Continuous ophthalmic treatment using an osmotic pump in a bull calf following surgical removal of an ocular dermoid: A case report

Abstract

An intact male, six-month-old Hanwoo bull calf (native Korean beef breed) was presented to the Animal Medical Centre, Chonbuk National University because the owner had noticed a conjunctival and corneal abnormality in the left eye (OS). On ophthalmic examination, a small, elevated and skin-like mass lesion, containing hair was found on the ventronasal cornea and the conjunctiva of the third eyelid. In the light of its characteristic appearance, the lesion was classified clinically as a corneal dermoid. Under general anaesthesia, superficial lamellar keratectomy and conjunctivectomy was performed to remove the abnormal tissue. As the owner could not apply topical medications regularly, a drug-filled osmotic pump (Alzet; Alza, Palo Alto, CA) was implanted subconjunctivally under the upper eyelid and connected to a catheter at the lateral limbus. The catheter was fixed to the conjunctiva with 3-0 polyglactin 910 (Vicryl®; Ethicon, Johnson and Johnson, Somerville, USA) and a partial temporary tarsorrhaphy was placed. In order to determine the efficacy of medication delivery, a sample of aqueous humour was collected via aqueocentesis from the anterior chamber at two weeks and four weeks after implantation of the pump. The presence and concentration of ciprofloxacin was determined via mass spectroscopy. Aqueous concentration of ciprofloxacin was 0.093 μg/ml at two weeks and 0.107 μg/ml at four weeks. The calf healed without incident and returned to normal function six weeks following the procedure.

Full text

282
Case Report Veterinarni Medicina, 60, 2015 (5): 282–287
doi: 10.17221/8181-VETMED
Continuous ophthalmic treatment using an osmotic
pump in a bull calf following surgical removal
of an ocular dermoid: a case report
J.H. B1, C.E. P2, J. K1, M.S. K1, N.S. K1
1College of Veterinary Medicine, Chonbuk National University, Jeonju, Republic of Korea
2Small Animal Clinical Sciences, University of Florida, Gainesville, USA
ABSTRACT: An intact male, six-month-old Hanwoo bull calf (native Korean beef breed) was presented to the
Animal Medical Centre, Chonbuk National University because the owner had noticed a conjunctival and corneal
abnormality in the left eye (OS). On ophthalmic examination, a small, elevated and skin-like mass lesion, contain-
ing hair was found on the ventronasal cornea and the conjunctiva of the third eyelid. In the light of its character-
istic appearance, the lesion was classified clinically as a corneal dermoid. Under general anaesthesia, superficial
lamellar keratectomy and conjunctivectomy was performed to remove the abnormal tissue. As the owner could
not apply topical medications regularly, a drug-filled osmotic pump (Alzet; Alza, Palo Alto, CA) was implanted
subconjunctivally under the upper eyelid and connected to a catheter at the lateral limbus. The catheter was
fixed to the conjunctiva with 3-0 polyglactin 910 (Vicryl®; Ethicon, Johnson and Johnson, Somerville, USA) and
a partial temporary tarsorrhaphy was placed. In order to determine the efficacy of medication delivery, a sample
of aqueous humour was collected via aqueocentesis from the anterior chamber at two weeks and four weeks after
implantation of the pump. The presence and concentration of ciprofloxacin was determined via mass spectroscopy.
Aqueous concentration of ciprofloxacin was 0.093 µg/ml at two weeks and 0.107 µg/ml at four weeks. The calf
healed without incident and returned to normal function six weeks following the procedure.
Keywords: calf; topical antibiotics; aqueous humour; keratectomy
Supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded
by the Ministry of Education (Grant No.NRF-2014R1A2A2A01007969).
Ocular dermoids, as reported, are peculiar de-
fects characterised by normal tissue in an abnormal
location, usually skin or skin-like masses of tis-
sue arising on the limbus, conjunctivae, and cor-
nea and occasionally on the eyelids (Gelatt 1981;
Barkyoumb and Leipold 1984; Neumann 1984;
Yeruham et al. 2002). They are typically benign
and non-progressive; however, they are a source
of irritation which can usually be easily addressed
by superficial lamellar keratectomy and/or con-
junctivectomy and then supportive care while the
surgical defect heals (Gelatt 1971). Post-operative
medical therapy typically consists of topical anti-
biotics to prevent infection of the surgical wound
and other topical and/or systemic medications to
control pain and inflammation as needed. However,
the post-operative topical treatment of cattle is dif-
ficult because of poor patient and farm compli-
ance and the frequency of topical medical therapy
necessary. It can also be very stressful for cattle to
undergo frequent therapy which can increase the
danger to the handler.
In order to solve the problem of frequent medica-
tion administration in this bull calf, we employed
an osmotic pump to deliver topical ciprofloxacin
to the eye following surgical removal of the ocular
dermoid. An osmotic pump is a delivery system
for delivering drugs or other topical agents at a
continuous and controlled rate (Theeuwes 1975).
It delivers the agent via the osmotic pressure dif-
ference between compartments within the pump,
called the osmotic layer, and the tissue environ-

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doi: 10.17221/8181-VETMED
ment in which the pump is implanted (Figure 1).
That is, when the osmotic pump is exposed to an
aqueous environment, the osmotic layer imbibes
water through a semipermeable membrane which
forms the outer surface of the pump. The imbibed
water compresses the flexible impermeable reser-
voir, which collapses and displaces the contents
from the pump at a controlled, predetermined rate
(Theeuwes and Yum 1976). Pumps such as the one
used here have been used at a variety of sites in-
cluding the spinal cord, spleen, liver, organ or tissue
transplants, and wound sites (Eldridge et al. 1990;
Xu et al. 1995). Despite their use elsewhere in the
body, there are only a few reports regarding the use
of osmotic pumps for delivery of medication to the
eye (Blair et al. 1999; Ambati et al. 2000). However,
these earlier studies revealed the potential useful-
ness of the osmotic pump for ocular diseases.
Case description
A six-month-old intact male Hanwoo bull calf (na-
tive Korean beef breed) was presented to the Animal
Medical Centre, Chonbuk National University after
the owner noticed a conjunctival and corneal abnor-
mality in the left eye (OS). On ophthalmic examina-
tion, a small, elevated and skin-like mass, containing
hair was found on the ventronasal cornea and the
conjunctiva of the third eyelid (Figure 2). Ocular
irritation, mild blepharospasm, and epiphora were
evident. In both eyes, menace response and ocular
reflexes were present, and Schirmer tear test values
were 17.2 mm/min (OS), 16.4 mm/min (OD) and
intraocular pressure values were 24 mmHg (OS) and
23 mmHg (OD). Fluorescein test was negative and
aqueous fluid was clear on slit lamp examination.
In the light of its characteristic appearance, the le-
sion was classified clinically as a corneoconjunctival
dermoid. Given the irritation and discomfort caused
by the mass, surgical removal of the lesion under
general anaesthesia was planned.
The calf was anaesthetised with intramuscu-
lar injection (i.m.) of Zoletile® (2 mg/kg, Virbac,
Carros cedex, France) and xylazine (0.05 mg/kg,
Bayer Korea, Seoul, Korea). Local anaesthesia was
induced using cotton swabs with 0.5% proparacaine
hydrochloride (Alcaine; Alcon, Fort Worth, TX)
applied directly to the surgical site. The eye was
prepped routinely. Using a EL-5700 scleral blade
(Eagle Laboratories Inc, Rancho Cucamonga, CA)
and electrocautery (Cautery High Temp 2200 °F,
Jorgensen Laboratories Inc, Loveland, Co), super-
ficial lamellar keratectomy (at a depth of about one
third of the cornea) and conjunctivectomy was per-
formed with a surgical loupe (×4 magnification) to
remove the offending tissue as has been previously
described (Figure 3a,b) (Shaw-Edwards 2010). The
resultant wound bed was left open to heal by second
Figure 1. Illustration of the operation of the osmotic
pump. When the osmotic pump is exposed to an aqueous
environment, the osmotic layer imbibes water through a
semipermeable membrane which forms the outer surface
of the pump. e imbibed water compresses the imper-
meable reservoir, which collapses and displaces the con-
tents from the pump at a controlled, predetermined rate
Figure 2. On ophthalmic examination, a small, elevated
and skin-like mass, containing hair was found on the ven-
tronasal cornea and the conjunctiva of the third eyelid

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doi: 10.17221/8181-VETMED
intention. Since the owner could not apply topi-
cal antibiotics regularly, we employed an osmotic
pump (ALZET; ALZA, Palo Alto, CA) in order
to administer topical medications. The osmotic
pump was filled with 200 µl 0.3 % ciprofloxacin
(Cipex®, Samil, Seoul, Korea) using a syringe and
a blunt-tipped filling unit and the flow moderator
of the pump was then inserted. A translucent cap
(Figure4a) on the flow moderator was removed to
expose a piece of the flow moderator (Figure 4b)
which would connect to the catheter later accord-
ing to the manufacturer›s instructions. The pump
was incubated in sterile saline at 37 °C for 40 h prior
to implantation. All of these steps were performed
in a laminar flow hood using sterile technique.
After a lateral canthotomy (1 cm) with a straight
blunt-ended scissor, an incision (1 cm) was made
through the conjunctiva of the upper eyelid with a
tenotomy scissor and the osmotic pump was pre-
loaded with antibiotic (Figure 5a) and then im-
planted subconjunctivally (Figure 5b). The pump
was connected to the lateral limbus using a catheter
(Polyethylene; ALZA, Palo Alto, CA) with an inside
diameter of 0.76mm (Figure 5c). e tip of the cath-
eter was heated briefly using an alcohol lamp before
fixation to the conjunctiva. e catheter was fixed
with 3-0 polyglactin 910 (Vicryl®; Ethicon, Johnson
and Johnson, Somerville, USA) using two simple in-
terrupted patterns at intervals of 0.5 cm along the
palpebral conjunctiva of the lower eyelid. Following
implantation and fixation of the pump and catheter,
three partial temporary tarsorrhaphy sutures of 4-0
nylon (Ethilon; Ethicon, Somerville, NJ) were per-
formed, leaving the area of the medial canthus open.
e sutures were tied with one end left long. e lat-
eral canthotomy was closed with a figure-eight suture
using 3-0 nylon (Ethilon; Ethicon, Somerville, NJ).
In order to assess the efficacy of delivery of drug
to the eye, samples of aqueous humour were ac-
quired via aqueocentesis to establish the presence
and concentration of the drug in the anterior cham-
ber. The drug used in this case to prevent infec-
tion of the surgical wound bed was ciprofloxacin,
a fluoroquinolone known for its superior ability to
penetrate the cornea and accumulate at sufficient
levels in the anterior chamber. To measure the
concentration of ciprofloxacin, 0.1 ml of aqueous
humour was collected from the anterior chamber
using a 30 g needle and a 1 ml syringe at two weeks
and four weeks while the calf was under general
and topical anaesthesia as for the keratectomy.
The collected samples were stored at –70 °C until
the assay could be performed. The tarsorrhaphy
and figure-eight suture were removed two weeks
Figure 3. Using a EL-5700 scleral blade (a) and electrocautery (b), superficial lamellar keratectomy (a depth of 0.2–0.3mm)
and conjunctivectomy was performed to remove the offending tissue
Figure 4. A translucent cap (a) on the flow moderator
was removed to expose a piece of the flow moderator (b)
which would connect to the catheter later
Translucent cap A piece of
the flow
moderator
(a) (b)

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following the initial procedure (at the time of the
first aqueous humour collection) and the osmotic
pump was removed four weeks post-operatively
(at the time of the second aqueous humour collec-
tion). The calf recovered appropriately after each
of his anaesthetic events and healed well following
surgery. Six weeks postoperatively (Figure 6), the
calf was comfortable and there was no evidence of
residual irritation or epiphora. It then returned to
its normal functions without restriction.
Ciprofloxacin was detected in the aqueous hu-
mour, demonstrating that the osmotic pump was
able to deliver topical medications to the eye. The
concentration of ciprofloxacin in aqueous humour
was measured following chromatographic separa-
tion and mass spectrometric detection using a pro-
tocol adopted from Cantor et al. (2001) Aqueous
concentration of ciprofloxacin was 0.093 µg/ml at
two weeks and 0.107 µg/ml at four weeks. The re-
sidual volume of agent in the pump reservoir was
also measured following removal. A filling tube
attached to the syringe was used to aspirate the
remaining agent from the pump reservoir accord-
ing to the manufacturer’s instructions. However,
the residual volume in the reservoir was too low
to measure its pure weight using a filling tube.
Therefore, the osmotic pump was weighed before
and after aspirating the agent several times for dry-
ing by using a filling tube and syringe. The weight
of the osmotic pump was 2.302 g (before aspiration)
and 2.285 g (after aspiration). Therefore, the re-
sidual volume of agent was 17 µg following removal.
Figure 5. e osmotic pump pre-loaded with antibi-
otic before implantation (a); the osmotic pump was
implanted subconjunctivally on the upper eyelid (b); the
pump was then connected to the lateral limbus using a
catheter (c)
(a) (b)
(c))

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DISCUSSION AND CONCLUSIONS
To the authors’ knowledge, this is the first reported
case of the use of an osmotic pump for continuous
administration of antibiotic solution after superficial
keratectomy in a Bovid. For long-term treatment of
ocular disorders in large animals, especially horses,
subpalpebral lavage catheters (SPL) are used routinely
to deliver topical solutions to the eye (Rebhun 1979;
Abrams and Brooks 1990). However, even though
these devices dramatically enhance topical ocular
therapy, they still require the physical instillation of
topical solutions through the system at regular in-
tervals and are usually used for pulse therapy, rather
than continuous delivery. is necessitates frequent
handling of patients, which is impractical when treat-
ing cattle. ere is an automated constant rate fluid
delivery pump available that has been used in combi-
nation with an SPL in the horse (Myrna and Herring
2006). is external installation pump is replenishable
and designed to deliver an agent at a predetermined
rate (0.02–4.0ml/h) for up to seven days. However,
sevendays of infusion is often insufficient to complete
a course of treatment and it can be difficult to replen-
ish the drug reservoir in an animal that is not handled
regularly, such as a beef bull. ese external instal-
lation devices can be easily broken or dislodged by
animals that are not stalled and/or that are housed in
groups. Subconjunctival implanted pumps have been
described for continuous ocular treatment in horses
(Blair et al. 1999). However, these pumps, too, have
limited duration of delivery (seven days) and a very
limited capacity (100 µl). Additionally, implants that
are inserted into the subconjunctival space without
an egress such as a catheter will not deliver drug to
the corneal surface and therefore are not suitable for
treatment of corneal epithelial diseases. e pump
used in this case had a reservoir of 200 µl and was
designed to deliver a continuous rate of 0.25 µl/h for
four weeks. is pump with lavage catheter satisfied
the requisite duration of infusion time and stability of
installation for appropriate post-operative treatment
of this bull calf.
It has been reported that the mean aqueous con-
centration after topical administration of 0.3 % cipro-
floxacin is 0.15 ± 0.11 µg/ml (range 0.09–0.58µg/ml)
in humans and 0.17 µg/ml (range 0.09–0.95 µg/ml)
in dogs (Solomon et al. 2005; Yu-Speight et al. 2005). e
aqueous concentration of ciprofloxacin (0.093 µg/ml
at two weeks and 0.107 µg/ml at four weeks after im-
plantation) was lower than that previously reported
in humans and dogs. ese concentration levels did
not exceed the values (Table 1) for Streptococcus sp.,
Staphylococcus sp., Corynebacterium sp. and E. coli
(Osato et al. 1989; Donnenfeld et al. 1994; Cekic et
al. 1999). ese results suggest that filling the pump
with a high concentration of ciprofloxacin is neces-
sary to reach comparable effectiveness for topical ad-
ministration. However, it is clear that the osmotic
infusion pump maintained the aqueous concentra-
tion of ciprofloxacin at a reasonable steady state
until its removal four weeks after implantation.
The amount of drug remaining in the pump was
about 17 µg/ml after four weeks. This also dem-
onstrates the reliability of the pump. Connecting
an ocular catheter to the pump can be associated
with complications, such as eyelid abscesses and
corneal ulcers (Friedman et al. 1989). However, in
the current case, no complications with the cath-
eter or its connection to the pump were observed.
In conclusion, the current case indicates that an
Figure 6. At follow-up 6 weeks after the keratectomy and
conjunctivectomy, the surgical wound had healed appro-
priately, no ocular irritation or discomfort was observed
and the calf had returned to its normal activities
Table 1. Ciprofloxacin MIC90 values for canine aqueous
humour organisms commonly reported as ocular con-
taminants in dogs
Organism Ciprofloxacin
MIC90 (µg/ml) References
Staphylococcus sp. 0.5 eeuwes and Yum
1976; Yeruham et al.
2002
Streptococcus sp. 2
Corynebacterium sp. 0.5 Xu et al. 1995
Escherichia coli ≤ 0.25

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osmotic pump may be an effective treatment device
for ocular disease in group-housed large animals.
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Received: 2015–01–15
Accepted after corrections: 2015–04–02
Corresponding Author:
Namsoo Kim, Chonbuk National University, College of Veterinary Medicine, 567 Baekje-daero, Jeonju,
561-756, Republic of Korea
E-mail: namsoo@jbnu.ac.kr