Comparison of Autologous Serum Versus Preservative Free Artificial Tear
Condition: Dry Eye
MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca
Study type: Interventional
Phase: Phase 4

Summary: 
      Dry eye is a significant adverse effect of isotretinoin causing patients to use ophthalmic
      medications. For this reason, many patients using isotretinoin are referred to ophthalmology
      clinic because of discomfort symptoms. In the literature, there are studies suggesting
      superiority of Autologous serum drops regarding effects on ocular surface when compared to
      artificial tear. In addition, Autologous serum was also used in several corneal pathologies
      with successful outcomes. No data regarding use in the ocular adverse effects of isotretinoin
      was found in the literature; however, investigators think that it may be an effective
      alternative in the treatment of dry eye developed during isotretinoin use due to positive
      effects on ocular surface, epithelial regeneration and anti-inflammatory effect. Autologous
      serum can be a choice of ophthalmologists in routine practice by increasing number of
      comprehensive studies investigating effectiveness, safety and long-terms effects of
      Autologous serum therapy.In this study, it was aimed to investigate dry eye development in
      the patients receiving systemic retinoic acid therapy and to compare effectiveness of
      Autologous serum and Preservative free artificial tear in the patients with dry eye disease.
    

Detailed description: 
      This prospective, cross-sectional, double blind study was conducted by Ophthalmology Clinic
      on patients who have drye eye due to systemic isotretinoin treatment for several reasons in
      Niğde State Hospital between October, 2015 and March 2016. Patients determined as having drye
      eye during systemic isotretinoin treatment were included to our study. At baseline, 1.and 2.
      month of study, detailed ocular examination, best corrected visual acuity measurement,
      intraocular pressure measurement, Tear Break-Up time(TBUT)(5 µL of fluorescein sodium 2 % eye
      drops was used per each measurement using a pipette for standardization, and the mean value
      of two readings per patient was recorded) and Schirmer Test I (ST I) without topical
      anesthesia were performed. Effect on daily life was assessed by using Ocular Surface Disease
      Index (OSDI) score. TBUT<10 seconds, ST I <10 mm without local anesthesia, corneal and
      conjunctival staining was interpreted in favor of dry eye. In the follow-up period,
      investigators investigated the efficacy of autologous serum eye drops for the patients having
      dry eye illness during isotretinoin treatment. After informed consent, peripheral venous
      blood (14-20 ml) was drawn from antecubital vein of patients to prepare AS. Blood sample was
      left at room temperature over 2 hours for clotting. Serum was obtained after centrifugation
      at 4000 revolutions per minute (rpm) for 10 minutes at 4 °C using a centrifugal device(Nuve
      NF1200R). Next, in a laminar flow cabinet under sterile conditions, approximately 10 mL of
      supernatant was collected and diluted to 40 % with isotonic (0.9 % NaCl) saline solution and
      then 25 mL of preparation was aliquoted into 1.5-mL Eppendorf vials, each of which was
      wrapped with aluminum foil by the other specialist(Erkut Küçük) for protection against
      ultraviolet light (to prevent vitamin A degradation), and blinding the patients to the
      treatment. PFAT eye drops were also placed into different 1.5-ml Eppendorf vials and likewise
      wrapped with aluminum foil by the other specialist(Erkut Küçük) for blinding the patients.
      The droppers were also wrapped with aluminum foil for further blinding the patient while
      applying the eye drops. Patients were randomised via assigned laterality numbers and sealed
      regime envelopes by the other specialist(Erkut Küçük). Preservative-free isotonic saline was
      used for washout for 2 weeks prior to beginning of the study.

      After the first treatment period (1 month) all patients underwent a 2-week washout period
      with isotonic saline (0.9 % NaCl) eye drops. Ten a new set of vials (AS or PFAT) was assigned
      to each patient by the other specialist(Erkut Küçük) for the second treatment period.

      After the first 1-month treatment period, patients who had conventional PFAT treatment were
      switched to AS treatment and the patients who had AS treatment in the first 1-month treatment
      period were switched to conventional PFAT treat- ment in the second 1-month treatment period,
      according to the study's crossover nature. The examining ophthalmologist (Uğur Yılmaz) that
      performed tear function and ocular surface evaluations was blinded to the type of eye drops
      given to each patient. In addition, the patients were blinded to which treatment they were
      receiving.

      Only the Other specialist (Erkut Küçük), who was not responsible for patient evaluation, knew
      which patient received which treatment during study periods. All patients were instructed to
      keep the vials (containing either AS or PFAT) in a refrigerator at 4 °C. All patients were
      advised to change the vial every other day during the treatment period. TBUT and ST I were
      administered by the same ophthalmologist (Uğur Yılmaz).

      The study was approved Institutional Review Board of Erciyes University, Medicine School. The
      study was conducted in accordance to Helsinki Declaration. All patients gave written informed
      consent.
    

Intervention name(s): %40 diluted Autologous serum; Preservative free artificial tears(Tears naturale free, Refresh single dose eye drop)
Intervention type(s): Drug; Drug
Intervention description(s): Serum that obtained after centrifugation of blood sample; Preservative free artificial tears is a group naming for drops commonly used for drye disease
Other intervention name(s): Tears naturale free(hydroxypropyl methylcellulose); Refresh single dose(polyvinyl Alcohol + Povidone)
Intervention MeSH terms: Dextrans; Povidone; Ophthalmic Solutions; Lubricant Eye Drops
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Dry eye; isotretinoin, AS; Autologous serum