Efficacy and Potential Complications of Difluprednate Use for Pediatric Uveitis


To evaluate the clinical effect of topical difluprednate in pediatric patients for treatment of noninfectious uveitis.


Retrospective, observational case series.


Twenty-six eyes of 14 pediatric patients with noninfectious uveitis who were treated with topical difluprednate were evaluated. Anterior and posterior cell grade, visual acuity, intraocular pressure (IOP), and cystoid macular edema (CME) were recorded at each visit. Main outcome measures were changes in anterior segment cell, CME, visual acuity, and IOP and development of a visually significant cataract.


A significant (≥ 2-grade decrease or decrease to 0 in anterior segment cell) reduction in anterior segment inflammation was observed during treatment with topical difluprednate in 88% of eyes (22/25) when used as an adjuvant to systemic immunomodulatory therapy. In addition, improvement in CME associated with uveitis was seen in response to topical therapy with difluprednate in 78% of eyes with CME (7/9). A significant IOP response (IOP increase of ≥ 10 mm Hg from baseline and IOP ≥ 24 mm Hg) was seen in 50% of eyes (13/26) and in 50% of patients (7/14); 3 eyes of 2 patients required glaucoma surgery. Cataract formation or progression was observed in 39% of eyes (10/26) and in 43% of patients (6/14); 5 eyes of 3 patients required cataract surgery.


Difluprednate is an effective agent for both control of anterior segment inflammation and reduction of CME in pediatric patients with uveitis when used as an adjuvant to systemic immunomodulatory therapy. A high rate of steroid-induced IOP elevation and cataract formation is seen in this population. Close monitoring of pediatric patients receiving difluprednate is recommended.

Pediatric uveitis is uncommon, with estimates of incidence between 4.3 and 4.9 per 100 000 persons. The visual outcomes of children with uveitis are complicated by high rates of cataract, ocular hypertension, glaucoma, and cystoid macular edema (CME). It is known that pediatric patients have a high rate of increased intraocular pressure (IOP) in response to topical or local corticosteroids. Nevertheless, topical and local corticosteroid therapy in pediatric uveitis remains a mainstay of therapy.

Topical difluprednate 0.05% (Durezol; Alcon Laboratories, Fort Worth, Texas, USA) is a topical corticosteroid that has been approved for the control of postoperative pain and inflammation, but also has been used for treatment of anterior uveitis. Difluprednate may have superior intraocular penetration compared with other topical corticosteroids. A recent pilot study, for example, showed similar anatomic outcomes between topical difluprednate and sub-Tenon triamcinolone acetonide in treatment of postvitrectomy diabetic macular edema. We sought to analyze our clinical experience with topical difluprednate in pediatric uveitis patients since its approval for use in the United States.


A database search was carried out for all patients younger than 18 years treated with difluprednate at a referral uveitis clinic (R.N.V.G.) and a referral pediatric ophthalmology clinic (E.H.) from January 1, 2009, through January 1, 2010. After initial review, patients with fewer than 6 months of follow-up were excluded.

Best-corrected visual acuity, IOP, anterior segment cell and flare, posterior segment cell, cataract grade, and presence and degree of CME were recorded for the visit at which difluprednate therapy was initiated. CME and macular thickness were evaluated at initial and follow-up visits using a Heidelberg Spectralis spectral-domain optical coherence tomography device (Heidelberg Engineering, Heidelberg, Germany) or a Stratus optical coherence tomography device (Carl Zeiss Meditec, Dublin, California, USA). Disease activity was recorded according to the Standardization of Uveitis Nomenclature Working Group recommendations. Systemic immunomodulatory medication regimens and other topical ocular therapies also were recorded. The same data were recorded for each follow-up visit throughout the treatment course of difluprednate and continuing through the end of the study period if difluprednate was discontinued during the study period. Statistical analyses were carried out using PASW Statistics version 18.0.0 (IBM SPSS, Inc, New York, New York, USA).


Our initial database search yielded 18 patients who met the inclusion criteria of having been prescribed difluprednate while younger than 18 years. Two patients were unable to fill the prescription for financial reasons and were excluded. Two patients did not have 6 months of follow-up and were excluded. The mean age of the remaining 14 patients was 12 ± 3 years. Seven male patients and 7 female patients were included. The underlying diagnosis was idiopathic chronic anterior and intermediate uveitis in 4 patients, tubulointerstitial nephritis with uveitis in 3 patients, juvenile idiopathic arthritis in 2 patients, Vogt-Koyanagi-Harada syndrome in 2 patients, and acute zonal occult outer retinopathy, pars planitis, and multifocal choroiditis with panuveitis in 1 patient each ( Table 1 ). Twelve patients had bilateral disease activity; 2 patients were affected in 1 eye only.


Pediatric Patients with Refractory Uveitis Treated with Topical Difluprednate: Baseline Characteristics and Results

Age (years)
Median 12
Range 7 to 18
Sex, % (n/N)
Female 50% (7/14)
Diagnosis, % (n/N)
Idiopathic chronic anterior and intermediate uveitis 29% (4/14)
Tubulointerstitial nephritis with uveitis 21% (3/14)
Juvenile idiopathic arthritis 14% (2/14)
Vogt-Koyanagi-Harada syndrome 14% (2/14)
Pars planitis 7% (1/14)
Multifocal choroiditis with panuveitis 7% (1/14)
Acute zonal occult outer retinopathy 7% (1/14)
Duration of difluprednate therapy (wks)
Median 27
Range 4 to 63
Total length of follow up after initiation on difluprednate (weeks)
Median 51
Range 27 to 63
Change in BCVA while taking difluprednate (logMAR)
Mean −0.08
95% Confidence interval −0.17 to 0.02
Two-grade or more decrease in anterior segment cell (SUN criteria) 88% (22/25)
Change in IOP while taking difluprednate (mm Hg)
Mean 11.2
95% Confidence interval 6.4 to 15.6
Range −6 to 36
Developed visually significant cataract, % (n/N) 39% (10/26)

BCVA = best-corrected visual acuity; IOP = intraocular pressure; logMAR = logarithm of the minimal angle of resolution; SUN = Standardization of Uveitis Nomenclature Working Group.

The median duration of therapy with topical difluprednate was 27 weeks (range, 4 to 63 weeks). The initial dosage regimen ranged from every 2 hours to 4 times daily, depending on disease activity. Changes in dosing frequency were made according to clinical response. Seven eyes of 4 patients were continued on difluprednate therapy for more than 1 year. Nine eyes of 5 patients discontinued difluprednate therapy before 6 months of treatment. In these eyes, therapy was discontinued in 8 eyes of 4 patients because of elevated IOP and was discontinued in 1 eye of 1 patient because of lack of clinical response. Of the remaining 10 eyes of 5 patients who discontinued difluprednate therapy between 6 months and 1 year of treatment, 1 patient discontinued therapy because of elevated IOP, 3 patients discontinued therapy because of subsequent control of uveitis, and 1 patient discontinued therapy for financial reasons. The median length of follow-up after discontinuation for the 19 eyes of 10 patients who stopped difluprednate therapy was 42 weeks ( Table 2 ).


Pediatric Patients with Refractory Uveitis Treated with Topical Difluprednate: Patient Data at 6-Month Follow-up Visit

Patient No. Age (years) Diagnosis Medications before Initiation of Difluprednate Other Medications Given Simultaneously with Difluprednate Change in BCVA (logMAR) >2-Grade Decrease in AC Cell (SUN Criteria) Maximum Change in IOP (mm Hg) Time to Maximum Change in IOP (wks) Developed Visually Significant Cataract Other
Right Eye Left Eye Right Eye Left Eye Right Eye Left Eye Right Eye Left Eye Right Eye Left Eye
1 a 10 Acute zonal occult outer retinopathy None Oral prednisone, FML Started LP, ended 1.6 (left eye) N/A −6 (left eye) 7 (left eye) No (left eye) Stopped at 7 wks for lack of response
2 9 Juvenile idiopathic arthritis MTX, prednisolone acetate, FML MTX 0.18 0.13 Yes Yes 2 3 38 38 No No
3 a 16 Vogt-Koyanagi-Harada syndrome MMF MMF −0.07 −0.22 Yes No 22 14 10 10 Yes Yes Stopped at 10 wks because of IOP
4 18 Tubulointerstitial nephritis with uveitis MMF, oral prednisone, prednisolone acetate MMF −0.18 0.00 Yes Yes 6 4 30 30 No Yes
5 13 Multifocal choroiditis with panuveitis MTX, prednisolone acetate MTX 0.00 −0.08 Yes Yes −2 −3 35 29 No No
6 7 Chronic anterior and intermediate uveitis Prednisolone acetate None −0.20 −0.45 Yes Yes 16 6 24 24 No Yes
7 13 Chronic anterior and intermediate uveitis Prednisolone acetate Oral prednisone, MTX, nepafenac −0.07 0.12 Yes Yes 16 13 5 5 Yes Yes
8 12 Tubulointerstitial nephritis with uveitis MMF, prednisolone acetate MMF −0.22 0.00 No No 7 4 36 36 No No
9 a 10 Chronic anterior and intermediate uveitis Infliximab, MTX Infliximab, MTX, nepafenac 0.60 −0.10 Yes Yes 33 33 6 6 Yes Yes Stopped at 6 wks because of IOP
10 14 Tubulointerstitial nephritis with uveitis Prednisolone acetate None −0.30 0.00 Yes Yes 21 20 2 2 No No
11 a 8 Juvenile idiopathic arthritis Adalimumab, prednisolone acetate Adalimumab 0.18 0.00 Yes Yes 36 34 13 13 Yes Yes Stopped at 13 wks because of IOP
12 17 Vogt-Koyanagi-Harada syndrome Oral prednisone Oral prednisone, MTX −0.6 −0.48 Yes Yes 5 1 21 21 No No
13 15 Chronic anterior and intermediate uveitis Prednisolone acetate None 0.00 (right eye) Yes (right eye) 2 (right eye) 27 (right eye) No (right eye)
14 a 10 Pars planitis None Nepafenac −0.30 0.00 Yes Yes 16 11 4 4 No No Stopped at 4 wks because of IOP

AC = anterior chamber; BCVA = best-corrected visual acuity; FML = fluorometholone ointment; IOP = intraocular pressure; LP = light perception; MMF = mycophenolate mofetil; MTX = methotrexate; N/A = Not applicable; SUN = Standardization of Uveitis Nomenclature Working Group; wks = weeks.

a Stopped difluprednate before 6 months.

At the 6-month follow-up after initiation of treatment with topical difluprednate, mean visual acuity improved by −0.08 logarithm of the minimum angle of resolution units (95% confidence interval, −0.17 to 0.02). Improved disease activity (≥ 2-grade decrease or decrease to 0 in anterior segment cell, Standardization of Uveitis Nomenclature Working Group criteria) was seen in 88% (22/25) of eyes, and inactivity (cell grade, 0) was achieved in 56% (14/25) of eyes.

CME was observed at the initial examination in 35% (9/26) of eyes. Improvement in CME was noted by the first follow-up visit in 7 of 9 eyes ( Figure 1 and Table 3 ). One patient whose CME resolved while receiving difluprednate therapy had a recurrence after difluprednate was stopped because of elevated IOP ( Figure 2 and Table 3 ).

Jan 12, 2017 | Posted by in OPHTHALMOLOGY | Comments Off on Efficacy and Potential Complications of Difluprednate Use for Pediatric Uveitis
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