Comparing Outcomes of Femtosecond Laser-Assisted Cataract Surgery and Conventional Phacoemulsification in a Randomized Controlled Trial

Summary

This protocol describes a randomized trial workflow for comparing femtosecond laser-assisted cataract surgery with conventional phacoemulsification in age-related cataract. It standardizes screening, allocation, operative steps, follow-up, and outcome analysis to support reproducible evaluation of early visual recovery, intraoperative energy use, and corneal safety.

Abstract

This protocol compares femtosecond laser-assisted cataract surgery (FLACS) with conventional phacoemulsification cataract surgery (CPCS) for age-related cataract using a standardized randomized trial workflow. A total of 113 patients were allocated 1:1 to FLACS (n = 56) or CPCS (n = 57), stratified by nuclear hardness, and assessed at Day 1, Week 1, Month 1, and Month 3. The protocol specifies eligibility screening, concealed allocation, harmonized perioperative care, predefined intraoperative settings, and masked outcome assessment. Primary and secondary outcomes included corrected and uncorrected distance visual acuity, refractive prediction, corneal endothelial cell density, central corneal thickness, intraoperative energy metrics, and adverse events. FLACS reduced cumulative dissipated energy and effective phaco time and showed better Day 1 visual acuity, smaller early central corneal thickening, and milder anterior chamber inflammation (all P < 0.05). At Month 1 and Month 3, between-group differences in visual acuity, refractive prediction error, absolute prediction error, endothelial cell loss, and complications were not significant (all P > 0.05). The protocol supports reproducible evaluation of early recovery advantages while showing comparable short-term safety for both procedures.

Introduction

Cataract remains the leading cause of reversible blindness globally, with its incidence rising sharply in parallel with the aging population trend. Recent epidemiological data indicate that age-related cataracts account for significant visual impairment in hundreds of millions of individuals worldwide^1,2. Conventional phacoemulsification cataract surgery (CPCS) is generally regarded as a mature technical system that has proven effective in the clinical treatment of cataracts³. However, with advances in refractive ophthalmology, postoperative patient expectations have shifted from basic visual restoration to high-quality refractive outcomes. Despite its widespread success, conventional phacoemulsification presents inherent limitations when addressing the rigorous refractive demands of contemporary patients⁴. The roundness and centrality of manual continuous curvilinear capsulorhexis (CCC) are highly dependent on the surgeon's clinical experience, and irregular capsular openings often cause displacement or tilt of intraocular lenses (IOLs) in the capsular bag, leading to severe higher-order aberrations and impaired postoperative contrast sensitivity. In addition, for eyes with a hard nuclear consistency, the total dissipative energy generated during routine surgery and the mechanical friction of instruments are more likely to cause irreversible thermal injury to corneal endothelial cells; after surgery, such obliterating changes will not recover on their own and result in chronic damage to the corneal endothelium⁵.

The introduction of femtosecond laser-assisted cataract surgery marks a significant transition toward image-guided precision in ophthalmology. This technology automates critical steps that were previously dependent entirely on manual dexterity. It uses the micron-level accuracy of infrared laser light to conduct transparent corneal incisions, perfectly round capsular dissection, and lens pre-splitting in an enclosed intraocular space via non-contact operations. Under the automated operating mode, repetitive surgical procedures exhibit high reproducibility and precision⁶. Anatomically, the anterior capsulotomy performed by the femtosecond laser demonstrates high consistency and a substantial overlap area; therefore, it provides a reliable physical basis for maintaining the stable positioning of the intraocular lens. For patients receiving premium intraocular lenses, such as multifocal or toric designs, FLACS effectively reduces postoperative lens eccentricity and tilt by executing precise incisions guided by preoperative optical coherence tomography. Furthermore, this precision offers substantial clinical benefits for eyes with compromised endothelial reserves or dense cataracts, where minimizing intraoperative ultrasound energy is critical for preserving corneal clarity.

FLACS has significant technological advantages, but whether it is necessary to promote its general use in clinical practice remains a matter of debate among academics. The lens fragmentation function of the femtosecond laser significantly reduces the subsequent ultrasound energy requirement, thereby alleviating oxidative stress and thermal damage to the corneal endothelium^5,6. Nevertheless, clinical application of this technology presents specific challenges. Application of the vacuum suction ring can induce subconjunctival hemorrhage, and laser-induced prostaglandin release may provoke intraoperative miosis, potentially complicating the surgical procedure⁷. Additionally, the substantial capital investment and consumable costs associated with femtosecond laser platforms necessitate careful consideration of their cost-effectiveness ratio in routine clinical settings. Current academic evaluations of this technology remain divided. Some studies highlight its irreplaceable protective effect in high-risk cases, whereas other investigations report no statistical difference in final visual outcomes between this technique and conventional surgery for routine cases. Recent retrospective and prospective studies have likewise reported favorable visual outcomes after FLACS, including in eyes receiving extended-depth-of-focus intraocular lenses, while optical-quality measurements indicate that patient selection and lens-related factors remain important^8,9,10.

Despite these theoretical advantages, evidence-based comparative evaluations between FLACS and CPCS have yielded inconsistent conclusions, particularly for early recovery and subgroup safety. The present JoVE protocol therefore describes a standardized randomized trial workflow for screening eligible age-related cataract patients, allocating participants by stratified block randomization, performing FLACS or CPCS with harmonized perioperative care, and interpreting visual, refractive, corneal safety, and adverse-event outcomes. The protocol is most applicable to centers comparing these procedures in adults with age-related cataract, especially where early recovery, dense nuclei, endothelial reserve, or premium intraocular lens planning are clinically relevant.

Protocol

The study protocol was approved by the Institutional Ethics Committee of Taiyuan Central Hospital (Approval No. YK2025102) and was conducted in accordance with the principles of the Declaration of Helsinki. Prior to inclusion, comprehensive counseling was provided to all participants regarding the differences between femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification cataract surgery (CPCS). The patients were explicitly informed about the procedural specifics, potential risks, and the additional out-of-pocket costs associated with the FLACS procedure. Written informed consent was obtained from all participants, ensuring they fully understand their right to choose the surgical method or withdraw from the study at any time without affecting their standard medical care.

1. Participant Screening and Enrollment

1. Continuously enroll patients scheduled to undergo phacoemulsification and intraocular lens implantation.
2. Assess eligible subjects using baseline evaluations.
3. Verify that patients meet the required inclusion criteria.
   1. Confirm that the patient is at least 50 years old, has a clinically diagnosed age-related cataract as the primary cause of visual impairment, and is scheduled for cataract surgery.
   2. Include only one eye per patient. For bilateral sequential surgery, select the first operated eye for the final analysis.
   3. Confirm that the preoperative visual acuity reduction is consistent with lens opacity and that postoperative visual function can be assessed.
   4. Confirm corneal transparency and obtain a qualified, reproducible corneal endothelial examination.
   5. Collect axial length, corneal curvature, and anterior chamber depth measurements for intraocular lens power calculation.
      NOTE: The one-eye rule avoids statistical confounding from correlated bilateral data.
4. Exclude patients with a history of intraocular surgery or severe ocular trauma in the operative eye.
5. Exclude patients with coexisting fundus or optic nerve diseases capable of significantly affecting postoperative visual outcome interpretation.
   NOTE: These conditions include moderate to severe macular degeneration, diabetic macular edema, retinal vein occlusion with macular edema, and significant optic nerve atrophy requiring optical coherence tomography assistance for evaluation.
6. Exclude patients exhibiting corneal lesions or corneal endothelial dysfunction with reduced baseline endothelial cell counts.
   NOTE: Examples include corneal dystrophy, corneal scarring, significant corneal edema, and Fuchs endothelial dystrophic change.
7. Exclude patients with inadequate mydriasis or posterior synechiae and active uveitis precluding standardized surgical procedures.
8. Exclude patients with significant laxity or dislocation tendency of the ciliary zonule, pseudohypoplasia syndrome, or expected need for complex surgical intervention.
9. Exclude patients with poorly controlled glaucoma or other serious systemic diseases affecting surgical safety and follow-up compliance.
10. Exclude patients deemed unsuitable for inclusion or unable to complete follow-up¹¹.

2. Randomization and Masking

1. Use a computer-generated random sequence created by an independent researcher to allocate subjects in a 1 to 1 ratio to either the femtosecond laser-assisted cataract surgery group or the conventional phacoemulsification cataract surgery group.
2. Apply permuted block randomization with a fixed block size of four to ensure approximately equal subject numbers in each group within each nuclear hardness stratum.
3. Stratify the participants prior to randomization utilizing the Lens Opacities Classification System III to grade nuclear hardness. Create separate randomization blocks for moderate sclerosis and advanced sclerosis to prevent unbalanced allocation of dense cataracts, which can substantially confound ultrasound energy metrics and subsequent endothelial safety outcomes.
4. Ensure allocation concealment by utilizing sequentially numbered, opaque, sealed envelopes prepared by an independent coordinator. Keep these envelopes inaccessible to the surgical team and patients until the final enrollment and baseline assessments are completed.
5. Open the randomization results only after completing baseline examinations and confirming enrollment.
   NOTE: Blinding of the surgical method is not conducted due to the inherent differences in the procedures.
6. Assign outcome assessors who are unaware of the group allocations to measure and interpret the core outcomes¹².
7. Assign an independent analyst to conduct the statistical analysis under blind coding conditions to minimize measurement and analysis bias.
8. Refer to Figure 1 for the flowchart detailing participant enrollment, randomization, follow-up, and analysis.

3. Preoperative and Perioperative Management

1. Assign a single senior surgeon to perform all operations to eliminate inter-surgeon variability. Ensure the surgeon possesses extensive experience in both femtosecond laser platforms and conventional phacoemulsification techniques.
2. Position the patient supine on the operating table and continuously monitor vital signs.
3. Administer topical anesthesia with 0.5% proparacaine hydrochloride eye drops three times at 5 min intervals before surgery.
4. Disinfect the periocular skin with 10% povidone-iodine and instill 5% povidone-iodine into the conjunctival sac for 3 min. Drape the surgical field with a sterile adhesive aperture drape.
5. Prescribe topical 1% prednisolone acetate suspension and 0.1% bromfenac sodium ophthalmic solution four times daily for four weeks. Instruct the patient to taper the corticosteroid dosage according to the severity of the anterior chamber inflammatory response.
6. Administer 0.5% timolol maleate ophthalmic solution twice daily if the postoperative intraocular pressure exceeds 21 mmHg. Reassess the intraocular pressure after 2 h to confirm hemodynamic stabilization.

4. Surgical Interventions

1. For the femtosecond laser-assisted cataract surgery group, dock the approved femtosecond laser platform using a liquid optical interface. Verify complete liquid fill, stable suction, correct centration, and absence of corneal folds on the optical coherence tomography display.
2. Perform a 2.2 mm primary clear corneal incision at the 11 o'clock position and execute a 5.0 mm anterior capsulotomy using a pulse energy of 4.0 µJ.
3. Conduct cross-pattern lens fragmentation using a pulse energy of 8.0 µJ and a spot separation of 10 µm.
4. If the liquid fill is incomplete, corneal folds obscure optical coherence tomography guidance, or vacuum is lost, stop laser activation and release suction. Re-dock the eye and repeat optical coherence tomography centration before resuming laser delivery.
5. After capsulotomy, inspect the capsular disk. Free any microadhesions or tissue bridges with a cystotome or capsulorhexis forceps before nucleus manipulation.
6. Treat intraoperative miosis with an intracameral mydriatic and ophthalmic viscoelastic support according to the predefined rescue protocol.
7. Transition the patient to the surgical microscope and perform gentle hydrodissection with balanced salt solution until the nucleus rotates freely within the capsular bag.
8. Remove the pre-fragmented nucleus with maximum longitudinal ultrasound power of 60% and a vacuum limit of 400 mmHg. Aspirate residual cortical material with the automated irrigation and aspiration handpiece.
9. Inject an ophthalmic viscoelastic device into the capsular bag and implant the posterior chamber intraocular lens. Aspirate all retained viscoelastic material.
10. Hydrate the corneal incisions with balanced salt solution and apply gentle pressure to the wound edge with a surgical sponge. Confirm a watertight seal without fluid leakage.
11. For the conventional phacoemulsification cataract surgery group, construct a 2.2 mm primary clear corneal incision at the 11 o'clock position using a steel keratome. Inject a cohesive ophthalmic viscoelastic device to maintain the anterior chamber.
12. Perform a manual continuous curvilinear capsulorhexis with a target diameter of 5.0–5.5 mm using capsulorhexis forceps. Confirm that the capsular opening is central, circular, and intact.
13. Perform hydrodissection with balanced salt solution to achieve cortico-cleaving separation and confirm unhindered nuclear rotation.
14. Disassemble the nucleus with a standard stop-and-chop technique. Use a maximum longitudinal ultrasound power of 60%, an aspiration flow rate of 35 mL/min, and a vacuum limit of 400 mmHg.
15. Clear the epinucleus and residual cortex with the irrigation and aspiration handpiece.
16. If pupil dilation is inadequate, enlarge the pupil pharmacologically or with ophthalmic viscoelastic support according to the predefined rescue protocol.
17. If zonular instability is suspected, reduce ultrasound power and aspiration and proceed cautiously.
18. Document any capsular tear, vitreous loss, or conversion to an alternative technique immediately.
19. Inject an ophthalmic viscoelastic device into the capsular bag and implant the posterior chamber intraocular lens. Aspirate all retained viscoelastic material.
20. Hydrate the corneal incisions with balanced salt solution and apply gentle pressure to the wound edge with a surgical sponge. Confirm a watertight seal without fluid leakage.
    NOTE: Ensure the implantation of a standardized aspheric monofocal intraocular lens across all participants. Strictly apply identical optical biometry equipment and contemporary power calculation formulas for both groups to reduce the confounding effects of different lens designs on postoperative visual quality.
21. Record intraoperative parameters uniformly for all participants.
    NOTE: Track cumulative dissipated energy (CDE), defined as the phacoemulsification system's recorded cumulative ultrasound energy exposure in percentage-seconds, together with ultrasound time, perfusate volume, and any intraoperative complications. Record device settings, software or version identifiers, and any rescue maneuvers in the case report form.

5. Follow-up and Outcome Evaluation

1. Conduct comprehensive postoperative evaluations at the predefined follow-up intervals of Day 1, Week 1, Month 1, and Month 3.
2. Assess the primary outcomes of corrected distance visual acuity at 1 month postoperatively and the corneal endothelial cell loss rate.
3. Evaluate secondary visual outcomes, including the trend of uncorrected distance visual acuity and corrected distance visual acuity across different time points.
4. Record postoperative refractive results and predictive accuracy indicators such as spherical equivalent, predictive error, and absolute predictive error.
5. Assess incision-related astigmatism changes and the stability of incision-induced astigmatism.
6. Measure postoperative changes in central corneal thickness, corneal edema grade, anterior chamber inflammatory response, and intraocular pressure.
7. Monitor safety outcomes in four categories: intraoperative capsular-bag-related events, persistent postoperative corneal edema, acute intraocular pressure elevation, and cystoid macular edema.
8. Screen for complications at every scheduled visit and record any additional unscheduled safety visits.
9. For a suspected complication, perform a targeted assessment and arrange additional follow-up until the event resolves or clinically stabilizes. If the event remains ongoing at Month 3, continue follow-up for up to 30 additional days or until resolution or stabilization, whichever occurs first.
10. Document the date of onset or detection, diagnostic findings and criteria, confirmatory tests, treatment, severity, relationship to surgery, status at each contact, and the date and basis of resolution or stabilization. For an unresolved event at study closure, record the last assessment and planned clinical follow-up.

6. Data Analysis

1. Calculate the required sample size prior to enrollment based on the expected difference in early postoperative corneal endothelial cell loss. Ensure the study has adequate statistical power (at least 80%) with an alpha level of 0.05.
2. Reserve a specific proportion for loss to follow-up to ensure adequate statistical power for the primary endpoint.
3. Conduct the primary data analysis according to the intention-to-treat principle, including all randomly assigned participants in the groups to which they were allocated.
4. Include all randomly assigned subjects in the between-group comparison of the primary outcome.
5. Define the per-protocol set as participants who received the allocated procedure without major protocol deviations and completed the Month 1 primary endpoint; compare these estimates with the intention-to-treat results as a sensitivity analysis.
6. Compare continuous results between groups using linear models.
7. Analyze repeated measures data using mixed-effects models to evaluate the interaction of time and group.
8. Include appropriate baseline values and clinically relevant covariates such as nuclear hardness in the models.
9. Use chi-square tests or Fisher's exact tests for categorical outcomes to calculate relative risks or hazard ratios along with corresponding 95% confidence intervals.
10. Describe adverse events by occurrence number and type, and analyze between-group differences for key complications.
11. Employ a mixed-effects model to handle missing data dynamically during longitudinal follow-up analyses.
12. Perform multiple imputations in the sensitivity analysis to evaluate the robustness of the results.
13. Perform all statistical analyses using SPSS Statistics and the Generalized Linear Mixed Models module.
14. To construct repeated-measures models, select Analyze, then Mixed Models, and then Linear in the software interface.
15. Report intention-to-treat estimates as the primary results and per-protocol estimates as sensitivity results for the primary outcomes. If conclusions differ, identify protocol deviations and missing-outcome patterns.
16. Use two-tailed statistical tests and set the threshold for significance at P < 0.05.
17. Refer to Supplementary File 1 for details on model construction, covariate selection, and imputation procedures.

Results

A total of 113 participants were included, with 56 allocated to the FLACS group and 57 allocated to the CPCS group. Baseline demographic, ocular, biometric, cataract-grade, refractive, and corneal safety variables were balanced between groups, supporting comparability for subsequent outcome assessment (Table 1).

Intraoperative measurements showed lower ultrasound-energy exposure in the FLACS group. CDE and effective phaco time were lower with FLACS than with CPCS (

Discussion

This protocol emphasizes reproducible implementation of FLACS and CPCS rather than outcome comparison alone. The principal procedural safeguards are standardized patient selection, concealed stratified randomization, identical perioperative care, controlled phacoemulsification settings, systematic recording of CDE and rescue maneuvers, and masked outcome assessment. These steps reduce avoidable variation and allow differences in energy use, early visual recovery, and anterior segment response to be interpreted within a c...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Case report form and device logs	Study site	N/A	Records software/version identifiers, device settings, rescue maneuvers, and protocol deviations; Reproducibility audit trail for surgical and statistical protocol
CellChek XL	Konan Medical	https://konanmedical.com/cellchek-sl-xl/	Specular microscope used for measurement of corneal endothelial cell density and morphology
CENTURION Vision System	Alcon Laboratories	https://www.myalcon.com/professional/cataract-surgery/surgical-equipment/centurion/	Phacoemulsification system for ultrasound emulsification and removal of cataract lens nucleus; ; maximum longitudinal ultrasound power 60%; vacuum limit 400 mmHg; aspiration flow 35 mL/min
IOLMaster 700	Carl Zeiss Meditec	https://www.zeiss.com/meditec/en/products/optical-biometers/iolmaster-700-us/specifications-us.html	Optical biometry device used for Measurement of axial length, corneal curvature, and intraocular lens power calculation
LenSx Laser System	Alcon Laboratories	https://www.myalcon.com/professional/cataract-surgery/surgical-equipment/lensx-laser-system/	Femtosecond laser system for cataract surgery for performing laser-assisted corneal incision, capsulotomy, and lens fragmentation; ; capsulotomy 5.0 mm at 4.0 microjoules; lens fragmentation 8.0 microjoules with 10 micrometer spot separation
SL-D701	Topcon Corporation	https://topconhealthcare.jp/products/sl701/	Slit-lamp biomicroscope used for preoperative and postoperative anterior segment examination
SPSS Statistics	IBM Corporation	v26.0; https://www.ibm.com/products/spss-statistics	Generalized Linear Mixed Models module; multiple imputation sensitivity analysis; Statistical analysis of clinical outcomes and group comparisons