Cellulose Acetate Phthalate-Based pH-Responsive Cyclosporine A-Loaded Contact Lens for the Treatment of Dry Eye.

Cyclosporine A (CsA) as an eye drop is an effective treatment for dry eye. However, it has potential side effects and a short ocular residence time. To overcome these obstacles, we developed a cellulose acetate phthalate-based pH-responsive contact lens (CL) loaded with CsA (CsA-CL). The CsA was continuously released from the CsA-CL at physiological conditions (37 °C, pH 7.4) without an initial burst. CsA was well-contained in the selected storage condition (4 °C, pH 5.4) for as long as 90 days. In safety assays, cytotoxicity, ocular irritation, visible light transmittance, and oxygen permeability were in a normal range. CsA concentrations in the conjunctiva, cornea, and lens increased over time until 12 h. When comparing the therapeutic efficacy between the normal control, experimental dry eye (EDE), and treatment groups (CsA eye drop, naïve CL, and CsA-CL groups), the tear volume, TBUT, corneal fluorescein staining at 7 and 14 days, conjunctival goblet cell density, and corneal apoptotic cell counts at 14 days improved in all treatment groups compared to EDE, with a significantly better result in the CsA-CL group compared with other groups (all p < 0.05). The CsA-CL could be an effective, stable, and safe option for inflammatory dry eye.

Melatonin Type 2 Receptor Activation Regulates Blue Light Exposure-Induced Mouse Corneal Epithelial Damage by Modulating Impaired Autophagy and Apoptosis.

The MT1/2 receptors, members of the melatonin receptor, belong to G protein-coupled receptors and mainly regulate circadian rhythms and sleep in the brain. Previous studies have shown that in many other cells and tissues, such as HEK293T cells and the retina, MT1/2 receptors can be involved in mitochondrial homeostasis, antioxidant, and anti-inflammatory responses. In our study, we aimed to investigate the effects of blue light (BL) exposure on the expression of melatonin and its receptors in the mouse cornea and to evaluate their functional role in corneal epithelial damage. After exposing 8-week-old C57BL/6 mice to BL at 25 and 100 J/cm2 twice a day for 14 days, a significant increase in the expression of 4-HNE and MT2 was observed in the cornea. MT2 antagonist-treated mice exposed to BL showed an increased expression of p62 and decreased expression of BAX and cleaved caspase 3 compared with mice exposed only to BL. In addition, MT2 antagonist-treated mice showed more enhanced MDA and corneal damage. In conclusion, BL exposure can induce MT2 expression in the mouse cornea. MT2 activation can modulate impaired autophagy and apoptosis by increasing the expression of BAX, an apoptosis activator, thereby regulating the progression of corneal epithelial damage induced by BL exposure.

Blue Light Induces Impaired Autophagy through Nucleotide-Binding Oligomerization Domain 2 Activation on the Mouse Ocular Surface.

In this study, we investigated the effects of blue light exposure on nucleotide-binding oligomerization domain 2 (NOD2) expression on the mouse ocular surface and evaluated the role of NOD2 activation in light-induced cell death. Mice were divided into wild-type (WT), NOD2-knock out (KO), WT + blue light (WT + BL), and NOD2-KO + blue light (NOD2-KO + BL) groups, and the mice in the WT+BL and NOD2-KO + BL groups were exposed to blue light for 10 days. After 10 days of blue light exposure, increased reactive oxygen species and malondialdehyde were observed in the WT + BL and NOD2-KO + BL groups, and the WT + BL group showed a higher expression of NOD2 and autophagy related 16 like 1. Although both WT+BL and NOD2-KO + BL groups showed an increase in the expression of light chain 3-II, NOD2-KO + BL mice had a significantly lower p62 expression than WT + BL mice. In addition, NOD2-KO+BL mice had significantly lower corneal epithelial damage and apoptosis than WT + BL mice. In conclusion, blue light exposure can induce impaired autophagy by activation of NOD2 on the ocular surface. In addition, the reactive oxygen species (ROS)-NOD2-autophagy related 16 like 1 (ATG16L) signaling pathway may be involved in the blue-light-induced autophagy responses, resulting in corneal epithelial apoptosis.

Effects of eye drops containing a mixture of 3% diquafosol sodium and tocopherol acetate (vitamin E) on the ocular surface of murine dry eye.

PURPOSE: To investigate the efficacy of topical application of 3% diquafosol sodium (DQS) and tocopherol (TCP) acetate mixtures in a mouse model of experimental dry eye (EDE). METHODS: After exposure to desiccating stress for 5 days, eye drops consisting of 3% DQS alone, 0.01% TCP alone, or 3% DQS and 0.005% or 0.01% TCP mixture were applied for the treatment of EDE. Tear volume, tear film break-up time (TBUT), corneal fluorescein staining scores (CFSS), and tear film lipid layer grades (TFLLG) were measured at 0, 5 and 10 days after treatment. The 2',7'-dichlorodihydrofluorescein diacetate assay (DCFDA) for reactive oxygen species (ROS) production, enzyme-linked immunosorbent assay (ELISA) for malondialdehyde (MDA), and flow cytometry for CD4 + interferon (IFN)-γ+ T cells were evaluated on the ocular surface at 10 days after treatment. In addition, levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and chemokine CC motif ligand 4 (CCL4) in the conjunctiva were measured using a multiplex immunobead assay, and conjunctival goblet cells were counted by periodic acid-Schiff staining at 10 days after treatment. RESULTS: Both the TCP mixture groups indicated a significant improvement in TBUT, ROS production, and MDA concentrations compared to those in the DQS alone group. Furthermore, the 0.01% TCP mixture group also showed higher tear film lipid layer grades and conjunctival goblet cell density and lower corneal fluorescein staining scores, number of CD4 + IFN-γ+ T cells, and levels of TNF-α, IL-1ß, and CCL4 than the DQS alone group (P < 0.05). CONCLUSIONS: Application of eye drops containing the mixture of DQS and TCP could stabilize the tear film lipid layer, improve TBUT and corneal epithelial damages, decrease ROS production, inflammatory molecules, and T cells, and increase conjunctival goblet cell density on the ocular surface. Topical DQS and TCP mixtures may have a greater therapeutic effect on clinical signs, oxidative damage, and inflammation of dry eye than DQS eye drops.

Influence of virtual reality on visual parameters: immersive versus non-immersive mode.

BACKGROUND: To investigate the differences in refraction, accommodative factors, visual parameters, and subjective symptoms after using two types of virtual reality (VR) content with different depths of perception. METHODS: Twenty-three volunteers, who played VR games in two modes (immersive and non-immersive) for 30 min, were enrolled. Visual parameters were examined before and after using VR. Accommodative factors were measured using static and dynamic methods. Subjective symptoms were assessed using a questionnaire. Differences according to VR content were compared, and correlations between each visual parameter were analyzed. RESULTS: There were no changes in refraction or accommodative factors after use of the VR. However, there was a significant increase in the near point of accommodation (NPA), the near point of convergence (NPC), and subjective symptom scores after using the immersive mode. Correlation analysis revealed a positive correlation between baseline values of near exophoria and mean accommodative lag of the dominant eye, and also revealed a negative correlation between NPA and mean accommodative lag in the non-dominant eye. CONCLUSIONS: The use of VR for 30 min increased NPA and NPC, especially after the immersive mode was used. In addition, higher exophoria and smaller NPA is associated with increased accommodative lag after using VR.

Clinical characteristics of dry eye with ocular neuropathic pain features: comparison according to the types of sensitization based on the Ocular Pain Assessment Survey.

BACKGROUND: To compare the clinical characteristics of dry eye patients with ocular neuropathic pain features according to the types of sensitization based on the Ocular Pain Assessment Survey (OPAS). METHODS: Cross-sectional study of 33 patients with dry eye and ocular neuropathic pain features. All patients had a comprehensive ophthalmic assessment including detailed history, the intensity and duration of ocular pain, the tear film, ocular surface, and Meibomian gland examination, and OPAS. Patients with < 50% improvement in pain intensity after proparacaine challenge test were assigned to the central-dominant sensitization group (central group) and those with ≥50% improvement were assigned to the peripheral-dominant sensitization group (peripheral group). All variables were compared between the two groups. RESULTS: No significant differences were observed in age, sex, underlying diseases, history of ocular surgery, duration of ocular pain, tear film, ocular surface and Meibomian gland parameters (all p > 0.05). Ocular pain and non-ocular pain severity and the percentage of time spent thinking about non-ocular pain were significantly higher in the central group than in the peripheral group (all p < 0.05). Central group complained more commonly of a burning sensation than did the peripheral group (p = 0.01). CONCLUSIONS: Patients with central-dominant sensitization may experience more intense ocular and non-ocular pain than the others and burning sensation may be a key symptom in those patients.

Effect of epidermal growth factor ointment on persistent epithelial defects of the cornea.

BACKGROUND: Healthy corneal epithelium acts as a barrier against damage to the deeper structures in the eye. Failure in the mechanisms of corneal epithelization can lead to persistent epithelial defects of the cornea (PEDs) and can compromise its function. Epidermal growth factor (EGF) promotes the proliferation, migration, and differentiation of epithelial cells, endothelial cells, and fibroblasts during wound healing and may be beneficial in treating patients with PEDs. We, therefore, investigated the effect of EGF ointment on patients with PEDs. METHODS: Fifteen patients with PEDs refractory to conventional treatment were treated twice a day with EGF ointment. Patient demographics and comorbidities were noted. The epithelial healing time was determined along with the primary outcome measures in the areas of the epithelial defects, visual acuity, visual analog scale (VAS) scores, and esthesiometer scores 1 month and 2 months after treatment. RESULTS: Five eyes of herpetic keratitis (33.3%), 3 eyes of dry eye disease (20.0%), 3 eyes of bacterial keratitis (20.0%), 2 eyes of limbal stem cell deficiency (13.3%), 1 eye of diabetic neurotrophic keratitis (6.7%), and 1 eye of filamentary keratitis (6.7%) were associated with PEDs, respectively. Two months following treatment with EGF ointment, there was a reduction in the area of the epithelial defects (5.7 ± 3.9 to 0.1 ± 0.3 mm2) as well as a significant improvement in best-corrected visual acuity (0.9 ± 0.8 to 0.6 ± 0.5 LogMAR) and VAS scores (4.5 ± 1.2 to 2.5 ± 0.7) in 12 eyes (80%). Among these cases, the mean epithelial healing time was 5.5 ± 1.8 weeks. Amniotic membrane transplantation was performed on the remaining 3 (20.0%) patients that did not respond to EGF treatment. CONCLUSIONS: EGF ointment could reduce symptoms and promotes corneal epithelialization of refractory PEDs. It may, therefore, be well-tolerated and a potentially beneficial addition in the management of refractory PEDs.

Comparison of the Therapeutic Efficacies of Topical Rivoceranib and Topical Bevacizumab in a Murine Model of Corneal Neovascularization.

Background and Objectives: Corneal neovasculariziation (CNV) is a serious vision-threatening complication; however, all therapeutics have their clinical limitations. The aim of this study is to investigate the efficacy of topical rivoceranib compared with topical bevacizumab in a murine model of corneal neovascularization (CNV). Materials and Methods: Murine CNV was induced by means of total de-epithelization and alkali burn. Mice were divided into five groups according to topical treatment: untreated control, phosphate-buffered saline (PBS), 0.1% and 0.5% rivoceranib, and 0.5% bevacizumab. CNV area and index were measured 7 and 14 days after treatment. After corneal tissues were excised at day 14, the blood and lymphatic vessels were quantified by cluster of differentiation 31 (CD31) and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) immunofluorescence, respectively. Results: After 14 days, treatment groups with 0.1% and 0.5% rivoceranib and 0.5% bevacizumab showed a decrease in CNV area and index compared with the untreated and PBS groups (all p < 0.01). Blood and lymphatic vascularization significantly decreased in the 0.5% rivoceranib and 0.5% bevacizumab groups, as measured by CD31 and LYVE1 immunofluorescence. There was no significant difference of vascularization between the 0.5% rivoceranib and bevacizumab groups. Conclusions: Topical application of rivoceranib could effectively decrease CNV equivalent to topical bevacizumab in a murine model.

Effectiveness of photodynamic therapy with verteporfin combined with intrastromal bevacizumab for corneal neovascularization in Stevens-Johnson syndrome.

PURPOSE: To investigate the effectiveness of combined photodynamic therapy with verteporfin and intrastromal injection of bevacizumab for the treatment of corneal neovascularization in patients with Stevens-Johnson syndrome (SJS). METHODS: Eight eyes of eight patients with SJS having corneal neovascularization who were refractory to 1% prednisolone instillation received photodynamic therapy with verteporfin (6 mg/m2) combined with intrastromal bevacizumab injection (2.5 mg/0.1 mL). Best-corrected visual acuity and intraocular pressure were assessed, and slit-lamp biomicroscopic examination was performed before treatment and at 1 week and every month. A chronic ocular manifestation score was assigned based on the involvement area or the severity before treatment. The cumulative length of corneal blood vessels and area of corneal neovascularization were measured by anterior segment photographs before and after treatment. RESULTS: At 3 and 6 months after treatment, all eyes showed regression of corneal neovascularization. Complete regression was achieved in five eyes (62.5%) and partial regression in three eyes (37.5%). Among five patients who were followed up for more than 1 year, two eyes maintained complete regression and one eye maintained partial regression at 1 year. However, two eyes with severe chronic ocular manifestation showed revascularization. CONCLUSIONS: Combined photodynamic therapy with intrastromal bevacizumab injection can effectively inhibit corneal neovascularization in patients with SJS. However, patients with severe chronic ocular manifestation may exhibit revascularization.

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

Purpose: 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). Methods: 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 10.0 mg/kg Bd-SOD) groups. Tear volume, tear-film break-up time (TBUT), and corneal fluorescein-staining scores (CFS) were measured at zero, five, and 10 days after treatment. Ten days 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. Results: 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 2.5 mg/kg Bd-SOD-treated group showed increased TBUT and decreased inflammatory T cells, and the 5.0 mg/kg Bd-SOD-treated group showed decreased CFS and increased conjunctival goblet cells. Conclusions: 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.

Long-term clinical outcomes and predictive factors in patients with chronic ocular graft-versus-host disease.

We investigate long-term clinical outcomes and predictive factors associated with poor vision outcomes in patients with ocular graft-versus-host disease (oGVHD). This retrospective cohort study involved 94 patients with chronic oGVHD, classified into severe (n = 25) and non-severe (n = 69) groups. Factors associated with oGVHD severity and poor vision outcomes were examined using multivariate logistic regression. In the severe oGVHD group, the disease activity pattern tended to be persistent, whereas flare-up episodes were more frequent and occurred over shorter intervals in this group. Myelodysplastic syndrome (MDS) and lung GVHD were more common and systemic calcineurin inhibitors were used more frequently in the severe group than in the non-severe group. Finally, 5-year survival rates were poorer in the severe group. Multivariate analysis revealed that MDS, lung GVHD involvement, and no history of systemic calcineurin inhibitor use were risk factors for severe oGVHD. Risk factors for poor vision outcomes were conjunctival scarring and persistent epithelial defects. In conclusion, MDS, lung GVHD, and no history of systemic calcineurin inhibitors are associated with severe oGVHD. Conjunctival scarring and persistent epithelial defects are risk factors for poor vision outcomes.

Tear Neuromediators in Subjects with and without Dry Eye According to Ocular Sensitivity.

To investigate differences of tear neuromediators between subjects with and without dry eye (DE) depending on the ocular sensitivity. Thirty-one subjects with DE and 29 subjects without DE were recruited in this study. The eyes were stimulated by exposure to an irritating product applied to the periocular region. Both DE and non-DE subjects were divided into the high sensitivity and low sensitivity groups based on the degree of ocular sensitivity to ocular irritation. Baseline tear film break-up time (TBUT) and corneal staining score were examined, and tear samples were collected. The concentrations of the tear neuromediators, including nerve growth factor (NGF), serotonin, calcitonin gene-related peptide (CGRP), substance P, neuropeptide Y, and vasoactive intestinal peptide were measured using the enzyme-linked immune sorbent assay. The baseline neuromediator concentrations were compared between subjects with and without DE based on ocular sensitivity. In both DE and non-DE subjects, baseline TBUT was significantly lower in the high sensitivity group than in the low sensitivity group. In the high sensitivity group, baseline tear NGF levels were higher in subjects with DE than in those without DE. In the low sensitivity group, baseline levels of tear CGRP were lower in subjects with DE than in those without DE. Tear neuromediators associated with DE had differences in their concentrations depending on ocular sensitivity. In patients with DE, tear NGF levels increased with high ocular sensitivity to ocular irritation, whereas tear CGRP levels decreased with low ocular sensitivity.

Clinical Comparison of Fusarium Keratitis according to the Initial Potassium Hydroxide (KOH) Smear: A Retrospective Study in South Korea.

Purpose: This study aimed to compare predisposing factors, clinical characteristics, treatment, and prognosis of Fusarium keratitis according to the result of the initial potassium hydroxide (KOH) smear. Methods: This is a retrospective study of cases with Fusarium keratitis between January 2000 and December 2019 at two tertiary hospitals in South Korea. Patients were divided into two groups depending on the KOH smear result (KOH-positive and KOH-negative group), and its clinical factors were analyzed. Results: Among 319 fungal keratitis, seventy-nine cases were identified with Fusarium keratitis. Forty-seven cases (59.5%) were negative in the initial KOH smear prior to their diagnosis. The most common predisposing factor for Fusarium keratitis was ocular trauma (55.7%). There were no significant differences in sex, occupation, ulcer size or shape, hypopyon, and initial visual acuity between the two groups. Differences were observed between the KOH-positive group and the KOH-negative group in terms of deep corneal infiltration (50.0% vs. 78.7%, p=0.008) and evisceration treatment (3.1% vs. 25.5%, p=0.008). The delayed time to initiate antifungal eye drops was longer in the KOH-negative group (1.13 ± 0.49 vs. 3.93 ± 4.89, p=0.002). Only the KOH-negative group combined bacterial infection. The significant risk factors for poor clinical outcomes were the central corneal lesion (odds ratio (OR) 3.50, p=0.047), a large ulcer size (size ≥ 7.5 mm2) (OR 4.98, p=0.009), and endothelial plaque (OR 7.00, p=0.031). Conclusion: Initial KOH-negative patients often needed evisceration and had worse final visual outcomes. The delay of prompt initiation of antifungal treatment and combined bacterial infection result in a poor prognosis. This study highlights the initial KOH effect on early diagnosis and early treatment of Fusarium keratitis.

Comparative analysis of 0.1% cyclosporin A cationic emulsion and 0.05% cyclosporin A emulsion in murine dry eye cases with different severities.

Dry eye (DE), especially severe DE (SDE), can cause ocular surface defects and reduce the patient's quality of life. Several clinical studies have shown that 0.1% cyclosporin A cationic emulsion (CsA CE) could decrease corneal damage. However, no experimental study has reported the effect of 0.1% CsA CE on SDE. The present study aimed to compare the efficacy of 0.1% CsA CE with that of 0.05% CsA emulsion for ocular surface damage and inflammation in the cases of murine DE with different severities. Following exposure to desiccating stress and subcutaneous injection of scopolamine for 5 days, C57BL/6 female mice were divided into SDE and non-SDE (NSDE) groups based on corneal fluorescein staining scores (CFSs). Mice from both groups were topically treated with 0.05% CsA emulsion or 0.1% CsA CE for 10 days. The results demonstrated that 0.1% CsA CE-treated mice in the SDE and NSDE groups exhibited significant improvements in all the clinical and experimental parameters. Furthermore, the CFS of 0.1% CsA CE-treated mice in the SDE group was lower compared with that of the 0.05% CsA-treated mice. In addition, in the SDE group, 0.1% CsA CE-treated mice had significantly lower levels of nuclear factor-κB activation, inflammatory infiltrations and apoptosis on the ocular surface, and they also exhibited higher conjunctival goblet cell density compared with the 0.05% CsA-treated mice. In summary, these findings indicated that 0.1% CsA CE was more effective than topical 0.05% CsA emulsion at improving corneal epithelial injury and decreasing the levels of inflammatory cytokines and T cells in mice with SDE.

Effects of prolonged use of virtual reality smartphone-based head-mounted display on visual parameters: a randomised controlled trial.

We investigated the effects of using a virtual reality smartphone-based head-mounted display (VR SHMD) device for 2 h on visual parameters. Fifty-eight healthy volunteers were recruited. The participants played games using VR SHMD or smartphones for 2 h on different days. Visual parameters including refraction, accommodation, convergence, stereopsis, and ocular alignment and measured choroidal thickness before and after the use of VR SHMD or smartphones were investigated. Subjective symptoms were assessed using questionnaires. We analyzed the differences in visual parameters before and after the use of VR SHMD or smartphones and correlations between baseline visual parameters and those after the use of the devices. Significant changes were observed in near-point convergence and accommodation, exophoric deviation, stereopsis, and accommodative lag after the use of VR SHMD but not after that of smartphones. The subjective discomfort associated with dry eye and neurologic symptoms were more severe in the VR group than in the smartphone group. There were no significant changes in refraction and choroidal thickness after the use of either of the two devices. The poorer the participants' accommodation and convergence ability the greater the resistance to changes in these visual parameters, and participants with a large exophoria were more prone to worsening of exophoria than those with a small exophoria.

Efficacy of Switching from Cyclosporine A 0.05% Anionic Emulsion to Cyclosporine A 0.1% Cationic Emulsion in Patients with Dry Eye Associated with Sjögren's Syndrome.

Purpose: To evaluate the clinical efficacy of switching from cyclosporine A (CsA) 0.05% anionic emulsion (CsA AE) to CsA 0.1% cationic emulsion (CsA CE) in patients with dry eye (DE) associated with Sjögren's syndrome (SS). Methods: Forty patients with SS-associated DE who were unresponsive to CsA AE for 6 months were enrolled. After baseline measurements, the CsA AE was switched to CsA CE. The ocular surface disease index (OSDI), Sjögren's International Collaborative Clinical Alliance (SICCA), and Schirmer's test scores and tear film breakup time (TBUT) were evaluated at baseline and 1 and 3 months after switching. Results: Two patients dropped out, and 38 were analyzed. OSDI and SICCA ocular staining scores were significantly reduced at 1 and 3 months after switching, compared with the baseline scores (all P < 0.01). Although no significant changes were noted in the corneal staining scores (CSSs), patients with higher baseline CSS (≥4) showed an improvement in the scores at 1 month (P = 0.03) and 3 months (P = 0.01) after switching. There were no significant changes in TBUT and Schirmer's test scores during the follow-up periods. Conclusions: In patients with SS-associated DE, switching from CsA AE to CsA CE was effective in improving ocular symptoms and conjunctival staining. In addition, corneal staining was decreased in patients with severe keratitis.

Topical TRPM8 Agonist for Relieving Neuropathic Ocular Pain in Patients with Dry Eye: A Pilot Study.

BACKGROUND: Activation of TRPM8, a cold-sensing receptor located on the cornea and eyelid, has the potential to relieve the neuropathic ocular pain (NOP) in dry eye (DE) by inhibiting other aberrant nociceptive inputs. We aimed to investigate the effect of a topical TRPM8 agonist, cryosim-3 (C3), on relieving DE-associated NOP. METHODS: We conducted a prospective pilot study of 15 patients with DE-associated NOP. These patients applied topical C3 to their eyelid, 4 times/day for 1 month. The patients underwent clinical examinations. They also completed the Ocular Pain Assessment Survey (OPAS), which is a validated questionnaire for NOP, at baseline, 1 week, and 1 month after treatment. RESULT: At 1 week, the OPAS scores of eye pain intensity, quality of life (driving/watching TV, general activity, sleep, and enjoying life/relations with other people), and associated factors (burning sensation, light sensitivity, and tearing) improved. The total OPAS scores of eye pain intensity, quality of life, and associated factors remained improved at 1 month. The Schirmer test scores also improved at 1 month. CONCLUSION: TRPM8 agonist (C3) could be a novel agent for treating patients with DE-associated NOP who are unresponsive to conventional treatments.

Usefulness of virtual reality-based training to diagnose strabismus.

To study the usefulness of virtual reality (VR)-based training for diagnosing strabismus. Fourteen residents in ophthalmology performed at least 30 VR training sessions to diagnose esotropia and exotropia. Examinations of real patients with esotropia or exotropia before and after the VR training were video-recorded and presented to a strabismus expert to assess accuracy and performance scores for measuring the deviation angle and diagnosing strabismus with anonymization. A feedback survey regarding the usefulness and ease of use of the VR application was conducted for participants. The mean age of the 14 ophthalmology residents (10 men and 4 women), was 29.7 years. Before VR training, participants showed a mean accuracy score of 14.50 ± 5.45 and a performance score of 9.64 ± 4.67 for measuring the deviation angle and diagnosing strabismus in real patients with strabismus. After VR training, they showed a significantly improved accuracy score of 22.14 ± 4.37 (p = 0.012) and a performance score of 15.50 ± 1.99 (p = 0.011). According to the survey, most participants agreed on the usefulness of VR applications. This study suggests that VR-based training improved ophthalmology residents' clinical diagnostic skills for strabismus in a short period.

Treatment Response to Gabapentin in Neuropathic Ocular Pain Associated with Dry Eye.

PURPOSE: To investigate the response to gabapentin treatment in patients with dry eye (DE) accompanied by features of neuropathic ocular pain (NOP), and to analyze the differences between clinical manifestations of the groups according to treatment response. METHODS: We retrospectively reviewed the records of 35 patients with DE accompanied by NOP features and obtained information on their medical history and previous ocular history. The patients underwent clinical examinations of the tear film, ocular surface, and meibomian gland and completed the Ocular Pain Assessment Survey (OPAS). One month after treatment with topical eye drops, add-on of gabapentin treatment was determined according to the Wong-Baker FACES Pain Rating Scale (WBFPS). A reduction of 2 points or more on the WBFPS was considered a positive treatment response. Enrolled patients were divided into three groups according to the treatment response: topical treatment response group (group 1, n = 11); gabapentin response group (group 2, n = 13); and gabapentin non-response group (group 3, n = 11). The medical history, clinical parameters, and OPAS scores were compared between groups. RESULTS: The incidence of systemic comorbidities was higher in group 2 than in other groups. The corneal staining scores were lower in groups 2 and 3 than in group 1. Among the treatment response groups, group 2 showed improvements in OPAS scores of ocular pain severity, pain other than eyes, and quality of life, while group 1 showed improved OPAS scores of ocular pain severity and ocular associated factors. Group 2 exhibited lower scores of pains aggravated by mechanical and chemical stimuli than group 3. CONCLUSIONS: Gabapentin could be effective in patients who have systemic comorbidity and less pain evoked by mechanical and chemical stimuli for the treatment of DE patients with NOP, which is refractory to topical treatment.

Tear Osmolarity and Matrix Metallopeptidase-9 in Dry Eye Associated with Sjögren's Syndrome.

PURPOSE: To evaluate the correlations between tear osmolarity and matrix metallopeptidase-9 (MMP-9) and dry eye (DE) indices in patients with DE associated with Sjögren's syndrome (SS). METHODS: Sixty-three patients with DE associated with SS who underwent tear analysis were included. DE tests performed were ocular surface disease index, tear break-up time, Schirmer's test, ocular staining score, and tear osmolarity and MMP-9 tests. Correlations between tear osmolarity and DE indices, differences between patients with abnormal and normal tear osmolarity, and those between positive and negative MMP-9 patients were analyzed. Patients were classified into four groups according to tear osmolarity and MMP-9 results, and between-group differences were analyzed (group 1: abnormal tear osmolarity, MMP-9 positive; group 2: abnormal tear osmolarity, MMP-9 negative; group 3: normal tear osmolarity, MMP-9 positive; group 4: normal tear osmolarity, MMP-9 negative). RESULTS: Mean age of patients was 54.2 ± 13.9 years, and 96.2% were female. Thirty-five patients had abnormal tear osmolarity and 40 patients were MMP-9 positive. DE indices differed between groups with abnormal and normal tear osmolarity (p < 0.01), but not between positive and negative MMP-9 groups. There were 22 patients in group 1, 13 in group 2, 18 in group 3, and 10 in group 4. Compared to group 4, tear break-up time was shorter in groups 1 (p < 0.01) and 2 (p = 0.02). Schirmer's test values in group 1 were lower than those in group 4 (p = 0.03). Ocular staining score was higher in groups 1 (p < 0.01) and 2 (p < 0.05) than in group 4. CONCLUSIONS: Tear osmolarity was correlated with ocular surface indices in DE associated with SS. Combination of tear osmolarity and MMP-9 test results may be helpful to determine the severity of DE associated with SS.