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Despite mechanically strengthening the posterior sclera, PSR may halt axial elongation by ameliorating
[127]
hypoxia of sclera. During myopia development, scleral hypoxia plays a pivotal role in sclera remodeling .
[128]
Choroidal ischemia is a possible cause of myopic maculopathy . A thinner choroid is associated with
faster AL growth . Increasing choroidal vascular perfusion can improve oxygenation of the sclera and
[129]
slow down myopia development in guinea pigs . Zhang et al. considered that the allogeneic scleral graft
[130]
[131]
caused a secondary non-specific inflammatory reaction and increased the choroidal blood flow. Whether
the improved choroidal circulation after surgery could prevent eye globe elongation still requires further
investigation.
Currently, PSR is regarded as an effective way to limit the progression of pathological myopia and reduce
the occurrence of myopic maculopathy, especially in patients with fast myopic progression. Studies on the
treatment effect of PSR on pathological myopia are listed in Table 3.

Posterior pole buckle
Posterior pole buckle, or macular buckle, is similar to PSR. The main procedure of PSR is to reinforce the
ectatic posterior pole, while that of posterior pole buckle is an application of stronger positive forces over
[132]
the posterior pole to make an iatrogenic dome-shaped macula . Due to scleral protrusion caused by
silicone sponge, posterior pole buckle diminishes the high myopia . The diminution degree is correlated
[133]
with silicone sponge stretching and fixation. Posterior pole buckle is mostly applied in patients with
macular membrane, macular schisis, and myopic macular hole with a retinal detachment to release the
myopic macular traction . It could be done alone or combined with pars plana vitrectomy [135,136] .
[134]

The complications of both PSR and posterior pole buckles include lateral rectus weakness, intraocular
pressure increase, diplopia, metamorphopsia, and choroidal effusion [134,137] . However, most complications
are transient. Both PSR and posterior pole buckles are safe and effective with accurate placement of strip or
buckle.

Scleral collagen cross-linking
Cross-linking was first used in keratoconus to increase the stiffness of cornea . Then, in 2004,
[138]
[139]
Wollensak introduced scleral cross-linking for the treatment of high myopia. Cross-linking is the
technique to enhance the tensile strength of collagen by the physical way (riboflavin–ultraviolet A ) or
[140]
[142]
[141]
chemical agents (genipin and glyceraldehyde ). Cross-linking strengthens the sclera by forming
[143]
covalent bonds between collagen molecules and reducing the enzymatic degradation by MMP1 . Until
[144]
now, animal experiments including guinea pig , rat , and rhesus monkeys have proved the efficiency
[145]
[147]
[146]
and safety of scleral cross-linking, but no protocol has been brought to clinical use. Only one study
conducted by Xue et al. showed the genipin-crosslinked sclera strip used in PSR showed better strength
[148]
and larger surgical effect size. Further clinical studies are required.
CURRENT STEM CELL-BASED THERAPIES FOR MACULOPATHY
Stem cell-based therapies have been mainly applied in degenerative corneal and retinal diseases. The
following summarizes the stem cell-based clinical trials in maculopathy.
The stem cell ophthalmology treatment study
The Stem Cell Ophthalmology Treatment Study (SCOTS) is a series of clinical studies treating incurable
optic and retinal diseases with autologous bone marrow-derived stem cells (BMSCs). The completed clinical
trials include studies on Usher syndrome , dominant optic atrophy , Leber’s hereditary optic
[149]
[150]
[151]
neuropathy , relapsing auto-immune optic neuropathy , and serpiginous choroidopathy . In these
[152]
[153]