Comparison between Ringer’s lactate and balanced salt solution on postoperative outcomes a ft er phacoemuls (cid:222) cation: A randomized clinical trial

and postoperative anterior chamber in (cid:223) ammation following phacoemulsi (cid:222) cation. This prospective, randomized examiner and patient masked study comprised 90 of 90 patients with uncomplicated Aim: To compare the effects of balanced salt solution (BSS) and Ringer’s lactate (RL) on corneal thickness, endothelial morphology, and postoperative anterior chamber in (cid:223) ammation in eyes undergoing phacoemulsi (cid:222) cation. Se tt Ahmedabad, India. Materials and Methods: This prospective randomized study comprised 90 consecutive patients with age-related cataract who were randomly assigned to either Group 1 (n = 45) with BSS or Group 2 (n = 45) with RL. Observations made included measurement of central corneal thickness (CCT), presence of anterior chamber (cid:223) are and cells, endothelial cell loss, and change in coe ﬃ cient of variation (CV). Data was analyzed using Mann Whitney test and test of proportion. Results: Mean increase in CCT on postoperative Day 1 was 58 (cid:181)m and 97 (cid:181)m in Groups 1 and 2 respectively ( P = 0.01). Increase in CCT at one month was 10 (cid:181)m and 11 (cid:181)m in Groups 1 and 2 respectively ( P = 0.99); increase in CCT at three months was 3 (cid:181)m and 6 (cid:181)m in Groups 1 and 2 respectively ( P = 0.86). Number of eyes with (cid:223) are grades in a range of 0 to 3 was statistically higher in Group 2 on postoperative Day 1 ( P = 0.004, 0.016, <0.001, 0.047 for Grade 0, 1, 2 and 3 respectively). Number of eyes with cells of Grade 3 on (cid:222) rst postoperative day was signi (cid:222) cantly higher in Group 2 as compared to Group 1 ( P = 0.004). Three months postoperatively, endothelial cell loss was 5.5% and 7.8% in Groups 1 and 2 ( P = 0.21) and change in CV was 3 and 5.4 in Groups 1 and 2 ( P = 0.20) respectively. Conclusion: BSS o ﬀ ers a signi (cid:222) cant advantage over RL in terms of increase in corneal thickness and postoperative in (cid:223) ammation on the (cid:222) rst postoperative day in patients undergoing phacoemulsi (cid:222) cation.

senile cataract, aged between 55 to 70 years, scheduled for phacoemulsiÞ cation. Informed consent was obtained from all patients before they were enrolled in the study. The study followed the tenets of Helsinski. Patients with coexisting corneal pathologies, an endothelial cell count of <1500 cells/mm 3 , glaucoma, diabetes mellitus, uveitis, trauma, or prior intraocular surgery were excluded from the study. Other exclusion criteria were patients on systemic or topical steroids. All types of cataract and grades of nuclear sclerosis ranging on a scale of 1 to 4 as per Emery's classiÞ cation were included in the study. [9] The preoperative investigation included a slit-lamp examination and fundus evaluation. Specular microscopy was performed with a non-contact specular microscope (Topcon, Tokyo, Japan) to analyze the central corneal endothelium. One hundred contiguous cells were analysed. [10] The endothelial cell density (ECD) and coeffi cient of variation (CV) were measured in all cases. CV was calculated by dividing the standard deviation of the cell areas measured in each specular micrograph by the mean cell area. This index provided a measurement of the cell size variability (polymegathism) which is independent of cell area and density. Central corneal thickness (CCT) was assessed by ultrasonic pachymetry (Ocuscan, Alcon, Texas, USA) performed by a single observer. The subject was asked to look at a Þ xation target placed at a certain distance while the ultrasound probe was placed perpendicular to the central cornea without applying any undue pressure. An average of three readings was considered. [11] Prior to surgery, the patients were randomized into two groups using computer-generated random numbers. Group 1 received BSS and Group 2 received RL as an irrigating solution [ Table 1] during surgery. The ß uids were stored in a room and brought inside the operation theater immediately prior to the surgery to maintain a temperature of 23 degrees celcius during surgery.
A single surgeon (ARV) performed all surgeries under topical anesthesia using a standardized surgical technique. Two limbal paracentesis incisions of 1mm were made in the clear cornea 180 degrees apart using an angled dual beveled 1-mm knife (Alcon Laboratories, Fort Worth, USA). Viscoat ® (Alcon Laboratories, Fort Worth, USA) was injected into the anterior chamber to coat the corneal endothelium followed by the injection of Provisc (Alcon laboratories, USA) to maintain the depth of the anterior chamber. [12] A 2.2-mm single plane temporal clear corneal incision was made. A bent 26G cystotome was used to initiate a small nick in the anterior capsule and capsulorrhexis was completed using Utt rata forceps. Thorough multiquadrant hydrodissection was performed. Microcoaxial phacoemulsification was performed on the Infiniti Vision System (Alcon Laboratories, Fort Worth, USA) using stepby-step, chop in situ, lateral separation [13] and step-down [14] techniques.
The parameters used during diff erent stages of surgery were a power of 30-50%, microburst with burst width of 5-30 milliseconds, a vacuum of 250-650 mm Hg, and an aspiration ß ow rate of 25-30 cc/min. The bott le height was raised to a maximum of 110 cm from a minimum of 90 cm during fragment removal. Care was taken to perform phacoemulsiÞ cation at the posterior plane. Constant anterior chamber depth was maintained with injection Viscoat ® before removing any instrument from the eye. Bimanual irrigation / aspiration was performed for cortex removal. An Acrysof Natural IQ intraocular lens (IOL) (SN60WF, 6 mm optic, 13 mm overall diameter) was implanted in the bag. The residual viscoelastic was removed with bimanual irrigation/aspiration. The main incision as well as the paracentesis was hydrated. [15] The postoperative regime was also standardized in both groups.
The following intraoperative observations were made: amount of ß uid used from commencement of sculpting to the end of viscoelastic removal aft er IOL implantation, surgical clock time from commencement of sculpting to the end of epinucleus removal, eff ective phaco time (average ultrasound (u/s) power x average u/s time/100), occurrence of excessive iris manipulation, Descemet's detachment, incisional burns, and posterior capsule rupture.
Postoperatively, the patient was examined on Day 1, and at one and three months. At each follow-up visit, corneal clarity was noted as the presence or absence of Descemet's folds and intrastromal or epithelial edema. Anterior chamber ß are and cells were graded as per Hogan's criteria. [16] The CCT was measured by ultrasound pachymetry at postoperative Day 1 and at one and three months postoperatively. At three months follow-up, specular microscopy was performed. These examinations were done by the same observer who performed the tests preoperatively and was masked to the allocation.
The main outcome measures were an increase in CCT from the baseline preoperative value, percentage loss of ECD, change in the CV from preoperative values, and change in the anterior chamber ß are and cells between the groups.
The increase in CCT in microns was calculated by noting the diff erence between CCT on the Þ rst postoperative day and the preoperative CCT. Similarly, change in CCT was also calculated at the one and three months follow-up visits.
Percentage decrease in endothelial cell density (ECD) was calculated as follows: ECD at 3 months follow-up -preoperative ECD × 100 Preoperative ECD The change in the CV was calculated as the diff erence between CV at the three months follow-up and the preoperative CV.
Data were entered in an Excel Þ le and computed using a statistical soft ware package (SPSS 3.1, SPSS Inc, Chicago). Statistical analysis was done using the non-parametric Mann-Whitney test, as the data were not normally distributed and 95% conÞ dence intervals were calculated for diff erences in mean results. A P value of <0.05 was considered statistically signiÞ cant.

Results
Of the 90 patients enrolled in the study, 83 patients completed the last postoperative follow-up. Two patients were transferred to a distant destination, one suff ered an acute ischemic heart disease and expired. One patient refused to continue with his participation in the study as a macular hole was detected during a follow-up visit. Two patients were recuperating from illness and therefore their results were excluded from the analysis. The groups were comparable in terms of gender, age, and distribution of the type and density of cataract. The mean age of the patients was 58 ± 13.3 years in Group 1 and 56.5 ± 15.7 years in Group 2. The mean follow-up was 3.1 ± 0.2 months and 2.9 ± 0.2 months in Group 1 and 2 respectively.
The preoperative CCT in both the groups was comparable (533 + 27 in BSS versus 523 + 31 um in RL). The surgical clock time and amount of ß uid used in both the groups was also comparable [ Table 1]. In both the groups, the CCT increased from the preoperative baseline on the Þ rst postoperative day. This increase was signiÞ cantly higher in Group 2 as compared with Group 1 [ Table 2]. There was no signiÞ cant diff erence in CCT between the groups at the one month or three month follow-up.
The mean endothelial cell (ECD) loss at three months was 5% in Group 1 and 8% in Group 2. The mean change in CV from preoperative values was 3 in Group 1 and 5 in Group 2. The ECD loss and change in CV at three months were statistically insigniÞ cant.
On postoperative Day 1, none of the eyes in either group had ß are of Grade 4 severity. A higher percentage of individuals in the BSS group had statistically signiÞ cant lower levels of ß are [ Table 3]. The percentage of individuals with cells of Grade 3 severity was signiÞ cantly higher in the group subjected to RL. In subsequent examinations, ß are and cells were not evident in any eye of either group.

Discussion
A majority of clinical studies have compared BSS Plus to BSS. [2,6,17,18] This study was conÞ ned to a comparison between RL and BSS because of the widespread use and cost-eff ectiveness of RL in comparison to BSS Plus. Moreover, comparing RL and BSS would be clinically more relevant in the context of minimally traumatic modern cataract surgeries. We chose not to include BSS Plus in the comparison because suffi cient evidence already exists about its ability to induce minimal corneal alterations both in experimental [1,2,19] and clinical trials [18,20] and also because of its selective use owing to its high cost.
Ringer lactate contains potassium, calcium, and lactate ions which maintain corneal endothelial cells for long periods. Calcium is essential for protecting the endothelial cell functions. [21] However, RL is hypotonic and slightly acidic (osmolality 280 mmol, pH 6.0) as compared to BSS (osmolality 302 mmol, pH 7.4) and aqueous (osmolality 302 mmol, pH 7.4). It lacks a buff er system and energy source for the endothelium. In addition to potassium, calcium, and lactate, BSS contains magnesium (essential for the Mg-ATPase endothelial pump) and an acetate citrate buff er system. It is only slightly hypotonic to the aqueous ß uid and has an alkaline pH. Previous studies have shown that BSS is superior to RL, though not as ideal as BSS Plus. [4]    Corneal thickness increases when the pump and barrier functions of the endothelium are compromised. Measuring CCT helps gauge the extent of the surgically induced endothelial trauma. There was an acute, signiÞ cant increase in the CCT on postoperative Day 1 in both the groups. BSS induced signiÞ cantly lower corneal swelling than RL on the Þ rst postoperative day. The increase in CCT observed on the Þ rst postoperative day and its reversal to values close to the preoperative baseline at three months concurs with the observations of Kiss et al. [6] Standardization of the surgical technique by a single experienced surgeon eliminated mechanically induced trauma as a cause for endothelial damage. The similarity in the distribution of type and grade of nuclear sclerosis eliminated energy dissipation as a cause for increased corneal thickness. Since the duration of the surgical time and amount of ß uid used was comparable in both the groups, diff erences in the constitution appear to be responsible for higher short-term damage to the corneal endothelium in the RL group. This is reß ected by the increased corneal swelling in the immediate postoperative period in the group subjected to RL. [4] This may, in turn, delay visual rehabilitation. In addition, the increased corneal swelling with RL may be even more signiÞ cant in eyes with compromised corneas.
The average decrease in postoperative endothelial cell density was comparable to values observed in previous studies. [22,23] There was no diff erence in terms of cell density between the two groups at three months postoperatively. The changes in the morphology of the endothelial cells are sensitive indicators of loss of endothelial function. [24] The CV of cell areas (polymegathism) was determined by measuring 100 cells in each group. It was observed that both the groups had similar compositions of small and large cells. The Viscoat ® used in every case may have provided substantial barrier protection that resulted in the lack of signiÞ cant diff erence in endothelial cell counts between the two groups. [25] A majority of studies have evaluated the impact of irrigating ß uids on the corneal endothelial function. However, very few studies have evaluated postoperative inß ammation. [17,26] The use of cooled irrigating ß uids has been recommended as a method of reducing postoperative inß ammation. [26] However, such cooled ß uids have only a short-term impact. The presence of a low grade of ß are and cells on the Þ rst postoperative day in a majority of our patients in the BSS group supports our hypothesis that cooling the irrigating ß uid is not necessary to reduce inß ammation. [27] Since the surgeries were done by a single surgeon experienced in phacoemulsification, the diff erence in the inß ammatory response can be solely att ributed to the composition of the ß uid. Our results concur with the favorable response on inß ammation observed with BSS. We believe that a statistically signiÞ cant larger number of patients with ß are and cells of Grades 2 and 3 in Group 2 on the Þ rst postoperative day may be due to the slightly acidic ß uctuating pH and lack of buff er system in RL which could aff ect the blood aqueous barrier stability. On the other hand, BSS has an acetate citrate buff er system and the pH, though slightly alkaline, is stable. This is one of the few studies evaluating the impact of irrigating ß uids for a postoperative duration of three months. [6] The present study has shown the clinical advantages of BSS in the immediate postoperative period and its use seems justiÞ ed in eyes undergoing cataract surgery. Along with appropriate technique and technology, the clinical beneÞ t off ered by BSS on the Þ rst postoperative day helps the patient achieve clear cornea on Day 1 with immediate visual rehabilitation. We believe the impact of using RL in eyes with low endothelial reserve can be magniÞ ed. Therefore, BSS should atleast be considered in lieu of RL in selective eyes with a lower endothelial cell reservoir, anticipated prolonged surgical duration, and those requiring excessive surgical manipulation.
In conclusion, the results of this prospective randomized masked trial demonstrated that eyes receiving BSS had signiÞ cantly lesser corneal thickness and inß ammation on the Þ rst postoperative day as compared to eyes that received RL, however, there was no signiÞ cant diff erence at one and three months postoperatively.