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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