Semiconductor Diode Laser Photocoagulation in Retinal Vascular Disease MARK W. BALLES, MD,t CARMEN A. PULIAFITO, MD,t DONALD J. D'AMICO, MD,t JOHN J. JACOBSON, MD,l REGINALD BIRNGRUBER, PhD2
Abstract: The authors successfully performed clinical transpup illary retinal photocoagulation in 30 eyes of 26 patients with retinal vascular disease using a gallium-aluminum-arsenide (GaAIAs) diode laser emitting at 805 nm. Retinal photocoagulation was performed at treatment powers of 300 to 1300 mW and exposure durations of 0.2 to 0.5 seconds with a 200-1Lm diameter treatment spot. Patients treated with both diode and argon green lasers required 4.5 ± 1.8 times greater mean laser energy with diode compared with argon to create ophthalmoscopically similarlesions. Parallel experimental retinalphotocoagulation in Chinchilla rabbits required 3.1 ± 0.9 times more power to create ophthalmoscopically similar lesions with the diode laser than with the argon laser. Intraoperat ive subretinal hemorrhage occ urred rarely in patients with an incidence of 4 (0.044%) of 9021 treatment spots . Patients complained of moderate-tomarked pain in 10 (43%) of 23 treatments initiated under topical anesthesia. A transpup illary diode laser may be used clinically to perform therapeutic retinal photocoagulation. Ophthalmology 1990; 97: 1553-1561
The current treatment of many retinal vascular diseases involves laser photocoagulation of the retina. The risk of severe visual loss associated with proliferative diabetic retinopathy, clinically significant diabetic macular edema , branch and central retinal vein occlusion , and subretinal neovascularization is decreased after argon or krypton laser photocoagulation. 1-1 0 Originally received : March 21 , 1990 . Revision accepted : May 25, 1990 . Laser Research Laboratory, Dep artment of Op hthalmology, Massac husetts Eye and Ear Infirmary , Harvard Medical Scho ol, Bost on. 2 Wellman Laborato ries of Photomedi cine, Harvard Medical School, Boston. 1
Supported in part by NIH gran ts 5 ROI GM354 59 -04 and IRE 4074 71, and ONR contract NOOO14-K0117 . The author s certify that they have no affiliation with or financ ial involvement in any organi zation or entity with a direct financial interest in the subject matter or materials discussed in this article. Reprint requests to Carmen A. Puliafito, MD, Laser Research Lab oratory, Massachusetts Eye and Ear Infirmary , 243 Charles St, Boston , MA 02114 .
The semiconductor laser diode was developed in 1962, but practical medical therapeutic applications have been limited by relatively low power outputs. Recent advan ces in semiconductor technology have led to the development of gallium aluminum arsenide (GaAIAs) laser diodes which can emit continuous wave monochromatic coherent laser light in excess of I W. The light emitted by currentl y available laser diodes is in the near infrared with wavelengths from 780 to 840 nm. At this comparatively long wavelength, light penetration through cataract and hemorrhage is improved compared with blue, green, yellow, or red laser light. I I Preclinical diode laser retinal photocoagulation has been described using endophotocoagulation and transpupillary delivery systems. 12-1 6 Initial clinical experience with diode laser transpupillary retinal photocoagulation in 33 eyes with various retinal vascular diseases was reported by McHugh and co-workers' ? in England in 1989. These authors reported no treatment associated complications and minimal patient discomfort. We report our results of clinical transpupillary retinal photocoagulation using a
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semiconductor GaAIAs laser diode in 30 eyes with retinal vascular disease.
METHODS PATIENTS
Study patients were recruited from the Retina Service at the Massachusetts Eye and Ear Infirmary between August 1989 and November 1989. Patients with retinal vascular disease meeting standard accepted criteria for laser photocoagulation were enrolled after informed written consent was obtained. We treated 30 eyes in 26 patients; 18 eyes had received prior retinal photocoagulation (Table 1). Patients ranged in age from 30 to 87 years (mean, 56 years). Twelve patients were women and 14 were men. Seventeen eyes were treated for proliferative diabetic retinopathy, five eyes for choroidal neovascular membrane (CNVM) associated with age-related macular degeneration, four eyes for branch retinal vein occlusion (BRVO), two eyes for central retinal vein occlusion (CRVO), one eye for clinically significant diabetic macular edema, and one eye for macular edema associated with Coats' disease. Follow-up evaluation is available in all 30 eyes at 5 to 31 weeks after treatment (mean follow-up, 4 months). Treatment. Color fundus photographs were obtained in all patients before treatment; intravenous fluorescein angiography was performed in the standard fashion preoperatively in those patients with CNVMs, BRYO, CRVO, diabetic macular edema, and macular edema secondary to Coats' disease. Before treatment, the patient's Snellen acuity was measured and the pupils were dilated with topical tropicamide hydrochloride 1% and phenylephrine hydrochloride 2.5%. Corneal anesthesia was obtained with topical proparacaine hydrochloride; nine eyes also received 3 ml lidocaine 2% retrobulbar anesthesia delivered through a 25-gauge Atkinson needle. Three of five patients with macular CNVM underwent indocyanine green (ICG) infrared videoangiography 20 minutes before laser photocoagulation. Angiography was performed using ICG (5 rug/kg) injected into a peripheral arm vein followed by a 5-ml normal saline flush." The presence and localization of dye at the site of the neovascular membrane was confirmed by infrared videoangiography immediately before initiating diode laser photocoagulation. Indocyanine green accumulates in and around subretinal neovascular nets after being cleared from the surrounding circulation.l'' thereby acting as a chromophore for selective absorption of 805-nm laser light, potentially enhancing thermal damage to neovascular membranes (unpublished data, Balles MW et al, presented at the 1990 AR VO Annual Meeting). A single stripe GaAIAs diode laser (Candela Lasers, Inc, Wayland, MA) was coupled to a standard slit lamp (Zeiss 30-SL, West Germany) through a 200-J.Lm diameter fiber optic. The focused diode laser spot had a 200-J.Lm diameter, an 110 full cone angle, and a maximum power output of 1300 mW. Transpupillary retinal photocoagulation was carried out in the standard fashion using a pan-funduscopic Rodenstock (Rodenstock, Danbury, 1554
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CT), Mainster (Ocular Instruments, Bellevue, WA), or Goldmann lens, giving calculated retinal laser spot diameters of 280, 210, and 220 J.Lm, respectively. Hydroxypropyl methylcellulose 2.5% was used to provide mechanical and optical contact between the cornea and treatment lens. Photocoagulation was performed using 300 to 1300 mW (measured at the cornea) and exposure durations of 0.2 to 0.5 seconds. Power and exposure duration were adjusted and recorded during each treatment to obtain gray-white retinal lesions. Treatments were imaged with a high-resolution color video camera attached to a beam splitter on the slit lamp and recorded on 3/4-inch magnetic videotape. Wide-angle color fundus photographs were obtained 30 minutes after treatment and on follow-up examination. Intravenous fluorescein angiography was performed in the standard fashion when indicated. Patients were questioned at the completion of each treatment session regarding discomfort, sensation of "flash" or other subjective comments. The clinical impression of the treating physician also was recorded. ANIMAL STUDY
Four Chinchilla gray-pigmented rabbits, weighing 2 to 3 kg, were anesthetized with intramuscular ketamine hydrochloride (50 mg/kg) and xylazine (2 mg/kg) and with topical proparacaine hydrochloride. Both eyes ofeach animal were dilated preoperatively with topical tropicamide hydrochloride 1% and phenylephrine hydrochloride 2.5%. An OGFA contact fundus lens (Ocular Instruments) and methylcellulose were placed on the cornea to allow visualization of the central fundus with conventional slitlamp delivery systems. An argon green laser emitting at 514 nm and a single stripe GaAIAs diode laser emitting at 840 nm were used to create a series of retinal coagulations in the central fundus by transpupillary slit-lamp delivery. Exposure duration and retinal spot size were held constant at 100 ms and 150 J.Lm, respectively. The laser power for both wavelengths was chosen to produce three different classes of retinal effects ranging from the ophthalmoscopically visible threshold through mild-tostrong retinal lesions. A total of 227 argon laser coagulations and 250 diode laser coagulations were placed in the central fundus in eight eyes of four rabbits. Color fundus photographs (Canon CF-60ZA fundus camera, [Lake Success, NY)) were taken 2 hours and 7 days after laser treatment.
RESULTS CLINICAL TRIAL
We successfully created clinical retinal coagulations using a GaAIAs diode laser with a modified slit-lamp transpupillary delivery. Fairly uniform gray-white round retinal lesions could be produced at treatment powers of 300 to 1300 mWand exposure durations of 0.2 to 0.5 seconds. Scatter panretinal photocoagulation lesions were noted to have a creamy white appearance initially and develop chorioretinal scar formation similar to argon laser
V1 V1 V1
-
PRP PRP PRP
PRP PRP PRP PRP PRP PRP PRP PRP PRP PRP Macula, focal Macula, local] Macula, tocalt macula, focal Macula, tocalt PRP, sector Macula, grid Macula, grid PRP, sector PRP Macula, grid PRP, sector Macula, focal
PDR, VH PDR, NVD PDR, NVE
PDR, VH PDR, VH PDR PDR, NVD PDR, CSME, NVE PDR, VH , CSME PDR, NVD PDR, NVD, VH PDR PDR, NVD CNVM, AMD CNVM, AMD CNVM, AMD CNVM, AMD CNVM, AMD BRVO, NVE, VH BRVO, CSME BRVO, CSME BRVO, NVE, VH CRVO, ischemic CRVO, CSME Coats' disease PDR, CSME
5 6 7
8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 400 1100 1050 750 1175 1250 1000 1000 725 1000 800 900 1200 500 800 500 650 700 330 975 1200 600 1000
1000 1000 350
650 750 800 800
Mean Power Diode (mW)
0.2-0.5 0.2-0.3 0.2-0.5 0.2-0.5 0.2-0.3 0.2-0.35 0.2-0.4 0.2-0.4 0.2-0.3 0.3-0.5 0.5 0.2-0.5 0.5 0.5 0.2 0.2-0.5 0.2 0.2-0.5 0.2 0.2-0.5 0.5 0.2 0.2
0.2 0.2-0.5 0.2
0.2-0.5 0.2-0.5 0.2 0.2
Duration (sees)
140 275 368 263 294 344 300 300 181 400 400 315 600 250 160 175 130 245 66 341 600 120 200
200 350 70
228 263 160 160
Mean Energy Diode (mJ) Argon green PRP* Argon green PRP* Argon green PRP* Krypton red macular grid None Argon green PRP ' Argon green macular grid Argon green PRP ' Argon blue-green Argon green PRP ' Argon green PRP ' None Argon green parafoveal None None None Argon green PRP ' None None None Dye yellow, focal macula Dye yellow, focal macula Argon green PRP ' Dye yellow and red PRP None None None None Argon green PRP ' Argon green PRP
Other Laser Treatments
-
-
-
350 -
-
280
-
0.1-0.2
-
-
-
53
28
-
-
0.1
48
80 30
24
50
70 62 105
20/60 20/260 20/10020/133 20/2520/50 20/2520/60 20/2520/301/200 20/200 4/200 20/4020/260 20/5020/100 20/260 20/20 20/133 20/5020/133 20/40-3
20/4020/3020/60
20/2520/40+ 20/4020/30
HM
20/60 20/130 20/60 20/100 20/3020/7020/40 20/50 20/30 20/501/200 20/400 5/200 20/50 20/400 20/50+ 20/6020/400 20/25 20/200 20/40+ 20/60
20/80 20/3020/30
20/30+ 20/30 20/3020/30
13 8 16 24 12 9 11 10 9 10 5 26 20 7 22 15 27 5 16 32 15 14 22
14 7 15
31 23 23 19
Mean Energy Visual Acuity Argon Green Follow-up (mJ) Pretreatment Posttreatment (wks)
-
-
-
-
0.2
-
-
-
240
-
-
-
-
-
-
0.2 0.1-0.2
-
0.2
-
400 200
120
-
0.2
-
-
250
0.2 0.2 0.2
350 310 525
Mean Power Duration Argon (mW) (sees)
t Choroidal neovascular membrane treated after indocyanine green administered.
• Diode and argon green PRP in same eye.
PDR = proliferative diabetic retinopathy; PRP = scatter panretinal photocoagulation; NVE = neovascularization elsewhere; VH = vitreous hemorrhage; NVD = neovascularization of the disc; CSME = clinically significant macular edema; CNVM = choroidal neovascular membrane; AMD = age-related macular degeneration; BRVO = branch retinal vein occlusion; CRVO = central retinal vein occlusion; HM = hand motions.
PRP PRP, sector PRP, sector PRP
PDR PDR, NVE PDR, NVE PDR, NVE
Diagnosis
Treatment Diode Laser
1 2 3 4
Patient No.
Table 1. Clinical Diode Laser Photocoagulation in Retinal Vascular Disease
}>
OJ
rn
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c r
o
0 --t 0 0 0
I
\l
:0
m
(j)
s;:
0
-c
0
20 70
90
110
130
150
170
190
210
230
250
Diode laser power (mW)
Fig 6. This graph illustrates the power required in each of eight Chinchilla rabbit eyes (represented by squares) to produce retinal lesions with the argon green laser (514 nm) that appear ophthalmoscopically similar to lesions produced with the diode laser (840 nm). The central line represents the linear regression plot of these data points. The slope of this line (3.1) is the factor by which the argon laser power would have to be multiplied to produce a similar retinal lesion with the diode laser at 840 nm. The upper and lower curves represent the 95% confidence limits of this linear regression.
patients to complete treatment. The authors stated that their patients tolerated the treatment well and commented on absence of noise during treatment as an optical filter protects the operator instead of a mechanical shutter common in current visible light emission lasers (e.g., argon and krypton). Patients were not aware of a bright "flash" during laser treatment which may sometimes contribute to patient anxiety."? Analysis of the power required to create a retinal photocoagulation lesion in our patients and in parallel experimental retinal photocoagulation in the rabbit indicates that the diode laser requires three to four times as much power or longer exposure duration to create clinical photocoagulation lesions than comparable treatment with the argon green laser. Our clinical and experimental observations are in agreement with the experimentally measured absorption of light energy by the retinal pigment epithelium and choroid. Compared with the 95% absorption of argon green light at 514 nm, only 20% of diode laser light at 800 nm incident on the retina is absorbed by the retinal pigment epithelium and choroid. 19 Assuming that the product of total energy absorption (in the retinal pigment epithelium and choroid) and laser power should be the same to produce similar retinal coagulations with different wavelength light sources, a diode laser emitting at 800 nm would need to supply 4.8 times as much power as an argon laser emitting at 514 nm to produce similar retinal coagulations due to this wavelengthdependent difference in energy absorption in the retinal pigment epithelium and choroid. Of course, less intense retinal lesions could be produced with lower diode laser power, however, this would represent a divergence from the standard clinical treatment endpoint used in the randomized, controlled trials of laser photocoagulation. 1-10
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Choroidal hemorrhage and rupture of Bruch's membrane was observed in four eyes with an incidence of 0.044% of all treatment spots in our series. We attempted to minimize this complication by using relatively longer exposure durations, with a mean of 0.33 second, and minimizing overtreatment. Peyman and co-workers" compared argon blue-green and krypton red (647 nm) laser retinal lesions in cynomolgus monkeys and showed that rupture of Bruch's membrane and choroidal hemorrhage occurred frequently with the longer wavelength krypton laser when short coagulation times were used. In the animal model, hemorrhage could be avoided by increasing the coagulation time to greater than 0.35 seconds. In Singerman's" report of 400 cases with retinal vascular disease treated with krypton red laser, an increased incidence of choroidal hemorrhage was initially noted. He avoided this complication in the last 200 cases in his series by increasing exposure time to 0.2 to 0.5 seconds. Singerman noted that most of these patients experienced greater discomfort with these laser parameters and required retrobulbar anesthesia to complete treatment. As with krypton red laser scatter photocoagulation," pain seemed to be more intense with diode infrared photocoagulation than with argon treatment. This may be due to greater penetration depths because of decreased energy absorption in the retinal pigment epithelium, allowing more energy to penetrate deeper into the choroid and stimulate pain receptors in the ciliary nerves. Approximately one fourth of our patients who had treatment initiated under topical anesthetic alone complained of marked pain. Retrobulbar anesthesia effectivelyalleviated patient discomfort, and was necessary in two patients to complete treatment. Clinical advantages of the diode laser include decreased light scatter at longer wavelengths and little absorption of light in nuclear sclerotic cataracts, mild intravitreal hemorrhage or intraretinal hemorrhage. Excellent laser penetration through macular edema and serous retinal thickening was apparent. Indocyanine green infrared videoangiography is a useful adjunctive method of imaging choroidal neovascularization. Persistence and recurrence of CNVMs is a major cause of poor visual outcome in affected patients." Enhancement of selective laser photocoagulation of subretinal neovascular membranes in macular degeneration may be possible with ICG which absorbs at 805 nm and accumulates at the site of neovascular membranes. We treated three patients with choroidal neovascularization after ICG angiography in an attempt to close the neovascular membrane with a less intense treatment endpoint, with the goal of both decreasing the extent of damage to the overlying neurosensory retina and providing a more definitive closure of the new vessels. In all three cases, closure of the neovascular membrane was achieved using an ophthalmoscopic treatment endpoint of a mild gray-white color change in the lesion, rather than the intense retinal whitening typically used. This finding suggests that ICG might be useful in potentiating diode laser effects on vascular structures within the eye. 1560
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Technical disadvantages noted with the diode laser include a greater beam divergence cone angle than standard argon and krypton lasers. This requires a greater intraocular focusing cone angle and limits the ability to direct the beam in the periphery. Standard laser treatment lenses currently have anti-reflective coatings effective in the visible spectrum from 400 to 700 nm and new lenses with additional infrared anti-reflective coatings may be useful. In addition, the current laser diodes emit light with a longer wavelength than was used in the controlled randomized trials of retinal photocoagulation where argon laser wavelengths (488 and 514 nm) were used and became the standard of treatment. Diode lasers can be used to perform transpupillary retinal photocoagulation. Treatment with diode lasers emitting in the near infrared appears clinically similar to the krypton red laser. The gross clinical similarity of these retinal photocoagulation lesions may demonstrate similar potential for therapeutic applications. The long-term clinical response to treatment with the diode laser, however, remains to be determined.
ACKNOWLEDGMENT The authors thank Aram Mooradian, PhD, of MIT Lincoln Laboratories, for supporting the animal study by providing the GaA IAs laser diodes.
REFERENCES 1. The Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy: the second report of diabetic retinopathy study findings. Ophthalmology 1978; 85:82-106. 2. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol1985; 103:1796806. 3. The Moorfields Macular Study Group. Treatment of senile disciform macular degeneration: a single-blind randomised trial by argon laser photocoagulation. Br J Ophthalmol1982; 66:745-53. 4. Macular Photocoagulation Study Group. Argon laser photocoagulation for senile macular degeneration: results of a randomized clinical trial. Arch Ophthalmol1982; 100:912-8. 5. Macular Photocoagulation Study Group. Argon laser photocoagulation for neovascular maculopathy: three-year results from randomized clinical trials. Arch Ophthalmol 1986; 104:694-701. 6. Macular Photocoagulation Study Group. Argon laser photocoagulation for ocular histoplasmosis: results of a randomized clinical trial. Arch Ophthalmol1983; 101:1347-57. 7. Macular Photocoagulation Study Group. Krypton laser photocoagulation for neovascular lesions of ocular histoplasmosis: results of a randomized clinical trial. Arch Ophthalmol1987; 105:1499-507. 8. Branch Vein Occlusion Study Group. Argon laser scatter photocoagulation for prevention of neovascularization and vitreous hemorrhage in branch vein occlusion. A randomized clinical trial. Arch Ophthalmol 1986; 104:34-41.
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9. The Branch Vein Occlusion Study Group. Argon laser photocoagulation for macular edema in branch vein occl usion. Am J Ophthalmol 1984; 98:271-82. 10. Magargal LE, Brown GC, Augsburger JJ, Donoso LA. Efficacy of panretinal photocoagulation in preventing neovascular glaucoma following ischemic central retinal vein obstruct ion. Ophthalmology 1982; 89:80-4. 11. Mainster MA. Wavelength selection in macular photocoagulation: tissue optics, thermal effects, and laser systems. Ophthalmolo gy 1986; 93: 952-8. 12. Puliafito CA, Deutsch TF, Boll J, To K. Semiconductor laser endo photocoagulation of the retina. Arch Ophthalmol1987; 105:424-7. 13. Brancato R, Pratesi R. App lications of diode lasers in ophthalmology. Lasers Light Ophth almol1 98 7; 1:119- 29. 14. Brancato R, Pratesi R, Leoni G, et al. Retinal photocoagulation with diode laser operating from a slit lamp microsco pe. Lasers Light Ophthalm ol1988: 2:73- 8. 15. Brancato R, Pratesi R, Leoni G, et al. Histopathology of diode and argon laser lesions in rabbit retina. Invest Ophthalmol Vis Sci 1989; 30:1504-10.
16. McHugh JDA, Marshall J, Capon M, et al. Transpupillary retinal photocoagulation in the eyes of rabbit and human using a diode laser. Lasers Light Ophthalmol 1988; 2:125-43. 17. McHug h JDA, Marshall J, Ffytche TJ, et at. Initial clinical experience using a diod e laser in the treatment of retinal vascular disease. Eye 1989; 3:516- 27. 18. Destro M, Puliafito CA. Indocyanine green videoangiography of cho roidal neovascularization. Ophthalmology 1989; 96:846-53. 19. Gabel V-P, Bimgruber R, Hillenkamp F. Visible and near infrared light absorption in pigment epithelium and choroid. In: Acta XXIII Concilium Ophthalmologic um (Kyoto), 1978. Vol. 1; 658- 62. 20. Peyman GA, Li M, Yoneya S, et al. Fundus photocoagulation with the argon and krypton lasers: a comparative study. Ophthalmic Surg 1981; 12:481-90. 21. Singerman LJ. Red krypton laser therapy of macular and retinal vascular diseases . Retina 1982; 2:15-28. 22. Macular Photocoagulation Study Group. Persistent and recurrent neovascularization after krypton laser photocoagulation for neovascular lesions of ocular histoplasmosis. Arch Ophthalmol 1989; 107:344-52.
1561
Abstract: The authors successfully performed clinical transpup illary retinal photocoagulation in 30 eyes of 26 patients with retinal vascular disease using a gallium-aluminum-arsenide (GaAIAs) diode laser emitting at 805 nm. Retinal photocoagulation was performed at treatment powers of 300 to 1300 mW and exposure durations of 0.2 to 0.5 seconds with a 200-1Lm diameter treatment spot. Patients treated with both diode and argon green lasers required 4.5 ± 1.8 times greater mean laser energy with diode compared with argon to create ophthalmoscopically similarlesions. Parallel experimental retinalphotocoagulation in Chinchilla rabbits required 3.1 ± 0.9 times more power to create ophthalmoscopically similar lesions with the diode laser than with the argon laser. Intraoperat ive subretinal hemorrhage occ urred rarely in patients with an incidence of 4 (0.044%) of 9021 treatment spots . Patients complained of moderate-tomarked pain in 10 (43%) of 23 treatments initiated under topical anesthesia. A transpup illary diode laser may be used clinically to perform therapeutic retinal photocoagulation. Ophthalmology 1990; 97: 1553-1561
The current treatment of many retinal vascular diseases involves laser photocoagulation of the retina. The risk of severe visual loss associated with proliferative diabetic retinopathy, clinically significant diabetic macular edema , branch and central retinal vein occlusion , and subretinal neovascularization is decreased after argon or krypton laser photocoagulation. 1-1 0 Originally received : March 21 , 1990 . Revision accepted : May 25, 1990 . Laser Research Laboratory, Dep artment of Op hthalmology, Massac husetts Eye and Ear Infirmary , Harvard Medical Scho ol, Bost on. 2 Wellman Laborato ries of Photomedi cine, Harvard Medical School, Boston. 1
Supported in part by NIH gran ts 5 ROI GM354 59 -04 and IRE 4074 71, and ONR contract NOOO14-K0117 . The author s certify that they have no affiliation with or financ ial involvement in any organi zation or entity with a direct financial interest in the subject matter or materials discussed in this article. Reprint requests to Carmen A. Puliafito, MD, Laser Research Lab oratory, Massachusetts Eye and Ear Infirmary , 243 Charles St, Boston , MA 02114 .
The semiconductor laser diode was developed in 1962, but practical medical therapeutic applications have been limited by relatively low power outputs. Recent advan ces in semiconductor technology have led to the development of gallium aluminum arsenide (GaAIAs) laser diodes which can emit continuous wave monochromatic coherent laser light in excess of I W. The light emitted by currentl y available laser diodes is in the near infrared with wavelengths from 780 to 840 nm. At this comparatively long wavelength, light penetration through cataract and hemorrhage is improved compared with blue, green, yellow, or red laser light. I I Preclinical diode laser retinal photocoagulation has been described using endophotocoagulation and transpupillary delivery systems. 12-1 6 Initial clinical experience with diode laser transpupillary retinal photocoagulation in 33 eyes with various retinal vascular diseases was reported by McHugh and co-workers' ? in England in 1989. These authors reported no treatment associated complications and minimal patient discomfort. We report our results of clinical transpupillary retinal photocoagulation using a
1553
OPHTHALMOLOGY
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NOVEMBER 1990
semiconductor GaAIAs laser diode in 30 eyes with retinal vascular disease.
METHODS PATIENTS
Study patients were recruited from the Retina Service at the Massachusetts Eye and Ear Infirmary between August 1989 and November 1989. Patients with retinal vascular disease meeting standard accepted criteria for laser photocoagulation were enrolled after informed written consent was obtained. We treated 30 eyes in 26 patients; 18 eyes had received prior retinal photocoagulation (Table 1). Patients ranged in age from 30 to 87 years (mean, 56 years). Twelve patients were women and 14 were men. Seventeen eyes were treated for proliferative diabetic retinopathy, five eyes for choroidal neovascular membrane (CNVM) associated with age-related macular degeneration, four eyes for branch retinal vein occlusion (BRVO), two eyes for central retinal vein occlusion (CRVO), one eye for clinically significant diabetic macular edema, and one eye for macular edema associated with Coats' disease. Follow-up evaluation is available in all 30 eyes at 5 to 31 weeks after treatment (mean follow-up, 4 months). Treatment. Color fundus photographs were obtained in all patients before treatment; intravenous fluorescein angiography was performed in the standard fashion preoperatively in those patients with CNVMs, BRYO, CRVO, diabetic macular edema, and macular edema secondary to Coats' disease. Before treatment, the patient's Snellen acuity was measured and the pupils were dilated with topical tropicamide hydrochloride 1% and phenylephrine hydrochloride 2.5%. Corneal anesthesia was obtained with topical proparacaine hydrochloride; nine eyes also received 3 ml lidocaine 2% retrobulbar anesthesia delivered through a 25-gauge Atkinson needle. Three of five patients with macular CNVM underwent indocyanine green (ICG) infrared videoangiography 20 minutes before laser photocoagulation. Angiography was performed using ICG (5 rug/kg) injected into a peripheral arm vein followed by a 5-ml normal saline flush." The presence and localization of dye at the site of the neovascular membrane was confirmed by infrared videoangiography immediately before initiating diode laser photocoagulation. Indocyanine green accumulates in and around subretinal neovascular nets after being cleared from the surrounding circulation.l'' thereby acting as a chromophore for selective absorption of 805-nm laser light, potentially enhancing thermal damage to neovascular membranes (unpublished data, Balles MW et al, presented at the 1990 AR VO Annual Meeting). A single stripe GaAIAs diode laser (Candela Lasers, Inc, Wayland, MA) was coupled to a standard slit lamp (Zeiss 30-SL, West Germany) through a 200-J.Lm diameter fiber optic. The focused diode laser spot had a 200-J.Lm diameter, an 110 full cone angle, and a maximum power output of 1300 mW. Transpupillary retinal photocoagulation was carried out in the standard fashion using a pan-funduscopic Rodenstock (Rodenstock, Danbury, 1554
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CT), Mainster (Ocular Instruments, Bellevue, WA), or Goldmann lens, giving calculated retinal laser spot diameters of 280, 210, and 220 J.Lm, respectively. Hydroxypropyl methylcellulose 2.5% was used to provide mechanical and optical contact between the cornea and treatment lens. Photocoagulation was performed using 300 to 1300 mW (measured at the cornea) and exposure durations of 0.2 to 0.5 seconds. Power and exposure duration were adjusted and recorded during each treatment to obtain gray-white retinal lesions. Treatments were imaged with a high-resolution color video camera attached to a beam splitter on the slit lamp and recorded on 3/4-inch magnetic videotape. Wide-angle color fundus photographs were obtained 30 minutes after treatment and on follow-up examination. Intravenous fluorescein angiography was performed in the standard fashion when indicated. Patients were questioned at the completion of each treatment session regarding discomfort, sensation of "flash" or other subjective comments. The clinical impression of the treating physician also was recorded. ANIMAL STUDY
Four Chinchilla gray-pigmented rabbits, weighing 2 to 3 kg, were anesthetized with intramuscular ketamine hydrochloride (50 mg/kg) and xylazine (2 mg/kg) and with topical proparacaine hydrochloride. Both eyes ofeach animal were dilated preoperatively with topical tropicamide hydrochloride 1% and phenylephrine hydrochloride 2.5%. An OGFA contact fundus lens (Ocular Instruments) and methylcellulose were placed on the cornea to allow visualization of the central fundus with conventional slitlamp delivery systems. An argon green laser emitting at 514 nm and a single stripe GaAIAs diode laser emitting at 840 nm were used to create a series of retinal coagulations in the central fundus by transpupillary slit-lamp delivery. Exposure duration and retinal spot size were held constant at 100 ms and 150 J.Lm, respectively. The laser power for both wavelengths was chosen to produce three different classes of retinal effects ranging from the ophthalmoscopically visible threshold through mild-tostrong retinal lesions. A total of 227 argon laser coagulations and 250 diode laser coagulations were placed in the central fundus in eight eyes of four rabbits. Color fundus photographs (Canon CF-60ZA fundus camera, [Lake Success, NY)) were taken 2 hours and 7 days after laser treatment.
RESULTS CLINICAL TRIAL
We successfully created clinical retinal coagulations using a GaAIAs diode laser with a modified slit-lamp transpupillary delivery. Fairly uniform gray-white round retinal lesions could be produced at treatment powers of 300 to 1300 mWand exposure durations of 0.2 to 0.5 seconds. Scatter panretinal photocoagulation lesions were noted to have a creamy white appearance initially and develop chorioretinal scar formation similar to argon laser
V1 V1 V1
-
PRP PRP PRP
PRP PRP PRP PRP PRP PRP PRP PRP PRP PRP Macula, focal Macula, local] Macula, tocalt macula, focal Macula, tocalt PRP, sector Macula, grid Macula, grid PRP, sector PRP Macula, grid PRP, sector Macula, focal
PDR, VH PDR, NVD PDR, NVE
PDR, VH PDR, VH PDR PDR, NVD PDR, CSME, NVE PDR, VH , CSME PDR, NVD PDR, NVD, VH PDR PDR, NVD CNVM, AMD CNVM, AMD CNVM, AMD CNVM, AMD CNVM, AMD BRVO, NVE, VH BRVO, CSME BRVO, CSME BRVO, NVE, VH CRVO, ischemic CRVO, CSME Coats' disease PDR, CSME
5 6 7
8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 400 1100 1050 750 1175 1250 1000 1000 725 1000 800 900 1200 500 800 500 650 700 330 975 1200 600 1000
1000 1000 350
650 750 800 800
Mean Power Diode (mW)
0.2-0.5 0.2-0.3 0.2-0.5 0.2-0.5 0.2-0.3 0.2-0.35 0.2-0.4 0.2-0.4 0.2-0.3 0.3-0.5 0.5 0.2-0.5 0.5 0.5 0.2 0.2-0.5 0.2 0.2-0.5 0.2 0.2-0.5 0.5 0.2 0.2
0.2 0.2-0.5 0.2
0.2-0.5 0.2-0.5 0.2 0.2
Duration (sees)
140 275 368 263 294 344 300 300 181 400 400 315 600 250 160 175 130 245 66 341 600 120 200
200 350 70
228 263 160 160
Mean Energy Diode (mJ) Argon green PRP* Argon green PRP* Argon green PRP* Krypton red macular grid None Argon green PRP ' Argon green macular grid Argon green PRP ' Argon blue-green Argon green PRP ' Argon green PRP ' None Argon green parafoveal None None None Argon green PRP ' None None None Dye yellow, focal macula Dye yellow, focal macula Argon green PRP ' Dye yellow and red PRP None None None None Argon green PRP ' Argon green PRP
Other Laser Treatments
-
-
-
350 -
-
280
-
0.1-0.2
-
-
-
53
28
-
-
0.1
48
80 30
24
50
70 62 105
20/60 20/260 20/10020/133 20/2520/50 20/2520/60 20/2520/301/200 20/200 4/200 20/4020/260 20/5020/100 20/260 20/20 20/133 20/5020/133 20/40-3
20/4020/3020/60
20/2520/40+ 20/4020/30
HM
20/60 20/130 20/60 20/100 20/3020/7020/40 20/50 20/30 20/501/200 20/400 5/200 20/50 20/400 20/50+ 20/6020/400 20/25 20/200 20/40+ 20/60
20/80 20/3020/30
20/30+ 20/30 20/3020/30
13 8 16 24 12 9 11 10 9 10 5 26 20 7 22 15 27 5 16 32 15 14 22
14 7 15
31 23 23 19
Mean Energy Visual Acuity Argon Green Follow-up (mJ) Pretreatment Posttreatment (wks)
-
-
-
-
0.2
-
-
-
240
-
-
-
-
-
-
0.2 0.1-0.2
-
0.2
-
400 200
120
-
0.2
-
-
250
0.2 0.2 0.2
350 310 525
Mean Power Duration Argon (mW) (sees)
t Choroidal neovascular membrane treated after indocyanine green administered.
• Diode and argon green PRP in same eye.
PDR = proliferative diabetic retinopathy; PRP = scatter panretinal photocoagulation; NVE = neovascularization elsewhere; VH = vitreous hemorrhage; NVD = neovascularization of the disc; CSME = clinically significant macular edema; CNVM = choroidal neovascular membrane; AMD = age-related macular degeneration; BRVO = branch retinal vein occlusion; CRVO = central retinal vein occlusion; HM = hand motions.
PRP PRP, sector PRP, sector PRP
PDR PDR, NVE PDR, NVE PDR, NVE
Diagnosis
Treatment Diode Laser
1 2 3 4
Patient No.
Table 1. Clinical Diode Laser Photocoagulation in Retinal Vascular Disease
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OJ
rn
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c r
o
0 --t 0 0 0
I
\l
:0
m
(j)
s;:
0
-c
0
20 70
90
110
130
150
170
190
210
230
250
Diode laser power (mW)
Fig 6. This graph illustrates the power required in each of eight Chinchilla rabbit eyes (represented by squares) to produce retinal lesions with the argon green laser (514 nm) that appear ophthalmoscopically similar to lesions produced with the diode laser (840 nm). The central line represents the linear regression plot of these data points. The slope of this line (3.1) is the factor by which the argon laser power would have to be multiplied to produce a similar retinal lesion with the diode laser at 840 nm. The upper and lower curves represent the 95% confidence limits of this linear regression.
patients to complete treatment. The authors stated that their patients tolerated the treatment well and commented on absence of noise during treatment as an optical filter protects the operator instead of a mechanical shutter common in current visible light emission lasers (e.g., argon and krypton). Patients were not aware of a bright "flash" during laser treatment which may sometimes contribute to patient anxiety."? Analysis of the power required to create a retinal photocoagulation lesion in our patients and in parallel experimental retinal photocoagulation in the rabbit indicates that the diode laser requires three to four times as much power or longer exposure duration to create clinical photocoagulation lesions than comparable treatment with the argon green laser. Our clinical and experimental observations are in agreement with the experimentally measured absorption of light energy by the retinal pigment epithelium and choroid. Compared with the 95% absorption of argon green light at 514 nm, only 20% of diode laser light at 800 nm incident on the retina is absorbed by the retinal pigment epithelium and choroid. 19 Assuming that the product of total energy absorption (in the retinal pigment epithelium and choroid) and laser power should be the same to produce similar retinal coagulations with different wavelength light sources, a diode laser emitting at 800 nm would need to supply 4.8 times as much power as an argon laser emitting at 514 nm to produce similar retinal coagulations due to this wavelengthdependent difference in energy absorption in the retinal pigment epithelium and choroid. Of course, less intense retinal lesions could be produced with lower diode laser power, however, this would represent a divergence from the standard clinical treatment endpoint used in the randomized, controlled trials of laser photocoagulation. 1-10
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OPHTHALMOLOGY
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NOVEMBER 1990
Choroidal hemorrhage and rupture of Bruch's membrane was observed in four eyes with an incidence of 0.044% of all treatment spots in our series. We attempted to minimize this complication by using relatively longer exposure durations, with a mean of 0.33 second, and minimizing overtreatment. Peyman and co-workers" compared argon blue-green and krypton red (647 nm) laser retinal lesions in cynomolgus monkeys and showed that rupture of Bruch's membrane and choroidal hemorrhage occurred frequently with the longer wavelength krypton laser when short coagulation times were used. In the animal model, hemorrhage could be avoided by increasing the coagulation time to greater than 0.35 seconds. In Singerman's" report of 400 cases with retinal vascular disease treated with krypton red laser, an increased incidence of choroidal hemorrhage was initially noted. He avoided this complication in the last 200 cases in his series by increasing exposure time to 0.2 to 0.5 seconds. Singerman noted that most of these patients experienced greater discomfort with these laser parameters and required retrobulbar anesthesia to complete treatment. As with krypton red laser scatter photocoagulation," pain seemed to be more intense with diode infrared photocoagulation than with argon treatment. This may be due to greater penetration depths because of decreased energy absorption in the retinal pigment epithelium, allowing more energy to penetrate deeper into the choroid and stimulate pain receptors in the ciliary nerves. Approximately one fourth of our patients who had treatment initiated under topical anesthetic alone complained of marked pain. Retrobulbar anesthesia effectivelyalleviated patient discomfort, and was necessary in two patients to complete treatment. Clinical advantages of the diode laser include decreased light scatter at longer wavelengths and little absorption of light in nuclear sclerotic cataracts, mild intravitreal hemorrhage or intraretinal hemorrhage. Excellent laser penetration through macular edema and serous retinal thickening was apparent. Indocyanine green infrared videoangiography is a useful adjunctive method of imaging choroidal neovascularization. Persistence and recurrence of CNVMs is a major cause of poor visual outcome in affected patients." Enhancement of selective laser photocoagulation of subretinal neovascular membranes in macular degeneration may be possible with ICG which absorbs at 805 nm and accumulates at the site of neovascular membranes. We treated three patients with choroidal neovascularization after ICG angiography in an attempt to close the neovascular membrane with a less intense treatment endpoint, with the goal of both decreasing the extent of damage to the overlying neurosensory retina and providing a more definitive closure of the new vessels. In all three cases, closure of the neovascular membrane was achieved using an ophthalmoscopic treatment endpoint of a mild gray-white color change in the lesion, rather than the intense retinal whitening typically used. This finding suggests that ICG might be useful in potentiating diode laser effects on vascular structures within the eye. 1560
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VOLUME 97
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NUMBER 11
Technical disadvantages noted with the diode laser include a greater beam divergence cone angle than standard argon and krypton lasers. This requires a greater intraocular focusing cone angle and limits the ability to direct the beam in the periphery. Standard laser treatment lenses currently have anti-reflective coatings effective in the visible spectrum from 400 to 700 nm and new lenses with additional infrared anti-reflective coatings may be useful. In addition, the current laser diodes emit light with a longer wavelength than was used in the controlled randomized trials of retinal photocoagulation where argon laser wavelengths (488 and 514 nm) were used and became the standard of treatment. Diode lasers can be used to perform transpupillary retinal photocoagulation. Treatment with diode lasers emitting in the near infrared appears clinically similar to the krypton red laser. The gross clinical similarity of these retinal photocoagulation lesions may demonstrate similar potential for therapeutic applications. The long-term clinical response to treatment with the diode laser, however, remains to be determined.
ACKNOWLEDGMENT The authors thank Aram Mooradian, PhD, of MIT Lincoln Laboratories, for supporting the animal study by providing the GaA IAs laser diodes.
REFERENCES 1. The Diabetic Retinopathy Study Research Group. Photocoagulation treatment of proliferative diabetic retinopathy: the second report of diabetic retinopathy study findings. Ophthalmology 1978; 85:82-106. 2. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Arch Ophthalmol1985; 103:1796806. 3. The Moorfields Macular Study Group. Treatment of senile disciform macular degeneration: a single-blind randomised trial by argon laser photocoagulation. Br J Ophthalmol1982; 66:745-53. 4. Macular Photocoagulation Study Group. Argon laser photocoagulation for senile macular degeneration: results of a randomized clinical trial. Arch Ophthalmol1982; 100:912-8. 5. Macular Photocoagulation Study Group. Argon laser photocoagulation for neovascular maculopathy: three-year results from randomized clinical trials. Arch Ophthalmol 1986; 104:694-701. 6. Macular Photocoagulation Study Group. Argon laser photocoagulation for ocular histoplasmosis: results of a randomized clinical trial. Arch Ophthalmol1983; 101:1347-57. 7. Macular Photocoagulation Study Group. Krypton laser photocoagulation for neovascular lesions of ocular histoplasmosis: results of a randomized clinical trial. Arch Ophthalmol1987; 105:1499-507. 8. Branch Vein Occlusion Study Group. Argon laser scatter photocoagulation for prevention of neovascularization and vitreous hemorrhage in branch vein occlusion. A randomized clinical trial. Arch Ophthalmol 1986; 104:34-41.
BALLES et al
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SEMICONDUCTOR DIODE LASER PHOTOCOAGULATION
9. The Branch Vein Occlusion Study Group. Argon laser photocoagulation for macular edema in branch vein occl usion. Am J Ophthalmol 1984; 98:271-82. 10. Magargal LE, Brown GC, Augsburger JJ, Donoso LA. Efficacy of panretinal photocoagulation in preventing neovascular glaucoma following ischemic central retinal vein obstruct ion. Ophthalmology 1982; 89:80-4. 11. Mainster MA. Wavelength selection in macular photocoagulation: tissue optics, thermal effects, and laser systems. Ophthalmolo gy 1986; 93: 952-8. 12. Puliafito CA, Deutsch TF, Boll J, To K. Semiconductor laser endo photocoagulation of the retina. Arch Ophthalmol1987; 105:424-7. 13. Brancato R, Pratesi R. App lications of diode lasers in ophthalmology. Lasers Light Ophth almol1 98 7; 1:119- 29. 14. Brancato R, Pratesi R, Leoni G, et al. Retinal photocoagulation with diode laser operating from a slit lamp microsco pe. Lasers Light Ophthalm ol1988: 2:73- 8. 15. Brancato R, Pratesi R, Leoni G, et al. Histopathology of diode and argon laser lesions in rabbit retina. Invest Ophthalmol Vis Sci 1989; 30:1504-10.
16. McHugh JDA, Marshall J, Capon M, et al. Transpupillary retinal photocoagulation in the eyes of rabbit and human using a diode laser. Lasers Light Ophthalmol 1988; 2:125-43. 17. McHug h JDA, Marshall J, Ffytche TJ, et at. Initial clinical experience using a diod e laser in the treatment of retinal vascular disease. Eye 1989; 3:516- 27. 18. Destro M, Puliafito CA. Indocyanine green videoangiography of cho roidal neovascularization. Ophthalmology 1989; 96:846-53. 19. Gabel V-P, Bimgruber R, Hillenkamp F. Visible and near infrared light absorption in pigment epithelium and choroid. In: Acta XXIII Concilium Ophthalmologic um (Kyoto), 1978. Vol. 1; 658- 62. 20. Peyman GA, Li M, Yoneya S, et al. Fundus photocoagulation with the argon and krypton lasers: a comparative study. Ophthalmic Surg 1981; 12:481-90. 21. Singerman LJ. Red krypton laser therapy of macular and retinal vascular diseases . Retina 1982; 2:15-28. 22. Macular Photocoagulation Study Group. Persistent and recurrent neovascularization after krypton laser photocoagulation for neovascular lesions of ocular histoplasmosis. Arch Ophthalmol 1989; 107:344-52.
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