Laser is an abbreviation for (Light Amplification by Stimulated Emission of Radiation). The concept of ocular therapy using light was published first by Meyer-Schwickerath, who used the sunlight to treat patients with ocular melanoma in 1949. On the other hand, many experiments on retinal damage from sunlight were performed in the late 1800's, but they are not published.
Monochromatic, Coherent, & Collimated
Lasers have properties to produce highly monochromatic coherent beam that is collimated and has limited divergence. Monochromatic electromagnetic wave means that it has single wavelength eliminating chromatic aberration. Coherence of lasers is classified as either spatial or temporal. Spatial coherence allows precise focusing of the laser beam to widths as small as a few microns, while temporal coherence allows selection of specific monochromatic wavelengths within a single laser or a group of lasers. Practically, spatial coherence, allow extremely small burns to pathologic tissue, with minimal disturbance to surrounding normal tissue; on the other hand, temporal coherence allows treatment of specific tissue sites by selecting laser wavelengths that are preferentially absorbed by these tissue sites.
Principles of Laser Emission
Atoms are composed of a positively charged nucleus and negatively charged electrons at various energy levels. Light is composed of individual packets of energy, called photons. Electrons can jump from one orbit to another by either absorbing energy and moving to a higher level (excited state), or emitting energy and transitioning to a lower level. Such transitions can be accompanied by absorption or spontaneous emission of a photon.
“Stimulated Emission” is the interaction of an atom in the excited state with a passing photon leading to photon emission. The emitted photon by the atom in this process will have the same phase, direction of propagation, and wavelength as the “stimulating photon”. The “stimulating photon” does not lose energy during this interaction it simply causes the emission and continues on. For this stimulated emission to occur more frequently, the optical material should have more atoms in an excited state than in a lower state.
Laser System and Media
The lasering medium is contained in an optical cavity (resonator) with mirrors at both ends, which reflect the light into the cavity and thereby circulate the photons through the lasing material multiple times to efficiently stimulate emission of radiation from excited atoms. One of the mirrors is partially transmitting, thereby allowing a fraction of the laser beam to emerge. The lasing medium can be Solid (e.g, Ruby laser, neodymium-doped yttrium aluminum-garnet (Nd:YAG) ), Liquid : (e.g Fluorescent dye ) or Gas (e.g, Argon , Krypton ). Lasers can be pumped by continuous discharge lamps and by pulsed flash lamps. Laser pulse durations can vary from femtoseconds to infinity.
Laser- Tissue Interaction
Laser-tissue interactions can occur in several ways:
Photothermal (photocoagulation and photovaporization)
Photothermal effects include photocoagulation and photovaporization. In photocoagulation, absorption of light by the target tissue results in a temperature rise, which causes denaturization of proteins. Typically, argon, krypton, diode (810nm) and Frequency doubled ND:YAG lasers cause this type of effect. Photovaporization occurs when higher energy laser light is absorbed by the target tissue, resulting in vaporization of both intracellular and extracellular water. The advantage of this type of tissue response is that adjacent blood vessels are also treated, resulting in a bloodless surgical field. The carbon dioxide laser, with its wavelength in the far infrared (10,600 nm), uses this method of action.
Photochemical (photoablation and photoradiation)
Photochemical effects include photoradiation and photoablation. In photoradiation, intravenous administration of photosensitizing agent, which is taken up by the target tissue, causes sensitization of the target tissue. Exposure of this sensitized tissue to red laser light (690 nm) induces the formation of cytotoxic free radicals. Photoablation occurs when high-energy laser wavelengths in the far ultraviolet (< 350 nm) region of the spectrum and are used to break long-chain tissue polymers into smaller volatile fragments. The exposure times in the photoablation process is usually much shorter (nanoseconds) compared to photoradiation. Photodynamic therapy (PDT) is an example of photoradiation therapy while Excimer laser is a photoablative process.
In Photoionization high-energy light (1064 nm) is deposited over a short interval to target tissue, stripping electrons from the molecules of that tissue which then rapidly expands, causing an acoustic shock wave that disrupts the treated tissue. The ND:YAG laser works via a photodisruptive mechanism.
Laser Types in Retina
Argon blue-green laser (70% blue (488 nm) and 30% green(514nm))
Absorbed selectively at retinal pigment epithelial layer (RPE), hemoglobin pigments, choriocapillaries, inner and outer nuclear layer of the retina. It coagulates tissues between the choriocapillaris and inner nuclear layer. The main adverse effects of these lasers are high intraocular scattering, macular damage in photocoagulation near the fovea, and choroidal neovascularization (if Bruch's membrane is ruptured).
Frequency-doubled Nd-YAG Laser (532 nm)
Highly absorbed by hemoglobin, melanin in retinal pigment epithelium and trabecular meshwork. It can be used either continuously or in pulsed mode.
PASCAL (Pattern Scan Laser) is one such type of laser that incorporates semi-Automated multiple pattern, short pulse, multiple shots with precise burn in very short duration using frequency-doubled Nd-YAG Laser (532 nm). It is commonly used nowadays in treatment of many retinal conditions (proliferative diabetic retinopathy, diabetic macular edema, vein occlusions etc.). It has many advantages when compared with conventional single spot laser, as it is produced at a very short duration (10-20 msec) compared to (100-200 msec) of conventional single spot one which leads to less collateral retinal damage. Other advantages include relatively stable scar size, less destructive same efficiency. It also permits the application of different patterns that gives more regular spots on retina with less duration.
Krypton red (647 nm)
Well absorbed by melanin and can pass through hemoglobin which makes it suitable for treatment of subretinal neovascular membrane. It also has low intraocular scattering with good penetration through media opacity or edematous retina and has ability to coagulate the choriocapillaries and the choroid.
Diode laser (805-810 nm)
It is well absorbed by melanin. The near to infrared spectrum (near invisible) makes it more comfortable to use due to absence of flashes of light. It has very deep penetration through the retina and choroid making it the laser of choice in treatment of Retinopathy of Prematurity (ROP) and some types of retina lesions. It is also used via trans-scleral route to treat the ciliary body in some cases of refractory glaucoma.
Laser-Tissue Absorption in the Retina
Found mainly in the RPE (Retinal pigment epithelium) and choroid, and absorbs mainly wavelength between 400-700 nm. The longer the wavelength of light, the more the melanin is penetrated. For example, Diode laser with wavelength of 810 nm can penetrate deeply into the choroid.
Located in the inner and outer plexiform retinal layers. It protects the photoreceptors from short-wavelength light damage, but can be damaged by blue light which is why Argon green is preferred in macular photocoagulation over Argon blue.
Absorption varies according to oxygen saturation. It absorbs yellow, green, and blue wavelengths, but red light is absorbed poorly. Thus, macular lasers may, uncommonly, damage retinal vessels.
Laser delivery systems
It is the most popular and common delivery system. Laser settings such as power, spot size and exposure time can be changed easily.
Commonly used via a fiberoptic cable to deliver diode or argon lasers. It is ideal in the treatment of peripheral retina e.g. peripheral breaks and cases of retinopathy of prematurity. The spot size is altered by the dioptric effect of the condensing lens used. It may even vary depending on the refractive status of the eye (i.e. in hyperopic eyes the spot size will be smaller, and in myopic eyes it will be larger).
It delivered mainly argon green and diode lasers. Often used during retinal detachment repair following pars plana vitrectomy and extrusion of the subretinal fluid or in the surgical treatment of proliferative diabetic retinopathy.
Micropulse laser therapy
Micropulse laser describes a method of retinal laser delivery and can be applied with lasers of different wavelengths, such as 532 nm, 577 nm, or 810 nm. This type of delivery essentially divides the treatment into repeated microsecond impulses with intervals separating these where the retinal tissue is allowed to cool down. The laser power is set to a low level, and in general, the spots are not visible on the retina; the intention is to treat the retina on a subclinical basis while avoiding thermal damage to the underlying retina that can occur with conventional photocoagulation. While this type of laser therapy appears to be safe, its efficacy continues to be debated.
Lenses Used for Laser Delivery
Selection of lens depend on many factors include, desired field of view, amount of magnification, area to be treated, and ophthalmologist preference. The commonly used contact lenses for panretinal and focal/grid retinal photocoagulation are listed in table 1 and 2. It is important to remember that most of the commonly used lenses magnify the image size; thus, the laser spot size on the machine must be set accordingly.
|Lens||Image Magnification||Laser Spot Magnification||Field of View|
|Mainster PRP 165||0.51x||1.96x||165-180◦|
|Volk Super Quad 160||0.50x||2.00x||160-165◦|
|Lens||Image Magnification||Laser Spot Magnification||Field of View|
|Mainster high magnification||1.25x||0.8x||75-88◦|
|Ocular PDT 1.6X||0.63x||1.6x||120-133◦|
|Volk area centralis||1.06x||0.94x||70-84◦|
Panretinal Photocoagulation for Treatment of Proliferative Diabetic Retinopathy
The Diabetic Retinopathy Study (DRS) established panretinal photocoagulation (PRP) as an effective treatment for high risk PDR which includes eyes with one of the three of the following risk factors: NVD greater than 1/3 disc area, any NVD with vitreous hemorrhage or NVE greater than half a disc area with preretinal or vitreous hemorrhage. The Early Treatment Diabetic Retinopathy Study (ETDRS) recommended careful follow-up without PRP for mild or moderate nonproliferative diabetic retinopathy. Laser settings for conventional retinal laser photocoagulation for diabetic retinopathy is typically performed with a continuous wave (cw) laser at 514 or 532 nm with exposure durations from 100 to 200 ms, spot sizes from 100 to 500 µm, and powers from 250 to 750 mW. If Patterned scanning laser is used, it typically utilizes settings of 532 nm wavelength, 200 µm spot size, 20 ms duration, and powers from 300 to 750 mW. Area of treatment reaches approximately 1300–1500 500 micron-sized burns spaced between one half and 1 burn width apart, beginning temporally just outside the vascular arcades and 3-disc diameters temporal to the macula, and extending to or just beyond the equator. Some providers prefer to divide treatment into two or more sessions while others elect to perform treatment in a single session. On the nasal side of the fundus, burns begin about 1-disc diameter nasal to the optic disc and also extend to or just beyond the equator. However, specific regimens vary by practitioner.
Treatment of Diabetic Macular Edema with Laser Photocoagulation
The ETDRS recommended macular laser for Clinically significant macular edema (CSME) which was defined as any of the following based on stereoscopic fundus examination:
- Retinal thickening within 500 µm of the foveal center;
- Hard exudates within 500 µm of the foveal center associated with adjacent retinal thickening; or
- Retinal thickening more than 1 disc area in size within 1 disc diameter from the foveal center
Focal photocoagulation is directed to microaneurysms more than 500 µm away from the foveal center. Treatment up to 300 µm from the foveal center is allowed if vision is 20/40 or worse. Grid photocoagulation is applied to areas of diffuse leakage and capillary non-perfusion on fluorescein angiography. Focal laser setting is a 50 to 100 µm spot size, 50 to 100 ms pulse duration, and power titrated to barely whiten the microaneurysm. Grid laser setting is a 50 to 200 µm spot size, 50 to 100 ms pulse duration, and power titrated to achieve mild burn intensities.
Transpupillary Thermotherapy (TTT)
A more intense, destructive modality, this is occasionally used for the treatment of choroidal melanomas, retinoblastoma, subfoveal choroidal neovascular membranes (CNVM) and other ocular tumors. TTT involves long exposures (~60 s) of a large spot (1.2–3 mm) at low irradiance (~10 W/cm2), using a near-infrared Diode (810 nm) laser that is thought to induce intralesional hyperthermia and subsequent vascular occlusion and lesion shrinkage.
Laser Photocoagulation in Branch and Central Retinal Vein Occlusions
In branch or central vein occlusions, retinal hypoxia occurs in the distribution of the occluded veins and may elicit a neovascular response in the affected area. Sector or panretinal photocoagulation is then the treatment of choice. It has been shown that macular grid laser photocoagulation can be used to treat persistent macular edema (> 3 months, vision worse than 20/40) resulting from branch vein occlusion with improvement of vision in some cases, although anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections have become the standard of care.
Laser Photocoagulation in Age-Related Macular Degeneration and Related Diseases
Thermal Laser Photocoagulation
Before the era of intravitreal injections, thermal photocoagulation with the argon blue-green laser or krypton red was the first-line of treatment for exudative age-related macular degeneration (AMD) in cases of extrafoveal CNVM. However, treatment of subfoveal and juxtafoveal lesions usually yielded a dense scotoma with a high recurrence rates for the CNVM.
Photodynamic Therapy (PDT)
PDT is a form of selective laser therapy, leading to closure of the choroidal neovascular process and other active proliferating vessels, while leaving normal retinal tissue unharmed. It was first described to treat exudative AMD and studied in the VIP/TAP clinical trials, although the gold standard in treating exudative AMD has since become anti-VEGF therapy. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin. Two year results of 2 randomised clinical trials—TAP report 2. Arch Ophthalmol 2001;119:198–207.</ref>. It works by photoradiation mechanism in which previously hematoporphyrin derivative and currently verteporfin (Visudyne) is used as a photosensitizing agent followed by local application of light in the absorption spectrum of that agent (i.e. 689 nm). This will release free radicals that destroy endothelial cells causing closure of hyperproliferative vessels, as in an actively growing tumor, or in an area of active choroidal neovascularization. It remains a useful adjuvant therapy for other intraocular vascular disorders, as well as posterior segment neoplasms. PDT is now frequently used for cutaneous and subcutaneous tumors. Treatment with PDT should be guided by a recent fluorescein angiography or indocyanine green study. A light dose of 50 J/cm2 (full-fluence PDT), or 25 J/cm2 (half-fluence PDT) has been described for the treatment of choroidal neovascularization of various conditions, in addition to other choroidal vascular pathologies, including chronic central serous choroidopathy, polypoidal choroidal vasculopathy, as well as choroidal neoplasms, such as circumscribed choroidal hemangiomas.
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