Because cataract is the most common cause for blindness, cataract surgery is the most frequently performed ophthalmic operation.1 In conventional cataract surgery (CCS), corneal incisions are performed with a keratome blade, and a curvilinear capsulorhexis is performed with a forceps or cystotome. After the fragmentation of the lens nucleus, phacoemulsification and nucleus removal are conducted. CCS is one of the safest surgical procedures in ophthalmology, but some intraoperative steps could be difficult, such as corneal incision, anterior capsulotomy, and lens fragmentation. Certainly, these steps are dependent on the surgeons' experience and proficiency. Assistance from a more automated technique could compensate for human error and help to achieve reproducible results. Ten years ago, Nagy et al. introduced the femtosecond laser that has been used in recent years to assist in these critical steps during cataract surgery.2 Numerous studies show potential advantages of femtosecond laser–assisted cataract surgery (FLACS), such as improved circularity of capsulotomies, reduction of endothelial cell loss (ECL), better IOL position, less corneal swelling in the early postoperative period, and decreased effective phacoemulsification time (EPT).3–7 The mechanical trauma compared with manual corneal incisions also seems to be reduced.8 Corneal incisions from a laser result in lower endothelial gaping, endothelial misalignment, Descemet membrane detachment, and posterior wound retraction.9 Although FLACS was reported to result in more pronounced cell death, no effect on the development of posterior capsule opacification (PCO) was detected in vitro, whereas clinical studies showed higher PCO rates after CCS.10–12 The high purchase price and costs of use associated with FLACS are passed on to patients, making it a more expensive procedure. For this reason, FLACS was not viewed as a cost-effective procedure.13 Another concern in some clinics is the need for shuttling the patient between the sterile operating room and the room where laser application is performed, prolonging the operating time.14
To date, various groups have published meta-analyses to evaluate the differences between FLACS and CCS but without proving the superiority of either procedure.15–19 It should be noted that Day et al. and Chen et al. only included randomized controlled trials (RCTs).16,17 Ye et al. only analyzed prospective studies.19 Furthermore, the latest meta-analysis that performed literature search was in May 2016.17 Since then, additional trials have been published. Because the need for cataract surgery will increase due to demographic ageing, it is of prime importance to find out the most effective, safe, and satisfying options for patients.1 Our updated meta-analysis of literature investigates the role of laser-assisted cataract surgery compared with CCS and aims to provide clinical guidance.
Search Strategy and Data Extraction
PubMed, Cochrane Library, and EMBASE databases were searched using the following keywords: “femtosecond laser–assisted cataract,” “femtosecond laser cataract,” “femto cataract,” “laser lens surgery,” “laser cataract surgery,” and “FLACS.” Complete and published clinical prospective and retrospective trials whose primary aim was to compare FLACS and CCS were selected. Case reports, letters, reviews, editorials, and pediatric trials were not considered. Only publications in English were included. The reference sections of retrieved original articles and reviews were scanned for studies that might have been missed in the primary searches.
Research and data extraction were performed independently by 2 authors (C.K. and M.S.) from December 8, 2017, to January 30, 2019. Disagreements between authors were resolved by discussion or by a third author (T.K.). Articles were identified first by screening of title and abstract and then by full-text screening. Zotero (version 5.0.21, Roy Rosenzweig Center for History and New Media) and Cochrane Review Manager (RevMan, version 5.3, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014) were used to manage the included studies. Data were extracted using a standard data-extraction form. The searches were repeated just before the final analyses.
The analysis of the literature and writing of the manuscript were performed according to “The PRISMA statement for reporting systematic reviews and meta-analysis of studies that evaluate healthcare interventions: explanation and elaboration.”20 The ethics committee ruled out that approval was not required for this study. Nonetheless, the tenets of the Declaration of Helsinki were followed throughout the study. It was registered at the international prospective register of systematic reviews (PROSPERO) with the registration number CRD42015024076.
The following visual and refractive outcomes were documented at different time points: uncorrected distance visual acuity (UDVA; 1 week, 1 month to 3 months, and 6 months or more), corrected distance visual acuity (CDVA; 1 week, 1 month to 3 months, and 6 months or more), spherical equivalent (SE; 1 week, 3 weeks to 3 months, and 6 months or more), mean absolute refractive prediction error (MAE; 1 week, 1 month to 3 months, and 6 months or more), and surgically induced astigmatism (SIA). The surgical endpoints analyzed were total phacoemulsification time, EPT, cumulative dissipated energy (CDE), and circularity of the capsulotomy. Safety factors analyzed consisted of anterior and posterior capsular ruptures, elevated intraocular pressure (IOP) within 24 hours postoperatively, cystoid macular edema (CME), central corneal edema (3 to 6 weeks and 6 months or more), magnitude of central corneal thickness (CCT; 1 day, 1 month to 3 months, and 6 months or more), and ECL (1 week, 3 to 6 weeks, 3 months, and 6 months or more). Because statistics show that complications occur more often in the first cases of laser-assisted surgery, the rates of anterior and posterior capsule ruptures in trials reporting results of first cases of FLACS in their institution and surgical results from resident surgeons were excluded from the comparison.21 If an absence of intraoperative complication was reported, it was concluded that no capsular tear occurred.
When necessary, values of visual acuity were transformed from the decimal to the logarithm of minimum angle of resolution (logMAR) scale. For this study reporting, EPT is total phacoemulsification time in seconds multiplied by the average phacoemulsification power in percentage. It is a value of the length of phacoemulsification time at 100% power in continuous mode. In some trials, phacoemulsification time was not clearly defined. Only studies reporting EPT were included. The CDE is the EPT in seconds divided by 6000 or the EPT in minutes divided by 100. It is measured in percentage-seconds. A circularity value of 1.0 represents perfect regularity of the shape of the capsulotomy. If only absolute numbers for endothelial cell density were described, ECL was calculated by the method described by Chen et al.15 The mean values were recorded with corresponding SDs. When no SD was reported, data were not included.
Data Analysis and Quality Assessment
The meta-analysis was performed by computing weighted mean differences (WMDs) with 95% CIs for continuous data types and odds ratios (ORs) with 95% CI for dichotomous outcomes. Statistical methods were inversed variance for continuous data and Mantel-Haenszel for dichotomous data. Heterogeneity among the studies was determined using the χ2 test and computing the I2 statistic, with I2 measures more than 50% being attributed to strong heterogeneity. When heterogeneity was indicated, random effects models were used, otherwise fixed effect models.22 Subgroup analyses of RCTs were performed. Funnel plots were analyzed for evaluation of publication bias and small study effects. One-study-removal analysis was conducted to evaluate the sensitivity or rather the change if a single study was left out.23 A P value less than .05 was considered statistically significant; 95% CI are presented in all forest plots.
Cochrane Collaboration's tool for risk of bias was used for the assessment of the quality of RCTs.24 In this tool, the following parameters were graded as low, high, or unclear risk of bias according to Chapter 8.5 of the Cochrane Handbook for Systematic Reviews of Interventions: random sequence generation and allocation concealment (selection bias), blinding of participants and personnel (performance bias), blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), and selective reporting (reporting bias). For the evaluation of the quality of cohort studies, the Newcastle–Ottawa Quality Assessment Scale was used.25 A total of 9 stars can be reached: 4 in patient selection, 2 in comparability, and 3 in outcome assessment. A follow-up of at least 3 weeks was considered to be adequate, except for studies reporting only intraoperative parameters. The minimum threshold of complete follow-up was set at 90%. More than 6 stars indicate high quality. Funding from industry sponsors was reported. The risk of bias assessment was performed independently by 2 authors (C.K. and M.S.).
Characteristics of Included Trials
Initially, a total of 5603 studies were identified. Duplicates were rejected and remaining studies screened by title and abstract. A full-text review was performed when necessary. After the removal of studies that did not fulfill our inclusion criteria or did not evaluate the predetermined variables, 73 trials remained.4–8,12,26–50,51–70,71–92 A total of 12 769 eyes underwent FLACS, and a total of 12 274 eyes underwent CCS. Characteristics of all the trials are presented in Table 1 (see Supplemental Digital Content 2, available at https://links.lww.com/JRS/A87). Of the included studies, 25 were RCTs (3541 eyes [14%]) and 48 comparative cohort studies (21 502 eyes [86%]). For geographical location, 11 trials were conducted in Australia (10 856 eyes [43%]), 37 in Europe (5470 eyes [22%]), 7 in America (4016 eyes [16%]), and 17 in Asia (3311 eyes [13%]). Levitz et al. did not report where surgery had taken place (1390 eyes [6%]). Five different laser platforms were used:
- Catalys (Johnson & Johnson Vision Care, Inc.): 24 studies, 7119 eyes
- LenSx (Alcon Laboratories, Inc.): 38 studies, 3673 eyes
- Victus (Bausch & Lomb, Inc.): 9 studies, 1533 eyes
- Femto LDV Z8 (Ziemer Ophthalmic Systems AG): 4 studies, 218 eyes
- LENSAR (LENSAR, Inc.): 3 studies, 102 eyes
Mastropasqua et al. and Tognetto et al. each evaluated 2 different laser platforms.3,83 The results were treated as 2 separate studies comparing 1 specific laser with manual surgery. Two studies used more than 1 specific laser system without accurately reporting the correlating patient data.32,92 Ferreira et al. evaluated results of temporal (162 eyes FLACS and 169 eyes CCS) and superior oblique (138 eyes FLACS and 131 eyes CCS) clear corneal incisions.57 These results were also treated as 2 separate trials in the analysis. The results of subgroup analyses of RCTs are presented in Table 2 (see Supplemental Digital Content 3, available at https://links.lww.com/JRS/A88).
Absolute values of the SE in diopters (D) were recorded. There was no significant difference for UDVA after 1 week (WMD −0.04, 95% CI, −0.12 to 0.03) (P = .28) and at the final visit (WMD −0.04, 95% CI, −0.11 to 0.03) (P = .3) (see Figure 1a, Supplemental Digital Content 1, available at, https://links.lww.com/JRS/A86). Similarly, CDVA was comparable after 1 week (WMD −0.03, 95% CI, −0.06 to 0.00) (P = .07) and 6 months or more (P = .12) (see Figure 1b, Supplemental Digital Content 1, available at, https://links.lww.com/JRS/A86) and SE after 1 week (WMD −0.03, 95% CI, −0.10 to 0.04) (P = .38) and 6 months or more (WMD −0.11, 95% CI, −0.23 to 0.01) (P = .08) (see Figure 1c, Supplemental Digital Content 1, available at, https://links.lww.com/JRS/A86). At medium term, the differences in UDVA (WMD −0.02, 95% CI, −0.04 to −0.00) (P = .04), CDVA (WMD −0.01, 95% CI, −0.02 to −0.00) (P = .005), and SE (WMD −0.05, 95% CI, −0.08 to −0.01) (P = .007) were better after FLACS. Zhu et al. did not report absolute values but stated no difference in the changes of CDVA after FLACS compared with CCS.92 Chen et al. did not report any absolute values as well. However, evaluating both procedures in patients with hard nuclear cataracts did not reveal any significant difference of CDVA at 3 months and of UDVA throughout the follow-up. Improved CDVA was measured after 1 month (P < .001).43 Regarding CDVA, no difference was observed in the studies by Pajic et al. (P = .37) and Panthier et al.74,75
With FLACS, MAE improved at the 1-week follow-up (WMD −0.10, 95% CI, −0.19 to −0.02) (P = .02) but differences became insignificant at later follow-ups (1 month to 3 months: WMD −0.04, 95% CI, −0.10 to 0.01, P = .15; 6 months or more: WMD 0.00, 95% CI, −0.13 to 0.14, P = .96) (see Figure 1d, Supplemental Digital Content 1, available at, https://links.lww.com/JRS/A86). Abell et al. reported mean absolute errors of −0.51 D and −0.45 D, respectively.30 These values were not included because absolute errors are without any algebraic sign by definition. Depending on which IOL power calculation formula was used, Whang et al. observed lower MAE using FLACS.89
Astigmatism induced by both procedures was shown to be comparable (WMD −0.04, 95% CI, −0.12 to 0.05) (P = .43) (see Figure 1e, Supplemental Digital Content 1, available at, https://links.lww.com/JRS/A86). Fernández et al. evaluated the SIA separately in right and left eyes without finding any significant difference between FLACS and CCS.56
In the subgroup analyses of RCTs, UDVA after 6 months or more was better with FLACS, in addition to CDVA at 1 week and 6 months or more. Using the laser, better MAE and SE were found throughout the follow-up. Details are presented in Table 2 (see Supplemental Digital Content 3, available at, https://links.lww.com/JRS/A88).
Total phacoemulsification time (WMD −10.36, 95% CI, −14.49 to −6.22) (P < .001) (see Figure 2a, Supplemental Digital Content 4, available at, https://links.lww.com/JRS/A89) and EPT (WMD −1.88, 95% CI, −2.21 to −1.55) (P < .001) (see Figure 2b, Supplemental Digital Content 4, available at, https://links.lww.com/JRS/A89) of the laser procedure were significantly shorter than those of the manual cataract surgery. Statistical significance in subgroups was not present regarding EPT using the Victus (P = .11) or LDV Z8 (P = .39). EPT in 2 studies was very high.76,86 However, results remained statistically significant excluding these reports.
CDE was less in the FLACS group (WMD −1.95, 95% CI, −2.48 to −1.42) (P < .001) (see Figure 2c, Supplemental Digital Content 4, available at, https://links.lww.com/JRS/A89). Hida et al. also found less CDE without reporting absolute values (P < .001).60
A value of 1.00 describes perfect circularity. It could be measured with 2 different approaches: circularity = minor diameter/major diameter or circularity = 4π × (area/perimeter2).3,5,62,72,76,82 Circularity of the capsulotomy improved when it was performed with the laser (WMD 0.04, 95% CI, 0.02 to 0.06) (P < .001) (see Figure 2d, Supplemental Digital Content 4, available at, https://links.lww.com/JRS/A89). Panthier et al. stated that FLACS resulted in a more precise and round-shaped capsulotomy.75
In 8022 eyes treated with FLACS, 78 (0.97%) events of anterior capsular rupture occurred, in comparison with 16 (0.20%) events in 7951 eyes treated with CCS (OR 4.80, 95% CI, 2.86 to 8.05) (P < .001) (see Figure 3a, Supplemental Digital Content 5, available at, https://links.lww.com/JRS/A90). Posterior capsular ruptures were reported in 30 of 7191 eyes (0.42%) with FLACS and 19 of 7102 eyes (0.27%) with CCS, and a significant difference was not found (OR 1.53, 95% CI, 0.88 to 2.66) (P = .13) (see Figure 3b, Supplemental Digital Content 5, available at, https://links.lww.com/JRS/A90). The subgroup analysis for anterior and posterior capsule tears revealed a significant difference using the Catalys laser (P < .001 and P = .02, respectively). Regarding anterior capsule ruptures, differences between the laser procedure with the LenSx or Victus and CCS were not statistically significant (P = .13 and P = .93, respectively). No event occurred using the LDV Z8 or LENSAR. For posterior capsule rupture, there was no difference in the LenSx and LENSAR subgroups (P = .91 and P = .50, respectively), similar to absence of events in eyes treated with Victus and LDV Z8 systems. The estimates of the effect in the included studies were different (ranging from 0.33 to 15.61 for anterior capsule rupture and 0.07 to 4.99 for posterior capsule rupture), and CIs were wide. Considering anterior capsule ruptures in RCTs, there was no significant difference between both groups (OR 1.54, 95% CI, 0.54 to 4.36) (P = .42). Zero posterior capsule ruptures occurred in the FLACS group compared with 7 in the CCS group (0.63%), missing statistical significance (OR 0.12, 95% CI, 0.01 to 0.98) (P = .05).
There was no significant difference in number of incidences with increased IOP within the first 24 hours postoperatively (OR 0.86, 95% CI, 0.30 to 2.50) (P = .79) (see Figure 4a, Supplemental Digital Content 6, available at, https://links.lww.com/JRS/A91). Alvarez-Rementería et al. found elevated IOP in 9 of 25 eyes and 8 of 25 eyes after FLACS and CCS, respectively.33 Yu et al. reported increased IOP in only 1 of 29 eyes in the CCS group, and IOP was not elevated in the FLACS group.90 For both studies, data were not included because it was unclear at which time postoperatively IOP was measured.
No significant difference could be observed for the occurrence of CME, with OR of 1.24 (95% CI, 0.74 to 2.08) (P = .40), ranging from 0.32 to 7.24 (see Figure 4b, Supplemental Digital Content 6, available at, https://links.lww.com/JRS/A91). Nagy et al. found that CME was mainly detectable in the outer nuclear layer in both groups but was significantly less in the FLACS group.71
The incidence of central corneal edema after approximately 1 month (OR 1.51, 95% CI, 0.95 to 2.39) (P = .08) and 6 months or more (OR 1.65, 95% CI, 0.72 to 3.79) (P = .24) was comparable for both procedures (see Figure 5a, Supplemental Digital Content 7, available at, https://links.lww.com/JRS/A92). At 3 to 6 weeks postoperatively, corneal edema was found in 1.8% after the laser procedure and 1.9% after manual surgery. Regarding central corneal edema after 1 day, there was an advantage of FLACS in the study by Ang et al.34 Zhu et al. stated no difference in incidences of prolonged edema between FLACS and CCS. Severe edema with reduced visual ability was more often after FLACS, with most cases recovering after 1 week.92 Abell et al. measured the central corneal volume as a representation of corneal edema and found less corneal edema with FLACS at 1 day postoperatively.29
CCT was significantly higher at 1 day (WMD −16.49, 95% CI, −22.78 to −10.20) (P < .001) and 1 to 3 months (WMD −9.33, 95% CI, −15.64 to −3.02) (P = .004) after manual cataract surgery (see Figure 5b, Supplemental Digital Content 7, available at, https://links.lww.com/JRS/A92), but the difference decreased at later stages (WMD −4.53, 95% CI, −11.88 to 2.83) (P = .23). Al-Mohtaseb et al. did not report any significant changes in CCT after 1 month (P = .18).32 In hard nuclear cataracts, Chen et al. found CCT to return to baseline parameters after 1 month with FLACS and 3 months with CCS, representing shorter recovery time after the femtosecond laser procedure.43
ECL at intermediate term after 3 to 6 weeks (WMD −2.58, 95% CI, −4.18 to −0.97) (P = .002) and 3 months (WMD −4.83, 95% CI, −6.94 to −2.73) (P < .001) was significantly less after FLACS (see Figure 5c, Supplemental Digital Content 7, available at, https://links.lww.com/JRS/A92). Differences were not significant at the 1-week follow-up (WMD −3.89, 95% CI, −8.15 to 0.37) (P = .07) or at 6 months (WMD −0.52, 95% CI, −2.74 to 1.71) (P = .65). Wei Dayna et al. had a follow-up period between 3 and 46 months. ECL was statistically significantly higher after CCS (347 ± 421 cells/mm2, 15.3% ± 17.5%) compared with FLACS (112 ± 435 cells/mm2, 4.4% ± 25.0%) (P = .006).87
Risk of Bias, Heterogeneity, and Analysis of Sensitivity
Figure 1 shows the risk of bias graph of the RCTs. The risk of bias assessment using the Newcastle–Ottawa Quality Assessment Scale is presented in Table 3 (see Supplemental Digital Content 8, available at, https://links.lww.com/JRS/A93). Except for 1 trial, all studies reached 5 stars or more indicating medium or high quality (5 to 6 stars: 46%, 7 to 9 stars: 52%).76 Funding from industry sponsors was reported in 2 RCTs and 3 observational studies.40,69,71,77,85 For 2 observational trials, it was unclear whether there was direct funding.33,63 Heterogeneity was displayed for the following outcomes: UDVA, CDVA, SE, MAE, SIA, EPT, circularity, CCT, and ECL. Funnel plots indicate that analysis of MAE at 1 to 3 months might suffer from publication bias in favor of CCS. Regarding the CDE, a slight asymmetry was found in favor of FLACS using the LenSx system. The other funnel plots did not indicate publication bias. Omission of single studies did not change statistical significance in most cases. Results became nonsignificant excluding few different studies for the UDVA at 1 to 3 months,3,41,61,64,67 1 trial for the SE at 3 weeks to 3 months, and 1 study for the MAE.3,41 The sensitivity analysis showed that if the data from 2 trials for the CDVA at 1 week,34,51 one study for the SE at 1 week and after 6 months or more, respectively, one trial for posterior capsule ruptures, one study for central corneal edema at 3 to 6 weeks, and one trial for ECL after 1 week were excluded, the differences of comparator arms became significant.33,34,51,52,77,91
In cataract surgery, patients expect rapid visual rehabilitation and spectacle independence. This study analyzed whether and to which extent there is a difference between FLACS and CCS in key clinical outcome parameters and incidences of complications. We aimed to assemble the differences in a structured and objective manner to facilitate the decision whether to use FLACS or CCS. The main difference of our analysis compared with already published meta-analyses was to implement broader inclusion criteria, for example to include retrospective studies. This approach allowed us to analyze some important outcomes where not enough studies have been performed as RCTs. Furthermore, we performed subgroup analysis for certain outcomes depending on the laser system used. Two other meta-analyses have also included retrospective studies; however, the numbers of eyes were considerably less than that in our analysis.15,18 Chen et al. enrolled only 2861 eyes in the FLACS group and 2072 eyes in the CCS group, and complications were not analyzed.15 Popovic et al. analyzed 7127 and 7440 eyes, respectively, without performing subgroup analysis of laser systems or different time points.18
Visual and refractive results are the most important endpoints for patients' satisfaction. Although our findings were statistically significant at 1month to 3 months, WMD of visual acuity was less than −0.05 logMAR (UDVA: −0.02 logMAR, CDVA: −0.01 logMAR), and WMD of SE was −0.05 D. Therefore, these results were not believed to carry any clinical importance. By contrast, the analysis of RCTs revealed a better long-term UDVA after the laser procedure, with the WMD of −0.10 logMAR. Furthermore, the SE after FLACS was found to be better throughout the follow-up, especially in the long term (WMD −0.19 after 6 months or more).
In general, better visual ability after FLACS could be expected owing to a more accurate capsulotomy, thus better predictability of the effective lens position and better lens centration.21 Our results did not confirm this expectation. Regarding the overall analysis, there was only a difference at medium term.
Because the study by Manning et al. had a follow-up from 7 to 60 days, data could not be assigned to a certain subgroup. The analysis of 2814 eyes with FLACS and 4987 with CCS showed greater improvement of CDVA with CCS (FLACS: 0.05 ± 0.15 logMAR; CCS: 0.03 ± 0.16 logMAR). However, this difference is not of clinical importance.93
Complications that frequently occur after several months such as optical tilt or PCO affect visual acuity at later stages. Both complications were reported to occur less frequently after FLACS.12 Because of zonular stress, capsular bag shrinkage was shown to be more pronounced after CCS, resulting in greater decentration or tilt of the IOL.50 Significantly higher levels of IOL decentration and worse CDVA in the CCS group were stated by Kránitz et al. after 1 month and 1 year.61 Similarly, Reddy et al. observed an IOL decentration in 17.5% of CCS cases compared with only 1.8% in the FLACS group.5 According to Dick et al., less capsular shrinkage after FLACS leads to less lens position changes, which is important because the lens position plays a major role for exact IOL power calculations.50
Correlations between vertical IOL tilt and PCO and more pronounced PCO after CCS were found by Kovács et al.12 By contrast, Manning et al. found reduced visual acuity because of PCO in 0.9% of 2814 eyes treated with FLACS, whereas 0.0% of 4987 eyes in the CCS group showed PCO with impeded visual acuity.93 One reason for this finding might be higher levels of profibrotic cytokines after FLACS.42 Nevertheless, Tran et al. analyzed Nd:YAG capsulotomy rates in 969 eyes undergoing FLACS and 565 eyes undergoing CCS and found a significantly lower rate in the FLACS cohort (11.6% vs 15.2%).94 Overall, PCO occurs more often after FLACS, but further interventions are less often required. Patients deciding on the laser procedure often use a range of premium lenses. Because the threshold for lasering a patient with multifocal IOL is significantly less than that for a patient with monofocal IOL, the lower rate of Nd:YAG capsulotomies after FLACS is surprising. One possible explanation might be that the PCO after FLACS was detectable but less relevant for visual acuity. Primary posterior laser capsulotomy might be an effective possibility for the prevention of PCO.95
UDVA was better after FLACS in the meta-analysis by Chen et al. (WMD −0.07).15 However, no subgroup analysis for different follow-ups was performed. Day et al. and Ye et al. found comparable values of visual acuity by analyzing RCTs.17,19 A tendency for this was also revealed by Popovic et al.18
The mean absolute error represents the refractive predictability. Concerning short-term results, analysis of 3 studies revealed the postoperative SE to be more predictable after FLACS. However, after 6 months, no observable difference was noted, similar to what was found by Popovic et al.18 The analysis of RCTs by Day et al. revealed a distinct advantage in favor of FLACS concerning MAE at the final follow-up (WMD −0.18); however, only 3 studies were included.17 In analyzing only RCTs, we found a clinically important difference of MAE after 1 month to 3 months, with a WMD of −0.17 in favor of FLACS.
Another factor for visual acuity is SIA. This form of astigmatism is caused by the wound healing processes at the place where the corneal incision took place.70 Ferreira et al. reported better reproducibility of laser-assisted corneal incisions.57 Mastropasqua et al. supposed that different tunnel morphologies and less mechanical and thermal injury to be the reasons for the lower magnitude of SIA with FLACS.8 However, statistical significance was missed, and the study by Nagy et al. found that only the difference of the previously planned and achieved SIA axis to be significantly smaller in the FLACS group.70 Recently, a study by Lee et al. concluded internal aberrations to be less and astigmatic changes to be more predictable with FLACS.96 The amount and axis of SIA are especially important when toric IOLs are implanted. Similar to our finding, the meta-analysis by Chen et al. did not reveal any differences regarding SIA (P = .26).15
There was a distinct advantage of FLACS regarding surgical endpoints such as less EPT and CDE and better circularity of the capsulotomy. The EPT is a value of the length of phacoemulsification time at 100% power in continuous mode.35 Oxidative stress is rather associated with the phacoemulsification time than with the procedure.66 Less EPT results in less potentially injurious sonic waves used to remove the lens nucleus. It should be remarked that EPT was shown to be dependent on the fragmentation patterns. In general, EPT was less with the grid pattern although the segmentation pattern is recommended for eyes with high lens density.97 In our meta-analysis, the EPT of the laser procedure was less. The considerable differences in EPT between the included trials might be due to the different cataract grades. Hatch et al. stated the EPT to be less with FLACS when treating dense and brunescent cataracts.59 Furthermore, Ang et al. found low EPT to be worthwhile in eyes with mature cataracts and compromised corneas. In their study on 735 eyes, the use of less laser energy resulted in a lower risk for corneal edema, anterior chamber inflammation, and ECL, aspects that contribute to a better postoperative recovery.34 Regarding the mean values of the reported EPT, we suppose the authors to assume different definitions of the EPT. Because we did not evaluate the absolute time values but rather focused on the differences between FLACS and CCS, we do not expect any influence on the informative value of this comparison.
The CDE represents the amount of ultrasound energy, and thus the thermal injury, delivered to the incision site.34 To decrease CDE, both time and power have to be reduced. Chen et al. also found that FLACS required shorter EPT and less CDE.15 Similarly, EPT was less in the analysis by Popovic et al. and another meta-analysis by Chen et al.16,18
Circularity of the capsulotomy was better when it was noninvasively created with the laser. It results in reduced aberrations and a better lens centration and lower risk for lens rotation, tilting, and decentration.34,96 Tilt or decentration deteriorates the optical performance of the IOL.98 Several studies achieved better reproducibility and significantly more uniform capsulotomies with the laser.99–101 These results should be especially important for surgeons with less experience.101
Overall, capsule ruptures occurred rarely after both procedures. Compromised capsulotomy integrity might affect the postoperative lens stability, the effective lens position, and, thus, the visual outcome.73 Although anterior capsule tears occurred more often during the laser procedure, the long-term visual outcomes were not worse in our analysis. The highest rate of anterior capsule ruptures in the FLACS group was 3% of all eyes. One reason for the higher rates might be additional aberrant pulses and postage-stamp radial patterns, possibly because of fixational eye movements, compromising anterior capsulotomy integrity.28 Another reason might be incomplete capsulotomies performed by the laser, requiring manual completion that is likely to result in further complications, such as anterior capsule rupture.5,27 Although capsular tears might cause the need for unplanned vitrectomies, 2 large studies did not reveal differences among FLACS and CCS.93,102 In most cases, complications lead to only a longer surgery time, without affecting the visual results.93
In our subgroup analysis of RCTs, the difference in anterior capsule tears was no longer significant. Posterior capsule ruptures seemed less with FLACS, which was of clinical importance even if statistical significance was missed (FLACS: zero cases in 1090 eyes, CCS: 7 cases in 1104 eyes).
A recent RCT proved the possible superiority of FLACS regarding safety of the surgery. Roberts et al. reported no posterior capsule rupture and no vitreous loss in the laser group, being statistically significant compared with CCS. Posterior capsule ruptures with CCS occurred especially during the phacoemulsification or segment removal steps. They concluded them to be the critical stages in CCS that are facilitated using the laser.77
The subgroup analysis of the laser platforms showed significant differences regarding anterior capsular tears with the Catalys laser compared with CCS. Three trials reported complications from 2 centers (Tasmanian Eye Institute, Launceston, Australia; Newcastle Eye Hospital, Newcastle, Australia).27,28,53 When excluding these 3 studies, the subgroup analyses of capsular tears using the Catalys laser were not significantly greater (anterior: P = 1.00; posterior: P = .62), rather similar to the overall anterior capsule rupture rate (P = .18).
Laser characteristics such as laser pulse frequency, energy levels, and spot and layer separation play an important role regarding capsule ruptures. For instance, less pulse energy and greater spot spacing was shown to result in a higher cut quality and, thus, a stronger capsulotomy.103,104 The optimal combination of pulse energy levels and spot formation for each laser system needs to be further investigated.
Complication rates were excluded from our analysis when unexperienced surgeons performed the cataract extraction and lens implantation.38,49,64 However, in the study by Brunin et al., FLACS performed similar to CCS regarding intraoperative and postoperative complications, corneal edema, and visual outcomes.38 Daya et al. did not report any posterior capsule rupture, but there were 4 anterior radial tears during FLACS.49 In the trial by Lawless et al., no intraoperative complications occurred.64 Chen et al., also reporting results of their first cases of laser-assisted cataract surgery, stated a lower intraoperative complication rate with FLACS (1.8% vs 5.8%) (P < .05).105 In 3 trials, the surgeons' experience was not specified, but they had to perform 10 accreditation cases before starting the study.27,31,85 It is not clear whether these were their first laser procedures. Lack of experience might be the reason for the high rate of anterior capsule ruptures in the study by Vasquez-Perez et al., although the comparison of complications was statistically significant even if these studies were excluded.27
It is important to acknowledge the considerable learning curve in performing laser lens surgery.106 Dick and Schultz reported that 59% of the first 200 to 400 cases required phacoemulsification, whereas ultrasound energy was necessary only in 9% of the case numbers 1200 to 1400.107 Roberts et al. compared the complication rates of their first 200 FLACS procedures to the following 1300, showing a significant decrease in anterior radial tears from 4% to 0.31% and similarly a decrease in posterior capsular tears from 3.5% to 0.31%.21 This was confirmed by other studies finding considerably less intraoperative complications over time.108,109 Nevertheless, studies have described benefits of laser-assisted surgery, especially for surgeons in training.38,77 Because surgical expertise could not be adjusted rigorously in our meta-analysis, large studies reporting results of very experienced surgeons are desirable.
Higher cataract grades require more ultrasound energy, and thus, more complications might occur.107 Lens fragmentation of white cataracts cannot be performed with the laser. Anterior capsulotomy is possible but rates of intraoperative complications such as anterior capsule ruptures are higher.110 Titiyal et al. stated that the femtosecond laser could be used to facilitate this step in these cases; however, it was not possible to evaluate the grade of lens opacification in a subgroup analysis.82 Further studies are necessary comparing both procedures in patients with similar cataract grades.
In general, comparing one procedure with another for postoperative complications is difficult when complications themselves are rare. Long observation periods, large study populations, and well-designed prospective trials are necessary to adequately study the complications. In addition, the definition of CME is not consistent. Although subclinical macular edema might predispose to clinical manifestation of CME, it only becomes important when visual acuity is affected.111 We included all reports of macular edema whether they were clinically important or subclinical. Regarding CME and elevated IOP, a significant difference was not found in our study, which is similar to what was shown in the studies by Chen et al., Day et al., and Ye et al.16,17,19
With FLACS, lower macular thickness in the inner retinal ring was reported by Ecsedy et al., whereas OCT measurements of total macular volume, foveal thickness, and outer macular ring thickness were not different among groups.51 Similarly, in 3 other studies, the differences of postoperative retinal thickness between both cohorts were marginal, being less than 20 μm.35,45,71
More requirement of ultrasound energy during CCS was considered to be disadvantageous because of increased inflammatory response in the posterior segment of the eye.45,99 Less inflammation after laser surgery was shown by Abell et al.26 Similarly, a study on 44 eyes evaluating a multitude of cytokines, chemokines, and growth factors found higher levels of antiinflammatory cytokines after the laser procedure.42 Enz et al. found a lower central macular volume within 2 weeks after FLACS compared with conventional surgery. Hence, they reported an advantage of the laser procedure for patients with macular vulnerability regarding the short follow-up period.112
Contradictory statements concerning postoperative inflammation are published. As it was mentioned in the Postoperative Complications section, several studies found higher inflammation rates after CCS. By contrast, higher prostaglandin levels in the anterior chamber were found when capsulotomy was performed with the laser.66,101 Because of disruption of the blood–aqueous barrier and residual lens material after FLACS, augmented inflammation processes in the anterior segment was reported. The authors assumed this to lead to higher ECL in the long term and, thus, to a malfunction of the endothelial pump function and corneal edema with decelerated visual recovery.30,93 This, however, was not proven by our findings.
Corneal edema might also occur due to Descemet membrane detachment. With FLACS, the incidence of Descemet membrane detachment was reported to be less compared with a corneal incision with a keratome.81 In general, the use of less energy during the laser procedure contributes to less collateral damage of ambient structures. The prefragmentation of the lens nucleus can diminish the need for manipulation and, hence, the volume of irrigation solution required and mechanical trauma on the endothelium.36 This was proven in the study by Abell et al., reporting less corneal edema and ECL with FLACS.30 Especially in hard nuclear cataracts, when generally more phacoemulsification energy is used, the laser helped to reduce ECL compared with the conventional procedure.43 We found the reduction of EPT with FLACS to translate into short- and medium-term differences in CCT and ECL.
Corneal biomechanic properties after 1 week were better protected using the femtosecond laser in the study by Wei et al. Differences missed statistical significance at 1 month postoperatively.88 Two other studies found no significant difference in loss in hexagonality, representing endothelial cell damage, after 3 months and 6 months between both groups.36,63
Greater ECL is a risk factor of reduced resistance to injury in the long term, which is particularly important in patients with endothelial cell dysfunctions.55 Three studies evaluated the outcomes in patients with Fuchs endothelial dystrophy.55,87,92 In these patients, the endothelium is under greater preoperative stress. Postoperative corneal swelling is an indicator for impaired visual acuity and a risk factor of corneal decompensation and subsequent necessary corneal transplantation.55 Because short EPT was shown to alleviate ECL and central corneal thickening, FLACS seems to be the better choice in patients with Fuchs endothelial dystrophy or corneal guttata to treat the endothelium with care.6
In their meta-analysis, Chen et al. ascertained distinct results, that is, significantly less ECL and lower CCT after the laser procedure at 1 week, 3 to 4 weeks, and 3 to 6 months.15 Popovic et al. also reported findings favoring FLACS, although the clinical importance of the differences in CCT (Chen et al.: maximum WMD 16.63; Popovic et al.: WMD 6.37) remains unclear, just as in our analysis (1 week: WMD 16.49, 1 to 3 months: WMD 9.33).18 In the analysis of 5 studies by Ye et al., endothelial cell count at final follow-up after FLACS were significantly higher than after CCS (WMD 170.58).19 Contrary to our study, absolute values of endothelial cells were analyzed. Although being higher than 150 cells/mm2, the differences in endothelial cell count in the study by Chen et al. were not statistically significant (1 week: WMD 166.86; 4 to 6 weeks: WMD 226.40).16 Overall, we consider less injury on corneal tissues and better corneal biomechanics to be especially relevant in the long term.
Although our findings can facilitate the choice of a certain procedure, limitations of our meta-analysis need to be considered. Heterogeneity among the studies might be attributed to various regional backgrounds, study protocols, differences in laser and CCS platforms, variability in the steps performed with the laser, and surgical expertise.
For instance, the postoperative visual acuity depends on the preoperative measurements, the choice of the implanted IOL, and the formula used for IOL power calculation. In general, nonmonofocal IOLs are more often used in femtosecond laser surgery. These patients often desire excellent visual results and decide on bifocal, multifocal, or toric IOLs.93 However, in most studies, it was not reported that which IOL was implanted. For this reason, we did not differentiate between trials using either toric IOLs or monofocal, bifocal, or multifocal IOLs.
Because the laser itself is a main factor influencing the clinical outcome, comparing studies in which different lasers were used is not a balanced comparison. Regarding total phacoemulsification time and circularity, an analysis that would additionally consider different laser systems would have resulted in cohorts too small to make a proper analysis. It should also be remarked that it was not possible to differentiate between results from earlier femtosecond laser units and the newer, more advanced systems. In addition, the different settings of the laser platforms could not be considered in our analysis. More studies evaluating different settings are desirable.
In the main analyses, we did not differentiate between different study designs. RCTs evaluating obviously different surgical procedures are not blinded anyway and, thus, suffer from equal biases such as observational trials. Furthermore, too few RCTs are published, resulting in safety outcomes to be underpowered if only RCTs had been analyzed. The additional inclusion of observational studies might outweigh the disadvantages of including only RCTs.113 Within-person trials were included without considering the paired nature of the data. Because several studies were conducted in the same institution, it might be possible that they were just expanded cohorts within the same population.
Data concerning patients' satisfaction were limited and were not part of our analysis. In general, comparisons are difficult because of the heterogeneous manner of reporting. Future analyses of this aspect are desirable.
In conclusion, there are certain advantages of laser-assisted cataract surgery compared with CCS. The main outcome determining patients' satisfaction is the uncorrected and corrected visual acuities that, in most studies, were better with the laser procedure at medium term. The research shows that FLACS is a safe technique and complication rates are likely to reduce further with increased surgical skills. Less requirement of ultrasound energy leads to less injury to corneal tissues, which is especially important in the long term. Critical stages in CCS can be facilitated using the laser. Standardization of surgical steps and higher precision are beneficial to both the surgeon and the patient, especially for patients with low endothelial cell density or dense cataract. Solving logistical problems and improving cost effectiveness is desirable. Further development and improvements using the relatively young laser technique can be expected. Large studies comparing different settings of more current and advanced systems are necessary.
WHAT WAS KNOWN
- Study results comparing femtosecond laser–assisted cataract surgery (FLACS) with conventional cataract surgery are contradictory.
- Regarding clinical outcomes, FLACS needs to prove its superiority to justify the high costs and logistic difficulties.
WHAT THIS PAPER ADDS
- Both procedures are effective and safe. Complications occur rarely.
- Visual acuity, at the medium-term follow-up, is slightly better after FLACS.
- FLACS is beneficial in the short term for patients with low endothelial cell density and dense cataract because of the reduction of required harmful sonic waves for phacoemulsification and, thus, a decreased risk for injury of surrounding tissue.
1. National Guideline Alliance. Cataracts in Adults: Management. London, UK: National Institute for Health and Care Excellence (UK); 2017
2. Nagy Z, Takacs A, Filkorn T, Sarayba M. Initial clinical evaluation of an intraocular femtosecond laser in cataract surgery. J Refract Surg 2009;25:1053–1060
3. Mastropasqua L, Toto L, Mattei PA, Vecchiarino L, Mastropasqua A, Navarra R, Di Nicola M, Nubile M. Optical coherence tomography and 3-dimensional confocal structured imaging system-guided femtosecond laser capsulotomy versus manual continuous curvilinear capsulorhexis. J Cataract Refract Surg 2014;40:2035–2043
4. Takács AI, Kovács I, Miháltz K, Filkorn T, Knorz MC, Nagy ZZ. Central corneal volume and endothelial cell count following femtosecond laser-assisted refractive cataract surgery compared to conventional phacoemulsification. J Refract Surg 2012;28:387–391
5. Reddy KP, Kandulla J, Auffarth GU. Effectiveness and safety of femtosecond laser-assisted lens fragmentation and anterior capsulotomy versus the manual technique in cataract surgery. J Cataract Refract Surg 2013;39:1297–1306
6. Conrad-Hengerer I, Al Juburi M, Schultz T, Hengerer FH, Dick HB. Corneal endothelial cell loss and corneal thickness in conventional compared with femtosecond laser-assisted cataract surgery: three-month follow-up. J Cataract Refract Surg 2013;39:1307–1313
7. Mayer WJ, Klaproth OK, Hengerer FH, Kohnen T. Impact of crystalline lens opacification on effective phacoemulsification time in femtosecond laser-assisted cataract surgery. Am J Ophthalmol 2014;157:426–432.e1
8. Mastropasqua L, Toto L, Mastropasqua A, Vecchiarino L, Mastropasqua R, Pedrotti E, Di Nicola M. Femtosecond laser versus manual clear corneal incision in cataract surgery. J Refract Surg 2014;30:27–33
9. Grewal DS, Basti S. Comparison of morphologic features of clear corneal incisions created with a femtosecond laser or a keratome. J Cataract Refract Surg 2014;40:521–530
10. Mayer WJ, Klaproth OK, Ostovic M, Terfort A, Vavaleskou T, Hengerer FH, Kohnen T. Cell death and ultrastructural morphology of femtosecond laser-assisted anterior capsulotomy. Invest Ophthalmol Vis Sci 2014;55:893–898
11. Wertheimer CM, Shajari M, Kohnen T, von Studnitz A, Kassumeh S, Dimitriou S, Lieberz R, Hakim I, Priglinger SG, Mayer WJ. Comparison of fibrotic response in the human lens capsular bag after femtosecond laser-assisted cataract surgery and conventional phacoemulsification. J Cataract Refract Surg 2018;44:750–755
12. Kovács I, Kránitz K, Sándor GL, Knorz MC, Donnenfeld ED, Nuijts RM, Nagy ZZ. The effect of femtosecond laser capsulotomy on the development of posterior capsule opacification. J Refract Surg 2014;30:154–158
13. Abell RG, Vote BJ. Cost-effectiveness of femtosecond laser-assisted cataract surgery versus phacoemulsification cataract surgery. Ophthalmology 2014;121:10–16
14. Dick HB, Gerste RD. Plea for femtosecond laser pre-treatment and cataract surgery in the same room. J Cataract Refract Surg 2014;40:499–500
15. Chen X, Chen K, He J, Yao K. Comparing the curative effects between femtosecond laser-assisted cataract surgery and conventional phacoemulsification surgery: a meta-analysis. PLoS One 2016;11:e0152088
16. Chen X, Xiao W, Ye S, Chen W, Liu Y. Efficacy and safety of femtosecond laser-assisted cataract surgery versus conventional phacoemulsification for cataract: a meta-analysis of randomized controlled trials. Sci Rep 2015;5:13123
17. Day AC, Gore DM, Bunce C, Evans JR. Laser-assisted cataract surgery versus standard ultrasound phacoemulsification cataract surgery. Cochrane Database Syst Rev 2016;7:CD010735
18. Popovic M, Campos-Möller X, Schlenker MB, Ahmed IIK. Efficacy and safety of femtosecond laser-assisted cataract surgery compared with manual cataract surgery: a meta-analysis of 14 567 eyes. Ophthalmology 2016;123:2113–2126
19. Ye Z, Li Z, He S. A meta-analysis comparing postoperative complications and outcomes of femtosecond laser-assisted cataract surgery versus conventional phacoemulsification for cataract. J Ophthalmol 2017;2017:3849152
20. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 2009;339:b2700
21. Roberts TV, Lawless M, Bali SJ, Hodge C, Sutton G. Surgical outcomes and safety of femtosecond laser cataract surgery: a prospective study of 1500 consecutive cases. Ophthalmology 2013;120:227–233
22. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Introduction to Meta-Analysis. 1st ed. Chichester, UK: Wiley; 2009
23. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–634
24. Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA; Cochrane Bias Methods Group; Cochrane Statistical Methods Group. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928
25. Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp
. Accessed July 26, 2019
26. Abell RG, Allen PL, Vote BJ. Anterior chamber flare after femtosecond laser-assisted cataract surgery. J Cataract Refract Surg 2013;39:1321–1326
27. Abell RG, Darian-Smith E, Kan JB, Allen PL, Ewe SYP, Vote BJ. Femtosecond laser-assisted cataract surgery versus standard phacoemulsification cataract surgery: outcomes and safety in more than 4000 cases at a single center. J Cataract Refract Surg 2015;41:47–52
28. Abell RG, Davies PEJ, Phelan D, Goemann K, McPherson ZE, Vote BJ. Anterior capsulotomy integrity after femtosecond laser-assisted cataract surgery. Ophthalmology 2014;121:17–24
29. Abell RG, Kerr NM, Howie AR, Mustaffa Kamal MAA, Allen PL, Vote BJ. Effect of femtosecond laser-assisted cataract surgery on the corneal endothelium. J Cataract Refract Surg 2014;40:1777–1783
30. Abell RG, Kerr NM, Vote BJ. Toward zero effective phacoemulsification time using femtosecond laser pretreatment. Ophthalmology 2013;120:942–948
31. Abell RG, Kerr NM, Vote BJ. Femtosecond laser-assisted cataract surgery compared with conventional cataract surgery. Clin Exp Ophthalmol 2013;41:455–462
32. Al-Mohtaseb Z, He X, Yesilirmak N, Waren D, Donaldson KE. Comparison of corneal endothelial cell loss between two femtosecond laser platforms and standard phacoemulsification. J Refract Surg 2017;33:708–712
33. Alvarez-Rementería L, Blázquez V, Contreras I. Surgical induced astigmatism in femtosecond laser assisted cataract surgery. J Emmetropia 2012;3:61–65
34. Ang RET, Quinto MMS, Cruz EM, Rivera MCR, Martinez GHA. Comparison of clinical outcomes between femtosecond laser-assisted versus conventional phacoemulsification. Eye Vis Lond Engl 2018;5:8
35. Asena BS, Karahan E, Kaskaloglu M. Retinal and choroidal thickness after femtosecond laser-assisted and standard phacoemulsification. Clin Ophthalmol 2017;11:1541–1547
36. Bascaran L, Alberdi T, Martinez-Soroa I, Sarasqueta C, Mendicute J. Differences in energy and corneal endothelium between femtosecond laser-assisted and conventional cataract surgeries: prospective, intraindividual, randomized controlled trial. Int J Ophthalmol 2018;11:1308–1316
37. Berk TA, Schlenker MB, Campos-Möller X, Pereira AM, Ahmed IIK. Visual and refractive outcomes in manual versus femtosecond laser-assisted cataract surgery: a single-center retrospective cohort analysis of 1838 eyes. Ophthalmology 2018;125:1172–1180
38. Brunin G, Khan K, Biggerstaff KS, Wang L, Koch DD, Khandelwal SS. Outcomes of femtosecond laser-assisted cataract surgery performed by surgeons-in-training. Graefes Arch Clin Exp Ophthalmol 2017;255:805–809
39. Cavallini GM, Fornasari E, De Maria M, Lazzerini A, Campi L, Verdina T. Bimanual femtosecond laser-assisted cataract surgery compared to standard bimanual phacoemulsification: a case-control study. Eur J Ophthalmol 2019;29:629–635
40. Chan T, Pattamatta U, Butlin M, Meades K, Bala C. Intereye comparison of femtosecond laser-assisted cataract surgery capsulotomy and manual capsulorhexis edge strength. J Cataract Refract Surg 2017;43:480–485
41. Chee SP, Yang Y, Ti SE. Clinical outcomes in the first two years of femtosecond laser-assisted cataract surgery. Am J Ophthalmol 2015;159:714–719
42. Chen H, Lin H, Zheng D, Liu Y, Chen W, Liu Y. Expression of cytokines, chmokines and growth factors in patients undergoing cataract surgery with femtosecond laser pretreatment. PLoS One 2015;10:e0137227
43. Chen X, Yu Y, Song X, Zhu Y, Wang W, Yao K. Clinical outcomes of femtosecond laser-assisted cataract surgery versus conventional phacoemulsification surgery for hard nuclear cataracts. J Cataract Refract Surg 2017;43:486–491
44. Conrad-Hengerer I, Al Sheikh M, Hengerer FH, Schultz T, Dick HB. Comparison of visual recovery and refractive stability between femtosecond laser-assisted cataract surgery and standard phacoemulsification: six-month follow-up. J Cataract Refract Surg 2015;41:1356–1364
45. Conrad-Hengerer I, Hengerer FH, Al Juburi M, Schultz T, Dick HB. Femtosecond laser-induced macular changes and anterior segment inflammation in cataract surgery. J Refract Surg 2014;30:222–226
46. Conrad-Hengerer I, Hengerer FH, Schultz T, Dick HB. Effect of femtosecond laser fragmentation on effective phacoemulsification time in cataract surgery. J Refract Surg 2012;28:879–883
47. Conrad-Hengerer I, Schultz T, Jones JJ, Hengerer FH, Dick B. Cortex removal after laser cataract surgery and standard phacoemulsification: a critical analysis of 800 consecutive cases. J Refract Surg 2014;30:516–520
48. Day AC, Smith PR, Tang HL, Aiello F, Hussain B, Maurino V, Marshall J, Saleh GM. Surgical efficiency in femtosecond laser cataract surgery compared with phacoemulsification cataract surgery: a case-control study. BMJ Open 2018;8:e018478
49. Daya SM, Nanavaty MA, Espinosa-Lagana MM. Translenticular hydrodissection, lens fragmentation, and influence on ultrasound power in femtosecond laser-assisted cataract surgery and refractive lens exchange. J Cataract Refract Surg 2014;40:37–43
50. Dick HB, Conrad-Hengerer I, Schultz T. Intraindividual capsular bag shrinkage comparing standard and laser-assisted cataract surgery. J Refract Surg 2014;30:228–233
51. Ecsedy M, Miháltz K, Kovács I, Takács A, Filkorn T, Nagy ZZ. Effect of femtosecond laser cataract surgery on the macula. J Refract Surg 2011;27:717–722
52. Espaillat A, Pérez O, Potvin R. Clinical outcomes using standard phacoemulsification and femtosecond laser-assisted surgery with toric intraocular lenses. Clin Ophthalmol 2016;10:555–563
53. Ewe SYP, Abell RG, Oakley CL, Lim CH, Allen PL, McPherson ZE, Rao A, Davies PE, Vote BJ. A comparative cohort study of visual outcomes in femtosecond laser-assisted versus phacoemulsification cataract surgery. Ophthalmology 2016;123:178–182
54. Ewe SYP, Oakley CL, Abell RG, Allen PL, Vote BJ. Cystoid macular edema after femtosecond laser-assisted versus phacoemulsification cataract surgery. J Cataract Refract Surg 2015;41:2373–2378
55. Fan W, Yan H, Zhang G. Femtosecond laser-assisted cataract surgery in Fuchs endothelial corneal dystrophy: long-term outcomes. J Cataract Refract Surg 2018;44:864–870
56. Fernández J, Rodríguez-Vallejo M, Martínez J, Tauste A, Piñero DP. Prediction of surgically induced astigmatism in manual and femtosecond laser-assisted clear corneal incisions. Eur J Ophthalmol 2018;28:398–405
57. Ferreira TB, Ribeiro FJ, Pinheiro J, Ribeiro P, O'Neill JG. Comparison of surgically induced astigmatism and morphologic features resulting from femtosecond laser and manual clear corneal incisions for cataract surgery. J Refract Surg 2018;34:322–329
58. Filkorn T, Kovács I, Takács A, Horváth E, Knorz MC, Nagy ZZ. Comparison of IOL power calculation and refractive outcome after laser refractive cataract surgery with a femtosecond laser versus conventional phacoemulsification. J Refract Surg 2012;28:540–544
59. Hatch KM, Schultz T, Talamo JH, Dick HB. Femtosecond laser-assisted compared with standard cataract surgery for removal of advanced cataracts. J Cataract Refract Surg 2015;41:1833–1838
60. Hida WT, Tzelikis PF, Vilar C, Chaves MAPD, Motta AFP, Carricondo PC, Ventura BV, Ambrosio R, Nosé W, Alves MR. Outcomes study between femtosecond laser-assisted cataract surgery and conventional phacoemulsification surgery using an active fluidics system. Clin Ophthalmol 2017;11:1735–1739
61. Kránitz K, Miháltz K, Sándor GL, Takacs A, Knorz MC, Nagy ZZ. Intraocular lens tilt and decentration measured by Scheimpflug camera following manual or femtosecond laser-created continuous circular capsulotomy. J Refract Surg 2012;28:259–263
62. Kránitz K, Takacs A, Miháltz K, Kovács I, Knorz MC, Nagy ZZ. Femtosecond laser capsulotomy and manual continuous curvilinear capsulorrhexis parameters and their effects on intraocular lens centration. J Refract Surg 2011;27:558–563
63. Krarup T, Holm LM, la Cour M, Kjaerbo H. Endothelial cell loss and refractive predictability in femtosecond laser-assisted cataract surgery compared with conventional cataract surgery. Acta Ophthalmol 2014;92:617–622
64. Lawless M, Bali SJ, Hodge C, Roberts TV, Chan C, Sutton G. Outcomes of femtosecond laser cataract surgery with a diffractive multifocal intraocular lens. J Refract Surg 2012;28:859–864
65. Levitz L, Reich J, Roberts TV, Lawless M. Incidence of cystoid macular edema: femtosecond laser-assisted cataract surgery versus manual cataract surgery. J Cataract Refract Surg 2015;41:683–686
66. Liu YC, Setiawan M, Ang M, Yam GHF, Mehta JS. Changes in aqueous oxidative stress, prostaglandins, and cytokines: comparisons of low-energy femtosecond laser-assisted cataract surgery versus conventional phacoemulsification. J Cataract Refract Surg 2019;45:196–203
67. Makombo PM, Shao Y, Yang Q. Surgically induced astigmatism using femtosecond laser clear corneal incision for cataract surgery compared to conventional phacoemulsification. Int J Sci Eng Res 2016;7:175–180
68. Miháltz K, Knorz MC, Alió JL, Takács AI, Kránitz K, Kovács I, Nagy ZZ. Internal aberrations and optical quality after femtosecond laser anterior capsulotomy in cataract surgery. J Refract Surg 2011;27:711–716
69. Mursch-Edlmayr AS, Bolz M, Luft N, Ring M, Kreutzer T, Ortner C, Rohleder M, Priglinger SG. Intraindividual comparison between femtosecond laser-assisted and conventional cataract surgery. J Cataract Refract Surg 2017;43:215–222
70. Nagy ZZ, Dunai A, Kránitz K, Takács AI, Sándor GL, Hécz R, Knorz MC. Evaluation of femtosecond laser-assisted and manual clear corneal incisions and their effect on surgically induced astigmatism and higher-order aberrations. J Refract Surg 2014;30:522–525
71. Nagy ZZ, Ecsedy M, Kovács I, Takács Á, Tátrai E, Somfai GM, Cabrera DeBuc D. Macular morphology assessed by optical coherence tomography image segmentation after femtosecond laser-assisted and standard cataract surgery. J Cataract Refract Surg 2012;38:941–946
72. Nagy ZZ, Kránitz K, Takacs AI, Miháltz K, Kovács I, Knorz MC. Comparison of intraocular lens decentration parameters after femtosecond and manual capsulotomies. J Refract Surg 2011;27:564–569
73. Oakley CL, Ewe SY, Allen PL, Vote BJ. Visual outcomes with femtosecond laser-assisted cataract surgery versus conventional cataract surgery in toric IOL insertion. Clin Exp Ophthalmol 2016;44:570–573
74. Pajic B, Cvejic Z, Pajic-Eggspuehler B. Cataract surgery performed by high frequency LDV Z8 femtosecond laser: safety, efficacy, and its physical properties. Sensors 2017;17:1429
75. Panthier C, Costantini F, Rigal-Sastourné JC, Brézin A, Mehanna C, Guedj M, Monnet D. Change of capsulotomy over 1 year in femtosecond laser-assisted cataract surgery and its impact on visual quality. J Refract Surg 2017;33:44–49
76. Ranjini H, Murthy PR, Murthy GJ, Murthy VR. Femtosecond laser-assisted cataract surgery versus 2.2 mm clear corneal phacoemulsification. Indian J Ophthalmol 2017;65:942–948
77. Roberts HW, Wagh VK, Sullivan DL, Hidzheva P, Detesan DI, Heemraz BS, Sparrow JM, O'Brart DPS. A randomized controlled trial comparing femtosecond laser-assisted cataract surgery versus conventional phacoemulsification surgery. J Cataract Refract Surg 2019;45:11–20
78. Saeedi OJ, Chang LY, Ong SR, Karim SA, Abraham DS, Rosenthal GL, Hammer A, Spagnolo BV, Betancourt AE. Comparison of cumulative dispersed energy (CDE) in femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification. Int Ophthalmol 2019;39:1761–1766
79. Schargus M, Suckert N, Schultz T, Kakkassery V, Dick HB. Femtosecond laser-assisted cataract surgery without OVD: a prospective intraindividual comparison. J Refract Surg 2015;31:146–152
80. Serrao S, Lombardo G, Schiano-Lomoriello D, Ducoli P, Rosati M, Lombardo M. Effect of femtosecond laser-created clear corneal incision on corneal topography. J Cataract Refract Surg 2014;40:531–537
81. Titiyal JS, Kaur M, Ramesh P, Shah P, Falera R, Bageshwar LMS, Kinkar A, Sharma N. Impact of clear corneal incision morphology on incision-site Descemet membrane detachment in conventional and femtosecond laser-assisted phacoemulsification. Curr Eye Res 2018;43:293–299
82. Titiyal JS, Kaur M, Singh A, Arora T, Sharma N. Comparative evaluation of femtosecond laser-assisted cataract surgery and conventional phacoemulsification in white cataract. Clin Ophthalmol 2016;10:1357–1364
83. Tognetto D, De Giacinto C, Perrotta AA, Candian T, Bova A, Rinaldi S, Turco G. Scanning electron microscopy analysis of the anterior capsulotomy edge: a comparative study between femtosecond laser-assisted capsulotomy and manual capsulorhexis. J Ophthalmol 2018;2018:8620150
84. Toto L, Mastropasqua R, Mattei PA, Agnifili L, Mastropasqua A, Falconio G, Di Nicola M, Mastropasqua L. Postoperative IOL axial movements and refractive changes after femtosecond laser-assisted cataract surgery versus conventional phacoemulsification. J Refract Surg 2015;31:524–530
85. Vasquez-Perez A, Simpson A, Nanavaty MA. Femtosecond laser-assisted cataract surgery in a public teaching hospital setting. BMC Ophthalmol 2018;18:26
86. Wang X, Zhang Z, Li X, Xie L, Zhang H, Koch DD, Wang L, Zhang S. Evaluation of femtosecond laser versus manual clear corneal incisions in cataract surgery using spectral-domain optical coherence tomography. J Refract Surg 2018;34:17–22
87. Wei Dayna YW, Hui-Chen Charmaine C, Liang S, Manotosh R, Tien Anna TW. Comparing outcomes of phacoemulsification with femtosecond laser-assisted cataract surgery in patients with Fuchs endothelial dystrophy. Am J Ophthalmol 2018;196:173–180
88. Wei Y, Xu L, Song H. Application of Corvis ST to evaluate the effect of femtosecond laser-assisted cataract surgery on corneal biomechanics. Exp Ther Med 2017;14:1626–1632
89. Whang WJ, Yoo YS, Joo CK, Yoon G. Comparison of refractive outcomes between femtosecond laser-assisted cataract surgery and conventional cataract surgery. Medicine (Baltimore) 2018;97:e13784
90. Yu AY, Ni LY, Wang QM, Huang F, Zhu SQ, Zheng LY, Su YF. Preliminary clinical investigation of cataract surgery with a noncontact femtosecond laser system. Lasers Surg Med 2015;47:698–703
91. Yu Y, Chen X, Hua H, Wu M, Lai K, Yao K. Comparative outcomes of femtosecond laser-assisted cataract surgery and manual phacoemusification: a six-month follow-up. Clin Exp Ophthalmol 2016;44:472–480
92. Zhu DC, Shah P, Feuer WJ, Shi W, Koo EH. Outcomes of conventional phacoemulsification versus femtosecond laser-assisted cataract surgery in eyes with Fuchs endothelial corneal dystrophy. J Cataract Refract Surg 2018;44:534–540
93. Manning S, Barry P, Henry Y, Rosen P, Stenevi U, Young D, Lundström M. Femtosecond laser-assisted cataract surgery versus standard phacoemulsification cataract surgery: study from the European Registry of quality outcomes for cataract and refractive surgery. J Cataract Refract Surg 2016;42:1779–1790
94. Tran DB, Vargas V, Potvin R. Neodymium:YAG capsulotomy rates associated with femtosecond laser-assisted versus manual cataract surgery. J Cataract Refract Surg 2016;42:1470–1476
95. Schojai M, Schultz T, Haeussler-Sinangin Y, Boecker J, Dick HB. Safety of femtosecond laser-assisted primary posterior capsulotomy immediately after cataract surgery. J Cataract Refract Surg 2017;43:1171–1176
96. Lee JA, Song WK, Kim JY, Kim MJ, Tchah H. Femtosecond laser-assisted cataract surgery versus conventional phacoemulsification: refractive and aberrometric outcomes with a diffractive multifocal intraocular lens. J Cataract Refract Surg 2019;45:21–27
97. Shajari M, Khalil S, Mayer WJ, Al-Khateeb G, Böhm M, Petermann K, Hemkeppler E, Kohnen T. Comparison of 2 laser fragmentation patterns used in femtosecond laser-assisted cataract surgery. J Cataract Refract Surg 2017;43:1571–1574
98. Lawu T, Mukai K, Matsushima H, Senoo T. Effects of decentration and tilt on the optical performance of 6 aspheric intraocular lens designs in a model eye. J Cataract Refract Surg 2019;45:662–668
99. Palanker DV, Blumenkranz MS, Andersen D, Wiltberger M, Marcellino G, Gooding P, Angeley D, Schuele G, Woodley B, Simoneau M, Friedman NJ, Seibel B, Batlle J, Feliz R, Talamo J, Culbertson W. Femtosecond laser-assisted cataract surgery with integrated optical coherence tomography. Sci Transl Med 2010;2:58ra85
100. Friedman NJ, Palanker DV, Schuele G, Andersen D, Marcellino G, Seibel BS, Batlle J, Feliz R, Talamo JH, Blumenkranz MS, Culbertson WW. Femtosecond laser capsulotomy. J Cataract Refract Surg 2011;37:1189–1198
101. Schultz T, Joachim SC, Tischoff I, Dick HB. Histologic evaluation of in vivo femtosecond laser-generated capsulotomies reveals a potential cause for radial capsular tears. Eur J Ophthalmol 2015;25:112–118
102. Song C, Baharozian CJ, Hatch KM, Grassett GC, Talamo JH. Rate of unplanned vitrectomies in femtosecond laser-assisted cataract surgery compared to conventional phacoemulsification. J Refract Surg 2018;34:610–614
103. Sándor GL, Kiss Z, Bocskai ZI, Kolev K, Takács ÁI, Juhász É, Kránitz K, Tóth G, Gyenes A, Bojtár I, Juhász T, Nagy ZZ. Evaluation of the mechanical properties of the anterior lens capsule following femtosecond laser capsulotomy at different pulse energy settings. J Refract Surg 2015;31:153–157
104. Schultz T, Joachim SC, Noristani R, Scott W, Dick HB. Greater vertical spot spacing to improve femtosecond laser capsulotomy quality. J Cataract Refract Surg 2017;43:353–357
105. Chen M, Swinney C, Chen M. Comparing the intraoperative complication rate of femtosecond laser-assisted cataract surgery to traditional phacoemulsification. Int J Ophthalmol 2015;8:201–203
106. Roberts TV, Lawless M, Sutton G, Hodge C. Anterior capsule integrity after femtosecond laser-assisted cataract surgery. J Cataract Refract Surg 2015;41:1109–1110
107. Dick HB, Schultz T. On the way to zero phaco. J Cataract Refract Surg 2013;39:1442–1444
108. Bali SJ, Hodge C, Lawless M, Roberts TV, Sutton G. Early experience with the femtosecond laser for cataract surgery. Ophthalmology 2012;119:891–899
109. Nagy ZZ, Takacs AI, Filkorn T, Kránitz K, Gyenes A, Juhász É, Sándor GL, Kovacs I, Juhász T, Slade S. Complications of femtosecond laser-assisted cataract surgery. J Cataract Refract Surg 2014;40:20–28
110. Conrad-Hengerer I, Hengerer FH, Joachim SC, Schultz T, Dick HB. Femtosecond laser-assisted cataract surgery in intumescent white cataracts. J Cataract Refract Surg 2014;40:44–50
111. Lauschke JL, Amjadi S, Lau OCF, Parker RT, Chui J, Win S, Sim BW, Ku JJ, Lim CH, Singh R, Aggarwala A, Wei MC, Cohn GS, Chan DG, Armstrong PA, Agar A, Francis IC. Comparison of macular morphology between femtosecond laser-assisted and traditional cataract surgery. J Cataract Refract Surg 2013;39:656–657
112. Enz TJ, Faes L, Bachmann LM, Thiel MA, Howell JP, Boehni SC, Bittner M, Schmid MK. Comparison of macular parameters after femtosecond laser-assisted and conventional cataract surgery in age-related macular degeneration. J Cataract Refract Surg 2018;44:23–27
113. Shrier I, Boivin JF, Steele RJ, Platt RW, Furlan A, Kakuma R, Brophy J, Rossignol M. Should meta-analyses of interventions include observational studies in addition to randomized controlled trials? A critical examination of underlying principles. Am J Epidemiol 2007;166:1203–1209