To compare rates and severity of complications between infants undergoing cataract surgery with and without intraocular lens (IOL) implantation.
Prospective randomized clinical trial.
A total of 114 infants were enrolled in the Infant Aphakia Treatment Study, a randomized, multi-center (12) clinical trial comparing the treatment of unilateral aphakia in patients under 7 months of age with a primary IOL implant or contact lens. The rate, character, and severity of intraoperative complications, adverse events, and additional intraocular surgeries during the first 5 postoperative years in the 2 groups were examined.
There were more patients with intraoperative complications (28% vs 11%, P = .031), adverse events (81% vs 56%, P = .008), and more additional intraocular surgeries (72% vs 16%, P < .0001) in the IOL group than in the contact lens group. However, the number of patients with adverse events in the contact lens group increased (15 to 24) in postoperative years 2–5 compared to the first postoperative year, while it decreased (44 to 14) in years 2–5 compared to the first postoperative year in the IOL group. If only one half of the patients in the contact lens (aphakic) group eventually undergo secondary IOL implantation, the number of additional intraocular surgeries in the 2 groups will be approximately equal.
The increased rate of complications, adverse events, and additional intraocular surgeries associated with IOL implantation in infants <7 months of age militates toward leaving babies aphakic if it is considered likely that the family will be successful with contact lens correction.
Implantation of an intraocular lens (IOL) at the time of cataract surgery is commonly done for most patients above 1 year of age. There is considerably less consensus on the proper role of IOL implantation in infants. Theoretical advantages of primary IOL implantation at the time of cataract surgery in infants include having a constant, albeit partial, optical correction during the early years of visual development, the ability to place the IOL within the capsular bag, and the avoidance of contact lens use, with the associated cost and effort required of the child’s caregivers. Advantages of leaving the baby aphakic and visually rehabilitating the eye with a contact lens include the ability to change the contact lens power as needed to keep up with the rapidly growing eye’s refractive needs, not subjecting the baby to the increased rate of complications and subsequent need for additional surgeries associated with IOL implantation, and not requiring spectacle wear during the first few years of life.
The Infant Aphakic Treatment Study (IATS) is a multicenter, randomized clinical trial that compares the use of primary IOL implantation with spectacle correction of residual hyperopia to the correction of aphakia with a contact lens after cataract surgery performed in infants with a unilateral congenital cataract between 1 and 7 months of age. The study found no significant difference in grating visual acuity between the 2 groups at 1 year of age, but there was a significantly higher rate of complications, adverse events, and need for additional intraocular surgeries in the IOL group at that time. The optotype visual acuities obtained at 4.5 years in the IATS were recently reported. Consistent with the 1-year grating acuities, the 4.5-year optotype acuities showed no significant difference between the 2 study groups.
The purpose of this report is to examine in greater depth the rate and character of adverse events and additional intraocular surgeries required by age 5 years. It is hoped that this analysis will assist in formulating recommendations for the use of IOL implantation in infants.
The study design (multicenter randomized clinical trial), surgical techniques, follow-up schedule, and patient characteristics at baseline, as well as the clinical findings at 1 year of age, have been reported in detail previously and are only summarized here. This study was approved by the Institutional Review Boards of all 12 participating institutions and was in compliance with the Health Insurance Portability and Accountability Act. Informed consent was obtained from all parents or guardians. The off-label research use of the Acrysof SN60AT and MA60AC IOLs (Alcon Laboratories, Fort Worth, Texas, USA) was covered by US Food and Drug Administration investigational device exemption #G020021. The trial is registered at www.clincaltrials.gov (Identifier: NCT00212134 ).
The main inclusion criteria were a visually significant congenital cataract (>3 mm central opacity) in 1 eye and an age of 28 days to <210 days at the time of cataract surgery. Infants with a unilateral cataract attributable to persistent fetal vasculature were allowed in the study as long as the persistent fetal vasculature was not associated with visible stretching of the ciliary processes or involvement of the retina or optic nerve.
Infants randomized to the contact lens group underwent a lensectomy and anterior vitrectomy. Infants randomized to the IOL group had the lens contents aspirated followed by the implantation of an AcrySof SN60AT IOL into the capsular bag. In the event that both haptics could not be implanted into the capsular bag, an AcrySof MA60AC IOL was implanted into the ciliary sulcus. The IOL power was calculated based on the Holladay 1 formula targeting a postoperative refractive error of +8 diopters (D) for infants 4–6 weeks of age and +6 D for infants older than 6 weeks. Following IOL placement, a posterior capsulectomy and an anterior vitrectomy were performed through the pars plana/plicata. When either a pre-existing opening was present, as sometimes occurs with posterior lenticonus defects, or a rent developed intraoperatively in the posterior capsule and in some eyes with mild persistent fetal vasculature, the posterior capsulectomy and anterior vitrectomy were performed through the anterior incision prior to IOL implantation.
There were 114 children enrolled in the study, with 57 randomized to each treatment group. In years 2–5 following surgery, the patients were examined by an Infant Aphakia Treatment Study certified investigator every 3 months until 4½ years of age and then a final examination occurred at age 5 years. One hundred and thirteen patients had a clinical examination at age 5 years (mean, 5.0 years; range, 4.7–5.4 years) with an average length of follow-up of 4.8 years (range, 4.4–5.3 years) after cataract surgery. One patient in the IOL group was lost to follow-up at age 18 months.
Intraocular pressure (IOP) was measured using rebound tonometry (ICare Finland, Helsinki, Finland), a Tonopen (Reichert Technologies, Depew, New York, USA), or Goldmann applanation tonometry.
Glaucoma was defined as IOP >21 mm Hg with 1 or more of the following anatomical changes: (1) corneal enlargement; (2) asymmetrical progressive myopic shift coupled with enlargement of the corneal diameter and/or axial length; (3) increased optic nerve cupping, defined as an increase of ≥0.2 in the cup-to-disc ratio; or (4) the use of a surgical procedure to lower IOP.
Glaucoma suspect was defined as either: (1) 2 consecutive IOP measurements above 21 mm Hg on different dates after topical corticosteroids had been discontinued without any of the anatomical changes listed above; or (2) glaucoma medications were used to control IOP without any of the anatomical changes listed above.
A corneal ulcer was defined as a corneal epithelial defect with an associated corneal infiltrate, whereas a corneal abrasion was defined as a corneal epithelial defect with no infiltrate.
Lens reproliferation into the visual axis was defined as lens regrowth extending into the pupillary space and interfering with vision.
Other adverse events encountered that were deemed to not require definition include pupillary membrane, corectopia, vitreous hemorrhage, hyphema, retained cortex, retinal detachment, corneal edema, wound leak, IOL capture, endophthalmitis, and phthisis bulbi.
The percentage of patients experiencing 1 or more adverse events was compared between the treatment groups using Fisher exact test. The analysis was done for the first year following cataract surgery, for the follow-up period after the first year, and over the entire follow-up period. The same approach was used to compare the percentage of patients undergoing 1 or more additional ocular surgical procedures. The rate for the number of adverse events per patient-year of follow-up was compared between the treatment groups using the exact binomial test for comparing 2 Poisson means. This analysis was done for the first postoperative year and for the follow-up period after the first year. This same method was also used to compare the rate of ocular surgery procedures per patient-year of follow-up.
Table 1 shows the adverse events that occurred in each treatment group during the first year after cataract surgery as previously reported (11) as well as those that occurred in years 2–5 of follow-up.
|CL (57 Patients)||IOL (57 Patients)|
|During First Post-op Year||After First Post-op Year||Total||During First Post-op Year||After First Post-op Year||Total|
|# Ev||# Pat||# Ev||# Pat||# Ev||# Pat (%)||# Ev||# Pat||# Ev||# Pat||# Ev||# Pat (%)|
|Lens reproliferation into visual axis||1||1||1||1||2||2 (4%)||27||23||1||1||28||23 a (40%)|
|Pupillary membrane||0||0||2||2||2||2 (4%)||20||16||5||3||25||16 b (28%)|
|Corectopia||1||1||0||0||1||1 (2%)||15||13||4||4||19||16 c (28%)|
|Glaucoma||3||3||6||6||9||9 (16%)||7||7||4||4||11||11 (19%)|
|Glaucoma suspect||2||2||10||10||11||11 d (19%)||3||3||3||3||5||5 d (9%)|
|CL-related AEs h||4||3||14||7||18||10 (18%)||0||0||0||0||0||0 (0%)|
|Vitreous hemorrhage||2||2||0||0||2||2 (4%)||4||4||1||1||5||5 (9%)|
|Retinal hemorrhage||2||2||0||0||2||2 (4%)||3||3||0||0||3||3 (5%)|
|Hyphema||1||1||0||0||1||1 (2%)||3||3||2||1||5||4 (7%)|
|Retained cortex||2||2||0||0||2||2 (4%)||4||3||0||0||4||3 (5%)|
|Retinal detachment||2||2||0||0||2||2 (4%)||0||0||0||0||0||0 (0%)|
|Endophthalmitis||1||1||0||0||1||1 (2%)||0||0||0||0||0||0 (0%)|
|Phthisis bulbi||1||1||0||0||1||1 (2%)||0||0||0||0||0||0 (0%)|
|Corneal Edema >30 days||0||0||0||0||0||0 (0%)||1||1||0||0||1||1 (2%)|
|Wound leak/dehiscence||0||0||0||0||0||0 (0%)||1||1||0||0||1||1 (2%)|
|Iol capture||0||0||0||0||0||0 (0%)||0||0||1||1||1||1 (2%)|
|Total g||22||15||33||24||54 d||32 e (56%)||88||44||21||14||108 d||46 f (81%)|
a One patient had lens reproliferation into the visual axis in both time periods.
b Three patients had pupillary membrane in both time periods.
c One patient had corectopia in both time periods.
d One patient in the CL group and 1 patient in the IOL group changed from glaucoma suspect in the first time period to glaucoma in the second time period.
e Seven patients in the CL group had at least 1 adverse event in both time periods.
f Twelve patients in the IOL group had at least 1 adverse event in both time periods.
g For number of patients the total refers to the number of patients with at least 1 adverse event.
h Contact lens–related AEs included corneal abrasions, corneal ulcers, and episodes of keratitis.
During the first year after cataract surgery a lower percentage of contact lens patients experienced 1 or more adverse events compared to IOL patients (contact lens: 15/57; 26%, IOL: 44/57; 77%, P < .0001). After the first year there was a trend for a higher percentage of contact lens patients to experience an adverse event (contact lens: 24/57; 42%, IOL: 14/57; 25%, P = .073). Over the entire follow-up period, the proportion of contact lens patients experiencing an adverse event was lower than that of the IOL patients (contact lens: 32/57; 56%, IOL: 46/57; 81%, P = .008).
Table 1 further shows the number of patients who had at least 1 adverse event. For the majority, there was 1 event per patient. The exceptions are the following: In the contact lens group there were 4 contact lens–related adverse events among 3 patients in the first year and 14 events among 7 patients after the first year, for a total of 18 events among 10 patients. In the IOL group, during the first year, there were multiple instances of the following adverse events: lens reproliferation (27 among 23 patients); pupillary membrane (20 among 16 patients); corectopia (15 among 13 patients); and retained cortex (4 among 3 patients). The following adverse events occurred after the first year: pupillary membrane (5 among 3 patients) and hyphema (2 in 1 patient).
During the first year, in the contact lens group there were 22 adverse events among 15 patients and in the IOL group there were 88 events among 44 patients. When translated to an annual rate, the number of adverse events per year of follow-up was significantly lower in the contact lens group compared to the IOL group (contact lens: 0.4, IOL: 1.6, P < .0001). After the first year, there were 33 events among 24 patients in the contact lens group and 21 events among 14 patients in the IOL group, which yielded rates that were not significantly different in the 2 groups (contact lens: 0.2, IOL: 0.1, P = .15).
Compared to the first postoperative year, in which there was a total of 110 adverse events (contact lens: 22, IOL: 88), there were only 54 adverse events (contact lens: 33, IOL: 21) in years 2–5. A large majority of the adverse events during the 5 years of follow up in the IOL group occurred in the first year (88 of 108, 81%). Conversely, more adverse events in the contact lens group developed in years 2–5 than occurred in the first year (33 of 54, 61%).
Thirty of the 33 adverse events that developed in the contact lens group in years 2–5 were glaucoma related (n = 16) or contact lens related (n = 14). Seventeen of the 21 adverse events that developed in the IOL group in years 2–5 were visual axis related (n = 10) or glaucoma related (n = 7).
Additional Intraocular Surgeries
As shown in Table 2 , there were more patients with unplanned intraocular procedures in the IOL group (n = 8) than in the contact lens group (n = 4) during postoperative years 2–5. In the IOL group, 8 patients had procedures to clear visual axis opacities, 2 had glaucoma surgery, and 2 had an IOL exchange. In the contact lens group, 3 patients had procedures to clear visual axis opacities and 1 had glaucoma surgery.
|Type of Surgical Procedure a||Treatment|
|CL Group (57 Patients)||IOL Group (57 Patients)|
|During First Post-op Year||After First Post-op Year||Total||During First Post-op Year||After First Post-op Year||Total|
|# Pro||# Pat||# Pro||# Pat||# Pro||# Pat||# Pro||# Pat||# Pro||# Pat||# Pro||# Pat|
|Clearing visual axis opacities||8||6||3||3||11||8 b (14%)||44||34||10||8||54||39 b (68%)|
|Glaucoma surgery||1||1||1||1||2||2 (4%)||4||4||2||2||6||5 c (9%)|
|Repair retinal detachment||3||2||0||0||3||2 (4%)||0||0||0||0||0||0 (0%)|
|Repair wound dehiscence||0||0||0||0||0||0 (0%)||1||1||0||0||1||1 (2%)|
|IOL exchange||–||–||–||–||–||–||1||1||2||2||3||3 (5%)|
|Iridectomy/iridotomy||1||1||0||0||1||1 (2%)||1||1||0||0||1||1 (2%)|
|Lysis of vitreous wick||0||0||0||0||0||0 (0%)||1||1||0||0||1||1 (2%)|
|Additional surgical procedures||13||7||4||4||17||9 d (16%)||52||36||14||8||66||41 d (72%)|