aponte 2010

EPIDEMIOLOGY

Incidence and Clinical Characteristicsof Childhood Glaucoma

A Population-Based Study

Elisabeth P. Aponte, MD; Nancy Diehl, BS; Brian G. Mohney, MD

Objective: To describe the incidence and clinical char-acteristics of childhood glaucoma in a defined popula-tion of the United States.

Methods: The medical records of all pediatric patientsyounger than 20 years living in Olmstead County, Min-nesota, from January 1, 1965, through December 31, 2004,who met diagnostic criteria for glaucoma or glaucomasuspect were reviewed.

Results: Thirty children were diagnosed as having glau-coma during the 40-year study period. The incidence ofchildhood glaucoma was 2.29 (95% confidence interval,1.47-3.12) per 100 000 residents younger than 20 years,with the following types and incidences: 19 acquired (1.46/100 000; 0.80-2.12), 6 secondary (0.45/100 000; 0.08-

0.82), and 5 primary glaucoma (0.38/100 000; 0.05-0.72). The birth prevalence of primary congenital glaucomaduring the 40-year period was 1 per 68 254 residentsyounger than 20 years or 1.46 per 100 000 (95% confi-dence interval, 0.03-8.16). Twenty-four individuals withglaucoma suspect were also identified, yielding an inci-dence of 1.9 per 100 000 residents younger than 20 years(95% confidence interval, 1.14-2.66).

Conclusion: The incidence of childhood glaucoma in thispopulationwas2.29per100 000residentsyounger than20years or 1 per 43 575 residents younger than 20 years. Ac-quiredandsecondaryformsofglaucomawerethemostcom-mon, whereas congenital and juvenile glaucoma were rare.

Arch Ophthalmol. 2010;128(4):478-482

C HILDHOOD GLAUCOMA IS AN

uncommon pediatric con-dition often associatedwith significant visualloss.1,2 It consists of a he-

terogeneous group of diseases leading tooptic neuropathy and visual field changesthat can be categorized into primary, sec-ondary, and acquired subtypes.3 Primaryglaucoma in children is generally divided

into primary congenital glaucoma (frombirth to early childhood) and juvenile pri-mary open-angle glaucoma (4 years to earlyadulthood).3,4 Primary congenital glau-coma (PCG) has previously been reportedas the most common type of glaucoma seeninchildhood.4-6 Secondaryglaucoma isusu-ally defined as including syndromic disor-ders or other medical conditions present atbirth, suchasaniridia,Axenfeld-Rieger syn-drome, retinopathy of prematurity, Rubin-stein-Taybi syndrome, Sturge-Weber syn-drome, and persistent hyperplastic primaryvitreous and congenital rubella.3,4 Ac-quired glaucoma, often classified as sec-

ondary glaucoma, is the result of otherprocesses not present at birth, such as in-flammation, drugs, trauma, and surgery.3

The incidence of childhood glaucomawithin the United States, including PCG, toour knowledge, has not been reported. Thepurpose of this study is to describe the in-cidence and clinical characteristics of child-hood glaucoma diagnosed during a 40-year period among patients younger than20 years who were residents of OlmstedCounty, Minnesota.

METHODS

The medical records of all patients younger than20 years who were residents of Olmsted Countywhen diagnosed as having glaucoma from Janu-ary 1, 1965, through December 31, 2004, wereretrospectively reviewed. Although the termchildhood typically excludes patients older than18 years, we extended the age limit to youngerthan 20 years because juvenile glaucoma is anentity that has been diagnosed in patients up tothe fourth decade of life.7,8 Institutional reviewboard approval was obtained for this study. In-dividuals who met diagnostic criteria for glau-coma or glaucoma suspect were identified usingthe resources of the Rochester EpidemiologyProject, a medical record linkage systemdesigned to capture data on any patient-physician encounter in Olmsted County.9

CME available online atwww.jamaarchivescme.comand questions on page 400

Author Affiliations: MayoMedical School (Dr Aponte)and Division of Biostatistics(Ms Diehl), Mayo ClinicCollege of Medicine,Department of Ophthalmology(Dr Mohney), Mayo Clinic andMayo Foundation for MedicalEducation and Research,Rochester, Minnesota.

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The racial distribution of Olmsted County residents in 1990was 95.7% white, 3.0% Asian American, 0.7% African Ameri-can, and 0.3% Native American; the remaining 0.3% were ofother race. The population is relatively isolated from other ur-ban areas, and virtually all medical care is provided to its resi-dents by Mayo Clinic, Olmsted Medical Group, and their af-filiated hospitals. Patients not residing in Olmsted County atthe time of their diagnosis were excluded from the study.

Glaucoma was defined generally in this study as an opticneuropathy and/or a visual field change, frequently associatedwith elevated intraocular pressure (IOP). Clinical signs, suchas elevated IOP (�21 mm Hg), optic nerve cupping, asym-metric or progressive disc cupping, visual field defects, oranterior segment changes, such as enlarged corneas or Haabstriae, alone or in combination, were used to make the diag-nosis of glaucoma. The primary congenital glaucoma groupincluded patients who displayed ocular signs of enlargementcombined with 1 or more classic findings, such as photopho-bia, epiphora, Haab striae, corneal clouding, or optic nervecupping, and ranging in age from birth to early childhood.The term juvenile glaucoma referred to primary open-angleglaucoma diagnosed when the patient was between 4 and 20years of age. Secondary glaucoma referred to a systemic or ocu-lar condition present at birth, whereas acquired glaucomareferred to secondary processes occurring after birth. No ret-rospective diagnosis of glaucoma was made, and all patientsincluded had been diagnosed as having glaucoma by the oph-thalmologists who participated in their care.

Glaucoma suspect was defined according to the American Acad-emy of Ophthalmology guidelines10 as open anterior-chamberangles by gonioscopy and 1 or more of the following clinical find-ings: (1) appearance of the optic disc or retinal nerve fiber layersuggestive of glaucomatous damage, (2) a visual field suggestiveof glaucomatous damage, and/or (3) consistently elevated IOPassociated with normal appearance of the optic disc and retinalnerve fiber layer and with normal visual field test results. We in-cluded patients with an IOP greater than 21 mm Hg for 6 monthsor longer as meeting the third American Academy of Ophthal-mology clinical criteria. Patients who did not meet the glaucomasuspect diagnosis guideline, as established by the American Acad-emy of Ophthalmology, were excluded. In addition, patients di-agnosed as merely having large physiologic cups or whose ex-amination appeared to reveal isolated optic nerve cupping werealso excluded. Other patients with normal examination resultsinitially diagnosed with glaucoma suspect based on a positive fam-ily history of glaucoma were also excluded. Except for patientswith a 6-month history of elevated IOP, those who were no longerconsidered to have glaucoma suspect at their last follow-up ex-amination were also excluded from the study. Only those pa-tients who had at least 2 ophthalmologic examinations with a di-agnosis of glaucoma suspect were included in this study.

Continuous data are presented as a mean, and categoricaldata are presented as counts and percentages. To determine theincidence of childhood glaucoma in Olmsted County, annual

age- and sex-specific incidence rates were constructed usingthe age- and sex-specific population figures for this county fromthe US Census. Because PCG is often diagnosed within the firstyear of life, a birth prevalence for PCG was also calculated fromthe number of births occurring from January 1, 1965, throughDecember 31, 2004, using the annual birth incidence for thiscounty. The 95% confidence intervals (CIs) were calculated usingassumptions based on the Poisson distribution.

RESULTS

Thirty patients younger than 20 years were diagnosed ashaving glaucoma in Olmsted County during the 40-yearstudy period. This number corresponds to an age- and sex-adjusted incidence of 2.29 per 100 000 residents youngerthan 20 years (95% CI, 1.47-3.12). Twenty-one (70%) ofthe children had their glaucoma diagnosed in the secondhalf of the study (Table 1). Fifteen (50%) of the childrenhad bilateral disease, affecting a total of 45 eyes. The inci-dence of PCG and other forms of childhood glaucoma di-agnosed in this population are given in Table 2, whereas

Table 1. Residents Younger Than 20 Years Diagnosed as Having Glaucoma and Glaucoma Suspect by Decade

YearNo. of Residents�20 Years of Age Decade

No. (%) of Children �20 YearsDiagnosed as Having Glaucoma

(n=30)

No. (%) of Children �20 YearsDiagnosed With Glaucoma Suspect

(n=24)

1965 30 423 1965-1974 3 (10) 01975 32 346 1975-1984 6 (20) 2 (8)1985 31 186 1985-1994 12 (40) 5 (21)1995 34 269 1995-2004 9 (30) 17 (71)2004 39 183 NA NA NA

Abbreviation: NA, not applicable.

Table 2. Incidence of Diagnosed Glaucoma and GlaucomaSuspect Among Residents Younger Than 20 Years

Glaucoma TypeNo. of

Residents

Incidenceper 100 000Residents�20 Years

SingleIncidence

in Residents�20 Years

All glaucoma 30 2.29 1/43 575Primary glaucoma

All primary glaucoma 5 0.38 1/260 688Primary congenital glaucoma 1 0.07 NAJuvenile glaucoma 4 0.32 NA

Secondary glaucomaAll secondary glaucoma 6 0.45 1/221 877Sturge-Weber syndrome 2 0.14 NACutis marmorata 1 0.07 NARubenstein-Taybi syndrome 1 0.07 NARetinopathy of prematurity 1 0.08 NACoates disease 1 0.10 NA

Acquired glaucomaAll acquired glaucoma 19 1.46 1/68 470Traumatic or surgical cause 14 1.09 NA

Trauma 8 NA NASurgery 6 NA NAUveitic 4 0.30 NADrug induced 1 0.07 NA

Glaucoma suspect 24 1.90 1/52 579

Abbreviation: NA, not applicable.




the clinical and demographic characteristics are given inTable 3. There were 16 boys and 14 girls, whose condi-tions were diagnosed at a mean age of 10.4 years (range,15 days to 19.7 years), of the following races: 18 white(60%), 4 black (13%), 2 Asian (7%), 1 American Indian(3%), and 5 (17%) of unknown race. A family history ofglaucoma was present in 6 (20%) study patients, whereasthe mean presenting IOP and mean cup-disc ratio at thefirst visit were 30.8 mm Hg (range, 14-56 mm Hg) and 0.5(range, 0.1-1) in the glaucomatous eye, respectively.

Nineteen (63%) of the 30 children with glaucoma werediagnosed as having acquired glaucoma at a mean age of11.1 years (range, 3.0-18.8 years), and the incidence ofglaucoma was 1.46 per 100 000 residents or 1 in 68 470patients younger than 20 years (95% CI, 0.80-2.12). Thisgroup consisted of 12 boys and 7 girls, among whom 14developed glaucoma secondary to trauma or surgery, 4from uveitis, and 1 after topical corticosteroid use(Table 3). Seven (37%) of the 19 patients had bilateralglaucoma, and 3 (16%) had a family history of glau-coma. The mean IOP and cup-disc ratio at presentationwere 34.8 mm Hg (range, 20-56 mm Hg) and 0.4 (range,0.1-1) in the affected eye, respectively.

Six of the 30 children with glaucoma (20%) were di-agnosed as having secondary glaucoma, including 2 withSturge-Weber syndrome, 2 with neovascular glaucoma (1patient with Coates disease and 1 with retinopathy of pre-maturity), and 1 each with Rubinstein-Taybi syndrome andcutis marmorata telangiectatica congenita, yielding an age-and sex-adjusted incidence of 0.45 per 100 000 residentsor 1 per 221 877 patients younger than 20 years (95% CI,0.08-0.82). The mean age at diagnosis for the 6 childrenwas 6.4 years (range, 2 months to 18.4 years), with a meaninitial IOP of 19.7 mm Hg (range, 14-27.5 mm Hg) in theglaucomatous eye. Three of 6 patients (50%) with sec-ondary glaucoma had bilateral disease.

Primarychildhoodglaucomawasdiagnosedin4childrenwith juvenile glaucoma and 1 child with PCG. This findingcorresponds to incidencesof0.38(95%CI,0.00-0.20),0.32

(0.08-0.82), and 0.07 (0.00-0.20) per 100 000 patientsyounger than20years forprimarychildhoodglaucoma, ju-venileglaucoma,andPCG,respectively.Inaddition,becausePCG frequently occurs during the first year of life, its birthprevalencewasalsocalculatedas1per68 254birthsor1.46per100 000births.Threeofthe4childrenwithjuvenileglau-comaweregirls,2(50%)hadapositivefamilyhistoryofglau-coma, and all had glaucoma diagnosed between 13 and 19yearsofagewithbilateralocular involvement.ThemeanIOPforjuvenileglaucomaatpresentationwas27.6mmHg(range,23.5-31.0mmHg),withameancup-discratioof0.85(range,0.7-1.0) in the glaucomatous eye.

Twenty-four additional children were diagnosed as hav-ing glaucoma suspect, generating an incidence of 1.90 per100 000 residents younger than 20 years (95% CI, 1.14-2.66) (Table 4). Twelve of the 24 children (50%) werediagnosed as having glaucoma suspect on the basis of el-evated IOP greater than 21 mm Hg for at least 6 months.Five patients (21%) were considered to have glaucoma sus-pect based on cup-disc asymmetry and 1 based on vary-ing disc cupping, whose ocular health was stable at finalfollow-up with a normal visual field and IOP. Six addi-tional patients with glaucoma suspect were identified basedon other factors, including 1 patient with pigmentary dis-persion syndrome and others with different combina-tions of unusual disc appearance, suspicious visual fields,cupping, and elevated IOP. The mean age at diagnosis forthe 24 patients was 13.7 years (range, 6.7-19.7 years), witha mean initial IOP of 20.1 mm Hg (range, 8.0-26.0 mm Hg)in the affected eye. All patients diagnosed as having glau-coma suspect included in the study were still consideredto have this condition at the final follow-up by their oph-thalmologist and had not developed glaucoma.

COMMENT

Childhood glaucoma was diagnosed in 30 children or 1per 43 575 residents younger than 20 years during the

Table 3. Clinical and Demographic Characteristics of 30 Residents Younger Than 20 Years Diagnosed as Having Glaucoma

Glaucoma TypeNo. of

Patients

PatientsWith Bilateral

Glaucoma, No. (%)

Age atDiagnosis,

Mean (Range), ya

Sex, No. Family Historyof Glaucoma,

No. (%)

Initial IOP,Mean (Range),

mm Hgb

Initial Cup-DiscRatio, Mean

(Range)bMale Female

All glaucoma types 30 15 (50) 10.4 (0.04-19.7) 16 14 6 (20) 30.8 (14.0-56.0) 0.5 (0.1-1.0)Primary glaucoma 5 5 (100) 12.3 (0.04-19.7) 2 3 2 (40) 28.6 (23.5-32.5) 0.7 (0.45-1.0)

PCG 1 1 (100) 15 dc 1 0 0 32.5c 0.45c

Juvenile glaucoma 4 4 (100) 15.4 (12.7-19.7) 1 3 2 (50) 27.6 (23.5-31.0) 0.85 (0.7-1.0)Secondary glaucoma 6 3 (50) 6.4 (0.1-18.4) 2 4 1 (17) 19.7 (14.0-27.5) 0.35c

Sturge-Weber syndrome 2 0 3.2 (0.1-6.3) 1 1 0 14.0c NACutis marmorata 1 1 (100) 2 moc 0 1 0 27.5c 0.35c

Rubenstein-Taybi syndrome 1 1 (100) 7 moc 0 1 0 16.0c NARetinopathy of prematurity 1 1 (100) 12.8c 0 1 1 (100) 20.0c NACoates disease 1 0 18.4c 1 0 0 21.0c NA

Acquired glaucoma 19 7 (37) 11.1 (3.0-18.8) 12 7 3 (16) 34.8 (20.0-56.0) 0.4 (0.1-1.0)Traumatic or surgical 14 3 (21) 12.0 (3.0-18.8) 11 3 2 (14) 35.5 (20.0-56.0) 0.5 (0.2-1.0)Uveitic 4 3 (75) 9.7 (5.0-17.3) 1 3 1 (25) 34.6 (26.5-54.0) 0.25 (0.1-0.5)Drug induced 1 1 (100) 4.2c 0 1 0 26.0c 0.35c

Abbreviations: IOP, intraocular pressure; NA, not applicable; PCG, primary congenital glaucoma.aAge is presented in years unless otherwise indicated.bMeasurements reported are from the affected eye. If both eyes were affected, the mean measure of the right and left eyes was used.cValue is based on a single patient.




40-year study period. Among this heterogeneous group,19 were diagnosed as having acquired glaucoma, 6 as hav-ing secondary glaucoma, 4 as having primary juvenileglaucoma, and 1 as having PCG. The birth prevalence ofPCG in this population was 1 per 68 254 residents youngerthan 20 years or 1.46 per 100 000 (95% CI, 0.03-8.16).The clinical characteristics of these patients, by glau-coma type, were consistent with prior reports.

The incidence of PCG in this population is lower thanthat in all prior reports. The highest reported preva-lence has been among individuals of Slovakian Roma (1per 1250)11 and Saudi Arabian (1 per 2500) racial de-scent.12 Although the incidence of PCG in Western coun-tries has been estimated at 1 per 10 000 population3,13,14

to 1 per 12 500 population5 in previous reports, a recentpopulation-based study conducted in the United King-dom reported the incidence of diagnosis of PCG in GreatBritain to be 5.41 per 100 000 population (1 per 18 500population) and 3.31 per 100 000 population (1 per30 200 population) in the Republic of Ireland.4 In addi-tion, a birth prevalence of 2.85 per 100 000 population(1 per 38 000 population) was recently reported in Spain,15

which was similar to an incidence of 1 in 30 000 birthsfound in an Australian study.16

This study, to our knowledge, is the first population-based report on the incidence of childhood glaucoma andPCG in the United States. The difference in incidence be-tween this and other studies may be attributable to a num-ber of reasons. First, some of the reported incidences arenot population based and are likely to have been artifi-cially elevated.14 Second, the diagnostic classification andinclusion criteria for childhood glaucomas have been in-consistent among studies.5,16-19 Finally, race and consan-guinity may affect the incidence of PCG, as shown in theBritish Infantile and Childhood Glaucoma Eye Study,4

which reported a 9-fold increased incidence of PCG in chil-dren of Pakistani descent compared with white chil-dren.4 Olmsted County, during the years of this study, was96% white, a demographic with lower rates of PCG andother forms of glaucoma. Although only 4% of the coun-ty’s population was of a race other than white, one-fourthof the patients diagnosed as having glaucoma were of otherraces. Although this disproportionate incidence of glau-coma in children of races other than white is similar tothe findings of the British Infantile and Childhood Glau-coma Eye Study, none of the patients of other races in thisstudy had PCG. Instead, the types of glaucoma seen in ourracial populations were traumatic or surgical (n=4), ju-venile (n=2), and uveitic (n=1). The low incidence of PCG

in Olmsted County may reflect a lower occurrence of con-sanguineous practices in the county.5

Acquired glaucoma was the most prevalent type ofchildhood glaucoma diagnosed in Olmsted County, com-prising more than 63% of cases and occurring in 1 per68 470 patients younger than 20 years. The relative pre-dominance of boys in this glaucoma subtype likely re-flects the higher rate of traumatic glaucoma among boys(11 boys and 3 girls). The incidence of traumatic hy-phema from the same population was 12 per 100 000,with a male to female ratio of 5:1.20 Fourteen of the 19children (74%) with acquired glaucoma had either trau-matic or iatrogenic causes for the development of theirglaucoma. The larger proportion of patients whose glau-coma was attributable to traumatic and aphakic causesin this study highlights the importance of protective eye-wear and limiting the glaucomatous effects of anteriorsegment surgery.

Secondary glaucoma was found in 6 children, for anincidence of 0.45 per 100 000 or 1 in 221 877 patientsyounger than 20 years (95% CI, 0.08-0.82). In the Brit-ish Infantile and Childhood Glaucoma Eye Study, 52 of99 children with glaucoma who were younger than 16years were diagnosed as having secondary glaucoma, aclassification that included lens-related conditions andother medical or syndromic diseases. In our population-based study, secondary and acquired glaucoma cases con-sisted of most glaucoma cases seen. Although the dis-tinction between secondary and acquired glaucomas wasnot made in prior studies, our population-based reportshows that secondary glaucoma manifested itself earlierthan acquired glaucoma, possibly because of the asso-ciation of other disorders present at birth.

Glaucoma suspect was diagnosed in 24 patients, or 1.90per 100 000 residents younger than 20 years, in this study.We are unaware of any other population-based inci-dence rate of glaucoma suspect among children. How-ever, the incidence rate reported in this study is likelyan underestimation, given the asymptomatic nature ofthe disease. None of the children with glaucoma sus-pect in this study were known to develop visual field losscharacteristic of glaucoma during their follow-up. Inter-estingly, patients with cup-disc asymmetry were identi-fied earlier than other patients with glaucoma suspect andwere more likely to have a positive family history.

The findings in this study have several limitations. Theretrospective design is limited by nonstandardized andincomplete data collection. The pressure measurementsand other clinical findings were not all performed by a

Table 4. Clinical and Demographic Characteristics of 24 Patients Younger Than 20 Years Diagnosed With Glaucoma Suspect

No. ofPatients

Age atDiagnosis,

Mean (Range), y

Sex, No. Family Historyof Glaucoma,

No. (%)

Initial IOP,a

Mean (Range),mm Hg

InitialCup-Disc Ratio,Mean (Range)aMale Female

All patients diagnosed with glaucoma suspect 24 13.7 (6.7-19.7) 8 16 13 (54) 20.1 (8.0-26.0) 0.42 (0.10-0.85)Elevated IOP at �6 mo 12 14.5 (9.4-19.7) 3 9 5 (42) 23.5 (21.0-26.0) 0.26 (0.10-0.55)Cup-disc asymmetry or anomaly 6 10.7 (6.7-14.5) 1 5 4 (67) 16.8 (12.0-22.5) 0.49 (0.30-0.70)Other patients diagnosed with glaucoma suspect 6 14.8 (7.3-17.2) 4 2 4 (67) 16.6 (8.0-23.0) 0.59 (0.25-0.85)

Abbreviation: IOP, intraocular pressure.aMeasurements reported are from the affected eye. If both eyes were affected, the mean measure of the right and left eyes was used.




single examiner or a glaucoma specialist, potentially in-troducing the uncertainty of examiner error. In addi-tion, some forms of glaucoma are asymptomatic or oth-erwise unrecognized by the patient or outside observer,particularly juvenile glaucoma and glaucoma suspect. Asa result, the incidence of these forms, unlike that of PCG,is likely to be underestimated. Similarly, the apparent in-crease in the incidence of glaucoma and glaucoma sus-pect in this cohort during the later years of the study ismost likely owing to an improved understanding and rec-ognition of the disease.21 Moreover, although a rela-tively isolated community, some residents of OlmstedCounty with glaucoma may have sought care outside theregion, leading to a further underestimation of diseaseoccurence. Finally, the low incidence of childhood glau-coma in this population makes it difficult to extrapolatethe findings of the various subtypes of glaucoma. The gen-eralization of data from this study is further limited bythe demographics of Olmsted County, a relatively ho-mogeneous, semiurban, white population.

This study provides population-based incidence ratesfor childhood glaucoma diagnosed during a 40-year pe-riod. Childhood glaucoma was found in 1 per 43 575 pa-tients younger than 20 years. The most common type ofglaucoma was acquired glaucoma (traumatic, surgical, uve-itic, or drug induced), accounting for 63% of patients withglaucoma, whereas the secondary and primary forms wereless common. Primary congenital glaucoma was diag-nosed in 1 per 68 254 residents younger than 20 years ofage (1.46 per 100 000 residents younger than 20 years ofage), a rate that is lower than that reported in the Span-ish, British, or Australian general population.

Submitted for Publication: January 6, 2009; final revi-sion received October 11, 2009; accepted November 10,2009.Correspondence: Brian G. Mohney, MD, Department ofOphthalmology, Mayo Clinic, 200 First St SW, Roches-ter, MN 55905 ([email protected]).Author Contributions: Drs Aponte and Mohney had fullaccess to all the data in the study and take responsibilityfor the integrity of the data and the accuracy of the dataanalysis.Financial Disclosure: None reported.Funding/Support: This study was supported in part by

an unrestricted grant from Research to Prevent Blind-ness Inc, New York, New York.

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