INTRARETINAL DEPOSITION OF TRIAMCINOLONE ACETONIDE AFTER TREATMENT OF DIABETIC MACULAR EDEMA Varsha Manjunath, BS, Jay S. Duker, MD
Purpose: To report a case of intraretinal triamcinolone acetonide crystal deposition visualized both clinically and on optical coherence tomography after intravitreal injection for diabetic macular edema refractory to focal/grid laser treatment. Methods: Observational case report. A 46-year-old man with severe bilateral diabetic macular edema underwent focal/grid laser therapy, Avastin (Genetech, Inc., South San Francisco, CA) injections, and multiple intravitreal triamcinolone acetonide treatments but remained refractory to treatment. Results: Visual acuity continued to worsen, and clinical and optical coherence tomography examination revealed scattered hyperreflective deposits throughout the retina. Conclusion: Intravitreal triamcinolone acetonide can deposit within the retina after treatment of refractory diabetic macular edema. RETINAL CASES & BRIEF REPORTS 5:241–244, 2011
be effective in the short term in reducing macular edema and improving visual acuity.3 Optical coherence tomography is useful in tracking progression of retinal pathology and response to treatment. Reduction in macular edema after treatment with IVTA has been documented using optical coherence tomography.4 Intravitreal triamcinolone acetonide is used widely in clinical practice; however, several studies have demonstrated adverse effects of IVTA because of the ocular effects of the drug (ocular hypertension, glaucoma, and cataracts), injection-related complications (endophthalmitis, vitreous hemorrhage, and retinal detachment), and potential toxicity of triamcinolone acetonide (TA) or its carrier.3,5 Intraretinal TA deposition after treatment of diabetic macular edema in the clinic, to our knowledge, has not been reported.
From the New England Eye Center, Tufts Medical Center, Boston, Massachusetts.
acular edema affects approximately one third of patients with long-term diabetes, accounting for a significant degree of visual loss in this population.1 Diabetic macular edema is thought to occur because of the breakdown of the blood-retinal barrier in intraretinal vessels.2 Laser treatment is considered first-line treatment of diabetic macular edema; however, patients with the diffuse form of macular edema have a poorer prognosis.3 In patients with diabetic macular edema refractory to laser treatment, intravitreal triamcinolone acetonide (IVTA) has been shown to
This work was supported in part by a Research to Prevent Blindness Challenge grant to the New England Eye Center, Tufts University School of Medicine, National Institutes of Health contracts RO1-EY11289-23, R01-EY13178-07, Air Force Office of Scientific Research FA9550-07-1-0101 and FA9550-07-1-0014, and the Lions Club of Massachusetts. The sponsors had no role in the design or conduct of this research. J.S. Duker received research support from Carl Zeiss Meditech, Inc, Optovue, Inc, and Topcon Medical Systems, Inc. Reprint requests: Jay S. Duker, MD, Department of Ophthalmology, Tufts Medical Center, 800 Washington Street, Box #450, Boston, MA 02111; e-mail: [email protected]
Case Report A 46-year-old man, with a medical history significant for 13 years of poorly controlled Type 2 diabetes mellitus and hypertension, was referred to the New England Eye Center, Boston, MA, for retina consultation after 1.5 years of bilateral severe diabetic macular edema refractory to treatment. Between April 2007 and October 2008, the patient underwent focal/grid laser treatment 6 times in the right eye and 5 times in the left eye. He was also treated with Avastin
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Fig. 1. A. Color fundus photograph of the left eye demonstrating fine TA crystal deposits scattered throughout the retina. B. Cirrus HD-OCT three-dimensional volume rendering with TA deposits visible in the optical coherence tomography image suspended in the vitreous, resting on the surface, and within the retina (red arrows).
(Genetech, Inc., South San Francisco, CA) twice in the right eye and IVTA twice in each eye. Intravitreal triamcinolone acetonide provided only subjective temporary improvement in vision, but the patient’s vision in both eyes severely deteriorated despite treatment within the 2 months before his visit. On examination, the patient’s visual acuity in the right eye was 20/300 and improved to 20/200 through pinhole and 20/50 in the left eye with no improvement through pinhole. The intraocular pressure was 21 mmHg in the right eye and 22 mmHg in the left eye. A slit-lamp examination revealed significant posterior subcapsular cataract with the right eye more severely affected than the left eye. Significant cystoid macular edema with scattered hard exudates was noted over moderate background retinopathy. Multiple highly refractive crystals were observed to be resting on the surface of the eye (Figure 1A). Fluorescein angiography demonstrated some late leakage, which was worst in the left eye. Spectral domain optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditech, Inc, Dublin, CA) showed massive intraretinal thickening bilaterally within the inner and outer retinas, subretinal fluid, and discrete hyperreflective deposits scattered throughout the retina (Figure 1B).
Discussion To the best of our knowledge, there are no previously reported cases of intraretinal TA deposition after treatment of diabetic macular edema. Subretinal TA deposition has been reported after pars plana vitrectomy.6,7 In previously reported cases, TA deposits were noted to spontaneously resolve with no residual gross or function abnormalities; thus, surgical removal could not be justified.6,7 It was hypothesized that without the vitreous to trap TA, it could accumulate in the macula of vitrectomized eyes because of the effects of gravity.6 In this case, TA was deposited throughout the retina despite an intact vitreous. Hyperreflective intraretinal foci seen on optical coherence tomography have also been reported
Fig. 2. High-definition fiveline raster images. Measurements between two separate deposits seen on the fundus image shown to have the same distances between the retinal surface deposits visible on the corresponding optical coherence tomography image.
INTRARETINAL TRIAMCINOLONE DEPOSITION
Fig. 3. Macular cube scan (512 3 128). A. Fundus image with pink and blue navigators corresponding to optical coherence tomography image on right. B. Optical coherence tomography image demonstrating intraretinal deposits (red arrow) located equidistant on both optical coherence tomography and fundus images.
in patients with diabetic macular edema, which were characterized as protein and lipid deposits.8 The images obtained for our patient are unique, however; the fundus image shows a scattering of discrete white deposits rather than yellow plaques as seen with exudates, and optical coherence tomography reveals both intravitreal and intraretinal deposits. The deposits seen suspended in the vitreous and resting on the surface (Figure 2) appear to be the same as those embedded within the retina (Figure 3), all measuring approximately 50 mm in diameter. Many recent studies have investigated the potential retinotoxicity of intraocular TA on retinal pigment epithelial cells possibly related to the vehicle carrier, benzyl alcohol, or the potentiating effects of the carrier. Chang et al5 in their in vitro studies found TA with benzyl alcohol at clinical concentrations to cause retinal pigment epithelial cell damage in a dose- and
time-dependent fashion with cell death occurring because of a necrotic response. However, when Lang et al.9 studied the functional effects of a standard 4-mg dose of TA on patients with severe diabetic macular edema using electroretinography, no demonstrable toxicity to the outer retina was identified. Considering the large volume of data on this topic and the discrepancy between in vitro and in vivo outcomes and animal and human studies, it is difficult to say if drug toxicity has any role in our patient’s deteriorating vision or if there is a relationship with the intraretinal deposits. Interestingly, Schulze-Do¨bold and Weber10 reported a case of repeated treatments of IVTA for uveitis and cystoid macular edema. The patient experienced initial improvement; however, edema reoccurred between injections and the patient experienced continuous decrease in visual acuity down to finger counting. The patient demonstrated global retinal functional loss shown in the electroretinography, an atypical finding in idiopathic uveitis and may have been a consequence of the toxic property of the repeatedly injected substance.10 For a patient with diabetic macular edema, IVTA has been shown to be effective at reducing edema and improving visual acuity in the short term.3 However, because these patients will likely require long-term treatment, potential toxicity from IVTA should be taken into consideration. The current report is limited in follow-up, so the cause of the deposits seen in this patient is unclear and if they in fact have a role in the patient’s continued vision decline or if it is a result of diabetes advancement. It is possible that TA accumulated in the eye with multiple high-dose injections; however, it is difficult to speculate on the cause of precipitation. Intravitreal triamcinolone acetonide is a useful drug in the treatment of refractory diabetic macular edema; however, deposition can occur with unknown long-term consequences. Key words: intraretinal deposits, optical coherence tomography, refractory diabetic macular edema, triamcinolone acetonide deposition.
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