The GvHD-DED-MGD links, emerging treatments and a new drug
What is GvHD?
For those unfamiliar with the term, Graft-v-Host Disease (GvHD) is a condition that can happen after a donated bone marrow transplant. One of its features can be severe dry eye with a lot of challenging features.
#1 Ocular surface system alterations in ocular graft-versus-host disease: all the pieces of the complex puzzle.
Giannaccare et al, Graefes Archives of Clinical and Experimental Archaeology, April 2019
Did you know that graft-v-host-disease affects every part of the tear system, including:
nasolacrimal duct and
Thankfully, there are emerging treatments for those who are not helped enough by conventional dry eye disease treatments, as this review study highlights, such as amniotic membrane or limbal transplantation. PROSE and scleral lenses are not mentioned in any of these studies, but many GvHD patients use them successfully as well.
Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cells transplantation, occurring in about half of transplanted patients. This condition seems to be the result of a progressive immune-mediated damage that can involve various tissues, including the eyes. The ocular surface system is the ocular structure most frequently impaired, and dry eye disease is considered the hallmark of ocular GVHD. Given the increasing prevalence and the frequent severe involvement of the ocular surface with vision-threatening complications, ocular GVHD represents a current diagnostic and therapeutic challenge. The purpose of this literature review is to describe all the clinical manifestations occurring in the setting of ocular GVHD, and to further report the outcomes of conventional and novel therapies.
A literature search about ocular GVHD was performed in PubMed, Scopus, Medline databases, and ClinicalTrials.gov as well as through the reference lists of identified publications until January 2019. We have included RCTs, prospective observational studies, prospective and retrospective cohort studies, pilot studies, and review articles.
Overall, 107 articles, 3 book chapters, and 6 ongoing registered clinical trials were collected and analyzed. Ocular GVHD can affect all the structures of the entire ocular surface system, including lacrimal and meibomian glands, cornea, conjunctiva, eyelids, nasolacrimal duct, and tears. Current medical treatment is mainly focused on lubrication and control of drainage, tear evaporation, and ocular surface inflammation. Surgical treatment may be necessary in severe, recalcitrant, or complicated cases. Amniotic membrane and tectonic keratoplasty can be valid options to restore the integrity of the cornea. Recently, conjunctival and limbal transplantation from the same living-related bone marrow donor has been proposed to manage both dry eye and limbal stem cell deficiency, without any risk of immunologic rejection.
This review provides an up-to-date analysis on clinical findings and current and future management of ocular GVHD. A correct and prompt diagnosis along with an appropriate and aggressive treatment are fundamental for avoiding the occurrence of vision-threatening complications.
#2 Ocular instillation of vitamin A-coupled liposomes containing HSP47 siRNA ameliorates dry eye syndrome in chronic GVHD.
Ohigashi et al, Blood Advances, April 2019
Interesting-sounding new eye drop developed specifically for ocular GvHD.
Chronic graft-versus-host disease (GVHD) profoundly affects the quality of life of long-term survivors of allogeneic hematopoietic stem cell transplantation (SCT). The eyes are frequently involved, and dry eye syndrome is the most common manifestation of ocular chronic GVHD. We explored the role of heat shock protein 47 (HSP47) in ocular GVHD and developed a novel antifibrotic topical therapy using vitamin A-coupled liposomes containing HSP47 small interfering RNA (siRNA) against HSP47 (VA-lip HSP47). In a mouse model of chronic GVHD, infiltration of HSP47+ fibroblasts and massive fibrosis surrounding the lacrimal ducts were observed after allogeneic SCT, leading to impaired tear secretion. After ocular instillation, VA-lip HSP47 was distributed to the lacrimal glands, knocked down HSP47 expression in fibroblasts, reduced collagen deposition, and restored tear secretion after allogeneic SCT. Ocular instillation of VA-lip HSP47 also ameliorated established lacrimal gland fibrosis and dry eye syndrome. VA-lip HSP47 eye drops are a promising prophylactic and therapeutic option against dry eye syndrome in chronic GVHD.
#3 Comparison of the meibomian gland dysfunction in patients with chronic ocular graft-versus-host disease and Sjögren's syndrome.
Choi et al, International Journal of Ophthalmology, March 2019
Unfortunately it seems GvHD patients may generally have it worse as regards MGD than other dry eye disease patients, in some ways at least. That makes the current plethora of emerging meibomian gland treatments just that much more important.
To investigate the abnormalities in the meibomian gland in patients with dry eye disease (DED) associated with chronic ocular graft-versus-host disease (coGVHD) in comparison with Sjögren's syndrome (SS), a major form of aqueous deficient DED and meibomian gland dysfunction (MGD), a common cause of evaporative DED.
A total 135 eyes of 135 subjects included in this study: patients with DED associated with coGVHD (n=30), patients with SS (n=35), patients with MGD (n=35), and normal controls (n=35). All participants completed the Ocular Surface Disease Index (OSDI) questionnaire, ocular surface examination [Schirmer test, tear film breakup time (TFBUT), and ocular surface staining], and meibomian gland assessment [meiboscore (gland dropout detected on meibography using infrared camera of the Keratograph 5M), meibum expressibility score (MES), meibum quality score (MQS), lid margin abnormality]. In addition, correlations of meibomian gland characteristics with ocular surface parameters as well as disease severity score were investigated in coGVHD group.
The coGVHD group showed significantly higher meiboscore, MES, and MQS than the other 3 groups (all P<0.05). In the coGVHD group, parameters of meibomian gland showed a significant correlation each other and those of ocular surface. The correlation between meibomian gland parameters and severity score of coGVHD was also established (meiboscore, r=0.62; MES, r=0.47; MQS, r=0.47; lid margin abnormality score, r=0.55; all P<0.05).
Patients with DED associated with coGVHD show poorer gland morphology and worse gland function than other types of DED. In addition, meibomian gland damage is not only associated with ocular surface damage but also disease severity of coGVHD.