Severe interferon associated retinopathy
Accepted for publication 29 July 2002&5.(0c;, 百拇医药
Keywords: interferon; retinopathy&5.(0c;, 百拇医药
Interferon alfa is used in various human malignancies for its antitumour activity. One of its ocular side effects is retinopathy.1 Interferon associated retinopathy is generally mild and resolves completely. We describe a severe retinopathy in a hypertensive patient treated with interferon for multiple myeloma.&5.(0c;, 百拇医药
Case report&5.(0c;, 百拇医药
A 56 year old man presented with a 3 week history of deterioration and distortion of right vision. Visual acuities (VA) were 6/60 right and 1/60 left. Funduscopy revealed bilateral extensive peripapillary cotton wool spots, retinal thickening, optic disc hyperaemia, and blot haemorrhages. Arteriolar changes were minimal.&5.(0c;, 百拇医药
He was anaemic (Hb 10.6 gdl/l) and slightly thrombocytopenic (platelets 93 x 109/l). Plasma viscosity was 1.59 (normal 1.5–1.7). Renal function was normal at presentation.
He underwent peripheral blood stem cell transplant for multiple myeloma 8 months previously after having melphalan 110 mg/m2 and total body irradiation (including the head) in a total dose of 1200 cGy given in six fractions over 3 days. He then had interferon alfa therapy for 4 months, initially 3 mega units three times a week, later reduced to twice a week. It was stopped immediately after visual deterioration.;jx, 百拇医药
Five years previously, he had macular laser treatment following left inferotemporal branch retinal vein occlusion. On discharge 1 year later, VAs were right 6/5, left 6/36.;jx, 百拇医药
He was a known hypertensive, taking lisinopril, but control was poor around the time his VA began to deteriorate, with readings up to 150/100 mm Hg. He was not diabetic. His myeloma status was stable. Cytomegalovirus (CMV) antigen checked by polymerase chain reaction (PCR) and pretransplant HIV status were negative.;jx, 百拇医药
One week after presentation at the eye clinic, VAs dropped to right 2/60, left finger counting and did not improve after a course of intravenous methylprednisolone (1 g/day for 3 days). He was registered blind.
A further 3 weeks later, bilateral cotton wool spots and haemorrhages were more numerous and both foveas showed gross thickening with exudates (Fig 1w!6;/*, http://www.100md.com
). Fundus fluorescein angiography revealed retinal ischaemia with capillary non-perfusion, pruning, and tortuosity of vessels, vessel wall staining, and leakage (Fig 2w!6;/*, http://www.100md.com
).w!6;/*, http://www.100md.com
fig.ommitteedw!6;/*, http://www.100md.com
Figure 1 Bilateral (right eye (A) and left eye (B)) extensive peripapillary cotton wool spots, retinal thickening with exudates, optic disc hyperaemia, and blot haemorrhages.w!6;/*, http://www.100md.com
fig.ommitteedw!6;/*, http://www.100md.com
Figure 2 Fundus fluorescein angiography of the right eye: early frame (A) showing retinal ischaemia with capillary non-perfusion, pruning, and tortuosity of vessels; late frame (B) showing vessel wall staining and leakage.w!6;/*, http://www.100md.com
Five months later preproliferative retinopathy was noted and subsequent proliferative changes were treated with bilateral panretinal laser photocoagulation. At 9 months, VAs were 1/60 right and left.
Comment;krn, 百拇医药
In a review article on interferon retinopathy, initial interferon alfa doses ranged from 3–9 mega units three to six times per week for several weeks.1 In a prospective randomised placebo controlled trial of interferon alfa therapy for macular degeneration, retinopathy was noted with increasing frequency in the highest dose group (5% of the patients taking 6 mega units three times a week).2 The interferon doses in our patient were at the lower level of these regimens.;krn, 百拇医药
Severity of retinopathy was found to be related to the presence of the following risk factors: large initial dosages, long duration of treatment, and systemic diseases like diabetes mellitus or hypertension. Early onset of retinopathy was also a good indicator of severity and fundal examination up to 8 weeks from start of treatment was advocated for those at risk.3;krn, 百拇医药
Significant visual impairment attributed to interferon therapy was associated with macular oedema in a hypoalbuminaemic but non-hypertensive, non-diabetic patient4; and in two other cases in a case series report, one of whom had poor control of blood pressure and the other an occasional mildly elevated blood glucose level.5 All three patients had resolution of the lesions by 2 months and subsequently made good visual recoveries, unlike in our case.
In another case series report, two out of seven patients on high dose interferon alfa-2b suffered permanent visual loss after developing macular oedema. Both patients were hypertensive and one had radiation treatment to the brain. The latter later developed proliferative retinopathy as well.6mny)$ew, 百拇医药
Deposition of immune complexes in the retinal vasculature has been postulated as a pathogenetic mechanism for the retinopathy.5 Interferon alfa was also found to induce leucocyte capillary trapping in rat retinal microcirculation.7mny)$ew, 百拇医药
Radiation may have contributed to the development of the clinical picture although its use in the treatment of myeloma is frequent and ocular side effects have not been widely recognised in the past. Low doses to the eye similar to that used in our patient have been associated with retinopathy after treatment of age related macular degeneration.8mny)$ew, 百拇医药
Retinal oedema is an indicator of severity in interferon associated retinopathy. Early detection of it, especially in hypertensives and diabetics, may help avoid progression to permanent visual loss.
Referenceswk{67, http://www.100md.com
Hayasaka S, Nagaki Y, Matsumoto M, et al. Interferon associated retinopathy. Br J Ophthalmol 1998;82:323–5.wk{67, http://www.100md.com
Pharmacological Therapy for Macular Degeneration Study Group. Interferon alfa-2a is ineffective for patients with choroidal neovascularization secondary to age-related macular degeneration. Arch Ophthalmol 1997;115:865–72.wk{67, http://www.100md.com
Soushi S, Kobayashi F, Obazawa H, et al. Evaluation of risk factors of interferon-associated retinopathy in patients with type C chronic active hepatitis. Nippon Ganka Gakkai Zasshi 1996;100:69–76. (English extract)wk{67, http://www.100md.com
Tokai R, Ikeda T, Miyaura T, et al. Interferon-associated retinopathy and cystoid macular edema. Arch Ophthalmol 2001;119:1077–9wk{67, http://www.100md.com
Guyer DR, Tiedeman J, Yannuzzi LA, et al. Interferon associated retinopathy. Arch Ophthalmol 1993;111:350–6.wk{67, http://www.100md.com
Henjy C, Sternberg P Jr, Lawson DH, et al. Retinopathy associated with high-dose interferon alfa-2b therapy. Am J Ophthalmol 2001;131:782–7.wk{67, http://www.100md.com
Nishiwaki H, Ogura Y, Miyamoto K, et al. Interferon alfa induces leukocyte capillary trapping in rat retinal microcirculation. Arch Ophthalmol 1996;114:726–30.wk{67, http://www.100md.com
Mauget-Faysse M, Chiquet C, Milea D, et al. Long term results of radiotherapy for subfoveal choroidal neovascularization in age related macular degeneration. Br J Ophthalmol 1999;83:923–8.(K L Tu J Bowyer K Schofield and S Harding)
Keywords: interferon; retinopathy&5.(0c;, 百拇医药
Interferon alfa is used in various human malignancies for its antitumour activity. One of its ocular side effects is retinopathy.1 Interferon associated retinopathy is generally mild and resolves completely. We describe a severe retinopathy in a hypertensive patient treated with interferon for multiple myeloma.&5.(0c;, 百拇医药
Case report&5.(0c;, 百拇医药
A 56 year old man presented with a 3 week history of deterioration and distortion of right vision. Visual acuities (VA) were 6/60 right and 1/60 left. Funduscopy revealed bilateral extensive peripapillary cotton wool spots, retinal thickening, optic disc hyperaemia, and blot haemorrhages. Arteriolar changes were minimal.&5.(0c;, 百拇医药
He was anaemic (Hb 10.6 gdl/l) and slightly thrombocytopenic (platelets 93 x 109/l). Plasma viscosity was 1.59 (normal 1.5–1.7). Renal function was normal at presentation.
He underwent peripheral blood stem cell transplant for multiple myeloma 8 months previously after having melphalan 110 mg/m2 and total body irradiation (including the head) in a total dose of 1200 cGy given in six fractions over 3 days. He then had interferon alfa therapy for 4 months, initially 3 mega units three times a week, later reduced to twice a week. It was stopped immediately after visual deterioration.;jx, 百拇医药
Five years previously, he had macular laser treatment following left inferotemporal branch retinal vein occlusion. On discharge 1 year later, VAs were right 6/5, left 6/36.;jx, 百拇医药
He was a known hypertensive, taking lisinopril, but control was poor around the time his VA began to deteriorate, with readings up to 150/100 mm Hg. He was not diabetic. His myeloma status was stable. Cytomegalovirus (CMV) antigen checked by polymerase chain reaction (PCR) and pretransplant HIV status were negative.;jx, 百拇医药
One week after presentation at the eye clinic, VAs dropped to right 2/60, left finger counting and did not improve after a course of intravenous methylprednisolone (1 g/day for 3 days). He was registered blind.
A further 3 weeks later, bilateral cotton wool spots and haemorrhages were more numerous and both foveas showed gross thickening with exudates (Fig 1w!6;/*, http://www.100md.com
). Fundus fluorescein angiography revealed retinal ischaemia with capillary non-perfusion, pruning, and tortuosity of vessels, vessel wall staining, and leakage (Fig 2w!6;/*, http://www.100md.com
).w!6;/*, http://www.100md.com
fig.ommitteedw!6;/*, http://www.100md.com
Figure 1 Bilateral (right eye (A) and left eye (B)) extensive peripapillary cotton wool spots, retinal thickening with exudates, optic disc hyperaemia, and blot haemorrhages.w!6;/*, http://www.100md.com
fig.ommitteedw!6;/*, http://www.100md.com
Figure 2 Fundus fluorescein angiography of the right eye: early frame (A) showing retinal ischaemia with capillary non-perfusion, pruning, and tortuosity of vessels; late frame (B) showing vessel wall staining and leakage.w!6;/*, http://www.100md.com
Five months later preproliferative retinopathy was noted and subsequent proliferative changes were treated with bilateral panretinal laser photocoagulation. At 9 months, VAs were 1/60 right and left.
Comment;krn, 百拇医药
In a review article on interferon retinopathy, initial interferon alfa doses ranged from 3–9 mega units three to six times per week for several weeks.1 In a prospective randomised placebo controlled trial of interferon alfa therapy for macular degeneration, retinopathy was noted with increasing frequency in the highest dose group (5% of the patients taking 6 mega units three times a week).2 The interferon doses in our patient were at the lower level of these regimens.;krn, 百拇医药
Severity of retinopathy was found to be related to the presence of the following risk factors: large initial dosages, long duration of treatment, and systemic diseases like diabetes mellitus or hypertension. Early onset of retinopathy was also a good indicator of severity and fundal examination up to 8 weeks from start of treatment was advocated for those at risk.3;krn, 百拇医药
Significant visual impairment attributed to interferon therapy was associated with macular oedema in a hypoalbuminaemic but non-hypertensive, non-diabetic patient4; and in two other cases in a case series report, one of whom had poor control of blood pressure and the other an occasional mildly elevated blood glucose level.5 All three patients had resolution of the lesions by 2 months and subsequently made good visual recoveries, unlike in our case.
In another case series report, two out of seven patients on high dose interferon alfa-2b suffered permanent visual loss after developing macular oedema. Both patients were hypertensive and one had radiation treatment to the brain. The latter later developed proliferative retinopathy as well.6mny)$ew, 百拇医药
Deposition of immune complexes in the retinal vasculature has been postulated as a pathogenetic mechanism for the retinopathy.5 Interferon alfa was also found to induce leucocyte capillary trapping in rat retinal microcirculation.7mny)$ew, 百拇医药
Radiation may have contributed to the development of the clinical picture although its use in the treatment of myeloma is frequent and ocular side effects have not been widely recognised in the past. Low doses to the eye similar to that used in our patient have been associated with retinopathy after treatment of age related macular degeneration.8mny)$ew, 百拇医药
Retinal oedema is an indicator of severity in interferon associated retinopathy. Early detection of it, especially in hypertensives and diabetics, may help avoid progression to permanent visual loss.
Referenceswk{67, http://www.100md.com
Hayasaka S, Nagaki Y, Matsumoto M, et al. Interferon associated retinopathy. Br J Ophthalmol 1998;82:323–5.wk{67, http://www.100md.com
Pharmacological Therapy for Macular Degeneration Study Group. Interferon alfa-2a is ineffective for patients with choroidal neovascularization secondary to age-related macular degeneration. Arch Ophthalmol 1997;115:865–72.wk{67, http://www.100md.com
Soushi S, Kobayashi F, Obazawa H, et al. Evaluation of risk factors of interferon-associated retinopathy in patients with type C chronic active hepatitis. Nippon Ganka Gakkai Zasshi 1996;100:69–76. (English extract)wk{67, http://www.100md.com
Tokai R, Ikeda T, Miyaura T, et al. Interferon-associated retinopathy and cystoid macular edema. Arch Ophthalmol 2001;119:1077–9wk{67, http://www.100md.com
Guyer DR, Tiedeman J, Yannuzzi LA, et al. Interferon associated retinopathy. Arch Ophthalmol 1993;111:350–6.wk{67, http://www.100md.com
Henjy C, Sternberg P Jr, Lawson DH, et al. Retinopathy associated with high-dose interferon alfa-2b therapy. Am J Ophthalmol 2001;131:782–7.wk{67, http://www.100md.com
Nishiwaki H, Ogura Y, Miyamoto K, et al. Interferon alfa induces leukocyte capillary trapping in rat retinal microcirculation. Arch Ophthalmol 1996;114:726–30.wk{67, http://www.100md.com
Mauget-Faysse M, Chiquet C, Milea D, et al. Long term results of radiotherapy for subfoveal choroidal neovascularization in age related macular degeneration. Br J Ophthalmol 1999;83:923–8.(K L Tu J Bowyer K Schofield and S Harding)