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children (6-16 years old) with low to moderate myopia. Compared with the single-vision spectacles group,
the axial elongation of the Ortho-K group was reduced by 36%-63% in the ROMIO study (the Retardation
[85]
[86]
of myopia in Orthokeratology) , HM-PRO study (the High Myopia-Partial Reduction Ortho-k study) ,
and other clinical trials [87-89] . According to the existing studies, Ortho-K showed benefits to children with low
to moderate myopia.

Interventions to myopic CNV
Anti-VEGF therapy
As mentioned above, the angiogenic stimulant VEGF is involved in the pathogenesis of mCNV. Therefore,
VEGF is the target to treat choroidal angiogenesis. Nowadays, the widely used anti-VEGF drugs include
ranibizumab, aflibercept, and conbercept. These drugs are divided into two groups based on their molecular
structure. Ranibizumab is a recombinant, humanized, monoclonal antibody. It is an antigen-binding
fragment (Fab) that can neutralize all isoforms of VEGF-A . Aflibercept and conbercept are fusion
[90]
[91]
proteins made of key domains of VEGFR1 and VEGFR2 fused with a portion of human antibody . They
[92]
act as a decoy receptor for VEGF and prevent VEGF from activating the real VEGFR .
[93]
Recently, anti-VEGF therapy has become the major treatment and provided good visual acuity benefits .
The safety and efficacy of these anti-VEGF agents have been proved in many studies. Similar visual gains
and morphological improvements of mCNV patients were achieved by each of these anti-VEGF agents [94-96] .
In the REPAIR study published in 2013 , the efficacy of intravitreal 0.5 mg ranibizumab in mCNV was
[97]
evaluated. Eyes with mCNV received ranibizumab at baseline and monthly injections as needed. Patients
gained 13.8 letters at 12 months on average. The median number of injections was three. In the MYRROR
study published in 2015 , the efficacy of intravitreal aflibercept was evaluated. Patients were divided into
[97]
the aflibercept and sham groups. Patients in the aflibercept group received one injection of 2 mg aflibercept
at baseline and additional injections monthly when mCNV persisted or recurred. Primary efficacy was
assessed at Week 24; patients in the aflibercept group gained 12.1 letters, while patients in the sham group
lost two letters on average. Then, patients in the sham group received mandatory aflibercept injections for
another 24 weeks with the same regimen. By Week 48, patients gained 13.5 and 3.9 letters in the aflibercept
and sham/aflibercept groups, respectively. In the aflibercept group, the median number of injections was
two during the first eight weeks, and no additional injections were applied during the remaining 40 weeks.
In the sham/aflibercept group, the median number of injections was two during Weeks 25-36 and one
during Weeks 37-48. Different from exudative age-related macular degeneration or diabetic macular edema,
which requires frequent injection [98,99] , the management of mCNV required a limited number of injections.

Severe adverse effects have been reported, including subretinal fibrosis , retinal detachment , and
[100]
[100]
[101]
macular hole . The common adverse events are conjunctival hemorrhage, transient increase in intraocular
pressure, corneal punctate keratitis, and posterior capsule opacification . Very few systemic complications
[96]
associated with anti-VEGF therapy have been reported in clinical trials of mCNV patients. Due to favorable
visual outcomes and safety profiles, anti-VEGF agents have become the standard treatment for mCNV .
[102]
Laser photocoagulation and photodynamic therapy
Laser photocoagulation and vPDT had been used to treat mCNV before the availability of anti-VEGF drugs
in the past decades [103,104] . Laser photocoagulation is only employed in juxtafoveal CNV. The laser destroys
the CNV and causes thermal damage in the outer retina, RPE, and choriocapillaris . Successful laser
[105]
photocoagulation could improve visual acuity because it prevents the CNV from extending to the fovea .
[106]
However, the long-term visual outcome is not favorable. Neovascular recurrence is one of the reasons for
the deterioration of visual acuity. The incidence of recurrence ranges from 48.2% to 72% [106-108] . Furthermore,