Glaucoma-Related Adverse Events at 10 Years in the Infant Aphakia Treatment Study: A Secondary Analysis of a Randomized Clinical Trial

Abstract

Importance: Glaucoma-related adverse events constitute serious complications of cataract removal in infancy, yet long-term data on incidence and visual outcome remain lacking.

Objective: To identify and characterize incident cases of glaucoma and glaucoma-related adverse events (glaucoma + glaucoma suspect) among children in the Infant Aphakia Treatment Study (IATS) by the age of 10.5 years and to determine whether these diagnoses are associated with optic nerve head (ONH) and peripapillary retinal nerve fiber layer (RNFL) assessment.

Design, setting, and participants: Analysis of a multicenter randomized clinical trial of 114 infants with unilateral congenital cataract who were aged 1 to 6 months at surgery. Data on long-term glaucoma-related status and outcomes were collected when children were 10.5 years old (July 14, 2015, to July 12, 2019) and analyzed from March 30, 2019, to August 6, 2019.

Interventions: Participants were randomized at cataract surgery to either primary intraocular lens (IOL), or aphakia (contact lens [CL]). Standardized definitions of glaucoma and glaucoma suspect were created for IATS and applied for surveillance and diagnosis.

Main outcomes and measures: Development of glaucoma and glaucoma + glaucoma suspect in operated-on eyes up to age 10.5 years, plus intraocular pressure, axial length, RNFL (by optical coherence tomography), and ONH photographs.

Results: In Kaplan-Meier analysis, for all study eyes combined (n = 114), risk of glaucoma after cataract removal rose from 9% (95% CI, 5%-16%) at 1 year, to 17% (95% CI, 11%-25%) at 5 years, to 22% (95% CI, 16%-31%) at 10 years. The risk of glaucoma plus glaucoma suspect diagnosis after cataract removal rose from 12% (95% CI, 7%-20%) at 1 year, to 31% (95% CI, 24%-41%) at 5 years, to 40% (95% CI, 32%-50%) at 10 years. Risk of glaucoma and glaucoma plus glaucoma suspect diagnosis at 10 years was not significantly different between treatment groups. Eyes with glaucoma (compared with eyes with glaucoma suspect or neither) had longer axial length but relatively preserved RNFL and similar ONH appearance and visual acuity at age 10 years.

Conclusions and relevance: Risk of glaucoma-related adverse events continues to increase with longer follow-up of children following unilateral cataract removal in infancy and is not associated with primary IOL implantation. Development of glaucoma (or glaucoma suspect) after removal of unilateral congenital cataract was not associated with worse visual acuity outcomes at 10 years.

Trial registration: ClinicalTrials.gov Identifier: NCT00212134.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Freedman, Nizam, VanderVeen, and Drews-Botsch reported grants from the National Eye Institute during the conduct of the study. Dr Nizam reported grants from National Eye Institute during the conduct of the study. Dr VanderVeen reported grants from Retrophin Inc and personal fees from Ophtec outside the submitted work. Dr Drews-Botsch reported grants from US Department of Health and Human Services during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.. Number of IATS Participants Diagnosed as Having Glaucoma, Glaucoma Suspect, or Normal at 1, 5, and 10 Years After Surgery in the Intraocular Lens (IOL) and Contact Lens (CL) Groups

Arrows indicate the number of participants with changes in status from 1 point to the next. Where there is more than 1 number in a box, the leftmost number is the number of participants whose status did not change from the previous point, and number that is added represents changes in status from the previous point to the current point.

Figure 2.. Kaplan-Meier Curves Showing Cumulative Probability of Glaucoma (A) and Glaucoma + Glaucoma Suspect (B) vs Time (in Years) Since Cataract Surgery for 114 Study Participants

The shading denotes 95% confidence intervals for the cumulative probability. The numbers of participants at risk and the cumulative numbers of events are shown below the x-axis. The 10-year cumulative probability was 22% (95% CI, 16%-31%) for glaucoma and 40% (95% CI, 32%-50%) for glaucoma + glaucoma suspect.

Figure 3.. Kaplan-Meier Curves Showing the Cumulative Probability of Glaucoma (A) and Glaucoma + Glaucoma Suspect (B) vs Time (in Years) Since Cataract Surgery for the Contact Lens (CL) and Intraocular Lens (IOL) Groups (57 Participants in Each Group)

The numbers of participants at risk and the cumulative numbers of events are shown below the x-axis. At 10.5 years, the cumulative probability of glaucoma was 23% (95% CI, 14%-37%) for the CL group and 21% (95% CI, 13%-35%) for the IOL group. The 10-year cumulative probability of glaucoma + glaucoma suspect was 46% (95% CI, 34%-60%) for the CL group and 36% (95% CI, 25%-50%) for the IOL group.

Figure 4.. Examples of Optic Nerve Head (ONH) Images for the Treated (A) and Fellow Eye (B) of the Same Infant Aphakia Treatment Study (IATS) Participants Whose ONH Optical Coherence Tomography Images Are Shown in eFigure 4A and B in the Supplement

The treated eye was diagnosed as having glaucoma based both on the IATS criteria (eTable 1 in the Supplement) and ONH imaging, while the fellow eye was graded as normal (neither glaucomatous nor glaucoma suspect). The peripapillary retinal nerve fiber layer for the ONH of the treated eye (eFigure 4A in the Supplement) was 105 μm; the peripapillary RNFL for the ONH of the fellow eye (eFigure 4B in the Supplement) was 117 μm.