February 2019


EyeWorld journal club
A review of “Changes in aqueous oxidative stress, prostaglandin, and cytokines: Comparisons of low-energy femtosecond laser-assisted cataract surgery versus conventional phacoemulsification”

by Christine Bokman, MD, Eric Shieh, MD, and Patrick Lee, MD

Kevin Miller, MD, chief of the cataract and refractive surgery division, David Geffen School of Medicine at UCLA

UCLA residents, from left: Eric Shieh, MD, Patrick Lee, MD, and Christine Bokman, MD
Source: UCLA

Aqueous prostaglandin and cytokine levels provide insight into the severity and duration of low-grade surgical inflammation. I asked the UCLA residents to review this randomized study from the current issue of JCRS comparing FLACS and phaco and the efficacy of topical NSAIDs.
—David F. Chang, MD,
EyeWorld journal club editor



As ophthalmology residents at the University of California, Los Angeles (UCLA), we perform cataract surgery at four different hospitals. During our final year of residency, we spend 6 weeks in the cataract and refractive clinic at Stein Eye Institute, where we can offer our patients femtosecond laser-assisted cataract surgery (FLACS). Only a few other residencies in the country give residents the unique opportunity to perform FLACS. As cataract surgery continues to evolve, it has become increasingly important for ophthalmologists in training to have access to the latest technologies, since these advancements have the potential to improve patient safety and outcomes.
From a training perspective, residents must learn to critically evaluate the impact of new technologies, as the adoption of technologies like FLACS affects surgical outcomes and alters the cataract surgery learning curve. Prechopping the nucleus with a femtosecond laser has the advantage of minimizing phacoemulsification power, postoperative corneal edema, and corneal endothelial trauma.1 On the other hand, when compared to conventional phacoemulsification, high-energy FLACS has been shown to be associated with higher prostaglandin levels and a different cytokine profile in the aqueous.2,3 The spike in prostaglandin levels is associated with intraoperative miosis, which hampers surgical exposure, may require the placement of a pupil-expanding device, and can make nearly every step of phacoemulsification more challenging.4
Prior studies have focused on the inflammatory profile of the aqueous after femtosecond laser pretreatment but not at the end of phacoemulsification, which is likely a better measure of the immediate postoperative inflammatory response. The effect of a low-energy femtosecond platform on these measures had also not been investigated previously.
In this study, Liu and colleagues compared aqueous cytokine and prostaglandin levels, oxidative stress, pupil size, and clinical flare between low-energy FLACS and conventional phacoemulsification. Aqueous profiles before laser pretreatment or at the beginning of surgery and after phacoemulsification were measured. The effect of preoperative non-steroidal anti-inflammatory drug (NSAID) use on these parameters was also evaluated.

Study summary

A randomized controlled trial was designed to compare low-energy femtosecond laser-assisted cataract surgery (FLACS) to conventional phacoemulsification. The study took place at a Singaporean eye hospital and consisted of 70 patients. Thirty-five patients with bilateral cataracts received conventional phacoemulsification in one eye and FLACS (FLACS group) using the LDV Z8 system (Ziemer Ophthalmic Systems, Port, Switzerland) in the other eye 3–4 weeks later. An additional age-matched and cataract density-matched prospective cohort of 35 subjects received FLACS with preoperative NSAID administration (FLACS-N group, which received 0.4% topical ketorolac tromethamine four times daily 24 hours prior to surgery). For the FLACS and FLACS-N groups, the femtosecond laser performed the corneal incision, anterior capsulotomy, and lens fragmentation steps.
With limbal paracentesis, aqueous humor was collected after laser pretreatment for the FLACS and FLACS-N groups, before phacoemulsification for the conventional phacoemulsification group, and after phacoemulsification for all groups. Levels of malondialdehyde (MDA, a free radical and measure of oxidative stress), prostaglandin E2 (PGE2), and 45 different cytokines were measured. Pupil size and clinical flare between the groups were compared.
After laser pretreatment, FLACS had statistically significant higher levels of PGE2 and interleukin-1 receptor antagonist (IL-1RA) as compared to conventional phacoemulsification. Preoperative NSAID use significantly decreased the level of PGE2 in FLACS to the same level as that in conventional phacoemulsification. FLACS caused intraoperative miosis, but the frequency of clinically significant intraoperative miosis in FLACS was significantly reduced by preoperative NSAID use (20% vs. 46%). MDA levels and clinical flare were insignificantly higher in FLACS than conventional phacoemulsification.
After phacoemulsification, PGE2 levels increased in all groups, and there was no significant difference among the groups. After phacoemulsification, MDA levels also increased in all groups. The increase in MDA levels was significantly correlated with effective phacoemulsification time, which was shown in a separate analysis to be significantly higher in the conventional phacoemulsification group than the FLACS group.


Since the advent of FLACS, several studies have compared FLACS to conventional phacoemulsification. The study by Liu et al. is the first to analyze aqueous fluid both after laser pretreatment and after phacoemulsification, which provides insight into the immediate postoperative inflammatory response in FLACS.
After laser pretreatment, the FLACS group had higher prostaglandin levels than the conventional phacoemulsification group. The addition of preoperative NSAIDs (FLACS-N group) significantly reduced prostaglandin levels and frequency of intraoperative miosis, but did not decrease the rise in post-phacoemulsification prostaglandin levels. The finding that 20% of patients in the FLACS-N group still developed intraoperative miosis implies that other factors aside from prostaglandins may contribute to miosis.
Another unique and clinically relevant aspect of this study is its measurement of MDA, a marker of oxidative stress that had only been collected in vitro in prior studies. Oxygen free radicals are created during phacoemulsification and aspiration and irrigation, and can potentially damage the corneal endothelium.5 This study showed that although oxidative stress was greater in FLACS compared to conventional phacoemulsification, this difference was not significant. FLACS may therefore cause similar levels of oxidative stress as conventional phacoemulsification but have the added potential advantage of decreased effective phacoemulsification time due to the laser lens fragmentation step.
It is important to note that a low-energy femtosecond laser platform was utilized in this study. As such, these results may not translate to a higher-energy machine, such as the LenSx (Alcon, Fort Worth, Texas). A high-energy machine may potentially increase MDA concentration to the point of statistical significance when compared to conventional phacoemulsification. A study that measures MDA levels and other markers of oxidative stress after phacoemulsification with a high-energy machine is warranted.
The major strength of the study is its randomized controlled design, which randomized patients to receive FLACS in one eye and conventional phacoemulsification in the other eye. Performing both interventions in a single patient reduces confounders by limiting patient-to-patient variation. However, the study is limited by its small sample size. A larger sample size could have given the study greater power to detect true differences, and borderline and insignificant results in this study could well have become statistically significant.
Overall, the study demonstrates that low-energy FLACS has the advantage of decreasing effective phacoemulsification time, while having similar levels of inflammation and oxidative stress at the end of cataract surgery as conventional phacoemulsification. While the risk of intraoperative miosis is higher with FLACS, that risk can be mitigated but not completely eliminated with the use of preoperative topical NSAIDs. The findings of this study add to the many factors influencing the decision to choose FLACS over conventional phacoemulsification or vice versa, which includes but is not limited to safety profile, visual outcome, and patient preference. By continually reviewing the literature both during and after residency, we will be able to advise our patients on the best treatments and technology available.


1. Takacs AI, et al. Central corneal volume and endothelial cell count following femtosecond laser-assisted refractive cataract surgery compared to conventional phacoemulsification. J Refract Surg. 2012;28:387–91.
2. Schultz T, et al. Changes in prostaglandin levels in patients undergoing femtosecond laser-assisted cataract surgery. J Refract Surg. 2013;29:742–7.
3. Chen H, et al. Expression of cytokines, chmokines and growth factors in patients undergoing cataract surgery with femtosecond laser pretreatment. PLoS One. 2015;10:e0137227.
4. Jun JH, et al. Effects of topical ketorolac tromethamine 0.45% on intraoperative miosis and prostaglandin E2 release during femtosecond laser-assisted cataract surgery. J Cataract Refract Surg. 2017;43:492–497.
5. Takahashi H, et al. Free radicals in phacoemulsification and aspiration procedures. Arch Ophthalmol. 2002;120:1348–52.

Contact information

Miller: miller@jsei.ucla.edu

A review of “Changes in aqueous oxidative stress, prostaglandin, and cytokines: Comparisons of low-energy femtosecond laser-assisted cataract surgery versus conventional phacoemulsification” A review of “Changes in aqueous oxidative stress, prostaglandin, and cytokines: Comparisons of low-energy
Ophthalmology News - EyeWorld Magazine
283 110
220 115
True, 2