JP2012236077A - Use of trypan blue for visualizing anterior lens capsule of human eyeball - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method, a composition, and use for visualizing an anterior lens capsule during the removal of a cataract and replacement with a lens within the eye.SOLUTION: The use of trypan blue in producing a composition for visualizing an anterior lens capsule of the eye during the procedure of the removal of a cataract and replacement with a lens within the eye is provided. Also, a method for the visualization of the anterior lens capsule and a method for cataract treatment are provided.

Description

  The present invention relates to therapeutic methods, compositions and uses, and in particular to eye-related therapeutic methods, compositions and uses, such as cataract treatment.

  Cataract is an exceptionally universal condition that affects people of all racial groups. Cataracts cause vision loss. In essence, cataract is the opacity of the lens, which is the most important component in the focus system of the eye. The degree of opacity of the lens varies from those that affect the entire lens to those that affect only a portion. The cloudy area blocks or delays the passage of light to the retina. Apart from affecting the ability to visualize objects, cataracts scatter light and thus cause discomfort from sunlight and bright light, ie glare. Cataracts also affect animals such as dogs and cats.

  Cataracts are most commonly associated with aging, but may be associated with congenital or genetic malformations, or with various diseases or certain drugs. Cataract is the most common cause of vision loss (cannot be corrected with glasses), but it is also the disease most successfully treated by surgery.

  The standard treatment for cataracts is the removal of the lens parenchyma and the replacement of the cataract human lens with an intraocular lens. Intraocular lenses are inserted into the eye instead of the removed cataractous lens to maintain vision or often maintain vision at normal levels.

  The technique of cataract treatment has advanced by phacoemulsification surgery. This involves a very small corneo-limbal incision to access the lens capsule, making an incision in the lens capsule to approach the lens parenchyma (cortex and nucleus), and ultrasound and aspiration along with irrigation Remove. The capsule (the base membrane surrounding the lens) and its appendages, and the tubules that suspend the lens from the ciliary body, remain largely intact except for the anterior capsulotomy. An anterior capsulotomy is an incision in which the lens is removed and an alternative is inserted. This preservation of the internal ocular structure (ie capsules and tubules) is a mechanism for implanting an intraocular lens (such as occurs with an intraocular lens that is supported by an angle or an iris) so that the intraocular lens does not hit an essential structure. Thereby avoiding chronic complications such as uveitis, glaucoma and corneal dysfunction.

  During phacoemulsification surgery, the anterior capsular bag is ruptured to form a round opening that allows the lens parenchyma to be removed (continuous curvilinear capsulorhexis). This creates a sturdy sac edge that resists rupture even when stretched-generally increasing safety during surgery. In extracapsular surgery, so-called canned sac incisions are performed, but the irregular ends of the sac are prone to radial rupture rupture, which can cause loss of the glass body or loss of the lens to the glass body. These undesirable events often cause suboptimal results and complications. In addition, capsular fibrosis after insertion of the intraocular lens may cause dispersion of the intraocular lens (resulting in astigmatism and glare caused by the lens edge). However, this does not occur so often after capsulorhexis because the forces generated within the sac are more symmetric. Therefore, capsulotomy is an important step in producing good surgical results.

  Visualization of the sac, especially the anterior lens capsule, is critical in the capsulotomy procedure. A capsulotomy is generally performed in the presence of a red reflex. The light is then reflected by the retina and highlights the anterior capsule against a red background. In patients with extreme cataracts (adults usually white or very extreme), capsulotomy is difficult because the red reflex is difficult to see or not at all. In these cases, electroextracapsular surgery is usually performed with inherent deficiencies and difficulties. A capsulotomy is also difficult if there is opacity of the vitreous, such as corneal opacity (such as a wound) or vitreous hemorrhage (such as is sometimes seen in diabetic patients).

Various approaches have been taken to improve the success rate of capsulotomy in patients with severe cataracts or anterior capsular capsules that cannot be visualized for any reason. These include the following:
1. Use high magnification, dimming the operating room illumination, and use side illumination with a fiber optic light source so that the sac looks good. These procedures are tedious, expensive and not particularly effective.
2. A dye, in particular fluorescein, is used to stain the sac so that it is highlighted against the underlying opaque lens fibers that are not stained. Such dyes are difficult to use in the eye, because the dye diffuses rapidly into the lens and cornea and must be fitted with a suitable filter on the surgical microscope in order to optimize visualization . The problem of potential toxicity of the dye also arises.
3. The sac is colored with the patient's own blood.
4). Development of professional cutting technology such as high frequency cutting equipment. This requires expensive additional instruments and has been found to produce a round hole in the anterior lens capsule that is less intense than a standard capsulotomy. None of these technologies have been widely used.

  There remains a clear means of method, composition and use that allows for immediate visualization of the anterior lens capsule. That is, performing a capsulotomy so that the removal of the cataract and the replacement of the intraocular lens can be done safely, efficiently and economically.

  The present invention relates to methods, compositions and uses for visualizing the anterior lens capsule during cataract removal and intraocular lens replacement. The present invention is based on the surprising discovery that the dye trypan blue used in living biological tissue can be used immediately to stain the anterior lens capsule without the disadvantages associated with other dyes.

  According to a first aspect of the present invention, it is provided that trypan blue is used in the manufacture of a composition for visualizing the anterior lens capsule of the eye during a cataract removal and intraocular lens replacement procedure. Is done.

  In accordance with another aspect of the present invention, there is provided a method of visualizing a human anterior lens capsule comprising dropping a trypan blue solution dissolved in an eye-acceptable medium into an anterior chamber. .

  According to yet another aspect of the invention, introducing trypan blue into the anterior chamber followed by adding a viscoelastic substance to the anterior lens capsule to confine trypan blue in the anterior lens capsule. A method of visualizing an anterior capsular bag is provided.

  According to yet another aspect of the invention, filling the anterior lens capsule of the eye with viscoelastic materials of different viscosities, about 0.05% to under the viscoelastic material for a time sufficient to stain the anterior lens capsule. Introducing a trypan blue solution containing 3% w / w trypan blue, removing excess trypan blue solution and viscoelastic material from the anterior chamber, reintroducing the viscoelastic material into the anterior chamber and then A method is provided for visualizing the anterior lens capsule during a capsulorhexis procedure comprising performing capsulorhexis, lens removal and replacement with an intraocular lens.

  In yet another aspect, the present invention fills the anterior chamber with a viscoelastic material, about 0.05% to 3% w / w trypan blue under the viscoelastic material for a time sufficient to stain the anterior lens capsule. Introducing trypan blue solution containing, removing excess trypan blue solution and viscoelastic material from the anterior chamber, reintroducing viscoelastic material into the anterior chamber and then capsulotomy, lens removal and eyeball It relates to a method for the treatment of cataracts, comprising performing replacement with an inner lens.

  The present invention utilizes trypan blue in methods, compositions and uses, particularly in the replacement of lenses affected by cataracts. Surprisingly, trypan blue selectively stains the anterior lens capsule, which can be detected simply by using the standard illumination system of a surgical microscope used in cataract surgery. It has been found that specifically allows visualization of the sac. More specifically, as in the routine case, the easily visualized anterior capsule can be subjected to capsulorhexis and then proceed to lens extraction.

  According to a first aspect of the present invention, it is provided that trypan blue is used in the manufacture of a composition for visualizing the anterior lens capsule of the eye during a cataract removal and intraocular lens replacement procedure. Is done. The lens of the cataract may be a human lens or an animal lens such as a domestic animal. The composition is preferably provided as a 2 part composition. The first part contains trypan blue powder and the second part contains an eye acceptable solution. Trypan blue is then mixed with the solution to give a composition for dripping into the eye.

  Trypan blue is a widely available dye that has been used for many years in medical applications. The FDA is also approved for both in vivo and in vitro use. Trypan blue is preferably freshly prepared for use. This is separated by two barrier units containing dry trypan blue (in powder form) in one room and in the other room containing an eye-acceptable solution, eg barrier means that can be opened, such as a rubber stopper. This can be done conveniently by two room units that are mixed after opening the means to produce a composition acceptable to the eye. This composition is introduced into the anterior chamber to stain the anterior lens capsule and subsequently visualize it. As another option, trypan blue solution may be prepared. Generally, the trypan blue solution contains trypan blue in an amount of 0.05% to 3% w / w, preferably 0.1% to 1.5% w / w, more preferably 0.1% w / w.

  Trypan blue compositions in a carrier acceptable to the eye, such as containing 0.05% to 3% w / w of trypan blue, can be prepared by conventional methods. Such a solution can be stored, for example, according to established procedures for storing solutions for medical use. The composition is generally isotonic. For introduction into the eye, the solution must be sterile, buffered and free of particulate matter. A preferred solution is a w / w saline solution. Using the pharmacy at Prince of Whales Hospital, the inventor made a 0.1% trypan blue solution shortly before using it on patients. Under aseptic conditions, trypan blue was dissolved in Balanced Salt Solution and filtered through a 0.22 micron filter. By testing a number of different concentrations of dye in the pig eye, the inventors concluded that this 0.1% w / w solution is the preferred concentration in terms of cost and performance. Nevertheless, trypan blue solutions in amounts of about 0.05% to 3% w / w may also be used.

  The term “composition” is used herein in two ways. First, a two-part composition is described that contains trypan blue powder as the first part and a solution acceptable to the eye as the second part. Each part is separated by an open barrier means. In another sense, “composition” is used to describe a solution for instillation into the eye, obtained by mixing trypan blue powder with a solution acceptable to the eye.

  In accordance with another aspect of the present invention, there is provided a method of visualizing a human anterior lens capsule comprising dropping a trypan blue solution dissolved in an eye-acceptable medium into an anterior chamber. .

  Another aspect of the present invention is to provide a method for visualizing the anterior lens capsule comprising adding a viscoelastic material to the anterior chamber prior to introducing trypan blue into the anterior chamber. To use trypan blue to visualize the anterior capsular bag, trypan blue is introduced into the anterior capsule of the eye so that the corneal margin of the corneal vitiligo is incised through which the probe can be introduced. Trypan blue solutions usually consist of 0.05% w / w to 3% w / w trypan blue. After making an appropriate small incision in the corneal margin, a viscoelastic material is introduced into the anterior chamber using a probe to prevent the anterior chamber from collapsing during the procedure, making it easier to access the capsular bag. The trypan blue solution is introduced into the bottom of the viscoelastic layer using a probe, where the front lens capsule is dyed. Unbound trypan blue is removed, and then the viscoelastic material is removed. After reintroducing new viscoelastic material into the anterior chamber, the anterior sac is visualized and undergoes a capsulotomy, ie, the formation of a circular hole. Basic lens ultrasonic aspiration of the cataract lens is performed, and after removal by the lens ultrasonic aspiration, the intraocular lens is inserted into the lens capsule bag. Following this, the viscoelastic material is removed by suction and the probe used for this procedure is removed from the eye.

  Eye dissection is well established and comprehensively described. For example, Duke-Elder S and Wybar KC. Ophthalmology, Visual System Dissection, Volume II, Henry Kimpton, London. 1961, and Bron, AG, Tripathi R, Tripathi B. These include Wolff's eye and orbit anatomy, Lippincott-Raven, 1998. For this purpose, the eye includes a pupil edge limited by an iris that regulates its entry into the light lens. The dilation of the pupil caused by the contraction of the iris dilator muscle means the part of the pupil that is located above the pupil edge and lens.

  The nature of the viscoelastic material is not critical in the present invention. As a preferred technique, a more viscous viscoelastic agent (Healon GV, Pharmacia & Upjohn) is used at the pupil edge, and a less viscous viscoelastic agent (Healon) is used in the pupil. Leakage of trypan blue from the part lens capsule can be minimized (for example, a large amount of trypan blue dripping will stain the rear lens capsule and cloud the field of view for the remainder of the procedure). Such compositions are widely used in connection with other ophthalmic treatments and surgery, and are commercially available in many grades and purity for ophthalmic applications from a number of suppliers. There are numerous preparations of this type, including Duovisc Viscoelastic System (Alcon), AMO Vitrax (Allergan), and Ocucoat (Storz).

  According to another aspect of the present invention, filling the anterior lens capsule of the eye with a viscoelastic material, about 0.05% to 3% w / w under the viscoelastic material for a time sufficient to stain the anterior lens capsule. Introducing a trypan blue solution containing w trypan blue, removing excess trypan blue solution and viscoelastic material from the anterior chamber, reintroducing viscoelastic material into the anterior chamber and then removing capsulehexis, lens And a method of visualizing the anterior lens capsule during a capsulorhexis procedure comprising performing replacement with an intraocular lens.

  Certain techniques have been described in connection with performing a capsulorhexis process that includes filling the anterior chamber with air. Such techniques are problematic because air contact can cause damage to the corneal endothelial cells, resulting in keratoma.

  In general, the pupil is enlarged by known drugs for pupil enlargement prior to the process of the present invention. Local and periocular anesthesia is routinely used to anesthetize the eye. Two very small corneal-limbal incisions are made on one side of the eye and a probe is inserted to perform the process of the present invention. Through this very small incision, a fluid introduction aspiration probe is introduced to add the viscoelastic agent prior to trypan blue and to remove the solution added to the eye. Capsulorhexis needles and lens ultrasound aspiration probes can be easily inserted through other incisions. The intraocular lens can be easily inserted through the incision used for the phacoemulsification probe. The incision generally closes naturally and no suture is required or sometimes a single stitch.

  In yet another aspect, the present invention fills the anterior chamber with a viscoelastic material, about 0.05% to 3% w / w trypan blue under the viscoelastic material for a time sufficient to stain the anterior lens capsule. Introducing trypan blue solution containing, removing excess trypan blue solution and viscoelastic material from the anterior chamber, reintroducing viscoelastic material into the anterior chamber and then capsuleorhexis, lens removal and intraocular lens It relates to a method for the treatment of cataract, comprising making a replacement with.

The present invention can be applied in various aspects to human and cataractous lenses of animals such as dogs and cats.
EXAMPLES The present invention will be described below with reference to examples, but the present invention is not limited to the examples.

Patient A
The lady was presented as blind by law. Her cause of visual deficit was adult white cataract. Her capsulorhexis phase of surgery was expected to be difficult due to poor visualization of the capsular bag against white lens material. She underwent routine cataract surgery except that trypan blue was used to stain the anterior lens capsule in each prescription (performed several weeks apart). Healon GV was instilled into the anterior chamber at the pupil edge. Healon dripped into the center of the ring of Healon GV, so the less viscous Healon covered the anterior lens capsule. 0.1% trypan blue was injected under the Healon and maintained contact with the anterior capsule for about 30 seconds. Typically, up to 0.1 ml trypan blue solution was used. Capsulorhexis was performed routinely and the anterior lens capsule stained blue was in sharp contrast to the underlying cataract lens material. The result of the operation was excellent and visual acuity returned to normal levels. Following up to 11 months, no side effects from the prescription appeared.

Patient B
This patient had poor vision due to corneal injury. Her cataract seemed to contribute to vision deficiency, although eventually a corneal transplant would be necessary. The corneal transplant material has a long waiting time, it is safer to perform this prescription instead of performing the cataract surgery at the same time as the corneal transplant surgery, and the cataract surgery is supported by trypan blue Was done. Staining with trypan blue not only helps in the performance of capsulehexis, it can identify a flat anterior sac (the residual anterior sac retains blue color during treatment) through a relatively opaque cornea, thereby Since it was performed as a landmark, the remaining treatment was made easier. The patient had a marked improvement in vision after safe cataract extraction.

Patient C
This patient was legally blind due to the visual complications of diabetes. In addition to cataracts, he suffered from retinal disease and vitreous hemorrhage. In order to treat his retinal disease, it was first necessary to remove the cataract. We expected this to be difficult because vitreous hemorrhage obscures the light reflecting back from the retina (red reflex) during cataract surgery. Trypan blue also helped both perform a capsule incision (capsulorhexis) as well as provide landmarks for the remainder of the surgery. The prescription was performed safely and the patient underwent vitreo-retinal surgery.

  All capsulorhexis specimens were submitted for histopathology examination. Although trypan blue stains the anterior half of the capsule, it has been confirmed that it does not penetrate the lens and therefore gives a sharp contrast between the stained capsule and the unstained underlying cataract lens material. We used trypan blue in 31 cases as of June 24, 1999. The longest follow-up was 11 months. There were no side effects that could be attributed to the use of trypan blue.

  Throughout the specification and claims, unless otherwise required by context, the term “comprise”, or variations thereof, “comprises” or “comprising” can be used to refer to individual elements or processes individually. It does not include all, whether collectively, or exclude any other element or process, either individually or collectively. In this specification, references to the prior art should not be taken as an acknowledgment or any form of suggestion that the prior art forms part of the common general knowledge.

Claims (7)

  A composition comprising a trypan blue solution of 0.05% (w / w) to 3% (w / w) trypan blue in a solvent acceptable to the eye, the composition filling the anterior chamber with air Without filling the anterior chamber with a viscoelastic material, dropping a trypan blue solution into the anterior chamber, followed by a capsulotomy, lens removal and intraocular lens exchange. A composition which is used for visualization.   A composition comprising a trypan blue solution of 0.05% (w / w) to 3% (w / w) trypan blue in a solvent acceptable to the eye, the composition filling the anterior chamber with air Without filling the anterior chamber with viscoelastic material, dripping the trypan blue solution for a time sufficient to stain the anterior lens capsule, removing excess trypan blue and viscoelastic material from the anterior chamber, and viscoelastic material For use in visualizing the anterior lens capsule in a capsulotomy comprising the steps of reintroducing the capsulotomy into the anterior capsule followed by capsulotomy, lens removal and intraocular lens exchange .   A composition comprising a trypan blue solution of 0.05% (w / w) to 3% (w / w) trypan blue in a solvent acceptable to the eye, the composition filling the anterior chamber with air First, fill the anterior chamber with viscoelastic material, introduce a trypan blue solution under the viscoelastic material for a time sufficient to stain the anterior lens capsule, and remove excess trypan blue and viscoelastic material from the anterior chamber. A composition for use in the treatment of cataract comprising the steps of removing and reintroducing viscoelastic material into the anterior capsule followed by capsulotomy, lens removal and intraocular lens exchange.   To minimize trypan blue leakage from the anterior lens capsule when viscoelastic material is introduced into the anterior chamber, a less viscous material is present on the lens capsule and on the pupil edge of the eye The composition in any one of Claims 1-3 including the process of introduce | transducing a viscous substance with higher viscosity.   Use of trypan blue to produce a composition for enhancing visualization of the anterior capsular bag during capsulotomy surgery that does not fill the anterior chamber with air, the composition comprising 0.05% (w / w) ~ 3% (w / w) trypan blue in trypan blue solution in eye acceptable solvent, capsulotomy fills the anterior chamber with viscoelastic material and anteriorly under viscoelastic material Introduce trypan blue solution for sufficient time to stain the lens capsule, remove excess trypan blue and viscoelastic material from the anterior chamber, reintroduce viscoelastic material into the anterior capsule, then capsulotomy, lens removal And use of trypan blue, characterized in that it includes a step of performing intraocular lens exchange.   Use of trypan blue to produce a composition for enhancing visualization of the anterior lens capsule of the eye during a cataract treatment in which the anterior chamber is not filled with air, the composition comprising 0.05% (w / w) to 3% (w / w) of trypan blue in a solvent acceptable to the eye containing a trypan blue solution, the capsulotomy filling the anterior chamber with viscoelastic material and anteriorly under the viscoelastic material Dripping trypan blue solution for a sufficient time to stain the cervical lens capsule, removing excess trypan blue and viscoelastic material from the anterior chamber, reintroducing the viscoelastic material into the anterior capsule, then capsulotomy, lens Use of trypan blue, comprising the steps of removing and replacing the intraocular lens.   To minimize trypan blue leakage from the anterior lens capsule when viscoelastic material is introduced into the anterior chamber, a less viscous material is present on the lens capsule and on the pupil edge of the eye Use of trypan blue according to claim 5 or 6, comprising the step of introducing a viscous material having a higher viscosity.