Effects of Subtenon-injected Autologous Platelet-rich Plasma on Visual Functions in Eyes With Retinitis Pigmentosa
Condition: Retinitis Pigmentosa
MeSH terms: Retinitis; Retinitis Pigmentosa
Study type: Interventional

Summary: 
      Purpose One of the main reasons for apoptosis and dormant cell phases in degenerative retinal
      diseases such as retinitis pigmentosa (RP) is growth factor withdrawal in the cellular
      microenvironment. Growth factors and neurotrophins can significantly slow down retinal
      degeneration and cell death in animal models. One possible source of autologous growth
      factors is platelet-richplasma.The purpose of this study was to determine if subtenon
      injections of autologous platelet-rich plasma (aPRP) can have beneficial effects on visual
      function in RP patients by reactivating dormant photoreceptors.
    

Detailed description: 
      More than 240 genetic mutations are involved in inherited retinal dystrophies, which
      constitute an overlapping group of genetic and clinical heterogeneous disorders. Retinitis
      pigmentosa (RP) is a heterogeneous genetic disorder (autosomal dominant, autosomal recessive,
      X-linked, or sporadic cases from spontaneous mutations) characterized by the progressive
      devolution of the retina and affecting 1/3000- 8000 people worldwide. Symptoms include
      generally diminishing visual fields starting in the mid-periphery and advancing toward the
      fovea, ultimately leading to visual impairment and blindness with waxy-colored optic atrophy.
      RP is also described as rod-cone dystrophy because of the primary degeneration of rods along
      with secondary degeneration of cones, with photoreceptor rods appearing to be more affected
      than cones. Diseased photoreceptors face apoptosis,which results in reducing the thickness of
      the outer nuclear layer and the retinal pigment epithelium layer with abnormal pigmentary
      deposits. Although apoptosis and photoreceptor loss are common outcomes of all genetic types,
      their clinical features and progression are not homogeneous. It is currently known that while
      some photoreceptor cells do die, others appear to be in suspended animation . In the
      photoreceptor microenvironment,when growth factor (GF) levels or their receptor activities
      decrease over an extended period, apoptosis and cell death occur. The length of this period
      differs with each genetic type. The time during which there is a decrease in the effects of
      growth factors until cell death, the photoreceptors can be described as being in sleep mode,
      on standby, or in a dormant phase. In this phase, cone photoreceptors are alive, but they
      cannot function. GFs and neurotrophins, such as basic fibroblast growth factor (bFGF), neural
      growth factor (NGF), ciliary neurotrophic factor (CNTF), and brain-derived neurotrophic
      factor (BDNF), can significantly slow retinal degeneration and cell death in animal models.
      One possible source of autologous GFs is platelet-rich plasma (PRP). PRP is defined as a
      biological product that features platelet concentration; it is collected from centrifuged
      whole blood. Through the activation ofa reactivator (such as sodium chloride or citrate),
      accumulated platelets can secrete a large quantity of preparations rich in growth factors
      (PRGFs) via the release of intracellular α-granules. PRGFs are an aggregation of cytokines
      that include transforming growth factors (TGF-β), interleukine-6 (IL-6), BDNF, and vascular
      endothelial growth factors (VEGF). The strong restoring function of autologous PRP (aPRP) is
      based mainly on the trophic capacity of PRGFs . Currently, PRP is being tested as a
      therapeutic option in some clinical situations, for example in orthopedics, ophthalmology,
      and healing therapies. Some pre-clinical and clinical trials have addressed the use of PRP
      and various GFs, such as the intravitreal injection of bFGF in retinal dystrophy and the
      topical applications of NGF to treat glaucoma and neurotrophic keratitis. The use of PRGFs in
      ophthalmology has been successfully applied to ocular surface disorders, including the
      treatment of ocular surface syndrome and flap necrosis after LASIK surgery. A recent study
      observed that administration of platelet-derived proteins adjacent to the lacrimal gland
      restored lacrimal function in all patients. The clinical and pre-clinical use of aPRP in
      ophthalmology has encouraged practitioners to use it through subtenon injection in the
      treatment of retinal diseases. Through the subtenon injection of PRP, the level of
      neurotrophic growth factors may be increased in the microenvironment around the
      photoreceptors, thus potentially reactivating photoreceptors that are in sleep mode.Fetal
      bovine serum,allogeneic serum,and umbilical cord serum have also been used as sources of
      growth factors, but they are heterologous products with a higher risk of allergic reactions
      and infectious disease transmission. In order to avoid these issues, and because of the
      accessibility and relatively safe nature of aPRP, we chose to use aPRP as a source of growth
      factors in our study. The purpose of this prospective open-label clinical trial was to
      determine whether the subtenon injection of aPRP may have beneficial effects on visual
      functions-such as best corrected visual acuity (BCVA), visual field (VF), multifocal
      electroretinography (mfERG), and microperimetry (MP)-in RP patients with various degrees of
      narrowed visual fields.
    

Intervention name(s): Platelet rich plasma
Intervention type(s): Biological
Intervention description(s): blood is drawn from the patient's antecubital vein and inserted into four 3.0 ml vacutainer tubes that contain trisodium citrate. These four tubes were placed in a centrifuge machine, and centrifugation was carried out at 2500 rpm (580×g) for 8 min within a 30-min blood collection period. As a result of centrifugation, the plasma was separated in the vacutainer tubes from the remaining blood components. Three different layers formed in the tubes: red blood cells at the bottom, aPRP in the middle layer, and aPPP in the top layer. A total of 1.5 ml of the middle layer (which mainly contained platelets) was withdrawn by syringe, and it was immediately injected into the subtenon space of each eye.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Prospective open-label, before-after-control group comparisions
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Retinitis pigmentosa; Growth factors; Platelet rich plasma; Visual functions