Ocular cGVHD Research Articles

Ruxolitinib As Sparing Agent for Steroid-Dependent Chronic Graft-Versus-Host Disease (cGVHD)

Ruxolitinib (RUX) is an oral selective Janus-associated kinase 1 (JAK1) and JAK2 inhibitor that is approved by the FDA for the treatment of patients with myeloproliferative neoplasms. JAKs transmit the signaling of ligand binding to inflammatory cytokine receptors into intracellular responses, and inhibition of JAK is effective in the treatment of autoimmune disorders. In MHC-mismatched mouse transplant models, pharmacologic inhibition of IFNγR signaling with RUX reduced graft-versus-host disease (GVHD) and improved survival (Choi et al Blood 2012); and preliminary reports have shown that 13/14 patients with steroid-refractory acute (10) and chronic (4) GVHD responded to RUX therapy. (Sporell et al Blood 2014). Between 09/2014 and 7/2015, 16 patients (12M/4F), with hematological malignancies and recipients of unrelated donor (14), matched sibling (2) blood (15) or marrow (1) transplant developed quiescent (12) or de novo (4) severe (NIH criteria) steroid-dependent cGVHD and received RUX as 2nd (4), 3d (7) 4th (4) or 5th (1) line salvage. 12 had prior grades 1 (3) 2 (6) 3(2) or 4 (1) acute GVHD that affected the skin (12) and gastrointestinal system (GI, 5). Median time of onset of cGVHD was d+130 (range, 90-299), and affected skin (16) eyes (12), mouth (10), GI (8), lungs (4), liver (3) and the musculoskeletal system (3). cGVHD was steroid dependent with recurrences of cGVHD symptoms with steroid tapers that were attempted a median of 4 times(range, 2-10). Median duration of continuous exposure to steroids for cGVHD was 24 months (range, 6-53). RUX was administered at the dose of 5 mg BID. Median weight was 82 kg (range, 56-158). RUX dose was increased to 15 mg/d (4) or 20 mg/d (3) due to physician preference (4), patient weight (1), or flare of cGVHD after initial response due to discontinuation of immunosuppression (1) or temporary perioperative hold of RUX (1). Median duration of RUX therapy was 6 months (range 1-14). All patients were evaluable for response. Complete resolution of clinical manifestations of cGVHD was observed in the following organs: lungs (dyspnea/O2 dependence), mouth (oral ulcerations), skin (non-sclerodermatous erythema), liver (sGOT, sGPT, alkaline phosphatase), musculoskeletal and GI (dysphagia, diarrhea). Subjective improvement was reported in sclerodermatous and ocular cGVHD. Responses were observed early after initiation of RUX (median 14 days). Prednisone was successfully reduced to physiologic doses (n=2) or discontinued (n=10) in 12 (75%), and taper is currently in progress for the 4 patients who started RUX in the past 8 weeks. Median time from initiation of RUX to prednisone discontinuation was 72 days (range, 31-120). With a median follow-up of 4 months (range, 1-12) from prednisone discontinuation/reduction to physiologic doses, 2 patients experienced a transient flare of cGVHD symptoms associated with discontinuation of immunosuppression (1) and temporary hold of RUX. None of the other patients required a restart of prednisone or increased immunosuppression. We conclude that RUX is an effective steroid-sparing agent in steroid-dependent severe cGVHD. Validation of these results in prospective trials is needed. DisclosuresJillella:Seattle Genetics, Inc.: Research Funding.

Ocular Chronic Graft Versus Host Disease after Bone Marrow Transplantation

PurposeAllogeneic bone marrow transplantation (BMT) is a curative therapy for a number of hematological diseases. Ocular chronic graft versus host disease (cGVHD) is a major contributor to long‐term morbidity after BMT. The purpose of this study was to report the frequency of ocular cGVHD after BMT and onset in relation to systemic cGVHD.MethodsRetrospective examination of medical records of patients who underwent consecutive allogeneic BMT from 1980‐2011 at Copenhagen University Hospital (Rigshospitalet). This study included adults (>16 years) with no dry eye disease prior to BMT. The patients were seen by an ophthalmologist before BMT and annually after BMT. The ophthalmological examination included tear break‐up time, Schirmers test, corneal fluorescein stain, slit lamp examination and ophthalmoscopy. The criteria proposed by the “International Chronic Ocular GVHD Consensus Group” was used to diagnose ocular cGVHD.ResultsOut of the 939 patients included, 222 patients (23.6%) developed ocular cGVHD. We found no significant difference between gender and the development of ocular GVHD (p = 0.67). Median age at time of BMT was 41 years (rage 16–73) and 46 years (17–68) in the group who developed ocular cGVHD. Median time of onset of ocular cGVHD was 20 months (0.4–196) after BMT. Diagnosis of ocular cGVHD preceded systemic cGVHD in 33 cases (15%). Twenty‐seven patients (12%) had ocular cGVHD without systemic cGVHD. Ocular cGVHD was significantly higher in patients with systemic cGVHD involving the skin (p < 0.001).ConclusionsOcular cGVHD is common after BMT. It can occur at any age, but is more common in elder patients. Ocular cGVHD can occur in patients without systemic cGVHD. We recommend ophthalmological examinations in all patients before and after allogeneic BMT due to the high frequency of ocular cGVHD.

Use of Prosthetic Replacement of the Ocular Surface Ecosystem Scleral Lenses in Patients with Ocular Chronic Graft-versus-Host Disease.

The purpose of this study was to evaluate the impact of prosthetic replacement of the ocular surface ecosystem (BostonSight PROSE, Boston Foundation for Sight, Needham, MA) treatment, utilizing customized scleral devices, on visual acuity, visual function, and ocular surface changes in patients with ocular chronic graft-versus-host disease (cGVHD). A retrospective analysis was performed on 79 eyes of 40 patients with cGVHD referred to the University of Southern California department of ophthalmology between November 2009 and July 2013 for PROSE treatment. This analysis included an assessment of ocular symptoms and visual function before and after treatment using the Ocular Surface Disease Index (OSDI) survey. Pre- and post-treatment visual acuity and clinical data were also compared. Twenty-eight male patients and 12 female patients were included in this study. The average age was 56.1 years (range, 27 to 74). Of the 79 eyes treated, 71 (90%) showed improved visual acuity with PROSE treatment. Fifty-seven eyes (72%) experienced a 2- or greater line visual acuity improvement and 14 eyes (18%) experienced a 1-line improvement. Average logarithm of the minimal angle of resolution improved from .49 ± .52 to .16 ± .44 (P < .0001), which correlates to a Snellen score improvement of approximately 20/60 to 20/30. Sixty-six of 79 eyes (84%) showed decreased corneal staining after treatment. All 9 eyes presenting with filamentary keratitis and 3 eyes with epithelial defects demonstrated complete healing of the epithelial surface after PROSE fitting. At post-treatment follow-up, 8 patients had died and 3 stopped wearing their devices. Of the remaining 29 patients, average OSDI scores improved from 72.6 ± 20.1 to 21.1 ± 14.9 (P < .0001). PROSE therapy, utilizing customized scleral lenses, can reduce ocular symptoms, improve visual acuity, and improve ocular surface integrity or appearance in patients with ocular cGVHD.

Tear osmolarity in ocular graft-versus-host disease.

The aim of this study was to evaluate tear osmolarity in patients with chronic graft-versus-host disease (cGVHD) with ocular involvement. In this observational cross-sectional study of 56 patients with ocular cGVHD referred to the tertiary-care Ocular Immunology and Uveitis Service at the San Raffaele Scientific Institute, Milan, from May 2010 to November 2013, we evaluated the following clinical parameters: Ocular Surface Disease Index (OSDI) symptoms questionnaire, tear osmolarity, Schirmer test, tear film break-up time (TBUT), corneal and conjunctival staining. All patients developed systemic GVHD after undergoing allogeneic hematologic stem cell transplantation. Mean osmolarity was 314.0 ± 22.1 mOsm/L, mean OSDI score was 26.4 ± 21.2, mean TBUT was 6.50 ± 4.75 seconds, and mean Schirmer test value was 3.8 ± 3.3 mm. Tear osmolarity significantly inversely correlated with TBUT (r = 0.681; P < 0.001). Statistically significant inverse correlation was present with the Schirmer test (r = 0.203; P < 0.001), and positive correlation with the OSDI score (r = 0.188; P < 0.001), but both with low correlation strength. Osmolarity was statistically different in the subgroups according to the Oxford corneal staining scale (P = 0.0006) and to the van Bijsterveld conjunctival staining score (P = 0.006). Tear osmolarity increased in patients with ocular cGVHD, significantly correlated with TBUT and, to a lesser extent, with the Schirmer test value and OSDI. These results emphasize the role of aqueous-deficient and evaporative dry eye disease in patients with cGVHD after undergoing allogeneic hematologic stem cell transplantation. Tear osmolarity may be considered a useful test in diagnostic assessment of dry eye disease associated with cGVHD.

Ocular chronic graft versus host disease after allogeneic hematopoietic stem cell transplantation – preliminary data

AbstractPurpose Allogeneic hematopoietic stem cell transplantation(HSCT) is a curative therapy for a number of malignant and non‐malignant hematological diseases. Allogeneic HSCT can be performed in several ways; donor cells can be obtained from bone marrow(BMT), peripheral blood(PBSCT) or cord blood(CBT). Ocular chronic graft versus host disease(cGVHD) is a major contributor to long‐term morbidity after HSCT. The purpose of this study was to report the frequency of ocular cGVHD after allogeneic HSCT.Methods Retrospective examination of 233 charts of patients (adults&gt;15years) who underwent consecutive allogeneic HSCT from January 2000‐june 2011 at Copenhagen University Hospital (Rigshospitalet). All allogeneic HSCT in Denmark are performed at this hospital. All patients were examined ophthalmologically before the transplant, yearly after the transplant and ad hoc if any ophthalmic problems occurred. The diagnosis of ocular cGVHD was made according to the NIH consensus criteria.Results Fifty‐eight(25.3%) fulfilled the diagnostic criteria of ocular cGVHD, 16 out of 78(20.5%) in the BMT group, 41 out of 152(27.0%) in the PBSCT group and 1 out of 3(33.3%) in the CBT group. Male:female ratio was 40:18(2.22) (in the cohort 146:87(1.68)). Median time of onset was 24.3 months after HSCT(range 4.9‐146.1). In the cohort median age was 45.2 years(rage 15.2‐71) at transplantation time and 55.5 years(18.43‐69.0) when ocular cGVHD was diagnosed. Median time of follow‐up was 24.8 months(range 0.4‐147.6).Conclusion Out of 233 patients who received allogeneic HSCT, 59(25.3%) developed ocular cGVHD. The median time of onset was 24.3months after transplantation and median age at onset was 55.5 years.

In vivo confocal microscopic characterisation of the cornea in chronic graft-versus-host disease related severe dry eye disease

AimsTo first describe in vivo confocal microscopic (IVCM) corneal findings in severe dry eye syndrome due to ocular chronic graft versus host disease (cGvHD) after allogeneic stem cell transplantation.MethodsIVCM of...

Diagnosis and Treatment of Ocular Chronic Graft-Versus-Host Disease: Report From the German–Austrian–Swiss Consensus Conference on Clinical Practice in Chronic GVHD

Ocular chronic graft-versus-host disease (cGVHD) is one of the most frequent long-term complications after hematopoietic stem cell transplantation and is often associated with significant morbidity and reduced quality of life. The German/Austrian/Swiss Consensus Conference on Clinical Practice in cGVHD aimed to summarize the currently available evidence for diagnosis and (topical) treatment and to summarize different treatment modalities of ocular cGVHD. The presented consensus was based on a review of published evidence and a survey on the current clinical practice including transplant centers from Germany, Austria, and Switzerland. Ocular cGVHD often affects the lacrimal glands, the conjunctiva, the lids (including meibomian glands), and the cornea but can also involve other parts of the eye such as the sclera. Up to now, there have been no pathognomonic diagnostic features identified. The main therapeutic aim in the management of ocular cGVHD is the treatment of inflammation and dryness to relieve patients' symptoms and to maintain ocular integrity and function. Therapy should be chosen in the context of the patient's overall condition, systemic immunosuppressive therapy, symptoms, ocular surface integrity, and inflammatory activity. The consensus conference proposed new grading criteria and diagnostic recommendations for general monitoring of patients with graft-versus-host-disease for use in clinical practice. The evidence levels for diagnosis and treatment of ocular cGVHD are low, and most of the treatment options are based on empirical knowledge. Topical immunosuppression, for example, with cyclosporine, represents a promising strategy to reduce inflammation and dryness in ocular cGVHD. Further clinical trials are necessary to elucidate risk factors for eye manifestation, complications, and visual loss and to evaluate staging criteria and diagnostic and therapeutic measures for ocular cGVHD.

Nonpharmacologic Treatment of Chronic Graft-versus-Host Disease in Children and Adolescents

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many children with life-threatening diseases. One of the most significant long-term complications of transplantation is chronic graft-versus-host disease (cGVHD). Although the rates of cGVHD after HSCT are lower in the pediatric population than in adults, cGVHD remains a significant cause of morbidity and mortality. Medicines used to prevent and treat cGVHD remain unsatisfactory, with protracted use of immune suppression necessary and high rates of first-line treatment failure. Efforts to improve salvage treatment are urgently required. Nonpharmacologic strategies attempt to modulate the cellular inflammation response and possibly allow reduction or cessation of immunosuppressive drugs. Mesenchymal stromal cells (MSC) have been shown invitro to mediate a wide variety of immune responses. MSC have been used in the prophylaxis of acute GVHD (aGVHD) and for the treatment of established steroid refractory aGVHD and, more recently, in the management of cGVHD. Extracorporeal photochemotherapy (ECP) has shown promising efficacy in graft-versus-host disease, and may allow a significant reduction in the use of systemic steroids and other immunosuppressants, reducing long-term morbidity and mortality. The accumulated experience shows ECP to be well tolerated, with no clinically significant side effects.

Long-term oral complications of allogeneic haematopoietic SCT

This study assessed the incidence of long-term oral complications in 88 survivors of allogeneic haematopoietic cell transplantation (HCT). Patients examined were between 6 months and 6 years post-HCT and aged from 19 to 65 years. Subjects were investigated for both the subjective and objective features of long-term adverse oral effects of HCT. The most common oral symptoms reported were xerostomia (44%, n=39) and reduction in taste (20%, n=18). Only a minority of patients (15%) reported that oral disease had a significant adverse impact upon their quality of life. The majority of patients (53%) had clinical markers of oral chronic GVHD (cGVHD). The most frequently identified feature was salivary hypofunction, with 34% of subjects demonstrating a reduction in stimulated saliva. Oral mucosal changes consistent with cGVHD affected 21% of subjects. Oral cGVHD commonly occurs after allogeneic HCT, often coexists with cutaneous, hepatic or ocular cGVHD and may lead to debilitating symptoms. Transplant type and pre-existing acute GVHD are the major risk factors for oral cGVHD. The identification of risk factors specific for oral cGVHD may allow clinicians some foresight into identifying patients at high risk of developing oral cGVHD and encourage attention to education, regular oral surveillance and rigorous preventative oral health strategies both pre- and post-transplant.

Ocular Involvement in Chronic Graft-Versus-Host Disease: Therapeutic Approaches to Complicated Courses

Chronic graft-versus-host disease (cGvHD) is a major concomitant phenomenon in recipients of allogeneic hematopoietic stem cell transplantations, affecting multiple organ systems including the eye. Ocular structures, such as lacrimal gland, conjunctiva, and eyelids with meibomian glands, are frequently involved with clinical features ranging from dry eyes and common inflammatory conjunctival disease to severe complications like corneal ulcerations or even perforations. We present 2 patients with complicated courses of ocular cGvHD. In both cases, keratoconjunctivitis sicca refractory to systemic immunosuppressive therapy and to conventional topical treatment resulted in progressive binocular corneal melting and finally repeated perforations. According to our 2 cases and to the current pathophysiological understanding, we discuss possible strategies for the treatment and prevention of ocular cGvHD complications.

Immune Processes and Pathogenic Fibrosis in Ocular Chronic Graft-Versus-Host Disease and Clinical Manifestations after Allogeneic Hematopoietic Stem Cell Transplantation

Activation of the immune system and progressive fibrosis are prominent features of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation. The main histologic findings in affected exocrine glands are marked fibrosis of the interstitium and prominent increase in the number of fibroblasts, accompanied by mild lymphocytic infiltration. Clinically, the severity of dry eye is correlated with the degree of fibrotic changes, rather than with the amount of lymphocytic infiltration, indicating that excessive extracellular matrix accumulation primarily contributes to the exocrine dysfunction. We have found that accumulated fibroblasts in the lacrimal gland of patients with cGVHD have a chimeric status. Thus, fibroblasts originating from circulating donor-derived precursors and recipient-derived fibroblasts by local epithelial mesenchymal transition may participate in the excessive fibrosis in patients with cGVHD by interacting with T cells. In this article, the immune response and pathogenic fibrosis in ocular cGVHD will be discussed. In addition, clinical findings of ocular complications after hematopoietic stem cell transplantation and currently available treatment will also be discussed.

Epithelial Mesenchymal Transition in Human Ocular Chronic Graft-Versus-Host Disease

Chronic graft-versus-host disease (cGVHD) of the ocular surface and lacrimal gland is a vision-threatening condition that occurs after allogeneic bone marrow transplantation. In this study, we used immunohistochemistry and electron microscopy to investigate whether epithelial mesenchymal transition (EMT) contributed to the pathogenesis of ocular cGVHD. We detected down-regulation of E-cadherin and translocation of beta-catenin from the intercellular junction to the cytoplasm and nucleus of cGVHD conjunctival basal epithelia and lacrimal gland myoepithelia. Notable findings included expression of Snail, an inducer of EMT, in the nucleus of ocular cGVHD epithelia. The fibrosis markers heat shock protein 47, alpha-smooth muscle actin, and fibroblast specific protein-1 were overexpressed in ocular cGVHD epithelia. In addition, p63, a marker of conjunctival basal epithelia, was observed in the nuclei of subconjunctival cells beneath disrupted basal lamina. Disrupted basal lamina and the presence of altered collagen bundles were observed in the cytoplasm and beneath cGVHD epithelia. In contrast, these observations were rarely observed in the normal conjunctiva and in Sjögren's syndrome lacrimal gland epithelia. These findings together indicate that ocular cGVHD epithelia gain the mesenchymal phenotype and the capacity to migrate into the subepithelial stroma. Our findings suggest that EMT may be partially responsible for the conjunctival and lacrimal gland fibrosis found in patients with cGVHD.

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

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 factor-beta-induced matrix production. We conducted a non-randomized 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 (P<0.05). 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 (P<0.05). These results suggest the hypothesis that topical tranilast may effectively retard the progression of mild dry eye associated with cGVHD.

Late Onset Eosinophilia (beyond Day 100), Rather Than Early Onset Eosinophilia, Has a Significant Prognostic Impact on Transplant Outcomes after Allogeneic Peripheral Blood Stem Cell Transplantation (PBSCT).

Background: The significance of eosinophilia after allogeneic stem cell transplantation (SCT) is presently unknown. The eosinophil activation pathway involves Th2 cytokines and thus eosinophilia after PBSCT may reflect Th2 pathway activation. Previous data suggest that blood eosinophilia precedes or coincides with the development of acute or chronic graft-verus-host disease (aGVHD or cGVHD). In a recent report, Aisa et al reported that patients with peripheral eosinophilia within 100 days post-SCT had a superior overall survival (OS) and transplant-related mortality (TRM) along with a lower incidence of cGVHD compared to those who did not (Transplant Int 2007). Methods: A retrospective analysis of 237 recipients who received allogeneic PBSC from related donors at PMH was performed (myeloablative:reduced intensity conditioning 162:75). The present study evaluated the impact of early (before day 100: EEo) or late onset (beyond day 100: LEo) eosinophilia (≥0.5x109/L in peripheral blood) on transplant outcomes after allogeneic PBSCT. The patient population included 237 recipients of allogeneic PBSC from related donors (male:female 137:100, median age 51 years-old). Results: Biphasic pattern of eosinophilia with 2 peaks before day 100 and beyond day 100 was observed after PBSCT. The cumulative incidence of early onset eosinophilia was 43% at day 100. EEo was not associated with the development of grade 3–4 aGVHD (p=0.1), but there was a trend in the development of grade 2–4 aGVHD (p=0.053). In univariate analyses, the group with EEo showed favorable OS (p=0.002), TRM (p=0.05) and a lower relapse incidence (p=0.05) compared to those without EEo but did not have improved GVHD-specific survival (GSS). EEo did not predict the grade of aGVHD or response to steroid therapy for aGVHD. EEo was significantly associated with the development of late onset eosinophilia (p=0.000004 by chi-square test, p=0.00007 by McNemar test). The cumulative incidence of LEo was 62% at 2 years with median onset of 1 year after SCT. There was an association with the onset of cutaneous (p=0.001), oral (p=0.04), ocular (p=0.02) or pulmonary cGVHD (p=0.03). In univariate analyses, with median follow-up durations of 773 days (patients with LEo) and 679 days (patients without LEo), significant differences were observed in favor of those with LEo in terms of 3 year OS (86% vs 41%, p=0.00000000005), TRM at 3 years (10% vs 37%, p=0.000003), 3 year relapse rate (11% vs 31%, p=0.00003) and 3-year GSS (90% vs 64%, p=0.00001). In multivariate analyses, the LEo, rather than EEo, was identified as a significant favorable prognostic factor for OS (p=0.000006, hazard ratio [HR] 0.21), TRM (p=0.0006, HR 0.24), relapse incidence (p=0.003, HR 0.28) and GSS (p=0.001, HR 0.26). Conclusion: The late onset eosinophilia (beyond day 100), not EEo, seemed to have an important prognostic implication for outcome after allogeneic PBSCT. Further studies are warranted to validate its prognostic impact on SCT outcomes. Figure 1. Comparisonof overall survival (A) and GVHD-specific survival (B) between patients with and without late onset eosinophilia after allogeneic PBSCT Figure 1. Comparisonof overall survival (A) and GVHD-specific survival (B) between patients with and without late onset eosinophilia after allogeneic PBSCT

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. Results: Among the 119 recipients, SLPO was diagnosed in 8. All the patients with SLPO after HSCT had meibomian gland dysfunction (MGD), dry eye, and systemic cGVHD. The percentage of patients with dry eye, MGD, and systemic cGVHD were significantly higher in recipients with SLPO than non-SLPO recipients (p < 0.0013, p < 0.00015, p < 0.0008, respectively). Conclusions: SLPO is a clinical presentation of ocular cGVHD and may be an indicator of the severity of dry eye and systemic cGVHD after HSCT.

Use of Fluid-Ventilated, Gas-Permeable Scleral Lens (SL) for Management of Severe Keratoconjunctivitis Sicca Secondary to Chronic Graft-Versus-Host Disease.

Dry eyes or keratoconjunctivitis sicca (KCS) occur in 50 % of patients (pts) with chronic graft-versus-host-disease (cGVHD) after allogeneic hematopoietic cell transplantation (HCT) and may represent the only, or most significant, clinical manifestation of cGVHD in some pts. Artificial tears, long-acting ocular lubricants, punctal plugs, ophthalmic cyclosporine, topical corticosteroids, moisture chamber eyewear and oral cholinergic agents are the primary supportive therapies of ocular cGVHD. The liquid corneal bandage provided by a fluid-ventilated, gas-permeable scleral lens (Boston Scleral Lens, BSL) has been effective in mitigating symptoms and resurfacing corneal erosions in pts with a variety of causes of KCS refractory to conventional therapies. Here we report outcomes in 9 pts with cGVHD after related and unrelated HCT who had severe KCS treated by fitting a BSL because of debilitating ocular discomfort, visual impairment, or keratopathy despite systemic and local therapies and other supportive care. Diagnoses at time of HCT were CML (n=3), MDS (n=2), AML (n=1), AA (n=1), CLL (n=1) and MM (n=1). Median pt age at the time of SL fitting was 56 (range, 25–64) yrs. All pts had prior cGVHD involving multiple sites that required immunosuppression therapy (IS) with prednisone, +/− calcineurin inhibitors, +/− mycophenolate mofetil or other therapies. Manifestation of cGVHD other than eyes at the time of SL fitting were skin (n=2), mouth (n=5), liver (n=3), GI (n=1), lungs (n=1) and vagina (n=1). At the time of SL, 7 pts were receiving IS and 2 pts had discontinued all IS because of resolution of other manifestation of cGVHD. The response to the SL was assessed by patient-reported ocular disability and use of ancillary eye care, and by use of the Ocular Surface Disease Index (OSDI) in 5 pts. The OSDI is a valid and reliable tool used to assess severity of dry eye symptoms and vision-related function on a 0–100 scale, with higher scores correlating with increasing symptom severity and vision-related disability. Table below presents patients-reported outcomes. The use of the BSL led to ocular improvement in all cases. No serious adverse events or infections attributable to the BSL occurred. The median OSDI available improved from 87.7 to 20.8 within 2 weeks of BSL fitting and was 12.5 (4.2–52.7) at the time of last contact, 8–23 months (median, 15.2) after BSL fitting. Seven pts were no longer disabled by KCS after the BSL. All 9 pts reported reduced use of artificial tears, and 2 of 3 who were using moisture chamber eye glasses pre BSL were able to discontinue them. One pt had significant difficulty inserting the BSL, even with assistance. We conclude that BSL can be a safe and effective procedure for pts suffering from severe cGVHD-related KCS that is refractory to other therapies.No. of Patients9Artificial Tear Use (Times per day, N)- Before fitting Scleral Lens (SL)> 100- After fitting SL (median, range)3 (0–50)Punctal Plugs (times replaced, N)- Before fitting SL (median, range)3 (1–>6)- After fitting SL1 (1 pt)Subjective Assessment of Disability- Before fitting SLYes (7 pts)- After fitting SLYes (1 pt)