SAFETY AND EFFICACY OF FLUOCINOLONE ACETONIDE INTRAVITREAL IMPLANT (0.59 mg) IN BIRDSHOT RETINOCHOROIDOPATHY ASIMA BAJWA, MD,*† KANZA AZIZ, BS,*† C. STEPHEN FOSTER, MD*†‡ Purpose: To report the treatment outcomes of the fluocinolone acetonide intravitreal implant (0.59 mg) in patients with birdshot retinochoroidopathy whose disease is refractory or intolerant to conventional immunomodulatory therapy. Methods: A retrospective case series involving 11 birdshot retinochoroidopathy patients (11 eyes). Eleven patients (11 eyes) underwent surgery for fluocinolone acetonide implant (0.59 mg). Treatment outcomes of interest were noted at baseline, before fluocinolone acetonide implant, and then at 6 months, 1 year, 2 years, 3 years, and beyond 3 years. Disease activity markers, including signs of ocular inflammation, evidence of retinal vasculitis, Swedish interactive threshold algorithm–short wavelength automated perimetry Humphrey visual field analysis, electroretinographic parameters, and optical coherence tomography were recorded. Data on occurrence of cataract and raised intraocular pressure were collected in all eyes. Results: Intraocular inflammation was present in 54.5, 9.9, 11.1, and 0% of patients at baseline, 6 months, 1 year, 2 years, 3 years, and beyond 3 years after receiving the implant, respectively. Active vasculitis was noted in 36.3% patients at baseline and 0% at 3 years of follow-up. More than 20% (47.61–67.2%) reduction in central retinal thickness was noted in all patients with cystoid macular edema at 6 months, 1 year, 2 years, and 3 years postimplant. At baseline, 54.5% patients were on immunomodulatory agents. This percentage decreased to 45.45, 44.4, and 14.28% at 1 year, 2 years, and 3 years postimplant, respectively. Adverse events included increased intraocular pressure (54.5%) and cataract formation (100%). Conclusion: The data suggest that fluocinolone acetonide implant (0.59 mg) helps to control inflammation in otherwise treatment-refractory cases of birdshot retinochoroidopathy. It is associated with significant side effects of cataract and ocular hypertension requiring treatment. RETINA 34:2259–2268, 2014

B

prominence of “birdshot” choroidal lesions. The late stage is characterized by cystoid macular edema (CME), vascular attenuation, and retinal pigment epithelial, choroidal, and optic nerve atrophy. Although 20% of patients may go into remission without treatment, 80% have a relentlessly progressive course. The BSRC can remain active and produce severe vision loss over 2 to 3 decades.6,7 The disease course is monitored by visual acuity, vitreous cellular reaction, retinal vascular leakage, and the appearance of the chorioretinal lesions. Periodic ancillary testing such as fluorescein angiography (FA), indocyanine green angiography, optical coherence tomography, blue on yellow perimetry, and electroretinography (ERG) are strongly suggested to monitor disease activity.8–11

irdshot retinochoroidopathy (BSRC) was first described in 1980, when Ryan and Maumenee1 noticed hypopigmented retinal lesions in the eyes of 13 patients resembling a pattern seen in birdshot by pellets from a shotgun. This intraocular disease is rare, bilateral, chronic, and inflammatory in nature, leading to painless, progressive visual loss. It is characterized by the presence of multiple depigmented ovoid spots in the retinal pigment epithelium and the choroid.1–3 Birdshot retinochoroidopathy is a rare entity, reported to be the cause of posterior uveitis in 7.9% of cases.4 It has been strongly associated with the HLA-A29 gene, with as many as 97.5% of patients being positive for this gene.5 Early-stage disease is characterized by retinal vascular leakage, whereas the mid phase shows increasing 2259

2260 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES

Because of the chronic, progressive course of this disease, treatment can be challenging. Treatment with systemic corticosteroids is generally ineffective in the long term.7,12 Most cases are now being treated with conventional immunomodulatory therapy (IMT) or biologic agents.7,13–16 However, in some cases, even conventional IMT alone fails to induce remission. A search for other treatment modalities could prove to be of therapeutic benefit to patients with this vision-robbing disease. Because there are no known or suspected systemic associations with BSCR, intraocular drug delivery provides a potentially useful alternative to immunosuppressive medication or systemic corticosteroids.17,18 We report our experience with implantation of an Food and Drug Administration–approved, sustainedrelease intraocular drug delivery device containing 0.59 mg of fluocinolone acetonide (Bausch & Lomb, Rochester, NY) in 11 eyes of 11 patients with BSRC refractory or intolerant to conventional IMT. It has previously been shown to be effective in the treatment of noninfectious posterior uveitis,19–21 macular edema,22,23 and BSRC.24 Methods Study Population Eleven eyes from 11 BSRC patients who received fluocinolone acetonide at the Massachusetts Eye Research and Surgery Institution, a tertiary care center, Cambridge, Massachusetts, from July 2005 through October 2011 were included in this report. Patients met the research criteria for BSRC defined by an international consensus: bilateral presence of at least 3 peripapillary birdshot typical lesions with low-grade anterior segment inflammation (,1+ cells) and vitreous inflammation (#2+ vitreous haze).25 The data were collected From the *Massachusetts Eye Research and Surgery Institution, Cambridge, Massachusetts; †Ocular Immunology & Uveitis Foundation, Cambridge, Massachusetts; and ‡Harvard School of Medicine, Cambridge, Massachusetts. None of the authors have any financial/conflicting interests to disclose. A. Bajwa: concept and design, analysis and interpretation, writing, critical revision, final approval, statistical expertise, data collection, and administrative/technical support. K. Aziz: concept and design, analysis and interpretation, writing, critical revision, final approval, statistical expertise, data collection, and administrative/ technical support. C. S. Foster: concept and design, analysis and interpretation, writing, critical revision, final approval, data collection, statistical expertise, obtaining funding, literature search, and administrative/technical support. Reprint requests: C. Stephen Foster, MD, Massachusetts Eye Research and Surgery Institution, Ocular Immunology & Uveitis Foundation, 5 Cambridge Center, 8th Floor, Cambridge, MA 02142; e-mail: [email protected]



2014  VOLUME 34  NUMBER 11

retrospectively. Institutional Review Board approval was obtained before initiating the study; investigators adhered to the tenants of the Declaration of Helsinki. Data Collection A chart review was performed at the Massachusetts Eye Research and Surgery Institution. Collected variables included demographic data, including age, gender, and HLA-A29 status. Previous and concomitant treatments and follow-up times were also noted. Disease activity monitoring was based on signs of ocular inflammation, blue on yellow SITA-SWAP (Swedish interactive threshold algorithm—short wavelength automated perimetry) Humphrey visual field analysis, the results of ERG, optical coherence tomography, and FA/indocyanine green angiography. Data on previous and concomitant treatment included use of corticosteroids, conventional immunosuppressive medication, and other biologic agents. Side effects of fluocinolone acetonide insert were also noted. Outcomes The outcome features of primary interest were evidence of active inflammation, change in visual acuity, and persistent or resolving CME. The treatment results were assessed at 6 months, 1 year, 2 years, 3 years, and maximum follow-up available after fluocinolone acetonide insertion. Standardization of Uveitis Nomenclature Working Group criteria were used for grading inflammation.26 Electroretinography was performed semiannually on an SG 2002 system (LKC Technologies, Gaithersburg, MD) to monitor retinal function, measurements were performed in accordance with the international standard protocol and, 30-Hz flicker implicit time was chosen as the primary parameter of interest based on previous observations on this matter in patients with BSRC.8 Perimetry blue on yellow SITA-SWAP was recorded. Prolongation of implicit time or progression of mean deviation (MD) was considered as evidence of active disease. Control of inflammation was defined as the absence of intraocular inflammation, resolution of vasculitis observed on fluorescein angiogram, stability or improvement of 30-Hz flicker implicit time shown on an ERG, and MD on SITA-SWAP blue on yellow visual fields after initiating therapy. Relapse of BSRC was defined as increase in inflammation, recurrence of vasculitis on FA, prolongation of 30-Hz flicker implicit time on ERG, or worsening of MD on Humphrey visual field analysis. Fluorescein angiography was used for monitoring markers of disease activity, including vasculitis and papillitis, as evidenced by late vascular or optic nerve head staining, or both. The FA findings

2261

BSRC AND RETISERT  BAJWA ET AL Table 1. Patient Demographics and Immunomodulatory Therapy Use Patient No.

Age (Years)

Study Sex Eye HLA Status

Previous Treatment (Systemic/Ocular) IMT

Other

1

58

F

OD

Data not available

Mycophenolate mofetil, cyclosporin A

2

54

M

OD

HLA-A29

3

44

F

OD

HLA-A29

4

62

F

OD

Data not available

5

62

M

OD

HLA-A29

6

68

F

OD

HLA-A29

7

51

F

OD

HLA-A29

8

56

F

OD

HLA-A29

9

52

M

OD

HLA-A29

10

44

M

OS

Data not available

11

42

F

OD

HLA-A29

Mycophenolate mofetil, cyclosporin A, intravenous immunoglobulin, prednisone Methotrexate, daclizumab, cyclosporin A, mycophenolate mofetil, prednisone Mycophenolate mofetil, azathioprine, methotrexate, cyclosporin A Mycophenolate mofetil, cyclosporin A, prednisone Mycophenolate mofetil, cyclosporin A, prednisone Mycophenolate mofetil, cyclosporin A, infliximab Mycophenolate mofetil, cyclosporin A, sirolimus Mycophenolate mofetil, cyclosporin A Methotrexate, infliximab, mycophenolate mofetil, cyclosporin A, prednisone Methotrexate, daclizumab, infliximab, cyclophosphamide, rituximab, intravenous immunoglobulin

Side Effects of IMT Before Retisert Implant

Followup Time (Years)

1

None

3.1

2

Worsening kidney functions Systemic hypertension

4.3

4

—

1.5

5

Raised Blood Urea Nitrogen and Creatinine

1.4

Patient No.

3

3.5

6 Months

Retisert Indication

Intravitreal triamcinolone acetonide, intravitreal bevacizumab Topical prednisone, intravitreal triamcinolone acetonide

Persistent CME

Topical prednisolne

Persistent CME

IMT failure and intolerance

None

IMT failure

Trans-septal triamcinolone

IMT failure and intolerance

None

IMT intolerance

Dexamethasone intravitreal implant None Intravitreal bevacizumab Topical prednisone

1 Year

IMT intolerance IMT failure Persistent CME IMT intolerance and failure

None

IMT failure

2 Years

3 Years

IMT Use After Fluocinolone Acetonide Intravitreal Implant Mycophenolate mofetil, Mycophenolate cyclosporin A mofetil Mycophenolate mofetil, Mycophenolate sirolimus mofetil Mycophenolate mofetil Mycophenolate mofetil, celecoxib

None

None

Mycophenolate mofetil Mycophenolate mofetil, celecoxib

Mycophenolate mofetil, celecoxib

Mycophenolate mofetil, Intravenous intravenous immunoglobulin immunoglobulin Mycophenolate mofetil, None cyclosporin A (continued on next page)

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2014  VOLUME 34  NUMBER 11

Table 1. (Continued )

Patient No. 6

7

8 9 10 11

Followup Time (Years)

6 Months

Elevated liver enzymes, raised Blood Urea Nitrogen and Creatinine Tingling in toes and legs along with cramping, burning sensation Hypertension, nausea —

3.1

None

None

None

3.2

None

None

None

3.1

None

None

None

3.0

Gastritis —

3.8 3.1

Mycophenolate mofetil, cyclosporin A None None

Side Effects of IMT Before Retisert Implant

1 Year

2 Years

3 Years

IMT Use After Fluocinolone Acetonide Intravitreal Implant

in active disease also included leakage of dye from capillaries and venules and delayed arterial filling time. Optical coherence tomography or FA was used to evaluate CME. Macular edema was defined as a retinal thickness of 315 mm or greater in the central subfield.27 Improvement in CME was defined as a 20% reduction in macular thickness or resolution of edema if a ,20% decrease led to normalization in the macular thickness.28 Resolution of CME was defined as a decrease in macular thickness to a normal level (,315 mm).29 Adverse events of fluocinolone acetonide were also recorded. Failure was defined as disease progression despite IMT, intolerance to significant side effects, or both. Disease progression was defined as persistent active inflammation, vasculitis on FA, prolongation of 30-Hz flicker implicit time on ERG, and progression of MD on SITA-SWAP blue on yellow visual field analysis. Statistical Analysis Descriptive data analysis was performed. The IBM SPSS statistical software package version 17 (IBM Co, Chicago, IL) was used for data analysis and to calculate the percentages. Observed outcomes at 6 months and 1 year, 2 years, and 3 years and beyond were calculated. Side effects of fluocinolone acetonide insert were also calculated as a proportion. Results Clinical characteristics of the study population are summarized in Table 1. Eleven BSRC patients (11

Mycophenolate mofetil, Mycophenolate cyclosporin A mofetil None None Ranibizumab None

None None

eyes) with a median follow-up of 31 months were included in this report; 63.6% were women. Eight patients were HLA-A29 positive while 3 had missing data. The mean age was 53.9 ± 8.37 years. Before fluocinolone acetonide implant insertion, seven patients had either failed or were intolerant to conventional immunosuppressive therapy. Four patients had persistent CME. At the time of insertion of the implant, all patients were either on immunosupressants, biologic agents, or intravenous immunoglobulin. Among 11 patients, 90.9, 90.9, 36.36, 18.18, 18.18, 18.18, and 9.99% received mycophenolate mofetil, cyclosporine, methotrexate, azathioprine, octreotide acetate, intravenous immunoglobulin, and sirolimus, respectively. Five patients (45.45%) had received another biologic agent, infliximab, daclizumab, or rituximab, and 5 (45.45%) were on oral corticosteroids. The proportion of patients off IMT increased steadily to 5/11 (45.4%) at 6 months and 12 months, and 6/9 (44.4%) and 3/4 (75%) at 2 years and 3 years postimplant, respectively (Table 2). Seven of 11 patients (63.6%) were treated with ocular therapy at baseline. These patients received prior topical corticosteroids, intravitreal or periocular triamcinolone acetonide, or intravitreal bevacizumab. None of patients required topical or intravitreal corticosteroid after the implant. At baseline visit, 6 of 11 patients (54.5%) had active intraocular inflammation. Six months after fluocinolone acetonide implant, the number dropped to 1 (9.99%). One of 9 patients (11.1%) at 2 years and none of the 7 patients at 3 years postimplant had evidence of intraocular inflammation on slit-lamp biomicroscopy. Eight patients had a follow-up beyond 3 years ranging

Table 2. Intraocular Pressure Management Patient IOP No. Baseline

Peak IOP 0–6 SLT 0–6 Months Months

Medical Treatment 0–6 Months, No. of Medication

Surgical Treatment 0–6 Months

Peak IOP 6–12 Months

SLT 6–12 Months

Surgical Rx 6–12 Months

Peak IOP 12–24 Months

1 None 2 None 1 None None 4 medications and acetazolamide

26 25 18 24 20 24 21 26

30 24

1 2 3 4 5 6 7 8

13 9 14 10 12 11 16 9

20 16 20 15 20 12 31 50

None None None None None None None None

None None None None None None 2 4

None None None None None None None None

26 18 21 10 22 14 18 44

None None None None None None None None

9

17

44

None

4

23

None

3

10 11

11 10

37 18

None None

2 None

Ahmed glaucoma valve Trabeculectomy None

None None None None None None None Ahmed glaucoma valve None

25 21

None None

2 1

None None

SLT 12–24 Months

Medical Treatment 12–24 Months; No. of Medication

Surgical Treatment 12–24 Months

Peak IOP 24–36 Months

1 2 3

None None None

1 None 2

None None None

20 26 25

4 5 6 7 8 9 10

None None None None None None None

2 3 1 None 4 3 3

None None None None None None None

11

None

None

None

Patient No.

Peak IOP After 36 SLT Months After 36 Date Months

21

Medical Rx 24–36 Months, No. of Medication 1, 2, .2

Surgical Treatment

None None None

2 None 2

None None None

— — 25

— — None

— — —

N/A — 26 — — — 60

None — None — — — None

Trabeculectomy — None — — — Ahmed glaucoma valve

6 — 29 — — — 15

None — None — — — —

None — 3 — — — —

32

None

2 — 1 — — — 4 medications and acetazolamide 2

— — Ahmed glaucoma valve None — None — — — —

None

42

None

4 medications and acetazolamide

Ahmed glaucoma valve

SLT

Medical Treatment After 36 Months

Surgical Treatment After 36 Months

BSRC AND RETISERT  BAJWA ET AL

Medical Treatment 6–12 Months, No. of Medication

SLT, Selective Laser Trabeculoplasty.

2263

Patient No.

CRT/FA Baseline

CRT/FA 6 CRT/FA 1 Months Year

CRT/FA 2 Years

CRT 3 Years

1

364

210

205

2 3

— 606

No No leakage leakage on FA on FA — — 272 263

4 5 6 7 8 9 10

— — — — — 420 374

— — — — — 267 271

11

—

—

Patient No.

Vitirits Baseline

3 4 5

Negative Negative 2.5+ cells 1+ haze Negative Vitreous haze 1+ 2+ cells Negative Negative 1+ cells, haze 1+

6 7 8 9 10 11

Vitirits 6 Vitirits 1 Vitirits 2 Vitirits 3 Months Year Years Years

—

Anterior Uveitis 1 Year

Anterior Uveitis 2 Years

Anterior Uveitis .3 Years

Anterior Uveitis 3 Years

Negative

Negative

Negative

Negative

Negative

Negative

1.5+ cell Negative

Negative Negative

Negative Negative

Negative Negative

Negative Negative

— Negative

Negative Negative Negative Negative Negative Negative Negative

Negative Negative Negative Negative Negative Negative Negative

Negative Negative Negative Negative Negative Negative 3+ cells

Negative Negative Negative Negative Negative — Negative

Negative Negative Negative Negative Negative — 1+ cells

Negative Negative Negative Negative Negative

Negative

Negative

Negative

Negative

Negative

Negative

Vitirits .3 Years

Vasculitis Baseline

Vasculitis 6 months

Negative

Vasculitis 1 Year

Vasculitis Vasculitis 2 Years 3 Years

Vasculitis .3 Years

Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Papillitis positive, vasculitis negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Positive 2+ cells Negative Negative Negative — Positive

Negative Papillitis resolved, vasculitis negative Negative Negative Negative

Negative Negative

Negative Negative

Negative Negative

Negative Negative

Negative Negative Negative

Negative Negative Negative

Negative Negative Negative

Negative — —

Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative

Negative Negative

Negative Negative

Negative Negative

Negative Negative

Negative Negative

Negative Negative Negative Negative

Negative Negative Negative Negative

Negative Negative Negative Negative

Negative Negative Negative Negative

Negative — Negative Negative

Negative — Negative Negative

CRT, central retinal thickness.

Negative Negative Negative Negative Negative — — 3+ cells 2+ cells Negative Negative Negative Negative Negative Negative

Negative Negative Positive Positive

2014  VOLUME 34  NUMBER 11

Negative 2+ cells

—

Anterior Uveitis 6 Months



1 2

— — — — — 330 277, no leakage on FA —

— — No leakage 232 on FA — — — — — — — — — — — — Data not No leakage available on FA

Anterior Uveitis Baseline

2264 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES

Table 3. Inflammation Status, According to Optical Coherence Tomography, Fluorescein Angiography, and Slit-Lamp Examination Findings

2265

BSRC AND RETISERT  BAJWA ET AL

Fig. 1. Proportion of patients with active inflammation.

from a total of 1 month to 13 months and all of them were in remission (Table 3, Figure 1). At baseline, 4 of 11 patients had active vasculitis on fluorescein angiogram. At 6 months follow-up and onwards, none of the patients had active vasculitis. An initial visual acuity of $20/40 was found in 6 of 11 patients (54.5%), whereas 7 of 11 (63.6%) achieved visual acuity $20/40 at 6 months and 1 year. At 2 years and 3 years, respectively, 6 of 9 patients (66.6%) and 6 of 8 patients (75%) had a visual acuity of $20/40 (Table 4, Figure 2). Four patients in our study had a CRT $364 mg (average 441 mg, range 364–606 mg) at baseline. After 6 months of fluocinolone acetonide implant, all patients achieved complete resolution of CME. This remained unvarying till 2 years and 3 years of follow-up (Figure 4). Prolonged implicit time was initially seen in 88.8% and 60% at the end of 3 years (Table 4). On visual fields analysis, group mean was abnormal at all time points for the study period for both MDs and pattern standard deviation. Although MD improved at 6 months and then remained stable by the end of 3 years, pattern standard deviation did not show any change throughout the study period. Initially, 4 of 11 patients (36.36%) were pseudophakic. The cumulative proportion of pseudophakia increased to 85.7% by 12 months and was 100% by 3 years among eyes remaining in the study (Table 5). Before implantation, all 11 eyes had an intraocular pressure (IOP) ,20 mmHg (average 12 mmHg) without IOP-lowering medication. Average IOP increased to 26.2 mmHg to 31 mmHg (78.7–162.5%) during 3 years

Fig. 2. Proportion of patients who did not achieve visual acuity of $20/ 40 (only those patients who had visual acuity worse than 20/40 at baseline).

of follow-up (Table 2). During first 6 months, 4 of 11 eyes (36.3%) required 1 to 4 pressure-lowering medication. This proportion increased to 7 of 11 (63.6%) by 1 year and 6 of 7 (85.7%) by 3 years. Two of 11 eyes (18.2%) by 6 months and 4 of 7 eyes (57.1%) by 3 years required glaucoma surgery (Ahmed glaucoma valve, trabeculectomy) (Figure 3). Of the 11 patients, 4 patients received the implant in only 1 eye. These patients had active intraocular inflammation or CME. They attained bilateral remission and resolution of CME till the last follow-up. Discussion The patients in our study appeared to be identical to birdshot patients described in other series in terms of retinal vascular leakage, CME, abnormal ERG, and relatively preserved Snellen visual acuity.12,30 The baseline prevalence of cataract seemed to be similar to other studies but that of glaucoma was low.14 Implantation demonstrated beneficial effects by maintaining or improving visual acuity and vitreous clarity, by reducing cellular inflammation and retinal vascular leakage on FA, and by preserving implicit time on 30 Hz ERG throughout the course of the study. These clinical outcomes for birdshot patients seemed similar to those with other types of noninfectious posterior uveitis who were treated with the fluocinolone-containing intraocular device.21,30–33 In addition, our study shows 8 patients still in remission, with a follow-up beyond

Table 4. Visual and Electroretinography Changes

Visual acuity $20/40 Prolongation of 30 Hz implicit time on ERG

Baseline

6 Months

1 Year

2 Years

3 Years

6/11 (54.5%) 8/9 (88.8%)

7/11 (63.6%) 6/8 (75%)

7/11 (63.6%) 7/9 (77.7%)

6/9 (66.6%) 5/8 (62.5%)

5/7 (71.4%) 3/5 (60%)

2266 RETINA, THE JOURNAL OF RETINAL AND VITREOUS DISEASES



2014  VOLUME 34  NUMBER 11

Fig. 3. Glaucoma-related side effects of the implant.

3 years. We wonder if it is possible that, given a sufficiently long period of sustained control of inflammation, the patient’s deregulated immune system may have the opportunity to regain autoregulation such that even after the contents of the fluocinolone acetonide implant are expended, autoimmune inflammation does not return in some instances. Results from another study of 8 patients with sympathetic ophthalmia, treated with fluocinolone acetonide implant, demonstrated a reduction in the need for systemic immunosuppression after implantation.31 Whether local suppression of inflammation without systemic immunosuppression is adequate is of interest because both birdshot retinochoroidopathy and sympathetic ophthalmia are assumed to result from a systemic autoimmune response. Sympathetic ophthalmia can involve other pigmented tissues, whereas disease expression in birdshot is confined to the eye. Rush et al24 have reported implantation of a fluocinolone acetonide containing intraocular device in birdshot

Fig. 4. Mean central retinal thickness over time.

retinochoroidopathy patients with improved vision, controlled inflammation, and elimination of systemic therapy. They also reported a high incidence of cataract progression and intraocular hypertension or glaucoma.24 Our study differs as all 11 of our patients had at least 1 year of follow-up data available. Also, we had consistent 30 Hz ERG and optical coherence tomography monitoring that yielded significant results in terms of clinical outcomes. Moreover, in our study, fluocinolone acetonide implant permitted the successful reduction or discontinuation of systemic immunosuppressive therapy. Eight of these 11 patients had a follow-up beyond 3 years and were still in remission. Four patients in our study received fluocinolone acetonide in only one of the eyes. Three of these 4 patients achieved remission in both eyes at 1-year follow-up. This is obviously a very interesting phenomenon, which has not been reported in earlier studies. How is it possible for the implant in one eye to be beneficial for the fellow eye? Previous studies have reported bilateral ocular beta-blockade possibly by systemic absorption of timolol from the application to only one treated eye and redistribution to the fellow eye.34,35 Can flucinolone acetonide act the same way? Is it possible that for patients who have BSCR, if one eye is quiet for a sustained period, it has a beneficial influence on inflammation in the other eye simply by reducing immune responsiveness of the patient with the reduced target epitope burden? These topics may be amenable to further study, particularly in a larger cohort of BSCR patients. Intraocular pressure elevation has been recognized as a common complication of regional corticosteroid use. In 278 patients with noninfectious causes of posterior

2267

BSRC AND RETISERT  BAJWA ET AL Table 5. Side Effects of the Implant Baseline

6 Months

1 Year

2 Years

3 Years

Number of patients with IOP .20 mmHg 0/11 (0%) 4/11 (36.36%) 5/11 (45.45%) 4/9 (44.4%) 3/7 (42.85%) Number of patients on IOP-lowering 1/11 (9.09%) 4/11 (36.36%) 7/11 (63.63%) 8/9 (88.88%) 6/7 (85.71%) medications Number of patients who had to undergo — 2/11 (18.18%) — 3/9 (33.33%) 4/7 (57.14%) glaucoma surgery Number of patients who underwent cataract — 3/7 (42.85%)* 6/7 (85.71%) 7/7 (100%) — surgery *Four patients had cataract surgery before Retisert implant.

uveitis prospectively followed for 3 years after implantation of the fluocinolone acetonide–containing intravitreal device, 78% of implanted eyes required topical IOP-lowering therapy and 40% of implanted eyes required IOP-lowering surgery.32 In a larger series of 584 eyes, including many of the same patients, topical IOP-lowering medications were required in 74.8% of implanted eyes, and IOP-lowering surgeries were performed in 36.6% of implanted eyes by 3 years.35 We observed a similar IOP phenomenon in our study as is reported by recent cohort study of 48 eyes.30 Of the 11 patients in our study with ascertainable outcomes, 6 (85.7%) required medical therapy and 4 (57.1%) required glaucoma surgery. Additionally, the FA implant may be a poor choice for patients with preexisting glaucomatous damage, depending on the degree of damage; or if such glaucomatous damage exists, it may be prudent to perform the FA implantation in conjunction with a glaucoma surgery as has been described previously.36 The risk of requiring cataract surgery following implantation in this study is similar to previously published results in which 93% or 100% of phakic eyes were operated by 3 years after implantation.32 Birdshot retinochoroidopathy appears to confer no special risk for cataract formation, which is nearly universal following corticosteroid implantation, and the lack of clinically significant anterior segment inflammation favors uncomplicated cataract surgery. The benefit of well-controlled inflammation with fluocinolone intravitreal implant should be weighed against the high rate of progression of cataract and elevation of IOP because all phakic patients continuing under follow-up required cataract surgery and a significant number of patients required either medical or surgical management for high IOP at 3 years of follow-up. Candidates for fluocinolone acetonide implant must be willing to undergo cataract surgery, be available for frequent IOP monitoring, and be prepared to have IOP-lowering surgery if necessary. Despite these limitations, birdshot retinochoroidopathy is a purely ocular disease that may not need systemic immunosuppression, and the patients in this series appeared to have improved

vision, excellent control of inflammation, and preservation of global measures of retinal function such as visual fields and 30 Hz implicit time on ERG. Given the possible side effects of systemic immunosuppression, implantation of a corticosteroid-containing drug delivery device may be a realistic therapeutic alternative in selected patients with BSRC. Weaknesses of this study include its retrospective nature, the lack of a treatment comparator other than the baseline status, and few study participants. Additionally, our study population may differ from others, given our status as a tertiary care center.

Conclusion Fluocinolone acetonide intravitreal implant may be a reasonable option in improving or preserving visual acuity, controlling inflammation, preventing disease progression, eliminating the need for systemic therapy, and inducing remission in patients with birdshot retinochoroidopathy. However, it is associated with a significant risk of intraocular hypertension requiring medical or surgical intervention and cataract development. Key words: birdshot retinochoroidopathy, corticosteroid, fluocinolone acetonide, implant, uveitis. References 1. Ryan SJ, Maumenee AE. Birdshot retinochoroidopathy. Am J Ophthalmol 1980;89:31–45. 2. Kaplan HJ, Aaberg TM. Birdshot retinochoroidopathy. Am J Ophthalmol 1980;90:773–782. 3. Priem HA, Oosterhuis JA. Birdshot chorioretinopathy: clinical characteristics and evolution. Br J Ophthalmol 1988;72:646–659. 4. Rodriguez A, et al. Referral patterns of uveitis in a tertiary eye care center. Arch Ophthalmol 1996;114:593–599. 5. Nussenblatt RB, et al. Birdshot retinochoroidopathy associated with HLA-A29 antigen and immune responsiveness to retinal S-antigen. Am J Ophthalmol 1982;94:147–158. 6. Rothova A, Berendschot TT, Probst K, et al. Birdshot chorioretinopathy: long-term manifestations and visual prognosis. Ophthalmology 2004;111:954–959.

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