ORIGINAL ARTICLE Long-term safety and efficacy of autologous platelet lysate drops for treatment of ocular GvHD S Pezzotta 1 , C Del Fante 2 , L Scudeller 3 , GC Rossi 1 , C Perotti 2 , PE Bianchi 1 and E Antoniazzi 1 Current ocular GvHD (oGvHD) treatments are suboptimal. We investigated the safety and efficacy of long-term continuous treatment with autologous platelet lysate (PL) drops in patients with oGvHD Dry Eye Syndrome (DES) score 2–3 refractory to topical conventional therapy. Ophthalmic evaluation was performed at 6 month intervals. Symptoms were assessed using the Glaucoma Symptom Scale (GSS). Patients were defined 'responders' when showing a reduction at least one grade on National Institutes of Health Eye Score from baseline at the 6 month visit. Thirty-one patients were included, and 16 (51%) completed 36 months of follow-up (range 6.5–72.7). At 6 months all patients were classified as responders: median GSS symptom score decreased from 70 to 41 (33 at 36 months), median GSS function score reduced from 68 to 46 (33 at 36 months) (all P o0.001). Median Tear Break Up Time improved from 3 to 6 s after 6 months and was maintained over time. All signs improved at 6 and 36 months (clinical and statistical significance). No severe adverse events occurred. Long-term treatment with PL drops is secure and effective for oGvHD and can be an efficient therapy option from initial stages of oGvHD to prevent permanent ocular impairment and improving quality of life. Bone Marrow Transplantation (2017) 52, 101–106; doi:10.1038/bmt.2016.221; published online 5 September 2016 INTRODUCTION Ocular (oGvHD) occurs in 60% of HSCT recipients 1 and it is strongly associated with extensive chronic GvHD (cGvHD) (60–90%). 2 Clinical manifestations of oGvHD are diverse, and can affect conjunctiva, lacrimal gland, cornea, lid and vitreous. The most frequent ocular manifestation of GvHD is Dry Eye Syndrome (DES), observed in 69–77% of patients with chronic systemic GvHD and characterized by keratoconjunctivitis sicca, conjunctival inflammation and chronic blepharitis. 3 Though not life-threatening, oGvHD DES can greatly hinder patients’ quality of life and may be visually debilitating. 1 According to National Institutes of Health (NIH) guidelines revised in 2014, DES is classified with a range from 0 (‘no symptoms‘) to 3 (‘severe dry eye symptoms significantly affecting daily living (special eyeware to relieve pain) or unable to work because of ocular symptoms or loss of vision due to keratoconjunctivitis sicca’). 4 DES can rapidly progress to severe irreversible complications with an increased risk of corneal ulceration and occasional perforation leading to a permanent visual loss. 5–7 Autologous serum (AS) eye drops were the first peripheral blood-derived products used in the treatment of corneal diseases (for example, Sjogren syndrome); 8 in AS, growth factors such as EGF (epidermal growth factor), PDGF and FGF (fibroblast growth factor) mediate the corneal tissue repair process. However, AS may contain proinflammatory agents derived by leukocyte degranula- tion, which may hamper ocular tissue regeneration. 9 Despite many advances in the therapy of oGvHD, safety and efficacy data in long-term treatment are lacking: to our knowl- edge, the longest follow-up reported in oGvHD patients is 1 year in a sample of 12 patients treated with topical tacrolimus ointment. 10 Recently, our group demonstrated the clinical efficacy and safety of autologous platelet lysate (PL) eye drops in patients with oGvHD refractory to treatment with conventional therapy with 80% of responders after 1 month of treatment and maintained for 6 months. 11 Based on our initial data, we designed the present study with the aim of evaluating the long-term continuous treatment with PL drops in patients affected by oGvHD refractory to conventional therapy. The main goal of our study was to evaluate the long-term safety and efficacy of a continuous treatment with PL eye drops in a sample of patients with moderate–severe oGvHD. MATERIALS AND METHODS This prospective cohort study was approved by our Ethics Committee and conducted at the teaching Hospital of Pavia from January 2011 to January 2015. All patients gave their written consent prior to inclusion, were enrolled between 2011 and 2013 and followed-up for up to 3 years. Patients Eligibility criteria were: ● Age ⩾ 18 years. ● cGvHD with oGvHD showing score 2 or 3 of NIH Organ Scoring of Chronic GvHD for eyes. 4 ● Refractory to treatment with preservative-free artificial tears for at least 3 months. ● Platelets in peripheral blood4120000/μL. ● No systemic infection in process (including HIV, hepatitis B virus, hepatitis C virus) at time of enrollment and PL eye drops preparation. ● No ophthalmic infections in process, retinal disease, ocular hypertension disease or other than DES (except cataract) at the time of recruitment. 1 Department of Ophthalmology, University Eye Clinic of Pavia, IRCCS Policlinico S Matteo Foundation, Pavia, Italy; 2 Immunohaematology and Transfusion Service, Apheresis Unit, IRCCS Policlinico S Matteo Foundation, Pavia, Italy and 3 Biostatistic and clinical epidemiology unit, Scientific Direction, IRCCS Policlinic San Matteo Foundation, Pavia, Italy. Correspondence: Dr S Pezzotta, Department of Ophthalmology, University Eye Clinic Fondazione IRCCS Policlinico San Matteo di Pavia, V.le Golgi 19, Pavia 27100, Italy. E-mail: sarapezzottaoculista@gmail.com Received 21 March 2016; revised 13 July 2016; accepted 18 July 2016; published online 5 September 2016 Bone Marrow Transplantation (2017) 52, 101 – 106 © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 0268-3369/17 www.nature.com/bmt