From the Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago; and The Chicago Lighthouse for People Who Are Blind or Visually Impaired, Chicago, Illinois.
Supported by funds from the Foundation Fighting Blindness, Columbia, Maryland; Pangere Corporation; Grant Healthcare Foundation, Lake Forest, Illinois; NIH core grant EYO1792; and an unrestricted departmental grant from Research to Prevent Blindness.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Gerald A. Fishman, MD, The Chicago Lighthouse for People Who Are Blind or Visually Impaired, 1850 West Roosevelt Road, Chicago, IL 60608-1298. E-mail: email@example.com
Desferrioxamine is a chelating agent used for the treatment of transfusion-induced hemochromatosis in patients with thalassemia major and other hematologic diseases requiring regular blood transfusions.1
Ocular toxicity secondary to prolonged treatment with desferrioxamine may result in night blindness, visual field constriction, cataract, macular and/or peripheral pigmentary retinopathy, or optic neuropathy.2 Two previous reports showed the presence of vitelliform macular lesions in patients receiving desferrioxamine therapy.3,4
Topical and oral forms of carbonic anhydrase inhibitors have been shown to be effective for the improvement of macular cysts in patients with various retinal diseases such as retinitis pigmentosa,5,6 X-linked retinoschisis,7 and enhanced S-cone syndrome.8,9
We describe a patient who presented with a vitelliform lesion in the macula of the right eye as a result of long-term treatment with desferrioxamine. The use of brinzolamide ophthalmic suspension 1% (Azopt; Alcon Laboratories, Inc., Fort Worth, TX) three times a day in her right eye was associated with a marked resolution of the vitelliform lesion.
A 46-year-old woman had a 10-year history of progressive decrease in central vision of each eye. She had a known history of thalassemia major with regular blood transfusions and had been treated with intramuscular or subcutaneous desferrioxamine for the past 22 years. A review of the family pedigree showed no history for hereditary eye diseases.
Visual acuity was correctable to 1.00 logarithm of the minimum angle of resolution (LogMAR) (20/200 measured with a Snellen acuity chart) in the right eye with a refraction of +1.25 +1.25 × 65 and to 0.14 LogMAR (20/25−2) in the left eye with a +1.00 spherical lens. Color vision testing using Ishihara plates showed 10/17 plates read correctly in the right eye and 17/17 in the left eye. Anterior segment examination was unremarkable. Intraocular pressure measured by applanation tonometry was 15 mm Hg in the right eye and 16 mm Hg in the left eye.
At baseline (pretreatment), the fundus examination showed normal-appearing optic discs and retinal vessels in both eyes. The right eye showed an elevated vitelliform macular lesion with hyperpigmented changes at the margins (Fig. A). The macula of the left eye showed a hypopigmentary lesion with mild retinal pigment epithelium (RPE) pigment mottling. There was a flat choroidal nevus, approximately 1 by 1.5 disc diameters in size, noted inferior to the fovea of the left eye.
Figure. Fundus photographs of the right eye (A), demonstrating an elevated vitelliform macular lesion with hyperpigmented changes at the margins. After 6 months of treatment (B), the vitelliform macular lesion in the right eye was less apparent when compared to the baseline. The right eye showed a small residual yellowish lesion in the macula with pigment on the surface of the lesion. Fluorescein angiogram (late frames) of the right eye (C) shows window defects of hyperfluorescence in the macula with hypofluorescent loci centrally. (D) Spectral-domain optical coherence tomography scans at baseline: the right eye (OD) shows an elevation of the retinal pigment epithelium (RPE) associated with the vitelliform macular lesion and the left eye (OS) shows a small elevated RPE lesion with foveal disruption of the inner/outer segment junction of the photoreceptor layer. Spectral-domain optical coherence tomography scans demonstrate a reduction of the vitelliform macular lesion and retinal thickness while receiving treatment with topical brinzolamide 1% following 2 (E) and 6 (F) months of treatment. The left eye shows a shallow RPE elevation most evident at the 6-month visit.
Treatment with brinzolamide ophthalmic suspension 1% in each eye was initiated. At her 2-month visit, the patient did not notice any changes in her vision. Anterior segment examination and intraocular pressure were normal in each eye. Color vision screening with the Ishihara color plates was normal at both the 2- and 6-month visits, which was an improvement in the right eye compared to the baseline visit. After 2 months of treatment, visual acuity was correctable to 0.96 LogMAR (20/200) in the right eye and to 0.10 LogMAR (20/25) in the left eye. Visual acuity following 6 months of treatment did not significantly differ from that following 2 months of treatment.
Fundus examination showed that the vitelliform macular lesion in the right eye was less apparent at both the 2- and 6-month visits. The right eye showed a small residual yellowish lesion in the macula with pigment on the surface of the lesion at the 6-month visit (Fig. B). The left eye was essentially unchanged on ophthalmoscopic examination.
Fluorescein angiography obtained by another ophthalmologist after treatment of the right eye for 5 months showed a normal retinal vasculature. There were areas of hypofluorescence in the foveal region, which correlated with the hyperpigmentary changes seen by ophthalmoscopic examination. Window defects of hyperfluorescence were noted at the margins of the residual vitelliform macular lesion. There was no evidence of any fluorescein leakage or choroidal neovascularization in the late frames of the angiogram (Fig. C).
At the baseline and 2-month visits, a spectral-domain optical coherence tomography (SD-OCT) examination with the Optovue system (Optovue Inc., Fremont, CA) was used. At the 6-month visit, an SD-OCT/SLO system (OPKO Instrumentations, Miami, FL) was used as previously described.7,9 The SD-OCT examinations at the baseline visit indicated a highly reflective elevated lesion with accumulation of material in the sub-RPE space associated with the vitelliform macular lesion. Focal disruption of the inner segment/outer segment (IS/OS) junction of the photoreceptors over the lesion and an almost normal appearance of all major intraretinal layers was observed, although the macular region was elevated by the material, resulting in the partial disappearance of the foveal depression. The left eye showed a small elevated RPE lesion with disruption of the normal anatomy within the macula that involved the IS/OS junction of the photoreceptors with focal foveal areas of RPE loss and disruption (Fig. D).
The retinal thicknesses of the central 1-mm foveal subfields of the right and left eyes at each visit are provided in the table. At baseline, the retinal thickness of the right eye was considerably greater than normal, whereas the left eye was within normal limits. Following 2 months of treatment (Fig. E), the retinal thickness of the right eye decreased substantially, whereas the thickness of the left eye was essentially the same as that at baseline. A further reduction in the lesion size and macular thickness were noted after 6 months of treatment.
Table: Retinal Thickness and Visual Acuity for Each Visit
The SD-OCT scans of the right eye at the 6-month visit showed a residual irregular, broad-based, foveal lesion at the level of the RPE with focal disruption of the overlying IS/OS junction of the photoreceptors. The OCT scans of the left eye were similar to both the prior and baseline visits (Fig. F).
Chelating therapy with desferrioxamine is well established and widely used to remove excess iron. Unfortunately, visual disorders have been documented after desferrioxamine infusion.2,10 Several mechanisms have been proposed for desferrioxamine toxicity, such as the induction of oxidation, damage to the blood–retina barrier, or reduction in certain metallic ions (zinc and copper), which are essential for normal retinal function.10 Several previous studies have documented a retinopathy secondary to desferrioxamine therapy, such as RPE pigmentary mottling in the macular and/or equatorial regions, bull’s-eye maculopathy, and a vitelliform macular lesion.2–4
Our case showed that topical brinzolamide 1% eye drops may be effective in the treatment of a vitelliform macular lesion associated with desferrioxamine toxicity that was, at least partially, likely responsible for the loss of central vision in our patient. We observed a notable reduction in the lesion thickness on SD-OCT testing and an improvement in color vision in the right eye after treatment initiation.
To our knowledge, our study is the first to demonstrate a beneficial effect likely from the use of a carbonic anhydrase inhibitors in a patient with desferrioxamine vitelliform retinopathy. Of note, our case showed that the vitelliform macular lesion was apparent for at least 1 year without any gross anatomical changes in the lesion morphology and/or thickness until treatment was initiated, which lessens the possibility that the notable improvement in the lesion’s thickness was due to a natural history of spontaneous resolution in the macular lesion. The vitelliform macular lesion seen in our patient had a phenotype simulating the vitelliform lesion seen in Best disease and some forms of pattern dystrophy, which are also characterized by an abnormal accumulation of a yellow pigment (mainly lipofuscin).11 The patient’s history and clinical examination results, including a late-onset decrease in her central acuity (fourth decade of life), prolonged use of desferrioxamine, and negative family history of hereditary ocular diseases, favor an acquired cause for her maculopathy and is likely related to the use of desferrioxamine.
Of note, we decided to treat the left eye in our case, which showed a small degree of yellowish material in the macula 7 years previously, to determine any possible effects of the brinzolamide drops on macular thickness in the absence of a vitelliform lesion. There was no change in the retinal thickness after 6 months of treatment.
The current report will be added to the list of other retinal diseases5–9 that have shown an improvement in macular thickness after treatment with carbonic anhydrase inhibitors. Our patient showed no clinically significant change in her visual acuity during the follow-up visits, which raises the possibility of irreversible RPE and photoreceptor toxicity in the macula associated with an atrophic-appearing lesion from the prolonged use of desferrioxamine. The lack of any significant change in visual acuity did not correlate well with the improvement of the vitelliform macular lesion on SD-OCT.
One of our report’s limitations was using two different SD-OCT instruments. However, the differences in retinal thickness between both SD-OCT units used in our study were minimal and not likely to be clinically relevant as previously described.12
The use of brinzolamide 1% was associated with a marked reduction in a vitelliform macular lesion on spectral-domain OCT testing secondary to desferrioxamine retinopathy. This finding supports a recommendation that a trial of this topical carbonic anhydrase inhibitor should be considered in the treatment of vitelliform macular lesions in patients with desferrioxamine retinal toxicity.
- Chaston TB, Richardson DR. Iron chelators for the treatment of iron overload disease: relationship between structure, redox activity, and toxicity. Am J Hematol. 2003;73:200–210. doi:10.1002/ajh.10348 [CrossRef]
- Haimovici R, D’Amico DJ, Gragoudas ES, Sokol S. The expanded clinical spectrum of deferoxamine retinopathy. Ophthalmology. 2002;109:164–171. doi:10.1016/S0161-6420(01)00947-2 [CrossRef]
- Gonzales CR, Lin AP, Engstrom RE, Kreiger AE. Bilateral vitelliform maculopathy and deferoxamine toxicity. Retina. 2004;24:464–467. doi:10.1097/00006982-200406000-00024 [CrossRef]
- Genead MA, Fishman GA, Anastasakis A, Lindeman M. Macular vitelliform lesion in desferrioxamine-related retinopathy. Doc Ophthalmol. 2010;121:161–166. doi:10.1007/s10633-010-9236-z [CrossRef]
- Grover S, Apushkin MA, Fishman GA. Topical dorzolamide for the treatment of cystoid macular edema in patients with retinitis pigmentosa. Am J Ophthalmol. 2006;141:850–858. doi:10.1016/j.ajo.2005.12.030 [CrossRef]
- Genead MA, Fishman GA. Efficacy of sustained topical dorzolamide therapy for cystic macular lesions in patients with retinitis pigmentosa and Usher syndrome. Arch Ophthalmol. 2010;128:1146–1150. doi:10.1001/archophthalmol.2010.172 [CrossRef]
- Genead MA, Fishman GA, Walia S. Efficacy of sustained topical dorzolamide therapy for cystic macular lesions in patients with X-linked retinoschisis. Arch Ophthalmol. 2010;128:190–197. doi:10.1001/archophthalmol.2009.398 [CrossRef]
- Iannaccone A, Fung KH, Eyestone ME, Stone EM. Treatment of adult-onset acute macular retinoschisis in enhanced s-cone syndrome with oral acetazolamide. Am J Ophthalmol. 2009;147:307–312. doi:10.1016/j.ajo.2008.08.003 [CrossRef]
- Genead MA, Fishman GA, McAnany JJ. Efficacy of topical dorzolamide for treatment of cystic macular lesions in a patient with enhanced S-cone syndrome. Doc Ophthalmol. 2010;121:231–240. doi:10.1007/s10633-010-9247-9 [CrossRef]
- De Virgiliis S, Congia M, Turco MP, et al. Depletion of trace elements and acute ocular toxicity induced by desferrioxamine in patients with thalassaemia. Arch Dis Child. 1998;63:250–255. doi:10.1136/adc.63.3.250 [CrossRef]
- Marmorstein AD, Cross HE, Peachey NS. Functional roles of bestrophins in ocular epithelia. Prog Retin Eye Res. 2009;28:206–226. doi:10.1016/j.preteyeres.2009.04.004 [CrossRef]
- Wolf-Schnurrbusch UE, Ceklic L, Brinkmann CK, et al. Macular thickness measurements in healthy eyes using six different optical coherence tomography instruments. Invest Ophthalmol Vis Sci. 2009;50:3432–3437. doi:10.1167/iovs.08-2970 [CrossRef]
Retinal Thickness and Visual Acuity for Each Visit
|Visit||Retinal Thickness (μm)||ETDRS LogMAR Visual Acuity (Snellen Acuity)|
|Baseline||342||242||1.00 (20/200)||0.14 (20/25−2)|
|2-month follow-upa||236||229||0.96 (20/200)||0.10 (20/25)|
|6-month follow-upb||189||216||0.92 (20/200+1)||0.08 (20/25+1)|