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Editors Selection IGR 21-1

Surgical Treatment: Photcrosslinking the peripapillary sclera: a new promise?

Comment by Crawford Downs on:

92266 Transpupillary collagen photocrosslinking for targeted modulation of ocular biomechanics, Gerberich BG; Hannon BG; Hejri A et al., Biomaterials, 2021; 271: 120735

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Optic nerve head (ONH) biomechanics has been hypothesized to play an important role in the development and progression of glaucoma, but it is not fully understood. There is a large degree of biologic variability in the ONH load-bearing structure, which includes geometry (scleral thickness, neural canal shape and size, laminar pore size and beam thickness, etc.), and tissue stiffness, which may change with age, pathology, extracellular matrix composition, and connective tissue remodeling. Several investigators have hypothesized that altering peripapillary scleral stiffness could be a treatment to reduce ONH susceptibility to IOP. To that end, Gerberich and colleagues developed a transpupillary crosslinking technique that stiffened the peripapillary sclera in living rats. This was accomplished by retrobulbar injection of methylene blue, which crosslinked the peripapillary sclera using an annular beam of red light focused only on the peripapillary region, avoiding the optic disk and more peripheral posterior pole. This ingenious technique reduced peripapillary scleral mechanical strain by half at Day 0, which persisted through week 6 after the procedure, as measured with postmortem scleral inflation tests. There was a significant stiffening in the peripheral sclera observed at Day 0 as well, but that did not persist through the week 6 time point. As the authors acknowledge, this technique should be considered developmental due to the significant loss of axons, axon density, and the increase in the optic nerve damage score in the crosslinked eyes versus the sham control eyes treated with saline. This study is very important, as it represents a significant leap forward in our quest to selectively alter ONH biomechanics through reducing peripapillary scleral strain. That said, significant further development is necessary to eliminate the axonal damage associated with the technique, and to ensure that it is scalable to eyes larger than the rodent. In addition, it has not been shown that increasing peripapillary scleral stiffness is effective at increasing an eye's resistance to IOP-induced damage, although this technique could be used to test that hypothesis. Overall, this study represents significant progress toward a potential biomechanics-based treatment for glaucoma.

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