The effect of povidone-iodine 10% plus levofloxacin 0.5% before cataract surgery: a randomized clinical trial

Abstract

This study was designed to assess the efficacy of using povidone-iodine (PVI) 10% and levofloxacin 0.5% about one hour before cataract surgery in minimizing aqueous contamination compared with using PVI 10%. The intervention group received three drops of mixed povidone-iodine and levofloxacin (PVI/Levofloxacin) solution one hour before surgery. After making the corneal incision in cataract surgery, 0.1 cc aqueous humor sample was taken and sent for culture. We compared the intervention group and control group using t-test and chi-square test in SPSS 25(Chicago IL, USA). 147 eyes of 147 patients were analyzed. The intervention and control groups consisted of 72 and 75 patients, respectively. The Control group showed significantly more positive cultures (16 cultures: 22.2%). the intervention group had four positive cultures (5.3%). (P-value = 0.005). Topical levofloxacin 0.5% and povidone-iodine 10% mixture showed promising results in reducing the number of bacteria in the aqueous humor.

Introduction

Acute postoperative bacterial endophthalmitis is an infrequent but disastrous complication after cataract surgery. Based on the large number of cataract surgeries conducted each year, the overall incidence of endophthalmitis is considerable. In addition, endophthalmitis can lead to loss of sight or even a globe in some cases despite appropriate treatment [1]. Consequently, effective prevention is of paramount importance. The patient’s flora of the conjunctiva and the eyelids are the sources of bacterial contamination after cataract surgery [2]. Elimination of the bacterial source in the conjunctiva is a critical step to reduce endophthalmitis.It has been proved that using preoperative antiseptics in the surgical field and adhering to the sterile protocol in the surgical devices lead to preventing endophthalmitis [3, 4]. Povidone-iodine is the most common and available antiseptic used before cataract surgery. Different concentrations of PVI has been assessed in different studies [3]. Although in vitro studies concluded that lower PVI concentration has the same effect as higher concentration [5], clinical studies still approve a better impact of higher concentrations [6]. The role of additive antibacterial agents is still in question for providing sterility to the field of operation. Moreover, there is no consensus about the most appropriate PVI concentration and the ideal additive antibacterial agent [2, 7]. This study was designed to assess the efficacy of using PVI 10% and levofloxacin 0.5% about one hour before cataract surgery in reducing aqueous contamination compared with using PVI 10%.

Materials and methods

This study was a prospective double blinded randomized clinical trial. Study sample size was according to previous studies. 147 eyes of 147 patients were included in this study that 72 patients were included in intervention group and 75 patients were included in control group (Fig. 1). The inclusion criterion was immune-competent patients who were candidates for cataract surgery. Exclusion criteria consisted of patients with systemic diseases who received a systemic antibiotic in the last month, those with diabetes mellitus, Rheumatologic disorders, infectious diseases, previous surgery, trauma, nasolacrimal duct obstruction and ocular surface disorders, conjunctivitis; patients using topical antibiotics, corticosteroids, and non-steroidal anti-inflammatory drugs in the last month; and the individuals wearing contact lens. Patients were assigned randomly to either control or interventional groups using Research Randomizer software. Best-corrected visual acuity measurement, slit-lamp examination, fundoscopy, and IOP measurement was performed in Poostchi Eye Clinic, affiliated to Shiraz University of Medical sciences. Age and gender of both groups were compared.

Participants, surgeons who took the anterior chamber samples, pathologist who read the cultures and reported the results and statistician were blinded and unaware of treatment group assignments to prevent bias. Randomization was performed by an assistant who had no role in patient selection, aqueous sampling, culture reporting and statistical analysis using Research Randomizer software. This study was under the tenets of the Declaration of Helsinki and approved by the ethics committee of Shiraz University of Medical Sciences and the Iranian Registry of Clinical Trials (IR.SUMS.MED.REC.1398.610 and IRCT20191023045211N1). This study adheres to CONSORT guidelines and SPIRIT guidance for clinical trial protocols [8].

Fig. 1

The CONSORT diagram showing the allocation process throughout the trial

Intervention

The intervention group received three drops of mixed povidone-iodine and levofloxacin (PVI/Levofloxacin) solution one hour before the surgery. Replacing 50% from levofloxacin 0.5% drop with povidone-iodine (PVI) 10% in sterile conditions prepared solution. PVI 10% applied for periorbital disinfection for 5 min. After sterile draping, the surgeon instilled three drops of PVI 10% in the eye. Before the corneal incision, the surgeon irrigated the ocular surface with 30 ccs balanced salt solution for all patients. The 0.1 cc from the aqueous humor sample was taken after the corneal incision before mydriatic injection. Then, the samples were immediately transferred to thioglycolate broth. The pathologist assessed the tubes daily for a maximum of 5 days. Development of a cloudy appearance indicated bacterial growth in broth. If broth became cloudy, it was assumed as positive and transferred from the thioglycolate medium to the solid blood agar medium for further evaluation and typing. If bacteria grow on solid blood agar plate, it is possible to determine the colonial characteristics of the bacteria.The sample was considered sterile if the tube contained clear aqueous after five days.

Sterility of surgical instruments were checked and efforts were made to ensure that the instruments were not a source of infection. All patients were followed for one month.

Statistical analysis

Authors performed all statistical analyses using SPSS 25(Chicago IL, USA). We compared the intervention group and control group using t-test and chi-square test. P-values less than 0.05 were considered statistically significant.

Results

147 eyes of 147 patients were analyzed. The intervention group included 72 patients, and the control group contained 75 patients. Insufficient anterior chamber sample collection was the reason for the data loss in the study course.50.3% of the patients were male, 49.7% were female. (Table 1) The patients’ age ranged from 60 to 84 years old.

Table 1 Frequency distribution according to gender in intervention and control groups

The mean age of the participants was 69.63 + 6.41 years in the control group and 70.16 + 6.92 years in the intervention group. Sixteen cultures (22.2%) of the control group were positive, while four cultures (5.3%) of the intervention group were positive (P-value = 0.005) (Table 2).

Table 2 Frequency distribution according to culture in intervention and control groups

No significant difference was detected in the outcomes between males and females. The most common bacterial species detected from the aqueous humor sample in both groups was staphylococcus epidermidis. The mixture of topical levofloxacin 0.5% and povidone-iodine 10% showed a significant impact on bacterial count reduction in the aqueous humor. Applying this topical mixture showed no adverse effects such as corneal epithelial defect, corneal edema, endophthalmitis, and uveitis.

All patients were followed for one month and no endophthalmitis was reported.

Discussion

Endophthalmitis is one of the devastating complications following cataract surgery. This complication has an irrecoverable impact on visual outcomes. Although the number of cataract surgeries is rising worldwide there is no golden protocol to eliminate this complication. There are several retrospective studies and clinical trials addressed to resolve endophthalmitis most of these studies could introduce a new method but, none of them could provide a way to reach the frequency of zero in reports of endophthalmitis. The presence of highly resistant bacteria such as MRSA is one of the main reasons for failure to achieve the endophthalmitis omission. The goal of this study was to assess the rate of anterior chambersterility after applying a combination of antiseptics vs. standard protocol. The result of this study showed that a mixture of PVI/levofloxacin at about one hour before surgery resulted in lowering the frequency of endophthalmitis. Although, this finding does not imply that our strategy prevents endophthalmitis but provides a more sterile ocular surface. This strategy is more useful in a damaged ocular surface environment and impaired immune response cases. PVI had been used for perioperative sterilization in intraocular surgeries for many years. Also, there is controversy about the safest and the most effective method of preoperative PVI application. Single preoperative application of PVI 5% and 10% is a standard protocol for conjunctiva and periocular skin sterilization [9,10,11]. A recent study in 2022 proved that repetitive administration of diluted PVI has high safety profile and acts against resistant bacteria on the ocular surface [3]. Many parameters such as the concentration of applied PVI, exposure time, volume of applied PVI, and times of applying can change the effect of PVI application. For example, higher concentrations of PVI (10%) have a more sterilizing effect than lower concentrations. (5%, 1%) [12, 13]. Longer exposure time with PVI has more effect on disinfection. For maximum sterilization effect of PVI, Hosseini et al. suggested at least 15 min exposure time for 5% PVI and 5 min for 10% PVI. (12) More frequent and longstanding exposure to PVI has a more sterilization effect [9, 11, 14]. As mentioned before, multiple applications of PVI can guarantee the proper exposure time and volume. Different studies used types of fluoroquinolones as an adjunctive treatment. According to these studies, moxifloxacin couldn’t provide a more sterile environment and did not reduce the rate of endophthalmitis. In contrast He et al. study showed that application of topical moxifloxacin for 1 to 3 days before the surgery decreased the conjunctival flora [15]. Levofloxacin promise a decrease in bacterial count on the conjunctiva [16, 17]. InEslami J and et al. study, PVI 10% plus levofloxacin 0.5% eyedrop was used one hour before operation similar to our study and contributed to increase in the rate of conjunctival sterility. {Eslami, 2021 #156} Fluoroquinolones have controversial effects on the bacterial reduction count in combination with PVI. This finding might determine the change in antibacterial properties of these agents when combined. We chose levofloxacin regarding its high penetration into the ocular surface and results of previous studies. This combination can reduce the bacterial load in the conjunctiva and prevent endophthalmitis. Limitations of our study were detailed microbiological evaluation and colony counting of the specimens. Our study provides evidence that the application of mixed PVI 10% and levofloxacin 0.5% one hour before the surgery results in a reduction in bacterial load in the conjunctiva and a more sterility rate in the anterior chamber.

In conclusions, povidone-iodine (PVI) 10% and levofloxacin 0.5% about one hour before cataract surgery minimizes aqueous contamination compared with using PVI 10%. The results of our study were consistent with the metagenomic research performed in 2020 by Fan et al. This study used the same combination of PVI and levofloxacin with different concentrations and intervals. Pseudomonas bacteria was the most resistant bacteria to eliminate from the conjunctiva [1]. According to the results of our study and previous studies in this field, finding the gold standard protocol to eliminate endophthalmitis is yet to be determined.