- Email: [email protected]
Retinal Thickness Measured by Spectral-Domain Optical Coherence Tomography in Eyes Without Retinal Abnormalities: The Beaver Dam Eye Study
REFERENCES
1. Suzuki T, Ohashi Y, Oshika T, et al. Japanese Ophthalmological Society HOYA Intraocular Lens–Related Endophthalmitis Investigation Commission. Outbreak of late-onset toxic anterior segment syndrome after implantation of one-piece intraocular lenses. Am J Ophthalmol 2015;159(5):934–939.e2. 2. Savin LH. The effect of aluminium and its alloys on the eye. Br J Ophthalmol 1947;31(8):449–503. 3. Schwartz JG, Somerset JS, Harrison JM, Garriott JC, Castorena JL. Eye injuries with metal missiles presenting to an emergency center: a three year study. Am J Emerg Med 1991;9(4):313–327.
REPLY
postulated. The inflammation induced by the aluminum might also influence ocular tissues, similar to a previous report,2 and our cases seem to involve very complicated pathology. Because our study was an observational retrospective study, it is difficult to understand the exact pathology. To do so, ERG, OCT, and further investigations are needed. Regarding patient gender, there were 89 male (89 affected eyes) and 162 female patients (162 affected eyes). The order of the genders in Table 1 was wrong. We apologize for our mistake. We again thank Drs Go¨nu¨l and O¨ztu¨rk for their thoughtful comments and for giving us the opportunity to add the important information about aluminum toxicity to our published article. TAKASHI SUZUKI
WE APPRECIATE THE COMMENTS BY DRS GO¨NU¨L AND
O¨ztu¨rk regarding our published article.1 Our study reviewed the clinical findings associated with an outbreak of toxic anterior segment syndrome (TASS) after the implantation of one-piece intraocular lenses (IOLs; HOYA iSert 251 and 255, HOYA, Japan). To enroll many cases, the questionnaire did not include results of ophthalmic examinations such as electroretinography (ERG), which examines retinal function, and optical coherence tomography (OCT), which observes the retinal morphology. We can consider several possibilities regarding the pathology of late-onset TASS in our study. We postulated that inflammation induced by the aluminum could damage ocular tissues. As Drs Go¨nu¨l and O¨ztu¨rk suggested, aluminum toxicity might have caused a toxic retinopathy in our cases. We divided the patients into those who underwent surgical treatment (109 patients) and those who received only medical treatment (142 patients), and analyzed the initial and final best-corrected visual acuities (BCVA), and compared the difference between the initial and final BCVA. The BCVA data were analyzed using Student’s t-tests. A P value < .05 was taken to indicate statistical significance. The mean initial BCVA in the surgery and medicine groups was 0.334 6 0.477 and 0.196 6 0.372, respectively, and was significantly better in the medicine group (P < .05). The mean final BCVA was also significantly better in the medicine group (0.007 6 0.137 vs 0.077 6 0.328, P < .05). The difference in the initial and final BCVA in the surgery and medicine groups was 0.276 6 0.416 and 0.187 6 0.324, respectively, and was greater in the surgery group, although this was not statistically significant (P ¼ .08). These results suggest that the surgery group suffered greater retinal damage, although the recovery of BCVA after treatment was better in that group. Perhaps the reduction in aluminum levels in the eyes of these patients improved their recovery. Therefore, aluminum toxicity could affect retinas in patients with IOLs that had been contaminated with aluminum, as Drs Go¨nu¨l and O¨ztu¨rk VOL. 160, NO. 1
YUICHI OHASHI
Ehime, Japan TETSURO OSHIKA
Ibaraki, Japan HIROSHI GOTO AKITO HIRAKATA KIMIKO FUKUSHITA
Tokyo, Japan KAZUNORI MIYATA
Miyazaki, Japan CONFLICT OF INTEREST DISCLOSURES: SEE THE ORIGINAL article for any disclosures of the authors.
REFERENCES
1. Suzuki T, Ohashi Y, Oshika T, et al. Japanese Ophthalmological Society HOYA Intraocular Lens–Related Endophthalmitis Investigation Commission. Outbreak of late-onset toxic anterior segment syndrome after implantation of one-piece intraocular lenses. Am J Ophthalmol 2015;159(5):934–939.e2. 2. Calogero D, Buchen SY, Tarver ME, Hilmantel G, Lucas AD, Eydelman MB. Evaluation of intraocular reactivity to metallic and ethylene oxide contaminants of medical devices in a rabbit model. Ophthalmology 2012;119(7):e36–e42.
Retinal Thickness Measured by Spectral-Domain Optical Coherence Tomography in Eyes Without Retinal Abnormalities: The Beaver Dam Eye Study EDITOR: WE READ WITH GREAT INTEREST THE ARTICLE BY
Myers and associates,1 providing normative values of
CORRESPONDENCE
209
spectral-domain optical coherence tomography (SD OCT) macular thickness measurements in a large adult cohort without retinal disease, and examining relationships with age, sex, and other ocular and systemic covariates. The authors found that when adjusting for age, men had thicker retinas than women in the Early Treatment of Diabetic Retinopathy Study (ETDRS) center macula subfield (men vs women: 289.5 vs 273.8 mm, P < .001) and inner ring (337.1 vs 332.5 mm, P < .001) but not in the outer ring (290.7 vs 288.9 mm, P ¼ .08). These results were confirmed in multivariate analyses, where male sex was independently associated with a thicker retina in the center subfield and in the inner circle of the retina. These findings are consistent with several previous studies using SD OCT in adult populations from different ethnicities: American2 and also Japanese, Korean, Pakistani, and Chinese (studies summarized by Gupta and associates, Table 6).3 In their paper, Myers and associates advanced the hypothesis, raised by several authors, that the finding of foveal thinning in women compared to men could be attributed to hormonal changes at menopause and this may help to explain why women are at higher risk for developing macular holes than men. However, our findings in a large multicenter cohort of children (283 children with a mean age of 9.5 years)4 do not provide support for this hypothesis. We found similar differences at earlier ages and, in fact, a multivariate-adjusted linear regression model confirmed a significant association between sex and central macula thickness in children. Boys had a significantly thicker central macula than girls by 10.39 mm (b ¼ 10.39, 95% confidence interval: 5.96-14.83; P < .001). Although in our paper we did not publish any subsequent analyses, the results were also significantly higher for boys in average inner ring sectors (b ¼ 6.16 mm; P ¼ .001) but not in average outer macula ring sectors (b ¼ 1.04 mm; P ¼ .52). Only the temporal quadrant of the outer ring was significantly higher in boys (b ¼ 4.48 mm; P ¼ .02). In their study with 2068 12-year-old children, Huynh and associates found similar results using time-domain OCT.5 In a more recent study with 107 Turkish children, boys had also a significantly thicker central macula and inner macula ring than girls.6 Furthermore, the intersex quantitative difference of 10 mm in mean foveal thickness and of 6 mm in average inner ring sectors in our study were similar to those reported in other studies with children.5,6 Although in the studies with adults these intersex differences were a bit higher, they remained in a similar order of magnitude (between 10 and 15.7 mm in mean foveal thickness and between 4.6 and 9.11 mm in average inner ring sectors1–3). Our hypothesis is that, as these intersex differences are present from childhood, it is likely that they could be genetically induced instead of being hormonally caused. ´ S BARRIO-BARRIO JESU MIGUEL RUIZ-CANELA
210
Pamplona, Spain SUSANA NOVAL
Madrid, Spain ´S MARTA GALDO
Bilbao, Spain THE AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. The authors indicate no funding support.
REFERENCES
1. Myers CE, Klein BEK, Meuer SM, et al. Retinal thickness measured by spectral-domain optical coherence tomography in eyes without retinal abnormalities: the Beaver Dam Eye Study. Am J Ophthalmol 2015;159(3):445–456.e1. 2. Liu T, Hu AY, Kaines A, Yu F, Schwartz SD, Hubschman J-P. A pilot study of normative data for macular thickness and volume measurements using Cirrus highdefinition optical coherence tomography. Retina 2011; 31(9):1944–1950. 3. Gupta P, Sidhartha E, Tham YC, et al. Determinants of macular thickness using spectral domain optical coherence tomography in healthy eyes: the Singapore Chinese Eye Study. Invest Ophthalmol Vis Sci 2013;54:7968–7976. 4. Barrio-Barrio J, Noval S, Galdo´s M, et al. Multicenter Spanish study of spectral-domain optical coherence tomography in normal children. Acta Ophthalmol 2013;91(1): e56–e63. 5. Huynh SC, Wang XY, Burlutsky G, Rochtchina E, Stapleton F, Mitchell P. Retinal and optic disc findings in adolescence: a population-based OCT study. Invest Ophthalmol Vis Sci 2008; 49(10):4328–4335. 6. Turk A, Ceylan OM, Arici C, et al. Evaluation of the nerve fiber layer and macula in the eyes of healthy children using spectral-domain optical coherence tomography. Am J Ophthalmol 2012;153(3):552–559.
REPLY BARRIO-BARRIO AND ASSOCIATES, USING SPECTRAL-
domain optical coherence tomography (SD OCT) thickness data from their study of prepubertal children,1 report that male subjects are more likely than female subjects to have thicker retinas, leading them to conclude that genetic and not sex-hormonal differences may explain our finding of thicker retinas on SD OCT in older male compared to female adults. The notion of genetic factors explaining thicker central retina as determined by OCT is supported by a heritability estimate of 0.90 in a study using monozygotic and dizygotic female twin pairs.2 A different study of macular thickness found thicker retinas in younger persons, which led the authors to suggest that the differences between the sexes were due, in part, to gonadal hormone levels.3 The role of
AMERICAN JOURNAL OF OPHTHALMOLOGY
JULY 2015
genes and environmental factors that determine retinal thickness remain to be further elucidated. CHELSEA E. MYERS BARBARA E.K. KLEIN RONALD KLEIN
Madison, Wisconsin CONFLICT OF INTEREST DISCLOSURES: SEE THE ORIGINAL article for any disclosures of the authors.
VOL. 160, NO. 1
REFERENCES
1. Barrio-Barrio J, Noval S, Galdo´s M, et al. Multicenter Spanish study of spectral-domain optical coherence tomography in normal children. Acta Ophthalmol 2013;91(1): e56–e63. 2. Liew SH, Gilbert CE, Spector TD, Marshall J, Hammond CJ. The role of heredity in determining central retinal thickness. Br J Ophthalmol 2007;91(9):1143–1147. 3. Wexler A, Sand T, Elsas TB. Macular thickness measurements in healthy Norwegian volunteers: an optical coherence tomography study. BMC Ophthalmol 2010;10:13.
CORRESPONDENCE
211
©2015 Elsevier
1. Suzuki T, Ohashi Y, Oshika T, et al. Japanese Ophthalmological Society HOYA Intraocular Lens–Related Endophthalmitis Investigation Commission. Outbreak of late-onset toxic anterior segment syndrome after implantation of one-piece intraocular lenses. Am J Ophthalmol 2015;159(5):934–939.e2. 2. Savin LH. The effect of aluminium and its alloys on the eye. Br J Ophthalmol 1947;31(8):449–503. 3. Schwartz JG, Somerset JS, Harrison JM, Garriott JC, Castorena JL. Eye injuries with metal missiles presenting to an emergency center: a three year study. Am J Emerg Med 1991;9(4):313–327.
REPLY
postulated. The inflammation induced by the aluminum might also influence ocular tissues, similar to a previous report,2 and our cases seem to involve very complicated pathology. Because our study was an observational retrospective study, it is difficult to understand the exact pathology. To do so, ERG, OCT, and further investigations are needed. Regarding patient gender, there were 89 male (89 affected eyes) and 162 female patients (162 affected eyes). The order of the genders in Table 1 was wrong. We apologize for our mistake. We again thank Drs Go¨nu¨l and O¨ztu¨rk for their thoughtful comments and for giving us the opportunity to add the important information about aluminum toxicity to our published article. TAKASHI SUZUKI
WE APPRECIATE THE COMMENTS BY DRS GO¨NU¨L AND
O¨ztu¨rk regarding our published article.1 Our study reviewed the clinical findings associated with an outbreak of toxic anterior segment syndrome (TASS) after the implantation of one-piece intraocular lenses (IOLs; HOYA iSert 251 and 255, HOYA, Japan). To enroll many cases, the questionnaire did not include results of ophthalmic examinations such as electroretinography (ERG), which examines retinal function, and optical coherence tomography (OCT), which observes the retinal morphology. We can consider several possibilities regarding the pathology of late-onset TASS in our study. We postulated that inflammation induced by the aluminum could damage ocular tissues. As Drs Go¨nu¨l and O¨ztu¨rk suggested, aluminum toxicity might have caused a toxic retinopathy in our cases. We divided the patients into those who underwent surgical treatment (109 patients) and those who received only medical treatment (142 patients), and analyzed the initial and final best-corrected visual acuities (BCVA), and compared the difference between the initial and final BCVA. The BCVA data were analyzed using Student’s t-tests. A P value < .05 was taken to indicate statistical significance. The mean initial BCVA in the surgery and medicine groups was 0.334 6 0.477 and 0.196 6 0.372, respectively, and was significantly better in the medicine group (P < .05). The mean final BCVA was also significantly better in the medicine group (0.007 6 0.137 vs 0.077 6 0.328, P < .05). The difference in the initial and final BCVA in the surgery and medicine groups was 0.276 6 0.416 and 0.187 6 0.324, respectively, and was greater in the surgery group, although this was not statistically significant (P ¼ .08). These results suggest that the surgery group suffered greater retinal damage, although the recovery of BCVA after treatment was better in that group. Perhaps the reduction in aluminum levels in the eyes of these patients improved their recovery. Therefore, aluminum toxicity could affect retinas in patients with IOLs that had been contaminated with aluminum, as Drs Go¨nu¨l and O¨ztu¨rk VOL. 160, NO. 1
YUICHI OHASHI
Ehime, Japan TETSURO OSHIKA
Ibaraki, Japan HIROSHI GOTO AKITO HIRAKATA KIMIKO FUKUSHITA
Tokyo, Japan KAZUNORI MIYATA
Miyazaki, Japan CONFLICT OF INTEREST DISCLOSURES: SEE THE ORIGINAL article for any disclosures of the authors.
REFERENCES
1. Suzuki T, Ohashi Y, Oshika T, et al. Japanese Ophthalmological Society HOYA Intraocular Lens–Related Endophthalmitis Investigation Commission. Outbreak of late-onset toxic anterior segment syndrome after implantation of one-piece intraocular lenses. Am J Ophthalmol 2015;159(5):934–939.e2. 2. Calogero D, Buchen SY, Tarver ME, Hilmantel G, Lucas AD, Eydelman MB. Evaluation of intraocular reactivity to metallic and ethylene oxide contaminants of medical devices in a rabbit model. Ophthalmology 2012;119(7):e36–e42.
Retinal Thickness Measured by Spectral-Domain Optical Coherence Tomography in Eyes Without Retinal Abnormalities: The Beaver Dam Eye Study EDITOR: WE READ WITH GREAT INTEREST THE ARTICLE BY
Myers and associates,1 providing normative values of
CORRESPONDENCE
209
spectral-domain optical coherence tomography (SD OCT) macular thickness measurements in a large adult cohort without retinal disease, and examining relationships with age, sex, and other ocular and systemic covariates. The authors found that when adjusting for age, men had thicker retinas than women in the Early Treatment of Diabetic Retinopathy Study (ETDRS) center macula subfield (men vs women: 289.5 vs 273.8 mm, P < .001) and inner ring (337.1 vs 332.5 mm, P < .001) but not in the outer ring (290.7 vs 288.9 mm, P ¼ .08). These results were confirmed in multivariate analyses, where male sex was independently associated with a thicker retina in the center subfield and in the inner circle of the retina. These findings are consistent with several previous studies using SD OCT in adult populations from different ethnicities: American2 and also Japanese, Korean, Pakistani, and Chinese (studies summarized by Gupta and associates, Table 6).3 In their paper, Myers and associates advanced the hypothesis, raised by several authors, that the finding of foveal thinning in women compared to men could be attributed to hormonal changes at menopause and this may help to explain why women are at higher risk for developing macular holes than men. However, our findings in a large multicenter cohort of children (283 children with a mean age of 9.5 years)4 do not provide support for this hypothesis. We found similar differences at earlier ages and, in fact, a multivariate-adjusted linear regression model confirmed a significant association between sex and central macula thickness in children. Boys had a significantly thicker central macula than girls by 10.39 mm (b ¼ 10.39, 95% confidence interval: 5.96-14.83; P < .001). Although in our paper we did not publish any subsequent analyses, the results were also significantly higher for boys in average inner ring sectors (b ¼ 6.16 mm; P ¼ .001) but not in average outer macula ring sectors (b ¼ 1.04 mm; P ¼ .52). Only the temporal quadrant of the outer ring was significantly higher in boys (b ¼ 4.48 mm; P ¼ .02). In their study with 2068 12-year-old children, Huynh and associates found similar results using time-domain OCT.5 In a more recent study with 107 Turkish children, boys had also a significantly thicker central macula and inner macula ring than girls.6 Furthermore, the intersex quantitative difference of 10 mm in mean foveal thickness and of 6 mm in average inner ring sectors in our study were similar to those reported in other studies with children.5,6 Although in the studies with adults these intersex differences were a bit higher, they remained in a similar order of magnitude (between 10 and 15.7 mm in mean foveal thickness and between 4.6 and 9.11 mm in average inner ring sectors1–3). Our hypothesis is that, as these intersex differences are present from childhood, it is likely that they could be genetically induced instead of being hormonally caused. ´ S BARRIO-BARRIO JESU MIGUEL RUIZ-CANELA
210
Pamplona, Spain SUSANA NOVAL
Madrid, Spain ´S MARTA GALDO
Bilbao, Spain THE AUTHORS HAVE COMPLETED AND SUBMITTED THE ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. The authors indicate no funding support.
REFERENCES
1. Myers CE, Klein BEK, Meuer SM, et al. Retinal thickness measured by spectral-domain optical coherence tomography in eyes without retinal abnormalities: the Beaver Dam Eye Study. Am J Ophthalmol 2015;159(3):445–456.e1. 2. Liu T, Hu AY, Kaines A, Yu F, Schwartz SD, Hubschman J-P. A pilot study of normative data for macular thickness and volume measurements using Cirrus highdefinition optical coherence tomography. Retina 2011; 31(9):1944–1950. 3. Gupta P, Sidhartha E, Tham YC, et al. Determinants of macular thickness using spectral domain optical coherence tomography in healthy eyes: the Singapore Chinese Eye Study. Invest Ophthalmol Vis Sci 2013;54:7968–7976. 4. Barrio-Barrio J, Noval S, Galdo´s M, et al. Multicenter Spanish study of spectral-domain optical coherence tomography in normal children. Acta Ophthalmol 2013;91(1): e56–e63. 5. Huynh SC, Wang XY, Burlutsky G, Rochtchina E, Stapleton F, Mitchell P. Retinal and optic disc findings in adolescence: a population-based OCT study. Invest Ophthalmol Vis Sci 2008; 49(10):4328–4335. 6. Turk A, Ceylan OM, Arici C, et al. Evaluation of the nerve fiber layer and macula in the eyes of healthy children using spectral-domain optical coherence tomography. Am J Ophthalmol 2012;153(3):552–559.
REPLY BARRIO-BARRIO AND ASSOCIATES, USING SPECTRAL-
domain optical coherence tomography (SD OCT) thickness data from their study of prepubertal children,1 report that male subjects are more likely than female subjects to have thicker retinas, leading them to conclude that genetic and not sex-hormonal differences may explain our finding of thicker retinas on SD OCT in older male compared to female adults. The notion of genetic factors explaining thicker central retina as determined by OCT is supported by a heritability estimate of 0.90 in a study using monozygotic and dizygotic female twin pairs.2 A different study of macular thickness found thicker retinas in younger persons, which led the authors to suggest that the differences between the sexes were due, in part, to gonadal hormone levels.3 The role of
AMERICAN JOURNAL OF OPHTHALMOLOGY
JULY 2015
genes and environmental factors that determine retinal thickness remain to be further elucidated. CHELSEA E. MYERS BARBARA E.K. KLEIN RONALD KLEIN
Madison, Wisconsin CONFLICT OF INTEREST DISCLOSURES: SEE THE ORIGINAL article for any disclosures of the authors.
VOL. 160, NO. 1
REFERENCES
1. Barrio-Barrio J, Noval S, Galdo´s M, et al. Multicenter Spanish study of spectral-domain optical coherence tomography in normal children. Acta Ophthalmol 2013;91(1): e56–e63. 2. Liew SH, Gilbert CE, Spector TD, Marshall J, Hammond CJ. The role of heredity in determining central retinal thickness. Br J Ophthalmol 2007;91(9):1143–1147. 3. Wexler A, Sand T, Elsas TB. Macular thickness measurements in healthy Norwegian volunteers: an optical coherence tomography study. BMC Ophthalmol 2010;10:13.
CORRESPONDENCE
211
©2015 Elsevier