The Comparison of 50 % Concentration Autologous Serum Eye Drops Versus Preservative Free Artificial Eye Drop Plus 0.05 % Cyclosporin Ophthalmic Emulsion in the Treatment of Severe Dry Eye Syndrome: A Randomized Comparative Study
Phase: PHASE4
Conditions: Dry Eye Syndrome
Sponsor: Seref istek

This study is a prospective observational study. This clinical study compared the treatment 
effect of 50% diluted AS eye drops 8 times a day, as compared to conventional  PFAT 8 times 
a day plus 0.05 % COE  2 times a day  in patients with severe DES based on ocular surface 
disease index (OSDI), Oxford scale, TBUT, schirmer’s test score.  OSDI score more than 40 
and Schirmer’s test without anesthesia below 10 mm / 5 minutes were accepted as severe DES 
in our study. Informed consent was obtained from each patient in the study. The Erciyes 
University School of Medicine Institutional Review Board approved the study protocol, 
which adhered to the guidelines of the Declaration of Helsinki. The patients enrolled in the 
study all had dry eye whose schirmer’s test scores were below 5mm/5 minute. The Schirmer’s 
test I (without anaesthesia) was graded in millimetres after 5 min.(13) 18 patients had 50% 
diluted AS eye drops 8 times a day, the other 18 patients had conventional  PFAT(polivynil 
alcohol- povidone) 8 times a day plus 0.05 % COE (Restasis; Allergan, Inc., Irvine, CA) 2 
times a day. 36 patients (totally 72 eyes) with severe dry eye syndrome were refractory to 
conventional treatment (those that did not respond well to entire dry eye medications 
containing hydroxypropyl methylellulose, carboxyl methylcellulose, polyvinyl alcohol, 
polyethylene glycol-propylene glycol, sodium hyaluronate, mineral oil, dextran, and carbomer 
artificial tears with or without preservatives), had low TBUT (< 5 s) (5μL of fluorescein 
sodium 2% eye drops was used), low Schirmer’s test I score without topical anesthesia ( 
basic+reflex secretion), positive corneal and conjunctival fluorescein staining (≥grade 1 
according to the   OXFORD Scale) (3) and an OSDI score > 40 OSDI was a reliable and valid 
test for quantifying the severity of dry eye symptoms.(14) Patients  with an active ocular 
infection or any other inflammation not associated with dry eye, a severe associated ocular 
allergy, eyelid or eyelash abnormality, current contact lens use, history of refractive surgery, 
associated glaucoma, and current use of any type of topical eye drops other than dry eye 
medications, any known graft-versus host disease, known severe anemia (hemoglobin<11 

g/dL-1), and medically uncontrolled significant cerebrovascular and cardiovascular disease, 
pregnant and lactating patients were excluded. 
After informed consent was obtained, 15 mL venous whole-blood samples were drawn once 
from each patient at the beginning of the study for AS preparation. We followed the methods 
of Çelebi et al.(15) Serum drops were produced as a 50% formulation. After venosection 
blood in sterile container centrifuged at 4000 rpm for 10 minutes, serum was taken from the 
biochemistry blood tube and 50% formulation of AS was prepared in 50% concentration by 
mixing sterile isotonic 0.9% NaCl solution in the eye drop container. 50% diluted AS using 
patients were told to keep the AS drops at 4 °C in refrigerator. All the patients were instructed 
to use 8 drops a day time (1 drop every 2 h in awaken times) in each eye. The designation of 
the patient whether to use AS 8*1 or conventional PFAT 8*1 plus COE 2*1 was determined 
randomly. The beneficial effects of two therapeutic regimes were explained and the patient 
chose the treatment. The study data were collected and statistical analyzes were done after the 
enough number of participants were reached. OSDI, TBUT, Schirmer’s test I, and OXFORD 
scales were administered before and after first month. Statistical analyses were performed 
using SPSS version 15.0 for Windows Evaluation Version release (SPSS, Inc. , Chicago, IL). 
Descriptive statistics were presented as mean ± SD for the variables (OSDI score, Schirmer’s 
Test I and TBUT),  and as median with interquartile range (IQR) for the ordinal variable 
(OXFORD Scale). All the variables were normally distributed except Oxford scales data 
(Kolmogorov-Smirnov and Shapiro-Wilk tests). Student’s paired samples t-test and 
independent samples Student’s t-test were used to compare data. The Wilcoxon signed-rank 
test was used to compare the change in OXFORD scale scores. The Mann–Whitney U test 
was used to compare OXFORD scale scores between AS and PFAT+COE. All analyses were 
performed with a power of 80 % and 95 % CI. The level of statistical significance was set at 
p<0.05.