The role of primary intraocular lens implantation in the risk of secondary glaucoma following congenital cataract surgery: A systematic review and meta-analysis

Methodological quality of the review: Low confidence

Authors: Zhang S, Wang J, Li Y, Liu Y, He L, Xia X.

Region: Not stated

Sector: Service delivery

Subsector: Quality of clinical care

Equity focus: Not stated

Review type: Other review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background:
Cataract is a common ocular disease, characterised by the opacification of the crystalline lens. Based on etiology, cataracts can be divided into several categories: congenital, age-related, metabolic, drug-induced, toxic and traumatic.

With the development of surgical techniques and biomaterials in recent decades, most pediatric ophthalmologists reached the consensus that primary IOL implantation is valid and safe for children above the age of 2 years. However, considering the pros and cons of primary IOLs, the ocular anatomical factors in children, and the postoperative complications, it is still controversial which surgical option to choose for children with congenital cataract under the age of 2 years.

Objectives:
Evaluate the incidence of secondary glaucoma in patients under the age of 2 years who underwent congenital cataract surgery with or without primary intraocular lens (IOL) implantation.

Main findings:
A total of eight publications with 892 eyes were included in the final meta-analysis.

Authors note that when comparing primary IOL with aphakia only, the heterogeneity of effect size was 47% (P=0.09). A random effects model was used for the meta-analysis, with results favouring primary IOL (RR=0.61, 95% CI: 0.33-1.14). Authors found no statistically significant difference was found in the incidence of postoperative glaucoma between the two conditions (P=0.063).

When comparing primary IOL with aphakia and secondary IOL, the heterogeneity of effect size was 42% (P=0.10). The random effects model used for the meta-analysis favoured again primary IOL (RR=0.63, 95% CI: 0.35-1.12). However, the incidence of postoperative glaucoma between the two conditions was not significantly different (P=0.072).

When authors analysed data for the subpopulation with bilateral congenital cataract, they reported no heterogeneity (0%), and findings from the meta-analysis favouring primary IOL (RR=0.44, 95% CI: 0.24-0.83). Moreover, a significantly lower incidence of postoperative glaucoma was determined for patients with primary IOL (P=0.016).

When comparing primary IOL with aphakia and secondary IOL in bilateral congenital cataract, the heterogeneity of effect size was 27% (P=0.24). The results of a random effects model used for the meta-analysis favoured again primary IOL (RR=0.44, 95% CI: 0.19-1.00). Moreover, patients with primary IOL had a significantly lower incidence of postoperative glaucoma (P=0.042).

When authors analysed the data of patients with unilateral congenital cataract, in this population, the heterogeneity of effect size was 18% for primary IOL compared with aphakia alone (P=0.30). A random effects model was used for the meta-analysis, and no statistically significant difference was found in the incidence of postoperative glaucoma between these two conditions (RR=0.88, 95% CI: 0.45-1.72, P=0.710).

Lastly, when comparing primary IOL with aphakia and secondary IOL in patients with unilateral congenital cataract, the heterogeneity of effect size was 0% (P=0.44). The random effects model was used for meta-analysis. The incidence of postoperative glaucoma was not statistically different between the two conditions (RR=0.87, 95% CI: 0.50-1.50, P=0.612).

Methodology:
Studies comparing congenital cataract treatment with or without primary IOL implantation were identified by a literature search in the following databases: Medline/PubMed, Embase/Ovid, and Web of Science. Searches were performed in November 2018. Furthermore, authors conducted a manual search of the reference lists from each identified article to acquire additional related studies or references.

Selected trials fulfilling the following inclusion criteria were included in the analysis: (1) patients with a confirmed diagnosis of congenital cataract; (2) patients who underwent cataract extraction surgery; (3) age at cataract extraction was below 2 years; (4) the study compared cataract surgery with and without primary IOL implantation; (5) prospective or retrospective design; and (6) development of secondary glaucoma as the primary outcome measure. Two authors independently screened studies for inclusion and extracted data of included studies.

The outcome measure was defined as the long-term secondary glaucoma rate, which means glaucoma developed at least one year after cataract surgery.

Authors presented data as numbers or rates. Forest plots were performed using the software R version 3.5.1, and the R package “meta”. Authors selected the incidence of secondary glaucoma as the outcome, and the relative risk ratios (RRs) and 95% confidence intervals (CIs) of the results were compared. Due to the high likelihood of heterogeneity among the selected randomised trials and observational studies, a random effects model was used to evaluate pooled effects. Heterogeneity between studies was assessed using the I² statistic and the X² test. Publication bias was calculated using the Egger test (P>0.05 was considered no publication bias) and assessed visually with funnel plots.

Applicability/external validity:
Authors report that the incidence of secondary glaucoma is variable and depends on the age at the time of surgery, on the primary or secondary IOL implantation method, on the ocular anatomy, and on the follow-up duration. Therefore, ophthalmologists need to define personalised treatment strategies for patients with congenital cataract. In addition, it is important in clinical practice to detect IOP periodically during a long-term follow-up, because early intervention is the most effective way to reduce the risk of secondary glaucoma. Meanwhile, further studies are needed to better define the timing and approaches of the surgical procedures that can reduce the incidence of secondary glaucoma. In addition, authors highlighted some limitations which need to be considered when interpreting the results.

Geographic focus:
Authors do not discuss the applicability of findings to low and middle income countries.

Summary of quality assessment:
Low confidence was attributed to the conclusions about the effects of this study, as important limitations were identified. Authors did not conduct thorough searches of the literature to ensure that all relevant studies were included, therefore impacting on the validity of findings. In addition, it is not clear the level of methodological quality of each included study impacting on the review findings’ reliability.