Analysis of the performance of the CorneAI for iOS in the classification of corneal diseases and cataracts based on journal photographs.

CorneAI for iOS is an artificial intelligence (AI) application to classify the condition of the cornea and cataract into nine categories: normal, infectious keratitis, non-infection keratitis, scar, tumor, deposit, acute primary angle closure, lens opacity, and bullous keratopathy. We evaluated its performance to classify multiple conditions of the cornea and cataract of various races in images published in the Cornea journal. The positive predictive value (PPV) of the top classification with the highest predictive score was 0.75, and the PPV for the top three classifications exceeded 0.80. For individual diseases, the highest PPVs were 0.91, 0.73, 0.42, 0.72, 0.77, and 0.55 for infectious keratitis, normal, non-infection keratitis, scar, tumor, and deposit, respectively. CorneAI for iOS achieved an area under the receiver operating characteristic curve of 0.78 (95% confidence interval [CI] 0.5-1.0) for normal, 0.76 (95% CI 0.67-0.85) for infectious keratitis, 0.81 (95% CI 0.64-0.97) for non-infection keratitis, 0.55 (95% CI 0.41-0.69) for scar, 0.62 (95% CI 0.27-0.97) for tumor, and 0.71 (95% CI 0.53-0.89) for deposit. CorneAI performed well in classifying various conditions of the cornea and cataract when used to diagnose journal images, including those with variable imaging conditions, ethnicities, and rare cases.

A Possible Reciprocal Relationship Between Myopia and Dry Eye Disease in Japanese Teenagers.

Purpose: To investigate the relationship between dry eye disease (DED) and myopia in Japanese teenagers. Methods: This clinic-based, retrospective, cross-sectional study assessed DED condition in 10- to 19-year-old teenagers presenting at Japanese eye clinics. They included 106 high myopic patients (HM; mean age, 16.4 ± 2.2 years), 494 mild myopic patients (15.0 ± 2.6 years) and 82 non-myopic teenagers (NM; 13.8 ± 2.6 years). Subjective refraction and anisometropia were measured. Myopia grade was classified as HM (≤ -6.00 D), MM (> -6.00 D, < -0.50 D), or NM (≥ -0.5 D). The presence of DED-related symptoms including dryness, irritation, pain, fatigue, blurring and photophobia were assessed through a questionnaire. Tear film break-up time (BUT) and fluorescein corneal staining were investigated. Comparison among three groups and regression analysis of myopic error and other variables were conducted. Results: Anisometropia and astigmatic error were greatest in the HM group compared with the other groups (p < 0.001). The HM group reported less photophobia (p < 0.001) and less pain (p = 0.039) compared with the NM group. Regression analysis revealed that myopic error was correlated with astigmatic error (ß = -0.231, p <0.001), anisometropia (ß = -0.191, p <0.001), short BUT (ß = -0.086, p = 0.028) and the presence of diagnosed DED (ß = -0.112, p = 0.003). Dryness (ß = -0.127 p = 0.004), photophobia (ß = 0.117, p = 0.002) and pain (ß = 0.084, p = 0.034) correlated with myopic error. Conclusion: This study associated clinical findings of DED in HM teenagers. The present results suggest DED might be associated with myopia, possibly in a reciprocal relationship.

Corneal In Vivo Laser-Scanning Confocal Microscopy Findings in Dry Eye Patients with Sjögren's Syndrome.

PURPOSE: To evaluate the changes in cornea in Sjögren's syndrome (SS) with a novel confocal microscopy device. METHODS: Twenty-three right eyes of patients with SS (23 women; mean age, 65.4 ± 11.4 years) and 13 right eyes of 13 age- and sex-matched control subjects (13 women; mean age, 68.8 ± 9.8 years) were studied. Furthermore, eight right eyes of patients with SS (8 women; mean age, 66.9 ± 9.6 years) were studied to evaluate the corneal microscopic alterations after the treatment with topical 3% diquafosol sodium eye drops. All cases had tear quantity, tear breakup time (BUT), ocular surface staining measurements, and corneal in vivo laser-scanning confocal microscopy examinations. The density and area of corneal epithelial cells (superficial, wing, and basal), density of corneal stromal cells (anterior, intermediate, and posterior), density and area of corneal endothelial cells, density and morphology of corneal sub-basal nerve plexus, density of corneal sub-basal inflammatory cells were also assessed. RESULTS: The tear quantity, stability, and vital staining scores were significantly worse in patients with SS than in control subjects (p < 0.0001). Corneal superficial epithelial cell density was significantly lower in SS compared with control subjects (p < 0.0001). Corneal superficial epithelial cell area was significantly larger in SS compared with control subjects (p = 0.007). Corneal sub-basal nerve fiber density was lower in SS compared with control subjects (p < 0.0001). Morphological abnormality of nerve fibers was observed in SS patients. Corneal sub-basal inflammatory cell density was significantly higher in SS patients compared with control subjects (p < 0.0001). Furthermore, the mean corneal superficial epithelial cell density and area, inflammatory cell density, corneal sub-basal nerve fiber density, and morphological abnormality of nerve fibers, were improved with topical 3% diquafosol sodium treatment in the dry eye patients with SS (p < 0.05). CONCLUSIONS: The diagnostic modality using in vivo laser-scanning confocal microscopy was a useful method for the evaluation of the corneal cell density and area, nerve fiber density and morphology, and inflammatory cell density in patients with SS and also a useful tool in the assessment of treatment effect with topical 3% diquafosol sodium in the SS patients.

Corneal higher-order aberrations in Stevens-Johnson syndrome and toxic epidermal necrolysis.

PURPOSE: To characterize the topography patterns and quantify corneal higher-order aberrations (HOAs) in the chronic phase of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). METHODS: This retrospective, consecutive case series included 84 eyes of 49 patients in the chronic phase of SJS/TEN. HOAs of the total cornea, and of the anterior and posterior surfaces were measured using anterior segment optical coherence tomography (AS-OCT). Corneal topography patterns were classified into one of the 4 types: ectasia-, asymmetric-, flattening- and minimal change- patterns. RESULTS: Mean logarithm of the minimal angle of resolution (logMAR) was 0.93 ±â€¯0.95. AS-OCT showed ectasia pattern in 16 eyes (19.0%), asymmetric pattern in 28 eyes (33.3%), flattening pattern in 11 eyes (13.0%) and minimal change pattern in 29 eyes (34.5%). The HOAs of the total cornea were 1.23 ±â€¯1.04 µm within a 4-mm diameter, which were significantly larger than those in normal controls (P < 0.0001). LogMAR visual acuity was significantly correlated with corneal HOAs (4-mm: r = 0.793, P < 0.0001, 6-mm: r = 0.798, P < 0.0001) and corneal astigmatism (r = 0.508, P < 0.0001), but not with average keratometric value (r = 0.198, P = 0.065). When the participants were stratified based on corneal opacity, logMAR was significantly correlated with corneal HOAs within a 4-mm diameter in opacity grades 0 (35 eyes, r = 0.649, P < 0.0001), 1 (23 eyes, r = 0.678, P = 0.0004), and 2-3 (26 eyes, r = 0.570, P = 0.0024). Ectasia pattern was derived from either corneal thinning (68.7%) or epithelial hyperplasia (31.3%). CONCLUSIONS: The most common topographic patterns for SJS/TEN were minimal change pattern and asymmetric pattern. Corneal HOAs were associated with decreased visual acuity in SJS/TEN.

Application of In Vivo Confocal Microscopy in Dry Eye Disease.

Confocal microscopy is a new, emerging, noninvasive technology that can aid in the in vivo assessment of structural changes in several ocular surface diseases at the cellular level. In the dry eye field, in vivo confocal microscopy has been applied to the examination of the cornea, bulbar and palpebral conjunctiva, Meibomian gland, and lacrimal gland. The device can assess the morphology, including superficial/wing/basal epithelial cell density, stromal keratocyte density, endothelial cell density, nerve fiber density, the number of beadings, nerve tortuosity, nerve reflectivity, and inflammatory cell density in the cornea. Furthermore, the device can not only assess epithelial cell density and area, goblet cell, microcyst, and inflammatory cell density but also the cellular architecture, including nucleocytoplasmic ratio in conjunctiva. The device also can disclose acinar unit density, acinar unit longest diameter, acinar unit shortest diameter, and inflammatory cell density in the Meibomian gland and lacrimal gland by other potential applications. Relevant research in Europe and the United States focused on the morphologic changes in the cornea in the dry eye field, while Japanese research focused on the conjunctival, Meibomian gland, and lacrimal gland alterations. The application of in vivo confocal microscopy in dry eye disease will be a powerful method to evaluate the morphologic change of the ocular surface around the world in the future.

Eyelid cleansing with ointment for obstructive meibomian gland dysfunction.

PURPOSE: To investigate the efficacy of eyelid margin cleansing with ofloxacin ophthalmic ointment in obstructive meibomian gland dysfunction (MGD) patients. METHODS: Thirty-one eyes of 31 patients diagnosed with obstructive MGD were enrolled. All subjects were instructed to rub the eyelid edge with ofloxacin eye ointment once daily prior to bathing. Lid margin abnormalities, meibum properties, and tear stability were observed before and 3 months after ointment treatment. A questionnaire relating to the severity of MGD symptoms was administered after the treatment. RESULTS: Vascular engorgement, meibum, dandruff-like debris, and fluorescein staining scores significantly decreased after the treatment, whereas tear break-up time significantly increased (p < 0.05). Symptoms related to MGD improved after the treatment in 86.2 % of cases. CONCLUSIONS: Cleansing treatment ofloxacin ophthalmic ointment at the eyelid margin may be effective for patients with obstructive MGD.

Microwave Irradiation as a Promising Method of Sterilization for Acanthamoeba polyphaga in Cultures.

PURPOSE: To determine the killing effect of microwave irradiation on Acanthamoeba polyphaga. METHODS: The trophozoites and cysts of A. polyphaga both in water and on agar were exposed to microwave irradiation with a capacity of 750 W for 0, 1, 3, 5, and 10 minutes, respectively. Furthermore, the trophozoites and cysts of A. polyphaga in water were exposed to microwave irradiation with a capacity of 100, 300, and 500 W for 1 minute, respectively. RESULTS: The trophozoites and cysts of A. polyphaga on agar were completely killed by 3 minutes of microwave irradiation with a capacity of 750 W. The trophozoites and cysts of A. polyphaga in water were completely killed by microwave irradiation with a capacity of 300 W for 1 minute. CONCLUSIONS: We demonstrate that microwave treatment is effective in killing A. polyphaga both in water and on agar and may be a helpful modality to prevent Acanthamoeba keratitis.

The effect of Nrf2 knockout on ocular surface protection from acute tobacco smoke exposure: evidence from Nrf2 knockout mice.

Ocular surface mucosa is the first-line ocular tissue to be exposed to environmental stress. We evaluated tear functions and keratoconjunctival epithelial alterations after sidestream cigarette smoke (SCS) exposure and tried to clarify the role of the transcription factor nuclear factor erythroid 2-related factor 2 (Nfe2l2, also known as Nrf2), on the ocular surface. In wild-type and Nrf2(-/-) mice, tear volume did not change after SCS exposure. Tear film breakup time (tear stability) in Nrf2(-/-) mice was significantly shorter than that in wild-type mice after SCS exposure. Vital staining scores, including fluorescein and Rose Bengal staining, showed significantly higher values in Nrf2(-/-) mice than in wild-type mice after SCS exposure. Excessive oxidative stress accumulation was detected in Nrf2(-/-) mice after SCS exposure using immunohistochemical analysis. Immunohistochemical analysis also revealed decreased mucin 1 (Muc1) and Muc5ac staining in Nrf2(-/-) mice after SCS exposure. mRNA expression levels of Muc1, Muc4, and Muc5ac and of SAM-pointed domain epithelial-specific transcription factor in Nrf2(-/-) mice were lower than those in wild-type mice after SCS exposure. Mean tear IL-6 concentrations increased significantly in Nrf2(-/-) mice after SCS exposure. In conclusion, SCS exposure induced decreased tear stability, ocular surface damage, and altered conjunctival phenotype in Nrf2(-/-) mice. Nrf2 could play an important role in protection of the ocular surface against SCS exposure.

Effects of Oxidative Stress on the Conjunctiva in Cu, Zn-Superoxide Dismutase-1 (Sod1)-Knockout Mice.

PURPOSE: A healthy conjunctiva secreting mucins is essential for maintaining the integrity of the ocular surface epithelium. We used Cu, Zn-superoxide dismutase 1-deficient mice (Sod1-/- mice) and investigated the effect of oxidative stress on the tear function, conjunctival phenotype, and ocular surface mucin expression. METHODS: Fifty-week-old C57/B6 wild-type (WT) and Sod1-/- mice were used for evaluations of the tear film breakup time and periodic acid Schiff staining of the conjunctival specimens to detect goblet cell densities in the conjunctiva. Immunohistochemistry stainings with anti-Muc5AC, anti-Muc1, anti-4-hydroxy-2-nonenal, and anti-8-hydroxy-2'-deoxyguanosine antibodies were also performed. The mRNA expression levels of Muc1, Muc5AC, Spdef, involcurin, and transglutaminase 1 were quantified with real-time RT-PCR. RESULTS: The mean goblet cell density in the aged Sod1-/- mice was significantly lower than the aged WT mice. The mean number of Muc5ac-positive cells was significantly lower in the aged Sod1-/- mice compared with the aged WT mice. The conjunctival epithelium in the aged Sod1-/- mice displayed marked staining with lipid and DNA oxidative stress markers. The mRNA expression of transglutaminase 1 and involcurin in the aged Sod1-/- mice was significantly higher than the aged WT mice. The Spdef mRNA expression in the aged Sod1-/- mice was also significantly lower than the aged WT mice. CONCLUSIONS: Elevated oxidative stress status appears to affect the conjunctival differentiation and alter the conjunctival epithelial phenotype with aging in the Sod1-/- mice.

Functional visual acuity assessment of severe atopic keratoconjunctivitis.

PURPOSE: To evaluate changes in functional visual acuity (FVA) measurements before and after treatment with 0.1% cyclosporine ophthalmic solution for 3 months in patients with severe atopic keratoconjunctivitis (AKC). METHODS: Pairs of eyes were analyzed from 3 boys (mean age 9 ± 3.6 years) who complained of having severe AKC and were recruited for the study. Conventional Landolt visual acuity, FVA, and visual maintenance ratio (VMR) measurements were conducted before and after 3 months of 0.1% cyclosporine eye drop treatment. Tear film lipid layer interferometry, tear film break-up time, fluorescein and rose bengal vital stainings, and the Schirmer test were also performed before and after treatment. RESULTS: Eye drop treatment was associated not only with improvement of tear function and ocular surface status but also with better quality of visual function. The mean logarithm of the minimum angle of resolution FVA and Landolt visual acuity values improved from 0.45 ± 0.26 and 0.13 ± 0.17 before treatment to 0.16 ± 0.03 and -0.06 ± 0.05 after treatment, respectively. Similarly, the mean VMR values were markedly improved from 0.88 ± 0.06 to 0.95 ± 0.03 after treatment. CONCLUSIONS: FVA and VMR are promising parameters in the assessment of dynamic visual acuity changes in AKC-affected patients and evaluation of treatment outcome.

Oxidative stress induced age dependent meibomian gland dysfunction in Cu, Zn-superoxide dismutase-1 (Sod1) knockout mice.

PURPOSE: The purpose of our study was to investigate alterations in the meibomian gland (MG) in Cu, Zn-Superoxide Dismutase-1 knockout (Sod1-/-) mouse. METHODS: Tear function tests [Break up time (BUT) and cotton thread] and ocular vital staining test were performed on Sod1-/- male mice (n = 24) aged 10 and 50 weeks, and age and sex matched wild-type (+/+) mice (n = 25). Tear and serum samples were collected at sacrifice for inflammatory cytokine assays. MG specimens underwent Hematoxylin and Eosin staining, Mallory staining for fibrosis, Oil Red O lipid staining, TUNEL staining, immunohistochemistry stainings for 4HNE, 8-OHdG and CD45. Transmission electron microscopic examination (TEM) was also performed. RESULTS: Corneal vital staining scores in the Sod1-/- mice were significantly higher compared with the wild type mice throughout the follow-up. Tear and serum IL-6 and TNF-α levels also showed significant elevations in the 10 to 50 week Sod1-/- mice. Oil Red O staining showed an accumulation of large lipid droplets in the Sod1-/- mice at 50 weeks. Immunohistochemistry revealed both increased TUNEL and oxidative stress marker stainings of the MG acinar epithelium in the Sod1-/- mice compared to the wild type mice. Immunohistochemistry staining for CD45 showed increasing inflammatory cell infiltrates from 10 to 50 weeks in the Sod1-/- mice compared to the wild type mice. TEM revealed prominent mitochondrial changes in 50 week Sod1-/- mice. CONCLUSIONS: Our results suggest that reactive oxygen species might play a vital role in the pathogensis of meibomian gland dysfunction. The Sod1-/- mouse appears to be a promising model for the study of reactive oxygen species associated MG alterations.

Evaluation of a thermosensitive atelocollagen punctal plug treatment for dry eye disease.

PURPOSE: To evaluate the efficacy of a thermosensitive atelocollagen punctal plug in the treatment of dry eye disease. DESIGN: Prospective observational case series. METHODS: The thermosensitive atelocollagen punctal plug was warmed at 37 C, 39 C, 41 C, and 43 C to evaluate the appropriate temperature and time for solidification. Dry eye patients were divided into 2 groups according to the preparation method of the atelocollagen punctal plug. In the conventional implantation group, atelocollagen gel was kept at room temperature for 15 minutes before implantation (27 eyes of 14 patients). In the preheating group, atelocollagen was warmed at 41 C for 8 minutes before implantation (23 eyes of 13 dry eye patients). Strip meniscometry, vital stainings, tear film break-up time (BUT), and symptom scores were evaluated before and 1 month after plug implantation. RESULTS: In vitro experiments revealed that heating at 41 C for 8 minutes was sufficient to solidify the gel. The mean fluorescein score in the conventional implantation group significantly improved after treatment (before, 3.5 ± 2.3 points; after, 2.5 ± 0.9 points, P < .05). In the preheating group, the mean fluorescein score (before, 3.7 ± 1.7 points; after, 1.5 ± 1.2 points), strip meniscometry (before, 0.6 ± 0.7 mm; after, 1.1 ± 0.3 mm), BUT (before, 3.2 ± 0.7 seconds; after, 4.8 ± 1.0 seconds), and visual analog scale scores (before, 6.6 ± 1.5 points; after, 4.1 ± 0.9 points) significantly improved after treatment (P < .05). CONCLUSION: The thermosensitive atelocollagen punctal plug was effective for dry eye treatment. The preheating method was found to be useful to strengthen the efficacy of the thermosensitive atelocollagen punctal plug.

Visante optical coherence tomography and tear function test evaluation of cholinergic treatment response in patients with sjögren syndrome.

PURPOSE: To evaluate tear meniscus changes in patients with Sjögren syndrome (SS) receiving oral pilocarpine with Visante optical coherence tomography (OCT). METHODS: Eight patients with primary SS were recruited in this prospective interventional case series study. Patients received pilocarpine tablets twice a day for 3 months. Visual analog scale assessment for dry eye and dry mouth symptoms was carried out. Patients underwent OCT and slit-lamp microscopy graticule scale tear meniscus height (TMH) measurements, strip meniscometry testing, tear film breakup time measurement, fluorescein and Rose Bengal staining, and the Schirmer 1 test. The data were analyzed 1 week, 1 month, and 3 months after treatment. Mann-Whitney test was performed. RESULTS: Visual analog scale assessment showed a significant time-wise improvement (P < 0.05). OCT and graticule scale TMH measurements significantly improved after 1 week (P < 0.05), 1 month, and 3 months of treatment (P < 0.001). Strip meniscometry, mean tear film stability, and fluorescein and Rose Bengal scores remained improved 3 months after treatment (P < 0.001), whereas Schirmer 1 test values tended to improve without statistical significance. CONCLUSIONS: Visante OCT was effective in monitoring tear meniscus changes during the course of treatment noninvasively and quickly. Oral pilocarpine seemed to be effective in improving TMH, and the signs and symptoms of dryness in patients with SS.

Evaluation of lipid oxidative stress status in Sjögren syndrome patients.

PURPOSE: We evaluated the levels of lipid oxidative stress markers and inflammatory cells from tears and conjunctiva of patients with Sjögren syndrome (SS) and normal subjects. METHODS: We examined 31 eyes of 16 patients (16 females) with SS and 15 eyes of 10 healthy controls (2 males and 8 females) in this prospective study. All subjects underwent a Schirmer test, measurement of tear film break-up time, vital stainings, confocal microscopy of the conjunctiva, tear collection for hexanoyl-lysine (HEL), ELISA, and conjunctival brush cytology. Brush cytology samples underwent immunohistochemistry (IHC) staining with HEL and 4-hydroxy-2-nonenal (4HNE). Hematoxylin-eosin and IHC staining with HEL and 4HNE also were performed on conjunctival samples of SS patients and controls. RESULTS: The tear stability and vital staining scores were significantly worse in eyes of SS patients compared to the controls. Conjunctival inflammatory cell density was significantly higher in SS subjects compared to controls. The numbers of conjunctival cells stained positively for HEL and 4HNE were significantly higher in SS patients compared to controls. Tear HEL concentrations correlated significantly with staining scores and inflammatory cell density in confocal microscopy. Conjunctival specimens also revealed higher numbers of cells stained positively for inflammatory markers, as well as HEL and 4HNE in the IHC stainings. CONCLUSIONS: Increase of the oxidative stress status in the conjunctiva of SS patients appears to have a role in the pathogenesis of dry eye disease. A close relationship may exist between reactive oxygen species (ROS) production, lipid peroxidation related membrane damage, and inflammatory processes in dry eye.

In vivo confocal microscopy evaluation of meibomian gland dysfunction in atopic-keratoconjunctivitis patients.

PURPOSE: To clarify meibomian gland (MG) alterations in atopic keratoconjunctivitis (AKC) patients and compare the findings with obstructive MG dysfunction (MGD) patients and control subjects using in vivo confocal microscopy (CM). DESIGN: Prospective, controlled, single-center study. PARTICIPANTS: Twelve AKC patients (10 males, 2 females; mean age, 31.0±16.5 years), 12 obstructive MGD patients (7 males, 5 females; mean age, 37.6±5.6 years), and 26 control subjects (13 males, 13 females; mean age, 32.9±5.7 years) were recruited. No significant age or gender differences were observed between the 3 groups. METHODS: All subjects underwent assessment of tear evaporation rate from the ocular surface (TEROS), slit-lamp examinations, tear break-up time (BUT) measurements, vital staining, Schirmer test I, meibography, MG expressibility, and CM examination of the MG (HRTII-RCM). Statistical analysis was performed using the Mann-Whitney test. MAIN OUTCOME MEASURES: The MG acinar unit density, inflammatory cell density, MG acinar unit longest diameter, MG acinar unit shortest diameter, and MG acinar unit area as observed by in vivo CM, MG drop-out, MG expressibility grading, tear stability, tear evaporation, and vital staining scores. RESULTS: The TEROS values, mean BUT, vital staining scores, MG expressibility, and MG dropout grades were significantly worse in AKC patients compared with those in obstructive MGD patients and controls (P<0.05). The mean values of the CM parameters in AKC patients were significantly worse than those observed in the obstructive MGD patients and controls (P<0.001). CONCLUSIONS: Changes in MG in AKC patients seem to be more severe than in patients with obstructive MGD and controls. In vivo CM is a noninvasive, efficient tool in the assessment of MG status and ocular surface disease in AKC.

OCT assessment of tear meniscus after punctal occlusion in dry eye disease.

PURPOSE: To evaluate the tear meniscus changes after punctal occlusion in dry eye patients using Visante optical coherence tomography (OCT) in a prospective controlled study. METHODS: Thirty eyes of 15 symptomatic dry eye patients not responding to non-preserved artificial tears received additional upper and lower punctal occlusion with silicone plugs, and 30 eyes of 15 age- and sex-matched dry eye control patients received only non-preserved artificial tears treatment for 1 month. All subjects underwent tear meniscus height (TMH) measurements with Visante OCT. All study participants also underwent slitmicroscopy graticule scale TMH measurement, strip meniscometry testing, tear film break-up time measurement, ocular surface vital staining with fluorescein and Rose Bengal dyes, and the Schirmer-1 test. Both groups, dry eye and control group patients, were examined before and after 1-month treatment. Wilcoxon-matched pair test was performed. The study was conducted in compliance with the Tenets of the Declaration of Helsinki. RESULTS: TMH measurements by OCT and slitlamp graticule scale significantly improved after punctal occlusion (p < 0.001) and remain unchanged in the dry eye control patients. Similarly, strip meniscometry scores, mean tear stability values, Rose Bengal, and fluorescein staining scores showed significant improvement after punctal occlusion (p < 0.05). Schirmer-1 test values tended to be higher after 1 month of treatment in both groups without any statistical significance (p > 0.05). CONCLUSIONS: OCT TMH measurement appears to be effective in monitoring tear meniscus changes after punctal occlusion. OCT can be a valuable non-invasive and quick clinical tool for evaluation of treatment responses in dry eye patients.

Corneal and retinal effects of ultraviolet-B exposure in a soft contact lens mouse model.

PURPOSE: To investigate the lipid and DNA oxidative stress as well as corneal and retinal effects after ultraviolet B (UV-B) exposure in mice, with or without silicon hydrogel soft contact lenses (SCL). METHODS: Twenty-eight C57BL6-strain male mice were divided into four groups: group I, control group with no SCL (SCL [-]) and no UV-B exposure (UV-B [-]); group II, senofilcon A SCL (senofilcon [+]) with UV-B exposure (UV-B [+]); group III, lotrafilcon A SCL (lotrafilcon [+]) with UV-B exposure (UV-B [+]); and group IV, no SCL (SCL [-]), but with UV-B exposure (UV-B [+]). All mice except group I received UV-B exposure for 5 days for a total dose of 2.73 J/cm(2). All mice underwent tear hexanoyl-lysine (HEL) and tear cytokine ELISA measurements, and fluorescein and rose bengal corneal staining before and after UV-B exposure. Corneal specimens underwent immunohistochemistry staining with CD45, HEL, 4-hydroxynonenal (4-HNE), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) antibodies and evaluation with electron microscopy. RESULTS: All mice without SCL but exposed to UV-B developed corneal edema, ulcers, or epithelial damage compared with mice with senofilcon A SCL and exposure to UV-B. Tear HEL and cytokine levels significantly increased in mice without SCL after UV-B exposure. Immunohistochemistry showed a significantly higher number of cells positively stained for CD45, 8-OHdG, HEL, and 4-HNE in the corneas of mice without SCLs compared with those with senofilcon A after UV-B exposure. CONCLUSION: Silicon hydrogel SCL showed corneal and retinal protective effects, owing to UV blocking properties, against oxidative stress-related membrane lipid and cellular DNA damage.

Age-related dysfunction of the lacrimal gland and oxidative stress: evidence from the Cu,Zn-superoxide dismutase-1 (Sod1) knockout mice.

An imbalance between free radical generation and radical scavenging antioxidant systems results in oxidative stress, which has been associated with cell injury observed in many age-related diseases. The superoxide dismutase (SOD) family is a major antioxidant system, and deficiency of Cu,Zn-superoxide dismutase-1 (Sod1) in mice leads to many different phenotypes that resemble accelerated aging. In this study we examined the morphologic features and the secretory functions of the lacrimal glands in Sod1(-/-) mice. Lacrimal glands showed atrophy of acinar units; fibrosis; infiltration with CD4(+) T cells, monocytes, and neutrophils; increased staining with both 4-hydroxy-2-nonenal and 8-hydroxy-2'-deoxyguanosine; increases in apoptotic cells; and the presence of the epithelial-mesenchymal transition in senescent Sod1(-/-) mice. Electron microscopy findings revealed evidence of epithelial-mesenchymal transition, presence of swollen and degenerated mitochondria, and the presence of apoptotic cell death in the lacrimal glands of senescent Sod1(-/-) mice. These alterations were also associated with the accumulation of secretory vesicles in acinar epithelial cells, decreased production of both stimulated and nonstimulated tears, and a decline in total protein secretion from the lacrimal glands. Our results suggest that Sod1(-/-) mice may be a good model system in which to study the mechanism of reactive oxygen species-mediated lacrimal gland alterations.

IgE and eosinophil cationic protein (ECP) as markers of severity in the diagnosis of atopic keratoconjunctivitis.

AIMS: To evaluate tear and serum IgE and eosinophil cationic protein (ECP) as severity markers for atopic keratoconjunctivitis (AKC). METHODS: Thirty eyes of 30 patients with AKC and 10 eyes of 10 healthy control subjects were examined in this prospective study. All subjects underwent fluorescein staining, conjunctival injection, conjunctival oedema and papillary formation grading. Tear and serum IgE and ECP levels were measured, and correlations between them investigated with reference to the ocular surface clinical parameters. RESULTS: The mean fluorescein scores, conjunctival injection, oedema scores and papillary formation were significantly higher in AKC patients compared to controls (p<0.05). Higher total IgE and ECP levels were detected in AKC tears compared with the control group. Tear ECP levels showed a significant correlation with fluorescein staining, conjunctival injection and oedema scores (r=0.70, 0.62 and 0.62, respectively). Tear IgE had no correlation with clinical signs. Serum IgE and ECP levels were elevated in AKC patients but did not show any correlation with clinical signs. CONCLUSION: This study suggests the presence of an eosinophilic response in AKC disease independent of IgE sensitisation. Tear ECP was a useful marker delineating the severity of ocular surface disease in AKC.

Morphologic evaluation of meibomian glands in chronic graft-versus-host disease using in vivo laser confocal microscopy.

PURPOSE: To evaluate the morphological changes of the meibomian glands (MGs) using in vivo laser confocal microscopy (CM) in dry eye (DE) patients with chronic graft-versus-host disease (cGVHD). METHODS: Seventeen eyes from 9 patients with a diagnosis of DE associated with cGVHD (DE/cGVHD group; 6 males, 3 females; median 50.5 years) and 16 eyes of 8 hematopoietic stem cell transplantation (HSCT) recipients without DE (non-DE/non-cGVHD group; 5 males, 3 females; median 47.0 years) were enrolled. CM was used to investigate the MG and MG acinar unit density (MGAUD), MG acinar longest diameter (MGALD), MG acinar shortest diameter (MGASD), and the fibrosis grade. Clinical findings of the lid margin were obtained. Tear dynamics, ocular surface vital staining, meibography, and MG expressibility were also examined. Data were compared between the 2 groups using the unpaired t and Mann-Whitney tests. RESULTS: The mean MGAUD value was significantly lower in the DE/cGVHD group than in the non-DE/non-cGVHD group (p=0.01, 57.8±38.3 glands/mm(2), 88.8±26.6 glands/mm(2), respectively), and the mean MGALD and MGASD were significantly shorter in the DE/cGVHD group than in the non-DE/non-cGVHD group (p=0.0018, 37.3±24.4 µm and 60.4±11.8 µm, p=0.0106, 17.7±11.8 µm and 26.6±6.03 µm, respectively). The mean fibrosis grade was significantly higher in the DE/cGVHD group than the non-DE/non-cGVHD group (p<0.0001, 1.39±0.71 grade, 0.06±0.25 grade, respectively). Clinical findings in the lid margin, tear dynamics, and ocular surface findings were significantly worse in the DE/cGVHD group than in the non-DE/non-cGVHD group. CONCLUSIONS: CM clearly depicted the morphological changes of the MG in the DE/cGVHD group, and revealed the severity of the meibomian gland dysfunction. Patients with severe DE after HSCT showed atrophic MG and excessive fibrosis.