Table of Contents

Table of figure.............................................................................................................................................1
Introduction:...............................................................................................................................................2
Genetic possibility:......................................................................................................................................3
YAG Laser Application:.................................................................................................................................5
Artificial intra-ocular iris implants:..............................................................................................................6
- Complications:.................................................................................................................................7
- Artificial Iris Approved By FDA.........................................................................................................8
- Who Should Get an Artificial Iris Implant?.......................................................................................8
Conclusion...................................................................................................................................................9

Table of figure

Fig1: Histological description simplified IRIS. The anterior layer is formed of a collagen matrix
where is tangled fibroblasts, and pigment cells (melanocytes) located a little more in depth.
Brown, Hazel and green eyes have a variable proportion of these cells, which lack the blue eyes.

Fig2: Engineering the Perfect Baby

Fig3: slit lamp photographs taken at presentation of 7 patients with cosmetics implants. A: Right
eye. B: Left eye.

Fig 4: Three artificial irises

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Introduction:

The study of human eye color as a physical trait is based on the developmental biology,
morphology, chemistry and genetic determinants of the structure known as the iris, which is part
of the uveal tract of the eye. The iris is made up of connective and muscle tissue, is
approximately 11–12 mm in diameter, and has an opening at the center called the pupil. It
controls the amount of light entering the eye which is focused by the lens onto the retina to
provide the sense of vision. It contracts in bright light making the pupil smaller and dilates in
dark conditions making the pupil larger, which together with the source of the incident light can
influence the perception of an individual’s eye color and iris pattern. (Abbas Asghar 2016)

Iris tissue consists of 2 layers: on the inside there is iris pigment epithelia, which is made of
cuboidal pigment cells, and on the outside, there is a looser stromal layer consisting of
fibroblasts and melanocytes. Two kinds of pigment have been defined: eumelanin pigment is
brown-black in color and pheomelanin pigment is yellow-red. These pigments are stored inside
the melanosome organelles of melanocyte pigment cells (Prota et al. 1998). The main factors that
determine various eye colors are the density of the melanocytes located at the anterior superficial
layer of the stroma and the nature of the pigments inside the melanocytes (Wilkerson 1996).
Studies have shown that there is approximately 15% less melanin in blue irises than in brown
irises (Yildirim et al. 2016).

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Fig1: Histological description simplified IRIS. The anterior layer is formed of a collagen matrix where is tangled
fibroblasts, and pigment cells (melanocytes) located a little more in depth. Brown, Hazel and green eyes have a
variable proportion of these cells, which lack the blue eyes.

It is a fact that physical appearance is important for everyone, and a nice and beautiful
appearance makes people feel better. Because iris color is an important aspect of physical
appearance, people desire to have colored eyes. Moreover, different eye colors can develop in
one person because of some disorders such as Fuchs’ heterochromic iridocyclitis, Horner
syndrome, or due to use of prostaglandin analogs, trauma or surgery. Focal color changes can
occur due to iris nevi. As a result, people feel uncomfortable when they have heterochromic eye
colors.

In recent years, this problem has been resolved to some extent with use of colored contact lenses.
However, use of contact lenses has its own disadvantages such as allergic reactions, feeling of
foreign body, dryness and infections(Beljan J, Beljan K, and Beljan Z 2013). Another method
that is used to change eye color is the artificial intra-ocular iris implants that are placed on the
anterior surface of iris. This technique has not been commonly adopted due to its invasive nature
and the developing complications (Hoguet et al. 2012). The overall structure of the iris stroma is
similar in irides of all colors. Differences in color are related to the amount of pigmentation in
the anterior border layer and the deep stroma, thickness of stroma and accumulation type of
white collagen fibers (Sturm and Larsson 2009). The stroma of blue irides is lightly pigmented,
and brown irides have a densely pigmented stroma that absorbs light. Therefore, it is proposed
that eye color could be changed with this laser by reduction or elimination of melanin pigments
on the anterior surface of iris. The laser used for this purpose has the same properties with the
laser that is used in the treatment of glaucoma with SLT device; it is Q-switched, frequency
doubled, 532 nm wavelength Nd: YAG laser, with the only difference of having 900 μm spot
diameter instead of 400 μm. A novel method to change the eye color which has been developed
in recent years is application of laser on to the iris surface. There is no literature data regarding
the safety of these applications which have been in clinical use for aesthetic purposes without
obtainment of a license yet. (Yildirim et al. 2016)

Genetic possibility:

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Eye color often is the genetic trait that fascinates parents the most as a child develops. How a
child looks depends on the genetic material each parent contributes to the child. But the parents'
genes can mix and match in many different ways. The influences from each parent aren't known
until — surprise — after the child is born (Abbas 2016).

Eye colors have been divided into nine categories and as many as 16 genes have been associated
with eye color inheritance. The main genes associated with eye color include OCA2 and HERC2
and both are located in Chromosome 15. The HERPC2 gene generally regulates OCA2
expression and a specific mutation within HERC2 gene is partly responsible for blue eyes.
Different single-nucleotide polymorphism within OCA2 are associated with blue and green eyes.
(Abbas Asghar 2016)

Fig2: Engineering the Perfect Baby

Clustered Regularly-Interspaced Short Palindromic Repeats is a gene-editing tool that has

made genetic modification so inexpensive and precise that new research papers about its
applications seem to be published daily. Genome editing is widely used around the world to
allow parents to select some of the traits of their children, such as gender and eye color. The
process works by extracting around a dozen eggs from the mother and using in vitro
fertilization (INV) to fertilize the eggs with the father's sperm. Once the eggs are fertilized,
doctors can analyze the genomes of the embryos and tell the parents if the baby would be at
risk of genetic diseases as well as what gender they will be and what eye color they will

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have. The parents simply select one of the embryos with their preferred traits and have it
reinserted into the mother's womb. (Jay Benette 2016)

Gene editing, meanwhile, works by injecting a protein into an organism to cut part of its

genome out and replace it with new genes. CRISPR is the most widely used method of
editing genomes, and hundreds of experiments using CRISPR on animals and plants have
already been conducted. But CRISPR is not perfect—and it would be a very haphazard way
to edit human embryos, we are talking about taking the evolution of the human race into our
own hands, a frightening prospect to many. (Antonio Regalado 2015)

YAG Laser Application:

In SLT, the target for the laser is melanin content of trabecular cells. “Selective
photothermolysis” occurs by restriction of the thermal damage to the target, which is the melanin
pigment. Thus, only pigmented trabecular tissue is being treated, where intracytoplasmic
melanosomes are lysed without damaging the cell membranes or neighboring nonpigmented
tissues (Yildirim et al. 2016). Another factor for prevention of damage to neighboring structures
is the very short duration of laser pulse provided by the device (3 nanoseconds), and very short
heat relaxation time of the target melanin pigment (1 microseconds). Q-switched, frequency
doubled, 532 nm wavelength Nd: YAG laser bearing SLT applications have been shown not to
cause coagulation damage or scarring.

Unlike with the SLT device, applying laser to iris tissue with fewer pulses, at a larger area with
900 μm spot size. Application duration is 3 nanoseconds, being at two different energy levels as
0.8 mJ and 1.5 mJ. Total numbers of pulses are 440 in both groups. At the first week following
laser application, there were lighter spots in iris tissue in patchy appearance, as well as areas
showing hyperpigmentation from place to place due to pigment clumping. These dark granular
areas were present especially at the early period after laser application in the center of laser
spots; but they diminished at the end of eighth week. In the result, lightening of the iris color
became more profound and permanent. This change is thought to be resulting from clearing of
pigment laden macrophages which had increased in stroma after laser application. Because 900
μm spot size instead of 400 μm is supposed to lessen patchy appearance by decreasing

5
cumulative pigmentation, and also to act on larger areas by applying fewer pulses, inflammation
would be milder. SLT stimulates proliferation of endothelial cells in trabecular cells and
Schlemm’s canal, release of cytokines, monocytes and phagocytosis. Increased migration and
phagocytosis functions of monocytes help eliminate the debris in trabecular meshwork, and
endothelial cells are biologically stimulated by the effect of chemokines released from the
cells(Alvarado et al. 2010). Mononuclear phagocytes become pigment laden macrophages after
engulfing melanin granules; they have been reported to enter systemic venous circulation after
passing to the lumen of Schlemm’s canal. In SLT applications, biological effects of the release of
chemotactic and vasoactive cytokines such as interleukin-1 beta and tumor necrosis factor alpha
are known to play an important role in the control of IOP (Yildirim et al. 2016). Increased levels
of lipid peroxidase in aqueous humor and free oxygen radicals that are released from trabecular
meshwork have been suggested to take part in inflammation occurring after SLT application
(Gulati et al. 2013).

It is assumed that laser applications with large spot diameters would cause less patchiness
compared to smaller spot diameters. Several studies have reported that transient increases in IOP
may occur after SLT applications (Harasymowycz et al. 2005). There is no consensus on use of
post-procedure anti-inflammatory treatment for suppression of inflammation; it has been
proposed that inflammatory process is a requirement for the effectiveness of the procedure
(Latina and de Leon 2005). In glaucoma patients, because SLT application is directly on the
trabecular meshwork that provides outward flow of aqueous, low-grade inflammatory process
taking place here could play a role in the increment of IOP.

Following application of 532 nm wavelength Q-switched Nd: YAG laser on iris tissue has no
serious adverse effects or complications apart from mild inflammatory signs. Change in iris color
occurred because of reduction in pigmentation in the anterior surface of the iris, being especially
evident at the end of the second month.

Artificial intra-ocular iris implants:

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The implant is placed under topical anesthesia. Carbachol (Miostat) was first used in the anterior
chamber to constrict the pupil, with subsequent injection of an ophthalmic visco surgical device
(OVD). The foldable implant was inserted in the anterior chamber through a 3.2 mm clear
corneal incision (CCI), and the OVD was subsequently aspirated out of the anterior chamber.
(Rula Sinnokrot Azizi 1996) No sutures were required for this procedure. Follow-up data were
tabulated, including surgical interventions, visual acuity, IOP, ECC, and slit lamp examination
findings at themost recent presentation.

Fig3: slit lamp photographs taken at presentation of 7 patients with cosmetics implants. A: Right eye. B: Left eye .

- Complications:
As we have learned from more than 50 years of experience with anterior segment implants, poor
design can lead to chronic deleterious effects with severe visual loss and ocular morbidity.
(Garcia-Pous et al. 2011) In previous case reports, several hypotheses for the high complication
rate in eyes with New Color Iris implants were proposed. First, during the surgical procedure, the
corneal endothelium may be damaged during insertion and opening of the folded implant into the
anterior chamber. Second, the device is a single-piece silicone implant that has flaps instead of
haptics, which can place pressure on the corneoscleral trabecular meshwork, Schlemm canal, and

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collector channels. Using anterior segment imaging (anterior segment optical coherence
tomography and UBM), several studie (Arthur et al. 2009) (Hoguet et al. 2012) found that the
New Color Iris implants come in direct contact with the lens and the iris. Many authors (Arthur
et al. 2009) (George, Tsai, and Loewen 2011) also found pigment dispersion throughout the
anterior segment, thus speculating that pigment dispersion may be the primary mechanism of
elevated IOP. They speculate that these irregularities might promote contact between the implant
and the iris, thus enhancing pigment dispersion. The mobility of the implant might also cause
mechanical irritation to the corneal endothelium, iris stroma, and angle structures, damaging
these structures.

- Artificial Iris Approved By FDA

The FDA approved the CustomFlex Artificial Iris, the first standalone prosthetic iris in the
United States that will treat adults and children with a missing or damaged iris. It is a permanent
implant designed to replace the colored contact lenses currently used by patients with the
problem.
"Patients with iris defects may experience severe vision problems, as well as dissatisfaction with
the appearance of their eye," said the FDA's Dr. Malvina Eydelman. She added that the artificial
iris will treat defects that lead to reduced sensitivity to glare and bright lights, and will improve
the cosmetic appearance of patients with aniridia.(Katherine Ellen Foley 2018)

The CustomFlex Artificial Iris uses this foldable medical-grade silicone, and its size and color
are customized for each patient. To implant it, the surgeon will make a small incision on the
patient's eye, insert the artificial iris under the incision, and then unfold it using surgical
instruments. The artificial iris will be kept in its place by the eye's own structures, or by sutures
if required.

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 - Who Should Get an Artificial Iris Implant?
Missing or partially missing irises are the effect of congenital aniridia, a rare genetic disorder
that affects about one in 50,000 to 100,000 people in the United States. The iris controls how
much light enters the eye, so people with aniridia are very sensitive to light and suffer from
various vision issues. Traumatic injury, albinism, and surgical removal arising
from melanoma are other possible causes for a damaged iris.
These people are the ones who stand to benefit from the FDA approval of the CustomFlex
Artificial Iris.

Fig 4: Three artificial irises

It remains to be seen whether people will attempt to undergo the procedure to implant the
CustomFlex Artificial Iris purely for cosmetic purposes to change their eye color. However,
patients who medically need the implant will likely be prioritized. (BRANDON A. WEBER
2018)

The artificial iris is surgically inserted, and then held in place with the eye’s natural structures. In
some cases, stitches may be required. Since the iris can be colored due to its silicon makeup, it
can also change the appearance of the color of the human eye, which opens it to usage for
cosmetic as well as vision and structural eye issues. 

The results are promising; 70 percent of participants in trials showed measurable decreases in
glare and light sensitivity, and there are low side effects and negative reactions. 94 percent of
participants report that they're satisfied with the appearance of the artificial iris.(BRANDON A.
WEBER 2018)

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Conclusion.
In summary, changing iris color could be done by different ways but it’s a high-risk procedure. It
results in numerous complications, including corneal edema, increased IOP, pigment dispersion,
uveitis, corneal edema, a depressed ECC, UGH syndrome, glaucomatous optic neuropathy,
CME, trabecular meshwork damage, and suprachoroidal hemorrhage. In the absence of clear
safety data for these implants in the peer-reviewed literature, we recommend that this implant not
be used or offered as a cosmetic implant in phakic eyes.

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