近畿眼科先進医療研究会

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第8回近畿眼科先進医療研究会

日 時:
平成22年8月18日(水)18:00~19:00
場 所:
近畿大学医学部附属病院 円形棟3階『小講堂』
講 師:
James M. Hill Ph.D.
対象者:
近畿眼科先進医療研究会会員

研修テーマ

James M. Hill Ph.D.

James M. Hill Ph.D.

第1部「What has the Molecular Biology Taught Us about Ocular HSV and Effective Chemotherapy?」
Clinicians who treat ocular HSV infections know that many antiviral agents exhibit excellent therapeutic responses. Why are antiviral studies continuing to be conducted? Answer: The ocular problems associated with the damage to the corneal stroma produced by recurrent infections are irreversible and deleterious. This damage can lead to significantly reduced vision and in some cases loss of vision. Only a corneal transplant can restore vision. These clinical events can be reduced by proper therapy; however, therapy must be initiated at the appropriate dose and frequency. Current data indicate that contracting HSV and recurrent HSV infections are dependent on the live virus or its DNA being available through “shedding.” Based on recent data from human studies on tears and saliva, the evidence supports frequent, spontaneous, and continuous shedding of HSV-1 DNA into tears. In addition to human studies, we have expanded our HSV-1 latent rabbit model to assess viral DNA shedding into saliva. In HSV-1 latent rabbits treated with very high doses of Valtrex (valacyclovir), the frequency and copy numbers of HSV-1 DNA shed into tears and saliva were blocked or significantly reduced. Data from rabbits treated with Valtrex 2 or 3 times per day for 5-12 days at doses showed 10-20 times that of the “normal” dose. HSV-1 DNA shedding into tears and saliva was shown to be significantly reduced by these high doses of Valtrex. Also, there was no observed or detectable toxicity at these high oral doses. Taken together, our data suggest that the concept of HSV-1 latency as very dormant and inactive or non-infectious is not correct. Thus, although the majority of neurons that harbor latent virus at any one point in time are dormant, there is a subset of neurons that apparently is replicating HSV-1 DNA and that viral DNA is being “shed.” This has implications for the epidemiology of HSV-1 infections as well as the ability to investigate vaccines to reduce the viral shedding and acquisition of HSV. Thus, proper dosing and frequency of an antiherpetic such as Valtrex has great promise for successful therapy of serious herpes infections that otherwise could be catastrophic.
第2部「Clinical and antiviral efficacy of an ophthalmic formulation of dexamethasone povidone-iodine in a rabbit model of adenoviral keratoconjunctivitis」
Our purpose was to determine the efficacy of a new formulation of topical dexamethasone 0.1%/povidone-iodine 0.4% (FST-100) in reducing clinical symptoms and infectious viral titers in a rabbit model of adenoviral keratoconjunctivitis. Rabbit corneas were inoculated bilaterally with 2x106 PFU of adenovirus type 5 (Ad5) following corneal scarification and randomized 1:1:1:1 (5 rabbits per group) to FST-100, 0.5% cidofovir, Tobradex® (tobramycin/dexamethasone) ophthalmic suspension, and balanced salt solution (BSS). Treatment began 12 hours after viral inoculation and continued for 7 consecutive days. Eyes were clinically scored daily for scleral inflammation (injection), ocular neovascularization, eyelid inflammation (redness), friability of vasculature, inflammatory discharge (pus), and epiphora (excessive tearing). Eye swabs were collected daily before treatment for the duration of the study. Virus was eluted from the swabs and PFU determined by titration on human A549 cells following standard procedures. The FST-100 treatment resulted in significantly lower clinical scores (P < 0.05) compared with the other treatments. The 0.5% cidofovir exhibited the most ocular toxicity compared with FST-100, Tobradex, and BSS treatments. FST-100 and 0.5% cidofovir significantly (P < 0.05) reduced viral titers compared to Tobradex or BSS. In conclusion, FST-100 was the most efficacious in minimizing the clinical symptoms of adenovirus infection in rabbit eyes. FST-100 and 0.5% cidofovir were both equally effective in reducing viral titers and decreasing the duration of viral shedding. By providing symptomatic relief in addition to reducing infectious virus titers, FST-100 should become the only drug of choice for treatment of epidemic adenoviral keratoconjunctivitis.

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