Proceedings of the Symposium on Photonics Technologies for 7th Framework Program 351

Wroclaw 12-14 October 2006

Therapeutic application of lasers in ophthalmology

Misiuk-Hojlo M¹., Krzyzanowska P.¹, Hill- Bator A.¹

¹ Department of Ophthalmology, Wroclaw Medical University, Poland

Laser effects in biological tissues can be divided into three general categories:
photochemical, thermal, and ionizing.
With the improvement of laser technology, the techniques with using different types of
lasers (ruby, neodymium, neodymium: yttrium- aluminum- garnet, erbium, and argon) allowed
to utilize lasers in the treatment and diagnostics of many eye disorders.
Photoradiation takes place when photosensitized tumor tissues are exposed to laser
light for the purpose of producing photochemical damage. During photoablation, tissue is
removed in some way by light, such as when intermolecular bands of biological tissues are
broken, disintegrating target tissues, and the disintegrated molecules are volatilized. This can
be effected with, for example, excimer laser.
Photocoagulation causes denaturation of biomolecules when temperatures are
sufficiently high, about 600 C or more. Temperature rise in tissues is proportional to the
amount of light absorbed by that tissue. Absorption of certain light frequencies is high in
pigmented trabecular meshwork, iris, ciliary body, and retinal pigment epithelium (owing to
melanin), and in the blood vessels (owing to hemoglobin). Lasers commonly used
photocoagulation are argon, krypton, or diode Nd:YAG lasers.
Photovaporization occurs when the tissue temperature quickly reaches the boiling
point of water, causing disruption (evaporation) before denaturation (photocoagulation).
Examples of clinical uses of these lasers are holmium: YAG or erbium: YAG laser
sclerostomy.
In photodisruption, short-pulsed, high-power lasers disrupt tissues by delivering
enormous irradiance to tissue targets. The high level of irradiance ionizes molecules in a small
volume of space at the focal point of the laser beam, disintegrating into collections of ions and
electrons called plasma. This plasma expands rapidly, producing shock and acoustic waves
that mechanically disrupt tissues adjacent to the region of laser focus. (6) Examples of
photodisrupter lasers are the Q-switched and pulsed Nd:YAG laser.

Glaucoma laser treatment is often recommended when medical therapy alone is

insufficient in controlling intraocular pressure, for those patients who have contraindications
to glaucoma medications or, for any reason, are unable to use eye drops.
The most common glaucoma laser procedure is laser peripheral iridotomy (PI). A laser
iridotomy is performed for patients with narrow angles, acute angle closure glaucoma, in the
fellow eye of a patient with acute or chronic primary angle closure, or pupillary-block
glaucoma. (17) Laser peripheral iridotomy involves creating a tiny opening in the peripheral
iris, allowing aqueous fluid to flow from behind the iris directly to the anterior chamber of the
eye. This typically results in resolution of the forwardly bowed iris and thereby an opening up
of the angle of the eye. (9) There are two types of lasers in use today - Nd:YAG Q-switched
laser (2 – 8 mJ) or argon laser (800 – 1000 mW). Argon laser began to replace surgical
iridectomy as a safer, non-invasive method of making an iridotomy in the late 1970s. It was
demonstrated to be safe and effective, (15) but required melanin for tissue absorption of the
energy, making it less easy to penetrate lightly pigmented blue irides. The Nd:YAG laser
replaced argon as the most common means of performing LPI in the late 1980s. The Q-
switched mode of the Nd:YAG laser causes photodisruption of tissues by the formation of a
Proceedings of the Symposium on Photonics Technologies for 7th Framework Program 352
Wroclaw 12-14 October 2006

high energy ionic plasma at the location of focus of very intense energy. It has the advantage
of not requiring the presence of melanin pigment for iris absorption. Complications of laser
iridotomy include: irritation, blurred vision, iritis, iris hemorrhage, elevated intraocular
pressure, corneal injury or retinal burns.
Argon laser trabeculoplasty (ALT) is a procedure which has been proven to be
efficacious for different types of open angle glaucoma: primary open angle glaucoma,
pseudoexfoliation glaucoma and pigment dispersion glaucoma. Patients with poor medical
compliance can benefit from ALT before other surgical intervention is considered. (10) In the
ALT procedure, the eye surgeon directs a laser beam into the trabecular meshwork, which is
the primary aqueous (fluid) drainage region of the eye. In most cases, 180 up to 360 degrees
of the trabecular meshwork is treated with laser spots, which typically requires about 40 to 80
laser applications. The effect of the procedure is increased drainage of aqueous fluid out of
the eye and intraocular pressure reduction to 20 – 25%. Efficacy of the ALT procedure lasts
for about 5 years.
Modification of this procedure is selective laser trabeculoplasty (SLT) performed with
a Q-switched 532 Nd:YAG laser. SLT works by using a specific wavelength to irradiate and
target only the melanin-containing cells in the trabecular meshwork, without incurring
collateral thermal damage to adjacent non-pigmented trabecular meshwork cells and
underlying trabecular beams. The laser beam bypasses surrounding tissue leaving it
undamaged by light.(8) This is why, unlike ALT, SLT is repeatable several times. Indications
for this procedure and complications (intermittent intraocular pressure elevation, iritis or
heamorrhage) are similar like in ALT.
Another glaucoma laser procedure is argon laser peripheral iridoplasty (ALPI). ALPI
is a method of opening an appositionally closed angle in situations in which laser iridotomy
either cannot be performed or does not eliminate appositional angle-closure because
mechanisms other than pupillary block are present. The procedure consists of placing
contraction burns of low power, long duration, and large spot size in the extreme iris
periphery to contract the iris stroma between the site of the burn and the angle, physically
pulling open the angle. ALPI is recommended in plateau iris syndrome, or angle closure
glaucoma. (11,16) The argon laser is set to produce contraction burns (500 µm spot size, 0.5
to 0.7 second duration, and, 200-400 mW power).
Cyclodestructive procedures in glaucoma lower the intraocular pressure (IOP) by
reducing aqueous inflow as a result of distruction ciliary processes. The use of light energy to
ablate the ciliary body was first proposed by Weekers and co-workers (21) in 1961 using
xenon arc photocoagulation In 1972 Beckman and Waeltermann (2) performed the first
transscleral cyclophotocoagulation (TSCPC) procedure with the ruby laser. Since then, the
neodymium (Nd):YAG and diode lasers have been used for transscleral
cyclophotodestruction. Due to the high complications rate, and the unpredictability of the
amount of IOP reduction, these procedures are usually reserved for the following conditions:
eyes with glaucoma refractory to other forms of surgical or medicinal therapy, eyes with poor
visual potential, neovascular glaucoma, traumatic glaucoma, aphakic and pseudophakic
glaucoma, chronic partial or total angle-closure glaucoma, aniridia or iridocorneal endothelial
syndrome.

Light coagulation and laser treatment of the retina were introduced to ophthalmology
around middle of the last century. They are widely used for the treatment of diabetic
retinopathy and other ischemic retinopathies. Retinal laser photocoagulation improves inner
retinal oxygenation, which affects retinopathy through the relief of hypoxia and consequent
change in growth factor production and hemodynamics.
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Diabetic retinopathy is a leading cause of visual loss in industrialized countries. Its

classification includes preclinical, nonproliferative (mild, moderate, and severe or
preproliferative diabetic retinopathy) and proliferative stages (low risk, high risk, and
advanced). Diabetic maculopathy (exudative, edematous, or ischemic) may be associated with
either nonproliferative or proliferative retinopathy. Prevention requires the tightest possible
control of both blood glucose and blood pressure. Laser photocoagulation remains the only
procedure recommended for severe nonproliferative or proliferative retinopathy and
maculopathy. (14) The Diabetic Retinopathy Study (DRS) sho wed that the rate of severe
visual loss in high- risk proliferative diabetic retinopathy could be reduced by as much as 60%
following the timely application of panretinal laser photocoagulation therapy. (20) Results
from the Early Treatment Diabetic Retinopathy Study (ETDRS) demonstrated that focal laser
photocoagulation treatment to the macula region could substantially reduce the risk of visual
acuity loss in patients with clinically significant diabetic macular edema. (4)

Retinal vein occlusion (RVO) is a common retinal vascular disorder that frequently is
associated with severe visual loss. There are two forms of retinal vein occlusion, branch
retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). A branch retinal
vein occlusion is essentially a blockage of the portion of the circulation that drains the retina
of blood. Central retinal vein occlusion is closure of the final retinal vein (located at the optic
nerve) which collects all of the blood after it passes through the capillaries. There is presently
no effective treatment available to prevent or restore the visual loss from acute CRVO.(12)
Following a vein occlusion, the primary concern is to treat the secondary complications:
macular edema, macular ischemia (non-perfusion) and neovacularization (growth of new
abnormal blood vessels). Argon or diode laser treatment may be useful in managing these
complications. One type of laser treatment, focal laser, can be used to close off areas of
leakage from the blood vessels that cause macular edema. Another type of laser treatment,
panretinal photocoagulation, can cause neovascularization to regress by making the retina less
starved for oxygen.

Nowadays, laser treatment is also available in the age-related macular degeneration

(AMD), a disease of our civilization. Macular degeneration is a progressive eye condition
affecting the central vision and causing irreversible blindness in people over the age of 50.
AMD has two basic forms: dry and exsudative. Dry AMD accounts for about 90% of cases, is
the milder form of the disorder. Exsudative AMD is the much more visually debilitating form
of macular degeneration, often accompanied by choroidal neovascular membranes, which are
the leaky vascular structures under the retina. There are two basic forms of laser treatment for
exsudative AMD: conventional argon or diode laser therapy and the recently approved
photodynamic therapy (PDT). Conventional laser burns the abnormal blood vessels and thus
stops the leakage. However, since it also damages the normal retina structures, it may itself
lead to decreased vision. Hence, it is suitable only in selected cases where the new vessels are
not very close to the central macular area. The concept of the new treatment for exsudative
AMD is the closure of subretinal choroidal neovascularization (CNV) without significant
damage to the surrounding tissues, such as photoreceptors or retinal pigment epithelium
(RPE). (1) In PDT, a photosensitizer, Verteporfin is administered intravenously and allowed
to perfuse the CNV, as well as the remainder of the body. Fifteen minutes after the start of
intravenous infusion, the verteporfin is activated by a red laser of a specific wavelength
(689nm). The non-thermal laser light activates the verteporfin producing the singlet oxygen
that both coagulates and reduces the growth of abnormal blood vessels. This, in turn, inhibits
the leakage of fluid from the CNV.
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Wroclaw 12-14 October 2006

The first attempts to treat intraocular tumors by means of photocoagulation were

carried out in the late 1950s by G. Meyer-Schwickerath with the xenon arc photocoagulator.
(13) Nowadays, lasers are an irreplaceable tool in the management of malignant and benign
intraocular lesions. Transpupillary thermotherapy (TTT) using an 810nm infrared laser has
become one of the most popular treatments for small melanomas. (10) Lasers can be also used
as an adjunctive tool in combination with other treatment modalities in therapy regimens for
medium or even large melanomas. The main advantages of laser treatment compared to other
modalities like irradiation are the broad availability, the relatively easy performance and thus
reproducibility, the high precision during the treatment, and the safety for the adjacent tissues.

Corneal laser surgery with the modern excimer laser is known to be the most
frequently applied laser procedure in medicine. The interaction between corneal tissue and the
excimer laser was first investigated in 1981 by Taboada, who studied the response of the
epithelium to the argon fluoride (AF) and krypton fluoride (KrF) excimer laser. (19) The use
of lasers to reshape the anterior corneal curvature to correct refractive errors has become an
established clinical procedure. Surgical techniques such as photorefractive keratectomy
(PRK) and laser in-situ keratomileusis (LASIK) are used to correct optical aberrations of the
eye, such as myopia or hyperopia, as well as astigmatism. During PRK for the correction of
myopia, direct flattening is achieved by the removal of a convex-concave lenticule of tissue
from the outer surface of the central cornea. Clinical studies determined refractive success
rates of between 80 and 95% for corrections up to –6 D of myopia. (18) A modification of this
technique involves the microkeratome to make a lamellar flap (average thickness, 120-160
µm) of anterior corneal stroma, followed by refractive ablation of the exposed stromal bed.
This flap is then repositioned on the exposed stroma, and good adhesion is usually obtained
without the need for sutures. This procedure was particularly investiga ted in eyes needing
high myopic corrections if more than – 6 D.
In the recent years, a new method has been developed and used. This is called laser
subepithelial keratectomy (LASEK). (3) In this procedure, the epithelial layer is completely
removed, but about 900 of the circumference is allowed to remain as a short of hinge. After
the laser treatment, which is equivalent to PRK, the epithelium is replaced.

Laser photocoagulation is also mainly used in the retina abnormalities such as: tears,
breaks, holes, lattice degeneration or retinoschisis, which predispose to a rhegmatogenous
retinal detachment. With argon laser photocoagulation a thermal burn is created to surround
the lesion and any subretinal fluid associated with it. The burn becomes an adhesion between
the retina and retinal pigment epithelium, and this limits potential flow of fluid from the
vitreous cavity through a break.
Visual loss occurring secondary to opacification of the posterior capsule after
extracapsular cataract extraction is the major indication for laser capsulotomy. Posterior
capsulotomy for creating openings in an opacified posterior capsule can be performed with
the argon laser of the pulsed Neodymium- YAG laser.

It is impossible to imagine ophthalmology today without lasers, ubiquitously and

thoroughly do they dominate the field. A rapid explosion of argon laser techniques occurred
in the late 1970s and early 1980s. In the 1990s, another explosion occurred in the treatment of
posterior segment disorders, including macular dege neration and intraocular tumors. The
development of lasers for plastic surgery, cataract extraction, and ocular imaging is
progressing rapidly and is expected to find much greater use and usefulness in the coming
years.
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