Does Hyperbaric Chamber Improve the Functionality and Symptoms Related to Central Retinal Vein Occlusion (CRVO)?
Description:
Trial protocol V2.0 – Hyperbaric chamber treatment to CRVO patients
Assaf HaRofe Medical Center – Zerifin, Israel
Purpose: To determine whether hyperbaric chamber treatment improves the functionality and
symptoms related to CRVO
Introduction:
Central Retinal Vein Occlusion (CRVO) has profound effects on retinal circulation. As this
vein collects the entire venous outflow from the retina, retinal perfusion is greatly
impaired when it occludes. Even though, as compensation, the collateral outflow is expanded
but nevertheless there is an increase in retinal venous pressure, venous dilation, retinal
hemorrhage and retinal edema.
Reduction of blood flow leads to retinal hypoxia and upregulation of vascular endothelial
growth factor (VGEF )
In CRVO there is a variable degree of capillary nonperfusion visible on fluorescein
angiography (FA) which is divided into "ischemic" and "non ischemic" depending on the size of
the area of non perfusion on FA.
Possible complications of CRVO include chronic cystoid macular edema (CME),
neovascularization of retina, neovascular glaucoma and vitreous hemorrhage. These
complications are serious, sight threatening, and require prolonged treatment.
Current therapy of CRVO requires different treatment modalities depending on the
complication.
Neovascularization is treated mainly by laser photocoagulation (PRP – pan retinal
photocoagulation) and VEGF inhibitors. Photocoagulation is based on lowering the oxygen
consumption of peripheral retina.
Macular edema is treated with anti VEGF and/or steroidal injections. Most patients require
continuous monthly injections which may last for years in order to dehydrate their macula.
Recent clinical trials such as CRUISE and BRAVO have shown that the immediate monthly
injections of anti VEGF (Ranibizumab) during the first 6 months and then later as needed
decreased substantially the time to achieve visual acuity gain following CRVO5. In BRAVO
trial the cumulative proportion of patients who had gained 15 letters or more from baseline
by 12 month (from CRVO incidence) was 50% (sham), 68% (ranibizumab 0.3 mg), and 71%
(ranibizumab 0.5 mg) and in CRUISE trial 42%, 61%, and 66%, respectively.
Another trial which evaluated the effect of anti VEGF was the COPERNICUS trial in which
patients with CRVO received intravitreal aflibercept injection every 4 weeks up to 6 months
following the CRVO. The control group received sham injections and the proportion of patients
gaining ≥ 15 letters was 56.1% versus 12.3% (P<0.001) at week 24. Improved reduction in
central retinal thickness and increased vitreous hemorrhage as the major side effect (up to
6.8%) was also evident in patients treated with aflibercept.
Although effective, these anti VEGF injections expose the patient to many possible side
effects including sub conjunctival hemorrhage and transient hypertension at the mild end of
the spectrum or endophthalmitis and lens injury at the severe end.
An alternative treatment is the use of steroids such as dexamethasone intravitreal implant
(Ozurdex). However, this treatment may induce side effects such as increased ocular pressure,
cataract, allergy, conjunctival hemorrhage and eye pain.
Hypoxic induction of cytokines, such as VEGF, play a central role in CRVO and its
consequences such as retinal edema and iris neovascularization.
Hyperbaric chamber has the potential to increase oxygen perfusion and perhaps decrease
retinal hypoxia, thereby decreasing the induction of cytokines and improving retinal
functionality.
The investigators' broad experience in hyperbaric chamber treatment reveals that it is a
rather benign treatment compared to the alternatives where the most relevant side effect in
eligible patients is usually ear barotrauma.
Investigative Device:
Hyperbaric chamber assists in increasing the amount of oxygen in the plasma and in the
tissues and has been proven to be beneficial in treating different ischemic wounds, and acute
retinal artery occlusion (ARAO) but its effect hasn't been tested in CRVO patients yet.
Methods:
Patients with chronic CRVO who are receiving monthly injections of Bevacizumab treatment for
at least 12 months will be recruited. Upon recruitment each patient will undergo a screening
Ophthalmologic examination including visual acuity, refraction and OCT. This will be followed
by a series of 40 daily hyperbaric chamber treatments. A repeated ophthalmic examination will
be done after 20 and 40 hyperbaric sessions.
Condition:
Central Retinal Vein Occlusion
Treatment:
Hyperbaric chamber treatment
Start Date:
March 2015
Sponsor:
Assaf-Harofeh Medical Center
For More Information:
https://clinicaltrials.gov/show/NCT02405741