Multimodal imaging in a case of deferoxamine induced maculopathy

Abstract

Purpose

To report a case of deferoxomine induced maculopathy and present the use of multimodal retinal imaging to study this disease entity.

Methods

Observational case report of one patient. Multimodal imaging with fundus autofluorescence (FAF), infrared imaging (IR), and spectral-domain optical coherence tomography (SD-OCT) was used to investigate the macular changes induced by deferoxamine toxicity.

Results

A 53 year-old male with a history of beta-thalassemia presented with decreased vision in both eyes one month after initiating deferoxamine therapy. IR imaging showed areas of increased stippled infrared intensity through the macula. FAF revealed diffuse areas of stippled hyperautofluorescence and hypoautofluorescence. SD-OCT changes included disruption of the ellipsoid zone, attenuation of the photoreceptors, and deposits within the retinal pigment epithelium.

Conclusions

We describe a case of deferoxomine induced maculopathy and present the use of multimodal retinal imaging to study this disease entity.

Deferoxamine is an iron-chelating agent indicated for the treatment of acute iron intoxication and of chronic iron overload due to transfusion-dependent anemias. Ocular disturbances have been reported when deferoxamine was administered over prolonged periods of time, at high doses, or in patients with low ferritin levels. These disturbances include blurring of vision, cataracts, decreased visual acuity, visual defects, scotoma, impaired peripheral, color, and night vision, optic neuritis, corneal opacities, and retinal pigmentary abnormalities. In most cases, the ocular disturbances have been noted to be reversible upon immediate cessation of treatment.^1,2

We report a case of a 53 year-old male with beta-thalassemia who presented with decreased vision in both eyes that began upon starting deferoxamine therapy. We illustrate with multimodal retinal structural and functional imaging the changes caused by deferoxamine induced maculopathy.

Case Report

A 53-year old male presented with a one-month history of decreased vision in both eyes. His past medical history was significant for beta-thalassemia and receiving multiple blood transfusions. He was started on deferoxamine therapy to treat his iron overload complications from blood transfusions.

His best-corrected visual acuity (BCVA) was 20/80 OU. Intraocular pressures were normal and anterior segment examination was unremarkable in both eyes. There were no vitreous cells present in either eye. Dilated fundus examination showed normal appearing optic nerves but mottling and pigmentary changes in the macula of both eyes (figure 1).

Figure 1.

Color fundus photos (a) OD and (b) OS at presentation. Note the mottling and pigmentary changes in the maculas OU. Visual acuity was 20/80 OU.

Infrared (IR), fundus autofluorescence (FAF), and spectral-domain optical coherence tomography imaging were obtained with the Spectralis HRA/OCT (Heidelberg Engineering, Inc.; Vista, CA). IR imaging showed areas of increased stippled infrared intensity through the macula in both eyes (figure 2). FAF revealed diffuse areas of stippled hyperautofluorescence and hypoautofluorescence in both eyes (figure 2). FAF also showed a plaque of central hyperautofluorescence (similar to vitelliform maculopathy) surrounded by concentric distribution of stippled hyperautofluorescence (similar to drusen). Wide field (55-degree) FAF imaging confirmed that these changes were limited to the macular regions OU (figure 3). SD-OCT images through the foveal regions showed disruption of the ellipsoid zone, attenuation of the photoreceptors, and deposits within the retinal pigment epithelium(RPE) with central thickening of the RPE band of both eyes (figure 4). Microperimetry obtained with the MP-1 system (Nidek Technologies; Padova, Italy) revealed overall depression of macular sensitivity and severely reduced attenuation in the infero-temporal macular region in the right eye (figure 5).

Figure 2.

Infrared imaging (a) OD and (b) OS, showing areas of stippled increased infrared intensity through the maculas OU. Fundus autofluorescence (FAF) imaging (c) OD and (d) OS revealing diffuse areas of stippled hyperautofluorescence and hypoautofluorescence in both eyes. FAF also showed a plaque of central hyperautofluorescence (similar to vitelliform maculopathy) surrounded by concentric distribution of stippled hyperautofluorescence (similar to drusen).

Figure 3.

Wide field (55-degree) fundus autofluorescence imaging (a) OD and (b) OS showing that the diffuse areas of stippled hyperautofluorescence and hypoautofluorescence are limited to the macular regions OU.

Figure 4.

Horizontal SD-OCT images (a) OD and (b) OS through the fovea showing showed disruption of the ellipsoid zone, attenuation of the photoreceptors, and deposits within the retinal pigment epithelium (RPE) with central thickening of the RPE band. An epiretinal membrane is noted OD.

Figure 5.

MP-1 microperimetry OD revealed overall depression of macular sensitivity and severely reduced attenuation in the infero-temporal macular region.

Full-field electro-retinogram (ff-ERG) testing was performed under ISCEV standards and showed a delay in cone responses, but normal rod responses, rod implicit times, and cone implicit times. Electro-oculogram (EOG) testing showed normal Arden rations of 253% OD and 282% OS, and hence excluded a diagnosis of Best disease.

Based on the patient’s sudden temporal change in vision with a history of recent initiation of deferoxamine therapy and structural and functional imaging changes consistent with macular dysfunction, a diagnosis of deferoxamine-induced maculopathy was made. A recommendation to decrease the dosage of deferoxamine was made to the patient’s internist. On the next follow up visit, the patient reported improved vision and BCVA measured 20/30 OU.

Discussion

Deferoxamine can produce a myriad of ocular disturbances as described above. Previous case reports have described RPE changes, pattern dystrophy, vitelliform lesions, or Bull’s eye maculopathy in association with deferoxamine.^3-5

Haimovici et al. reported a case series of 16 patients who exhibited visual disturbances while on deferoxamine.⁶ Funduscopic features in their series included RPE opacification or loss of transparency and RPE pigment changes distributed in the foveomacular, macula and periphery, macula and paramacular, peripapillary, papillomacular, or peripheral regions. Fluorescein angiography in a subset of their patients showed early patchy blocked fundus fluorescence followed by late staining, while another subset showed mottled fluorescence without late staining.

With FAF imaging, which was not available at the time of their series, we showed in our patient an interesting pattern of diffuse stippled hypo- and hyper-autofluorescence in the macula. Haimovici et al. also noted in their series that the ff-ERG could range from normal to prolonged rod and cone implicit times or reduced scoptopic and photopic amplitudes. In addition, EOG testing was abnormal in their subset of patients that were tested. In our patient, we found only a delay in cone responses in the ff-ERG and a normal EOG, perhaps because our patient was not yet on chronic deferoxamine treatment.

With high resolution SD-OCT imaging, we found in our patient disruption of the ellipsoid zone, attenuation of the photoreceptors, and deposits within the RPE. Rahi et al. reported on a histological study of deferoxamine ocular toxicity and found patchy depigmentation of the RPE, which could correlate with the changes seen on FAF in our patient.⁷ Moreover, the RPE structural abnormalities seen in their transmission electron microscopy studies could account for the RPE deposits we observed on SD-OCT imaging.

An interesting finding in our case was the profound macular functional change induced by deferoxamine as assessed by microperimetry. In particular, we found an overall depression of macular sensitivity and severely reduced attenuation in the infero-temporal macular region, which closely correlated to the structural findings seen with FAF and SD-OCT imaging.

In summary, we report a case of a 53 year-old male with beta-thalassemia who presented with decreased vision in both eyes that began upon starting deferoxamine therapy. We note that lack of drusen and the temporal relationship of vision changes coinciding with deferoxamine therapy supported a diagnosis of deferoxamine toxicity over nonexudative age related macular degeneration to explain the observed macular findings. Although a previous case report described the FAF and SD-OCT findings in a vitelliform lesion associated with chronic deferoxamine therapy⁴, to our knowledge, this is the first case report to illustrate with multimodal retinal structural and functional imaging the changes caused by acute deferoxamine-induced maculopathy.