Safety, effectiveness, and cost-effectiveness of immediate versus delayed sequential bilateral cataract surgery in the Netherlands (BICAT-NL study): a multicentre, non-inferiority, randomised controlled trial

Summary

Background

In an ageing population, efficiency improvements are required to assure future accessibility of cataract care. We aim to address remaining knowledge gaps by evaluating the safety, effectiveness, and cost-effectiveness of immediate sequential bilateral cataract surgery (ISBCS) versus delayed sequential bilateral cataract surgery (DSBCS). We hypothesised that ISBCS is non-inferior to DSBCS, regarding safety and effectiveness, and being superior in cost-effectiveness.

Methods

We did a multicentre, non-inferiority, randomised controlled trial, which included participants from ten Dutch hospitals. Eligible participants were 18 years or older, underwent expected uncomplicated surgery, and had no increased risk of endophthalmitis or refractive surprise. Participants were randomly assigned (1:1) to either the ISBCS (intervention) group or DSBCS (conventional procedure) group, using a web-based system stratified by centre and axial length. Participants and outcome assessors were not masked to the treatment groups because of the nature of the intervention. The primary outcome was the proportion of second eyes with a target refractive outcome of 1·0 dioptre (D) or less 4 weeks postoperatively, with a non-inferiority margin of –5% for ISBCS versus DSBCS. For the trial-based economic evaluation, the primary endpoint was the incremental societal costs per quality-adjusted life-year. All analyses were done by a modified intention-to-treat principle. Costs were calculated by multiplying volumes of resource use with unit cost prices and converted to 2020 Euros (€) and US$. This study was registered with ClinicalTrials.gov, number NCT03400124, and is now closed for recruitment.

Findings

Between Sept 4, 2018, and July 10, 2020, a total of 865 patients were randomly assigned to either the ISBCS group (427 [49%] patients; 854 eyes) or DSBCS group (438 [51%] patients; 876 eyes). In the modified intention-to-treat analysis, the proportion of second eyes with a target refraction of 1·0 D or less was 97% (404 of 417 patients) in the ISBCS group versus 98% (407 of 417) in the DSBCS group. The percentage difference was –1% (90% CI –3 to 1; p=0·526), thereby establishing non-inferiority for ISBCS compared with DSBCS. Endophthalmitis was not observed or reported in either group. Adverse events were comparable between groups, with only a significant difference in disturbing anisometropia (p=0·0001). Societal costs were €403 (US$507) lower with ISBCS than with DSBCS. The cost-effectiveness probability of ISBCS versus DSBCS was 100% across the willingness-to-pay range of €2500–80 000 (US$3145–100 629) per quality-adjusted life-year.

Interpretation

Our results showed non-inferiority of ISBCS versus DSBCS regarding effectiveness outcomes, comparable safety, and superior cost-effectiveness of ISBCS. National cost savings could amount to €27·4 million (US$34·5 million) annually, advocating for ISBCS if strict inclusion criteria are applied.

Funding

Research grant from The Netherlands Organization for Health Research and Development (ZonMw) and Dutch Ophthalmological Society.

Introduction

In 2019, WHO reported that more than 65 million people have visual impairment or blindness due to cataract and an estimated 6·9 billion US dollars (US$) are needed to cover the gap of costs for unaddressed cataract globally.¹ In the Netherlands, approximately 224 800 new individuals were diagnosed with cataract in 2021.² Age-related cataract can be treated by surgical removal of the cloudy lens and replacement with an artificial intraocular lens, and is fully reimbursed by Dutch health insurance. The ageing population, a rising demand for care worldwide, and a sustained increase of health-care expenditures emphasise the need for improvements in efficiency of cataract care.

Routine practice consists of surgery in both eyes on separate days, known as delayed sequential bilateral cataract surgery (DSBCS). One way to improve efficiency is to perform same-day surgery on both eyes, called immediately sequential bilateral cataract surgery (ISBCS). Potential advantages include faster visual recovery, fewer hospital visits, less dependence on homecare, and lower costs. Some countries have started to implement ISBCS on a larger scale,³ and the COVID-19 pandemic has led to adjustment of national guidelines (eg, by the UK Royal College of Ophthalmologists) and subsequent implementation of ISBCS.⁴ Similarly, Dutch cataract guidelines were adjusted in November, 2021, allowing performance of ISBCS. Nevertheless, in most countries, DSBCS is still regarded best practice for cataract surgery.

Research in context

Evidence before this study

To identify available evidence before the start of the BICAT-NL trial, we searched the following databases up to Dec 15, 2016: MEDLINE, Cochrane library, Current Controlled Trials, ClinicalTrials.gov, and NHS Centre for Reviews and Dissemination. A combination of the following search terms was used: “bilateral cataract”, “adult”, “elderly”, “human”, “immediate sequential bilateral cataract surgery”, “ISBCS”, “same-day bilateral cataract surgery”, “simultaneous bilateral cataract surgery”, “phacoemulsification”, “delayed sequential bilateral cataract surgery”, “DSBCS”, “refraction”, “complications”, “visual acuity”, “patient satisfaction”, “patient-reported outcomes”, “PROMs”, “cost-effectiveness”, “economic evaluation”, “systematic review”, “randomized clinical trial”, “RCT”, “cohort study”, “case-control study”, “patient series”, “economic evaluation”, and “cost-effectiveness analysis”. We found only one systematic review and meta-analysis including three randomised controlled trials, and the quality of evidence was reported to be low to moderate. Only one of these randomised controlled trials reported on refractive outcomes, but this study was underpowered to report on refractive outcomes within currently accepted targets (1·0 dioptre [D] and 0·5 D). Pooled estimates on complications and patient-reported outcomes showed no differences between patients undergoing immediate sequential bilateral cataract surgery (ISBCS) and delayed sequential bilateral cataract surgery (DSBCS), but with considerable heterogeneity between studies. Furthermore, several economic evaluation studies were identified that indicated substantial cost savings in favour of ISBCS, but only one study evaluated cost-effectiveness of ISBCS compared with DSBCS. However, the identified study was designed as a decision analytic model study, was not based on a randomised controlled trial, and did not use preferred calculation methods for quality-adjusted life-years. Recently, a Cochrane systematic review reported the need for well designed cost-effectiveness studies comparing ISBCS and DSBCS.

Added value of this study

The BICAT-NL study was designed to address the knowledge gaps on refractive outcomes (as a safety and effectiveness measure) and cost-effectiveness of ISBCS compared with DSBCS. The results of our trial showed that ISBCS was non-inferior to DSBCS regarding the proportions of patients with a postoperative refraction within 1·0 D and 0·5 D in second eyes. In addition, this study provides evidence that ISBCS was superior to DSBCS in terms of cost-effectiveness.

Implications of all the available evidence

This trial provides robust and useful information about clinical outcomes and potential benefits of ISBCS for patients in need of cataract surgery and for cataract surgeons. Furthermore, it provides information about cost-effectiveness that can be used in the collaboration with health-care providers during the implementation process of the procedure in routine practice. Moreover, the results can assist policy makers in the development or adjustment of national cataract guidelines.

Reluctance towards ISBCS stems from concerns over bilateral complications, most importantly endophthalmitis, a rare but potentially devastating ophthalmic infection. However, incidence rates of endophthalmitis have decreased significantly over the years with widespread use of intraocular antibiotics,⁵ and the calculated risk of bilateral endophthalmitis is extremely low (one in 70 million cases).⁶ Reported cases of bilateral endophthalmitis in ISBCS can be attributed to faults in aseptic procedures and non-adherence to international principles for ISBCS.⁷ Another concern, albeit with little evidence in the literature, relates to the lack of having the refractive outcome of the first eye available when determining the intraocular lens power for second-eye surgery.⁸ Finally, high-quality evidence on cost-effectiveness of ISBCS versus DSBCS is scarce. Several studies reported costs of ISBCS,9, 10, 11, 12, 13 but only one model-based cost-utility analysis comparing ISBCS with DSBCS is available.¹⁴ Furthermore, quality-adjusted life-years (QALYs) were modelled based on visual acuity rather than directly assessed using health-related quality-of-life questionnaires, as recommended in guidelines for conducting and reporting cost-effectiveness studies.¹⁵

In the bilateral cataract surgery in the Netherlands (BICAT-NL) study, we aim to address remaining knowledge gaps by evaluating the safety, effectiveness, and cost-effectiveness of ISBCS compared with DSBCS. We hypothesised that ISBCS is non-inferior to DSBCS, regarding safety and effectiveness, and being superior in cost-effectiveness.