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Leon C Ho, Ian P Conner, Chi-wai Do, Seong-Gi Kim, Ed X Wu, Gadi Wollstein, Joel S Schuman, Kevin C Chan; Visualization of Aqueous Humor Dynamics upon Chronic Ocular Hypertension and Hypotensive Drug Treatment using Gadolinium-enhanced MRI. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2902.
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© ARVO (1962-2015); The Authors (2016-present)
While current clinically approved glaucoma treatments target at altering aqueous humor (AH) dynamics to lower elevated intraocular pressure (IOP), the contributions of imbalanced AH dynamics to the pathogenesis of ocular hypertension (OHT) and glaucoma are not fully elucidated. This study used a small-molecular-weight MRI contrast agent, gadolinium (Gd) to mimic AH and visualize AH dynamics in rats upon microbead (MB)-induced OHT or ocular hypotensive drug treatments.
8 Sprague-Dawley rats were injected with a mixture of 10 and 15μm MB into the right (R) anterior chamber (AC) to block aqueous outflow (AO) and induce sustained OHT for 2 weeks. 18 additional normotensive rats were topically applied to R eye with 0.005% latanoprost (Lat; n=6), 0.5% timolol maleate (Tim; n=6) and 0.2% brimonidine tartrate (BT; n=6) 1hr before MRI to lower IOP by facilitating AO, suppressing aqueous inflow (AI) and both respectively. Gd-DTPA was intraperitoneally injected to each rat, and T1-weighted images (30s each) were continuously acquired for 2hr in a 9.4 Tesla MRI scanner. 3 weeks later, saline was applied to R eyes of 2 rats from each drug group as sham control (Sal; n=6) and Gd-MRI was repeated. The MRI signal time course, initial increase rate (IIR) of Gd signal, peak signal intensity (PI) and time to peak (TP) in AC and vitreous body (VB) were computed.
Right before MRI, the mean % IOP changes of treated R eye relative to untreated left (L) eye were 100%, -29%, -27%, -36% and -4% for MB, Lat, Tim, BT and Sal groups (p<0.05 except Sal). IOP increase by AO reduction in MB gave higher IIR & PI and shorter TP in R than L AC (p<0.05), whereas IOP decrease by AO increase in Lat or AI reduction in Tim gave opposite Gd-MRI patterns to MB (p<0.05 for Lat; p=0.06-0.2 for Tim). For BT, both L and R AC showed lower IIR, higher PI and longer TP than other groups (p<0.05). Only MB had higher PI in R than L VB (p<0.05). No Gd-MRI difference was found between both eyes in Sal, whereas IIR in L AC was slightly higher in Lat and Tim than MB and Sal (p=0.09-0.16).
IIR, PI and TP in Gd-MRI may reflect altered AH dynamics quantitatively upon OHT or anti-glaucoma drug treatments. The drastic Gd-MRI changes in BT and the slight changes in untreated AC of Lat and Tim may also draw attention to the systemic effects of topical hypotensive drugs on AH dynamics.
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