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Hindawi Publishing CorporationJournal o Ophthalmology Volume , Article ID , pageshttp://dx.doi.org/.//

Clinical Study Is Hyperopia an Important Risk Factor for PACG inthe Dutch Population?—A Case Control Study

Saskia H. M. van Romunde, Gijs Thepass, and Hans G. Lemij

Te Rotterdam Ophthalmic Institute, Te Rotterdam Eye Hospital, P.O. Box , LM Rotterdam, Te Netherlands

Correspondence should be addressed to Gijs Tepass; [email protected]

Received July ; Accepted August

Academic Editor: Edward Manche

Copyright © Saskia H. M. van Romunde et al. Tis is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.

Objectives. o determine i hyperopia is a risk actor or primary angle-closure glaucoma (PACG) in the Dutch population and toidentiy other biometrical parameters as risk actors or PACG including axial length (AL), anterior chamber depth (ACD), and values. Methods. Te study population consisted o PACG patients that had undergone a laser peripheral iridotomy (LPI). Tecontrolgroup consisted o age-and gender-matched cataract patients. Te main outcomewas hyperopia (sphericalequivalent≥+.dioptres) measured with IOL Master or autoreractor. Reractive error, ACD, AL, and values were tested with a Mann-Whitney testand by logistic regression. Results. PACG patients and controlswereincluded(meanage = years ± .). Te prevalenceo hyperopia in patients and controls was .% and .%, respectively (Fisher’s test = 0.076). Mann-Whitney test showed no

statistically signicant relation with reractive error ( = 0.068) or values ( = 0.607). In contrast, ACD and AL were statistically signicant ( < 0.001). ested with logistic regression, only ACD was a signicant predictor o PACG ( < 0.001). Conclusion.Tere was no statistically signicant correlation between reractive error and PACG. ACD was strongly correlated, though, withPACG, whereas AL turned out to be a less signicant risk actor.

1. Introduction

Glaucoma is the most important cause o irreversible blind-ness in the world []. Primary angle-closure glaucoma(PACG) is highly prevalent in Asian countries. However, theEgna-Neumarkt Glaucoma Study stated that the burden o

PACG in Europe has been underestimated previously [].Teprevalence in this study was .%, which accounts or about aquarter o all primaryglaucomacases. Te most requent typewas chronic angle closure, which is more insidious and hencemore ofen missed. Further damage o PACG can be easily prevented by perorming a laser peripheral iridotomy (LPI)[]. It is important to know more about the pathophysiology and risk actors or PACG to improve prevention.

Several risk actors have been identied or PACG,including emale gender, older age, and shallow anteriorchamber depth (ACD) [, –]. Ophthalmologists in Europecommonly have the clinical impression that hyperopia is arisk actor or PACG. Te relation between hyperopia and

PACG was suggested as early as in []. Despite severalstudies, however, this relation has not been convincingly proven [, –]. A possible explanation or the mismatchbetween the clinical impression o such a relationship andthe lack o evidence might be that most researches have beendone in partso Asia, where the anatomy o the eyes might be

different rom eyes in Europeans and myopia is more preva-lent than in Europe []. Mechanisms or PACG vary amongdifferent ethnicities. Tereore, it has been suggested thatmechanisms and risk actors or PACG should be studied in

various populations []. o date,no studies on therisk actorsor PACG have been done in Europe. Our study investigatedthe risk actors or PACG in the Dutch population. We set outwith the assumption that hyperopia is an important risk ac-tor or PACG. We wanted to determine i our assumption wasright. In addition, we questioned whether other previously identied risk actors in other populations, including axiallength (AL), ACD, and values, play any role in the risk prole or PACG in the Dutch population.

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Journal o Ophthalmology

2. Methods

.. Study Population and Data Acquisition. Te data was col-lected rom all PACG patients that underwent an LPI in theRotterdam Eye Hospital between and ( = 238).PACG was dened as an occludable angle as assessed upongonioscopy together with structural or unctional damagedue to glaucoma in atleast one eye. Evidence o glaucoma wasinvestigated by undoscopy, standard automated perimetry,and scanning laser polarimetry with the GDx (Carl ZeissMeditec AG, Jena, Germany). Exclusion criteria were sec-ondary glaucoma and narrow angles without physical orunctional signs o glaucoma. Also, patients that underwentcataract surgery beore an LPI were excluded because o theanatomical changes in the anterior segment caused by thesurgery. Te PACG patients that underwent cataract surgery afer LPI treatment had been measured with the IOL MasterV. (Carl Zeiss Meditec AG, Jena, Germany) beore surgery.IOL Master measurements included reractive error, ACD,AL, and values. Tis data was used or the analysis. Te

PACG patients that did not undergo any cataract surgery andhad thereore not been measured with the IOL Master wereasked to visit the hospital and undergo biometric assays orthe current study.

Control data was obtained rom a database o all thecataract patients that underwent cataract surgery in theRotterdam Eye Hospital in the period between and ( = 15118). Tis database contains the data o the IOL Mas-ter measurements perormed beore surgery. Incomplete datawas removed rom the dataset. o reach a power o ., weselected two controls per PACG patient. In order to controlor conounding actors, controls were matched by age andgender. Control subjects were listed anonymously by their

randomly assigned patient ID number. Per PACG patient, weselected the rst two control subjects on the list that matchedin age and gender. One eye per patient was randomly selectedby a randomization table.In some cases only one eye wassuit-able or the study. Te same method was used or the controlgroup.

.. Additional Assessments. o minimize the burden on ourpatients, we did not recruit any patients that lived ar away rom the Rotterdam Eye Hospital. Other PACG patients thathad not been previously measured with the IOL Masterwere invited or additional assessment. Tese were preerably combined with a regular visit. I no visit was planned during

the course o the study, the patients were requested to visit theRotterdam Eye Hospital or research purposes only. Inormedconsent was obtained beore initiating the measurements. Inthese patients, the Lenstar LS (Haag-Streit AG, Köniz,Switzerland) was used or assessing ACD, AL, and values,because the IOL Master was not available or these purposes.Tree measurements were done in each eye. I a measurementailed due to eye movement or blinking, an additional mea-surement was made. Te mean o the measurementswas usedor the analysis. Reractive error could not be measured withthe Lenstar. Tereore, concurrently, an autoreractor ARKA (Nidek Co. Ltd. Gamagori, Japan) was used to assessany reractive error.

: Demographicso the study population andinstrument usedor measurements.

Patient ( = 117) Controls ( = 234)

Mean age (.–. %-CI) (.–. %-CI)

Gender

Women (%) (%)

Men (%) (%)

Instrument

IOL Master (%) (%)

Lenstar + AR (%) —

AR: autoreractor.

.. Statistical Analysis. All statistical analyses were per-ormed with commercial sofware (SPSS version orWindows, IBM, New York, USA). Statistical signicance wasassumed at < 0.05 levels. Hyperopia was dened as aspherical equivalent ≥+. dioptres (D) or the main analysis.Hyperopia is a common ocular condition. Hence, a spherical

equivalent ≥+. D may not be useul as a risk actor in clin-ical practice. Perhaps higher hyperopia might serve better toassessits role as a potential risk actor. Tereore, we redenedhyperopia in a subanalysis as a reractive error with a spher-ical equivalent ≥+. D. Hyperopia was evaluated with theone-sided Fisher’s test, odds ratios (OR), and its % con-dence intervals (CI). Logistic regression was used or calcu-lating a risk prediction or PACG based on reractive error.Reractive error, ACD, AL, and the mean o values wereevaluated or both the patients and the control group sep-arately. Te distributions o each parameter were tested ornormality with the one-sample Kolmogorov-Smirnov test.Because not all data were parametric, any differences weretested conservativelywith a Mann-Whitney test. Te resultswere urther analysed by logistic regression.

3. Results

A total o people were included in the study, patientsand controls.Te selection o the PACG patients hasbeenpresented in Figure . able shows the demographics o thepatients and control subjects. Fify-eight percent o the par-ticipants were women. Te mean age o the study populationwas years. Sixty-seven PACG patients had been measuredwith the IOL Master, their data was obtained rom patient

les. Fify patients were additionally assessed with the Lenstarand autoreractor. Out o the patients, ve patients hadmissing reractive error values. wenty-ve patients had only one eye suitable or the study because o cataract ( = 9), anLPI ( = 12), an enucleation ( = 2), trauma ( = 1), or a

vitreous haemorrhage ( = 1)inoneeye.Teeyesotheotherparticipants, in whom both eyes were eligible or inclusion,were randomly selected.

.. Hyperopia. able shows the distribution o hyperopiain the PACG group and in the control group. It demon-strates that a high percentage o both patients and controlsubjects was hyperopic with an .% difference between

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LPI treatment 2008–2012

n = 236

Invited for additional

assessment n = 97

Assessed with Lenstar

n = 51

Not used for analysis due

to refraction surgery n = 1

Lived far away from

REH n = 23

Patients’ data suitable

for study n = 11619

Deceased n = 15

n = 15

Cataract surgery before LPI n = 15

Missing data n = 9

Suitable for study

n = 187

IOL master data obtained

from patient les n = 67

Rejected

n = 46

Selected for analysis

n = 117

Selected for analysis

n = 234

Cataract surgery 2007–2012

n = 15118

Incomplete data

n = 3499

n = 6No signs of glaucoma

and autorefractor

Secondary glaucoma

F : Flowchart or selecting PACG patients and controls. REH = Rotterdam Eye Hospital.

: Hyperopia dened as a reractive error spherical equivalent (SE) ≥ . dioptres (D) or the main outcome and SE ≥ .D or asubanalysis. Odds ratios(OR) and their % condence intervals (CI) are shown. Results o the one-sided Fisher’s test < 0.05 were assumedto be signicant.

Patient ( = 112) Control ( = 234) OR (% CI) Fisher’s test

Hyperopia ≥ . D

Absent (.%) (.%) = 0.076

Present (.%) (.%) . (.–.)

Hyperopia ≥ . D

Absent (.%) (.%) = 0.259

Present (.%) (.%) . (.–.)

the two groups. Tis differencewas notstatistically signicant(Fisher’s test, = 0.076). Te odds ratios demonstratedno relation between PACG and hyperopia (OR .; % CI.–.).

... Subanalysis. In the subanalysis, the cut-off value orhyperopia waschosen to be +. D (spherical equivalent). Teresults have also been shown in able . Te Fisher test ( =0.259) and OR demonstrated no statistically signicantdiffer-ence between the PACG group and the control group or thesubanalysis.

.. Risk Prediction. Figure shows the distribution o thespherical equivalent in both the control group and the patientgroup. On the -axis,the control subjects have beendisplayedat a value o and the PACG patients at a value o . Mostpatients had a high reractive error. However, almost all o the patients’ data overlapped those o the control subjects.Te risk prediction has been integrated in Figure , wherethe maximum o means a % chance o being a PACGpatient. Te curve is at and the maximum does not reachthe top. A clear cut-off value or a high chance o PACG couldnot be identied. Tis indicated that reractive error is not astrong predictor or PACG in this population.

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: Mean andstandard deviation (SD) o the variables reractive error spherical equivalent (SE) in dioptres (D), anterior chamber depth(ACD) in millimetres (mm), axial length (AL) in mm, and mean o values in diopters. Differences were tested with the Mann-Whitney test (MWU). Results < 0.05 were assumed to be signicant.

Patient ( = 117) Controls ( = 234)MWU Logistic regression

Mean SD Mean SD

SE . . . . = 0.068 = 0.766

ACD . . . . < 0.001 < 0.001

AL . . . . < 0.001 < 0.671

values . . . . = 0.607 = 0.819

Spherical equivalence

15,0010,005,000,00

P a t i e n t o r c o n t r o

l

120

110

100

90

80

70

60

50

40

30

20

10

0

−5,00−10,00−15,00−10

F : Distribution o spherical equivalent (in dioptres) amongpatients ( = 100) and controls eyes ( = 0). Te curve representsthe risk prediction o PACG based on spherical equivalent reractiveerror.

.. Other Biometrical Parameters. Te means and standarddeviations o all variables have been listed in able . TeMann-Whitney test was statistically signicant or ACD( < 0.001) and AL ( < 0.001). Te results or reractiveerror, however, also or the values, were not statistically signicant ( = 0.068; = 0.607). When we evaluated withlogistic regression, only ACD remained statistically signi-cant ( < 0.001).

4. Discussion

o our knowledge, the current studyis the rst to present dataabout risk actors o PACG in a European population. We setout with the assumption that hyperopia would be a strongrisk actor or PACG. However, the results demonstratedotherwise. Hyperopia was not statistically signicantly moreprevalent in the PACG group than in the control group. In thesubanalysis, in which a higher hyperopiawas investigated, theresults also did not reach statistical signicance. Te rerac-tive error turned out to be not a valuable predictor or PACG.Even i a person had a spherical equivalent o + dioptres—an extremely high reraction—the risk o PACG was only %. In our population, the overall prevalence o PACG was

%, whereas in the normal population, the prevalence o PACG is approximately .% []. Tereore, we can concludethat the risk prediction based on reractive error is o no valuein a clinical setting.

A study dating back to stated that there is a relationbetween PACG and hyperopia []. In the patients that theauthors examined, both eyes were included in the study with-

out statistically adjusting or any intereye correlation, thereby probably introducing a selection bias. Tey stated that theresults were highly signicant. However, there was an overlaprom individual eyes between the PACG group and the groupo control subjects. Moreover, the characteristics o the con-trol group were not described. Tereore, the validity o thestudy may be questionable.

Since then, several studies on PACG and reractive errorhave been perormed in Asian countries. A relationshipbetween PACG and hyperopia was ound in a study done inan Indian urban area []. However, the same authors oundcontrary results in a research project that was perormed twoyears later in a rural area in India []. Neither the Andhra

Pradesh study nor the Namil study demonstrated a statisti-cally signicant relationship between PACG and hyperopia[, ]. It had been suggested by the authors that this was dueto nuclear cataract, which would have been responsible or anincrease in myopia and a decrease in hyperopia. Tis argu-ment does not apply to our study, since our control groupconsisted o cataract patients. A difference between the meth-odso thementioned studies and ourstudy is that we matchedthe control subjects by ageand gender, thereby controlling orpotentially relevant conounding actors.

Te Beijing study ound a relation between hyperopia andanterior chamber angle, suggesting that hyperopia is a pre-dominant risk actoror PACG []. Ithas beensuggested that

the role o hyperopia is important or PACG because hyper-opic eyes tend to have a larger lens/axial length actor (LAF)[], and larger LAFis associated with PACG [].In our pop-ulation, most o the PACG patients were hyperopic (able ).Te reason why no signicant difference between the twogroups was ound is that hyperopia was similarly prevalent inthe control group as well. Tough hyperopia may be involvedin the pathogenesis o PACG, it cannot be accounted as a risk actor.

AL and ACD were the only variables that were signi-cantly different in the two groups. ACD remained signicantin the logistic regression, which means that out o the evalu-ated parameters, ACD is the most predicting actoror PACG.

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Tese results, obtained in a Caucasian population, corre-spond with the results o other studies [–, , ].

.. Limitations. Te current study has several limitations.Te control subjects all had cataract, which may affect thereractive error, typically introducing a myopic shif, notably

in nuclear cataract. Tereore, any myopic shif in our controlgroup would have yielded a relativeincrease o the proportiono hyperopes in the PACG group. Nonetheless, no statistically signicant relation between hyperopia and PACG was ound.Hence, the results might be even less signicant i our PACGgroup had been compared to healthy control subjects withoutcataract. Obviously, a prospective study in which healthy controls had been recruited would have been designed better.Te advantage o the current study design, though, was thatthe biometric data o probably healthy eyes (except or theircataract) were readily available. A drawback o our methodswas that the control subjects were not tested or PACG withgonioscopy. However, since the prevalence o PACG in the

general population is estimated to be low, and probably sim-ilar to that in our control group, we assumed that this wouldnot have signicantly impacted on our results.

Te prevalence o hyperopia was higher in the PACGgroup than in the control group. Te difference between thegroups was not statistically signicant. With a bigger samplesize, smaller differences might have been detected. However,the clinical signicance o detecting such a slight difference inreractive error is debatable.

Te PACG patients had been treated with an LPI, whichgenerally causes the angle to open. None o our outcomeparameters, including the ACD, is affected by this treatment[]. For our measurements, we used the IOL Master, the

Lenstar, and the autoreractor. Several studies have investi-gated how well these instruments compare [–]. It turnedout that the AL and values are interchangeable, although theACD is signicantly different. Because the condence inter-

vals exceeded the difference, no adjustments had been madeo the results. Te primary objective o this study was rerac-tive. I the ocus o a uture study is on ACD, only one type o measurement device should be used better.

5. Conclusion

Although it is commonly believed that hyperopia is a risk ac-

toror PACG, we ound no such evidence in the current study.ACD was the only statistically signicant risk actor thatcould be identied. AL turned out to be a statistically weakerrisk actor than ACD. Since PACG is an underestimated dis-ease in Europe and preventive measures are relatively easy toperorm, clinicians should be aware that nonhyperopic eyesalso run the risk o angle closure. Tis risk calls or gonios-copy in all eyes, regardless o any reractive error. In addition,more research into hyperopia is needed.

Conflict of Interests

Te authors declare that they have no conict o interests.

Acknowledgments

Tis study was supported by the Rotterdam OphthalmicInstitute, Te Netherlands. Te authors o this paper grate-ully thank the patients that participated in the study andthe members o the Rotterdam Ophthalmic Institute or theirinvolvement in the research project. In particular, they wouldlike to thank R. Wubbels, A. Sicam, N. J. Reus, and . Sarneckior their support. Te authors thank proessor in Aung orhis critical review o the paper.

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