Glaucoma-Related Adverse Events in the Infant Aphakia Treatment Study 1-Year Results

CLINICAL SCIENCES

ONLINE FIRST Glaucoma-Related Adverse Events in the Infant Aphakia Treatment Study 1-Year Results

Allen D. Beck, MD; Sharon F. Freedman, MD; Michael J. Lynn, MS; Erick Bothun, MD; Daniel E. Neely, MD; Scott R. Lambert, MD; for the Infant Aphakia Treatment Study Group

Objectives: To report the incidence of glaucoma and glau- sistent fetal vasculature and 1.6 times higher for each coma suspects in the IATS, and to evaluate risk factors for month of age younger at cataract surgery. the development of a glaucoma-related adverse event in patients in the IATS in the first year of follow-up. Conclusions: Modern surgical techniques do not eliminate the early development of glaucoma following con- Methods: A total of 114 infants between 1 and 6 months genital cataract surgery with or without an intraocular of age with a unilateral congenital cataract were as- lens implant. Younger patients with or without persis- signed to undergo cataract surgery either with or with- tent fetal vasculature seem more likely to develop a glau- out an intraocular lens implant. Standardized defini- coma-related adverse event in the first year of follow- tions of glaucoma and glaucoma suspect were created and up. Vigilance for the early development of glaucoma is used in the IATS. needed following congenital cataract surgery, especially when surgery is performed during early infancy or for a Results: Of these 114 patients, 10 (9%) developed glau- child with persistent fetal vasculature. Five-year fol- coma and 4 (4%) had glaucoma suspect, for a total of 14 low-up data for the IATS will likely reveal more glaucoma- patients (12%) with a glaucoma-related adverse event in related adverse events. the treated eye through the first year of follow-up. Of the 57patients who underwent lensectomy and anterior vi- Trial Registration: clinicaltrials.gov Identifier: trectomy, 5 (9%) developed a glaucoma-related adverse NCT00212134 event; of the 57 patients who underwent an intraocular lens implant, 9 (16%) developed a glaucoma-related ad- Arch Ophthalmol. 2012;130(3):300-305. verse event. The odds of developing a glaucoma-related Published online November 14, 2011. adverse event were 3.1 times higher for a child with per- doi:10.1001/archophthalmol.2011.347

LAUCOMA IS AN IMPOR- tomy performed at the time of cataract sur- tant complication of pe- gery.2-10 Cataract surgery in the first year Author Affiliations: Emory Eye diatric cataract surgery, of life and a small corneal diameter have Center (Dr Beck) and with a wide range of re- been the most consistent risk factors for Department of Ophthalmology, ported frequencies of oc- glaucoma development in reported stud- School of Medicine (Drs Beck currence, depending on the definition used ies.3,5-10 The effect of the placement of an and Lambert), and Department G 1-3 and the length of follow-up. Two large, intraocular lens (IOL) at the time of cata- of Biostatistics and 4,5 Bioinformatics, Rollins School retrospective series reported a 15% to ract surgery on the risk of developing glau- of Public Health (Mr Lynn), 21% frequency of glaucoma being diag- coma is unknown, although one retro- 11 Emory University, Atlanta, nosed 5 years after cataract surgery. Nu- spective review suggested a decreased Georgia; Duke Eye Center, merous risk factors for the development incidence of glaucoma in patients who re- Durham, North Carolina of glaucoma have been noted, including ceived an IOL. However, the eyes that re- (Dr Freedman); Departments of cataract surgery in the first year of life, ceived an IOL in that report11 were older Ophthalmology and Pediatrics, at the time of surgery (mean age, 5.1 years University of Minnesota, for pseudophakia vs 2.7 years for apha- Minneapolis (Dr Bothun); and See also page 293 kia), and children with corneal diam- Department of Ophthalmology, eters less than or equal to 10 mm were ex- Indiana University, Indianapolis postoperative complications such as sec- 9,10 (Dr Neely). cluded from analysis. Other studies have Group Information: The ondary membrane surgery, small corneal noted similar rates of glaucoma in apha- members of the Infant Aphakia diameters, type of cataract, a family his- kic and pseudophakic children who had Treatment Study Group (IATS) tory of aphakic glaucoma, and primary cataract surgery performed in the first year are listed on page 304. posterior capsulotomy/anterior vitrec- of life.

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©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 The Infant Aphakia Treatment Study (IATS) is a mul- and/or axial length, (3) increased optic nerve cupping defined ticenter, randomized, controlled clinical trial sponsored as an increase of 0.2 or more in the cup-to-disc ratio, or (4) by the National Eye Institute. The objective of the study the use of a surgical procedure for IOP control. A patient was is to compare the use of primary IOL implantation to sur- designated as a glaucoma suspect if he or she had 2 consecu- gery without IOL implantation in infants with a unilat- tive IOP readings above 21 mm Hg on different dates after topi- cal corticosteroids had been discontinued without any of the eral congenital cataract removed between 1 and 6 months anatomical changes listed above or if he or she had received of age. The results of the IATS during the first year after glaucoma medication to control IOP without any of the ana- cataract surgery (including visual acuities, number of ad- tomical changes listed above. verse events, and number of additional surgery) have been 12 previously reported. In our study, we report the devel- ASSESSMENT OF IOP, OCULAR DIMENSIONS, opment of glaucoma-related adverse events in IATS pa- AND OPTIC NERVE tients through 1 year of follow-up. The investigator could perform tonometry with a Tono-Pen (Rei- METHODS chert, Depew, New York), a handheld Goldmann applanation tonometer, or a pneumatonometer. A protocol assessment of The study design, surgical technique, follow-up schedule, patch- IOP was performed at the initial examination of the patient un- ing and optical correction regimens, evaluation methods, and der anesthesia (ie, immediately after the induction of anesthe- patient characteristics at baseline have been previously re- sia prior to randomization and surgery) and at an examination ported in detail13 and are therefore only briefly summarized in of the patient under anesthesia at 1 year of age. All other IOP this report. Our study was approved by the institutional re- measurements were performed at the discretion of the princi- view boards of all the participating institutions and was in com- pal investigator. Corneal diameters (measured using cali- pliance with the Health Insurance Portability and Accountabil- pers), axial length assessment (A-scan biometry using immer- ity Act. The off-label research use of the Acrysof SN60AT and sion or applanation techniques), and indirect ophthalmoscopy MA60AC IOLs (Alcon Laboratories, Fort Worth, Texas) was of the optic nerve were also part of the protocol assessment dur- covered by US Food and Drug Administration investigational ing examination of the patient under anesthesia prior to ran- device exemption G020021. domization and at 1 year of age.

STUDY DESIGN STATISTICAL CONSIDERATIONS

The main inclusion criteria were a visually significant congen- Statistical comparisons were made between patients with and pa- ital cataract (Ն3 mm central opacity) in 1 eye and an age range tients without a glaucoma-related adverse event by using the of 28 days to less than 210 days at the time of cataract surgery. Fisher exact test for percentages, the independent groups t test Patients with a unilateral cataract due to persistent fetal vas- for means, and the Wilcoxon rank sum test for medians. The non- culature (PFV) were allowed in our study as long as the PFV parametric test was used for factors that were highly skewed (age was not associated with visible stretching of the ciliary pro- at surgery and visual acuity at 1 year of age). The exact bino- cesses or with involvement of the retina or optic nerve as de- mial method was used to compute the 95% CI for a proportion, termined by the treating IATS investigator. The other main ex- and the normal approximation was used to compute the 95% clusion criteria were an acquired cataract, a corneal diameter CI for the difference between 2 proportions. Stepwise logistic re- of less than 9 mm, and prematurity (Ͻ36 gestational weeks). gression was used to assess the relationship between the devel- Patients were randomly assigned to have either an IOL placed opment of glaucoma and a selected set of patient characteris- at the time of the initial surgery (with spectacle correction) or tics: age at surgery, diagnosis of PFV, and corneal diameter. A ␹2 to be left aphakic (with contact lens correction). Patients were significance level of .10 was set for the Wald statistic for in- examined at 1 day, 1 week, and 1, 3, 6, 9, and 12 months after cluding and retaining independent variables in the logistic re- surgery. Grating visual acuity was measured at 1 year of age gression model, and 90% CIs were calculated for the odds ra- Ͻ (±2 months) by a traveling examiner using Teller Acuity Cards tios. For all other analyses, a P .05 was considered statistically (Stereo Optical, Chicago, Illinois). significant, and 95% CIs were computed. No adjustment was made for multiple testing. Given that relatively few of the patients in our study developed glaucoma or were suspected of having glau- SURGICAL TECHNIQUE coma, the statistical power of our study is limited. Patients randomly assigned to the contact lens group underwent a lensectomy and anterior vitrectomy. Patients ran- RESULTS domly assigned to the IOL group had the lens contents aspi- rated followed by the implantation of an AcrySof SN60AT IOL DEVELOPMENT OF GLAUCOMA into the capsular bag. In the event that both haptics could not be implanted into the capsular bag, an AcrySof MA60AC IOL There were 114 patients enrolled in our study. During was implanted into the ciliary sulcus. Following IOL placement, a posterior capsulectomy and an anterior vitrectomy were the first year after cataract surgery, 10 patients (9%) de- performed through the pars plana/plicata. veloped glaucoma, and 4 patients (4%) had glaucoma suspect, for a total of 14 patients (12%) with a glaucoma- DEFINITIONS FOR ADVERSE EVENTS related adverse event in the treated eye (Table 1). There were 57 patients randomly assigned to each treatment Glaucoma was defined as intraocular pressure (IOP) greater than group (57 to the contact lens group and 57 to the IOL 21 mm Hg with one or more of the following anatomical changes: group). Glaucoma developed in 3 patients (5%) in the (1) corneal enlargement, (2) asymmetrical progressive my- contact lens group and in 7 patients (12%) in the IOL opic shift coupled with enlargement of the corneal diameter group (P=.32, with a 95% CI for the difference between

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©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 suspect status. An alpha level of .10 was set for a patient Table 1. Development of Glaucoma and Glaucoma Suspect characteristic to be included in the model. Persistent fe- Status During the First Year After Cataract Surgery tal vasculature was the first patient characteristic en-

a tered, followed by age. With PFV and age in the model, No. (% [95% CI ]) of Patients corneal diameter did not meet the entry criteria for in- CL Group IOL Group Total clusion in the model, which was not unexpected given Classification (n=57) (n=57) (n=114) the correlation between age and corneal diameter. As es- Glaucoma 3 (5 [1-15]) 7 (12 [5-24]) 10 (9 [4-16]) timated from the model and after adjusting for age, we Glaucoma 2 (4 [0.4-12]) 2 (4 [0.4-12]) 4 (4 [1-9]) found that the odds of developing a glaucoma-related ad- suspect verse event were 3.1 (90% CI, 1.2-8.6) times higher for Total 5 (9 [3-19]) 9 (16 [7-28]) 14 (12 [7-20]) a patient with PFV than for a patient without this diagnosis (P=.06). Also, after adjusting for PFV, we found Abbreviations: CL, contact lens (in this group, the eyes were left aphakic after primary cataract removal); IOL, intraocular lens (in this group, the eyes that the odds of developing a glaucoma-related adverse underwent a primary intraocular lens implant at the time of cataract removal). event were 1.6 (90% CI, 1.0-2.6) times higher for a pa- aThe 95% CIs (for the percentage of patients) were included to show the tient 1 month younger than another patient (P=.08). The level of uncertainty in the estimates. Hossmer-Lemmeshow test did not suggest a significant lack of fit for the model (P=.31). The relationship be- the groups of −3% to 17%). Two patients (4%) in the con- tween age, PFV, and the development of a glaucoma- tact lens group and 2 patients (4%) in the IOL group were related adverse event is demonstrated in Table 3. in the glaucoma suspect category. Combining glaucoma and glaucoma suspect, 5 patients (9%) in the contact lens INFLUENCE OF IOL PLACEMENT group and 9 patients (16%) in the IOL group developed a glaucoma-related adverse event (P=.39, with a 95% CI The rate of glaucoma or suspect status was 13% (7 of 52 for the difference between the groups of −5% to 19%). eyes) in patients who had the IOL placed in the capsular bag and 50% (2 of 4 eyes) in patients who had the IOL INFLUENCE OF PATIENT CHARACTERISTCS placed in the ciliary sulcus. This difference was not statistically significant (P=.12). Both of the eyes with a sul- We investigated the effect of age at surgery, corneal di- cus IOL and a glaucoma-related adverse event had PFV, ameter, a diagnosis of PFV, preoperative IOP, and addi- and one of these patients was enrolled in our study de- tional surgery performed after cataract surgery on the de- spite having met the exclusion criteria for PFV (stretch- velopment of a glaucoma-related adverse event. The median ing of the ciliary processes).12 The exclusion of this case age at surgery among patients in our study was 1.8 months with the protocol violation would leave 1 of 3 eyes (33%) (interquartile range, 1.2-3.2 months). The mean (SD) cor- with sulcus IOL placement and a glaucoma-related ad- neal diameter of the treated eyes was 10.5 (0.7) mm. A verse event (P=.38). diagnosis of PFV was made by the treating IATS investigator for 25 patients (22%).12 Patients who developed a TYPE OF GLAUCOMA AND TREATMENT glaucoma-related adverse event tended to be younger at surgery than those who did not (median age, 1.2 vs 2.2 Although detailed gonioscopic information was not col- months; P=.02; Table 2). There was a trend toward a lected as part of the IATS, 9 of 10 eyes with glaucoma (90%) smaller corneal diameter among patients developing glau- were assumed to be open angle, whereas only 1 eye (10%) coma or glaucoma suspect compared with the other pa- was noted to have iris bombe and angle closure. tients (mean diameter, 10.1 vs 10.5 mm; P=.08; Table 2). Glaucoma surgical procedures were required to con- There was also a trend toward a higher percentage of pa- trol the glaucoma in 6 of 10 eyes (60%): 4 of 7 eyes (57%) tients with PFV among those who developed glaucoma or in the IOL group and 2 of 3 eyes (67%) in the contact glaucoma suspect compared with those without this di- lens group. Three of the eyes with open-angle glaucoma agnosis (43% vs 19%; P=.08; Table 2). Preoperative IOP, underwent a trabeculotomy (1 eye underwent a stan- intraoperative complications, and additional surgery af- dard trabeculotomy, and 2 eyes underwent a 360° tra- ter cataract extraction failed to demonstrate any relation- beculotomy), and 2 eyes underwent a Baerveldt glau- ship with a glaucoma-related adverse event (analyses not coma drainage implant. The eye with angle closure had shown). As expected, we found some associations among a pupillary membrane removed and underwent a periph- these 3 patient characteristics. Age and corneal diameter eral iridectomy. In 3 of 6 eyes (50%) with glaucoma that were moderately correlated (r=0.56, PϽ.001). Corneal required surgical intervention, the patients were treated diameter tended to be slightly smaller for patients diag- with glaucoma medication 1 year after cataract surgery. nosed with PFV than for other patients (mean diameter, The remaining 4 of the 10 eyes with glaucoma (40%) were 10.5 vs 10.3 mm; P=.17), although this difference was not treated with glaucoma medication alone. All 4 patients statistically significant. However, age at surgery did not who received a diagnosis of glaucoma suspect were treated appear to be associated with PFV because the median age with glaucoma medication. was 2.5 months for patients with PFV compared with 2.3 months for those not having this diagnosis (P=.61). GLAUCOMA AND VISUAL ACUITY A multivariable analysis using stepwise logistic regression was performed to relate age, corneal diameter, The median visual acuity at 1 year of age was 0.3 log- and PFV to the development of glaucoma or glaucoma MAR units (3 Snellen lines) worse for patients who de-

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©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 Table 2. Patient Characteristics vs Development of Glaucoma and Glaucoma Suspect Status During the First Year After Cataract Surgery

Glaucoma or Glaucoma Suspect?

No Yes Difference Between Patient Characteristica (n=100) (n=14) P Value the Groups, 95% CI Age, median (IQR), mo 2.2 (1.2-3.2) 1.2 (1.0-1.7) .02 0.1 to 1.5 Corneal diameter, mean (SD), mm 10.5 (0.7) 10.1 (0.8) .08 −0.1 to 0.9 Persistent fetal vasculature, No. (%) 19 (19) 6 (43) .08 −33% to 3%

Abbreviation: IQR, interquartile range. a Refers to characteristics at initial cataract surgery.

veloped glaucoma or suspected glaucoma during the first year after surgery (1.1 logMAR) vs those without this ad- Table 3. Development of Glaucoma and Glaucoma Suspect verse event (0.80 logMAR). This difference was not sta- Status According to Persistent Fetal Vasculature and Age tistically significant (P=.15). Development of Glaucoma PFV Status, No. of and Glaucoma Suspect, COMMENT Age, d Patients No. (% [95% CI]) No PFV Glaucoma developed in the operated eyes of 10 of 114 in- Յ48 37 5 (14 [5-29]) fants (9%) with unilateral cataract who were enrolled in Ն49 52 3 (6 [1-16]) the IATS through the first year of follow-up. More eyes PFV Յ developed glaucoma after primary IOL implantation (7 of 48 13 4 (31 [9-61]) Ն49 12 2 (17 [2-48]) 57 eyes [12%]) than after cataract removal without IOL (3 of 57 [5%]). This difference was not statistically sig- Abbreviation: PFV, persistent fetal vasculature. nificant, although the power of this calculation is low. Mul- tivariate regression analysis showed that, after we adjusted for age, the odds of developing a glaucoma-related modern surgical techniques do not eliminate the early de- adverse event were 3.1 times higher for a patient with PFV velopment of glaucoma, with 10 of 114 eyes (9%) from than for a patient without this diagnosis and that, after we the total group developing glaucoma by the 1-year fol- adjusted for PFV, the odds of developing a glaucoma- low-up visit. Most cases were assumed to be open angle, related adverse event were 1.6 times higher for a patient with a single case (1 of 10 eyes [10%]) of angle closure 1 month younger than another patient. Corneal diameter reported. was not statistically significant in multivariate analysis, pos- A retrospective study11 of older children has sug- sibly owing to the correlation of corneal diameter with age gested that the placement of an IOL reduces the inci- and the small range of corneal diameters in the IATS. dence of glaucoma following congenital cataract surgery. Modern lensectomy/vitrectomy surgical techniques for Two other studies9,10 of congenital cataract surgery with pediatric cataract surgery have reduced the number of early and without an IOL failed to demonstrate a difference in postoperative complications, such as pupillary block, that the incidence of glaucoma. Although the number of eyes can cause angle-closure glaucoma.2 However, a signifi- developing glaucoma by the 1-year follow-up in the IATS cant percentage of children who have undergone congen- suggested a higher incidence in the pseudophakic eyes than ital cataract surgery go on to develop glaucoma, usually in the aphakic eyes (12% vs 5%), this difference was not with predominantly open angles, and the onset of glau- statistically significant. Continuing follow-up in the IATS coma frequently occurs years after the cataract sur- for the development of glaucoma and glaucoma suspect gery.2,3,5,6 Numerous potential mechanisms for the devel- status is critical, given that the mean interval between cata- opment of glaucoma have been postulated, including ract surgery and diagnosis of glaucoma has been reported congenital angle anomalies, postoperative inflammation to range from 4.0 to 5.2 years.5-7 leading to angle dysfunction or progressive synechial clo- Many previous studies2,5-7 of glaucoma in aphakic and sure, corticosteroid-induced mechanisms, and some un- pseudophakic children have lacked a consistent defini- known effect of the aphakic state or the vitreous interac- tion of glaucoma and a standard protocol for surveil- tion with the developing angle structures leading to reduced lance of at-risk eyes. Glaucoma has frequently been de- outflow facility.2-11,14,15 An ultrasound biomicroscopy study16 fined by elevated IOP alone, without structural change of the anterior segment after congenital cataract surgery to the eye as part of the diagnostic criteria.2,5-7 The defi- has demonstrated a more anterior iris insertion with a nition for glaucoma in the IATS included criteria for struc- smaller angle opening distance and a flatter pars plicata, tural change (enlarged ocular dimensions or an in- compared with normal controls. Because the IATS was not creased cup-to-disc ratio). A standardized definition of designed as a study of the development of glaucoma fol- a glaucoma suspect was also created for the IATS. lowing congenital cataract surgery, limited information on Persistent fetal vasculature is believed to be a risk fac- the mechanisms of glaucoma can be ascertained from the tor for the development of glaucoma following congen- 1-year follow-up outcome data. It is clear, however, that ital cataract surgery because of the associated microph-

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Clinical Coordinating Center Scott R. Lambert, MD (study chair), and Lindreth DuBois, MEd, MMSc (national coordinator), Emory University, Atlanta Georgia. Data Coordinating Center Michael J. Lynn, MS (director), Betsy Bridgman, BS, Marianne Celano, PhD, Julia Cleveland, MSPH, George Cotsonis, MS, Carey Drews-Botsch, PhD, Nana Freret, MSN, Lu Lu, MS, Azhar Nizam, MS, Seegar Swanson, and Thandeka Tutu-Gxashe, MPH, Emory University. Visual Acuity Testing Center E. Eugenie Hartmann, PhD (director), Clara Edwards, Claudio Busettini, PhD, and Samuel Hayley, BS, University of Ala- bama, Birmingham. Steering Committee Scott R. Lambert, MD, Edward G. Buckley, MD, David A. Plager, MD, M. Edward Wilson, MD, Michael J. Lynn, MS, Lin- dreth DuBois, MEd, MMSc, Carolyn Drews-Botsch, PhD, E. Eugenie Hartmann, PhD, and Donald F. Everett, MA. Contact Lens Committee Buddy Russell, COMT, and Michael Ward, MMSc. Participating Clinical Centers Medical University of South Carolina, Charleston (14 patients enrolled): M. Edward Wilson, MD, and Margaret Bozic, CCRC, COA. Harvard University, Boston, Massachusetts (14 patients enrolled): Deborah K. VanderVeen, MD, Theresa A. Mansfield, RN, and Kathryn Bisceglia Miller, OD. University of Minnesota, Minneapolis (13 patients enrolled): Stephen P. Christiansen, MD, Erick Bothun, MD, Ann Holleschau, BA, Jason Jedlicka, OD, Patricia Winters, OD, and Jacob Lang, OD. Cleveland Clinic, Ohio (10 patients enrolled): Elias I. Traboulsi, MD, Susan Crowe, BS, COT, and Heather Hasley Cimino, OD. Baylor College of Medicine, Houston, Texas (10 patients enrolled): Kimberly G. Yen, MD, Maria Castanes, MPH, Alma Sanchez, COA, and Shirley York. Oregon Health and Science University, Portland (9 patients enrolled): David T. Wheeler, MD, Ann U. Stout, MD, Paula Rauch, OT, CRC, Kimberly Beaudet, CO, COMT, and Pam Berg, CO, COMT. Emory University, Atlanta, Georgia (9 patients enrolled): Scott R. Lambert, MD, Amy K. Hutchinson, MD, Lindreth DuBois, MEd, MMSc, Rachel Robb, MMSc, and Marla J. Shainberg, CO. Duke University, Durham, North Carolina (8 patients enrolled): Edward G. Buckley, MD, Sha- ron F. Freedman, MD, Lois Duncan, BS, B. W. Phillips, FCLSA, and John T. Petrowski, OD. Vanderbilt University, Nashville, Tennessee (8 patients enrolled): David Morrison, MD, Sandy Owings, COA, CCRP, Ron Biernacki, CO, COMT, and Chris- tine Franklin, COT. Indiana University, Indianapolis (7 patients enrolled): David A. Plager, MD, Daniel E. Neely, MD, Mi- chele Whitaker, COT, Donna Bates, COA, and Dana Donaldson, OD. Miami Children’s Hospital (6 patients enrolled): Stacey Kruger, MD, Charlotte Tibi, CO, and Susan Vega. University of Texas Southwestern, Dallas (6 patients enrolled): David R. Weakley, MD, David R. Stager Jr, MD, Joost Felius, PhD, Clare Dias, CO, Debra L. Sager, and Todd Brantley, OD. Data and Safety Monitoring Committee Robert Hardy, PhD (chair), Eileen Birch, PhD, Ken Cheng, MD, Richard Hertle, MD, Craig Kollman, PhD, Marshalyn Yeargin- Allsopp, MD (resigned), Cyd McDowell, and Donald F. Everett, MA. Medical Safety Monitor Allen D. Beck, MD.

thalmos and the possibility of anterior segment anomalies, patients with ocular hypertension, with thinner central but previous studies4,6 have failed to confirm this opin- corneal measurements noted to be a powerful predictor ion. The IATS provides evidence that PFV is likely a risk for the development of open-angle glaucoma.19 Various factor for the development of glaucoma. Younger age at correction factors for applanation IOP measurements surgery was also noted in the IATS to be a risk factor for based on CCT measurements have been proposed,20,21 but the development of a glaucoma-related adverse event, de- statistical analyses of these formulas have demonstrated spite the fact that cataract surgery was deferred until at that the effect of CCT on IOP was less than predicted, least 4 weeks of age based on previous studies17,18 sug- potentially leading to erroneous conclusions about “cor- gesting an increased risk of glaucoma if surgery is per- rected” IOP.22 Aphakic and pseudophakic children have formed in the first 4 weeks of life. Cataract surgery in significantly thicker corneas than age-matched con- the IATS was performed between 1 and 6.9 months of trols, and CCT has been noted to increase following cata- age, providing 2 nearly equal-sized cohorts aged 48 days ract surgery.23 Furthermore, eyes that developed glau- or younger and 49 days or older (Table 3). Further evalu- coma (based on optic nerve changes) had a thicker CCT ation of the visual outcomes in the IATS cohort may pro- and higher IOP than those that did not, which argues vide information as to the optimum timing of cataract against the concept that a thicker CCT in children leads surgery in the setting of unilateral cataract. to a lower risk of glaucoma, as in adult patients with ocu- Central corneal thickness (CCT) is a recently recog- lar hypertension.23 The measurement of CCT was not part nized risk factor for the development of glaucoma in adult of the study protocol in the IATS. Children noted to have

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©2012 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 elevated IOP without structural change were placed in EY013287 and, in part, by National Institutes of Health the glaucoma suspect category. Departmental Core grant EY06360 and Research to Pre- Treatment of children who develop glaucoma follow- vent Blindness, New York, New York. ing congenital cataract surgery frequently requires surgical intervention. Chen et al7 noted that surgical treatment was performed in 57.1% of 170 eyes with aphakic REFERENCES glaucoma, with medical therapy recommended for 92% of eyes. However, in another study24 of pediatric apha- 1. Parks MM. Visual results in aphakic children. Am J Ophthalmol. 1982;94(4):441- kic glaucoma, surgical interventions were performed in 449. 2. Simon JW, Mehta N, Simmons ST, Catalano RA, Lininger LL. Glaucoma after only 15 of 55 eyes (27%) that were likely representative pediatric lensectomy/vitrectomy. 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Secondary glaucoma after paediatric cata- noted to be successful in 57% of 14 eyes with a mean fol- ract surgery. Br J Ophthalmol. 2007;91(12):1627-1630. 7. Chen TC, Walton DS, Bhatia LS. Aphakic glaucoma after congenital cataract surgery. low-up of 4.7 years (some patients required more than Arch Ophthalmol. 2004;122(12):1819-1825. 1 angle surgery) and may decrease the need for filtering 8. Kuhli-Hattenbach C, Lu¨chtenberg M, Kohnen T, Hattenbach LO. Risk factors for or shunt procedures.25 complications after congenital cataract surgery without intraocular lens implan- Visual acuity in children who develop glaucoma fol- tation in the first 18 months of life. Am J Ophthalmol. 2008;146(1):1-7. 9. Trivedi RH, Wilson ME Jr, Golub RL. Incidence and risk factors for glaucoma lowing congenital cataract surgery may be limited by glau- after pediatric cataract surgery with and without intraocular lens implantation. comatous optic nerve damage, amblyopia, pupillary mem- J AAPOS. 2006;10(2):117-123. branes, corneal decompensation, or complications from 10. Wong IB, Sukthankar VD, Cortina-Borja M, Nischal KK. Incidence of early-onset glaucoma surgical intervention.7,24,25 In the IATS, eyes that glaucoma after infant cataract extraction with and without intraocular lens developed a glaucoma-related adverse event had a me- implantation. Br J Ophthalmol. 2009;93(9):1200-1203. 11. Asrani S, Freedman SF, Hasselblad V, et al. Does primary intraocular lens im- dian visual acuity that was 3 Snellen lines worse than those plantation prevent “aphakic” glaucoma in children? J AAPOS. 2000;4(1):33- that did not. Although this difference did not reach sta- 39. tistical significance, likely owing to the small sample size 12. The Infant Aphakia Treatment Study Group. A randomized clinical trial compar- of the glaucoma group, it is reasonable to expect that a ing contact lens with intraocular lens correction of monocular aphakia during infancy: grating acuity and adverse events at age 1 year. Arch Ophthalmol. 2010; statistically significant difference in visual acuity will de- 128:810-818. velop in the glaucoma group with longer follow-up. 13. Lambert SR, Buckley EG, Drews-Botsch C, et al; Infant Aphakia Treatment Study The limitations of our study are the small sample size Group. The Infant Aphakia Treatment Study: design and clinical measures at of the group of patients with glaucoma-related adverse enrollment. Arch Ophthalmol. 2010;128(1):21-27. events, only 1 year of follow-up data, and the inclusion 14. Phelps CD, Arafat NI. Open-angle glaucoma following surgery for congenital cataracts. Arch Ophthalmol. 1977;95(11):1985-1987. of the glaucoma suspect group with the glaucoma group 15. Pressman SH, Crouch ER Jr. Pediatric aphakic glaucoma. Ann Ophthalmol. 1983; for statistical evaluation. The strengths of our study are 15(6):568-573. the prospective data collected and the standardized defi- 16. Nishijima K, Takahashi K, Yamakawa R. Ultrasound biomicroscopy of the ante- nitions of glaucoma, glaucoma suspect, and glaucoma- rior segment after congenital cataract surgery. Am J Ophthalmol. 2000;130 (4):483-489. related adverse events. Planned 5-year IATS follow-up 17. Lambert SR, Lynn M, Drews-Botsch C, et al. A comparison of grating visual acu- data should provide long-term incidence data and should ity, strabismus, and reoperation outcomes among children with aphakia and pseu- identify the risk factors for the development of glau- dophakia after unilateral cataract surgery during the first six months of life. J AAPOS. coma and the effect of glaucoma on visual outcomes in 2001;5(2):70-75. patients with unilateral cataract. 18. Vishwanath M, Cheong-Leen R, Taylor D, Russell-Eggitt I, Rahi J. Is early surgery for congenital cataract a risk factor for glaucoma? Br J Ophthalmol. 2004; 88(7):905-910. Submitted for Publication: March 15, 2011; final revi- 19. Gordon MO, Beiser JA, Brandt JD, et al. The Ocular Hypertension Treatment Study: sion received August 22, 2011; accepted September 2, baseline factors that predict the onset of primary open-angle glaucoma. Arch 2011. Ophthalmol. 2002;120(6):714-720, discussion 829-830. 20. Ehlers N, Bramsen T, Sperling S. Applanation tonometry and central corneal Published Online: November 14, 2011. doi:10.1001 thickness. Acta Ophthalmol (Copenh). 1975;53(1):34-43. /archophthalmol.2011.347 21. Orssengo GJ, Pye DC. Determination of the true intraocular pressure and modu- Correspondence: Allen D. Beck, MD, Emory Eye Cen- lus of elasticity of the human cornea in vivo. Bull Math Biol. 1999;61(3):551- ter, 1365-B Clifton Rd, Atlanta, GA 30322 (abeck@emory 572. .edu). 22. Dueker DK, Singh K, Lin SC, et al. Corneal thickness measurement in the man- agement of primary open-angle glaucoma: a report by the American Academy Author Contributions: Dr Beck and Mr Lynn had full of Ophthalmology. Ophthalmology. 2007;114(9):1779-1787. access to all the data in the study and take responsibility 23. Lim Z, Muir KW, Duncan L, Freedman SF. Acquired central corneal thickness in- for the integrity of the data and the accuracy of the data crease following removal of childhood cataracts. Am J Ophthalmol. 2011;151 analysis. (3):434-441. 24. Bhola R, Keech RV, Olson RJ, Petersen DB. Long-term outcome of pediatric apha- Financial Disclosure: None reported. kic glaucoma. J AAPOS. 2006;10(3):243-248. Funding/Support: This study was supported by Na- 25. Bothun ED, Guo Y, Christiansen SP, et al. Outcome of angle surgery in children tional Institutes of Health grants U10 EY13272 and U10 with aphakic glaucoma. J AAPOS. 2010;14(3):235-239.

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