Lasers

Ophthalmology was the first medical specialty to use lasers, and uses more kinds than almost any other: to seal the retina, open a pathway for aqueous, cut a capsule, sculpt the cornea and activate a drug. Each works because of what laser light is, and each acts on tissue in one of a few ways, chosen by its wavelength, its power and how long it lasts.

#What makes a laser

Laser stands for light amplification by the stimulated emission of radiation. An atom or molecule in an excited state can be triggered by a passing photon to emit a second photon identical to the first: the same wavelength, phase and direction. A laser has three parts:

• a gain medium (a gas, a crystal, a dye or a semiconductor) whose atoms can be excited;
• a pump (a flash lamp, another laser or an electric current) that excites more atoms than remain in the lower state: a population inversion, so that stimulated emission outweighs absorption;
• an optical cavity, two mirrors facing each other through the medium, that sends the light back and forth, amplifying it with each pass. One mirror is partly transparent and lets the beam out.

The result is light that is monochromatic (one wavelength, so it can be matched to a tissue’s absorption), coherent (its waves keep in step, in time because the spectrum is so narrow and across the beam because it comes from one mode of the cavity, so it forms stable interference fringes, as in laser interferometry; OCT, by contrast, relies on low-coherence light, Chapter 19), collimated (it hardly spreads, so it can be focused to a tiny spot) and very bright. Many are also polarised.

The gain medium sets the wavelength: argon gas (488 nm blue, 514 nm green), krypton (647 nm red), argon fluoride, the excimer (193 nm ultraviolet), neodymium-doped yttrium aluminium garnet, Nd:YAG (1064 nm infrared, or 532 nm green when its frequency is doubled by a crystal), semiconductor diodes (810 nm infrared, among others), optically pumped semiconductor lasers (577 nm yellow), helium–neon (633 nm red, used for aiming beams) and carbon dioxide (10,600 nm). Lasers run continuously or in pulses: Q-switching stores energy and releases it in a pulse of a few nanoseconds, and mode-locking gives picosecond or femtosecond pulses.

#How lasers act on tissue

What a laser does depends on how intense the light is and how long it lasts, more than on its colour alone. Plotted as irradiance against exposure time, the clinical lasers fall into distinct regions:

• Photochemical: low irradiance for a long time triggers a chemical reaction. In photodynamic therapy, verteporfin collects in abnormal vessels and, activated by 689 nm light, generates reactive oxygen that closes them. Corneal cross-linking is photochemical too: riboflavin activated by 370 nm ultraviolet A (classically 3 mW/cm² for 30 minutes, 5.4 J/cm²) stiffens the stroma (Chapter 17).
• Thermal: absorbed light heats tissue. At about 60 °C proteins denature: photocoagulation, which seals and scars the retina in panretinal and focal treatment, and acts on the trabecular meshwork and iris. At higher temperatures water boils and tissue vaporises (photovaporisation, as with the carbon dioxide laser, which water absorbs strongly).
• Photoablation: each 193 nm ultraviolet photon carries enough energy to break the bonds of corneal molecules directly, removing a fraction of a micrometre per pulse with little heating of the tissue around (Chapter 17).
• Photodisruption: a very short pulse focused to a tiny spot reaches such a high irradiance (above about 10¹⁰ W/cm²) that it strips electrons from atoms, forming a plasma whatever the tissue’s colour. The plasma expands as a shock wave and cavitation bubble that cut tissue mechanically: the Nd:YAG laser for capsulotomy and iridotomy, and the femtosecond laser for flaps, lenticules and capsulotomies. Femtosecond pulses reach breakdown with a thousand times less energy, so their bubbles are tiny and their cuts precise.

Selective photothermolysis sits between these. In selective laser trabeculoplasty a 532 nm pulse of only 3 ns, over a 400 µm spot, heats the melanin granules of pigmented trabecular cells. The pulse is shorter than the time heat takes to diffuse out of a granule (its thermal relaxation time, about a microsecond), so the heat stays where it is absorbed and the surrounding meshwork is spared.

#Choosing a wavelength

A thermal laser works only where its light is absorbed, by a chromophore. Melanin, in the pigment epithelium, choroid and trabecular meshwork, absorbs across the visible and near infrared, more strongly at shorter wavelengths. Oxyhaemoglobin absorbs blue, green and yellow strongly but red hardly at all. The macular pigment xanthophyll absorbs blue. Water absorbs little in the visible but strongly in the infrared beyond about 1400 nm, which is why the erbium:YAG (2940 nm) and carbon dioxide (10,600 nm) lasers act only within micrometres of the surface, as in skin resurfacing, and why a far-infrared beam injures the cornea rather than the retina. The excimer laser’s 193 nm ultraviolet is absorbed by the proteins of the corneal stroma.

• Blue light is avoided in the macula: xanthophyll absorbs it in the inner retina, and it scatters more and is more photochemically damaging.
• Green (532 nm) is absorbed well by melanin and blood: the standard for panretinal and focal photocoagulation.
• Yellow (577 nm) lies at a peak of oxyhaemoglobin absorption with little xanthophyll absorption and less scatter: good for vascular lesions and near the fovea.
• Red and infrared (647 and 810 nm) pass through a cataract, vitreous haemorrhage and blood with little absorption, acting deeper on the pigment epithelium and choroid; the diode laser treats retinopathy of prematurity and, through the sclera, the ciliary body. Deeper burns hurt more.

#Power, spot size and irradiance

A burn depends mainly on the energy delivered per unit area. With power P (watts) spread over a spot of diameter d for a time t,

Because the area goes with the square of the diameter, halving the spot size quadruples the irradiance at the same power. Contact lenses for retinal laser change the spot size: a wide-field lens that minifies the view of the fundus magnifies the laser spot, about two times, so the same settings give a spot of twice the diameter and a quarter of the irradiance. Switching lenses mid-treatment without adjusting the power is a classic cause of too light, or too heavy, burns. (The power needed does not fall quite as steeply as the area, because heat escapes faster from a small spot; pigmentation, oedema and hazy media change it too, so every treatment is titrated to the burn it produces.)

Pulsed lasers are described by the energy of each pulse. The peak power is the pulse energy divided by its duration, so 1 mJ delivered in 4 ns is a peak power of 250 kW, while the average power is the pulse energy times the number of pulses per second, which may be only milliwatts.

#Lasers in the clinic

• Retinal photocoagulation (532 or 577 nm, sometimes 810 nm): panretinal treatment for proliferative retinopathy, focal treatment, sealing retinal tears. Pattern-scanning lasers deliver a pattern of short (about 20 ms) burns in rapid sequence with one press of the pedal; subthreshold and micropulse treatment aims to act on the pigment epithelium without a visible burn.
• Glaucoma: selective trabeculoplasty (Q-switched 532 nm); argon laser trabeculoplasty; Nd:YAG peripheral iridotomy, sometimes after thermal pretreatment of a thick, dark iris; iridoplasty; diode cyclophotocoagulation.
• Nd:YAG capsulotomy for posterior capsule opacification. The plasma expands toward the laser, so the beam is focused just behind the capsule to avoid pitting the IOL. A contact lens (such as the Abraham lens) widens the cone of the focused beam, giving a smaller, more intense focal spot with lower irradiance at the cornea and retina. The pressure can spike afterwards, and there is a small risk of retinal detachment, higher in high myopes.
• Cornea and lens: the excimer laser for PRK, LASIK and phototherapeutic keratectomy; the femtosecond laser (near infrared, about 1030 to 1060 nm) for LASIK flaps, SMILE, keratoplasty and laser-assisted cataract surgery.
• Photodynamic therapy with verteporfin and a 689 nm diode laser, now used mostly for central serous chorioretinopathy and polypoidal choroidal vasculopathy.
• Oculoplastics: carbon dioxide and erbium:YAG lasers, absorbed by water, for resurfacing and cutting.

#Laser safety

The eye focuses a collimated beam to a tiny spot on the retina, concentrating its irradiance up to about 100,000 times. Light from 400 to 1400 nm reaches the retina this way, the retinal hazard region; ultraviolet and far infrared are absorbed in the cornea and lens. Lasers are classified by their hazard (the power limits given are for continuous visible lasers): class 1 (safe in normal use), class 2 (visible, below 1 mW, protected by the blink reflex), class 3R (up to 5 mW, a small risk), class 3B (up to 0.5 W, hazardous from the direct beam and its mirror reflections) and class 4 (above 0.5 W, hazardous to the eye even from scattered light, to the skin, and a fire risk). Photocoagulators, delivering watts, are class 4, and most treatment lasers are class 3B or 4. Everyone in the room wears eye protection of the right optical density for the laser’s wavelength, which is marked on the goggles (OD = log₁₀ of the factor by which it attenuates, so OD 4 transmits one ten-thousandth); the beam is never aimed where a reflection could reach an eye; and the treatment area is controlled. The surgeon is protected by a filter in the delivery system. Infrared beams, such as those of Nd:YAG and diode lasers, are invisible, so their aiming beam is a separate visible laser.

Light can also harm the retina photochemically, without heating it, when exposure is long: solar retinopathy, and phototoxicity from operating microscopes and endoilluminators (Chapter 21). Ophthalmologists who used argon blue-green lasers showed reduced blue–yellow colour contrast sensitivity from reflected blue light, one reason blue was abandoned.

#Recap

• Stimulated emission + population inversion + optical cavity: monochromatic, coherent, collimated, bright light.
• Photochemical (PDT, long and gentle), thermal (photocoagulation), photoablation (193 nm excimer), photodisruption (Nd:YAG, femtosecond: plasma). Selective photothermolysis: a pulse shorter than the target’s thermal relaxation time (SLT).
• Melanin absorbs most wavelengths; oxyhaemoglobin blue to yellow; xanthophyll blue (avoid near the fovea); water the far infrared.
• Red and infrared pass through cataract and haemorrhage. Yellow suits vascular lesions and the macula.
• Irradiance = P / area: halve the spot, quadruple the irradiance. A wide-field lens doubles the spot: a quarter of the irradiance at the same power.
• Retinal hazard region 400–1400 nm. Class 4 is above 0.5 W (photocoagulators): wavelength-specific eye protection for everyone in the room.

#Test yourself

#Further reading

• American Academy of Ophthalmology, Basic and Clinical Science Course, Section 3: Clinical Optics and Vision Rehabilitation, section on lasers.
• M. A. Mainster, Wavelength selection in macular photocoagulation: tissue optics, thermal effects, and laser systems. Ophthalmology 93 (1986) 952–958.
• M. A. Latina and C. Park, Selective targeting of trabecular meshwork cells: in vitro studies of pulsed and CW laser interactions. Experimental Eye Research 60 (1995) 359–371.
• American National Standards Institute, ANSI Z136.1: Safe Use of Lasers.