MyopiaX Treatment for the Reduction of Myopia Progression in Children and Adolescents: Safety and Efficacy Investigation

The prevalence of myopia, or nearsightedness, has increased at an alarming rate
over the past two decades and is expected to continue accelerating in the
coming years. It has been predicted that close to 50% of the world*s population
will be nearsighted by 2050 (Holden et al., 2016) and recent research suggests
that restrictions during the COVID-19 pandemic may exacerbate this trend due to
limited time outdoor (J. Wang et al., 2021).

Myopia is typically characterized by excessive ocular growth that increases the
risk of serious, sight-threatening complications in adulthood, including
cataract, glaucoma, retinal detachment, and myopic maculopathy. The risk of
developing any of these comorbidities increases with myopia severity
(Flitcroft, 2012; Haarman et al., 2020). Myopia is quickly becoming a global
health problem and there is a growing need for more effective interventions to
slow its development and progression.

Myopia is a progressive disease and children with early onset are at particular
risk of complications associated with myopia, as progression over time might
result in high myopia and myopic macular degeneration (Grzybowski et al., 2020).
Currently, there is no standard treatment for myopia progression, however a
range of myopia control approaches is available, including active spectacles,
contact lenses, and pharmacological treatments (Huang et al., 2016; Prousali et
al., 2019; Wildsoet et al., 2019).

While atropine and various contact lens types, including orthokeratology, have
been shown to be effective against myopia progression (Huang et al., 2016;
Prousali et al., 2019), both treatments are accompanied by several risks that
should be taken into consideration. Even if applied at low dosages, atropine
use is off label and has considerable side effects, such as photosensitivity,
poor near visual acuity, and temporary stinging or burning (Gifford et al.,
2019; Gong et al., 2017). The side effects of orthokeratology and other contact
lenses include mild blurry vision (Gifford et al., 2019), mild corneal erosion,
corneal staining, lens binding, reduced tear film (Prousali et al., 2019), and
infectious keratitis (Vagge et al., 2018).

Infectious keratitis can lead to corneal scars, which require surgical
treatment in 10% of cases (Prousali et al., 2019).
The recent approval of myopia control spectacle lenses, offer a new approach
with an acceptable
benefit-risk profile (H. Y. Zhang et al., 2020). Despite this new therapeutic
option in the
management of progressive myopia, the unmet need for additional, and
potentially complementary
therapies remains, as these lenses do not completely stop myopia progression,
and even when
prescribed, are not accessible for everyone, maybe difficult to fit and/or are
not consistently worn
by children.
The present clinical trial will evaluate treatment with MyopiaX, which aims to
slow myopia progression in a non-invasive and low-risk manner. MyopiaX is a
digital treatment that delivers flickering blue light to the optic nerve head
using a smartphone-compatible game. Played using a virtual reality (VR)
headset, there is almost no observable difference between MyopiaX and any other
video game, as the blue light stimulus is positioned so that it is not visible
to the user.

The intensity of the blue light stimulation does not surpass the normal
illuminance of commercially available smartphones. The blue light used in
MyopiaX targets the optic nerve head in order to minimize any adverse effects
to the retina. The goal of MyopiaX is to stimulate the axons of
melanopsin-containing intrinsically photosensitive retinal ganglion cells
(ipRGCs) at the optic nerve head with blue light in order to increase the
melanopsin-mediated release of retinal dopamine, which is an important
neurotransmitter that contributes to eye growth regulation.

Increased levels of dopamine can slow eye growth and, as a result, reduce the
rate of development or progression of myopia (Chakraborty et al., 2019). The
required usage of MyopiaX is twice a day for about 12 minutes, including set up
and removal of the device, breaks between levels, and a total of 10 minutes of
active stimulation with blue light.
The objective of the present clinical investigation is to evaluate the signals
of effect, the safety and tolerability of MyopiaX in slowing the progression of
myopia through stimulating the axons of melanopsin-containing intrinsically
photosensitive retinal ganglion cells (ipRGCs) at the optic nerve head with
blue light.

This study is also aimed at evaluating the safety of MyopiaX and its
acceptability to parents/guardians and their children.

Primary objective

To evaluate the effects of treatment with MyopiaX on the rate of myopia
progression in children
and adolescents as reflected in spherical equivalent refraction and axial
length changes at 6
months relative to baseline.

Secondary objectives

- Evaluate the safety of treatment with MyopiaX in terms of incidence of device
related adverse events (AEs), changes in visual acuity, and fundus.
imaging data at the beginning of the trial (baseline) and during the
treatment period.

Exploratory Objectives
- Evaluate the effect of MyopiaX relative to the effect of myopia control
spectacles after six
months of treatment
• Evaluate the effect of MyopiaX + myopia control spectacles relative to the
effect of myopia
control spectacles only (months 6 - 12)
• Explore the effect of MyopiaX on retinal and choroidal (such as choroidal
thickness) imaging
parameters under treatment
• Assess device usability information using a user feedback questionnaire.

This is a prospective, randomized, controlled, single-masked, multicenter,
international trial that
aims to evaluate the effect of MyopiaX treatment in myopia progression

Trial participants will be randomly assigned 2:1 to the MyopiaX treatment or
myopia control
spectacle lenses treatment

The study is single-masked, investigators assessing the outcome measures
(clinical assessors) at
each site will be masked towards the allocated treatment. The study subjects
that are already
randomized, are also masked to their study treatment (MyopiaX device or sham
device), whereas
the newly randomized subjects will be unmasked to their study treatment
allocation (MyopiaX or
spectacle lenses).

The blue light stimulation which is controlled by MyopiaX and then emitted by
the smartphone is delivered for 10 minutes (active stimulus duration) per
session. Participants receive a maximum of 10 minutes of blue light at their
optic nerve head depending on the blinking and fixation stability. Each session
consists of different levels lasting for 30-120 s. Breaks of 15-20 s are
included between levels. Including the time needed to setup the device, the
inter-level breaks, the active stimulus duration, and the removal of the
device, the overall session duration is about 12 minutes.

A session will be counted as successful if the participant receives at least 8
minutes of blue light stimulation (i.e., excluding the breaks between levels),
and his/her score indicates active playing.. The CIP section 6.5.3. describes
the procedures implemented when participants are not performing the sessions as
intended. Detailed information about the device and the treatment is provided
in the instructions for use (IFU) and the user manual.

The risks associated with the treatment do not surpass the risks associated
with the domestic use of electronic devices (smartphone, tablets, computers,
VR) for the children in the clinical investigation.

Participating in the study does not imply a higher risk for the children than
attending the regular check-ups that myopic children usually undergo to control
myopia progression. Furthermore, the medical examinations are implemented in
such way that any detrimental ocular changes can be detected early, thus
minimizing risks and ensuring prompt MyopiaX interruption and treatment if
necessary.

Furthermore, study participants that present, in the investigators` clinical
judgment an unacceptable rate of progression, clinically validated therapies
will be recommended thus ensuring that participants in the trial have access to
the clinically available and validated methods to manage myopia.