Biomedical Engineering Reference
In-Depth Information
7.3 EvaluationofNanoviricidesinaRabbitModelofEKC
Adenovirus. serotypes. are. the. most. common. etiologic. agents. of. external. ocular. viral.
infection.in.many.parts.of.the.world..Although.follicular.conjunctivitis.is.the.most.com-
mon,.epidemic.keratoconjunctivitis.(EKC).is.the.most.serious.adenoviral.ocular.disease.
responsible.for.global.and.community.epidemics..The.disease.is.very.contagious.and.can.
cause.community.and.medical.facility.epidemics.resulting.in.signiicant.patient.morbid-
ity,.societal.losses.from.worker.and.student.absenteeism,.and.increased.direct.medical.
costs.. EKC. has. a. variable. course,. but. the. appearance. of. immune-based. subepithelial.
iniltrates. (SEIs). can. impair. visual. acuity. for. months. in. some. patients.
23,24
. Currently,.
there. is. no. effective. topical. or. systemic. antiviral. therapy. to. reduce. the. symptoms. or.
duration. of. the. disease,. reduce. viral. shedding,. or. prevent. the. vision-threatening. sub-
epithelial.iniltrates.
25,26
.In.addition,.no.treatment.will.protect.the.second.eye.or.prevent.
transmission. within. households,. medical. ofices,. and. communities.. Nonsteroidal. anti-
inlammatory.eye.drops,.steroid.eye.drops,.and.artiicial.tears.have.been.used.as.sup-
portive.therapy.
The.animal.model.uses.New.Zealand.rabbits.utilizing.topical.and.intrastromal.ocular.
inoculation. with. adenovirus. type. 5.
27
. Viral. replication. is. associated. with. clinical. signs.
of.infection—acute.conjunctivitis,.blepharitis,.and.subepithelial.iniltrates..Three.groups.
of. rabbits. per. group. were. compared:. an. infected. control. group. treated. with. the. vehicle.
(group.A),.an.infected.experimental.group.treated.with.NNVC.B.(group.B),.and.an.infected.
experimental.group.treated.with.NNVC.C.(group.C).
On.day.0.both.eyes.of.each.rabbit.were.inoculated.with.adenovirus.(Ad).5.4.×.10
5
.PFU.
in.100.μl.by.intrastromal.injection.and.scariication..Fifteen.hours.after.viral.inoculation,.
the. rabbit. eyes. were. treated. with. two. drops. (50. μl. per. drop). twice. a. day. with. vehicle.
(group.A),.NNVC.B.(group.B),.or.NNVC.C.(group.C).for.10.days..All.rabbits.were.moni-
tored.daily.from.days.1-10,.and.then.at.days.21.and.37,.until.sacriice,.on.a.grading.sys-
tem.of.0-4.for.conjunctival.injection.(redness.and.dilation.or.prominence.of.conjunctival.
blood.vessels),.blepharitis.(crusting,.discharge,.and.inlammation.of.eyelid.margins),.iris.
hyperemia,.and.corneal.subepithelial.iniltrates.(SEIs)..As.shown.in.Figure 7.4,.the.vehicle.
Conjunctival Injection
Blepharitis
4
2
Vehicle
NNVC B
NNVC C
Vehicle
NNVC B
NNVC C
3
2
1
1
0
0
0
2
4
6
8
10
0
2
4
6
8
10
Day
Day
FIGURE 7.4
Time.course.of.the.clinical.scores.for.conjunctival.injection.(redness.and.dilation.or.prominence.of.conjunctival.
blood.vessels).and.blepharitis.(crusting,.discharge,.and.inlammation.of.eyelid.margins).in.vehicle.control-.and.
NNVC.B-.and.NNVC.C-treated.rabbits.following.adenovirus.5.ocular.infection..Treatment.(twice.daily).with.
two.drops.at.a.time.was.started.3.hours.postinfection.
