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Corneal flap thickness and tissue laser ablation in myopic lasik
recognized by the criteria, but in the fact that in the reported information based on the nonprotocol criteria, data were truncated after reaching a protocol endpoint criterion. We undertook analyses with many variations, and in every analysis the fundamental conclusion was the same—that progression was typically slow, but there was high variation such that some showed obvious progression as quickly as the criterion would permit, and others showed no sign of progression even after 7 years. Although our average follow-up was 4 years, there were ample subjects followed longer to estimate rates for longer disease duration with the Kaplan–Meier analysis. Moreover, the risk ratio for each subsequent year remained remarkably constant throughout, with no suggestion that the distribution of risk changed with duration of known disease. Glaucomatous progression is reflected in the mean deviation (MD) index, but as Drs. Caprioli and Maguire noted, it has several failings that limit its use as a sole criterion to use clinically. For very localized progression occurring over a short time, it is usually impractical to perform the necessary number of visual field examinations to show the small change of MD index with statistical significance by regression analysis. Over longer time, other diseases (cataracts in particular) will produce statistically significant change, whereas observable lens or disc changes are too subtle to make the causal distinction. However, this does not make the slope of the MD index unusable as a scientific measure, particularly when averaged across individuals to compare groups or to confirm by a different criterion the conclusion of often slow, but highly variable, deterioration. The radial plots consistently validate a statistical variation with instances of “improvement” in keeping with the 5% probability cutoff, but a larger fraction with deterioration. The proportion of progressors, variation in rates, and degree of confidence in the rate estimation are all quantified by using MD index, which could not be done with discrete endpoint criteria. We appreciate the care with which the editorialists contemplated our results. We agree with their concluding paragraphs that clinicians should be aware that although many patients progress slowly, others progress rapidly, and some may progress slowly or rapidly to blindness even while under observation and clinical care. All scientific data need to be interpreted to be sure the clinical context in which the data are being applied matches the circumstances under which the data were collected. We hope, however, that the readers will not get the impression that the data from the NTG study do not apply to their daily clinical practices, because great care was taken to evaluate and minimize the impact of the potential biases that worry Drs. Caprioli and Maguire. DOUGLAS R. ANDERSON, MD STEPHEN M. DRANCE, OC, MD Miami, Florida References 1. Caprioli J, Maguire M. The “not quite” natural history of normal-tension glaucoma. Ophthalmology 2001;108:245– 6. 2. Anderson DR, Drance SM, Schulzer M, Collaborative NormalTension Glaucoma Study Group. Natural history of normaltension glaucoma. Ophthalmology 2001;108:247–53.
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Corneal Flap Thickness and Tissue Laser Ablation in Myopic LASIK Dear Editor: Duraijai et al (Ophthalmology 2000;107:2140 –3) provide additional insight into the discrepancies that usually exist between intended and actual flap thickness and ablation depth in myopic laser in situ keratomileusis (LASIK). Using subtraction pachymetry, the authors found that actual flap thickness was consistently less than predicted for each of the plates of the ACS (Automatic Corneal Shaper) microkeratome: with the 160-m depth plate real flap measurements averaged 105 m and ranged from 48 to 141 m, with the 180-m depth plate real flap measurements averaged 125 m and ranged from 82 to 155 m, and with the 200-m depth plate real flap measurements averaged 144 m and ranged from 108 to 187 m. On the contrary, actual ablation depths were found to be on average at least 50% greater than expected. Previous studies have also found a generally thinner real than intended corneal flap using the same microkeratome system1 or the Hansatome unit.2 Whereas this fact is indubitable, it seems that creating a real 48-m-thick flap in 1 of 15 surgeries with the 160-m head of the ACS unit carries a rather high probability of producing a flap of almost entirely corneal epithelium, which averages 50-m thick in the human eye.3 Because the authors did not mention the occurrence of flap buttonholes, it is assumed that the measured thickness using subtraction ultrasonic pachymetry corresponded to an evenly thin flap. Were this true, the system would seem to be both unsafe and unacceptable, whereas in practice this unit is being widely used without showing such a high rate of microkeratome-related complications. Also, Duraijai et al found an astonishing average of 50% greater measured ablation depth than predicted using subtraction ultrasonic pachymetry. This contrasts with the result of a previous study that found an average 14% increase in measured ablation depth over the one predicted using pachymetric optical coherence tomography and another analogous broad-beam excimer laser.2 Were this 50% increase in ablation depth true, then we would be already seeing an epidemic of keratectasia among eyes operated with such laser units under similar environmental conditions. Whereas intraoperative subtraction pachymetry using an ultrasound probe may be of great help in approximating the actual residual stroma, and thus in avoiding stromal beds that are too thin after myopic LASIK, one consideration may be taken into account. Subtraction pachymetric measurement of the flap is usually obtained by comparing central corneal thickness at the beginning of the procedure with the stromal bed thickness immediately after passage of the microkeratome that has just been characteristically lubricated to facilitate the pass. This can lead to ultrasonic overestimation of a hydrated stromal bed, which in turn provides a smaller differential flap thickness value. It can also lead to an overestimated differential ablation depth if the ultrasonic reading after microkeratome pass is compared with the one of a generally dry residual stromal bed at the end of the ablative procedure. For the sake of accuracy, both measurements should then be made under the same conditions. Therefore, surgeons performing intraoperative ultrasound pachymetry may benefit from gently drying the exposed stroma just before the measurement. Because the
Letters to the Editor ablation rate depends on corneal hydration,4 a change in their nomogram may also be necessary. Finally, it should be remarked that this thorough study efficiently demonstrates significant variations between real and predicted values in myopic LASIK that deserve the attention of all surgeons performing laser vision correction. MIGUEL J. MALDONADO, MD, PHD JOSE´ RAMO´ N JUBER´ıAS, MD, PHD ROSA RODR´ıGUEZ-CONDE, MD Pamplona, Spain References 1. Pe´ rez-Santonja JJ, Bellot J, Claramonte P, et al. Laser in situ keratomileusis to correct high myopia. J Cataract Refract Surg 1997;23:372– 85. 2. Maldonado MJ, Ruiz-Oblitas L, Munuera JM, et al. Optical coherence tomography evaluation of the corneal cap and stromal bed features after laser in situ keratomileusis for high myopia and astigmatism. Ophthalmology 2000;107:81–7; discussion 88. 3. Reinstein DZ, Silverman RH, Rondeau MJ, Coleman DJ. Epithelial and corneal thickness measurements by high-frequency ultrasound digital signal processing. Ophthalmology 1994;101:140 – 6. 4. Dougherty PJ, Wellish KL, Maloney RK. Excimer laser ablation rate and corneal hydration. Am J Ophthalmol 1994;118:169 –76.
Verteporfin in Photodynamic Therapy (VIP) Study Group Dear Editor: In the recent article by the Verteporfin in Photodynamic Therapy (VIP) Study Group (Ophthalmology 2001;108: 841–52), the authors recommended verteporfin therapy for treatment of patients with subfoveal choroidal neovascularization from pathologic myopia. Data from that work suggested that this therapy can stabilize vision in such patients. The Abstract and the article itself emphasize that the treatment may also improve the vision of these patients. “Stabilizing vision” and “improving vision” are not equivalent concepts. Indeed, the authors stated, “Specifically, at month 12 examination, the verteporfin-treated group was approximately twice as likely to have improvement of at least five letters (one line) in visual acuity with 26 eyes (32%) of this group compared with 6 eyes (15%) of the placebo-treated group.” I am not convinced the evidence they provide supports that statement. No statistical analysis was provided, and the article only presented “absolute values.” We know that big differences may have less value than very little ones. Some calculations can bring this item to light. If we compare both groups (verteporfin versus placebo) and their results according to visual acuity (increase of one line or more versus no change or decrease of one line or more), we will obtain a statistically nonsignificant result (P ⫽ 0.085). In other words, we cannot conclude with confidence that verteporfin therapy will improve vision more than placebo. This could also have been easily seen if all data had included confidence intervals. It is true that the proportion of patients with improving vision is 32% with verteporfin and 15% with placebo, but their confidence intervals (0.22– 0.42 and 0.07– 0.29, respectively) overlap, and there were no statistically significant differences between groups.
Probably a bigger sample size will support more definitive results. We are not justified in offering myopic patients optimistic promises just yet. FRANCISCO RUIZ-OLIVA, MD JULIA CORTE´ S, MD Vitoria, Spain Author reply Dear Editor: We thank Drs. Ruiz-Oliva and Corte´ s for their letter regarding “Photodynamic Therapy of Subfoveal Choroidal Neovascularization in Pathologic Myopia with Verteporfin: One-year Results of a Randomized Clinical Trial—VIP Report No. 1,”1 which provides us an opportunity to comment on previously published statements from our report. Drs. Ruiz-Oliva and Corte´ s quote a line from the Results section of VIP Report No. 1 that the verteporfin-treated group was approximately twice as likely to have improvement of at least five letters (one line) in visual acuity compared with the placebo-treated group; they then state “I am not convinced the evidence they provide supports that statement.” The statement does accurately reflect the data that 26 (32%) of 81 verteporfin-treated patients compared with 6 (15%) of 39 placebo-treated patients gained at least five letters (approximately equivalent to one line) in visual acuity. These data, though, are not used in isolation to support the main conclusion of the report that verteporfin therapy safely increased the chance of stabilizing or improving vision. The main outcome measure prospectively defined was the proportion of eyes with fewer than eight letters lost at the month 12 examination, adhering to an intent-to-treat analysis. Avoiding this loss indicates that the vision was either stable or improved compared with the baseline visual acuity. Therefore, when the results from the month 12 examination demonstrated that 58 (72%) of the verteporfin-treated patients compared with 17 (44%) of the placebo-treated patients lost fewer than eight letters at the month 12 examination (P ⬍ 0.01), the VIP Study Group concluded that the therapy improved the chance of either stable or improved visual acuity. Drs. Ruiz-Oliva and Corte´ s state “no statistical analysis was provided . . . the paper only presented ‘absolute values.’” We presume they are referring to the lack of statistical analysis of the finding that 26 (32%) of 81 verteporfintreated patients compared with 6 (15%) of 39 placebotreated patients had at least small improvements in visual acuity. No formal statistical analysis was performed on this outcome, because it was not a planned primary or secondary outcome. However, if a Pearson chi-square test2 is used to compare these proportions, as was used in similar analyses performed in the VIP Trial,1 the P value would be 0.05. (Given the number of patients with pathologic myopia in the verteporfin-treated group and placebo-treated group, the VIP Study Group chose to report P values to two decimal places.) Drs. Ruiz-Oliva and Corte´ s do not state what method they used to obtain a P value of 0.085. If one uses Fisher’s exact test, a P value of 0.08 would be obtained; if one uses a corrected chi-square, a P value of 0.09 would be obtained using SAS software.3 However, these latter two tests are commonly used in tables with small sample sizes not reflective of the sample sizes of the VIP Trial.
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Corneal Flap Thickness and Tissue Laser Ablation in Myopic LASIK Dear Editor: Duraijai et al (Ophthalmology 2000;107:2140 –3) provide additional insight into the discrepancies that usually exist between intended and actual flap thickness and ablation depth in myopic laser in situ keratomileusis (LASIK). Using subtraction pachymetry, the authors found that actual flap thickness was consistently less than predicted for each of the plates of the ACS (Automatic Corneal Shaper) microkeratome: with the 160-m depth plate real flap measurements averaged 105 m and ranged from 48 to 141 m, with the 180-m depth plate real flap measurements averaged 125 m and ranged from 82 to 155 m, and with the 200-m depth plate real flap measurements averaged 144 m and ranged from 108 to 187 m. On the contrary, actual ablation depths were found to be on average at least 50% greater than expected. Previous studies have also found a generally thinner real than intended corneal flap using the same microkeratome system1 or the Hansatome unit.2 Whereas this fact is indubitable, it seems that creating a real 48-m-thick flap in 1 of 15 surgeries with the 160-m head of the ACS unit carries a rather high probability of producing a flap of almost entirely corneal epithelium, which averages 50-m thick in the human eye.3 Because the authors did not mention the occurrence of flap buttonholes, it is assumed that the measured thickness using subtraction ultrasonic pachymetry corresponded to an evenly thin flap. Were this true, the system would seem to be both unsafe and unacceptable, whereas in practice this unit is being widely used without showing such a high rate of microkeratome-related complications. Also, Duraijai et al found an astonishing average of 50% greater measured ablation depth than predicted using subtraction ultrasonic pachymetry. This contrasts with the result of a previous study that found an average 14% increase in measured ablation depth over the one predicted using pachymetric optical coherence tomography and another analogous broad-beam excimer laser.2 Were this 50% increase in ablation depth true, then we would be already seeing an epidemic of keratectasia among eyes operated with such laser units under similar environmental conditions. Whereas intraoperative subtraction pachymetry using an ultrasound probe may be of great help in approximating the actual residual stroma, and thus in avoiding stromal beds that are too thin after myopic LASIK, one consideration may be taken into account. Subtraction pachymetric measurement of the flap is usually obtained by comparing central corneal thickness at the beginning of the procedure with the stromal bed thickness immediately after passage of the microkeratome that has just been characteristically lubricated to facilitate the pass. This can lead to ultrasonic overestimation of a hydrated stromal bed, which in turn provides a smaller differential flap thickness value. It can also lead to an overestimated differential ablation depth if the ultrasonic reading after microkeratome pass is compared with the one of a generally dry residual stromal bed at the end of the ablative procedure. For the sake of accuracy, both measurements should then be made under the same conditions. Therefore, surgeons performing intraoperative ultrasound pachymetry may benefit from gently drying the exposed stroma just before the measurement. Because the
Letters to the Editor ablation rate depends on corneal hydration,4 a change in their nomogram may also be necessary. Finally, it should be remarked that this thorough study efficiently demonstrates significant variations between real and predicted values in myopic LASIK that deserve the attention of all surgeons performing laser vision correction. MIGUEL J. MALDONADO, MD, PHD JOSE´ RAMO´ N JUBER´ıAS, MD, PHD ROSA RODR´ıGUEZ-CONDE, MD Pamplona, Spain References 1. Pe´ rez-Santonja JJ, Bellot J, Claramonte P, et al. Laser in situ keratomileusis to correct high myopia. J Cataract Refract Surg 1997;23:372– 85. 2. Maldonado MJ, Ruiz-Oblitas L, Munuera JM, et al. Optical coherence tomography evaluation of the corneal cap and stromal bed features after laser in situ keratomileusis for high myopia and astigmatism. Ophthalmology 2000;107:81–7; discussion 88. 3. Reinstein DZ, Silverman RH, Rondeau MJ, Coleman DJ. Epithelial and corneal thickness measurements by high-frequency ultrasound digital signal processing. Ophthalmology 1994;101:140 – 6. 4. Dougherty PJ, Wellish KL, Maloney RK. Excimer laser ablation rate and corneal hydration. Am J Ophthalmol 1994;118:169 –76.
Verteporfin in Photodynamic Therapy (VIP) Study Group Dear Editor: In the recent article by the Verteporfin in Photodynamic Therapy (VIP) Study Group (Ophthalmology 2001;108: 841–52), the authors recommended verteporfin therapy for treatment of patients with subfoveal choroidal neovascularization from pathologic myopia. Data from that work suggested that this therapy can stabilize vision in such patients. The Abstract and the article itself emphasize that the treatment may also improve the vision of these patients. “Stabilizing vision” and “improving vision” are not equivalent concepts. Indeed, the authors stated, “Specifically, at month 12 examination, the verteporfin-treated group was approximately twice as likely to have improvement of at least five letters (one line) in visual acuity with 26 eyes (32%) of this group compared with 6 eyes (15%) of the placebo-treated group.” I am not convinced the evidence they provide supports that statement. No statistical analysis was provided, and the article only presented “absolute values.” We know that big differences may have less value than very little ones. Some calculations can bring this item to light. If we compare both groups (verteporfin versus placebo) and their results according to visual acuity (increase of one line or more versus no change or decrease of one line or more), we will obtain a statistically nonsignificant result (P ⫽ 0.085). In other words, we cannot conclude with confidence that verteporfin therapy will improve vision more than placebo. This could also have been easily seen if all data had included confidence intervals. It is true that the proportion of patients with improving vision is 32% with verteporfin and 15% with placebo, but their confidence intervals (0.22– 0.42 and 0.07– 0.29, respectively) overlap, and there were no statistically significant differences between groups.
Probably a bigger sample size will support more definitive results. We are not justified in offering myopic patients optimistic promises just yet. FRANCISCO RUIZ-OLIVA, MD JULIA CORTE´ S, MD Vitoria, Spain Author reply Dear Editor: We thank Drs. Ruiz-Oliva and Corte´ s for their letter regarding “Photodynamic Therapy of Subfoveal Choroidal Neovascularization in Pathologic Myopia with Verteporfin: One-year Results of a Randomized Clinical Trial—VIP Report No. 1,”1 which provides us an opportunity to comment on previously published statements from our report. Drs. Ruiz-Oliva and Corte´ s quote a line from the Results section of VIP Report No. 1 that the verteporfin-treated group was approximately twice as likely to have improvement of at least five letters (one line) in visual acuity compared with the placebo-treated group; they then state “I am not convinced the evidence they provide supports that statement.” The statement does accurately reflect the data that 26 (32%) of 81 verteporfin-treated patients compared with 6 (15%) of 39 placebo-treated patients gained at least five letters (approximately equivalent to one line) in visual acuity. These data, though, are not used in isolation to support the main conclusion of the report that verteporfin therapy safely increased the chance of stabilizing or improving vision. The main outcome measure prospectively defined was the proportion of eyes with fewer than eight letters lost at the month 12 examination, adhering to an intent-to-treat analysis. Avoiding this loss indicates that the vision was either stable or improved compared with the baseline visual acuity. Therefore, when the results from the month 12 examination demonstrated that 58 (72%) of the verteporfin-treated patients compared with 17 (44%) of the placebo-treated patients lost fewer than eight letters at the month 12 examination (P ⬍ 0.01), the VIP Study Group concluded that the therapy improved the chance of either stable or improved visual acuity. Drs. Ruiz-Oliva and Corte´ s state “no statistical analysis was provided . . . the paper only presented ‘absolute values.’” We presume they are referring to the lack of statistical analysis of the finding that 26 (32%) of 81 verteporfintreated patients compared with 6 (15%) of 39 placebotreated patients had at least small improvements in visual acuity. No formal statistical analysis was performed on this outcome, because it was not a planned primary or secondary outcome. However, if a Pearson chi-square test2 is used to compare these proportions, as was used in similar analyses performed in the VIP Trial,1 the P value would be 0.05. (Given the number of patients with pathologic myopia in the verteporfin-treated group and placebo-treated group, the VIP Study Group chose to report P values to two decimal places.) Drs. Ruiz-Oliva and Corte´ s do not state what method they used to obtain a P value of 0.085. If one uses Fisher’s exact test, a P value of 0.08 would be obtained; if one uses a corrected chi-square, a P value of 0.09 would be obtained using SAS software.3 However, these latter two tests are commonly used in tables with small sample sizes not reflective of the sample sizes of the VIP Trial.
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