Topical tacrolimus for high-risk corneal transplantation: a randomized, clinical trial.

BACKGROUND: The prevalence of rejection is 10-30% in penetrating keratoplasty (PKP) case, and the rate is higher in cases of high-risk patients. Although using topical corticosteroids is a standard method for management the rejection of post-PKP patients, it may not be sufficiently potent in high-risk patients. Topical administration of tacrolimus (TAC) may be effective in suppression rejection after corneal transplantation. This study aimed to investigate the efficacy and safety of topical TAC in high-risk PKP patients in Japan. METHODS: This study was a single centre, single-blinded, randomized controlled trial. Patients with a history of PKP, graft rejection, atopic dermatitis, or deep corneal neovascularisation who underwent PKP were enrolled. They were randomly assigned to receive 0.1% TAC ophthalmic suspension or artificial tear (AT) up to week 52 after surgery. All participants received 0.1% betamethasone up to week 13 after surgery then they received 0.1% fluorometholone up to week 52. The incidence of immunological rejection during the observation period was the main outcome measure in this study. RESULTS: Thirty patients were enrolled in this study, and 12 eyes in the TAC group and 13 eyes in the AT group completed the study, respectively. Five out of 30 patients discontinued participation after providing informed consent. No serious adverse effects were developed in patients who received 0.1% TAC ophthalmic suspension. No rejection episodes occurred in the TAC group, while one eye in the AT group had rejection. Graft clarity, best spectacle-corrected visual acuity, intraocular pressure, and corneal endothelial cell density were not significantly different between the TAC and AT groups. CONCLUSION: Our results demonstrated that good tolerability of 0.1% TAC ophthalmic suspension. However, we failed to demonstrate its efficacy in preventing immunological rejection in high-risk patients undergoing PKP. TRIAL REGISTRATION: This study was first registered in the University Hospital Medical Information Network (UMIN000029669, Date of registration: November 1, 2017). With the enforcement of the Clinical Trial Act in Japan, the study re-registered in the Japan Registry of Clinical Trials (jRCTs031180342, Date of registration: March 18, 2019).

Clinical Trial of Autologous Cultivated Limbal Epithelial Cell Sheet Transplantation for Patients with Limbal Stem Cell Deficiency.

PURPOSE: To confirm the efficacy and safety of Good Manufacturing Practice (GMP)-compliant autologous cultivated limbal epithelial cell sheets in government-controlled clinical trials that adhered to Good Clinical Practice stipulations for patients with unilateral limbal stem cell deficiency (LSCD). DESIGN: A prospective, multicenter, open-label, uncontrolled, single-arm clinical trial. PARTICIPANTS: Ten consecutive eyes of 10 patients with unilateral LSCD were followed for 2 years after surgery. Preoperative LSCD stage was IIB in 4 eyes and III in 6 eyes. METHODS: A limbal tissue biopsy was obtained from the healthy eye, after which limbal stem cells were dissociated and cultivated on temperature-responsive culture surfaces. All cell sheets were fabricated in a GMP-grade facility under established standard operating procedures. Cell sheets were evaluated using defined shipment criteria before transplantation, and only those that met the criteria were used. The cell sheet was transplanted onto each of the patients' diseased eye after removing the conjunctival scar tissue that covered the corneal surface. The severity of LSCD was determined according to a staging method agreed on by global consensus, with eyes evaluated as being in stages IA-C representing successful corneal epithelial reconstruction. Diagnosis and staging of LSCD were determined by the trial's Eligibility Judgment Committee and Effect Assessment Committee using slit-lamp photographs including fluorescein staining. Both committees comprised 2 or 3 third-party cornea specialists, who were provided with information anonymously and randomly. MAIN OUTCOME MEASURE: Corneal epithelial reconstruction rate was the primary end point. RESULTS: Corneal epithelial reconstruction was successful in 6 of 10 eyes (60%) 1 year postoperatively and was significantly higher than the 15% clinically significant efficacy rate achieved by allogeneic limbal transplantation. The reconstruction rate was 70% of eyes 2 years postoperatively. Additionally, improvements in visual acuity were noted in 50% and 60% of eyes at 1 and 2 years, respectively. No clinically significant transplantation-related adverse events were observed. CONCLUSIONS: The efficacy and safety of cultivated limbal epithelial cell sheet transplantation were thus confirmed, and the cell sheet, named "Nepic," is now approved as a cellular and tissue-based product in Japan. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Morphological alterations in corneal nerves of patients with dry eye and associated biomarkers.

The purposes of the present study were to (1) identify the relationship between dry eye symptoms and morphological changes in corneal subbasal nerves/ocular surfaces, and (2) discover tear film biomarkers indicating morphological changes in the subbasal nerves. This was a prospective cross-sectional study conducted between October and November 2017. Adults with dry eye disease (DED, n = 43) and healthy eyes (n = 16) were evaluated based on their subjective symptoms and ophthalmological findings. Corneal subbasal nerves were observed using confocal laser scanning microscopy. Nerve lengths, densities, branch numbers, and nerve fiber tortuosity were analyzed using ACCMetrics and CCMetrics image analysis systems; tear proteins were quantified by mass spectroscopy. Compared with the control group, the DED group had significantly lower tear breakup times (TBUT) and pain tolerance capacity, and significantly higher corneal nerve branch density (CNBD) and corneal nerve total branch density (CTBD). CNBD and CTBD showed significant negative correlations with TBUT. Six biomarkers (cystatin-S, immunoglobulin kappa constant, neutrophil gelatinase-associated lipocalin, profilin-1, protein S100-A8, and protein S100-A9) showed significant positive correlations with CNBD and CTBD. The significantly higher CNBD and CTBD in the DED group suggests that DED is associated with morphological alterations in corneal nerves. The correlation of TBUT with CNBD and CTBD further supports this inference. Six candidate biomarkers that correlate with morphological changes were identified. Thus, morphological changes in corneal nerves are a hallmark of DED, and confocal microscopy may help in the diagnosis and treatment of dry eyes.

Lost or fragmented bony septum of the optic canal facing the sphenoid sinus: a histological study using elderly donated cadavers.

PURPOSE: To histologically describe a direct contact (the so-called dehiscence) of the optic nerve (ON) and/or internal carotid artery (ICA) to the mucosa of posterior paranasal sinuses represented by the sphenoid sinus (SS). METHODS: Observations of histological sections of unilateral or bilateral skull bases (parasellar area and orbital apex) from 22 elderly cadavers were made. RESULTS: A bony septum was less than 300 µm between the SS and ICA and 200 µm between the SS and optic nerve. Parts of the septa were sometimes absent due to fragmentation and holes of the bony lamella (2/22 facing the ICA; 4 facing the ICA in combination with an absent bony septum facing the nerve). In these dehiscence sites, the SS submucosal tissue attached to a thick sheath (50-100 µm in thickness) enclosing the optic nerve and ophthalmic artery and/or the ICA adventitia (50-200 µm in thickness). The ICA sometimes contained a sclerotic plaque that attached to or even protruded into the SS. With or without dehiscence, the SS mucosa was always thin (50-100 µm in thickness) and accompanied no mononuclear cellular infiltration or tumor. CONCLUSIONS: A thin bony septum of the optic nerve or ICA had been notable as a danger point during surgery, but even a 0.05-mm-thick bone lamella might be an effective barrier against cellular infiltration or bacterial invasion from the SS. Fragmentation and holes of the bony lamella in 4 cadavers might allow cellular invasion to the optic nerve. Accordingly, unknown immunological cross talks might occur to cause demyelination.

Elevated Cytokine Levels in Aqueous Humor Are Associated with Peripheral Anterior Synechiae after Penetrating Keratoplasty.

Peripheral anterior synechiae (PAS) after corneal transplantation leads to refractory glaucoma and permanent loss of vision. However, the exact mechanism remains elusive. This study aimed to evaluate the association between cytokine levels in the aqueous humor (AqH) and the progression of PAS after penetrating keratoplasty (PKP). We measured 20 cytokine levels in AqH and assessed the correlation with PAS progression after PKP in 85 consecutive patients who underwent PKP. We also evaluated age-dependent alterations in PAS and cytokine levels in DBA2J mice. PAS developed in 38 (44.7%) of 85 eyes after PKP. The incidence of intraocular pressure increase after PKP was significantly greater in eyes with PAS (26.3%) than in those without PAS (2%, p = 0.0009). The PAS area at 12 months after PKP was significantly positively correlated with the preoperative levels of interleukin (IL)-6, interferon (IFN)-γ and monocyte chemotactic protein (MCP)-1 (p ≤ 0.049). In the DBA2J mice, an experimental glaucoma model that developed PAS at 50 weeks, the AqH levels of IL-2, IL-6, IL-10, IFN-γ, tumor necrosis factor-α, MCP-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly increased at 50 weeks compared to 8 weeks (p ≤ 0.021). In conclusion, inflammatory alterations in the AqH microenvironment, such as high preoperative specific cytokine levels, can lead to PAS formation and glaucoma.

A New Perspective on Dry Eye Classification: Proposal by the Asia Dry Eye Society.

The 2017 consensus report of the Asia Dry Eye Society (ADES) on the definition and diagnosis of dry eyes described dry eye disease as "Dry eye is a multifactorial disease characterized by unstable tear film causing a variety of symptoms and/or visual impairment, potentially accompanied by ocular surface damage." The report emphasized the instability of tear film and the importance of visual dysfunction in association with dry eyes, highlighting the importance of the evaluation of tear film stability. This report also discussed the concept of tear film-oriented therapy, which stemmed from the definition, and which is centered on provision of insufficient components in each tear film layer and ocular surface epithelium. The current ADES report proposes a simple classification of dry eyes based on the concept of tear film-oriented diagnosis and suggests that there are three types of dry eye: aqueous-deficient, decreased wettability, and increased evaporation. It is suggested that these three types respectively coincide with the problems of each layer: aqueous, membrane-associated mucins, and lipid/secretory mucin. Although each component cannot be quantitatively evaluated with the current technology, a practical diagnosis based on the patterns of fluorescein breakup is recommended. The Asia Dry Eye Society classification report suggests that for a practical use of the definition, diagnostic criteria and classification system should be integrated and be simple to use. The classification system proposed by ADES is a straightforward tool and simple to use, only through use of fluorescein, which is available even to non-dry eye specialists, and which is believed to contribute to an effective diagnosis and treatment of dry eyes.

Corneal Higher-Order Aberrations in Eyes With Corneal Scar After Traumatic Perforation.

OBJECTIVES: To evaluate corneal higher-order aberrations (HOAs) in eyes with corneal scar after traumatic perforation and their correlation with visual acuity. METHODS: This retrospective consecutive case study included 40 eyes of 40 consecutive patients (mean age, 39.2±21.6 years), treated for traumatic corneal perforation at Tokyo Dental College, and 18 normal control eyes. Higher-order aberrations of anterior and posterior corneal surfaces and total cornea were analyzed by swept-source optical coherence tomography. Correlations between corneal HOAs and visual acuity were analyzed. RESULTS: Higher-order aberrations within 4-mm diameter were significantly larger in eyes with corneal perforation (anterior surface, 0.51±0.54 µm; posterior surface, 0.20±0.14; and total cornea, 0.52±0.50) as compared to normal controls (0.10±0.02, 0.02±0.01, and 0.09±0.02, respectively; all P<0.001). Higher-order aberrations within 6-mm diameter were significantly larger in eyes with corneal perforation (anterior surface, 1.15±1.31; posterior surface, 0.31±0.23; and total cornea, 1.09±1.28) as compared to normal controls (0.21±0.06, 0.06±0.01, and 0.19±0.06, respectively; all P<0.001). The most common topography pattern observed was the minimal change pattern (37.5%), followed by asymmetric pattern (30.0%). Visual acuity significantly correlated with corneal HOAs (anterior surface: R=0.646, P<0.001; posterior surface: R=0.400, P=0.033; and total cornea: R=0.614, P<0.001). CONCLUSIONS: Corneal scar after traumatic perforations not only induces corneal opacity, but also increases corneal HOAs, which indicates a direct effect on visual acuity.

Impact of Corneal Higher-Order Aberrations on Visual Acuity After Deep Anterior Lamellar Keratoplasty in Treating Keratoconus.

PURPOSE: To evaluate the incidence of the Descemet membrane (DM) folds after deep anterior lamellar keratoplasty (DALK) in treating keratoconus. We also evaluated the influence of DM folds and corneal higher-order aberrations (HOAs) on visual acuity after DALK. METHODS: This retrospective study included 89 consecutive eyes of 87 patients who underwent DALK for the treatment of keratoconus at Tokyo Dental College Ichikawa General Hospital from April 2002 to June 2017. The presence or absence of DM folds was determined by slitlamp microscopy. Visual acuity after DALK was compared between the eyes with and without DM folds. Corneal HOAs of the anterior and posterior surfaces and the total cornea were measured by anterior segment optical coherence tomography. Correlations among the presence of DM folds, corneal HOAs, and visual acuity were analyzed. RESULTS: The Descemet membrane folds developed in 28.1% (25/89) eyes after DALK for the treatment of keratoconus. However, there were no significant differences in postoperative visual acuity between the eyes with and without DM folds at 1, 3, 6, and 12 months (P=0.739, P=0.106, P=0.223, and P=0.186, respectively). The visual acuity at 12 months was significantly correlated with corneal HOAs within a 4-mm diameter (anterior surface: R=0.546, P=0.003; total cornea: R=0.506, P=0.007). CONCLUSIONS: Larger corneal HOAs, but not the presence of DM folds, were associated with poor visual acuity after DALK. In treating advanced keratoconus with DALK, it is important to minimize postoperative corneal HOAs, although DALK improves visual acuity by reducing HOAs due to keratoconus.

Efficacy of Plate Expression of Meibum on Tear Function and Ocular Surface Findings in Meibomian Gland Disease.

PURPOSE: To evaluate the clinical effectiveness of expression treatment on meibomian gland disease (MGD). METHODS: Seventeen right eyes of 17 patients with MGD were divided into 3 groups in this randomized prospective clinical study: no expression group: routine treatment with no expression (five patients, five eyes); digital expression group: routine treatment with digital expression (five patients, five eyes); and plate expression group: routine treatment with plate expression (seven patients, seven eyes). All groups received the same routine treatment for 1 month. Tear film break-up time (TBUT), vital staining scores, meibum expressibility, and the dry eye-related quality of life score (DEQS) questionnaire results were assessed before and 1 month after treatment. RESULTS: There was a statistically significant difference of posttreatment TBUT among groups as determined by one-way analysis of variance (P<0.05). A post hoc test revealed that TBUT was statistically significantly higher in plate expression group compared with digital expression group. The fluorescein staining score did not show a statistically significant difference among the groups. Meibum expressibility and the DEQS scores improved in all groups. CONCLUSION: Plate expression when used as an adjunct to routine medical management of MGD has been found to be a comparatively effective treatment in terms of improvement of tear film stability compared with no expression or digital expression.

The Effect of Rebamipide Ophthalmic Solution on Cytokine and Mucin Secretion in Culture of Conjunctival Epithelial Cells From the Cu, Zn-Superoxide Dismutase-1 (SOD-1) Knock-Down Mouse.

OBJECTIVES: To evaluate the in vitro effects of 1-mM rebamipide ophthalmic solution on the expression of inflammatory cytokines and MUC5AC in Cu, Zn-superoxide dismutase-1 (SOD-1) knock-down conjunctival epithelium. METHODS: Conjunctival epithelium from C57BL/6 wild-type mice was cultured and treated with rebamipide ophthalmic solution. Using cytometric bead array, we examined the levels of interleukin-(IL)-6, IL-10, IL-17, monocyte chemoattractant protein-1, interferon-γ (INF-γ), tumor necrosis factor, and IL-12p70 in the culture supernatants. The culture supernatants were obtained from the culture medium of nontreated or SOD-1 knock-down conjunctival epithelium using small interfering RNA (siRNA). In addition, ELISA was performed to ascertain the MUC5AC concentration in the culture medium. RESULTS: After rebamipide ophthalmic solution was applied, IL-6 concentration in the supernatants of conjunctival epithelial cells treated with and without siRNA showed a significant timewise decrease from 0 to 24 hr (963±42 to 0.07±0.05 pg/mL and 932±168 to 2.2±0.05 pg/mL, respectively) (P<0.001). Compared with baseline values, MUC5AC concentrations significantly increased 24 hr after rebamipide application to the conjunctival cultures-both with and without SOD-1 siRNA treatment (P<0.05 in both cases). CONCLUSIONS: Rebamipide seems to increase MUC5AC levels and suppress inflammation by decreasing IL-6 levels in mouse conjunctival epithelial cell cultures. SOD-1 siRNA-treated mouse conjunctival epithelial cell culture is a practical method for investigating changes in mucosa-associated mucins and proinflammatory cytokines in response to therapeutic interventions.

Updated long-term outcomes after carbon-ion radiotherapy for primary renal cell carcinoma.

Long-term oncological outcomes for primary renal cell carcinoma (RCC) treated with carbon-ion radiotherapy (CIRT) are poorly understood. Patients with primary RCC were treated with 12 or 16-fraction CIRT at The Hospital of the National Institute of Radiological Sciences outside of clinical trials. Outcome data were pooled and retrospectively analyzed for toxicity, local control, and disease-free, cancer-specific, and overall survival. From 1997 to 2014, 19 RCC patients (11 with T1aN0M0, 4 with T1bN0M0, and 4 with inoperable advanced stage [T4N0M0, T3aN1M0, and T1aN0M1]) were treated with CIRT and followed up for a median of 6.6 (range, 0.7-16.5) years; 9 of these patients were inoperable because of comorbidities or advanced-stage disease. Diagnoses were confirmed by imaging in 11 patients and by biopsy in the remaining 8. In 4 of 5 patients with definitive renal comorbidities, including diabetic nephropathy, sclerotic kidney or solitary kidney pre-CIRT progressed to grade 4 chronic kidney disease (CKD). In contrast, the remaining 14 patients without definitive renal comorbidities did not progress to grade 3 or higher CKD. Furthermore, although 1 case of grade 4 dermatitis was observed, there were no other grade 3 or higher non-renal adverse events. Local control rate, and disease-free, cancer-specific, and overall survival rates at 5 years of all 19 patients were 94.1%, 68.9%, 100%, and 89.2%, respectively. This updated retrospective analysis based on long-term follow-up data suggests that CIRT is a safe treatment for primary RCC patients without definitive renal comorbidities pre-CIRT, and yield favorable treatment outcomes, even in inoperable cases.

Elevation of preoperative recipient aqueous cytokine levels in eyes with primary graft failure after corneal transplantation.

Purpose: Primary graft failure after corneal transplantation is caused by dysfunction of corneal endothelial cells. Recently, we demonstrated that preoperative recipients' aqueous cytokine levels are associated with rapid corneal endothelial cell loss after corneal transplantation. In the present study, we evaluated the preoperative inflammatory cytokine levels in the aqueous humor (AqH) of eyes with primary graft failure following corneal transplantation. Methods: Among the prospective consecutive case series (273 eyes), this study included patients who developed primary graft failure (eight eyes) and patients who underwent corneal transplantation for the treatment of bullous keratopathy (108 eyes) or cataract surgery (30 eyes). AqH samples were collected at the beginning of each surgery. The levels of the cytokines (interleukin [IL]-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, interferon [IFN]-γ, monocyte chemotactic protein [MCP]-1, E-selectin, P-selectin, and soluble intercellular adhesion molecule [sICAM]-1) in the AqH were measured with multiplex beads immunoassay. Results: In eyes with primary graft failure, the preoperative levels of aqueous protein (4.6-fold), interleukin (IL)-6 (179-fold), IL-17A (7.1-fold), MCP-1 (2.6-fold), IFN-γ (4.3-fold), E-selectin (2.3-fold), P-selectin (2.0-fold), and sICAM-1 (5.5-fold) were statistically significantly higher compared to the cataract controls (p<0.0021). There was no primary graft failure among the recipients who received corneal grafts of fellow eyes from the same donors. Conclusions: Preoperative levels of AqH cytokines, such as IL-6, IL-17A, MCP-1, IFN-γ, and sICAM-1, increased in eyes with primary graft failure after corneal transplantation. These cytokine levels could be prognostic biomarkers to predict primary graft failure after corneal transplantation.

The effects of 3% diquafosol sodium eye drop application on meibomian gland and ocular surface alterations in the Cu, Zn-superoxide dismutase-1 (Sod1) knockout mice.

PURPOSE: The purpose of the study is to investigate the effect of 3% diquafosol sodium eye drops on meibomian gland and ocular surface alterations in the superoxide dismutase-1 (Sod1 -/- ) mice in comparison to the wild-type mouse. METHODS: Three percent diquafosol sodium eye drop was instilled to 20 eyes of 10 50-week-old male Sod1 -/- mice and 22 eyes of 11 C57BL/6 strain 50-week-old wild-type (WT) male mice six times a day for 2 weeks. Aqueous tear secretion quantity was measured with phenol red-impregnated cotton threads without anesthesia. Tear film stability and corneal epithelial damage were assessed by fluorescein and lissamine green staining. We also performed oil red O (ORO) lipid staining to evaluate the lipid changes in the meibomian glands. Meibomian gland specimens underwent hematoxylin and eosin staining to examine histopathological changes and meibomian gland acinar unit density after sacrifice. Immunohistochemistry staining was performed using cytokeratin 4, cytokeratin 13, and transglutaminase-1 antibodies. Quantitative real-time polymerase chain reaction for cytokeratin 4, cytokeratin 13, and transglutaminase-1 mRNA expression was also performed. RESULTS: The aqueous tear quantity, the mean tear film breakup time, and the number of lipid droplets significantly improved in the Sod1 -/- mice with treatment. The mean meibomian acinar unit density did not change in the Sod1 -/- mice and WT mice after treatment. Application of 3% diquafosol sodium eye drop significantly decreased the corneal fluorescein and lissamine green staining scores in the Sod1 -/- mice after 2 weeks. We showed a notable increase in cytokeratin 4, cytokeratin 13 immunohistochemistry staining, and cytokeratin 4, cytokeratin 13 mRNA expressions with a marked decrease in immunohistochemistry staining and significant decline in mRNA expression of transglutaminase-1 after 3% diquafosol sodium treatment. CONCLUSION: Topical application of 3% diquafosol sodium eye drop improved the number of lipid droplets, tear stability, and tear production which in turn appeared to have a favorable effect on the ocular surface epithelium. Three percent diquafosol sodium eye drop may be a potential treatment for age-related meibomian gland and dry eye disease based on the observations of the current study.

Application of CASIA SS-1000 Optical Coherence Tomography Tear Meniscus Imaging in Testing the Efficacy of New Strip Meniscometry in Dry Eye Diagnosis.

PURPOSE: To investigate the applicability of CASIA SS-1000 anterior-segment optical coherence tomography (AS-OCT) imaging parameters in testing the efficacy of the new strip meniscometry (SM) namely "Strip Meniscometry Tube" (SMTube) in the diagnosis of dry eyes. METHODS: Forty-three eyes of 22 patients (4 men and 18 women) with definite dry eye disease (DED) and 49 eyes of 28 normal controls (6 men and 22 women) were studied. All subjects underwent symptom questionnaires, SMTube, the Schirmer-1 test, tear film break-up time measurement, vital staining examinations, as well as tear meniscus height (TMH) and TM area (TMA) measurements using an AS-OCT system. We evaluated the cutoff values for the diagnosis of DED, looked into the correlations between TMH, TMA, and SMTube scores and checked the sensitivity and specificity of these parameters in the diagnosis of DED. RESULTS: The mean values of TMH, TMA, and SMTube scores in the patient group were 0.138±0.102 mm, 0.013±0.015 mm and 1.4±2.3 mm, whereas those for the control group were 0.27±0.10 mm, 0.033±0.025 mm and 5.8±2.8 mm, respectively. The differences between both groups were significant (P<0.001). The cutoff values of TMH, TMA, and SMTube for DED were 0.197 mm, 0.020 mm and 3.8 mm, respectively. SMTube had significant correlations with TMH (r=0.82, P<0.001) and TMA (r=0.86, P<0.001). CONCLUSIONS: The SMTube was useful in DED diagnosis, the validity of which could be effectively evaluated by the CASIA SS-1000 AS-OCT TM parameters.

Evaluation of the Effect of Moist Chamber Spectacles in Patients With Dry Eye Exposed to Adverse Environment Conditions.

PURPOSE: To evaluate the effect of moist chamber spectacle wear on the ocular surface and tear functions in a controlled wind exposure environment. METHODS: Twenty-eight eyes of 14 probable dry eye subjects (4 men, 10 women; mean age: 34.5 years) underwent constant wind exposure for 10 min without spectacle, with conventional spectacle wear, and with moist chamber spectacle wear. Dryness Visual Analog Scale (VAS) scores, tear evaporation, blink rate, tear film breakup testing, and fluorescein staining were performed before and after wind exposure. RESULTS: The mean dryness VAS score after wind exposure was significantly higher when no spectacles were worn or when conventional spectacles with no moist chambers were worn compared with after exposure scores when moist chamber spectacles were worn (P=0.02). The mean of tear evaporation rate from the ocular surface and blink rate increased significantly with wind exposure when no spectacles were worn or when conventional spectacles with no moist chambers were worn (P=0.04). There were no significant changes before and after wind exposure when the moist chamber spectacles were worn (P=0.1). CONCLUSION: Moist chamber spectacles appear to have favorable effects on dry eye symptomatology, tear stability, and blink rates in adverse environment conditions such as wind exposure.

Decreased Visual Acuity by an Irregular Corneal Posterior Surface After Repeat Descemet Stripping Automated Endothelial Keratoplasty.

PURPOSE: To investigate the impact of higher-order aberrations (HOAs) on visual acuity after repeat Descemet stripping automated endothelial keratoplasty (DSAEK) in the same eyes. METHODS: This retrospective comparative case series includes 23 patients who underwent DSAEK twice in the same eyes (46 DSAEK in total). We evaluated the HOAs of the anterior and posterior corneal surfaces, and total cornea using the Fourier analysis data from anterior segment optical coherence tomography. Eyes were divided into one of the following groups, based on the improvement and decline in the best-corrected visual acuity (BCVA) after repeat DSAEK; group A: 12 eyes with an improvement ≥ 2 lines, group B: 12 eyes with a decline ≤ 2 lines, and group C: 11 eyes with no change or change within 1 line. RESULTS: The HOAs of the posterior surface in group B were significantly greater than those of group A (P=0.028), whereas there were no significant differences in the anterior surface and total corneal HOAs between groups A and B (P=0.12 and 0.08). There were no significant differences in the anterior and posterior surface as well as total cornea HOAs between initial DSAEK and repeat DSAEK in group C (P=0.87, 0.65, and 0.42). The postoperative BCVA had a significant correlation with the HOAs of the anterior and posterior surfaces as well as the total cornea (R=0.40, 0.46, and 0.53; P=0.01, 0.002, and 0.001). CONCLUSIONS: Posterior corneal HOAs can have a negative influence on the visual acuity after endothelial keratoplasty.

Association of Epithelial Atypia With Recurrence After Surgical Excision in Conjunctival Papilloma.

PURPOSE: To investigate the association between recurrence of conjunctival papillomas and presence of atypical epithelial changes in patients undergoing surgical excision for conjunctival papilloma. METHODS: We retrospectively reviewed 1,195 ophthalmic pathology specimens from 2004 to 2014 at Ichikawa General Hospital. Pathologic specimens of 5 patients with a final diagnosis of "conjunctival papilloma" were stained with hematoxylin-eosin, Ki 67, p53, human papillomavirus (HPV) 16 and 18 antibodies. RESULTS: Of 1,195 patients, 5 patients (4 men, 1 woman; age range: 27∼57 years, mean age: 38.4 years) had a diagnosis of conjunctival papilloma, which constituted to 0.42% of the pathologic diagnosis made for the ophthalmology specimens. All specimens displayed multiple fronds of thickened conjunctival epithelium that enclosed cores of vascularized connective tissues. Three patients with recurrence after surgical excision demonstrated moderate to severe epithelial atypia, who also showed higher staining with Ki67 and p53 compared with patients with no recurrence. HPV16 and 18 antibodies staining did not appear to relate to recurrences. CONCLUSIONS: Conjunctival papillomas with higher positive staining for Ki67 and p53 seem to have a higher risk of recurrence even after complete surgical excision and necessitate careful follow-up.

Caruncular and Pericaruncular Sebaceous Gland Hyperplasia: A Report of 2 Cases and Literature Review.

PURPOSE: To report the clinical and histopathological features of two patients with caruncular and pericaruncular sebaceous gland hyperplasia (SGH) with a literature review. METHODS: We performed a retrospective pathology database search of 1195 ophthalmic specimens receiving the clinical diagnosis of SGH for caruncular/pericaruncular lesions during 2004 to 2014 at Tokyo Dental College, Ichikawa General Hospital. Paraffin sections were stained with hematoxylin and eosin. A retrospective patient record and literature review was also performed. RESULTS: Database search disclosed 2 male patients with SGH of 1195 specimens (0.15%). Pathological specimens revealed neither any cellular/nuclear atypia nor any mitotic figures and invasive features. No recurrences were observed in these 2 cases 12 to 18 months after excision. CONCLUSIONS: Caruncle and pericaruncular SGH is an uncommon lesion which needs careful histopathological evaluation for differentiation especially from caruncular neoplasias.

Epidermal Fatty Acid-Binding Protein: A Novel Marker in the Diagnosis of Dry Eye Disease in Sjögren Syndrome.

PURPOSE: Sjögren syndrome (SS) is a chronic inflammatory autoimmune disease of the lacrimal and salivary glands. This study compared the concentrations of epidermal fatty-acid binding protein (E-FABP) in the saliva, serum, and tears of SS patients with dry eye and dry mouth, with those of healthy adults to investigate the usefulness of E-FABP as a diagnostic marker for SS. DESIGN: Prospective, observational case series. PARTICIPANTS: The subjects were 11 new patients with untreated Sjogren syndrome and 12 healthy control individuals. METHODS: The diagnosis of SS was in accordance with the Ministry of Health, Labour and Welfare (Japan) Diagnostic Criteria (1999). Saliva, serum, and tear specimens were collected during internal medicine, dental, and ophthalmological examinations. The ophthalmological tests included the Dry Eye-related Quality of life Score (DEQS), tear break-up time (BUT), vital staining with fluorescein (FS) and lissamine green (LG), and the Schirmer test-1. The E-FABP concentration in the tears, saliva, and serum was measured by enzyme-linked immunosorbent assay (ELISA). MAIN OUTCOME MEASURE: The E-FABP concentrations were compared between patients and controls. RESULTS: There were significant differences between the patient and healthy control groups in all ophthalmological test results. There were no significant differences between the groups in the E-FABP concentrations in the saliva (p = 0.1513) or the serum (p = 0.4799), but the E-FABP concentration in the tears significantly differed between groups. The E-FABP concentration in tears tended to be significantly lower in patients with SS (mean, 323.5 ± 325.6 pg/mL) than healthy control subjects (mean, 4076 pg/mL; p = 0.0136). The E-FABP concentration in tears significantly correlated with the results of dry eye parameters. CONCLUSION: The E-FABP concentration in tears appears to be related to ocular surface epithelial damage and tear stability and may be a promising novel biomarker in the diagnosis of SS.

Cancer-specific mortality of high-risk prostate cancer after carbon-ion radiotherapy plus long-term androgen deprivation therapy.

The treatment outcomes of patients with high-risk localized prostate cancer (PC) after carbon-ion radiotherapy (CIRT) combined with long-term androgen deprivation therapy (LTADT) were analyzed, and compared with those of other treatment modalities, focusing on PC-specific mortality (PCSM). A total of 1247 patients were enrolled in three phase II clinical trials of fixed-dose CIRT between 2000 and 2013. Excluding patients with T4 disease, 608 patients with high-risk or very-high-risk PC, according to the National Comprehensive Cancer Network classification system, who received CIRT with LTADT were evaluated. The median follow-up time was 88.4 months, and the 5-/10-year PCSM rates were 1.5%/4.3%, respectively. T3b disease, Gleason score of 9-10 and percentage of positive biopsy cores >75% were associated with significantly higher PCSM on univariate and multivariate analyses. The 10-year PCSM rates of patients having all three (n = 16), two (n = 74) or one of these risk factors (n = 217) were 27.1, 11.6 and 5.7%, respectively. Of the 301 patients with none of these factors, only 1 PCSM occurred over the 10-year follow-up (10-year PCSM rate, 0.3%), and significant differences were observed among the four stratified groups (P <0.001). CIRT combined with LTADT yielded relatively favorable treatment outcomes in patients with high-risk PC and very favorable results in patients without any of the three abovementioned factors for PCSM. Because a significant difference in PCSM among the high-risk PC patient groups was observed, new categorization and treatment intensity adjustment may be required for high-risk PC patients treated with CIRT.