With increasing expectations of fast visual recovery after cataract surgery, corneal cell integrity and functionality are important. Previous studies1–5 of phacoemulsification parameters and different techniques provide evidence of optimizing outcomes while reducing ultrasound (US) energy settings. Endothelial cell protection during surgery using an ophthalmic viscosurgical device (OVD) also improves postoperative results.6,7 Femtosecond lasers to assist in cataract surgery are available and have intraoperative and postoperative advantages.8–17 One advantage is a reduction in US phacoemulsification energy after lens softening.18–20 However, published studies have not yet established the long-term safety of femtosecond laser cataract surgery in terms of its effect on the cornea.21
This clinical study was performed to evaluate the impact of femtosecond laser–assisted cataract surgery on endothelial cell loss and corneal thickening over a 3-month follow-up and to compare the results intraindividually with those of standard optimized phacoemulsification. To our knowledge, this is the first clinical study performed at a single center based on an intraindividual prospective randomly distributed trial comparing the 2 surgical techniques.
Patients and methods
This prospective trial received approval of the Ethical Committee, Ruhr University, Bochum, Germany, and followed all aspects of the Declaration of Helsinki. Patients were enrolled from February to July 2012. The follow-up was 3 months.
All patients enrolled had a visually significant cataract, dilated pupil width of 6.0 mm or larger, and were willing to volunteer for the trial after giving informed consent. The exclusion criteria included a history of serious coexisting ocular disease, uncontrolled glaucoma, optic atrophy or ocular tumors, use of topical or systemic steroids or nonsteroidal antiinflammatory drugs (NSAIDs) during the previous 3 months, relevant corneal opacities, poorly dilating pupils (pupil ≤6.0 mm), known zonular weakness, age less than 22 years, or participation in another clinical study.
Preoperative and Intraoperative Measurements
A preoperative slitlamp examination to grade nuclear and cortical density of the lens was performed by an independent physician certified by the European Vision Clinical Research Institute.A The Lens Opacities Classification System III (LOCS III) nuclear opalescence grading was used.22,23 Preoperative nuclear opalescence was estimated using a BQ 900 slitlamp (Haag-Streit AG) at maximum illumination without light filtering.
Intraoperative measurements included the effective phacoemulsification time (EPT). The EPT is measured in seconds and represents the total phacoemulsification time multiplied by the average percentage power used. It is a metric of the length of phacoemulsification time at 100% power in continuous mode. All cases were videotaped to measure the total operating time. In the standard phacoemulsification group (control group), the starting point was defined by the first corneal incision and the measurement was stopped after successful hydration of the incisions. In the femtosecond laser–assisted group (study group), the measurement was started with activation of the vacuum and stopped after hydration of the incisions. Furthermore, in some cases, the irrigation fluid that went into the eye was measured. At the end of surgery, the unused irrigation fluid was added to the fluid amount necessary to calibrate the phaco machine. This was subtracted from the unopened balanced salt solution bottle and defined as the amount of balanced salt solution infused into the eye. Intraocular lens (IOL) power calculations were performed using noncontact partial coherence laser interferometry (IOLMaster, Carl Zeiss Meditec AG).
All patients had the same preoperative standardized management before surgery. After the patient was placed on the operating bed of the laser system, the surgeon opened the corresponding envelope, receiving information about the procedure to use in each eye; that is, femtosecond laser–assisted or standard phacoemulsification. Thereafter, sterile draping was placed. In the cases of standard phacoemulsification, the position of the bed remained fixed and the surgeon started with the procedure as described below. In the femtosecond laser–assisted procedure, the patient’s bed was unlocked and the position was turned toward the laser system (Catalys Precision Laser System, Optimedica Corp.). Next, the patient’s eye was engaged with a liquid optics interface.
All femtosecond laser–assisted and phacoemulsification procedures and IOL implantations were performed by the same experienced surgeon (H.B.D.). Before surgery, all patients were treated with topical ofloxacin 4 times daily for 3 days. According to the standard protocol, no NSAIDs were applied.
All patients had small-incision phacoemulsification using topical anesthesia. The 2-step clear corneal main incision was created at 12 o’clock using a 2.75 mm metal keratome (slit knife 2.75 angled, Alcon Laboratories, Inc.). The single-plane side-port incisions were created at 9 o’clock and 3 o’clock with a 1.2 mm metal keratome (side-port knife, dual bevel, angled, Alcon Laboratories, Inc.). After instillation of the ophthalmic viscosurgical device (OVD) sodium hyaluronate 1.0% (Healon) into the anterior chamber to protect the endothelium, a continuous curvilinear capsulorhexis was created using a self-bent 19-gauge needle through a side-port incision. The intended diameter was 5.0 mm.
Cataract surgery was performed using a Stellaris phaco machine (Bausch & Lomb). The standard microflow needle with an inner tip diameter of 0.91 mm, decreasing to 0.51 mm, and an angulation of 30 degrees at the opening was used. The US phacoemulsification settings used were maximum phaco power 60%, bottle height 100 cm, and maximum vacuum created by venturi pump 600 mm Hg. The technique was to establish a central groove followed by cracking of the nucleus with the help of a Neuhann Chopper (Geuder AG). After half the nucleus was flipped, further chopping under continuous phaco aspiration was performed. For removal of the remaining cortex, bimanual irrigation/aspiration (I/A) through the nasal and temporal incisions were performed followed by polishing of the posterior capsule. Vacuum settings were 600 mm Hg at maximum in all cases.
Femtosecond Laser–Assisted Phacoemulsification
A capsulotomy diameter of 5.0 mm was intended in all cases, and a standardized lens-softening pattern (quadrant grid size) with a 350 μm grid was used (Table 1). The femtosecond laser–assisted treatment technique was applied before US phacoemulsification and IOL implantation, as recently described.18,19 After the laser was docked, spectral domain optical coherence tomography imaging of the anterior segment was performed followed by automatic identification of the ocular surfaces. With the help of the graphic user interface, the surgeon confirmed the predefined laser settings according to the actual anatomic measurements with respect to the safety margins. After verification of the treatment plan, the surgeon started the laser treatment. The capsulotomy was performed, followed by lens fragmentation and softening as previously described.19 After disconnection of the laser and the liquid optics interface before lens removal, all side-port and main incisions were created as described in the standard phacoemulsification section because at the time the data were collected, the laser had not received the Conformité Européenne (CE) mark approval for corneal incisions. It gained the CE approval in March 2012. The 2-step clear corneal main incision was created at 12 o’clock using a 2.75 mm metal keratome (slit knife 2.75 angled). The single-plane side-port incisions were created at 9 o’clock and 3 o’clock with a 1.2 mm metal keratome (side-port knife, dual bevel, 1.2 angled, Alcon Laboratories, Inc.).The precut anterior capsule was extracted with a Koch capsulorhexis microforceps (Geuder AG).
Identical phacoemulsification parameters and OVD were used in both groups. First, the supranuclear cortex was removed by aspiration using the phaco tip. A second instrument (Neuhann chopper) was inserted through 1 paracentesis and the nucleus grooved by the stop-and-chop technique in the fragmented area (quadrant grid size19). The softened nucleus was aspirated with or without US phacoemulsification energy. Residual cortex removal and posterior capsule polishing were performed using bimanual I/A through the nasal and temporal incisions.
After the anterior chamber and capsular bag were reinflated with the OVD, a preloaded heparin-coated hydrophobic IOL (Polylens H10, Polytech Ophthalmologie GmbH) was implanted in the capsular bag without enlarging the corneal tunnel. The OVD was removed, and the corneal incisions were hydrated. Then, all eyes were covered with a patch.
Topical ofloxacin eyedrops were administered 3 times daily for 5 days. Dexamethasone eyedrops were administered 4 times daily for the first week, after which the dosage was gradually tapered over 6 weeks.
The endothelial cell count (ECC) and corneal thickness were measured preoperatively, and 1 day and 3 to 4 days postoperatively (only pachymetry), 7 to 10 days, 50 to 60 days, and 90 to 100 days after surgery. All patients had a full clinical examination by the same masked trained technician. The examination included manifest refraction, corrected distance visual acuity (CDVA), ECC using an endothelial noncontact computer-assisted specular microscope (Sea Eagle, Rhine-Tec), and Scheimpflug imaging of the anterior segment including corneal pachymetry, topography, and keratometry (Pentacam HR, Oculus Optikgeräte GmbH).11 The surface of the endothelium was measured at 970 μm2 × 720 μm2 using the noncontact specular microscope. Fifty images were generated automatically to analyze the center of the cornea. Automatic hexagonal cell counts were performed, and the mean values were derived. The percentage of endothelial cell loss was calculated using the following formula, where pre = preoperative and post = postoperative:
All descriptive statistical analysis was performed using SPSS software (version 19.0, SPSS, Inc.). The t test was used to compare the sample means. A P value less than 0.05 was considered statistically significant. Continuous variables were described with the mean, standard deviation (SD), median, minimum, and maximum values. Boxplots were used for analysis of endothelial cell loss and corneal thickness. Correlation analysis was performed using the Pearson correlation coefficient (r). The sample size was chosen to achieve a statistical power of more than 80% for the group comparison using a 2-sample Wilcoxon test at a 5% significance level.
According to the study protocol, 75 patients (150 eyes) were recruited. Two patients were excluded at the 3-month follow-up because they missed their previous visits. One patient had cancer and was not available for further visits; the other moved to another county. Thus, the study evaluated 146 eyes of 73 patients (46 women). The mean age of the patients was 70.9 years (range 46 to 86 years).
The mean applied EPT was 0.0 second ± 0.1 (SD) in the study group and 1.4 ± 0.1 seconds in the control group. Table 2 shows the LOCS III grades and the correlated EPT by group. In the study group, 47 eyes (64.4%) had an EPT of 0.00 second, 66 eyes (90.4%) had an EPT of 0.07 second or less, and all eyes had a maximum EPT of 0.54 second (nuclear opalescence 4). In the control group, all eyes required an EPT of at least 0.07 second; 23 eyes (31.5%) had an EPT of 0.54 second, 37 eyes (50.7%) had an EPT of less than 1.27 seconds, and 66 eyes (90.4%) had an EPT of less than 2.76 seconds.
Three months postoperatively, 146 eyes were included and analyzed. In the study group, the mean endothelial cell loss was 7.9% ± 7.8% 1 week after surgery and 8.1% ± 8.1% at 3 months. In the control group, the loss was 12.1% ± 7.3% and 13.7% ± 8.4%, respectively (Figure 1). The change in cell loss between the 2 groups was statistically significantly different over the whole postoperative period (P < .001).
Table 3 and Figure 2 show the absolute endothelial cell values over time. At the 3-month postoperative visit, there was a slight statistically significant difference between the study group and the control group (P = .049).
The mean relative change in corneal thickness from the preoperative values was −0.0% ± 1.9% at 1 day, 2.8% ± 1.8% at 1 week, and 3.3% ± 1.7% at 3 months in the study group and −0.9% ± 2.3%, 2.4% ± 1.5%, and 3.2% ± 1.4%, respectively, in the control group (Figure 3). Table 4 shows the absolute corneal thickness values.
The mean irrigation fluid that entered the eye was 91 ± 12 mL (range 72 to 114 mL) in the study group (n = 39) and 89 ± 10 mL (range 69 to 105 mL) in the control group (n = 39). The mean surgical time was 396 ± 23 seconds (range 341 to 442 seconds) and 390 ± 22 seconds (range 332 to 435 seconds), respectively (n = 73). There were no significant differences between the 2 groups (P > .05) (Figure 4).
The endothelial cell loss at the 3-month postoperative visit (r = 0.433) and the CDVA 1 day after surgery (r = 0.262) showed a positive correlation with the EPT. The endothelial cell density at the 3-month postoperative visit (r = 0.163), the endothelial cell loss at the 3-month postoperative visit (r = −0.325), and the CDVA at day 1 (r = 0.217), 3 to 4 days (r = 0.181), and 1 week after surgery (r = 0.167) were correlated with the EPT. There was a correlation between the CDVA at 1 day (r = 0.182) and nuclear density according to the amount of EPT.
In 1 eye in the control group, an anterior capsule tear occurred intraoperatively without further complications. The intraoperative course in the study group was uneventful in all cases. Postoperatively, 5 eyes (2 in study group, 3 in control group) developed clinically significant macular edema with a reduction in CDVA (20/63 to 20/32) and 2 eyes (both in control group) developed subclinical macular edema. After therapy, the CDVA increased to 20/25 or better in all cases. Elevated intraocular pressure was measured immediately after surgery in 4 eyes (study group: 30 mm Hg and 33 mm Hg; control group: 29 mm Hg and 39 mm Hg) and 1 week postoperatively in 1 eye (study group: 26 mm Hg).
In our study, we compared endothelial cell loss and corneal thickness changes over a 3-month follow-up in 146 eyes of 73 patients having standard cataract surgery with phacoemulsification in 1 eye (control group) and femtosecond laser–assisted cataract surgery followed by phacoemulsification with or without US energy in the other eye (study group). Corneal endothelial cells are responsible for the corneal transparency by actively reducing the amount of stromal edema resulting from perioperative and postoperative stress. The study was designed to be intraindividual to control for biological responses.
It is well known that the US application during phacoemulsification can lead to endothelial cell damage in cataract surgery due to mechanical trauma from sonic waves and from thermal injury.24 Since the introduction of US phacoemulsification, technology and techniques have evolved to reduce the amount of US energy used in the eye to limit collateral damage.25,26 Mencucci et al.4 report endothelial cell loss between 4% and 25%. After endothelial cell damage, the timeframe for endothelial cell recovery ranges from 1 to 6 months.7 In our study, the standard phacoemulsification technique was optimized with technology and techniques known to limit endothelial cell loss. This included using Healon, power modulations for the phacoemulsification, and microincision cataract surgery. Our findings in the phacoemulsification group are comparable to the corneal endothelial cell loss reported in the literature.
Since femtosecond laser applications for assistance in cataract surgery have been available, evidence has shown significant reductions in the amount of US energy used during surgery.18 Based on the settings of each laser system, the nucleus can be fragmented and softened to different degrees, enabling the surgeon to aspirate the remaining particles with less US energy if necessary. In our study, the use of a femtosecond laser followed by minimal US energy (mean EPT 0.0 ± 0.1 second) led to significantly lower endothelial cell loss than in eyes in our control group.
Furthermore, in many eyes (64.4%) in the study group, no US energy was needed to remove the lens fragments; these eyes should be compared with eyes in studies of refractive lens exchange (RLE) in which minimal US energy was used. Xiao et al.27 report a corneal endothelial cell loss rate of 1.9% 1 year after RLE in patients with high myopia. In our study, the cell loss after femtosecond laser–assisted surgery after 3 months was slightly higher but still much lower than that reported by Mencucci et al.4 One possible explanation for this difference is the deeper anterior chamber in myopic eyes than in the average cataractous eyes in our study and the resulting larger distance and smaller effect between the phaco tip and corneal endothelium in deep eyes.
There was a significant reduction in central corneal thickness after femtosecond laser–assisted surgery, suggesting that in these cases, pretreatment softening of the nucleus reduces phacoemulsification time and US energy. Less corneal edema leads to a faster visual recovery after IOL implantation and therefore is beneficial for patients. This was shown in our study; that is, the visual results 1 day after surgery were significantly better in the study group than in the control group.
Although not primary endpoints in this study, other variables had an affect on the corneal endothelium during cataract surgery. These included biochemical and mechanical effects of the irrigating solution, (eg, the solution volume or turbulence of the solution) and direct mechanical trauma from manipulations of instruments in the eye, both of which are related to total case time and technique. One study28 found that endothelial cell loss was mostly related to increased cumulative US energy, aspiration time, and volume of balanced salt solution used. Another study29 found a strong relationship between total US energy and endothelial cell loss but not between total infused fluid and endothelial cell loss. Given the significant results shown here with a reduction in US energy alone, perhaps the relative contributions of the other variables, such as total infused fluid, are smaller. Postoperative corneal health is multivariate, and future studies should continue to isolate these variables and correlate them independently to endothelial cell loss, corneal edema, and visual outcomes.
In our prospective randomized intraindividual study, the study group, with the near elimination of US energy in dense cataracts (mean nuclear opalescence 3.1 ± 0.8), had statistically significantly less endothelial cell loss (41%) at 3 months than the control group in eyes with comparable nuclear density. The femtosecond laser did not add to the endothelial cell damage caused by the cataract surgery and is therefore beneficial in eyes with preoperative low ECCs, such as in cases of cornea guttata and Fuchs dystrophy. These results are promising and increase the evidence of the safety and benefits of femtosecond laser–assisted cataract surgery. Because the potential for cell recovery after intraocular surgery lasts up to 6 months, our next step in this ongoing study is to evaluate the measurements over a longer follow-up and to compare the findings with those reported in the literature.
What Was Known
- Ultrasound energy used in phacoemulsification during cataract surgery leads to endothelial cell damage and corneal edema.
What This Paper Adds
- Femtosecond laser–assisted cataract surgery with softening of the lens before phacoemulsification led to a significant reduction in endothelial cell loss and faster visual recovery.
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