Acute Macular Neuroretinopathy Clinical Trial
Official title:
Management of Deep Retinal Capillary Ischemia by Electromagnetic Stimulation and Platelet- Rich Plasma
To investigate the efficacy of retinal electromagnetic stimulation and sub-tenon autologous platelet rich plasma in the treatment of deep retinal capillary ischemia.
Deep retinal capillary ischemia (DRCI) is a recently described entity in patients presenting
with an acute-onset paracentral scotoma. Subclinical macular lesions of DRCI were formerly
best visualized on near-infrared reflectance imaging. The development of optical coherence
tomography angiography (OCTA) has facilitated studies of the retinal capillary structures.
The multiplanar superficial capillary plexus is located in the inner plexiform layer (IPL)
and contains synapses between bipolar and ganglion cells as well as amacrine cells. The deep
capillary plexus (DCP) is located in the outer plexiform layer (OPL), which is thinner than
the IPL. The DCP is composed of synapses of photoreceptors, bipolar cells, and horizontal
cells. This area is also at the border of the oxygen diffusion from the choroid. It is likely
that the oxygen coming from the choroid has been completely consumed by the photoreceptors
because of the low partial pressure of oxygen level in the outer nuclear layer (ONL). The DCP
supplies both the bipolar cells and the synaptic structure of the OPL and Henle fibers.
Deep retinal capillary ischemia is an ischemic event in the middle and deep layers of the
retina due to various systemic or local vascular pathologies. It is obvious in the
intraretinal hyper-reflective bandlike zone located superior or inferior to the OPL
conjointly on in a structural cross-sectional B-scan of the spectral domain optical coherence
tomography (SD-OCT) examination along with an acute-onset paracentral scotoma and subjective
complaints of the patient. Ophthalmologists often face a significant diagnostic challenge
because of a lack of noticeable changes in the appearance of the retina.
DRCI has two different appearances on B-scan SD-OCT exams according to the level of the
involved DCP. If the hyper-reflective bandlike zone is located on the outer plexiform
layer-inner nuclear layer (OPL-INL) junction, then it is termed "Paracentral Acute Middle
Maculopathy (PAMM)" or type-1 deep retinal capillary ischemia. If the hyper-reflective band
is seen on the OPL-ONL junction, then it is termed as type-2 deep retinal capillary ischemia.
This might be a new variant of "Acute Macular Neuroretinopathy (AMN)". These intraretinal
hyperreflective zones are seen as patchy areas of various patterns on en-face OCT image, and
atrophic areas in the inner and the outer nuclear layer respectively are developed in the
late stage of the diseases. The pathophysiologic features of DCP ischemia is considered to be
ischemic hypoxia leading to cell death with swelling of the middle retinal tissues. This may
lead to severe vision loss and permanent paracentral scotoma depending on the underlying
cause and depth of ischemia. It can also be observed by slowing metabolic activity in
photoreceptors and neural retina. The metabolic slowdown is defined as a dormant phase in
photoreceptors and OFF mode in the neural retina.
The retinal deep capillary plexus is a single monoplanar capillary plexus located in the OPL.
It has the lowest vessel density—this is a significant finding that might be used to evaluate
retinal vascular diseases accurately. For this reason, the changes in the percentage of the
vessel density in DCP during the follow-up were preferred as an assessment parameter of the
treatment modalities used in this prospective clinical study.
Platelets are anucleated cells that contain many types of growth factors including
platelet-derived growth factor(PDGF), transforming growth factor-β(TGF-β), vascular
endothelial growth factor(VEGF), and epidermal growth factor(EGF) in alpha granules. Thus,
the supplementation of growth medium with autologous platelet-rich plasma (aPRP) could be
desirable for clinical applications and could lead to some functional improvement.
High-frequency repetitive electromagnetic stimulation (rEMS) has promising therapeutic
potential in ischemic neurological patients. The rationale of rEMS is that it modulates
neural excitability and increases neural plasticity; thus, it improves the functional
outcome. These neuroprotective effects of rEMS are dependent on the increase in the level of
brain-derived neurotrophic factor (BDNF), VEGF, and increased tyrosine kinase A, B, and C
(TrkA, TrkB, and TrkC) receptor activation. Therefore, high-frequency rEMS might be a
promising therapeutic strategy for ischemic retinal disorders such as DRCI.
There is no known and proven specific treatment for DRCI to date except for systemic
check-ups and treatment of the underlying diseases or predisposing factors. The aim of this
preliminary clinical study is to investigate the efficacy of high-frequency rEMS alone or in
combination with sub-tenon fresh aPRP as a treatment modality in the treatment of DRCI. To
the best of our knowledge, this is the first prospective clinical trial on this subject in
the ophthalmic literature.
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