- Email: [email protected]
Corneal Dystrophy Recurrence
Letters to the Editor NORMAN A. SAFFRA, MD RAJEN U. DESAI, MD NURIT HAR-ZVI, OD Brooklyn, New York References 1. Longmuir SQ, Pfeifer W, Leon A, et al. Nine-year results of a volunteer lay network photoscreening program of 147 809 children using a photoscreener in Iowa. Ophthalmology 2010; 117:1869 –75. 2. Schmidt P, Maguire M, Dobson V, et al. Vision in Preschoolers Study Group. Comparison of preschool vision screening tests as administered by licensed eye care professionals in the Vision In Preschoolers Study. Ophthalmology 2004;111:637–50. 3. Donahue SP, Johnson TM, Leonard-Martin TC. Screening for amblyogenic factors using a volunteer lay network and the MTI photoscreener: Initial results from 15,000 preschool children in a statewide effort. Ophthalmology 2000;107:1637– 46.
Corneal Dystrophy Recurrence Dear Editor: We read with interest the recently published article by Germundsson et al1 titled, “Clinical outcome and recurrence of epithelial basement membrane dystrophy after phototherapeutic keratectomy: a cross-sectional study.” The authors state that the study followed a cross-sectional design, describing use of medical records at a postoperative visit as their source of data. However, the authors also describe patients as having 3 visits (i.e., preoperative, postoperative, and an additional follow-up visit) with varying lengths of time among patients, suggesting a longitudinal design. Since patients were included based upon having excimer laser phototherapeutic keratectomy (i.e., the exposure) and then observed for a period up to 100 months for recurrence of epithelial basement membrane dystrophy (i.e., the outcome), this is more appropriately described as a cohort study. As a result, the analysis of the study may not be appropriate given the nature of the study design and associated data. While the authors’ use of exact logistic regression is not invalid due to the limited sample size, given the prospective nature of the study data and the common occurrence of the outcome, we express concern that the regression technique may not be the most appropriate choice. Instead, we suggest that the authors use a method that can estimate risk and simultaneously account for the intereye correlation such as generalized estimating equations with a log-binomial distribution2 or a Cox proportional hazards model stratified by the number of eyes a patient included in the study.3 We hope the authors will consider our comments and update the analysis. JUSTIN BLACKBURN, MPH RUSSELL GRIFFIN, MPH GERALD MCGWIN, JR, PHD Birmingham, Alabama References 1. Germundsson J, Fagerholm P, Lagali N. Clinical outcome and recurrence of epithelial basement membrane dystrophy after
phototherapeutic keratectomy: a cross-sectional study. Ophthalmology 2010;118:515–22. 2. Murdoch IE, Morris SS, Cousens SN. People and eyes: statistical approaches in ophthalmology. Br J Ophthalmol 1998; 82:971–3. 3. Williams KA, Lowe M, Bartlett C, et al. Risk factors for human corneal graft failure within the Australian corneal graft registry. Transplantation 2008;86:1720 – 4.
Author reply Dear Editor: We wish to thank the correspondents for their interest in our recently published article,1 and we welcome this opportunity to clarify details of the study. Our study design was stated as “cross-sectional” because patients were operated between the years 2001–2008, but not enrolled until a study visit which took place during a 6-month period from December 2008 –May 2009. Patients had only 1 study visit, which was the only visit where clinical and morphological recurrence was assessed, as described in the Methods. We accessed medical records retrospectively to obtain preoperative data such as best spectacle-corrected visual acuity, refraction, and symptoms. The 1–2 month postoperative visit is standard in our clinic and was mentioned for completeness, but the vision data from that visit was not used in the study or subsequent analysis, as we wished to report long-term outcomes. Only data from preoperative records and the final, study visit was used. The exact logistic regression method we applied was suited to the study design, given its nonprospective nature. We additionally conditioned the regression to account for variable follow-up time and inter-eye correlation, as described in the Methods. Importantly, one limitation of the cross-sectional design of the study is that it did not yield information about exactly when the dystrophy recurred (either symptomatically or morphologically). Questioning at the study visit only revealed whether patients had experienced erosive events postoperatively, and examination at the study visit only revealed reduced visual acuity and/or morphological signs of recurrence at that point in time. Survival analysis would therefore be inappropriate as this requires knowledge of time-to-recurrence. A prospective study design could be used to identify onset of clinical recurrence (if patients immediately reported symptoms), but morphological recurrence would be more difficult to assess, as our study shows that this form of recurrence does not always accompany clinical symptoms. One way to assess onset of morphological recurrence would be to perform slit lamp and in vivo confocal microscopy examination at regular, monthly postoperative intervals in a longitudinal study design. Although we were unable to identify time-to-recurrence in our study, we could still examine the proportion of patients with recurrence stratified by the number of postoperative years (Figure 5). A tendency toward an increased proportion of recurrence with increasing postoperative time was noted, and was particularly evident in the case of morphological recurrence.
1223
Corneal Dystrophy Recurrence Dear Editor: We read with interest the recently published article by Germundsson et al1 titled, “Clinical outcome and recurrence of epithelial basement membrane dystrophy after phototherapeutic keratectomy: a cross-sectional study.” The authors state that the study followed a cross-sectional design, describing use of medical records at a postoperative visit as their source of data. However, the authors also describe patients as having 3 visits (i.e., preoperative, postoperative, and an additional follow-up visit) with varying lengths of time among patients, suggesting a longitudinal design. Since patients were included based upon having excimer laser phototherapeutic keratectomy (i.e., the exposure) and then observed for a period up to 100 months for recurrence of epithelial basement membrane dystrophy (i.e., the outcome), this is more appropriately described as a cohort study. As a result, the analysis of the study may not be appropriate given the nature of the study design and associated data. While the authors’ use of exact logistic regression is not invalid due to the limited sample size, given the prospective nature of the study data and the common occurrence of the outcome, we express concern that the regression technique may not be the most appropriate choice. Instead, we suggest that the authors use a method that can estimate risk and simultaneously account for the intereye correlation such as generalized estimating equations with a log-binomial distribution2 or a Cox proportional hazards model stratified by the number of eyes a patient included in the study.3 We hope the authors will consider our comments and update the analysis. JUSTIN BLACKBURN, MPH RUSSELL GRIFFIN, MPH GERALD MCGWIN, JR, PHD Birmingham, Alabama References 1. Germundsson J, Fagerholm P, Lagali N. Clinical outcome and recurrence of epithelial basement membrane dystrophy after
phototherapeutic keratectomy: a cross-sectional study. Ophthalmology 2010;118:515–22. 2. Murdoch IE, Morris SS, Cousens SN. People and eyes: statistical approaches in ophthalmology. Br J Ophthalmol 1998; 82:971–3. 3. Williams KA, Lowe M, Bartlett C, et al. Risk factors for human corneal graft failure within the Australian corneal graft registry. Transplantation 2008;86:1720 – 4.
Author reply Dear Editor: We wish to thank the correspondents for their interest in our recently published article,1 and we welcome this opportunity to clarify details of the study. Our study design was stated as “cross-sectional” because patients were operated between the years 2001–2008, but not enrolled until a study visit which took place during a 6-month period from December 2008 –May 2009. Patients had only 1 study visit, which was the only visit where clinical and morphological recurrence was assessed, as described in the Methods. We accessed medical records retrospectively to obtain preoperative data such as best spectacle-corrected visual acuity, refraction, and symptoms. The 1–2 month postoperative visit is standard in our clinic and was mentioned for completeness, but the vision data from that visit was not used in the study or subsequent analysis, as we wished to report long-term outcomes. Only data from preoperative records and the final, study visit was used. The exact logistic regression method we applied was suited to the study design, given its nonprospective nature. We additionally conditioned the regression to account for variable follow-up time and inter-eye correlation, as described in the Methods. Importantly, one limitation of the cross-sectional design of the study is that it did not yield information about exactly when the dystrophy recurred (either symptomatically or morphologically). Questioning at the study visit only revealed whether patients had experienced erosive events postoperatively, and examination at the study visit only revealed reduced visual acuity and/or morphological signs of recurrence at that point in time. Survival analysis would therefore be inappropriate as this requires knowledge of time-to-recurrence. A prospective study design could be used to identify onset of clinical recurrence (if patients immediately reported symptoms), but morphological recurrence would be more difficult to assess, as our study shows that this form of recurrence does not always accompany clinical symptoms. One way to assess onset of morphological recurrence would be to perform slit lamp and in vivo confocal microscopy examination at regular, monthly postoperative intervals in a longitudinal study design. Although we were unable to identify time-to-recurrence in our study, we could still examine the proportion of patients with recurrence stratified by the number of postoperative years (Figure 5). A tendency toward an increased proportion of recurrence with increasing postoperative time was noted, and was particularly evident in the case of morphological recurrence.
1223