http://informahealthcare.com/cot ISSN: 1556-9527 (print), 1556-9535 (electronic) Cutan Ocul Toxicol, Early Online: 1–3 ! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/15569527.2014.951450
CASE REPORT
Post-operative refractory cystoid macular edema in a vitrectomized eye treated with slow-release dexamethasone implant (Ozurdex) Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by University of Melbourne on 09/15/14 For personal use only.
Ilias Georgalas1, Petros Petrou1, Dimitrios Papakonstantinou1, Vagelis Droumouchtsis1, and Ioannis Tservakis2 1
Department of Ophthalmology, University of Athens, Athens, Greece and 2Department of Ophthalmology, NHS, Athens, Greece
Abstract
Keywords
Introduction: The use of a slow-release dexamethasone implant (Ozurdex) for the treatment of post-operative macular edema (ME) in a vitrectomized eye has never been used before. We herein report a case of a 70-year-old woman with post-vitrectomy ME refractory to topical, sub-tenon’s and intravitreal steroid administration that responded well to the implantation of a slow-release dexamethasone implant (Ozurdex) in a previously vitrectomized eye. Methods: Interventional case presentation. Results: One week post-implantation, the central retinal thickness was reduced to 383 mm from 640 mm and the best corrected visual acuity (BCVA) improved to 6/36 from counting fingers (CF). At six months’ follow-up visit, the improvement of the ME was sustained as indicated by the optical coherence tomography (OCT) measurements and the BCVA remained stable. No serious topical or systemic adverse events were observed from the implantation of Ozurdex in the vitrectomized eye. Conclusion: The use of Ozurdex in our case resulted in rapid improvement of the post-operative resistant ME. To the best of our knowledge, this is the first report in the literature demonstrating the use of the slow-release dexamethasone implant (Ozurdex) to treat postoperative ME in a vitrectomized eye.
Dexamethasone implant, Ozurdex, post-operative macular edema, vitrectomy
Introduction Although the clinical characteristics and management of macular edema (ME) following cataract surgery have been adequately described in the literature, there is limited data describing the development and incidence of ME following vitrectomy1. Parolini and Sartore in a recent paper reported an overall incidence of post-vitrectomy ME of 10.8% in a homogenous series of eyes that underwent epiretinal membrane (ERM) peeling, although the incidence of postvitrectomy ME reported by Kim et al. in a prospective cohort study was found much higher (47%)2,3. Post-operative ME represents a result of surgical trauma and the underlying pathophysiological mechanism involves the metabolism of arachidonic acid to prostaglandins and leucotrienes by cyclooxygenase (COX-1 and COX-2)4. The combination of topical application of non-steroid antiinflammatory drugs (NSAIDs) and steroids blocks two different arms of this pathway, inhibiting the synthesis of prostaglandins. NSAIDs interfere with the activity of COX-1 and COX-2, and corticosteroids interfere with the activity of phospholipase A2, both inhibiting the release of arachidonic acid and the production of its metabolites, including prostaglandins4. Address for correspondence: Dr Petros Petrou, Department of Ophthalmology, University of Athens, Athens, Greece. E-mail: [email protected]
History Received 6 June 2014 Revised 6 July 2014 Accepted 30 July 2014 Published online 29 August 2014
We herein report a case of a 70-year-old woman with post-vitrectomy ME refractory to topical, sub-tenon’s and intravitreal steroid administration that responded well to the implantation of a slow-release dexamethasone implant (Ozurdex) in a previously vitrectomized eye.
Case report A 70-year-old Caucasian woman was referred to our Department with reduced vision in the left eye (LE). She had a history of vitrectomy, removal of dislocated intraocular lens (IOL) and anterior chamber lens implantation (ACIOL) six months prior to presentation. She had undergone phacoemulsification and IOL implantation 2 years prior to the referral. On examination, the best corrected visual acuity (BCVA) was counting fingers (CF) in the LE and 6/6 in the right eye (RE). Anterior segment examination revealed a wellcentered ACIOL (Figure 1) and the intraocular pressure was 16 mmHg in both eyes. Fundus examination demonstrated an attached retina with post-operative cystoid ME that was confirmed on optical coherence tomography (OCT) and fluorescein angiography (FA) (Figure 2). The central retinal thickness (CRT) at that point was measured at 640 mm. The initial management of the cystoid macular edema involved a combination of topical steroids (dexamethasone 0.1%) and topical NSAIDs (nepafenac 1 mg/ml) four times a day for 6 weeks. in view of the lack of response to treatment,
2
I. Georgalas et al.
Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by University of Melbourne on 09/15/14 For personal use only.
sub-tenon’s injections of 1 ml of 4 mg betamethasone and intravitreal triamcinolone injections were performed in addition to the topical therapy. The edema was refractory to treatment and therefore the implantation of an Ozurdex was carried out. One-week post-implantation, the CRT was reduced to 383 mm (Figure 2C) and the BCVA improved to 6/36. At six months’ follow-up visit, the improvement of the ME was sustained and the BCVA remained stable. No serious topical or systemic adverse events were observed from the implantation of Ozurdex in the vitrectomized eye and the implant was not observed migrating in the anterior chamber during the follow-up period.
Figure 1. Anterior segment photo of the left eye demonstrating a well-centered ACIOL.
Cutan Ocul Toxicol, Early Online: 1–3
Discussion Although the use of the slow-release dexamethasone implant (Ozurdex) in previously vitrectomized eyes has been discussed in the literature, the reports are mainly limited to case reports or to case series of patients with central retinal vein (CRVO)-related, diabetic or uveitic ME5–9. Dexamethasone is a potent corticosteroid which has been shown to suppress inflammation by inhibiting multiple inflammatory cytokines10,11. The Ozurdex’s drug delivery system, by providing sustained delivery of 700 mg of preservative-free dexamethasone to the vitreous cavity can lead to a prolonged effect even in vitrectomized eyes with a tolerable safety profile12. The efficacy and the vitreoretinal pharmacokinetic profile of Ozurdex has been recently studied in vitrectomized and non-vitrectomized eyes in rabbits. The findings of this study showed that there was no statistically significant difference of the dexamethasone concentration between the two groups in any time points9. Furthermore, recent data from a study in vitrectomized and non-vitrectomized eyes with ME related to central retinal vein occlusion support that the duration and efficacy of the dexamethasone intravitreal implant is similar in both groups12. Recently, Macle`s et al.13 reported that patients with inadequate zonular/posterior capsular integrity are of higher risk for anterior chamber migration of the OzurdexÕ implant, a conclusion based on three pseudophakic patients (two with iris claw anterior chamber lenses and one with a posterior chamber IOL and zonular rupture). A similar occurrence was not observed in our patient and although it is difficult to draw an accurate conclusion based on the experience of one patient, it is possible that the classic ACIOL
Figure 2. (A) Fluorescein angiography (FA) examination at the baseline visit, which showed the characteristic late dye leak age in a petaloid pattern. (B) Optical Coherence Tomography (OCT) examination prior to the dexamethasone 0.7 mg intravitreal implantation. Central retinal thickness is 640 mm. (C) OCT in week 1 post-dexamethasone 0.7 mg intravitreal implantation. Central retinal thickness is significantly reduced by 257 mm.
DOI: 10.3109/15569527.2014.951450
Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by University of Melbourne on 09/15/14 For personal use only.
provides a better ‘‘isolation’’ of the anterior chamber and subsequent protection from implant-migration. In our case, the post-operative ME was refractory to any form of steroid or NSAID delivery (topical, sub-tenon’s, intravitreal) prior to Ozurdex implantation. The use of slowrelease dexamethasone implant resulted in reduction of the CRT and improvement in visual acuity in our patient. No adverse events were observed and the implantation was performed without problems in the absence of vitreous. To the best of our knowledge, this is the first report in the literature demonstrating the use of the slow-release dexamethasone implant (Ozurdex) to treat resistant postoperative ME in a vitrectomized eye.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.
References 1. Parke DW, Sisk RA, Murray TG. Intraoperative intravitreal triamcinolone decreases macular edema after vitrectomy with phacoemulsification. Clin Ophthalmol 2012;6:1347–1353. 2. Parolini B, Sartore M. Incidence of cystoid macular edema after vitrectomy for ERM. Presented at EVRS 2012 Congress; 2012 Sept 15–18; Dresden, Germany. 3. Kim SJ, Martin DF, Hubbard 3rd GB, et al. Incidence of postvitrectomy macular edema using optical coherence tomography. Ophthalmology 2009;116:1531–1537.
Ozurdex for refractory post-operative ME
3
4. Cho H, Madu A. Etiology and treatment of the inflammatory causes of cystoid macular edema. J Inflamm Res 2009;2:37–43. 5. Chen TH, Wang JK, Chang SW. Intravitreal dexamethasone implant for a vitrectomised eye with diabetic macular edema. Taiwan J Ophthalmol 2013. Available from: http://www. e-tjo.com/article/S2211-5056%2813%2900029-X/abstract [last accessed Aug 2014]. 6. Reibaldi M, Russo A, Zagari M, et al. Resolution of persistent cystoid macular edema due to central retinal vein occlusion in a vitrectomized eye following intravitreal implant of dexamethasone 0.7 mg. Case Rep Ophthalmol 2012;3:30–34. 7. Feiner L. Dexamethasone implant for treatment of DME in vitrectomized patients. Retina Today 2010:62–63. 8. Ada´n A, Pelegrı´n L, Rey A, et al. Dexamethasone intravitreal implant for treatment ofuveitic persistent cystoid macular edema in vitrectomized patients. Retina 2013;33:1435–1440. 9. Chang-Lin JE, Burke JA, Peng, Q. Pharmacokinetics of a sustained release dexamethasone intravitreal implant in vitrectomized and non vitrectomized eyes. Invest Ophthalmol Vis Sci 2011;52:4605–4609. 10. Shahsuvaryan ML. Therapeutic potential of intravitreal pharmacotherapy in retinal vein occlusion. Int J Ophthalmol 2012;5: 759–770. 11. Robinson LR, Whitcup SM. Pharmacologic and clinical profile of dexamethasone intravitreal implant. Expert Rev Clin Pharmacol 2012;5:629–647. 12. Shaikh AH, Petersen MR, Sisk RA, et al. Comparative effectiveness of the dexamethasone intravitreal implant in vitrectomized and non-vitrectomized eyes with macular edema secondary to central retinal vein occlusion. Ophthalmic Surg Lasers Imaging Retina 2013;44:28–33. 13. Malcle`s A, Janin-Manificat H, Yhuel Y, et al. Anterior chamber migration of intravitreal dexamethasone implant (OzurdexÕ ) in pseudophakic eyes: report of three cases. J Fr Ophthalmol 2013; 36:362–367.
CASE REPORT
Post-operative refractory cystoid macular edema in a vitrectomized eye treated with slow-release dexamethasone implant (Ozurdex) Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by University of Melbourne on 09/15/14 For personal use only.
Ilias Georgalas1, Petros Petrou1, Dimitrios Papakonstantinou1, Vagelis Droumouchtsis1, and Ioannis Tservakis2 1
Department of Ophthalmology, University of Athens, Athens, Greece and 2Department of Ophthalmology, NHS, Athens, Greece
Abstract
Keywords
Introduction: The use of a slow-release dexamethasone implant (Ozurdex) for the treatment of post-operative macular edema (ME) in a vitrectomized eye has never been used before. We herein report a case of a 70-year-old woman with post-vitrectomy ME refractory to topical, sub-tenon’s and intravitreal steroid administration that responded well to the implantation of a slow-release dexamethasone implant (Ozurdex) in a previously vitrectomized eye. Methods: Interventional case presentation. Results: One week post-implantation, the central retinal thickness was reduced to 383 mm from 640 mm and the best corrected visual acuity (BCVA) improved to 6/36 from counting fingers (CF). At six months’ follow-up visit, the improvement of the ME was sustained as indicated by the optical coherence tomography (OCT) measurements and the BCVA remained stable. No serious topical or systemic adverse events were observed from the implantation of Ozurdex in the vitrectomized eye. Conclusion: The use of Ozurdex in our case resulted in rapid improvement of the post-operative resistant ME. To the best of our knowledge, this is the first report in the literature demonstrating the use of the slow-release dexamethasone implant (Ozurdex) to treat postoperative ME in a vitrectomized eye.
Dexamethasone implant, Ozurdex, post-operative macular edema, vitrectomy
Introduction Although the clinical characteristics and management of macular edema (ME) following cataract surgery have been adequately described in the literature, there is limited data describing the development and incidence of ME following vitrectomy1. Parolini and Sartore in a recent paper reported an overall incidence of post-vitrectomy ME of 10.8% in a homogenous series of eyes that underwent epiretinal membrane (ERM) peeling, although the incidence of postvitrectomy ME reported by Kim et al. in a prospective cohort study was found much higher (47%)2,3. Post-operative ME represents a result of surgical trauma and the underlying pathophysiological mechanism involves the metabolism of arachidonic acid to prostaglandins and leucotrienes by cyclooxygenase (COX-1 and COX-2)4. The combination of topical application of non-steroid antiinflammatory drugs (NSAIDs) and steroids blocks two different arms of this pathway, inhibiting the synthesis of prostaglandins. NSAIDs interfere with the activity of COX-1 and COX-2, and corticosteroids interfere with the activity of phospholipase A2, both inhibiting the release of arachidonic acid and the production of its metabolites, including prostaglandins4. Address for correspondence: Dr Petros Petrou, Department of Ophthalmology, University of Athens, Athens, Greece. E-mail: [email protected]
History Received 6 June 2014 Revised 6 July 2014 Accepted 30 July 2014 Published online 29 August 2014
We herein report a case of a 70-year-old woman with post-vitrectomy ME refractory to topical, sub-tenon’s and intravitreal steroid administration that responded well to the implantation of a slow-release dexamethasone implant (Ozurdex) in a previously vitrectomized eye.
Case report A 70-year-old Caucasian woman was referred to our Department with reduced vision in the left eye (LE). She had a history of vitrectomy, removal of dislocated intraocular lens (IOL) and anterior chamber lens implantation (ACIOL) six months prior to presentation. She had undergone phacoemulsification and IOL implantation 2 years prior to the referral. On examination, the best corrected visual acuity (BCVA) was counting fingers (CF) in the LE and 6/6 in the right eye (RE). Anterior segment examination revealed a wellcentered ACIOL (Figure 1) and the intraocular pressure was 16 mmHg in both eyes. Fundus examination demonstrated an attached retina with post-operative cystoid ME that was confirmed on optical coherence tomography (OCT) and fluorescein angiography (FA) (Figure 2). The central retinal thickness (CRT) at that point was measured at 640 mm. The initial management of the cystoid macular edema involved a combination of topical steroids (dexamethasone 0.1%) and topical NSAIDs (nepafenac 1 mg/ml) four times a day for 6 weeks. in view of the lack of response to treatment,
2
I. Georgalas et al.
Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by University of Melbourne on 09/15/14 For personal use only.
sub-tenon’s injections of 1 ml of 4 mg betamethasone and intravitreal triamcinolone injections were performed in addition to the topical therapy. The edema was refractory to treatment and therefore the implantation of an Ozurdex was carried out. One-week post-implantation, the CRT was reduced to 383 mm (Figure 2C) and the BCVA improved to 6/36. At six months’ follow-up visit, the improvement of the ME was sustained and the BCVA remained stable. No serious topical or systemic adverse events were observed from the implantation of Ozurdex in the vitrectomized eye and the implant was not observed migrating in the anterior chamber during the follow-up period.
Figure 1. Anterior segment photo of the left eye demonstrating a well-centered ACIOL.
Cutan Ocul Toxicol, Early Online: 1–3
Discussion Although the use of the slow-release dexamethasone implant (Ozurdex) in previously vitrectomized eyes has been discussed in the literature, the reports are mainly limited to case reports or to case series of patients with central retinal vein (CRVO)-related, diabetic or uveitic ME5–9. Dexamethasone is a potent corticosteroid which has been shown to suppress inflammation by inhibiting multiple inflammatory cytokines10,11. The Ozurdex’s drug delivery system, by providing sustained delivery of 700 mg of preservative-free dexamethasone to the vitreous cavity can lead to a prolonged effect even in vitrectomized eyes with a tolerable safety profile12. The efficacy and the vitreoretinal pharmacokinetic profile of Ozurdex has been recently studied in vitrectomized and non-vitrectomized eyes in rabbits. The findings of this study showed that there was no statistically significant difference of the dexamethasone concentration between the two groups in any time points9. Furthermore, recent data from a study in vitrectomized and non-vitrectomized eyes with ME related to central retinal vein occlusion support that the duration and efficacy of the dexamethasone intravitreal implant is similar in both groups12. Recently, Macle`s et al.13 reported that patients with inadequate zonular/posterior capsular integrity are of higher risk for anterior chamber migration of the OzurdexÕ implant, a conclusion based on three pseudophakic patients (two with iris claw anterior chamber lenses and one with a posterior chamber IOL and zonular rupture). A similar occurrence was not observed in our patient and although it is difficult to draw an accurate conclusion based on the experience of one patient, it is possible that the classic ACIOL
Figure 2. (A) Fluorescein angiography (FA) examination at the baseline visit, which showed the characteristic late dye leak age in a petaloid pattern. (B) Optical Coherence Tomography (OCT) examination prior to the dexamethasone 0.7 mg intravitreal implantation. Central retinal thickness is 640 mm. (C) OCT in week 1 post-dexamethasone 0.7 mg intravitreal implantation. Central retinal thickness is significantly reduced by 257 mm.
DOI: 10.3109/15569527.2014.951450
Cutaneous and Ocular Toxicology Downloaded from informahealthcare.com by University of Melbourne on 09/15/14 For personal use only.
provides a better ‘‘isolation’’ of the anterior chamber and subsequent protection from implant-migration. In our case, the post-operative ME was refractory to any form of steroid or NSAID delivery (topical, sub-tenon’s, intravitreal) prior to Ozurdex implantation. The use of slowrelease dexamethasone implant resulted in reduction of the CRT and improvement in visual acuity in our patient. No adverse events were observed and the implantation was performed without problems in the absence of vitreous. To the best of our knowledge, this is the first report in the literature demonstrating the use of the slow-release dexamethasone implant (Ozurdex) to treat resistant postoperative ME in a vitrectomized eye.
Declaration of interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.
References 1. Parke DW, Sisk RA, Murray TG. Intraoperative intravitreal triamcinolone decreases macular edema after vitrectomy with phacoemulsification. Clin Ophthalmol 2012;6:1347–1353. 2. Parolini B, Sartore M. Incidence of cystoid macular edema after vitrectomy for ERM. Presented at EVRS 2012 Congress; 2012 Sept 15–18; Dresden, Germany. 3. Kim SJ, Martin DF, Hubbard 3rd GB, et al. Incidence of postvitrectomy macular edema using optical coherence tomography. Ophthalmology 2009;116:1531–1537.
Ozurdex for refractory post-operative ME
3
4. Cho H, Madu A. Etiology and treatment of the inflammatory causes of cystoid macular edema. J Inflamm Res 2009;2:37–43. 5. Chen TH, Wang JK, Chang SW. Intravitreal dexamethasone implant for a vitrectomised eye with diabetic macular edema. Taiwan J Ophthalmol 2013. Available from: http://www. e-tjo.com/article/S2211-5056%2813%2900029-X/abstract [last accessed Aug 2014]. 6. Reibaldi M, Russo A, Zagari M, et al. Resolution of persistent cystoid macular edema due to central retinal vein occlusion in a vitrectomized eye following intravitreal implant of dexamethasone 0.7 mg. Case Rep Ophthalmol 2012;3:30–34. 7. Feiner L. Dexamethasone implant for treatment of DME in vitrectomized patients. Retina Today 2010:62–63. 8. Ada´n A, Pelegrı´n L, Rey A, et al. Dexamethasone intravitreal implant for treatment ofuveitic persistent cystoid macular edema in vitrectomized patients. Retina 2013;33:1435–1440. 9. Chang-Lin JE, Burke JA, Peng, Q. Pharmacokinetics of a sustained release dexamethasone intravitreal implant in vitrectomized and non vitrectomized eyes. Invest Ophthalmol Vis Sci 2011;52:4605–4609. 10. Shahsuvaryan ML. Therapeutic potential of intravitreal pharmacotherapy in retinal vein occlusion. Int J Ophthalmol 2012;5: 759–770. 11. Robinson LR, Whitcup SM. Pharmacologic and clinical profile of dexamethasone intravitreal implant. Expert Rev Clin Pharmacol 2012;5:629–647. 12. Shaikh AH, Petersen MR, Sisk RA, et al. Comparative effectiveness of the dexamethasone intravitreal implant in vitrectomized and non-vitrectomized eyes with macular edema secondary to central retinal vein occlusion. Ophthalmic Surg Lasers Imaging Retina 2013;44:28–33. 13. Malcle`s A, Janin-Manificat H, Yhuel Y, et al. Anterior chamber migration of intravitreal dexamethasone implant (OzurdexÕ ) in pseudophakic eyes: report of three cases. J Fr Ophthalmol 2013; 36:362–367.
