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Quan Hoang, Quan Wen, Stanley Chang, Stephen Trokel, Ronald Silverman, David Paik; In Vivo Crosslinking of Scleral Collagen in the Rabbit Using Sub-Tenon Injection of Nitroalcohol. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5169.
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Myopic progression occurs in up to 50% of myopic patients. Scleral weakness and abnormal scleral collagen are possible etiologic factors. We evaluate the efficiency of non-light-activated collagen crosslinking to increase biomechanical strength and stunt axial length growth in vivo.
Ten (~35-51 day-old) New Zealand White rabbits underwent baseline B-scan ultrasonography (US) axial length recordings. Rabbits then received 5+ posterior sub-tenon injections over 2-4 weeks composed of 0.9% NaCl in the left eye (OS) and collagen crosslinking agents in the right eye (OD). Nine rabbits received 2-hydroxymethyl-2-nitro-1,3-propanediol (Triol) and 1 rabbit received glyceraldehyde (GLY) dissolved in 0.9% NaCl. 8 rabbits were sacrificed immediately after the treatment period. A pair of rabbits (1 treated with Triol, and 1 with GLY) were followed with weekly US axial length measurements until sacrifice at 105 days of life.
Baseline axial length ranged from 13.82 +/- 0.2 (mean +/- standard deviation, in mm) OD and 13.76 +/- 0.2 OS (n = 2) among 35 day-old rabbits to 14.62 +/- 0.4 OD and 14.62 +/- 0.4 OS (n = 8) among ~51 day-old rabbits. Postmortem biochemical testing showed, in terms of half-maximal shrinkage temperature, Triol-treated eyes had a shift ranging from negligible to 2.6 degrees, with a mean shift of 0.9 (n = 9). A 0.9 degree shift was also seen in the GLY-treated rabbit. Also, Triol-treated eyes had 28% resistance to enzymatic digestion compared to 37.8% in GLY-treated eyes. Histologic studies did not show toxicity in either Triol- or GLY-treated eyes. In the longitudinally-followed rabbits, 1 week after completion of Triol treatment, OD AL had grown 0.15 mm over baseline, which was 43% of the 0.35 growth in the contralateral control OS. This difference diminished. By 105 days of life, axial growth (1.1 mm) was equivalent among treated and control eyes. In contrast, 1 week after completion of GLY, OD axial length had grown 0.58 mm over baseline, which was 90.6% of the 0.64 growth in the control OS. Difference was maintained at 105 days of life (axial length growth OD was 1.0 mm, 91.8% of the 1.1 mm growth OS).
Sub-Tenon delivery of Triol increased scleral biomechanical rigidity in vivo and delayed axial length growth transiently with no noted side effects on the retina. The induced scleral crosslinking may become a treatment modality to prevent myopic progression.
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