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Aya Ikeda, Asami Shimokawa, Kazuhiro Harada, Tomoko Tsukahara-Kawamura, Jane Huang, Hiroaki Ozaki, Eiichi Uchio Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, JapanCorrespondence: Eiichi Uchio, Department of Ophthalmology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan, Tel +81 92 801 1011, Fax +81 92 865 4445, Email euchio@fukuoka-u.ac.jpBackground: We have previously studied the physiological and mechanical responses of the eye to blunt trauma in various situations using finite element analysis (FEA). In this study, we evaluated the volume kinetics of an airbag impact on the eye using FEA to sequentially determine the volume change rates of intraocular segments at various airbag deployment velocities.Methods: The human eye model we created was used in simulations with the FEA program PAM-GENERISTM (Nihon ESI, Tokyo, Japan). Different airbag deployment velocities, 30, 40, 50, 60 and 70 m/s, were applied in the forward direction. The volume of the deformed eye impacted by the airbag was calculated as the integrated value of all meshes in each segment, and the decrease rate was calculated as the ratio of the decreased volume of each segment at particular timepoints to the value before the airbag impact.Results: The minimum volume of the anterior chamber was 63%, 69% and 50% at 50, 60 and 70 m/s airbag impact velocity, respectively, showing a curve with a sharp decline followed by gradual recovery. In contrast to the anterior chamber, the volume of the lens recovered promptly, reaching 80– 90% at the end of observation, except for the case of 60 m/s. Following the decrease, the volume increased to more than that of baseline at 60 m/s. The rate of volume change of the vitreous was distributed in a narrow range, 99.2– 100.4%.Conclusion: In this study, we found a large, prolonged decrease of volume in the anterior chamber, a similar large decrease followed by prompt recovery of volume in the lens, and a time-lag in the volume decrease between these tissues. These novel findings may provide an important insight into the pathophysiological mechanism of airbag ocular injuries through this further evaluation, employing a refined FEA model representing cuboidal deformation, to develop a more safe airbag system.Keywords: airbag, ocular trauma, computer simulation, lens, anterior chamber, vitreous body, finite element analysis, volume

Asami Shimokawa, Aya Ikeda, Kazuhiro Harada, Rie Takahashi, Jane Huang, Tomoko Tsukahara-Kawamura, Hiroaki Ozaki, Eiichi Uchio Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, JapanCorrespondence: Eiichi Uchio, Department of Ophthalmology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan, Tel +81 92 801 1011, Fax +81 92 865 4445, Email euchio@fukuoka-u.ac.jpPurpose: Vernal keratoconjunctivitis (VKC) is a refractory ocular allergic disorder that mainly affects boys. Long-term follow-up has been rarely reported for VKC. We investigated the long-term clinical outcome of VKC to identify relevant clinical features of prognostic value based on follow-up for a median of 70 months.Methods: In total, 45 consecutive patients clinically diagnosed with VKC aged 4 to 12 years at onset at the Department of Ophthalmology of Fukuoka University Hospital were included. Patients were treated with immunosuppressive eye drops without simultaneous corticosteroid eye drops, except for the occurrence of exacerbations. Collated variables were gender, age at onset, clinical score of ocular lesions (conjunctival giant papillae, limbal edema and corneal epithelial lesions) at the first visit, and clinical score of atopic dermatitis (AD) at baseline. Cumulative cure rate was estimated using Kaplan–Meier method. A binomial logistic predictive model was used to determine the most reliable clinical predictors of VKC outcome.Results: The observation period ranged from 24 to 188 months, with median of 70 months. Among the 45 cases enrolled, all non-cured cases (14 cases) observed clinically were complicated by AD. Cumulative cure rate was 74.5% and 84.9% at eight- and ten-year follow-up, respectively. Ten-year cumulative cure rates of cases with and without AD were 50.5% and 100%, respectively, and a significant difference was found between these cumulative cure curves. Binomial regression analysis revealed that AD and gender were significantly related to worse outcome, and this binomial regression model had high sensitivity and specificity.Conclusion: This study demonstrated that th eclinical outcomeof VKC might be predicted by several factors that can beobtained in the early clinical phase. Information on the long-term prognosis of VKC patients might play an important role for precision medicine for VKC in childhood.Keywords: vernal keratoconjunctivitis, cumulative cure rate, atopic dermatitis, immunosuppressive eye drops, binomial logistic analysis

Shuji Suzuki,1 Aya Ikeda,1 Takashi Uemura,1 Kazuhiro Harada,1 Rie Takahashi,1 Jane Huang,1 Tomoko Tsukahara-Kawamura,1 Hiroaki Ozaki,1 Kazuaki Kadonosono,2 Eiichi Uchio1 1Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, Japan; 2Department of Ophthalmology, Yokohama City University Medical Center, Yokohama, JapanCorrespondence: Eiichi Uchio, Department of Ophthalmology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan, Fukuoka, 814-0180, Japan, Email euchio@fukuoka-u.ac.jpPurpose: We studied the kinetic phenomenon of an airbag impact on eyes after trabeculectomy using finite element analysis (FEA), a computerized method for predicting how an object reacts to real-world physical effects and showing whether an object will break, to sequentially determine the responses at various airbag deployment velocities.Methods: A human eye model was used in the simulations using the FEA program PAM-GENERISTM (Nihon ESI, Tokyo, Japan). A half-thickness incised scleral flap was created on the limbus and the strength of its adhesion to the outer sclera was set at 30%, 50%, and 100%. The airbag was set to hit the surface of the post-trabeculectomy eye at various velocities in two directions: perpendicular to the corneal center or perpendicular to the scleral flap (30° gaze-down position), at initial velocities of 20, 30, 40, 50, and 60 m/s.Results: When the airbag impacted at 20 m/s or 30 m/s, the strain on the cornea and sclera did not reach the mechanical threshold and globe rupture was not observed. Scleral flap lacerations were observed at 40 m/s or more in any eye position, and scleral rupture extending posteriorly from the scleral flap edge and rupture of the scleral flap resulting from extension of the corneal laceration through limbal damage were observed. Even in the case of 100% scleral flap adhesion strength, scleral flap rupture occurred at 50 m/s impact velocity in the 30° gaze-down position, whereas in eyes with 30% or 50% scleral flap adhesion strength, scleral rupture was observed at an impact velocity of 40 m/s or more in both eye positions.Conclusion: An airbag impact of ≥ 40 m/s might induce scleral flap rupture, indicating that current airbags may induce globe rupture in the eyes after trabeculectomy. The considerable damage caused by an airbag on the eyes of short-stature patients with glaucoma who have undergone trabeculectomy might indicate the necessity of ocular protection to avoid permanent eye damage.Keywords: airbag, trabeculectomy, sclera, flap, rupture, finite element analysis

Tomohiro Ueno, Hideaki Fujita, Aya Ikeda, Kazuhiro Harada, Tomoko Tsukahara-Kawamura, Hiroaki Ozaki, Eiichi Uchio Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, JapanCorrespondence: Eiichi Uchio, Department of Ophthalmology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan, Tel +81 92 801 1011, Fax +81 92 865 4445, Email euchio@fukuoka-u.ac.jpBackground: We studied the kinetic phenomenon of an airbag impact on eyes with different axial lengths using finite element analysis (FEA) to sequentially determine the physical and mechanical responses of intraocular segments at various airbag deployment velocities.Methods: The human eye model we created was used in simulations with the FEA program PAM-GENERISTM. The airbag was set to impact eyes with axial lengths of 21.85 mm (hyperopia), 23.85 mm (emmetropia) and 25.85 mm (myopia), at initial velocities of 20, 30, 40, 50 and 60 m/s. The deformation rate was calculated as the ratio of the length of three segments, anterior chamber, lens and vitreous, to that at the baseline from 0.2 ms to 2.0 ms after the airbag impact.Results: Deformation rate of the anterior chamber was greater than that of other segments, especially in the early phase, 0.2– 0.4 ms after the impact (P < 0.001), and it reached its peak, 80%, at 0.8 ms. A higher deformation rate in the anterior chamber was found in hyperopia compared with other axial length eyes in the first half period, 0.2– 0.8 ms, followed by the rate in emmetropia (P < 0.001). The lens deformation rate was low, its peak ranging from 40% to 75%, and exceeded that of the anterior chamber at 1.4 ms and 1.6 ms after the impact (P < 0.01). The vitreous deformation rate was lower throughout the simulation period than that of the other segments and ranged from a negative value (elongation) in the later phase.Conclusion: Airbag impact on the eyeball causes evident deformation, especially in the anterior chamber. The results obtained in this study, such as the time lag of the peak deformation between the anterior chamber and lens, suggest a clue to the pathophysiological mechanism of airbag ocular injury.Keywords: airbag, ocular trauma, computer simulation, lens, anterior chamber, vitreous body, finite element analysis, deformation

Hideaki Fujita, Tomohiro Ueno, Shuji Suzuki, Kazuhiro Harada, Tomoko Tsukahara-Kawamura, Hiroaki Ozaki, Eiichi Uchio Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, JapanCorrespondence: Eiichi Uchio, Department of Ophthalmology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan, Tel +81 92 801 1011, Fax +81 92 865 4445, Email euchio@fukuoka-u.ac.jpBackground: Vernal keratoconjunctivitis (VKC) is a refractory ocular allergic disorder that mainly affects boys. A few studies have attempted to develop a classification of subtypes of VKC. In this study, we investigated a computational approach called cluster analysis to separate VKC cases into groups based on clinically relevant characteristics.Methods: In total, 41 consecutive patients clinically diagnosed with VKC at the Department of Ophthalmology of Fukuoka University Hospital were included. Patients were treated with immunosuppressive eye drops without simultaneous corticosteroid eye drops, except for the occurrence of exacerbations. Collated variables were age at onset, clinical score of ocular lesions at baseline, clinical score of ocular lesions at final visit, clinical score of atopic dermatitis (AD) at baseline, frequency of exacerbations of VKC, serum total IgE level and peripheral blood eosinophil count.Results: VKC patients were grouped into three clusters by cluster analysis, and cluster 1, 2, and 3 comprised 25, 9 and 7 cases, respectively. There were differences in the incidence of complications of AD and age at onset among the clusters; therefore, we named the three clusters for better understanding as traditional VKC (cluster 1), early-onset atopic keratoconjunctivitis (AKC)/VKC (cluster 2) and puberty-onset AKC (cluster 3).Conclusion: We found in this study that VKC in childhood has three phenotypes which were previously unknown. Our findings may help to establish precision medicine by focusing on the phenotype of each case to develop individualized medicine to prevent exacerbations.Keywords: vernal keratoconjunctivitis, subtype, atopic dermatitis, atopic keratoconjunctivitis, cluster analysis

Tatsuya Mimura,1 Hiroshi Fujishima,2 Eichi Uchio,3 Kazumi Fukagawa,4,5 Yuji Inoue,1 Makoto Kawashima,1 Kazuma Kitsu,1 Atsushi Mizota1 1Department of Ophthalmology, Teikyo University School of Medicine, Tokyo, Japan; 2Department of Ophthalmology, Tsurumi University School of Dental Medicine, Kanagawa, Japan; 3Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, Japan; 4Ryogoku Eye Clinic, Sumida-Ku, Tokyo, Japan; 5Department of Ophthalmology, Keio University School of Medicine, Tokyo, JapanCorrespondence: Tatsuya Mimura, Tel +81-3-3964-1211, Fax +81-3-3964-1402, Email mimurat-tky@umin.ac.jpPurpose: Asian dust poses a serious global health hazard. Airborne particles adhering to contact lenses may cause substantial damage to the ocular surface. The recently released one-day disposable silicone hydrogel soft contact lens (SCL), the verofilcon A, has a smooth surface with SMARTSURFACE® technology, which is designed to prevent adhesion of protein components and foreign bodies. The purpose of this study was to verify the protective quality of verofilcon A SCL against adhesion of Asian dust particles to its surface.Methods: Verofilcon A and etafilcon A (control lens) SCLs were used (n=16 per group), and 0.2 mL of physiological saline containing 0.01 mg/mL of Asian dust particles was dropped on the surface of SCLs, allowed to stand for 1 hour, shaken for 1 minute, and rinsed three times with saline (after rinsing). In addition, the samples were agitated by a vortex mixer for 1 minute and rinsed three times with saline (after vortex). The number of Asian dust particles adhering to the SCLs and percentage of the surface area occupied by the Asian dust particles was determined before washing, after rinsing, and after vortexing.Results: The number of adherent Asian dust particles was lower on verofilcon A SCL (297 ± 116 after rinsing, and 5 ± 14 after vortexing) than on etafilcon A SCL (523 ± 212 after rinsing, p=0.003, and 378 ± 268 after vortexing, p< 0.001). The Asian dust adhesion area was also lower on verofilcon A SCL (3.6 ± 2.3% after rinsing and 0.0 ± 0.1% after vortexing than on etafilcon A (10.2 ± 2.1% after rinsing, p=0.002, and 5.2 ± 3.0% after vortexing, p< 0.001).Conclusion: These findings indicate that verofilcon A SCL has the property of low adhesion of Asian dust particles. Verofilcon A SCL can be recommended for SCL wearers during windy and Asian dust days.Keywords: Asian dust, daily soft contact lens, etafilcon A, silicone hydrogel, verofilcon A

Ryosuke Izaki,1 Ayaka Kobayashi,1 Hideaki Fujita,1 Kazuhiro Harada,1 Hiroaki Ozaki,1 Kazuaki Kadonosono,2 Eiichi Uchio1 1Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, Japan; 2Department of Ophthalmology, Yokohama City University Medical Center, Yokohama, JapanCorrespondence: Eiichi Uchio, Department of Ophthalmology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan, Tel +81 92 801 1011, Fax +81 92 865 4445, Email euchio@fukuoka-u.ac.jpPurpose: We have previously studied clinical and allergological aspects of sick building syndrome (SBS) cases with ocular disorders and found that SBS is suggested to be partially induced by an allergic response. We analyzed the cytokine production profiles of conjunctival and peripheral blood lymphocytes in patients with SBS with ocular manifestations to further evaluate the pathophysiology of SBS from an immunological standpoint.Methods: We obtained conjunctival samples and peripheral blood mononuclear cells (PBMC) from 15 cases of SBS with ocular findings, 49 cases of allergic conjunctival diseases (ACD) (allergic conjunctivitis (AC), atopic keratoconjunctivitis (AKC), and vernal keratoconjunctivitis (VKC)), and normal controls. Frequencies of cytokine-producing T cells were analyzed by flow cytometry based on an intracellular cytokine staining method.Results: Although no significant difference was observed in the percentage of interferon (IFN)-γ-producing CD4+ T cells in PBMC between patients with SBS and controls, the percentage of interleukin (IL)-4-producing PBMC CD4+ T cells in patients with SBS was significantly higher than that in controls. The percentage of IL-4-producing CD4+ T cells in the conjunctiva in patients with SBS was significantly higher than that in controls, whereas it was significantly lower than that in AKC and VKC. A significant correlation was observed between the percentage of IL-4-producing CD4+ T cells in the conjunctiva and clinical score.Conclusion: These results suggest that SBS may be a kind of allergic disorder and that IL-4 plays a role in the development of allergic disorders in SBS ocular lesions.Keywords: sick building syndrome, allergic conjunctival disease, interferon-γ, interleukin-4, lymphocyte

Tatsuya Mimura,1 Hiroshi Fujishima,2 Eiichi Uchio,3 Kazumi Fukagawa,4,5 Makoto Kawashima,1 Kazuma Kitsu,1 Hiroaki Horikawa,1 Atsushi Mizota1 1Department of Ophthalmology, Teikyo University School of Medicine, Tokyo, Japan; 2Department of Ophthalmology, Tsurumi University School of Dental Medicine, Yokohama, Kanagawa, Japan; 3Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, Japan; 4Ryogoku Eye Clinic, Tokyo, Japan; 5Department of Ophthalmology, Keio University School of Medicine, Tokyo, JapanCorrespondence: Tatsuya Mimura Tel +81-3-3964-1211Fax +81-3-3964-1402Email mimurat-tky@umin.ac.jpPurpose: Pollen and proteins attached to soft contact lenses (SCLs) exacerbate allergic conjunctivitis. The material of SCLs may affect the pollen adhesion to the SCLs. The factors associated with the number of pollen particles that are adherent to daily disposable SCL were investigated.Methods: Pollen particles were experimentally exposed to the contact lens surface of 12 types of SCLs for 1 hour, and the SCLs were washed and rinsed with a physiological saline (n=10 for each SCL type). A total of 120 contact lenses were used in this study. The pollen particles attached to the SCL were observed and photographed under a microscope. The influence of the materials of the SCLs on the degree of pollen adhesion were investigated.Results: The number of residual pollen particles attached to SCLs was in the range from 0– 293/area of 200× 200 μm. Percentage of pollen adhesion area of the surface of the SCL was in the range from 0.01% to 3.25%. There were significant differences in both the number and adhesion area of pollen particles among the 12 types of SCLs tested (P< 0.0001 and P< 0.0001, respectively). The number of pollen particles adhered to SCLs was significantly higher in colored SCLs than clear SCLs (unpaired t-test, p< 0.001). The portion of pollen adhesion area was the lowest in the silicone hydrogel SCLs made with delefilcon-A (0.01 ± 0.02%).Conclusion: Pollen adhesion in daily disposable SCLs depends on the characteristics and materials of the SCLs and was high in colored SCLs and lowest in delefilcon-A silicone hydrogel SCL. These results suggest that colored SCLs are not preferred during pollen season.Keywords: daily soft contact lens, delefilcon-A, pollen, silicone hydrogel

Rie Takahashi, Kanno Okamura, Tomoko Tsukahara-Kawamura, Kazuhiro Harada, Yusuke Saeki, Hiroaki Ozaki, Eiichi Uchio Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, JapanCorrespondence: Eiichi UchioDepartment of Ophthalmology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Fukuoka, Jonan-Ku 814-0180, JapanTel +81 92 801 1011Fax +81 92 865 4445Email euchio@fukuoka-u.ac.jpPurpose: We have carried out three-dimensional finite element analysis (FEA) to determine the physical and mechanical response in several ocular injuries. We applied this FEA model to evaluate an airsoft gun impact on an eye and the deformation rate of eyes of various axial lengths at various velocities.Methods: This study was carried out on a human eye model using an FEA program created by Nihon, ESI Group. The airsoft gun pellet was set to impact the eye at initial velocities of 45, 60 and 75 m/s with the addition of variation in axial length of 20 mm (hyperopia), 22 mm (emmetropia), 24 mm (myopia) and 26 mm (high myopia). Deformation of the eye was calculated as the decrease rate of the volume of the eyeball and the decrease rate of the axial length.Results: In all emmetropic cases, the cornea reached its strain threshold during the impact, and scleral strain showed a patchy strength distribution in the simulation. The deformation was most evident in the anterior segment, while deformation of the posterior segment was less. The decrease rate of the volume of the eyeball and decrease rate of the axial length were highest in the hyperopic eye, followed by the emmetropic eye and myopic eye, and the high myopic eye showed the lowest decrease rates among the four axial lengths in all impact velocity simulations.Conclusion: These results suggest that hyperopic eyes are most susceptible to deformation by an airsoft gun impact compared with other axial length eye models in this simulation. The considerable deformation by an airsoft gun impact shown in this study might indicate the necessity of ocular protection to avoid permanent eye injury. FEA using a human eyeball model might be a useful method to analyze and predict the mechanical features of ocular injury by an airsoft gun.Keywords: airsoft gun, finite element analysis, globe, cornea, rupture, deformation

Kanno Okamura, Asami Shimokawa, Rie Takahashi, Yusuke Saeki, Hiroaki Ozaki, Eiichi Uchio Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, JapanCorrespondence: Eiichi UchioDepartment of Ophthalmology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, JapanTel +81 92 801 1011Fax +81 92 865 4445Email euchio@fukuoka-u.ac.jpPurpose: Due to the mechanical vulnerability of eyes that have undergone penetrating keratoplasty (PKP), it is clinically important to evaluate the possibility of corneal wound dehiscence by blunt impact. We have previously developed a simulation model resembling a human eye based on information obtained from cadaver eyes and applied three-dimensional finite element analysis (FEA) to determine the physical and mechanical response to an air gun impact at various velocities on the post-PKP eye.Methods: Simulations in a human eye model were performed with a computer using a FEA program created by Nihon, ESI Group. The air gun pellet was set to impact the eye at three-different velocities in straight or 12° up-gaze positions with the addition of variation in keratoplasty suture strength of 30%, 50% and 100% of normal corneal strength.Results: Furthermore to little damage in the case of 100% strength, in cases of lower strength in a straight-gaze position, wound rupture seemed to occur in the early phase (0.04– 0.06 ms) of impact at low velocities, while regional break was observed at 0.14 ms after an impact at high velocity (75 m/s). In contrast, wound damage was observed in the lower quadrant of the suture zone and sclera in 12° up-gaze cases. Wound damage was observed 0.08 ms after an impact threatening corneoscleral laceration, and the involved area being larger in middle impact velocity (60 m/s) simulations than in lower impact velocity simulations, and larger damaged area was observed in high impact velocity cases and leading to corneoscleral laceration.Conclusion: These results suggest that the eye is most susceptible to corneal damage around the suture area especially with a straight-gaze impact by an air gun, and that special precautionary measures should be considered in patients who undergo PKP. FEA using a human eyeball model might be a useful method to analyze and predict the mechanical features of eyes that undergo keratoplasty.Keywords: air gun, finite element analysis, cornea, rupture, keratoplasty

Eiichi Uchio,1 Yusuke Saeki,1 Tomoko Tsukahara-Kawamura,1 Kazuaki Kadonosono,2 Hiroaki Ozaki1 1Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, Japan; 2Department of Ophthalmology, Yokohama City University Medical Center, Yokohama, JapanCorrespondence: Eiichi UchioDepartment of Ophthalmology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, JapanTel +81 92 801 1011Fax +81 92 865 4445Email euchio@fukuoka-u.ac.jpPurpose: Fungal keratitis remains an important disorder because of difficulty in its diagnosis, and some patients do not respond to medical treatment using antifungal local and systemic agents. This study was carried out to determine the therapeutic value of air-assisted manual therapeutic deep anterior lamellar keratoplasty (TDALK) in the treatment of fungal keratitis not curable by antifungal chemotherapy.Methods: Seventeen patients (18 eyes) who were referred to Fukuoka University Hospital and treated surgically from January 2006 to April 2018, in whom a diagnosis of fungal keratitis was confirmed by typical clinical findings and microbiological or histological analysis of corneal specimens, and who were poorly responsive to topical and systemic antifungal medication, whereas the lesion had not resulted in corneal perforation, were enrolled in this study and were treated by air-assisted manual TDALK. Clinical outcomes including treatment course, therapeutic success rate, visual acuity outcomes and graft clarity rate were analyzed.Results: The most common pathogen was Fusarium, followed by Candida and Aspergillus. Beneficial therapeutic results (a clear or translucent graft) were achieved in 15 of 18 eyes (83%). There was no recurrence of infection and resulting visual acuity ≤0.15 logarithm of minimal angle of resolution unit was achieved in 15 eyes (83%). Intraoperative microperforation of Descemet’s membrane (DM) was not observed in any patients.Conclusion: Air-assisted manual TDALK can be effective for treating severe fungal keratitis. In addition, air-assisted manual TDALK might be an alternative procedure to big-bubble DALK, because it can provide ambulatory vision and can preserve potentiality of vision with less risk of intraoperative perforation of DM.Keywords: fungal keratitis, lamellar keratoplasty, fusarium, candida, therapeutic keratoplasty

Takashi Uemura,1 Hironori Migita,2 Tomohiro Ueno,1 Tomoko Tsukahara-Kawamura,1,3 Yusuke Saeki,1 Tsuguto Fujimoto,3 Eiichi Uchio1 1Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, Japan; 2Migita Eye Clinic, Chikushino, Japan; 3Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo, Japan Background: Human adenovirus type 54 (HAdV-54) is a novel type of adenovirus that belongs to species D and has thus far been detected only in Japan in patients with epidemic keratoconjunctivitis (EKC). There was a large nationwide outbreak of HAdV-54 EKC from 2015 to 2016 in Japan. The clinical characteristics of an outbreak of HAdV-54 conjunctivitis treated in a regional ophthalmic clinic in Fukuoka, Japan, in 2016 were analyzed.Patients and methods: A consecutive series of 55 cases diagnosed clinically as EKC confirmed by HAdV-54 detection from conjunctival scrapings by polymerase chain reaction (PCR) method between 17 June 2016 and 29 August 2016 were enrolled. Viral DNA copies were counted by real-time PCR method. The clinical findings were recorded at the first visit to the clinic and evaluated.Results: In the analysis of the relationship between mean clinical score groups and several factors, such as days after onset, sex, HAdV DNA number on a logarithmic scale, and age, most factors did not show a significant difference in clinical score between groups. However, mean clinical score of cases aged

Yusuke Saeki,1 Kazuaki Kadonosono,2 Eiichi Uchio1 1Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, 2Department of Ophthalmology, Yokohama City University Medical Center, Yokohama, Japan Purpose: The disease concept of sick building syndrome (SBS) is still unclear. Ocular mucous membrane irritation is one of the major symptoms of SBS. However, the immunological aspects of the ocular complications of SBS are not yet clarified. The clinical and allergological aspects of SBS cases with ocular disorders with special reference to allergic conjunctival diseases (ACD) were analyzed, especially with respect to local immunological features. Methods: Twelve cases of SBS with ocular findings and 49 cases of ACD (allergic conjunctivitis [AC], atopic keratoconjunctivitis [AKC], and vernal keratoconjunctivitis [VKC]) for comparison were evaluated. The clinical findings in SBS and ACD were scored, and tear film breakup time (BUT) was measured. Cytokine (interferon-γ [IFN-γ], interleukin [IL]-2, IL-4, IL-5, IL-6, IL-8, and IL-13) concentrations in tears were analyzed by cytometric bead arrays. Eosinophil count in peripheral blood, total IgE in serum, and multiple allergen simultaneous test (MAST) for antigen-specific IgE were also measured. Results: In SBS, conjunctival lesions were observed in all cases, and corneal abnormalities were found in two-thirds of the cases. Limbal lesions were observed in 2 pediatric cases. Mean serum total IgE level in SBS was significantly higher than that in AC; however, it was significantly lower than that in AKC and VKC. Eosinophil count in peripheral blood and number of positive allergens in MAST were significantly lower in SBS than in AKC and VKC. Significant elevation of tear IL-4 was observed in SBS and ACD. However, in contrast to ACD, elevation of other cytokines in tears was not observed in SBS. Mean tear BUT in SBS was in the normal range. Conclusion: From these results, SBS is thought to be partially induced by an allergic response. However, clinical dissociation of the ocular clinical findings and local immunological features in tear cytokines may suggest that SBS belongs to a different entity from ACD. Keywords: sick building syndrome, allergic conjunctival disease, cytokine, vernal keratoconjunctivitis, IgE

Kazuhiro Harada,1 Tsuguto Fujimoto,2 Yoshimori Asato,3 Eiichi Uchio1 1Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, 2Infectious Disease Surveillance Center, National Institute of Infectious Disease, Tokyo, 3Asato Eye Clinic, Itoman, Japan Background: Acute hemorrhagic conjunctivitis (AHC) is a highly contagious enterovirus infection of the conjunctiva and cornea. Coxsackievirus A24 variant (CA24v) is one of its etiological agents. We report a clinical, epidemiological, and virological analysis of a large epidemic of AHC that occurred from May to September, 2011, in Okinawa, Japan.Methods: Clinical and epidemic aspects were evaluated for 435 AHC patients (348 bilateral and 87 unilateral, 783 eyes). Virological studies were carried out on nine isolates from ten patients. Virus isolation and direct detection of the enterovirus genome by the reverse transcription polymerase chain reaction method and complete nucleotide sequencing of the VP1 gene and phylogeny-based classification using the VP4 sequences were carried out.Results: The 11–15-year age group comprised the highest (62.0%) proportion of cases among all age groups. Conjunctival hyperemia was present in all patients, and subconjunctival hemorrhage, superficial punctate keratitis, and preauricular lymphadenopathy were present in 25.4%, 10.3%, and 7.8% of eyes, respectively. CA24v was isolated from the epidemic strain, and phylogenetic analysis based on a fragment of the VP1 gene showed 96%–97% identity between the current strain and the recent China/GD01/2010 strain.Conclusion: These findings demonstrate that the clinical and epidemiological features of AHC observed in this study were similar to those of the past epidemic in the same region. It should be noted that sequential outbreaks of AHC due to CA24v might occur in the same location after a considerable period of time, and public health precautions are necessary to control this explosive epidemic. Keywords: enterovirus, coxsackievirus, acute hemorrhagic conjunctivitis, polymerase chain reaction, epidemiology

Jane Huang,1 Eiichi Uchio,1 Satoru Goto2 1Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, 2Nihon ESI KK Technical Division, Tokyo, Japan Purpose: To determine the biomechanical response of an impacting airbag on eyes with different axial lengths with transsclerally fixated posterior chamber intraocular lens (PC IOL).Materials and methods: Simulations in a model human eye were performed with a computer using a finite element analysis program created by Nihon, ESI Group. The airbag was set to be deployed at five different velocities and to impact on eyes with three different axial lengths. These eyes were set to have transsclerally fixated PC IOL by a 10-0 polypropylene possessing a tensile force limit of 0.16 N according to the United States Pharmacopeia XXII.Results: The corneoscleral opening was observed at a speed of 40 m/second or more in all model eyes. Eyes with the longest axial length of 25.85 mm had the greatest extent of deformity at any given impact velocity. The impact force exceeded the tensile force of 10-0 polypropylene at an impact velocity of 60 m/second in all eyes, causing breakage of the suture. Conclusion: Eyes with transsclerally fixated PC IOL could rupture from airbag impact at high velocities. Eyes with long axial lengths experienced a greater deformity upon airbag impact due to a thinner eye wall. Further basic research on the biomechanical response for assessing eye injuries could help in developing a better airbag and in the further understanding of ocular traumas. Keywords: airbag, ocular trauma, computer simulation, transsclerally fixated posterior chamber intraocular lens, finite element analysis

Jane Huang,1 Kazuaki Kadonosono,2 Eiichi Uchio1 1Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, 2Department of Ophthalmology, Yokohama City University Medical Center, Yokohama, Japan Purpose: The most common external ocular viral infections are caused by several human adenovirus (HAdV) types. Ganciclovir has been reported to inhibit cytomegalovirus, herpes simplex virus types 1 and 2, varicella zoster virus, and Epstein–Barr virus. Ganciclovir ophthalmic gel, 0.15% (Virgan®) is commercially available for cytomegalovirus or herpes virus keratitis. However its inhibitory activity against HAdV is reported only for types 2 and 5. We investigated the antiadenoviral activity of ganciclovir in vitro in several common types currently inducing keratoconjunctivitis. Materials and methods: A549 cells were used for viral cell culture, and adenovirus types 3 (HAdV3; species B), 4 (species E), and 8, 19a, and 37 (species D) were used. After pretreatment of A549 with serial dilutions of ganciclovir for 24 hours, adenovirus was cultured for 7 days, and adenoviral deoxyribonucleic acid was quantitatively measured by real-time polymerase chain reaction (PCR). Results: The 50% cytotoxic concentration of ganciclovir was 212 mg/mL. The 50% effective concentration of ganciclovir obtained by real-time PCR ranged between 2.64 and 5.10 mg/mL. A significant inhibitory effect of ganciclovir on adenoviral proliferation was found in all types in a dose-dependent manner. The selectivity index of ganciclovir ranged between 41.6 and 80.3. Conclusion: Ganciclovir showed significant inhibitory activity against HAdV3, 4, 8, 19a, and 37, which induce epidemic keratoconjunctivitis. These results indicate that ganciclovir is a possible candidate for the treatment of HAdV keratoconjunctivitis, and ganciclovir ophthalmic gel could be applied to adenoviral keratoconjunctivitis in the future. Keywords: adenovirus, ganciclovir, epidemic keratoconjunctivitis, nucleoside analog, A549 cell line

Kaori Yanai,1 Jane Huang,1 Kazuaki Kadonosono,2 Eiichi Uchio1 1Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, Japan; 2Department of Ophthalmology, Yokohama City University Medical Center, Yokohama, Japan Purpose: To evaluate the safety of bromfenac sodium eye drops from the standpoint of corneal sensitivity and tear secretion in healthy controls following instillation for 1 month. Methods: A prospective single-blind parallel clinical study was conducted in 20 eyes of ten healthy volunteers with no history of ocular or systemic allergic disease, dry eye, contact lens wear, or ocular surgery. Participants were instructed to instill either bromfenac sodium or artificial tears in each eye twice daily for 28 days. Corneal sensitivity tested using a Cochet–Bonnet esthesiometer was evaluated before and immediately after instillation at 7, 14, and 28 days after the initiation of treatment. Tear secretion was also evaluated by Schirmer's eye test before and at 28 days. Results: No significant difference in mean corneal sensitivity and tear-secretion rate was observed between the bromfenac and artificial-tear treatment groups at any time. Conclusion: These results indicate that bromfenac sodium eye drops are safe with respect to corneal sensitivity and tear secretion in subjects with a normal ocular surface condition. Further evaluation is still necessary to determine whether bromfenac is safe in pathological conditions, such as inflammatory disorders and postsurgical cases. Keywords: bromfenac sodium, cornea, sensitivity, tear, nonsteroidal anti-inflammatory drug

Kaori Hirai1,4, Yoji Takano2, Eiichi Uchio3, Kazuaki Kadonosono41Department of Ophthalmology, International Goodwill Hospital, 2Department of Ophthalmology, Kitasato Institute Hospital, 3Department of Ophthalmology, Fukuoka, Fukuoka, Japan; 4Department of Ophthalmology, Yokohama City University Medical Center, Yokohama, JapanPurpose: To evaluate the therapeutic effects of atelocollagen absorbable punctal plugs.Method: Seventy-four eyes in 37 patients with dry eye disease (DED) underwent punctal plug occlusion using atelocollagen plugs and were followed up for 24 weeks. Subjective symptoms were evaluated using the ocular surface disease index (OSDI) questionnaire. Ocular surface disease parameters, including the Schirmer test, phenol red thread test, tear break-up time (TBUT), and fluorescein and Rose Bengal staining, were recorded before and 1, 4, 8, 16, and 24 weeks after treatment.Results: In comparison with the pretreatment data, the subjective symptoms and ocular surface disease parameters showed significant improvement after atelocollagen punctal occlusion. The average time of relapse was 17.4 ± 5.1 weeks. No severe complications occurred, and none of the plugs had to be removed because of local discomfort or epiphora.Conclusion: Atelocollagen absorbable punctal plugs effectively improved ocular surface disorders in DED. These plugs are a safe and effective alternative in the treatment of DED.Keywords: atelocollagen, absorbable punctual plug, dry eye

Makoto Ishikawa1, Masabumi Kubo2, Seiji Maeda3, Yu Sawada1, Eiichi Uchio4, Takeshi Yoshitomi11Department of Ophthalmology, Akita University School of Medicine, Akita, Japan; 2Fukiage Eye Clinic, Hachinohe, Japan; 3Maeda Eye Clinic, Honjo, Japan; 4Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, JapanPurpose: To examine structural changes in the lacrimal sac epithelium and associated lymphoid tissue of rabbits with experimentally induced dacryocystitis.Methods: Experimental dacryocystitis was induced by an inoculation of Staphylococcus aureus into the lacrimal sac. The histological changes of the inflamed lacrimal sac epithelium and associated lymphoid tissue were studied by light and electron microscopy.Results: After 1 month, numerous inflammatory cells (CD20-positive B lymphocytes, CD3-positive T lymphocytes, IgA-positive plasma cells, and polymorphonuclear leukocytes) infiltrated the lamina propria and the epithelium overlying the diffuse lymphoid tissue. Three months later, the density of the infiltrated leukocytes was markedly decreased. The epithelial lining overlying the diffuse lymphoid tissue became thicker with numerous secretory granules in the supranuclear regions.Conclusion: The lacrimal sac epithelium and associated lymphoid tissue play a major role in the defense mechanism during inflammation. Overproduction of secretory granules after bacterial inoculation could enhance the antimicrobial defense.Keywords: experimental dacryocystitis, lacrimal sac epithelium, lymphoid tissue, structure, rabbit