Abstract
Importance
Glaucoma-related adverse events constitute major sight-threatening complications of cataract removal in infancy, yet their relationship to aphakia versus primary intraocular lens (IOL) implantation remains unsettled.
Objective
To identify and characterize cases of glaucoma and glaucoma-related adverse events (glaucoma+glaucoma suspect) among children in the Infant Aphakia Treatment Study (IATS) by the age of five years.
Design, Setting, and Participants
A multicenter randomized controlled trial of 114 infants with unilateral congenital cataract who were between age 1–6 months at surgery.
Interventions
Participants were randomized at cataract surgery to either primary IOL, or no IOL implantation (contact lens [CL]). Standardized definitions of glaucoma and glaucoma suspect were created for IATS and applied for surveillance and diagnosis.
Main Outcome Measures
Development of glaucoma and glaucoma+glaucoma suspect in operated eyes up to age five years, plus intraocular pressure, visual acuity, and axial length at age five years.
Results
Product limit estimates of the risk of glaucoma and glaucoma+glaucoma suspect at 4.8 years after surgery were 17% (95%CI=11%–25%) and 31% (95%CI=24%–41%), respectively. The CL and IOL groups were not significantly different for either outcome: glaucoma (hazard ratio(HR)=0.8[95%CI=0.3–2.0],p=0.62); glaucoma+glaucoma suspect: (HR=1.3[95%CI=0.6–2.5],p=0.58). Younger (versus older) age at surgery conferred increased risk of glaucoma (26% versus 9%, respectively at 4.8 years after surgery (HR=3.2[95%CI=1.2–8.3]), and smaller (versus larger) corneal diameter showed increased risk for glaucoma+glaucoma suspect (HR=2.5[95%CI=1.3–5.0]). Age and corneal diameter were significantly positively correlated. Glaucoma was predominantly open angle (19/20 cases, 95%), most eyes received medication (19/20, 95%), and 8/20 (40%) eyes had surgery.
Conclusions and Relevance
These results suggest that glaucoma-related adverse events are common and increase between one and five years in infants after unilateral cataract removal at 1–6 months of age; primary IOL placement does not mitigate their risk, but surgery at a younger age increases the risk. Longer follow-up of these children may further characterize risk factors, long-term outcomes, potential differences between eyes having primary IOL vs. aphakia, and optimal timing of unilateral congenital cataract removal.
Glaucoma is a well-documented and serious complication after childhood cataract removal, with reported frequency and risk factors for glaucoma and glaucoma suspect varying by study population, definition, and follow-up time, in a variety of retrospective studies.1–12 The Infant Aphakia Treatment Study (IATS) - a multi-center, randomized, controlled clinical trial sponsored by the National Eye Institute – compares outcomes of surgery for unilateral cataract with primary intraocular lens (IOL) implantation to surgery without IOL implantation in infants between 1 and 6 months of age.13–17
Definitive knowledge of the relationship between primary IOL placement at the time of congenital cataract removal and glaucoma risk remains to be ascertained. While some studies reported decreased glaucoma frequency among eyes with primary IOL implantation after cataract removal in the first year of life,18–20 others noted a similar frequency,1,10–12,21 but all lacked randomization regarding primary IOL placement.
In this paper we report 5 year results of the development of glaucoma-related adverse events in IATS participants.
METHODS
The IATS design, surgical technique, follow-up schedule, patching and optical correction regimens, evaluation methods, and patient characteristics at baseline have been previously reported in detail [see supplemental material].14 The definitions for Glaucoma, Glaucoma suspect, and Glaucoma-related adverse events (Glaucoma+Glaucoma suspect) were established and rigorously applied, as previously reported (Table 1).13
Table 1.
Definitions of Glauoma, Glaucoma Suspect and Glaucoma-Related Adverse Event
| Term | Definition |
|---|---|
| Glaucoma | A study eye was diagnosed as having Glaucoma if the intraocular pressure (IOP) was >21 mmHg with one or more of the following anatomical changes: a) corneal enlargement, b) asymmetrical progressive myopic shift coupled with enlargement of the corneal diameter and/or axial length, c) increased optic nerve cupping defined as an increase of ≥ 0.2 in the cup-to-disc ratio; or d) a surgical procedure was performed for IOP control. |
| Glaucoma suspect | A study eye was designated as a Glaucoma suspect if there was either: a) recording of two consecutive IOP measurements above 21 mmHg on different dates after topical corticosteroids had been discontinued without any of the anatomical changes listed above for Glaucoma; or b) glaucoma medication was used to control IOP without any of the anatomical changes listed above. |
| Glaucoma-related adverse event | Glaucoma and glaucoma suspect together (glaucoma+glaucoma suspect).* |
In the statistical analyses, for an eye originally diagnosed as a glaucoma suspect that developed glaucoma, that eye was considered in the glaucoma group when analyzing the glaucoma outcome and in the glaucoma suspect group when analyzing the glaucoma-related adverse event outcome. For all other analyses the eye was considered in the glaucoma group. Throughout the text, eye is synonymous with child, since no fellow eye (without cataract) has developed glaucoma or glaucoma suspect in this study to date.
IATS was not originally designed to capture detailed information about the diagnosis, treatment and course of glaucoma. However, medical record information was obtained from sites to enable the medical monitor to: 1) verify application of standard definitions for glaucoma and glaucoma suspect, and 2) confirm that appropriate care was provided to study participants. Available information on intraocular pressure (IOP), optic nerve head (cup:disc ratios recorded by the clinician), medications and glaucoma surgery was gathered from these records.
Statistical Considerations [see supplemental material].
RESULTS
Development of Glaucoma
IATS randomized 114 infants (57 each to CL and IOL): 113 completed clinical examination at age 5 years (mean 5.0, range 4.7–5.4), with mean post-surgical follow-up 4.8 years (range 4.4–5.3); 1 subject (IOL group) was lost to follow-up at 18 months.
By the 5-year-old follow-up, 20 eyes (18%) had developed glaucoma, and 16 additional eyes were glaucoma suspects (36 eyes total [32%] glaucoma+glaucoma suspect). The CL group had 9 eyes (16%) with glaucoma and 11 (19%) were glaucoma suspects (20 eyes total [35%] glaucoma+glaucoma suspect). The IOL group had 11 eyes (19%) with glaucoma and 5 (9%) were glaucoma suspects (16 eyes total [28%] glaucoma+glaucoma suspect).
In Kaplan Meier analysis, for all study eyes combined, risk of glaucoma after cataract removal rose from 9% (95%CI=5%–16%) at one year, to 17% (95%CI=11%–25%) at 4.8 years (Figure 1A; eTable 1 in supplement); risk of glaucoma+glaucoma suspect diagnosis after cataract removal rose from 12% (95%CI=7%–20%) at one year, to 31% (95%CI=24%–41%) at 4.8 years (Figure 1B; eTable 1 in supplement).
Figure 1.
Kaplan Meier curve showing cumulative probability of glaucoma (A) and glaucoma+glaucoma suspect (B) against time after cataract surgery. One additional child in the CL group had glaucoma diagnosed at 4.9 years which increased the cumulative probability to 43% (95% CI=12% – 91%).
Kaplan-Meier curves for developing glaucoma after cataract removal were not significantly different between the CL and IOL treatment groups (Figure 2A, eTable 1 in supplement, HR=0.8[95%CI=0.3–2.0],p=0.62) with the risk rising in the CL and IOL groups from 5% (95%CI=2%–15%) and 12% (95%CI=6%–24%), respectively, at one year, to 14% (95%CI=7%–26%) and 19% (95%CI=11%–32%), respectively, at 4.8 years. Kaplan-Meier curves for developing glaucoma+glaucoma suspect diagnosis after cataract removal were also not significantly different between the treatment groups (Figure 2B, eTable 1 in supplement, HR=1.3[95%CI=0.6–2.5],p=0.58), with the risk rising in the CL and IOL groups from 9% (95%CI=4%–20%) and 16% (95%CI=9%–28%), respectively, at one year, to 34% (95%CI=23%–48%) and 28% (95%CI=18%–42%), respectively, at 4.8 years.
Figure 2.
Kaplan Meier curve showing cumulative probability of glaucoma (A) and glaucoma+glaucoma suspect (B) against time after cataract surgery according to the treatment assignment.
Cases of Glaucoma and Glaucoma Suspect Since the One-Year Follow-up
Glaucoma was diagnosed in 10 eyes between the one-year postoperative and 5-year-old visits (6 CL, 4 IOL). Six eyes which were glaucoma suspects at one year converted to glaucoma by the 5-year-old visit. Thirteen eyes became glaucoma suspects during the same time interval (10 CL and 3 IOL).
Influence of Baseline Characteristcs of enrolled Children/Study Eyes
Bivariate analyses evaluated selected baseline characteristics relative to the development of glaucoma and glaucoma+glaucoma suspect (Table 2). Children in the younger age strata at cataract surgery were at higher risk of developing glaucoma than older children by 4.8 years post-operatively (26% versus 9%, respectively, p=0.014) and glaucoma+glaucoma suspect (45% versus 21%, respectively, p=0.006). Eyes with smaller corneal diameter (≤ 10 mm) at cataract removal were also at higher risk of glaucoma+glaucoma suspect (but not of glaucoma) than those having larger corneas by 4.8 years post-operatively (50% versus 20%, respectively, p=0.001). Neither persistent fetal vasculature (PFV) diagnosis nor IOP at surgery was associated with risk of either glaucoma or glaucoma+glaucoma suspect diagnoses by 4.8 years.
Table 2.
Baseline Characteristics of children in the Infant Aphakia Treatment Study versus Development of Glaucoma and Glaucoma+Glaucoma Suspect
| Baseline Characteristic |
n | # Events (%) |
Probability by Year 1 |
Probability by Year 4.8* |
p- value† |
Hazard Ratio (95% CI)‡ |
|---|---|---|---|---|---|---|
| Glaucoma | ||||||
| Age Strata (days) | ||||||
| 28 – 48 | 50 | 14 (28%) | 16% (8%–29%) | 26% (16%–41%) | 0.014 | 3.2 (1.2 – 8.3) |
| 49 – 210 | 64 | 6 (9%) | 3% (1%–12%) | 9% (4%–20%) | ||
| PFV | ||||||
| No | 90 | 13 (14%) | 7% (3%–14%) | 13% (8%–22%) | 0.083 | 2.2 (0.9 – 5.5) |
| Yes | 24 | 7 (29%) | 17% (7%–39%) | 29% (15%–52%) | ||
| Corneal Diameter (mm)§ | ||||||
| ≤ 10 | 45 | 11 (24%) | 13% (6%–27%) | 22% (13%–38%) | 0.13 | 1.9 (0.8 – 4.7) |
| > 10 | 69 | 9 (13%) | 6% (2%–15%) | 13% (7%–24%) | ||
| IOP (mmHg) | ||||||
| < 12¶ | 57 | 12 (21%) | 12% (6%–24%) | 19% (11%–32%) | 0.28 | 0.6 (0.3 – 1.5) |
| ≥ 12 | 57 | 8 (14%) | 5% (2%–15%) | 14% (7%–26%) | ||
| Glaucoma+Glaucoma Suspect | ||||||
| Age Strata (days) | ||||||
| 28 – 48 | 50 | 23 (46%) | 18% (10%–32%) | 45% (32%–60%) | 0.006 | 2.5 (1.3 – 5.0) |
| 49 – 210 | 64 | 13 (20%) | 8% (3%–18%) | 21% (13%–34%) | ||
| PFV | ||||||
| No | 90 | 26 (29%) | 10% (5%–18%) | 28% (20%–39%) | 0.24 | 1.5 (0.7 – 3.2) |
| Yes | 24 | 10 (42%) | 21% (9%–43%) | 43% (26%–65%) | ||
| Corneal Diameter (mm)§ | ||||||
| ≤ 10 | 45 | 22 (49%) | 20% (11%–35%) | 50% (36%–65%) | 0.001 | 2.9 (1.5 – 5.7) |
| > 10 | 69 | 14 (20%) | 7% (3%–17%) | 20% (12%–32%) | ||
| IOP (mmHg) | ||||||
| < 12¶ | 57 | 15 (26%) | 16% (9%–28%) | 27% (17%–41%) | 0.30 | 1.4 (0.7 – 2.8) |
| ≥ 12 | 57 | 21 (37%) | 9% (4%–20%) | 35% (24%–49%) | ||
n = number of children (number of eyes).
PFV = persistent fetal vasculature (diagnosed at the time of cataract removal).
IOP = intraocular pressure at time of cataract removal.
The product limit estimate (95% confidence interval) of the cumulative probability of the adverse event.
The p-value for the logrank test comparing the Kaplan Meier curves of the two categories of each characteristic.
The hazard ratio estimated from a proportional hazards regression model with the characteristic as the only factor in the model. The relative categories are: Age (28 – 48 day versus 49 – 210 days), PFV (Yes versus No), Corneal Diameter (≤ 10 mm versus > 10 mm), IOP (≥ 12 mmHg versus < 12 mmHg).
Measured using calipers during examination under anesthesia prior to randomization.
The median for IOP at baseline among all 114 patients was 11.75 mmHg.
Multivariate analysis for glaucoma considered factors including age strata, CL vs IOL group, PFV, corneal diameter and IOP at surgery: age strata was associated with glaucoma [HR (younger versus older)=3.2, 95%CI=1.2–8.3, p=0.02]; no association was identified with any of the other factors after accounting for age. In the multivariate analysis for glaucoma+glaucoma suspect diagnoses, corneal diameter was associated with glaucoma+glaucoma suspect [HR (≤ 10 mm versus > 10 mm)=2.9, 95%CI=1.5–5.7, p=0.002]; no association was identified with any of the other factors after accounting for corneal diameter. Not surprisingly, there was a moderately high positive correlation between age and corneal diameter (r=0.65, p<0.0001); hence when one of these variables was in the model, a an association with outcome was not identified for the other variable. Similar results were found for the bivariate and multivariate analyses with age at surgery, IOP and corneal diameter in continous form and are reported in eTable 2.
Glaucoma characteristics, treatment, and outcomes
Although detailed gonioscopic information was not collected as part of IATS, 19/20 eyes with glaucoma were assumed to be open angle, while one eye had iris bombe and angle closure. All 16 eyes with glaucoma suspect diagnosis were assumed to have open angles.
Diagnostic criteria for diagnosis
Among the 20 eyes diagnosed with glaucoma, 13 (65%) showed IOP> 21 mmHg with anatomic changes: corneal enlargement (3 eyes, 2 having myopic shift), increased optic nerve cupping (8 eyes, 1 having myopic shift), and myopic shift only (2 eyes). Seven eyes (35%) were diagnosed either by requiring glaucoma surgery (4), or by ≥2 other diagnostic criteria (3). Among the 16 eyes diagnosed as glaucoma suspect, 10 eyes (63%) met criteria by elevated IOP (> 21 mm Hg), while 6 eyes (38%) were treated with glaucoma medications, without strictly meeting IOP diagnostic criteria.
The mean maximum IOP recorded was elevated in eyes with glaucoma and with glaucoma suspect diagnoses (32.1 ±9.0 vs 28.9 ±4.9 mm Hg, respectively) compared with eyes having neither diagnosis (18.8 ±2.9, mm Hg, p<0.0001 for both comparisons). Mean maximum IOP recorded was similar for eyes with glaucoma in the CL (n=9) vs. IOL groups (n=11): 34.7 ±6.6 vs. 30.0 ±10.5 mm Hg, respectively, p=0.26. The mean maximum recorded IOP in eyes diagnosed as glaucoma suspects was similar in the CL and IOL groups (27.9 ±3.0 vs 30.9 ±7.8, respectively, p=0.44).
The optic nerve head cup:disc ratio (CD ratio) was recorded subjectively by investigators without imaging. While maximum recorded CD ratio varied widely, mean CD was larger in eyes diagnosed as glaucoma (n=19, 0.45 ±0.22) vs. glaucoma suspect (n=15, 0.19 ±0.10, p=0.0001), with no significant difference between the CL and IOL groups within each respective diagnostic group.
Glaucoma treatment (eTable 3 in supplement)
Glaucoma medications were prescribed for 19/20 (95%) eyes with glaucoma, and 12/16 (75%) eyes diagnosed as glaucoma suspects; 8/20 eyes with glaucoma (40%) had glaucoma surgery by the 5-year-old visit. The eye with angle closure (CL group) had limited anterior vitrectomy, pupillary membrane removal, and surgical peripheral iridectomy; despite glaucoma control postoperatively, the eye subsequently suffered retinal detachment and ultimately, phthisis. Glaucoma surgical procedures were performed in 7/19 (37%) eyes with open angle glaucoma: 5/11 (45.5%) in the IOL group, and 2/9 (22.2%) in the CL group (p=0.37). Surgical procedures (eTable 3 in supplement) included trabeculotomy, Baerveldt glaucoma drainage implant, and endoscopic diode laser.
Of the 10 additional glaucoma cases diagnosed between the 1 year postoperative visit and the 5-year-old follow-up, only one additional eye (10%) has had glaucoma surgery. Of the 7 eyes requiring glaucoma surgery for open angle glaucoma, 5 occurred within the first year following cataract removal. At the 5-year-old follow-up, these 7 eyes had mean IOP 18.3 +3.9 mm Hg, 4 were on glaucoma medication.
Glaucoma and ocular parameters at the 5-year-old follow-up
IOP at approximately age 5 was available for 112 patients. Mean IOP was similar in eyes diagnosed as either glaucoma (n=19) or glaucoma suspect (n=16), 20.2 ±6.5 mm Hg vs 21.6 ±4.5 mm Hg, respectively, and different from the eyes with neither diagnosis (n=77, 16.8 ±3.9 mm Hg), p<0.01 for both comparisons. Mean axial length at the age 5 year follow-up visit was significantly longer in eyes with glaucoma (n=13, 23.3 ±2.0 mm), than those diagnosed as neither glaucoma nor glaucoma suspect (n=72, 21.4 ±1.6 mm, p=0.001); eyes diagnosed as glaucoma suspects (n=12) had mean axial length 22.0 ±2.2 mm, not different from the means of either of the other two groups.
Glaucoma and Visual Acuity
Median visual acuity at age 4.5 years was 20/283 in eyes with glaucoma (n=20), 20/141 in eyes with glaucoma suspect (n=16), and 20/100 in eyes with neither diagnosis (n=76); these three groups are not statistically different (p=0.13). Results according to visual acuity categories are provided in eTable 4.
DISCUSSION
Glaucoma developed in the operated eyes of 20/113 infants (18%) with unilateral cataract enrolled in the IATS by age 5 years; an additional 16 eyes were glaucoma suspects, for a total 36 operated eyes (32%) with glaucoma+glaucoma suspect diagnosis. The risk of developing glaucoma rose in both CL and IOL groups between one and 4.8 years after cataract surgery (from 5% to 14%, and from 12% to 19%, respectively), as did the risk of glaucoma+glaucoma suspect diagnosis (from 9% to 34%, and from 16% to 28%, respectively). Of the 13 additional cases of glaucoma suspect diagnosed between the one year post-operative and the age five year visits, 10 were in the CL group; these differences by treatment group were not statistically significant. Additionally, we noted a relative “lull” in the diagnosis of glaucoma+glaucoma suspect diagnoses between one and three years post cataract removal. However, the IATS protocol only required IOP assessment at the 1-year-old exam under anesthesia and the age 4, 4.5 or 5 years visits, so surveillance bias was possible.
While most retrospective studies of glaucoma following cataract removal in infancy have lacked uniform diagnostic criteria for that complication, the 17% chance of glaucoma by 4.8 years after surgery in the IATS is remarkably consistent with other studies,5,6 including a recent, meta-analysis reporting glaucoma in 80/470 (17%) eyes after cataract surgery at median age 3 months with median onset 4.3 years post-surgery.19 Despite varying definitions of glaucoma used in published studies, it is clear that a significant percentage of children undergoing congenital cataract surgery develop glaucoma (or at least elevated IOP), usually with open angles, and the onset of glaucoma frequently occurs years after cataract surgery.1,2,6,7,22
Numerous mechanisms for the development of glaucoma after cataract removal in infancy have been postulated.2,6,7,9–11,18,22–25 Since the IATS was not designed to investigate the mechanism of glaucoma-related adverse events, we cannot differentiate amongst various proposed mechanisms of open angle glaucoma, but confirm that modern surgical techniques do not eliminate this complication.2,14
There is controversy surrounding the possible protective effect of primary IOL implantation (vs. aphakia) against glaucoma after cataract removal in infancy, with published reports both supporting18,19 and failing to demonstrate this protective effect.10,11 Trivedi et al noted that all glaucoma cases occurred in eyes having cataract surgery in the first 4.5 months of life, with similar rates in aphakic vs. pseudophakic eyes (19% vs. 24%, respectively).10 Mataftsi and colleagues, noted a protective effect of primary IOL vs aphakia in their large meta analysis (hazard ratio 0.1, p=0.02);19 however, eyes were not randomized to primary IOL vs. aphakia, and a consistent definition of glaucoma was not applied. The IATS – by virtue of its randomization and prospective design – lacks the potential bias of prior non-randomized studies.14 Neither glaucoma, nor glaucoma+glaucoma suspect diagnoses, were statistically different between pseudophakic and aphakic eyes at the one-year follow-up.13 We report an increase in both glaucoma and glaucoma suspect cases by the 5-year-old visit in the IATS, but no statistically significant difference in either complication by treatment group (IOL vs CL). Continued follow-up will be critical to more definitively answer the question of the possible protective effect of primary IOL placement, especially since reported onset of glaucoma occurs at a mean 4–5 years after cataract removal.6,7,19,23
Standard definitions of glaucoma and glaucoma suspect were developed and uniformly applied for surveillance and diagnosis of eyes within IATS, with the former requiring not only elevated IOP, but also associated structural changes in the infant eye or need for glaucoma surgery.13 Many prior studies have defined glaucoma solely by elevated IOP, or by the physician’s decision to start treatment,19 without including secondary structural change among the diagnostic criteria.2,6,7,23 The importance of a uniformly accepted definition of glaucoma as well as glaucoma suspect will facilitate future research and comparison amongst different published works.26 The definitions of glaucoma and glaucoma suspect developed for IATS13 were adopted by the International Consensus group.26
Among various risk factors previously evaluated for the development of glaucoma following cataract surgery in children, young age at surgery has been frequently identified.10,27,28,29 Younger patient age at surgery (28–48 vs. 49–210 days old) was also noted as a risk factor for the development of a glaucoma related-adverse event in IATS at one year,13 despite deferring cataract surgery until at least age 4 weeks based on previous studies suggesting increased glaucoma risk if surgery is performed in the first 4 weeks of life.27,30 At the 5-year-old visit, children in the younger age strata (28–48 vs. >48 days old) at cataract surgery were again noted to be at higher risk of developing glaucoma and glaucoma-related adverse events.
Multivariate analysis (considering age at surgery, corneal diameter, presence of persistent fetal vasculature, and IOP at surgery) showed that only younger age at surgery increased the risk of developing glaucoma (by 3.2 times); only smaller corneal diameter at surgery (≤ 10 mm versus > 10 mm) increased the risk of developing a diagnosis of glaucoma+glaucoma suspect (by 2.9 times). This was not unexpected, since young age at surgery and smaller corneal diameter were highly correlated. Since eyes with severe PFV were excluded from IATS, it is not surprising that this feature was not noted to confer additional risk of glaucoma+glaucoma suspect diagnosis by five years. Evaluation of the relationship between visual acuity at 4.5 years of age and age at surgery in IATS (28–48 vs. 49–210 days at surgery) revealed median visual acuity was significantly better for eyes operated younger vs. older (0.50 versus 1.10 logMAR, p=0.046).31 Therefore, the desire to achieve maximum visual acuity must be counterbalanced against an increased risk of glaucoma or glaucoma suspect diagnosis in an infant with a unilateral congenital cataract.
As expected based upon the definitions of glaucoma and glaucoma suspect in the IATS, eyes with these diagnoses had higher maximum recorded IOP than those without them by the 5-year-old visit. The optic nerves showed a larger CD ratio in eyes with glaucoma than those with glaucoma suspect or without either diagnosis; axial length was longer in eyes with glaucoma than in eyes with glaucoma suspect or without glaucoma-related adverse event, consistent with the IOP-related structural changes required to diagnose glaucoma in IATS. Glaucoma following removal of a childhood cataract may require surgical treatment, or remain medically controlled for some time, depending upon its severity. Hence surgical treatment was performed in 57% of 170 eyes with aphakic glaucoma in the large retrospective series by Chen et al.,23 while Bhola et al noted surgical intervention in only 15/55 eyes (27%).32 At one year, 60% of eyes with glaucoma in IATS received surgical intervention.13 By the 5-year-old visit, glaucoma medications had been used in 19/20 (95%) eyes diagnosed with glaucoma, and 12/16 (75%) diagnosed as glaucoma suspects. Surgery had been performed in 8 eyes, 1 for angle closure glaucoma (with initial control, but later retinal detachment and phthisis). Five of 7 eyes with open angle glaucoma requiring surgery by 5 years old, had that surgery in the first year after cataract removal, and have remained controlled (eTable 3). Surgery performed in the 7 eyes with open angle glaucoma, included trabeculotomy, glaucoma drainage implantation and endoscopic diode cyclophotocoagulation, reflecting lack of uniform initial surgery chosen by different surgeons for this type of glaucoma.26
Visual acuity in children who develop glaucoma following congenital cataract surgery may be limited by glaucomatous optic nerve damage, amblyopia, pupillary membranes, corneal decompensation, or complications from glaucoma surgery. At the 5-year-old visit, the visual acuity differences between those eyes with versus without glaucoma, did not reach statistical significance, perhaps due to the small sample size of each group; reduced visual acuity may nonetheless develop in the glaucoma group with longer follow-up.
Limitations of this study include the relatively small sample size of the entire cohort (reducing power to adequately assess some factors), intermediate follow-up of 4.8 years following cataract surgery, and lack of study-related treatment protocols for glaucoma-related adverse events. In addition, we could not evaluate IOL position as a risk factor for glaucoma-related adverse events since most eyes had in-the-bag IOLs.33 Nor could we separate out the influence of additional intraocular surgery because glaucoma-related adverse events likely affected timing of non-urgent additional surgeries. This study’s strengths include its prospective design with randomization to primary IOL implantation vs. aphakia, as well standardized definitions of glaucoma and glaucoma suspect. Planned follow-up data at age 10 years for all IATS participants should provide additional important information about risk factors for the development of glaucoma and the effect of glaucoma on visual outcomes in unilateral cataract patients, and may help better delineate potential differences in glaucoma severity and treatment success between eyes in the IOL and CL study groups.
Supplementary Material
ACKNOWLEDGEMENTS
Michael Lynn and Allen Beck had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Sharon Freedman additionally had full access to all of the data involved in this present manuscript regarding glaucoma and glaucoma suspect at the five-year-old visit.
Supported by National Institutes of Health Grants U10 EY13272 and U10 EY013287 and in part by NIH Departmental Core Grant EY06360 and Research to Prevent Blindness, Inc, New York, New York
Role of the Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.
The Infant Aphakia Treatment Study Group
Administrative Units and Participating Clinical Centers
Clinical Coordinating Center (Emory University): Scott R. Lambert, M.D. (Study Chair), Lindreth DuBois MEd, MMSc (National Coordinator)
Data Coordinating Center (Emory University): Michael 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, Thandeka Tutu-Gxashe MPH
Vision and Developmental Testing Center (University of Alabama, Birmingham): E. Eugenie Hartmann, PhD (Director); Anna K Carrigan, MPH; Clara Edwards;
Eye Movement Reading Center (University of Alabama, Birmingham and Retina Foundation of the Southwest, Dallas, TX): Claudio Busettini, PhD, Samuel Hayley, Joost Felius, PhD
Steering Committee: Scott R Lambert MD, Edward G. Buckley MD, David A. Plager MD, M. Edward Wilson MD, Michael Lynn MS, Lindreth DuBois Med MMSc, Carolyn Drews-Botsch PhD, E. Eugenie Hartmann PhD, Donald F Everett MA
Contact Lens Committee: Buddy Russell COMT, Michael Ward MMSc
Participating Clinical Centers (In order by the number of patients enrolled):
Medical University of South Carolina; Charleston, South Carolina (14): M. Edward Wilson MD, Margaret Bozic CCRC, COA
Harvard University; Boston, Massachusetts (14): Deborah K. VanderVeen MD, Theresa A Mansfield RN, Kathryn Bisceglia Miller OD
University of Minnesota; Minneapolis, Minnesota (13): Stephen P. Christiansen MD, Erick D. Bothun MD, Ann Holleschau, Jason Jedlicka OD, Patricia Winters OD, Jacob Lang OD
Cleveland Clinic; Cleveland, Ohio (10): Elias I. Traboulsi MD, Susan Crowe BS, COT, Heather Hasley Cimino OD
Baylor College of Medicine; Houston, Texas (10): Kimberly G Yen MD, Maria Castanes MPH, Alma Sanchez COA, Shirley York
Oregon Health and Science University; Portland, Oregon (9): David T Wheeler MD, Ann U. Stout MD, Paula Rauch OT, CRC, Kimberly Beaudet CO, COMT, Pam Berg CO, COMT
Emory University; Atlanta, Georgia (9): Scott R. Lambert MD, Amy K. Hutchinson MD, Lindreth DuBois Med, MMSc, Rachel Robb MMSc, Marla J. Shainberg CO
Duke University; Durham, North Carolina (8): Edward G. Buckley MD, Sharon F. Freedman MD, Lois Duncan BS, B.W. Phillips, FCLSA, John T. Petrowski, OD
Vanderbilt University: Nashville, Tennessee (8): David Morrison MD, Sandy Owings COA, CCRP, Ron Biernacki CO, COMT, Christine Franklin COT
Indiana University (7): David A Plager MD, Daniel E. Neely MD, Michele Whitaker COT, Donna Bates COA, Dana Donaldson OD
Miami Children’s Hospital (6): Stacey Kruger MD, Charlotte Tibi CO, Susan Vega
University of Texas Southwestern; Dallas, Texas (6): David R. Weakley MD, David R. Stager, Jr., Joost Felius PhD, Clare Dias CO, Debra L. Sager, Todd Brantley OD
Case Western Reserve, Cleveland, Ohio (1): Faruk Orge, M.D.
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, Donald F. Everett MA
Medical Safety Monitor: Allen Beck MD
Footnotes
Proprietary interests: none
Presented in part as a paper at the American Academy of Ophthalmology 2014 Annual Scientific Meeting, Chicago IL.
Trial Registration clinicaltrials.gov Identifier NCT00212134
Contribution of authors:
Study concept and design: Lambert, Lynn.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Freedman, Lynn.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Lynn.
Administrative, technical, or material support: Lambert, Freedman.
Study supervision: Lambert, Lynn.
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