A comparative study of the effects of topical dexamethasone 0.1% and loteprednol etabonate 0.5% on clinical ocular parameters in Iraqi patients following cataract surgery

Introduction

One of the most frequent operations performed in ophthalmology clinics is the removal of cataracts and the implantation of posterior chamber intraocular lenses. The word cataract refers to a heterogeneous group of conditions characterized collectively by an opacification in the substance or capsule of the crystalline lens.¹ Cataract remains the leading cause of global blindness, accounting for approximately 21.2% to 91.1% of blindness; this wide range is attributed to the demographic characteristics of the studied samples and, most importantly, to the level of socioeconomic development in their countries of origin.² However, cataract is categorized into two types: congenital and acquired; the latter is frequently age-related, but can also occur as a result of trauma, chemical exposure, radiation, drugs, systemic diseases such as diabetes, and others.^3,4 Diabetic Mellitus (DM) is the primary cause of visual impairment among individuals between 20 and 65. While total blindness in diabetes is rare, affecting less than 2% of individuals, the fear of losing vision is significant. This is validated by diabetics who experience changes in their vision and eye examination is recommended to address any potential issues.^5,6 Although the prevalence of diabetes has been increasing at a faster rate in middle- and low-income countries, the association between diabetes and cataracts is still ongoing.⁶ One theory is the sorbitol accumulation theory, which states that an increase in blood glucose raises the glucose content of the aqueous humour beyond the lens tissue’s ability to metabolize it, which increases sorbitol production through alternative pathways and causes areas of increased density^7–9 Excess glucose metabolism may increase oxygen-free radical production, according to another theory.^10–14

Phacoemulsification cataract surgery (PCS) was initially introduced over 50 years ago, initially devised visual by Charles Kelman in 1967. His objective was to eliminate the cataract with a smaller incision, reduce pain, and a shortened recovery period, presently, it is the preferable method, and satisfactory outcomes are typically associated with this uneventful surgery.^15,16 Opacification of the lens in cataracts is a function of increased light attenuation due to the accumulation of crosslinked proteins and pigments. The exact cause and portion of the lens affected by this accumulation differ according to the type of cataract; in age-related cataracts, for example, the cause is cumulative oxidative stress over time, which denatures proteins and reduces their solubility.^17,18

The intraocular pressure might be changed postoperatively, for example, low intraocular pressure can present postoperatively either due to aqueous loss during the operation or due to continuous leak from the non-sutured incision during the postoperative period or inflammation. This reduction in intraocular pressure is documented following uncomplicated phacoemulsification.^19–21 On the other hand, a transient increase in intraocular pressure can occur following 18% of cataract extraction surgeries due to reduced drainage of aqueous humor by the trabecular meshwork.^17,22 Despite recent developments in surgical techniques, complications are still possible while undergoing regional anesthesia.^23,24 To reduce postoperative inflammation and its consequences, including corneal edema and cystoid macular edema, topical antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroid drops might be used for the first one to four weeks after the operation. In addition, it is usually recommended to use eye patches on day one postoperatively and protective shields during the night for the first few days after surgery.¹⁷ Follow-up is indicated at one day, one week, four weeks, and three months after the operation. However, there is controversy over the choice of anti-inflammatory medication and whether NSAIDs or corticosteroids give a superior prophylactic alternative for postoperative inflammation.²⁵ Different countries and regions can opt for both based on specific regulations, but no agreement has been achieved, and there are no gold standard treatment choices. This discussion also includes which drugs to use within the same class of anti-inflammatory treatment, such as how two corticosteroids, Loteprednol Etabonate and topical dexamethasone, compare in terms of efficacy and safety in the treatment of postoperative inflammation.^26,27

Corticosteroids constitute the first-line therapy for a variety of ocular disorders impacting the ocular surface, anterior and posterior portions of the eye thanks to their anti-inflammatory, anti-mitotic, vasoconstrictive, immunosuppressive, and anti-edematous characteristics.^28–31 The pharmacological action of glucocorticoids is achieved by the cytosolic glucocorticoid receptors which when activated induces structural modifications and relocates to the nucleus.^32–36 The excited glucocorticoid receptor promotes or represses transcriptional elements, resulting in both therapeutic and detrimental consequences. These activities prevent the synthesis of arachidonic acids and their related eicosanoid metabolites.^37–41 This has prompted an effect on the blood-tissue barriers, reducing fibroblast replication, collagen and scar development, ocular swelling, fibrin accumulation, vascular leakages, inflammatory cells escaping into the retina, and vascular endothelial growth factor (VEGF) levels.^42–46

To reduce postoperative inflammation and its consequences, including corneal edema and cystoid macular edema, corticosteroid drops might be used for the first few weeks after the operation, however, corticosteroids might affect intraocular pressure Steroid-induced IOP elevation has been reported to occur in 18–36 % of patients, termed steroid responders, with risk factors including a history of glaucoma, a familial predisposition toward glaucoma, or high myopia.^47,48 Older corticosteroids, such as prednisolone and dexamethasone, are associated with a greater impact on IOP compared to newer corticosteroids.⁴⁹ Dexamethasone is a glucocorticoid drug with a potent anti-inflammatory but virtually no mineralocorticoid effects on the kidney. It is the drug of choice in the prevention of respiratory distress syndrome (RDS) of premature infants and to investigations for Cushing syndrome.^39,50 Usage of dexamethasone is also indicated in situations where fluid retention can be a problematic side effect such as in the treatment of cerebral edema due to tumors and, in its topical forms, it can be used for inflammatory skin conditions and different types of ophthalmologic conditions including the postoperative prevention and treatment of complications following cataracts surgery.^51,52 Loteprednol Etabonate, unlike dexamethasone, is a corticosteroid designed specifically for inflammatory eye conditions and is administered as an eye drop for allergic conjunctivitis, uveitis, and episcleritis and the treatment or prevention of inflammation following eye surgery, including lens removal and replacement in cataracts.⁵³ Loteprednol etabonate is a corticosteroid produced by retro-metabolic design; an inactive and nontoxic metabolite of a reference compound is utilized as a starting point for conversion to a therapeutically active, metabolically labile compound. Structurally, loteprednol etabonate differs from prednisolone in that the ketone at the carbon-20 (C-20) position is replaced with a chloromethyl ester, and the 17α-hydroxyl group is replaced with a carbonate moiety and after exerting its effects, loteprednol etabonate is rapidly metabolized, thereby limiting any potential adverse effects associated with its use.⁵³

Methods

This prospective examine turned into performed at the Jena Ophthalmic Center in Iraq over a duration from December 1, 2023, to August 28, 2024. As Iraq does not have its own number one registries, the examine was reviewed and accepted through the Institutional Review Board (IRB) of the College of Medicine, University of Baghdad. Approval turned into granted on November 27, 2023, beneath report authorization range UoB.Med.21. Participants have been furnished with a concise clarification of the have a look act’s objectives and methodologies before enrolling in the research.

The study complied with the tenets of the Declaration of Helsinki, and all participants provided written informed consent before recruitment. The study enrolled adult patients diagnosed with cataracts, 18 years old or older, who prepared for and underwent cataract extraction surgery by phacoemulsification. The operations were done at Jena Ophthalmic Center in Baghdad, Iraq. Patients who had uveitis or a history of uveitis or glaucoma, used antiglaucoma medications, had complications during surgery, or didn’t comply with follow-up or medication were excluded from the study. The patients were examined preoperatively within one week of the surgery with complete history and examination and then the surgery was done by the same surgeon with preoperative pupillary dilatation by tropicamide 0.1% drop then phacoemulsification under local anesthesia using a 2.4mm limbal incision then filling the AC with sodium hyaluronate 1.4% (Aurogel) (is a cohesive viscoelastic formulation used for filling anterior chamber and better adhesiveness on the corneal endothelium during phacoemulsification pH 7.0 to 7.8/Available in a 1ml syringe/Catalogue number 803878032506/Aurolab-India) and anterior capsulorhexis was done then hydro dissection and application of methylcellulose HPMC2% (Aurovisc) to AC for corneal endothelial protection followed by phacoemulsification and cortical material removal and later the implantation of the intra-ocular lens (® is a monofocal foldable, single-piece posterior chamber acrylic lens with an Intraocular Lens 15.5D, Length 13.0 mm, Optic 6.0 mm/Fort Worth and Cork, Ireland) and lastly removal of methylcellulose and stromal hydration of the wound and padding.and lastly removal of methylcellulose and stromal hydration of the wound and padding.

All the patients removed the pad 6 hours after the surgery and began the topical treatment and the Patients undergoing cataract surgery were randomly assigned to two groups using a computer-generated randomization table.

Group 1: Patients received topical treatment with moxifloxacin (AROX Jamjom) drops and loteprednol drops 0.5% (Ajanta) four times daily.

Group 2: Patients received topical treatment with moxifloxacin (AROX Jamjom) drop and dexamethasone 0.1% suspension drop (Edol) four times per day.

In one week, all the patients were examined by the same physician and recorded IOP, AC reaction, AC flare, conjunctival congestion, and pain according to the questionnaire for both groups and then repeated the examination in four weeks and recording the same parameters.

Results

Sixty-six eyes of 66 patients were enrolled in the study with 33 participants with a mean age of 65±6.3 years assigned to group A and another 33 participants with a mean age of 64±12.7 assigned to group B with no clinically significant differences (P-value was 0.81), group A was dominated by males (60.6%) while group B was dominated by females (51.5%) but with no statistically significant distinction between the genders in distribution as shown in Table 4. Based on the t-test and Mann-Whitney Test (p-value > 0.05), no statistically significant differences were observed between groups A and B regarding intraocular pressure preoperatively, one week post-operatively, and four weeks post-operatively as shown in Table 5.

There was no increase of IOP of ≥ 5 mmHg in either Group A or Group B after one week of treatment, while an increase of IOP of ≥5 mmHg occurred in only 3 patients (3/33 patients representing about 9.1%) treated with dexamethasone (Group B) after 4 weeks of treatment and none in group A. The Pearson chi-square test revealed no statistically significant difference between group A and group B regarding the AC grading one week post-operatively (p-value=0.607). With a p-value of 0.043, a statistically significant difference in the AC grading was observed between groups A and B after four weeks of operation ( Table 6).

The Pearson chi-square test revealed no statistically significant difference between groups A and B in terms of flare grading after one week and four weeks post-operatively (p-value=0.23, p=0.067) ( Table 7).

The Pearson chi-square test revealed no statistically significant difference between groups A and B in terms of Grading of conjunctival congestion after one week and four weeks post-operatively (p-value=0.091, p=0.165), as seen in Table 8.

There was no statistically significant difference between group A and group B regarding pain scores one and four weeks post-operatively (p-value=0.354, p=0.197), as determined by the Pearson chi-square test. However, group B had a greater proportion of patients who reported no pain during the initial week (69.7%) and again by the fourth week following the operation (93.9%) ( Table 9).

Discussion

Loteprednol etabonate 0.5% has been proven to be efficacious, well-tolerated, and safe in clinical trials for treating postoperative inflammation and pain after cataract surgery.^56–58 Research has shown that using loteprednol etabonate 0.5% suspension effectively decreases the presence of anterior chamber cells and flare reactions in patients undergoing cataract surgery leading to better clinical results and decreased inflammation.⁵⁹ Moreover, loteprednol etabonate has demonstrated effectiveness in treating inflammation associated with different eye conditions, such as cataract surgery.⁶⁰ Also dexamethasone 0.1% has been assessed for its efficacy in reducing inflammation following cataract surgery. Studies have demonstrated that sustained-release dexamethasone is advantageous for treating ocular pain and inflammation following cataract surgery. Nevertheless, in a direct comparison, loteprednol etabonate 0.5% has demonstrated equivalent effectiveness to prednisolone acetate 1.0% in managing postoperative inflammation in patients undergoing routine cataract surgery.⁶¹

Randomized controlled studies have shown that loteprednol etabonate ophthalmic suspension 0.5% is clinically effective and safe for treating postoperative inflammation in patients who have undergone cataract surgery. These studies have found that very few patients, if any, experience a significant increase (≥10 mmHg) in intraocular pressure (IOP). In addition, studies have uncovered that loteprednol etabonate has a minimal impact on intraocular pressure (IOP) when used for a long period of time or in steroid-sensitive people. Furthermore, loteprednol etabonate has a significantly lower likelihood of increasing IOP than prednisolone acetate or dexamethasone.⁶² Also, Thanathanee O. et al. reported that both loteprednol and dexamethasone were effective in post-photorefractive keratectomy (PRK) treatment. The dexamethasone group had a higher IOP increase of ≥ 5 mmHg than the loteprednol group (3/16 patients in the dexamethasone group vs. 1/16 patients in the loteprednol group). In our investigation, the dexamethasone group showed a mild increase in IOP after 4 weeks postoperatively compared to preoperatively but was clinically nonsignificant.⁶³ Our findings align with these aforementioned results, as we noticed no statistically significant difference in IOP between loteprednol etabonate and dexamethasone one week and four weeks following operation. However, dexamethasone showed a higher, although not statistically significant IOP increase in week 4. In contrast, Bilgin et al. (2019) found that loteprednol etabonate had no effect on IOP while dexamethasone increased IOP significantly,²⁶ and this difference in comparison to our study could be attributed to the fact that the Bilgin study was conducted for post-vitrectomy patients rather than post-cataract patients, those with more frequent dexamethasone usage.

Regarding anterior chamber cells and pain score, a previous meta-analysis study showed that a significantly greater percentage of patients who received the dexamethasone intracanalicular insert, compared to those who received the placebo insert, experienced no pain on day 8 (7 days after the operation) in three important phases III trials. Additionally, the desired outcome of reduced inflammation (absence of anterior chamber cells) on day 14 (13 days after the operation) was achieved in two out of three trials.⁶⁴ In line with our findings, group B (the dexamethasone group) exhibited a higher percentage of patients who experienced no pain during the first week and the fourth week after the surgery. Also, our findings indicate that the dexamethasone group (group B) improved anterior chamber cells more than the group receiving Loteprednol etabonate 0.5% four weeks after the surgery. In summary, the dexamethasone intracanalicular insert proved effective and generally well tolerated in treating post-surgical ocular pain and inflammation after cataract surgery.

Another study demonstrated that the intent-to-treat population consisted of 406 patients, with 203 patients assigned to each treatment group. By day 8, 30.5% of patients in the loteprednol etabonate group and 16.3% of patients in the vehicle group experienced complete resolution of ACC. Additionally, 72.9% and 41.9% of patients in the respective groups reported grade 0 pains. These differences were statistically significant (P<.001) for both comparisons. Statistically significant differences in the effectiveness of treating ACC and grade 0 pain were observed in favour of loteprednol etabonate on day 15 and day 18.⁶⁵ Our results differ slightly from the previous findings. We observed that the group treated with loteprednol etabonate did not achieve complete resolution of ACC and did not report grade 0 pain. These disparities could arise from variations in sample size, sociodemographic characteristics, and risk factors.

Another research study demonstrated both groups exhibited decreased inflammation during the subsequent visits. No statistically significant distinction was observed between the LE/T and DM/T groups in terms of postoperative scores or measurements, such as discomfort, chemosis, secretion, conjunctival hyperemia, and conjunctival gap size (p>0.05), during the follow-up visits. No patients reported experiencing any allergic reactions to the medications. The intraocular pressures were within the normal range in both groups.⁶⁶ The results we obtained regarding flare grading and conjunctival congestion are comparable to the previous study, as no discernible distinction was observed between the two groups.

Conclusion

Topical loteprednol etabonate 0.5% and topical dexamethasone 0.1% have comparable impacts on ocular indicators such as IOP, AC response, flare, conjunctival congestion, and pain following cataract surgery but dexamethasone tends to have a high spike of IOP ≥ 5mmHg in about 9.1% after four weeks of treatment. The comparison between loteprednol etabonate and dexamethasone in treating post-cataract surgery inflammation indicates that both medications are effective and well-tolerated. The choice amongst these corticosteroids may be based on the patient’s wishes and requirements

Ethical approval

The research project has been approved by the Institutional Review Board (IRB) of the University of Baghdad’s College of Medicine. The Declaration of Helsinki’s requirements and guidelines were scrupulously adhered to in the course of conducting the current research. On November 27, 2023, a local ethics authority (document permission number UoB.Med.21) verified the relevant documents and client data to verify the methodology of the study

Author contributions

L.B.T. conducted the investigation, wrote and refined the first draft of the document, participated in its design and provided financing and other forms of assistance, donated supplies, equipment, and lab animals, and finished the final copy of the research article. M.Q.Y.M.A.A. created the theoretical framework for the researched project, specified the parameters of the exploratory analysis, and outlined the main goals through.an in-depth assessment of the findings, supplemented with insightful criticism and supervision. Z.R.H. investigated and gathered material to supplement the printed paper, incorporated the methodological selection, and assisted with practicalities.