BILATERAL CHOROIDAL NEOVASCULARIZATION IN BIRDSHOT RETINOCHOROIDOPATHY TREATED WITH INTRAVITREAL INJECTIONS OF TRIAMCINOLONE AND BEVACIZUMAB Claudia Brue`, MD, Daniela C. Ferrara, MD, Yale L. Fisher, MD, Richard F. Spaide, MD
Purpose: To describe a patient with birdshot retinochoroidopathy (BRC) with bilateral choroidal neovascularization (CNV) who was treated with intravitreal injection of bevacizumab and antiinflammatory medications. Method: Interventional case report. Patient: A 35-year-old woman with bilateral CNV associated with BRC. Results: The patient was treated with intravitreal injection of triamcinolone, photodynamic therapy, and intravitreal injection of bevacizumab in one eye, while the fellow eye was treated with intravitreal injection of triamcinolone. Immunosuppressive therapy was performed in the course of the treatment. Not only did the neovascularization respond, but the birdshot lesions vanished as well. Discussion: BRC can have secondary CNV that, as in the current case, responds favorably to treatment. We serendipitously observed regression of the choroidal inflammatory lesions with intravitreal injection of triamcinolone. RETINAL CASES & BRIEF REPORTS 3:42– 46, 2009
From the Vitreous, Retina, Macula Consultants of New York, and the LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital, New York, New York.
investigators suggesting that treatment of the underlying inflammatory disorder does not modify the course of the disease.1 However, therapy is often instituted late in the disease process, after there has been a large amount of inflammatory damage. On rare occasion, choroidal neovascularization (CNV) may develop in patients with BRC.2 We describe a patient who had early BRC and developed bilateral CNV. We treated the CNV with intravitreal injection of triamcinolone in both eyes and with intravitreal injection of bevacizumab in one eye. Not only did the CNV respond, but the birdshot lesions regressed as well.
B
irdshot retinochoroidopathy (BRC) is an idiopathic chronic bilateral inflammatory disease affecting the retina and choroid that is characterized by multiple cream ovoid spots. Late in the disease process, patients can have visual field loss, color vision abnormalities, nyctalopia, and decreased central visual acuity. Therapy for BRC is controversial, with some
This work was supported by The Macula Foundation, Inc. (New York, NY). The authors have no financial interest in this report. Dr. Claudia Brue` is currently affiliated with the University Politecnica delle Marche, Ancona, Italy. Reprint requests: Richard Spaide, MD, Vitreous, Retina, Macula Consultants of New York, 460 Park Avenue, 5th Floor, New York, NY 10022; e-mail: [email protected]
Case Report A 35-year-old woman presented with decreased vision, floaters, and nyctalopia in both eyes. Visual acuity was 20/60 in the right eye and 20/20 in the left eye. Cellular infiltrates were detected in the vitreous cavity. Multiple cream– colored spots, each about one fourth of a disk diameter, were found at the level of the choroid.
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Fig. 1. Color photograph of the right eye with subtle cream spots in the fundus consistent with birdshot retinochoroidopathy (BRC) showed a grayish subretinal lesion with hemorrhage (A). Visual acuity was 20/60. Early-phase (B) and late-phase (C) fluorescein angiograms demonstrated choroidal neovascularization (CNV) and multiple spots at the level of the choroid. Fluorescein angiogram of the left eye showed typical BRC spots without any evidence of CNV (D). Both eyes had late-phase staining of the nerve.
She also had a submacular hemorrhagic lesion in the right eye consistent with CNV. Fluorescein angiography confirmed the presence of CNV. In the early phases of fluorescein angiography, multiple hypofluorescent spots were seen at the level of the choroid, but by the middle and late phases, these spots were not visible (Fig. 1). The patient had late-phase staining of the optic nerve. Indocyanine green angiography showed dark spots radiating from the optic nerve to the periphery in all four quadrants. In addition to CNV, a tentative diagnosis of BRC was made. Because the patient had CNV associated with uveitis, treatment of both inflammatory and neovascular aspects was thought to be best accomplished by intravitreal injection of triamcinolone, followed later by photodynamic
Fig. 2. Fluorescein angiography demonstrating a slight reduction in the size of the choroidal neovascularization and absence of the birdshot retinochoroidopathy (BRC) lesions in the right eye 1 week after intravitreal triamcinolone injection (A). Visual acuity was 20/40. The left eye continued to have typical BRC lesions (B).
therapy (PDT) using verteporfin. The patient presented before the availability of effective anti–vascular endothelial growth factor agents. The patient underwent a complete workup, including serologic tests negative for angiotensin-converting enzyme, antinuclear antibodies, and antibodies to Borrelia burgdorferi. Serology was checked using the VDRL test, the results of which were negative. Chest roentgenography did not show any abnormalities, and results of the tuberculin test were negative. HLA-A29 testing was positive. The patient was initially treated with intravitreal injection (4 mg) of triamcinolone. When examined 1 week later, visual acuity was 20/40, there was a slight reduction in the CNV size, and the birdshot lesions were not visible in the right eye (Fig. 2). She did
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Fig. 3. One month after intravitreal triamcinolone injection, the patient had reduction in the size of the neovascular lesion with an increase in pigmentation (A). Fluorescein angiography showed slight leakage at the foveal aspect of the neovascularization (B). The patient received photodynamic therapy and when examined 1 month later continued to have slight leakage during fluorescein angiography (C) and intraretinal edema by optical coherence tomography (D).
not have staining of the optic nerve. One month after the triamcinolone injection, visual acuity was 20/60, and the birdshot lesions were undetectable. She had leakage from the CNV and was treated with PDT (Fig. 3). When examined 1 month after PDT, she did not have any changes in the CNV appearance or in the amount of leakage visible during fluorescein angiography. She was asked to return in 1 month for additional follow-up but did not return until 3 months later. Visual acuity in the right eye dropped to 20/200, the birdshot lesions returned, and she had signs of exudation associated with the CNV (Fig. 4). Intravitreal injection of triamcinolone was administered. One month later, visual acuity was 20/50, chorioretinal spots once again regressed, and the activity in the choroidal neovascular lesion had reduced but was still present. The patient was treated with intravitreal injection (1.25 mg) of bevacizumab
(Avastin; Genentech, Inc., South San Francisco, CA). One month after the bevacizumab injection, visual acuity was 20/60, leakage from the CNV was reduced, and spots were still undetectable (Fig. 5). The patient received additional bevacizumab injections over the follow-up of 8 months because the choroidal neovascular lesion showed signs of leakage or bleeding. She received 8 injections of bevacizumab in the right eye over 20 months, with a marked improvement in the anatomical appearance and visual acuity. She received two intravitreal triamcinolone injections and one sub– Tenon space triamcinolone injection to suppress the BRC lesions. Because the BRC lesions in the right eye appeared to have a good response to triamcinolone injection, a sub–Tenon space injection (40 mg) of triamcinolone was administered in the left eye (Fig. 6), which caused regression of the BRC lesions. Ten months
Fig. 4. The patient returned 4 months later with visual acuity of 20/200. Early-phase (A) and late-phase (B) fluorescein angiograms revealed enlargement of the choroidal neovascularization with a return of the birdshot retinochoroidopathy lesions.
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Fig. 5. Two weeks after repeated triamcinolone injection, early-phase (A) and late-phase (B) fluorescein angiograms showed regression of the birdshot retinochoroidopathy lesions. There was somewhat less leakage from the choroidal neovascularization but no change in lesion size. Visual acuity was 20/50. The patient received intravitreal injection (1.25 mg) of bevacizumab. One month later, the choroidal neovascularization was much smaller (C) and showed less leakage (D). Visual acuity was 20/60. After addition bevacizumab injections, visual acuity improved to 20/30.
later, the patient presented with obvious birdshot lesions and a new focus of CNV in the left eye. She was treated initially with intravitreal injection (4 mg) of triamcinolone, which caused regression of both the birdshot lesions and the CNV. Initially, the patient refused systemic immunosuppressive therapy. After she realized the chronic nature of her problem and the repeated injections that were required, she agreed to immunosuppression. Treatment with mycophenolate mofetil and prednisone was started 12 months after the initial presentation. When last examined 18 months after presentation, visual acuity was 20/30 in the right eye and 20/20 in the left eye. She had no observable BRC lesions, and CNV had regressed in both eyes.
Discussion There is no established treatment of CNV associated with intraocular inflammatory conditions.2,3 We reported good results of PDT used alone for inflammatory disorders such as multifocal choroiditis and panuveitis.4 Subsequent to that report, we had patients with CNV secondary to multifocal choroiditis and panuveitis who had profound visual acuity loss with PDT. We theorized that the collateral damage may have resulted from excessive leakage of verteporfin from inflamed choroidal vessels. Because some patients with CNV and inflammatory disorders may respond to corticosteroid treatment alone,5 we began treating patients with intravitreal injection of triamcinolone followed by subsequent PDT only if the CNV showed an inadequate response to triamcino-
lone. The current patient had BRC complicated with CNV and had an inadequate response to intravitreal injection of triamcinolone. Unfortunately, CNV did not show any short-term change with subsequent PDT. She was then treated with intravitreal injections of bevacizumab and had a good response. The patient initially presented before the availability of intravitreal bevacizumab, and it is possible that she may have had a good response to bevacizumab treatment alone. However, a main stimulus for the neovascularization appeared to be underlying inflammation, which would not be expected to be altered by bevacizumab injections alone. Indeed, in this patient, the BRC lesions appeared to regress with triamcinolone injections, and the neovascularization in the left eye responded to intravitreal triamcinolone injection alone. BRC appears to cause two different types of lesions that have a very similar appearance. The first is a cream– colored inflammatory lesion. The second is a depigmented atrophic lesion, which is a sequela to the first. Over time, the depigmented atrophic lesions appear to account for a greater proportion of the lesions present. It is likely that the inflammatory lesions are responsive to antiinflammatory approaches, while the atrophic lesions would not be. Our patient had local treatment with repeated corticosteroid injections, which delivered powerful antiinflammatory treatment
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Fig. 6. Because the patient had disappearance of birdshot retinochoroidopathy (BRC) lesions in the right eye after triamcinolone injection (A), later she received a sub– Tenon space injection of triamcinolone in the left eye. This resulted in the disappearance of the BRC lesions. Ten months later, she presented with metamorphopsia. She had an early focus of choroidal neovascularization (arrow) and faintly visible BRC lesions (B). Later in angiography, the BRC lesions were slightly more visible, and the choroidal neovascularization (CNV) showed leakage (C). Note the staining of the optic nerve. She was treated with intravitreal injection (4 mg) of triamcinolone. Seven months later, there was regression of the CNV, and no BRC lesions were visible (D).
to her eye. Later, addition of systemic immunosuppression augmented the antiinflammatory effects. The treatment appeared to have caused regression of the inflammatory lesions before the development of the atrophic spots. It is possible that instituting therapy late in the disease process or one that does incompletely suppress inflammation may not appear to favorably affect the disease process. This patient had successful treatment of CNV associated with BRC using a strategy that targeted the underlying inflammation and the neovascularization; in the process, a serendipitous improvement in the appearance of the underlying inflammatory process, BRC, was seen. This effect was not permanent and required additional injections of triamcinolone and, later, systemic immunosuppression to maintain the effect. This finding suggests that aggressive early antiinflammatory treatment may avert some of the late sequela of BRC, and additional study is required.
Key words: bevacizumab, birdshot retinochoroidopathy, choroidal neovascularization, triamcinolone.
References 1.
2.
3.
4.
5.
Rothova A, Berendschot TT, Probst K, et al. Birdshot chorioretinopathy: long-term manifestations and visual prognosis. Ophthalmology 2004;111:954–959. Brucker AJ, Deglin EA, Bene C, Hoffman ME. Subretinal choroidal neovascularization in birdshot retinochoroidopathy. Am J Ophthalmol 1985;99:40–44. Lim JI, Flaxel CJ, LaBree L. Photodynamic therapy for choroidal neovascularization secondary to inflammatory chorioretinal disease. Ann Acad Med Singapore 2006;35:198–202. Spaide RF, Freund KB, Slakter J, et al. Treatment of subfoveal choroidal neovascularization associated with multifocal choroiditis and panuveitis with photodynamic therapy. Retina 2002;22:545–549. Flaxel CJ, Owens SL, Mulholland B, et al. The use of corticosteroids for choroidal neovascularisation in young patients. Eye 1998;12:266–272.
Purpose: To describe a patient with birdshot retinochoroidopathy (BRC) with bilateral choroidal neovascularization (CNV) who was treated with intravitreal injection of bevacizumab and antiinflammatory medications. Method: Interventional case report. Patient: A 35-year-old woman with bilateral CNV associated with BRC. Results: The patient was treated with intravitreal injection of triamcinolone, photodynamic therapy, and intravitreal injection of bevacizumab in one eye, while the fellow eye was treated with intravitreal injection of triamcinolone. Immunosuppressive therapy was performed in the course of the treatment. Not only did the neovascularization respond, but the birdshot lesions vanished as well. Discussion: BRC can have secondary CNV that, as in the current case, responds favorably to treatment. We serendipitously observed regression of the choroidal inflammatory lesions with intravitreal injection of triamcinolone. RETINAL CASES & BRIEF REPORTS 3:42– 46, 2009
From the Vitreous, Retina, Macula Consultants of New York, and the LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital, New York, New York.
investigators suggesting that treatment of the underlying inflammatory disorder does not modify the course of the disease.1 However, therapy is often instituted late in the disease process, after there has been a large amount of inflammatory damage. On rare occasion, choroidal neovascularization (CNV) may develop in patients with BRC.2 We describe a patient who had early BRC and developed bilateral CNV. We treated the CNV with intravitreal injection of triamcinolone in both eyes and with intravitreal injection of bevacizumab in one eye. Not only did the CNV respond, but the birdshot lesions regressed as well.
B
irdshot retinochoroidopathy (BRC) is an idiopathic chronic bilateral inflammatory disease affecting the retina and choroid that is characterized by multiple cream ovoid spots. Late in the disease process, patients can have visual field loss, color vision abnormalities, nyctalopia, and decreased central visual acuity. Therapy for BRC is controversial, with some
This work was supported by The Macula Foundation, Inc. (New York, NY). The authors have no financial interest in this report. Dr. Claudia Brue` is currently affiliated with the University Politecnica delle Marche, Ancona, Italy. Reprint requests: Richard Spaide, MD, Vitreous, Retina, Macula Consultants of New York, 460 Park Avenue, 5th Floor, New York, NY 10022; e-mail: [email protected]
Case Report A 35-year-old woman presented with decreased vision, floaters, and nyctalopia in both eyes. Visual acuity was 20/60 in the right eye and 20/20 in the left eye. Cellular infiltrates were detected in the vitreous cavity. Multiple cream– colored spots, each about one fourth of a disk diameter, were found at the level of the choroid.
42
BILATERAL CNV IN BRC
43
Fig. 1. Color photograph of the right eye with subtle cream spots in the fundus consistent with birdshot retinochoroidopathy (BRC) showed a grayish subretinal lesion with hemorrhage (A). Visual acuity was 20/60. Early-phase (B) and late-phase (C) fluorescein angiograms demonstrated choroidal neovascularization (CNV) and multiple spots at the level of the choroid. Fluorescein angiogram of the left eye showed typical BRC spots without any evidence of CNV (D). Both eyes had late-phase staining of the nerve.
She also had a submacular hemorrhagic lesion in the right eye consistent with CNV. Fluorescein angiography confirmed the presence of CNV. In the early phases of fluorescein angiography, multiple hypofluorescent spots were seen at the level of the choroid, but by the middle and late phases, these spots were not visible (Fig. 1). The patient had late-phase staining of the optic nerve. Indocyanine green angiography showed dark spots radiating from the optic nerve to the periphery in all four quadrants. In addition to CNV, a tentative diagnosis of BRC was made. Because the patient had CNV associated with uveitis, treatment of both inflammatory and neovascular aspects was thought to be best accomplished by intravitreal injection of triamcinolone, followed later by photodynamic
Fig. 2. Fluorescein angiography demonstrating a slight reduction in the size of the choroidal neovascularization and absence of the birdshot retinochoroidopathy (BRC) lesions in the right eye 1 week after intravitreal triamcinolone injection (A). Visual acuity was 20/40. The left eye continued to have typical BRC lesions (B).
therapy (PDT) using verteporfin. The patient presented before the availability of effective anti–vascular endothelial growth factor agents. The patient underwent a complete workup, including serologic tests negative for angiotensin-converting enzyme, antinuclear antibodies, and antibodies to Borrelia burgdorferi. Serology was checked using the VDRL test, the results of which were negative. Chest roentgenography did not show any abnormalities, and results of the tuberculin test were negative. HLA-A29 testing was positive. The patient was initially treated with intravitreal injection (4 mg) of triamcinolone. When examined 1 week later, visual acuity was 20/40, there was a slight reduction in the CNV size, and the birdshot lesions were not visible in the right eye (Fig. 2). She did
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Fig. 3. One month after intravitreal triamcinolone injection, the patient had reduction in the size of the neovascular lesion with an increase in pigmentation (A). Fluorescein angiography showed slight leakage at the foveal aspect of the neovascularization (B). The patient received photodynamic therapy and when examined 1 month later continued to have slight leakage during fluorescein angiography (C) and intraretinal edema by optical coherence tomography (D).
not have staining of the optic nerve. One month after the triamcinolone injection, visual acuity was 20/60, and the birdshot lesions were undetectable. She had leakage from the CNV and was treated with PDT (Fig. 3). When examined 1 month after PDT, she did not have any changes in the CNV appearance or in the amount of leakage visible during fluorescein angiography. She was asked to return in 1 month for additional follow-up but did not return until 3 months later. Visual acuity in the right eye dropped to 20/200, the birdshot lesions returned, and she had signs of exudation associated with the CNV (Fig. 4). Intravitreal injection of triamcinolone was administered. One month later, visual acuity was 20/50, chorioretinal spots once again regressed, and the activity in the choroidal neovascular lesion had reduced but was still present. The patient was treated with intravitreal injection (1.25 mg) of bevacizumab
(Avastin; Genentech, Inc., South San Francisco, CA). One month after the bevacizumab injection, visual acuity was 20/60, leakage from the CNV was reduced, and spots were still undetectable (Fig. 5). The patient received additional bevacizumab injections over the follow-up of 8 months because the choroidal neovascular lesion showed signs of leakage or bleeding. She received 8 injections of bevacizumab in the right eye over 20 months, with a marked improvement in the anatomical appearance and visual acuity. She received two intravitreal triamcinolone injections and one sub– Tenon space triamcinolone injection to suppress the BRC lesions. Because the BRC lesions in the right eye appeared to have a good response to triamcinolone injection, a sub–Tenon space injection (40 mg) of triamcinolone was administered in the left eye (Fig. 6), which caused regression of the BRC lesions. Ten months
Fig. 4. The patient returned 4 months later with visual acuity of 20/200. Early-phase (A) and late-phase (B) fluorescein angiograms revealed enlargement of the choroidal neovascularization with a return of the birdshot retinochoroidopathy lesions.
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Fig. 5. Two weeks after repeated triamcinolone injection, early-phase (A) and late-phase (B) fluorescein angiograms showed regression of the birdshot retinochoroidopathy lesions. There was somewhat less leakage from the choroidal neovascularization but no change in lesion size. Visual acuity was 20/50. The patient received intravitreal injection (1.25 mg) of bevacizumab. One month later, the choroidal neovascularization was much smaller (C) and showed less leakage (D). Visual acuity was 20/60. After addition bevacizumab injections, visual acuity improved to 20/30.
later, the patient presented with obvious birdshot lesions and a new focus of CNV in the left eye. She was treated initially with intravitreal injection (4 mg) of triamcinolone, which caused regression of both the birdshot lesions and the CNV. Initially, the patient refused systemic immunosuppressive therapy. After she realized the chronic nature of her problem and the repeated injections that were required, she agreed to immunosuppression. Treatment with mycophenolate mofetil and prednisone was started 12 months after the initial presentation. When last examined 18 months after presentation, visual acuity was 20/30 in the right eye and 20/20 in the left eye. She had no observable BRC lesions, and CNV had regressed in both eyes.
Discussion There is no established treatment of CNV associated with intraocular inflammatory conditions.2,3 We reported good results of PDT used alone for inflammatory disorders such as multifocal choroiditis and panuveitis.4 Subsequent to that report, we had patients with CNV secondary to multifocal choroiditis and panuveitis who had profound visual acuity loss with PDT. We theorized that the collateral damage may have resulted from excessive leakage of verteporfin from inflamed choroidal vessels. Because some patients with CNV and inflammatory disorders may respond to corticosteroid treatment alone,5 we began treating patients with intravitreal injection of triamcinolone followed by subsequent PDT only if the CNV showed an inadequate response to triamcino-
lone. The current patient had BRC complicated with CNV and had an inadequate response to intravitreal injection of triamcinolone. Unfortunately, CNV did not show any short-term change with subsequent PDT. She was then treated with intravitreal injections of bevacizumab and had a good response. The patient initially presented before the availability of intravitreal bevacizumab, and it is possible that she may have had a good response to bevacizumab treatment alone. However, a main stimulus for the neovascularization appeared to be underlying inflammation, which would not be expected to be altered by bevacizumab injections alone. Indeed, in this patient, the BRC lesions appeared to regress with triamcinolone injections, and the neovascularization in the left eye responded to intravitreal triamcinolone injection alone. BRC appears to cause two different types of lesions that have a very similar appearance. The first is a cream– colored inflammatory lesion. The second is a depigmented atrophic lesion, which is a sequela to the first. Over time, the depigmented atrophic lesions appear to account for a greater proportion of the lesions present. It is likely that the inflammatory lesions are responsive to antiinflammatory approaches, while the atrophic lesions would not be. Our patient had local treatment with repeated corticosteroid injections, which delivered powerful antiinflammatory treatment
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Fig. 6. Because the patient had disappearance of birdshot retinochoroidopathy (BRC) lesions in the right eye after triamcinolone injection (A), later she received a sub– Tenon space injection of triamcinolone in the left eye. This resulted in the disappearance of the BRC lesions. Ten months later, she presented with metamorphopsia. She had an early focus of choroidal neovascularization (arrow) and faintly visible BRC lesions (B). Later in angiography, the BRC lesions were slightly more visible, and the choroidal neovascularization (CNV) showed leakage (C). Note the staining of the optic nerve. She was treated with intravitreal injection (4 mg) of triamcinolone. Seven months later, there was regression of the CNV, and no BRC lesions were visible (D).
to her eye. Later, addition of systemic immunosuppression augmented the antiinflammatory effects. The treatment appeared to have caused regression of the inflammatory lesions before the development of the atrophic spots. It is possible that instituting therapy late in the disease process or one that does incompletely suppress inflammation may not appear to favorably affect the disease process. This patient had successful treatment of CNV associated with BRC using a strategy that targeted the underlying inflammation and the neovascularization; in the process, a serendipitous improvement in the appearance of the underlying inflammatory process, BRC, was seen. This effect was not permanent and required additional injections of triamcinolone and, later, systemic immunosuppression to maintain the effect. This finding suggests that aggressive early antiinflammatory treatment may avert some of the late sequela of BRC, and additional study is required.
Key words: bevacizumab, birdshot retinochoroidopathy, choroidal neovascularization, triamcinolone.
References 1.
2.
3.
4.
5.
Rothova A, Berendschot TT, Probst K, et al. Birdshot chorioretinopathy: long-term manifestations and visual prognosis. Ophthalmology 2004;111:954–959. Brucker AJ, Deglin EA, Bene C, Hoffman ME. Subretinal choroidal neovascularization in birdshot retinochoroidopathy. Am J Ophthalmol 1985;99:40–44. Lim JI, Flaxel CJ, LaBree L. Photodynamic therapy for choroidal neovascularization secondary to inflammatory chorioretinal disease. Ann Acad Med Singapore 2006;35:198–202. Spaide RF, Freund KB, Slakter J, et al. Treatment of subfoveal choroidal neovascularization associated with multifocal choroiditis and panuveitis with photodynamic therapy. Retina 2002;22:545–549. Flaxel CJ, Owens SL, Mulholland B, et al. The use of corticosteroids for choroidal neovascularisation in young patients. Eye 1998;12:266–272.
