Masao Matsubara

Airborne particulate matter (PM2.5) and the prevalence of allergic conjunctivitis in Japan

OBJECTIVE Exposure to particulate matter less than 2.5 μm in diameter (PM2.5) is associated with asthma and respiratory symptoms, but little is known about the influence of PM2.5 on allergic conjunctivitis. The purpose of this study was to examine the association of PM2.5 with outpatient attendance for allergic conjunctivitis. METHODS We conducted a time-series analysis of the association between outpatient attendance for allergic conjunctivitis and PM2.5 levels from May to July (non-pollen season) and from August to October (the autumnal pollen season) in 2012. Air pollution data (including the levels of PM2.5, oxidants, nitric oxide, nitrogen dioxide, nitrogen oxide, carbon monoxide, methane, non-methane hydrocarbons, and total hydrocarbons) and data on the daily weather conditions (temperature, wind speed, and humidity) were collected at a centrally located monitoring station in Tokyo. We calculated weekly average values for the daily number of outpatient visits, as well as the air pollution and weather data, and used the weekly average values for analysis. RESULTS There was a significant association between the number of outpatient visits for allergic conjunctivitis and the PM2.5 level (r=0.62, p=0.0177) from May to July, while no correlation was found between the number of outpatient visits and any variable assessed from August to November. Multivariate analysis also showed that PM2.5 was a significant predictor of the number of outpatient visits from May to July (odds ratio=9.05, p=0.0463), while there were no significant predictors of the number of outpatient visits from August to October. From May to July, PM2.5 showed a negative correlation with humidity (r=-0.53, p=0.0499). CONCLUSIONS These findings suggest a possible role of PM2.5 in the development of allergic conjunctivitis during the non-pollen season. This association between PM2.5 and allergic conjunctivitis may have broad public health implications in relation to allergic diseases.

Histologic and histochemical changes in rabbit cornea produced by an orthokeratology lens

Purpose: To report the histologic and histochemical properties of rabbit cornea after insertion of an orthokeratology lens. Methods: An orthokeratology lens was placed on the left corneas of rabbits for 8 hours daily, and their eyes were enucleated after 7, 14, 21, and 28 days and examined histologically and histochemically. The right eyes were used as controls. Results: After 7–14 days, hematoxylin and eosin staining of the cornea revealed that the epithelial layer was slightly thinner in the central area and thicker in the intermediate area, but its thickness gradually became normal toward the limbus. Periodic acid-Schiff staining showed no abnormal distribution of glycogen granules or glycogen producing cells. 5-bromo-2-deoxyuridine staining revealed more mitoses in the central area than in the intermediate area. Histochemical staining showed lactic dehydrogenase activity in the central area of the lens, whereas alkaline phosphatase activity and beta-glucuronidase activity were slightly increased in the intermediate area. There were no other clearly abnormal findings. Conclusions: The thickness of the corneal epithelium showed topographical variation consistent with the effect of orthokeratology. The result of histochemical studies suggested that there were no marked alterations in epithelial function.

Effects of the Immunosuppressant FK506 on a Penetrating Keratoplasty Rejection Model in the Rat

PURPOSE The immunosuppressive effects of FK506 on allogeneic corneal transplantation were tested in a rat model. METHODS Inbred-strain Lewis rats were used as recipients, and Fisher rats were used as donors. Intraperitoneal injection of FK506 (0.3, 1.0, and 3.0 mg/kg per day) was administered for 2 weeks, and the grafts were inspected by clinical evaluation. Mixed lymphocyte culture assay, using lymphocytes from recipients of penetrating keratoplasty as responder cells and irradiated splenocytes from naive Fisher or Brown Norway as stimulator cells, was used to identify allogeneic stimulation. The rejection process was studied by histology and immunohistochemistry. RESULTS The rat strain combination developed 100% graft rejection in about 2 weeks after the penetrating keratoplasty. FK506 prolonged the graft survival in a dose-dependent manner, as observed by clinical evaluation. In mixed lymphocyte culture assay, Lewis rats that had been primed to allogeneic stimulation at the time of cornea transplantation presented significant proliferation to Fisher stimulator splenocytes. FK506 suppressed this primed lymphocyte proliferation. Immunohistochemical and histologic studies confirmed the clinical evaluations. Untreated rat corneas, at the second postoperative week, presented a large number of helper/inducer T cells, macrophages, IL-2 receptor-expressing cells, and Ia-antigen-expressing cells. In the same period, FK506-treated rats appeared normal and had no cellular infiltration. Corneas rejected after FK506 cessation had less intense cell infiltration than the control corneas. CONCLUSIONS These data indicate that FK506 prolonged the corneal graft survival and can be a potentially useful drug in the immunotherapeutic arsenal to suppress corneal graft rejection.

The acute effects of cigarette smoking on human optic nerve head and posterior fundus circulation in light smokers

Purpose To study the acute effects of cigarette smoking on tissue circulation in the optic nerve head (ONH) and posterior fundus in smokers with a short smoking history.Methods Ten healthy smokers whose length of smoking history was within 2 years (age 25 ± 1 years; smoking index (number of cigarettes smoked per day x length of smoking history in years) 16 ± 4, mean ± SE) were included in the study. Using the laser speckle method, normalised blur (NB) value, a quantitative index of tissue blood velocity, was measured every 0.125 s and averaged over three pulses across an area located in the temporal site of the ONH free of visible surface vessels (NBonh) and across an area located halfway between the macula and the ONH with no discrete vessels visible (NBch-ret)- NBonh, NBch-ret and intraocular pressure (lOP) in one randomly chosen eye, and blood pressure (BP) and pulse rate (PR) were measured before, and 1, 5, 10, 15, 20, 25, 30, 45, 60 and 90 min after sham smoking. One week later, NBonh, NBch-ret and lOP in the same eye, and BP and PR were measured after cigarette smoking according to the same time schedule as in the control experiment.Results After sham smoking, no parameter showed a significant change during the experiment. Differences in NBonh from the baseline were not significant between the smoking experiment and sham smoking experiment, while NBch-ret showed a significant difference at 30 min. Inter-group difference in the time course of the difference from baseline was significant (ANOVA, p = 0.0246, 0.0021). BP and PR were significantly increased between 1 and 20 min after smoking while lOP showed no significant change at any time of measurement.Conclusions In light smokers, cigarette smoking showed little effect on tissue blood velocity in the ONH and slightly decreased that in the posterior fundus, suggesting a significant increase in vascular resistance in these tissues.

Sensitization to Asian dust and allergic rhinoconjunctivitis.

OBJECTIVE Asian dust storms frequently occur in northeast Asia and the dust occasionally even spreads as far as North America during spring. Asian dust can be harmful to human health and the environment, and thus has become one of the most serious problems for Asian countries. In the present study, we evaluated sensitization to Asian dust in Japanese patients with rhinoconjunctivitis. METHODS In March 2011, a prospective, non-randomized, cross-sectional study was conducted in 10 patients with allergic rhinoconjunctivitis (allergic group), 3 patients with atopic keratoconjunctivitis (atopic group), and 10 age- and sex-matched healthy control subjects (control group). Skin prick tests (SPT) were performed with untreated Asian dust, Asian dust extract, heat-sterilized Asian dust, silicon dioxide (SiO2), and phosphate-buffered saline (PBS). A panel of 14 allergen extracts was also tested, comprising extracts of pollens (cedar, orchard grass, ragweed, and mugwort), house dust (house dust mixture and Dermatophagoides pteronyssinus), animal dander (cat and dog), fungi (Alternaria tenuis, Candida, and Aspergillus), and foods (milk, egg, and wheat). Then the SPT-positive rate and the mean wheal diameter for each allergen were compared among the three groups. RESULTS The SPT-positive rates for untreated Asian dust, Asian dust extract, and sterilized Asian dust were significantly higher in the allergic and atopic groups than in the control group (all p<0.05). In the allergic group, there were a significant differences of the SPT-positive rates for untreated Asian dust (70%), Asian dust extract (50%), sterilized Asian dust (20%), SiO2 (20%), and PBS (0%) (p=0.0068). The SPT response to untreated Asian dust was correlated with the mean wheal diameters for four plant pollens (r=0.71, p=0.0104) and for three fungi (r=0.57, p=0.0426). Multivariate logistic regression analysis showed that significant predictors of the SPT reaction to untreated Asian dust were the mean wheal diameter for the four plant pollen (odds ratio=2.54, p=0.0138) and that for the three fungi (odds ratio=1.84, p=0.0273). CONCLUSIONS Asian dust may act as an adjuvant to promote allergic disease induced by inhaled allergens such as pollen and fungi.

Specific IgE in Tear Fluid and Features of Allergic Conjunctivitis

Abstract Purpose: The level of specific class E immunoglobulins (IgE) in tear fluid is a useful diagnostic indicator for allergic conjunctivitis, but it is still unclear whether the measurement of tear fluid IgE is helpful for assessing the severity of allergic conjunctivitis. In this study, we evaluated the relation between tear fluid levels of specific IgE and features of allergic conjunctivitis. Methods: A prospective, nonrandomized, cross-sectional study was conducted in patients with allergic conjunctivitis (n = 55, allergic group) and age- and sex-matched healthy control subjects (n = 50, control group). Levels of specific IgE for cedar pollen, cat epithelium/dander and Dermatophagoides pteronyssinus were measured in tear fluid with the Immfast Check J1®. A severity score (0, 1, 2 or 3) was assigned for various changes of the palpebral and bulbar conjunctiva, as well as for limbal and corneal lesions. Results: The levels of specific IgE for both cedar pollen, and D. pteronyssinus were significantly higher in the allergic group compared with the control group (p < 0.0001), while the level of specific IgE for cat epithelium/dander showed no significant difference between the two groups (p = 0.0777). When IgE levels were divided into four classes, the classes for both D. Pteronyssinus and cat epithelium/dander IgE were correlated with four features of allergic conjunctivitis. On the other hand, no correlation was found between the class of cedar pollen IgE and any of the features of allergic conjunctivitis. Conclusions: This study demonstrated that measurement of specific IgE in tear fluid may be useful for determining the severity of allergic conjunctivitis induced by indoor allergens. Although measurement of IgE in tear fluid is only a supplemental tool for evaluating the clinical activity of allergic conjunctivitis, the test can be useful for detecting specific IgE antibodies responsible for this condition.

Glycolysis in Patients with Age-Related Macular Degeneration

Purpose: Retinal adenosine triphosphate is mainly produced via glycolysis, so inhibition of glycolysis may promote the onset and progression of age-related macular degeneration (AMD). When glycolysis is inhibited, pyruvate is metabolized by lactic acid fermentation instead of entering the mitochondrial tricarboxylic acid (TCA) cycle. We measured urinary pyruvate and lactate levels in patients with AMD. Methods: Eight patients with typical AMD (tAMD group) and 9 patients with polypoidal choroidal vasculopathy (PCV group) were enrolled. Urinary levels of pyruvate, lactate, α-hydroxybutyrate, and β-hydroxybutyrate were measured in all patients. Results: The mean urinary levels of pyruvate and lactate were 8.0 ± 2.8 and 7.5 ± 8.3 μg/mg creatinine (reference values: 0.5-6.6 and 0.0-1.6), respectively, with the mean increase over the reference value being 83.6 ± 51.1% and 426.5 ± 527.8%, respectively. In 12 patients (70.6%), the lactate/pyruvate ratio was above the reference range. Urinary levels of α-hydroxybutyrate and β-hydroxybutyrate were decreased by -31.9 ± 15.2% and -33.1 ± 17.5% compared with the mean reference values. There were no significant differences of any of these glycolysis metabolites between the tAMD and PCV groups. Multivariate analysis revealed that none of the variables tested, including patient background factors (age, hypertension, diabetes, hyperlipidemia, cerebrovascular disease, alcohol, smoking, visual acuity, and AMD phenotype), were significantly associated with the lactate/pyruvate ratio. Conclusion: A high lactate/pyruvate ratio is a well-known marker of mitochondrial impairment, and it indicates poor oxidative function in AMD. Our results suggest that increased lactate levels may be implicated in the pathogenesis of AMD.

Influence of axial length on conjunctivochalasis.

Purpose: To investigate the relation between the severity of conjunctivochalasis and the axial length (AL) of the eyeball. Methods: A prospective nonrandomized study was performed on 165 patients aged 51 to 88 years. The age, gender, medical history, ocular history, grade and other parameters of inferior conjunctivochalasis (classified as nasal, middle, and temporal), and AL were determined in all patients. Patients were divided into a short AL group (⩽22.0 mm), a medium AL group (>22.0 to ⩽24.0 mm), and a long AL group (>24.0 mm). Results: The short AL group tended to have higher grades of temporal and nasal conjunctivochalasis compared with the medium and long AL groups. Multivariate logistic regression analysis showed that the total conjunctivochalasis score (the sum of the scores for the temporal, middle, and nasal regions) was significantly associated with the age [odds ratio (OR) = 1.32, P = 0.001] and the AL (OR = 0.81, P = 0.029). In addition, the AL was independently associated with the grade of conjunctivochalasis after adjustment for age (OR = 0.80, P = 0.020). Conclusions: This was the first assessment of the relationship between the AL and the grade of conjunctivochalasis. Our findings suggest that the severity of conjunctivochalasis is dependent on the AL, with a short AL contributing to the pathogenesis of conjunctivochalasis.

Specific IgE for wheat in tear fluid of patients with allergic conjunctivitis

Abstract Context: Allergy to hydrolyzed wheat protein in facial soap has become a major social issue in Japan. It has been reported that the most frequent early symptoms of allergy to hydrolyzed wheat protein in soap are allergic conjunctivitis and rhinitis, while wheat-dependent exercise-induced anaphylaxis can be induced by long-term use. Objective: We evaluated the relation between tear fluid levels of specific IgE for wheat and the features of allergic conjunctivitis. Methods: A prospective, non-randomized, cross-sectional study was conducted in 103 patients with moderate to severe allergic conjunctivitis (allergic group) and 20 age- and sex-matched healthy control subjects (control group). Specific IgE for wheat was measured in tear fluid with an immunochromatography assay, and a skin prick test (SPT) was also performed. Symptoms (sneezing, rhinorrhea, nasal obstruction, ocular itching, and lacrimation) were assessed in each subject along with the activities of daily living (ADL) score and the total ocular symptom score for allergic conjunctivitis. A severity score (0, 1, 2, or 3) was assigned for various changes of the palpebral and bulbar conjunctiva, as well as for limbal and corneal lesions associated with allergic conjunctivitis. Results: The IgE positive rate and specific IgE score were both higher in the allergic group than in the control group (71.8% versus 40.0% and 1.9 ± 0.7 versus 1.4 ± 0.5). A positive SPT for wheat was also more frequent in the allergic group than in the control group (6.8% versus 0.0%). Within the allergic group, patients with a positive SPT had higher specific IgE scores than patients with a negative SPT (3.3 ± 0.5 versus 1.8 ± 0.6, p < 0.001). In the allergic group, the wheat IgE level in tear fluid was correlated with the severity of allergic conjunctivitis symptoms, including ocular itching (r = 0.665), tearing (r = 0.672), and the total ocular symptom score (r = 0.204). Wheat IgE in tear fluid was also correlated with the severity of rhinitis symptoms, including sneezing (r = 0.610), nose blowing (r = 0.640), and nasal obstruction (r = 0.677). Furthermore, the tear fluid wheat IgE score was correlated with five objective features of allergic conjunctivitis (p < 0.05). Conclusions: These results suggest that wheat allergy may be involved in the development of allergic conjunctivitis.

Effect of 3 years of treatment with a dorzolamide/timolol (1%/0.5%) combination on intraocular pressure.

Purpose We aimed to evaluate the effect on the intraocular pressure (IOP) of a dorzolamide/timolol (1%/0.5%) fixed combination (DTFC) ophthalmic agent for 3 years. Participants A total of 19 consecutive patients who had previously been treated with mono-therapy or any combination of a beta-blocker, carbonic anhydrase inhibitor, or prostaglandin analog, for primary open-angle glaucoma (POAG) (n=5) or normal tension glaucoma (N=14) were enrolled. Methods Patients were switched to DTFC from their prior glaucoma therapy. The IOP was measured at intervals of 4–6 weeks for 3 years. Treatment failure was defined as an increase of IOP by ≥10% from baseline after switching to DTFC. Results The average IOP decreased significantly from 14.1±2.9 mmHg at baseline to 12.2±2.2, 11.8±2.4, 12.1±2.5, 11.6±1.8, and 12.1±2.7 mmHg at 3, 6, 12, 24, and 36 months, respectively, after switching therapy (all P<0.05). The mean percent decrease of IOP was 12.0%±13.0%, 14.5%±14.2%, 12.2%±18.7%, 16.0%±12.8%, and 12.8%±15.2% at 3, 6, 12, 24, and 36 months, respectively, after switching. Univariate or multivariate analysis revealed the percent decrease of IOP was associated with the type of glaucoma (POAG) at 3 and 12 months, and with the baseline IOP at 3, 12, 24, and 36 months. Kaplan–Meier analysis demonstrated that the percentage of patients who remained on treatment with DTFC was 94.7%, 94.7%, 84.2%, 78.9%, and 78.9% at 3, 6, 12, 24, and 36 months, respectively. Cox proportional hazards analysis showed that the type of glaucoma (POAG) was associated with an increased risk of failure to control the IOP. Conclusion The IOP-lowering effect of DTFC was demonstrated for 3 years in this study. The baseline IOP had an important influence on the reduction of IOP achieved by DTFC.