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IOLs in Uveitis Patients
Letters to the Editor come measures besides membrane size and foveal threshold need to be evaluated in future studies. As the authors note, more information could be obtained from a prospective, randomized study that has adequate sample size. The importance of Poliner et al's study is its usefulness for determining the sample size necessary to make an observed treatment effect statistically significant. We hope that when a future prospective study is performed, it will include objective outcome measures such as perimetry, the pre-trial determination of what is considered a "clinically significant" difference, and adequate statistical power to support any "negative" concluslon. SEAN P. DONAHUE, MD, PHD MICHAEL WALL, MD THOMAS A. WEINGEIST, MD, PHD
Iowa City, Iowa
Reference 1. Freiman JA, Chalmers TC, Smith H, Kuebler RR. The importance of beta, the type II error and sample size in the design and interpretation of the randomized control trial. N Eng! J Med 1978;299:690-5.
Authors' reply Dear Editor: We appreciate the comments of Drs. Donahue, Wall, and Weingeist concerning our article. We agree that, in small prospective trials of this nature, study power is often insufficient to draw definitive conclusions with regard to statistical significance. However, issues related to sample size and power calculations often are more relevant to study design, not to analysis of study results. 1 Before the publication of our randomized trial, only one Letter to the Editor had been published suggesting a beneficial effect of interferon alpha-2a. 2 In Fung's2 correspondence, there was no measurement of subretinal neovascular involution documented. As a consequence, in the study design phases of our trial, there was little information to suggest what might represent a significant difference in the neovascular growth pattern comparing treatment and control. After randomizing 20 patients, we found that the difference between our treated and control groups would not have been detected as significant until recruitment of more than 400 patients had been accomplished. Given the side effects of interferon alpha-2a, this recruitment goal was believed to be unrealistic. In our article, we did not state that there was either a positive or negative effect for interferon in the treatment of subfoveal neovascularization, but that no effect could be proven with our small sample size. These assertions are stated clearly in the Results section of our article and should not mislead readers with regard to the statistical analysis. Donahue et al also suggest that the extent of neovascular growth should have been tied to either degree of visual change or change in visual field. They also suggest that "foveal threshold" probably is not adequate. Given that Fung2 had reported improvement in visual function
without regard to measurements of neovascular growth, we believed that change in subretinal neovascular complex size and change in visual acuity should be evaluated independently. We question why Donahue et al contend that visual acuity and membrane size should be evaluated dependently, in their definition of "clinically significant growth." At issue for patients is their final visual outcome, regardless of the neovascular growth pattern. Regarding visual field assessment, foveal thresholds were believed to represent a reasonable reflection of fixation function, whereas assessment with a Humphrey 10-2 would reflect scotoma size. It was not our intent to assess scotoma size, although other studies in the future may wish to do so. In addition, other measures not mentioned, such as reading time, performance of daily activities, and mapping by laser interferometry, probably would provide more accurate information regarding macular function. We agree that further studies may prove of value, but, with the significant side effects of interferon, other related compounds and growth factors may need to be considered. LON S. POLINER, MD PAUL E. TORNAMBE, MD
La Jolla, California
References 1. Matthews D, Farewell V. Using and Understanding Medical
Statistics. Basel: Karger, 1985;187-8. 2. Fung WE. Interferon alpha 2a for treatment of age-related macular degeneration [letter]. Am J OphthalmoI1991;112: 349-50.
IOLs in Uveitis Patients Dear Editor: In the article entitled, "Intraocular Lens Implantation versus No Intraocular Lens Implantation in Patients with Chronic Iridocyclitis and Pars Planitis" (Ophthalmology 1993;100:1206-9), Drs. Tessler and Farber present the results of their randomized prospective study assessing the safety of intraocular lens (IOL) implantation in patients with uveitis. The authors acknowledge the following limitations: small number of patients with possible recruitment bias; lack of standardization of surgical technique or surgeon; and variability of testing method for final outcome (visual acuity at 1 year) with no tester masking. Statistical methods and numerical significance are not shown. The investigators conclude, "given the confines of this limited study, it is probably safe to place an IOL in patients with uveitis." The authors' data in their Table 1 regarding patients with chronic iridocyclitis and excluding those with pars planitis are summarized in our Table 1. At 1 year, the percentage of patients with visual acuity 20/40 or better was approximately equal in the two treatment groups. However, at a lower visual outcome threshold there was a marked difference. Thirty percent of the patients with pseudophakia were left with a best-corrected visual acuity worse than 20/80, whereas all the aphakic patients had a visual acuity of 20/80 or better.
625
Ophthalmology
Volume 101, Number 4, April 1994
Table 1. Sumary of Data All Patients (n = 22)
8 67
30 50
45
50 100
40 70
Postoperative Visual Acuity-% of Patients 20/40 or better 20/80 or better
86
intraocular lens.
In the abstract of this article, the authors state that "IOLs are relatively safe in patients with chronic iridocyclitis." The authors' data would suggest that nearly a third of patients in whom IOLs are implanted may have a poor visual outcome. Clearly, more study is required before IOL placement in patients with uveitis is considered safe and routine. WARREN ANDERSON, MD
Bethesda, Maryland Authors' reply
Dear Editor: We thank Dr. Anderson for his thoughts. We agree with
626
18
59
=
IOL
(n = 10)
Preoperative Visual Acuity-% of Patients 20/100 or better 20/200 or better
IOL
NoIOL
(n = 12)
his conclusions and stated them in our article. Statistically, there was no difference between those patients who received an intraocular lens (IOL) and those who did not. Given the small number of patients, the trend to better vision without an IOL in chronic iridocyclitis could not be verified. We found that recruitment became more difficult because both ophthalmologists and patients desired IOLs and did not wish to participate in the study. We terminated the study and compiled results. A larger study with 250 patients initially was planned. HOWARD H. TESSLER, MD MARILYN FARBER, PHD
Chicago, Illinois
Iowa City, Iowa
Reference 1. Freiman JA, Chalmers TC, Smith H, Kuebler RR. The importance of beta, the type II error and sample size in the design and interpretation of the randomized control trial. N Eng! J Med 1978;299:690-5.
Authors' reply Dear Editor: We appreciate the comments of Drs. Donahue, Wall, and Weingeist concerning our article. We agree that, in small prospective trials of this nature, study power is often insufficient to draw definitive conclusions with regard to statistical significance. However, issues related to sample size and power calculations often are more relevant to study design, not to analysis of study results. 1 Before the publication of our randomized trial, only one Letter to the Editor had been published suggesting a beneficial effect of interferon alpha-2a. 2 In Fung's2 correspondence, there was no measurement of subretinal neovascular involution documented. As a consequence, in the study design phases of our trial, there was little information to suggest what might represent a significant difference in the neovascular growth pattern comparing treatment and control. After randomizing 20 patients, we found that the difference between our treated and control groups would not have been detected as significant until recruitment of more than 400 patients had been accomplished. Given the side effects of interferon alpha-2a, this recruitment goal was believed to be unrealistic. In our article, we did not state that there was either a positive or negative effect for interferon in the treatment of subfoveal neovascularization, but that no effect could be proven with our small sample size. These assertions are stated clearly in the Results section of our article and should not mislead readers with regard to the statistical analysis. Donahue et al also suggest that the extent of neovascular growth should have been tied to either degree of visual change or change in visual field. They also suggest that "foveal threshold" probably is not adequate. Given that Fung2 had reported improvement in visual function
without regard to measurements of neovascular growth, we believed that change in subretinal neovascular complex size and change in visual acuity should be evaluated independently. We question why Donahue et al contend that visual acuity and membrane size should be evaluated dependently, in their definition of "clinically significant growth." At issue for patients is their final visual outcome, regardless of the neovascular growth pattern. Regarding visual field assessment, foveal thresholds were believed to represent a reasonable reflection of fixation function, whereas assessment with a Humphrey 10-2 would reflect scotoma size. It was not our intent to assess scotoma size, although other studies in the future may wish to do so. In addition, other measures not mentioned, such as reading time, performance of daily activities, and mapping by laser interferometry, probably would provide more accurate information regarding macular function. We agree that further studies may prove of value, but, with the significant side effects of interferon, other related compounds and growth factors may need to be considered. LON S. POLINER, MD PAUL E. TORNAMBE, MD
La Jolla, California
References 1. Matthews D, Farewell V. Using and Understanding Medical
Statistics. Basel: Karger, 1985;187-8. 2. Fung WE. Interferon alpha 2a for treatment of age-related macular degeneration [letter]. Am J OphthalmoI1991;112: 349-50.
IOLs in Uveitis Patients Dear Editor: In the article entitled, "Intraocular Lens Implantation versus No Intraocular Lens Implantation in Patients with Chronic Iridocyclitis and Pars Planitis" (Ophthalmology 1993;100:1206-9), Drs. Tessler and Farber present the results of their randomized prospective study assessing the safety of intraocular lens (IOL) implantation in patients with uveitis. The authors acknowledge the following limitations: small number of patients with possible recruitment bias; lack of standardization of surgical technique or surgeon; and variability of testing method for final outcome (visual acuity at 1 year) with no tester masking. Statistical methods and numerical significance are not shown. The investigators conclude, "given the confines of this limited study, it is probably safe to place an IOL in patients with uveitis." The authors' data in their Table 1 regarding patients with chronic iridocyclitis and excluding those with pars planitis are summarized in our Table 1. At 1 year, the percentage of patients with visual acuity 20/40 or better was approximately equal in the two treatment groups. However, at a lower visual outcome threshold there was a marked difference. Thirty percent of the patients with pseudophakia were left with a best-corrected visual acuity worse than 20/80, whereas all the aphakic patients had a visual acuity of 20/80 or better.
625
Ophthalmology
Volume 101, Number 4, April 1994
Table 1. Sumary of Data All Patients (n = 22)
8 67
30 50
45
50 100
40 70
Postoperative Visual Acuity-% of Patients 20/40 or better 20/80 or better
86
intraocular lens.
In the abstract of this article, the authors state that "IOLs are relatively safe in patients with chronic iridocyclitis." The authors' data would suggest that nearly a third of patients in whom IOLs are implanted may have a poor visual outcome. Clearly, more study is required before IOL placement in patients with uveitis is considered safe and routine. WARREN ANDERSON, MD
Bethesda, Maryland Authors' reply
Dear Editor: We thank Dr. Anderson for his thoughts. We agree with
626
18
59
=
IOL
(n = 10)
Preoperative Visual Acuity-% of Patients 20/100 or better 20/200 or better
IOL
NoIOL
(n = 12)
his conclusions and stated them in our article. Statistically, there was no difference between those patients who received an intraocular lens (IOL) and those who did not. Given the small number of patients, the trend to better vision without an IOL in chronic iridocyclitis could not be verified. We found that recruitment became more difficult because both ophthalmologists and patients desired IOLs and did not wish to participate in the study. We terminated the study and compiled results. A larger study with 250 patients initially was planned. HOWARD H. TESSLER, MD MARILYN FARBER, PHD
Chicago, Illinois