Baseline profiles of ocular surface and tear dynamics after allogeneic hematopoietic stem cell transplantation in patients with or without chronic GVHD-related dry eye

Wang, Y; Ogawa, Yoko; Doğru, Murat; Tatematsu, Yukako; Uchino, Makoto; Kamoi, Mizuka; Okada, Naoko; Okamoto, Shinichiro; Tsubota, Kazuo

doi:10.1038/bmt.2009.312

Cited by 75 publications

(79 citation statements)

References 30 publications

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“…In addition to deficient tear production, tear evaporation rate and meibomian gland functions also appear to be significantly compromised in cGVHD. This is in agreement with the inferences drawn in previous studies, 7,8,14 although there are differences in the instrumentation used in the different studies. It is noteworthy that Wang et al 14 did not find a statistically detectable difference between tear evaporation rates of BM transplant recipients with and without cGVHD.…”

Section: Lipid Layer Unstable Stablesupporting

confidence: 82%

“…Unquantifiable reflex secretion following the insertion of Schirmer strips makes it difficult to assess the agreement of our findings with previous reports of Schirmer test results in cGVHD. The general trend observed with cGVHD dry eye patients was of low Schirmer test values, 2,7,8,14,20,21 supporting the impairment of tear production in cGVHD-associated dry eye. A histological study has shown that there is a predominant infiltration of T-cells into the periductal area, an increase in the number of stromal fibroblasts and excessive fibrosis in Although no statistically significant differences were found, the data indicates that the tear osmolarity values for cGVHD-associated dry eye are higher than that for the other groups.…”

Section: Discussionmentioning

confidence: 99%

“…One study 7 evaluated spread of the lipid layer with an interferometer and a more recent one measured tear evaporation. 14 These studies offer an initial foray into these important aspects of tear physiology. However, for the purpose of acquiring crucial information of tear deficiency, it is critical to evaluate other aspects of tear physiology.…”

Section: Introductionmentioning

confidence: 99%

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Tear physiology in dry eye associated with chronic GVHD

Khanal

Tomlinson

2011

Bone Marrow Transplant

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The purpose of this study was to compare tear physiology characteristics of chronic GVHD (cGVHD)-associated dry eye to dry eye caused by Sjogren's syndrome (SS), a extreme form of aqueous-deficient dry eye, and meibomian gland dysfunction (MGD), the major cause of evaporative dry eye. Tear turnover rate, evaporation and osmolarity along with meibomian gland dropout and lipid layer interferometric patterns were assessed in the right eyes of 12 patients with dry eye associated with cGVHD, 12 age-matched patients with SS and 12 age-sex matched subjects with MGD. In cGVHD, the decrease in tear turnover rate was similar (P ¼ 0.33), but the number of non-functioning meibomian glands was significantly higher (Po0.01) than in SS. Tear evaporation rate in cGVHD dry eye was found to be similar to that in MGD (P ¼ 0.36) and significantly higher than in SS (Po0.01). The lipid layer was most unstable in cGVHD compared with other groups. There was no variation in tear volume across all groups. Although statistical significance was not detected, the mean tear osmolarity (333.51± 14.67mOsm/L) was highest in cGVHD. Major aspects of tear physiology were severely impaired in cGVHDassociated dry eye.

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Section: Lipid Layer Unstable Stablesupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tear physiology in dry eye associated with chronic GVHD

Khanal

Tomlinson

2011

Bone Marrow Transplant

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“…Of these, 18 showed clinical signs of chronic oGvHD. In contrast to earlier research studies [44,45], this study failed to demonstrate a correlation between oGvHD status and HLA-DR expression in conjunctival epithelial cells [12]. The authors did, however, report an association between CD8-stained lymphocytes and oGvHD.…”

Section: Ocular Graft-versus-host Diseasecontrasting

confidence: 55%

Biomarkers of Ocular Surface Disease Using Impression Cytology

Hagan

2017

Biomark. Med.

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Impression cytology (IC) is a technique which permits the retrieval of the outermost layer of ocular surface cells via the use of various types of filters. It is a minimally invasive method of evaluating human conjunctival epithelial cell morphology in the diagnosis of dry eye disease, a common and distressing disorder associated with ageing, contact lens wear, autoimmune disorders and refractive (LASIK) surgery. IC may also be utilized in the diagnosis of other ocular diseases, such as keratoconus and thyroid orbitopathy. More recently, IC has been utilized for the subsequent investigation of gene and protein expression of conjunctival cells in order to identify novel diagnostic biomarkers and to further our understanding of the mechanisms underlying ocular surface disease. This review will therefore examine the literature concerning the role of IC in identifying cellular markers of eye disease, systemic diseases with ocular involvement and potential novel therapeutic targets. Impression cytology (IC) is a minimally invasive method of evaluating human ocular surface cells and is considered as the 'gold standard' technique for assessing cell morphology. Introduced by Thatcher et al. [1] and Egbert et al. [2], IC is an easy-to-use technique of directly retrieving (mainly conjunctival) cells, using various filter types which are gently applied to exposed (interpalpebral) conjunctival surfaces. The filters used include cellulose acetate [3], polycarbonate (Biopore, Millipore UK Ltd, Watford, UK) [4], nitrocellulose [5] or polyethersulfone (PES) [6] which are gently applied to exposed (interpalpebral) conjunctival surfaces. Recently, a more standardized tool for IC sampling has been introduced (Figures 1 & 2). The Eyeprim is a new single-use PES filter sampling medical device for retrieval of conjunctival cells (Opia Technologies, France) and a recent study by Lopez-Miguel et al. [7] performed an analysis of this tool versus the traditional IC method (PES). On a cohort of 20 healthy individuals, they extracted and compared RNA from both devices and found no significant differences in the mean yield (p ≥ 0.45), the total RNA amount (μg), or the amount normalized to membrane area [7]. Although an earlier study of the Eyeprim [8], suggested that it recovered more cells than traditional IC, Lopez-Miguel et al. [7] did not observe differences in the RNA collected between this device and PES.Historically, IC has been used to analyze pathological changes to conjunctival cells for indicators of squamous metaplasia in ocular surface disease (OSD) [9]. More recently, however, researchers have used IC to examine specific markers of inflammation, for example, HLA-DR, ICAM-1 and CD8 [10][11][12], and to examine novel biomarkers of dry eye disease (DED). The latter is performed in an attempt to understand the mechanisms underpinning DED pathophysiology and is now feasible, due to vast improvements in the assay sensitivities for gene and protein examination [13]. As a result, IC membranes can be subsequently analyzed using techniq...

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“…2 The local therapies most commonly used to reduce ocular inflammation and corneal lesions (corticosteroids, CsA, tacrolimus and others) in association with artificial tears, demonstrated poor tolerance and unsatisfactory response. 3,5,9 For instance, a recent meta-analysis estimated that topical lubricants provide an overall improvement that is no greater than 25% from baseline, while topical CsA achieved improvement in only 10/16 (62%) patients. 10,11 Recently, borrowing from the experience of patients with severe DES in Sjö gren's disease, 12,13 treatment with autologous serum eye drops has been proposed to treat refractory keratoconjuntivitis sicca in GVHD patients with good results, demonstrating that serum is safe and effective in the majority of patients after 4 weeks of treatment.…”

Section: Introductionmentioning

confidence: 99%

Autologous platelet lysate for treatment of refractory ocular GVHD

Pezzotta

Fante

Scudeller

et al. 2012

Bone Marrow Transplant

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Current treatment of ocular GVHD (oGVHD), represented by systemic immunosuppressive regimens and local therapies (mainly artificial tears and corticosteroids), gives unsatisfactory results. We investigated the safety and efficacy of autologous plasma rich in PDGFs to treat oGVHD unresponsive to standard medications. A total of 23 patients with refractory oGVHD (grade II-IV) unresponsive to standard therapy were treated with autologous plasma rich in PDGFs eye drops (PRGD) four times/day for 6 months. Symptoms and signs (best visual acuity, Schirmer's test and tear break up time (TBUT), evaluation of the anterior segment and fluorescein and lissamine staining) were always assessed by the same ophthalmologist. Patients were defined as 'responders' when showing improvement for total complaints and at least one sign. At 30 days of treatment, 17 patients (73.9%) were classified as responders. The symptom that improved most was photophobia (improved in 19 patients, 82.6%). TBUT improved in 20 patients (86.9%) and anterior segment score in 19 patients (82.6%). Response was maintained over time. No serious adverse events occurred. PRGD proved to be safe and effective in treating oGVHD and may be a valid treatment option from the early stages of the disease to avoid irreversible ocular damage.

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Baseline profiles of ocular surface and tear dynamics after allogeneic hematopoietic stem cell transplantation in patients with or without chronic GVHD-related dry eye

Cited by 75 publications

References 30 publications

Tear physiology in dry eye associated with chronic GVHD

Tear physiology in dry eye associated with chronic GVHD

Biomarkers of Ocular Surface Disease Using Impression Cytology

Autologous platelet lysate for treatment of refractory ocular GVHD

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