RESOLUTION OF REFRACTORY MACULAR EDEMA BECAUSE OF BRANCH RETINAL VEIN OCCLUSION AFTER OZURDEX IMPLANTATION Christine N. Kay, MD,* Kori A. Elkins, MD,* James C. Folk, MD*†
Purpose: To report a case of a woman with a branch vein occlusion and macular edema refractory to grid laser, intravitreal bevacizumab, pars plana vitrectomy with sheathotomy of the arteriovenous branch site, and intravitreal triamcinolone, who had complete resolution of fluid after injection of a dexamethasone intravitreal implant (DEX implant, Ozurdex; Allergan, Inc, Irvine, CA). Methods: A 75-year-old woman with a branch vein occlusion and macular edema was treated with grid laser, intravitreal bevacizumab, pars plana vitrectomy with sheathotomy, and intravitreal triamcinolone. Neither edema nor vision improved. She was treated with an Ozurdex intravitreal implant. Results: One month after Ozurdex intravitreal implantation, the patient’s visual acuity and edema had improved dramatically. The macula remained flat until 5 months after injection when the edema returned and a second Ozurdex was injected. One month later, the macular edema was significantly less and visual acuity had improved to 20/50 with pinhole. Conclusion: Ozurdex may be effective in reducing macular edema because of a branch retinal vein occlusion in eyes refractory to multiple other treatments. RETINAL CASES & BRIEF REPORTS 6:72–75, 2012
vitrectomy with or without sheathotomy of the arteriovenous crossing site.6 The DEX implant is a biodegradable intravitreal implant that enables the extended release of dexamethasone via the NOVADUR solid polymer delivery system. The Phase II results revealed a lower rate of both cataract and intraocular pressure (IOP) increases with DEX implant than had been reported with other corticosteroids, including triamcinolone acetonide.5 The Phase III, multicenter, masked, randomized, 6month, sham-controlled clinical trial results showed that the percentage of eyes with a $15-letter improvement in BCVA was significantly higher in both the 0.35-mg and the 0.7-mg DEX implant groups compared with sham at Days 30 to 90 (P , 0.001) and the percentage of eyes with a $15-letter loss in BCVA was significantly lower in the 0.7-mg DEX implant group compared with sham at all follow-up visits (P # 0.036).7 We describe in this case report a patient with BRVO and persistent ME refractory to grid laser, intravitreal
From the *Vitreoretinal Service, Department of Ophthalmology and Visual Sciences, and †Carver Center for Macular Degeneration, Carver School of Medicine, The University of Iowa, Iowa City, Iowa.
R
etinal vein occlusion is the second most common retinal vascular disorder after diabetic retinopathy, with a prevalence varying from 0.7% to 1.6%.1 In a population-based study, the incidences of branch retinal vein occlusion (BRVO) and central retinal vein occlusion were 1.8% and 0.5%, respectively.2 Macular edema (ME) is a common cause of vision loss in both BRVO and central retinal vein occlusion. Treatment options for ME from retinal vein occlusions include laser photocoagulation,3 anti–vascular endothelial growth factor therapy,4 intravitreal triamcinolone acetonide,3 intravitreal dexamethasone,5 and The authors have no conflicts of interest to disclose. Reprint requests: Christine N. Kay, MD, 1196 D Pomerantz Family Pavilion, 200 Hawkins Drive, Iowa City, IA 52242; e-mail: [email protected]
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bevacizumab, pars plana vitrectomy with sheathotomy of branch site, and intravitreal triamcinolone. An injection of the DEX implant resulted in dramatic improvement in the visual acuity and ME with no increase in IOP. Case Report A 75-year-old woman with a medical history of well-controlled hypertension presented with a superotemporal BRVO and ME in the right eye in May 2008. Grid laser was performed initially before transfer of her care to the University of Iowa. She presented to us in August with a visual acuity of 20/60 and persistent ME. She was treated with 5 consecutive intravitreal bevacizumab injections at 4-week to 6-week intervals. There was no improvement in her visual acuity or in the ME, so a pars plana vitrectomy with peeling of the internal limiting membrane and sheathotomy at the site of the branch vein occlusion with air–fluid exchange was performed in April 2009. One month postoperatively, her vision dropped to 20/100, her ME appeared worse, and increased cataract was noted. Repeat grid laser and an intravitreal triamcinolone injection were performed, which resulted in modest improvement in the ME but worsening of the cataract. Cataract extraction with posterior intraocular lens implantation was performed in July. Best-corrected visual acuity after cataract removal was 20/80 one month later in August; however, her ME had worsened despite treatment with topical
Fig. 1. Color fundus photograph (A) and fluorescein angiography (B–D: early, middle, and late) of the right eye reveal findings consistent with a superotemporal branch vein occlusion and associated ME.
prednisolone and topical ketorolac each four times a day since cataract surgery. In November, her visual acuity dropped again to 20/100 because of worsening of the ME. Figure 1 shows fluorescein angiography findings at this visit, demonstrating leakage in the superotemporal macula. A DEX implant was injected. One month later, her visual acuity improved to 20/80, her IOP remained normal (14 mmHg), and her ME had significantly improved. Twelve weeks after DEX implant injection, the visual acuity improved to 20/50 with pinhole, and there was no ME. At 5 months posttreatment, her vision had dropped to 20/100 with pinhole, and her ME had recurred, so another DEX implant was injected at that time. One month later, the ME was significantly less and visual acuity had improved to 20/50 with pinhole. Best-corrected visual acuity at final follow-up at 12 weeks after second treatment with DEX implant was 20/50 and IOP was 16 mmHg. Figure 2 shows optical coherence tomography findings before treatment with DEX implant, at 1, 3, and 5 months after treatment with DEX implant, and 1 month after second treatment with DEX implant. Figure 3 shows color fundus photograph at 12 weeks after second treatment with DEX implant.
Discussion Our patient had severe ME that had responded only partially and recurred after multiple modes of treatment, including focal laser, intravitreal bevacizumab and triamcinolone acetonide, and vitrectomy with
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Fig. 3. Color fundus photograph of the right eye 12 weeks after second treatment with DEX implant, depicting moderate interval improvement in retinal hemorrhages and exudates in region of BRVO.
sheathotomy. Treatment with the DEX implant provided improvement in visual acuity, resolution of ME, and no rise in IOP. The ME recurred 5 months after injection of the implant and a second DEX implant was injected. Although some patients do spontaneously regain vision after a BRVO within 1 year without treatment,8 the temporal association of dramatic improvement in ME after treatment with DEX implant and the subsequent recurrence of this ME after 5 months argues for a treatment-related effect rather than spontaneous resolution. The worsening of the ME after cataract surgery and the finding of mild increased hyperfluorescence of the optic nerve on fluorescein angiography could argue for a pseudophakic or postoperative element to the ME; however, the ME did not respond to topical steroid and nonsteroidal drops, and the primary site of leakage noted on
Fig. 2. Six-millimeter horizontal line optical coherence tomography pre- and posttreatment with DEX implant. A. Optical coherence tomography of the right eye before treatment with DEX implant shows extensive central ME with large cysts and a central macular thickness of 557 mm. B. Optical coherence tomography of the right eye 1 month after treatment with DEX implant demonstrates reduced ME with a central macular thickness of 295 mm. C. Optical coherence tomography of the right eye 3 months after treatment with DEX implant shows a central macular thickness of 281 mm. D. Optical coherence tomography of the right eye 5 months after treatment with DEX implant demonstrates recurrence of ME with a central macular thickness of 473 mm. E. Optical coherence tomography of the right eye 1 month after second treatment with DEX implant demonstrates resolution of edema with a central macular thickness of 310 mm.
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fluorescein angiography remained within a superotemporal vascular distribution. The DEX implant resulted in prolonged remission of the ME and excellent vision in our patient. The DEX implant appears to be an effective treatment for ME associated with branch vein occlusive disease and may be a valuable option in patients who have persistent ME refractory to multiple other treatments.
4.
5.
Key words: branch retinal vein occlusion, dexamethasone, macular edema, Ozurdex, vein occlusion. References 1. Rehak J, Rehak M. Branch retinal vein occlusion: pathogenesis, visual prognosis, and treatment modalities. Curr Eye Res 2008; 33:111–131. 2. Klein R, Moss SE, Meuer SM, Klein BE. The 15-year cumulative incidence of retinal vein occlusion: the Beaver Dam Eye Study. Arch Ophthalmol 2008;126:513–518. 3. Scott IU, Ip MS, VanVeldhuisen PC, et al. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone
6.
7.
8.
with standard care to treat vision loss associated with macular edema secondary to branch retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 6. Arch Ophthalmol 2009;127:1115–1128. Campochiaro PA, Hafiz G, Shah SM, et al. Ranibizumab for macular edema due to retinal vein occlusions: implication of VEGF as a critical stimulator. Mol Ther 2008;16: 791–799. Kuppermann BD, Blumenkranz MS, Haller JA, et al. Randomized controlled study of an intravitreous dexamethasone drug delivery system in patients with persistent macular edema. Arch Ophthalmol 2007;125:309–317. National Institute for Health and Clinical Excellence. Arteriovenous Sheathotomy for Branch Retinal Vein Occlusion. Interventional Procedure Guidance IPG72. London: NICE; 2004. 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.e3–1146.e3. Finkelstein D. Ischemic macular edema. Recognition and favorable natural history in branch vein occlusion. Arch Ophthalmol 1992;110:1427–1434.
Purpose: To report a case of a woman with a branch vein occlusion and macular edema refractory to grid laser, intravitreal bevacizumab, pars plana vitrectomy with sheathotomy of the arteriovenous branch site, and intravitreal triamcinolone, who had complete resolution of fluid after injection of a dexamethasone intravitreal implant (DEX implant, Ozurdex; Allergan, Inc, Irvine, CA). Methods: A 75-year-old woman with a branch vein occlusion and macular edema was treated with grid laser, intravitreal bevacizumab, pars plana vitrectomy with sheathotomy, and intravitreal triamcinolone. Neither edema nor vision improved. She was treated with an Ozurdex intravitreal implant. Results: One month after Ozurdex intravitreal implantation, the patient’s visual acuity and edema had improved dramatically. The macula remained flat until 5 months after injection when the edema returned and a second Ozurdex was injected. One month later, the macular edema was significantly less and visual acuity had improved to 20/50 with pinhole. Conclusion: Ozurdex may be effective in reducing macular edema because of a branch retinal vein occlusion in eyes refractory to multiple other treatments. RETINAL CASES & BRIEF REPORTS 6:72–75, 2012
vitrectomy with or without sheathotomy of the arteriovenous crossing site.6 The DEX implant is a biodegradable intravitreal implant that enables the extended release of dexamethasone via the NOVADUR solid polymer delivery system. The Phase II results revealed a lower rate of both cataract and intraocular pressure (IOP) increases with DEX implant than had been reported with other corticosteroids, including triamcinolone acetonide.5 The Phase III, multicenter, masked, randomized, 6month, sham-controlled clinical trial results showed that the percentage of eyes with a $15-letter improvement in BCVA was significantly higher in both the 0.35-mg and the 0.7-mg DEX implant groups compared with sham at Days 30 to 90 (P , 0.001) and the percentage of eyes with a $15-letter loss in BCVA was significantly lower in the 0.7-mg DEX implant group compared with sham at all follow-up visits (P # 0.036).7 We describe in this case report a patient with BRVO and persistent ME refractory to grid laser, intravitreal
From the *Vitreoretinal Service, Department of Ophthalmology and Visual Sciences, and †Carver Center for Macular Degeneration, Carver School of Medicine, The University of Iowa, Iowa City, Iowa.
R
etinal vein occlusion is the second most common retinal vascular disorder after diabetic retinopathy, with a prevalence varying from 0.7% to 1.6%.1 In a population-based study, the incidences of branch retinal vein occlusion (BRVO) and central retinal vein occlusion were 1.8% and 0.5%, respectively.2 Macular edema (ME) is a common cause of vision loss in both BRVO and central retinal vein occlusion. Treatment options for ME from retinal vein occlusions include laser photocoagulation,3 anti–vascular endothelial growth factor therapy,4 intravitreal triamcinolone acetonide,3 intravitreal dexamethasone,5 and The authors have no conflicts of interest to disclose. Reprint requests: Christine N. Kay, MD, 1196 D Pomerantz Family Pavilion, 200 Hawkins Drive, Iowa City, IA 52242; e-mail: [email protected]
72
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OZURDEX IN REFRACTORY MACULAR EDEMA
bevacizumab, pars plana vitrectomy with sheathotomy of branch site, and intravitreal triamcinolone. An injection of the DEX implant resulted in dramatic improvement in the visual acuity and ME with no increase in IOP. Case Report A 75-year-old woman with a medical history of well-controlled hypertension presented with a superotemporal BRVO and ME in the right eye in May 2008. Grid laser was performed initially before transfer of her care to the University of Iowa. She presented to us in August with a visual acuity of 20/60 and persistent ME. She was treated with 5 consecutive intravitreal bevacizumab injections at 4-week to 6-week intervals. There was no improvement in her visual acuity or in the ME, so a pars plana vitrectomy with peeling of the internal limiting membrane and sheathotomy at the site of the branch vein occlusion with air–fluid exchange was performed in April 2009. One month postoperatively, her vision dropped to 20/100, her ME appeared worse, and increased cataract was noted. Repeat grid laser and an intravitreal triamcinolone injection were performed, which resulted in modest improvement in the ME but worsening of the cataract. Cataract extraction with posterior intraocular lens implantation was performed in July. Best-corrected visual acuity after cataract removal was 20/80 one month later in August; however, her ME had worsened despite treatment with topical
Fig. 1. Color fundus photograph (A) and fluorescein angiography (B–D: early, middle, and late) of the right eye reveal findings consistent with a superotemporal branch vein occlusion and associated ME.
prednisolone and topical ketorolac each four times a day since cataract surgery. In November, her visual acuity dropped again to 20/100 because of worsening of the ME. Figure 1 shows fluorescein angiography findings at this visit, demonstrating leakage in the superotemporal macula. A DEX implant was injected. One month later, her visual acuity improved to 20/80, her IOP remained normal (14 mmHg), and her ME had significantly improved. Twelve weeks after DEX implant injection, the visual acuity improved to 20/50 with pinhole, and there was no ME. At 5 months posttreatment, her vision had dropped to 20/100 with pinhole, and her ME had recurred, so another DEX implant was injected at that time. One month later, the ME was significantly less and visual acuity had improved to 20/50 with pinhole. Best-corrected visual acuity at final follow-up at 12 weeks after second treatment with DEX implant was 20/50 and IOP was 16 mmHg. Figure 2 shows optical coherence tomography findings before treatment with DEX implant, at 1, 3, and 5 months after treatment with DEX implant, and 1 month after second treatment with DEX implant. Figure 3 shows color fundus photograph at 12 weeks after second treatment with DEX implant.
Discussion Our patient had severe ME that had responded only partially and recurred after multiple modes of treatment, including focal laser, intravitreal bevacizumab and triamcinolone acetonide, and vitrectomy with
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RETINAL CASES & BRIEF REPORTS´ 2012 VOLUME 6 NUMBER 1
Fig. 3. Color fundus photograph of the right eye 12 weeks after second treatment with DEX implant, depicting moderate interval improvement in retinal hemorrhages and exudates in region of BRVO.
sheathotomy. Treatment with the DEX implant provided improvement in visual acuity, resolution of ME, and no rise in IOP. The ME recurred 5 months after injection of the implant and a second DEX implant was injected. Although some patients do spontaneously regain vision after a BRVO within 1 year without treatment,8 the temporal association of dramatic improvement in ME after treatment with DEX implant and the subsequent recurrence of this ME after 5 months argues for a treatment-related effect rather than spontaneous resolution. The worsening of the ME after cataract surgery and the finding of mild increased hyperfluorescence of the optic nerve on fluorescein angiography could argue for a pseudophakic or postoperative element to the ME; however, the ME did not respond to topical steroid and nonsteroidal drops, and the primary site of leakage noted on
Fig. 2. Six-millimeter horizontal line optical coherence tomography pre- and posttreatment with DEX implant. A. Optical coherence tomography of the right eye before treatment with DEX implant shows extensive central ME with large cysts and a central macular thickness of 557 mm. B. Optical coherence tomography of the right eye 1 month after treatment with DEX implant demonstrates reduced ME with a central macular thickness of 295 mm. C. Optical coherence tomography of the right eye 3 months after treatment with DEX implant shows a central macular thickness of 281 mm. D. Optical coherence tomography of the right eye 5 months after treatment with DEX implant demonstrates recurrence of ME with a central macular thickness of 473 mm. E. Optical coherence tomography of the right eye 1 month after second treatment with DEX implant demonstrates resolution of edema with a central macular thickness of 310 mm.
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OZURDEX IN REFRACTORY MACULAR EDEMA
fluorescein angiography remained within a superotemporal vascular distribution. The DEX implant resulted in prolonged remission of the ME and excellent vision in our patient. The DEX implant appears to be an effective treatment for ME associated with branch vein occlusive disease and may be a valuable option in patients who have persistent ME refractory to multiple other treatments.
4.
5.
Key words: branch retinal vein occlusion, dexamethasone, macular edema, Ozurdex, vein occlusion. References 1. Rehak J, Rehak M. Branch retinal vein occlusion: pathogenesis, visual prognosis, and treatment modalities. Curr Eye Res 2008; 33:111–131. 2. Klein R, Moss SE, Meuer SM, Klein BE. The 15-year cumulative incidence of retinal vein occlusion: the Beaver Dam Eye Study. Arch Ophthalmol 2008;126:513–518. 3. Scott IU, Ip MS, VanVeldhuisen PC, et al. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone
6.
7.
8.
with standard care to treat vision loss associated with macular edema secondary to branch retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 6. Arch Ophthalmol 2009;127:1115–1128. Campochiaro PA, Hafiz G, Shah SM, et al. Ranibizumab for macular edema due to retinal vein occlusions: implication of VEGF as a critical stimulator. Mol Ther 2008;16: 791–799. Kuppermann BD, Blumenkranz MS, Haller JA, et al. Randomized controlled study of an intravitreous dexamethasone drug delivery system in patients with persistent macular edema. Arch Ophthalmol 2007;125:309–317. National Institute for Health and Clinical Excellence. Arteriovenous Sheathotomy for Branch Retinal Vein Occlusion. Interventional Procedure Guidance IPG72. London: NICE; 2004. 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.e3–1146.e3. Finkelstein D. Ischemic macular edema. Recognition and favorable natural history in branch vein occlusion. Arch Ophthalmol 1992;110:1427–1434.
