Pediatric chronic graft-versus-host disease-related dry eye disease and the diagnostic association of potential clinical findings.

Pediatric graft-versus-host-disease (GVHD)-related dry eye disease (DED) is often overlooked due to a lack of subjective symptoms and reliable testing, leading to irreversible corneal damage. To study the clinical findings contributing to the accurate detection of pediatric GVHD-related DED, a retrospective study of pediatric patients treated with hematopoietic stem cell transplantation (HSCT) at Keio University Hospital between 2004 and 2017 was conducted. Association and diagnostic values of ophthalmological findings for DED were analyzed.

Corneal higher-order aberrations in eyes with chronic ocular graft-versus-host disease.

Purpose: Chronic ocular graft-versus-host disease (GVHD) is a long-term complication after hematopoietic stem cell transplantation (HSCT) and leads to irreversible visual morbidity due to severe ocular surface impairments including visual disfunction. However, knowledge about the optical function in chronic ocular GVHD is limited because it is difficult to assess quantitative optical function objectively. The development of anterior segment optical coherence tomography has allowed objective quantification of optical function by evaluating corneal higher-order aberrations (HOAs).

Commensal microflora in human conjunctiva; characteristics of microflora in the patients with chronic ocular graft-versus-host disease.

Purpose: To investigate the transformation in the composition of ocular surface microflora. Evidence shows that microbial diversity correlates with autoimmune disorders. Chronic ocular graft-versus-host disease (GVHD) is the lethal complication after hematopoietic stem cell transplantation (HSCT) which influences patients' quality of life.

A novel and innovative paper-based analytical device for assessing tear lactoferrin of dry eye patients.

Purpose: To elucidate the correlation between lactoferrin concentration in the tear film and signs and symptoms of severe dry eye disease (DED) using a novel microfluidic paper-based analytical device (μPAD) and enzyme-linked immunosorbent assay (ELISA).

Methods: Twenty-four patients were recruited at the Keio University Hospital. Using a novel μPAD, lactoferrin concentrations were measured in 4 patients with GVHD-related DED, 3 patients with other types of DED and 2 controls (Group A).

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.

Reduced Expression of VAMP8 in Lacrimal Gland Affected by Chronic Graft-versus-Host Disease.

Purpose: To investigate whether the SNARE protein vesicle-associated membrane protein 8 (VAMP8) was implicated in the development of chronic ocular graft-versus-host disease (GVHD).

Methods: Firstly, the chronic GVHD (cGVHD) and Sjögren's syndrome (SS)-impaired lacrimal gland (LG) tissue sections from humans for diagnostic purpose were evaluated for VAMP8 expression by histopathology and immunohistochemistry. Next, serial changes of tear secretion and VAMP8 expression at both protein and mRNA level of LG in an animal cGVHD model compared with the syngeneic control.

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.

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.

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.

Accumulation of secretory vesicles in the lacrimal gland epithelia is related to non-Sjögren's type dry eye in visual display terminal users.

Previous observations in a rat model of a non-Sjögren's syndrome (non-SS) type of dry eye seen in users of visual display terminals (VDT) indicated that secretory vesicle (SV) accumulation in the lacrimal gland epithelia contributes to the condition. Here, to examine this possibility in humans, we compared the lacrimal gland histology and percent SV area in the cytoplasm of acinar epithelial cells using light microscopy and transmission electron microscopy, in patients with VDT work-related non-SS dry-eye (VDT group), SS-induced dry-eye, and autopsied normal controls. In addition, the VAMP8 (vesicle-associated membrane protein 8, an exocrine-pathway molecule) and Rab3D (mature vesicle marker) were histochemically examined in lacrimal gland tissue sections.

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.

Comparison of telomere length and association with progenitor cell markers in lacrimal gland between Sjögren syndrome and non-Sjögren syndrome dry eye patients.

Purpose: Indicators of aging such as disruption of telomeric function due to shortening may be more frequent in dysfunctional lacrimal gland. The aims of this study were to 1) determine the viability of quantitative fluorescence in situ hybridization of telomeres (telo-FISH) for the assessment of telomere length in lacrimal gland in Sjögren and non- Sjögren syndrome patients; and 2) investigate the relationship between progenitor cell markers and telomere length in both groups.

Methods: Quantitative fluorescence in situ hybridization with a peptide nucleic acid probe complementary to the telomere repeat sequence was performed on frozen sections from human lacrimal gland tissues.

Spontaneous lacrimal punctal occlusion associated with ocular chronic graft-versus-host disease.

Purpose: To investigate the clinical features of spontaneous lacrimal punctal occlusion (SLPO) after allogeneic hematopoietic stem cell transplantation (HSCT).

Methods: One hundred nineteen recipients after HSCT who visited Keio University between 2001 and 2004 were examined. The condition of the lacrimal punctum, severity of dry eye, meibomian gland secretion, and presence of systemic chronic graft-versus-host disease (cGVHD) were determined with or without SLPO by retrospective chart review.

Tear evaporation rates in Sjögren syndrome and non-Sjögren dry eye patients.

Purpose: To reinvestigate tear evaporation rates in Sjögren syndrome (SS) and non-Sjögren (non-SS) dry eye patients with a recently reported ventilated chamber evaporimeter system.

Design: Prospective case-control study.

Methods: A ventilated chamber evaporimeter system was used to measure tear evaporation rates.

Electrolysis for corneal opacities in a young patient with superficial variant of granular corneal dystrophy (Reis-Bücklers corneal dystrophy).

Purpose: To report the efficacy of electrolysis as a treatment of corneal opacities in a young patient with the superficial variant of granular corneal dystrophy.

Design: Interventional case report.

Methods: An 11-year-old boy presented with subepithelial opacities in both eyes.