Ethnic Variation in Optic Disc Size by Fundus Photography

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<ul><li><p>2013</p><p>Current Eye Research, 2013; 38(11): 11421147! Informa Healthcare USA, Inc.</p><p>ISSN: 0271-3683 print / 1460-2202 online</p><p>DOI: 10.3109/02713683.2013.809123</p><p>ORIGINAL ARTICLE</p><p>Ethnic Variation in Optic Disc Size byFundus Photography</p><p>Roland Y. Lee1, Andrew A. Kao1, Toshimitsu Kasuga1,2, Baotran N. Vo1, Qi N. Cui1,Cynthia S. Chiu1, Robert N. Weinreb3 and Shan C. Lin1</p><p>1Department of Ophthalmology, University of California, San Francisco, CA, USA,2Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan, and 3Department of</p><p>Ophthalmology, University of California, San Diego, California, USA</p><p>ABSTRACT</p><p>Purpose: To compare optic disc size among Caucasian, Chinese, African, Filipino and Hispanic subjects recruitedfrom a university-based general ophthalmology clinic.</p><p>Methods: In this retrospective cross-sectional study, optic disc size was calculated from fundus photographs.Differences in age, sex and spherical equivalent among the ethnic groups were examined with either KruskalWallis test or Chi-square test. Ethnic differences in optic disc size were evaluated with linear mixed-effectsregression models that adjusted for age, sex, spherical equivalent, glaucoma status, lens status and use of botheyes in the same subject.</p><p>Results: Five hundred and seventy-four eyes of 305 subjects were analyzed. The mean and standard deviationof the optic disc size were 2.16 0.41 mm2 for Caucasian, 2.30 0.56 mm2 for Chinese, 2.31 0.41 mm2 forFilipino, 2.38 0.40 mm2 for African and 2.40 0.38 mm2 for Hispanic subjects. Age and spherical equivalentdiffered among the ethnic groups by KruskalWallis test (p50.05). Sex differed among the ethnic groups byChi-square test (p50.05). Ethnic differences in optic disc size were not observed among African, Hispanic,Filipino and Chinese subjects in linear mixed-effects regression analyses (p40.05). However, Caucasian differedfrom the other ethnicities in linear mixed-effects regression analyses (p50.05).</p><p>Conclusions: Optic disc size was significantly smaller in Caucasian compared to the other ethnic groups.Optic disc size differences among non-Caucasian ethnic groups were not significant.</p><p>Keywords: Ethnicity, fundus photography, glaucoma, optic disc size, race</p><p>INTRODUCTION</p><p>Glaucoma is the leading cause of irreversible blind-ness worldwide, and is projected to affect 70 millionpeople by 2020.1 A comprehensive ophthalmic exam-ination is a cornerstone to diagnosing glaucomabecause early stages of the disease are asymptomatic.2</p><p>Clinical screening of the optic disc provides usefulinformation for distinguishing patients with impend-ing glaucomatous visual field loss.3 Evaluation ofthe optic disc size is important as optic cup size, opticdisc rim area and cup-to-disc ratio vary with opticdisc size.49 The optic disc size may also influence the</p><p>likelihood a clinician assigns a diagnosis of glaucomaas glaucomatous optic neuropathy has been shownto be missed more frequently in glaucomatous eyeswith small optic nerve heads due to misleadingly lowcup-to-disc ratios.10</p><p>Measurements of optic disc size have previouslybeen documented in African,1118 Caucasian,1118</p><p>Asian,17,18 Hispanic17,18 and Filipino17 populations.However, most of these studies examined the ethnicgroups in isolation or in pairs, making it difficult tocompare variability in optic disc size across the fullspectrum of ethnic groups. A review of the literaturepublished between the years 1970 and 2004 indicated</p><p>Correspondence: Shan C. Lin, Department of Ophthalmology, University of California, San Francisco, School of Medicine, Box 0730, 10 KoretStreet, San Francisco, CA 94143-0730, USA. E-mail: LinS@vision.ucsf.edu</p><p>Received 29 December 2012; revised 11 April 2013; accepted 22 May 2013; published online 9 July 2013</p><p>1142</p><p>Cur</p><p>r E</p><p>ye R</p><p>es D</p><p>ownl</p><p>oade</p><p>d fr</p><p>om in</p><p>form</p><p>ahea</p><p>lthca</p><p>re.c</p><p>om b</p><p>y U</p><p>nive</p><p>rsite</p><p>it T</p><p>wen</p><p>te o</p><p>n 11</p><p>/29/</p><p>14Fo</p><p>r pe</p><p>rson</p><p>al u</p><p>se o</p><p>nly.</p></li><li><p>that the different instruments and techniques avail-able for optic disc size measurements providedestimates that are not interchangeable.4 The compar-ability of optic disc size measurements derivedfrom a collection of studies without the contextof instrumentation and technique may be poor.This university-based retrospective cross-sectionalstudy simultaneously examined optic disc sizes inCaucasian, Chinese, African, Filipino and Hispanicsubjects using fundus photography to provide anestimation of optic disc size variability among the fiveethnic groups.</p><p>METHODS</p><p>This study received institutional review board app-roval from the University of California, San Francisco(UCSF) Committee on Human Research beforecommencing data collection. Medical records frompatients who had consecutively received fundusphotography from a university-based general oph-thalmology clinic (Adult Eye Care at the UCSF,Department of Ophthalmology) between June 2006and August 2009 were retrospectively reviewed. Thefollowing information was retrieved from the medicalrecords: age, sex, visual field results, vertical cup-to-disk ratio, refractive error, glaucoma status, lensstatus and ethnicity. Visual field data were onlyavailable for patients with glaucoma or glaucomasuspicion. The patients self-description of ethnicitydetermined their classification into one of the follow-ing ethnic study groups: Caucasian, Chinese, African,Filipino and Hispanic. Data were mostly collectedfrom the same date in which the fundus photographswere taken. If the patient was not seen on the sameday, the record from their next clinic visit was used.</p><p>Visual field examination was performed withHumphrey Field Analyzer (model 750i; Carl ZeissMeditec, Inc., Dublin, CA). Vertical cup-to-disk ratiowas measured with the use of slit lamp biomicroscopy(model BM900; Haag-Streit AG, Koeniz, Switzerland).The spherical equivalent was derived from refractiveerror using the following formula: sphere plus half ofthe cylinder. The International Society of Geographicand Epidemiologic Ophthalmology (ISGEO) schemeprovided the basis for the diagnosis of glaucoma.19</p><p>Glaucomatous optic nerve damage is confirmed by aglaucomatous optic nerve appearance (vertical cup-to-disk ratio40.6) and a corresponding reliable visualfield defect. A glaucomatous visual field defect isconsidered present when the hemifield test is gradedoutside normal limits (with a probability of less than5% based upon comparison with age-matched con-trols in the pattern deviation plot) and showed acluster of three or more nonedge contiguous pointsthat did not cross the horizontal meridian. Visualfields were defined as reliable if they fulfilled the</p><p>following criteria: fixation losses533%, false positives520% and false negatives520%.</p><p>All fundus photographs were captured by the sametechnician using a digital fundus camera (Topcon TRC50EX; Topcon Corporation, Tokyo, Japan). If fundusphotographs of different magnification were available(either 20x or 35x magnification), the photographswith the highest magnification were utilized. Thesame glaucoma subspecialist (S.C.L) outlined theoptic disc margin in each fundus photograph byusing the magnetic lasso tool in Adobe Photoshop(version CS5; Adobe Systems, Inc., San Jose, CA). Themeasurement tool was then used to count the numberof pixels enclosed in the tracings. Due to a lack of axiallength measurements, the Littman formula couldnot be applied to determine the true size of the opticdisc in the study subjects. Heidelberg RetinaTomograph (HRT; Heidelberg Engineering, Carlsbad,CA) is widely considered the gold standard formeasuring optic disc size as it demonstrates goodreproducibility20 and correlates well with in-vivomeasurements of the optic disc obtained duringvitrectomy.21 By matching the number of pixels ina subset of fundus photos to optic disc size asdetermined by HRT, we constructed a formulathat allowed the conversion of pixel numbers tooptic disc size. The same glaucoma subspecialist(S.C.L) outlined the optic disc margin in all thecorresponding HRT images. Since fundus photo-graphs of two different magnifications (20x and 35x)were utilized, a separate conversion formula wascalculated for each magnification based on a ran-domly selected subset of 20 patients. The conversionformula for calculating optic disc size from the fundusphotographs at 20x magnification was 0.000002349photo pixel 1.196 with a Pearsons correlation coef-ficient of 0.864. The formula for calculating the opticdisc size from the fundus photographs at 35x magni-fication was 0.000006772photo pixel 1.711 withPearsons correlation coefficient of 0.621. These twoequations, corrected for magnification, were utilizedto convert the number of pixels enclosed in theoptic disc outline to optic disc size for all subjects inthe study population.</p><p>All statistical analyses were conducted withR-statistics (v2.15.1 software for Macintosh; RFoundation for Statistical Computing, Vienna,Austria) and p values 50.05 were considered toindicate statistical significance. Differences in age,spherical equivalent and optic disc size among theethnic groups were examined with the KruskalWallistest, while differences in sex among the ethnic groupswere examined with the Chi-square test. The associ-ation between optic disc size and glaucoma statuswas examined with a linear mixed-effects regressionmodel that adjusted for age, sex, spherical equivalent,lens status, ethnicity and use of both eyes in the samesubject. The association between optic disc size and</p><p>Ethnic Variation in Optic Disc Size 1143</p><p>! 2013 Informa Healthcare USA, Inc.</p><p>Cur</p><p>r E</p><p>ye R</p><p>es D</p><p>ownl</p><p>oade</p><p>d fr</p><p>om in</p><p>form</p><p>ahea</p><p>lthca</p><p>re.c</p><p>om b</p><p>y U</p><p>nive</p><p>rsite</p><p>it T</p><p>wen</p><p>te o</p><p>n 11</p><p>/29/</p><p>14Fo</p><p>r pe</p><p>rson</p><p>al u</p><p>se o</p><p>nly.</p></li><li><p>lens status was examined with a linear mixed-effectsregression model that adjusted for age, sex, sphericalequivalent, glaucoma status, ethnicity and use of botheyes in the same subject. Ethnic differences in opticdisc size were analyzed first by pairwise comparisonsof optic disc size among Chinese, African, Hispanicand Filipino subjects and then followed by a com-parison of optic disc size between Caucasian andother ethnicities. The linear mixed-effects regressionmodels used to analyze the ethnic differences in opticdisc size were adjusted for age, sex, glaucoma status,lens status, spherical equivalent and use of both eyesin the same subject.</p><p>RESULTS</p><p>Five hundred and seventy-four eyes of 305 subjectswere included in the analysis. The inability to assessthe excluded 36 eyes encompassed the followingreasons: 22 had poor quality photographs due tocataract, five had choroidal nevus, three had enucle-ation, two had phthisis, three had photographs thatdid not capture the entire optic nerve and one hadsevere age-related macular degeneration. Table 1summarizes the demographics, clinical characteristics,glaucoma status, lens status and optic disc size of thestudy subjects by ethnicity. The mean and standarddeviation of the optic disc size were 2.16 0.41 mm2for Caucasian, 2.30 0.56 mm2 for Chinese, 2.310.41 mm2 for Filipino, 2.38 0.40 mm2 for African and2.40 0.38 mm2 for Hispanic subjects. Optic disc size,age, and spherical equivalent significantly differedamong the ethnic groups by the KruskalWallis test(p50.05). Sex was significantly different amongthe ethnic groups by the Chi-square test (p50.05).</p><p>The association between optic disc size and glaucomastatus was not significant in the linear mixed-effectsregression analysis, which adjusted for age, sex,spherical equivalent, lens status, ethnicity and useof both eyes in the same subject (p40.05).The association between optic disc size and lensstatus was not significant in the linear mixed-effectsregression analysis, which adjusted for age, sex,spherical equivalent, glaucoma status, ethnicity anduse of both eyes in the same subject (p40.05).</p><p>Table 2 shows the pairwise comparisons of opticdisc size among Chinese, African, Hispanic andFilipino subjects. Ethnic differences in optic disc sizewere not observed among the African, Hispanic,Filipino and Chinese subjects in the linear mixed-effects regression analyses (p40.05). The optic discsize was significantly smaller in Caucasian comparedto the other ethnic groups in linear mixed-effectsregression analyses (p50.05). The linear mixed-effectsregression models used to analyze the ethnic differ-ences in optic disc size were adjusted for age, sex,glaucoma status, lens status, spherical equivalent anduse of both eyes in the same subject.</p><p>Optic disc size was calculated from fundus photo-graphs based on conversion formulas developedby corresponding pixel counts from the fundusphotographs with optic disc size in the HRT images.Since our study utilized fundus photographs of twodifferent magnifications, 20x and 35x, a separateconversion equation was calculated for each magni-fication based on a randomly selected subset of 20patients with fundus photographs of that magnifica-tions. The number of fundus photographs in eachmagnification for the five ethnic groups are listedin the following as (numbers of 20x magnification:numbers of 35x magnification): Caucasian (115:35);</p><p>TABLE 1 Demographics and clinical characteristics of the study population.</p><p>Ethnicity Caucasian Chinese Filipino African Hispanic p Value</p><p>DemographicsNumber of patients 79 73 35 70 48Number of eyes 150 136 66 130 92Age (years)a 65.6 14.8 71.0 11.9 63.7 16.2 68.0 13.9 66.0 14.6 0.007bSex (male:female) 87:63 55:81 29:37 47:83 36:56 0.002c</p><p>Glaucoma statusNon-glaucoma 12 12 8 22 16Glaucoma suspect 73 70 47 53 60Glaucoma 65 54 11 55 16</p><p>Non-glaucoma eyesDiabetes 2 10 0 6 1Age-related macular degeneration 2 0 0 0 2Hypertension 1 0 0 0 2Pseudophakic 21.3% 21.3% 25.8% 30.0% 16.3%</p><p>Clinical characteristicsSpherical equivalent (diopters)a 0.86 2.63 1.43 3.44 1.13 3.71 0.443 2.27 0.55 2.27 0.003bOptic disc size (mm2)a 2.16 0.41 2.30 0.56 2.31 0.41 2.38 0.40 2.40 0.38 50.0001b</p><p>aData are expressed as mean value standard deviation.bp Value by KruskalWallis test.cp Value by Chi-square test.</p><p>1144 R. Y. Lee et al.</p><p>Current Eye Research</p><p>Cur</p><p>r E</p><p>ye R</p><p>es D</p><p>ownl</p><p>oade</p><p>d fr</p><p>om in</p><p>form</p><p>ahea</p><p>lthca</p><p>re.c</p><p>om b</p><p>y U</p><p>nive</p><p>rsite</p><p>it T</p><p>wen</p><p>te o</p><p>n 11</p><p>/29/</p><p>14Fo</p><p>r pe</p><p>rson</p><p>al u</p><p>se o</p><p>nly.</p></li><li><p>Chinese (111:25); Filipino (49:17); African (80:50) andHispanic (53:39).</p><p>DISCUSSION</p><p>This study evaluated the optic disc size amongCaucasian, Chinese, African, Hispanic and Filipinosubjects from a university-based general ophthalmol-ogy clinic using fundus photography. Our resultsshowed that optic disc size was significantly smallerin Caucasian compared to other ethnic groups.Comparisons of optic disc size among the ethnicgroups were corrected for age, sex, glaucoma status,lens status and spherical equivalent. These findingssuggest that ethnicity is an independent determinantof optic disc size.</p><p>This study provided strong evidence thatCaucasians possess smaller optic disc size comparedto Chinese, African, Hispanic and Filipino subjects.This finding is in line with results from otherethnicity-based comparisons of optic disc size usingnumerous imaging modalities. In particular, a smaller...</p></li></ul>

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