Treatment of Chronic Central Serous Chorioretinopathy Via Electromagnetic Stimulation and Platelet- Rich Plasma
Condition: Central Serous Chorioretinopathy; Chronic Central Serous Chorioretinopathy
MeSH terms: Central Serous Chorioretinopathy
Study type: Interventional

Summary: 
      Purpose: To investigate the efficacy of combined use of retinal repetitive electromagnetic
      stimulation and subtenon autologous platelet-rich plasma in the treatment of recalcitrant or
      unresponsive chronic central serous chorioretinopathy.
    

Detailed description: 
      Central serous chorioretinopathy (CSCR) is a retinal disorder that is mostly unilateral, and
      predominantly affects young and middle-aged male patients who are otherwise healthy. It is
      characterized by leaking fluid through a dysfunctional retinal pigment epithelium (RPE) to
      submacular area resulting in serous neuroretinal detachment. The main risk factors for CSCR
      include emotional stress, systemic arterial hypertension, pregnancy, use of corticosteroids,
      and the presence of pachychoroid under the RPE layer.

      Although several clinical presentations are described, two forms of CSCR can be
      distinguished: acute and chronic. Acute CSCR usually presents with sudden visual loss of
      central vision, disturbed color vision and dark adaptation, central or paracentral scotoma,
      metamorphopsia, and/or micropsia caused by the rapid accumulation of subretinal fluid (SRF).
      While spontaneous resolution is common and self-limiting with little or no residual damage in
      the acute variant, the chronic variant is usually progressive with persistence of SRF.
      Persistent serous detachment for more than 3 months can result in progressive photoreceptor
      (PR) compromise, which explains the worsening visual outcomes versus the acute form.

      The chronic form of CSCR is characterized by diffuse multifocal irregular hyper-fluorescence
      seen on fluorescein angiography (FA) and indocyanine green angiography (ICGA) in addition to
      widespread RPE changes. B-scan optical coherence tompgraphy (OCT) shows elongated PR outer
      segments and a shallow heterogenous RPE detachment surrounded by subretinal fluid containing
      fibrin/fluorophore. Widespread diffuse RPE abnormalities including RPE atrophy, intraretinal
      fluid, and cystic retinal changes, retinal atrophy, subretinal fibrinous accumulation,
      subretinal fibrosis, and secondary choroidal neovascularization (CNV) are late complications
      that can lead to permanent visual loss.

      The etiology of this disease remains incompletely understood with systemic associations and a
      complex pathogenesis that involves diffuse dysfunction of the RPE cells, the choroid, or
      both. Various treatment modalities have been used nowadays with varying success rates. These
      are selected according to the stage of the disease and diffusiveness and presence of CNV.
      Examples include acetazolamide, mineralocorticoid receptor antagonists, intravitreal
      anti-VEGF injections, photodynamic therapy (PDT), and subthreshold micropulse lasers (MPL).
      However, some of the CSCR cases are recalcitrant or unresponsive to currently available
      therapy modalities. The disease can be recurrent in 15-50% of cases or bilateral in
      approximately one-third of cases. Secondary CNV is an important vision-threatening
      complication of longstanding CSCR with an incidence ranging from 2% to 9%. Thus, new
      treatment options and approaches, addressing the complex nature of the etiopathogenesis are
      necessary in patients who would otherwise be disabled.

      Platelets are anucleated cells containing many types of growth factors (GFs) such as
      epithelial growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor
      (TGF), nerve growth factor (NGF), platelet-derived growth factor (PDGF), and insulin-like
      growth factor (IGF). These growth factors and their receptors are expressed in epithelial and
      endothelial cells and play a key role in tissue healing. EGF stimulates the proliferation and
      migration of epithelial cells. NGF is a neurotrophin that stimulates growth and survival of
      intraretinal glial cells, Müller's cells, and neurons; it can restore the function of injured
      neurons. NGF also plays a key role in the integrity and function of the both epithelial cells
      and nerve fibers. Autologous platelet-rich plasma (aPRP) that contains many GFs has been used
      to treat retinitis pigmentosa and deep retinal capillary ischemia with promising clinical
      functional and structural improvements.

      Repetitive high frequency electromagnetic stimulation (rEMS) has shown promising potential in
      epithelization and wound healing. rEMS creates a stimulated focus in the tissue by increasing
      blood flow and platelets at the capillary level. rEMS can also change the growth factor
      balance and tyrosine kinase (Trk) receptor activities in damaged microenvironment.
      Electromagnetic stimulation along with growth factors has shown synergetic effects toward
      enhanced epithelial integrity and neural functions. With the addition of possible
      iontophoresis effects in the rEMS, the passage of the various active molecules can be
      augmented at the tissue level thereby increasing the widespread effect of the GFs in the
      damaged choroidal and outer retinal microenvironment. Indeed, the combined use of rEMS and
      aPRP in the treatment of the eyes with deep retinal capillary ischemia due to various
      etiologies has shown favorable results in otherwise untreatable cases.

      The primary aim of this prospective clinical study is to present the utility and efficacy of
      rEMS together with subtenon aPRP as a new treatment modality in the treatment of chronic CSCR
      cases which were recalcitrant or unresponsive to the current gold standard treatments. The
      second aim of the study is to evaluate whether there is ischemic evidences in
      choriocapillaris and the outer retina as well as their changes with this novel combination
      therapy.
    

Intervention name(s): Source of growth factors: autologous platelet-rich plasma (aPRP) + repetitive electromagnetic stimulation for iontophoresis
Intervention type(s): Combination Product
Intervention description(s): Autologous platelet rich plasma is containing many types of growth factors (GFs) such as epithelial growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor (TGF), nerve growth factor (NGF), platelet-derived growth factor (PDGF), and insulin-like growth factor (IGF).
Repetitive high frequency electromagnetic stimulation (rEMS) creates a stimulated focus in the tissue by increasing blood flow and platelets at the capillary level. Electromagnetic stimulation along with growth factors has shown synergetic effects toward enhanced epithelial integrity and neural functions. With the addition of possible iontophoresis effects in the rEMS, the passage of the various active molecules can be augmented at the tissue level thereby increasing the widespread effect of the GFs in the damaged choroidal and outer retinal microenvironment.
Intervention MeSH terms: Mitogens
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Intervention model description: Prospective, open label study; The cases resistant to all known conventional treatment methods were compared before and after the application. The control group cannot be formed because there are cases resistant to all treatment methods.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Central serous chorioretinopathy; Electromagnetic stimulation; Platelet rich plasma; Growth factors; Iontophoresis