Rika Shirakawa

Increased Tear Fluid Production as a Compensatory Response to Meibomian Gland Loss: A Multicenter Cross-sectional Study

PURPOSE To compare tear film parameters as well as meibomian gland morphologic features and function among patients with meibomian gland dysfunction (MGD), those with non-Sjögren syndrome aqueous-deficient dry eye (non-SS ADDE), those with non-SS ADDE and MGD, and normal subjects. DESIGN Multicenter, cross-sectional, observational case series. PARTICIPANTS Forty-one eyes of 41 patients (all women; mean age ± standard deviation, 62.1±9.9 years) with non-SS ADDE, 70 eyes of 70 patients (all women; 66.0±8.7 years) with MGD, 17 eyes of 17 patients (all women; 72.4±7.8 years) with non-SS ADDE and MGD, and 70 eyes of 70 normal control subjects (all women; 65.0±7.1 years). METHODS Ocular symptoms were scored from 0 to 14 and lid margin abnormalities from 0 to 4 according to their respective number. Meibomian gland changes were scored from 0 to 6 (meiboscore) on the basis of noncontact meibography findings, and meibum was graded from 0 to 3 depending on its volume and quality. Conjunctival and corneal epithelial damage were scored from 0 to 9 (fluorescein score). Tear film break-up time (TBUT) was measured as an index of tear film stability, and tear fluid production was evaluated with Schirmers test. MAIN OUTCOME MEASURES Ocular symptom score, lid margin abnormality score, meiboscore, meibum grade, fluorescein score, TBUT, and Schirmers test value. RESULTS The ocular symptom score did not differ significantly between the MGD and non-SS ADDE groups (P = 0.762). The lid margin abnormality score, meiboscore, and meibum grade were significantly higher in the MGD group than in the non-SS ADDE group (P = 0.0012, P < 0.0001, and P < 0.0001, respectively). The fluorescein score, TBUT, and Schirmers test value were significantly worse in the non-SS ADDE group than in the MGD group (P < 0.0001, P = 0.0061, and P < 0.0001, respectively). The meiboscore correlated significantly with Schirmers test value only in the MGD group (ρ = 0.508, P = 8.3×10(-6)). CONCLUSIONS An increase in tear fluid production likely compensates for loss of meibomian glands in individuals with MGD.

Objective image analysis of the meibomian gland area

Aims To evaluate objectively the meibomian gland area using newly developed software for non-invasive meibography. Methods Eighty eyelids of 42 patients without meibomian gland loss (meiboscore=0), 105 eyelids of 57 patients with loss of less than one-third total meibomian gland area (meiboscore=1), 13 eyelids of 11 patients with between one-third and two-thirds loss of meibomian gland area (meiboscore=2) and 20 eyelids of 14 patients with two-thirds loss of meibomian gland area (meiboscore=3) were studied. Lid borders were automatically determined. The software evaluated the distribution of the luminance and, by enhancing the contrast and reducing image noise, the meibomian gland area was automatically discriminated. The software calculated the ratio of the total meibomian gland area relative to the total analysis area in all subjects. Repeatability of the software was also evaluated. Results The mean ratio of the meibomian gland area to the total analysis area in the upper/lower eyelids was 51.9±5.7%/54.7±5.4% in subjects with a meiboscore of 0, 47.7±6.0%/51.5±5.4% in those with a meiboscore of 1, 32.0±4.4%/37.2±3.5% in those with a meiboscore of 2 and 16.7±6.4%/19.5±5.8% in subjects with a meiboscore of 3. Conclusions The meibomian gland area was objectively evaluated using the developed software. This system could be useful for objectively evaluating the effect of treatment on meibomian gland dysfunction.

Effects of Eyelid Warming Devices on Tear Film Parameters in Normal Subjects and Patients with Meibomian Gland Dysfunction

PURPOSE To evaluate the effects of commercially available eyelid warming devices on ocular temperatures, tear film function, and meibomian glands in normal subjects and patients with meibomian gland dysfunction (MGD). METHODS Ten healthy volunteers were enrolled to evaluate the effects of a single warming and of repeated warming for 2 weeks. Ten MGD patients were enrolled for evaluation of repeated warming over 1 month. Two non-wet (Azuki no Chikara, Eye Hot R) and three wet (hot towel, Hot Eye Mask, Memoto Este) devices were compared in a masked manner. Visual analog scale (VAS) score for ocular symptoms, tear film breakup time (TFBUT), meibum grade, temperatures (eyelid skin, tarsal conjunctiva, central cornea), Schirmer test value, and meibomian gland area were measured before and after warming application. RESULTS The single application of the five warming devices improved the VAS score, TFBUT, and ocular temperatures. In the repeated warming application, Azuki no Chikara as a representative non-wet warming device induced a stable and significant improvement in TFBUT and increased the tarsal conjunctival temperature and meibomian gland area in both normal subjects and MGD patients. It also improved meibum grade in MGD patients. CONCLUSION Our results suggest that repeated eyelid warming with a non-wet device improves tear film function in normal individuals and may have beneficial effects on both tear film and meibomian gland function in MGD patients.

Subconjunctival Hemorrhage and Conjunctivochalasis

OBJECTIVE Subconjunctival hemorrhage (SCH) is a relatively common disease, but there have been no reports concerning the relationship between SCH and conjunctivochalasis (CCh). We compared the grade of CCh between patients with SCH and control patients. DESIGN Prospective, nonrandomized study. PARTICIPANTS A total of 104 patients with SCH aged 41 to 94 years and 120 age- and gender-matched controls aged 41 to 94 years were enrolled. METHODS The conjunctiva was divided into the following 8 equal areas: superior, superior/nasal, nasal, inferior/nasal, inferior, inferior/temporal, temporal, and superior/temporal. The age, gender, medical history, ocular history, site of hemorrhage, grade of CCh at 3 locations (nasal, middle, and temporal), and other parameters of CCh were determined in all subjects. MAIN OUTCOME MEASURES Grade of each CCh parameter and location of SCH. RESULTS The mean grade of CCh was higher in patients with SCH than in control patients at the nasal (P<0.00001), middle (P<0.00001), and temporal areas (P<0.00001). The downward gaze- or digital pressure-dependent changes of CCh and the frequency of superficial punctate keratitis were all increased in SCH patients compared with control patients (P<0.00001, P<0.00001, and P = 0.00106, respectively). The number of areas involved by SCH and the presence of SCH in each area were positively correlated with the grade of each CCh-related parameter (P<0.05). CONCLUSIONS This was the first assessment of the grade of CCh in a large series of consecutive patients with SCH. Our results strongly suggest that CCh may have an important role in the pathogenesis of SCH.

Rapid identification of fatty acids and (O-acyl)-ω-hydroxy fatty acids in human meibum by liquid chromatography/high-resolution mass spectrometry

We report a rapid liquid chromatography/quadrupole Orbitrap Fourier transform mass spectrometry (LC-FTMS) method for identifying free fatty acids (FAs) and (O-acyl)-ω-hydroxyFAs (OAHFAs) in human meibum without derivatization. Meibum is a lipid-rich secretion and an important component of the tear film lipid layer. FAs are commonly detected by gas chromatography (GC) or GC/MS after methyl ester derivatization. We developed high-throughput lipid profiling using LC-FTMS and lipid identification software, Lipid Search, without derivatization and applied the method to human meibum. Chromatographic separation was performed on a C18 column. We selected negative electrospray ionization [M-H](-), and applied high-resolution full scan mode to FA analysis and data-dependent MS(2) mode to OAHFA analysis. High-resolution Orbitrap MS proved to be an excellent tool for the rapid analysis of lipids from meibum, and 100 FA and 61 OAHFA molecular species were detected. The analysis times were 12 and 16.5min, respectively. Very long chain FAs (up to C37) and OAHFAs (up to C56) were also detected. The results clearly showed that retention time correlates with the number of double bonds and carbon chains. This LC/MS method can be applied to the identification of FAs and OAHFAs in human meibum.

In situ ultrahigh-resolution optical coherence tomography characterization of eye bank corneal tissue processed for lamellar keratoplasty

Purpose: To use optical coherence tomography (OCT) as a noninvasive tool to perform in situ characterization of eye bank corneal tissue processed for lamellar keratoplasty. Methods: A custom-built ultrahigh-resolution OCT (UHR-OCT) was used to characterize donor corneal tissue that had been processed for lamellar keratoplasty. Twenty-seven donor corneas were analyzed. Four donor corneas were used as controls, whereas the rest were processed into donor corneal buttons for lamellar transplantation by using hand dissection, a microkeratome, or a femtosecond laser. UHR-OCT was also used to noninvasively characterize and monitor the viable corneal tissue immersed in storage medium over 3 weeks. Results: The UHR-OCT captured high-resolution images of the donor corneal tissue in situ. This noninvasive technique showed the changes in donor corneal tissue morphology with time while in storage medium. The characteristics of the lamellar corneal tissue with each processing modality were clearly visible by UHR-OCT. The in situ characterization of the femtosecond laser-cut corneal tissue was noted to have more interface debris than shown by routine histology. The effects of the femtosecond laser microcavitation bubbles on the corneal tissue were well visualized at the edges of the lamellar flap while in storage medium. Conclusions: The results of our feasibility study show that UHR-OCT can provide superb, in situ microstructural characterization of eye bank corneal tissue noninvasively. The UHR-OCT interface findings and corneal endothelial disc thickness uniformity analysis are valuable information that may be used to optimize the modalities and parameters for lamellar tissue processing. The UHR-OCT is a powerful approach that will allow us to further evaluate the tissue response to different processing techniques for posterior lamellar keratoplasty. It may also provide information that can be used to correlate with postoperative clinical outcomes. UHR-OCT has the potential to become a routine part of tissue analysis for any eye bank or centers creating customized lamellar corneal tissue for transplantation.

Tear meniscus volume changes in dacryocystorhinostomy evaluated with quantitative measurement using anterior segment optical coherence tomography.

PURPOSE To evaluate tear meniscus (TM) changes in external dacryocystorhinostomy (ex-DCR) with quantitative measurement of tear meniscus height (TMH), area (TMA), and volume (TMV) using anterior segment optical coherence tomography (AS-OCT). METHODS Twenty-five eyes from 21 patients (11 males and 10 females) with primary acquired nasolacrimal duct obstruction (PANDO) who received ex-DCR from May 2010 to April 2011 were evaluated prospectively on their TMH, TMA, and TMV changes by AS-OCT. Measurements were performed before surgery (Pre) and 2 weeks (2W), 2 months (2M), and 6 months (6M) after surgery. Data were analyzed using Kruskal-Wallis test, Wilcoxon signed-rank test with Bonferroni adjustment, and Spearmans rank correlation coefficient. RESULTS All patients had a good clinical course, and there were significant differences in the values of each TM parameter before and after surgery (P < 0.0001). The median values of TMH (mm) throughout the observation period were 0.707 (Pre), 0.334 (2W), 0.278 (2M), and 0.277 (6M). The TMA median values (mm(2)) were 0.1097 (Pre), 0.0483 (2W), 0.0255 (2M), and 0.0224 (6M). The TMV median values (mm(3)) were 0.7799 (Pre), 0.1614 (2W), 0.1071 (2M), and 0.1553 (6M). There were significant differences in TMH, TMA, and TMV reduction at each postoperative visit as compared to preoperative values (P < 0.001). In addition, TMH change 6 months after ex-DCR showed a significant positive correlation with age (r = 0.4434, P = 0.0264). CONCLUSIONS The perioperative TM changes in ex-DCR can be evaluated noninvasively and quantitatively by using AS-OCT.

Meibum Color and Free Fatty Acid Composition in Patients With Meibomian Gland Dysfunction.

PURPOSE We measured the components of meibum in patients with meibomian gland dysfunction (MGD) and control subjects and then examined the relation between meibum composition and clinical parameters. METHODS Thirty-eight patients with MGD (13 men and 25 women; mean age ± SD, 66.9 ± 15.0 years) and 20 control subjects (8 men and 12 women; 64.5 ± 6.7 years) were enrolled. Ocular symptom score, keratoconjunctival staining score, tear film breakup time, and Schirmers test value were determined. Lid margin abnormalities and meibomian gland morphology were assessed for upper and lower eyelids, and meibum properties were evaluated at temporal, central, and nasal sites of each lid. Free fatty acid (FFA) composition of meibum was analyzed by liquid chromatography-Fourier transform mass spectrometry. RESULTS Upper meibum color score was significantly correlated with epiphora and sticky sensation in MGD patients. Meibum grade, color, or viscosity did not differ significantly among the sites evaluated. A total of 103 species of FFA--including very long chain (such as C36 and C37) and odd-numbered chain (such as C17, C19, and C21) FFAs--were detected in meibum. Free fatty acid composition differed between clear and colored (cloudy or yellow) meibum, with unsaturated FFAs tending to be more abundant in colored meibum. CONCLUSIONS Free fatty acid composition of human meibum correlates with meibum color as determined with a slit-lamp microscope. This finding may provide insight into the pathogenesis of MGD.

Decreased Surface Temperature of Tarsal Conjunctiva in Patients With Meibomian Gland Dysfunction

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Stromal bed quality and endothelial damage after femtosecond laser cuts into the deep corneal stroma

Aim To evaluate the stromal bed quality and endothelial damage after femtosecond laser (FSL) cuts into the deep corneal stroma. Methods Using a 150-kHz FSL, a lamellar cut was aimed at a depth of 100, 300, or 500 μm in porcine corneas. Stromal bed smoothness was graded from light microscopy and scanning electron microscopy images. Rabbit corneas were cut at remaining thicknesses of 70, 100 and 150 μm using the FSL. The effects of peeling off the corneal flap and the distance between laser spots (2 or 4 μm) were examined. Results The ratio of damaged cells in the group with a remaining depth of 70 μm was significantly larger than that in the groups with a remaining depth of 150 μm. The ratio of damaged cells in the group with a 4-μm spot separation and the flap peeled off was significantly larger than that in the group with a 4-μm spot separation and the flap not peeled off. Conclusions Corneal endothelial damage is likely to increase when the remaining depth is less than 70 μm, and peeling off the flap damages corneal endothelial cells when the remaining depth is less than 100 μm.