Download Shortening ocular pain duration following intravitreal injections

DOI: 10.5301/ejo.5000147
Eur J Ophthalmol 2012; 22 ( 6 ): 1008-1012
ORIGINAL ARTICLE
Shortening ocular pain duration following intravitreal
injections
Lana Rifkin, Shlomit Schaal
Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, Kentucky - USA
Purpose. To determine ocular pain duration after routine in-office intravitreal injection and to determine
whether topical eyedrops are beneficial in increasing patient comfort.
Methods. Forty injection-naïve patients receiving routine intravitreal injections of bevacizumab for agerelated macular degeneration were randomized into 3 groups: group 1 (control, no drops), group 2
(generic artificial tears), and group 3 (ketorolac tromethamine 0.4% eyedrops). Those who received
topical medications were given a Visual Analog Pain score survey and asked to record their pain on
a scale from 0 (no distress) to 10 (unbearable distress) daily until a score of 0 was achieved, at which
point they were instructed to discontinue use of their given drops. Self-reported pain scores were
assessed.
Results. Pain after routine intravitreal injection lasts on average between 3 and 7 days. Patients receiving topical ketorolac eyedrops reported the fewest average number of pain days (2.25±1.22)
vs patients receiving artificial tears (3.54±1.13) or those who received no postprocedure eyedrops
(5.13±1.25); p<0.05. At most, patients receiving ketorolac eyedrops reported 3 days of recordable
pain. Those who received artificial tears reported at most 5 days of recordable pain, and patients who
did not receive any postprocedure eyedrops reported at most 7 days of recordable pain.
Conclusions. Pain after intravitreal injection is generally mild, may be reduced by postinjection topical
ketorolac eyedrops, and lasts less than 1 week.
Key Words. Age-related macular degeneration, Artificial tears, Intravitreal injection, Nonsteroidal antiinflammatory drugs, Ocular pain
Accepted: February 27, 2012
INTRODUCTION
Intravitreal injections are widely used nowadays as an inoffice procedure to deliver anti-infectious, anti-inflammatory, anticancer, anti-VEGF medications, as well as gas
into the eye (1). One of the most common side effects due
to this treatment is discomfort or pain at the site of injection. Although pain and intraocular procedures, such as
cataract surgery (2) and vitrectomy (3), have been studied, until recently, factors alleviating patients’ discomfort
during intravitreal injections were unknown. However,
several studies have recently been published, investi1008
gating the differences in methods of anesthesia, as well
as specific factors associated with decreased pain perception during intravitreal injection. Blaha et al showed
that the overall pain experience is similar, regardless of
method used: proparacaine topical eyedrops, tetracaine
topical eyedrops, lidocaine pledget, or subconjunctival lidocaine (4). Yau et al also showed no difference between
topical anesthetic agents for intravitreal injection (5). Our
study demonstrated that pain associated with intravitreal
injection is mild and may be associated with certain factors, such as gender, age, and perceived visual improvement. We also showed that pain decreases significantly
with each consecutive injection (6).
© 2012 Wichtig Editore - ISSN 1120-6721
Rifkin and Schaal
This prospective, randomized study is the first to aim at
identifying a class of eyedrops given postprocedure that
would decrease the pain intensity after intravitreal injections
as well as decrease the number of days of recordable pain.
Artificial tears are often used as an eye lubricant to treat
ocular surface disorders such as dry eyes by reestablishing
the ocular surface and thereby reducing irritation (7). Topical nonsteroidal anti-inflammatory agents such as ketorolac work by presumably inhibiting prostaglandin synthesis,
specifically, the cyclooxygenase pathway (8), and are currently indicated to decrease ocular pain and irritation associated with corneal refractive surgery (Acular package insert). Although systemic side effects of ketorolac exist and
include headache, dizziness, nausea, tachycardia, unusual
bleeding or bruising, as well as others (9), the use of topical ketorolac is quite common and has been shown to be
safe and effective in treating both inflammation and pain
following cataract surgery (10), after femtosecond laser in
situ keratomileusis (11), as well as after excimer photorefractive keratectomy (12).
METHODS
This prospective, randomized study included 40 patients
in a single center receiving routine intravitreal injections of
bevacizumab (1.25 mg/0.1 cc) for age-related macular degeneration. After informed consent was properly obtained,
each patient was randomized and assigned to one of 3
groups: group 1 (control: no postprocedure drops), group
2 (generic sterile artificial tears lubricant eyedrops, McKesson, San Francisco, CA), and group 3 (ketorolac tromethamine 0.4%, Apotex, Weston, FL, USA). Patient demographics are shown in Table I.
Injections were performed by a single surgeon (S.S.) and
standard procedure for intravitreal injection was followed
(13). All patients were naïve to this procedure prior to enrollment and each received one drop of povidone before and
after the intravitreal injection. Standard eye calipers were
used to measure the distance from the limbus (3.5 mm for
pseudophakic patients and 4.0 mm for phakic patients). All
patients were anesthetized with topical tetracaine HCl ophthalmic solution (Alcon Surgical, Fort Worth, TX, USA). All
injections were performed in the superotemporal quadrant
of each eye with a 32-gauge needle. Following treatment,
patients were given either no postinjection eyedrop, generic
artificial tears, or ketorolac eyedrops, based on their randomly assigned group. Those who received topical medications were given instructions to place one drop in the injected eye twice daily and record on a Visual Analog Pain
score survey their pain on a scale from 0 to 10, where 0
= no pain/no distress and 10 = agonizing pain/unbearable
distress, until a score of 0 was achieved. When a score of
0 was reached, patients were instructed to discontinue use
of their given drops. Patients were not given information on
the mechanism of action of the drops they were receiving.
The Visual Analog Pain Scale used in this study has
been demonstrated to be a reliable and reproducible
method of measuring patient pain (14, 15). Thirty-five
patient surveys were included, as 5 patients failed to
complete and return their surveys. Patients with any
prior eye surgery other than routine and uncomplicated
cataract surgery and patients with known dry eye disease or a history of keratopathy or keratitis were excluded. Patients with diabetes, peripheral neuropathy,
and those diagnosed with povidone-induced keratitis
were also excluded.
Statistical analysis was performed using SPSS software (11.0) for Windows. Analysis of variance with the
Bonferroni correction was used to compare the groups.
TABLE I - DEMOGRAPHICS OF STUDY PARTICIPANTS
No. of participants
No. male
No. female
Age, y
Caucasian
Group 1 (Control)
Group 2 (artificial tears)
Group 3 (ketorolac)
15
6
9
75.7
15
13
5
8
75.3
13
12
4
8
74.2
12
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Ocular pain after intravitreal injections
RESULTS
Overall pain duration
The duration of pain after intravitreal injection is demonstrated in Figure 1. A statistically significant difference was
found between the last recordable pain day among all 3
groups (p<0.05), with the duration of pain being longest
for group 1 (5.07±1.16 days). For group 2 pain duration
was 3.54±1.13 days. Pain duration was shortest for group
3 (1.75±0.75 days). The duration of pain was found to differ significantly between group 3 (p<0.05) and the other 2
groups, but not between group 1 and group 2.
Difference in pain sensation according to age
and sex
Pain duration was no different in older and younger patients among the 3 groups (p=0.32) nor between men and
women’s postinjection pain sensation in all 3 groups (group
1: p=0.41, group 2: p=0.36, group 3: p= 0.44).
Pattern of decrease in pain sensation during the
first postinjection week
Decrease in pain sensation following an intravitreal injection followed a different pattern in the 3 groups (Fig. 2). For
group 1, the average pain score decreased significantly
with each day for the first 2 days (p<0.05), but not thereafter. For group 2, the average pain score also decreased
Fig. 1 - Comparison of average last recordable pain day for patients
receiving no postprocedure eyedrops (group 1), patients receiving
artificial tears (group 2), and patients receiving ketorolac (group 3)
after injection. Analysis of variance detected a statistically significant
difference among the 3 groups. The duration of pain was different
significantly between group 3 (p=0.02) and the other 2 groups, but
not between group 1 and group 2.
significantly with each day for the first 2 days (p<0.05), but
not thereafter. For group 3, the average pain score did not
decrease significantly (p=0.07) as time went by.
DISCUSSION
Intravitreal injections have become an invaluable treatment
option for patients being treated for age-related macular
degeneration, diabetic macular edema (16), uveitis (17),
Fig. 2 - Comparison of average
pain recorded for patients in each
of the 3 groups, until a pain score
of 0 was reached. For patients in
group 1, the average pain score decreased significantly with each day
for the first 2 days (p<0.05), but not
thereafter. For patients in group 2,
the average pain score also decreased significantly with each day
for the first 2 days (p<0.05), but not
thereafter. For patients in group 3,
the average pain score did not
decrease significantly (p=0.07) as
time went by.
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© 2012 Wichtig Editore - ISSN 1120-6721
Rifkin and Schaal
and macular edema due to vein occlusion (18). As it has
become such a widely used procedure, the physician must
identify factors that may lessen the discomfort associated
with this treatment. Recent studies have elucidated factors
associated with pain during intravitreal injection; however,
this is the first randomized, prospective study shedding
light on the duration of pain after intravitreal injection and
on identifying topical eyedrops that may decrease postprocedural pain.
Our results indicate that ketorolac not only decreased the
average pain score over time, but also significantly shortened the duration of pain for patients after intravitreal injection. A recent study by Donnenfeld et al (10) showed that
ketorolac effectively treated both inflammation and pain
following cataract surgery. Nonsteroidal anti-inflammatory
agents have also been shown to be effective and safe in
the management of pain after femtosecond laser in situ
keratomileusis (11) as well as after excimer photorefractive
keratectomy (12). This is the first study to demonstrate that
ketorolac may be used to shorten the duration of pain following intravitreal injection.
Shortcomings of this study include the fact that baseline
pain levels were not obtained prior to initiating treatment.
Despite the results of our previous study showing a decrease in report of pain intensity with consecutive injection (6), patients who underwent uncomplicated cataract
surgery were included in the current study, as we are not
aware of any studies that have indicated prior surgery to be
a factor in decreasing pain perception. Also, compliance
with given medication was not measured. Previous glaucoma studies have shown that compliance with medications
is quite low (19), and may be influenced by age (although
not a consistent risk factor), cost of medication, and complicated dosing strategies (20). The average age of the patients in our study was 75 years and they were both physically and mentally capable of instilling drops themselves or
had caregivers who were able to instill for them. The cost
of medication was not an issue as we provided a sample
of both generic artificial tears and ketorolac to those who
were assigned to these groups.
Patients can be informed that pain duration is expected
to decrease significantly during the first several days after
intravitreal injection, and that pain duration rarely exceeds
1 week. Based on this study, it may be advisable to supply
patients with topical ketorolac eyedrops for the day of the
injection and 1 day after. This may be especially useful for
patients who complain of ocular sensitivity and increased
pain sensation after previous ophthalmic procedures.
The authors report no proprietary interest or financial support.
Address for correspondence:
Shlomit Schaal, MD, PhD
301E Muhammad Ali Blvd.
Louisville, KY 40202, USA
[email protected]
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