Topical tranilast for treatment of the early stage of mild dry eye associated with chronic GVHD

Abstract

Fibrosis and excessive extracellular matrix production are characteristic features of lacrimal gland chronic GVHD (cGVHD). Tranilast (n-[3,4-anthoranilic acid]), used for fibrotic skin disease, inhibits transforming growth factorb-induced matrix production. We conducted a nonrandomized study comparing 8 patients (five men, three women; median age, 47 years) given topical tranilast with 10 patients (three men, seven women; median age, 37 years) receiving therapy with topical artificial tears, sodium hyaluronate and vitamin A for mild ocular cGVHD. The tranilast group instilled topical tranilast and artificial tears q.i.d., beginning the day of dry eye diagnosis. The ocular surface and tear dynamics of each patient were evaluated before hematopoietic stem cell transplant, at the onset of dry eye and after 3 months of treatment. At 3 months, the scores of the Rose Bengal test and Schirmer test with nasal stimulation had significantly improved in the tranilast group compared with that in the control group (Po0.05). Furthermore, although five control patients (50%) developed severe dry eye within the treatment period, only one tranilast-treated patient (12.5%) did; the rest still had mild dry eye (Po0.05). These results suggest the hypothesis that topical tranilast may effectively retard the progression of mild dry eye associated with cGVHD.

Tear physiology in dry eye associated with chronic GVHD

“…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.…”

Allogeneic Serum Eye Drops for the Treatment of Dry Eye Patients with Chronic Graft-Versus-Host Disease

“…[27][28][29] Clinical data are currently insufficient for evaluating the efficacy and safety of topical tacrolimus and tranilast, and these drugs are generally not easy to use for ophthalmologists. 30,31 Growth factors, vitamins, and neuropeptides secreted from lacrimal glands support the proliferation, migration, and differentiation of the ocular surface epithelia. As part of inflammatory processes, additional proteins, including the adhesion factor fibronectin, complement factors, and antimicrobial proteins are secreted from conjunctival vessels.…”

Evidence For Dry Eye Treatment In Hematopoietic Stem Cells Post-Transplantation

“…Moreover, the topic Tranilast® can act in preventing fibrosis of the surface around the holes of the tear ducts near the exterior ocular surface, where the intact acini of the lacrimal gland are present in the light phase of dry eye. Therefore, this therapy is effective in the initial stage of the dry eye [6].…”

“…One of the main complications of GVHD chronic phase is the dry eye syndrome, characterized by a multifactorial disease of the ocular surface that results in discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface resulting mucin dysfunction [5] of immunemediated inflammation and fibrosis [6].…”