Isolation of Aspergillus udagawae in Canaliculitis: A Case Report.

Aspergillus udagawae is a cryptic species of Aspergillus section Fumigati. Here, we report a case of canaliculitis with isolated A. udagawae. Fungal canaliculitis is a rare lacrimal disease, and its clinical features are poorly understood. The causative fungus was initially misclassified as Aspergillus thermomutatus by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) but was finally identified as A. udagawae by ß-tubulin genetic analysis. The patient showed rapid improvement and did not experience relapse after drainage alone, without antifungal therapy. A. udagawae has low virulence, which may be related to the minimally invasive nature of the infection.

Eyelid blood vessel and meibomian gland changes in a sclerodermatous chronic GVHD mouse model.

PURPOSE: To investigate pathological changes in blood vessels and meibomian glands (MGs) in the eyelids of sclerodermatous chronic graft-versus-host disease (cGVHD) model mice. METHODS: We used an established major histocompatibility complex compatible, multiple minor histocompatibility antigen-mismatched sclerodermatous cGVHD mouse model. Blood vessels and MGs of eyelids from allogeneic bone marrow transplantation (allo-BMT) recipient mice and syngeneic bone marrow transplantation (syn-BMT) recipient mice were assessed by histopathology, immunohistochemistry and transmission electron microscopy. Peripheral blood samples from the recipients were examined by flow cytometry. RESULTS: Allo-BMT samples showed dilating, tortuous and branching vessels and shrunk MGs in the eyelids; showed significantly higher expression of VEGFR2 (p = 0.029), CD133 (p = 0.016), GFP (p = 0.006), and α-SMA (p = 0.029) in the peripheral MG area; showed endothelial damage and activation, fibrotic change, and immune cell infiltration into MGs compared with syn-BMT samples. Fewer Ki-67+ cells were observed in allo- and syn-BMT samples than in wild-type samples (p = 0.030). Ultrastructural changes including endothelial injury and activation, fibroblast activation, granulocyte degranulation, immune cell infiltration into MGs, and necrosis, apoptosis of MG basal cells were found in allo-BMT samples compared with syn-BMT samples. CONCLUSION: A series of our studies indicated that cGVHD can cause eyelid vessel and MGs changes, including endothelial injury and activation, neovascularization, early fibrotic changes, immune cell infiltration, MG basal cell necrosis and apoptosis, and resultant MG atrophy.

Case of primary intraocular lymphoproliferative disorder caused by Epstein-Barr Virus.

BACKGROUND: Cases of panuveitis caused by Epstein-Barr virus (EBV) associated with primary intraocular lymphoproliferative disorder (LPD) are rare in immunocompetent individuals. CASE PRESENTATION: A 67-year-old man noted blurred vision in both eyes and was referred to our hospital. His best-corrected visual acuity (BCVA) was 20/20 in both eyes. He had mild inflammation in the anterior chamber but not in the vitreous of both eyes. The inflammation was resolved with topical corticosteroid but 10 months later both eyes presented recurrence. Treatment with a sub-Tenon's injection of steroid was effective for OS but not for OD and 2 months after, the inflammation in the anterior chamber and vitreous opacities got worsen in OD and BCVA decreased to 6/20 OD. Thus, pars plana vitrectomy was performed on OD, and EBV was detected in the aqueous humor by multiplex polymerase chain reaction, and an infiltration of CD19κ positive B cells was revealed in the vitreous specimens by flow cytometry. Systemic workup revealed no other sites of lymphoproliferation, no active EBV infection, or underlying immunodeficiency. CONCLUSION: Panuveitis caused by EBV associated with primary intraocular LPD can occur in patients with no history of congenital or acquired immunodeficiencies.

Long-Term Topical Diquafosol Tetrasodium Treatment of Dry Eye Disease Caused by Chronic Graft-Versus-Host Disease: A Retrospective Study.

OBJECTIVES: The aim of this study was to assess the safety and efficacy of long-term use of 3% diquafosol ophthalmic solution (DQS), an eye drop for mucin production and water secretion, for treating dry eye disease (DED) caused by chronic graft-versus-host disease (cGVHD). METHODS: We retrospectively evaluated the safety and efficacy of DQS in 10 patients with mild to moderate cGVHD-induced DED. The efficacy was assessed by (1) degree of symptoms, (2) Schirmer I test value, (3) tear film breakup time (TFBUT), and (4) fluorescein and rose bengal scores. RESULTS: The median duration of DQS treatment was 12.0 months (range 6-17 months). DQS was effective for relieving severe pain caused by cGVHD-related DED. Although the Schirmer I test value was enhanced only marginally, the long-term application of DQS significantly improved the corneal/conjunctival epitheliopathy and tear film stability: the fluorescein score improved from 5.9±0.6 to 1.3±1.1 points (P=1.771×10); rose bengal staining from 4.7±1.6 to 2.0±1.5 points (P=0.008); and TFBUT from 2.6±0.9 to 4.6±1.6 mm (P=0.009). Furthermore, the long-term DQS treatment caused no major adverse events. CONCLUSIONS: This study suggested that long-term DQS treatment is a safe and robust approach for alleviating cGVHD-related DED.

In Vivo Confocal Microscopy Evaluation of Ocular Surface with Graft-Versus-Host Disease-Related Dry Eye Disease.

Dry eye disease (DED) is often elicited by graft-versus-host disease (GVHD), an extensive complication of hematopoietic stem cell transplantation (HSCT). To unravel the mechanism of this type of DED, in vivo confocal microscopy (IVCM) was used to investigate alterations in the state of the sub-basal nerves, dendritic cells (DCs) and globular immune cells (GICs) in the central cornea and limbal epithelia. In this study, we examined 12 HSCT recipients with GVHD-caused DED and 10 HSCT recipients without GVHD-associated DED and evaluated the clinical parameters in the 2 groups. Analysis of the central cornea and limbal epithelia using IVCM was conducted to investigate the density of the corneal sub-basal nerves, DCs and GICs as well as the tortuosity and branching of the sub-basal nerves. As suggested by our data, the clinical variables in the GVHD group were significantly different from those in the non-GVHD group. Additionally, GVHD-triggered DED conceivably increased the density of DCs and GICs in the central cornea and the density of DCs in limbal epithelia and altered the morphology of the sub-basal nerves. These phenomena are presumably correlated with the degree of inflammation. Thus, our findings may be translated into non-invasive diagnostic methods that indicate the severity of inflammation on the ocular surface in HSCT recipients.

Effectiveness of bandage contact lens application in corneal epithelialization and pain alleviation following corneal transplantation; prospective, randomized clinical trial.

BACKGROUND: To assess the efficacy of bandage contact lens (BCL) application to promote epithelialization and alleviate pain following corneal transplantation. METHODS: Twenty-six consecutive patients who underwent corneal transplantation were randomly assigned to undergo BCL application (BCL group, n = 14) or no BCL application (control group, n = 12) at the end of the surgery. Corneal epithelialization was analyzed by photography using fluorescein staining, and ocular pain was measured using a visual analog scale. RESULTS: The mean size of the epithelial defect relative to the graft area in the BCL group was 21.80 ± 35.10 % at the end of surgery, 18.20 ± 31.10 % on postoperative day 1, and 5.45 ± 11.10 % on postoperative days 3 to 5. These values in the control group were 9.64 ± 17.60 % at the end of surgery, 11.50 ± 25.70 % on postoperative day 1, and 0.00 ± 0.00 % on postoperative days 3 to 5. There were no significant differences in the speed of epithelialization between the two groups. The mean preoperative pain score in the BCL group was slightly higher than that control (4.27 ± 1.96 vs. 2.41 ± 2.18, respectively; P = 0.039). The scores significantly increased on postoperative day 1 and promptly returned to preoperative levels by day 7 in both groups, and there were no significant differences between the groups. CONCLUSIONS: No significant benefits of BCL application at the time of corneal transplantation were observed in this study. The efficacy and safety of BCLs in eyes with compromised epithelialization require further study. TRIAL REGISTRATION NUMBER: UMIN 000019091 . Date of registration: 2015/09/22.

Long-term rebamipide and diquafosol in two cases of immune-mediated dry eye.

PURPOSE: Two new drugs with mucin-inducing and secretion-promotive effects, rebamipide and diquafosol, were recently approved as topical dry-eye treatments. We report two cases in which the long-term use of mucin-inducing eye drops improved chronic ocular graft-versus-host disease (cGVHD)-related dry eye and ocular cicatricial pemphigoid (OCP)-like disease. CASE REPORTS: Case 1. A 61-year-old woman had cGVHD-related dry eye that resisted traditional medications. Next, we use topical diquafosol in addition to conventional treatments. The patient used diquafosol for 6 months without experiencing any side effects. The symptoms, including dry-eye sensation, ocular pain, foreign body sensation, and photophobia, as well as ocular surface findings including fluorescein and rose bengal scores and tear break-up time (TBUT), partly improved. To further improve the clinical signs and symptoms and decrease chronic inflammation, rebamipide was added to diquafosol. The symptoms, TBUT, and fluorescein and rose bengal scores markedly improved after long-term dual treatment without any side effects for 6 months. Case 2. A 77-year-old woman had OCP-like disease with dry eye. The patient did not improve using the currently available conventional treatments. Next, we use topical rebamipide in addition to conventional treatments. Symptoms including asthenopia, dry-eye sensation, ocular pain, and dull sensation, as well as fluorescein and rose bengal scores and TBUT, partly improved. Specifically, functional visual acuity was markedly improved after commencement of rebamipide. To further improve the clinical signs and symptoms and increase tear film stability and tear film volume, diquafosol was added to rebamipide. The combination of diquafosol and rebamipide worked for the patient. Improvements were seen in several symptoms, fluorescein and rose bengal scores, Schirmer test value, and TBUT without any side effects for 12 months. CONCLUSIONS: Long-term treatment with topical rebamipide and diquafosol can improve dry eye in patients with cGVHD or OCP-like disease.

Grading criteria for chronic ocular graft-versus-host disease: comparing the NIH eye score, Japanese dry eye score, and DEWS 2007 score.

Ocular graft-versus-host disease (GVHD) is a common complication after hematopoietic stem cell transplantation (HSCT). Here we compared the diagnostic rates of ocular GVHD, including its severity, prognosis and the agreement, obtained using three grading scales: the National Institutes of Health (NIH) eye score, Japanese dry eye score, and dry eye workshop score, by retrospectively reviewing the records of 82 patients who underwent HSCT. Tear dynamics and ocular surface assessments made 6-9 months after HSCT were used to determine ocular GVHD severity with the three scales. By the three scales, ocular GVHD was diagnosed in 56 patients (68.3%), 51 patients (62.2%), and 52 patients (63.4%), respectively. The Kappa coefficient was calculated to determine the agreement between scales for diagnosing ocular GVHD. The severity progression within two years after onset was also assessed by tear dynamics and ocular surface examination. The patients were categorized as no change, improved, or progressive. The three grading scales showed good agreement (Kappa = 0.87 to 0.97) in diagnosing patients with ocular GVHD, and the scores by all three were significantly associated with the patients' prognosis (p < 0.01). We recommend that multi-center research is needed for further validation and investigation.

Morphological evaluation of meibomian glands using noncontact infrared meibography.

Meibography is used to study morphological changes in the meibomian glands (MGs), and semiquantitative analysis has been used for MG assessment. We conducted a detailed morphometric assessment of MGs using noncontact infrared meibography (NIM) and investigated the relationship between MG morphology and the ocular surface and MG morphology associated with aging and sex in 37 subjects. The MGs in the upper and lower eyelids showed significant correlations in their morphology, with the former having longer ducts than the latter. The mean length of the MG ducts, percent area of MG acini, and number of gland dropouts were significantly correlated with age. The mean length of the MG ducts in the upper and lower eyelids showed negative correlations with the meibum (P=.043) and fluorescein staining score (P=.008), respectively. The percent area of MG acini in the upper eyelid showed a positive correlation with tear film breakup time (P=.012) and negative correlations with tear film lipid layer interferometry and meibum (P=.005 and .002, respectively). The mean length of the male's MG ducts in the lower eyelid was significantly longer than that of the females (P=.03). These results indicate that morphometric analysis using NIM may be useful for assessing ocular surface conditions.

Morphologic evaluation of meibomian glands in chronic graft-versus-host disease using in vivo laser confocal microscopy.

PURPOSE: To evaluate the morphological changes of the meibomian glands (MGs) using in vivo laser confocal microscopy (CM) in dry eye (DE) patients with chronic graft-versus-host disease (cGVHD). METHODS: Seventeen eyes from 9 patients with a diagnosis of DE associated with cGVHD (DE/cGVHD group; 6 males, 3 females; median 50.5 years) and 16 eyes of 8 hematopoietic stem cell transplantation (HSCT) recipients without DE (non-DE/non-cGVHD group; 5 males, 3 females; median 47.0 years) were enrolled. CM was used to investigate the MG and MG acinar unit density (MGAUD), MG acinar longest diameter (MGALD), MG acinar shortest diameter (MGASD), and the fibrosis grade. Clinical findings of the lid margin were obtained. Tear dynamics, ocular surface vital staining, meibography, and MG expressibility were also examined. Data were compared between the 2 groups using the unpaired t and Mann-Whitney tests. RESULTS: The mean MGAUD value was significantly lower in the DE/cGVHD group than in the non-DE/non-cGVHD group (p=0.01, 57.8±38.3 glands/mm(2), 88.8±26.6 glands/mm(2), respectively), and the mean MGALD and MGASD were significantly shorter in the DE/cGVHD group than in the non-DE/non-cGVHD group (p=0.0018, 37.3±24.4 µm and 60.4±11.8 µm, p=0.0106, 17.7±11.8 µm and 26.6±6.03 µm, respectively). The mean fibrosis grade was significantly higher in the DE/cGVHD group than the non-DE/non-cGVHD group (p<0.0001, 1.39±0.71 grade, 0.06±0.25 grade, respectively). Clinical findings in the lid margin, tear dynamics, and ocular surface findings were significantly worse in the DE/cGVHD group than in the non-DE/non-cGVHD group. CONCLUSIONS: CM clearly depicted the morphological changes of the MG in the DE/cGVHD group, and revealed the severity of the meibomian gland dysfunction. Patients with severe DE after HSCT showed atrophic MG and excessive fibrosis.

Acute audiovestibular deficit with complete ocular tilt reaction and absent VEMPs.

A patient presenting with vertical diplopia along with ocular tilt reaction (OTR) due to peripheral vestibular dysfunction is a rare occurrence. OTR is an eye-head postural reaction consisting of head tilt, skew deviation, conjugated eye cyclotorsion, and alteration of vertical perception, and is thought to occur with central lesions, mainly brainstem lesions. Here, we report a case of a patient who was suffering from left acute peripheral cochleovestibular loss. He had profound deafness and absence of caloric response on the left side. No central lesion was observed on magnetic resonance images. Neuro-ophthalmological examination showed OTR consisting of head tilt, skew deviation with left hypotropia, excyclotorsion, and tilt of the static visual vertical directed to the left side. Both utricular and saccular dysfunctions were identified by the absence of cervical vestibular evoked myogenic potential (cVEMP) and ocular VEMP (oVEMP) on the left side. Within a month, the OTR disappeared completely probably because of vestibular compensation. This is the first report to state that the peripheral otolith dysfunction causing reversible vertical diplopia was identified by objective examinations (VEMP).

Introduction of the Low Vision Evaluator (LoVE) for children.

PURPOSE: To determine whether the Low Vision Evaluator (LoVE) can grade the visual acuity of young children with light perception and hand movement acuity into finer acuity steps and at what age reliable measurements can be obtained. METHODS: Two hundred twenty children were tested with the LoVE. Each eye was tested separately, and each stimulus magnitude (intensity x duration) was presented three times. Three catch trials per eye also were presented. RESULTS: Scores ranged from -8 to -1 on variable-duration tests and from 22.5 to 37.5 dB on fixed-duration tests for four children with hand movement vision. Scores ranged from -12 to 0 on variable-duration tests and from 12.5 to 40 dB on fixed-duration tests for five children with light perception vision. Reliable measurements were obtained at different times on different days. Mean scores for children with counting finger vision or better were significantly better than scores for eyes with light perception and hand movement (P < .001 and P < .01, respectively). Reliability was less for children younger than age 4 years. CONCLUSIONS: The LoVE is capable of grading the visual function of children with light perception and hand movement vision into finer steps. Reliable measurements can be obtained for children age 4 years and older.