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Ординатура / Офтальмология / Английские материалы / Drug Product Development for the Back of the Eye_Kompella, Edelhauser_2011.pdf
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B.E. McCarey

Fa

= c

×

Vc

×

Cc

aV2 ,

V

 

 

 

 

 

C

a

 

 

 

 

a

 

 

 

where Fa is aqueous humor flow (m3/s), c is corneal fluorescein concentration exponential decay constant (min−1), Vc is corneal volume, Va is aqueous humor volume,­ and aa is aqueous humor fluorescein concentration exponential decay constant­ (min−1).

3.5  Retinal/Choroid and Vitreous Fluorescein

Uptake and Release

3.5.1  Transscleral Pathways

Transscleral pathway for ophthalmic drug delivery to the posterior globe, i.e., the uveal track, vitreous, choroid, and retina, must overcome the protective barriers of the sclera and the local capillary bed of the choroid. Noncorneal absorption route involves penetration across the sclera and conjunctiva into the intraocular tissue. Most reports have been limited euthanizing the laboratory animal to collect tissue samples of a penetrating drug at various time points in the intraocular tissue after presenting the drug to the eye. With a noninvasive fluorophotometer the progression of uptake and loss of sodium fluorescein into cornea, vitreous, and retina following periorbital injections can be performed on the unanesthetized test subject (McCarey and Walter 1998). The technique permits a continuum of data noninvasively in the rabbit. Tracing the movement of fluorescein has several advantages in the study of ocular barriers. Fluorescein has a high fluorescence quantum yield and low toxicity. The optical design of the fluorophotometer will measure the fluorescence of the ocular­ tissue on a linear scan along the optical axis of the eye. A suprachoroidal or vitreous injection of fluorescein cannot be detected until the fluorescein enters the optical axis of the eye Fig. 3.13. The intravitreous injection of fluorescein initial is observed 1 h after injecting into the peripheral vitreous cavity, bottom row, and middle column­ . The cornea, lens, and retina fluorescence remain unchanged. As the fluorescein continues­ to diffuse through the vitreous, the fluorophotometer measures a plateau in vitreous fluorescence without increases in cornea, lens, or retina.

3.5.2  Suprachoroidal Injection

The suprachoroidal injection of fluorescein is distributed by a difference modality. One hour after the suprachoroidal fluorescein injection, the retinal fluorescence has increased with overlapping increase in vitreous fluorescence. The vitreous increase is an artifact from the fluorophotometer focal diamond passing through the retina. In Fig. 3.13, the principle of the focal diamond measuring a symmetrical fluorescence curve as it passes through a thin highly fluorescence structure is illustrated. The phenomenon is referred

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