Study Design
Single-centre, prospective, single-masked, randomised case-control study in a university teaching hospital. Ethics approval was obtained (19/WA/0272) and written informed consent obtained for all patients The study adhered to the tenets of the Declaration of Helsinki and the UK Data Protection Act (2018).
Inclusion criteria were adult patients over 18 years of age with full capacity and symptomatic cataract(s) and at least 1.50D of corneal astigmatism on IOL Master 700 biometer (Carl Zeiss Meditec, AG, Germany). Regularity of the corneal astigmatism was confirmed by Scheimpflug tomography (Oculus Inc, Arlington, Washington, USA). Exclusion criteria were amblyopia; corneal scarring; glaucoma; previous ocular surgery; retinal pathology causing visual impairment; or any ocular/neurological condition affecting vision. Patients with corneal astigmatism of over 5.00D were excluded.
Patients were randomised to either the ‘fully tailored’ (FT) or the ‘off the shelf’ group (OTS). Randomisation was performed using a shuffled envelope system, performed by non-clinical member of staff not involved in the study. The first treated eye was used as the ‘study eye’ for statistical analysis. The surgical team were not masked to the treatment arm. All other participants including patients were masked.
The refractive target for all subjects was emmetropia. The Rayner aspheric RayOne single-piece, hydrophilic acrylic TIOL RAO610T (Rayner, Worthing, West Sussex, UK) was implanted in both study arms.
In the FT group patients received a TIOL with full correction of the corneal astigmatism, with keratometry readings from the IOL Master 700 (Carl Zeiss Meditec, AG, Germany) entered in the online Raytrace Premium calculator (Rayner Ltd, Worthing, UK), with an on-axis surgically induced astigmatism (SIA) estimate of 0.25D for each case. The posterior corneal astigmatism option was not utilised as this function was installed following study commencement.
The OTS group subjects received either a 2.00D or 4.00D cylinder TIOL, with residual corneal astigmatism corrected by OCCI. The amount of astigmatism corrected by OCCI was estimated to be 0.25D, when using a 2.4-millimetre (mm) keratome, and 0.50D when using a 2.75mm keratome, permitting up to 1.00D of correction 9-10. The choice of 2.00D or 4.00D TIOLs was based on the patient’s baseline biometric astigmatism. For example, a patient with astigmatism of 2.50D would receive a 2.00D cylinder TIOL along with an on-axis OCCI using 2.4mm keratome to induce a further 0.25D of correction (in addition to the 0.25D induced by the on-axis main wound incision). Where a total of 1.00D of additional astigmatism correction was required, the main wound was enlarged using a 2.75mm keratome, and this was coupled with an OCCI using the 2.75mm keratome. In cases where an astigmatic overcorrection was calculated pre-operatively, ‘off-axis’ incisions were used to offset this. The total estimated surgically corrected astigmatism delivered via the main corneal wound (and any required OCCI) was applied as the SIA into the Raytrace software.
Surgical technique
Prior to surgery, eyes were marked at the slit-lamp under topical anaesthesia using a 30-gauge insulin needle and a sterile marker pen, with limbal markings placed at 0o and 180°. All surgeries were performed by senior surgeons under local or general anaesthesia using a phacoemulsification technique. Intra-operatively, a Mendez ring was used to mark the eye and align the TIOL to its intended axis. In the OTS group, OCCIs were performed using a 2.40mm or 2.75mm keratomes.
Follow-up
Patients received a post-operative regimen of 0.5% chloramphenicol drops four times per day for 2 weeks, and dexamethasone 0.1% drops four times per day for four weeks. Patients were reviewed within two weeks (to check rotational stability of the TIOL) and then at 4 weeks (4W) and 6 months (6M). The stability of the TIOL was reviewed using the scale on the vertical arm of the slit lamp following pupil dilatation.
Primary outcome measures were post-operative monocular uncorrected distance visual acuity (UDVA) and best-corrected distance visual acuity (BCVA) in logMAR, and residual subjective refractive cylinder (D).
Secondary outcome measures included patient-reported outcome measures (PROMs) including CATPROM-5 (11) and EuroQoL EQ-5D-3L questionnaire scores (12), TIOL rotational stability, and adverse events. Vectoral analysis was performed using the Alpins vector method 13 with analysis of the target induced astigmatism (TIA), surgically induced astigmatism (SIA), difference vector, angle of error, magnitude of error, correction index, index of success, and coefficient of adjustment. Patients underwent corneal Scheimpflug tomography (Oculus Inc, Arlington, Washington, USA), Spectralis optical coherence tomography (Heidelberg Engineering Inc, Heidelberg Germany), and corneal endothelial cell counts (Nidek Co. Ltd.).
Statistical analysis
Statistical analysis was performed using GraphPad Prism version 8.0.0 for Mac (GraphPad Software, San Diego, California USA). Alpins vector analysis was performed using the online VekTrAK software (available at http://www.assort.com).
Parametric data were analysed with student unpaired t-test with statistical significance set at p<0.05. The Rasch-calibrated Cat-PROM5 scores were analysed using the Excel macros system provided by the CATPROM-5 developer 11. The EQ-5D-3L index scores were analysed using the methods outlined for UK data sets 12. Patient demographic data was compared using the Fisher’s exact test.
Sample Size Power Calculations
This study was largely undertaken during the COVID pandemic, when lockdown periods unfortunately limited the numbers of patients we could recruit. Our sample size of 41 subjects in the FT group (43 in the OTS group) at 6 M was determined sufficient to achieve a 95% chance of detecting a 0.10logMar visual acuity difference post-operatively at a = 0.05 considering a SD (derived from those documented at 6M in the FT group (Table 2)) of 0.13logMAR UDVA and 0.09logMAR BDVA, and a 95% chance of detecting a 0.33D difference in post-operative refractive cylinder at a = 0.05 considering a SD in post-operative refractive cylinder of 0.42D (Table 2).