
==== Front
Medicine (Baltimore)
Medicine (Baltimore)
MD
Medicine
0025-7974
1536-5964
Lippincott Williams & Wilkins Hagerstown, MD

MD-D-24-02904
00050
10.1097/MD.0000000000039667
3
5800
Research Article
Observational Study
The effect of different potency glucocorticosteroids treatments on tear inflammatory factors and corneal optical density after femtosecond-assisted laser in situ keratomileusis
https://orcid.org/0009-0005-6568-8306
Zheng Jun MM a
Hong Xiangbo MM 1974355164@qq.com
b
Li Shuangle MM a*
a Department of Ophthalmology, Zigong First People’s Hospital, Zigong, Sichuan, China
b Department of Internal Medicine, Zigong First People’s Hospital, Zigong, Sichuan, China.
* Correspondence: Shuangle Li, Department of Ophthalmology, Zigong First People’s Hospital, Zigong, Sichuan, China (e-mail: 985750247@qq.com).
13 9 2024
13 9 2024
103 37 e3966718 3 2024
18 8 2024
22 8 2024
Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

To assess the impact of glucocorticosteroids with varying potencies on inflammatory mediators in tears and corneal optical density after femtosecond-assisted laser in situ keratomileusis (FS-LASIK). In a prospective study, 110 patients (220 eyes) who underwent FS-LASIK were divided into 2 groups: 55 patients (110 eyes) received dexamethasone, and another 55 patients (110 eyes) received fluorometholone. Visual acuity, intraocular pressure, and corneal optical density were measured before, 1 week, and 1 month after surgery. Tear fluid samples were also collected to assess expression levels of TNF-α, IL-1α, IL-6, and TGF-β1. One week after the procedure, the dexamethasone group exhibited elevated intraocular pressure (IOP) levels (P > .05) and a decreased expression of TNF-α in tears (P < .001) compared to the fluorometholone group. Within the 0 to 2 mm range from the corneal apex, the anterior corneal layer’s optical density in the fluorometholone group surpassed that of the dexamethasone group (P < .05). At 1 month post-surgery, the IOP in the fluorometholone group was higher than that in the dexamethasone group (P < .05). In both the 0 to 2 mm and 2 to 6 mm intervals from the corneal apex, the optical density of the anterior corneal layer was significantly higher in the fluorometholone group compared to the dexamethasone group (P < .05). There was no statistically significant difference in visual acuity between the 2 groups at any postoperative time point. Short-term use of potent corticosteroids after FS-LASIK can swiftly address ocular surface inflammation, enhance corneal wound healing, reduce corneal edema, and accelerate the restoration of corneal transparency, in contrast to prolonged use of milder corticosteroids post-surgery.

corneal optical density
femtosecond-assisted laser in situ keratomileusis
glucocorticoids
tear inflammatory mediators
Sichuan Province Science and Technology Support Program 10.13039/100012542 No. 2022JDXM012 Shuangle LiOPEN-ACCESSTRUE
==== Body
pmc 1. Introduction

Due to its excellent safety, effectiveness, predictability, and long-term stability, femtosecond-assisted laser in situ keratomileusis (FS-LASIK) has emerged as one of the most prevalent refractive correction procedures.[1] However, during the intraoperative processes of flap fabrication and stromal ablation, corneal nerves can be compromised, leading to reduced corneal sensitivity, compromised barrier function, and decreased stability of the tear film. Extensive research, both in vivo and in vitro, has elucidated the multifaceted nature of corneal wound healing, involving various chemokines, growth factors, and cytokines. The release of inflammatory mediators during this process alters tear composition, disrupts ocular surface homeostasis, induces dry eye, and results in discomfort, significantly impacting patients’ quality of life and surgical rehabilitation.[2,3] Hou et al[4] have highlighted a correlation between corneal edema, inflammation, and corneal optical density (COD), which can affect postoperative vision quality. COD serves as a valuable tool for pre-surgery keratoconus screening and postoperative problem tracking, potentially enhancing surgical outcomes and safety through the monitoring of COD changes. Surgically induced edema, inflammation, and mechanical damage to the cornea influence the subsequent healing process. Postoperative local anti-inflammatory medication can play a crucial role in preventing corneal subepithelial turbidity, minimizing edema, limiting cytokine-mediated ocular surface inflammation, and aiding in ocular surface recovery.[5] The goal of this research was to determine the optimal medication schedule following FS-LASIK by comparing the expression of postoperative inflammatory mediators in tears and the corneal optical density value to assess the postoperative effects of various hormone regimens.

2. Methods

2.1. Patients

In this prospective clinical study, a total of 110 patients (220 eyes) who underwent FS-LASIK surgery at the ophthalmology department of Zigong First People’s Hospital between June 2022 and June 2023 were enrolled. Inclusion criteria comprised: Age range: 18 to 40 years old; Preoperative equivalent spherical lens degree: −10.0D ~ −1.0D; The refractive status is stable for at least 1 year, and the degree increase is <0.5D; Stop wearing soft contact lenses for more than 2 weeks, hard contact lenses for more than 1 month, and orthokeratology lenses for more than 3 months before surgery; Optimal preoperative corrected visual acuity ≥ 1.0; Preoperative central corneal thickness ≥ 470 μm, and postoperative stromal bed remaining ≥ 280 μm. Exclusion criteria included a history of eye surgery (refraction or otherwise), a topographic map showing possible keratoconus or another corneal dilatation condition, eye disease, and systemic conditions such as connective tissue disease and diabetes that may impede the healing of wounds.

Based on different postoperative hormone use, the 110 patients (220 eyes) were split into 2 groups: the fluorometholone group (55 patients, 110 eyes) and the dexamethasone group (55 patients, 110 eyes). This research received approval from the hospital Ethics Committee (Lot Number: Ethics [Research] 2023 NO. 43) and adhered to the standards outlined in the Declaration of Helsinki. Each patient provided informed consent and signed the necessary documentation.

2.2. Medication and preoperative evaluation

A comprehensive set of assessments was conducted for each patient, including a fundus examination, slit lamp microscopy, uncorrected and best-corrected visual acuities (UCVA and BCVA), computerized optometry (KR-1 computerized keratometer, Topcon, Japan), intraocular pressure (IOP; TX-20P non-contact tonometer, Canon, Japan), anterior segment analysis (Pentacam 70100, Oculus, Germany), etc. The TX-20P non-contact tonometer from Canon Japan features a corneal thickness measurement function that captures optical section images of central corneal thickness using corneal scattered light. Utilizing these measurements, the device automatically calculates compensated IOP values to minimize potential underestimation of IOP after LASIK surgery. During the examination process, patients were dilated using Rui Mu Shu (Compound Tropicamide Eye Drops; Changchun Dirui Pharmaceutical, China). Additionally, patients received preoperative treatment consisting of Wanhan Runshu (0.5% Levofloxacin Eye Drops; Zhongshan Wanhan Pharmaceutical Co., Ltd., China) and Hycosan Preservative-Free (0.1% Sodium Hyaluronate Eye Drops; URSAPHARM, Germany) 3 times a day for 3 days. On the day of surgery, a final examination of the anterior segment was performed. Patients exhibiting no abnormalities during this assessment were admitted for the surgical procedure.

2.3. Surgical technique

During FS-LASIK surgery, meticulous cleaning and disinfection of the conjunctival sac and the surrounding periocular area were conducted. Surface anesthesia was administered using Akacaine (0.5% Proparacaine Hydrochloride Eye Drops; Alcon, Fort Worth). The temporal corneal flap, with dimensions of approximately 8.5 mm in diameter and 105 to 110 μm in thickness, was precisely fashioned using the Wavelight FS200 femtosecond laser (Alcon, Fort Worth). Subsequently, stromal ablation treatment within the optical zone, ranging from 6.0 to 6.5 mm, was performed using the WaveLight EX500 excimer laser. The parameters of this ablation were contingent upon the individual patient’s ocular condition. Following the ablation, the corneal flap underwent thorough rinsing with a balanced salt solution, was securely reset, ensuring a minimum residual corneal stroma thickness of at least 300 μm. All the surgeries were skillfully performed by the same experienced refractive surgeon.

2.4. Medication and postoperative examination

Following FS-LASIK, all patients were randomly assigned to either the fluorometholone or dexamethasone group. The fluorometholone group underwent the following postoperative medication regimen: Flumetholon (0.1% Fluorometholone Eye Drops; Santen Pharmaceutical Co., Ltd., China) 4 times to 1 time per day with a drop decrease per week for 1 month following surgery; Tobrex (0.3% Tobramycin Eye Drops; Alcon, Fort Worth) 4 times daily for 1 week. In the dexamethasone group, postoperative medication included Tobradex (0.3% Tobramycin and 0.1% Dexamethasone Eye Drops; Alcon, Fort Worth) administered 4 times a day for 1 week, followed by cessation. Both groups received Beifushu (Recombinant Bovine Basic Fibroblast Growth Factor Ophthalmic Gel; Zhuhai Yisheng Biopharmaceutical Co., Ltd., China) 4 times daily for 2 weeks, after which the treatment was discontinued. Additionally, Hycosan were administered 4 times a day for a minimum of 1 month. Patients underwent slit-lamp microscopy, visual acuity assessment, computerized optometry, intraocular pressure measurement, and corneal optical density (COD) examinations (Pentacam 70100, Oculus, Germany) at 1 day, 1 week, and 1 month postoperatively.

2.5. Tear collection

Tear samples were collected on the day of the operation, 1 week later, and 1 month thereafter. A 20-μL stretched micro-dropper tip (Bailey Medical Devices Co. Ltd., Taizhou, China) was carefully positioned on the lower edge of the tear river, and 20 μL of tear fluid was extracted from the conjunctival sac. Subsequently, these samples were stored in 0.2 mL Eppendorf centrifuge tubes (Corning Incorporated, USA) at −80°C to maintain their integrity. To analyze the tear composition, an enzyme-linked immunosorbent assay (ELISA) test was performed using a human serum ELISA kit (Wuhan Doctoral Bioengineering Co. Ltd., Wuhan, China). The expression levels of cytokines, including tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), interleukin-1α (IL-1α), and interleukin-6 (IL-6), were quantified.

2.6. Statistical analysis

Statistical analysis for this study utilized SPSS 25.0. The gender distribution of patients in the 2 groups was assessed using a Chi-square test, represented by proportions. Firstly, measurement data underwent tests for variance homogeneity and normal distribution using the Shapiro–Wilk test. For data that satisfied both requirements in the fluorometholone and dexamethasone groups, an independent sample t-test was applied. In cases where variance homogeneity and normal distribution criteria were not met, the Mann–Whitney U test or Kruskal-Wallis H test was employed for comparison. A significance level of P < .05 was considered statistically significant.

3. Results

3.1. General patient information

Incision bleeding happened in 3 patients (3 eyes) in the fluorometholone group; significant corneal spot staining necessitated a change in treatment in 3 patients (6 eyes); and 7 patients (14 eyes) were lost to follow-up. Ultimately, 42 patients, totaling 84 eyes, underwent follow-up, included 21 males and 21 females. Within the group receiving dexamethasone, 3 patients (6 eyes) required a medication modification because of hormonal hypertension, 5 patients (10 eyes) were lost to follow-up, and 47 patients (94 eyes) were eventually followed up, with 24 males and 23 females. Comparable characteristics were observed between the 2 groups, including gender, age, best-corrected visual acuity (BCVA), intraoperative optic zone diameter, and corneal cutting thickness. None of these differences reached statistical significance (P > .05; Table 1).

Table 1 Characteristics of the fluorometholone and dexamethasone groups.

Characteristics	Fluorometholone	Dexamethasone	t/χ2/Z	P	
Patients, n	42	47			
Eyes, n	84	94			
Male/female	21/21	24/23	0.02	.887	
Age (yr)	21.79 ± 3.23	21.38 ± 3.75	0.77	.442	
SE (D)	−5.82 ± 1.98	−5.63 ± 1.67	−0.69	.49	
BCVA					
(logMAR)	−0.06 ± 0.042	−0.062 ± 0.045	0.19	.849	
Preop	6.25 ± 0.23	6.29 ± 0.23	−1.02	.31	
OZD (mm)					
CCT (µm)	85.5 (62, 93.75)	86.5 (73, 95)	−1.61	.11	
IOP (mm Hg)					
 Preop	14.81 ± 2.2	14.06 ± 2.09	1.56	.122	
 1 wk postop	10.69 ± 2.27*	10.71 ± 1.75*	−0.05	.965	
 1 mo postop	10.01 ± 2.04*	9.01 ± 1.15*	2.64	.011	
UCVA (logMAR)					
 1 d postop	−0.042 ± 0.034	−0.041 ± 0.035	−0.26	.799	
 1 wk postop	−0.09 ± 0.036	−0.095 ± 0.031	0.93	.355	
 1 mo postop	−0.11 ± 0.026	−0.11 ± 0.023	0.97	.33	
Data were expressed as means ± standard deviations or M (Q1, Q3).

1mo = 1 month, 1wk = 1 week, BCVA = best corrected visual acuity, CCT = corneal cutting thickness, F = female, IOP = intraocular pressure, M = male, OZD = optical zone diameter, postop = postoperative, preop = preoperative, SE = spherical equivalent, UCVA = uncorrected visual acuity.

* P < .001, significant differences between postoperative and preoperative values.

3.2. IOP and UCVA

After surgery, both groups exhibited a significant decrease in IOP at 1 week and 1 month compared to the preoperative period (P < .001). Prior to surgery, no statistically significant difference in IOP existed between the 2 groups (t = 1.56, P = .122). One week post-surgery, the dexamethasone group showed a slightly higher IOP than the fluorometholone group, but this difference was not statistically significant (t = −0.05, P = .965). However, at 1 month post-surgery, the dexamethasone group’s IOP was significantly lower than that of the fluorometholone group (t = 2.64, P = .011). The variation in uncorrected visual acuity (UCVA) between the 2 groups at different time points after surgery was not statistically significant (Table 1, Fig. 1).

Figure 1. Intraocular pressure changes following FS-LASIK in the dexamethasone and fluorometholone groups. Pre-op = preoperative, 1 wk = 1 week, 1 mo = 1 month, post = postoperative. bP < .001, preoperative and postoperative values differ significantly; cP < .05, significant difference between groups after surgery.

3.3. Tear inflammatory factor

When examining the expression of tear fluid IL-1α, IL-6, and TGF-β1 in both groups 1 week and 1 month after surgery, no statistically significant differences were observed compared to preoperative levels (P > .05). Additionally, no statistically significant variations in the expression of these cytokines were noted between the 2 groups at the preoperative, 1-week, and 1-month postoperative time points (P > .05). Interestingly, tear TNF-α expression exhibited a significant increase in both groups at 1 week postoperatively when compared to the preoperative period (P < .001). Furthermore, the elevation in TNF-α levels was notably higher in the fluorometholone group (t = 4.26, P < .001) compared to the dexamethasone group. However, no statistically significant differences in tear TNF-α expression were found between the 2 groups at the preoperative period and 1 month postoperatively (P > .05; Table 2, Figs. 2–5).

Table 2 Tear inflammatory mediators of the fluorometholone and dexamethasone groups.

Parameters	Fluorometholone	Dexamethasone	t	P	
IL-1α					
 Preop	3.45 ± 0.37	3.38 ± 0.45	0.81	.417	
1 wk postop	3.42 ± 0.69	3.34 ± 0.42	0.69	.494	
1 mo postop	3.59 ± 0.62	3.59 ± 0.6	0.01	.99	
IL-6					
 Preop	16.41 ± 0.03	16.41 ± 0.05	−1.01	.314	
1 wk postop	16.43 ± 0.11	16.41 ± 0.07	1.23	.222	
1 mo postop	16.42 ± 0.07	16.43 ± 0.09	−0.89	.374	
TGF-β1					
 Preop	244.47 ± 10.85	248.39 ± 10.83	−1.69	.096	
1 wk postop	245.83 ± 17.81	243.08 ± 12.81	0.83	.409	
1 mo postop	247.40 ± 38.01	245.76 ± 21.45	0.249	.804	
TNF-α					
 Preop	42.20 ± 3.40	43.55 ± 3.01	−1.99	.051	
1 wk postop	61.80 ± 12.1*	52.14 ± 9.24*	4.26	<.001	
1 mo postop	43.81 ± 7.75	42.43 ± 6.04	0.93	.355	
Data were expressed as means ± standard deviations.

1mo = 1month, 1wk = 1 week, IL-1α = interleukin-1α, IL-6 = interleukin-6, postop = postoperative, preop = preoperative, TNF-α = tumor necrosis factor-α, TGF-β1 = transforming growth factor-β1.

* P < .001, significant differences between postoperative and preoperative values.

Figure 2. Tear fluid inflammatory mediator expression of IL-6 changes following FS-LASIK surgery in the fluorometholone and dexamethasone groups. 1mo = 1 month, 1wk = 1 week, IL-6 = interleukin-6, post = postoperative, pre-op = preoperative.

Figure 3. Tear fluid inflammatory mediator expression of IL-1α changes following FS-LASIK surgery in the fluorometholone and dexamethasone groups. 1mo = 1 month, 1wk = 1 week, IL-1α = interleukin-1α, post = postoperative, pre-op = preoperative.

Figure 4. Tear fluid inflammatory mediator expression of TGF-β changes following FS-LASIK surgery in the fluorometholone and dexamethasone groups. 1mo = 1 month, 1wk = 1 week, post = postoperative, pre-op = preoperative, TGF-β1 = transforming growth factor-β1.

Figure 5. Tear fluid inflammatory mediator expression of TNF-α changes following FS-LASIK surgery in the fluorometholone and dexamethasone groups. 1mo = 1 month, 1wk = 1 week, post = postoperative, pre-op = preoperative, TNF-α = tumor necrosis factor-α. bP < .001, preoperative and postoperative values differ significantly. cP < .05, significant difference between groups after surgery.

3.4. Corneal optical density

The analysis specifically focused on the corneal optical densities within defined ranges from the corneal apex: 0 to 2 mm, 2 to 6 mm, and 6 to 10 mm. Corneal optical densities were measured and recorded in gray scale units ranging from 0 to 100, where 0 represents maximum transparency and 100 indicates minimum transparency.[6]

The study revealed a noteworthy increase in the optical density of the anterior layer 120 µm of the cornea within the 0 to 2 mm range from the corneal apex in both groups at 1 week postoperatively, compared to the preoperative period (P < .05). However, no statistically significant difference was observed at 1 month postoperatively compared to the preoperative period (P > .05). Likewise, the middle and posterior 60 μm of corneal optical density did not exhibit any statistically significant differences when compared with the preoperative period (P > .05). Comparing the 2 groups, the fluorometholone group demonstrated higher optical densities in the anterior 120 μm and total cornea at 1 week and 1 month after surgery compared to the dexamethasone group (P < .05). Nevertheless, there was no statistically significant difference in the optical densities of the middle and posterior 60um of the cornea between the 2 groups (P > .05). Additionally, no significant disparity was found in the preoperative optical densities of the cornea’s various layers between the 2 groups (P > .05).

Within the 2 to 6 mm range from the corneal apex, the anterior 120 μm optical density of the cornea exhibited a significant increase in both groups at 1 week postoperatively compared to the preoperative period (P < .05). However, this elevation returned to preoperative levels at 1 month postoperatively. The optical densities of the middle and posterior 60 μm corneas did not show statistically significant differences from the preoperative period at 1 week and 1 month postoperatively (P > .05). Prior to surgery and 1 week postoperatively, no statistically significant differences were found in corneal optical density across all layers between the 2 groups (P > .05). However, at 1 month postoperatively, the fluorometholone group exhibited a higher anterior 120 μm corneal optical density compared to the dexamethasone group (P < .05), But there were no statistically significant differences between the 2 groups in terms of corneal mid-layer and posterior 60 μm corneal optical densities at this time point (P > .05).

The variations in corneal optical density for each layer at preoperative, 1 week, and 1 month postoperatively showed no statistically significant differences in either group within the 6 to 10 mm range from the corneal apex (P > .05). Likewise, the differences in corneal optical density for each layer at 1 week and 1 month postoperatively were not statistically significant in either group when compared to the preoperative values (P > .05; Table 3).

Table 3 Corneal optical density of the fluorometholone and dexamethasone groups.

Parameters	Fluorometholone	Dexamethasone	Z	P	
0–2 mm					
Preop					
 Anterior 120 µm	21.2 (20.8, 21.8)	21 (20.58, 21.7)	−1.86	.064	
 Central	12.9 (12.6, 13.38)	13 (12.6, 13.4)	−0.30	.768	
 Posterior 60 µm	11.9 (11.6, 12.6)	11.9 (11.6, 12.3)	−0.78	.435	
 Total 1 wk postop	15.4 (15, 15.8)	15.3 (15.08, 15.7)	−0.82	.411	
 Anterior 120 µm	22.25 (21.4, 22.98)**	21.75 (21.18, 22.43)**	−2.38	.017	
 Central	13 (12.53, 13.7)	13.15 (12.7, 13.5)	−0.46	.649	
 Posterior 60 µm	11.8 (11.33, 12.4)	11.7 (11.18, 12.2)*	−1.96	.05	
 Total 1 mo postop	15.7 (15.2, 16.2)	15.5 (15.1, 15.9)	−2.16	.031	
 Anterior 120 µm	21.5 (21, 22.28)	20.75 (20.1, 21.73)	−3.62	<.001	
 Central	12.9 (12.6, 13.58)	13.15 (12.6, 13.43)	−0.17	.869	
 Posterior 60 µm	11.65 (11.2, 12.48)	11.6 (11.1, 12)**	−1.3	.195	
 Total 2−–6 mm	15.4 (15, 16)	15.2 (14.8, 15.63)	−2.33	.02	
Preop					
 Anterior 120 µm	19.3 (18.9, 19.99)	19.4 (18.88, 19.83)	−0.40	.693	
 Central	12 (11.6, 12.34)	11.9 (11.6, 12.3)	−0.93	.355	
 Posterior 60 µm	11.1 (10.7, 11.5)	11.1 (10.8, 11.4)	−0.28	.783	
 Total 1 wk postop	14.1 (13.8, 14.6)	14.2 (13.9, 14.5)	−0.45	.655	
 Anterior 120 µm	20.25 (19.4, 20.7)**	20 (19.45, 20.7)**	−0.73	.468	
 Central	12.1 (11.43, 12.4)	12 (11.6, 12.4)	−0.24	.809	
 Posterior 60 µm	11 (10.8, 11.48)	11.05 (10.6, 11.4)	−0.72	.47	
 Total 1 mo postop	14.45 (14, 14.8)	14.3 (13.9, 14.8)	−1.14	.256	
 Anterior 120 µm	19.45 (19, 20.48)	19.1 (18.5, 20.1)	−2.40	.016	
 Central	11.85 (11.6, 12.3)	11.9 (11.6, 12.23)	−0.09	.931	
 Posterior 60 µm	11.05 (10.5, 11.5)	10.9 (10.6, 11.2)	−−1.1	.274	
 Total 6–10 mm	14.3 (13.8, 14.7)	14.1 (13.7, 14.7)	−1.32	.186	
Preop					
 Anterior 120 µm	19 (17.8, 21)	19 (17.5, 21.22)	−0.19	.853	
 Central	12.56 (11.43, 13.6)	12.25 (11.48, 13.2)	−0.66	.507	
 Posterior 60 µm	11.9 (10.9, 12.78)	11.55 (10.98, 12.1)	−1.49	.135	
 Total 1 wk postop	14.4 (13.5, 15.85)	14.1 (13.38, 15.4)	−1.26	.209	
 Anterior 120 µm	19.2 (17.1, 20.78)	19.4 (17.78, 20.83)	−1.0	.317	
 Central	12.4 (11.2, 13.18)	12 (11.4, 12.73)	−1.15	.252	
 Posterior 60 µm	11.6 (10.7, 12.5)	11.2 (10.8, 11.9)	−1.33	.184	
 Total 1 mo postop	14.6 (13.1, 15.58)	14.35 (13.2, 15)	−0.76	.45	
 Anterior 120 µm	18.3 (17, 21.25)	19.75 (17.5, 21.3)	−1.83	.067	
 Central	12.4 (11.2, 13.28)	12.15 (11.48, 12.9)	−0.35	.728	
 Posterior 60 µm	11.8 (10.7, 12.6)	11.25 (10.88, 12)	−1.07	.283	
 Total	14.45 (13.1, 15.58)	14.2 (13.28, 15.13)	−0.05	.963	
Data were expressed as M (Q1, Q3).

1mo = 1month, 1wk = 1 week, postop = postoperative, preop = preoperative.

* P < .05, significant differences between preoperative and postoperative values.

** P < .001, significant differences between postoperative and preoperative values.

4. Discussion

One prevalent method for refractive correction is FS-LASIK. The surgical creation of corneal flaps and stromal laser ablation mechanically impact the cornea, leading to edema and an inflammatory response. Postoperatively, medications such as fluorometholone and tobramycin dexamethasone are employed to manage inflammation and prevent ocular infections. These medications serve to protect and promote corneal healing, reduce corneal edema, and improve postoperative comfort and visual acuity.[5]

The surgical procedure itself and the healing of the corneal wound post-surgery can trigger an inflammatory response leading to the release of cytokines and inflammatory mediators such as interleukins and tumor necrosis factor.[2] Cells like monocytes, macrophages, and keratocytes produce IL-1, with diverse biological consequences including the stimulation of other cytokines and chemokines, immune response regulation, and activation of pro-inflammatory pathways.[7] IL-6, another crucial cytokine in the inflammatory response and in the control of metabolism and regeneration, is produced by ocular surface macrophages, mast cells, fibroblasts, conjunctival and corneal epithelial cells, and vascular endothelial cells.[8,9] TGF-β, involved in immunity and extracellular matrix regulation, drives fibroblast and inflammatory responses in corneal stromal wound healing. TGF-β1 plays a key role in immune cell development, maturation, immune tolerance, homeostasis maintenance, and general immune response regulation. Following acute tissue damage, TGF-β1 significantly contributes to the healing process, affecting all involved cell types.[10] In the context of refractive surgery, particularly following FS-LASIK, the disruption of the epithelial barrier leads to the expression of TNF-α and IL-1α by corneal stroma and epithelial cells, regulating wound healing in both layers.[11] TNF-α, primarily produced by activated macrophages and T cells, as well as resident corneal cells, contributes to corneal inflammation, activates neutrophils, and induces chemokine secretion synergistically with IL-1α.[12] Major inflammatory cytokines involved in ocular surface inflammation include IL-1α, IL-6, TGF-β1, and TNF-α. Previous studies have demonstrated a significant increase in the expression of these cytokines within 24 hours following excimer laser surgery.[2,13,14] After FS-LASIK, our follow-up observations showed that 1 week and 1 month post-surgery, the expression levels of IL-1α, IL-6, and TGF-β1 on the ocular surface had essentially returned to preoperative levels. These results align with the findings of Tsai et al[15] and can be attributed to the well-embedded corneal flap, precise incisions, easy wound healing, and routine use of anti-inflammatory and antibiotic medications post-surgery.[16] However, our study revealed a significant increase in tear fluid TNF-α expression 1 week after surgery, particularly higher in the fluorometholone group compared to the dexamethasone group, returning to preoperative levels 1 month after surgery. The higher hormonal potency and superior tissue permeability of dexamethasone compared to fluorometholone may contribute to the observed difference in postoperative TNF-α expression between the 2 groups.[17]

The follow-up of postoperative IOP in this study revealed that 3 patients (six eyes) in the dexamethasone group exhibited elevated hormonal IOP. This elevation ultimately prompted a modification in the medication regimen, leading to their withdrawal from the study. Notably, 1 week postoperatively, the IOP in the dexamethasone group surpassed that of the fluorometholone group. This observation aligns with the findings of Hovanesian and Donnenfeld[18] suggesting that the potent nature of dexamethasone, with its higher corneal permeability, contributed to a more pronounced effect on IOP elevation. Our study further identified a noteworthy shift in results at 1 month postoperatively, where the IOP in the fluorometholone group was significantly higher than that in the dexamethasone group. This disparity was statistically significant, indicating that the prolonged use of low-potency hormones, such as fluorometholone, could still lead to IOP elevation. However, it’s crucial to emphasize that the trend of IOP elevation caused by fluorometholone was substantially lower than that induced by dexamethasone, as reported in previous studies.[19,20] In light of these findings, vigilant monitoring of IOP is imperative when employing glucocorticosteroids in the postoperative phase. Moreover, the protracted use of these hormones should be approached with caution, emphasizing the need for judicious and time-limited administration to mitigate the risk of IOP elevation.

To maintain corneal transparency, it is imperative to uphold the regular arrangement of stromal collagen fibers, preserve an intact corneal epithelium and endothelium, and ensure normal material metabolism.[21] Through the modification of tight junction protein distribution during corneal wound healing, glucocorticoids enhance the functionality of the epithelial barrier,this modification contributes to a reduction in corneal edema and promotes more effective wound healing.[22] COD serves as a crucial indicator for evaluating the severity of corneal disease, damage, and recovery post-refractive surgery. Hypoxia in the cornea can lead to acidosis in corneal epithelial cells, compromising corneal transparency.[23] Type I collagen constitutes the majority of collagen fibers in the corneal stroma; after refractive surgery, thicker diameter and irregularly arranged type III collagen may emerge, altering the corneal stroma’s structure and diminishing corneal transparency.[24] The Pentacam Scheimpflug imaging system divides the corneal area into 3 layers of varying depths and 4 concentric circles of varying sizes.[25] As the region of 10 to 12 mm from the corneal apex is beyond the scope of surgical operation. Additionally, this region is characterized by poor reliability and repeatability, justifying its exclusion from the study.[6] In our study, we observed statistically significant differences in COD within 0–2 mm from the corneal apex at 1 week and 1 month postoperatively between the 2 groups, with significantly higher COD in the anterior layer of the cornea in the fluorometholone group compared to the dexamethasone group. This may be due to the differences in anti-inflammatory mechanisms and drug permeability between fluorometholone and dexamethasone. Dexamethasone, being a stronger corticosteroid with higher permeability,[26] may be more effective in reducing inflammation and edema, thus decreasing COD and resulting in significant differences during the initial phase. In the 2 to 6 mm range from the corneal apex, the COD in the fluorometholone group was still higher than in the dexamethasone group at 1 week postoperatively, but the difference was not statistically significant. However, the difference between the 2 groups became statistically significant at 1 month postoperatively. This may be related to the corneal thickness in this area and the distribution of the therapeutic drugs. During the recovery process, corneal tissue in this area may respond differently to the 2 drugs, leading to differences in COD. In the 6 to 10 mm area from the corneal apex, there was no statistically significant difference in COD between the 2 groups at any time point. This is likely because this area is farther from the surgical center, less affected by the surgery, and the concentration and effect of the drugs are more consistent, resulting in non-significant changes in COD at different time points. These findings imply that the use of a more potent hormone during the postoperative period facilitates a quicker recovery of corneal clarity.

In summary, the judicious use of high-potency hormones for a brief duration in the initial postoperative phase following FS-LASIK offers multiple advantages, including the reduction of corneal edema, acceleration of corneal wound healing, and effective management of ocular surface inflammation. This approach also expedites the restoration of corneal transparency. Conversely, the prolonged use of low-potency hormones may still lead to increased IOP, despite the elevated risk associated with high-potency hormones. Moreover, the preservatives in these medications can exacerbate postoperative dry eye discomfort and compromise tear film stability. Therefore, to enhance patient recovery from surgery, it is recommended to administer high-potency glucocorticosteroids for a brief period, coupled with vigilant monitoring of IOP throughout this timeframe.

This study has notable limitations. It lacked a comprehensive preoperative dry eye assessment and a “fellow eye” comparison, which limits the ability to directly compare treated and untreated eyes and affects the study’s validity. The focus on outcomes only within the first month after FS-LASIK leaves long-term effects unaddressed, potentially missing delayed complications or benefits. The small sample size and limited observational parameters further reduce the study’s generalizability and robustness. Future research should include larger and more diverse patient populations, extend follow-up periods to capture long-term outcomes, and incorporate a “fellow eye” design and thorough preoperative assessments. More detailed investigations into various hormone treatment regimens post-FS-LASIK are needed to determine the most effective therapeutic strategies for optimizing patient outcomes.

Author contributions

Data curation: Jun Zheng.

Investigation: Jun Zheng.

Software: Xiangbo Hong.

Supervision: Shuangle Li.

Validation: Jun Zheng.

Writing – original draft: Jun Zheng.

Writing – review & editing: Shuangle Li.

Abbreviations:

BCVA best-corrected visual acuities

COD corneal optical density

FS-LASIK femtosecond assisted laser in situ keratomileusis

IL-1α interleukin-1α

IL-6 interleukin-6

IOP intraocular pressure

TGF-β1 transforming growth factor-β1

TNF-α tumor necrosis factor-α

UCVA uncorrected visual acuities.

This study was funded by Science and Technology Project of Sichuan Provincial Health and Health Commission grant number No. 2022JDXM012.

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Zigong First People’s Hospital (lot number: Ethics [Research] 2023 No. 43).Informed consent was obtained from all individual participants included in the study.

The authors have no conflicts of interest to disclose.

All data generated or analyzed during this study are included in this published article [and its supplementary information files].

How to cite this article: Zheng J, Hong X, Li S. The effect of different potency glucocorticosteroids treatments on tear inflammatory factors and corneal optical density after femtosecond-assisted laser in situ keratomileusis. Medicine 2024;103:37(e39667).
==== Refs
References

[1] Kim TI Alió DBJ Wilkins M Cochener B Ang M . Refractive surgery. Lancet. 2019;393 :2085–98.31106754
[2] Resan M Vukosavljevic M Vojvodic D Pajic-Eggspuehler B Pajic B . The acute phase of inflammatory response involved in the wound-healing process after excimer laser treatment. Clin Ophthalmol. 2016;10 :993–1000.27313444
[3] Toda I . Dry eye after LASIK. Invest Ophthalmol Vis Sci. 2018;59 :DES109–S115.30481814
[4] Hou C Li J Li J Peng H Wang Q . In vivo confocal microscopy of sub-basal corneal nerves and corneal densitometry after three kinds of refractive procedures for high myopia. Int Ophthalmol. 2023;43 :925–35.36153757
[5] Yagi-Yaguchi Y Kojima T Higa K . The effects of 3% Diquafosol sodium eye drops on tear function and the ocular surface of Cu, Zn-Superoxide Dismutase-1 (Sod1) Knockout Mice treated with antiglaucoma eye medications. Diagnostics (Basel). 2020;10 :20.31906291
[6] Shajari M Wanner E Rusev V . Corneal densitometry after femtosecond laser-assisted in situ keratomileusis (Fs-LASIK) and small incision lenticule extraction (SMILE). Curr Eye Res. 2018;43 :605–10.29537886
[7] González L Rivera K Andia ME Martínez RG . The IL-1 family and its role in atherosclerosis. Int J Mol Sci. 2022;24 :17.36613465
[8] Torres PF Kijlstra A . The role of cytokines in corneal immunopathology. Ocul Immunol Inflamm. 2001;9 :9–24.11262664
[9] Scheller J Chalaris A Schmidt-Arras D Rose-John S . The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 2011;1813 :878–88.21296109
[10] Lodyga M Hinz B . TGF-β1 - A truly transforming growth factor in fibrosis and immunity. Semin Cell Dev Biol. 2020;101 :123–39.31879265
[11] Wang Q Wei C Ma L . Inflammatory cytokine TNF-α promotes corneal endothelium apoptosis via upregulating TIPE2 transcription during corneal graft rejection. Graefes Arch Clin Exp Ophthalmol. 2018;256 :709–15.29480366
[12] Matsumoto K Ikema K Tanihara H . Role of cytokines and chemokines in pseudomonal keratitis. Cornea. 2005;24 (8 Suppl ):S43–9.16227823
[13] Planck SR Rich LF Ansel JC Huang XN Rosenbaum JT . Trauma and alkali burns induce distinct patterns of cytokine gene expression in the rat cornea. Ocul Immunol Inflamm. 1997;5 :95–100.9234373
[14] Saikia P Thangavadivel S Medeiros CS Lassance L de Oliveira RC Wilson SE . IL-1 and TGF-β modulation of epithelial basement membrane components perlecan and nidogen production by corneal stromal cells. Invest Ophthalmol Vis Sci. 2018;59 :5589–98.30480706
[15] Tsai T Alwees M Rost A . Changes of subjective symptoms and tear film biomarkers following femto-LASIK. Int J Mol Sci . 2022;23 :7512.35886858
[16] Sekine-Okano M Lucas R Rungger D . Expression and release of tumor necrosis factor-alpha by explants of mouse cornea. Invest Ophthalmol Vis Sci. 1996;37 :1302–10.8641833
[17] Diestelhorst M Aspacher F Konen W Krieglstein GK Hilgers RD . Effect of dexamethasone 0.1% and prednisolone acetate 1.0% eye drops on the blood-aqueous barrier after cataract surgery: a controlled randomized fluorophotometric study. Graefes Arch Clin Exp Ophthalmol. 1992;230 :451–3.1521812
[18] Hovanesian JA Donnenfeld ED . Intracameral dexamethasone 9% vs prednisolone acetate 1% in controlling postoperative pain and inflammation in patients undergoing cataract surgery. J Cataract Refract Surg. 2022;48 :906–11.35067660
[19] Akingbehin AO . Comparative study of the intraocular pressure effects of fluorometholone 0.1% versus dexamethasone 0.1%. Br J Ophthalmol. 1983;67 :661–3.6615752
[20] Fan DS Ng JS Lam DS . A prospective study on ocular hypertensive and antiinflammatory response to different dosages of fluorometholone in children. Ophthalmology. 2001;108 :1973–7.11713064
[21] Mohan RR Kempuraj D D’Souza S Ghosh A . Corneal stromal repair and regeneration. Prog Retin Eye Res. 2022;91 :101090.35649962
[22] Kadmiel M Janoshazi A Xu X Cidlowski JA . Glucocorticoid action in human corneal epithelial cells establishes roles for corticosteroids in wound healing and barrier function of the eye. Exp Eye Res. 2016;152 :10–33.27600171
[23] Moreno VC Aguilella-Arzo M Del CR Espinós FJ Del CL . A refined model on flow and oxygen consumption in the human cornea depending on the oxygen tension at the interface cornea/post lens tear film during contact lens wear. J Optom. 2022;15 :160–74.33589396
[24] Abdelkader A . Effect of fibrin glue on corneal lamellar healing and how it correlates to biomechanical properties: biomechanical wavefront analysis and confocal study. Eye Vis (Lond). 2016;3 :15.27257609
[25] Li S Siggel R Guo Y . Corneal densitometry: a potential indicator for early diagnosis of Fabry disease. Graefes Arch Clin Exp Ophthalmol. 2021;259 :941–8.33258999
[26] Cagini C Cometa F Torroni G Pellegrino A Pellegrino R Cavallini GM . Dexamethasone disodium phosphate penetration into the human aqueous humor after topical application. Curr Eye Res. 2016;41 :897–9.26580978
