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PURPOSE The purpose of this article was to study the impact of instillation of 1% fluorescein and mydriatics on measurements made by Scheimpflug imaging. METHODS This was a cross-sectional study of patients who had measurements of corneal shape (maximum keratometry and best fit sphere of anterior and posterior corneal surfaces), pachymetry (at the pupil center, corneal apex, and thinnest location), and anterior chamber parameters (depth, volume, and angle of anterior chamber and corneal volume) using the Pentacam HR before and after the instillation of fluorescein and mydriatics. Group A had baseline measurements that were repeated 1.5 hours after the instillation of 1% fluorescein and 0.8% tropicamide+ 5% phenylephrine eye drops. Group B had baseline measurements that were repeated 10 minutes after the instillation of 1% fluorescein, and group C had baseline measurements that were repeated 1.5 hours after the instillation of mydriatics. RESULTS Overall, 131 eyes of 131 patients were studied: 87 in group A, 28 in group B, and 16 in group C. Significant differences and wide variations were noted in corneal pachymetry and anterior chamber parameters in all 3 groups. The highest magnitude and range of difference was observed in pachymetry at the pupil center (17 ± 53.5 μm) and in anterior chamber volume (26.7 ± 69.8 mm3). Corneal shape measurements of anterior and posterior corneal surfaces were not significantly affected by either fluorescein or mydriatics. Pupillary dilation also affected the ability of the Pentacam to accurately trace the pupil margin in 19.5% of cases. CONCLUSIONS For consistent and accurate measurements, it is important that Scheimpflug imaging be performed before other tests which may need the instillation of fluorescein or mydriatics.

Purpose: NOV03 has a unique dual mode of action to address dry eye disease (DED) associated with meibomian gland dysfunction. SEECASE evaluated the efficacy, safety, and tolerability of NOV03 at 2 dosing regimens compared with a saline comparator in patients with DED. Methods: SEECASE was a prospective, multicenter, randomized, double-masked, saline-controlled clinical study. A total of 336 DED patients [tear film breakup time ≤5 seconds, abnormal meibum secretion, total corneal fluorescein staining (tCFS) score of 4 ≤ X ≤ 11 (National Eye Institute scale), Schirmer of ≥5 mm] were randomized in a 2:2:1:1 manner to NOV03 4 times daily (QID), NOV03 twice daily (BID), saline BID, and saline QID, respectively. The primary efficacy endpoint was tCFS staining at 8 weeks for both regimens. Secondary endpoints included visual analog scales and the Ocular Surface Disease Index questionnaire for symptom assessment. Results: The study met its primary endpoint, change from baseline of tCFS over control, for both dosing regimens QID and BID (P < 0.001 and P = 0.009, respectively). NOV03 also showed pronounced improvement in various symptoms. For the Eye Dryness Score, changes from baseline were statistically significant compared with those of the control at week 8 [P < 0.001 (QID) and P = 0.002 (BID)]. Benefits on tCFS and symptoms started at 2 weeks after start of treatment and were maintained over the study duration. The effects were dosing schedule dependent. NOV03 was well tolerated with instillation site reactions below 3% in both treatment regimes. Conclusions: The SEECASE study demonstrated that NOV03 improves signs and symptoms in patients with highly symptomatic evaporative dry eye disease.

PURPOSE To compare the degree of tear film instability and severity of meibomian gland dysfunction between subjects who use eyeliner and those who do not use eyeliner. METHODS This cross-sectional study included 42 healthy volunteer women who had no dry eye symptoms (Ocular Surface Disease Index score < 13) and aged between 18 and 40 years. The subjects were classified into 2 groups: an eyeliner-use group (EL: regularly used eyeliner ≥3 d/wk and continuously used ≥6 mo) and a noneyeliner-use group as controls. A questionnaire for ocular surface symptoms using a visual analog scale was administered. Then, a number of eye tests were performed [grading of conjunctival inflammation, fluorescein tear breakup time, ocular surface fluorescein staining, Schirmer I, evaluation of meibomian gland (MG) function, detection of eyelid margin abnormalities, and Demodex detection]. RESULTS Tear breakup time was significantly lower in the EL group compared with controls (3.0 ± 1.9 vs. 5.8 ± 2.1 s, P < 0.001). MG grading was significantly higher in the EL group than in controls (P = 0.004); higher grade (grades 2-3) was found in 85.7% of EL and 47.6% of controls. Meiboscore was also higher in EL than in controls (P = 0.001). Regarding the morphological changes in lid margin, only telangiectasia was detected significantly more in EL (28.6%) compared with controls (4.8%) (P = 0.041). Conjunctival inflammation was observed 4 times more in EL (66.7%) than in controls (14.3%), P = 0.001. Other outcomes included ocular surface symptoms and fluorescein staining scores, and Schirmer I and Demodex detection were not significantly different between both groups. CONCLUSIONS The regular use of eyeliner induces tear film instability and MG dysfunction.

Purpose:To test the safety and efficacy of high frequency electrotherapy (ET) on the clinical signs and symptoms of patients affected by dry eye and meibomian gland dysfunction (MGD).Methods:Twenty-five patients affected by MGD were enrolled. Quantum Molecular Resonance ET was administered by means of the Rexon-Eye device 4 times, once per week for 4 weeks. Patients were reexamined 1 month after the last treatment. The primary endpoint was reduction in corneal fluorescein staining. Additional endpoints were tear break-up time, Ocular Surface Disease Index score, meibomian gland secretion score, and the number of expressible meibomian glands. Safety endpoints were Logarithm of the Minimum Angle of Resolution (LogMar) best spectacle-corrected visual acuity and intraocular pressure.Results:Corneal fluorescein staining improved by 62.5% (P < 0.0001), tear breakup time increased by 30.9% (P < 0.0001), and the Ocular Surface Disease Index score improved by 37% (P < 0.001). The meibum quality and the number of expressible meibomian glands also increased (35.7% and 12%, P < 0.001 and P < 0.0001, respectively). Schirmer test scores increased after treatment by 16.5% (P = 0.01). No adverse events were observed.Conclusions:Quantum Molecular Resonance ET appears to be safe and significantly reduces symptoms and signs associated with MGD. It may have a relevant role in the treatment of evaporative dry eye disease.

To investigate changes in the clinical features of patients with dry eye disease (DED) according to short-term outdoor ground-level ozone exposure.This prospective observational study included patients with DED who were treated with the same topical drugs (0.05% cyclosporine or 3% diquafosol) and visited the hospital twice at 2-month intervals. Patients who showed a short tear film breakup time and positive ocular surface staining were assigned to the diquafosol and cyclosporine groups, respectively. The ocular surface disease index (OSDI) score, tear secretion, tear film breakup time, and corneal fluorescein staining score were measured at each visit. The mean ground-level ozone concentration for 1 week before the ocular examinations was used as the ozone exposure level. Changes in dry eye parameters according to changes in ozone concentration were analyzed using univariate and multivariate linear analyses.Thirty-three patients were included in the analysis. The mean age was 55.2 ± 10.5 years. Ozone concentrations were significantly associated with increased OSDI scores (R = 0.304, P = 0.0006) and a decreased tear secretion (R = -0.355, P = 0.0012) in univariate models. In multivariate models, the results were consistent; the OSDI score increased by 3.43 points (β = 3.43, P = 0.002), and tear secretion decreased by 1.43 mm (β = -1.43, P = 0.015) per 0.01 ppm increase in ozone concentrations over a 2-month interval. Notably, the cyclosporine group showed more prominent changes in the OSDI score and tear secretion with changes in the ozone concentration (P0.05).Short-term exposure to increased ground-level ozone concentration led to increased ocular discomfort and decreased tear secretion in patients with DED.

Dry eye disease (DED) is defined by the International Dry Eye Workshop (TFOS DEWS II) as a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles.1 In DED patients, activities requiring prolonged gazing with involuntary suppression of blinking can lead to ocular surface irregularities and corneal epithelium damage,2 both affecting visual function3 and eventually preventing patients from performing basic activities of daily life such as reading, driving, or working with screens.4 Consequently, DED negatively impacts quality of life comparable with other severe diseases.5 Recently, the impact of DED on reading speed has been increasingly investigated,6–11 suggesting that reading speed might be substantially affected by the level of corneal staining, especially under straining conditions in daily life such as prolonged duration of reading. The treatment under investigation, CyclASol 0.1%, is a clear topical water-free ophthalmic solution of cyclosporine A in a novel vehicle, the semifluorinated alkane (SFA)-based EyeSol technology, using the SFA perfluorobutylpentane (abbreviated F4H5). This topical formulation was developed for the treatment of DED with the goal of increasing local bioavailability, avoiding the use of oils, surfactants, and preservatives. Cyclosporine A is an antiinflammatory agent with immunomodulatory properties with proven efficacy in DED.12 Potential benefits of the CyclASol 0.1% formulation in a water-free SFA solution include improved tolerability and decreased visual disturbance compared with typical cyclosporine A formulations, which frequently involve surfactants and oils. A further potential benefit is an improved clinical efficacy because of better local bioavailability. CyclASol has been investigated previously in one phase 1 clinical study with healthy volunteers and one phase 2 clinical study in patients with DED. Both clinical studies showed an excellent tolerability and safety profile. The CyclASol phase 2 study was a randomized, double-masked, vehicle-controlled, dose finding study with CyclASol 0.05% and CyclASol 0.1% and an open-label active comparator and showed a consistent reduction in corneal and conjunctival staining after treatment with CyclASol compared with the vehicle and with the active comparator, with an early onset of effect as of week 2.13 The central area of the cornea, which is an important region relevant to visual function, benefitted most. Thus, reading assessments were included in the present phase 2B/3 study. The treatment effect on cornea staining parameters was more pronounced in patients with higher baseline values of total corneal fluorescein staining (CFS). Therefore, patients with total CFS scores ≥10 [National Eye Institute (NEI) scale] at baseline were chosen for the confirmatory clinical phase 2B/3 study. The 0.1% concentration was selected for its trend toward a better effect on symptoms in the target population. This work presents the results of the phase 2B/3 study CYS-003 (ESSENCE) designed to confirm the efficacy, safety, and tolerability of CyclASol 0.1% ophthalmic solution in comparison with its vehicle (F4H5) for the treatment of signs and symptoms of DED.

To compare the symptoms and signs of dry eye disease (DED) in children with systemic lupus erythematosus (SLE) with those in healthy children using common diagnostic tools.Prospective, observational, single-center cohort study. Thirty-four subjects with SLE and 15 healthy subjects were recruited from the Hospital for Sick Children in Toronto, Canada. Subjects underwent subjective and objective dry eye assessments using the Canadian Dry Eye Assessment (CDEA) questionnaire, tear film osmolarity, slit lamp examination, tear film break-up time, corneal fluorescein staining, Schirmer test 1, and conjunctival lissamine green staining.No difference in symptoms was found between children with SLE and healthy children (CDEA score 6.4 ± 5.4 vs. 3.8 ± 3.2; P = 0.09). Corneal staining was more prevalent in children with SLE than in healthy children (58.8% vs. 20.0%; P = 0.01), and children with SLE had higher mean corneal fluorescein staining scores (1.7 ± 1.7 vs. 0.2 ± 0.4; P = 0.002). No statistically significant differences in tear osmolarity, inter-eye differences in tear osmolarity, tear film break-up time, Schirmer test 1, or lissamine green staining scores were observed between the 2 groups. In healthy children, CDEA scores weakly correlated with corneal fluorescein staining score (r = 0.53, P = 0.04). In children with SLE, no correlation between CDEA score and any of the diagnostic test outcomes was found.There is discordance between symptoms and signs of DED in children with SLE. Corneal fluorescein staining is essential for the diagnosis of DED in these children.

PURPOSE To investigate the temporal and spatial distribution of tear film breakup time via a noninvasive topographer in normal subjects and patients with dry eye disease (DED). METHODS A total of 77 subjects were separated into normal and DED groups based on their symptoms and tear film instabilities. In noninvasive evaluation with Oculus Keratograph, the precorneal tear film was recorded and reconstructed into a two-dimensional map that evolved with time. Whether or not each sector broke and the breakup time if it did were recorded. The map was further grouped into 4 quadrants to reveal the spatial variation. RESULTS By the end of recording, the inferior quadrant in DED subjects had a higher number of broken sectors than other quadrants (P < 0.01). Over the recording period, the cumulative percentage of sectors that were broken rose much quicker in the inferior quadrants, and the inferior quadrant is the only quadrant that showed a significant difference between the normal and DED groups (P < 0.01). This difference peaked at 12 seconds and declined after 15 seconds. Receiver operating characteristic curve for each index always showed the largest differential value in the inferior quadrant. CONCLUSIONS Tear film breakup is not homogenously distributed, with sectors in the inferior quadrant being more likely to break and to break earlier. Between normal and DED subjects, a significant difference of tear film instability is more likely to be found in the inferior quadrant.

Purpose To report a case of microsporidia (Encephalitozoon hellem) keratoconjunctivitis acquired through avian transmission in an immunocompetent adult, diagnosed by metagenomic deep sequencing (MDS), and confirmed by polymerase chain reaction. Methods A case report. Results An 18-year-old woman was referred with unilateral keratoconjunctivitis unresponsive to topical and systemic therapy after exposure to birdcage debris. Slit-lamp examination of the left eye revealed a follicular papillary reaction of the palpebral conjunctiva and multiple corneal punctate epithelial opacities that stained minimally with fluorescein. In vivo confocal microscopy revealed bright double-walled structures and smaller bright round structures in the superficial epithelial debris and epithelium. Molecular diagnosis with MDS of E. hellem was confirmed by polymerase chain reaction. Clinical resolution and normalization of in vivo confocal microscopy was observed after a 6-week course of topical azithromycin. The patient elected a 3-week course of topical voriconazole 1% for definitive antimicrosporidial treatment, with no evidence of persistent infection 1 month later. Conclusions Microsporidial (E. hellem) keratoconjunctivitis can occur through avian transmission in immunocompetent hosts. Topical azithromycin may be effective against this pathogen. MDS has utility in the diagnosis of atypical keratoconjunctivitis.

To evaluate sleep and mood status in patients with dry eye disease (DED) and analyze the association between sleep quality, mood status, and ocular surface characteristics.Consecutive patients with DED (N = 106) and age- and sex-matched healthy controls (N = 50) were enrolled. Tear fluid break up time (TBUT), corneal fluorescein staining, and Schirmer I tests were performed in the order listed here to evaluate dry eye. A visual analog scale was used to assess dry eye symptom severity. All subjects also completed the Pittsburgh Sleep Quality Index (PSQI, scores ≥5.5 indicated poor sleep), Patient Health Questionnaire (scores ≥5 indicated depression), and General Anxiety Disorder Scale (scores ≥5 indicated anxiety).Mean Pittsburgh Sleep Quality Index global score was significantly higher in patients with DED than that in controls (7.8 ± 3.9 vs. 5.4 ± 3.0, respectively; P0.001). Patients with DED demonstrated higher respective depression and anxiety scores compared with controls (P0.001 and 0.013, respectively). In the DED group, patients with poor sleep quality had more severe DED indicated by shorter TBUT and lower Schirmer I findings. A significant correlation was found between sleep quality and mood status in patients with DED. Regression analysis revealed that shorter TBUT and lower Schirmer I test results were associated with poorer sleep quality (adjusted p = 0.011 and 0.037, respectively). More severe symptoms of dry eye were significantly associated with a higher level of anxiety in patients with DED (adjusted p = 0.011).Sleep quality may play an important role in the development of DED by influencing tear secretion and tear film stability and/or by indirectly aggravating anxiety and depression, leading to higher self-reported symptom scores. It is also possible that DED contributes to reduced sleep quality, as well as the development of anxiety and depression.

WOS: 000429590300011 PubMed ID: 29300260 Purpose:To evaluate tear osmolarity and tear film parameters in patients with vitiligo.Methods:A total of 25 eyes of 25 patients with vitiligo with periocular involvement (group 1), 30 eyes of 30 patients with vitiligo without periocular involvement (group 2), and 20 eyes of 20 controls (group 3) were evaluated using the Ocular Surface Disease Index (OSDI) questionnaire, Schirmer I test, tear film breakup time, scoring of ocular surface fluorescein staining using a modified Oxford scale, and tear osmolarity.Results:Mean tear osmolarity was 332 16.3 mOsm/L in group 1, 308.8 +/- 19.5 mOsm/L in group 2, and 286.3 +/- 23.4 mOsm/L in group 3 (P < 0.001). There was no significant difference in Schirmer I test results among the 3 groups (16.5 +/- 3.2 mm in group 1, 16.3 +/- 4.7 mm in group 2, and 17.4 +/- 4.2 mm in group 3) (P = 0.175). Tear film breakup time measurements in groups 1 (9.8 +/- 3.5 seconds) and 2 (10.1 +/- 4.3 seconds) were significantly lower than those in group 3 (18.5 +/- 4.0 seconds) (P

Purpose To investigate the relationship between topical glaucoma medications and meibomian gland dysfunction (MGD) in early middle-aged patients with glaucoma. Methods In this cross-sectional study, 50 patients with glaucoma younger than 50 years who had used topical glaucoma medications for more than 6 months and 40 normal controls of similar age were included. Patients in each group were graded for MGD (0-4) using slit-lamp microscopy. Tear film breakup time (BUT), ocular surface staining, and Marx line scores were also evaluated. Differences between both groups were analyzed statistically. Results The prevalence of MGD was 82% in the group using topical glaucoma medications and 52.5% in the control group. The average period of topical glaucoma medication use was 27.4 months. There were significant differences in the breakup time and Marx line score according to the presence of MGD. Although the duration of topical glaucoma medication use and the severity of MGD did not show a significant correlation, the degree of MGD and the Marx line score were significantly correlated. Conclusions Glaucoma eye drops may be one factor affecting the eyelid changes associated with MGD. The Marx line score may be used as an index to evaluate MGD in patients with glaucoma.

Purpose: We measured tear film parameters, including the morphology and function of meibomian glands, in junior high school students at 15 years of age. Methods: A total of 111 eyes of 111 students (56 males and 55 females) were enrolled in the study. The ocular symptom score (0–14), after-school study time, lipid layer thickness (LLT) of the tear film, partial blink rate, lid margin abnormalities (0–4), tear film breakup time, corneal and conjunctival epithelial damage (fluorescein staining score, 0–9), meiboscore as determined by noncontact meibography (0–6), Schirmer test value, and meibum grade (0–3) were determined. The relationships between parameters were evaluated with the Spearman correlation coefficient (ρ). Results: The meiboscore was 2.8 ± 1.2, and the meibum grade was 1.8 ± 1.2. The meiboscore significantly correlated with the meibum grade (ρ = 0.272, P = 0.004), Schirmer test value (ρ = −0.220, P = 0.021), and LLT (ρ = −0.264, P = 0.005). The breakup time significantly correlated with LLT (ρ = 0.261, P = 0.006), meibum grade (ρ = −0.338, P < 0.001), and fluorescein staining score (ρ = −0.214, P = 0.025). The partial blink rate significantly correlated with the Schirmer test value (ρ = −0.240, P = 0.011). The meiboscore (P < 0.001) and meibum grade (P = 0.032) were significantly greater in males than in females. Conclusions: The morphology and function of meibomian glands are altered even at 15 years of age, with the changes being more prominent in males than in females.

Diquafosol ophthalmic solution improves objective findings in the ocular surface and subjective symptoms in patients with dry eye. The Dry Eye-Related Quality-of-Life Score (DEQS) questionnaire was developed to assess dry eye symptoms and their effects on quality of life. However, because little research using the DEQS has been reported, we evaluated the effects of diquafosol ophthalmic solution on ocular surface findings and quality of life using the DEQS in patients with dry eye.Sixty-three patients with dry eye were assigned to the control group (artificial tears) or diquafosol group. Both groups instilled 1 drop of the solution in both eyes 6 times daily and were evaluated after 2 weeks; the diquafosol group also was instructed to be examined at 1 and 3 months. We evaluated the subjective symptoms using the DEQS, fluorescein staining score, tear film breakup time (BUT), Schirmer testing, and lower tear meniscus height with anterior-segment optical coherence tomography.In the diquafosol group, the fluorescein staining score, BUT, tear meniscus height, and DEQS scores improved significantly compared with before treatment in contrast to the control group. Furthermore, in the diquafosol group, the staining score and BUT improved significantly compared with the control group. Analysis of each DEQS item indicated that diquafosol ophthalmic solution relieved foreign body sensation and problems when reading and using visual display terminals compared with the control group.Diquafosol ophthalmic solution was effective in patients with dry eye, especially those with foreign body sensation and problems when reading and using visual display terminals.

Purpose To describe the feasibility of an attachment-free iOS-based cobalt blue light application to accurately detect corneal injury. Methods Corneal epithelium from New Zealand White rabbits was removed by gentle scraping with a dulled scalpel or by using a classic biopsy punch (2 mm in diameter). Each cornea was then examined using a smartphone-enabled blue light after applying a fluorescein sodium ophthalmic strip. Photographs of each cornea before and after using the smartphone-based light were captured with a second smartphone device. Results The iOS-based (Apple Inc., Cuptertino, CA) cobalt blue light effectively illuminated fluorescein dye in all ex vivo samples. Both circular punch biopsy and linear scalpel-induced corneal injuries were readily identified. Conclusions The iOS-based cobalt blue light is a portable, low-cost, and effective alternative to commercially available cobalt blue lights.

PurposeTo examine the effects of volume and method on fluorescein tear breakup time (TBUT) values and to evaluate test efficacy in an independent sample free of selection bias.MethodsSubjects were assessed using a battery of dry eye tests (DETs). Efficacy study: Subjects were randomized to the DET, standard strip, and liquid NaFl on separate days. A masked examiner measured TBUTs from video recordings. Verification study: Subjects were investigated for efficacy using volumes of 5.0 and 2.0 μL mL of NaFl for TBUT.ResultsEfficacy study: 46 subjects completed the study. Log-transformed TBUTs were significantly different, normal subjects versus dry subjects, for all 3 methods (all P values < 0.001). Area under the curves (AUCs), cut-points, sensitivity, and specificity were 1) DET: 0.873, 4.4 seconds, 0.97, and 0.67, respectively; 2) 2.0 mL: 0.901, 3.22 seconds, 0.90, and 0.87, respectively; and 3) standard strip: 0.912, 3.42 seconds, 0.97, and 0.80, respectively. Verification study: Data splitting analysis for the 2.0 μL data (n = 174 dry subjects and 97 normal subjects) generated an AUC of 0.917 and a cut-point of 6.05 seconds for a sensitivity of 0.87 and a specificity of 0.81. The 5.0 μL sample yielded an AUC of 0.940, with a sensitivity and specificity of 0.92 and 0.83, respectively, at a cut-point of 5.5 seconds.ConclusionsLittle difference in TBUT was found using the 3 clinical methods with video recordings. Analysis using liquid NaFl suggests that the TBUT test has excellent diagnostic accuracy and that a cut-point of 5.3 to 6.0 seconds is the optimum to differentiate normals from persons with dry eye.

To assess the ability of a new device (Eyeprim; Opia Technologies) designed for impression cytology (IC) to harvest RNA from conjunctival cells as compared with the conventional technique.Cell collection was performed in both eyes using both techniques (conventional and Eyeprim) in different eyes randomized to each technique to avoid bias. The collection order was also randomized. Subjective discomfort assessment was performed using the Symptom Assessment in Dry Eye questionnaire. RNA was quantified in a spectrophotometer. RNA yield and discomfort using each technique were evaluated. A P value ≤0.05 was considered significant.Twenty healthy subjects (8 men and 12 women) aged 24.7 ± 5.8 years were recruited. The mean corneal fluorescein staining scores were 0.10 ± 0.30 for both eyes (P = 1.0), and the mean phenol red thread tear scores were 28.6 ± 1.9 mm for the Eyeprim and 28.7 ± 2.5 mm for the conventional IC eye group (P = 0.64). No significant (P ≥ 0.45) differences were observed in the mean RNA yield between the Eyeprim and the conventional IC, neither in the total amount (0.32 ± 0.28 μg and 0.26 ± 0.28 μg, respectively) nor in the amount normalized to the membrane area (0.0046 ± 0.0040 μg/mm and 0.0040 ± 0.0043 μg/mm, respectively). No significant differences were observed during (P ≥ 0.17) and after sample collection (P ≥ 0.36) in the frequency or intensity of discomfort (Symptom Assessment in Dry Eye scores).This pilot study shows that the Eyeprim provides similar RNA yield as the conventional harvesting conjunctival IC technique. It provides enough quantities of material useful for molecular analysis producing comparable levels of discomfort without using anesthesia.

Purpose: To assess the effect of oral re-esterified omega-3 fatty acids on tear osmolarity, matrix metalloproteinase-9 (MMP-9), tear break-up time (TBUT), Ocular Surface Disease Index (OSDI), fluorescein corneal staining, Schirmer score, meibomian gland dysfunction (MGD) stage and omega-3 index in subjects with dry eyes and confirmed MGD. Methods: This was a multicenter, prospective, interventional, placebo-controlled, double-masked study. Subjects were randomized to receive 4 softgels containing a total of 1680 mg of eicosapentaenoic acid/560 mg of docosahexaenoic acid or a control of 3136 mg of linoleic acid, daily for 12 weeks. Subjects were measured at baseline, week 6, and week 12 for tear osmolarity, TBUT, OSDI, fluorescein corneal staining, and Schirmer test with anesthesia. MMP-9 testing and omega-3 index were done at baseline and at 12 weeks. Results: One hundred five subjects completed the study. They were randomized to omega-3 (n = 54) and control group (n = 51). Statistically significant reduction in tear osmolarity was observed in the omega-3 group versus control group at week 6 (−16.8 ± 2.6 vs. −9.0 ± 2.7 mOsm/L, P = 0.042) and week 12 (−19.4 ± 2.7 vs. −8.3 ± 2.8 mOsm/L, P = 0.004). At 12 weeks, a statistically significant increase in omega-3 index levels (P < 0.001) and TBUT (3.5 ± 0.5 s vs. 1.2 ± 0.5 s, P = 0.002) was also observed. Omega-3 group experienced a significant reduction in MMP-9 positivity versus control group (67.9% vs. 35.0%, P = 0.024) and OSDI scores decreased significantly in omega-3 (−17.0 ± 2.6) versus control group (−5.0 ± 2.7, P = 0.002). Conclusions: Oral consumption of re-esterified omega-3 fatty acids is associated with statistically significant improvement in tear osmolarity, omega-3 index levels, TBUT, MMP-9, and OSDI symptom scores.

PURPOSE To evaluate the size distribution of epithelial lesions of superficial punctate keratitis (SPK) in dry eye after staining of the ocular surface by sodium fluorescein. METHODS Fluorescein was instilled in 10 patients with dry eye graded using the Oxford Scheme. Pictures were taken using a standard Topcon slit lamp with cobalt blue light, without barrier filter. Two magnifications (×10 and ×16) were used and calibrated using a certified standard reference grating, allowing the diameter of the observed objects to be determined with ImageJ software. The most visible and isolated SPK lesions (green dots) were selected. The size of 254 SPK lesions was measured by tracing the irradiance profile and manually measuring the full width at half maximum. RESULTS For all patients, with the 2 magnifications combined, the median diameter was 20.9 μm (15.2-26.6 μm, 10-90 percentile). There was a significant difference between the size of SPK lesions measured with ×10 and ×16 magnifications, respectively, 24.3 μm (18.2-29.8) versus 19.0 μm (15.2-26.6) (P < 0.001). CONCLUSIONS Lesions seem to be smaller than normal superficial epithelial cells (which are approximately 25 × 50 μm) and might correspond to the staining of dying shrunken cells, according to recent investigations. These new quantitative data will help in developing automated recognition algorithms to obtain reliable objective classification of corneal staining.

Supplemental Digital Content is Available in the Text., Purpose: To describe a new method of enhancing the visualization of amniotic membrane grafts with fluorescein staining during pterygium surgery. Methods: Pterygium excision surgery using intraoperatively stained cryopreserved amniotic membranes was performed on 346 eyes. A sterile 0.6 mg sodium fluorescein strip was placed directly onto the amniotic membrane in the manufacturer's original packaging, and the stained allograft was then transplanted onto the planned site. Staining intensities, at 3, 5, and 10 minutes of dye immersion, were compared. Immediate postoperative pain rating (scale 0–10), visibility of the fluorescein-stained amniotic membrane graft, and conjunctival autograft and amniotic membrane graft elevation, dehiscence, retraction, or displacement were recorded. The recurrence rate of the study population was compared with that of a previous cohort of 121 patients who underwent pterygium excision with conjunctival autograft without stained amniotic membrane. Results: Direct contact of the fluorescein strip on the amniotic membrane at 3, 5, and 10 minutes showed no differences in subjective staining intensity. Fluorescein-stained amniotic membrane was easily detected on the ocular surface during and 24 hours after pterygium surgery. The average immediate postoperative pain rating was 0.8 ± 1.8. No intraoperative complications or postoperative amniotic membrane graft dehiscence, retraction, or displacement occurred. The recurrence rate using fluorescein-stained amniotic membrane (3 patients, 0.9%, mean follow-up time 31.8 ± 18.6 weeks) did not differ from that of the previous cohort without the stained amniotic membrane (2.5%; χ2(1) = 1.837, P = 0.183). Conclusions: Fluorescein strip staining of the amniotic membrane is a novel and safe intraoperative method to enhance visualization and handling of the graft during and after ocular surgeries.

Purpose Tear secretion from the main lacrimal gland (LG) is mainly regulated by parasympathetic nerves. We performed several innervation studies to investigate lacrimation. Methods In male rabbits, we performed a retrograde dye-tracing study of LG innervation, evaluated preganglionic parasympathetic denervation, and administered glial cell-derived neurotrophic factor (GDNF) in the surgical area after parasympathetic denervation. Results Accumulation of fluorescent dye was observed in the pterygopalatine ganglion cells on the same side as the dye injection into the main LG. Fewer stained cells were observed in the cervical and trigeminal ganglia. After parasympathetic denervation surgery, tear secretion was decreased, and fluorescein and rose bengal staining scores were increased at day 1 after surgery and remained increased for 3 months on the denervated side only. Most of the effects in rabbits with parasympathetic denervation were not recovered by administration of GDNF. Conclusions The main LG is primarily innervated by parasympathetic nerves to stimulate tear secretion. After preganglionic parasympathetic denervation, lacrimation was decreased, resulting in dry eyes, and this was maintained for at least 3 months. Administration of GDNF only minimally altered the effects of denervation.

PURPOSE To evaluate the efficacy and safety of autologous serum (AS) eye drops combined with punctal plugs (PPs) in patients with Sjogren syndrome (SS)-related dry eye. METHODS A retrospective clinical study was performed in patients with dry eye caused by SS. We evaluated the Schirmer test value, tear breakup time (tBUT), and fluorescein and Rose Bengal (RB) staining scores at baseline, 3 months, 6 months, 1 year, and >1 year after treatment. The dry eye indexes were also evaluated in 2 subgroups, which determined by the using of PPs, including the AS + PP group and AS only group. RESULTS A total of 56 eyes of 28 patients were investigated with a mean follow-up of 42.3 ± 26.1 months. After the application of AS eye drops, the Schirmer test showed no significant changes. The tBUT (2.7 ± 1.9 seconds) was significantly improved at each time point (3.9 ± 3.1, 4.5 ± 3.1, 3.7 ± 2.5, and 5.1 ± 4.0; P < 0.01), fluorescein staining (4.3 ± 2.8) was significantly improved at each time point (2.2 ± 2.2, 1.9 ± 1.9, 1.8 ± 1.6, and 1.8 ± 1.8; P < 0.01), and RB (2.6 ± 3.0) staining was significantly improved from 6-month treatment (1.5 ± 1.9, 1.9 ± 1.9, and 1.4 ± 1.8; P < 0.05, 0.01, and 0.01, respectively). When combined with PPs, the tBUT and RB staining scores were found to be significantly improved in the AS + PP group compared with those of the AS only group. CONCLUSIONS Long-term application of AS eye drops was found to be an effective and apparently safe treatment for SS dry eye. Furthermore, PPs in combination with AS eye drops were considered to have an additive effect on SS dry eye.

To investigate the changes of meibomian gland (MG) and tear film stability in subjects with eyelid tattoos.Forty female subjects were recruited. Ten subjects had eyelid tattoos and 30 subjects did not (control group). Tear film break-up time (TBUT) measurement and fluorescein staining were performed to evaluate the tear film. Distances between the eyelid tattoo and the MGs were measured and used to assign a tattoo score. The overall tattoo score, defined as the sum of upper and lower lid tattoo scores, was determined for each eye. MG loss was scored for each eyelid and added together to obtain the total "meiboscore" for each eye using meibography. Values between the tattoo and control groups were examined and compared.The TBUT in the tattoo group (4.3 ± 0.9 seconds) was shorter than that in the control group (11.0 ± 4.3 seconds; P0.001). Corneal erosion, measured with fluorescein staining, was more severe in the tattoo group (1.6 ± 0.5) than that in the control group (0.2 ± 0.2; P0.001). MG loss was also more severe in the tattoo group (3.4 ± 1.5) than that in the control group (0.9 ± 0.6; P0.001). The total tattoo score was correlated with the total meiboscore (r = 0.852, P0.001, Spearman correlation coefficient).Eyelid tattooing shortened TBUT, increased fluorescein staining, and induced MG loss. Therefore, eyelid tattooing increases tear film instability through MG disturbance, and patients could have exacerbated signs and symptoms of ocular surface disease.

To evaluate the efficacy and safety of topical diquafosol ophthalmic solution for treatment of dry eye.Randomized clinical trials (RCTs) from MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were identified to evaluate the efficacy and safety of topical administration of diquafosol to patients with dry eyes. Data evaluation was based on endpoints including Schirmer test, tear film break-up time, ocular surface staining score, subjective symptom score, and adverse events.A total of 8 RCTs involving 1516 patients were selected based on the prespecified criteria. Significant improvement of Schirmer test values and tear film break-up time were reported in 40% (2 of 5) and 80% (4 of 5) studies, respectively. Ocular surface staining scores significantly decreased in 100% (fluorescein corneal staining, 6 of 6; Rose Bengal corneal and conjunctival staining, 4 of 4) RCTs. Symptoms significantly improved in 75% (6 of 8) RCTs in patients with dry eyes. No severe adverse events were reported with the concentration of diquafosol from 0.5% to 5%. Heterogeneity in study design prevented meta-analysis from statistical integration and summarization.Topical diquafosol seems to be a safe therapeutic option for the treatment of dry eye. The high variability of the selected RCTs compromised the strength of evidence and limits the determination of efficacy. However, the topical administration of diquafosol seems to be beneficial in improving the integrity of the epithelial cell layer of the ocular surface and mucin secretion in patients with dry eyes. This review indicates a need for standardized criteria and methods for evaluation to assess the efficacy of diquafosol in the future clinical trials.

Purpose The aim of this study was to investigate the effects of androgen on the ultrastructure of corneal epithelium and function of the tear film in a mouse model. Methods Healthy adult male BALB/c mice were randomly apportioned to normal control, sham-operated, or orchiectomy groups. In the orchiectomy group, 4 subgroups with treatment [blank group, dihydrotestosterone (DHT) eye drop group, DHT injection group, and dimethyl sulfoxide (DMSO) eye drop group] were further established at 3 weeks after orchiectomy. Tear production, tear break-up time, and corneal fluorescein staining were evaluated in all groups at multiple time points. Serum androgen concentrations were measured by competitive radioimmunoassay, and ultrastructure of corneal epithelial cells was examined by transmission electron microscopy. Results Before orchiectomy, the mean serum concentration of androgen was 43.4 ng/μL, which decreased to approximately 0 ng/μL at 1 week after orchiectomy. Significantly less tear production, shorter tear break-up time, higher corneal fluorescein staining score, shorter and flattened corneal epithelial microvilli, and looser intercellular desmosomes were observed in mice after orchiectomy. DHT supplements increased serum androgen levels, and some of the tear film functions and morphological features of microvilli and desmosomes were gradually close to those at baseline in the DHT injection group. Conclusions Persistent corneal staining, decreased tear production, short break-up time, and unhealthy corneal ultrastructure were observed in mice that received orchiectomy for at least 8 weeks. A mouse that received orchiectomy could be used as a dry eye model. Exogenous DHT supplement improved corneal epithelial ultrastructure and tear film function in this model.

PURPOSE: The aim of this study was to determine the effect of nicergoline in patients with neurotrophic keratopathy. METHODS: This is a prospective, noncomparative interventional study. The study included 27 eyes of 24 patients with neurotrophic keratopathy who were unresponsive to conventional therapy. Patients were treated with 10 mg of oral nicergoline twice daily for at least 2 weeks. Slit-lamp examination, photography, corneal fluorescein dye testing, Cochet-Bonnet corneal sensitivity, and best-corrected visual acuity tests were performed before and after treatment. Tear nerve growth factor levels were measured before and after treatment. RESULTS: In 23 eyes (85%), epithelial defects healed completely between 7 and 30 days of treatment with nicergoline (mean, 15.6 ± 8.0 days). Epithelial defects persisted in 4 eyes (15%). The mean corneal sensitivity before and after treatment with nicergoline was 20.5 ± 8.5 and 30.2 ± 10.8 mm, respectively (P < 0.001). The best-corrected visual acuity (measured in units according to the logarithm of the minimum angle of resolution) was significantly improved from 1.1 ± 0.6 to 0.8 ± 0.6 (P < 0.001). The tear nerve growth factor levels were significantly higher ranging from 3.2 ± 0.3 to 6.2 ± 0.3 pg/mL (P < 0.001). CONCLUSIONS: Treatment with nicergoline helps patients with neurotrophic keratopathy in whom conventional treatment has failed.

Purpose:Corneal lymphatic vessels are clinically invisible because of their thin walls and clear lymph fluid. There is no easy and established method for in vivo imaging of corneal lymphatic vessels so far. In this study, we present a novel approach to visualize corneal lymphatic vessels in vivo by

Purpose The aim of this study was to evaluate the effectiveness of punctal occlusion using hypromellose 2% in patients with dry eye. Methods In this prospective, randomized single-blinded clinical trial, we evaluated 76 eyes of 38 patients (36 women and 2 men) with dry eye secondary to rheumatic diseases. In each patient, the lower lacrimal punctum of 1 eye was occluded using hypromellose 2%, whereas the contralateral eye underwent a simulation of the procedure (control group). Patients' eyes were assessed for burning, itching, redness, foreign body sensation, and tearing based on a visual scale questionnaire (score, 0-10). We also performed objective tests for evaluation of dry eye using a Schirmer test with anesthesia (basal tear secretion test), the tear film break-up time test, and fluorescein and rose bengal staining tests at 0, 28, and 56 days after treatment. Results Fluorescein and rose bengal staining tests showed that there was a significant reduction in signs after occlusion using hypromellose. The symptoms measured by the visual scale were significantly reduced. The values of the Schirmer test with anesthesia and the break-up time test increased significantly. The effects persisted for up to 8 weeks. There were no dropouts or reported side effects during the 24-month follow-up. Conclusions Our results suggest that punctal occlusion using hypromellose 2% is a low-cost and safe additional treatment for dry eye.

The aim of this study was to evaluate the treatment effect of diquafosol 3% with preservative-free sodium hyaluronate 0.1% eye drops in dry eye syndrome.In total, 150 patients with dry eye syndrome were divided randomly into 3 groups. Group 1 (50 patients) was treated 4 times daily with preserved sodium hyaluronate 0.1%, group 2 (50 patients) was treated 4 times daily with diquafosol 3%, and group 3 (50 patients) was treated 4 times daily with diquafosol 3% and preservative-free sodium hyaluronate 0.1% eye drops for 3 months. Ocular surface disease index (OSDI) score, tear film break-up time, Schirmer I test, corneal fluorescein staining, and impression cytology were evaluated.There were significant improvements in the OSDI score, tear film break-up time, Schirmer I score, fluorescein and Rose Bengal staining, goblet cell density, and impression cytological findings in groups 2 and 3 compared with those for group 1 in patients with dry eye syndrome at 1, 2, and 3 months (P0.05). There were statistically significant improvements in the OSDI score (-8.48 ± 0.97, -5.69 ± 0.78; P = 0.02), fluorescein (-1.43 ± 0.21, -1.02 ± 0.18; P = 0.03), and Rose Bengal staining (-1.12 ± 0.26, -0.75 ± 0.12; P = 0.03), goblet cell density (89.65 ± 14.39, 70.36 ± 16.75; P = 0.03), and impression cytological findings (-0.53 ± 0.12, -0.34 ± 0.90; P = 0.01) in group 3 compared with those in group 2 at 3 months.Treatment with diquafosol 3% with preservative-free sodium hyaluronate 0.1% was more effective than diquafosol 3% monotherapy or treatment with preserved sodium hyaluronate 0.1% in dry eye syndrome. Preservative-free sodium hyaluronate 0.1% eye drops can increase the effect of diquafosol 3% in dry eye syndrome.

Purpose The aim of this study was to establish a new rhesus monkey model of severe dry eye. Methods A total of 8 rhesus monkeys were used for the study. Four monkeys had their main lacrimal gland and nictitating membrane surgically removed (group 1). Another 4 monkeys had a similar surgery with further application of 50% trichloroacetic acid on the bulbar conjunctiva (group 2). The ocular surface was evaluated before and after the surgery (1, 4, 8, 12, and 24 weeks) using Schirmer-1 test, corneal fluorescein staining, and the lissamine green test. Conjunctival impression cytology was also performed before and 24 weeks after the surgery. Finally, the cornea and the conjunctiva were evaluated using light microscopy. Results A significant decrease in tear secretion was observed in all operated eyes. Schirmer test data measured were ≤4 mm in all the operated eyes. Slit-lamp examination also revealed abnormal staining in all the operated eyes that remained stable until the end of the experiment. In group 2, corneal fluorescein staining and lissamine green test values were always ≥5 (max 12) and ≥4 (max 9), respectively. Impression cytology specimens of both the treated groups showed conjunctival squamous metaplasia and a decreased number of goblet cells. Under light microscopy, the corneal epithelium appeared irregular with edematous basal epithelial cells. The conjunctiva showed a decreased goblet cell density with infiltration of inflammatory cells. Conclusions Complete removal of the principal lacrimal gland and nictitating membrane associated with the application of 50% trichloroacetic acid on the conjunctiva could induce severe dry eye in rhesus monkeys.

Purpose To investigate the effect of benzalkonium chloride (BAK) on corneal nerves. Methods Fifty-four adult New Zealand Albino rabbits were randomly divided into 3 groups. BAK at concentrations of 0.005%, 0.01%, or 0.02% was applied once daily to 1 eye of each rabbit for 9 days. The contralateral untreated eyes were used as controls. Corneal mechanical sensitivity, aqueous tear production, tear break-up time (BUT), fluorescein, and Rose Bengal staining scores were compared with those of control values on days 3, 6, and 9. Corneal whole mounts were immunostained with a specific antitubulin βIII antibody to label nerve fibers. Epithelial superficial nerve terminal, subbasal, and stromal nerve fiber densities were quantified. The structure of the central cornea was examined by means of in vivo confocal microscopy on day 9. Results The topical application of BAK resulted in lower corneal sensitivity and higher Rose Bengal staining scores on day 3, whereas there were no significant changes in the BUT, Schirmer, and corneal fluorescein scores. Decreased nerve densities in superficial and subbasal layers were observed in BAK-treated eyes on days 3 and 6, respectively. The eyes treated with 0.02% BAK exhibited significantly reduced Schirmer scores, BUT, and stromal nerve fiber density, and increased fluorescein staining scores on day 9. Corneal superficial epithelial cell size was significantly larger in all BAK-treated eyes compared with that in control eyes. Conclusions The topical application of BAK can quickly cause corneal hypoesthesia without tear deficiency. Changes in corneal innervation significantly correlate with BAK-induced ocular surface changes.

Supplementation with gamma-linolenic acid (GLA) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) has been found to decrease the production of disease-relevant inflammatory mediators that are implicated in the pathogenesis of chronic dry eye. This study evaluated the effect of a supplement containing both GLA and n-3 PUFAs on signs and symptoms of moderate-to-severe keratoconjunctivitis sicca in postmenopausal patients.This multicenter, double-masked placebo-controlled clinical trial enrolled 38 patients (both eyes) with tear dysfunction who were randomized to supplemental GLA + n-3 PUFAs or placebo for 6 months. Disease parameters, including Ocular Surface Disease Index, Schirmer test, tear breakup time, conjunctival fluorescein and lissamine green staining, and topographic corneal smoothness indexes (surface asymmetry index and surface regularity index), were assessed at baseline and at 4, 12, and 24 weeks. The intensity of dendritic cell CD11c integrin and HLA-DR expression was measured in conjunctival impression cytologies.The Ocular Surface Disease Index score improved with supplementation and was significantly lower than placebo (21 ± 4 vs. 34 ± 5) after 24 weeks (P = 0.05, n = 19 per group). The surface asymmetry index was significantly lower in supplement-treated subjects (0.37 ± 0.03, n = 15) than placebo (0.51 ± 0.03, n = 16) at 24 weeks (P = 0.005). Placebo treatment also significantly increased HLA-DR intensity by 36% ± 9% and CD11c by 34% ± 7% when compared with supplement treatment (n = 19 per group, P = 0.001, 24 weeks). Neither treatment had any effect on tear production, tear breakup time, or corneal or conjunctival staining.Supplemental GLA and n-3 PUFAs for 6 months improved ocular irritation symptoms, maintained corneal surface smoothness, and inhibited conjunctival dendritic cell maturation in patients with postmenopausal keratoconjunctivitis sicca.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00883649.

PURPOSE: To evaluate the effects of oral ambroxol on tear film and ocular surface. METHODS: Twenty healthy male subjects with no ocular disease were recruited. Subjects were divided into 2 groups: a control group and an ambroxol group. Ambroxol hydrochloride was administered orally to the ambroxol group. The tear film and ocular surface were evaluated at baseline (10 AM), 12 PM, 6 PM, and 10 AM the next day. Visual analog pain scale, tear film break-up time, fluorescein corneal staining, Schirmer test, tear osmolality, and fluorescein clearance test were measured. RESULTS: The mean visual analog pain scale score increased at 6 PM and 10 AM the next day in the ambroxol group (P = 0.007 and P = 0.018, respectively). The tear film break-up time did not show any significant change in the control group and shortened at 6 PM in the ambroxol group (P = 0.011). The fluorescein corneal staining scores increased at 6 PM in both groups (P = 0.007 and P = 0.004, respectively), and they were higher in the ambroxol group compared with control group at 10 AM the next day (P = 0.035). The mean tear secretion did not show a significant change in the control group and increased at 10 AM the next day in the ambroxol group (P = 0.022). In both groups, the tear osmolality increased at 6 PM (P = 0.009 and P = 0.005, respectively), but the tear osmolality in the ambroxol group was higher compared with control group at 6 PM (P = 0.043). CONCLUSIONS: Oral ambroxol may disturb tear film and ocular surfaces by attenuating the mucin layer of the tear film.

We previously reported 2 new methods, anterior segment optical coherence tomography (AS-OCT) and polymethylmethacrylate particles suspended in fluorescein solution (PPF), for the evaluation of tear clearance and rapid tear flow after blinking (tear Krehbiel flow). Here, we investigated age-related OCT tear clearance and tear film thickness (TFT) and the potential correlation of OCT tear clearance and PPF velocity indicative of tear Krehbiel flow. Normal subjects separated into young and older groups received 5 μL of saline solution into the lower conjunctival sac, and an image of the central lower eyelid tear meniscus was captured by AS-OCT immediately and 30 seconds after natural blinking. Tear meniscus height (TMH) and tear meniscus area (TMA) were measured, and their percentage decrease was defined as OCT clearance rate. A Spectralis OCT Anterior Segment Module captured the central corneal tear film layer for TFT measurements. OCT clearance rates were significantly higher in young versus older subjects (P = 0.0002). When all subjects were analyzed, age was significantly and negatively correlated with TMH clearance rate (r = -0.4928, P = 0.0003) and TMA clearance rate (r = -0.4596, P = 0.0008). TFT values were significantly and negatively correlated with age (r = -0.6662, P < 0.0001). A second experiment examined tear Krehbiel flow by measuring PPF velocity in frontal and medial gaze positions. The medial gaze position showed significantly increased PPF velocity compared with the frontal gaze position (P = 0.006). Significant and positive correlations were found between OCT clearance rates and PPF velocity (TMH rate: r = 0.2926, P = 0.0392; TMA rate: r = 0.3274, P = 0.0205). AS-OCT and PPF might be novel techniques for quantitative evaluation of tear clearance and Krehbiel flow.

Multipurpose contact lens solution (MPS)/preservative-associated transient corneal hyperfluorescence has been suggested to represent corneal injury. To determine the validity of this assumption, the molecular-level interactions of common disinfectants in soft contact lens MPS and the corneal epithelium using an in vitro model were assessed.A liposome-based model of the corneal epithelial surface was developed and used to assess the interactions of polyhexamethylene biguanide (PHMB), polyquaternium-1 (PQ-1), and fluorescein with membrane components and the effects of PHMB and PQ-1 on membrane integrity. The fluorescence anisotropy (a measure of interactions between molecules) was determined. Liposome integrity was assessed by measuring the liposome melting point temperature.Free fluorescein did not associate with the liposome (P0.4). Both fluorescein-tagged PHMB and PQ-1 associated with liposomes (P0.002 and P≤0.01, respectively); however, only PHMB induced free fluorescein association with membrane components. At physiological temperature, no significant shift in the melting point temperature was observed when liposomes were exposed to PHMB from 0 to 100 ppm (P0.05). In contrast, exposure of7 ppm PQ-1 disrupted the liposomes.Based on this study, PHMB-to-liposome bilayer interaction is nondestructive, even at concentrations 100 times higher than found in commercially available MPS products. In contrast, PQ-1-to-liposome bilayer interaction led to liposome disruption. This study presents molecular-level evidence to support that preservative-associated transient corneal hyperfluorescence is a benign transient phenomenon and its evaluation clinically may be an ambiguous strategy for determining biocompatibility and cell surface integrity.

Purpose To evaluate visual function changes after punctal plug (PP) occlusion in patients with short breakup time of tear film (BUT) type of dry eyes. Methods A prospective comparative study was performed in 43 eyes of 43 dry eye patients with short BUTbreakup time of tear film receiving PP occlusion. Patients were divided into 2 groups as those receiving only upper or only lower occlusion. Functional visual acuity measurements, tear function evaluations, and questionnaire on satisfaction with treatment in relation to presence of epiphora were performed before and 1 month after PP insertion. Results Twenty eyes of 43 eyes (46.5%) with only lower occlusion and 17 eyes of 43 eyes (39.5%) with only upper occlusion showed satisfactory outcomes with treatment. One of 43 eyes (2.3 %) had epiphora. Vital staining scores and BUT values significantly improved in both groups after occlusion. The mean logarithm of the minimum angle of resolution functional visual acuity value significantly improved only in eyes receiving upper PP occlusion. Conclusion Upper PP occlusion seems to be associated not only with improvement of tear stability, vital staining scores, and treatment-related satisfaction but also with better quality of visual function.

PURPOSE To assess possible cellular damage in the corneal and conjunctival epithelium after corneal cross-linking treatment. METHODS Riboflavin-dextran solution was applied every 5 minutes to the right eyes of 3 rabbits 10 minutes before and 30 minutes during the irradiation with UVA light of 370 nm and an irradiance of 3 mW/cm at the 8- to 10-o'clock position, including conjunctival, limbal, and central corneal epithelium. In addition, 3 rabbits were treated with UVA light only. The rabbits were killed 24 hours later. The treated eyes were examined histologically using hematoxylin-eosin and periodic acid-Schiff staining, immunohistochemistry, and a terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) apoptosis assay and compared with the left fellow eyes, which served as controls. RESULTS There was no epithelial defect on fluorescein staining. No apoptosis was found in the corneal limbal epithelium, keratocytes, or endothelial cells in the irradiated area. In the adjacent conjunctival epithelium, rare superficial conjunctival epithelial cells were positive in TUNEL staining in all animals. Anti-multicytokeratin-positive staining was demonstrated in both the limbal corneal and the conjunctival epithelium. The proliferation marker Ki-67 was identified in the basal cell layer of the limbal epithelium. The frequency and distribution pattern of goblet cells, multicytokeratin, and the proliferation marker Ki-67 were the same in all eyes compared with the untreated fellow control eyes. CONCLUSIONS Standard corneal cross-linking does not induce significant cellular epithelial damage as assessed by histological methods. Further studies on possible genotoxic and long-term changes would be helpful to complete the risk assessment.

To determine the relative staining characteristics of the nasal and temporal conjunctiva as compared with other measures of dry eye and evaluate the qualitative clinical impression of the utility of the double vital staining with fluorescein and lissamine green.Ocular surface staining was performed with a mixture of 1% fluorescein and 1% lissamine green in 50 patients with dry eye (12 patients with Sjögren syndrome and 38 patients with non-Sjögren syndrome). Ocular surface disease index (OSDI), tear breakup time (BUT), and Schirmer test were evaluated. Digital photographs were taken after vital staining on the ocular surface, and the grade of staining in various areas was assessed. Correlation among the degrees of staining, OSDI, and ocular surface parameters was analyzed.The nasal conjunctiva evidenced greater staining compared with the temporal conjunctiva and cornea (P = 0.04). Staining of the nasal conjunctiva showed significant correlation with OSDI (P0.01) and BUT (P = 0.03). Staining of the temporal conjunctiva correlated significantly with OSDI (P = 0.01), and staining of the cornea correlated with BUT (P = 0.02).Double vital staining with 1% fluorescein and 1% lissamine green correlates with symptoms and some ocular surface parameters in patients with dry eye and helps to identify ocular surface changes easily. It may be a useful method for the diagnosis of dry eye and the assessment of the therapeutic effect in patients with dry eye syndrome.

Purpose The study purpose was to evaluate corneal barrier function and staining relative to potential bioincompatibilities. Methods This was a randomized double-masked study (n = 25 subjects). Three lens material-care solution combinations were tested: (1) lotrafilcon B/polyhexamethylene biguanide (PHMB)-based multipurpose (MPS) solution (MPS-1); (2) lotrafilcon B/polyquaternium-1 and myristamidopropyl dimethylamine-based solution (MPS-2); and (3) lotrafilcon B and another PHMB-based solution (MPS-3). Saline served as the control. New lenses were soaked in the preserved solutions or saline and then worn for 2 hours before corneal measurements. Barrier function was characterized by the fluorescein penetration rate, corneal amount, both measured with an objective scanning fluorometer. The dye penetration rate ratio, test to control; amount ratio, test to control, and corneal staining were evaluated. Results The mean rate ratios (± SD) for the combinations were 2.98 (± 3.04), 1.23 (± 1.01), and 1.83 (± 1.77) for MPS-1, MPS-2, and MPS-3 solutions, respectively. Significant ratio differences were found across regimens (P = 0.007); for MPS-1 compared with baseline (P = 0.031) and for MPS-1 compared with MPS-2 (P = 0.007). The statistical results for staining were similar. Conclusions Use of an objective quantitative physiological method suggests that significant differences in lens solution bioincompatibilities occur that mirror corneal staining data relative to corneal compromise.

To evaluate the efficacy of topical cyclosporine-A 0.05% (CsA) in the treatment of dry eye syndrome in ocular graft-versus-host disease after bone marrow transplantation (BMT) of hematopoietic stem cells.One-hundred five patients were enrolled in a retrospective, comparative, interventional case series. Eighty-one patients received topical CsA starting 1 month before BMT (treatment group), and 24 patients did not receive CsA until at least 6 months after the transplantation (control group). Mean follow-up time was 17.5 ± 11.0 months (range: 6.0-49.0 months). Clinical history, ocular surface disease index questionnaire, slit-lamp examination, lissamine green and fluorescein staining of the ocular surface, tear breakup time, and Schirmer test with topical anesthesia were obtained to create a composite dry eye-grading score.Dry eye symptoms were significantly more severe in the control group at 3 months, 1 year, and 2 years (P0.05). There was no correlation with type of stem cell transplant (related vs. unrelated donor), presenting indication for BMT, or concurrent systemic immunosuppressive medications.Pre-BMT initiation of topical CsA may reduce the inflammatory response in the lacrimal glands that may be responsible for the development of post-BMT keratitis sicca.

Cosmetic product application may be an etiologic risk factor for dry eye syndrome. This study aimed to investigate whether a cosmetic product material (CPM) could migrate onto the ocular surface and whether eyedrop instillation might exacerbate this migration.CPM was prepared by mixing equal volumes of hydroxyethyl cellulose gel (Scopisol; Senju Pharmaceutical Co. Ltd., Osaka, Japan) and a 10% fluorescein solution. Seventy-five female volunteers were randomly separated into three groups: the outer eyelash line group, in which CPM was applied on the upper and lower eyelids approximately 2 mm from the eyelash line; the eyelash line (EL) group, in which CPM was applied close to the eyelash line but without touching it; and the inner eyelash line group, in which CPM was applied on the eyelash line extending to the margin of the eyelids. The right eye was used for this study. At 5 and 30 minutes after CPM application, slit-lamp examination was carried out to detect fluorescence, an indication of CPM migration and contamination of the ocular surface. A strip of Schirmer test paper was used to collect tears, and the color of the paper was scored (contamination score: 0-5) to determine the relative quantity of CPM contamination on the ocular surface. In another set of experiments, 5 minutes after CPM application, one drop of balanced saline solution was instilled into the eye. Thirty seconds later, eyes were examined by slit-lamp microscopy and tears were collected to determine the migration percentage (eyes with CPM migration/total eyes) and contamination score.At 5 minutes after CPM application, the inner eyelash line group displayed a significantly higher migration percentage (96%) and average contamination score (3.35 ± 0.77) compared with the outer eyelash line (12%; 0.15 ± 0.34) and EL (20%; 0.35 ± 0.32) groups. At 30 minutes, both the migration percentage and the average contamination score increased remarkably in the EL group (60% and 2.71 ± 1.01). The migration percentage and average contamination score in the outer eyelash line group (P = 0.005 and P = 0.003, respectively) and EL group (P = 0.009 and P = 0.006, respectively) were significantly higher after eyedrop instillation compared with values before eyedrop instillation.CPM can migrate onto the ocular surface when applied close to the eyelid margin. This migration increases with time and can be exacerbated by eyedrop instillation.

To compare the effects of Viscofresh 0.5% (carmellose sodium 0. 5%) versus Lubristil (sodium hyaluronate 0.15%) in dry eye syndrome and to study the influence of these two treatments on the expression of various inflammatory markers by flow cytometry in impression cytology specimens.In this randomized, masked-observer, parallel group, single-center study, 15 patients with dry eye syndrome were randomized to sodium carmellose 0.5% or sodium hyaluronate 0.15% 1-month treatment after a 1-week washout period. Corneal staining with flurescein, breakup time, Schirmer 1 test with anesthesia (Jones test), and tear clearance were assessed. Besides, conjunctival impression cytology was performed to investigate inflammatory markers (CD3, CD11b, and HLA-DR) using flow cytometry.Carmellose group shows statistical improvement compared with the hyaluronate group in breakup time, corneal staining, and HLA-DR. The two other inflammatory markers had also a tendency for a decreased expression in both groups, with no statistical significance. There were neither visual acuity loss nor other complications related to treatment.Both artificial tears improve dry eye signs and symptoms and inflammatory markers expression, with significant better results in carmellose group.

Aim: The aim of this study was to attempt to visualize herpes simplex keratitis in an ex vivo model using currently available ophthalmological equipment and anti-herpes simplex virus I (HSV-1) fluorescein isothiocynate-labeled antibody. Methods: Sixteen donor human corneas were included in this study. Eight corneas were infected with HSV-1, whereas 8 remained uninfected. Abrasions were made on 2 infected and 2 uninfected corneas to assess a possible nonspecific absorption of antibodies in the sites of corneal epithelial defects. Corneas were examined before and after antibody application using a slit lamp, the fluorescein enhancing filter settings of fundus camera, and Confoscan 3. All corneas were further imaged using multiphoton laser confocal microscopy. Results: Before anti-HSV-1 antibody application, no fluorescence was detected in donor corneas with the blue light of the slit lamp and fundus camera at fluorescein enhancing filter settings. Examination with the fundus camera after antibody application detected increased background fluorescence in all the corneas with more highlighted areas of epithelial defects in abraded infected and uninfected corneas. Confoscan 3 did not show a significant difference between the appearances of HSV-1-infected and control corneas with and without application of the antibody. However, specific staining was confirmed by multiphoton laser confocal microscopy in all infected corneas. Conclusion: Further refinement of currently available ophthalmological tools is required to aid in vivo visualization of herpes simplex keratitis using fluorescein isothiocynate-labeled antibodies.

PURPOSE To determine the interleukin (IL)-6 and IL-8 levels in the tear samples of patients with conjunctivochalasis (CCh) and to correlate the severity of symptoms with tear IL levels. METHODS Fifty-one eyes at different stages of CCh and 10 eyes of healthy controls were recruited for this prospective study undertaken at a single university-based hospital. CCh was graded based on the extent of inferior lid margin involvement as follows: 1 = single (temporal) location, 2 = 2 locations, and 3 = whole lid. The presence of punctal occlusion and fluorescein clearance patterns were recorded. Enzyme-linked immunosorbent assay was used to determine IL levels. Severity of symptoms was assessed with the ocular surface disease index. RESULTS Of the 51 study patients (mean age = 63.4 +/- 6.9 years), 16 had grade 1, 21 had grade 2, and 14 had grade 3 CCh. Tear IL-6 and IL-8 levels were significantly higher in patients with CCh than in controls (P

To report the case of a patient with Fabry disease (FD) whose ocular presentation with chronic chemosis we feel is related to FD and to describe the conjunctival fluorescein angiographic findings.A 51-year-old male patient with FD on enzyme replacement therapy presented with 1-month chemosis and mild irritation in the left eye. Ocular examination revealed pronounced noninflammatory chemosis inferotemporally in the left eye with conjunctival tortuosity and microaneurysms bilaterally. There was mild corneal verticillata, spoke-like lens opacities, and retinal vascular tortuosity bilaterally, with no evidence of disc or macular edema. Evaluation revealed no systemic cause for his chemosis, including an orbital computerized tomography scan, which showed clear sinuses and no evidence of an intraorbital mass.Conjunctival fluorescein angiography revealed rapid subconjunctival accumulation of dye in the involved eye but failed to demonstrate leakage from tortuous conjunctival vessels or microaneurysms.Although the pathology of chronic chemosis in patients with FD is as yet unknown, we believe that FD should be considered in the differential diagnosis of patients presenting with chronic chemosis of unknown etiology.