- Email: [email protected]
Retinal Nerve Fiber Layer Thickness in Amblyopic Eyes
Retinal Nerve Fiber Layer Thickness in Amblyopic Eyes
indications are still unclear, but tear film condition is one of the critical factors that influence the prognosis for transplantation. Although some cases scored 0 mm by the Schirmer test, there is still the potential for successful epithelial transplantation if the preoperative surface maintained nonkeratinized epithelium with minimal tear film secretion. Therefore, observation of the preoperative epithelial condition may provide the most appropriate prognosis of epithelial survival. Needless to say, the biological behavior of ectopicallytransplanted oral mucosal epithelium raises a variety of questions such as vascular response, transparence, and cell longevity. We have just reported that keratin expressions of survived oral mucosal epithelium are similar to original oral buccal mucosa.1 As we expected, all cases showed peripheral neovascularization to some extent, however, primary diseases and postoperative inflammation were modified in a time dependent manner. We avoided detailed grading to exclude the case variability and indicate the overall difference from cultivated corneal epithelial transplantation. We defined a stable ocular surface as one which required no additional epithelial transplantation and contained no prolonged, untreatable epithelial defect. With the exception of two cases, most epithelial damages were treatable by the conventional procedure for persistent epithelial defect using a medical use contact lens, preservation free artificial tears, or tape tarsorrhaphy. However, further observation showed frequent epithelial damage in StevensJohnson syndrome cases. Clearly, the characteristics and long-term viability of oral mucosal epithelium in StevensJohnson syndrome needs to be investigated in future studies. Tissue-engineered cultivated epithelial transplantation has only recently been introduced into the field of ocular surface reconstruction, and the stem cell content and longevity of the transplanted epithelium is still unclear. Stem cells in oral buccal mucosa appear to be widely distributed and not confined to a limited area, but preoperative cleaning and past history of oral mucosal cicatrisation seems to influence the integrity of cell sheets. To address these questions, a biological study focused on locating oral mucosal stem cells is proceeding.
EDITOR: A RECENT ARTICLE BY REPKA AND ASSOCIATES1 CONTAINS
an apparent misreading of a referenced article on abnormal optic disk topography in 205 amblyopic patients.2 Repka and associates replaced “dysversion” with “hypoplasia.” The relevant statement was “Optic nerve dysversion (emphasis added) was identified in 45.4% of patients. . .”1 A subsequent article, which included data on computer analysis of disk areas of 263 subjects also noted that one-hundred thirty-three (48%) of the presumably amblyopic subjects had optic nerve deformities consistent with dysversion.3 As a consequence of this initial apparent misreading, the authors studied retinal nerve fiber layer thickness in 17 minimally amblyopic patients with ocular coherence tomography (OCT). This imaging method has no referenced application to optic nerve dysversion or possible misrouting of optic nerve fibers. The subject group had a mean visual acuity of 20/40 and measurements on one patient with 20/80 acuity in the poorer eye were not included. Significant anatomic disparities would not be anticipated in a group with near normal acuity in the poorer eyes. In addition, there were no normal controls. Although the instrument employed by the authors, Humphrey-Zeiss Stratus (OCT3), is capable of optic disk imaging, they chose not to utilize that capability to evaluate and compare the optic disk topography. Moreover, the authors’ assertion that OCT measurements are unaffected by refractive error has been contradicted by others.4 Despite their study being prompted by earlier articles on congenital optic disk structural anomalies, Repka and associates used a “surrogate marker for the assessment of the optic nerve in patients with glaucoma”1 instead of directly viewing the optic disk. Also, it is not clear that OCT analysis, which is known to have wide variations, provides statistically useful information in a very small group of amblyopes with good bilateral visual acuity.5 The time-honored way of confirming or denying a scientific finding is to repeat the experiment. I look forward to their future studies.
TSUTOMU INATOMI, MD, PHD
PHILIP LEMPERT, MD
TAKAHIRO NAKAMURA, MD, PHD
Ithaca, New York
SHIGERU KINOSHITA, MD, PHD
Kyoto, Japan REFERENCES
1. Repka MX, Goldenberg-Cohen N, Edwards AR. Retinal nerve fiber layer thickness in amblyopic eyes. Am J Ophthalmol 2006;142:247–251. 2. Lempert P, Porter L. Dysvrsion of the optic disk and axial length measurements in a presumed amblyopic population. J AAPOS 1998;2:207–213.
REFERENCE
1. Inatomi T, Nakamura T, Kojyo M, et al. Ocular surface reconstruction with combination of cultivated autologous oral mucosal epithelial transplantation and penetrating keratoplasty. Am J Ophthalmol 2006;142:757–764.
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3. Lempert P. Optic nerve hypoplasia and small eyes in presumed amblyopia. J APPOS 2000;258 –266. 4. Salchow DJ, Oleynikov YS, Chiang MF, et al. Retinal nerve fiber layer thickness in normal children measured with optical coherence tomography. Ophthalmology 2006;113:786 –791. 5. Beck RW. Sample size for a clinical trial: why do some trials need only 100 patients and others 1000 patients or more? Ophthalmology. 2006;113:721–722.
REPLY DR LEMPERT HAS SUGGESTED AN ASSOCIATION BETWEEN
optic nerve pathology and amblyopia. In his studies of optic disk photos, he has found that abnormal optic nerves, which he termed “dysversion,” occur in about 45% of children presumed to be amblyopic.1 While Dr Lempert may quibble with our use of the term hypoplasia, in fact he has used it in his reports.1,2 Many clinicians have been unable to reconcile an optic neuropathy as the cause of amblyopia with their clinical examinations and the demonstration of improvement in visual acuity with treatment. We performed a pilot study to determine whether we could detect a difference in retinal nerve fiber layer (RNFL) thickness between sound and amblyopic fellow eyes, to evaluate test-retest variability in this population, as well as to refine a testing protocol to be used in a future clinical trial. We elected to use ocular coherence tomography (OCT) of RNFL thickness, since it is a widely accepted measure of the cross section volume of the nerve fiber layer and, thus, the number of optic nerve axons emanating from the optic disk. RNFL thickness correlates with disk area in children.3 About 75% of amblyopic eyes have visual acuity of 20/100 or better at diagnosis.4 Our patients fell into this range when initially seen, improving to 20/40. We noted in our report that our patients differed from Dr Lempert’s as many of his patients were treatment failures.2 As for the presence of axonal misrouting, neither two-dimensional disk photos nor OCT images can demonstrate misrouting. We used the sound eye of our patients as the control for this study to test the hypothesis of a difference between sound and amblyopic eyes. This analysis reduces the effect of age, gender, and ametropia on the comparison. We and others have noted most of the variability in OCT measurement is between patients,5 making an intrapatient comparison ideal for comparing sound to amblyopic fellow eyes. The development of normative data will allow comparison of both eyes of amblyopic patients to normal patients. Magnification has been a concern with OCT.6 To mitigate concern about the effect of refraction on magnification, we performed only intrapatient comparisons and did not enroll patients with any myopia or hypermetropia ⬎5.00 diopters (D). The 12 children with anisometropic or strabismic/anisometropic amblyopia had a mean anisoVOL. 143, NO. 1
metropia of 2.40 D. Dr Lempert noted that a recent cross-sectional study in children has found that there is an increase in mean RNFL thickness with increasing hypermetropia.5 From those data, we can estimate the difference attributable to the anisometropia in our patients to be 4.01 microns, with the hypermetropic nerves being slightly thicker than the less hypermetropic nerves. When this error due to magnification is subtracted from the amblyopic eye RNFL thickness, it would not change our conclusion that there is a small but not clinically significant reduction in RNFL thickness of amblyopic eyes. Lastly, as described in the published manuscript, our data are from a pilot study. We have used the results to develop a protocol to collect a larger sample during an ongoing clinical trial. MICHAEL X. REPKA, MD NITZA GOLDENBERG-COHEN, MD
Baltimore, Maryland ALLISON R. EDWARDS, MS
Tampa, Florida
REFERENCES
1. Lempert P, Porter L. Dysversion of the optic disk and axial length measurements in a presumed amblyopic population. J AAPOS 1998;2:207–213. 2. Lempert P. Optic nerve hypoplasia and small eyes in presumed amblyopia. J AAPOS 2000;4:258 –266. 3. Huynh SC, Wang XY, Rochtchina E, et al. Distribution of optic disk parameters measured by OCT: findings from a population-based study of six-year-old Australian children. Invest Ophthalmol Vis Sci 2006;47:3276 –3285. 4. Woodruff G, Hiscox F, Thompson JR, Smith LK. Factors affecting the outcome of children treated for amblyopia. Eye 1994;8:627– 631. 5. Salchow DJ, Oleynikov YS, Chiang MF, et al. Retinal nerve fiber layer thickness in normal children measured with optical coherence tomography. Ophthalmology 2006;113:786 –791. 6. Schuman JS, Pedut-Kloizman T, Hertzmark E, et al. Reproducibility of nerve fiber layer thickness measurements using optical coherence tomography. Ophthalmology 1996;103:1889 – 1898.
Management of Patients With Ocular Hypertension: A Cost-Effectiveness Approach From the Ocular Hypertension Treatment Study EDITOR: DR KYMES AND ASSOCIATES1 ADVOCATE TREATING AS
many as one third of the glaucoma-suspect patients, with intraocular pressures of 24 or greater, as being cost effective. Several years ago, I attended a meeting at which one of the participants in the Ocular Hypertension Treatment Study (OHTS)2 gave an excellent power point presenta-
CORRESPONDENCE
191
indications are still unclear, but tear film condition is one of the critical factors that influence the prognosis for transplantation. Although some cases scored 0 mm by the Schirmer test, there is still the potential for successful epithelial transplantation if the preoperative surface maintained nonkeratinized epithelium with minimal tear film secretion. Therefore, observation of the preoperative epithelial condition may provide the most appropriate prognosis of epithelial survival. Needless to say, the biological behavior of ectopicallytransplanted oral mucosal epithelium raises a variety of questions such as vascular response, transparence, and cell longevity. We have just reported that keratin expressions of survived oral mucosal epithelium are similar to original oral buccal mucosa.1 As we expected, all cases showed peripheral neovascularization to some extent, however, primary diseases and postoperative inflammation were modified in a time dependent manner. We avoided detailed grading to exclude the case variability and indicate the overall difference from cultivated corneal epithelial transplantation. We defined a stable ocular surface as one which required no additional epithelial transplantation and contained no prolonged, untreatable epithelial defect. With the exception of two cases, most epithelial damages were treatable by the conventional procedure for persistent epithelial defect using a medical use contact lens, preservation free artificial tears, or tape tarsorrhaphy. However, further observation showed frequent epithelial damage in StevensJohnson syndrome cases. Clearly, the characteristics and long-term viability of oral mucosal epithelium in StevensJohnson syndrome needs to be investigated in future studies. Tissue-engineered cultivated epithelial transplantation has only recently been introduced into the field of ocular surface reconstruction, and the stem cell content and longevity of the transplanted epithelium is still unclear. Stem cells in oral buccal mucosa appear to be widely distributed and not confined to a limited area, but preoperative cleaning and past history of oral mucosal cicatrisation seems to influence the integrity of cell sheets. To address these questions, a biological study focused on locating oral mucosal stem cells is proceeding.
EDITOR: A RECENT ARTICLE BY REPKA AND ASSOCIATES1 CONTAINS
an apparent misreading of a referenced article on abnormal optic disk topography in 205 amblyopic patients.2 Repka and associates replaced “dysversion” with “hypoplasia.” The relevant statement was “Optic nerve dysversion (emphasis added) was identified in 45.4% of patients. . .”1 A subsequent article, which included data on computer analysis of disk areas of 263 subjects also noted that one-hundred thirty-three (48%) of the presumably amblyopic subjects had optic nerve deformities consistent with dysversion.3 As a consequence of this initial apparent misreading, the authors studied retinal nerve fiber layer thickness in 17 minimally amblyopic patients with ocular coherence tomography (OCT). This imaging method has no referenced application to optic nerve dysversion or possible misrouting of optic nerve fibers. The subject group had a mean visual acuity of 20/40 and measurements on one patient with 20/80 acuity in the poorer eye were not included. Significant anatomic disparities would not be anticipated in a group with near normal acuity in the poorer eyes. In addition, there were no normal controls. Although the instrument employed by the authors, Humphrey-Zeiss Stratus (OCT3), is capable of optic disk imaging, they chose not to utilize that capability to evaluate and compare the optic disk topography. Moreover, the authors’ assertion that OCT measurements are unaffected by refractive error has been contradicted by others.4 Despite their study being prompted by earlier articles on congenital optic disk structural anomalies, Repka and associates used a “surrogate marker for the assessment of the optic nerve in patients with glaucoma”1 instead of directly viewing the optic disk. Also, it is not clear that OCT analysis, which is known to have wide variations, provides statistically useful information in a very small group of amblyopes with good bilateral visual acuity.5 The time-honored way of confirming or denying a scientific finding is to repeat the experiment. I look forward to their future studies.
TSUTOMU INATOMI, MD, PHD
PHILIP LEMPERT, MD
TAKAHIRO NAKAMURA, MD, PHD
Ithaca, New York
SHIGERU KINOSHITA, MD, PHD
Kyoto, Japan REFERENCES
1. Repka MX, Goldenberg-Cohen N, Edwards AR. Retinal nerve fiber layer thickness in amblyopic eyes. Am J Ophthalmol 2006;142:247–251. 2. Lempert P, Porter L. Dysvrsion of the optic disk and axial length measurements in a presumed amblyopic population. J AAPOS 1998;2:207–213.
REFERENCE
1. Inatomi T, Nakamura T, Kojyo M, et al. Ocular surface reconstruction with combination of cultivated autologous oral mucosal epithelial transplantation and penetrating keratoplasty. Am J Ophthalmol 2006;142:757–764.
190
AMERICAN JOURNAL
OF
OPHTHALMOLOGY
JANUARY 2007
3. Lempert P. Optic nerve hypoplasia and small eyes in presumed amblyopia. J APPOS 2000;258 –266. 4. Salchow DJ, Oleynikov YS, Chiang MF, et al. Retinal nerve fiber layer thickness in normal children measured with optical coherence tomography. Ophthalmology 2006;113:786 –791. 5. Beck RW. Sample size for a clinical trial: why do some trials need only 100 patients and others 1000 patients or more? Ophthalmology. 2006;113:721–722.
REPLY DR LEMPERT HAS SUGGESTED AN ASSOCIATION BETWEEN
optic nerve pathology and amblyopia. In his studies of optic disk photos, he has found that abnormal optic nerves, which he termed “dysversion,” occur in about 45% of children presumed to be amblyopic.1 While Dr Lempert may quibble with our use of the term hypoplasia, in fact he has used it in his reports.1,2 Many clinicians have been unable to reconcile an optic neuropathy as the cause of amblyopia with their clinical examinations and the demonstration of improvement in visual acuity with treatment. We performed a pilot study to determine whether we could detect a difference in retinal nerve fiber layer (RNFL) thickness between sound and amblyopic fellow eyes, to evaluate test-retest variability in this population, as well as to refine a testing protocol to be used in a future clinical trial. We elected to use ocular coherence tomography (OCT) of RNFL thickness, since it is a widely accepted measure of the cross section volume of the nerve fiber layer and, thus, the number of optic nerve axons emanating from the optic disk. RNFL thickness correlates with disk area in children.3 About 75% of amblyopic eyes have visual acuity of 20/100 or better at diagnosis.4 Our patients fell into this range when initially seen, improving to 20/40. We noted in our report that our patients differed from Dr Lempert’s as many of his patients were treatment failures.2 As for the presence of axonal misrouting, neither two-dimensional disk photos nor OCT images can demonstrate misrouting. We used the sound eye of our patients as the control for this study to test the hypothesis of a difference between sound and amblyopic eyes. This analysis reduces the effect of age, gender, and ametropia on the comparison. We and others have noted most of the variability in OCT measurement is between patients,5 making an intrapatient comparison ideal for comparing sound to amblyopic fellow eyes. The development of normative data will allow comparison of both eyes of amblyopic patients to normal patients. Magnification has been a concern with OCT.6 To mitigate concern about the effect of refraction on magnification, we performed only intrapatient comparisons and did not enroll patients with any myopia or hypermetropia ⬎5.00 diopters (D). The 12 children with anisometropic or strabismic/anisometropic amblyopia had a mean anisoVOL. 143, NO. 1
metropia of 2.40 D. Dr Lempert noted that a recent cross-sectional study in children has found that there is an increase in mean RNFL thickness with increasing hypermetropia.5 From those data, we can estimate the difference attributable to the anisometropia in our patients to be 4.01 microns, with the hypermetropic nerves being slightly thicker than the less hypermetropic nerves. When this error due to magnification is subtracted from the amblyopic eye RNFL thickness, it would not change our conclusion that there is a small but not clinically significant reduction in RNFL thickness of amblyopic eyes. Lastly, as described in the published manuscript, our data are from a pilot study. We have used the results to develop a protocol to collect a larger sample during an ongoing clinical trial. MICHAEL X. REPKA, MD NITZA GOLDENBERG-COHEN, MD
Baltimore, Maryland ALLISON R. EDWARDS, MS
Tampa, Florida
REFERENCES
1. Lempert P, Porter L. Dysversion of the optic disk and axial length measurements in a presumed amblyopic population. J AAPOS 1998;2:207–213. 2. Lempert P. Optic nerve hypoplasia and small eyes in presumed amblyopia. J AAPOS 2000;4:258 –266. 3. Huynh SC, Wang XY, Rochtchina E, et al. Distribution of optic disk parameters measured by OCT: findings from a population-based study of six-year-old Australian children. Invest Ophthalmol Vis Sci 2006;47:3276 –3285. 4. Woodruff G, Hiscox F, Thompson JR, Smith LK. Factors affecting the outcome of children treated for amblyopia. Eye 1994;8:627– 631. 5. Salchow DJ, Oleynikov YS, Chiang MF, et al. Retinal nerve fiber layer thickness in normal children measured with optical coherence tomography. Ophthalmology 2006;113:786 –791. 6. Schuman JS, Pedut-Kloizman T, Hertzmark E, et al. Reproducibility of nerve fiber layer thickness measurements using optical coherence tomography. Ophthalmology 1996;103:1889 – 1898.
Management of Patients With Ocular Hypertension: A Cost-Effectiveness Approach From the Ocular Hypertension Treatment Study EDITOR: DR KYMES AND ASSOCIATES1 ADVOCATE TREATING AS
many as one third of the glaucoma-suspect patients, with intraocular pressures of 24 or greater, as being cost effective. Several years ago, I attended a meeting at which one of the participants in the Ocular Hypertension Treatment Study (OHTS)2 gave an excellent power point presenta-
CORRESPONDENCE
191