Congenital cataract is one of the leading causes of visual impairment and blindness in children worldwide. It is estimated that the prevalence of congenital cataract is 4 to 5 patients per 10 children.1 It mostly appears at birth or the first decade of life and can be unilateral or bilateral.2 Early diagnosis and timely treatment of congenital cataract play important roles in saving vision and developing normal visual function. Cataract is a disease that can be treated by surgery. It is generally accepted that the treatment for patients with congenital cataract older than 2 years is cataract extraction combined with primary intraocular lens (IOL) implantation.3 As for patients younger than 2 years, wearing contact lenses or spectacles is the mainstream treatment to correct the refractive errors after cataract extraction.4,5 However, this treatment would cause many problems, such as noncooperation in wearing the lens, risk of corneal infection, and the high cost of the contact lens.6,7 In recent years, with the increasing use of primary IOL implantation after cataract extraction in patients younger than 2 years, some ophthalmologists advocated this practice.8,9 They considered that the permanent correction had the advantage of improving vision development and avoided the disadvantage of wearing contact lenses as we mentioned earlier.10 However, other researchers hold an objective opinion because primary IOL implantation in patients younger than 2 years would cause a higher risk for postoperative complications, such as glaucoma, visual axis opacification (VAO), strabismus, and inflammatory response.11 In addition, the elongation of the eye axis might lead to an insufficient correction so that the patients have to wear additional spectacles when they grow up. Controversies still exist on whether to undergo primary IOL implantation after cataract extraction in patients younger than 2 years because of the single study design and small sample sizes in individual studies. Herein, we performed a meta-analysis to evaluate the visual acuity and complications between the primary IOL implantation group and contact lens–wearing aphakia group after cataract extraction in patients with congenital cataract younger than 2 years.
Inclusion and Exclusion Criteria
The study included patients with congenital cataract who underwent cataract extraction, either with primary IOL implantation or contact lens wearing. The outcomes included visual acuity measured using the logarithm of the minimum angle of resolution notation at least. The age of the patients was younger than 2 years. Patients with persistent fetal vasculature, microphthalmos, microcornea, uveitis, congenital glaucoma, and Lowe syndrome were excluded. The non–English language publications were excluded from this study.
Databases and Search Strategy
PubMed, Web of Science, EMBASE, Cochrane Library, and Google Scholar were searched for the study in March 2019. One or a combination of the following terms was searched: infant cataract, congenital cataract, pediatric cataract, IOL implantation, IOL, aphakia, contact lens, and CL. Two independent investigators (J.C. and Y.C.) completed the screening process. If 2 investigators disagreed with each other, it was solved by the third investigator (Y.Z.) who would participate in the discussion.
Quality Assessment and Data Extraction
Cochrane Collaboration's tool for risk of bias was used to assess the qualities of included documents from 7 portions12: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other sources of bias. Data were extracted from every study individually. The number of the following events was extracted: glaucoma, VAO, and strabismus. Visual acuity recorded by the logarithm of the minimum angle of resolution unit was extracted: mean value and SD.
All statistical analyses were performed using STATA (version 14.1). Continuous outcomes were estimated by weighted mean difference (WMD) with 95% CI. Categorical outcomes were estimated by relative risk (RR) with 95% CI. If the P value was less than .05, the comparison was statistically significant. The heterogeneity across studies was assessed with the Q test and I2 statistic.13,14 Because the enrolled study included randomized controlled trials (RCTs) and non-RCTs, we performed subgroup analyses. Sensitivity analyses were also performed by excluding one study at a time to explore the results. The Begg funnel plot was used to measure the publication bias.15
The process of our search is shown in Figure 1. A total of 2916 records were identified through database searching. After duplicates were removed, 1436 records were excluded, and 36 records of full-text studies were assessed for eligibility and further screening. Finally, we included 7 studies in this meta-analysis.16–22
Characteristics of Included Studies and Risk of Bias
The characteristics of the included studies are shown in Table 1A and 1B. This meta-analysis enrolled 3 RCTs, one cohort study, and 3 comparative studies. Overall, 675 eyes (337 in the aphakia group and 338 in the IOL group) were analyzed. Two studies were performed in India, one in China, one in the Czech Republic, and one in the United Kingdom, and 2 studies were multicenter studies. The follow-up durations ranged from 1 to 5 years. The risk of bias for all studies is shown in Figure 2.
The visual acuities were compared between the 2 groups at the end of the follow-up period in all included studies. The forest plot showed that vision after primary IOL implantation was significantly better than vision after contact lens wearing (WMD = 0.161; 95% CI, 0.108-0.214; P = .000). The heterogeneity of this analysis was 14.6% when the fixed-effects model was applied23 (Figure 3). A subgroup analysis stratified by study design indicated that it was not the source of statistical heterogeneity (Figure 4). In the sensitivity analysis, omitting a single study at a time did not show a significant change in the overall results. The Begg test indicated no evidence of publication bias (PBegg = .368).
Five studies with a total of 597 eyes compared the occurrence of glaucoma between the primary IOL implantation group and the contact lens–wearing group. The forest plot showed no statistically significant difference between the 2 groups (RR = 1.30; 95% CI, 0.63-2.67; P = .478). The heterogeneity of this analysis was 47.9% when the fixed-effects model was applied (Figure 5). The subgroup analysis stratified by study design and the sensitivity analysis revealed no significant change in the overall results.
Visual Axis Opacification
Five studies with a total of 597 eyes compared the occurrence of VAO between the primary IOL implantation group and the contact lens group. The forest plot showed that there was a statistically significant difference between the 2 groups. It was indicated that primary IOL implantation increases the incidence of VAO compared with contact lens wearing (RR = 0.23; 95% CI, 0.13-0.42; P = .000). The heterogeneity of this analysis was 31.1% when the fixed-effects model was applied (Figure 6). The subgroup analysis stratified by study design and the sensitivity analysis were stable, proving the rational outcome (Figure 7).
Five studies that involved 266 patients compared the strabismus occurrence between the 2 groups. The forest plot showed no statistically significant difference (RR = 1.06; 95% CI, 0.91-1.24; P = .436). The heterogeneity of this analysis was 0% when the fixed-effects model was applied (Figure 8).
Although primary IOL implantation for patients younger than 2 years is highly debated, studies comparing outcomes between primary IOL implantation and contact lens wearing are still limited. Therefore, we conducted the current meta-analysis to summarize stronger evidence based on the published literature.
In this analysis, the IOL group had better visual outcomes than the aphakia group. The results indicated that primary IOL implantation achieved better visual outcomes than contact lens wearing after cataract extraction in patients younger than 2 years. The IOL implantation process provides a stable retinal image with minimal aniseikonia and improved biocular vision.24 Awner et al.25 showed that visually immature children with unilateral traumatic cataracts had better visual outcomes than those with infantile cataracts. They suggested that preinjury visual maturation may have played a role in these results. The development of the visual pathway begins with ganglion cells forming the optic nerve. After processing, it guides these neurons to the lateral geniculate nucleus and finally onto the visual cortex. After birth, visual stimuli modify and refine the genetically programmed process. The constant stimuli produced by the IOL can maintain visual development progress. Hence, it was presumed that primary IOL implantation in patients with congenital cataract younger than 2 years is more effective than contact lens wearing.
For glaucoma, there was no significant difference between the 2 groups in our analysis. Another meta-analysis suggested that the IOL seemed to have a reduced risk for early- to intermediate-onset glaucoma,26 but the selective bias caused by the study design of included studies might exist. Zhang et al.27 also found the same conclusion through the meta-analysis. Of interest, the prevalence of glaucoma in unilateral congenital cataract was similar in eyes with or without primary IOL implantation. A theory was proposed that IOL implantation can block the chemical material from the vitreous to the anterior chamber. The lack of structural support and the damage of the trabecular meshwork appeared in the aphakia state, which may induce glaucoma. The drainage angle was supported by the IOL in case of the collapse of the trabecular meshwork.28 However, Kirwan et al.29 considered that surgery for congenital cataract at an early age increased the risk for glaucoma development regardless of whether the eye was aphakic or pseudophakic. Trivedi et al.30 found different prevalence between the IOL group and the aphakia group at all ages but no different prevalence in the operation under 4.5 months. This might be the reason why our results had no significant difference because the mean surgical time of our study is very young. Therefore, it is hard to draw any conclusions.
After cataract surgery, anisometropia or aniseikonia is the main reason for strabismus formation. The more difficulty in fusion leads to a higher incidence of amblyopia by 2 eyes competition. The worse cooperation with occlusive treatment causes secondary strabismus more frequently. A study found that the visual acuity preoperatively and postoperatively and the presence or absence of amblyopia postoperatively were associated with the appearance of strabismus.31 It seems that primary IOL implantation may decrease the risk for strabismus. On the contrary, there was no significant difference between the 2 groups in our results. Our analysis had found no higher risk of strabismus among primary IOL implantation compared with contact lens wearing. David et al.32 found a similar prevalence of strabismus between IOL groups and aphakia groups, whereas the lower prevalence of strabismus in IOL groups (13%) compared with aphakia groups (36%) was found in the study of Lim et al.33 We considered that the small sample size and short follow-up duration could result in difference. According to the literature, eye misalignment during infancy under 2-year-old was associated with severe deficits in stereopsis.34 No evidence showed that primary IOL implantation had a high prevalence of strabismus till now. Therefore, early correction of refractive errors and cataract extraction are essential to patients with congenital cataract younger than 2 years.
Visual axis opacification is due to fibrous membranes caused by lens epithelial cell (LEC) proliferation, and it is one of the major issues in pediatric cataract surgery. Rowe et al.35 speculated that the vitreous scaffold, humoral inflammatory medium, and the presence of fibrins were the keys to enhance LEC proliferation. The VAO incidence of the IOL group was higher than that of the aphakia group according to our analysis. We assumed that the structure of the IOL provided a path for LEC migration, which is in accordance with most previous studies.36–38 Many factors could lead to the incidence of VAO such as surgeon's experience, surgical techniques, prolonged use of topical steroids, and the type of IOL. The gold standard in congenital cataract surgery is the combination of cataract extraction, posterior continuous curvilinear capsulorhexis, and anterior vitrectomy,39 and most of our included studies were operated with such techniques. However, 44% of patients still occur VAO after performing the aforementioned surgery techniques.37 For the implanted IOL, the hydrophilic material had a higher risk to induce VAO than the hydrophobic material. It is probably because the IOL material attracts phosphorus and calcium ions to form the deposits. However, there is no significant difference between the single-piece and 3-piece IOLs.40 According to Van Looveren et al.41, long-term follow-up reported, children maintained a clear visual axis after performing bag-in-the-lens (BIL) IOL implantation. In addition, a vitro study also showed that LEC proliferation was decreased when using this technique.42 Concerning the optic capture techniques, posterior capsulorhexis with optic capture developed by Gimbel could prevent opacification of the visual axis.43 Posterior vertical capsulotomy with optic entrapment of the IOL developed by Robert Stegmann also showed the effect in reducing VAO.44 Both techniques kept the Elschnig pearls in the sealed bag to prohibit LEC migration and achieved stable IOL fixation. Hence, it brings us helpful enlightenment that choosing the appropriate surgical technique, the hydrophobic IOLs with square edge, and BIL IOL implantation might decrease the incidence of VAO. Though with its high occurrence, VAO can be removed by secondary surgery. It would be inappropriate to dismiss the primary IOL treatment based on a treatable complication.
However, there were still several limitations in this meta-analysis. First, our study included 3 RCTs, one cohort study, and 3 comparative studies; therefore, the presence of selection bias is possible. Second, these data were extracted from several studies so that it is hard to unify surgeons, surgical procedures, types of IOLs, and the wearing time of contact lenses. Last but not the least, some studies did not provide sufficient data or difference of the measuring units, which may lead to bias. Finally, there might be language bias because the meta-analysis included only studies published in English.
In conclusion, we suggest implantation of the primary IOL during congenital cataract surgery for children younger than 2 years. In addition, the techniques to reduce the incidence of VAO, such as optic capture techniques and BIL IOL implantation techniques, should be used. Multicenter, randomized clinical trials with long-term follow-up are required to further clarify this conclusion.
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