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Histopathologic confirmation of cutaneous eyelid lesions
Letters to the Editor Giant Cell Arteritis and Intravenous Methylprednisolone Dear Editor: Cornblath and Eggenberger concluded in "Progressive Visual Loss from Giant Cell Arteritis Despite High-dose Intravenous Methylprednisolone" ( Ophthahnology 1997; 104:854- 8) that, ' 'The results of intravenous methylprednisolone (IVMP) treatment of patients with visual loss from GCA are similar to the results of treatment with oral corticosteroids, with IVMP treatment being more costly and having a small risk of sudden death." In our neuro-ophthalmology clinic, we use IVMP treatment for patients with giant cell arteritis (GCA) and visual loss who are monocular, have bilateral or severe visual loss, or develop progressive loss or fellow eye involvement despite oral prednisone therapy. I wonder whether the decision to use IVMP (versus oral therapy alone) at other institutions (including the huthors' series) is biased by treating only more severe disease. This selection bias might result in a falsely lower rate of visual recovery for patients treated with IVMP compared with standard oral steroid therapy. As the authors point out, in the literature visual recovery in patients with GCA and visual loss treated with oral steroids or IVMP is not common, and it is not clear that IVMP improves the visual recovery rate or decreases the rate of visual loss. Nevertheless, Liu et ai ~ reported that in 41 patients with visual loss due to GCA treated with oral prednisone alone or IVMP, fellow eye involvement was observed only with oral therapy. Two of the five cases reported by Cornblath and Eggenberger were treated with oral steroids for variable periods of time prior to the initiation of IVMP. The remaining three cases had bilateral symptoms or signs prior to initiation of IVMP. I wonder if the authors could comment on the role of IVMP in the possible prevention of fellow eye involvement. ANDREW G. LEE, MD
Houston, Texas Reference I. Liu GT, Glaser JS, Schatz NJ, Smith JL. Visual morbidity in giant cell arteritis. Clinical characteristics and prognosis for vision. Ophthalmology 1994; 101:1779-85. Authors' reply Dear Editor: As in other areas of medicine in which there is no definitive proven treatment, physicians must use their judgment and weigh the risks and benefits when, deciding on a course of treatment. Dr. Lee presents his criteria for the use of intravenous methylprednisolone (IVMP) in selected cases of giant cell arteritis (GCA). It is quite possible that our group of patients was subject to referral bias
and represented a more severe spectrum of GCA. However, this does not change the point of the paper: there is no proven efficacy to using IVMP for GCA, and as in all treatments with little data, physicians must make a case-by-case decision and weigh the factors of risk, cost, and possible improved outcome. We still use IVMP in select cases. Dr. Lee raises a question of prevention of fellow eye involvement through the use IVMP. In our two cases with visual loss in the uninvolved eye, patients were seen within 3 to 5 days of the onset of visual loss and treated with oral prednisone for 2 to 4 days. The patients then lost vision 48 hours after IVMP had started. It is possible that starting IVMP at the first onset of symptoms might have prevented second eye involvement, but this remains unknown. Liu et al 2 reported no patients losing vision in a previously uninvolved eye when treated with IVMP. However, the numbers in their report were too small to have statistical significance. The role of IVMP treatment in GCA, i.e., if it improves visual outcome or reduces involvement of the uninvolved second eye, remains unclear, and physicians must use individual circumstances when making these treatment decisions. WAYNE T. CORNBLATH, MD ERIC EGGENBERGER, DO
Ann Arbor, Michigan References 1. Cornblath WT, Eggenberger ER. Progressive visual loss from giant cell arteritis despite high-dose intravenous methylprednisolone. Ophthalmology 1997; 104:854-8. 2. Liu GT, Glaser JS, Schatz NJ, Smith JL. Visual morbidity in giant cell arteritis. Clinical characteristics and prognosis for vision. Ophthalmology 1994; 101:1779-85. Histopathologic Confirmation of Cutaneous Eyelid Lesions Dear Editor: Drs. Kersten et al, are to be con~atulated for their prospective study of the accuracy of clinical diagnosis of cutaneous eyelid lesions. ~ Their report emphasizes the high index of suspicion for malignancy one must have for benign-appearing lesions. However, I do not believe their conclusion that all excised eyelid lesions should be submitted for histopathologic confirmation follows from their data. Prior to excision, each lesion was categorized as most likely to represent a benign, malignant, or premalignant process. I believe the lesions in the " m o s t likely benign" category could be further subdivided into two categories: (1) "appears benign but could possibly be malignant"' and (2) "appears benign and could not possibly be malignant." I submit that there are lesions, such as xanthel-
203
Ophthalmology
Volume 105, Number 2, February •998
asma, in the second category, and that lesions in this category do not require histopathologic confirmation. In this study, 13 of 692 lesions that were thought to be benign turned out to be malignant. Ten of those 13 lesions were basal cell carcinomas. I wonder exactly how much morbidity is generated by excising an occasional undiagnosed basal cell carcinoma. Since these lesions are usually quite small at the time of excision, I suspect that a number of them would have been completely excised, and thus would not recur. Of those undiagnosed basal cell carcinomas that were not completely excised, one would expect only one third of them to recur. 2 Unless they occurred in a particularly treacherous location, I believe that recurrences could be dealt with quite satisfactorily with excision using frozen sections or the Mohs' technique. It is not clear that falling to diagnose malignancy in these ten lesions would have any significant consequences for the patients involved. I recently removed approximately 50 lesions that appeared to be papillomas from a patient's periocular area and face. Had I submitted these for histopathologic confirmation, the mere task of labeling each specimen and mapping exactly where it came from would have been daunting. Furthermore, using the authors' reported cost o~ $62.49 per lesion for examination and reporting by the pathologist, a pathology bill of over $3000 would have been generated, with dubious value to the patient. While this study demonstrates that some lesions that appear benign may in fact be malignant or premalignant, it does not support the sweeping generalization that all excised eyelid lesions require histopathologic confirmation. Clihical judgment, while not perfect, still has a role to play. LAWRENCE H. QUIST, MD
Minneapolis, Minnesota References
1. Kersten RC, Ewing-Chow D, Kulwin DR, Gallon M. Accuracy of clinical diagnosis of cutaneous eyelid lesions. Ophthalmology 1997; 104:479-84. 2. Gooding CA, White G, Yatsuhashi M. Significance of marginal extension in excised basal-cell carcinoma. N Engl J Med 1965;273:923-4. Author's reply Dear Editor: At the onset of this study I too believed that it would be possible to clinically identify those lesions that "appear benign and could not possibly be malignant." Dr. Quist suggests that xanthelasmas, and by inference, "papillomas" are lesions that fall into this category, and would not require histopathologic confirmation. Only a few xanthelasmas were included in our study, as we limited it to those lesions that were completely removed in the office chair. We did, however, remove over 300 "papillomas," all of which were thought to be benign, and yet 6 proved histopathologically to harbor malignancies. Of the 154 "epidermal inclusion cysts," all of which we thought could not possibly be malignant, 2 were cystic basal cell carcinomas. Eighty-seven "me|anocytic nevi," all of
204
which were presumed to be benign, harbored I basal cell carcinoma and 1 non-Hodgkin lymphoma, and 75 "hydrocystomas" also contained 2 unsuspected malignancies. Clinical medicine does require us to make cost-benefit decisions. I do agree with Dr. Quist that the morbidity arising from excising an occasional undiagnosed basal cell carcinoma may not be high. On the other hand, a "papilloma" could conceivably also represent an amelanotic melanoma. If one elects to depend on clinical judgement rather than histopathologic evaluation, one is obliged to thoroughly educate the patient about the potential for missing a malignancy and the need for assiduous follow-up should a "benign" lesion recur. ROBERT C. KERSTEN, MD
Cincinnati, Ohio Pointwise Univariate Linear Regression of Perimetric Sensitivity Against Follow-up Time in G l a u c o m a Dear Editor: The Appendix of the article by Wild et al, "Pointwise Univariate Linear Regression of Perimetric Sensitivity Against Follow-up Time in Glaucoma" (Ophthalmology 1997; 104:808-15) contains some statistical mistakes and misconceptions. 1. The formula given for standard error is wrong. In the formula as stated, the right-hand side is identically zero. 2. The t-statistic given for comparison of individual slopes with those derived from the normal database is not correct. The decline in sensitivity of a test location with age presumably varies between healthy individuals, yet this variability does not appear in the authors' statistic. Thus, the statistic provides no information about how significant an individual slope really is. For example, they might determine that an individual slope is almost certainly less than the population average, but we would expect a large percentage of nomaal slopes to fall into this category, the exact proportion depending on how certain we are of the individual slope as well as the magnitude of variation in the population. They might also say that their slope estimate is five or ten times as large in absolute value as the population average, but, again, a high percentage of healthy individuals could share this characteristic. Also, since the "normal slope" that they use is an estimate of the true (unknown) population average, it contributes an additional element of uncertainty that should be included in the formula. These additional variance terms should appear in the denominator of the test statistic. Thus, the statistic that they use is too small, and it is possible that far too many significant values will be found. Since most of the content of the paper depends on this formula, few of their results and conclusions are correct. 3. An additional source of error in their test statistics is the failure to account for temporal dependence between measurements. Let us assume that sensitivity at a location is measured on five different occasions and that the correlation between measurements varies with time in an autoregressive pattern, i.e., correlation decreases the further apart measurements are taken. We fit a regression line to the data using ordinary least squares, as do the authors.
Houston, Texas Reference I. Liu GT, Glaser JS, Schatz NJ, Smith JL. Visual morbidity in giant cell arteritis. Clinical characteristics and prognosis for vision. Ophthalmology 1994; 101:1779-85. Authors' reply Dear Editor: As in other areas of medicine in which there is no definitive proven treatment, physicians must use their judgment and weigh the risks and benefits when, deciding on a course of treatment. Dr. Lee presents his criteria for the use of intravenous methylprednisolone (IVMP) in selected cases of giant cell arteritis (GCA). It is quite possible that our group of patients was subject to referral bias
and represented a more severe spectrum of GCA. However, this does not change the point of the paper: there is no proven efficacy to using IVMP for GCA, and as in all treatments with little data, physicians must make a case-by-case decision and weigh the factors of risk, cost, and possible improved outcome. We still use IVMP in select cases. Dr. Lee raises a question of prevention of fellow eye involvement through the use IVMP. In our two cases with visual loss in the uninvolved eye, patients were seen within 3 to 5 days of the onset of visual loss and treated with oral prednisone for 2 to 4 days. The patients then lost vision 48 hours after IVMP had started. It is possible that starting IVMP at the first onset of symptoms might have prevented second eye involvement, but this remains unknown. Liu et al 2 reported no patients losing vision in a previously uninvolved eye when treated with IVMP. However, the numbers in their report were too small to have statistical significance. The role of IVMP treatment in GCA, i.e., if it improves visual outcome or reduces involvement of the uninvolved second eye, remains unclear, and physicians must use individual circumstances when making these treatment decisions. WAYNE T. CORNBLATH, MD ERIC EGGENBERGER, DO
Ann Arbor, Michigan References 1. Cornblath WT, Eggenberger ER. Progressive visual loss from giant cell arteritis despite high-dose intravenous methylprednisolone. Ophthalmology 1997; 104:854-8. 2. Liu GT, Glaser JS, Schatz NJ, Smith JL. Visual morbidity in giant cell arteritis. Clinical characteristics and prognosis for vision. Ophthalmology 1994; 101:1779-85. Histopathologic Confirmation of Cutaneous Eyelid Lesions Dear Editor: Drs. Kersten et al, are to be con~atulated for their prospective study of the accuracy of clinical diagnosis of cutaneous eyelid lesions. ~ Their report emphasizes the high index of suspicion for malignancy one must have for benign-appearing lesions. However, I do not believe their conclusion that all excised eyelid lesions should be submitted for histopathologic confirmation follows from their data. Prior to excision, each lesion was categorized as most likely to represent a benign, malignant, or premalignant process. I believe the lesions in the " m o s t likely benign" category could be further subdivided into two categories: (1) "appears benign but could possibly be malignant"' and (2) "appears benign and could not possibly be malignant." I submit that there are lesions, such as xanthel-
203
Ophthalmology
Volume 105, Number 2, February •998
asma, in the second category, and that lesions in this category do not require histopathologic confirmation. In this study, 13 of 692 lesions that were thought to be benign turned out to be malignant. Ten of those 13 lesions were basal cell carcinomas. I wonder exactly how much morbidity is generated by excising an occasional undiagnosed basal cell carcinoma. Since these lesions are usually quite small at the time of excision, I suspect that a number of them would have been completely excised, and thus would not recur. Of those undiagnosed basal cell carcinomas that were not completely excised, one would expect only one third of them to recur. 2 Unless they occurred in a particularly treacherous location, I believe that recurrences could be dealt with quite satisfactorily with excision using frozen sections or the Mohs' technique. It is not clear that falling to diagnose malignancy in these ten lesions would have any significant consequences for the patients involved. I recently removed approximately 50 lesions that appeared to be papillomas from a patient's periocular area and face. Had I submitted these for histopathologic confirmation, the mere task of labeling each specimen and mapping exactly where it came from would have been daunting. Furthermore, using the authors' reported cost o~ $62.49 per lesion for examination and reporting by the pathologist, a pathology bill of over $3000 would have been generated, with dubious value to the patient. While this study demonstrates that some lesions that appear benign may in fact be malignant or premalignant, it does not support the sweeping generalization that all excised eyelid lesions require histopathologic confirmation. Clihical judgment, while not perfect, still has a role to play. LAWRENCE H. QUIST, MD
Minneapolis, Minnesota References
1. Kersten RC, Ewing-Chow D, Kulwin DR, Gallon M. Accuracy of clinical diagnosis of cutaneous eyelid lesions. Ophthalmology 1997; 104:479-84. 2. Gooding CA, White G, Yatsuhashi M. Significance of marginal extension in excised basal-cell carcinoma. N Engl J Med 1965;273:923-4. Author's reply Dear Editor: At the onset of this study I too believed that it would be possible to clinically identify those lesions that "appear benign and could not possibly be malignant." Dr. Quist suggests that xanthelasmas, and by inference, "papillomas" are lesions that fall into this category, and would not require histopathologic confirmation. Only a few xanthelasmas were included in our study, as we limited it to those lesions that were completely removed in the office chair. We did, however, remove over 300 "papillomas," all of which were thought to be benign, and yet 6 proved histopathologically to harbor malignancies. Of the 154 "epidermal inclusion cysts," all of which we thought could not possibly be malignant, 2 were cystic basal cell carcinomas. Eighty-seven "me|anocytic nevi," all of
204
which were presumed to be benign, harbored I basal cell carcinoma and 1 non-Hodgkin lymphoma, and 75 "hydrocystomas" also contained 2 unsuspected malignancies. Clinical medicine does require us to make cost-benefit decisions. I do agree with Dr. Quist that the morbidity arising from excising an occasional undiagnosed basal cell carcinoma may not be high. On the other hand, a "papilloma" could conceivably also represent an amelanotic melanoma. If one elects to depend on clinical judgement rather than histopathologic evaluation, one is obliged to thoroughly educate the patient about the potential for missing a malignancy and the need for assiduous follow-up should a "benign" lesion recur. ROBERT C. KERSTEN, MD
Cincinnati, Ohio Pointwise Univariate Linear Regression of Perimetric Sensitivity Against Follow-up Time in G l a u c o m a Dear Editor: The Appendix of the article by Wild et al, "Pointwise Univariate Linear Regression of Perimetric Sensitivity Against Follow-up Time in Glaucoma" (Ophthalmology 1997; 104:808-15) contains some statistical mistakes and misconceptions. 1. The formula given for standard error is wrong. In the formula as stated, the right-hand side is identically zero. 2. The t-statistic given for comparison of individual slopes with those derived from the normal database is not correct. The decline in sensitivity of a test location with age presumably varies between healthy individuals, yet this variability does not appear in the authors' statistic. Thus, the statistic provides no information about how significant an individual slope really is. For example, they might determine that an individual slope is almost certainly less than the population average, but we would expect a large percentage of nomaal slopes to fall into this category, the exact proportion depending on how certain we are of the individual slope as well as the magnitude of variation in the population. They might also say that their slope estimate is five or ten times as large in absolute value as the population average, but, again, a high percentage of healthy individuals could share this characteristic. Also, since the "normal slope" that they use is an estimate of the true (unknown) population average, it contributes an additional element of uncertainty that should be included in the formula. These additional variance terms should appear in the denominator of the test statistic. Thus, the statistic that they use is too small, and it is possible that far too many significant values will be found. Since most of the content of the paper depends on this formula, few of their results and conclusions are correct. 3. An additional source of error in their test statistics is the failure to account for temporal dependence between measurements. Let us assume that sensitivity at a location is measured on five different occasions and that the correlation between measurements varies with time in an autoregressive pattern, i.e., correlation decreases the further apart measurements are taken. We fit a regression line to the data using ordinary least squares, as do the authors.