Ursodeoxycholic Acid for Rhegmatogenous Retinal Detachment
Condition: Rhegmatogenous Retinal Detachment
MeSH terms: Retinal Detachment; Dissociative Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      26 patients presenting a rhegmatogenous retinal detachment with more than 4 days of duration
      will be prospectively included.

      A single dose of ursodeoxycholic acid will be administered orally before surgery at different
      time-points in 22 subjects. Standard surgery will be performed and ocular samples will be
      collected during the procedure. Ursodeoxycholic acid treatment will be continued in treated
      patients during 3 months after surgery.

      Ocular and serum samples from the 4 untreated patients will serve as negative controls for
      the determination of UDCA levels.
    

Detailed description: 
      Retinal detachments consist in a separation of the neuroretina from the retinal pigment
      epithelium. The most common form is rhegmatogenous retinal detachment (RRD), which occurs as
      a result of a full-thickness retinal break and the presence of vitreoretinal tractions.
      Photoreceptor cell death occurs rapidly after RRD and is the ultimate cause of vision loss in
      these patients. Reattachment of the retina by a surgical procedure allows a recovery of
      vision. However, the degree of visual recovery differs among patients, despite successful
      reattachment. This is mainly related to the preoperative visual acuity level, the presence of
      a macular detachment and its duration. Predicting factors of worse visual acuity are the
      height of retinal detachment in the macula and the presence of edema, separation, cyst and
      undulation at the level of the outer nuclear layer showed by optical coherence tomography
      (OCT). Most patients usually consult with a RRD already involving the macular area after 3
      days or more, leading to a worse visual prognostic even with successful surgery. The need for
      adjuvant neuroprotective agents is then critical to improve photoreceptor survival,
      functional recovery and subsequent quality of life in patients affected by RRD.

      Tauroursodeoxycholic acid (TUDCA) is the taurine conjugate of ursodeoxycholic acid (UDCA), a
      secondary bile acid produced by intestinal bacteria. UDCA was approved by the Food and Drug
      Administration (FDA) for the treatment of cholestatic liver disease. Both UDCA and TUDCA are
      potent inhibitors of apoptosis, in part by interfering with the upstream mitochondrial
      pathway of cell death, inhibiting oxygen-radical production, reducing endoplasmic reticulum
      (ER) stress, and stabilizing the unfolded protein response (UPR). TUDCA has been proposed as
      anti-apoptotic agent in several neurodegenerative diseases, including amyotrophic lateral
      sclerosis, Alzheimer's, Parkinson's, and Huntington's diseases.

      In certain degenerative retinal disorders, such as retinitis pigmentosa, TUDCA plays an
      important role in preventing cell death. In an animal model of RRD, systemic treatment by
      TUDCA has been shown to protect photoreceptors from cell death.

      The aim of this study is to determine whether detectable levels of UDCA reach the vitreous
      cavity when administered orally at different time points before surgery for RRD, and to
      analyze its ocular safety.

      20 patients presenting a rhegmatogenous retinal detachment with more than 4 days of duration
      will be prospectively included.

      A single dose of ursodeoxycholic acid will be administered orally before surgery at different
      time-points in 16 subjects. Standard surgery will be performed and ocular samples will be
      collected during the procedure. Ursodeoxycholic acid treatment will be continued in treated
      patients during 3 months after surgery.
    

Intervention name(s): Ursodeoxycholic Acid
Intervention type(s): Drug
Intervention MeSH terms: Ursodeoxycholic Acid
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment