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Clinical Applications for Opto Advant 532 Clinical Applications for Opto Advant 532 Important Note
The information contained within this section is intended to provide Opto Global Distributors and their sales and marketing personnel with an overview summarizing the most common treatment modalities that may be performed with the Opto Advant 532 Photocoagulator. The information provided is not exhaustive, nor does Opto Global claim to provide professional clinical advice or recommend treatment procedure. It is intended for personal research only and not for external distribution to including customers, competitors and others outside your company. The Opto Advant 532 Photocoagulator is designed for use by ophthalmologists who have the expertise and patient consent to choose and perform the most appropriate treatment for each patient. Summary of conditions treated
The most common conditions treated are: ƒ Diabetic Retinopathy — proliferative and maculopathy ƒ Branch Retinal Vein Occlusion — macular oedema or ƒ Central Retinal Vein Occlusion — ischemia/rubeosis iridis ƒ Glaucoma — open angle: Argon Laser Trabeculoplasty (ALT) ƒ Retinal ƒ Choroidal Neovascular Membrane — Age-Related Macular Laser photocoagulation principles and diseases treated
Laser photocoagulation produces controlled, localised, therapeutic, thermal damage by absorption of a brief burst of laser light to the tissue that will absorb a particular wavelength. It is mainly used in treating common retinal vascular diseases and other less common conditions. 3 clinical principles and disease processes are summarized in the Clinical Applications for Opto Advant 532 vascular diseases
Retinal blood vessels enter and leave the eye at the optic nerve. The
vessels are highly specialised and have tight cell junctions that do not
allow fluid to leak out. All retinal vascular diseases cause problems by
either leakage or blockage of these vessels.
Leakage
ƒ Damage to the vessel walls allows fluid to leak and accumulate in the
retina. This causes localised swelling, retinal thickening (oedema) sometimes with the accumulation of large fat molecules (lipids) seen as 'hard exudates'. ƒ Leakage is particularly likely to accumulate in the macula and track towards the fovea, which then causes a drop in vision. If leakage persists for some time, there is permanent structural and vision damage. ƒ Leakage from damaged or abnormal vessels can be modified with laser photocoagulation. This treatment is very effective at resolving small amounts of leakage but if the amount of leakage is too great the laser treatment may not successfully dry the retina.
The main diseases causing macular oedema requiring retinal laser
photocoagulation are:
Diabetic macular oedema
Small blood vessels in the back of the eye are damaged by the effects of
diabetes. Laser photocoagulation treatment is usually applied to the
areas of maximal retinal thickening/oedema, and is very successful in
most cases in reversing, stabilising or slowing the progression of diabetic
macular oedema.
Retinal vein occlusions
Damage here occurs following sudden occlusion of venous outflow,
which usually occurs as a sudden event. Laser treatment may have to be
delayed until superficial retinal haemorrhages absorb sufficiently to allow
laser to the underlying pigment epithelium. In the majority of patients,
laser photocoagulation can significantly reduce the oedema and help
stabilise the condition, or even improve it. The success of treatment
depends on the amount of oedema present.
Other causes of macular oedema due to retinal vascular
abnormalities
Other causes are less common and include Coats’ disease and macro- aneurism. Treatment principles remain the same. Blockage
The other mechanism by which retinal vascular disease threatens vision is when retinal vascular disease closes tiny capillaries in the retina. If the damage is severe enough, the retinal tissues can become starved of Clinical Applications for Opto Advant 532 oxygen and there may be abnormal growth of new blood vessels into the eye (Neovascularisation). These abnormal vessels are small and fragile, and easily break, and bleed into the vitreous in the eye. This can result in shrinkage and the growth of scar tissue, and in serious cases, retinal detachment and even total blindness. Blockage most commonly occurs in prolonged diabetes. In some cases the new vessels may grow in the front of the eye in the drainage angle of the anterior chamber and on the surface of the iris, and cause a particularly nasty blinding form of glaucoma. Laser photocoagulation can very successfully treat the vast majority of cases, however, if the disease is too advanced, surgical intervention may be necessary. 2. Other uses of laser photocoagulation

Peripheral retinal tear
In most people, as we get older, the vitreous humor the eye becomes
more fluid and the solid portion of the vitreous tends to collapse forward,
leaving clear fluid behind it (posterior vitreous detachment). This occurs
at a younger age and is more obvious in large, short-sighted eyes. When
this occurs, the vitreous may remain stuck to one or two areas in the
outer part of the retina and as the vitreous collapses, traction is caused
on these areas. The patient often perceives the sudden development of
multiple floaters, sometimes associated with flashing lights.
The area of abnormal attachment will often spontaneously release the
vitreous, but in some patients it will tear a hole in the inner retina instead.
This hole, if left untreated, will usually lead to a retinal detachment due to
fluid passing through the hole and separating the inner retina from the
outer retina.
Once a retinal detachment due to a tear starts, it usually progresses and
leads to a total retinal detachment. Retinal detachments can usually be
repaired by fairly major surgical intervention but a small number cannot,
and only limited visual recovery is possible. It is therefore important to
detect and treat a retinal tear before there is a detachment or when a
detachment is localised.
In this situation, laser photocoagulation is usually very successful, either
delivered via a contact lens, or using a Laser Indirect Ophthalmoscope. The attached retina around the hole is treated with an intense barrier of laser photocoagulation, which permanently seals off the tear and prevents any fluid from passing through it under the attached retina. Glaucoma
Glaucoma is a large group of conditions in which there is progressive damage to the optic nerve, giving rise to a particular pattern of Clinical Applications for Opto Advant 532 progressive visual field loss. If left untreated, glaucoma causes the death
of the nerve and vision damage or blindness.
Open Angle Glaucoma
This is the most common form of glaucoma seen in the population as we
age. In the majority of these glaucoma patients there is an increase in
pressure in the eye (intraocular pressure), and if this pressure can be
reduced the progression of the glaucoma can be stopped or slowed
down.
Open angle glaucoma is usually treated with different types of eye drops
to lower the intraocular pressure, but this can also be achieved to some
extent in many patients by treating the trabecular meshwork with laser
photocoagulation (laser trabeculoplasty). The laser burns tiny holes in the
trabecular meshwork and opens a channel for the fluid to drain.
In laser trabeculoplasty, a small spot size of high-intensity laser is applied
to the trabecular meshwork with a Slit Lamp and a special contact lens,
which allows the Ophthalmologist to view the anterior chamber drainage
angle, between the cornea and iris. Two or three treatment sessions can
be used, but in some patients laser trabeculoplasty is not effective and
further re-treatments result in little benefit. Laser treatment may often be
combined with topical eye drops.

Angle closure glaucoma
In some patients there is a narrow anterior chamber angle between the
iris and trabecular meshwork. This angle can close, giving rise to acute
angle closure glaucoma.
The passage of fluid from the posterior chamber to the anterior chamber
and trabecular meshwork can be re-established by making an opening
(iridotomy or iridectomy) through the iris. The Nd:YAG Photodisruptor
laser is the most commonly used for this, but photocoagulation can often
achieve the same result. Some Ophthalmologists initially use
photocoagulation to close blood vessels in the iris before then making a
final opening with the Nd:YAG Photodisruptor laser.
diseases
Laser photocoagulation is less commonly used for these diseases but still plays a very important therapeutic role. Age-related macular degeneration (AMD)
Age-Related Macular Degeneration (AMD) is the main cause of legal blindness in the western societies, in age groups above 50 years. It is estimated that in the United States of America there are approximately 6% of patients with AMD, in age groups above 50, and approximately Clinical Applications for Opto Advant 532 In addition to ageing, other factors are among the known causes of AMD:
ƒ Fair skin and light iris
ƒ Smoking
ƒ Excessive consumption of food rich in vegetable oil and fat
ƒ Cumulative exposure to sun light
The physiopathology of the AMD is related, roughly speaking, to the
gradual loss of the retina and pigmented epithelium to metabolize and
eliminate its residues, which end up being accumulated in the form of
Drusen. In 90% of the affected patients it is observed the dry or non-
exudative form or AMD, often characterized by the presence of Drusen
and areas with atrophy of the Retina Pigmented Epithelium (RPE). Of the
remaining 10%, besides Drusen, it is observed as a serous-exudative
process associated with the presence of Sub-retinal Neovascular
Membrane or Choroidal Neovascular Membrane (CNV). This group, due
to its characteristics, is described as exudative form of AMD.
Although less frequent, the exudative form is associated to more abrupt
and severe vision impairment than the non-exudative form, which
progresses more slowly and is less harmful to the central vision.
Annually, there are 200,000 new cases of the exudative form in the USA.
The dry form has less harmful anatomic-functional form than the
exudative form, responsible for the presence of haemorrhage, exudates a
sub-retinal liquid, and later by the formation of extensive fibrous scars at
the posterior pole with significant vision loss. It is estimated that the risk
of the second eye be affected by AMD after the involvement of the first
eye, is approximately 5-8% per year.
Diagnostic
Since the first clinical suspicion of AMD, the diagnosis is confirmed
through complementary examination, especially through angiography,
using dyes with fluorescent properties such as Fluorescein and
Indocyanine Green (ICG). This exam consists of the injection of Sodium
Fluorescein and/or Indocyanine Green into the peripheral vein, usually in
the forearm, followed by capturing images of the retinal and choroidal
circulation, which are printed and recorded in photographic paper or
digital media. The AMD is classified through the fluorescein angiography
in 2 main types: classic or occult, by the pattern of the dye leakage.
Recently, the terms ‘predominantly classic’, for membranes with more
than 50% area with classic membrane pattern, and ‘minimally classic’, for
membranes in <50% of well defined area, are being commonly used. The ICG angiography is more effective for the study and identification of the Recently the Optical Coherence Tomography (OCT) is being used in the evaluation of the macula anatomy, especially in diseases with anatomic variation effects and accumulation of sub-retinal liquid. It is a non-invasive method that provides detailed visualization of cross sections of Clinical Applications for Opto Advant 532 the retina, allowing topographic assessment and measurements (in
micrometers) of the alterations. In the exudative AMD this method has
been used with increasing interest in the pre-operation assessment and
post-treatment evaluation of AMD.
Treatment
Various therapeutic modalities have been studied for the treatment of the
exudative AMD. Despite some advances in the prevention of severe
vision impairment, there is no efficacious and standard treatment for the
majority of the affected patients. Following is a summary of the main
available treatments.
Approved Treatments

Photocoagulation
The photocoagulation (thermal laser) was the first modality described for
the treatment of CNV secondary to AMD. The largest study for the
evaluation of the efficacy and scope of the treatment through the laser
therapy for the Macular Photocoagulation Study (MSP), through which it
was possible to confirm the benefits of the use of the thermo laser in the
treatment of the CNV, in comparison to the natural history of the disease.
It was assessed in the MPS, the use of the laser for the photocoagulation
of areas of the choroidal neovascularization. The photocoagulation
causes irreversible lesion of the neurosensory retina above the
neovascular membrane, precluding the maintenance of visual function in
the treated area. Due to this property, its use is limited to the treatment of
extrafoveal or juxtafoveal membranes, which benefits 10-15% of the
population of the patients bearing CNV secondary to AMD. Moreover, it
was observed that ±50% of the treated patients have recurrence of the
disease.
Photodynamic Therapy with Verteporfin (PDT)
The Photodynamic Therapy (PDT) is characterized by the intravenous
injection of a photosensitizer verteporfin (Visudyne; Novartis
Ophthalmics), followed by irradiation of the CNV with a laser which
wavelength corresponds to the peak absorption (excitation) of the
photosensitizer (690nm), generating free radicals and a type of highly
reactive oxygen, called singlet, which is capable of causing lesion to cell
membranes and the endothelium leading to selective intravascular
thrombosis of the CNV. Two large multicentric studies assessed the
efficacy and safety of this therapy. The treatment with PDT was studied and indicated for patients with predominantly classic CNV, being in study its use in minimally classic or occult membranes, restricting its use to less than 25% of the total number of patients affected by exudative AMD. Within the group of treated patients, in average 15% present visual acuity improvement, 20% achieve stabilization and 65% have deterioration of the visual acuity. The average rate of applications required in the first Clinical Applications for Opto Advant 532 year is 3.4 and in the second year, 2.1, and more than 90% of the
patients require re-treatment after 3 months from the initial therapy.
Alternative Forms under Investigation

Transpupillary Thermotherapy (TTT)
The Transpupillary Thermo Therapy is a technique used in
Ophthalmology for more than 10 years in the treatment of choroidal and
retinal tumours such as hemangiomas, melanomas and retinoblastomas.
It was first used in the treatment of choroidal neovascularization in
patients with AMD in the late 90’s. Reichel et al assessed in a study the
effect of TTT after 13 months in 16 eyes of 15 patients with exudative
AMD and found: improved acuity in 19% of the eyes; stabilized acuity in
56% and deterioration of the acuity in 25%. An 810nm wavelength diode
laser is used for the treatment of AMD with the TTT technique. At this
wavelength the absorption of the laser by the neurosensory retina is low
and the absorption by the choroid (where the neovascularization in
patients with AMD is located) is high. Despite being potentially
efficacious, this therapeutic modality requires more studies that confirm
its efficacy and generate a standard protocol for the possible technique to
be used. To date, no controlled study has been undertaken.
Anti-angiogenic Treatment
A new perspective in the treatment of CNV with medication is currently
being designed, through the control of the stimulus of the neovascular
growth (angiogenesis). Various angiogenic drugs have been rigorously
studied. Studies in phase III evaluated the use of angiogenic drugs such
as the anti-VEGF rhuFab and the Anecortave Acetate. A third study
already performed (aptamer anti-VEGF) showed favourable results for
the 3 subtypes of CNV aforementioned. The clinical use of Triamcinolone
Acetonide, an intravenously applied corticosteroid, has been proposed
due to its assumed angiogenic property, especially when associated to
the Photodynamic Therapy (PDT).
Indocyanine Green-Mediated Photothrombosis (i-MP)
Costa et al proposed in 2001 a new therapeutic modality for the treatment
of Exudative AMD. Indocyanine Green-Mediated Photothrombosis (i-MP)
is based in the use of intravenous Indocyanine Green (ICG), followed by
irradiation with infrared laser, obtaining the selective closure of the CNV
through a combined process of thrombosis and phototherapy which is
The ICG dye is widely used in ophthalmology for the study of the choroidal circulation. Through the ICG angiography it is possible to observe the uptake of photosensitive dye by the choroidal neovascularization and obtain objective data for the indication of this Clinical Applications for Opto Advant 532 The ICG absorbs and emits light in the wavelength near infrared
(805nm), and due to this property, it can be stimulated by the infrared
diode laser at 810nm. Many studies have demonstrated the uptake of
ICG in the neovascular membranes and, due to this, it is assumed that
ICG has the capability to potentiate the laser in that tissue. It is also
suspected that it can trigger the generation in cascade of “singlet” oxygen
and the consequent selective thrombosis of the choroidal vascularization.
In fact, pilot studies demonstrated efficacy in the elimination of choroidal
vessels with minimal or no damage to the retina after i-MP. Due to the
selective thermo-dynamic effect induced by the ICG, it is not necessary to
use the laser in the same power levels of TTT, to achieve occlusion of the
choroidal vessels. The longer wavelength of the infrared laser allows
lower absorption by the retinal tissue, leading to lower collateral effects
than the green, yellow or red light, thus reducing the risk of causing
iatrogenic retinal burn.
Indocyanine Green (ICG)
The Indocyanine Green (ICG) dye is approved by the FDA in the United
States of America and is widely used for more than 30 years in liver
disease studies and, in Ophthalmology; it has been used for studying the
circulation of the choroid.
The Indocyanine Green is a hydrosoluble dye, with fluorescence
activated in the wavelengths between 790 – 805nm (infrared light), which
makes it ideal for the study of deeper structures, such as the choroid. In
blood, it circulates 98% attached to the plasma proteins, mainly to the
globumines.
Note: reference materials, including clinical papers available upon
request from Opto Global. For personal research only

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