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Tais H Wakamatsu,
Murat Dogru,
Yukihiro Matsumoto,
Takashi Kojima,
Minako Kaido, Osama M A Ibrahim,
Enrique A Sato,
Ayako Igarashi,
Yoshiyuki Ichihashi,
Yoshiyuki Satake,
Jun Shimazaki,
Kazuo Tsubota
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ABSTRACT: PURPOSE: To evaluate the levels of lipid oxidative stress markers and inflammatory cells from tears and conjunctiva of patients with Sjogren Syndrome (SS) and normal subjects. METHODS: Thirty-one eyes of 16 patients (16 females) with SS and 15 eyes of 10 healthy controls (2 males and 8 females) were examined in this prospective study. All subjects underwent Schirmer test, tear break up time, vital stainings, confocal microscopy of the conjunctiva, tear collection for HEL (hexanoyl-lysine) ELISA and conjunctival brush cytology. Brush cytology samples underwent immunohistochemistry (IHC) staining with HEL and 4HNE (4-hydroxy-2-nonenal). Haematoxylin-Eosin and IHC staining with HEL, 4HNE were also 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 controls. Conjunctival inflammatory cell density was significantly higher in SS subjects compared to controls. The numbers of conjunctival cells positively stained for HEL and 4HNE were significantly higher in SS patients compared with controls. Tear HEL concentrations correlated significantly with staining scores and inflammatory cell density in confocal microscopy. Conjunctival specimens revealed higher numbers of cells positively stained for inflammatory markers as well as HEL and 4HNE in the IHC stainings. CONCLUSION: Increase of the oxidative stress status in the conjunctiva of SS patients appears to have a role in the pathogenesis of the dry eye disease. A close relationship may exist between ROS production, lipid peroxidation related membrane damage and inflammatory processes in dry eye.
Investigative ophthalmology & visual science 11/2012; · 3.43 Impact Factor
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ABSTRACT: 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.
Cornea 11/2012; · 1.73 Impact Factor
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ABSTRACT: 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).
Prospective, controlled, single-center study.
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.
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.
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.
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).
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.
The authors have no proprietary or commercial interest in any of the materials discussed in this article.
Ophthalmology 06/2012; 119(10):1961-8. · 5.45 Impact Factor
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ABSTRACT: To evaluate the tear meniscus changes after punctal occlusion in dry eye patients using Visante optical coherence tomography (OCT) in a prospective controlled study.
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.
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).
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.
Optometry and vision science: official publication of the American Academy of Optometry 03/2012; 89(5):E770-6. · 1.53 Impact Factor
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Takashi Kojima,
Tais H Wakamatsu,
Murat Dogru,
Yoko Ogawa,
Ayako Igarashi, Osama M A Ibrahim,
Takaaki Inaba,
Takahiko Shimizu,
Setsuko Noda,
Hiroto Obata,
Shigeru Nakamura,
Alda Wakamatsu,
Takuji Shirasawa,
Jun Shimazaki,
Kazuno Negishi,
Kazuo Tsubota
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ABSTRACT: 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.
American Journal Of Pathology 03/2012; 180(5):1879-96. · 4.89 Impact Factor
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Osama M A Ibrahim,
Takashi Kojima,
Tais Hitomi Wakamatsu,
Murat Dogru,
Yukihiro Matsumoto,
Yoko Ogawa,
Junko Ogawa,
Kazuno Negishi,
Jun Shimazaki,
Yasuo Sakamoto,
Hiroshi Sasaki,
Kazuo Tsubota
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ABSTRACT: 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).
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.
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.
Silicon hydrogel SCL showed corneal and retinal protective effects, owing to UV blocking properties, against oxidative stress-related membrane lipid and cellular DNA damage.
Investigative ophthalmology & visual science 03/2012; 53(4):2403-13. · 3.43 Impact Factor
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ABSTRACT: To evaluate tear and serum IgE and eosinophil cationic protein (ECP) as severity markers for atopic keratoconjunctivitis (AKC).
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.
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.
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.
The British journal of ophthalmology 01/2012; 96(4):581-6. · 2.92 Impact Factor
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ABSTRACT: To evaluate the effect of contact lens (CL) wear and visual display terminal (VDT) work on the ocular surface and tear functions.
Prospective case-control study.
Sixty-nine CL wearers (45 women and 24 men; mean age, 35.2 ± 7.3 years), and 102 age- and sex-matched non-CL wearers were enrolled in the study (66 women and 36 men; mean age, 36.7 ± 7.3 years). Ocular surface and tear function tests, including vital stainings (fluorescein and rose bengal), Schirmer test, tear meniscus height measurement, and tear film break-up time were performed. The subjective symptoms of dry eyes were evaluated using a dry eye symptom questionnaire. The participants were divided into 4 subgroups according to the total time of VDT work in 1 day (VDT work time in 1 day ≥ 4 hours or < 4 hours) and presence of CL wear. Main outcome measures included ocular surface vital staining scores, Schirmer test results, tear film break-up time, tear meniscus height measurement, and symptom questionnaire score.
CL users and long-term VDT workers showed significantly worse tear meniscus height values than non-CL users and short-term VDT workers (P < .001). The mean visual symptom scores in CL wearers and long-term VDT workers were significantly higher than the other groups (P < .001).
Office workers who wore CLs and spent more than 4 hours engaged in VDT work had a lower tear meniscus volume with significant dry eye and visual symptoms triggered by environmental factors.
American journal of ophthalmology 08/2011; 152(6):933-940.e2. · 3.83 Impact Factor
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ABSTRACT: To evaluate the extent of corneal inflammation and the response to treatment in patients with Mooren's ulcer, by in vivo confocal microscopy (IVCM).
Twenty-two eyes of 15 patients with Mooren's ulcer were enrolled in this prospective study. All subjects underwent routine ophthalmic examinations, IVCM, and conjunctival histopathologic examination of specimens in patients undergoing conjunctival excision. Eyes with active ulcer were treated with topical corticosteroids and additional therapy, depending on the signs and symptoms. Eyes in remission continued to receive the previous treatment protocols. The relation between the severity of ulcer and inflammation status as assessed by IVCM was also studied. The endpoints were inflammatory cell density (ICD), counted by IVCM, and the extent of the limbal arc involved with ulcers.
Ten eyes had active corneal ulcers, and 12 eyes had been in remission for the past year. The mean ICD of eyes with active ulcers before treatment was 2092.7 ± 1538.6 cells/mm(2) (range, 835.3-7832.7; 95% CI, 3232.5-952.9). Nine of the eyes improved at 8 weeks, with a decrease in ICD to 249.1 ± 109.0 cells/mm(2) (range, 100.3-595.3; 95% CI, 329.8-168.3). One eye had corneal perforation, and ICD immediately before perforation was 1677.6 ± 247.6 cells/mm(2). The mean ICD of 12 eyes in remission was 357.5 ± 266.8 cells/mm(2) (range, 12.7-1127.0; 95% CI, 555.2-159.8). The correlation of the ICD and the extent of limbal involvement with ulcers was strong (R(2) = 0.8119).
ICD evaluated by IVCM is a useful and promising parameter for evaluation of the degree of inflammation in eyes with Mooren's ulcer and for assessment of response to treatment.
Investigative ophthalmology & visual science 06/2011; 52(9):6680-9. · 3.43 Impact Factor
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ABSTRACT: 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).
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.
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.
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.
Molecular vision 01/2011; 17:2533-43. · 2.20 Impact Factor
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ABSTRACT: To prospectively evaluate the effect of controlled adverse chamber environment (CACE) exposure on tear function, including tear osmolarity, in subjects wearing narafilcon A versus those wearing etafilcon A soft contact lens (SCL).
Thirty-one healthy subjects with no history of contact lens wear (13 women, 18 men; average age, 30.5 ± 6.5 years) were randomly divided into age- and sex-matched groups (15 subjects wearing narafilcon A SCL; 16 subjects wearing etafilcon A SCL) and entered a CACE for 20 minutes. All subjects underwent tear osmolarity, tear evaporation rate, strip meniscometry, tear film breakup time, fluorescein vital staining, and functional visual acuity measurement before and after exposure to the controlled adverse chamber.
The mean blink rate increased with significant deteriorations in the mean symptom VAS scores, mean tear osmolarity, tear evaporation rate, strip meniscometry score, and tear stability with CACE exposure along with a decrease in visual maintenance ratio in functional visual acuity testing in etafilcon A wearers. The mean symptom VAS scores, mean tear evaporation rate, tear stability, blink rates, and visual maintenance ratios did not change significantly in narafilcon A wearers after CACE exposure.
This study suggested marked tear instability, higher tear osmolarity, and increased tear evaporation with marked dry eye and visual symptomatology in nonadapted hydrogel SCL wearers, suggesting that silicone hydrogel SCLs may be suitable for persons who live and work in cool, low-humidity, and windy environments, as tested in this study.
Investigative ophthalmology & visual science 01/2011; 52(12):8811-7. · 3.43 Impact Factor
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ABSTRACT: To investigate the applicability of in vivo laser scanning confocal microscopy in the diagnosis and follow-up of ocular demodicosis infestation in a prospective controlled study.
Fifteen right eyes of 15 patients with blepharitis associated with cylindrical dandruff (10 males, 5 females; mean age: 62.9 ± 9 years) and eight right eyes of eight age- and sex-matched control subjects underwent HRTII/RCM, evaluation of ocular symptom scores, tear function tests including vital stainings, Schirmer test, and tear clearance test, and evaluation of mite numbers in the eyelids.
In vivo confocal microscopy effectively disclosed the mites in the terminal bulbs of the eyelashes, which were not observed after treatment. Eyelids with demodicosis infestation showed marked inflammatory infiltrates around the meibomian glands and conjunctiva, which cleared with tea tree oil treatment.
Laser scanning confocal microscopy seems to be an efficient noninvasive tool in the diagnosis and follow-up of ocular demodicosis infestation.
Investigative ophthalmology & visual science 01/2011; 52(1):565-9. · 3.43 Impact Factor
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ABSTRACT: To evaluate the specificity and sensitivity of strip meniscometry (SM) testing in conjunction with tear function tests in the diagnosis of dry eye (DE) disease and to investigate the effect of SM on reflex tearing.
One hundred seven left eyes of 107 patients with definite DE disease according to the Japanese DE diagnostic criteria and 68 left eyes of 68 age- and sex-matched control subjects were studied. Tear meniscus height (TMH) measurements, fluorescein tear film break-up time (FTBUT), fluorescein (F) and rose bengal (RB) staining, and Schirmer's test-1 (ST) were also performed. The assessment of reflex tearing before and after SM application was assessed with a graticule scale at the slit lamp and by optical coherence tomography. The sensitivity and specificity of SM alone and in combination with tear function tests were also sought.
The SM scores, TMH measurements, FTBUTs, and STs were significantly lower in dry eye patients than in the controls (P < 0.001). The RB and F staining scores were significantly higher in the dry eye group than in the control group (P < 0.001). The meniscometry strips did not induce significant changes in relation to reflex tearing. SM had an acceptable sensitivity and specificity.
SM is a swift, noninvasive, promising method of assessing tear meniscus volume. The combined SM and FTBUT examination appears to be a sensitive approach to the assessment of dry eye disease.
Investigative ophthalmology & visual science 12/2010; 52(5):2194-8. · 3.43 Impact Factor
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ABSTRACT: To investigate the applicability of tear meniscus height (TMH) measurement using Visante optical coherence tomography (OCT) in the diagnosis of dry eye disease.
Prospective, controlled, single-center study.
Twenty-four right eyes of 24 patients (6 males, 18 females; mean age, 63.14±13.4 years) with definite dry eye according to the Japanese dry eye diagnostic criteria and 27 right eyes of 27 control subjects (12 males, 15 females; mean age, 56.04±14.22 years) were recruited.
All subjects underwent slit-lamp TMH measurement, OCT upper and lower TMH measurements, tear film breakup time (BUT) measurements, vital stainings, and Schirmer test. The results were compared between the 2 groups by Mann-Whitney test.
The correlation between the clinical findings of slit-lamp TMH, strip meniscometry examination, tear functions, vital staining scores, and the OCT upper and lower TMH parameters were tested by Spearman's correlation test. Receiver operating characteristic (ROC) curve technique was used to evaluate the sensitivity, specificity and cutoff values of OCT TMH examination in the diagnosis of dry eye.
The OCT upper and lower TMH values, slit-lamp TMH, strip meniscometry, tear film BUT, and vital staining scores were significantly lower in the dry eye patients compared with controls (P<0.001). A significant correlation between the OCT upper and lower TMH measurements as well as slit-lamp TMH, strip meniscometry, tear functions, vital staining scores, and the Schirmer test was found. The ROC curve technique analysis of the OCT lower TMH showed that, when the cutoff value was set at <0.30 mm, the sensitivity and specificity of the testing were 67% and 81%, respectively.
The Visante OCT is a quick, noninvasive method for assessing the TMH, with acceptable sensitivity, specificity, and repeatability, and may have potential applications for the diagnosis and evaluation of dry eye disease.
Ophthalmology 10/2010; 117(10):1923-9. · 5.45 Impact Factor
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Ophthalmology 06/2010; 117(6):1275.e4-7. · 5.45 Impact Factor
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Ophthalmology 05/2010; 117(5):1055-1055.e3. · 5.45 Impact Factor
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ABSTRACT: To evaluate the efficacy, sensitivity and specificity of confocal microscopy (CM) parameters: meibomian gland (MG) acinar longest diameter (MGALD), MG acinar shortest diameter (MGASD), inflammatory cell density (ICD), and MG acinar unit density (MGAUD) in the diagnosis of MG dysfunction (MGD).
Prospective, controlled, single-center study.
Twenty MGD patients (9 males, 11 females; mean age, 63.5+/-16.5 years) and 26 age- and gender-matched control subjects (13 males, 13 females; mean age, 53.2+/-15.7 years) were recruited.
All subjects underwent slit-lamp examinations, tear film break-up time (BUT) measurements, assessment of tear evaporation rate from the ocular surface (TEROS), vital stainings, Schirmer test, meibography, MG expressibility, and CM of the MG. Data were compared between the 2 groups using the Mann-Whitney and chi-square tests.
The correlation between the clinical findings of tear functions, vital staining scores, and the 4 CM parameters were tested by Spearman's correlation coefficient by rank test. Receiver operating characteristic curve technique was used to evaluate the sensitivity, specificity, and cutoff values of CM parameters.
The mean tear film BUT, vital staining scores, TEROS values, MG expressibility, and MG dropout grades by meibography were significantly worse in MGD patients compared with controls (P<0.001). The mean values of the MGALD, MGASD, ICD, and MGAUD in MGD patients were significantly worse than those observed in the controls with CM. All CM parameters showed a strong, significant correlation with tear functions, ocular surface vital stainings, MG expressibility, and MG dropout grades. The cutoff values for MGALD, MGASD, ICD, and MGAUD in the diagnosis of MGD were 65 microm, 25 microm, 300 cells/mm2, and 70 glands/mm2, respectively. The sensitivity and specificity values of these parameters under these cutoff values were 90% and 81% for MGALD, 86% and 96% for MGASD, 100% and 100% for ICD, 81% and 81% for MGAUD.
Confocal microscopy has the potential to diagnose the simple MGD with high sensitivity and specificity. The CM-based diagnostic parameters correlated significantly and strongly with the status of the ocular surface disease.
The authors have no proprietary or commercial interest in any of the materials discussed in this article.
Ophthalmology 02/2010; 117(4):665-72. · 5.45 Impact Factor
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Tais H Wakamatsu,
Murat Dogru,
Igarashi Ayako,
Yoji Takano,
Yukihiro Matsumoto, Osama M A Ibrahim,
Naoko Okada,
Yoshiyuki Satake,
Kazumi Fukagawa,
Jun Shimazaki,
Kazuo Tsubota,
Hiroshi Fujishima
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ABSTRACT: Although the oxidative stress status in atopic skin disease has been reported to be elevated, there are still no studies related to the status of oxidative stress in atopic ocular surface disease. The purpose of this study was to evaluate the ocular surface lipid oxidative stress status and inflammation in atopic keratoconjunctivitis (AKC) patients and normal subjects.
Twenty eight eyes of 14 patients (9 males, 5 females) with AKC and 18 eyes of 9 age and sex matched (4 males and 5 females) normal healthy controls were examined in this prospective study. The severity of atopic dermatitis (AD) was scored by the SCORing Atopic Dermatitis (SCORAD) index. All subjects underwent Schirmer test, tear film break up time (BUT), fluorescein/Rose Bengal stainings, tear collection, and brush cytology from the upper palpebral conjunctiva. The brush cytology samples were stained with Diff-Quik for differentiation of inflammatory cells and immunohistochemistry (IHC) staining with HEL (hexanoyl-lysine) and 4-HNE (4-hydroxy-2-nonenal) to study lipid oxidation. HEL and cytokine (interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ)) levels were measured by enzyme-linked immunosorbent assay (ELISA) from tear samples of AKC patients and control subjects. Toluidine Blue and IHC staining with HEL, 4-HNE and cluster of differentiation 45 (CD45) were performed on papillary samples of AKC patients. This study was conducted in compliance with the "Declaration of Helsinki."
The tear stability and vital staining scores were significantly worse in eyes of AKC patients (p<0.05) compared to the controls. Inflammatory cells and positively stained conjunctival epithelial cells for HEL and 4-HNE showed a significant elevation in brush cytology samples of AKC patients. Significantly higher levels of HEL and cytokines were detected in tears of AKC patients compared to controls. Papillary specimens also revealed many CD45 inflammatory cells as well as many cells positively stained with HEL and 4-HNE in IHC. A strong significant linear positive correlation between conjunctival inflammation and epithelial lipid oxidative stress status was observed. Conjunctival lipid oxidative stress also correlated strongly with tear HEL levels and epithelial damage scores.
The ocular surface disease in AKC was characterized by marked tear instability, ocular surface epithelial damage, increase in inflammatory infiltrates and presence of increased lipid oxidation.
Molecular vision 01/2010; 16:2465-75. · 2.20 Impact Factor
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ABSTRACT: To demonstrate the conjunctival alterations in patients with Sjögren's (SSDE) and non-Sjögren's syndrome dry eye (NSSDE) using a new generation confocal microscope (HRTII/ RCM; Heidelberg Engineering, Heidelberg, Germany), in a prospective controlled study.
Twenty-eight right eyes of 28 patients with SSDE (28 women; mean age, 58.2 +/- 14.3 years), 7 right eyes of patients with NSSDE (7 women; mean age, 66.1 +/- 14.4 years), and 14 right eyes of 14 age- and sex-matched control subjects were studied. All subjects underwent the Schirmer test, tear film breakup time (BUT), vital staining, and confocal microscopy of the temporal bulbar conjunctiva. The density of conjunctival epithelial cells, epithelial microcysts, and conjunctival and corneal inflammatory infiltrates were also assessed.
The tear quantity, stability, and vital staining scores were significantly worse in patients with SSDE or NSSDE than in control subjects (P < 0.001 and P < 0.05, respectively). Eyes of the patients with SSDE or NSSDE had a significantly higher density of conjunctival and corneal inflammatory infiltrates than did the control eyes (P < 0.001). Conjunctival inflammatory cell densities showed a negative correlation with tear stability and tear quantity and a positive correlation with the vital staining scores. Conjunctival epithelial cell densities were significantly lower in SSDE and NSSDE compared with control subjects (P < 0.05). The density of epithelial cysts was significantly higher in SS than in healthy control eyes (P < 0.001).
Confocal scanning laser microscopy was an efficient and a noninvasive tool for the quantitative assessment of the conjunctival inflammation and epithelial cell densities as well as evaluation of conjunctival morphologic alterations, such as microcysts in patients with SSDE and NSSDE dry eye disease.
Investigative ophthalmology & visual science 08/2009; 51(1):144-50. · 3.43 Impact Factor
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Tais Hitomi Wakamatsu,
Naoko Okada,
Takashi Kojima,
Yukihiro Matsumoto, Osama M A Ibrahim,
Murat Dogru,
Enrique Sato Adan,
Kazumi Fukagawa,
Chikako Katakami,
Kazuo Tsubota,
Jun Shimazaki,
Hiroshi Fujishima
[show abstract]
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ABSTRACT: To elucidate the status of the conjunctival inflammation in atopic keratoconjunctivitis (AKC) using laser scanning confocal microscopy and compare the relevant findings with conjunctival brush cytology in a prospective controlled study.
Twenty eyes from 20 AKC patients as well as 16 eyes from 16 age and sex matched normal subjects were studied. The subjects underwent tear film break-up time (BUT), fluorescein and Rose Bengal staining of the ocular surface, conjunctival confocal microscopy, Schirmer test, and brush cytology. Brush cytology specimens and in vivo confocal microscopy scans underwent evaluation for inflammatory cell densities.
Brush cytology specimens and in vivo confocal microscopy scans from AKC patients revealed significantly higher numbers of inflammatory cells (p<0.05). Conjunctival inflammatory cell density showed a negative correlation with tear stability and a positive correlation with vital staining scores and conjunctival injection grades. The extent of conjunctival inflammation assessed by in vivo confocal microscopy showed a strong positive linear correlation with the inflammation status evaluated by brush cytology. The corneal inflammatory cell density assessed by in vivo confocal microscopy showed a significant negative correlation with tear stability and a positive linear correlation with corneal fluorescein staining.
Confocal scanning laser microscopy is an efficient, noninvasive, and a promising tool for the quantitative assessment of conjunctival inflammation, a parameter of this new technology which correlated well with subjective and objective ocular surface clinical findings.
Molecular vision 01/2009; 15:1611-9. · 2.20 Impact Factor
