EFFECT OF INTRAVITREAL DEXAMETHASONE IMPLANT ON THE CONTRALATERAL EYE: A CASE REPORT Ashish Sharma, MD, Jay Sheth, DO, Rangasamy J. Madhusudan, DO, Selva K. Sundaramoorthy, FRCS
Purpose: To describe the effect of unilateral intravitreal injection of 0.7-mg dexamethasone implant on the other eye. Methods: Interventional case report and literature review. Results: A 54-year-old woman with bilateral, refractory, clinically significant macular edema was given an intravitreal injection of 0.7-mg dexamethasone sustained release implant in the right eye. The central foveal thickness improved in both the eyes with recurrence of edema after 16 weeks in both the eyes. Conclusion: An intravitreal dexamethasone injection seems to have bilateral effect after unilateral injection. RETINAL CASES & BRIEF REPORTS 7:217–219, 2013
From the Lotus Eye Care Hospital, Coimbatore, Tamil Nadu, India.
Case Report A 54-year-old woman of south Asian origin, with a history of Type 2 diabetes mellitus for the past 6 years, presented with diminished vision in both eyes for 6 months. Her best-corrected visual acuity was 6/24, N12 (right eye) and 6/12, N12 (left eye) on the Snellen visual acuity chart. Grid laser photocoagulation had been performed elsewhere 7 months previously, and the patient noticed progressive worsening of vision since then. She was diagnosed with bilateral moderate nonproliferative diabetic retinopathy and refractory clinically significant diabetic macular edema involving the right eye more than the left eye. With spectral-domain optical coherence tomography, the central foveal thickness (CFT) was found to be 586 mm and 450 mm in the right and left eyes, respectively. On this stage, 0.7-mg intravitreal dexamethasone implant (Ozurdex) was injected in the right eye (Visit 1) (Figures 1 and 2). A week later (Visit 2) (Figures 1 and 2), the patient showed a bilateral improvement on optical coherence tomography with the CFT decreased to 448 mm (right eye) and 388 mm (left eye), with a reduction of 23.55% and 13.78% in the macular edema in the right eye and left eye, respectively. The best-corrected visual acuity at this stage improved to 6/18, N8 in the right eye and 6/12, N10 in the left eye. Six weeks later (Visit 3) (Figure 1 and 2), the CFT had come down to 328 mm (right eye) and 361 mm (left eye), with a reduction of 44% and 19.78% in the macular edema in the right eye and left eye, respectively. The vision of the patient had also improved to 6/9, N6 in both the eyes. Sixteen weeks later (Visit 4) (Figure 1 and 2), the CFT again increased to 593 mm (right eye) and 381 mm (left eye), an increase of 1.2% in the right eye and a reduction of 15.33% in the left eye, respectively, from the time dexamethasone implant was injected. However, she had maintained
A
n intravitreal 0.7-mg dexamethasone implant (Ozurdex, Allergan, Inc., Irvine, CA) is a novel device composed of a biodegradable copolymer of lactic acid and glycolic acid that contains micronized dexamethasone. It has been approved by U.S. Food and Drug Administration to treat patients with noninfectious uveitis and macular edema that results from retinal vein occlusion, as described by Lowder et al1 and Haller et al.2 However, it is also used as an off-label treatment of diabetic macular edema.3 Al-Dhibi and Khan,4 Wu and Sadda,5 Rouvas et al,6 as well as Jonas et al7 have described the effects of intravitreal preparations, such as bevacizumab, ranibizumab, and triamcinolone, on the contralateral eye. However, after a thorough PubMed/MEDLINE search, it was found that the effect of intravitreal dexamethasone on the contralateral eye has not been described earlier. Supported by Lotus Vision Research fund. The authors report no conflicts of interest. Reprint requests: Ashish Sharma, MD, Consultant Retina and Research, Lotus Eye Care Hospital, Coimbatore, Tamil Nadu, India; e-mail- [email protected]
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Fig. 1. Central foveal thickness (in micrometers) of both eyes (y axis) and follow-up visits (x axis) from the day the intravitreal dexamethasone implant was injected in the right eye. Visit 1, dexamethasone implant injection in the right eye; Visit 2, 1 week after implant injection; Visit 3, 6 weeks after implant injection; Visit 4, 16 weeks after implant.
her best-corrected visual acuity at 6/9, N6 in both the eyes. Her HbA1c level was 7.1%, and the results of renal function tests were normal along with normal lipid profile on atorvastatin during the study period. Further management in the form of second implant could not be performed because the patient did not return to us for further care.
Discussion Macular edema is a major cause of visual impairment in the modern era. It can occur secondary to multiple etiologies, such as diabetic retinopathy,
Fig. 2. Macular optical coherence tomography at each visit. Visit 1, dexamethasone implant injection in the right eye; Visit 2, 1 week after implant injection; Visit, 3 weeks after implant injection; Visit 4, 16 weeks after implant injection; OD, right eye; OS, left eye.
retinal venous occlusions, uveitis, and postintraocular surgeries, to name a few. Corticosteroids administered as topical drops, sub-Tenon’s injection, intravitreal injections, implants, and systemically are used to treat macular edema. They acts as a potent anti-inflammatory agents, inhibit fibrin deposition and leukocyte movements, reduce vascular permeability, and inhibit the synthesis of prostaglandins, prostacyclins, vascular endothelial growth factor, and other cytokines. In a recently published study, Haller et al8 has shown that intravitreal dexamethasone implant helps to improve the visual acuity because it reduces macular thickness and fluorescein leakage in cases of persistent macular edema caused by diabetes. The response in the right eye of our patient illustrates the benefit in the presence of macular edema that had not responded to grid laser photocoagulation 7 months ago. In addition, it illustrates, in keeping with our experience (unpublished data), that the effect of intravitreal implant lasts between 3 months and 4 months in cases of refractory clinically significant macular edema. In addition, the case shows a significant reduction in CFT in the contralateral eye, with a peak reduction of 19.78% at the end of 6 weeks, which is an important observation to be looked at. The exact mechanism by which the dexamethasone affects the contralateral eye has not been elucidated nor has any such case been reported to the best of our knowledge. Improvement in CFT could be the result of good metabolic control while under our care, but such an improvement in CFT in an eye with refractory clinically significant macular edema seems unlikely from good metabolic control alone. In addition,
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recurrence of clinically significant macular edema after 16 weeks, which coincides with the weaning off effect of the implant, illustrates that good metabolic control alone may not be the sole responsible factor for the improvement in CFT. It can be hypothesized that corticosteroid molecules may escape into the systemic circulation and consequently reaches the contralateral eye. Systemic effects from topical application of medication are well-known. Recently, Rosenfeld et al9 described the systemic side effect, such as stroke, after intravitreal anti–vascular endothelial growth factor injections. This is a significant observation considering the fact that dexamethasone has diverse systemic and ocular adverse reactions, including deranged glycemic control, osteoporosis, immunosuppression, cataract formation, and an increase in the intraocular pressure, as described by Agnes et al.10 One limitation of our case report is that we could not get the drug assays from serum, aqueous humor, and vitreous humor of the patient to quantify the drug concentration at each visit. However, based on our case report, we can postulate that treatment with a dexamethasone implant in one eye can have a contralateral effect, which though beneficial in our case, can also be detrimental. This warrants further investigation into the pharmacokinetics of the drug and into the potential bilateral benefit after unilateral treatment. Key words: dexamethasone implant, clinically significant macular edema, contralateral effect.
References 1. Lowder C, Belfort R Jr, Lightman S, et al. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol 2011;129:545–553. 2. Haller JA, Bandello F, Belfort R Jr, et al. Randomized, shamcontrolled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology 2010;117:1134–1146. 3. Boyer DS, Faber D, Gupta S, et al. Dexamethasone intravitreal implant for treatment of diabetic macular edema in vitrectomized patients. Retina 2011;31:915–923. 4. Al-Dhibi H, Khan AO. Bilateral response following unilateral intravitreal bevacizumab injection in a child with uveitic cystoid macular edema. J AAPOS 2009;13:400–402. 5. Wu Z, Sadda SR. Effects on the contralateral eye after intravitreal bevacizumab and ranibizumab injections: a case report. Ann Acad Med Singapore 2008;37:591–593. 6. Rouvas A, Liarakos VS, Theodossiadis P, et al. The effect of intravitreal ranibizumab on the fellow untreated eye with subfoveal scarring due to exudative age-related macular degeneration. Ophthalmologica 2009;223:383–389. 7. Jonas JB, Harder B, Kamppeter BA. Inter-eye difference in diabetic macular edema after unilateral intravitreal injection of triamcinolone acetonide. Am J Ophthalmol 2008;145:854–861. 8. Haller JA, Kuppermann BD, Blumenkranz MS, et al. Randomized controlled trial of an intravitreous dexamethasone drug delivery system in patients with diabetic macular edema. Arch Ophthalmol 2010;128:289–296. 9. Rosenfeld PJ, Rich RM, Lalwani GA. Ranibizumab: phase III clinical trial results. Ophthalmol Clin North Am 2006;19:361–372. 10. Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol 2011; 335:2–13.
Purpose: To describe the effect of unilateral intravitreal injection of 0.7-mg dexamethasone implant on the other eye. Methods: Interventional case report and literature review. Results: A 54-year-old woman with bilateral, refractory, clinically significant macular edema was given an intravitreal injection of 0.7-mg dexamethasone sustained release implant in the right eye. The central foveal thickness improved in both the eyes with recurrence of edema after 16 weeks in both the eyes. Conclusion: An intravitreal dexamethasone injection seems to have bilateral effect after unilateral injection. RETINAL CASES & BRIEF REPORTS 7:217–219, 2013
From the Lotus Eye Care Hospital, Coimbatore, Tamil Nadu, India.
Case Report A 54-year-old woman of south Asian origin, with a history of Type 2 diabetes mellitus for the past 6 years, presented with diminished vision in both eyes for 6 months. Her best-corrected visual acuity was 6/24, N12 (right eye) and 6/12, N12 (left eye) on the Snellen visual acuity chart. Grid laser photocoagulation had been performed elsewhere 7 months previously, and the patient noticed progressive worsening of vision since then. She was diagnosed with bilateral moderate nonproliferative diabetic retinopathy and refractory clinically significant diabetic macular edema involving the right eye more than the left eye. With spectral-domain optical coherence tomography, the central foveal thickness (CFT) was found to be 586 mm and 450 mm in the right and left eyes, respectively. On this stage, 0.7-mg intravitreal dexamethasone implant (Ozurdex) was injected in the right eye (Visit 1) (Figures 1 and 2). A week later (Visit 2) (Figures 1 and 2), the patient showed a bilateral improvement on optical coherence tomography with the CFT decreased to 448 mm (right eye) and 388 mm (left eye), with a reduction of 23.55% and 13.78% in the macular edema in the right eye and left eye, respectively. The best-corrected visual acuity at this stage improved to 6/18, N8 in the right eye and 6/12, N10 in the left eye. Six weeks later (Visit 3) (Figure 1 and 2), the CFT had come down to 328 mm (right eye) and 361 mm (left eye), with a reduction of 44% and 19.78% in the macular edema in the right eye and left eye, respectively. The vision of the patient had also improved to 6/9, N6 in both the eyes. Sixteen weeks later (Visit 4) (Figure 1 and 2), the CFT again increased to 593 mm (right eye) and 381 mm (left eye), an increase of 1.2% in the right eye and a reduction of 15.33% in the left eye, respectively, from the time dexamethasone implant was injected. However, she had maintained
A
n intravitreal 0.7-mg dexamethasone implant (Ozurdex, Allergan, Inc., Irvine, CA) is a novel device composed of a biodegradable copolymer of lactic acid and glycolic acid that contains micronized dexamethasone. It has been approved by U.S. Food and Drug Administration to treat patients with noninfectious uveitis and macular edema that results from retinal vein occlusion, as described by Lowder et al1 and Haller et al.2 However, it is also used as an off-label treatment of diabetic macular edema.3 Al-Dhibi and Khan,4 Wu and Sadda,5 Rouvas et al,6 as well as Jonas et al7 have described the effects of intravitreal preparations, such as bevacizumab, ranibizumab, and triamcinolone, on the contralateral eye. However, after a thorough PubMed/MEDLINE search, it was found that the effect of intravitreal dexamethasone on the contralateral eye has not been described earlier. Supported by Lotus Vision Research fund. The authors report no conflicts of interest. Reprint requests: Ashish Sharma, MD, Consultant Retina and Research, Lotus Eye Care Hospital, Coimbatore, Tamil Nadu, India; e-mail- [email protected]
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Fig. 1. Central foveal thickness (in micrometers) of both eyes (y axis) and follow-up visits (x axis) from the day the intravitreal dexamethasone implant was injected in the right eye. Visit 1, dexamethasone implant injection in the right eye; Visit 2, 1 week after implant injection; Visit 3, 6 weeks after implant injection; Visit 4, 16 weeks after implant.
her best-corrected visual acuity at 6/9, N6 in both the eyes. Her HbA1c level was 7.1%, and the results of renal function tests were normal along with normal lipid profile on atorvastatin during the study period. Further management in the form of second implant could not be performed because the patient did not return to us for further care.
Discussion Macular edema is a major cause of visual impairment in the modern era. It can occur secondary to multiple etiologies, such as diabetic retinopathy,
Fig. 2. Macular optical coherence tomography at each visit. Visit 1, dexamethasone implant injection in the right eye; Visit 2, 1 week after implant injection; Visit, 3 weeks after implant injection; Visit 4, 16 weeks after implant injection; OD, right eye; OS, left eye.
retinal venous occlusions, uveitis, and postintraocular surgeries, to name a few. Corticosteroids administered as topical drops, sub-Tenon’s injection, intravitreal injections, implants, and systemically are used to treat macular edema. They acts as a potent anti-inflammatory agents, inhibit fibrin deposition and leukocyte movements, reduce vascular permeability, and inhibit the synthesis of prostaglandins, prostacyclins, vascular endothelial growth factor, and other cytokines. In a recently published study, Haller et al8 has shown that intravitreal dexamethasone implant helps to improve the visual acuity because it reduces macular thickness and fluorescein leakage in cases of persistent macular edema caused by diabetes. The response in the right eye of our patient illustrates the benefit in the presence of macular edema that had not responded to grid laser photocoagulation 7 months ago. In addition, it illustrates, in keeping with our experience (unpublished data), that the effect of intravitreal implant lasts between 3 months and 4 months in cases of refractory clinically significant macular edema. In addition, the case shows a significant reduction in CFT in the contralateral eye, with a peak reduction of 19.78% at the end of 6 weeks, which is an important observation to be looked at. The exact mechanism by which the dexamethasone affects the contralateral eye has not been elucidated nor has any such case been reported to the best of our knowledge. Improvement in CFT could be the result of good metabolic control while under our care, but such an improvement in CFT in an eye with refractory clinically significant macular edema seems unlikely from good metabolic control alone. In addition,
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recurrence of clinically significant macular edema after 16 weeks, which coincides with the weaning off effect of the implant, illustrates that good metabolic control alone may not be the sole responsible factor for the improvement in CFT. It can be hypothesized that corticosteroid molecules may escape into the systemic circulation and consequently reaches the contralateral eye. Systemic effects from topical application of medication are well-known. Recently, Rosenfeld et al9 described the systemic side effect, such as stroke, after intravitreal anti–vascular endothelial growth factor injections. This is a significant observation considering the fact that dexamethasone has diverse systemic and ocular adverse reactions, including deranged glycemic control, osteoporosis, immunosuppression, cataract formation, and an increase in the intraocular pressure, as described by Agnes et al.10 One limitation of our case report is that we could not get the drug assays from serum, aqueous humor, and vitreous humor of the patient to quantify the drug concentration at each visit. However, based on our case report, we can postulate that treatment with a dexamethasone implant in one eye can have a contralateral effect, which though beneficial in our case, can also be detrimental. This warrants further investigation into the pharmacokinetics of the drug and into the potential bilateral benefit after unilateral treatment. Key words: dexamethasone implant, clinically significant macular edema, contralateral effect.
References 1. Lowder C, Belfort R Jr, Lightman S, et al. Dexamethasone intravitreal implant for noninfectious intermediate or posterior uveitis. Arch Ophthalmol 2011;129:545–553. 2. Haller JA, Bandello F, Belfort R Jr, et al. Randomized, shamcontrolled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology 2010;117:1134–1146. 3. Boyer DS, Faber D, Gupta S, et al. Dexamethasone intravitreal implant for treatment of diabetic macular edema in vitrectomized patients. Retina 2011;31:915–923. 4. Al-Dhibi H, Khan AO. Bilateral response following unilateral intravitreal bevacizumab injection in a child with uveitic cystoid macular edema. J AAPOS 2009;13:400–402. 5. Wu Z, Sadda SR. Effects on the contralateral eye after intravitreal bevacizumab and ranibizumab injections: a case report. Ann Acad Med Singapore 2008;37:591–593. 6. Rouvas A, Liarakos VS, Theodossiadis P, et al. The effect of intravitreal ranibizumab on the fellow untreated eye with subfoveal scarring due to exudative age-related macular degeneration. Ophthalmologica 2009;223:383–389. 7. Jonas JB, Harder B, Kamppeter BA. Inter-eye difference in diabetic macular edema after unilateral intravitreal injection of triamcinolone acetonide. Am J Ophthalmol 2008;145:854–861. 8. Haller JA, Kuppermann BD, Blumenkranz MS, et al. Randomized controlled trial of an intravitreous dexamethasone drug delivery system in patients with diabetic macular edema. Arch Ophthalmol 2010;128:289–296. 9. Rosenfeld PJ, Rich RM, Lalwani GA. Ranibizumab: phase III clinical trial results. Ophthalmol Clin North Am 2006;19:361–372. 10. Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol 2011; 335:2–13.
