Clinical characteristics of patients with refractory meibomian gland dysfunction unresponsive to intense pulsed light treatment

Clinical characteristics of patients with refractory meibomian gland dysfunction unresponsive to intense pulsed light treatment | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Clinical characteristics of patients with refractory meibomian gland dysfunction unresponsive to intense pulsed light treatment Yoo Young Jeon, Nahyun Park, Hayoung Lee, Kyu Sang Eah, Yea Eun Lee, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6413260/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: To investigate the clinical characteristics of patients with meibomian gland dysfunction (MGD) who are unresponsive to additional intense pulsed light (IPL) therapy and to identify the risk factors for poor treatment response. Methods: Patients with moderate-to-severe MGD who had previously undergone four sessions of IPL treatment with a 590 nm filter at another clinic, received an additional four sessions of IPL therapy. A total of 66 eyes were analyzed. Patients' subjective assessments before and after the additional IPL treatments were scored on a scale from 0 to 4, where 0=moderate improvement, 1=mild improvement, 2=no change, and 3=aggravated MGD. Patients who scored 0 or 1 were classified as Group 1 (Responsive group), while those who scored 2 or 3 were classified as Group 2 (Refractory group). Results: After the additional IPL treatment, significant differences were observed between the groups in the Oxford and Sjögren’s International Clinical Collaborative Alliance (SICCA) staining scores (all P<0.001). Significant differences were found between the groups with regard to both upper and lower lid meibum quality and meibum consistency (all P<0.001). Group 2 had a significantly higher meibomian gland grade compared to Group 1 (P<0.001). Changes in the Oxford staining score (P=0.032), SICCA staining score (P=0.003), meibum quality (P<0.001), meibum consistency (P<0.001), and meibomian gland grade (P<0.001), before and after the additional treatment, were significantly greater in Group 1 than in Group 2. Logistic regression analysis identified higher Oxford staining scores (P=0.029; odds ratio 12.69) and elevated metalloproteinase-9 (MMP-9) levels (P=0.021; odds ratio 3.88) as significant risk factors for refractory MGD. Conclusions: Patients with refractory MGD, who did not respond to additional IPL treatment, exhibited poor ocular staining scores before treatment. High tear MMP-9 levels and elevated Oxford staining scores were identified as significant risk factors for poor treatment outcomes. Health sciences/Diseases/Eye diseases/Corneal diseases Health sciences/Diseases/Eye diseases/Eyelid diseases Intense pulsed light Matrix metalloproteinase-9 Refractory meibomian gland dysfunction Figures Figure 1 Introduction Dry eye disease (DED) is classified into two main subtypes: aqueous-deficient dry eye and evaporative dry eye, both of which involve pathology affecting the meibomian glands, lacrimal glands, eyelids, tear film, and ocular surface cells [ 1 , 2 ]. The most common cause of evaporative dry eye is meibomian gland dysfunction (MGD) [ 3 ]. MGD is characterized by significant changes in the consistency and quantity of meibum secretion, leading to eyelid inflammation and subsequent ocular surface dysfunction. Insufficient lipid secretion from the meibomian glands compromises tear film stability, resulting in dry eye symptoms, despite normal tear secretion [ 4 ]. While most cases of MGD are idiopathic, some may be secondary to dermatological conditions such as acne rosacea and Demodex infestation [ 5 ]. Various therapies have been used to treat MGD, including warm compresses, lid hygiene practices, dietary supplementation with omega-3 fatty acids, forced meibum expression, topical steroids, topical and oral antibiotics, topical cyclosporine, preservative-free artificial tears, lipid-containing eyedrops [ 6 ], topical diquafosol [ 7 ], and automated thermal pulsation [ 8 ]. Intense pulsed light (IPL) therapy has also been used to improve meibum secretion and quality, stabilize the tear film, and reduce eyelid inflammation [ 9 – 11 ]. In 2002, Dr. Toyos was the first to describe the positive effects of IPL on eyelids, noting that patients treated for facial rosacea experienced an improvement in the signs and symptoms of MGD following IPL treatment [ 12 ]. Although the exact mechanisms underlying IPL’s beneficial effects are complex and not fully understood, IPL is thought to reduce telangiectasia, eradicate Demodex mites, liquefy meibum through thermal effects, modulate the secretion of anti-inflammatory cytokines, and suppress matrix metalloproteinases [ 9 , 13 , 14 ]. Several studies have since reported the safety of IPL, with no adverse effects when proper eye protection is used. The use of IPL for treating MGD and dry eye has become increasingly common among ophthalmologists [ 14 – 17 ]. Despite the range of available treatments, some patients with MGD are refractory to therapy and do not achieve long-term symptom relief [ 18 ]. Wan et al. suggested that meibomian gland dropout may cause refractory MGD and analyzed potential factors affecting long-term meibomian gland recovery. According to their study, age, changes in corneal fluorescein staining, and the meibomian gland area ratio at baseline, were potential predictors of meibomian gland recovery [ 19 ]. However, there remain patients who do not respond to IPL treatment. Therefore, the present study aimed to analyze the risk factors for the non-responsiveness to additional IPL therapy in patients previously treated with IPL for MGD. Methods Study population and design A total of 66 eyes from 66 patients were retrospectively enrolled in this study. Among both eyes, the eye at a more severe MGD stage was selected. If both eyes showed the same MGD stage, one of the eyes was randomly selected. Patients with moderate-to-severe MGD who had previously undergone four IPL sessions using a 590 nm filter at another clinic received an additional four IPL treatments at the Department of Ophthalmology at Asan Medical Center. This study was reviewed and approved by the Institutional Review Board of the Asan Medical Center and University of Ulsan College of Medicine (IRB No. 2024 − 0595) and conducted in accordance with the tenets of the Declaration of Helsinki. Diagnosis and inclusion criteria Moderate-to-severe MGD was diagnosed based on the definition established by the international workshop on MGD, which is characterized by moderately or severely altered meibum expressiveness and secretion quality, along with moderate or greater peripheral and central corneal staining [ 20 ]. Individuals over 18 years of age with moderate-to-severe MGD, whose condition was unresponsive to four IPL sessions at other clinics, were included [ 21 ]. Patients were compared subjectively before and after IPL treatment at Asan Medical Center, and unresponsiveness was defined as no improvement or even worsening following IPL treatment. Before receiving four additional IPL treatments with a vascular filter, patients provided a subjective assessment of their post-IPL MGD status, which was scored on a scale from 0 to 4: 0 = moderate improvement; 1 = mild improvement; 2 = no change; and 3 = aggravated MGD. Patients scoring 0 or 1 were classified as Group 1 (responsive to additional IPL therapy), and those scoring 2 or 3 were classified as Group 2 (non-responsive or refractory to additional IPL therapy). Based on these criteria, a subgroup analysis was performed to identify the signs and symptoms of refractory MGD in Group 2 and to analyze the risk factors contributing to refractory MGD. Patients enrolled in this study were those who had previously received IPL treatment at other clinics and had not improved even with various treatments, including steroid and cyclosporine eyedrops, warm compresses, and eyelid scrubs. This study assumed that the impact of these treatments on the pre-additional IPL status of the refractory MGD group had been minimal. For this reason, this study focused on investigating the effect of additional IPL treatment with vascular filters in patients previously treated with IPL and other treatments for moderate and severe MGD and analyzing risk factors for non-responsiveness to additional IPL therapy. All enrolled patients had Fitzpatrick skin types I–IV. Exclusion criteria and eye selection Exclusion criteria included a diagnosis of Sjögren's syndrome, a history of intraocular or ocular surgery within the past six months, glaucoma treated with topical medications, eyelid malposition, ocular infection, non-dry eye ocular inflammation, ocular allergy, other autoimmune diseases, contact lens use during the study period, and pregnancy or lactation. All patients underwent four IPL sessions with a vascular filter at two-week intervals, followed by a one-month post-treatment evaluation. This procedure was performed on all four eyelids by a single trained physician (HL). Ophthalmic tests, conducted before and after the additional IPL treatments, included visual acuity, intraocular pressure, tear break-up time (TBUT) using fluorescein, corneal and conjunctival staining scores (Sjögren’s International Clinical Collaborative Alliance [SICCA]) staining score and Oxford staining score), Schirmer’s test I without topical anesthesia, and measurement of metalloproteinase-9 (MMP-9) levels. Slit-lamp microscopy was used to evaluate the lid margin (including lid wiper epitheliopathy and vascularity) and meibomian glands. Visual acuity was measured in decimal format, and a single ophthalmologist assessed the TBUT and corneal and conjunctival staining scores via slit-lamp examination. Evaluation of meibum and lid margin parameters Meibum quality, consistency, and telangiectasia of the eyelids were evaluated using methods previously described [ 22 , 23 ]. Lid margin telangiectasia was assessed via slit-lamp microscopy and scored from 0 to 3 as follows: 0 = no or slight redness in the lid margin conjunctiva with no telangiectasia crossing the meibomian gland orifices; 1 = redness in the lid margin conjunctiva without telangiectasia crossing the meibomian gland orifices; 2 = redness in the lid margin conjunctiva with telangiectasia crossing the meibomian gland orifices over less than half of the lid’s length; and 3 = redness in the lid margin conjunctiva with telangiectasia crossing the meibomian gland orifices over half or more of the lid’s length. Meibum grades were assessed based on the appearance of meibum when digital pressure was applied to the upper tarsus: grade 0 = clear meibum easily expressed; grade 1 = cloudy meibum expressed with mild pressure; grade 2 = cloudy meibum expressed with more than moderate pressure; and grade 3 = no meibum expression, even with firm pressure. To evaluate meibum consistency, both the upper and lower eyelids were evaluated using meibomian gland expressor forceps. Meibum consistency was graded on a scale from 1 to 3: 1 = oily; 2 = creamy; and 3 = toothpaste-like [ 24 ]. MMP-9 measurement MMP-9 levels were measured using the InflammaDry immunoassay (Rapid Pathogen Screening, Inc., Sarasota, FL, USA). The presence of both a blue line in the control zone and a red line in the result zone indicated a positive test result (MMP-9 ≥ 40 ng/mL). Signal intensity of the red line, indicating higher MMP-9 concentration, was graded on a scale from 0 to 4: 0 = none; 1 = trace; 2 = weak positive; 3 = positive; and 4 = strong positive, as described in a previous study [ 25 ]. IPL treatment protocol For IPL treatment, the ophthalmologist used the M22 Optima IPL device (Lumenis, Yokneam, Israel) with a specific pulse setting (fluence delivering in a 6-5-4 J/cm 2 decrement pattern) [ 23 ]. For the lower eyelid treatment, local anesthesia and ultrasonic gel were applied to the treatment area. Both eyelids were closed and covered with metal spatulas. After exposing the lower eyelid margin, the IPL probe was used to pull the lower eyelid slightly downward to increase the surface area of contact between the IPL probe and the lower eyelid margin to maximize the treatment effect. Patients received twelve light pulses (with slightly overlapping areas of application) from the left, preauricular area, to the right, preauricular area for two times (total: 24 light pulses). For the upper eyelid treatment, a metal spatula was inserted gently into the space between the bulbar conjunctiva and the upper eyelid. Patients then received two to three light pulses after tenting the metal spatula upward to protect the ocular surface. Gentle meibomian gland expression was performed on all four eyelids using expressor forceps immediately after IPL treatment. Throughout the follow-up period, patients were advised to use loteprednol 0.5% (Lotemax; Bausch & Lomb, Tampa, FL, USA) four times daily, cyclosporine 0.1% (Ikervis; cationic emulsion at 0.1% CsA; Santen) once daily, carbomer gel (Liposic; 2 mg/g carbomer eye gel; Bausch + Lomb), and 0.15% sodium hyaluronate (New Hyaluni; Taejoon, Seoul, Korea). Additionally, patients were instructed to use warm compresses and perform lid scrubs. Statistical analysis All statistical analyses were performed using SPSS statistical software for Windows (version 25.0; SPSS Inc., Chicago, IL, USA). The Shapiro–Wilk test was employed to analyze the normality of the data. The Mann-Whitney U test was used to compare clinical parameters between Group 1 (responsive to additional IPL therapy) and Group 2 (non-responsive to additional IPL therapy). Logistic regression analysis was performed to obtain odds ratios when more than one explanatory variable was present, aiming to identify factors associated with refractory MGD. Multicollinearity was controlled to analyze the effects of each independent variable. A P-value of < 0.05 was considered statistically significant. Result Among the 66 eyes from 66 patients, Group 1 comprised 32 eyes and Group 2 comprised 34 eyes. The mean age of Group 1 was 66.2 ± 10.8 years, while the mean age of Group 2 was 65.1 ± 9.1 years. The baseline clinical parameters for both groups are presented in Table 1 . No significant differences were observed between the two groups at baseline, except for the Oxford staining score. The Oxford staining scores were 2.5 ± 1.1 in Group 1 and 3.3 ± 1.4 in Group 2, with the responsive MGD group showing significantly lower staining scores (P = 0.020). Table 1 Baseline demographics and clinical parameters of the responsive group and refractory group before additional IPL treatment Group 1 (Responsive to addtional IPL) Group 2 (Refractory to additional IPL) P value* Number of eyes / Patients 32/32 34/34 Sex (Men : Women) 3:5 4:13 0.167 Age (years) 66.2 ± 10.8 65.1 ± 9.1 0.664 TBUT (sec) 1.8 ± 1.3 1.6 ± 0.9 0.626 Oxford score 2.5 ± 1.1 3.3 ± 1.4 0.020 SICCA score 6.4 ± 2.1 7.3 ± 2.3 0.092 Meibum quality UL LL UL LL 0.143, > 0.999 3.0 ± 0.0 3.0 ± 0.0 2.9 ± 0.2 3.0 ± 0.0 Meibum consistency UL LL UL LL 0.386, 0.105 2.8 ± 0.4 2.9 ± 0.4 2.9 ± 0.3 3.0 ± 0.2 Lid margin telangiectasia UL LL UL LL 0.079, 0.188 2.6 ± 0.5 2.7 ± 0.5 2.8 ± 0.4 2.9 ± 0.4 Meibomian gland grade 2.7 ± 0.5 2.9 ± 0.3 0.056 Tear MMP-9 level 2.2 ± 1.0 2.6 ± 1.2 0.155 IPL = intense pulsed light; TBUT = tear break-up time; SICCA = Sjögren’s International Clinical Collaborative Alliance; MMP-9 = metalloproteinase-9; UL = upper lid; LL = lower lid. *Statistical analysis was performed with a Mann–Whitney U test. After IPL treatment, the mean TBUT was 3.3 ± 1.1 seconds in Group 1 and 3.0 ± 1.2 seconds in Group 2, with no significant difference between the two groups (P = 0.199). However, significant differences were observed in the Oxford staining scores (Group 1 = 1.1 ± 0.3 vs. Group 2 = 2.1 ± 1.1, P < 0.001) and SICCA staining scores (Group 1 = 2.1 ± 1.9 vs. Group 2 = 4.9 ± 2.4, P < 0.001). The quality of meibum in both the upper and lower lids showed significant differences between the two groups (upper lid: Group 1 = 1.6 ± 0.5 vs. Group 2 = 2.5 ± 0.5, P < 0.001; lower lid: Group 1 = 1.6 ± 0.5 vs. Group 2 = 2.5 ± 0.50, P < 0.001). Similarly, significant differences in meibum consistency were noted for both the upper and lower lids (upper lid: Group 1 = 1.2 ± 0.4 vs. Group 2 = 2.0 ± 0.4, P < 0.001; lower lid: Group 1 = 1.3 ± 0.6 vs. Group 2 = 2.3 ± 0.4, P < 0.001). No significant differences were found in lid margin telangiectasia between the two groups. Meibomian gland grade was 1.1 ± 0.5 in Group 1 and 2.0 ± 0.5 in Group 2 (P < 0.001). MMP-9 levels were 1.8 ± 1.4 in Group 1 and 2.2 ± 1.0 in Group 2 (P = 0.202) (Table 2 ). Changes in the Oxford staining score (P = 0.032), SICCA staining score (P = 0.003), meibum quality (P < 0.001), consistency (P < 0.001), and meibomian gland grade (P < 0.001) were significantly greater in Group 1 than in Group 2 (Fig. 1 ). According to the logistic regression analysis, the Oxford staining score and MMP-9 results were identified as risk factors that had a statistically significant effect on refractory MGD status (P = 0.029, odds ratio: 12.69 for Oxford staining score; P = 0.021, odds ratio: 3.88 for MMP-9) (Table 3 ). Table 2 Comparison of MGD-related clinical parameters and subjective symptoms between groups at one month after additional IPL treatment Group 1 (Responsive to addtional IPL) Group 2 (Refractory to additional IPL) P value* TBUT (sec) 3.3 ± 1.1 3.0 ± 1.2 0.199 Oxford score 1.1 ± 0.3 2.1 ± 1.1 < 0.001 SICCA score 2.1 ± 1.9 4.9 ± 2.4 < 0.001 Meibum quality UL LL UL LL < 0.001, < 0.001 1.6 ± 0.5 1.6 ± 0.5 2.5 ± 0.5 2.5 ± 0.5 Meibum consistency UL LL UL LL < 0.001, < 0.001 1.2 ± 0.4 1.3 ± 0.6 2.0 ± 0.4 2.3 ± 0.4 Lid margin telangiectasia UL LL UL LL 0.055, 0.189 1.3 ± 0.5 1.7 ± 0.7 1.6 ± 0.7 1.7 ± 0.7 Meibomian gland grade 1.1 ± 0.5 2.0 ± 0.5 < 0.001 Tear MMP-9 level 1.8 ± 1.4 2.2 ± 1.0 0.202 Number of IPL treatment 4.0 ± 0.0 9.8 ± 3.5 < 0.001 MGD = meibomian gland dysfunction; IPL = intense pulsed light; TBUT = tear break-up time; SICCA = Sjögren’s International Clinical Collaborative Alliance; MMP-9 = metalloproteinase-9; UL = upper lid; LL = lower lid. *Statistical analysis was performed with a Mann–Whitney U test. Table 3 Logistic regression for MGD-related clinical parameters and subjective symptoms after one month of additional IPL treatment Odds Ratio 95% Confidence interval P value B Coefficient β Lowest Highest Sex Female 1 Male 0.59 0.12 2.80 0.503 -0.53 -0.25 Age (years) 0.95 0.86 1.04 0.944 -0.06 -0.57 TBUT (sec) 1.95 0.72 5.27 0.189 0.67 0.75 Oxford score 12.69 1.29 125.05 0.029 2.54 3.10 SICCA score 0.41 0.15 1.12 0.060 -0.89 -1.98 Meibum quality UL 0.00 0.00 0.00 0.999 0.00 0.00 LL 0.00 0.00 0.00 0.999 0.00 0.00 Meibum consistency UL 4.24 0.12 149.36 0.426 1.45 0.58 LL 0.51 0.01 24.39 0.732 -0.68 -0.19 Lid margin telangiectasia UL 0.69 0.04 10.72 0.790 -0.37 -0.18 LL 0.18 0.01 4.89 0.304 -1.75 -0.69 Meibomian gland grade 1.11 0.06 20.37 0.942 0.11 0.05 Tear MMP-9 level 3.88 1.22 12.32 0.021 1.35 1.47 MGD = meibomian gland dysfunction; IPL = intense pulsed light; TBUT = tear break-up time; SICCA = Sjögren’s International Clinical Collaborative Alliance; MMP-9 = metalloproteinase-9; UL = upper lid; LL = lower lid; B = Partial regression coefficient (B); β = Standardized partial regression coefficient (β). Discussion This study investigated the risk factors contributing to non-response to additional IPL therapy with a vascular filter in patients with moderate-to-severe MGD, who had previously undergone IPL treatment using a 590 nm filter and had not improved even with various treatments including steroid and cyclosporine eyedrops, warm compresses, and eyelid scrubs. Improvements in the Oxford staining scores, SICCA staining scores, meibum quality, consistency, and meibomian gland grade were significantly greater in the responsive group. Furthermore, patients with higher baseline corneal and conjunctival staining scores (Oxford staining score) and elevated tear MMP-9 levels before the additional IPL treatment were more likely to exhibit a refractory type MGD, demonstrating less responsiveness to further IPL therapy. Various treatment methods for MGD have been introduced in numerous studies, each demonstrating varying degrees of effectiveness. Lam et al. reported that self-applied eyelid warming, thermal pulsation, IPL, meibomian gland probing, antibiotics, Manuka honey, and lipid-containing or perfluorohexyloctane eye drops exhibited significant clinical efficacy [ 5 ]. Notably, IPL therapy has been highlighted as a highly effective option. Given that increased meibum viscosity is a hallmark of MGD, heat-based treatments, including warm compression, thermal pulsation, and IPL, are particularly effective at melting thickened meibum and are often superior to other treatment modalities for improving MGD [ 5 , 16 ]. Despite identical IPL treatment settings, responses varied among patients, prompting this study to investigate the characteristics of those with refractory MGD who did not respond well to additional IPL treatments. Previous studies have identified patient populations that respond well to IPL treatment. Tang et al. reported significant improvements in various parameters, including the Ocular Surface Disease Index (OSDI), TBUT, corneal fluorescein staining score, meibomian glands yielding secretion score, meibomian glands yielding clear secretion, and meibomian glands yielding liquid secretion after three cycles of IPL/meibomian gland expression (MGX) treatments [ 26 ]. Characteristics associated with better outcomes after IPL treatment included younger age (P = 0.012), longer TBUT (P = 0.010), better meiboscore (P = 0.012), and less meibomian gland loss (P = 0.008) before IPL/MGX [ 26 ]. Similarly, in a study by Chen et al. involving 48 patients, univariate analysis identified factors affecting IPL effectiveness. Patients aged 18–39 years, with moderate MGD, higher baseline Schirmer test results, and higher baseline OSDI scores, exhibited a higher effective rate for IPL treatment. MGD severity was strongly associated with IPL effectiveness; patients with moderate MGD had an odds ratio of 5.493 compared to those with severe MGD (P = 0.003) [ 27 ]. Monitoring the therapeutic effects of IPL is performed using TBUT, the corneal staining score, lid margin telangiectasia, and tear MMP-9 expression. Previous studies have demonstrated that MMP-9 can serve as a predictor for the effectiveness and treatment response of IPL [ 28 ]. The MMP-9 test is a convenient method for objectively evaluating ocular surface inflammation during outpatient visits. Elevated MMP-9 levels have been also detected in DED patients. Chotikanovich et al. measured tear MMP-9 activity in 46 patients newly diagnosed with DED, and 19 asymptomatic controls [ 29 ]. They found that DED patients had a significantly increased MMP-9 activity of 35.57 ± 17.04 ng/mL (P < 0.008) compared to controls, whose levels averaged 8.39 ± 4.70 ng/mL. Normal MMP-9 levels in human tears ranged from 3.0 to 41.0 ng/ml, with 90% of individuals having levels below 30 ng/ml. Patients in the highest severity category exhibited a mean MMP-9 activity of 381.24 ± 42.83 ng/mL (P < 0.001), which was significantly elevated compared to controls and all lower severity groups [ 29 , 30 ]. Previous studies have confirmed that MMP-9 levels and positivity decreased after IPL treatment compared to baseline [ 15 , 22 ]. The present study confirmed higher tear MMP-9 levels before IPL treatment as a risk factor for patients with refractory MGD who did not respond to the therapy [ 22 ]. In this study, vascular filters were used in the IPL treatment. IPL treatment with a vascular filter decreases ocular surface inflammation, as indicated by decreased tear MMP-9 levels, by targeting and disrupting lid margin telangiectasia. Additionally, light wavelengths between 600 and 800 nm, which are mainly absorbed by melanin, can cause pain. Hence, the vascular filter reduces pain by focusing light absorption on the vascular structures and avoiding wavelengths in the 600–800 nm range at the eyelid margin [ 23 ]. Patients were advised to use loteprednol 0.5%, and cyclosporine 0.1% throughout the IPL treatment follow-up period, along with warm compresses and lid scrubs. It is well-established that anti-inflammatory corticosteroids, tetracycline derivatives [ 31 , 32 ], and cyclosporine [ 33 ] can effectively reduce tear fluid MMP-9 levels. Therefore, since patients with poor responses to IPL therapy exhibited high MMP-9 levels despite the application of anti-inflammatory eye drops, combining various treatment modalities—including more potent anti-inflammatory agents that can lower tear MMP-9 levels—may be beneficial for the treatment of MGD by reducing ocular surface inflammation. Regarding the regression analysis, the inconsistency in results may be due to differences in the two analytical methods, as the parameter that was not significant before and after treatment analyzed by the Mann-Whitney U test was significant in the regression analysis. Regression analysis is used to model the relationship between dependent and independent variables. Regression considers the combined impact of variables and models in both linear and non-linear relationships. If other important variables influence the dependent variable, the Mann-Whitney U test may miss this impact, whereas regression can include these variables in the model and provide a more accurate picture [ 34 ] This study has some limitations, including a small sample size, a retrospective design, and selection bias. As this is a retrospective study, the sample size was not adequately considered when analyzing medical records. Therefore, future studies should calculate the required sample size in advance to ensure statistical significance and analyze a larger dataset to enhance the robustness of the findings. The way the study group was constructed may also have introduced selection bias, as group allocation was based on patient-reported improvements in MGD symptoms after additional IPL treatment with a vascular filter. This study did not have access to pre- or post-IPL treatment data from previous IPL sessions at other clinics. Therefore, it is possible that patients who had achieved significant improvements in MGD signs from previous IPL treatments were included in the study. Furthermore, the study was retrospective and limited by a lack of information on when each patient had been last treated with IPL and which protocol they were treated with at other clinics. Future research with larger patient populations and objective criteria for defining refractory MGD is necessary to identify factors influencing responsiveness to IPL treatment. In addition, the lack of a meibomian gland atrophy assessment may also be a limitation of this study. Meibomian gland dropout may cause refractory MGD, and this factor cannot be ruled out. MG dropout, using the Lipiview, needs to be evaluated in future studies. In conclusion, patients with refractory MGD who did not respond to additional IPL treatment were characterized by poor ocular staining scores before treatment. The identified risk factors for these refractory MGD cases included elevated tear MMP-9 levels and higher Oxford staining scores. Prior to this study, patients who had not responded well to IPL treatment had been clinically recognized, but their clinical characteristics had not been known. Therefore, there were no indications as to whether further IPL treatment should be continued. This question led us to conduct the current study, and the results of this study are significant because they provide a clinical characterization of the pre-and post-treatment characteristics of patients who do not respond to IPL treatment, which will be useful in planning future IPL treatments. Declarations Data availability statements The datasets generated and/or analysed during the current study are not publicly available due to patient privacy concerns and restrictions imposed by the Institutional Review Board. Participants did not provide consent for public sharing of their clinical data. However, the data may be available from the corresponding author on reasonable request and with appropriate ethical approvals. Consent statements Due to the retrospective nature of the study, this study does not need to obtain informed consent. This study was reviewed and approved by the Institutional Review Board of the Asan Medical Center and University of Ulsan College of Medicine (IRB No. 2024-0595) and conducted in accordance with the tenets of the Declaration of Helsinki. Author contribution statements Conception and design of study: Yoo Young Jeon, Hun Lee; acquisition of data: Nahyun Park, Yea Eun Lee, Chung Min Lee, Jeewon Han, Changmin Kim, Kyu Sang Eah, Hayoung Lee; analysis of data: Nahyun Park, Sanghyu Nam, Ho Seok Chung, Jae Yong Kim; drafting the manuscript: Yoo Young Jeon, Nahyun Park, Hun Lee; revising the manuscript critically for important intellectual content: Yoo Young Jeon, Hun Lee; approval of the version of the manuscript to be published: Yoo Young Jeon, Hun Lee References A.J. Bron, C.S. de Paiva, S.K. Chauhan, S. Bonini, E.E. Gabison, S. Jain, et al., TFOS DEWS II pathophysiology report, Ocul Surf 15 (3) (2017) 438-510. J.P. Craig, K.K. Nichols, E.K. Akpek, B. Caffery, H.S. Dua, C.K. 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Briscoe, Intense pulsed light treatment for dry eye disease due to meibomian gland dysfunction; a 3-year retrospective study, Photomed Laser Surg 33 (1) (2015) 41-46. G. Giannaccare, L. Taroni, C. Senni, V. Scorcia, Intense Pulsed Light Therapy In The Treatment Of Meibomian Gland Dysfunction: Current Perspectives, Clin Optom (Auckl) 11 (2019) 113-126. G.K. Vora, P.K.J.C.o.i.o. Gupta, Intense pulsed light therapy for the treatment of evaporative dry eye disease, 26 (4) (2015) 314-318. H.S. Chung, Y.E. Han, H. Lee, J.Y. Kim, H. Tchah, Intense pulsed light treatment of the upper and lower eyelids in patients with moderate-to-severe meibomian gland dysfunction, Int Ophthalmol 43 (1) (2023) 73-82. H. Lee, Y.Y. Jeon, K.S. Eah, N. Park, Y.E. Lee, J. Han, et al., A Comparative Study of Intense Pulsed Light with Two Different Filters in Meibomian Gland Dysfunction: A Prospective Randomized Study, Journal of Clinical Medicine 14 (1) (2025) 199. M.T. Wang, Z. Jaitley, S.M. Lord, J.P.J.O. Craig, V. Science, Comparison of self-applied heat therapy for meibomian gland dysfunction, 92 (9) (2015) e321-e326. R. Arita, S. Fukuoka, T. Mizoguchi, N. Morishige, Multicenter Study of Intense Pulsed Light for Patients with Refractory Aqueous-Deficient Dry Eye Accompanied by Mild Meibomian Gland Dysfunction, J Clin Med 9 (11) (2020). X. Wan, Y. Wu, Z. Zhai, P. Yang, S. Zhou, H. Ye, et al., Factors affecting long-term changes of meibomian gland in MGD patients, Graefe's Archive for Clinical and Experimental Ophthalmology 262 (2) (2024) 527-535. A. Tomlinson, A.J. Bron, D.R. Korb, S. Amano, J.R. Paugh, E.I. Pearce, et al., The international workshop on meibomian gland dysfunction: report of the diagnosis subcommittee, Invest Ophthalmol Vis Sci 52 (4) (2011) 2006-2049. P.K. Gupta, G.K. Vora, C. Matossian, M. Kim, S. Stinnett, Outcomes of intense pulsed light therapy for treatment of evaporative dry eye disease, Can J Ophthalmol 51 (4) (2016) 249-253. J.H. Jang, K. Lee, S.H. Nam, J. Kim, J.Y. Kim, H. Tchah, et al., Comparison of clinical outcomes between intense pulsed light therapy using two different filters in meibomian gland dysfunction: prospective randomized study, Sci Rep 13 (1) (2023) 6700. Y. Lee, J.H. Jang, S. Nam, K. Lee, J. Kim, J.Y. Kim, et al., Investigation of Prognostic Factors for Intense Pulsed Light Treatment with a Vascular Filter in Patients with Moderate or Severe Meibomian Gland Dysfunction, J Clin Med 11 (16) (2022). R. Arita, T. Mizoguchi, S. Fukuoka, N. Morishige, Multicenter Study of Intense Pulsed Light Therapy for Patients With Refractory Meibomian Gland Dysfunction, Cornea 37 (12) (2018) 1566-1571. J.Y. Han, Y. Lee, S. Nam, S.Y. Moon, H. Lee, J.Y. Kim, et al., Effect of intense pulsed light using acne filter on eyelid margin telangiectasia in moderate-to-severe meibomian gland dysfunction, Lasers Med Sci 37 (4) (2022) 2185-2192. Y. Tang, R. Liu, P. Tu, W. Song, J. Qiao, X. Yan, et al., A Retrospective Study of Treatment Outcomes and Prognostic Factors of Intense Pulsed Light Therapy Combined With Meibomian Gland Expression in Patients With Meibomian Gland Dysfunction, Eye Contact Lens 47 (1) (2021) 38-44. C. Chen, D. Chen, Y.-y. Chou, Factors Influencing the Effectiveness of Intense Pulsed Light for Meibomian Gland Dysfunction, (2020). N.L. Lanza, F. Valenzuela, V.L. Perez, A. Galor, The Matrix Metalloproteinase 9 Point-of-Care Test in Dry Eye, The Ocular Surface 14 (2) (2016) 189-195. S. Chotikavanich, C.S. de Paiva, J.J. Chen, F. Bian, W.J. Farley, S.C.J.I.o. Pflugfelder, et al., Production and activity of matrix metalloproteinase-9 on the ocular surface increase in dysfunctional tear syndrome, 50 (7) (2009) 3203-3209. R. Sambursky, T.P.J.C.o.i.o. O'Brien, MMP-9 and the perioperative management of LASIK surgery, 22 (4) (2011) 294-303. C.S. De Paiva, R.M. Corrales, A.L. Villarreal, W.J. Farley, D.-Q. Li, M.E. Stern, et al., Corticosteroid and doxycycline suppress MMP-9 and inflammatory cytokine expression, MAPK activation in the corneal epithelium in experimental dry eye, 83 (3) (2006) 526-535. M. Mori, E. De Lorenzo, E. Torre, M. Fragai, C. Nativi, C. Luchinat, et al., A highly soluble matrix metalloproteinase‐9 inhibitor for potential treatment of dry eye syndrome, 111 (5) (2012) 289-295. G.N.J.I.o.c. Foulks, Topical cyclosporine for treatment of ocular surface disease, 46 (4) (2006) 105-122. E.Y. Boateng, D. Abaye, A Review of the Logistic Regression Model with Emphasis on Medical Research, Journal of Data Analysis and Information Processing 07 (2019) 190-207. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6413260","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":456108404,"identity":"e407330b-32a9-4c41-aff4-4c79f69e2478","order_by":0,"name":"Yoo Young Jeon","email":"","orcid":"","institution":"Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yoo","middleName":"Young","lastName":"Jeon","suffix":""},{"id":456108405,"identity":"1d569e7d-3a1c-43ec-bc17-9d3270c93a80","order_by":1,"name":"Nahyun Park","email":"","orcid":"","institution":"Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Nahyun","middleName":"","lastName":"Park","suffix":""},{"id":456108406,"identity":"03edc679-72b0-468b-8617-df8c43be55f3","order_by":2,"name":"Hayoung Lee","email":"","orcid":"","institution":"Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hayoung","middleName":"","lastName":"Lee","suffix":""},{"id":456108407,"identity":"d6b34f6e-3e87-4bdb-a1c3-36516c0923ae","order_by":3,"name":"Kyu Sang Eah","email":"","orcid":"","institution":"Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kyu","middleName":"Sang","lastName":"Eah","suffix":""},{"id":456108408,"identity":"26e95d99-e92f-468f-b76a-65c41f8640d5","order_by":4,"name":"Yea Eun Lee","email":"","orcid":"","institution":"Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yea","middleName":"Eun","lastName":"Lee","suffix":""},{"id":456108409,"identity":"1c17f74b-528a-436a-90e4-1269aa124bfb","order_by":5,"name":"Chung Min Lee","email":"","orcid":"","institution":"Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Chung","middleName":"Min","lastName":"Lee","suffix":""},{"id":456108410,"identity":"c80e00ed-a892-4d4d-9b91-85958630ffc6","order_by":6,"name":"Jeewon Han","email":"","orcid":"","institution":"Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jeewon","middleName":"","lastName":"Han","suffix":""},{"id":456108411,"identity":"af8cfbe8-4cd2-4854-8ce1-35aa546da247","order_by":7,"name":"Sanghyu Nam","email":"","orcid":"","institution":"Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Sanghyu","middleName":"","lastName":"Nam","suffix":""},{"id":456108412,"identity":"b4048594-4ff5-4c9e-945d-9fa878caafd7","order_by":8,"name":"Changmin Kim","email":"","orcid":"","institution":"Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Changmin","middleName":"","lastName":"Kim","suffix":""},{"id":456108413,"identity":"d446faf1-6a24-459d-b36c-1f0c99214479","order_by":9,"name":"Ho Seok Chung","email":"","orcid":"","institution":"Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ho","middleName":"Seok","lastName":"Chung","suffix":""},{"id":456108414,"identity":"d894ee34-9092-4303-b2af-a91ca4f8242f","order_by":10,"name":"Jae Yong Kim","email":"","orcid":"","institution":"Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jae","middleName":"Yong","lastName":"Kim","suffix":""},{"id":456108415,"identity":"e4bcadf2-191a-49b7-8419-cf0f4ecdf435","order_by":11,"name":"Hun Lee","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAv0lEQVRIiWNgGAWjYDACCQYG5r///suB2AceEKuFgYeN2RisJYEULYkNIA5RWgxu95g9kOBhS58fdvgh0BY7Od0GQlrunDE3MJDgyd14O80AqCXZ2OwAIS03cswkEgwkcjfOTgBpOZC4jSgtBxIM0g1np38gXotkw4GEBHnpHCJtkbyRVibN2HDAcIN0TgHQNiL8wncjeRtIi7z87PTNHz5U2MkR1KIAU2AAZhgQUA4C8g3ojFEwCkbBKBgF6AAATmZFsBH6lNAAAAAASUVORK5CYII=","orcid":"","institution":"Department of Ophthalmology, Asan Medical Center, University of Ulsan College of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Hun","middleName":"","lastName":"Lee","suffix":""}],"badges":[],"createdAt":"2025-04-09 15:23:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6413260/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6413260/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82795819,"identity":"e8e82873-b7d1-46ff-8e3e-af4067a779ca","added_by":"auto","created_at":"2025-05-15 10:37:20","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":105275,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in MGD-related clinical parameters before and after the additional IPL treatment between the responsive and refractory groups. IPL=intense pulsed light; BUT=break-up time; SICCA Sjögren’s International Clinical Collaborative Alliance; MMP-9=metalloproteinase-9. *P\u0026lt;0.05\u003c/p\u003e","description":"","filename":"Figure1250409.png","url":"https://assets-eu.researchsquare.com/files/rs-6413260/v1/9655b521ed30351df9f8c780.png"},{"id":85649679,"identity":"90d4320a-8c6d-43b3-8039-896fabd8427d","added_by":"auto","created_at":"2025-06-30 09:02:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":817939,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6413260/v1/74a3a969-61ef-4d81-aba9-ac34de701a88.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical characteristics of patients with refractory meibomian gland dysfunction unresponsive to intense pulsed light treatment","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDry eye disease (DED) is classified into two main subtypes: aqueous-deficient dry eye and evaporative dry eye, both of which involve pathology affecting the meibomian glands, lacrimal glands, eyelids, tear film, and ocular surface cells [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The most common cause of evaporative dry eye is meibomian gland dysfunction (MGD) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. MGD is characterized by significant changes in the consistency and quantity of meibum secretion, leading to eyelid inflammation and subsequent ocular surface dysfunction. Insufficient lipid secretion from the meibomian glands compromises tear film stability, resulting in dry eye symptoms, despite normal tear secretion [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. While most cases of MGD are idiopathic, some may be secondary to dermatological conditions such as acne rosacea and Demodex infestation [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eVarious therapies have been used to treat MGD, including warm compresses, lid hygiene practices, dietary supplementation with omega-3 fatty acids, forced meibum expression, topical steroids, topical and oral antibiotics, topical cyclosporine, preservative-free artificial tears, lipid-containing eyedrops [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], topical diquafosol [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], and automated thermal pulsation [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Intense pulsed light (IPL) therapy has also been used to improve meibum secretion and quality, stabilize the tear film, and reduce eyelid inflammation [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In 2002, Dr. Toyos was the first to describe the positive effects of IPL on eyelids, noting that patients treated for facial rosacea experienced an improvement in the signs and symptoms of MGD following IPL treatment [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Although the exact mechanisms underlying IPL\u0026rsquo;s beneficial effects are complex and not fully understood, IPL is thought to reduce telangiectasia, eradicate Demodex mites, liquefy meibum through thermal effects, modulate the secretion of anti-inflammatory cytokines, and suppress matrix metalloproteinases [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Several studies have since reported the safety of IPL, with no adverse effects when proper eye protection is used. The use of IPL for treating MGD and dry eye has become increasingly common among ophthalmologists [\u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite the range of available treatments, some patients with MGD are refractory to therapy and do not achieve long-term symptom relief [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Wan et al. suggested that meibomian gland dropout may cause refractory MGD and analyzed potential factors affecting long-term meibomian gland recovery. According to their study, age, changes in corneal fluorescein staining, and the meibomian gland area ratio at baseline, were potential predictors of meibomian gland recovery [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, there remain patients who do not respond to IPL treatment. Therefore, the present study aimed to analyze the risk factors for the non-responsiveness to additional IPL therapy in patients previously treated with IPL for MGD.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population and design\u003c/h2\u003e \u003cp\u003eA total of 66 eyes from 66 patients were retrospectively enrolled in this study. Among both eyes, the eye at a more severe MGD stage was selected. If both eyes showed the same MGD stage, one of the eyes was randomly selected. Patients with moderate-to-severe MGD who had previously undergone four IPL sessions using a 590 nm filter at another clinic received an additional four IPL treatments at the Department of Ophthalmology at Asan Medical Center. This study was reviewed and approved by the Institutional Review Board of the Asan Medical Center and University of Ulsan College of Medicine (IRB No. 2024\u0026thinsp;\u0026minus;\u0026thinsp;0595) and conducted in accordance with the tenets of the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDiagnosis and inclusion criteria\u003c/h3\u003e\n\u003cp\u003eModerate-to-severe MGD was diagnosed based on the definition established by the international workshop on MGD, which is characterized by moderately or severely altered meibum expressiveness and secretion quality, along with moderate or greater peripheral and central corneal staining [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Individuals over 18 years of age with moderate-to-severe MGD, whose condition was unresponsive to four IPL sessions at other clinics, were included [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Patients were compared subjectively before and after IPL treatment at Asan Medical Center, and unresponsiveness was defined as no improvement or even worsening following IPL treatment. Before receiving four additional IPL treatments with a vascular filter, patients provided a subjective assessment of their post-IPL MGD status, which was scored on a scale from 0 to 4: 0\u0026thinsp;=\u0026thinsp;moderate improvement; 1\u0026thinsp;=\u0026thinsp;mild improvement; 2\u0026thinsp;=\u0026thinsp;no change; and 3\u0026thinsp;=\u0026thinsp;aggravated MGD. Patients scoring 0 or 1 were classified as Group 1 (responsive to additional IPL therapy), and those scoring 2 or 3 were classified as Group 2 (non-responsive or refractory to additional IPL therapy). Based on these criteria, a subgroup analysis was performed to identify the signs and symptoms of refractory MGD in Group 2 and to analyze the risk factors contributing to refractory MGD.\u003c/p\u003e \u003cp\u003ePatients enrolled in this study were those who had previously received IPL treatment at other clinics and had not improved even with various treatments, including steroid and cyclosporine eyedrops, warm compresses, and eyelid scrubs. This study assumed that the impact of these treatments on the pre-additional IPL status of the refractory MGD group had been minimal. For this reason, this study focused on investigating the effect of additional IPL treatment with vascular filters in patients previously treated with IPL and other treatments for moderate and severe MGD and analyzing risk factors for non-responsiveness to additional IPL therapy. All enrolled patients had Fitzpatrick skin types I\u0026ndash;IV.\u003c/p\u003e\n\u003ch3\u003eExclusion criteria and eye selection\u003c/h3\u003e\n\u003cp\u003eExclusion criteria included a diagnosis of Sj\u0026ouml;gren's syndrome, a history of intraocular or ocular surgery within the past six months, glaucoma treated with topical medications, eyelid malposition, ocular infection, non-dry eye ocular inflammation, ocular allergy, other autoimmune diseases, contact lens use during the study period, and pregnancy or lactation.\u003c/p\u003e \u003cp\u003eAll patients underwent four IPL sessions with a vascular filter at two-week intervals, followed by a one-month post-treatment evaluation. This procedure was performed on all four eyelids by a single trained physician (HL). Ophthalmic tests, conducted before and after the additional IPL treatments, included visual acuity, intraocular pressure, tear break-up time (TBUT) using fluorescein, corneal and conjunctival staining scores (Sj\u0026ouml;gren\u0026rsquo;s International Clinical Collaborative Alliance [SICCA]) staining score and Oxford staining score), Schirmer\u0026rsquo;s test I without topical anesthesia, and measurement of metalloproteinase-9 (MMP-9) levels. Slit-lamp microscopy was used to evaluate the lid margin (including lid wiper epitheliopathy and vascularity) and meibomian glands. Visual acuity was measured in decimal format, and a single ophthalmologist assessed the TBUT and corneal and conjunctival staining scores via slit-lamp examination.\u003c/p\u003e\n\u003ch3\u003eEvaluation of meibum and lid margin parameters\u003c/h3\u003e\n\u003cp\u003eMeibum quality, consistency, and telangiectasia of the eyelids were evaluated using methods previously described [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Lid margin telangiectasia was assessed via slit-lamp microscopy and scored from 0 to 3 as follows: 0\u0026thinsp;=\u0026thinsp;no or slight redness in the lid margin conjunctiva with no telangiectasia crossing the meibomian gland orifices; 1\u0026thinsp;=\u0026thinsp;redness in the lid margin conjunctiva without telangiectasia crossing the meibomian gland orifices; 2\u0026thinsp;=\u0026thinsp;redness in the lid margin conjunctiva with telangiectasia crossing the meibomian gland orifices over less than half of the lid\u0026rsquo;s length; and 3\u0026thinsp;=\u0026thinsp;redness in the lid margin conjunctiva with telangiectasia crossing the meibomian gland orifices over half or more of the lid\u0026rsquo;s length. Meibum grades were assessed based on the appearance of meibum when digital pressure was applied to the upper tarsus: grade 0\u0026thinsp;=\u0026thinsp;clear meibum easily expressed; grade 1\u0026thinsp;=\u0026thinsp;cloudy meibum expressed with mild pressure; grade 2\u0026thinsp;=\u0026thinsp;cloudy meibum expressed with more than moderate pressure; and grade 3\u0026thinsp;=\u0026thinsp;no meibum expression, even with firm pressure. To evaluate meibum consistency, both the upper and lower eyelids were evaluated using meibomian gland expressor forceps. Meibum consistency was graded on a scale from 1 to 3: 1\u0026thinsp;=\u0026thinsp;oily; 2\u0026thinsp;=\u0026thinsp;creamy; and 3\u0026thinsp;=\u0026thinsp;toothpaste-like [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eMMP-9 measurement\u003c/h3\u003e\n\u003cp\u003eMMP-9 levels were measured using the InflammaDry immunoassay (Rapid Pathogen Screening, Inc., Sarasota, FL, USA). The presence of both a blue line in the control zone and a red line in the result zone indicated a positive test result (MMP-9\u0026thinsp;\u0026ge;\u0026thinsp;40 ng/mL). Signal intensity of the red line, indicating higher MMP-9 concentration, was graded on a scale from 0 to 4: 0\u0026thinsp;=\u0026thinsp;none; 1\u0026thinsp;=\u0026thinsp;trace; 2\u0026thinsp;=\u0026thinsp;weak positive; 3\u0026thinsp;=\u0026thinsp;positive; and 4\u0026thinsp;=\u0026thinsp;strong positive, as described in a previous study [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eIPL treatment protocol\u003c/h2\u003e \u003cp\u003eFor IPL treatment, the ophthalmologist used the M22 Optima IPL device (Lumenis, Yokneam, Israel) with a specific pulse setting (fluence delivering in a 6-5-4 J/cm\u003csup\u003e2\u003c/sup\u003e decrement pattern) [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. For the lower eyelid treatment, local anesthesia and ultrasonic gel were applied to the treatment area. Both eyelids were closed and covered with metal spatulas. After exposing the lower eyelid margin, the IPL probe was used to pull the lower eyelid slightly downward to increase the surface area of contact between the IPL probe and the lower eyelid margin to maximize the treatment effect. Patients received twelve light pulses (with slightly overlapping areas of application) from the left, preauricular area, to the right, preauricular area for two times (total: 24 light pulses). For the upper eyelid treatment, a metal spatula was inserted gently into the space between the bulbar conjunctiva and the upper eyelid. Patients then received two to three light pulses after tenting the metal spatula upward to protect the ocular surface. Gentle meibomian gland expression was performed on all four eyelids using expressor forceps immediately after IPL treatment. Throughout the follow-up period, patients were advised to use loteprednol 0.5% (Lotemax; Bausch \u0026amp; Lomb, Tampa, FL, USA) four times daily, cyclosporine 0.1% (Ikervis; cationic emulsion at 0.1% CsA; Santen) once daily, carbomer gel (Liposic; 2 mg/g carbomer eye gel; Bausch\u0026thinsp;+\u0026thinsp;Lomb), and 0.15% sodium hyaluronate (New Hyaluni; Taejoon, Seoul, Korea). Additionally, patients were instructed to use warm compresses and perform lid scrubs.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed using SPSS statistical software for Windows (version 25.0; SPSS Inc., Chicago, IL, USA). The Shapiro\u0026ndash;Wilk test was employed to analyze the normality of the data. The Mann-Whitney U test was used to compare clinical parameters between Group 1 (responsive to additional IPL therapy) and Group 2 (non-responsive to additional IPL therapy). Logistic regression analysis was performed to obtain odds ratios when more than one explanatory variable was present, aiming to identify factors associated with refractory MGD. Multicollinearity was controlled to analyze the effects of each independent variable. A P-value of \u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Result","content":"\u003cp\u003eAmong the 66 eyes from 66 patients, Group 1 comprised 32 eyes and Group 2 comprised 34 eyes. The mean age of Group 1 was 66.2\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8 years, while the mean age of Group 2 was 65.1\u0026thinsp;\u0026plusmn;\u0026thinsp;9.1 years. The baseline clinical parameters for both groups are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. No significant differences were observed between the two groups at baseline, except for the Oxford staining score. The Oxford staining scores were 2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1 in Group 1 and 3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4 in Group 2, with the responsive MGD group showing significantly lower staining scores (P\u0026thinsp;=\u0026thinsp;0.020).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline demographics and clinical parameters of the responsive group and refractory group before additional IPL treatment\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGroup 1\u003c/p\u003e \u003cp\u003e(Responsive to addtional IPL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eGroup 2\u003c/p\u003e \u003cp\u003e(Refractory to additional IPL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of eyes / Patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e32/32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e34/34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (Men : Women)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e3:5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e4:13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.167\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e66.2\u0026thinsp;\u0026plusmn;\u0026thinsp;10.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e65.1\u0026thinsp;\u0026plusmn;\u0026thinsp;9.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.664\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTBUT (sec)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.626\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOxford score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSICCA score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e6.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e7.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.092\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMeibum quality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.143, \u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMeibum consistency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.386, 0.105\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLid margin telangiectasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.079, 0.188\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeibomian gland grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.056\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTear MMP-9 level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.155\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eIPL\u0026thinsp;=\u0026thinsp;intense pulsed light; TBUT\u0026thinsp;=\u0026thinsp;tear break-up time; SICCA\u0026thinsp;=\u0026thinsp;Sj\u0026ouml;gren\u0026rsquo;s International Clinical Collaborative Alliance; MMP-9\u0026thinsp;=\u0026thinsp;metalloproteinase-9; UL\u0026thinsp;=\u0026thinsp;upper lid; LL\u0026thinsp;=\u0026thinsp;lower lid.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e*Statistical analysis was performed with a Mann\u0026ndash;Whitney U test.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAfter IPL treatment, the mean TBUT was 3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1 seconds in Group 1 and 3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2 seconds in Group 2, with no significant difference between the two groups (P\u0026thinsp;=\u0026thinsp;0.199). However, significant differences were observed in the Oxford staining scores (Group 1\u0026thinsp;=\u0026thinsp;1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3 vs. Group 2\u0026thinsp;=\u0026thinsp;2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and SICCA staining scores (Group 1\u0026thinsp;=\u0026thinsp;2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9 vs. Group 2\u0026thinsp;=\u0026thinsp;4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The quality of meibum in both the upper and lower lids showed significant differences between the two groups (upper lid: Group 1\u0026thinsp;=\u0026thinsp;1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 vs. Group 2\u0026thinsp;=\u0026thinsp;2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; lower lid: Group 1\u0026thinsp;=\u0026thinsp;1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 vs. Group 2\u0026thinsp;=\u0026thinsp;2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Similarly, significant differences in meibum consistency were noted for both the upper and lower lids (upper lid: Group 1\u0026thinsp;=\u0026thinsp;1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4 vs. Group 2\u0026thinsp;=\u0026thinsp;2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001; lower lid: Group 1\u0026thinsp;=\u0026thinsp;1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6 vs. Group 2\u0026thinsp;=\u0026thinsp;2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No significant differences were found in lid margin telangiectasia between the two groups. Meibomian gland grade was 1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 in Group 1 and 2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5 in Group 2 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). MMP-9 levels were 1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4 in Group 1 and 2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 in Group 2 (P\u0026thinsp;=\u0026thinsp;0.202) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Changes in the Oxford staining score (P\u0026thinsp;=\u0026thinsp;0.032), SICCA staining score (P\u0026thinsp;=\u0026thinsp;0.003), meibum quality (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), consistency (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and meibomian gland grade (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were significantly greater in Group 1 than in Group 2 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). According to the logistic regression analysis, the Oxford staining score and MMP-9 results were identified as risk factors that had a statistically significant effect on refractory MGD status (P\u0026thinsp;=\u0026thinsp;0.029, odds ratio: 12.69 for Oxford staining score; P\u0026thinsp;=\u0026thinsp;0.021, odds ratio: 3.88 for MMP-9) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of MGD-related clinical parameters and subjective symptoms between groups at one month after additional IPL treatment\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGroup 1\u003c/p\u003e \u003cp\u003e(Responsive to addtional IPL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eGroup 2\u003c/p\u003e \u003cp\u003e(Refractory to additional IPL)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value*\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTBUT (sec)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e3.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e3.0\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.199\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOxford score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSICCA score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMeibum quality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001, \u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMeibum consistency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001, \u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLid margin telangiectasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eUL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eLL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.055, 0.189\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeibomian gland grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTear MMP-9 level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.202\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of IPL treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e9.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eMGD\u0026thinsp;=\u0026thinsp;meibomian gland dysfunction; IPL\u0026thinsp;=\u0026thinsp;intense pulsed light; TBUT\u0026thinsp;=\u0026thinsp;tear break-up time; SICCA\u0026thinsp;=\u0026thinsp;Sj\u0026ouml;gren\u0026rsquo;s International Clinical Collaborative Alliance; MMP-9\u0026thinsp;=\u0026thinsp;metalloproteinase-9; UL\u0026thinsp;=\u0026thinsp;upper lid; LL\u0026thinsp;=\u0026thinsp;lower lid.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e*Statistical analysis was performed with a Mann\u0026ndash;Whitney U test.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLogistic regression for MGD-related clinical parameters and subjective symptoms after one month of additional IPL treatment\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOdds Ratio\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e95% Confidence interval\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eCoefficient β\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLowest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHighest\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.503\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.944\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.57\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTBUT (sec)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.95\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.189\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOxford score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e125.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSICCA score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.060\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-1.98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMeibum quality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMeibum consistency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e149.36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.426\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.732\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eLid margin telangiectasia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.790\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.18\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.304\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-1.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.69\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMeibomian gland grade\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.06\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.942\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTear MMP-9 level\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eMGD\u0026thinsp;=\u0026thinsp;meibomian gland dysfunction; IPL\u0026thinsp;=\u0026thinsp;intense pulsed light; TBUT\u0026thinsp;=\u0026thinsp;tear break-up time; SICCA\u0026thinsp;=\u0026thinsp;Sj\u0026ouml;gren\u0026rsquo;s International Clinical Collaborative Alliance; MMP-9\u0026thinsp;=\u0026thinsp;metalloproteinase-9; UL\u0026thinsp;=\u0026thinsp;upper lid; LL\u0026thinsp;=\u0026thinsp;lower lid; B\u0026thinsp;=\u0026thinsp;Partial regression coefficient (B); β\u0026thinsp;=\u0026thinsp;Standardized partial regression coefficient (β).\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study investigated the risk factors contributing to non-response to additional IPL therapy with a vascular filter in patients with moderate-to-severe MGD, who had previously undergone IPL treatment using a 590 nm filter and had not improved even with various treatments including steroid and cyclosporine eyedrops, warm compresses, and eyelid scrubs. Improvements in the Oxford staining scores, SICCA staining scores, meibum quality, consistency, and meibomian gland grade were significantly greater in the responsive group. Furthermore, patients with higher baseline corneal and conjunctival staining scores (Oxford staining score) and elevated tear MMP-9 levels before the additional IPL treatment were more likely to exhibit a refractory type MGD, demonstrating less responsiveness to further IPL therapy.\u003c/p\u003e \u003cp\u003eVarious treatment methods for MGD have been introduced in numerous studies, each demonstrating varying degrees of effectiveness. Lam et al. reported that self-applied eyelid warming, thermal pulsation, IPL, meibomian gland probing, antibiotics, Manuka honey, and lipid-containing or perfluorohexyloctane eye drops exhibited significant clinical efficacy [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Notably, IPL therapy has been highlighted as a highly effective option. Given that increased meibum viscosity is a hallmark of MGD, heat-based treatments, including warm compression, thermal pulsation, and IPL, are particularly effective at melting thickened meibum and are often superior to other treatment modalities for improving MGD [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite identical IPL treatment settings, responses varied among patients, prompting this study to investigate the characteristics of those with refractory MGD who did not respond well to additional IPL treatments. Previous studies have identified patient populations that respond well to IPL treatment. Tang et al. reported significant improvements in various parameters, including the Ocular Surface Disease Index (OSDI), TBUT, corneal fluorescein staining score, meibomian glands yielding secretion score, meibomian glands yielding clear secretion, and meibomian glands yielding liquid secretion after three cycles of IPL/meibomian gland expression (MGX) treatments [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Characteristics associated with better outcomes after IPL treatment included younger age (P\u0026thinsp;=\u0026thinsp;0.012), longer TBUT (P\u0026thinsp;=\u0026thinsp;0.010), better meiboscore (P\u0026thinsp;=\u0026thinsp;0.012), and less meibomian gland loss (P\u0026thinsp;=\u0026thinsp;0.008) before IPL/MGX [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Similarly, in a study by Chen et al. involving 48 patients, univariate analysis identified factors affecting IPL effectiveness. Patients aged 18\u0026ndash;39 years, with moderate MGD, higher baseline Schirmer test results, and higher baseline OSDI scores, exhibited a higher effective rate for IPL treatment. MGD severity was strongly associated with IPL effectiveness; patients with moderate MGD had an odds ratio of 5.493 compared to those with severe MGD (P\u0026thinsp;=\u0026thinsp;0.003) [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMonitoring the therapeutic effects of IPL is performed using TBUT, the corneal staining score, lid margin telangiectasia, and tear MMP-9 expression. Previous studies have demonstrated that MMP-9 can serve as a predictor for the effectiveness and treatment response of IPL [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. The MMP-9 test is a convenient method for objectively evaluating ocular surface inflammation during outpatient visits. Elevated MMP-9 levels have been also detected in DED patients. Chotikanovich et al. measured tear MMP-9 activity in 46 patients newly diagnosed with DED, and 19 asymptomatic controls [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. They found that DED patients had a significantly increased MMP-9 activity of 35.57\u0026thinsp;\u0026plusmn;\u0026thinsp;17.04 ng/mL (P\u0026thinsp;\u0026lt;\u0026thinsp;0.008) compared to controls, whose levels averaged 8.39\u0026thinsp;\u0026plusmn;\u0026thinsp;4.70 ng/mL. Normal MMP-9 levels in human tears ranged from 3.0 to 41.0 ng/ml, with 90% of individuals having levels below 30 ng/ml. Patients in the highest severity category exhibited a mean MMP-9 activity of 381.24\u0026thinsp;\u0026plusmn;\u0026thinsp;42.83 ng/mL (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), which was significantly elevated compared to controls and all lower severity groups [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Previous studies have confirmed that MMP-9 levels and positivity decreased after IPL treatment compared to baseline [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. The present study confirmed higher tear MMP-9 levels before IPL treatment as a risk factor for patients with refractory MGD who did not respond to the therapy [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn this study, vascular filters were used in the IPL treatment. IPL treatment with a vascular filter decreases ocular surface inflammation, as indicated by decreased tear MMP-9 levels, by targeting and disrupting lid margin telangiectasia. Additionally, light wavelengths between 600 and 800 nm, which are mainly absorbed by melanin, can cause pain. Hence, the vascular filter reduces pain by focusing light absorption on the vascular structures and avoiding wavelengths in the 600\u0026ndash;800 nm range at the eyelid margin [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePatients were advised to use loteprednol 0.5%, and cyclosporine 0.1% throughout the IPL treatment follow-up period, along with warm compresses and lid scrubs. It is well-established that anti-inflammatory corticosteroids, tetracycline derivatives [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e], and cyclosporine [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] can effectively reduce tear fluid MMP-9 levels. Therefore, since patients with poor responses to IPL therapy exhibited high MMP-9 levels despite the application of anti-inflammatory eye drops, combining various treatment modalities\u0026mdash;including more potent anti-inflammatory agents that can lower tear MMP-9 levels\u0026mdash;may be beneficial for the treatment of MGD by reducing ocular surface inflammation.\u003c/p\u003e \u003cp\u003eRegarding the regression analysis, the inconsistency in results may be due to differences in the two analytical methods, as the parameter that was not significant before and after treatment analyzed by the Mann-Whitney U test was significant in the regression analysis. Regression analysis is used to model the relationship between dependent and independent variables. Regression considers the combined impact of variables and models in both linear and non-linear relationships. If other important variables influence the dependent variable, the Mann-Whitney U test may miss this impact, whereas regression can include these variables in the model and provide a more accurate picture [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThis study has some limitations, including a small sample size, a retrospective design, and selection bias. As this is a retrospective study, the sample size was not adequately considered when analyzing medical records. Therefore, future studies should calculate the required sample size in advance to ensure statistical significance and analyze a larger dataset to enhance the robustness of the findings. The way the study group was constructed may also have introduced selection bias, as group allocation was based on patient-reported improvements in MGD symptoms after additional IPL treatment with a vascular filter. This study did not have access to pre- or post-IPL treatment data from previous IPL sessions at other clinics. Therefore, it is possible that patients who had achieved significant improvements in MGD signs from previous IPL treatments were included in the study. Furthermore, the study was retrospective and limited by a lack of information on when each patient had been last treated with IPL and which protocol they were treated with at other clinics. Future research with larger patient populations and objective criteria for defining refractory MGD is necessary to identify factors influencing responsiveness to IPL treatment. In addition, the lack of a meibomian gland atrophy assessment may also be a limitation of this study. Meibomian gland dropout may cause refractory MGD, and this factor cannot be ruled out. MG dropout, using the Lipiview, needs to be evaluated in future studies.\u003c/p\u003e \u003cp\u003eIn conclusion, patients with refractory MGD who did not respond to additional IPL treatment were characterized by poor ocular staining scores before treatment. The identified risk factors for these refractory MGD cases included elevated tear MMP-9 levels and higher Oxford staining scores. Prior to this study, patients who had not responded well to IPL treatment had been clinically recognized, but their clinical characteristics had not been known. Therefore, there were no indications as to whether further IPL treatment should be continued. This question led us to conduct the current study, and the results of this study are significant because they provide a clinical characterization of the pre-and post-treatment characteristics of patients who do not respond to IPL treatment, which will be useful in planning future IPL treatments.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability statements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are not publicly available due to patient privacy concerns and restrictions imposed by the Institutional Review Board. Participants did not provide consent for public sharing of their clinical data. However, the data may be available from the corresponding author on reasonable request and with appropriate ethical approvals.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent statements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDue to the retrospective nature of the study, this study does not need to obtain informed consent. This study was reviewed and approved by the Institutional Review Board of the Asan Medical Center and University of Ulsan College of Medicine (IRB No. 2024-0595) and conducted in accordance with the tenets of the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution statements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConception and design of study: Yoo Young Jeon, Hun Lee; acquisition of data: Nahyun Park, Yea Eun Lee, Chung Min Lee, Jeewon Han, Changmin Kim, Kyu Sang Eah, Hayoung Lee; analysis of data: Nahyun Park, Sanghyu Nam, Ho Seok Chung, Jae Yong Kim; drafting the manuscript: Yoo Young Jeon, Nahyun Park, Hun Lee; revising the manuscript critically for important intellectual content: Yoo Young Jeon, Hun Lee; approval of the version of the manuscript to be published: Yoo Young Jeon, Hun Lee\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eA.J. Bron, C.S. de Paiva, S.K. Chauhan, S. Bonini, E.E. Gabison, S. 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Abaye, A Review of the Logistic Regression Model with Emphasis on Medical Research, Journal of Data Analysis and Information Processing 07 (2019) 190-207.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Intense pulsed light, Matrix metalloproteinase-9, Refractory meibomian gland dysfunction","lastPublishedDoi":"10.21203/rs.3.rs-6413260/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6413260/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e To investigate the clinical characteristics of patients with meibomian gland dysfunction (MGD) who are unresponsive to additional intense pulsed light (IPL) therapy and to identify the risk factors for poor treatment response.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Patients with moderate-to-severe MGD who had previously undergone four sessions of IPL treatment with a 590 nm filter at another clinic, received an additional four sessions of IPL therapy. A total of 66 eyes were analyzed. Patients' subjective assessments before and after the additional IPL treatments were scored on a scale from 0 to 4, where 0=moderate improvement, 1=mild improvement, 2=no change, and 3=aggravated MGD. Patients who scored 0 or 1 were classified as Group 1 (Responsive group), while those who scored 2 or 3 were classified as Group 2 (Refractory group).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e After the additional IPL treatment, significant differences were observed between the groups in the Oxford and Sjögren’s International Clinical Collaborative Alliance (SICCA) staining scores (all P\u0026lt;0.001). Significant differences were found between the groups with regard to both upper and lower lid meibum quality and meibum consistency (all P\u0026lt;0.001). Group 2 had a significantly higher meibomian gland grade compared to Group 1 (P\u0026lt;0.001). Changes in the Oxford staining score (P=0.032), SICCA staining score (P=0.003), meibum quality (P\u0026lt;0.001), meibum consistency (P\u0026lt;0.001), and meibomian gland grade (P\u0026lt;0.001), before and after the additional treatment, were significantly greater in Group 1 than in Group 2. Logistic regression analysis identified higher Oxford staining scores (P=0.029; odds ratio 12.69) and elevated metalloproteinase-9 (MMP-9) levels (P=0.021; odds ratio 3.88) as significant risk factors for refractory MGD.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Patients with refractory MGD, who did not respond to additional IPL treatment, exhibited poor ocular staining scores before treatment. High tear MMP-9 levels and elevated Oxford staining scores were identified as significant risk factors for poor treatment outcomes.\u003c/p\u003e","manuscriptTitle":"Clinical characteristics of patients with refractory meibomian gland dysfunction unresponsive to intense pulsed light treatment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-15 10:29:15","doi":"10.21203/rs.3.rs-6413260/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1c95b3df-6503-4c64-b4f7-96b2cff1db4d","owner":[],"postedDate":"May 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":48483391,"name":"Health sciences/Diseases/Eye diseases/Corneal diseases"},{"id":48483392,"name":"Health sciences/Diseases/Eye diseases/Eyelid diseases"}],"tags":[],"updatedAt":"2025-06-30T08:54:19+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-15 10:29:15","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6413260","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6413260","identity":"rs-6413260","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}