolerance to interferons, and epilepsy. It is strictly forbidden to use during pregnancy and breastfeeding. Interferons are not prescribed with drugs aimed at suppressing the immune system and central nervous system, as well as for persons with mental illness and suicidal tendencies. Side effects include local reactions to injection under the conjunctiva: headaches, nausea, sleep disturbances, allergies. Interferons can negatively affect reaction speed, so during treatment it is necessary to limit driving.
There are others. But it is with the drug “Reaferon EU” that injections are made into the eyes. The drugs, their names “Reaferon Lipint” and “Reaferon E.S. Lipint”, are used orally and serve for the treatment and prevention of influenza and ARVI, as well as other diseases.
"Emoxipin"
It is used for many diseases and has the following properties:
The active ingredient is methylethylpyridinol hydrochloride. In ophthalmology it is used to treat damage to the blood vessels of the eyes, eye thrombosis, glaucoma, cataracts, keratitis, complications of myopia, corneal burns. Side effects include local reactions in the form of itching, conjunctival hyperemia, and burning.
The drug is administered subconjunctivally (under the conjunctiva), retrobulbar (into the edge of the orbit through the lower eyelid), parabulbar (injections are made under the eyes through the skin of the lower eyelid). Some ophthalmologists prescribe, saying that this type of procedure is more effective for the eyes. There is no scientifically confirmed evidence for this statement, so this method is used extremely rarely. The method of administration of the drug, dosage and timing of treatment are determined by a specialist.
Contraindications: individual intolerance, allergies, hypersensitivity. Should be used with caution during pregnancy and breastfeeding. "Emoxipin" does not mix with other medications. If there is a combination treatment using additional drops, then “Emoxipin” is used last, 20 minutes after the previous drug.
Eye injections can only be prescribed by the attending physician and carried out by an experienced specialist. Eye injections in ophthalmology have proven to be an effective treatment for eye diseases with a long-lasting effect and a high cure rate.
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The concentration of drugs in the tissues and media of the eye largely depends on the methods of their administration. A significant obstacle to penetration into the inner membranes of the eye is the so-called blood-ophthalmic barrier. In ophthalmology, gentamicin sulfate (garamycin) is an antibiotic of the aminoglycoside group that penetrates the blood-ophthalmic barrier well.
In recent years, new antibiotics have appeared that have a stronger bactericidal and bacteriostatic effect and at the same time have fewer side effects (less toxic) - glucopeptides, streptogramins and drugs of other groups.
Medicines administered topically have unequal penetration into the eye tissue: water-soluble medicines have more penetration than fat-soluble ones. A higher effect is observed when medicinal substances are administered using iontophoresis and phonophoresis. Drugs administered parenterally cross the blood-ophthalmic barrier on their way. When administered locally, drugs, absorbed through the conjunctiva and cornea, quickly penetrate into the vascular bed and thus have an effect on the entire body.
For diseases of the choroid, retina and optic nerve, local use of drugs (instillation, retrobulbar administration) is often combined with their general (systemic) use.
With a combined treatment method, optimal conditions are achieved to create a sufficient concentration of the drug in the eye lesion.
As autoradiographic studies of subcutaneous, intramuscular, intravenous and parabulbar methods of administration of steroids and antibiotics have shown, parabulbar administration leads to the highest content of the drug in the vitreous body.
The retrobulbar method of administering drugs is close to the parabulbar method in terms of therapeutic effectiveness.
The orbital tissue is very loose and delicate, so the injected medicine spreads quite quickly in it. Recently, ophthalmologists have begun to use retrobulbar injections less frequently due to the possibility of various complications (hemorrhages in the orbit, needle injury to the sclera and optic nerve, penetration of the tip of the needle into the inferior orbital fissure).
Intravenous administration of antibiotics in ophthalmology is rarely practiced; they are prescribed according to strict indications and with great caution (small test dose followed by a transition to a therapeutic dose, slow administration into a vein). Treatment of purulent diseases of the auxiliary apparatus of the eye and orbit should be carried out according to the general principles of treatment of purulent-septic diseases of the body.
Of great importance in ophthalmological practice is the local use of antibiotics in the form of solutions of eye drops, eye ointments, and ophthalmic medicinal films. Antibiotic solutions are also administered under the conjunctiva, retrobulbar, into the anterior chamber and vitreous body. Antibiotics have a therapeutic effect when administered locally using electrophoresis and phonophoresis.
The peculiarities of the anatomical structure of the eye provide great opportunities for the local use of medicinal substances. This applies to the treatment of diseases of the auxiliary organs of the eye and its anterior section.
In this case, conditions are created for the direct effect of medicinal substances on the pathological focus.
Various concentrations of drugs are used, as well as different ways of using them:
a) instillation of solutions of eye drops;
b) administration of ointments;
c) introduction of ophthalmic medicinal films into the conjunctival sac;
d) injections under the conjunctiva;
e) administration of drugs into Tenon’s (episcleral) space;
f) retrobulbar administration;
g) introduction into the anterior chamber of the eye;
h) introduction into the vitreous body.
When administered locally, drugs, absorbed through the conjunctiva and cornea, quickly penetrate into the vascular bed and, thus, have an effect on the entire body. Often, for eye diseases, local therapy is the only treatment method. General treatment is added according to indications (diseases of the choroid, retina and optic nerve).
Drugs administered topically penetrate the eye tissue differently: water-soluble drugs have greater penetrating ability than lipid-soluble drugs. A higher effect is observed when medicinal substances are administered by iontophoresis and phonophoresis.
Incillations of eye drops
Medicinal solutions are able to have an effect within 30-40 seconds, penetrating through the cornea and ending up in the anterior chamber of the eyeball.
Instill 1-2 drops of the medicine onto the conjunctiva of the retracted eyelid.
When prescribing two or more different types of drugs to prevent dilution and washout of previously administered drops, the interval between installations should be at least 10-15 minutes. The optimal break between instillations is 30 minutes.
Eye ointment can be applied only after instillation of drops. Otherwise, the ointment will prevent the penetration of drugs into the eye.
In acute infectious diseases of the eye (bacterial conjunctivitis), the frequency of instillations can be up to 8-12 times a day; in chronic processes (glaucoma), the maximum regimen should not exceed 2-3 instillations per day.
In order to increase the amount of drug entering the eye, the technique of forced instillation is used. To do this, eye drops are instilled six times at 10-minute intervals for an hour. The effectiveness of forced instillation corresponds to subconjunctival injection.
You can increase the penetration of the drug into the eye by placing a cotton wool soaked in the drug or a soft contact lens saturated with the drug in the conjunctival sac.
Immediately after instillation, press the inner edge of the lower eyelid near the nose with your finger (here
Electrotherapy with an electric field with a frequency of 30 to 300 MHz is called UHF therapy.
The use of ultra-high frequency electromagnetic field energy (from 300 to 300,000 MHz) is called microwave therapy, which is used for herpetic keratitis, retinal vein thrombosis, and sclerotic retinal degeneration.
Direct electric current is used to introduce medicinal substances into the body using the method of electrophoresis. In this case, there is a combined effect on the body of an electric current and a medicinal substance administered through it. The cornea is an ideal semi-permeable membrane through which ions penetrate into the eye. Under the influence of current, the permeability of the blood-ophthalmic barrier increases, which leads to the penetration of more drugs into the eye tissue. This is also facilitated by direct contact of the drug with the pathologically altered organ.
Methods of medicinal electrophoresis:
On closed eyelids (orbito-occipital technique according to Bourguignon). A cotton swab moistened with a medicinal substance is placed behind the lower eyelid or between the edges of the eyelids. A hydrophilic pad moistened with the same preparation is applied to closed eyelids. Instead of a tampon, you can instill the drug into the conjunctival sac before the procedure. The patient is sitting.
Through the electrode - a bath on the open eye. The electrode (bath with a capacity of 3-5 ml) is applied to the skin of the eyelids with the palpebral fissure open and fixed with an elastic bandage or held by hand. In this case, the edges of the bath are tightly adjacent to the skin, corresponding to the orbital edges, without exerting pressure on the eyeball. The tray is filled with a medicinal substance at room temperature through a special hole in it, the main drugs are layered on the minor ones. During the procedure, the eye is in direct contact with the medicinal solution contained in the bath, which, after turning on the device, penetrates through the cornea into the eye. The patient is sitting. Endonasally - cotton wool is wound around the ends of the bifurcated electrode, moistened with the desired medicinal solution and inserted into the middle nasal passages (after first rinsing the nose with water); The procedure is carried out with the patient lying on his back.
For all the described methods, an indifferent electrode is placed on the skin of the back of the neck and secured with an elastic bandage.
The duration of the procedure is 10-20 minutes. Sessions are carried out daily or every other day. The course of treatment usually consists of 15-20 procedures (up to 40 procedures). You can repeat the course of treatment after 1-2 months.
Indications: inflammatory, degenerative-dystrophic processes, hemorrhages into the media of the eyeball.
The bath electrophoresis technique, as a more gentle method, is prescribed in the early stages after injury or surgery (especially with severe swelling of the wound edges and poor adaptation) and with pronounced changes in the epithelium of the cornea (epithelial forms of herpetic keratitis, early periods after burns and etc.).
The endonasal technique is used for pathological processes localized in the fundus and in the posterior layers of the vitreous body, especially in cases where the latter begins to show a tendency to formation. Endonasal electrophoresis makes it possible to bring medicinal substances to the posterior pole of the eye in the shortest possible way.
Local contraindications: maceration of the skin of the eyelids and its damage in the area where electrodes are applied, dermatitis, copious mucopurulent discharge, corneal erosion, severe phenomena of eye irritation, increased intraocular pressure, gross sclerotic changes in blood vessels, malignant neoplasms and individual intolerance .
General contraindications: coronary heart disease in the acute stage, the first 2-3 weeks after a cerebrovascular accident, bleeding or a tendency to it.
Drugs. Antibiotics: penicillin, biomycin, oxytetracycline and monomycin, gentamicin, chloramphenicol solution, etc.
Anti-tuberculosis drugs: saluzide solution, PAS solution, tubazide solution.
Since inflammation is usually accompanied by constriction of the pupil and the formation of adhesions between the iris and the lens, in order to prevent this complication, along with antibiotics in one bath, mydriatic (pupil dilator) agents are administered - an atropine solution and an adrenaline solution.
To enhance the anti-inflammatory and desensitizing effect, you can add a calcium chloride solution or a diphenhydramine solution to the antibiotics.
Absorbable drugs: proteolytic enzymes (chymotrypsin, fibrinolysin, streptodecase, lidase). By removing necrotic tissue and pus, they have a pronounced anti-edematous and anti-inflammatory effect, dissolving fibrin and diluting blood clots, accelerating the resorption of hemorrhages, and promoting more gentle scarring.
Corticosteroids help inhibit the development of inflammatory phenomena and have a pronounced antiproliferative effect, stopping the proliferation of connective tissue, which contributes to less severe scarring; have a noticeable desensitizing effect. A hydrocortisone solution and a prednisolone solution are used.
Vasodilators: no-spa, papaverine solution, aminophylline solution and nicotinic acid solution.
To stimulate metabolic processes and improve trophism, biogenic stimulants are used: aloe, vitreous, vitamin BP, ascorbic acid solution and taufon solution.