risk factors for steroid response among cataract patients

8/9/2019 Risk factors for steroid response among cataract patients

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Risk factors for steroid responseamong cataract patients

David F. Chang, MD, Jeffrey J. Tan, BS, Yorghos Tripodis, PhD

PURPOSE: To evaluate the age and ocular axial length (AL) of topical steroid responders afteruneventful cataract surgery.

SETTING: Private practice, Los Altos, California, USA.

DESIGN: Case-control study.

METHODS: This retrospective chart review comprised consecutive patients from a single-surgeonpractice who had cataract surgery during a 2-year period. All patients routinely received topicalprednisolone acetate 1.0% postoperatively. In addition to AL and patient age, the intraocularpressure (IOP) was recorded preoperatively, 1 day postoperatively, and at least 1 additional time

in the first postoperative month while the patient was taking a topical corticosteroid agent. Asteroid response was defined as an IOP increase greater than 25% while on topical prednisolone(minimum 28 mm Hg) followed by a decrease of more than 25% after topical prednisolone wasdiscontinued. The age and AL were compared between steroid responders with nonresponders.

RESULTS: Of the 1642 patients, 39 were diagnosed as steroid responders. Younger age and a longerAL were associated with a higher risk for steroid response, particularly in patients younger than65 years with an AL of at least 29.0 mm. These patients had a 39-fold increased risk for an IOPhigher than 28 mm Hg and a 35-fold increased risk for an IOP higher than 35 mm Hg than patientsolder than 65 years with a normal AL.

CONCLUSION: Younger patients with high myopia had a higher risk for a postoperative steroidresponse after uneventful cataract surgery and may require more frequent IOP monitoring or

alternative topical antiinflammatory medications.Financial Disclosure: No author has a financial or proprietary interest in any material or methodmentioned.

J Cataract Refract Surg 2011; 37:675–681 Q 2011 ASCRS and ESCRS

Supplemental material available at www.jcrsjournal.org.

Topical corticosteroid agents are routinely prescribedafter most intraocular surgical procedures, and these

patients should have their intraocular pressure (IOP)periodically monitored during this period. Clinically,a topical steroid response is most likely to be associ-ated with a history of glaucoma, ocular hypertension,or a previous steroid-induced IOP spike.1,2 Identifyingother significant risk factors might forewarn ophthal-mologists to use closer postoperative surveillance oralternative antiinflammatory medications for these in-dividuals. In this retrospective single-practice study,we sought to evaluate 2 potential quantifiable riskfactorsdage and axial length (AL)dfor a clinicallysignificant IOP response in patients taking topical

corticosteroid agents after uneventful cataract surgery.

PATIENTS AND METHODS

This retrospective chart review comprised consecutive pa-

tients who hadcataract surgery during the 2007 and2008 cal-endar years at a single ophthalmology practice in Los Altos,California, USA. An institutional review board (IRB Co.,Inc.) approved retrospective chart review of the studypopulation.

The same experienced surgeon (D.F.C.) performed all op-erations. Patient age, AL, and IOP measured by applanation tonometry were recorded for each patient preoperatively.Axial length was determined using partial coherence inter-ferometry (IOLMaster, Carl Zeiss Meditec AG). Patients on topical glaucoma therapy continued to take the same medi-cations during the perioperative period. After pupil dilation with topical phenylephrine 2.5%–tropicamide 1.0% or cyclo-pentolate 1.0%, cataract surgery was routinely performedusing topical anesthesia, intracameral lidocaine 1.0%,

Q 2011 ASCRS and ESCRS

Published by Elsevier Inc.

0886-3350/$ - see front matter 675doi:10.1016/j.jcrs.2010.10.051

ARTICLE

http://www.jcrsjournal.org/http://dx.doi.org/10.1016/j.jcrs.2010.10.051http://dx.doi.org/10.1016/j.jcrs.2010.10.051http://www.jcrsjournal.org/


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a temporal clear corneal incision, capsulorhexis, phacoemul-sification, and foldable intraocular lens implantation.Regional injection anesthesia was rarely used, and no patientrequired general anesthesia.

Starting immediately after surgery, all patients receivedtopical prednisolone acetate 1.0% 3 times daily for 2 weeks,after which the frequency was reduced to twice daily for

an additional 2 to 3 weeks. However, if the patient wasa known steroid responder or was diagnosed with a steroidresponse in the first operative eye, topical prednisolone 1.0%was used for less than 1 week in the second eye or was notused at all. Topical loteprednol etabonate was not prescribedin any case. A topical fluoroquinolone antibiotic agent andnonsteroidal antiinflammatory drugs (NSAIDs) were alsoroutinely prescribed postoperatively. A standard printedhandout explaining the topical medication dosing instruc-tions was provided to every patient postoperatively.

Applanation tonometry in the operative eye was per-formed at every postoperative visit, beginning on the dayafter surgery. Because of transportation issues, several pa-tients were examined on the afternoon of surgery instead

of on the following morning. At least 1 additional visit wasperformed between 2 weeks and 4 weeks postoperatively,at which time applanation tonometry was repeated.

In this study, patients were classified as steroidresponders based on the following criteria: IOP elevation of at least 25% while on topical prednisolone to a minimumof 28 mm Hg, followed by an IOP drop of at least 25% when topical prednisolone was discontinued. Any IOP elevation during the first 72 hours was not counted. Eyes with intraoperative complications such as hyphema, posteriorcapsule rupture, or vitreous loss or postoperative complica-tions such as endophthalmitis or toxic anterior segmentsyndrome were excluded from the analysis. Patients whodid not use topical steroids postoperatively or who usedthem for less than 1 week were also excluded. Patients

with eyes that received topical steroids and did not meetthe steroid-responder criteria were considered nonre-sponders. Nonresponder patients who had bilateral proce-dures were recorded once by taking only the eye with thelonger AL. In all steroid responders, the topical steroid wasdiscontinued at the time of diagnosis during the first postop-erative month and serial follow-up examinations were doneuntil a safe IOP level was reached.

Statistical Analysis

A logistic regression model was developed to evaluate theinfluence of each continuous variable (age or AL) on steroidresponsiveness. Steroid responders were arbitrarily

stratified according to 3 age and 4 AL subgroups to easethe analysis. The relationship of both variables to the occur-rence of a steroid response was tested with the chi-squaretest. Odds ratios (ORs) and 95% confidence interval (CI) es-timations were calculated as a result of the logistic regression model. All statistical tests were performed using the SASprogram (SAS Institute, Inc.), with a probability of less

than 5% (P!.05) being deemed statistically significant.

RESULTS

The chart review comprised 1642 patients. One patientwith a postoperative IOP elevation to 37 mm Hg wasexcluded because of mild hyphema associated with posterior capsule rupture and anterior vitrectomy.Theanalysis excluded an additional 28 patients whore-ceived topical steroids for less than 1 week or not at allbecause of relative contraindications to topical ste-roids, such as a known history of steroid response or

a history of herpetic keratitis. Of the remaining studypopulation (1613 patients), 39 patients (2.4%) met thecriteria for being steroid responders. The diagnosiswas usually based on a single elevated IOP reading,at which point the topical steroid was discontinued.The remaining 1574 patients were classified as nonre-sponders.Six of the 39steroid responders hada diagno-sis of open-angle glaucoma and were taking topicalglaucoma mediations at the time of surgery. Three of the glaucoma patients had an AL of more than 26.0 mm and were between the ages of 48 years and68 years; the other 3 patients were 80 to 84 years old,

and all had an AL of less than 24.0 mm. An additional6 steroid responders were prescribed temporary glau-coma topical medication to control IOP.

The mean age of steroid responders was 61.3 yearsG 11.8 (SD) (range 38 to 84 years) and of the nonre-sponders, 71.8 G 11.7 years (range 15 to 94 years).The mean AL was 25.59 G 3.00 mm (range 22.82 to34.94 mm) and 24.33 G 1.75 mm (range 19.34 to40.16 mm), respectively. The differences in age andAL between the 2 groups were statistically significant(both P!.01, unpaired t test). Figure 1 shows the dis-tribution of age and Figure 2, of AL.

Bivariate analysis using contingency tables and theFisher exact test showed that age and AL were statisti-cally significant variables (Table 1). There was a trendtoward decreasing occurrence of steroid responderswith increasing age. For example, 11 patients (9.5%)in the 40 to 54 year age group had a steroid responsecompared with 15 patients (1.2%) who were 65 yearsor older. There was an opposite relationship for AL;7 eyes (21.9%) with an AL of at least 29.0 mmhad a ste-roid response compared with 12 eyes (1.0%) with an AL shorter than 25.0 mm.

When the 2 continuous variables were entered into

a multiple logistic regression model, they were found

Submitted: August 29, 2010.Final revision submitted: October 13, 2010.Accepted: October 28, 2010.

From a private practice (Chang), Los Altos, California, and BostonUniversity School of Medicine (Tan), and the Department ofBiostatistics Boston University School of Public Health (Tripodis),Boston, Massachusetts, USA.

Corresponding author: David F. Chang, MD, 762 Altos Oaks Drive,Suite 1, Los Altos, California 94024, USA. E-mail: [email protected].

676 RISK FACTORS FOR STEROID-RESPONSE IN CATARACT PATIENTS

J CATARACT REFRACT SURG - VOL 37, APRIL 2011

mailto:[email protected]:[email protected]:[email protected]:[email protected]


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significant. The parameter estimates, OR, and 95% CIsconfirmed the inverse relationship of age and thedirect relationship of AL with the occurrence of a ste-

roid IOP response (Table A, available at http:// jcrsjournal.org). For example, for a 1-year increase in age, the odds of being a steroid responder decreasedby about 5%, while for a 1.0 mm increase in AL, theodds of a steroid IOP response increased by morethan 38%.

Table 2 shows a cross comparison of the 3 age and 4AL groups and tabulates the cumulative percentagesof eyes of steroid responders in these groups. Longereyes in the 40- to 54-year age group had the highestprevalence of steroid IOP response, with rates risingfrom 14% of eyes (n Z 9) with an AL longer than

25.0 mm to 17% of eyes (n Z

6) with an AL longerthan 27.0 mm and to 36% of eyes (n Z 5) with an ALlonger than 29.0 mm. In contrast, less than 1%(n Z 7) of the cases older than 64 years old and with an AL shorter than 25.0 mm developed a steroid IOPresponse.

Table 3 shows the odds of an IOP spike at the meansof each group relative to the odds at the means of

a reference group. The reference comprised eyes with an AL shorter than 25.0 mm and of patients olderthan 65 years. An eye with characteristics equal to

the means of the 40 to 54 years/over 29.0 mm ALgroup was over 46 times more likely to show an IOPspike than an eye at the means in the reference group.Based on the results of the logistic regression model,Table B (available at http://jcrsjournal.org) showsthe 95% CIs for the predicted probabilities of occur-rence of IOP spike for the mean value of age and ALin each age/AL group, as shown in Table C (availableat http://jcrsjournal.org). These values confirm thatthe youngest patients with the longest axial lengthshad the highest predicted probability of steroid IOPresponse (95% CI, 16.35%-45.71%).

Table 4 shows a comparable analysis for the sub-group of patients with the highest IOP responses;that is, the severe steroid responders in whom IOPspiked to at least 35 mm Hg. Because of the smallersize of this group, the age groups below 65 yearswere combined. For the severe steroid responder pop-ulation, the logistic regression was rerun and the ORrecalculated in each group at the mean values of ageand AL. For every AL subgroup, the steroid responderincidence and ORs were similar, whether the IOPthreshold was set at 28 mm Hg or at 35 mm Hg.

Table 5 shows the ORs for the continuous variables

(age and AL) from the 2 logistic regressions. Thefirst column applies to all steroid responders (IOPR28 mm Hg); the second applies to severe steroidresponders (IOP R35 mm Hg). The point estimatesare very close between the 2 groups. Partly as a resultof the smaller number of severe steroid responders, thestatistical significance of both parameters was slightlyreduced for the severe steroid responders.

DISCUSSION

Topical corticosteroid agents are used to treat and sup-

press inflammation postoperatively in most ocular

Figure 1. Comparative age distribution. Figure 2. Comparative AL distribution.

Table 1. Bivariate analysis of steroid responders in relation toage and axial length (AL).

Variable Steroid Responders, n (%) P Value*

Age group (y)

40–54 (n Z 116) 11 (9.5) !.0001

55–64 (n Z 278) 13 (4.7) d

R65 (n Z 1219) 15 (1.2) d

AL group (mm)

!25.0 (n Z 1158) 12 (1.0) !.0001

25.0–26.99 (n Z 334) 14 (4.2) d

27.0–28.99 (n Z 89) 6 (6.7) d

R29.0 (n Z 32) 7 (21.9) d

Al Z axial length

*Fisher exact test

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surgical patients. Considering that this includes cata-ract surgery, the single most commonly performedoperation in medicine, large global populations areannually exposed to the risk for a topical steroid re-sponse. Although the IOP rise is generally reversibleand treatable and is usually well tolerated, the eleva-

tions may be sufficiently high and prolonged to causeocular morbidity.

Detecting possible steroid-induced IOP elevation isan important reason for postoperative examinationsafter any intraocular surgical procedure. Aside frompatients with known glaucoma or ocular hyperten-sion, however, there are no other clear-cut risk factorsdefining which individuals are at greatest risk fora clinically significant topical steroid response.1,2 Ourstudy found that in a cataract surgical population, pa-tients with axial myopia had the highest risk, particu-larly those in the younger age range.

In the literature, the criteria for steroid responsive-ness vary widely between studies. To differentiatemild and inconsequential IOP changes from thosethat are more clinically worrisome in a postsurgicalpopulation, we arbitrarily defined a steroid IOP re-sponse as being an elevation to at least 28 mm Hg.This excluded patients who would have been

classified as steroid responders in other studies. How-ever, we believe that at this IOP level, many clinicianswould be concerned enough to stop the topical cortico-steroid, prescribe a topical IOP-lowering medication,or increase the frequency of follow-up visits. Tomore conclusively implicate the corticosteroid as the

cause, our criteria further required a minimum 25%rise (from the preoperative baseline) and fall (fromthe highest postoperative measurement) in IOP associ-ated with the commencement and cessation of topicalsteroid treatment. Furthermore, any IOP elevation during the first 72 hours was not counted because of the multifactorial etiology of immediate postsurgicalIOP spikes.

This study considered steroid responders as patientsrather than as individual eyes. This assumes that ste-roid responsiveness in 1 eye would translate to theother eye. Recording only 1 eye per patient minimized

the skewing of our statistical analysis caused by non-responders who had surgery in both eyes. This studydid not separately evaluate glaucoma history asa risk factor. Although glaucoma is a known risk factorfor a steroid response,3–5 the study surgeon routinelyprescribed topical prednisolone acetate for glaucomaor glaucoma-suspect patients with the expectation

Table 2. Cumulative percentages of steroid responders by age and AL.

Age (Y)

Number (%)

AL!25.0 mm AL R25.0 mm AL R27.0 mm AL R29.0 mm All Events

40–54 2/53 (3.8) 9/63 (14.3) 6/35 (17.1) 5/14 (35.7) 11/116 (9.5)

55–64 3/150 (2.0) 10/128 (7.8) 3/49 (6.1) 1/11 (9.1) 13/278 (4.7)

R65 7/955 (0.7) 8/264 (3.0) 4/39 (10.3) 1/7 (14.3) 15/1219 (1.2)

All events 12/1158 (1.0) 27/455 (5.9) 13/123 (10.6) 7/32 (21.9) 39/1613 (2.4)

AL Z axial length

Table 3. Cross tabulation of 39 steroid responders (IOPR28 mm Hg) by age and AL groups along with odds ratios relative to the referencegroup (age group R65 yrs and AL group !25.0 mm).

Age (Y) AL !25.0 mm AL 25.0–26.99 mm AL 27.0–28.99 mm AL R29.0 mm

40–54Number* (%) 2/53 (3.8) 3/30 (10.0) 1/19 (5.3) 5/14 (35.7)

Odds ratio 4.1 7.9 15.8 46.1

55–64

Number* (%) 3/150 (2.0) 7/79 (8.9) 2/38 (5.3) 1/11 (9.1)

Odds ratio 2.5 5.2 9.7 31.8

R65

Number* (%) 7/955 (0.7)† 4/225 (1.8) 3/32 (9.4) 1/7 (14.3)

Odds ratio 1† 2.4 5.4 14.4

AL Z axial length

*For each combination of age and AL group, the numerator Z the number of steroid responders and the denominator Z the total number of eyes in the study

population meeting those age and AL criteria†Reference group

678 RISK FACTORS FOR STEROID-RESPONSE IN CATARACT PATIENTS



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that most would not have a significant IOP elevation.We therefore did not exclude patients with these diag-noses. Of note, 33 of our 39 steroid responder patientshad no preoperative history of glaucoma or ocular hy-pertension. We did exclude patients with intraopera-tive or postoperative complications that would beexpected to increase IOP independent of corticosteroid

use. Any IOP increase during the first 72 hours wasexcluded because of potential confounding effects of corneal edema or retained ophthalmic viscosurgicaldevice.

Using these criteria to arbitrarily define what wouldbe clinically significant, we discovered a clear trend to-ward topical steroid IOP responsiveness that was mostcommon in axial myopes and younger patients. Therewas an elevated risk with increasing AL and with decreasing age. For an AL of 29.0 mm or longer, rela-tive to our reference group (patients older than 65 yearswith AL!25.0 mm), there was a 14-, 32-, or 46-fold in-

crease in steroid response risk in the 65C year, 55- to64-year, and 40- to 54-year age groups, respectively.

In the youngest age group, a steroid response occurredin 14% of patients with an AL of more than 25.0 mm,17% of patients with an AL of more than 27.0 mm,and 36% of patients with an AL over 29.0 mm. Further-more, myopic patients younger than 65 years with an AL of at least 29.0 mm had a 35-fold increased risk fora steroid response exceeding 34 mm Hg. Seven pa-

tients had IOP elevations of at least 40 mm Hg (range40 to 68 mm Hg). All patients but 1 were younger than 65 years, and 4 of 7 had high myopia. Although the lit-erature describes the typical steroid response occur-ring after several weeks of topical therapy, 6 of our 7severest responders were diagnosed between 5 daysand 14 days postoperatively, suggesting that youngerpatients with myopia may need to be checked sooner.

The expanding use of intravitreal triamcinolone ace-tonide therapy has led to numerous studies of the riskfactors for a steroid response in the population with vitreoretinal disease. Younger age was not a risk factor

in some studies6–

8 but was clearly associated with steroid responsiveness (defined as IOP O25 mm Hg)

Table 5. Odds ratios for the continuous variables age andAL from the logistic regression that defined a steroid responder as having an IOPof 28 mm Hg or greater and a severe steroid responder as having an IOP of 35 mm Hg or greater.

Variable

All Responders (R28 mm Hg) Severe Responders (R35 mm Hg)

Point Estimate P Value Point Estimate P Value

Age 0.95 .0031 0.95 .0654

AL 1.38 !.0001 1.36 .0040

AL Z axial length

Table 4. Cross tabulation of 15 severe steroid responders (IOP R35 mm Hg) by age and AL groups along with odds ratios relative to thereference group (age group R65 years and AL group !25.0 mm). Comparable data for all steroid responders (IOP R28 mm Hg) is alsoshown.

Group/Age (Y) !25.0 mm 25.0–26.99 mm 27.0-28.99 mm R29.0 mm

Severe steroid responders!65

Number* (%) 3/203 (1.5) 3/109 (2.8) 1/57 (1.8) 3/25 (12.0)

Odds ratio 2.8 5.6 10.6 34.5

R65

Number* (%) 3/955 (0.3)† 0/225 (0.0) 1/32 (3.1) 1/7 (14.3)

Odds ratio 1† – 5.0 12.7

All steroid responders

!65

Number* (%) 5/203 (2.5) 10/109 (9.2) 3/57 (5.3) 6/25 (24.0)

Odds ratio 2.8 5.7 11.3 38.9

R65

Number* (%) 7/955 (0.7)† 4/225 (1.8) 3/32 (9.4) 1/7 (14.3)

Odds ratio 1† 2.4 5.4 14.4

AL Z axial length

*For each combination of age and AL group, the numerator Z the number of steroid responders and the denominator Z the total number of eyes in the study

population meeting both criteria†Reference group




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First author:David F. Chang, MD

Private practice, Los Altos,California, USA


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risk factors for steroid response among cataract patients

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