Jphmedicalco Lasers in Retinal Diseases — A Subject Review Deepak Mishra, ONB* R. Kumar, MS* BP. Sinha, MS* Introduction Laser technology has brought a revolutionary change in the management of ophthalmic diseases, Laser tech- nology has been applied successfully in many problem. driven applications in which existing methods for treat- ment were inadequate or unacceptable. For example, laser photocoagulation for PDR has prevented blind- ress in great number of patients with diabetes mellitus. Because of the ability of a laser to generate an in- tense, collimated beam of radiation at a given wave- length, the laser is a unique instrument for ophthalmic use. Using the theories of Planck and Einstein, ‘Townes and Schawlow laid down the basic principles of the la- set”. This was followed by the construction of the first, visible laser by Maiman in 1960." Principles of Laser Theory °*° Atoms and molecules have distinet energy level. ‘Once raised to this higher energy level, the electrons are said to be in an “excited state.” For laser action to occur, itis necessary to excite a majority of the electron, in the ground state to an excited metastable state. ‘The rate at which the laser energy is delivered is im- portant because it helps determine the type of interac tion of the laser radiation with the exposed tissue. The rate of delivery depends on how the excitation energy is applied to the active medium and on how the reso- nance cavity is configured. The temporal ourput can be cither continuous of pulsed. Some lasers operate in a continuous mode where the emerging flow of photons A. Ainbastha, MS* RK, Satyapal, MS" is constant. The typical ophthalmic lasers that operate in the CW mode ate the At, Kr, He, Ne, and diode lasers. The power ouput of these lasers is typically on the order of miliwatts to wats Some lasers operate in a pulsed mode where the output lasts fom a few milliseconds to a few ferntoseconds. These pulses ean be single or a series of pulses. As a particular example of a pulsed laser, the Na: YAG laser can be operated in three different pulsed modes: free-running, Q-switched, or mode locked, Mechanism of Action Laser acts through different damage mechanisms; Photo thermal, Photochemical, Photo disruption (Photomechanical), Ocular Absorption Ocular ste ‘on wavelength cures absorb differentially depending Ultraviolet Region 1. Comea: In the UV-C (100 t0 280 nm) region, the cornea absorbs almost all of the radiation. In the UV-B (280 to 315 nm) and UV-A (315 to 400 nm) regions, the comea absorbs much of the radiation. 2. Lens: In the UV-B region, the lens absorbs most of the radiation that gets through the cornea. In the UV-A region, the lens absorbs the most. * Regional stitute of Ophthaalogy RO.) GUM. Patrica6 le (400 to 780nm) Region 1, Cornea and lens: Most visible radiation is trans- mitced through the comea and lens 2. Retina: Most visible radiation is absorbed in the retina by the hemoglobin, xanthophyll, and mela- rnin pigment. Infrared Re: 1. Retina: Most of the IR-A (780 to 1400 nm) is absorbed by the retina and choroid especially by the melanin in the retinal pigmented epithelium (RPE) 3 and the choroidal melanocytes. 2. Lens and comea: Some of the IR-A and a litle of the IR-B (1400 t0 3000 nm) is absorbed by the lens. Much of the IR-B and most of the IR-C {3000 to 10,000 nm) is absorbed by the cornea Type and Extent of Damage ‘The type and extent of damage is a function of a number of parameters A. Specific Body Organ on Tissue Expored The eye is the most susceptible to damage because of its variety of chromophores and because of the fo- cusing ability of the cornea and lens B. Wavelength Selective wavelength absorption allows the target tissue to be chosen by the selection of a particular wavelength. The depth of penetration is also selectable, C. Duration of Exposure ‘The dominant type of tissue damage can be selected primarily by picking the particular exposure duration. 1, For exposures lasting longer than about 10s that have an irradiance near threshold, the predomi- nant damage is photochemical. This is especially true for near-UV and blue exposures 2. For exposures in the region of microseconds to 10s, the predominant damage mechanism is pho- tothermal. The ophthalmic argon, krypton, dye, CO*, CW doubled Nd:YAG, and diode lasers op- crate in this region, 3. For exposures that last for less than 10s, the pri- ‘mary damage mechanism is photodistuption. The Nd:YAG and Ne:YLF ophthalmic lasers operate Highlights of Ophthalmology + Vl 3 in this region. For lasers that emit in the UV-C re- gion; like the ArP excimer, the damage mechanism can also be photochemical because of the highly energetic photons. Application of Lasers in Retinal Diseases Mainly Argon, krypton, Nd:YAG and diode lasers are commonly used in different retinal diseases, as follows (Table 1). 1, Central Retinal Vein Occlusion (CRVO) ‘The CRVO Study Group found that prophylactically trated ischemic eyes developed iris neovascularization less frequently than ischemic eyes that were followed (20% in the early treatment group versus 35% in the no-carly-treatment group), although the difference was not statistically significant, However, PRP is more likely to result in prompt regression of neovascularization of the iris in the previously treated group (56% versus 22%, respectively after one month), As a result, for ischemic CRVO, frequent follow-up examinations during the early months and prompt PRP if iris neovascularization develops is recommended treatment strategy. Pan retinal photocoagulation is applied in all four quadrants to give medium - white burns of dia- meter 400-500 microns (a total of 1000-2000 burns). 2, Branch Retinal Vein Occlusion (BRVO) BRVO Study found that a grid pattern laser treatment helped to reduce the macular edema and improved visual acuity. In patients who have 20/40 (6/12) or worse vision and macular edema on fluorescein angiography, laser treatment improved the chances of two co three lines of the Snellen chare when compared to untreated controls (65% versus 37%). Because visual acuity and macular edema may improve spontaneously, patients were not treated with laser for at least 3 months after the development of the vein obstruction, to allow for sponcancous improvement. Also, treatment was delayed if the intraretinal hemorrhage was too dense to allow either photocoagulation or Aluorescein angiography. Most patients required only one treatment. Typically a 50 to 100 microns spot size is used and medium- white burns, each of 0.1 second duration, are applied to the area of edema, In both treated and controlled groups,Jphmesica Table 1: Applications of Laser Wavelength (mm) 5435 (ren) anaes) rom ret ne: eae nen Cominaous CW) ee eer) Low-power Ophthalmology Possible Applications Aiming bers oy eee 488 (eg 5145 (gre) Gas ‘Argon Photochem Photchonsl Laser uaboclepaty Tecrsalvomy {sersdepiay etnalphstocogultion Photodyame evapy PDT) Oculplasti surgery Scaming as optthalmoscopy Taeermtre ye reared $31 (we) Set Gelom) ear es) Gu: Kington ow Pal Laser iidtony {ser tabecloplasy ‘Selo gery Retoal photocougulion PDT 10600 a) Ga C02 ow Photae ‘cutoplstiesugesy wa uv) “or Hunde ‘Laser nit eats (LAST Photterapeati heraeciomy (TR) {ser abeclar ablation Taser sles 532 (wee), aca) Sold ae ‘Neetu onan sysum, lama same mat ew ceswicked Photedinspion Guat) "Poca Poser aon Coty Ler tmbetlpay acne Geetbciegsation and E culos suzy 52 (ween) 1058 eae) Sold ae Neosymiem sonny, ‘alas ord cw) Pena atcha Modelocked Photoiption (used) Photothermal (CW) Totresromal PRK {isersnotmy {ter phaclss Taser eerny Poser epson 2540 (nid) Sold at Tear rs CW Pues ‘culo saaery oserphasly| Taser bit (ser sloateny Poser apslony 00-95 8 ‘shuninum rere hooters) Rein] photosoagaision {serpy {asersclonany ser utr ye {serabeelopaty (elopbotocgution Liter ponte ming beame Scanning ase optalnoscopy (Gps esherence tray (OCT) Real ser pore e200 WivisbierR) Florese dyes Photochem Photchon ‘Reina petosoaguiion Sao sry Taserieteny Taser sleoataey ase surely18 patients who had hypertension tended to respond less favorably to laser treatment. The BRVO Study Group also evaluated the efficiency and timing of ectorial PRP for retinal neovascularization and vitreous hemorthage. In patients with neovascularization treated with laser, only 29% developed vitreous hemorthage, versus 61% of those untreated. The data showed no advantage with treatment before neovascularization oceurted, even if capillary non-pesfusion existed. If laser is applied to all non-perfused BRVO, a large percentage of patients will be treated unnecessarily. A scatter pattern of laser is performed in the affected sector of neovascularization. ‘Typically, 500 microns sized medium- white burns are applied, extending from arcade out to periphery. Fill — in PRP may be applied if neovaseularization progeesses or if vitreous hemorthage occurs 3. Retinopathy of Prematurity Argon laser of diode laser is used co ablate the avas- cular retina in ROP The end point is near- confluent ablation, with burns spaced one half burns width apart, from ora- serrata up to, but not including the ridge up to 360. Laser is most effective for posterior Gone-t) disease 4, Diabetic Retinopathy ‘The Diabetic Retinopathy Study proved that argon. Jaser PRP significandly decrease the likelihood that an eye with high risk characteristics (HRC) will progress to severe visual loss. The goal of PRP is to arrest of cause regression of the neovascularization. The recom- mended therapy is 1200- 2000 burns, 500 microns, intense enough to whiten the retina which usually re- quires a power of 200- 600 mW and duration of 0.1 second. Most ophthalmologists use the argon blue- green or green laser, but a large clinical trial has shown that krypton red is equally effective. The number of burns necessary to achieve these goals has not been es- tablished. Some retinal specialists feel that there is no upper limic to the toral number of burns and that ment should be continued until regression occurs. The ETDRS found chat PRP significantly retards the devel- opment of high risk characteristics (HRC) in eyes with very severe NPDR and macular edema. Afier 7 yeats of follow up, 25% of eyes that received PRP developed HIRCas compared with, 75% of cyes PRP was deferred until HRC developed. Nevertheless, che ETDRS con- cluded the treatment of severe NPDR and PDR short of HRC was not indicated for three reasons. Fits, after Highlights of Ophthalmology + Vl 3 7 years of follow up 25% of eyes assigned to deferral of PRP had not developed HRC. Second, when pa- tients are closely monitored and PRP is given as soon as HRC develops, severe visual loss can be prevented. After 7 yeats of follow up, 4% of eyes that did not re- ceive PRP until HRC developed had a visual acuity of 51200 or less, as compared to with 2.5% of eyes as- signed to immediate teatment. The diflerence was nei ther clinically nor statistically significant. Third, PRP has significant complications. It often causes decreased visual acuity by increasing macular edema or by caus- ing macular pucker. Color vision and dark adaptation are impaired. 5. Macular Edema Dr. Amall Pace was fist to show that Argon photo- coagulation decreases or stabilizes the macular edema. Later, the ETDRS confirmed the results. The treat- ment study is to photocoagulate all leaking microaneu- rysms further than 500 microns from the center of the macula and to place a grid of 100-200 microns burns in atcas of diffuse capillary leakage and in atcas of capil- lary non-perfusion. The ETDRS and DRS conclusive- ly proved that timely laser photocoagulation of diabetic retinopathy can reduce the severe visual loss by 95%. 6. Sickle Hemoglobinopathies Cryotherapy, diathermy, xenon arc and argon laser photocoagulation have all been employed to treat pe- ripheral retinal neovascularization. Seater laser photo- coagulation of areas that surround sea-fan proliferation and associated areas of ischemic retina induces regres- sion of these lesions. Two laser techniques have been described, and both can induce regression of ‘neovas- culatization. The frst is localized or confined to areas anterior to the patent neovascular fronds. The seeond uses a 360 peripheral, circumferential retinal scatter technique to anterior retina, These techniques can be performed with light to moderate intensity burns, ap- proximately 500 microns in diameter placed one burn width apart 7. Coat’s Disease Laser photocoagulation is the treatment of choice in ld to moderate case of exudation from Coats disease. "The most extensive clinical experience has been with. the argon blue green laser, but more recentlyJphmedicalco have employed wave-lengths of light better absorbed by hemoglobin, such as the argon green — yellow and the diode green. Lesions that leak are treated directly with relatively large (200-500 microns) applications of | moderate-incensity light. 8. Age Related Macular Degeneration - Choroidal Neovascularization (Extrafoveal) Conventional laser photocoagulation and ocular photodynamic therapy (OPT) are the only proven laser treatments for neovascular AMD, having under- gone extensive study in large, prospective, random- ied tials. Other laser modalities currently under consideration include feeder vessel photocoagulation and vanspupillary thermotherapy. Lesions considered eligible for photocoagulation by MPS criteria should contain some classic CNV but may manifest occult NV. There may be associated blood, blocked fluo- rescence not corresponding to visible blood, or serous PED, provided the total atea of these components is less than the area of any classic and occult CNV. Laser photocoagulation is performed using initial treatment setting of 200 microns spot size, 0.2-0.5 second du- ration, and 100-200mW power. The lesion is treated so that the end result is a uniform, confluent, yellow- white laser burn. Photocoagulation should cover the entire lesion and extend 100 microns beyond the pe- ripheral boundaries of all lesion components except blood. For recurrent lesions, treatment should extend 100 microns beyond the perimeter of the lesion, ex- cept atthe interface of the recurrence and the previous area of photocoagulation, where the laser treatment should extend 300 microns into the area of previous laser reatment. Feeder vessels, when identified, should be treated for at least 100 microns on both sides, and 300 microns radially at the origin of the feeder vessel Complications associated with laser photocoagulation include hemorrhage, perforation of Bruch’s mem- brane, RPE teas, and arteriolar narrowing. Persistent or recurrent CNV after photocoagulation is expected. 9. Central Serous Chorioretinopathy (CSC) When indicated, the laser treatment of CSC is photocoagulation to the site of fluorescein leakage. The technique of laser photocoagulation involves using a green —wavelength laser to produce a light scar over the focal RPE leak. Typically, 6-12 laser burns of 50-200 microns spot size at 0.1 second duration and 75-200 ‘mW are used. Permanent RPE change is induced at the site of the laser scar. It has been suggested that while the scar facilitates the absorption of subretinal fluid via the choroids, it also destroys an area of abnormally hypersecreting RPE cells, The only definice benefit from laser therapy isis ability to decrease the duration of the neurosensory detachment. 10. Retinal Breaks ‘Two main modalities are utilized in the treatment of retinal breaks ~ cryopexy and laser photocoagulation Laser photocoagulation treatment of retinal breaks typically utilizes the argon green, argon blue — green, krypton red, or diode laser. No evidence exists that one wavelength is better than another. Two main delivery systems are used, the slit lamp and the indirect ophthalmoscope. In contrast to cryotherapy, chorio- retinal adhesion develops instantently when the laser photocoagulation is applied, but maximal adhesion oceuts 7-10 days later. The Goldmann three ~ mirror lens or panfundoscope lens may be used when treat- ment is through the slit-lamp delivery system. The tear should be surrounded completely by three to four rows of laser burns. Although the spots need not be con- fluent, thete should be no mote than half a spot size of untreated retina between burns. Typically, the settings are 200-500 microns spot size and 0.1-0.2 seconds application at the power necessary to generate a gray-whie burn. The indirect laser delivery system can also be used to treat retinal breaks. An advantage of this technique is that simultaneous scleral depression allows treatment of anterior tears and even dialysis. As with eryopexy, care should be taken to reat thoroughly the anterior margin of horseshoe tears to prevent ante- rior traction that reopens the break. 11, High Myopia Myopia ~ related choroidal neovascularization is a major cause of visual loss, especially when located in a subfoveal location, Excrafoveal choroidal neovascu- larization may also be treated with argon laser photo- coagulation. Confluent argon laser burns of diameter 100 ~ 200 microns delivered over 0.2 ~0.4 seconds are most effective.20 Ocular Photodynamic Therapy (OPT)® OPT is a more advanced technology that uses low- energy light to activate an intravenously injected pho- tosensitizing agent and induce closure of a choroidal neovascular complex. The goal of OPT is to specifical- ly target neovascular tissue while sparing surrounding and overlying retinal structures. No immediate, per- manent laser-induced scotoma is produced, and there is no corresponding RPE defect. The mechanism of action of OPT involves delivery of a photosensicizing agent to its site of action, followed by activation with vwavelength-specific light. Benzoporphyrin derivative monoacid (Verteporfin) is the only approved photo- sensitizer for OPT. Dosage is determined by body sur- face area (6mglm). The drug is infused intravenously over 10 minutes, followed by energy laser light for 83 seconds using a wavelength corresponding to its peak absorption at 689 nm and a fluence of 600mW /cm* A treatment spot size is chosen 1000m larger than cov- ‘erage of the neovascular complex. Afcer treatment, in- dividuals are advised co avoid disect sunlight or bright illumination for 5 days to prevent phototoxicity to ex- posed body surfaces. The most common side effects include visual disturbances (blurred vision, decreased vision, visual field defect) and injection site events (ex- travasation, rash). Allergic reaction and back pain have also been reported. Over dosage of the drugs or light may result in non-perfusion of the retinal vasculature, swith subsequent severe visual loss from macular infare- tion, OPT has generally replaced conventional laser photocoagulation for the treatment of predominantly subfoveal CNV due to AMD. Highlights of Ophthalmology + Vl 3 Transpupillary Themotherapy Ik is currently the focus of a large, randomized, prospective trial for the treatment of occult subfoveal CNV due to AMD. This technology uses subthreshold laser irradiation with long exposure duration and a large spot size to thermally treat CNV. The induced tissue temperature rise is estimated at 10 Celsius, well below the 42° rise encountered with laser photocoagulation. Using an 810 nm ~ diode laser, ttansmisted energy penetrates the RPE and choroids, minimizing absorption by the neurosensory retina. Proposed mechanisms of CNV closure include vascular thrombosis, apoptosis, and thermal inhibition of angiogenesis, References 1 Schau, Tounas CH, nares and optical lasers. Phys Rav 112: 1940-1949 (1958), 2, Maiman TH. Stimulated opal raion n ry. Natura 187 498-494 (1960), 3 Hecht J. Undorstancing lasrs. An entry tool gi. 2nd tio. Naw Yr EEE Pros, 1994, 4, ‘Sivast WT. Laser fundamental, New York: Cambridge Unies Pres, 1996, ‘5, Slay O, Wobarsh M, Safely with Lasers and Other Optical Sources: ‘A Comorehensve Handocok Naw Yor: Plenum ress, 1980.