CLINICAL SCIENCE
Subtenon Bupivacaine for Postoperative Pain
in Patients Undergoing Pterygium Excision:
A Double-Blinded Randomized Control Trial
Riyaz Bhikoo, MBChB,*† Karen Hughes, DipNurse, PGCertHSc,*
Ryash Vather, FRACS, PhD,‡ and Chris Murphy, FRANZCO*
Purpose: Patients undergoing primary pterygium excision with
autologous conjunctival autograft and human tissue adhesive in New
Zealand, currently receive subconjunctival anesthesia with oral
postoperative analgesia for pain. Our aim was to investigate the
potential added benefit of intraoperative subtenon bupivacaine to
this regimen.
Methods: A double-blinded, placebo-controlled, randomized trial
was conducted at 2 centers. All patients received topical and
subconjunctival anesthesia intraoperatively, with standardized oral
analgesia as required postoperatively. Participants were allocated to
receive subtenon bupivacaine 0.5% or placebo at the conclusion of
surgery. Corneal epithelial defect and conjunctival graft size were
recorded. Pain and ocular surface irritation were assessed (Likert
scale) immediately postoperatively at 3, 6, 12, 24, and 36 hours.
Cumulative oral analgesia consumption (doses) was reported at 24
and 36 hours.
Results: Forty-two patients were randomized with participants
evenly matched at baseline. Postoperative pain at all time points #24
hours was significantly less (2.4 vs. 1.2; P , 0.04) in the
bupivacaine arm with no difference at 36 hours (P = 0.27). Ocular
surface irritation was also significantly less at all time points #12
hours (4.8 vs. 1.3; P , 0.01) with no difference at 24 hours (P =
0.10). Analgesia consumption was less in the bupivacaine arm at 24
(6.5 vs. 2.5; P , 0.01) and 36 hours (7.6 vs. 3.4; P , 0.01). No
complications were observed.
Conclusions: Intraoperative subtenon bupivacaine improves
patient comfort after pterygium excision by reducing pain, irritation,
and requirement for oral analgesia after surgery.
Received for publication December 30, 2018; revision received March 7,
2019; accepted March 13, 2019. Published online ahead of print May 3,
2019.
From the *Department of Ophthalmology, Waikato District Health Board,
Hamilton, New Zealand; †Department of Ophthalmology, Mid-Central
District Health Board, Palmerston North, New Zealand; and ‡Department
of General Surgery, Waikato District Health Board, Hamilton, New
Zealand.
The authors have no funding or conflicts of interest to disclose.
Supplemental digital content is available for this article. Direct URL citations
appear in the printed text and are provided in the HTML and PDF
versions of this article on the journal’s Web site (www.corneajrnl.com).
Correspondence: Riyaz Bhikoo, MBChB, Department of Ophthalmology,
Waikato District Health Board, Pembroke St, Hamilton 3204, New
Zealand (e-mail: riyazbhikoo@gmail.com).
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Cornea  Volume 38, Number 8, August 2019
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Key Words: pterygium, subtenon, analgesia, pain
(Cornea 2019;38:959–963)
P ostoperative pain after pterygium excision is common
with clinically significant pain experienced in 60% of
patients undergoing surgery.1 The use of tissue adhesive to
secure the conjunctival graft (compared with sutures) has
been shown to improve patient comfort in the first few days
after surgery.2,3 Despite this, postoperative pain is a frequent
issue with oral analgesia having a relatively poor effect on
ocular surface-related discomfort.
In New Zealand, subtenon anesthesia is the preferred
technique for intraocular procedures, with peribulbar techni-
ques being rarely performed. However, as an extraocular
procedure, pterygium surgery is commonly performed under
topical or subconjunctival anesthesia which provides minimal
postoperative analgesia compared with these other forms of
regional anesthesia. The aim of our study was to determine
the postoperative analgesic efficacy of subtenon bupivacaine,
given in addition to subconjunctival bupivacaine, for primary
pterygium excision with autologous conjunctival graft and
tissue adhesive.
MATERIALS AND METHODS
Between October 2016 and January 2018, a random-
ized, double-blinded, placebo-controlled trial was conducted
at Waikato and Palmerston North Hospitals in New Zealand.
The trial was registered with the Australian New Zealand
Clinical Trials Registry (ANZCTR 12616001125415), and
ethics approval was obtained through the New Zealand
Health and Disability Ethics Committee (16/STH/144).
Study Protocol
Patients referred to Waikato or Palmerston North
Hospitals for pterygium surgery were assessed and screened
by 2 surgeons (R.B. and C.M.). Those with primary nasal
pterygium and older than 18 years of age were eligible for
enrollment. Exclusion criteria were those who required
general anesthesia, were having surgery for recurrence, had
contraindications to any of the study medications (including
postoperative analgesia), and could not speak English.
Enrolled participants were masked to the intervention and
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Bhikoo et al
were provided information about the study including a printed
patient information sheet. All participants provided written
informed consent.
Randomization
The randomization process was performed by an
independent third party using a number generator sequence,
with allocation to the treatment and control groups in a 1:1
ratio. The independent third party had a complete list of study
participants and assigned participants to the intervention. The
allocation and study number were secured in an opaque
envelope and submitted to the ophthalmic surgical booking
clerk and attached to the patients file on the day of surgery.
Intervention
The initial instillation of topical amethocaine is usually
associated with mild discomfort before the anesthetic effect is
appreciated. To obtain baseline pain scores for each eye, topical
amethocaine 1% was instilled into the operated eye by the
surgeon (R.B. or C.M.) using the methods described by Koranyi
et al.2 Separate pain scores were recorded for those undergoing
bilateral surgery. Patients were asked to quantify their pain on
a Likert scale from 0 (no pain) to 10 (extreme pain).
Masking
Participants were randomized to receive 2.0 mLs of
bupivacaine 0.5% or balanced salt solution (placebo) through
a 19-gauge subtenon cannula. The circulating theater nurse
was responsible for opening the opaque envelope and the
preparation of the subtenon injection. The solution was then
transferred to the scrub nurse and administered by the surgeon
(double blinded).
Surgery
The ocular surface and adnexa were prepared and draped
in a sterile fashion using topical povidone iodine 5%. Both
groups received subconjunctival bupivacaine 0.5% with adren-
aline 1:200,000 (1 mL) into the body of the pterygium at the
start of surgery. Our conjunctiva preserving technique allowed
us to minimize the amount of graft tissue required to cover the
exposed sclera. The border of healthy and diseased conjunctiva
overlying the pterygium was identified at the start of surgery
(usually at the limbus), and this is where the initial incision was
made. Using blunt dissection, the conjunctiva was then
separated off the diseased tenon tissue as far out as the plica.
The head of the pterygium was then peeled off the cornea using
Kelman–McPherson forceps and the body of the pterygium
then dissected off the underlying sclera, before being excised.
A crescent blade was used to polish the corneal bed of the
remaining tenons tissue. Bipolar cautery was used cautiously to
achieve hemostasis. The size of the corneal defect and the size
of the superior conjunctival autograft were measured using
a sterile flexible ophthalmic ruler (Viscot Medical, LLC, East
Hanover, NJ) to the nearest decimal point, and this was re-
corded in the patients’ notes. With the pterygium removed, the
inferior nasal subtenon space becomes easily accessible and
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Cornea  Volume 38, Number 8, August 2019
was dissected further, with the injection administered as pos-
terior as possible. The conjunctival graft was excised from its
limbal attachment and secured to the exposed scleral bed using
tissue adhesive (Artiss; Baxter International) and allowed to set
for 3 minutes. Tissue glue was also applied over the corneal
epithelial defect. A topical ointment (dexamethasone 0.1%,
polymyxin B sulfate 6000 units, neomycin 3.5 mg; Maxitrol;
Alcon Laboratories) was applied to the ocular surface at the
conclusion of surgery, and a paraffin gauze dressing and 2 eye
pads were placed over the eye. Patients requiring bilateral
surgery had both eyes padded closed. This was kept in place
until the following morning, with patients instructed to com-
mence Maxitrol ointment 3 times daily until review in clinic 1
week later. Postoperative oral pain relief was standardized and
to be used pro rata using the World Health Organization
analgesic ladder, starting with paracetamol 1 g (single dose;
max 4 g/d), followed by ibuprofen 400 mg (single dose; max
1200 mg/d) and tramadol 50 mg (single dose; max 200 mg/d).
Opioids were not prescribed.
In the recovery bay, patients were contacted by the study
nurse who was masked to the intervention (K.H.). The
postoperative questionnaire (see Appendix, Supplemental
Digital Content 1, http://links.lww.com/ICO/A788) was ex-
plained to participants who were asked to 1) quantify pain and
irritation using a 10-point Likert scale, 2) comment if their pain
had affected their overnight sleep, and 3) any oral analgesia
taken within the first 36 hours after surgery. All patients were
contacted at 24 and 48 hours after surgery by the study nurse
where the outcome parameters (as documented by the patient)
at 3, 6, 12, 24, and 36 hours were recorded. Patients were
formally assessed in clinic 1 week after surgery.
Outcomes
All study parameters were entered into a password-
protected Excel sheet (Microsoft Corporation, Redmond,
WA) including baseline patient characteristics such as age,
gender, baseline pain score, surgical time, size of pterygium
preoperatively as well as corneal and conjunctival defect
intraoperatively. Preoperative pterygium size was obtained
using an anterior segment photograph, and Microsoft Paint
(Microsoft Corporation) was used to measure the vertical and
horizontal corneal extent of the pterygium at the corneal limbus.
A flexible ophthalmic ruler had to be used intraoperatively
because the operating microscope at one of the hospital sites did
not have appropriate recording function capacity.
Assessment of postoperative pain and ocular surface
irritation were assessed on a Likert scale immediately post-
operatively and at 3, 6, 12, 24, and 36 hours after surgery.
Analgesia consumption was assessed at the same time points,
with the mean cumulative doses of analgesic agents con-
sumed reported at 24 and 36 hours after surgery. Adverse
events were also recorded.
Statistical Analysis
Statistical analysis and power calculations (R.V.) for
this study were based on earlier publications which compared
tissue adhesive to suturing for the conjunctival autograft.3
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Cornea  Volume 38, Number 8, August 2019 Subtenon Bupivacaine for Postoperative Pain

FIGURE 1. Eligibility, randomiza-

tion, and follow-up (Consort flow
chart).

To observe a 40% reduction in the average pain score did not reach significance [placebo 24% (5/21); bupivacaine
on the day of surgery from a Likert score of 5 to 3 and study 5% (1/21); P = 0.08].
power of 80%, it was calculated that a minimum of 16 A significant difference in ocular surface irritation
patients would be required in each arm. Groups were scores was reported #12 hours (4.8 vs. 1.3; P , 0.01) after
compared looking for statistical significance at the 0.05 level. surgery (Fig. 3), with no difference at 24 (5.1 vs. 3.8; P =
The Fisher exact or x2 tests were used for categorical 0.10) and 36 hours (4.6 vs. 3.5; P = 0.25).
variables, with the Mann-–Whitney U and Kruskal–Wallis Total analgesia consumption (doses taken) per eye was
tests for nonparametric variables. Results are displayed with significantly less in the bupivacaine arm at 24 and 36 hours
standard deviations included in parentheses. Analysis was postoperatively (Table 2). Further subanalyses were under-
carried out using the SPSS software package (IBM SPSS taken with all bilateral cases excluded (10 eyes), and it was
Statistics) on an intention-to-treat basis. found this effect persisted, with analgesia consumption
significantly less at 24 (7.3 vs. 3.1; P , 0.01) and 36 (8.2
vs. 4.1; P , 0.02) hours in those who received bupivacaine.
RESULTS There were no complications related to the subtenon
Between October 2016 and January 2018, 49 patients injection or surgery itself.
were screened of whom 42 met the eligibility criteria and
underwent randomization (Fig. 1). Both groups were evenly
matched at baseline regarding patient demographics, clinical, DISCUSSION
and intraoperative findings (Table 1), and follow-up data were In New Zealand, pterygium surgery is generally per-
available for all patients. No complications were observed. formed under topical and/or subconjunctival anesthesia. Both
There was a significant difference in pain scores at all techniques provide good intraoperative analgesia without
time points #24 hours (2.4 vs. 1.2; P , 0.04) between the 2 affecting ocular rotations typically associated with orbital
groups in favor of bupivacaine (Fig. 2), with no difference at anesthetic techniques, thus facilitating patient cooperation
36 hours (1.8 vs. 1.2; P = 0.27). There was a trend toward during pterygium excision and preparation of the conjunctival
pain severe enough to wake the patient from sleep, but this graft. However, even with a long acting anesthetic agent like
bupivacaine, subconjunctival anesthesia provides limited post-
operative analgesia. Adjunctive measures to reduce postoper-
ative pain in this context include the use of tissue glue to secure
TABLE 1. Baseline Characteristics the conjunctival graft, the application of glue over the corneal
Bupivacaine Placebo epithelial defect, the use of patching or a bandage contact lens,
0.5% (n = 21) (n = 21) P
and the use of a cycloplegic agent postoperatively.2–5 Studies
Age (yrs) 51 (12) 50 (11) 0.70 examining the effect of a bandage contact lens show
Gender (Male) 67% (14/21) 57% (12/21) 0.53 persistently high postoperative pain scores, which suggests
European ethnicity 90% (19/21) 90% (19/21) 1.00 disruption of trigeminal nerve endings beyond the cornea
Pterygium horizontal corneal 3.6 (1.0) 3.3 (0.9) 0.76 (ie, tenon and sclera) are also implicated.4 Thus, blockade
extent (mm) of the sensory pathways proximal to the globe ensures all
Pterygium vertical corneal 5.6 (1.3) 5.3 (1.1) 0.46 the relevant sensory pathways are inhibited. Although
extent (mm)
peribulbar anesthesia is favored by some surgeons, the
Corneal epithelial defect size (mm2) 23.9 (9.9) 26.3 (15.2) 0.56
risks of serious complications are higher than those
Conjunctival graft size (mm2) 35.9 (10.1) 37.4 (13.7) 0.69
associated with a subtenon injection.6
Surgical time (min) 27.3 25.4 0.34
The present study has shown that the addition of
Preoperative pain score (/10) 2.4 (1.4) 2.6 (1.2) 0.56
subtenon bupivacaine provided significantly improved pain

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Bhikoo et al
FIGURE 2. A significant reduction in
pain within the first 24 hours was
observed in those who received
subtenon bupivacaine.
relief compared with placebo. Although traditionally thought
to provide 4 to 8 hours of postoperative analgesia, those
receiving subtenon bupivacaine had significantly less pain
and needed oral analgesia in the 24 hours after surgery. By
administering the subtenon injection near the conclusion of
surgery, we are able to preserve ocular rotations and avoid
excessive swelling of the ocular coat tissues if administered at
the start of surgery.
The advantage of our study was that it was randomized,
double blinded and performed at 2 separate sites across NZ.
This allows generalizability to other centers where tissue
adhesive is used to secure the conjunctival autograft. It may
also be extended to those still using sutures, with evidence
from the strabismus literature demonstrating significantly
reduced postoperative pain in those who received subtenon
lidocaine at the conclusion of strabismus surgery, where
sutures were used to close the conjunctiva.7 The evaluation of
FIGURE 3. Less ocular surface irrita-
tion was observed in those who
received subtenon bupivacaine at
all time points within the first 12
hours.
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Cornea  Volume 38, Number 8, August 2019
pain is challenging because of the variability and subjective
nature of the description and severity. To overcome this, we
attempted to optimize baseline pain scores for patients using
the method described by Koranyi et al,2 with both groups
evenly matched at the outset. Furthermore, our outcome
measures of ocular surface irritation and analgesic consump-
tion were incorporated to capture the multifaceted expression
of pain.
The inclusion of patients who underwent bilateral
surgery may be perceived as a limitation in the ability to
lateralize pain to either eye. From our experience of perform-
ing bilateral surgery, however, we found that patients were
able to localize pain and irritation when there was a difference
present, much like any other paired structure in the body.
When we excluded cases in whom bilateral surgery was
performed, the results did not change, with less pain and
irritation in the bupivacaine arm. Analgesia consumption per
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Cornea  Volume 38, Number 8, August 2019
TABLE 2. Total Oral Analgesia Consumed (Doses) at 24 and
36 Hours
Hours After Surgery Bupivacaine 0.5% Placebo P
24 2.5 6.5 0.0001
36 3.4 7.6 0.0002
patient was also still significantly less at 24 and 36 hours
compared with placebo.
There are inherent difficulties with accurately measur-
ing corneal and conjunctival epithelial defect size, with
interphysician variation in measurements well reported in
the literature.8 Although we were able to quantify pterygium
height and horizontal extent preoperatively using anterior
segment photography and photo editing software, this
function was not available to us intraoperatively, and instead
a flexible ophthalmic ruler was used, which does represent
a limitation of our study design. Although our sample size
was small, our study was appropriately powered to appreciate
a significant difference between the groups.
In conclusion, it has been demonstrated that a subtenon
injection of a long-acting anesthetic agent at the conclusion of
surgery improves patient comfort. Consideration should be
given to its routine use for patients undergoing pterygium
excision under topical or subconjunctival anesthesia.
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Subtenon Bupivacaine for Postoperative Pain
ACKNOWLEDGMENTS
Aneesa Mussa (randomisation and allocation assign-
ment); Ophthalmology Trainees at Waikato Hospital; Theatre
Nurses at Waikato and Palmerston North Hospitals; Bhee-
managouda Patil (Clinical Director Waikato Hospital); John
A Chan (Clinical Director Palmerston North Hospital).
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