Ophthalmic Surgery, Lasers and Imaging Retina

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Imaging: Case Report 

Intravitreal Gentamicin-Induced Macular Infarction: SD-OCT Features

Anita R. Shirodkar, MD; Avinash Pathengay, MD, FRCS; Harry W. Flynn, MD

Abstract

A 75-year-old woman developed acute-onset endophthalmitis following phacoemulsification in the left eye. She was treated with intravitreal injections of vancomycin, ceftazidime, and gentamicin. The patient had persistent visual loss in the left eye after treatment. Her best-corrected visual acuity was 2/200 in the left eye and examination revealed a pale disc, retinal hemorrhages, and multiple nerve fiber layer infarcts. Fluorescein angiography showed retinal vascular non-perfusion in the macula. On spectral-domain optical coherence tomography (SD-OCT), there was diffuse retinal thinning, absence of the foveal depression, and increased reflectivity of the nerve fiber and ganglion cell layers, but with an intact inner segment/outer segment junction. This case demonstrates SD-OCT features in macular infarction following intravitreal gentamicin, specifically changes involving the inner retina with a relatively intact outer retina.

From the Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, Florida.

Supported by The National Institutes of Health Center grant P30-EY014801 and an unrestricted grant to the University of Miami from Research to Prevent Blindness, New York, New York.

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Harry W. Flynn Jr., MD, Bascom Palmer Eye Institute, 900 NW 17th Street, Miami, FL 33136. E-mail: hflynn@med.miami.edu

Received: February 24, 2011
Accepted: June 30, 2011
Posted Online: August 04, 2011

Abstract

A 75-year-old woman developed acute-onset endophthalmitis following phacoemulsification in the left eye. She was treated with intravitreal injections of vancomycin, ceftazidime, and gentamicin. The patient had persistent visual loss in the left eye after treatment. Her best-corrected visual acuity was 2/200 in the left eye and examination revealed a pale disc, retinal hemorrhages, and multiple nerve fiber layer infarcts. Fluorescein angiography showed retinal vascular non-perfusion in the macula. On spectral-domain optical coherence tomography (SD-OCT), there was diffuse retinal thinning, absence of the foveal depression, and increased reflectivity of the nerve fiber and ganglion cell layers, but with an intact inner segment/outer segment junction. This case demonstrates SD-OCT features in macular infarction following intravitreal gentamicin, specifically changes involving the inner retina with a relatively intact outer retina.

From the Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, Florida.

Supported by The National Institutes of Health Center grant P30-EY014801 and an unrestricted grant to the University of Miami from Research to Prevent Blindness, New York, New York.

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Harry W. Flynn Jr., MD, Bascom Palmer Eye Institute, 900 NW 17th Street, Miami, FL 33136. E-mail: hflynn@med.miami.edu

Received: February 24, 2011
Accepted: June 30, 2011
Posted Online: August 04, 2011

Introduction

Intravitreal antibiotic therapy is standard treatment in postoperative endophthalmitis. The Endophthalmitis Vitrectomy Study reported that the combination of vancomycin (1 mg/0.1 cc) and amikacin (0.4 mg/0.1 cc) is usually effective against the broad spectrum of bacteria causing postoperative endophthalmitis. 1 The aminoglycosides, an important component of intravitreal therapy, are more effective against gram-negative bacteria and can be synergistic with vancomycin for certain gram-positive species. However, there are multiple reports of toxicity following administration of intravitreal aminoglycosides, including macular infarction. 2

In this case, we report spectral-domain optical coherence tomography (SD-OCT) features of macular infarction in a patient following intravitreal gentamicin for acute-onset endophthalmitis following phacoemulsification.

Case Report

A 75-year-old woman developed culture-negative, acute-onset endophthalmitis in her left eye 1 week after phacoemulsification. Initial treatment consisted of an anterior chamber tap and intravitreal injection of gentamicin, vancomycin, and ceftazidime. After 4 days, pars plana vitrectomy with injection of the same three intravitreal antibiotics was performed for worsening inflammation. On clearance of the vitreous opacities, the surgeon observed retinal whitening in the macula. Three months after treatment, the patient sought a second opinion at our institution.

Best-corrected visual acuity was 20/20 in the right eye and 2/200 in the left eye. The posterior segment examination was within normal limits in the right eye. The left eye was noted to have a pale disc, narrowed and obstructed retinal arterioles, posterior pole retinal hemorrhages, and multiple nerve fiber layer infarcts nasal to the disc (Fig. 1 ). Based on the clinical history and characteristic features, a diagnosis of macular infarction secondary to intravitreal gentamicin was made. Fluorescein angiography showed incomplete filling of the narrowed arterioles in the macula and blocked fluorescence corresponding to the retinal hemorrhages. In the late phases of the angiogram, staining of retinal vessels in the macula and perivascular leakage of both the arterioles and venules superotemporally was noted (Fig. 1 ).

Fundus photography and fluorescein angiography of a patient with macular infarction after intravitreal gentamicin. (Top left) Normal retina in the right eye. (Top right) Affected left eye with a pale disc, retinal hemorrhages, macular edema, and multiple nerve fiber layer infarcts. (Bottom left) Fluorescein angiography, early phase, left eye, with incomplete filling of the narrowed arterioles in the macula. (Bottom right) Fluorescein angiography, late phase, left eye, with staining of the vessel walls and perivascular leakage.

Figure 1.

Fundus photography and fluorescein angiography of a patient with macular infarction after intravitreal gentamicin. (Top left) Normal retina in the right eye. (Top right) Affected left eye with a pale disc, retinal hemorrhages, macular edema, and multiple nerve fiber layer infarcts. (Bottom left) Fluorescein angiography, early phase, left eye, with incomplete filling of the narrowed arterioles in the macula. (Bottom right) Fluorescein angiography, late phase, left eye, with staining of the vessel walls and perivascular leakage.

SD-OCT (Spectralis OCT; Heidelberg Engineering, Inc., Heidelberg, Germany, and Cirrus OCT; Carl Zeiss Meditec, Dublin, CA) revealed increased reflectivity of both the nerve fiber and the ganglion cell layers and loss of the foveal depression. There was a lack of a clear differentiation of the other layers of inner retina, but the external limiting membrane and the inner segment/outer segment junction of the outer retina were intact. These findings indicate that the structural changes from toxicity were more prominent in the inner retina. The internal limiting membrane–retinal pigment epithelium thickness map obtained on Cirrus OCT showed a reduction in the thickness of the central (219 μm) and non-central subfields in the left eye when compared with the right eye (Figs. 2 and 3 ).

Spectral-domain optical coherence tomography (SD-OCT) features comparing the normal macula of the right eye and macular infarction of the left eye following intravitreal gentamicin. (Top left) Heidelberg SD-OCT (Heidelberg Engineering, Inc., Heidelberg, Germany), right eye. (Top right) Heidelberg SD-OCT, left eye. (Center left) Quantitative Cirrus SD-OCT (Carl Zeiss Meditec, Dublin, CA) thickness map, right eye. (Center right) Quantitative Cirrus SD-OCT thickness map, left eye. (Bottom left) Cirrus SD-OCT, right eye. Bottom right: Cirrus SD-OCT, left eye. Compared to the normal right eye, the affected left eye demonstrates increased reflectivity of the nerve fiber and the ganglion cell layers (A), loss of the foveal depression (B), thinning and lack of differentiation of other layers of the inner retina (C), and an intact external limiting membrane and inner segment/outer segment junction (D).

Figure 2.

Spectral-domain optical coherence tomography (SD-OCT) features comparing the normal macula of the right eye and macular infarction of the left eye following intravitreal gentamicin. (Top left) Heidelberg SD-OCT (Heidelberg Engineering, Inc., Heidelberg, Germany), right eye. (Top right) Heidelberg SD-OCT, left eye. (Center left) Quantitative Cirrus SD-OCT (Carl Zeiss Meditec, Dublin, CA) thickness map, right eye. (Center right) Quantitative Cirrus SD-OCT thickness map, left eye. (Bottom left) Cirrus SD-OCT, right eye. Bottom right: Cirrus SD-OCT, left eye. Compared to the normal right eye, the affected left eye demonstrates increased reflectivity of the nerve fiber and the ganglion cell layers (A), loss of the foveal depression (B), thinning and lack of differentiation of other layers of the inner retina (C), and an intact external limiting membrane and inner segment/outer segment junction (D).

Spectral-domain optical coherence tomography (SD-OCT) comparing internal limiting membrane–retinal pigment epithelium (ILM-RPE) thickness maps of the macula of both eyes. (Left) Cirrus OCT (Carl Zeiss Meditec, Dublin, CA) ILM-RPE thickness map of the macula in the normal right eye. (Right) Cirrus OCT ILM-RPE thickness map of the macula in the affected left eye. The left eye shows a decreased thickness of the central and non-central subfields when compared with the right eye.

Figure 3.

Spectral-domain optical coherence tomography (SD-OCT) comparing internal limiting membrane–retinal pigment epithelium (ILM-RPE) thickness maps of the macula of both eyes. (Left) Cirrus OCT (Carl Zeiss Meditec, Dublin, CA) ILM-RPE thickness map of the macula in the normal right eye. (Right) Cirrus OCT ILM-RPE thickness map of the macula in the affected left eye. The left eye shows a decreased thickness of the central and non-central subfields when compared with the right eye.

Discussion

Intravitreal gentamicin has been reported to cause macular toxicity at varying doses ranging from 0.1 to 0.4 mg. 2 Macular infarction has been noted in some patients treated with this antibiotic secondary to closure of the retinal vessels and possibly additional effects from toxins produced by microorganisms. 3–5 Changes consistent with this previously described macular infarction were noted in our patient. The presence of retinal hemorrhages associated with macular infarction has been hypothesized to be due to free radical damage to the vascular endothelium induced by the aminoglycoside. 6 The vascular endothelial damage could also possibly explain the staining of the retinal vessel walls and perivascular leakage noted in the late phase of the fluorescein angiogram in this patient.

The current report highlights the SD-OCT features of the macular infarction. In this patient, the inner layers of the affected macula showed increased reflectivity of both the nerve fiber and the ganglion cell layers, and there was no clear differentiation of other layers of the inner retina compared to the normal eye. The increase in reflectivity could be due to edema of the nerve fiber layer and necrosis of the ganglion cells, as demonstrated by Conway et al. in the histopathology of the primate retina. 7 A dose-dependent toxicity was observed in animal experiments, with a lower dose associated with inner retinal injury, and a higher dose causing full-thickness retinal necrosis. 8 The outer retina was intact in this patient and may indicate that a lower dose of gentamicin was used, but we do not have access to data regarding the exact dose of intravitreal gentamicin used in the initial and subsequent treatment of this patient. Studies have suggested that gentamicin is more toxic to the retina than other aminoglycosides. 9 The changes observed in the inner retina of this patient are similar to a previous report of macular infarction following amikacin toxicity noted on time-domain OCT. 10 With SD-OCT, by contrast, a relatively intact outer retina was observed in this patient.

SD-OCT imaging is useful for a more detailed in vivo depiction of the structural changes in macular toxicity following intravitreal gentamicin.

References

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  9. Penha FM, Rodrigues EB, Maia M, et al. Retinal and ocular toxicity in ocular application of drugs and chemicals—part II: retinal toxicity of current and new drugs. Ophthalmic Res . 2010;44:205–224. doi:10.1159/000316695 [CrossRef]
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10.3928/15428877-20110728-01

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