Levofloxacin susceptibility of Staphylococci from conjunctiva in patients with atopic dermatitis.

PURPOSE: The ocular surface in patients with atopic dermatitis (AD) is known to harbor an abundance of gram-positive cocci, particularly Staphylococcus aureus (S. aureus). This study reviewed the results of microbial cultures from the conjunctiva in AD patients, with special attention to the levofloxacin susceptibility of Staphylococci. STUDY DESIGN: Retrospective, single-center study. METHODS: This study involved 131 eyes of 112 Japanese patients with AD (87 men and 25 women, mean age: 40.4 ± 12.2 years) who underwent ocular surgery at Kyorin University Hospital. Bacterial isolates were collected from the conjunctival sacs in the preoperative period. Drug resistance to methicillin and levofloxacin was judged using the minimal inhibitory concentrations of oxacillin and levofloxacin determined by the broth dilution method. RESULTS: One hundred and fifty-seven strains were identified in 103 of the 131 eyes examined. S. aureus was isolated from 74 eyes (56.5%), followed by Staphylococcus epidermidis (S. epidermidis). In S. aureus, 11 strains (14.9%) were methicillin-resistant, and 18 (24.3%) were levofloxacin-resistant. In S. epidermidis, 15 strains (26.8%) were methicillin-resistant, and 17 (30.4%) were levofloxacin-resistant. No significant differences were observed in levofloxacin susceptibility with age, sex, previous ocular surgery, or duration of previous surgery. However, logistic multivariate analysis revealed that levofloxacin-resistant Staphylococci were concurrently resistant to methicillin, suggesting multidrug resistance. CONCLUSION: Distinctive bacterial distribution and drug resistance need consideration in the managing of ocular disorders among patients with AD.

Fulminant Marginal Keratitis Induced by Atezolizumab, a Programmed Death Ligand 1 Inhibitor for Lung Cancer.

Introduction: With the increasing use of immune checkpoint inhibitors, ocular adverse events have gained attention. We describe a case of atypical keratitis presumably induced by atezolizumab, a programmed cell death ligand 1 inhibitor. Case Presentation: A 73-year-old Japanese woman developed ring-shaped marginal infiltrations with epithelial breakdown of the corneas in both eyes. The patient had advanced small cell lung cancer and had received intravenous carboplatin, etoposide, and atezolizumab. She was treated with topical administration of 0.1% sodium phosphate betamethasone and 0.5% moxifloxacin six times daily. On day 14 following initial presentation, marked reduction of bilateral corneal infiltration was observed. During the succeeding cycles of chemotherapy, marginal keratitis did not recur, and then, the topical steroid was gradually tapered. Conclusions: Cancer immunotherapy, including atezolizumab, may lead to active T-cell recruitment into the cornea, which result in autoimmune corneal keratitis. We believe that this report is informative to both ophthalmologists and oncologists involved in the treatment of patients receiving cancer immunotherapy.

Ocular Manifestations of Peters Plus-Like Syndrome in 8q21.11 Microdeletion Syndrome.

PURPOSE: The aim of this study was to report a case of Peters plus-like syndrome, which revealed to have an 8q21.11 microdeletion by copy number variation analysis using exome data. METHODS: A 6-month-old Japanese boy presented with bilateral corneal opacity since birth. The right eye maintained central corneal transparency with slightly inferior nasal and superior peripheral corneal opacities. The entire cornea was opacified in the left eye, particularly in the superior quadrants with vascularization, suggesting Peters anomaly. Identification of intraocular structures in the left eye was difficult; however, hypoplasia of the circumferential anterior iris stroma appeared bilaterally present, and no abnormalities were present in the posterior segment on funduscopic examination of the right eye and ultrasonography in the left eye. He had several facial malformations in addition to corneal opacity, but no other external abnormalities. General examination, including biochemical tests of blood and urine, physiological and imaging tests including abdominal echo, auditory brain stem response, brain computed tomography, and magnetic resonance imaging, showed no abnormalities. However, the patient showed intellectual disability and delayed motor development. RESULTS: Although his karyotype was normal, copy number variation analysis using exome data and subsequent quantitative polymerase chain reaction identified a de novo 4.6-Mb deletion at 8q21.11q21.13; thus, the patient was diagnosed with 8q21.11 microdeletion syndrome. CONCLUSIONS: We identified a de novo 4.6-Mb deletion at 8q21.11q21.13 in a patient with ophthalmic anterior segment dysgenesis and systemic complications, clinically diagnosed as Peters plus-like syndrome. Clinically, the 8q21.11 microdeletion syndrome shows a phenotype similar to that of Peters plus syndrome, and a genetic diagnosis is required.

A pediatric case of congenital stromal corneal dystrophy caused by the novel variant c.953del of the DCN gene.

We report a 1-year-old girl with congenital stromal corneal dystrophy confirmed by genetic analysis. The ocular phenotype included diffuse opacity over the corneal stroma bilaterally. We performed a genetic analysis to provide counseling to the parents regarding the recurrence rate. Whole exome sequencing was performed on her and her parents, and a novel de novo variant, NM_001920.5: c.953del, p.(Asn318Thrfs*10), in the DCN gene was identified in the patient.

Severe Ocular Complications Associated With Wearing of Contact Lens in Japan.

OBJECTIVES: To examine the severe ocular complications associated with contact lens wearing in Japan. METHOD: A questionnaire was sent to 964 ophthalmologist training facilities inquiring for cases of contact lens-associated complications from April 2016 to March 2018. The inclusion criteria were as follows: (1) corrected distance visual acuity ≤0.1 decimal after treatment for 3 months, (2) corneal perforation observed during follow-up, and (3) requiring surgery. A secondary analysis was conducted, inquiring for further information on the type of contact lens, clinical manifestations, and course of treatment. RESULTS: Forty-two patients with infectious keratitis met the inclusion criteria. Eight patients were users of rigid gas-permeable contact lens, and 34 were users of soft contact lens. Microbiological tests were positive in 73.0%. The organisms isolated in microbiological culture were bacteria in 11 patients (Pseudomonas aeruginosa in 9 patients), fungi in 2 patients, and Acanthamoeba in 14 patients. Ten patients were treated with local antibiotics, 11 with a combination of systemic antibiotics, and 21 with a combination of surgical approaches, including 13 with corneal transplantation. CONCLUSIONS: The major cause of serious contact lens-associated ocular complications was microbial keratitis, and P. aeruginosa and Acanthamoeba were the major pathogens in Japan.

Tear protein analysis in patients with primary acquired nasolacrimal duct obstruction treated with lacrimal passage intubation.

PURPOSE: The pathophysiology of nasolacrimal duct obstruction (NLDO) may involve quantitative as well as qualitative changes in tears. We measured tear protein concentrations in patients with primary acquired NLDO and compared them with the tear proteins in healthy individuals and patients with dry eye disease. STUDY DESIGN: Case-control study. METHODS: Twenty-four patients diagnosed with primary acquired NLDO who underwent endoscopic lacrimal passage intubation were included in the study. Tear fluid was collected with Schirmer's test strips three times: before intubation, after intubation while the nasolacrimal tube was in place, and after extubation. At the same time, 24 age-matched normal controls and 24 patients with dry eye were selected from subjects whose tears were collected during the same study period. We measured the following components of tear fluid: total protein, lactoferrin, albumin, and interleukin 6 (IL-6) levels. RESULTS: Total proteins and albumin levels in tears of the NLDO group were significantly lower than those of the control group (P < 0.001 and P = 0.014, respectively, Mann-Whitney U test). Total proteins, albumin, and lactoferrin levels were significantly increased after extubation of nasolacrimal tube (P < 0.001, P = 0.004, and P = 0.029, respectively, Wilcoxon matched-pairs signed-rank test). There were no statistically significant differences in total protein, albumin, lactoferrin and IL-6 levels between patients with NLDO after lacrimal passage extubation and controls. CONCLUSIONS: Our study shows distinct differences in protein composition of tear fluid in NLDO eyes and demonstrates that these can be normalized by nasolacrimal tube placement.

Characteristics and Utility of Fluorescein Breakup Patterns among Dry Eyes in Clinic-Based Settings.

(1) Background: To evaluate the characteristics of fluorescein breakup patterns (FBUPs) among patients with dry eye disease (DED) and efficacy of FBUPs as a diagnostic test for DED subgroups. (2) Methods: The study enrolled 449 patients with DED. FBUPs were categorized as follows: area break (AB), line break (LB), spot break (SB), dimple break (DB), and random break (RB). Schirmer value, fluorescein breakup time (FBUT), keratoconjunctival score, DED subgroups and subjective symptoms were examined. (3) Results: LB patients presented with short FBUT and high keratoconjunctival score. AB patients presented with short FBUT, high cornea and keratoconjunctival scores. SB patients were young with short FBUT. DB patients exhibited low keratoconjunctival score. RB patients were young, with long FBUT and low keratoconjunctival scores. Among DED subgroups, LB and AB constituted 74.7% of aqueous-deficiency dry eye (ADDE). SB and DB constituted 42.4% of short FBUT dry eye (short FBUT-DE). Post-test probabilities and positive likelihood ratios for ADDE were 58.7% and 1.63, respectively; those for short FBUT-DE were 46.3% and 2.02, respectively. Patients with SB and AB exhibited significantly severe subjective symptoms than other FBUPs. (4) Conclusions: FBUPs are associated with both objective findings and symptoms of DED and may be a clinical tool for identification of DED subgroups.

Association of Systemic Comorbidities with Dry Eye Disease.

We investigated the association between dry eye disease and systemic comorbidities, including dry eye subtype, quality of life (QOL) and health utility among patients with dry eye disease. This cross-sectional, observational study enrolled 449 patients with dry eye disease (386 females; mean age, 62.6 ± 15.7 [range, 21-90] years). Ophthalmic examination findings included tear film break-up time (TBUT), Schirmer I value and keratoconjunctival staining score. QOL and health utility were evaluated using the Dry Eye-Related Quality-of-Life Score (DEQS) and Human Utility Index Mark 3 (HUI-3), respectively. Background information, including systemic comorbidities, was obtained. Prevalence of systemic comorbidities was 48.8% (219/449). No significant difference occurred between DEQS and systemic comorbidity. However, patients with dry eye disease and systemic comorbidities (depression and insomnia) exhibited significantly worse ocular surface parameters, particularly regarding TBUT, than those without. Dry eye disease with insomnia or depression comorbidity significantly correlated with friction-related diseases (including conjunctivochalasis or lid wiper epitheliopathy). A high prevalence of several systemic comorbidities occurred in patients with dry eye disease. This study shows an association between ocular signs and systemic comorbidities, particularly depression and insomnia. Ophthalmologists should be aware of patients' systemic comorbidities in the diagnosis and management of dry eye disease.

Tear protein analysis in presumed congenital alacrima.

OBJECTIVES: It is often hard to reach a definitive diagnosis of congenital alacrima because of the difficultly in proving the lack of lacrimal tissue. We report here the distinct tear protein profile in presumed congenital alacrima. PATIENTS AND METHODS: A 13-year-old girl with presumed congenital alacrima and 15 healthy volunteers aged 23-35 years were included in this study. Tears were collected using Schirmer strips, and tear protein analyses were performed. Tear samples were collected from the patient with alacrima before and after surgical punctal occlusion of both the upper and lower puncta, and tear protein extract was fractionated using HPLC. Lactoferrin and albumin concentrations in the tears were separately determined using ELISA. RESULTS: The chromatogram in the patient greatly differed from that in normal subjects with low concentrations of secretory IgA, lipocalin-1, and lysozyme. ELISA results indicated that the tear fluid in the patient contained a high concentration of albumin but a minimal concentration of lactoferrin. Punctal occlusion improved the ocular surface findings, but major lacrimal protein concentrations remained low and tear albumin concentrations further increased. CONCLUSION: The tear protein profile of a patient with presumed congenital alacrima greatly differed from that of normal subjects. Tear protein analysis may be useful in making a diagnosis of congenital alacrima and in assessing the efficacy and mechanism of punctal occlusion.

Quality of life measures and health utility values among dry eye subgroups.

BACKGROUND: To determine whether quality of life (QOL) and health utility are affected to the same extent among dry eye (DE) patients with short tear film break-up time dry eye (TBUT-DE) with minimal clinical signs were as severe as aqueous-deficient dry eye (ADDE). METHODS: A multicenter cross-sectional study was conducted among DE patients who visited one of 10 eye clinics in Japan. Among the 463 registered patients, this study involved 449 patients with DE who were aged 20 years or older. Ophthalmic examination findings were assessed, including tear film break-up time (TBUT), Schirmer I value, and keratoconjunctival staining score. QOL was evaluated with the Dry Eye-Related Quality-of-Life Score (DEQS; 0 [best], 100 [worst]) and health utility (1 [total health], 0 [worst]) with the Health Utilities Index Mark 3 (HUI-3); scores were stratified by DE subgroup. RESULTS: Median (interquartile range) of DEQS and HUI-3 scores across all participants were 21.7 (10.0-40.0) and 0.82 (0.69-0.91), respectively. Median (interquartile range) DEQS and HUI-3 scores in the ADDE group were 23.3 (10.0-40.0) and 0.79 (0.69-0.88), respectively; those in the short TBUT-DE group were 23.3 (13.3-38.3) and 0.82 (0.74-0.92), respectively. There were no significant between-group differences in questionnaire scores. Among the ophthalmic examination findings, a weak significant correlation between TBUT, corneal staining score and keratoconjunctival staining score to DEQS; TBUT and Schirmer test values to HUI-3, were seen. CONCLUSIONS: The burden of short TBUT-DE on QOL as assessed by the DEQS and HUI-3 was as severe as that in ADDE. Our findings suggest that clinicians should be aware of the impact of short TBUT-DE on patients QOL and utility values. TRIAL REGISTRATION: University Hospital Medical Information Network (registration no. UMIN 000015890). Registered 10th December 2014, retrospectively registered.

Conjunctival Eosinophilic Masses With Chronic Eosinophilic Pneumonia.

PURPOSE: To report a case of ocular findings associated with chronic eosinophilic pneumonia (CEP). CASE: A 63-year-old man was referred to the National Institution of Hospital Organization Tokyo Medical Center with bilateral eyelid swelling due to giant papillomatous changes, each measuring approximately 10 mm in diameter with severe hyperemia on the tarsal conjunctiva. He was followed for CEP for 8 years and systemically treated with 6 mg oral prednisolone for an average of 5 years. Because the lesions did not respond to topical 0.1% tacrolimus and 0.025% levocabastine treatment and because an increase in intraocular pressure was found to occur as a side effect of 0.01% betamethasone instillation for several months, we performed surgical resection of the bilateral conjunctival lesions. Histopathological findings revealed extreme eosinophil, plasma cell, and lymphocytic infiltration and interstitial fibrosis. These conjunctival specimen findings were similar to those seen in the alveolar lesions in CEP. Topical antiinflammatory therapy using 0.1% tacrolimus eye drops was administered after surgery, which relieved the patient's lid swelling and itching. However, the lesions concurrently changed to be consistent with exacerbation and remission of systemic CEP. CONCLUSIONS: Based on the clinical course and histopathology, the conjunctival proliferative masses in our case were assumed to be associated with CEP.

Determination of 5-fluorouracil and tegafur in tear fluid of patients treated with oral fluoropyrimidine anticancer agent, S-1.

PURPOSE: To establish a method for the measurement of 5-fluorouracil (5-FU), and tegafur (FT) in tear samples from patients treated with oral fluoropyrimidine anticancer agent S-1. STUDY DESIGN: Cross-sectional study. METHODS: High performance liquid chromatographic (HPLC) method reported for plasma samples was modified for tear samples. Simulated-tear solutions containing lactoferrin, lysozyme and standard solution containing 5-FU or FT were prepared for preliminary measurements. Tear samples from seven patients treated with S-1 were included. The tears were collected following S-1 administration using Schirmer's strips. RESULTS: 5-FU and FT concentrations of pure standard solution without extraction process were detected as original concentration. However, on extraction, FT samples in simulated-tear solution showed a peak for 5-FU but not for FT. FT was converted to 5-FU in the extraction process. Decomposition from FT to 5-FU was suppressed when 50 mg/mL bovine serum albumin was added during extraction. The mean concentrations of 5-FU and FT in tears during S-1 treatment were 0.17 ± 0.11 and 1.94 ± 0.71 µg/mL, respectively. CONCLUSION: A simple HPLC method to determine 5-FU and FT in tear samples was established.

Influence of Meibomian Gland Dysfunction and Friction-Related Disease on the Severity of Dry Eye.

PURPOSE: To evaluate the effect of meibomian gland dysfunction (MGD) and friction-related disease (FRD) on the severity of dry eye disease (DED). DESIGN: Cross-sectional observational study. PARTICIPANTS: This study enrolled 449 patients with DED (63 men and 386 women; mean age, 62.6±15.7 years [range, 21-90 years]) for analysis. METHODS: Subjective symptoms, the ocular surface, tear function, and the presence of MGD and FRD (superior limbic keratoconjunctivitis, conjunctivochalasis, and lid wiper epitheliopathy) were investigated. MAIN OUTCOME MEASURES: Schirmer value, tear film breakup time (TBUT), and keratoconjunctival score. RESULTS: We classified the participants into aqueous-deficient dry eye (ADDE; n = 231 [51.4%]) and short TBUT dry eye subtype (TBUT-DE; n = 109 [24.3%]) subgroups. The TBUT was shorter in patients with MGD than in those without MGD, whereas other ocular signs showed no difference (TBUT: MGD present, 1.97±1.02 seconds; MGD absent, 2.94±1.63 seconds [P < 0.001]; ADDE/MGD present, 1.94±1.08 seconds; ADDE/MGD absent, 2.77±1.61 seconds [P < 0.001]; short TBUT-DE/MGD present, 2.07±0.97 seconds; short TBUT-DE/MGD absent, 2.94±1.23 seconds [P = 0.01]). The ADDE patients with FRD showed a worse TBUT than ADDE patients without FRD (TBUT: ADDE/FRD present, 2.08±1.39 seconds; ADDE/FRD absent, 2.92±1.54 seconds; P < 0.001). CONCLUSIONS: This study showed associations between MGD, FRD, or both and ocular signs in DED. In the presence of MGD, FRD, or both, TBUT was significantly shortened regardless of the dry eye status or subtype.

Metagenomic analysis for detecting Fusarium solani in a case of fungal keratitis.

PURPOSE: To report a difficult-to-identify case of keratitis due to Fusarium solani, diagnosed with the help of exhaustive gene analysis. CASE: A 47-year-old woman attended our hospital with a refractory corneal ulcer associated with contact lens wear in her left eye that had appeared two weeks earlier. On her initial visit, slit lamp examination revealed a small double-ringed irregular hyphate ulcer in the center of the cornea, which had no epithelial defect, suggesting fungal infection. Microscopic visualization and culture of corneal scrapings were performed repeatedly, but the results were negative. Despite intensive antifungal treatment, infiltration of the cornea worsened and therapeutic keratoplasty was performed. Specimens from a corneal button were microbiologically and histologically negative for microorganisms. During irrigation of the anterior chamber with amphotericin B, aspirated corneal infiltrations were submitted for culture and metagenomic analysis. Genes belonging to F. solani were identified by metagenomic analysis, and an isolate presumed to be a Fusarium species was cultured. Genotypic identification of the isolates confirmed F. solani. CONCLUSION: The detection of microorganisms, especially fungi, can be extremely difficult. In difficult-to-culture cases, metagenomic analysis seems to be a promising technique for the identification of microbial pathogens.

The effect of rebamipide ophthalmic suspension on ocular surface mucins in soft contact lens wearers.

PURPOSE: To evaluate the changes in ocular surface mucins with 2%rebamipide ophthalmic suspension treatment in soft contact lens (SCL) wearers. Rebamipide suspension is a mucin secretagogue approved for the treatment of dry eye syndrome in Japan. In this study, the fluorescence intensity of wheat germ agglutinin conjugate of fluorescein (F-WGA) was used as a marker of membrane-associated mucins, and sialic acid concentration in tear fluids as a marker of secreted mucins. METHODS: Thirty-two eyes of 16 SCL wearers with discomfort were treated with rebamipide suspension at a dose of one drop in each eye four times daily for two weeks. The parameters of clinical efficacy were tear break-up time, fluorescein staining scores for the cornea and conjunctiva, and Schirmer test values. Fluorescence intensities in the central cornea were measured by fluorophotometry after the application of 5% F-WGA solution. Tears collected by Schirmer test strips were analyzed by high-performance liquid chromatography, and the concentrations of sialic acid, total protein, and the four major tear proteins, namely secretory IgA, lactoferrin, lipocalin-1, and lysozyme were measured. RESULTS: Significant increases in F-WGA fluorescence intensities (p < 0.005) were seen in the corneal surfaces. Sialic acid concentrations increased over time; however, the differences were not statistically significant. Except for a slight increase in kerato-conjunctival staining scores (p < 0.05) and secretory IgA (p < 0.05), no other significant differences were seen among clinical parameters or tear proteins. CONCLUSIONS: Topical application of rebamipide suspension significantly increased F-WGA intensity, a marker of membrane-associated mucins in SCL wearers.

A Clinic-based Survey of Clinical Characteristics and Practice Pattern of Dry Eye in Japan.

INTRODUCTION: The aim of this study was to investigate the clinical characteristics and practice pattern of patients with dry eye disease (DED) in eye clinics across Japan. METHODS: A multi-center, cross-sectional study was conducted among patients with DED who visited eye clinics in Japan. Subjective symptoms, patient's background, ocular surface features, and tear function were evaluated. Main outcome measures were tear break-up time (TBUT), Schirmer I value, kerato-conjunctival staining score, and dry eye symptom questionnaire score. RESULTS: Initially, 463 subjects were enrolled, and 449 cases (63 male and 386 female; mean age, 62.6 ± 15.7 years) were included in the final analysis. Overall, 94.9% of patients had a shortened TBUT (≤5 s), and 54.6% had an aqueous tear deficiency (Schirmer I value ≤5 mm). The most prevalent subtype of dry eye was aqueous-deficient dry eye, which was present in 35.0% of all patients, followed by short-BUT-type dry eye, which was seen in 26.7%. CONCLUSION: The two most common DED subtypes were aqueous-deficient and short-BUT-type dry eye. Shortened TBUT is the most common feature of dry eye, regardless of subtype. The current treatment choice mainly consisted of hyaluronic acid, two novel mucin secretagogues, diquafosol and rebamipide, and steroidal eye drops. TRIAL REGISTRATION: University Hospital Medical Information Network: UMIN (registries no. UMIN 000015890). FUNDING: Japan Dry Eye Society, Tokyo, Japan, and Santen Pharmaceutical Co., Ltd., Osaka, Japan.

Effectiveness of bandage contact lens application in corneal epithelialization and pain alleviation following corneal transplantation; prospective, randomized clinical trial.

BACKGROUND: To assess the efficacy of bandage contact lens (BCL) application to promote epithelialization and alleviate pain following corneal transplantation. METHODS: Twenty-six consecutive patients who underwent corneal transplantation were randomly assigned to undergo BCL application (BCL group, n = 14) or no BCL application (control group, n = 12) at the end of the surgery. Corneal epithelialization was analyzed by photography using fluorescein staining, and ocular pain was measured using a visual analog scale. RESULTS: The mean size of the epithelial defect relative to the graft area in the BCL group was 21.80 ± 35.10 % at the end of surgery, 18.20 ± 31.10 % on postoperative day 1, and 5.45 ± 11.10 % on postoperative days 3 to 5. These values in the control group were 9.64 ± 17.60 % at the end of surgery, 11.50 ± 25.70 % on postoperative day 1, and 0.00 ± 0.00 % on postoperative days 3 to 5. There were no significant differences in the speed of epithelialization between the two groups. The mean preoperative pain score in the BCL group was slightly higher than that control (4.27 ± 1.96 vs. 2.41 ± 2.18, respectively; P = 0.039). The scores significantly increased on postoperative day 1 and promptly returned to preoperative levels by day 7 in both groups, and there were no significant differences between the groups. CONCLUSIONS: No significant benefits of BCL application at the time of corneal transplantation were observed in this study. The efficacy and safety of BCLs in eyes with compromised epithelialization require further study. TRIAL REGISTRATION NUMBER: UMIN 000019091 . Date of registration: 2015/09/22.

Influence of Ophthalmic Solutions on Tear Components.

Tear fluids are a mixture of secretions derived from lacrimal glands, accessory lacrimal glands, conjunctiva, and meibomian glands. Compositional changes to tears occur in the normal state and during ocular surface disease, such as dry eye conditions. We have investigated compositional changes to tears after topical application of ophthalmic solutions, with regard to tear-specific proteins (secretory immunoglobulin A, lactoferrin, lipocalin-1, and lysozyme) and ocular surface mucin in normal and dry eye conditions using high-performance liquid chromatography. After application of saline solution (0.9% sodium chloride) in normal subjects, transient but significant decreases in all tear components were observed. The recovery of protein concentrations took up to 30 minutes and lasted longer when the saline solution was applied more frequently. When applying ophthalmic solutions, a balance between washout and dilutional effects should be considered in addition to the therapeutic effect. Investigation of the effect of diquafosol solution (3%) in normal subjects revealed a significant increase in sialic acid concentration, a marker of ocular mucin, at 5 minutes after application, whereas a significant decrease was observed with saline. This result indicates the accelerated secretion of mucin from ocular tissues induced by diquafosol. A clinical study to determine the efficacy of diquafosol in patients with dry eye revealed improvements in tear breakup time, keratoconjunctival staining scores, and Schirmer test score, accompanied by an increase in sialic acid concentration in tears. Investigating normal and dry eye conditions through tear analysis may clarify the pathophysiology of dry eye conditions and support the efficacy of treatments.

Abnormal Corneal Lesions Induced by Trastuzumab Emtansine: An Antibody-Drug Conjugate for Breast Cancer.

PURPOSE: To report a case of atypical corneal lesions presumably induced by trastuzumab emtansine, an antibody-drug conjugate that is designed to selectively deliver cytotoxic agents to human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells. CASE: A 64-year-old Japanese woman developed bilateral corneal epithelial abnormalities that originated from the limbus. The corneal lesions covered the superior area in the right eye and both superior and inferior areas including the visual axis in the left eye. The patient had advanced ductal carcinoma of the left breast and had been receiving anticancer treatment with trastuzumab emtansine for 15 months. After switching the chemotherapy from trastuzumab emtansine monotherapy to the combination of docetaxel, trastuzumab, and pertuzumab, the abnormal corneal lesions showed gradual improvement. CONCLUSIONS: As corneal epithelial cells express human epidermal growth factor receptor 2 under normal conditions, such cells may also be targeted by trastuzumab emtansine and lead to corneal epithelial lesions.

Diquafosol for Soft Contact Lens Dryness: Clinical Evaluation and Tear Analysis.

PURPOSE: To evaluate the efficacy of topical application of 3% diquafosol tetrasodium solution for the treatment of soft contact lens (SCL) wearers with dryness. In addition to clinical tests and subjective symptoms, we assessed the fluorescence intensity of wheat germ agglutinin conjugate of fluorescein (F-WGA) used as a marker of membrane-associated mucins and sialic acid concentration in tear fluids as a marker of secreted mucins. METHODS: Twelve SCL wearers with dryness symptoms were treated with diquafosol for 4 weeks. Clinical tests included the tear film break-up time (BUT), corneal and conjunctival fluorescein staining scores, and Schirmer values. Subjective symptoms were evaluated by the Dry Eye-Related Quality-of-Life Score (DEQS). Fluorescence intensities in the central cornea were measured by fluorophotometry at 5 minutes after a 5% F-WGA solution was applied to the eye. The tears collected by the Schirmer test strips were analyzed by high-performance liquid chromatography (HPLC), and the concentrations of sialic acid; total protein; and the four major tear proteins secretory IgA, lactoferrin, lipocalin-1, and lysozyme proteins were measured. RESULTS: Comparing the results before and after diquafosol treatment, BUT (p < 0.01), kerato-conjunctival staining score (p < 0.05), corneal staining score (p < 0.05), and DEQS score (p < 0.01) showed statistically significant improvements. The F-WGA fluorescence intensities (p < 0.0001) significantly increased after treatment, whereas the concentrations of sialic acid and tear proteins remained unchanged. CONCLUSIONS: Topical application of diquafosol solution to the SCL wearers with dryness improved biomarker of membrane-associated mucins, BUT, staining of cornea and conjunctiva, and subjective symptoms.