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Discussion by John T. Flynn, MD
Ng et al 䡠 Comparison of Laser and Cryotherapy for ROP Discussion by John T. Flynn, MD Doctor Connolly and his group have presented evidence that laser therapy for threshold retinopathy of prematurity (ROP) is a kinder, gentler form of treatment for the disease than is cryotherapy. This group, over the past decade, has led the way in making laser treatment more available for the infant with ROP.1– 4 Starting in the early 1990’s, they began publishing their first results comparing the therapy of ROP by cryo with the therapy by laser in a series of papers. This work culminates in the paper we have before us today. Let us start with their conclusions first. Drawing on patients previously reported in their 1991, 1992, and 1994 papers, they assembled a group of 25 patients from a total of 66 where laser and cryo had been administered under a somewhat randomized scheme. This cohort of patients now has an average age of 9.9 years. They were subjected to a complete battery of ophthalmological tests including acuity (logMar), refraction or auto-refractor, fundus photographs, and, where possible, ultrasonography to determine axial length, anterior chamber depth, lens thickness, corneal thickness, corneal curvature as well as a complete ophthalmological evaluation by an experienced ophthalmologist. Information was gathered from 66 patients. There are a total of 170 patients cited in the three studies and it would be helpful to know from which studies the patients were derived. The conclusions of the study are that laser therapy exhibits an advantage in all three areas to which research questions were addressed: ●
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Laser therapy is superior to cryotherapy in that it causes less anatomical distortion (dragging of the macula) than cryotherapy. Laser therapy results in better visual acuity measured by logMar method than does cryotherapy. Laser therapy results in less myopia than does cryotherapy although there is no significant difference in the amount of astigmatism between the two forms of therapy.
Interestingly, the authors are able in their study to shed new light on the myopia, i.e., it is refractive, not axial. The optical element causing the increase in power of the optical system is the thickness of the crystalline lens. This is an impressive triad of conclusions with which most ophthalmologists would intuitively concur. The neonatal nurses have told us from the very beginning of laser therapy that it is much better tolerated than cryotherapy. But before we accept the conclusions as facts, let us examine the robustness of the evidence. At the intake to the study (threshold reached in at least one eye) there were 66 patients admitted to the study. They were distributed as follows: 39 (59%) patients had bilateral symmetrical disease, and 27 (41%) patients asymmetrical disease. This gives us some pause because the number of patients From the Harkness Eye Institute, New York, New York. Reprint requests to John T. Flynn, MD, Harkness Eye Institute, 635 West 165th Street, New York, NY 10032.
with asymmetrical disease is more than three times higher than what it was in the Cryo-ROP study4 and therefore introduces the notion that perhaps the sample population was inadvertently biased at the outset. But let us look further. The symmetrical eyes were treated as we would expect, one eye laser, one eye cryo by random assignment. These patients would be ideal for this study since each is its own control. The asymmetrical patients, however, are not quite so clear-cut. Fifteen were assigned randomly to receive laser therapy to their threshold eye. Only 3 (20%) required cryotherapy at a later date to the fellow eye. Twelve were randomized to cryotherapy to their threshold eye. Ten of the twelve (80%) required therapy (laser) to their fellow eye. This suggests at least that the laser arm of the study had milder disease since far fewer needed fellow eye treatment. Finally let us look at the distribution of the 25 patients, at outcome. These 25 patients were 38% of the 66 patients they started with. Thirteen (20%) of the patients were direct cryo-tolaser, “head to head” comparisons. One patient (2 eyes) or 1.5% of the population received asymmetric laser first followed by cryotherapy and five patients (7.5%) (10 eyes) received cryo first followed by laser. In six eyes of six patients (9%), no treatment was required to the control eye. So less than a third of the patients admitted to the study had true comparisons of the most robust kind, i.e., each eye randomly assigned to either therapy. In conclusion we feel first, that the sample may be inadvertently biased at the outset so that the clinicians are dealing with a skewed population at start. The bias may also be unidirectional. The eyes in the arm assigned to cryo may have had more serious disease and it is this difference that may be the cause of the apparent findings of lasered eyes having better vision than eyes receiving cryotherapy. In my heart I think the authors are right. Laser is a kinder, gentler form of therapy. But the evidence to date does not yet support that conclusion. And if for no other reason than the environment we live in today, I would suggest being circumspect about reaching such conclusions without incontrovertible evidence. References 1. McNamara JA, Tasman W, Brown GC, Federman JL. Laser photocoagulation for stage 3⫹ retinopathy of prematurity. Ophthalmology 1991;98:576 – 80. 2. McNamara JA, Tasman W, Vander JF, Brown GC. Diode laser photocoagulation for retinopathy of prematurity. Preliminary results. Arch Ophthalmol 1992;110:1714 – 6. 3. Laser therapy for retinopathy of prematurity. The Laser ROP Study Group [letter]. Arch Ophthalmol 1994;112:154 – 6. 4. Multicenter trial of cryotherapy for retinopathy of prematurity. One-year outcome—structure and function. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol 1990;108:1408 –16.
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Laser therapy is superior to cryotherapy in that it causes less anatomical distortion (dragging of the macula) than cryotherapy. Laser therapy results in better visual acuity measured by logMar method than does cryotherapy. Laser therapy results in less myopia than does cryotherapy although there is no significant difference in the amount of astigmatism between the two forms of therapy.
Interestingly, the authors are able in their study to shed new light on the myopia, i.e., it is refractive, not axial. The optical element causing the increase in power of the optical system is the thickness of the crystalline lens. This is an impressive triad of conclusions with which most ophthalmologists would intuitively concur. The neonatal nurses have told us from the very beginning of laser therapy that it is much better tolerated than cryotherapy. But before we accept the conclusions as facts, let us examine the robustness of the evidence. At the intake to the study (threshold reached in at least one eye) there were 66 patients admitted to the study. They were distributed as follows: 39 (59%) patients had bilateral symmetrical disease, and 27 (41%) patients asymmetrical disease. This gives us some pause because the number of patients From the Harkness Eye Institute, New York, New York. Reprint requests to John T. Flynn, MD, Harkness Eye Institute, 635 West 165th Street, New York, NY 10032.
with asymmetrical disease is more than three times higher than what it was in the Cryo-ROP study4 and therefore introduces the notion that perhaps the sample population was inadvertently biased at the outset. But let us look further. The symmetrical eyes were treated as we would expect, one eye laser, one eye cryo by random assignment. These patients would be ideal for this study since each is its own control. The asymmetrical patients, however, are not quite so clear-cut. Fifteen were assigned randomly to receive laser therapy to their threshold eye. Only 3 (20%) required cryotherapy at a later date to the fellow eye. Twelve were randomized to cryotherapy to their threshold eye. Ten of the twelve (80%) required therapy (laser) to their fellow eye. This suggests at least that the laser arm of the study had milder disease since far fewer needed fellow eye treatment. Finally let us look at the distribution of the 25 patients, at outcome. These 25 patients were 38% of the 66 patients they started with. Thirteen (20%) of the patients were direct cryo-tolaser, “head to head” comparisons. One patient (2 eyes) or 1.5% of the population received asymmetric laser first followed by cryotherapy and five patients (7.5%) (10 eyes) received cryo first followed by laser. In six eyes of six patients (9%), no treatment was required to the control eye. So less than a third of the patients admitted to the study had true comparisons of the most robust kind, i.e., each eye randomly assigned to either therapy. In conclusion we feel first, that the sample may be inadvertently biased at the outset so that the clinicians are dealing with a skewed population at start. The bias may also be unidirectional. The eyes in the arm assigned to cryo may have had more serious disease and it is this difference that may be the cause of the apparent findings of lasered eyes having better vision than eyes receiving cryotherapy. In my heart I think the authors are right. Laser is a kinder, gentler form of therapy. But the evidence to date does not yet support that conclusion. And if for no other reason than the environment we live in today, I would suggest being circumspect about reaching such conclusions without incontrovertible evidence. References 1. McNamara JA, Tasman W, Brown GC, Federman JL. Laser photocoagulation for stage 3⫹ retinopathy of prematurity. Ophthalmology 1991;98:576 – 80. 2. McNamara JA, Tasman W, Vander JF, Brown GC. Diode laser photocoagulation for retinopathy of prematurity. Preliminary results. Arch Ophthalmol 1992;110:1714 – 6. 3. Laser therapy for retinopathy of prematurity. The Laser ROP Study Group [letter]. Arch Ophthalmol 1994;112:154 – 6. 4. Multicenter trial of cryotherapy for retinopathy of prematurity. One-year outcome—structure and function. Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol 1990;108:1408 –16.
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