- Email: [email protected]
Prorenin Levels in Retinopathy of Prematurity
Prorenin Levels in Retinopathy of Prematurity Harumasa Yokota, MD, PhD, Taiji Nagaoka, MD, PhD, Fumihiko Mori, MD, PhD, Taiichi Hikichi, MD, PhD, Hiromichi Hosokawa, PhD, Hiroshi Tanaka, PhD, Yuichi Ishida, PhD, Fumiaki Suzuki, PhD, and Akitoshi Yoshida, MD, PhD
FIGURE 3. Iris xanthogranuloma. Macrophages showed membranous staining (arrowhead), whereas multinucleated giant cells (arrow) revealed both cytoplasmic and cell membrane staining. (Immunohistochemical stain for CD68; original magnification, ⴛ100).
presentation. Observation may be appropriate in infants and children: the lesion has a variable clinical presentation, and it may sometimes resolve spontaneously within one to five years. In contrast, adult-onset xanthogranuloma rarely, if ever, undergoes spontaneous regression.4 These lesions in adults may be removed surgically if there is cosmetic deformity, functional impairment, or concern about malignancy. Surgery may be complicated by hyphema. The present case indicates that JXG in the elderly can mimic iris melanoma. THIS STUDY WAS SUPPORTED IN PART BY NATIONAL INSTItutes of Health, Bethesda, Maryland, core grant EY03040 and by a grant from Research to Prevent Blindness, Inc, New York, New York. The authors indicate no financial conflict of interest. Involved in design and conduct of study (S.S., N.A.R.); involved in collection, management, analysis, and interpretation of data, and preparation of the data (S.S., S.C., G.L., R.L.G., J.I.L., N.A.R.); involved in collection of data (S.S.); and involved in management, statistical analysis and interpretation of the data, and preparation of the manuscript (S.S.). REFERENCES
1. Zimmerman LE. Ocular lesions of juvenile xanthogranuloma. Nevoxanthoendothelioma. Am J Ophthalmol 1965;60:1011– 1035. 2. Tahan SR, Pastel-Levy C, Bhan AK, Mihm MC Jr. Juvenile xanthogranuloma. Clinical and pathologic characterization. Arch Pathol Lab Med 1989;113:1057–1061. 3. Zamir E, Wang RC, Krishnakumar S, Aiello Leverant A, Dugel PU, Rao NA. Juvenile xanthogranuloma masquerading as pediatric chronic uveitis: a clinicopathologic study. Surv Ophthalmol 2001;46:164 –171. 4. Rodriguez J, Ackerman AB. Xanthogranuloma in adults. Arch Dermatol 1976;112:43– 44.
VOL. 143, NO. 3
PURPOSE: To evaluate serum prorenin levels in preterm infants with or without retinopathy of prematurity (ROP). DESIGN: Noncomparative retrospective case control study. METHODS: Serum prorenin levels in children with a gestational age younger than 36 weeks were measured with antibody-activating direct enzyme kinetic assay. RESULTS: The mean prorenin concentrations were higher in preterm infants with ROP than in infants without ROP at every time point: from 26 to 30 weeks, 2326 ⴞ 334 g/ml (mean ⴞ SE [standard error]) (n ⴝ 3) and 1164 ⴞ 234 g/ml (n ⴝ 3), respectively (P < .05); from 31 to 35 weeks, 1760 ⴞ 496 g/ml (n ⴝ 10) and 957.1 ⴞ 139 g/ml (n ⴝ 25) (P < .05); from 36 to 40 weeks, 958.2 ⴞ 194.2 g/ml (n ⴝ 23) and 470.1 ⴞ 32.6 g/ml (n ⴝ 67) (P < .01); and from 41 to 45 weeks, 575.8 ⴞ 148.4 (n ⴝ 9) and 385.6 ⴞ 47.9 (n ⴝ 13), which is not significantly different. CONCLUSIONS: Prorenin levels in preterm infants can predict which infants will develop ROP. (Am J Ophthalmol 2007;143:531–533. © 2007 by Elsevier Inc. All rights reserved.)
R
ETINOPATHY OF PREMATURITY (ROP), WHICH REMAINS
a major problem in managing preterm infants, is characterized by retinal neovascularization. Although appropriate oxygen supplementation is considered essential for preventing ROP, the disease persists,1 suggesting that other factors are involved. In humans and experimental models of ROP, vascular endothelial growth factor (VEGF) plays a key role in the generation of ROP. In an experimental model of ROP, angiotensin II, an effective peptide in the renin-angiotensin system, induces an increase in VEGF to promote retinal neovascularization.2 Recently, local production of angioAccepted for publication Oct 21, 2006. From the Department of Ophthalmology (H.Y., T.N., F.M., T.H., A.Y.); and the Department of Clinical Laboratory (H.H.), Asahikawa Medical College, Asahikawa, Japan; Tokiwa Chemical Co (H.T.), Tokyo, Japan; Prevaqol Co (Y.I.), Tokyo, Japan; and Faculty of Applied Science, Gifu University, Gifu, Japan (F.S.). Inquiries to Harumasa Yokota, MD, PhD, Department of Ophthalmology, Asahikawa Medical College, 2-1-1-1 Midorigaoka Higashi, Asahikawa, 078-8510 Japan; e-mail: [email protected]
BRIEF REPORTS
531
The Figure shows the serum concentration of prorenin in preterm infants with and without ROP. In infants with a gestational age of 26 to 30 weeks, the mean prorenin concentration was higher in infants with ROP (n ⫽ 3) (2326 ⫾ 334 g/ml) (mean ⫾ SE [standard error]) than in those without ROP (n ⫽ 3) (1164 ⫾ 234 g/ml) (P ⬍ .05). From 31 to 35 weeks, the mean serum prorenin concentration was 1760 ⫾ 496 g/ml in those with ROP (n ⫽ 10) and 957.1 ⫾ 139 g/ml in those without ROP (n ⫽ 25) (P ⬍ .05). From 36 to 40 weeks, the mean serum prorenin concentration was 958.2 ⫾ 194.2 g/ml in those with ROP (n ⫽ 23) and 470.1 ⫾ 32.6 g/ml in those without ROP (n ⫽ 67) (P ⬍ .01). From 41 to 45 weeks, the mean serum prorenin concentration was 575.8 ⫾ 148.4 g/ml in those with ROP (n ⫽ 9) and 385.6 ⫾ 47.9 g/ml in those without ROP (n ⫽ 13), which did not reach significance. Our results showed that prorenin levels in preterm infants with ROP are significantly higher than those without ROP. Recently, prorenin, which had been believed to be an inactive form of renin, was reported to have an enzymatic activity similar to renin.3,4 Recent studies reported the mechanism of the local activation of prorenin in the eye and the kidney as described in the following section.3,4 Prorenin binding renin/prorenin receptor converts angiotensinogen to angiotensin I through nonproteolytic activation of prorenin, and then generated angiotensin I is converted to angiotensin II by angiotensin converting enzyme. Angiotensin II generated in the eye might induce an increase local production of VEGF, leading to the generation of ROP.2 In the current study, we evaluated the prorenin levels in preterm infants using the AAD-PR assay and showed that prorenin levels in preterm infants with ROP are significantly higher than those without ROP. The current results suggest that serum prorenin levels may have prognostic value for the development of ROP.
FIGURE. The mean serum prorenin levels for preterm infants with retinopathy of prematurity (ROP) (䡩) and without ROP (●) are shown (bars ⴝ standard error of the mean). AAD-PR ⴝ Antibody-Activating Direct Kinetic Assay.
tensin II was reported to be induced by an increased level of prorenin.3,4 We reported that in diabetes with proliferative diabetic retinopathy, which also is characterized by retinal neovascularization, serum levels of prorenin increase significantly.5 To our knowledge, no studies have reported the relation between ROP and prorenin levels. The current study showed that serum prorenin levels in preterm infants with ROP are higher than in those without ROP and that prorenin might be involved in the pathogenesis of ROP. All children born at Asahikawa Medical College Hospital with a gestational age younger than 36 weeks at birth and without obvious abnormalities were invited to participate in this study. The study adhered to the tenets of Declaration of Helsinki and Good Clinical Practice guidelines. After approval of the procedure by the ethics committee of our institution, informed consent was obtained from all parents. Blood (100 l) was obtained from each patient weekly from birth to hospital discharge. All fundus examinations were carried out by the same examiner who was blinded to the patient birth weight, gestational age, and concentration of prorenin. The concentration of prorenin was measured by the same blinded examiner using the Antibody-Activating Direct Kinetic Assay (AAD-PR) assay as previously described.5,6 The AAD-PR assay has a good sensitivity compared with conventional enzyme-activating methods.6 The severity of ROP was classified according to the International Classification of ROP. ROP stages 2 to 5 were defined as ROP (⫹) and stages 0 to 1, as ROP (⫺). 532
AMERICAN JOURNAL
THIS STUDY WAS SUPPORTED BY A GRANT-IN-AID FOR Scientific Research (C), 18591904 (Dr Yokota) and the Akiyama Foundation, Sapporo, Japan, (Dr Nagaoka). Involved in the design of study (H.Y., T.N., F.M., T.H., Y.I., F.S., A.Y.); involved in conduct of study (H.Y., T.N.); involved in the collection of the data, management of the data, analysis of the data, interpretation of data, preparation of the manuscript, review of the manuscript and approval of the manuscript (H.Y., H.H., H.T., T.N., A.Y.). The measurement of prorenin was supported by Tokiwa Chemical Co, Tokyo, Japan. REFERENCES
1. Quinn GE, Dobson V, Barr CC, et al. Visual acuity in infants after vitrectomy for severe retinopathy of prematurity. Ophthalmology 1991;98:5–13. 2. Moravski CJ, Skinner SL, Stubbs AJ, et al. The reninangiotensin system influences ocular endothelial cell proliferation in diabetes: transgenic and interventional studies. Am J Pathol 2003;162:151–160. 3. Ichihara A, Hayashi M, Kaneshiro Y, et al. Inhibition of diabetic nephropathy by a decoy peptide corresponding to the OF
OPHTHALMOLOGY
MARCH 2007
“handle” region for nonproteolytic activation of prorenin. J Clin Invest 2004;114:1128 –1135. 4. Satofuka S, Ichihara A, Nagai N, et al. Suppression of ocular inflammation in endotoxin-induced uveitis by inhibiting nonproteolytic activation of prorenin. Invest Ophthalmol Vis Sci 2006;47:2686 –2692. 5. Yokota H, Mori F, Kai K, et al. Serum prorenin levels and diabetic retinopathy in type 2 diabetes: new method to measure serum level of prorenin using antibody activating direct kinetic assay. Br J Ophthalmol 2005;89:871– 873. 6. Kawazu S, Minagawa S, Yazawa M, et al. Sex difference and possible relationship to microvascular complications of serum prorenin levels in type 2 diabetic patients, measured by a novel antibody-activating direct enzyme kinetic assay. J Diabetes Complications 2004;18:275–281.
Successful Treatment With Infliximab in a Patient With Diffuse Subretinal Fibrosis Syndrome Alfredo Adán, MD, Raimon Sanmartí, MD, Anniken Burés, MD, and Ricardo P. Casaroli-Marano, MD PURPOSE: To report a case of Diffuse Subretinal Fibrosis (DSF) syndrome refractory to immunosuppressive therapy who was successfully treated with anti-tumor necrosis factor-␣ (TNF)-␣ monoclonal antibodies infliximab. DESIGN: Interventional case report. METHODS: A 23-year-old male with bilateral choroiditis presented sudden dimness of vision associated to nasal scotoma in his right eye. Complete ophthalmic examination with appropriated clinical and laboratorial evaluations was carried out during all follow-up. Inform consent statement and Internal Ethics Board approval were also obtained for an open-label therapy schedule. RESULTS: Extensive temporal subretinal lesion in his right eye and DSF in the left eye were observed. The patient received intravenous infliximab infusion (5 mg/kg) schema. Four weeks after starting treatment his visual acuity improved with decrease in ocular inflammation. CONCLUSIONS: This report describes a case of DSF syndrome that responded remarkably well to infliximab treatment suggesting that TNF-␣ could play an important pathogenetic role in this syndrome. (Am J Ophthalmol 2007;143:533–534. © 2007 by Elsevier Inc. All rights reserved.) Accepted for publication Oct 21, 2006. From the Department of Ophthalmology (A.A., A.B., R.P.C.-M.) and Rheumatology (R.S.), Hospital Clinic de Barcelona, Universidad de Barcelona, Barcelona, Spain Inquiries to Alfredo Adán, MD, Department of Ophthalmology, Hospital Clinic de Barcelona, Calle Villarroel 170, 08036 Barcelona, Spain; e-mail: [email protected]
VOL. 143, NO. 3
FIGURE. Diffuse Subretinal Fibrosis (DSF) syndrome and treatment with anti-tumor necrosis factor (TNF)-␣ humanized monoclonal antibodies infliximab. (Top) DSF lesions scattered on the all posterior pole in left eye was observed after one-year systemic treatment with immunosuppressive agents (cyclosporine A and azathioprine) and steroids. (Middle) Right eye presented sudden decrease of vision with an extensive and active subretinal lesion temporally located to the macula. Treatment with infliximab was started while immunosuppressive agents and steroids was progressively tapered and discontinued. (Bottom) Inactive lesions were noted in the right eye after 12 months of follow-up.
BRIEF REPORTS
533
FIGURE 3. Iris xanthogranuloma. Macrophages showed membranous staining (arrowhead), whereas multinucleated giant cells (arrow) revealed both cytoplasmic and cell membrane staining. (Immunohistochemical stain for CD68; original magnification, ⴛ100).
presentation. Observation may be appropriate in infants and children: the lesion has a variable clinical presentation, and it may sometimes resolve spontaneously within one to five years. In contrast, adult-onset xanthogranuloma rarely, if ever, undergoes spontaneous regression.4 These lesions in adults may be removed surgically if there is cosmetic deformity, functional impairment, or concern about malignancy. Surgery may be complicated by hyphema. The present case indicates that JXG in the elderly can mimic iris melanoma. THIS STUDY WAS SUPPORTED IN PART BY NATIONAL INSTItutes of Health, Bethesda, Maryland, core grant EY03040 and by a grant from Research to Prevent Blindness, Inc, New York, New York. The authors indicate no financial conflict of interest. Involved in design and conduct of study (S.S., N.A.R.); involved in collection, management, analysis, and interpretation of data, and preparation of the data (S.S., S.C., G.L., R.L.G., J.I.L., N.A.R.); involved in collection of data (S.S.); and involved in management, statistical analysis and interpretation of the data, and preparation of the manuscript (S.S.). REFERENCES
1. Zimmerman LE. Ocular lesions of juvenile xanthogranuloma. Nevoxanthoendothelioma. Am J Ophthalmol 1965;60:1011– 1035. 2. Tahan SR, Pastel-Levy C, Bhan AK, Mihm MC Jr. Juvenile xanthogranuloma. Clinical and pathologic characterization. Arch Pathol Lab Med 1989;113:1057–1061. 3. Zamir E, Wang RC, Krishnakumar S, Aiello Leverant A, Dugel PU, Rao NA. Juvenile xanthogranuloma masquerading as pediatric chronic uveitis: a clinicopathologic study. Surv Ophthalmol 2001;46:164 –171. 4. Rodriguez J, Ackerman AB. Xanthogranuloma in adults. Arch Dermatol 1976;112:43– 44.
VOL. 143, NO. 3
PURPOSE: To evaluate serum prorenin levels in preterm infants with or without retinopathy of prematurity (ROP). DESIGN: Noncomparative retrospective case control study. METHODS: Serum prorenin levels in children with a gestational age younger than 36 weeks were measured with antibody-activating direct enzyme kinetic assay. RESULTS: The mean prorenin concentrations were higher in preterm infants with ROP than in infants without ROP at every time point: from 26 to 30 weeks, 2326 ⴞ 334 g/ml (mean ⴞ SE [standard error]) (n ⴝ 3) and 1164 ⴞ 234 g/ml (n ⴝ 3), respectively (P < .05); from 31 to 35 weeks, 1760 ⴞ 496 g/ml (n ⴝ 10) and 957.1 ⴞ 139 g/ml (n ⴝ 25) (P < .05); from 36 to 40 weeks, 958.2 ⴞ 194.2 g/ml (n ⴝ 23) and 470.1 ⴞ 32.6 g/ml (n ⴝ 67) (P < .01); and from 41 to 45 weeks, 575.8 ⴞ 148.4 (n ⴝ 9) and 385.6 ⴞ 47.9 (n ⴝ 13), which is not significantly different. CONCLUSIONS: Prorenin levels in preterm infants can predict which infants will develop ROP. (Am J Ophthalmol 2007;143:531–533. © 2007 by Elsevier Inc. All rights reserved.)
R
ETINOPATHY OF PREMATURITY (ROP), WHICH REMAINS
a major problem in managing preterm infants, is characterized by retinal neovascularization. Although appropriate oxygen supplementation is considered essential for preventing ROP, the disease persists,1 suggesting that other factors are involved. In humans and experimental models of ROP, vascular endothelial growth factor (VEGF) plays a key role in the generation of ROP. In an experimental model of ROP, angiotensin II, an effective peptide in the renin-angiotensin system, induces an increase in VEGF to promote retinal neovascularization.2 Recently, local production of angioAccepted for publication Oct 21, 2006. From the Department of Ophthalmology (H.Y., T.N., F.M., T.H., A.Y.); and the Department of Clinical Laboratory (H.H.), Asahikawa Medical College, Asahikawa, Japan; Tokiwa Chemical Co (H.T.), Tokyo, Japan; Prevaqol Co (Y.I.), Tokyo, Japan; and Faculty of Applied Science, Gifu University, Gifu, Japan (F.S.). Inquiries to Harumasa Yokota, MD, PhD, Department of Ophthalmology, Asahikawa Medical College, 2-1-1-1 Midorigaoka Higashi, Asahikawa, 078-8510 Japan; e-mail: [email protected]
BRIEF REPORTS
531
The Figure shows the serum concentration of prorenin in preterm infants with and without ROP. In infants with a gestational age of 26 to 30 weeks, the mean prorenin concentration was higher in infants with ROP (n ⫽ 3) (2326 ⫾ 334 g/ml) (mean ⫾ SE [standard error]) than in those without ROP (n ⫽ 3) (1164 ⫾ 234 g/ml) (P ⬍ .05). From 31 to 35 weeks, the mean serum prorenin concentration was 1760 ⫾ 496 g/ml in those with ROP (n ⫽ 10) and 957.1 ⫾ 139 g/ml in those without ROP (n ⫽ 25) (P ⬍ .05). From 36 to 40 weeks, the mean serum prorenin concentration was 958.2 ⫾ 194.2 g/ml in those with ROP (n ⫽ 23) and 470.1 ⫾ 32.6 g/ml in those without ROP (n ⫽ 67) (P ⬍ .01). From 41 to 45 weeks, the mean serum prorenin concentration was 575.8 ⫾ 148.4 g/ml in those with ROP (n ⫽ 9) and 385.6 ⫾ 47.9 g/ml in those without ROP (n ⫽ 13), which did not reach significance. Our results showed that prorenin levels in preterm infants with ROP are significantly higher than those without ROP. Recently, prorenin, which had been believed to be an inactive form of renin, was reported to have an enzymatic activity similar to renin.3,4 Recent studies reported the mechanism of the local activation of prorenin in the eye and the kidney as described in the following section.3,4 Prorenin binding renin/prorenin receptor converts angiotensinogen to angiotensin I through nonproteolytic activation of prorenin, and then generated angiotensin I is converted to angiotensin II by angiotensin converting enzyme. Angiotensin II generated in the eye might induce an increase local production of VEGF, leading to the generation of ROP.2 In the current study, we evaluated the prorenin levels in preterm infants using the AAD-PR assay and showed that prorenin levels in preterm infants with ROP are significantly higher than those without ROP. The current results suggest that serum prorenin levels may have prognostic value for the development of ROP.
FIGURE. The mean serum prorenin levels for preterm infants with retinopathy of prematurity (ROP) (䡩) and without ROP (●) are shown (bars ⴝ standard error of the mean). AAD-PR ⴝ Antibody-Activating Direct Kinetic Assay.
tensin II was reported to be induced by an increased level of prorenin.3,4 We reported that in diabetes with proliferative diabetic retinopathy, which also is characterized by retinal neovascularization, serum levels of prorenin increase significantly.5 To our knowledge, no studies have reported the relation between ROP and prorenin levels. The current study showed that serum prorenin levels in preterm infants with ROP are higher than in those without ROP and that prorenin might be involved in the pathogenesis of ROP. All children born at Asahikawa Medical College Hospital with a gestational age younger than 36 weeks at birth and without obvious abnormalities were invited to participate in this study. The study adhered to the tenets of Declaration of Helsinki and Good Clinical Practice guidelines. After approval of the procedure by the ethics committee of our institution, informed consent was obtained from all parents. Blood (100 l) was obtained from each patient weekly from birth to hospital discharge. All fundus examinations were carried out by the same examiner who was blinded to the patient birth weight, gestational age, and concentration of prorenin. The concentration of prorenin was measured by the same blinded examiner using the Antibody-Activating Direct Kinetic Assay (AAD-PR) assay as previously described.5,6 The AAD-PR assay has a good sensitivity compared with conventional enzyme-activating methods.6 The severity of ROP was classified according to the International Classification of ROP. ROP stages 2 to 5 were defined as ROP (⫹) and stages 0 to 1, as ROP (⫺). 532
AMERICAN JOURNAL
THIS STUDY WAS SUPPORTED BY A GRANT-IN-AID FOR Scientific Research (C), 18591904 (Dr Yokota) and the Akiyama Foundation, Sapporo, Japan, (Dr Nagaoka). Involved in the design of study (H.Y., T.N., F.M., T.H., Y.I., F.S., A.Y.); involved in conduct of study (H.Y., T.N.); involved in the collection of the data, management of the data, analysis of the data, interpretation of data, preparation of the manuscript, review of the manuscript and approval of the manuscript (H.Y., H.H., H.T., T.N., A.Y.). The measurement of prorenin was supported by Tokiwa Chemical Co, Tokyo, Japan. REFERENCES
1. Quinn GE, Dobson V, Barr CC, et al. Visual acuity in infants after vitrectomy for severe retinopathy of prematurity. Ophthalmology 1991;98:5–13. 2. Moravski CJ, Skinner SL, Stubbs AJ, et al. The reninangiotensin system influences ocular endothelial cell proliferation in diabetes: transgenic and interventional studies. Am J Pathol 2003;162:151–160. 3. Ichihara A, Hayashi M, Kaneshiro Y, et al. Inhibition of diabetic nephropathy by a decoy peptide corresponding to the OF
OPHTHALMOLOGY
MARCH 2007
“handle” region for nonproteolytic activation of prorenin. J Clin Invest 2004;114:1128 –1135. 4. Satofuka S, Ichihara A, Nagai N, et al. Suppression of ocular inflammation in endotoxin-induced uveitis by inhibiting nonproteolytic activation of prorenin. Invest Ophthalmol Vis Sci 2006;47:2686 –2692. 5. Yokota H, Mori F, Kai K, et al. Serum prorenin levels and diabetic retinopathy in type 2 diabetes: new method to measure serum level of prorenin using antibody activating direct kinetic assay. Br J Ophthalmol 2005;89:871– 873. 6. Kawazu S, Minagawa S, Yazawa M, et al. Sex difference and possible relationship to microvascular complications of serum prorenin levels in type 2 diabetic patients, measured by a novel antibody-activating direct enzyme kinetic assay. J Diabetes Complications 2004;18:275–281.
Successful Treatment With Infliximab in a Patient With Diffuse Subretinal Fibrosis Syndrome Alfredo Adán, MD, Raimon Sanmartí, MD, Anniken Burés, MD, and Ricardo P. Casaroli-Marano, MD PURPOSE: To report a case of Diffuse Subretinal Fibrosis (DSF) syndrome refractory to immunosuppressive therapy who was successfully treated with anti-tumor necrosis factor-␣ (TNF)-␣ monoclonal antibodies infliximab. DESIGN: Interventional case report. METHODS: A 23-year-old male with bilateral choroiditis presented sudden dimness of vision associated to nasal scotoma in his right eye. Complete ophthalmic examination with appropriated clinical and laboratorial evaluations was carried out during all follow-up. Inform consent statement and Internal Ethics Board approval were also obtained for an open-label therapy schedule. RESULTS: Extensive temporal subretinal lesion in his right eye and DSF in the left eye were observed. The patient received intravenous infliximab infusion (5 mg/kg) schema. Four weeks after starting treatment his visual acuity improved with decrease in ocular inflammation. CONCLUSIONS: This report describes a case of DSF syndrome that responded remarkably well to infliximab treatment suggesting that TNF-␣ could play an important pathogenetic role in this syndrome. (Am J Ophthalmol 2007;143:533–534. © 2007 by Elsevier Inc. All rights reserved.) Accepted for publication Oct 21, 2006. From the Department of Ophthalmology (A.A., A.B., R.P.C.-M.) and Rheumatology (R.S.), Hospital Clinic de Barcelona, Universidad de Barcelona, Barcelona, Spain Inquiries to Alfredo Adán, MD, Department of Ophthalmology, Hospital Clinic de Barcelona, Calle Villarroel 170, 08036 Barcelona, Spain; e-mail: [email protected]
VOL. 143, NO. 3
FIGURE. Diffuse Subretinal Fibrosis (DSF) syndrome and treatment with anti-tumor necrosis factor (TNF)-␣ humanized monoclonal antibodies infliximab. (Top) DSF lesions scattered on the all posterior pole in left eye was observed after one-year systemic treatment with immunosuppressive agents (cyclosporine A and azathioprine) and steroids. (Middle) Right eye presented sudden decrease of vision with an extensive and active subretinal lesion temporally located to the macula. Treatment with infliximab was started while immunosuppressive agents and steroids was progressively tapered and discontinued. (Bottom) Inactive lesions were noted in the right eye after 12 months of follow-up.
BRIEF REPORTS
533