Fluorescein Staining Scores Research Articles

Comparison of 2 Different Treatments for Conjunctivochalasis: Plasma-Based Conjunctivoplasty Versus Argon Laser Photocoagulation.

The aim of this study was to compare the clinical outcomes of plasma-based conjunctivoplasty and argon laser photocoagulation techniques used in the treatment of conjunctivochalasis. The study included 119 eyes from 67 patients who underwent plasma-based conjunctivoplasty or argon laser photocoagulation for conjunctivochalasis in our clinic between February 2021 and March 2022. Group 1 included 62 eyes from 35 patients who had plasma-based conjunctivoplasty. Group 2 included 57 eyes from 32 patients who had argon laser photocoagulation. Main outcomes were patient symptoms, the degree of conjunctivochalasis, fluorescein staining score, tear breakup time, the amount of conjunctival shrinkage, and complications. Before surgery, Group 1 had grade 1 conjunctivochalasis in 8 eyes (12.9%), grade 2 in 20 eyes (32.2%), and grade 3 in 34 eyes (54.8%). In Group 2, 9 eyes (15.7%) had grade 1, 21 eyes (36.8%) had grade 2, and 27 eyes (47.3%) had grade 3 conjunctivochalasis ( P = 0.43). At the sixth postoperative month, only 2 eyes (3.2%) in Group 1 had grade 1 conjunctivochalasis, whereas the other cases (96.7%) had no conjunctivochalasis. However, Group 2 had grade 1 conjunctivochalasis in 16 eyes (28.0%), grade 2 in 21 eyes (36.8%), and grade 3 in 2 eyes (3.5%). Conjunctival shrinkage in Group 1 (5.1 ± 1.2 mm) was significantly higher than in Group 2 (3.3 ± 0.9 mm; P < 0.001). Postoperative tear breakup time in Group 1 (10.2 ± 2.1 seconds) was significantly longer than in Group 2 (8.8 ± 2.0 seconds; P < 0.001). Plasma-based conjunctivoplasty demonstrated greater clinical improvement and efficacy than argon laser photocoagulation for the treatment of conjunctivochalasis.

Effect of phospholipid‐eluting contact lens on dry eye in rabbit

Aims/Purpose: To investigate the effects of new phosphatidylcholine‐eluting contact lenses (PC‐CL) on dry eye in Rabbit.Methods: 18 New Zealand rabbits were used in this study. Meibomian gland orifices were electrocauterized in the dry eye group. PC‐CL were provided from Neo Vision (Yongin, Korea). Rabbits were fitted with control contact lens on one eye and 0.1% PC‐CL on the other eye or with 0.1% PC‐CL on one eye and 0.3% PC‐CL on the other eye. Tear break‐up time (TBUT), tear osmolarity, and corneal fluorescein staining score (FSS), central corneal thickness (CCT), and conjunctival histology were evaluated.Results: In both dry eye and non‐dry eye group, TBUT was longer and tear osmolarity was lower in 0.1% PC‐CL compared to control lens. Cornea was stained with fluorescein in dry eye group, but not in non‐dry eye group. CCT showed no difference in PC‐CL and control lens on both dry eye and non‐dry eye group. In dry eye group, goblet cell density tended to be slightly higher in PC‐CL compared to control. There was no significant difference in TBUT, tear osmolarity, CCT, FSS, and goblet cell density between 0.1% PC‐CL and 0.3% PC‐CL.Conclusions: PC‐CL stabilized tear film and lowered tear osmolarity in dry eye. Thus, it may reduce dry eye symptoms and contact lens complications in clinical practice.

Long‐term results and persistence of topical cyclosporine a 0.1% treatment in patients with dry eye disease in a tertiary eye centre

Aims/Purpose: This study aims to assess clinical effectiveness, outcome and safety of long‐term topical Cyclosporine A 0.1% Cationic Emulsion (CsA 0.1% CE; Ikervis®) treatment in patients with dry eye disease.Methods: Retrospective chart review of 55 patients (110 eyes) with dry eye disease and severe keratitis treated with Ikervis® since 2016 for at least 12 months without interruption was performed. Study outcomes were median change from baseline in corneal fluorescein staining (CFS, Oxford Grade Scale) score, clinical outcome, treatment discontinuation reason, ocular symptom severity and adverse events (AEs) during long follow‐up.Results: The mean age of patients was 65.96 ± 1.9 years, 81.8% women and 18.2% men. The mean follow‐up was 33.8 ± 19.1 (12–80) months. 43.6% eyes had grade III of CFS at baseline and 4.5% had grade I of CFS at the last follow up. The median CFS score reduced from 2 (1–3) at baseline to 0 (0–1) at the last follow up and this reduction was statistically significant (p &lt; 0.001) from the fourth week. Clinical outcome was defined as active/worsening in 1.8%, stabilization in 14.5%, improvement in 69.1% and resolution in 14.5% of the cases. 65.5% of the patients have continued the treatment without interruption during the whole follow‐up, the treatment discontinuation in 35.5% of the cases were due to improvement (14.5%), AEs (5.5%), patient decision (5.5%), treatment failure (3.6%), other reason (5.5%). Ocular symptom severity was significantly reduced from baseline during the follow up (p &lt; 0.001). In 27.3% cases treatment‐related AEs were reported, most of them (64.7%) were mild.Conclusions: This study shows a long‐term clinical effectiveness and persistence of the topical CsA 0.1% CE treatment in patients with dry eye disease. The significantly reduction of the dry eye symptoms severity from the fourth week of the initiated Ikervis® treatment sustains for a long follow up, and thus definitely improves the quality of life of patients.Reference1. Geerling G, Hamada S, Trocmé S, Ræder S, Chen X, Fassari C, Lanzl I; PERSPECTIVE study group. Real‐World Effectiveness, Tolerability and Safety of Cyclosporine A 0.1% Cationic Emulsion in Severe Keratitis and Dry Eye Treatment. Ophthalmol Ther 2022; 11(3): 1101–1117. doi: 10.1007/s40123‐022‐00487‐x.

Atmospheric pollutant black carbon induces ocular surface damage in mice

The threats of air pollution to human health have been gradually discovered, including its effects on eyes. The purpose of the study is to investigate the potential correlation between ocular surface exposure to black carbon and ocular surface structural damage as well as tear film dysfunction. To achieve this goal, 60 6-8-week-aged male BALB/C mice were randomly divided into 4 groups (n = 15). 0.5 mg/ml (group A), 1 mg/ml (group B), 5 mg/ml (group C) black carbon suspension droplets and PBS solution (group D) were used in the right eyes, 4 μl per time of three times per day. Tear break-up time, corneal fluorescein staining scores, and tear volume were assessed before treatment (day 0) and on days 4, 7, 10, and 14 after treatment. On day 14, the mice were sacrificed, and corneal and conjunctival tissues were collected for histological analysis. As the exposure time increased, there were no significant changes in the measured parameters from PBS-treated group of mice (P > 0.05). However, in the black carbon-treated group, there were significant decreases in tear film break-up time, significant increases in corneal fluorescein staining scores, and significant reductions in tear secretion (all P < 0.05). After 14 days, H&E staining of the corneal epithelium showed that in the PBS-treated group of mice, the corneal epithelial cells were neatly arranged, with no inflammatory cell infiltration, while in the black carbon-treated group, the corneal epithelium was significantly thickened, the basal cell arrangement was disrupted, the number of cell layers increased, and there was evidence of inflammatory cell infiltration. In the ultrastructure of the corneal epithelium, it could be observed that the black carbon-treated group had an increased amount of corneal epithelial cell detachment compared to the PBS-treated group, at the same time, the intercellular connections were looser, and there was a decrease in the number of microvilli and desmosomes in the black carbon-treated group. The results indicate that the ocular surface exposure to black carbon can result in a decrease in tear film stability and tear secretion in mice. Moreover, it can induce alterations in the corneal structure.

An enhanced model for environmental dry eye: Exploring pathological features and underlying factors

This study aimed to develop an enhanced environmental dry eye (EDE) model that accurately reproduces the etiology of prolonged visual fatigue and investigates the underlying pathological features. A total of 40 adult SPF-grade Wistar rats were randomly assigned to control (n = 20) and model (n = 20) groups. Rats in the control group were maintained under normal conditions, while rats in the model group were exposed to a controlled frontal airflow of 2–4 m/s from a fan for 7.5 h daily while placed on a suspended cylindrical wire mesh frame. Various assessments were performed at different time points during the 14-day experiment, including blink frequency, tear secretion (phenol red thread test), tear film breakup time (BUT), fluorescein staining (FL), corneal epithelial status (light microscopy), ultrastructure of corneal epithelial cells (electron microscopy), and expression levels of inflammatory cytokines (IL-1β, TNF-α) in tears (enzyme-linked immunosorbent assay). Additionally, mRNA and protein expression levels of MMP-9, IL1β, IL6, TNF-α, IFN-γ, and caspase-3 in corneal tissues were quantified (real-time quantitative PCR and Western blotting). Compared to the control group, the model group rats exhibited significant decreases in blink frequency (P < 0.001), tear secretion (Schirmer I test) values (P < 0.001), and tear film breakup time levels (P < 0.001). There was also a significant increase in fluorescein staining scores (P < 0.001) in the model group. Histological examination revealed distinct differences of the corneal epithelium between groups. The corneal epithelium of the model group appeared thicker, with disorganized cell arrangement in the superficial and basal layers, partial defects or detachment of superficial epithelial cells, and a rough, uneven surface. Scanning electron microscopy observations showed a rough corneal epithelial surface with numerous cracks and scattered vesicular-like structures in the model group. Furthermore, the model group rats exhibited a significant increase in expression of IL-1β and TNF-α in tears (P < 0.001), and upregulated expression levels of MMP-9, TNF-α, IL-1β, caspase-3, IL-6, and IFN-γ at both the mRNA and protein levels in corneal tissues (P < 0.001). In conclusion, the modified “wire-meshing cylindrical board” model effectively overcomes the limitations of the traditional “jogging board " dry eye model and successfully simulates the etiology of prolonged visual fatigue. This innovative EDE model demonstrates a high degree of relevance to dry eye conditions resulting from prolonged visual tasks, with a high success rate of model induction. Moreover, it proves to be a simple, practical, and easily replicable model, making it highly suitable for further studies on prolonged visual fatigue and facilitating its widespread adoption in research and clinical applications.

A New Treatment for Recalcitrant Neurotrophic Keratopathy of Ocular Graft-Versus-Host Disease with Virus Infection.

Neurotrophic keratopathy (NK) is a rare degenerative ocular disease that can be difficult to treat. There were no effective resolutive treatments for severe NK caused by ocular graft-versus-host disease (oGVHD) along with virus infection. To address this question, we designed a prospective cohort study to evaluate the efficacy and safety of topical recombinant human nerve growth factor (rhNGF) in patients with recalcitrant NK of oGVHD and viral infection. This prospective cohort study enrolled patients with recalcitrant NK diagnosed with oGVHD and treated with rhNGF. Clinical evaluations included the range of epithelial defects, best corrected visual acuity, intraocular pressure, slit-lamp examination, and corneal fluorescein staining. Examinations of the central corneal thickness, corneal sensitivity, and nerve fiber regeneration were performed at each visit at 4, 8, 12, 20weeks and 6months, respectively, after initiating rhNGF treatment. All enrolled patients were diagnosed with NK at stage2 (7 eyes, 63.6%) or stage3 (4 eyes, 36.4%) and responded to rhNGF treatment. Five of 11 (45.5%) and 9 of 11 eyes (81.8%) achieved complete corneal epithelial healing after 4 and 8weeks, respectively. All 11 eyes (100%) achieved complete corneal healing after 12weeks. There was also a significant reduction in the corneal ulcer area during each visit (P < 0.001), as well as in the corneal fluorescein staining score (P < 0.010). There was a significant improvement in corneal sensation when compared to the baseline (P < 0.050). Topical treatment with rhNGF effectively promoted the complete corneal healing of persistent epithelial defects and corneal ulcers in patients with recalcitrant NK in oGVHD and viral infection.

Safety and Efficacy of Human Amniotic Epithelial Stem Cells Eye Dropin Ocular Chronic Graft-Versus-Host Disease

Background Approximately 50% of patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) suffer from ocular chronic GVHD (ocGVHD), which causes severe dryness and visual impairment. However, current clinical treatments for ocGVHD, such as artificial tears, immunosuppression therapy, and punctual occlusion, typically offer only limited benefits. Amniotic membrane transplantation (AMT) can significantly alleviate ocular symptoms in patients with ocGVHD, but it is an invasive procedure that is not appropriate for all patients with ocGVHD. Therefore, we designed a clinical trial to demonstrate the safety and efficacy of eye drops containing human amniotic epithelial stem cells (hAESC) in ocGVHD. M ethods Register Number: ChiCTR2200057857. The enrolled eyes received 1*10 6 cells/mL of hAESC eye drops four times daily for one to three treatment cycles (A cycle was defined as two weeks of continuous administration and two weeks without hAESC eye drops). The primary outcome measure is safety following treatment with hAESC eye drops. In addition, other clinical indices, such as the ocular surface disease index (OSDI), NIH score(eye), Schirmer's test, corneal fluorescein staining (CFS) score, fluorescein tear breakup time (FTBUT), and in vivo confocal microscopy (IVCM) were essential parameters. Results ： 19 of the 25 patients included in the study completed at least one round of treatment. The average length of follow-up was 9.4 months. There were no adverse events associated with hAESC. After one round of treatment(n=19), there was a significant decrease in OSDI score (P=0.0003) and eye NIH score (P0.0001), an increase in Schirmer basal secretion score (P=0.0237), and a significant improvement in CFS score (P0.0001), corneal subbasal nerve density(P=0.006), and corneal epithelial cell density(P=0.0349). It also produced statistically significant improvements in FTUBT after two rounds of treatment (n=14) (P= 0.024). After three rounds of treatment (n=11), we observed additional improvements in the OSDI (P=0.0001) and CFS (P0.001) scores. Conclusion ： The findings of this study indicated that hAESC eye drops are safe and effective at alleviating symptoms and signs in patients with ocGVHD, making them a promising therapeutic option for the treatment of ocGVHD.

Long-Term Safety and Efficacy of Perfluorohexyloctane Ophthalmic Solution for the Treatment of Patients With Dry Eye Disease: The KALAHARI Study.

The aim of this study was to assess the long-term safety and efficacy of perfluorohexyloctane (PFHO) ophthalmic drop (formerly NOV03) for treatment of dry eye disease (DED). KALAHARI was a phase 3, multicenter, single-arm, open-label extension study in patients aged 18 years or older with DED associated with Meibomian gland dysfunction who completed the randomized, double-masked, hypotonic saline-controlled GOBI study. Patients instilled 1 drop of PFHO (MIEBO, Bausch + Lomb) 4 times daily in both eyes for 52 weeks. Safety assessments included adverse events, best-corrected visual acuity, slit-lamp biomicroscopy, intraocular pressure, and dilated fundoscopy. Efficacy end points included change from GOBI study baseline in total corneal fluorescein staining and eye dryness score (0-100 visual analog scale). Overall, 208 patients from GOBI (PFHO [n = 97]; saline [n = 111]) were rolled over into KALAHARI. Twenty-nine patients (13.9%) had ≥1 ocular adverse event, with most being mild or moderate in severity; the most common ocular adverse events were vitreous detachment (1.9%), allergic conjunctivitis (1.4%), blurred vision (1.4%), and increased lacrimation (1.4%). Other safety end points were unremarkable. For patients continuing PFHO from GOBI, improvements in total corneal fluorescein staining and visual analog scale dryness scores observed in GOBI were maintained throughout KALAHARI. Patients treated with saline in GOBI and switched to PFHO in KALAHARI showed improvements in total corneal fluorescein staining and visual analog scale scores by week 4 that were maintained for the rest of the study. PFHO was safe and well tolerated and maintained efficacy for improving signs and symptoms of DED in this year-long study of patients with DED associated with Meibomian gland dysfunction.

Effect of dry eye on the reliability of keratometry for cataract surgery planning

This study aimed to evaluate the effects of dry eye on the reproducibility of keratometry (K) measurements in patients presenting for cataract surgery. A non-randomized controlled clinical study was performed. Eighty-three eyes of eighty-three patients with cataracts who were enrolled in our hospital from March 2020 to July 2020 were studied. The mean non-invasive tear film break-up time (NIBUT), corneal fluorescein staining score, and ocular surface disease (OSD) SPEED II questionnaire were measured and recorded prior to surgery, and the patients were assigned to a "dry eye" group (n=35) or a "non-dry eye" group (n=48). The K of the patients was measured twice by a Tomey OA-2000 (an average of three times each). The difference of the mean K (ΔKm) and astigmatism vector (ΔKvector) between the two measurements was calculated. The ΔKm and ΔKvector between the two groups were compared. The relationship between the measurement parameters of dry eyes and the accuracy of the preoperative K values was analyzed. ΔKm was 0.09 D [0.03; 0.19] in the non-dry eye control group and 0.28 D [0.18; 0.50] in the dry eye group, with a statistical difference between the two groups (P=0.005). The ΔKvector of the non-dry eye control group was 0.22 D [0.14; 0.42], and that of the dry eye group was 0.50 D [0.28; 1.06]. There was a significant difference between the two groups (P=0.010). Between the two groups, the percentage of the ΔKm and ΔKvector values greater than 0.5 D were statistically different (P<0.05). There was no significant difference in ΔKm between the groups with NIBUT>5s and NIBUT≤5s (P=0.537). There was no significant difference in ΔKm between groups≥2 and<2 on the OSD SPEED II questionnaire scores (P=0.442). Dry eye can affect the reliability of keratometry measurements before cataract surgery, thereby affecting the accuracy of intraocular lens power calculations. In cataract surgery planning, it is necessary to detect subjective and objective indicators of dry eye in patients and carry out effective intervention so as to avoid refractive errors caused by inaccurate keratometry measurements.

NOVATIVE: A Phase II/III, Multicenter, Double-masked, Randomized Study of Cyclosporine A 0.05% and 0.1% Ophthalmic Cationic Emulsion Versus Vehicle in Patients with Vernal Keratoconjunctivitis

PurposeThis study evaluates the efficacy and tolerability of cyclosporine A cationic emulsion (CsA-CE) in patients ≥4 years of age with moderate-to-severe vernal keratoconjunctivitis (VKC). MethodsThis Phase II/III, multicenter, double-masked, dose-ranging study had 2 treatment periods: a 4-week, randomized, vehicle-controlled period in which patients received 0.05% CsA-CE, 0.1% CsA-CE, or vehicle eye drops 4 times daily (period 1) and a 3-month period in which patients received 0.05% CsA-CE or 0.1% CsA-CE 2 or 4 times daily (period 2). The primary efficacy end point was rating of subjective symptoms at day 28 in period 1 per the BenEzra scale. FindingsAll groups showed improvement in subjective VKC symptoms at day 28, without a statistically significant difference between 0.05% or 0.1% CsA-CE vs vehicle. Both CsA-CE doses produced statistically significant improvements in corneal fluorescein staining scores vs vehicle at day 28; improvements were evident as early as week 1 and continued through month 1. Progressive reduction in subjective itching was evident after week 1 and continued through month 1. Treatment for an additional 3 months further improved subjective symptoms and objective signs of VKC in both CsA-CE groups. Improvement was most notable with 0.1% CsA-CE in patients with severe keratitis. The safety and tolerability profile is favorable. ImplicationsAlthough treatment with 0.05% and 0.1% CsA-CE showed clinical efficacy in alleviating keratitis and itching as early as week 1, with sustained benefit through 1 month, the primary efficacy end point was not met. These findings informed the design of the Phase III trial of 0.1% CsA-CE (Vernal Keratoconjunctivitis Study). ClinicalTrials.gov identifier: NCT00328653.

Efficacy evaluation of 0.05% cyclosporine A and 0.1% tacrolimus eye drops in the treatment of severe dry eye associated with chronic graft-versus-host disease

Objective: To evaluate the effectiveness and safety of 0.05% cyclosporine A and 0.1% tacrolimus eye drops in treating severe dry eye associated with chronic graft-versus-host disease (cGVHD). Methods: This non-randomized concurrent control trial enrolled 83 eyes from 83 patients with cGVHD-associated severe dry eye. The treatment had two phases. During the initial shock treatment period (0-3 months), 44 patients received 0.05% cyclosporine A eye drops (4 times/day; group A) and 39 patients received 0.1% tacrolimus eye drops (twice/day; group B) alongside basic treatment. In the maintenance treatment period (3-6 months), both groups used 0.05% cyclosporine A eye drops (twice/day) and sodium hyaluronate. Examinations were conducted at 1, 3, and 6 months after treatment initiation, assessing the Ocular Surface Disease Index (OSDI), corneal fluorescein staining (CFS) score, and fluorescein tear break-up time (BUT) for efficacy. visual acuity and intraocular pressure (IOP) were evaluated for safety, and patients' post-medication irritation symptoms were recorded. Results: The study included 52 males and 31 females, aged (28.57±15.67) years. After 1 month of treatment, the CFS score in group A significantly decreased from 10.0 (6.0, 14.0) to 5.0 (3.0, 8.5) (P<0.001). in group B, the CFS score also significantly decreased from 10.0 (6.0, 15.0) to 6.0 (2.0, 10.0), and the BUT increased from 2.0 (1.0, 2.0) s to 2.0 (1.8, 3.3) s (P<0.001). No significant OSDI decrease was observed in either group. No significant differences were found in OSDI, CFS score, and BUT between the two groups. After 3 months, group A showed significant improvement in OSDI, CFS score, and BUT (P<0.05), while group B only demonstrated significant CFS score decrease (P<0.05). OSDI was significantly lower in group A than group B (P<0.05). No significant differences were noted in CFS score and BUT between groups. After 6 months, OSDI, CFS score, and BUT were 18.9 (9.3, 34.2), 7.0 (3.0, 8.5), and 2.0 (1.0, 3.0) s in group A, and 10.9 (3.6, 35.4), 5.5 (2.8, 10.0), and 2.0 (1.0, 10.0) s in group B. In both groups, CFS scores significantly decreased and BUT increased (P<0.05). Visual acuity improved significantly in group A at 1, 3, and 6 months (P<0.05), while no significant changes were seen in group B. Irritation symptoms were transient and self-resolving in both groups. Conclusions: Both 0.05% cyclosporine A and 0.1% tacrolimus eye drops, when combined with local glucocorticoids, exhibited significant anti-inflammatory effects, effectively and safely treating severe dry eye in cGVHD patients. Although the onset of 0.05% cyclosporine A was slower than 0.1% tacrolimus, it offered more stable long-term effects and better symptom improvement.

Bacillus-Derived Manganese Superoxide Dismutase Relieves Ocular-Surface Inflammation and Damage by Reducing Oxidative Stress and Apoptosis in Dry Eye.

We hypothesized that antioxidative enzymes supplementation could be a treatment option for dry eye. We investigated the efficacy of oral administration of Bacillus-derived superoxide dismutase (Bd-SOD) in a murine experimental dry eye (EDE). In part I, mice were randomly assigned to normal control, EDE, and mice groups that were treated with oral Bd-SOD after induction of EDE (EDE + Bd-SOD group; four mice in each group). Expression of SOD2, a major antioxidant enzyme with manganese as a cofactor, was assessed by immunofluorescence staining. In part II, mice were divided into seven groups (six mice in each group): normal control, EDE, vehicle-treated, topical 0.05% cyclosporin A (CsA)-treated, and oral Bd-SOD-treated (2.5, 5.0, and 10.0mg/kg Bd-SOD) groups. Tear volume, tear-film break-up time (TBUT), and corneal fluorescein-staining scores (CFS) were measured at zero, five, and 10days after treatment. Tendays after treatment, 2',7'-dichlorodihydrofluorescein diacetate for reactive oxygen species (ROS), enzyme-linked immunosorbent for malondialdehyde, and TUNEL assays for corneal apoptosis, flow cytometry inflammatory T cells, and histological assessment were performed. Compared to the normal control group in part I, the EDE group showed significantly decreased SOD2 expression by immunofluorescence staining. However, the EDE + Bd-SOD group recovered similar to the normal control group. In part II, ROS, malondialdehyde, and corneal apoptosis were decreased in CsA and all Bd-SOD-treated groups. Corneal and conjunctival inflammatory T cells decreased, and conjunctival goblet cell density increased in CsA-treated and Bd-SOD-treated groups. Compared to the CsA-treated group, the 2.5mg/kg Bd-SOD-treated group showed increased TBUT and decreased inflammatory T cells, and the 5.0mg/kg Bd-SOD-treated group showed decreased CFS and increased conjunctival goblet cells. Oral Bd-SOD administration might increase autogenous SOD2 expression in ocular surface tissue in EDE and could be developed as a complementary treatment for DE in the future.

Comparative Evaluation of Matrix Metalloproteinase-9 Immunoassay and Tear Osmolarity Measurement for Diagnosing Severity of Dry Eye Disease.

To evaluate and compare the clinical efficacy of matrix metalloproteinase-9 (MMP-9) immunoassay and tear osmolarity measurement in diagnosing dry eye severity. Dry eye disease (DED) patients underwent diagnostic tests including MMP-9 assay, tear osmolarity measurement, fluorescein tear breakup time, ocular surface staining, anesthetized Schirmer test, Ocular Surface Disease Index questionnaire, and slit-lamp examination. The dry eye parameters were compared according to positive MMP-9 status and increased tear osmolarity. The correlation between dry eye profiles and MMP-9 positivity and high tear osmolarity was also analyzed. Those who tested positive in MMP-9 immunoassay had significantly higher corneal fluorescein staining score and worse DED severity than those who tested negative. The intensity of MMP-9 positivity showed positive correlation with the corneal staining score and DED severity. However, DED patients with high tear osmolarity above 308 mOsm/L did not show significantly different dry eye signs and symptoms compared to those with lower tear osmolarity values. Tear osmolarity was associated with ocular surface staining score in severe DED patients. MMP-9 positivity was associated with ocular surface staining and worse dry eye severity. Therefore, it may be used as a useful indicator of disease severity in conjunction to other diagnostic tests.

Clinical Characteristics and Tear Film Biomarkers in Patients With Chronic Dry Eye Disease After Femtosecond Laser-Assisted Laser in Situ Keratomileusis.

To investigate clinical characteristics and tear film biomarkers of patients with chronic dry eye disease (DED) following femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). Patients were divided into the chronic DED after FS-LASIK (n = 36), DED without FS-LASIK (n = 39), and normal control (without FS-LASIK; n = 34) groups. Dry eye, pain, and psychological-related symptoms were evaluated using the Ocular Surface Disease Index (OSDI), Numerical Rating Scale (NRS), Neuropathic Pain Symptom Inventory Modified for the Eye (NPSI-Eye), and Hamilton Anxiety Rating Scale (HAMA) questionnaires. Ocular surface parameters, tear cytokines, and neuropeptide concentrations were evaluated with specific tests. The DED after FS-LASIK group showed higher corneal fluorescein staining scores, but lower OSDI and NPSI-Eye scores than the DED without FS-LASIK group (all P < .05). Corneal sensitivity and nerve density decreased in the DED after FS-LASIK group (all P < .01). Granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-17A, IL-23, alpha-melanocyte stimulating hormone (α-MSH), oxytocin, and substance P levels were highest in the DED after FS-LASIK group, followed by the DED without FS-LASIK and normal control groups (all P < .05). Interferon-γ and neurotensin levels were only significantly higher in the DED after FS-LASIK group (all P < .05). Patients with chronic DED after FS-LASIK showed milder ocular symptoms, greater epithelial damage, and higher levels of tear inflammatory cytokines and neuropeptides than patients with DED without FS-LASIK, indicating that the nervous and immune systems may play significant roles in FS-LASIK-related chronic DED development. [J Refract Surg. 2023;39(8):556-563.].

Clinical Features of Sjögren Syndrome-Related Dry Eye Disease in Anterior Segment Photographs.

Dry eye disease (DED) is a major complication of autoimmune disorders, including Sjögren syndrome (SS), ocular graft-versus-host disease, and other rheumatic diseases. DED often affects patients' quality of life, necessitating early detection and treatment. However, no simple screening method for DED has yet been established in ophthalmologic practice. This retrospective study aimed to identify the characteristic features of SS-related DED from anterior segment images. Five hundred two cases (SS, 68 cases; ocular graft-versus-host disease, 50 cases; other conditions, 27 cases; simple DED, 72 cases; and no DED, 97 cases) were enrolled. The inferior corneal fluorescein staining score (CFS_I) was significantly higher in the SS group ( P < 0.001). Moreover, the nasal lissamine green staining score (LG_N) was high in the SS group ( P < 0.001). The sensitivity, specificity, and area under the curve of the receiver operating characteristic curve were calculated for the CFS_I plus LG_N in relation to the SS-positive and SS-negative statuses; the sensitivity and specificity were 80.6% and 91.1%, respectively, with an area under the curve of 0.926. A positive CFS_I combined with a positive LG_N correlates with a high risk for SS. A positive CFS_I and a positive LG_N are important signs for an immune-related DED, especially SS, and may be useful in the early detection of SS-related DED.

Effectiveness and Adherence of Dry Eye Patients Who Switched from Short- to Long-Acting Diquafosol Ophthalmic Solution.

Long-acting (lasting extend) diquafosol ophthalmic solution 3% (DQSLX) is administered three times daily versus six times daily for the currently approved diquafosol ophthalmic solution (DQS). We investigated the efficacy and adherence of switching from DQS to DQSLX in patients with dry eye disease. We retrospectively enrolled 54 patients (17 men and 37 women) with eye drop prescription changes from DQS to DQSLX between December 2022 and March 2023. The number of eye drops, subjective symptoms, tear breakup time (TBUT), and fluorescein staining scores from baseline to 4 weeks after starting DQSLX were evaluated. Participants then chose between DQSLX and DQS. Patients administered DQSLX three times per day, as listed on the package insert, 88.9% of the time; significantly higher than the 5.6% of patients who used DQS six times per day, as instructed. The DQSLX group showed significant improvements in symptoms and fluorescein staining scores (23.3 ± 20.1 and 0.8 ± 1.7, respectively) compared with the baseline (37.8 ± 24.1 and 1.1 ± 1.5, p = 0.01 and <0.001, respectively). The TBUT in the DQSLX group (5.0 ± 2.5 s) did not significantly improve compared to the DQS group (4.5 ± 1.7 s) (p = 0.75). Fifty-one (94.4%) patients opted to continue DQSLX because of the pleasant feeling of the eye drops, long-lasting moisture, and less frequent administration. The efficacy and adherence of DQSLX was comparable to DQS.

Increased METTL3 expression and m6A RNA methylation may contribute to the development of dry eye in primary Sjögren’s syndrome

BackgroundPrimary Sjögren’s syndrome (pSS) is a chronic autoimmune disorder defined by xerostomia and keratoconjunctivitis sicca, and its etiology remains unknown. N6-methyladenosine (m6A) is the predominant posttranscriptional modification in eukaryotic mRNAs and is dynamically regulated by m6A regulators. Dysregulation of m6A modification is closely associated with several autoimmune disorders, but the role of m6A modification in pSS remains unknown. This study investigated the potential role of m6A and m6A-related regulators in pSS patients with dry eye.MethodsThis cross-sectional study included forty-eight pSS patients with dry eye and forty healthy controls (HCs). Peripheral blood mononuclear cells (PBMCs) were isolated, and the level of m6A in total RNA was measured. The expression of m6A regulators was determined utilizing real-time PCR and western blotting. The serological indicators detected included autoantibodies, immunoglobulins (Igs), complement factors (Cs), and inflammatory indicators. Dry eye symptoms and signs were measured, including the ocular surface disease index, Schirmer’s test (ST), corneal fluorescein staining score (CFS), and tear break-up time. Spearman’s correlation coefficient was employed to assess the associations of m6A and m6A-related regulator expression with clinical characteristics.ResultsThe expression level of m6A was markedly increased in the PBMCs of pSS patients with dry eye compared to HCs (P value<0.001). The relative mRNA and protein expression levels of the m6A regulators methyltransferase-like 3 (METTL3) and YT521-B homology domains 1 were markedly elevated in pSS patients with dry eye (both P value<0.01). The m6A RNA level was found to be positively related to METTL3 expression in pSS patients (r = 0.793, P value<0.001). Both the m6A RNA level and METTL3 mRNA expression correlated with the anti-SSB antibody, IgG, ST, and CFS (all P values < 0.05). The m6A RNA level was associated with C4 (r = -0.432, P value = 0.002), while METTL3 mRNA expression was associated with C3 (r = -0.313, P value = 0.030).ConclusionsOur work revealed that the upregulation of m6A and METTL3 was associated with the performance of serological indicators and dry eye signs in pSS patients with dry eye. METTL3 may contribute to the pathogenesis of dry eye related to pSS.

Systemic antibiotic treatment for meibomian gland dysfunction-A systematic review and meta-analysis.

To review the efficacy and safety of oral doxycycline antibiotics versus macrolides in the treatment of meibomian gland dysfunction (MGD). Systematic review and meta-analysis. We performed a systematic search of electronic databases for all peer-reviewed published studies which included clinical outcomes of oral antibiotic MGD treatment. Individual study data were extracted and evaluated in a weighted pooled analysis, including total sign and symptom scores, meibomian gland secretion score, tear break-up time (TBUT), fluorescein staining score and rate of complications. Two thousand nine hundred and thirty-three studies were found, of which 54 were eligible for the systematic review, and six prospective studies were ultimately included for analysis, reporting on 563 cases from three countries. Age of affected patients ranged between 12 and 90 years. Overall, both treatment methods induced improvement in MGD signs and symptoms. In pooled analysis, macrolides were significantly superior in the total signs score (pooled standardized mean difference (SMD) -0.51, 95% confidence interval (CI): -0.99 to -0.03), meibomian gland secretion score (pooled SMD -0.25, 95%CI: [-0.48, -0.03]), TBUT (SMD -0.31, 95%CI: [-0.50, -0.13]) and fluorescein staining score (SMD -1.01, 95%CI: [-1.72, -0.29]). Moreover, while no severe complications were reported for both treatments, the macrolide group exhibited significantly less adverse events (pooled odds ratio 0.24 with a 95% CI of 0.16 to 0.34). Both macrolides and tetracyclines are effective treatments for MGD. In this study, macrolides exhibited better efficacy and safety profile compared to tetracyclines.

Combination therapy with 3% diquafosol tetrasodium ophthalmic solution and sodium hyaluronate: an effective therapy for patients with dry eye after femtosecond laser-assisted in situ keratomileusis.

To assess the effect of combination therapy with 3% diquafosol tetrasodium (DQS) and sodium hyaluronate (HA) for dry eye after femtosecond laser-assisted in situ keratomileusis (FS-LASIK). Prospective nonrandomized comparative trial. The prospective study included 80 eyes of 40 patients who underwent FS-LASIK with or without preoperative dry eye. Patients were divided into a combination group and a HA group according to their willingness and the doctor's advice. The combination group was treated with DQS six times a day and HA four times a day, and the HA group was treated with HA four times a day after FS-LASIK. Ocular surface disease index (OSDI), ocular symptom score, vision-related score, environmental score, tear meniscus height (TMH), first non-invasive tear breakup time (NIBUT-First), average non-invasive tear breakup time (NIBUT-Ave), tear breakup time (TBUT), Schirmer I test (SIT), corneal fluorescein staining score (CFS), bulbar redness score, limbal redness score, lipid layer grade (LLG), meiboscore, lid margin abnormality, corneal sensitivity, and corneal nerve parameters were examined before surgery and at 1 week and 1 month after surgery. Surface regularity index (SRI) was also examined before surgery and at 1 month postoperatively. OSDI score (p = 0.024) and vision-related score (p = 0.026) were significantly lower in the combination group than in the HA group at 1 month after FS-LASIK, especially in patients with preoperative dry eye symptoms. The increasements of CFS (p = 0.018), bulbar redness score (p = 0.021), and limbal redness score (p = 0.009) were significantly lower in the combination group than in the HA group at 1 week after FS-LASIK. But other ocular surface parameters showed no difference between both groups at 1 week and 1 month after FS-LASIK. LLG was significantly higher in the combination group than in the HA group at 1 week (p = 0.004) and 1 month (p < 0.001) after surgery, especially in patients with high meiboscore. Additional DQS significantly improved corneal sensitivity in patients without preoperative dry eye symptoms at 1 month after FS-LASIK (p = 0.041). The combination therapy with DQS and HA significantly relieved subjective symptoms, improved ocular surface status, and had the potential to promote corneal nerve growth in patients after FS-LASIK.

A preliminary study on the tear matrix metalloproteinase 9 point-of-care assay using a domestic kit

Objective: To compare the point-of-care assays for tear matrix metalloproteinase 9 (MMP-9) using domestic and InflammaDry kits, and to evaluate the feasibility of diagnosing dry eye with the domestic kit. Methods: It was a cross-sectional study. Thirty dry eye patients and 30 age-and sex-matched normal volunteers were continuously enrolled in this cross-sectional study from June 2022 to July 2022. Both domestic and InflammaDry kits were used to detect the tear MMP-9 levels. The positive rates were recorded for qualitative analysis, and the gray ratios of bands (the gray value of detection bands to that of control bands) were collected for quantitative analysis. The correlations of MMP-9 levels with age, ocular surface disease index, fluorescence tear break-up time, tear meniscus height, Schirmer's Ⅰ test score, corneal fluorescein staining score, and meibomian gland dropout were analyzed. The Mann-Whitney U test, paired Chi-square test, Kappa test, and Spearman's correlation coefficient were used for statistical analysis. Results: There were 14 males and 16 females (30 eyes) in the control group, and their age was (39.37±19.55) years. In the dry eye group, 11 males and 19 females (30 eyes), aged (46.87±17.85) years, had moderate to severe dry eye. The positive rates of MMP-9 in tear fluid were significantly different between dry eye patients (InflammaDry: 86.67%; domestic kit: 70.00%) and controls (InflammaDry: 16.67%, P<0.001; domestic kit: 6.67%, P<0.001). Although the sensitivity of the domestic kit was lower than that of the InflammaDry kit (70.0% vs. 86.7%, P=0.001), the specificity was higher (93.3% vs. 83.3%, P=0.001). In dry eye patients, the positive coincidence rate was 80.7% (21/26), the negative coincidence rate was 100% (4/4), and the total coincidence rate was 83.3% (25/30), with no significant difference between the two kits (McNemar test: χ2=3.20, P>0.05), and the results of both kits were consistent (Kappa=0.53, P=0.001). The Spearman's correlation coefficient showed the gray ratios using both kits were positively correlated with the corneal fluorescein staining score (InflammaDry: ρ=0.48, P<0.05; domestic kit: ρ=0.52, P=0.003). Conclusion: The performances of the domestic and InflammaDry kits are consistent in the point-of-care assay for tear MMP-9, and the domestic kit has lower sensitivity but higher specificity.