The Influence of Intraocular Pressure on the Transscleral Diffusion of High-Molecular-Weight Compounds

Cruysberg, Lars P J; Nuijts, Rudy M.M.A.; Geroski, Dayle H.; Gilbert, Jake A.; Hendrikse, Fred; Edelhauser, Henry F.

doi:10.1167/iovs.04-1414

Cited by 26 publications

(17 citation statements)

References 22 publications

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“…This method ensures the intactness of the ocular tissues and maintains the intraocular pressure. We notice that the passive intrascleral diffusivity measured using this set up is similar to the data reported by Maurice and Polgar (1977), but lower than some other reports in literature (Ambati et al, 2000;Cruysberg et al, 2005;Anderson et al, 2008). The difference may be due to the variation in the setup by different groups.…”

Section: Discussionsupporting

confidence: 83%

Ultrasound-enhanced intrascleral delivery of protein

Cheung

Tay

et al. 2010

International Journal of Pharmaceutics

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Section: Discussionsupporting

confidence: 83%

Ultrasound-enhanced intrascleral delivery of protein

Cheung

Tay

et al. 2010

International Journal of Pharmaceutics

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“…Scleral permeability has also been investigated after imposing physical effects such as hydration in human [47] and rabbit [30] sclera, cryotherapy [48] , transscleral diode laser [48] , surgical thinning [48] and variations in transscleral pressure [47,49,50] . The diffusion of solutes was found to increase with increase in tissue hydration [30,47] , but removal of glycosaminoglycans did not have a significant effect [30] .…”

Section: Scleramentioning

confidence: 99%

Transport Barriers in Transscleral Drug Delivery for Retinal Diseases

et al. 2007

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Transscleral delivery has emerged as an attractive method for treating retinal disorders because it offers localized delivery of drugs as a less invasive method compared to intravitreal administration. Numerous novel transscleral drug delivery systems ranging from microparticles to implants have been reported. However, transscleral delivery is currently not as clinically effective as intravitreal delivery in the treatment of retinal diseases. Transscleral drug delivery systems require drugs to permeate through several layers of ocular tissue (sclera, Bruch’s membrane-choroid, retinal pigment epithelium) to reach the neuroretina. As a result, a steep drug concentration gradient from the sclera to the retina is established, and very low concentrations of drug are detected in the retina. This steep gradient is created by the barriers to transport that hinder drug molecules from successfully reaching the retina. A review of the literature reveals 3 types of barriers hindering transscleral drug delivery: static, dynamic and metabolic. While static barriers have been examined in detail, the literature on dynamic and metabolic barriers is lacking. These barriers must be investigated further to gain a more complete understanding of the transport barriers involved in transscleral drug delivery.

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“…It indicated that drug injected into the eyes would be drained out of the eye ball as easy as they go into it through peribulbar injections. Lars (Cruysberg et al 2005) and his colleague reported that higher intraocular pressure (IOP) may reduce the outside-in permeability of sclera. Lower IOP, higher peribulbar pressure, thin sclera and avoiding contact with peribulbar tissue may be an ideal combination for transscleral drug delivery.…”

Section: Discussionmentioning

confidence: 99%

Diffusion of macromolecules through sclera

Miao

Wu²,

Tao

et al. 2012

Acta Ophthalmologica

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ABSTRACT.Purpose: To quantify the in vitro permeability coefficient over different topographical locations of porcine sclera to macromolecules with different molecular weight. Methods: Fresh equatorial and posterior superotemporal porcine sclera was mounted in a two-chamber diffusion apparatus, and its permeability to fluorescein isothiocyanate (FITC)-conjugated dextrans ranging in molecular weight from 40 kDa to 150 kDa was determined by fluorescence spectrophotometry. The sclera was processed as frozen sections and viewed with a fluorescence microscope. The thickness of the area and the thickness that macromolecules enriched in the surface of sclera were measured. Results: The permeability coefficient (Pc) of porcine sclera to macromolecules was significantly higher (40 kDa, p = 0.028; 70 kDa, p = 0.033; 150 kDa, p = 0.007) in equatorial region than posterior, which could be attributed to the significant difference of thickness (p < 0.001, Kruskal-Wallis) between them. Moreover, linear regression indicated a significant negative relationship (40 kDa, p < 0.001; 70 kDa, p = 0.015; 150 kDa, p < 0.001) between scleral permeability coefficient and thickness. Also, Pc declined significantly with increasing molecular weight (MW, p < 0.001, Kruskal-Wallis). The area that the macromolecules enriched in the scleral surface was thicker for those with larger MW (p < 0.001, Kruskal-Wallis). The maximum MW and size for equatorial and posterior superotemporal scleral tissue were 185.01 KDa and 180.42 KDa, 9.92 nm and 9.67 nm, respectively. Conclusions: The permeability coefficient of porcine sclera has a significant negative relationship with scleral thickness and MW of macromolecules. Larger macromolecules are more likely to accumulate in scleral surface. The difference between topographical locations may have pharmacokinetic implications when considering transscleral diffusion of macromolecules.

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The Influence of Intraocular Pressure on the Transscleral Diffusion of High-Molecular-Weight Compounds

Cited by 26 publications

References 22 publications

Ultrasound-enhanced intrascleral delivery of protein

Ultrasound-enhanced intrascleral delivery of protein

Transport Barriers in Transscleral Drug Delivery for Retinal Diseases

Diffusion of macromolecules through sclera

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