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Astigmatism and Periocular Hemangioma
Ophthalmology Volume 115, Number 10, October 2008 microperimetry data would have admirably supported the claims made by the authors.2,3 Despite these limitations and those listed by the authors, we admire the authors’ ingenuity in bringing forth the utility of this simple technique to the aid of the treating retinal physicians and their patients. ABHIJIT DATTA, MS ANIRUDDHA MAITI, DNB MAHESH UPARKAR, MS, MRCOPHTH(LON) Mumbai, India References 1. Vaclavik V, Vujosevic S, Dandekar SS, et al. Autofluorescence imaging in age-related macular degeneration complicated by choroidal neovascularization: a prospective study. Ophthalmology 2008;115:342– 6. 2. Midena E, Vujosevic S, Convento E, et al. Microperimetry and fundus autofluorescence in patients with early age-related macular degeneration. Br J Ophthalmol 2007;91:1499 –503. 3. Trieschmann M, Spital G, Lommatzsch A, et al. Macular pigment: quantitative analysis on autofluorescence images. Graefes Arch Clin Exp Ophthalmol 2003;241:1006 –12.
Author reply Dear Editor: Until now, the study of age-related macular degeneration has been limited to the analysis of color fundus photographs, fluorescein angiography images, and optical coherence tomography (OCT) findings.1 However, with the higher expectations of current treatments based on biological agents, the assessment of the viability of the retina and retinal pigment epithelium (RPE) will give an indication of the possible therapeutic success.2,3 Therefore, the evaluation of the health of the RPE has become an important step in understanding the disease process. Autofluorescence (AF) imaging provides highly detailed information about the level and distribution of lipofuscin of the RPE, revealing a previously invisible structure. AF allows analysis of the sequence of pigment epithelial changes and gives indirect information on the level of metabolic activity of the RPE. In our study, we analyzed whether the AF at the macula was present and continuous or not. We did take into consideration some widespread areas of punctiform hypofluorescence caused by the presence of drusen. Those areas were identified and compared with the color photos and fluorescein angiography. We could clearly identify areas of irregular hypofluorescence caused by drusen from larger areas of hypofluorescence caused by RPE dysfunction. The high kappa value of 2 independent readers implies that the decision on the continuity of AF was reliable. OCT is a noninvasive technique that provides optical cross-sections of the retina4 and gives information about the anatomic state of the outer retina and the thickness of retinal layers. However, OCT gives information only on optical interfaces and not on the functional characteristics of the outer retina. In addition, OCT imaging does not always allow a clear distinction between an occult and a classic choroidal neovascularization. We did not analyze the sectoral distribution of AF or perform microperimetry, which requires fixation of the patient. Good fixation is difficult to obtain in patients with
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subfoveal choroidal neovascularization. Also, microperimetry was not part of our study. We hope we have provided additional information to permit a better understanding of our results. VERONIKA VACLAVIK, MD ALAN C. BIRD, MD London, England References 1. The Age-Related Disease Study Research Group. The Age-Related Eye Disease Study system for classifying age-related macular degeneration from stereoscopic color fundus photographs: The Age-Related Eye Disease Study Report Number 6. Am J Ophthalmol 2001;132:668 – 81. 2. Holz FG, Pauleikhoff D, Klein R, Bird AC. Pathogenesis of lesions in late age-related macular disease. Am J Opthalmol 2004;137:504 –10. 3. Wing GL, Blanchard GC, Weiter JJ. The topography and age relationship of lipofuscin concentration in the retinal pigment epithelium. Invest Ophthalmol Vis Sci 1978;17:601–7. 4. Treatment of age-related macular degeneration with photodynamic therapy Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in AMD with verteporfin: one-year results of 2 randomized clinical trials—TAP Report 1. Arch Ophthalmol 1999;117:1329 – 45.
Astigmatism and Periocular Hemangioma Dear Editor: Weiss and Kelly1 are to be congratulated for putting some evidentiary flesh on the bones of the rationale for treatment of eyelid capillary hemangioma; however, they may have underestimated the effectiveness of their intervention when reporting 63% reduction of the astigmatism in eyes treated with intralesionsal corticosteroid. This figure seems to have been derived by subtracting the mean power of the remaining postoperative cylinder from the equivalent preoperative cylinder power (“the cylinder subtraction method”). The surgically induced astigmatic effect of their treatment is likely to be considerably greater than this because the cylinder subtraction method generally underestimates the surgical effect of any treatment of astigmatism. Consider the following example. If a pretreatment cylinder was ⫹4 diopters (D) at 90 degrees and a posttreatment cylinder was ⫹1 D at 180 degrees, it is intuitively obvious that this was a 5-D change in cylinder power (in other words, the cylinder at 90 degrees went from ⫹4 D to ⫺1 D), not a 3-D change. By cylinder subtraction, this would be a 75% (⫹4 to ⫹1) reduction when it was, in fact, a 125% (⫹4 to ⫺1 D) change, taking the axis into account. Because cylinder change is not always on axis, the conventional way to establish the true surgical change is to apply vector analysis.2– 4 It is interesting how close the treated eyes came, it terms of astigmatism, to the fellow eyes, suggesting that the effect of the treatment was to return the eyes to their native astigmatic state. Most eyes have some minor degree of astigmatism, which is commonly symmetric with the fellow eye, so the likely best end state of these eyes would closely match the astigmatism of the fellow eyes. It would not be reasonable to assume that the cylinder power might go to zero. It would be of considerable interest to set the targeted remaining astigmatism as an astigmatic state symmetric
Letters to the Editor with the other eye and see how close to that target the treatment got.2 Given the results they report, the authors might be pleasantly surprised that they achieved more than a 63% reduction. Even if the endpoint was not zero astigmatism, the reduction of amblyogenesis by making the 2 eyes isometropic, not free of astigmatism, is considerable. MICHAEL GOGGIN, FRCSI(Ophth), FRANZCO, MS Adelaide, Australia References 1. Weiss AH, Kelly JP. Reappraisal of astigmatism induced by periocular capillary hemangioma and treatment with intralesional corticosteroid injection. Ophthalmology 2008;115:390 –7. 2. Alpins NA. A new method of analyzing vectors for changes in astigmatism. J Cataract Refract Surg 1993;19:524 –33. 3. Holladay JT, Cravy TV, Koch DD. Calculating the surgically induced refractive change following ocular surgery. J Cataract Refract Surg 1992;18:429 – 43. 4. Alpins NA, Goggin M. Practical astigmatism analysis for refractive outcomes in cataract and refractive surgery. Surv Ophthalmol 2004;49:109 –22.
Author reply Dear Editor: We thank Dr Goggin for bringing the vector analysis of astigmatism to our attention. Vector analysis provides a more precise measure of astigmatic changes because it takes both the magnitude and axis of astigmatism into account. For those patients with a shift in the axis of astigmatism, we agree that the percentage of reduction in astigmatism is greater than stated in our manuscript. We calculate that the mean reduction in astigmatism for 8 of 13 patients with an axis shift is 2.76⫾1.38 diopters using vector analysis and 2.44⫾1.35 diopters using linear analysis. The largest difference between the linear and vector analysis was 1.125 diopters. For the remaining 5 patients without a shift in astigmatic axis, the mean reduction is the same for both analyses. AVERY H. WEISS, MD JOHN P. KELLY, PHD Seattle, Washington
Lines of Blaschko Dear Editor: Vajaranant et al1 investigated the mosaic pattern of retinal dysfunction in female carriers of X-linked choroideremia by multifocal electroretinography (mfERG) testing. Although the fundus examination demonstrated a patchy depigmentation and clumping of the retinal pigment epithelium (RPE) in the midperiphery, the mfERG findings corresponded well to the severity of the biomicroscopic changes. The authors state, “The presented pattern of mosaic retinal dysfunction on mfERG is predicted by the Lyon hypothesis of random chromosome inactivation in heterozygotic carriers and reminded us of the pattern in sectorially oriented or grouped congenital hyperpigmentations of the retinal pigment epithelium (CHRPE) resembling animal footprints ‘bear tracks.’” Grouped CHRPE are well-delineated hyperpigmentations in one or more quadrants of the ocular fundus. Recently, we
described a patient with grouped CHRPE in the left eye and additional unilateral sectorial hyperpigmented skin lesions on his left shoulder.2 These sectorial pigmentations were noted during the first months of life, did not correspond to the distribution of cutaneous nerves (dermatomes), and followed the lines of Blaschko. These lines of Blaschko may reflect the dorsoventral outgrowth of precursor of the skin, and hence may manifest the stream, distribution, migration, and proliferation of embryonic tissue. They originate during early embryogenesis by various genetic mechanisms, including functional X-chromosomal mosaicism, postzygotic mutations, gametic half-chromatid mutations, or loss of a heterozygosity. If one of these events occurs, both homozygosity and heterozygosity may predispose the individual to sectorial pigmentation of these somatic cells. The clones of these distinct stem cells may give rise to sectorial mosaicism with areas of excessively pigmented lesions.3 Additional studies evaluated the pattern of grouped CHRPE from previously published data and determined the developmental lines of pigmentary lesions in the human eye according to Alfred Blaschko’s concept.4 Small lesions extended from the margin of the optic disc and radiated with larger lesions in sectors to the fundus periphery.5 The stream of growth did not follow the pattern of the retinal nerve fiber layer because the clusters of pigmented cells crossed the midline raphe, not sparing the macular area. Pigmentary mosaicisms therefore may be a modified wild-type allele in a somatic cell clone during early embryogenesis following developmental lines analogous to the cutaneous lines of Blaschko. The sectorial RPE changes in grouped CHRPE may reflect the stream, outgrowth, and migration of the RPE during embryogenesis, similar to functional changes demonstrated as mfERG changes in carriers of X-linked choroideremia or retinitis pigmentosa.6 CARSTEN H. MEYER EDUARDO B. RODRIGUES PETER KROLL Marburg, Germany References 1. Vajaranant TS, Fishman GA, Szlyk JP, et al. Detection of mosaic retinal dysfunction in choroideremia carriers electroretinographic and psychophysical testing. Ophthalmology 2008;115:723–9. 2. Meyer CH, Freyschmidt-Paul P, Happle R, Kroll P. Unilateral linear hyperpigmentation of the skin with ipsilateral sectorial hyperpigmentation of the retina. Am J Med Genet A 2004; 126A:89 –92. 3. Rott HD, Koniszewski G. Analogy of Blaschko lines in the eye. J Genet Hum 1987;35:19 –27. 4. Meyer CH, Rodrigues EB, Mennel S, et al. Grouped congenital hypertrophy of the retinal pigment epithelium follows developmental patterns of pigmentary mosaicism. Ophthalmology 2005;112:841–7. 5. Augsburger JJ, Henson GL, Hershberger VS, Trichopoulos N. Topographical distribution of typical unifocal congenital hypertrophy of retinal pigment epithelium. Graefes Arch Clin Exp Ophthalmol 2006;244:1412– 4. 6. Vajaranant TS, Seiple W, Szlyk JP, Fishman GA. Detection using the multifocal electroretinogram of mosaic retinal dysfunction in carriers of x-linked retinitis pigmentosa. Ophthalmology 2002;109:560 – 8.
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Author reply Dear Editor: Until now, the study of age-related macular degeneration has been limited to the analysis of color fundus photographs, fluorescein angiography images, and optical coherence tomography (OCT) findings.1 However, with the higher expectations of current treatments based on biological agents, the assessment of the viability of the retina and retinal pigment epithelium (RPE) will give an indication of the possible therapeutic success.2,3 Therefore, the evaluation of the health of the RPE has become an important step in understanding the disease process. Autofluorescence (AF) imaging provides highly detailed information about the level and distribution of lipofuscin of the RPE, revealing a previously invisible structure. AF allows analysis of the sequence of pigment epithelial changes and gives indirect information on the level of metabolic activity of the RPE. In our study, we analyzed whether the AF at the macula was present and continuous or not. We did take into consideration some widespread areas of punctiform hypofluorescence caused by the presence of drusen. Those areas were identified and compared with the color photos and fluorescein angiography. We could clearly identify areas of irregular hypofluorescence caused by drusen from larger areas of hypofluorescence caused by RPE dysfunction. The high kappa value of 2 independent readers implies that the decision on the continuity of AF was reliable. OCT is a noninvasive technique that provides optical cross-sections of the retina4 and gives information about the anatomic state of the outer retina and the thickness of retinal layers. However, OCT gives information only on optical interfaces and not on the functional characteristics of the outer retina. In addition, OCT imaging does not always allow a clear distinction between an occult and a classic choroidal neovascularization. We did not analyze the sectoral distribution of AF or perform microperimetry, which requires fixation of the patient. Good fixation is difficult to obtain in patients with
1854
subfoveal choroidal neovascularization. Also, microperimetry was not part of our study. We hope we have provided additional information to permit a better understanding of our results. VERONIKA VACLAVIK, MD ALAN C. BIRD, MD London, England References 1. The Age-Related Disease Study Research Group. The Age-Related Eye Disease Study system for classifying age-related macular degeneration from stereoscopic color fundus photographs: The Age-Related Eye Disease Study Report Number 6. Am J Ophthalmol 2001;132:668 – 81. 2. Holz FG, Pauleikhoff D, Klein R, Bird AC. Pathogenesis of lesions in late age-related macular disease. Am J Opthalmol 2004;137:504 –10. 3. Wing GL, Blanchard GC, Weiter JJ. The topography and age relationship of lipofuscin concentration in the retinal pigment epithelium. Invest Ophthalmol Vis Sci 1978;17:601–7. 4. Treatment of age-related macular degeneration with photodynamic therapy Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in AMD with verteporfin: one-year results of 2 randomized clinical trials—TAP Report 1. Arch Ophthalmol 1999;117:1329 – 45.
Astigmatism and Periocular Hemangioma Dear Editor: Weiss and Kelly1 are to be congratulated for putting some evidentiary flesh on the bones of the rationale for treatment of eyelid capillary hemangioma; however, they may have underestimated the effectiveness of their intervention when reporting 63% reduction of the astigmatism in eyes treated with intralesionsal corticosteroid. This figure seems to have been derived by subtracting the mean power of the remaining postoperative cylinder from the equivalent preoperative cylinder power (“the cylinder subtraction method”). The surgically induced astigmatic effect of their treatment is likely to be considerably greater than this because the cylinder subtraction method generally underestimates the surgical effect of any treatment of astigmatism. Consider the following example. If a pretreatment cylinder was ⫹4 diopters (D) at 90 degrees and a posttreatment cylinder was ⫹1 D at 180 degrees, it is intuitively obvious that this was a 5-D change in cylinder power (in other words, the cylinder at 90 degrees went from ⫹4 D to ⫺1 D), not a 3-D change. By cylinder subtraction, this would be a 75% (⫹4 to ⫹1) reduction when it was, in fact, a 125% (⫹4 to ⫺1 D) change, taking the axis into account. Because cylinder change is not always on axis, the conventional way to establish the true surgical change is to apply vector analysis.2– 4 It is interesting how close the treated eyes came, it terms of astigmatism, to the fellow eyes, suggesting that the effect of the treatment was to return the eyes to their native astigmatic state. Most eyes have some minor degree of astigmatism, which is commonly symmetric with the fellow eye, so the likely best end state of these eyes would closely match the astigmatism of the fellow eyes. It would not be reasonable to assume that the cylinder power might go to zero. It would be of considerable interest to set the targeted remaining astigmatism as an astigmatic state symmetric
Letters to the Editor with the other eye and see how close to that target the treatment got.2 Given the results they report, the authors might be pleasantly surprised that they achieved more than a 63% reduction. Even if the endpoint was not zero astigmatism, the reduction of amblyogenesis by making the 2 eyes isometropic, not free of astigmatism, is considerable. MICHAEL GOGGIN, FRCSI(Ophth), FRANZCO, MS Adelaide, Australia References 1. Weiss AH, Kelly JP. Reappraisal of astigmatism induced by periocular capillary hemangioma and treatment with intralesional corticosteroid injection. Ophthalmology 2008;115:390 –7. 2. Alpins NA. A new method of analyzing vectors for changes in astigmatism. J Cataract Refract Surg 1993;19:524 –33. 3. Holladay JT, Cravy TV, Koch DD. Calculating the surgically induced refractive change following ocular surgery. J Cataract Refract Surg 1992;18:429 – 43. 4. Alpins NA, Goggin M. Practical astigmatism analysis for refractive outcomes in cataract and refractive surgery. Surv Ophthalmol 2004;49:109 –22.
Author reply Dear Editor: We thank Dr Goggin for bringing the vector analysis of astigmatism to our attention. Vector analysis provides a more precise measure of astigmatic changes because it takes both the magnitude and axis of astigmatism into account. For those patients with a shift in the axis of astigmatism, we agree that the percentage of reduction in astigmatism is greater than stated in our manuscript. We calculate that the mean reduction in astigmatism for 8 of 13 patients with an axis shift is 2.76⫾1.38 diopters using vector analysis and 2.44⫾1.35 diopters using linear analysis. The largest difference between the linear and vector analysis was 1.125 diopters. For the remaining 5 patients without a shift in astigmatic axis, the mean reduction is the same for both analyses. AVERY H. WEISS, MD JOHN P. KELLY, PHD Seattle, Washington
Lines of Blaschko Dear Editor: Vajaranant et al1 investigated the mosaic pattern of retinal dysfunction in female carriers of X-linked choroideremia by multifocal electroretinography (mfERG) testing. Although the fundus examination demonstrated a patchy depigmentation and clumping of the retinal pigment epithelium (RPE) in the midperiphery, the mfERG findings corresponded well to the severity of the biomicroscopic changes. The authors state, “The presented pattern of mosaic retinal dysfunction on mfERG is predicted by the Lyon hypothesis of random chromosome inactivation in heterozygotic carriers and reminded us of the pattern in sectorially oriented or grouped congenital hyperpigmentations of the retinal pigment epithelium (CHRPE) resembling animal footprints ‘bear tracks.’” Grouped CHRPE are well-delineated hyperpigmentations in one or more quadrants of the ocular fundus. Recently, we
described a patient with grouped CHRPE in the left eye and additional unilateral sectorial hyperpigmented skin lesions on his left shoulder.2 These sectorial pigmentations were noted during the first months of life, did not correspond to the distribution of cutaneous nerves (dermatomes), and followed the lines of Blaschko. These lines of Blaschko may reflect the dorsoventral outgrowth of precursor of the skin, and hence may manifest the stream, distribution, migration, and proliferation of embryonic tissue. They originate during early embryogenesis by various genetic mechanisms, including functional X-chromosomal mosaicism, postzygotic mutations, gametic half-chromatid mutations, or loss of a heterozygosity. If one of these events occurs, both homozygosity and heterozygosity may predispose the individual to sectorial pigmentation of these somatic cells. The clones of these distinct stem cells may give rise to sectorial mosaicism with areas of excessively pigmented lesions.3 Additional studies evaluated the pattern of grouped CHRPE from previously published data and determined the developmental lines of pigmentary lesions in the human eye according to Alfred Blaschko’s concept.4 Small lesions extended from the margin of the optic disc and radiated with larger lesions in sectors to the fundus periphery.5 The stream of growth did not follow the pattern of the retinal nerve fiber layer because the clusters of pigmented cells crossed the midline raphe, not sparing the macular area. Pigmentary mosaicisms therefore may be a modified wild-type allele in a somatic cell clone during early embryogenesis following developmental lines analogous to the cutaneous lines of Blaschko. The sectorial RPE changes in grouped CHRPE may reflect the stream, outgrowth, and migration of the RPE during embryogenesis, similar to functional changes demonstrated as mfERG changes in carriers of X-linked choroideremia or retinitis pigmentosa.6 CARSTEN H. MEYER EDUARDO B. RODRIGUES PETER KROLL Marburg, Germany References 1. Vajaranant TS, Fishman GA, Szlyk JP, et al. Detection of mosaic retinal dysfunction in choroideremia carriers electroretinographic and psychophysical testing. Ophthalmology 2008;115:723–9. 2. Meyer CH, Freyschmidt-Paul P, Happle R, Kroll P. Unilateral linear hyperpigmentation of the skin with ipsilateral sectorial hyperpigmentation of the retina. Am J Med Genet A 2004; 126A:89 –92. 3. Rott HD, Koniszewski G. Analogy of Blaschko lines in the eye. J Genet Hum 1987;35:19 –27. 4. Meyer CH, Rodrigues EB, Mennel S, et al. Grouped congenital hypertrophy of the retinal pigment epithelium follows developmental patterns of pigmentary mosaicism. Ophthalmology 2005;112:841–7. 5. Augsburger JJ, Henson GL, Hershberger VS, Trichopoulos N. Topographical distribution of typical unifocal congenital hypertrophy of retinal pigment epithelium. Graefes Arch Clin Exp Ophthalmol 2006;244:1412– 4. 6. Vajaranant TS, Seiple W, Szlyk JP, Fishman GA. Detection using the multifocal electroretinogram of mosaic retinal dysfunction in carriers of x-linked retinitis pigmentosa. Ophthalmology 2002;109:560 – 8.
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