Composition for preventing clouding of posterior capsule after extracapsular cataract eye surgery and method of performing cataract surgery

The present invention relates to compositions for killing undifferentiated epithelial cells during cataract surgery on an eye to prevent posterior capsule clouding after the surgery and to a method for performing cataract surgery on an eye including injecting a cell-killing substance between the anterior capsule and the natural lens prior to removing the natural lens from the eye. The cell-killing substance is preferably an acid or base adjusted aqueous solution having a pH in the range between about 1.0 to below 6.5 or about above 7.5 to 14.0; or a hypotonic solution having a salinity less than 0.9% or a pH adjusted hypotonic solution having a salinity less than 0.9% and a pH either below 6.5 or above 7.5. The compositions of the present invention also incorporates a viscoelastic material, a dye or a mixture thereof, in combination with the cell-killing substance.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention pertains to cataract surgery and, more particularly, 
to the prevention of clouding of the posterior capsule after extracapsular 
cataract extraction. 
2. Discussion of the Prior Art 
Clouding of the posterior capsule after extracapsular cataract extraction, 
with or without the implant of an intraocular lens, has been a principal, 
later occurring, complication of such extracapsular cataract surgery. 
During cataract surgery, it is preferable to extract the natural lens 
while leaving the posterior portion of the lens capsule intact in front of 
the vitreous cavity of the eye to provide a barrier to prevent anterior 
movement or loss of the vitreous which fills the cavity and to also 
provide a support for an intraocular lens implanted in the posterior 
chamber. If the natural lens is removed intact with the capsule, referred 
to as intracapsular cataract extraction, the vitreous can move through the 
pupil causing vitreous loss and increasing the chances of complications, 
such as glaucoma, corneal opacity, displacement of an intraocular lens, 
retinal hemorrhage, holes, breaks and detachment, and cystoid macula 
edema. 
In many cases after extracapsular cataract extraction, with or without the 
implant of an intraocular lens, the posterior capsule becomes opacified or 
clouded due to migration of proliferating undifferentiated epithelial 
cells into the optical zone which, clustered, form Elschnig's pearls. 
Along with Elschnig's pearls, visual acuity is also reduced by invading 
fibroblasts through metaplasia developing into myoepithelial fibers, lens 
fibers, collagen, fibrosis and Sommering rings. This opacification or 
clouding of the posterior capsule, referred to as secondary cataract, 
occurs in a large percentage of extracapsular cataract extractions and is 
a primary cause of post operative complications. 
One procedure to remove secondary cataracts is discission using a needle or 
scissors to punch or cut a hole in the posterior capsule. Another 
procedure includes the use of a YAG laser focused through the pupil to 
open the posterior capsule. Such procedures, referred to as posterior 
capsulotomy, remove the opacification to improve sight; however, they also 
create the adverse effects discussed above with respect to intracapsular 
cataract extraction due to the removal of the barrier to vitreous 
movement. 
Other attempts to prevent clouding of the posterior capsule include 
constructing intraocular lenses to produce barriers to movement of the 
undifferentiated epithelial cells from the equator of the posterior 
capsule toward the optical zone; however, such intraocular lenses have 
been difficult to implant in the posterior capsule and have not created 
effective barriers to prevent clouding. 
Still another attempt to prevent proliferation of lens epithelial cells 
after extracapsular cataract extraction is shown in U.S. Pat. No. 
4,432,751, to Emery et al, which instills monoclonal antibodies specific 
to lens epithelial cells into the anterior chamber to cause lysis or other 
damage to the lens epithelial cells and prevent the cells from multiplying 
and covering the posterior lens capsule. 
Accordingly, there is a great need for a manner in which to prevent 
opacification of the posterior capsule, particularly in view of the great 
number of cataract surgeries performed each year and the substantial 
likelihood of most individuals having cataract surgery due to the natural 
forming of cataracts in the natural lens with aging. As noted above, the 
preferable procedure for cataract surgery is extracapsular cataract 
extraction; and, thus, much effort has been directed toward overcoming the 
late capsule clouding complication associated with such cataract surgery. 
SUMMARY OF THE INVENTION 
Accordingly, it is a primary object of the present invention to prevent 
clouding of the posterior capsule after extracapsular cataract extraction 
without requiring removal, puncturing or discission of the posterior 
capsule. 
A further object of the present invention is to prevent clouding of the 
posterior capsule after extracapsular cataract extraction by killing 
remaining undifferentiated epithelial cells by either osmotic cellular 
destruction in a hypotonic environment and/or lysis by destructive pH 
alteration. 
Another object of the present invention is to provide a method of 
performing cataract surgery on an eye to prevent capsule clouding after 
the surgery by injecting a cell-killing substance between the capsule and 
the natural lens and thereafter removing the natural lens from the eye. 
Yet another object of the present invention is to provide a cell-killing 
substance of a hypotonic (hypo-osmotic) solution, a pH altering solution 
having a pH either below 6.5 or above 7.5, or a hypotonic solution having 
a pH either below 6.5 or above 7.5, for injection between the capsule and 
the natural lens of an eye prior to removal of the natural lens to kill 
the undifferentiated epithelial cells by osmotic cellular destruction 
and/or by destructive pH alteration. 
It is still another object of the present invention to utilize a 
viscoelastic material in admixture with the cell-killing substance to 
facilitate the spread of the admixture to assure contact of the 
cell-killing substance with all undifferentiated epithelial cells and to 
promote increased contact time between the cell-killing substance and the 
undifferentiated epithelial cells. 
It is still another object of the present invention to incorporate a dye in 
admixture with the cell-killing substance so that the area of 
administration of the resultant colored mixture is visually apparent. 
Yet an additional object of the present invention is to place a 
viscoelastic material in the anterior chamber of an eye prior to injecting 
a cell-killing substance between the capsule and the natural lens such 
that the viscoelastic material prevents any cell-killing substance 
escaping from the capsule opening from reaching the corneal endothelium. 
The present invention is characterized by a novel composition for 
adminstration between the anterior capsule and the lens during cataract 
surgery. This composition includes a cell-killing substance having 
properties to kill undifferentiated lens epithelial cells by osmolysis 
and/or destructive pH alteration and optionally contains a viscoelastic 
material, a dye or both. 
The present invention is further characterized in a method of performing 
cataract surgery on an eye to prevent capsule clouding after the surgery 
comprising the steps of: (1) injecting the novel composition including a 
cell-killing substance between the capsule and the natural lens, the 
substance having properties to kill undifferentiated epithelial cells; (2) 
maintaining the cell-killing substance in contact with the 
undifferentiated epithelial cells for a sufficient period of time to kill 
these cells by osmotic cellular destruction or destructive pH alteration, 
and removing the natural lens from the eye. 
Some of the advantages of the present invention over prior art methods of 
preventing or eliminating capsule clouding are that the composition and 
method of the present invention can be utilized along with the procedures 
of normal cataract surgery requiring only a single additional procedure, 
no difficult or complex surgical procedures are required, safety is 
assured by the use of viscoelastic materials and the nature of the 
composition assures the killing or destruction of all undifferentiated 
epithelial cells. 
Other objects and advantages of the present invention will become apparent 
from the following description of the preferred embodiment taken in 
conjunction with the accompanying drawings.

DESCRIPTION OF THE PREFERRED EMBODIMENT 
The present invention will be explained with respect to FIGS. 1 and 2 which 
illustrate an eye including a cornea 12, an iris 14, a natural lens 16 and 
a capsule 18 surrounding the lens formed of an anterior capsule segment 20 
and a posterior capsule segment 22. In conventional extracapsular cataract 
surgery, an incision 24 is made in the cornea and an anterior capsulotomy 
is performed to remove a portion of the anterior segment 20 of the 
capsule. Thereafter, the natural lens 16 is removed; and, if desired, an 
intraocular lens can be positioned in either the anterior chamber 26, 
defined as the region between the cornea and the iris, or the posterior 
chamber 28, defined as the region behind the iris, posterior chamber 
intraocular lenses being positioned normally in the posterior capsule 22 
or in the sulcus. 
In accordance with the present invention, after the incision 24 is made, a 
syringe is inserted therethrough having a hollow hypodermic needle 32. The 
surgeon punctures the anterior segment 20 of the capsule 18 with the 
needle 32; and, once the needle 32 is so positioned, the syringe is 
operated to force a cell-killing substance between the capsule 18 and the 
lens 16 to form a fluid pocket 40, the substance at least completely 
surrounding the anterior surface of the lens to completely contact the 
anterior capsule segment 20. The cell-killing substance is maintained in 
contact with the undifferentiated epithelial cells for a period sufficient 
to kill all of the undifferentiated epithelial cells. A particularly 
effective syringe for introducing the cell-killing 21 substance is shown 
and described in application Ser. No. 07/173,625 and includes an 
aspirating tube having an open distal end disposed adjacent the capsule to 
evacuate any cell-killing substance escaping from the capsule. 
Furthermore, to ensure that the cell-killing substance does not come into 
contact with the cornea or other eye tissues, the anterior chamber 26 is 
filled with a viscoelastic material, such as VISCOAT produced by Cilco. 
The cell-killing substances destroy the undifferentiated epithelial cells 
by osmolysis or by destructive pH alteration. Upon contacting the 
undifferentiated epithelial cells with a hypotonic solution cell-killing 
substance, the cells continuously absorb the cell-killing substance by 
osmosis until the cells are destroyed by bursting or exploding within 
approximately thirty seconds. The undifferentiated epithelial cells 
undergo a destructive pH change by contacting the cells with a pH adjusted 
solution thereby killing the cells within approximately a minute by 
altering the normal chemical reactions required for metabolic activity 
essential for the life of the cell. Thus, the cell-killing substance 
should be maintained in contact with the epithelial cells for a period of 
time sufficient to complete destruction of the cells by osmolysis or by 
altered pH lysis. The cell-killing substances of the present invention 
include hypotonic solutions, pH adjusted solutions, or pH adjusted 
hypotonic solutions. Hypotonic (hypo-osmotic) solutions are defined herein 
as any solution having an osmotic pressure lower than the pressure 
naturally existing in the undifferentiated epithelial cells. Thus, any 
solution providing an osmotic pressure below normal saline solution can be 
employed in accordance with the present invention. Organic hypotonic 
solutions can be utilized including, but not limited to, alcohols, 
ketones, ethers or aldehydes. 
Preferred hypotonic solutions include distilled water or water having a 
salinity less than 0.9%. Preferably the hypotonic solution injected as a 
cell-killing substance has a salinity of from 0 to 0.6%, it being found 
that salinity percentages of from 0 to 0.3 are highly effective. Suitable 
salts such as NaCl or other pharmaceutically acceptable salts are utilized 
to effect the desired percentage of salinity. 
The pH adjusted solutions of the present invention have either a pH in the 
acidic pH range between approximately 1.0 to below 6.5 or in the basic pH 
range between approximately above 7.5 to 14.0. The preferred pH adjusted 
solutions used as cell-killing substances possess a pH in either of the 
following two ranges: 3.5.ltoreq.pH&lt;6.4 or 7.8.ltoreq.pH.ltoreq.10.5. More 
preferably the pH adjusted solutions possess a pH ranging either between 
5.8 to 6.2 or between 8.0 to 8.4, while the most preferable pH adjusted 
solutions are pH adjusted aqueous solution having a pH of either 
approximately 6.0 or 8.2. 
The pH adjusted solutions used as pH altering cell-killing substances are 
organic or inorganic, aqueous preferably and are produced by adding either 
basic or acid components to organic or inorganic diluents. The acidic pH 
adjusted solutions are produced by adding an appropriate amount of HCl, 
preferably, or other ophthalmically acceptable acids to a diluent such as 
water. The basic pH adjusted solutions are produced by adding an 
appropriate amount of NaOH, preferably, or other ophthalmically acceptable 
bases to a diluent such as water. Other ophthalmically acceptable acids 
for use in the present invention to prepare the pH adjusted solutions 
include but are not limited to: mineral acids and organic acids such as 
H.sub.2 SO.sub.4, HNO.sub.3, H.sub.3 PO.sub.4, acetic, proprionic, oxalic, 
maleic, benzoic acids and the like. Other ophthalmically acceptable bases 
include but are not limited to: alkali or alkaline earth hydroxides, 
carbonates or bicarbonates or the like, preferably potassium hydroxide. 
The hypotonic solutions for use in the present invention can also be pH 
adjusted to enhance the ability of the solution to destroy 
undifferentiated epithelial cells. The previously discussed hypotonic 
solutions are pH adjusted with the aforementioned acids or bases utilized 
to adjust the pH in the pH adjusted solutions. The pH adjusted hypotonic 
solutions formed in this manner have a pH either below 6.5 or above 7.5 
and have the same preferred pH ranges as the pH adjusted solutions. The pH 
adjusted hypotonic solutions destroy undifferentiated epithelial cells by 
both osmolysis and by destructive pH alteration to assure that all cells 
are destroyed. 
The pocket 40 is essentially a "potential" space in that the capsule is 
contracted tightly around the lens. Since all undifferentiated epithelial 
cells must be contacted by the cell-killing substance, the potential space 
must be expanded in all areas between the lens and the anterior capsule 
segment to form pocket 40, and it has been found that use of a 
viscoelastic material in admixture with the cell-killing substance, 
preferably premixed prior to injection, facilitates the even flow of the 
admixture to form fluid pocket 40 and assures that all areas of the 
anterior surface of lens 16 and the posterior surface of anterior capsule 
segment 20 come into contact with the cell-killing substance. The 
admixture of the viscoelastic material with the cell-killing substance 
facilitates the spread of the admixture onto the surface of the outer 
periphery of lens 16. Furthermore, the use of the viscoelastic material 
increases the contact time between the cell-killing substance and the 
undifferentiated epithelial cells through retention of the cell-killing 
substance against the epithelial cells by the viscoelastic material. 
Preferred viscoelastic materials for use in admixture with the cell-killing 
substances of the instant invention include, but are not limited to, 
HEALON, VISCOAT, ORCOLON, methylcellulose, methyl hyaluronate, 
polyacrylamide and polymethacrylamide. The viscoelastic material is 
preferably utilized in amounts ranging from 0.5 to 5.0%, preferably 1 to 
3% by weight of the cell-killing substance injected into fluid pocket 40. 
As pointed out above, it is important to contact all undifferentiated 
epithelial cells with the cell-killing substance; however, it is extremely 
difficult for the surgeons to visually determine that the cell-killing 
substance has completely filled the pocket and expanded all portions of 
the anterior capsule segment. Accordingly, a dye is admixed with the 
cell-killing substance prior to or after injection of the cell-killing 
substance between the inner surface of the anterior capsule 20 and the 
lens 16. The use of such a dye provides visually recognizable color to the 
injected solution so that a surgeon can visually determine the extent of 
the flow of the injected solution between the anterior capsule 20 and the 
lens 16. The surgeon can thus visually confirm that the cell-killing 
substance has completely filled the capsule space forming fluid pocket 40 
between the anterior capsule 20 and the lens 16 so that all of the 
anterior capsule 20 comes in fluid contact with the cell-killing 
substance. 
Preferred dyes for use in combination with the cell-killing substance of 
the present invention include, but are not limited to, methylene blue and 
triptolene blue. It has been determined that blue, purple and green dyes 
provide the best contrast for visualization during insertion of the 
cell-killing substance; however, any dye providing sufficient contrast to 
show the extent of the area of coverage of the cell-killing substance 
between the anterior capsule 20 and the lens 16 can be utilized. When 
utilized, the aforementioned preferred colors also provide the best 
contrast with cataracts which appear to be amber in color. 
The dyes should be utilized in amounts to effectively provide color to the 
cell-killing substance upon visual examination. It is preferable to 
incorporate a dye in extreme dilution to provide a visually apparent 
amount, preferably from 0.1 to 10 parts per million of the cell-killing 
substance. 
The cell-killing substances may be administered alone, in combination with 
a dye or a viscoelastic material, or in combination with both a dye and a 
viscoelastic material in accordance with the present invention. Any 
combination of the aforementioned substances, namely the cell-killing 
substance alone or together with the dye and/or the viscoelastic material, 
is preferably administered by injection in an amount of less than 2.0 cc, 
most preferably less than 1.5 cc, between the lens 16 and the anterior 
segment 20 of the capsule 18 such that there is minimal opportunity for 
the substance to escape from the capsule while still providing full fluid 
contact of the injected cell-killing substance solution between the inner 
anterior capsule surface and the lens surface, preferably at least 0.5 cc. 
In use, a syringe is filled with the cell-killing substance, which may be 
optionally admixed with a dye and/or a viscoelastic material; and, as a 
piston is forced into a chamber in the syringe, the cell-killing substance 
or mixture thereof is forced through needle 32 between the anterior 
capsule 20 and the natural lens 16 with sufficient pressure to surround 
the lens and kill epithelial cells therein by osmotic pressure. The 
injected cell-killing substance may completely surround the lens 16 
between both the anterior capsule 20 and the posterior capsule 22; however 
as illustrated in FIG. 2, it is important only that a sufficient amount of 
solution be injected to form a fluid pocket 40 allowing the cell-killing 
substance to contact all portions of the anterior capsule segment since 
undifferentiated epithelial cells only habitat in the lens capsule 18 
between the anterior capsule 20 and the lens 16. Any cell-killing 
substance inadvertently escaping from the capsule through the puncture is 
constrained to move along the needle and through incision 24 due to the 
viscoelastic in the anterior chamber 26 or can be collected by an 
aspirating tube. Accordingly, the cell-killing substance is prevented from 
contact with any eye tissue. 
In view of the above, it will be appreciated that the method of preventing 
capsule clouding according to the present invention is extremely simple 
and efficacious in that the capsule is used to confine the cell-killing 
substance but is not a living cell and, therefore, is not affected by the 
cell-killing substance. 
Inasmuch as the present invention is subject to many variations and 
modifications in detail, it is intended that all subject matter discussed 
above o shown in the accompanying drawings be interpreted as illustrative 
and not in a limiting sense.