Download Evaluation of Sub-Tenon Triamcinolone Acetonide Injections in the

Evaluation of Sub-Tenon Triamcinolone Acetonide
Injections in the Treatment of Scleritis
KEEGAN S. JOHNSON AND DAVID S. CHU
● PURPOSE:
To suggest that sub-Tenon triamcinolone
acetonide (TA) injections may be a helpful supplement in
patients with scleritis.
● DESIGN: Retrospective, interventional case series.
● METHODS: A retrospective chart review was conducted
of all patients at our institution receiving sub-Tenon TA
injections for scleritis between August 2001 and August
2007. Outcome measures included subjective improvement, presence of inflammation, and adverse events.
● RESULTS: Eleven patients (12 eyes) were included in
this study. The mean age was 50 years; 2 patients were
male and 9 female. Six patients had systemic autoimmune
disease. All patients were receiving systemic medications
for scleritis at the time of injection. Mean initial follow-up time was 3 weeks. Ten of 11 patients reported
subjective improvement, and 10 patients had improvement in objective inflammation. Three patients had
adverse side effects, including ocular hypertension, worsening of cataract, and subconjunctival hemorrhage with
periorbital ecchymosis.
● CONCLUSIONS: Sub-Tenon TA injections may be a
useful adjunct to achieving transient, partial improvement
of subjective pain and objective inflammation in patients
with scleritis while awaiting systemic medications to take
effect. Adverse events were manageable in this small series.
(Am J Ophthalmol 2010;149:77– 81. © 2010 by Elsevier
Inc. All rights reserved.)
S
CLERITIS IS AN INFLAMMATORY OCULAR CONDITION
with potentially serious complications. It is characterized by severe pain and deep, destructive granulomatous inflammation in the sclera.1 Approximately 40%
to 50% of patients with scleritis have an associated
systemic disorder such as rheumatoid arthritis, Wegener
granulomatosis, systemic lupus erythematosus, inflammatory
bowel disease, or relapsing polychondritis. Rheumatoid arthritis is the most commonly associated condition.2,3 The
disease is classified as anterior or posterior; anterior scleritis is
further subdivided into diffuse, nodular, and necrotizing
patterns.4
Accepted for publication Jul 28, 2009.
From the Department of Ophthalmology, New Jersey Medical
School—University of Medicine and Dentistry of New Jersey, Newark,
New Jersey.
Inquiries to David S. Chu, Department of Ophthalmology, New Jersey
Medical School—University of Medicine and Dentistry of New Jersey,
Doctors Office Center, 90 Bergen Street, Suite 6100, Newark, NJ 07103;
e-mail: [email protected]
0002-9394/10/$36.00
doi:10.1016/j.ajo.2009.07.035
©
2010 BY
The management of scleritis presents a challenge. Because
of the severity and depth of the inflammation, topical agents
frequently are ineffective. Systemic administration of nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids,
nonsteroidal immunosuppressive agents, or a combination,
is the mainstay of treatment.2 These therapies can have
serious adverse side effects and morbidity. Although regional steroid injections have been used in the treatment
of uveitis, this approach in scleritis generally has been
avoided because of concerns about poor efficacy and
adverse side effects, including scleral perforation or melt,
glaucoma, or cataract.5–7 However, a few reports have
challenged this paradigm and have described case series of
scleritis patients receiving subconjunctival corticosteroid
injections (SCI) with positive responses.8 –11 Local corticosteroid treatment may be an attractive adjunct to systemic therapy by achieving timely improvement while
systemic medications begin to take effect. We conducted a
retrospective chart review to review our experience using
these injections.
METHODS
RECORDS WERE REVIEWED FOR ALL PATIENTS WITH SCLERI-
tis who underwent sub-Tenon corticosteroid injections
from August 2001 through August 2007 by the principal
investigator at the University of Medicine and Dentistry of
New Jersey. We used Current Procedural Terminology
(CPT) code 67515 and identified patients with scleritis.
Patients with initial follow-up data within 5 weeks after
injection were included, because we wanted to observe the
rapid effects of injections. The indications for sub-Tenon
injection included active inflammation despite systemic
treatment with NSAIDs, corticosteroids, other immunosuppressant agents, or a combination thereof, and nonnecrotizing disease. The risks, benefits, and alternatives of
injections were explained to all patients before administration. Patients underwent a detailed evaluation, including systemic and ocular history, slit-lamp examination,
intraocular pressure (IOP), dilated fundus examination,
and laboratory tests. All patients received sub-Tenon
triamcinolone acetonide (TA) injection (1 mL of a 40
mg/mL suspension). The medication was delivered with
3-mL syringe using a 25-gauge 5/8 –inch needle transcutaneously into the sub-Tenon space in the inferior temporal
aspect of the orbit.
ELSEVIER INC. ALL
RIGHTS RESERVED.
77
Outcome measures included subjective data such as
pain, foreign body sensation, discomfort, or redness, objective inflammation observed on slit-lamp examination,
IOPs, and any adverse side effects. Subjective improvement was noted if the patient reported a decrease in
symptoms. Objective improvement was defined as external
slit-lamp biomicroscopic findings of decreased scleral inflammation on a 4-point grading scale by the principal
investigator. Resolution was defined as the absence of
inflammation on examination.
mation. At the most recent examination 9 weeks later, he
had mild inflammation in both eyes while receiving
prednisone (Deltasone; Pfizer Inc) and methotrexate. Patient 6 had a history of refractory scleritis and rheumatoid
arthritis. She experienced a recurrence 21 weeks after
injection while being treated with methotrexate and prednisone. The methotrexate was changed to adalimumab
(Humira; Abbott Laboratories, Parsippany, New Jersey,
USA) with which she initially achieved quiescence, but
ultimately recurrence took place again. Her regimen subsequently was changed to infliximab (Remicade; Horsham,
Pennsylvania, USA), methotrexate, and prednisone, and
her disease was quiet on most recent examination approximately 2 years after her initial presentation.
Three patients had adverse side effects. In Patient 5,
ocular hypertension and worsening of her posterior subcapsular cataract developed. The maximum IOP across all
injections of 31 mm Hg was well controlled with topical
medications, and neither glaucoma nor optic nerve
changes developed. The topical medications were discontinued after 14 months, and her IOPs remained normal.
Visual acuity resulting from the posterior subcapsular
cataract was 20/30 at the most recent follow-up 14 months
after injection. Patient 9 had ocular hypertension with a
maximum pressure of 26 mm Hg, including all injections.
Patient 7 had subconjunctival hemorrhage and periorbital
ecchymosis, which resolved spontaneously. There were no
cases of perforation or clinically detectable scleral
thinning.
RESULTS
TWELVE EYES FROM 11 PATIENTS WITH NONNECROTIZING
scleritis were treated with SCI between August 2001 and
August 2007 and were included in the study (Table). The
mean age at injection was 50 years; 2 patients were male
and 9 female. One patient had bilateral disease. Six
patients had a concomitant systemic autoimmune disease,
including Wegener granulomatosis, rheumatoid arthritis,
celiac sprue, and systemic lupus erythematosus. One patient was a Wegener granulomatosis suspect. All patients
were receiving systemic medications before the time of
injection. Five patients were receiving NSAIDs, one of
whom was concurrently being treated with methotrexate.
Six patients were being treated with prednisone. Of these,
one was concomitantly receiving methotrexate and another simultaneously was taking mycophenolate mofetil.
Two patients were excluded because they were lost followup. One patient did not meet inclusion criteria of follow-up
within 5 weeks. At 8 weeks after injection on celecoxib
(Celebrex; Pfizer Inc, New York, New York, USA), she
experienced some discomfort, but the scleritis had resolved.
The initial follow-up visit after injection ranged from 2
to 5 weeks (mean, 3 weeks). Ten (90%) of 11 patients
reported subjective improvement in symptoms, 3 of whom
experienced complete resolution of their pain. In one
patient, subjective information was not available. In terms
of objective signs of inflammation, 10 (90%) of 11 patients
improved after injection. In 4 eyes, complete resolution of
scleral inflammation was achieved. One of these eyes was
from the patient with bilateral scleritis; the contralateral
eye had partial resolution of inflammation.
During follow-up, 8 patients had recurrent scleritis
(73%). The mean time to recurrence was 18 weeks (range,
4 to 21 weeks); median time was 16 weeks. The rate of
recurrence was 3.3 cases per person-year. Six of these
patients received and responded favorably to repeat TA
injections. The other 2 patients were managed with
systemic medications. Patient 3 had recurrent scleritis in
both eyes (20 weeks after injection in the right eye, 14
weeks after injection in the left eye). He required an
increase in baseline prednisone dose and initiation of
methotrexate (Trexall; Duramed Pharmaceuticals Inc,
Woodcliff Lake, New Jersey, USA) to control the inflam78
AMERICAN JOURNAL
DISCUSSION
SCLERITIS IS AN UNCOMMON BUT SEVERE OCULAR INFLAM-
mation that often is associated with complications. Standard treatments include systemic NSAIDs, steroids, and
systemic nonsteroidal immunosuppressive agents. SubTenon corticosteroid injections have been used in other
ocular inflammatory conditions. However, they generally
have been avoided in the treatment of scleritis because of
concerns about poor efficacy and the risk of scleral thinning or perforation. The literature supporting this notion is
comprised of a few case reports. Watson reported that
perforation and acute thinning can occur because of local
steroid injection in scleritis patients and warned against
SCI. However, detailed case descriptions were not provided. Furthermore, the steroid suspension used is unknown.5 In a response discussion to a prospective study by
Zamir and associates, Jabs briefly described one patient
with scleral melting that was believed to be secondary to
prior subconjunctival steroid injection.7,10 A literature
review revealed a few cases of scleral thinning in scleritis
patients attributed to subconjunctival steroid injections.
However, reports of rare events like scleral melts are
circumstantial by nature and preclude an accurate assessment of a true occurrence rate.
OF
OPHTHALMOLOGY
JANUARY 2010
VOL. 149, NO. 1
TABLE. Sub-Tenon Triamcinolone Acetonide Injections for Anterior Non-necrotizing Scleritis
Patient
No.
REGIONAL STEROID INJECTIONS
Age
(years)
Gender
Affected
Eye
Systemic Diagnosis
1
2
3
3
4
5
52
50
43
43
56
42
F
F
M
M
M
F
Right
Right
Left
Left
Right
Right
Rheumatoid arthritis
Idiopathic
Idiopathic
Idiopathic
Celiac sprue
Wegener granulomatosis
Celecoxib
Prednisone
Prednisone
Prednisone
Prednisone
Prednisone
2
3
5
4
5
2
6
7
45
44
F
F
Right
Left
Rheumatoid arthritis
HLA-B27⫹
Prednisone, methotrexate
Ibuprofen
8
9
10
35
66
59
F
F
F
Left
Left
Left
11
63
F
Left
Idiopathic
Idiopathic
Systemic Lupus
erythematosus
Wegener granulomatosis
suspect
Rofecoxib, methotrexate
Valdecoxib
Prednisone,
mycophenolate mofetil
Celebrex
Prior Systemic Therapy
Follow-up
(wks)
Subjective
Improvement
Tmax
Adverse Effects
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Resolved
Yes
Resolved
Yes
19.5
17
17
15
20
31
3
3
No data
Resolved
Yes
Yes
15
21
3
3
4
Yes
Resolved
Resolved
Yes
Resolved
Resolved
11
26
19
None
None
None
None
None
Worsening of posterior
subcapsular cataract
and ocular
hypertension
None
Subconjunctival
hemorrhage and
ecchymosis
None
Ocular hypertension
None
5
Yes
No
15.5
None
IN
Objective
Improvement
SCLERITIS
F ⫽ female; M ⫽ male; wks ⫽ weeks.
Recurrence
(wks)
Response to Repeat
Injection
21
18
14
20
None
4
Resolved, 4 wks
Improved, 2 wks
Managed systemically
Managed systemically
21
None
Managed systemically
16
12
None
Improved, 5 wks
Improved, 4 wks
15
Improved, 7 wks
Improved, 3 wks
79
Four published uncontrolled case series have suggested
efficacy and a low rate of side effects of SCI in scleritis
treatment. One report was a prospective series by Zamir
and associates, later expanded on retrospectively by Albini
and associates.10,11 In their group, 36 (95%) of 38 eyes
experienced complete resolution of scleral inflammation
within 6 weeks of injection, without any cases of scleral
necrosis or thinning over a median follow-up of 29
months. SCI also reduced the requirement for systemic
therapy from 94% to 49%. Tu and associates reported 18
(90%) of 20 patients achieving subjectively improved pain
and objectively reduced inflammation after SCI.8 Nine
patients (45%) had a recurrence of symptoms. No cases of
progressive scleral thinning were observed. Croasdale and
associates retrospectively described 8 patients undergoing
SCI with overall favorable results and no serious complications.9 One patient had a poor response. This same
patient had bilateral scleromalacia that occurred gradually
over several years. Finally, Sen and associates published a
retrospective case series of 4 patients receiving SCI, all of
whom achieved rapid reduction in inflammation.12 Each
patient required repeat injection in either the treated or
fellow eye after a mean of 7.4 months. Cumulatively, these
reports describe a total of 65 (93%) of 70 cases with a
beneficial response to SCI and no evidence of perforation
or observable thinning resulting from the local injection.
Our retrospective, interventional case series was intended to add further data on SCI in the treatment of
scleritis. We did not have patients with necrotizing scleritis. Our group of 11 patients (12 eyes) had roughly similar
characteristics compared with a large series describing 97
scleritis patients.2 Our group had fewer males and a slightly
larger percentage diagnosed with systemic rheumatic disease compared with the large series.
At median follow-up of 3 weeks after injection, 10
(90%) of 11 patients had improvement in subjective pain
and scleral inflammation. No cases of perforation or
observable scleral thinning were encountered. Adverse
events included ocular hypertension, worsening of posterior subcapsular cataract, and subconjunctival hemorrhage
and periorbital ecchymosis. One patient with worsened
cataract and ocular hypertension also was receiving systemic prednisone, which might have contributed to these
side effects. Given the side effect profile of systemic
prednisone including hyperglycemia, osteoporosis, and
psychiatric disturbance observed in approximately 22% of
patients combined,2 SCI in contrast are well tolerated and
may be a useful supplement to systemic therapy. Recent
studies have shown methotrexate has a favorable side
effect profile, good efficacy, and corticosteroid-reducing
effect in scleritis treatment.13–15
Our results may be confounded by concomitant systemic
medications before injection. NSAIDs have an analgesic
effect and may influence reports of clinical symptoms, and
systemic treatment likely continued to take effect on
inflammation after the injections. Our described efficacy
might have resulted from a combined or synergistic effect
of systemic and local treatment.
In conclusion, this study describes in our small population
that sub-Tenon corticosteroid injections in nonnecrotizing
scleritis can provide a rapid, transient improvement in
subjective pain and scleral inflammation with a high
relapse rate. Adverse events were manageable, but our
series is too small to evaluate the risk of severe adverse
events such as scleral melting. The general avoidance of
SCI in scleritis patients seems based on limited reports in
the literature, rather than convincing evidence suggesting
a causal relationship. Our series adds to the limited body of
data that this technique may have value and should be
considered a useful adjunct in the treatment of nonnecrotizing scleritis.
THIS STUDY WAS SUPPORTED BY AN UNRESTRICTED GRANT FROM RESEARCH TO PREVENT BLINDNESS INC, NEW YORK, NEW
York. The authors indicate no financial conflict of interest. Both authors were involved in design and conduct of study; collection of data; management,
analysis, and interpretation of data; and preparation, review, and approval of the manuscript. This study was approved by the Institutional Review Board
of the University of Medicine and Dentistry of New Jersey in accordance with Health Insurance Portability and Accountability Act regulations.
6. Watson PG. Diseases of the sclera and episclera. In: Tasman
W, Jaeger EA, editors. Duane’s Ophthalmology on CDROM. Philadelphia, Pennsylvania: Lippincott William &
Wilkins, 2007.
7. Jabs DA. Subconjunctival corticosteroids should not be used
in the treatment of scleritis (Discussion). Ophthalmology
2002;109:806 – 807.
8. Tu EY, Culbertson WW, Pflugfelder SC, Huang A, Chodosh
JC. Therapy of nonnecrotizing anterior scleritis with subconjunctival corticosteroid injection. Ophthalmology 1995;102:
718 –724.
9. Croasdale CR, Brightbill FS. Subconjunctival corticosteroid
injections for nonnecrotizing anterior scleritis. Arch Ophthalmol 1999;117:966 –968.
REFERENCES
1. Fong LP, de la Maza MS, Rice BA, et al. Immunopathology
of scleritis. Ophthalmology 1991;98:472– 479.
2. Jabs DA, Mudun A, Dunn JP, Marsh MJ. Episcleritis and
scleritis: clinical features and treatment results. Am J Ophthalmol 2000;130:469 – 476.
3. Akpek EK, Thorne JE, Qazi FA, Do DV, Jabs DA. Evaluation of patients with scleritis for systemic disease. Ophthalmology 2004;111:501–506.
4. Watson PG, Hayreh SS. Scleritis and episcleritis. Brit J
Ophthal 1976;60:163–191.
5. Watson PG. Treatment of scleritis and episcleritis. Trans
Ophthal Soc UK 1974;94:76 –79.
80
AMERICAN JOURNAL
OF
OPHTHALMOLOGY
JANUARY 2010
10. Zamir E, Read RW, Smith RE, Wang RC, Rao NA. A
prospective evaluation of subconjunctival injection of triamcinolone acetonide for resistant anterior scleritis. Ophthalmology 2002;109:798 – 807.
11. Albini TA, Zamir E, Read RW, Smith RE, See RF, Rao NA.
Evaluation of subconjunctival triamcinolone for nonnecrotizing
anterior scleritis. Ophthalmology 2005;112:1814 –1820.
12. Sen HN, Ursea R, Nussenblatt RB, Buggage RR. Subconjunctival corticosteroid injection for the treatment of non-necrotising anterior scleritis. Br J Ophthalmol 2005;89:917–929.
13. Jachens AW, Chu DS. Retrospective review of methotrexate
therapy in the treatment of chronic, noninfectious, nonnecrotizing scleritis. Am J Ophthalmol 2008;145:487– 492.
14. Kaplan-Messas A, Barkana Y, Avni I, Neumann R. Methotrexate as a first-line corticosteroid-sparing therapy in a
cohort of uveitis and scleritis. Ocul Immunol Inflamm
2003;11:131–139.
15. Shah SS, Lowder CY, Schmitt MA, Wilke WS, Kosmorsky
GS, Meisler DM. Low-dose methotrexate therapy for ocular
inflammatory disease. Ophthalmology 1992;99:1419 –1423.
REPORTING VISUAL ACUITIES
The AJO encourages authors to report the visual acuity in the manuscript using the same nomenclature that was used in
gathering the data provided they were recorded in one of the methods listed here. This table of equivalent visual acuities
is provided to the readers as an aid to interpret visual acuity findings in familiar units.
Table of Equivalent Visual Acuity Measurements
Snellen Visual Acuities
4 Meters
6 Meters
20 Feet
Decimal Fraction
LogMAR
4/40
4/32
4/25
4/20
4/16
4/12.6
4/10
4/8
4/6.3
4/5
4/4
4/3.2
4/2.5
4/2
6/60
6/48
6/38
6/30
6/24
6/20
6/15
6/12
6/10
6/7.5
6/6
6/5
6/3.75
6/3
20/200
20/160
20/125
20/100
20/80
20/63
20/50
20/40
20/32
20/25
20/20
20/16
20/12.5
20/10
0.10
0.125
0.16
0.20
0.25
0.32
0.40
0.50
0.63
0.80
1.00
1.25
1.60
2.00
⫹1.0
⫹0.9
⫹0.8
⫹0.7
⫹0.6
⫹0.5
⫹0.4
⫹0.3
⫹0.2
⫹0.1
0.0
⫺0.1
⫺0.2
⫺0.3
From Ferris FL III, Kassoff A, Bresnick GH, Bailey I. New visual acuity charts for clinical research. Am J Ophthalmol 1982;94:91–96.
VOL. 149, NO. 1
REGIONAL STEROID INJECTIONS
IN
SCLERITIS
81