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Abstract Objective The cross-sectional study was designed to evaluate the association of ocular surface inflammation with systemic conditions in patients with systemic lupus erythematosus (SLE). Methods The study enrolled 30 SLE patients and 30 controls. Ocular symptoms were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. Tear samples from all participants were collected for tear multi-cytokine and chemokine concentration analysis. All participants were assessed for dry eye disease (DED), including Schirmer I test, tear break-up time (TBUT), corneal fluorescein staining (CFS), meibomian gland secretion (MGS), lid-parallel conjunctival folds (LIPCOF), corneal clarity, and symblepharon. Besides, all participants were also examined for conjunctival impression cytology to measure the density of conjunctival goblet cells (CGCs). The peripheral blood indicators from SLE patients were also collected to measure the SLE-associated autoantibody specificities and systemic inflammatory indicators. Pearson and Spearman’s analysis were uesd to examine the correlation between tear cytokines, CGCs, DED-related indicators, and systemic conditions. Results The two groups were matched for age and gender in this study. 36.67% of eyes (11 in 30) of SLE patients and 13.33% of eyes (4 in 30) of controls were diagnosed with DED. OSDI scores, abnormal TBUT percentages, CFS percentages, and DED grading were all higher in SLE patients than in control group, while density of CGCs was lower. There were no significant differences in Schirmer I test, MGS, LIPCOF, corneal clarity, and symblepharon between SLE patients and controls. The levels of tear chemokine (C-X-C motif) ligand 11 (CXCL11) and cytokine interleukin-7 (IL-7) in patients with SLE were significantly higher than those in control group. Moreover, among SLE patients, the severity of DED and the level of tear chemokine CXCL11 were significantly positively correlated with SLE-associated autoantibody specificities. Conclusion Dry eye and tear cytokines and chemokines-mediated ocular surface inflammation persist in SLE patients and are associated with systemic conditions. Therefore, it is necessary for patients with SLE to combine systemic and ocular assessments.

Objective: The cross-sectional study was designed to evaluate the association of ocular surface inflammation with systemic conditions in patients with systemic lupus erythematosus (SLE). Methods: The study enrolled 30 SLE patients and 30 controls. Ocular symptoms were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. Tear samples from all participants were collected for tear multi-cytokine and chemokine concentration analysis. All participants were assessed for dry eye disease (DED), including Schirmer I test, tear break-up time (TBUT), corneal fluorescein staining (CFS), meibomian gland secretion (MGS), lid-parallel conjunctival folds (LIPCOF), corneal clarity, and symblepharon. Besides, all participants were also examined for conjunctival impression cytology to measure the density of conjunctival goblet cells (CGCs). The peripheral blood indicators from SLE patients were also collected to measure the SLE-associated autoantibody specificities and systemic inflammatory indicators. Pearson and Spearman's analysis were uesd to examine the correlation between tear cytokines, CGCs, DED-related indicators, and systemic conditions. Results: The two groups were matched for age and gender in this study. 36.67% of eyes (11 in 30) of SLE patients and 13.33% of eyes (4 in 30) of controls were diagnosed with DED. OSDI scores, abnormal TBUT percentages, CFS percentages, and DED grading were all higher in SLE patients than in control group, while density of CGCs was lower. There were no significant differences in Schirmer I test, MGS, LIPCOF, corneal clarity, and symblepharon between SLE patients and controls. The levels of tear chemokine (C-X-C motif) ligand 11 (CXCL11) and cytokine interleukin-7 (IL-7) in patients with SLE were significantly higher than those in control group. Moreover, among SLE patients, the severity of DED and the level of tear chemokine CXCL11 were significantly positively correlated with SLE-associated autoantibody specificities. Conclusion: Dry eye and tear cytokines and chemokines-mediated ocular surface inflammation persist in SLE patients and are associated with systemic conditions. Therefore, it is necessary for patients with SLE to combine systemic and ocular assessments. Key points: SLE patients have higher OSDI scores, abnormal TBUT percentages, CFS percentages, DED grading, and lower density of CGCs compared to controls. SLE patients have higher levels of tear chemokine CXCL11 and cytokine IL-7 compared to controls. Among SLE patients, the severity of DED and the level of tear chemokine CXCL11 are significantly positively correlated with SLE-associated autoantibody specificities. [ABSTRACT FROM AUTHOR]

This review aimed to evidence the predisposing conditions for Salzmann nodular degeneration (SND), where particular attention was paid to its association with ocular and systemic diseases. SND is a rare disease characterized by bluish-white nodules located in the mid-periphery of the cornea, which are otherwise completely clear. SND has been found in association with different systemic and ocular diseases, and it may have unilateral or bilateral presentation. Initial forms are only diagnosed occasionally as they are asymptomatic, whereas, in advanced disease, the visual acuity might be seriously impaired. Although SND is well described, its exact etiopathology is currently still unknown and is frequently misdiagnosed. It is associated with ocular surface inflammatory conditions and previous corneal surgery, and it has been described in different systemic diseases. Diagnosis is clinically based with slit lamp examinations, and instrumental assessments with corneal topography permit one to observe the alterations of the corneal profile, whereas anterior segment–optical coherence tomography (AS-OCT) is used to investigate the stromal depth of the nodules. Therapy might be conservative with the objective of improving the ocular surface homeostasis and surgical outcomes, where the aim is to restore the corneal regularity and visual acuity. Ophthalmologists should pay particular attention when detecting nodules in patients with ocular and non-ocular inflammatory diseases to guarantee the patient a timely diagnosis and a better therapeutic outcome. Additionally, collaboration between specialists who deal with treating patients suffering from disorders potentially associated with SND is recommended. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Traditional treatment options are often insufficient in treating severe dry eyes caused by systemic diseases. This case demonstrates that ocular immersion hydrotherapy significantly alleviated symptoms and ocular surface inflammation in ocular graft‐versus‐host disease. Based on these findings, we propose it as a promising option for managing severe dry eye disease. This case report investigates the efficacy of ocular immersion hydrotherapy (OIH) in treating severe dry eye secondary to ocular graft‐versus‐host disease (oGVHD). A 35‐year‐old female with a history of acute myeloid leukemia‐M2 and subsequent hematopoietic stem cell transplantation (HSCT) developed high‐intensity oGVHD unresponsive to conventional treatments, including topical corticosteroids and lubricants. We introduced OIH, utilizing sterilized swimming goggles filled with intraocular irrigating solutions, providing a moist microenvironment for the ocular surface. Symptoms were significantly relieved after treatment. Corneal filaments and epithelial defects were significantly reduced, and in vivo confocal microscopy (IVCM) demonstrated resolution of inflammation and reappearance of corneal nerves. This case indicates that OIH could be a promising therapeutic approach for severe dry eye conditions arising from oGVHD, particularly for patients refractory to traditional treatments. Further studies are warranted to elucidate the long‐term benefits and mechanisms of OIH in oGVHD management. [ABSTRACT FROM AUTHOR]

Sundas Ejaz Maqsood,1,2 Samer Hamada,1 Damian Lake,1 Artemis Matsou,1 Mohamed Elalfy1– 3 1Corneao- Plastic Unit, Queen Victoria Hospital, East Grinsted, West Sussex, UK; 2Cornea Service, Ophthalmology, Maidstone and Tunbridge Wells NHS Trust, Kent, UK; 3Cornea Department, Research Institute of Ophthalmology, Giza, EgyptCorrespondence: Mohamed Elalfy, Ophthalmology Department, Maidstone and Tunbridge Wells NHS Trust, Hermitage Lane, Maidstone, Kent, ME16 9QQ, UK, Email Mohamed.elalfy@nhs.netPurpose: To report the outcomes of using a sutureless human amniotic membrane dehydrated matrix (HAMDM) in the management of a range of ocular surface conditions utilizing a digital ocular surface disease assessment tool.Methods: Two UK NHS Trusts — Queen Victoria Hospital Foundation Trust (East Grinstead and Maidstone) and Tunbridge Wells Trust (Kent) — prospectively treated patients with ocular surface disease with sutureless HAMDM. The patient cohort was assessed for resolution of epithelial defects, ocular surface inflammation, and best-corrected visual acuity pre- and posttreatment. Measurements of ocular surface inflammation and epithelial defect size were assessed using AOS digital imaging software, a validated tool for objective grading of bulbar conjunctival redness and measurement of corneal epithelial defects.Results: A total of 47 applications of sutureless HAMDM on 46 eyes of 46 patients (25 male, 21 female, age 9– 94 years) were assessed across various etiologies for an average of 24.0± 14.1 days. Patients with limbal stem-cell deficiency (n=17), persistent epithelial defects (n=16), neurotrophic corneal disease (n=7), filamentary keratitis (n=2), corneal erosion (n=1), corneal thinning (n=1), ocular surface inflammation (n=1), and traumatic corneal laceration (n=1) were included in the study. Across all patents, 63% of eyes showed complete healing of epithelial defects and 32.6% of eyes showed partial resolution. The average rate of healing (wound closure) was 0.36 mm2 per day across the overall patient cohort, and the rate of healing in cases with complete resolution of epithelial defects was 0.41 mm2 per day. Inflammation across all four quadrants of the ocular surface remained stable. Visual acuity across the patient cohort remained stable (61%) and improved in 26% of patients (0.06± 0.51 logMAR).Conclusion: Sutureless HAMDM application can be accomplished in just a few minutes and effectively treat a range of ocular surface disease in a clinical, nonsurgical setting. The AOS imaging software offered a quantitative methodology for measuring epithelial defect size and inflammation state.Keywords: dehydrated human amniotic membrane, sutureless, ocular surface inflammation, persistent epithelial defect, digital imaging

Purpose: Low doses of systemic doxycycline (LD-SD) inhibit angiogenesis and the expression of matrix metalloproteases, which are determinants of pterygium progression. This study aimed to compare the recurrence rate and visual outcome of pterygium excision in patients undergoing chronic treatment with LD-SD for chronic refractory blepharitis and LD-SD-naive patients. Methods: A retrospective analysis of patients that underwent surgical excision and conjunctival graft apposition was conducted. Patients were divided in a TETRA group (under LD-SD treatment at the moment of surgery) and a control group. The main outcome was the rate of recurrence at 1 year postoperatively. Secondary outcomes were the comparisons of surface regularity, visual quality, and dry-eye symptoms at 6-week, 6-month, and 1-year follow-up in the two groups. Results: The TETRA group showed a significantly lower rate of 1-year recurrence both in primary (p = 0.034) and recurrent (p < 0.001) pterygia. The best corrected visual acuity (BCVA), astigmatic error, corneal total root mean square (RMS), and ocular surface disease index (OSDI) significantly reduced during the follow-up in both groups. The surface asymmetry index and high-order aberrations (HOAs) significantly reduced only in the TETRA group. The final BCVA was significantly higher, while the OSDI score and total RMS and HOAs were significantly lower in the TETRA group compared to the control. Conclusions: Patients under treatment with LD-SD showed a lower rate of recurrence at 1-year follow-up compared to controls. These patients also experienced higher BCVA and surface regularity and less dry-eye symptoms. [ABSTRACT FROM AUTHOR]

AIM: To investigate the effect of modified Chufeng Yisun Decoction on ocular surface inflammation after pterygium surgery.METHODS: A total of 60 patients(60 eyes)with primary pterygium who underwent pterygium surgery were randomly divided into control group and study group, with 30 cases(30 eyes)in each group. In the control group, patients were treated with pranoprofen eye drops, tobramycin dexamethasone eye drops, and deproteinized calf blood extract eye gel after the surgery. In the study group, patients were treated by oral modified Chufeng Yisun Decoction in addition to the treatments in the control group. The changes of ocular irritation symptoms, ocular inflammatory signs, tear interleukin 6(IL-6)levels, and tear ferning test(TFT)of patients in the two groups were assessed.RESULTS: The visual analogue scale(VAS)in patients of both groups was significantly lower at 2d and 1wk after the surgery than that at 1d after the surgery(all P

To examine whether corneal epithelial dendritic cells (CEDC) could serve as an indicator to distinguish obstructive meibomian gland dysfunction (MGD) with or without ocular surface inflammation (OSI). We performed a case-control study on patients with diagnosed obstructive MGD between August 2017 and November 2019. 30 MGD cases and 25 healthy controls were recruited. The classification of MGD patients with and without OSI was based on the tear pro-inflammatory cytokine levels. Compared with the MGD without OSI and the control group, a higher CEDC density was detected in the MGD with OSI subgroup. The presence of >15.6 cells/mm2 CEDC had a sensitivity of 73% and specificity of 75% for the diagnosis of MGD with OSI. OSI is not present in all patients with obstructive MGD. Evaluation of CEDC density in the central cornea may help identify whether MGD is concomitant with OSI. [ABSTRACT FROM AUTHOR]

Abstract Background Filamentary keratitis is an ocular condition that is tricky to handle for the difficulty to find the underlying cause. Here we report a case of filamentary keratitis associated with Demodex infestation which highlights the importance of Demodex mites as an easily-overlooked risk factor. Case presentation A 63-year-old woman had recurrent symptoms of foreign body sensation and sometimes painful feelings in her left eye soon after her surgical correction of ptosis in this eye. She was then diagnosed as conjunctivitis and given antibiotic eye drops. After one week, the patient complained of aggravation of symptoms with small corneal filaments in the left eye under slit-lamp examination. Despite the removal of filaments and addition of topical corticosteroids and bandage contact lenses, the patient’s condition persisted with enlarged filaments and severe ocular discomfort. 3 days later, eyelashes with cylindrical dandruff were noticed and Demodex infestation was confirmed by microscopic examination of these eyelashes at our clinic this time. She was asked to use tea tree oil lid scrub twice daily. After 3 weeks, her filamentary keratitis was resolved with a dramatic improvement in symptoms and signs. And no recurrence of filamentary keratitis was noticed during the one-year follow-up. Conclusions In this case, filamentary keratitis was resolved only with treatment of Demodex infestation while conventional treatment failed. Considering the fact that Demodex infestation is a common but easily overlooked condition, it may be suggestive to take Demodex infestation into account as a risk factor of filamentary keratitis, especially in refractory cases.

Abstract Introduction We aimed to determine the expression of inflammatory cytokines in the tears of patients with unilateral total limbal stem cell deficiency (TLSCD) caused by chemical burns before and after autologous cultivated limbal epithelial stem cell transplantation (CLET). Methods Tear samples were collected from both eyes of 23 patients with unilateral TLSCD and 11 healthy controls, at fixed timepoints before and after CLET. Dissolved molecules were extracted from Schirmer’s strips using a standardised method and analysed on an array plate of ten inflammatory cytokines (V-Plex Proinflammatory Panel 1 Human Kit, MSD). Results IL1β expression was significantly elevated in the TLSCD eye compared with the unaffected eye at baseline (p

Purpose: To investigate the accompanying ocular findings in patients with obstructive sleep apnea syndrome (OSAS) and evaluate the susceptibility to ophthalmological diseases. Materials and methods: In this cross-sectional study, qualifying study subjects were patients who had been diagnosed with severe OSAS (apnea/hypopnea index (AHI > 30/h), n = 31), and control subjects (n = 30) who had an AHI index of < 5 (as normal). General ophthalmological examination, eyelid laxity measurements, corneal topography, visual field, retinal nerve fiber layer parameters, dry eye tests were performed on the patients. Results: It was observed that the two groups had similar characteristics in terms of gender, age, presence of hypertension, diabetes, and body mass index. According to eyelid laxity measurements, the incidence of loose eyelids was higher in the OSAS patient group. Choroidal thickness was thinner in the study group than in the control group. Schirmer test and tear break-up time were significantly lower in the study group than in the control group. The percentage of meibomian gland loss in meibography and the ocular surface disease index score for symptoms was significantly higher in the study group than in the control group. Conclusion: In this study, we found significant changes in ocular surface parameters, eyelid laxity, choroidal thickness, and visual field indices in OSAS patients. Dry eye syndrome might be related eyelid laxity and inflammation in OSAS patients. Early diagnosis and follow-up of ocular diseases in OSAS, which affect the quality of life and visual prognosis in advanced ages, are important. [ABSTRACT FROM AUTHOR]

Background: Filamentary keratitis is an ocular condition that is tricky to handle for the difficulty to find the underlying cause. Here we report a case of filamentary keratitis associated with Demodex infestation which highlights the importance of Demodex mites as an easily-overlooked risk factor. Case presentation: A 63-year-old woman had recurrent symptoms of foreign body sensation and sometimes painful feelings in her left eye soon after her surgical correction of ptosis in this eye. She was then diagnosed as conjunctivitis and given antibiotic eye drops. After one week, the patient complained of aggravation of symptoms with small corneal filaments in the left eye under slit-lamp examination. Despite the removal of filaments and addition of topical corticosteroids and bandage contact lenses, the patient's condition persisted with enlarged filaments and severe ocular discomfort. 3 days later, eyelashes with cylindrical dandruff were noticed and Demodex infestation was confirmed by microscopic examination of these eyelashes at our clinic this time. She was asked to use tea tree oil lid scrub twice daily. After 3 weeks, her filamentary keratitis was resolved with a dramatic improvement in symptoms and signs. And no recurrence of filamentary keratitis was noticed during the one-year follow-up. Conclusions: In this case, filamentary keratitis was resolved only with treatment of Demodex infestation while conventional treatment failed. Considering the fact that Demodex infestation is a common but easily overlooked condition, it may be suggestive to take Demodex infestation into account as a risk factor of filamentary keratitis, especially in refractory cases. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to determine the expression of inflammatory cytokines in the tears of patients with unilateral total limbal stem cell deficiency (TLSCD) caused by chemical burns before and after autologous cultivated limbal epithelial stem cell transplantation (CLET). Methods: Tear samples were collected from both eyes of 23 patients with unilateral TLSCD and 11 healthy controls, at fixed timepoints before and after CLET. Dissolved molecules were extracted from Schirmer's strips using a standardised method and analysed on an array plate of ten inflammatory cytokines (V-Plex Proinflammatory Panel 1 Human Kit, MSD). Results: IL1β expression was significantly elevated in the TLSCD eye compared with the unaffected eye at baseline (p < 0.0001) but decreased to normal 3 months post-CLET (p = 0.22). IL6 and IL8 were unaffected at baseline but significantly elevated in the TLSCD eyes at 1 month post-CLET (p = 0.001 and p < 0.0001, respectively). IL6 returned to normal at 3 months and IL8 at 6 months post-CLET. There was a significant renewed increase in IL1β, IL6 and IL8 expression at 12 months post-CLET (p < 0.0001, p = 0.0001 and p = 0.0003, respectively). IFNγ, IL10 and IL12p70 expression were significantly reduced in both eyes of patients with unilateral TLSCD at all timepoints. Conclusion: IL1β is a specific marker of inflammation in TLSCD eyes that could be therapeutically targeted pre-CLET to improve stem cell engraftment. At 12 months post-CLET the spike in levels of IL1β, IL6 and IL8 coincides with cessation of topical steroids, suggesting ongoing subclinical inflammation. We therefore recommend not discontinuing topical steroid treatment in cases where penetrating keratoplasty is indicated; however, further investigation is needed to ascertain this. Trial Registration: European Union Drug Regulating Authorities Clinical Trials Database (EuDRACT 2011—000608-16); ISRCTN (International Standard Randomised Controlled Trial Number (isrctn51772481). [ABSTRACT FROM AUTHOR]

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Purpose: Our aim was to evaluate the ocular surface in chronic smokers and to assess the benefit of sodium hyaluronate (SH) versus semi-fluorinated alkane (SFA) eyedrops on tear film, meibomian glands, and corneal epithelial thickness (CET). Methods: This prospective randomized single-blinded study included smokers, who applied one eyedrop of Hyabak® on one eye (SH group) and one eyedrop of EvoTears® on the fellow eye (SFA group) 4 times daily for 2 months, and age-matched non-smokers. Ocular surface parameters, including tear film break-up time (TBUT) test and corneal fluorescein staining (CFS) score, lipid layer thickness (LLT), meibography (LipiView®), and CET measurements (Zeiss Cirrus HD-5000®), were assessed at baseline and after treatment. Results: Seventy-eight eyes were included in the smokers group (39 in the SH subgroup and 39 in the SFA subgroup) and 42 eyes in the control group. At baseline, the smokers group had a higher prevalence of dry eye (100% vs 0%, p < 0.001) and of meibomian gland dysfunction (MGD) and lower CET measurements than controls (p < 0.05). TBUT, CFS, and LLT (controls vs SFA group: 64.02 ± 1.87 nm vs 49.56 ± 4.33 nm, p = 0.05) improved in the SFA subgroup after treatment, but not in the SH subgroup, and became equivalent to those of controls. Prevalence of dry eye decreased in the smokers group after treatment (controls vs SH group vs SFA group: 0% vs 12.82% vs 16.26%, p > 0.05). Meibomian gland morphological parameters and CET did not improve after treatment (p < 0.05). Conclusions: Smoking is associated with dry eye, MGD, and corneal epithelial thinning that seem to be only partially reversible with topical lubricants, preferably SFA. [ABSTRACT FROM AUTHOR]

Nandini Venkateswaran,1 Yandong Bian,1 Preeya K Gupta2 1Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA; 2Triangle Eye Consultants, Cary, NC, USACorrespondence: Preeya K Gupta, Email preeyakgupta@gmail.comAbstract: Dry eye disease (DED) is a prevalent ocular surface disease. Like with any chronic disease, patients with DED can experience episodic flares. There are many existing and upcoming treatments for the chronic treatment of DED, yet treatments for DED flares are limited. Loteprednol etabonate 0.25% is an FDA approved treatment modality for the short-term treatment of the signs and symptoms of DED. This medication is formulated with the customized mucus-penetrating particle (MPP) technology, which has a greater ability to penetrate the ocular surface and more effectively deliver the active steroid to the ocular surface tissues as compared with conventional steroid preparations. There is also increasing utility of loteprednol etabonate 0.25% in the treatment of DED before and/or after cataract or refractive surgery or as induction therapy prior to starting chronic immunomodulatory medication for DED.Keywords: dry eye disease, dry eye disease flares, loteprednol etabonate 0.25%, mucus penetrating particle technology, ocular surface inflammation

Graft-versus-host disease (GVHD) is characterized by tissue inflammation in the host following an allogeneic hematopoietic cell transplantation (HCT). The pathophysiology is complex and only incompletely understood yet. Donor lymphocyte interaction with the histocompatibility antigens of the host plays a crucial role in the pathogenesis of the disease. Inflammation may affect multiple organs and tissues, e.g., the gastrointestinal tract, liver, lung, fasciae, vaginal mucosa, and the eye. Subsequently, alloreactive donor-derived T and B lymphocytes may lead to severe inflammation of the ocular surface (i.e., cornea and conjunctiva) and the eyelids. Furthermore, fibrosis of the lacrimal gland may lead to severe dry eye. This review focuses on ocular GVHD (oGVHD) and provides an overview of current challenges and concepts in the diagnosis and management of oGVHD. Ophthalmic manifestations, diagnostic procedures, grading of severity and recommendations for ophthalmic examination intervals are provided. Management of ocular surface disease with lubricants, autologous serum eye drops, topical anti-inflammatory agents and systemic treatment options are described based on the current evidence. Ocular surface scarring and corneal perforation are severe complications of oGVHD. Therefore, ophthalmic screening and interdisciplinary treatment approaches are highly relevant to improve the quality of life of patients and to prevent potentially irreversible visual loss.

Dysfunction of the meibomian glands alters secreted meibum quantitatively and qualitatively that can lead to damage to the ocular surface epithelium. In response to an unstable tear film cause by meibomian gland dysfunction, ocular surface epithelium is damaged and expresses inflammatory cytokines leading to secondary ocular inflammation. In turn, inflammatory disorders of the palpebral conjunctiva and lid margin may affect the structure and function of meibomian gland. The disorders include allergic conjunctivitis, long-term usage of contact lenses, dermatological diseases that affect conjunctival homeostasis, Stevens-Johnson's syndrome or chemical burning of the ocular surface and lid margin.

The ocular surface inflammatory disorders (OSID) are caused by systemic disorders that conduct a persistent inflammatory reaction in the ocular adnexal connective tissues, such as the conjunctiva, lacrimal gland (LG) and meibomian glands (MGs), which cause an inflammatory dry eye. The etiologies of OSID are a subset of systemic pathologies such as graft versus host disease, Sjögren’s syndrome, allergies, cicatrizing conjunctivitis, and more. These cause a purely inflammatory dry eye syndrome as a consequence of the persistent surrounding inflammation in the adnexal tissues, which is distinct from the age-related dry eye disease. A limitation toward management of these conditions is the lack of available biomarkers that can detect presence of inflammation and quantify damage on the conjunctiva and LG, even though these are considered to be drivers of the inflammatory milieu. The OSID and dry eye syndrome are caused by different immune cells which are not exclusively limited to T cell lymphocytes, but rather derive from an orchestrated multicellular immunologic response. Recognition of this syndrome is crucial to direct research in a direction that clarifies the potential role of inflammation and its associated immune phenotype on the conjunctiva and adnexal ocular tissues in OSID and dry eye syndrome. On this paper, we review the basic and clinical research evidence for the existence of OSID with focus on the different immune cells involved, the target tissues and potential consequences and OSIDs diagnostic and therapeutic implications.

Kyung Jae Ryu,1 Seunghoon Kim,2 Mee Kum Kim,3 Hae Jung Paik,1 Dong Hyun Kim1 1Department of Ophthalmology, Gil Medical Center, Gachon University College of Medicine, Incheon, Korea; 2RudaCure Co., LTD, Incheon, Korea; 3Department of Ophthalmology, Seoul National University College of Medicine, Seoul, KoreaCorrespondence: Dong Hyun KimDepartment of Ophthalmology, Gachon University College of Medicine, Gil Medical Center, 1198, Guwol-dong, Namdong-Gu, Incheon, 21565, KoreaEmail amidfree@gmail.comPurpose: To compare the short-term therapeutic effects of topical corticosteroids in patients with refractory dry eye disease (DED) according to the tear matrix metalloproteinase 9 (MMP-9) point-of-care positivity.Methods: This study was conducted on 137 patients who were referred from other eye clinics, complaining of irresponsive DED or acute DED flares despite routine treatment with topical cyclosporin or diquafosol. The patients received treatment with topical corticosteroids for 1 month. DED was evaluated by SANDE (Symptom Assessment in Dry Eye) questionnaire, tear film breakup time, ocular surface staining score, and meibomian gland dysfunction stage. The InflammaDry MMP-9 immunoassay was conducted in more symptomatic eyes of all patients. The changes in the subjective symptoms were additionally surveyed as symptom improvement score.Results: The mean age of the patients was 57.8± 13.4 years, and the tear MMP-9 positivity was 73.0%. Topical corticosteroids treatment showed significant improvement of symptoms and signs in the patients with refractory DED irrespective of the positivity of MMP-9 (each p< 0.001). The changes in SANDE score and OSS, and symptom improvement score were higher in the MMP-9 positive group than in the MMP-9 negative group (p=0.002/0.010/0.011). The overall rates of subjective symptoms improvement and SANDE reduction were 73.0% and 90.6% after topical corticosteroids treatment, respectively.Conclusion: Short-term topical corticosteroids had excellent therapeutic effects in patients with refractory DED or acute DED flares, irrespective of the tear MMP-9 level. Tear MMP-9 positivity may serve as a reliable response predictor of topical corticosteroids treatment in DED.Keywords: dry eye disease, ocular surface inflammation, tear MMP-9 positivity, corticosteroid

AIM: To investigate the concentration of leptin in tears and its correlation with dry eye symptoms and signs. METHODS: The study enrolled individuals (n=39) responding to an advertising or dry eye patients (n=58) from the Ophthalmology Department. Tear samples were collected for leptin concentration measuring. Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), tear break up time (TBUT), cornea fluorescein staining, Schirmer test (ST) and impression cytology (IC) were assessed. Leptin concentration in tears of dry eye patients and healthy controls, and its correlation with clinical features of dry eye disease (DED) were analyzed. RESULTS: Age, body mass index (BMI), OSDI scores and cornea fluorescein staining scores showed a negative correlation with leptin concentration in tears (r=-0.340, P=0.001; r=-0.332, P=0.001; r=-0.258, P=0.011; r=-0.424, P

Objective: To evaluate the effect of full-thickness wedge resection (FTWR) on ocular surface and in vivo confocal microscopy (IVCM) findings in patients with floppy eyelid syndrome (FES)., Methods: The study included two groups: a surgical treatment (ST) group (26 eyes) consisting of patients who underwent FTWR surgery, and a conservative treatment (CT) group (30 eyes). Pre-treatment and post-treatment ocular surface disease index (OSDI), tear break-up time (TBUT), corneal fluorescein staining (CFS), IVCM findings along with the body mass index (BMI), FES grade, the presence and the treatment of obstructive sleep apnea syndrome (OSAS) were recorded and compared between the groups., Results: The groups were comparable in terms of BMI, FES grade, and OSAS data. After six months, TBUT in the ST group significantly increased to 12.92 ± 1.15, compared to 8.10 ± 1.60 in the CT group ( p  = 0.000). The CFS and OSDI scores were significantly lower in the ST group (0.15 ± 0.37, 18.0 ± 8.3, respectively) compared to the CT group (0.90 ± 0.61, 27.3 ± 9.3, respectively) ( p  = 0.000). IVCM analysis revealed a significant decrease in dendritic cell count (ST: 22.0 ± 12.4, CT: 39.5 ± 15.1, p  = 0.000) and nerve tortuosity (ST: 1.38 ± 0.64, CT: 2.00 ± 0.59, p  = 0.000), with a significant increase in total nerve density (ST: 4.27 ± 0.83, CT: 3.57 ± 0.90, p  = 0.002) in the ST group compared to the CT group after six months., Conclusion: In our retrospective cohort, FTWR surgery was shown to be an effective and reliable surgical treatment for FES, improving both ocular surface and IVCM findings. Patients with moderate to severe stages of FES not responding to conservative treatment may benefit from eyelid tightening., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The development of long lasting therapeutic agents is critically important for efficient treatment of chronic diseases. We herein report a rational strategy to develop a therapeutic thermogel featured with prolonged anti-inflammatory and corneal-protective effects. Specifically, a hyaluronic acid with different sulfation degrees and an amine-terminated poly(N-isopropylacrylamide) are conjugated to achieve the thermogels. In vitro studies reveal that the thermogels are highly biocompatible to statens seruminstitut rabbit cornea cells and their anti-inflammatory properties are strongly dependent on the sulfation degree. In a rabbit model of ocular inflammation, single-dose topical administration of a thermogel formulation could repair defects in corneal epithelium (∼99% thickness restored), prevent corneal cell apoptosis (∼68.3% cells recovered), and suppress ocular surface inflammation (∼4-fold decrease) for a follow-up period of 7 days. This high treatment efficacy of the thermogel can be attributed to its potent inhibition in selectin-mediated leukocyte infiltration as well as effective corneal protection. These findings show a great promise for topical treatment of ocular inflammation and advancement of ophthalmic formulations using the bioactive thermogel as a therapeutic component that is not rapidly cleared from the eye and thus considerably reduces administration times.

Blood vessels and nerves travel together to supply most tissues in the body. However, there is a knowledge gap in the mechanisms underlying the direct regulation of angiogenesis by nerves. In the current study, we examined the regulation of angiogenesis by sensory nerves in response to inflammation using the cornea, a normally avascular and densely innervated ocular tissue, as a model. We used desiccating stress as an inflammatory stimulus in vivo and found that sub‐basal and epithelial nerve densities in the cornea were reduced in dry eye disease (DED). We established a co‐culture system of trigeminal ganglion sensory neurons and vascular endothelial cells (VEC) and found that neurons isolated from mice with DED directly promoted VEC proliferation and tube formation compared with normal controls. In addition, these neurons expressed and secreted higher levels of substance P (SP), a proinflammatory neuropeptide. SP potently promoted VEC activation in vitro and blockade of SP signaling with spantide I, an antagonist of SP receptor Neurokinin‐1, significantly reduced corneal neovascularization in vivo. Spantide I and siRNA knockdown of SP abolished the promotion of VEC activation by DED neurons in vitro. Taken together, our data suggested that sensory neurons directly promote angiogenesis via SP signaling in response to inflammation in the cornea. [ABSTRACT FROM AUTHOR]

Purpose: Despite the widespread practice of fasting, there are no studies looking at ocular surface inflammation, specifically matrix metalloproteinase 9 (MMP-9) testing, during fasting. In this prospective study, we wanted to evaluate the effect of Ramadan fasting on the level of tear film MMP-9 as well as other standard indicators of dry eye disease. Methods: Forty healthy patients without history of ocular disease were tested before and toward the end of Ramadan. Each patient was assessed at each timepoint for tear film MMP-9 positivity as measured by a commercially available test (InflammaDry; Quidel Corp., San Diego, CA, USA) which detects MMP-9 levels of more than 40 ng/ml. Ocular surface disease index (OSDI) scores, tear breakup time (TBUT), Schirmer I test (S1T) and corneal fluorescein staining (CFS) were also evaluated at each timepoint. Results: InflammaDry was positive in 10 patients (25%) prior to Ramadan and 21 patients (52.5%) during Ramadan fasting, and this change was statistically significant (p = 0.02). Mean TBUT decreased from 7 s prior to Ramadan to 5.3 s during Ramadan fasting, and this change was statistically significant (p = 0.01). OSDI, CFS and S1T did not show any statistically significant changes (p > 0.05 for all). Conclusion: Ramadan fasting has a significant impact on TBUT and ocular surface inflammation detected by Inflamma Dry testing. Patients who suffer from dry eye disease and those who develop symptoms during Ramadan are advised to consult with a physician before or during Ramadan fasting. [ABSTRACT FROM AUTHOR]

Purpose: To describe a case of bilateral conjunctivitis and cicatricial ectropion associated with dupilumab therapy for atopic dermatitis. Observations: Severe hyperemia of the conjunctiva and eyelid margins, as well as cicatricial ectropion, began two months after starting weekly dupilumab injections for atopic dermatitis. The findings worsened over the next several months and improved after discontinuing dupilumab. Conclusions and importance: Dupilumab is a promising intervention in the management of atopic dermatitis and asthma, however, little is known about its potential ocular adverse effects. We report the first case of dupilumab-associated ocular inflammation leading to cicatricial ectropion.

Aims Tear cytokine levels indicate severity of ocular surface inflammation. Previous reports of cytokine concentrations were based on hospital-based studies or non-Chinese populations. We determine the range of tear concentration of cytokines in a representative adult Chinese population. Methods Thirty-nine participants were recruited from a population-based study of Chinese adults in Singapore, and standardized clinical ocular surface/eyelid features evaluated. Tear was extracted from Schirmer strips and analysed using a multiplex bead-based assay. Results Tear concentrations of 14 cytokines were investigated and quantifiable in each participant. Eight cytokines increased with increasing age, and 4 cytokines (IL-4, IL-12, IL-10 and IFN-γ) were increased in people with increased frequency of ocular discomfort. Three cytokines (MCP-1, IP-10 and IL-13) had increased levels in people with lower Schirmer tests, while 9 other cytokines were increased in patients with eyelid crusting (TNF-α, IL-1β, IL-17α, IL-2, IL-4, IL-6, IL-12, IL-10 and IFN-γ). Twelve percent of participants had eyelid crusting. Conclusion Using a convenient collection technique that is a routine clinical test, 14 tear cytokines could be quantifiable even in Singapore Chinese adults without a dry eye diagnosis. Elevation of different tear cytokines may be linked to subclinical aqueous tear deficiency or eyelid inflammation even in asymptomatic people. [ABSTRACT FROM AUTHOR]

Conjunctivochalasis (CCH) is a conjunctival condition characterized by loose, redundant conjunctival folds, most typically in the inferior bulbar conjunctiva of both eyes. Although CCH is a common cause of ocular irritation and discomfort, especially in the elderly, it is often overlooked in clinical practice. CCH may be associated with various ocular and nonocular conditions; however, the most important risk factor is aging. Although often asymptomatic, CCH may cause symptoms related to tear film instability and/or delayed tear clearance. Pathogenesis of CCH remains largely unknown but may involve different elements such as aged conjunctiva, unstable tear film, mechanical friction, ocular surface inflammation, and delayed tear clearance. Contradictory results have been reported on histopathologic changes in CCH, with some studies showing a normal microscopic structure. For symptomatic CCH, medical treatment may include lubrication and anti-inflammatory medications. For symptomatic patients who fail to respond to medical treatment, a surgical procedure may be considered. Although various surgical procedures have been used for CCH, more often, it consists of conjunctival cauterization or excision of the redundant conjunctiva, with or without amniotic membrane transplantation. [ABSTRACT FROM AUTHOR]

Purpose: Simultaneous analyses of the contents and ratios of 12 cytokines and growth factors in single samples of human tears were performed, and the results were compared between a group of healthy subjects and a group of patients with Graves’ hyperthyreosis (GH) without thyroid-associated orbitopathy (TAO).Methods: Determinations and concentration measurements of interleukins (IL-2, IL4, IL-6, IL-8, IL-10, IL-1α, and IL-1β) interferon (IFN-γ), tumor necrosis factor (TNF-α), monocyte chemoattractant protein (MCP-1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were performed with single tear samples from 21 patients with hyperthyreosis and 22 healthy subjects. The analyses were performed using a Randox microchip with an Evidence Biochip Array Analyzer.Results: We found significant differences between the healthy donor group and the hyperthyreosis group in the levels of IL-6, IL-10, VEGF, IL-1α, and MCP-1. The concentration of IL-6 was considerably higher in the hyperthyreosis group, IL-10 was higher in the healthy donor group, and VEGF and MPC-1 were higher in the hyperthyreosis group. The IL-8 and IFN-γ levels were higher in the hyperthyreosis group. The ratios of all of the cytokines to anti-inflammatory IL-10 were significantly elevated in the hyperthyreosis group.Conclusion: There are clear differences in the levels of cytokines and growth factors in the tears of healthy subjects and patients with GH without TAO. Tear cytokine changes and related dysfunctional tear syndrome (DTS) could be an early sign of occult TAO in Graves’ hyperthyreosis patients. [ABSTRACT FROM AUTHOR]

Purpose: To describe an unusual case of unilateral, chronic symptoms and signs of dry eye, and recurrent episodes of ocular irritation related to pinguecula, which were refractory to prior medical treatments, successfully treated with argon laser photocoagulation. Methods: A 36-year-old man presented with an elevated yellowish mass on his conjunctiva in his left eye, which was associated with dry eye symptoms and general discomfort, such as "tightening sensation" and "stiffness". On clinical assessment, the left eye revealed a mild conjunctival injection, a fluorescein break-up time (FBUT) of 3.5 s, an abnormal fluorescein staining, and a Schirmer I test of 5 mm. Optical coherence tomography (OCT) imaging evidenced a height at the most elevated point of the pinguecula of 740 μm. The patient underwent argon-laser photocoagulation. Results: After 2 weeks postoperatively, no residual of pinguecula or focal injection of the conjunctiva was detected by slit-lamp biomicroscopy and there was a significant improvement of clinical symptoms and signs: Schirmer I test and FBUT increased to 12 mm and >10 s, respectively, and fluorescein staining was absent. OCT imaging revealed a smooth structure of conjunctival contour, with a height of 404 μm. According to an ex juvantibus line of reasoning, definitive diagnosis was pinguecula-related dry eye disease. Conclusion: Based on the concept that tear film instability and inflammation are two key components of the pathogenesis of dry eye, we coined the term "pinguecula-related dry eye disease," which can be successfully treated by a complete, accurate removal of the lesion with argon laser photocoagulation. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate conjunctival impression cytology and HLADR expression changes after wearing scleral contact lenses (ScCLs) for moderate to severe dry eye disease (DED).Design: Prospective interventional case series.Methods: Forty-one eyes from 25 patients with moderate to severe DED were evaluated for Esclera ScCL treatment. Best-corrected visual acuity (BCVA) and slit-lamp findings were assessed. Impression cytology specimens were obtained from DED patients at the baseline and after wearing ScCLs for 12 months. The impression cytology specimens were analyzed using morphological results score, and HLA-DR positive cells were detected and quantified. The values were compared to assess the IC changes after wearing ScCLs.Results: Forty-one eyes from 25 patients were fitted with ScCLs to manage DED. The underlying diseases were Stevens-Johnson syndrome (22 eyes), Sjogren's syndrome (11 eyes), graft-versus-host disease (2 eyes), dry eye after keratomileusis (2 eyes) and undifferentiated ocular surface disease (4 eyes). The HE-PAS impression cytology score did not differ significantly before and after wearing ScCLs for 12 months in DED patients (p>0.05). The percentage of eyes expressing the HLA-DR antigen in the temporal conjunctiva after wearing ScCL for 12 months significantly increased in patients with Sjogren's syndrome (11.11% to 66.66%; p=0.0498). In groups with Stevens Johnson syndrome and other ocular surface disorders, we did not observe statistically significant differences (p>0.05).Conclusions: The ScCLs did not change the parameters used to evaluate inflammatory processes, which were measured using conjunctival impression cytology and HLA-DR expression, except in Sjogren syndrome, in which there was an unexpected increase in HLA expression. [ABSTRACT FROM AUTHOR]

Background: Preserved anti-glaucoma drops cause ocular surface disease (OSD), which is increasingly being recognized as a likely cause of trabeculectomy failure. Aim: To determine the routine pre-trabeculectomy management of the ocular surface by glaucoma specialists. Methods: A questionnaire consisting of 11 questions was posted to 146 UK glaucoma specialists. Results: The first-time response rate was 43.8%. Regarding routine pre-operative management, 40.6% of specialists use preservative-free drops, 29.7% commence a drop holiday, and 53% advise lid hygiene. 42.1% prescribe lubricants, 50% prescribe topical steroids, 7.8% topical NSAIDs, and 34.4% systemic tetracyclines. 84.4% of specialists change their routine management if OSD is present. Pre-operative optimization of the ocular surface is viewed "necessary" by 48.4% and "beneficial" by 85.9%. Conclusion: A wide variation exists in the routine pre-operative management of the ocular surface. Research to determine the impact of different pre-operative interventions upon trabeculectomy outcomes is required. [ABSTRACT FROM AUTHOR]

Graft versus H\host disease (GVHD) can be a devastating complication following bone marrow transplantation. Acute or chronic systemic GVHD can be lethal, and severe damage of different organs and tissues can occur with both types of GVHD. Ocular involvement, either in an acute or chronic presentation, may range from mild to severe with accompanying vision loss present in 60-90 % of patients. Chronic ocular GVHD, the most common form of GVHD, affects mainly the lacrimal gland, meibomian glands, cornea and conjunctiva, mimicking other immunologically mediated inflammatory diseases of the ocular surface without specific symptoms or signs. However, dry eye disease is the main manifestation of GVHD. The long-term treatment of ocular GVHD continues to be challenging and involves a multidisciplinary approach wherein the ophthalmologist plays a major role. Besides systemic immunosuppression and ocular lubricants, topical steroids and topical cyclosporine are commonly prescribed. Newer therapeutic interventions for moderate and severe ocular GVHD include the use of serum eye drops and scleral contact lenses. In this manuscript, we review the mechanisms, clinical findings, and treatment of ocular GVHD. [ABSTRACT FROM AUTHOR]

Human tear is a biological fluid rich in lipids that is increasingly collected in clinical and biological research. The repertoire of small lipids or lipid mediators (often termed eicosanoids or oxylipins) found in human tear provides insight into metabolism of fatty acids and physiology of the ocular surface and Meibomian glands. Disturbances in the tear lipid mediators profile also occur during inflammation of the ocular surface that is not directly linked to lipid metabolism. The changes in the levels of pro-inflammatory and pro-resolution lipid mediators in the tear help assess the severity and stage of inflammation in ocular surface tissues. Mass spectrometry, used in the evaluation of tear lipid mediators, is an emerging tool in clinical diagnostics and personalized medicine. Here we describe the reproducibility, accuracy, and precision of quantifying lipid mediators in human tears, with a suggested method for tear collection and sample handling. The ranges of lipid mediators concentrations in tear fluid of healthy and diseased individuals with Meibomian gland dysfunction are reported, as well as the impact of age and disease on individual lipid mediators. We would like to recommend a set of guidelines, which can be further discussed in workshops. This will facilitate harmonization of future tear lipid mediators data across different instrument platforms in various laboratories. We hope that other fields requiring lipid mediators assays will also benefit from such an effort., (Copyright © 2020. Published by Elsevier Inc.)

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The pathophysiology of Dry Eye Disease (DED) is complex, and therapy may be a challenge. Tear film instability, tear film hyperosmolarity, ocular surface damage and ocular surface inflammation are accepted key events in the pathogenesis of the disease. New anti-inflammatory targets have been identified and novel anti-inflammatory treatments may enrich our therapeutic armamentarium in the future. Neurosensory changes in DED secondary to neuroinflammation in the corneal nerves, the trigeminal ganglion, and the trigeminal brainstem sensitivity complex have recently been reported and may play an important role in the pathophysiology of DED. Receptor complexes on the axonal membranes of corneal nerves may be promising novel therapeutic targets. Recent studies have shown changes in the both the systemic and local (conjunctival) microbiomes with DED as well as an association of DED with laryngopharyngeal reflux. These new insights into DED suggest new treatment approaches. In hyperevaporative DED typically associated with meibomian gland dysfunction (MGD), hyperkeratinized and obstructed meibomian glands are important treatment targets, and novel techniques may be available soon to better manage patients with MGD. The observation of changes in brain function in patients with DED sheds a completely new light on the pathophysiology of the disease. Increased understanding of the pathogenetic events described above may define novel treatment targets, guide management and may allow customized treatment of DED in the future. Pathophysiological events in Dry Eye Disease (DED) targeted by new treatment options include: • Ocular surface inflammation • Changes in the conjunctival/intestinal microbiota and the association of DED with laryngopharyngeal reflux • Neurosensory changes and neuroinflammation • Hyperkeratinized and obstructed meibomian glands [ABSTRACT FROM AUTHOR]

Purpose: To report four patients with unusually severe acute keratitis sicca secondary to lacrimal tissue and ocular surface inflammation who eventually required systemic immunosuppressive therapy. Methods: Observational case series of four patients with extremely severe acute dry eye syndrome who were profoundly disabled by pain and photophobia (to the extent of staying in dark rooms) despite aggressive conventional therapy. Clinical data including visual acuities, other treatments administered for dry eye, systemic medical conditions, Schirmer and rose bengal staining results, degree of conjunctival injection, and medications were recorded. All four patients were treated with systemic immunomodulatory therapy. Results: All four patients were female with a mean age at presentation of 40 years (range 22-58 years), and all had systemic autoimmune diseases: systemic lupus erythematosus (SLE) and Sjogren's syndrome (n = 2), Sjogren's syndrome (n = 1), rheumatoid arthritis (RA) and psoriasis (n = 1). Schirmer test values at onset ranged from 0 to 2 mm. All patients had failed aggressive lubrication, topical cyclosporine, lid care, and punctual plugs. In two patients, serum tears and hyphrecation punctal occlusion were tried without success. Various systemic immunosuppressive agents were used to control inflammation of the lacrimal glands: methotrexate and cyclosporine A (patient 1), cyclosporine A (patient 2), prednisone (patient 3), and methotrexate and infliximab (patient 4). Treatment with systemic immunomodulatory agents resulted in resolution of the acute inflammatory assault on the lacrimal glands and control of signs and symptoms of keratoconjunctivitis sicca in all four patients, and visual acuities improved in all of them. Post-treatment Schirmer values ranged from 7 to 10 mm. Conclusion: Systemic immunosuppressive agents may be required in the treatment of recalcitrant primary and secondary Sjogren's syndrome caused by systemic autoimmune conditions. We show that systemic immunomodulatory therapy leads to significantly improved tear production and resolution of the keratoconjunctivitis in these rare but severe cases. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effectiveness of different treatment modalities for dry eye in primary Sjögren's syndrome with their potential overlapping influences. Methods: This study included 199 patients with newly diagnosed primary Sjögren's syndrome from 2005 to 2020. Various treatment modalities for primary Sjögren's syndrome were compared. Improvement of corneal staining based on Sjögren's International Collaborative Clinical Alliance (SICCA) scores was the primary outcome. Results: The average follow-up period was 5.4 ± 3.1 (range, 2.0–14.1) years. Analysis of the individual treatments showed that punctal plug insertions in the lower and upper eyelids were strongly associated with improvement of SICCA scores (β = 2.70 and 1.80, p < 0.001 and <0.001, respectively). With ocular surface inflammation, corneal staining scores improved significantly with steroid eye drops. Prednisolone (1%) had the strongest association with improvement of corneal staining scores (β = 1.48, p < 0.001); this was based on the frequency of administration. Without ocular surface inflammation, diquafosol (3%), carbomer gel, and lanolin ointment were effective (β = 1.37, 1.06, and 1.17; p = 0.003, 0.003, and <0.001, respectively). Conclusions: Punctal plug insertion, primarily targeting aqueous deficiency, is the mainstay of the treatment for dry eye in primary Sjögren's syndrome even in the presence of ocular surface inflammation. Furthermore, the effectiveness of treatment modalities for dry eye in primary Sjögren's syndrome was dependent on the presence of ocular surface inflammation. [ABSTRACT FROM AUTHOR]