Two or more dexamethasone intravitreal implants as monotherapy or in combination therapy for macular edema in retinal vein occlusion: subgroup analysis of a retrospective chart review study

Michael A Singer, Antonio Capone Jr, Pravin U Dugel, Richard F Dreyer, David G Dodwell, Daniel B Roth, Rui Shi, John G Walt, Lanita C Scott, David A Hollander, SHASTA Study Group, Michael A Singer, Antonio Capone Jr, Pravin U Dugel, Richard F Dreyer, David G Dodwell, Daniel B Roth, Rui Shi, John G Walt, Lanita C Scott, David A Hollander, SHASTA Study Group

Abstract

Background: Dexamethasone intravitreal implant (DEX implant) is a sustained-release biodegradable implant approved for treatment of macular edema associated with retinal vein occlusion (RVO). The safety and efficacy of treatment of RVO-associated macular edema with sequential DEX implants in clinical practice was evaluated in patients who received DEX implant as monotherapy compared with patients who received DEX implant in combination with other RVO treatments.

Methods: A multicenter, retrospective, open-label chart review study (one study eye/patient) evaluated use of DEX implant and outcomes in 289 patients with branch or central RVO who received at least 2 DEX implant treatments in the study eye. Data were collected from the time of the first implant (baseline) to 3-6 months after the last implant. Subgroup analysis evaluated outcomes in patients receiving only DEX implant during the study versus patients receiving DEX implant plus adjunctive RVO treatments. Endpoints included best-corrected visual acuity (BCVA) and central retinal thickness (CRT) change from baseline.

Results: DEX implant was used as monotherapy in 84 (29.1%) patients and in combination with other therapy in 205 (70.9%) patients. Mean number of DEX implant treatments received was 3.1 in the monotherapy group and 3.3 in the combination therapy group (P = 0.344). Mean time between implants was longer in the combination therapy group (177 vs. 151 days, P < 0.001). Mean change from baseline BCVA after the first through sixth DEX implants ranged from +0.6 to +3.4 lines in the monotherapy group and +1.3 to +2.8 lines in the combination therapy group. Mean decrease from baseline CRT ranged from 165 to 230 μm in the monotherapy group and 136 to 175 μm in the combination therapy group. Increased intraocular pressure was more common in the combination therapy group.

Conclusions: Treatment of RVO-associated macular edema with at least 2 sequential DEX implants was safe and effective both when used alone and when combined with other RVO treatments. Improvements in BCVA and CRT were generally similar in the monotherapy and combined therapy groups.

Trial registration: ClinicalTrials.gov NCT01411696 .

Figures

Figure 1
Figure 1
Mean change in best-corrected visual acuity from baseline after each dexamethasone intravitreal implant (DEX implant). Numbers in parentheses indicate number (n) of patients. Error bars, standard deviation. *P ≤ 0.026 vs. baseline, †P = 0.037 vs. monotherapy.
Figure 2
Figure 2
Mean change in central retinal thickness from baseline after each dexamethasone intravitreal implant (DEX implant). Numbers in parentheses indicate number (n) of patients. Error bars, standard deviation. *P ≤ 0.028 vs. baseline, †P = 0.041 vs. combination therapy.
Figure 3
Figure 3
Improvement in best-corrected visual acuity of at least 2 or 3 lines. The percentage of patients who gained at least (A) 2 lines or (B) 3 lines in best-corrected visual acuity from baseline after each dexamethasone intravitreal implant (DEX implant) injection is shown. Numbers in parentheses indicate number (n) of patients.
Figure 4
Figure 4
Worsening in best-corrected visual acuity of at least 2 or 3 lines. The percentage of patients who had at least (A) 2 lines or (B) 3 lines loss in best-corrected visual acuity from baseline after each dexamethasone intravitreal implant (DEX implant) injection is shown. Numbers in parentheses indicate number (n) of patients.
Figure 5
Figure 5
Timing of first increase in intraocular pressure (IOP) to ≥25 mm Hg by injection number. DEX implant, dexamethasone intravitreal implant; VEGF, vascular endothelial growth factor.

References

    1. Rehak J, Rehak M. Branch retinal vein occlusion: pathogenesis, visual prognosis, and treatment modalities. Curr Eye Res. 2008;33:111–31. doi: 10.1080/02713680701851902.
    1. Mohamed Q, McIntosh RL, Saw SM, Wong TY. Interventions for central retinal vein occlusion: an evidence-based systematic review. Ophthalmology. 2007;114:507–19. doi: 10.1016/j.ophtha.2006.11.011.
    1. The Branch Vein Occlusion Study Group Argon laser photocoagulation for macular edema in branch vein occlusion. Am J Ophthalmol. 1984;98:271–82. doi: 10.1016/0002-9394(84)90316-7.
    1. Scott IU, Ip MS, VanVeldhuisen PC, Oden NL, Blodi BA, Fisher M, et al. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone 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;127:1115–28. doi: 10.1001/archophthalmol.2009.233.
    1. Haller JA, Bandello F, Belfort R, Jr, Blumenkranz MS, Gillies M, Heier J, et al. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology. 2010;117:1134–46. doi: 10.1016/j.ophtha.2010.03.032.
    1. Campochiaro PA, Heier JS, Feiner L, Gray S, Saroj N, Rundle AC, et al. Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010;117:1102–12. doi: 10.1016/j.ophtha.2010.02.021.
    1. Ip MS, Scott IU, VanVeldhuisen PC, Oden NL, Blodi BA, Fisher M, et al. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with observation to treat vision loss associated with macular edema secondary to central retinal vein occlusion: the standard care vs corticosteroid for retinal vein occlusion (SCORE) study report 5. Arch Ophthalmol. 2009;127:1101–14. doi: 10.1001/archophthalmol.2009.234.
    1. Brown DM, Campochiaro PA, Singh RP, Li Z, Gray S, Saroj N, et al. Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010;117:1124–33. doi: 10.1016/j.ophtha.2010.02.022.
    1. Boyer D, Heier J, Brown DM, Clark WL, Vitti R, Berliner AJ, et al. Vascular endothelial growth factor Trap-Eye for macular edema secondary to central retinal vein occlusion: six-month results of the phase 3 COPERNICUS study. Ophthalmology. 2012;119:1024–32. doi: 10.1016/j.ophtha.2012.01.042.
    1. Coscas G, Loewenstein A, Augustin A, Bandello F, Battaglia Parodi M, Lanzetta P, et al. Management of retinal vein occlusion—consensus document. Ophthalmologica. 2011;226:4–28. doi: 10.1159/000327391.
    1. Daien V, Navarre S, Fesler P, Vergely L, Villain M, Schneider C. Visual acuity outcome and predictive factors after bevacizumab for central retinal vein occlusion. Eur J Ophthalmol. 2012;22:1013–8. doi: 10.5301/ejo.5000162.
    1. Yeh WS, Haller JA, Lanzetta P, Kuppermann BD, Wong TY, Mitchell P, et al. Effect of the duration of macular edema on clinical outcomes in retinal vein occlusion treated with dexamethasone intravitreal implant. Ophthalmology. 2012;119:1190–8. doi: 10.1016/j.ophtha.2011.12.028.
    1. Chang-Lin JE, Attar M, Acheampong AA, Robinson MR, Whitcup SM, Kuppermann BD, et al. Pharmacokinetics and pharmacodynamics of a sustained-release dexamethasone intravitreal implant. Invest Ophthalmol Vis Sci. 2011;52:80–6. doi: 10.1167/iovs.10-5285.
    1. Haller JA, Bandello F, Belfort R, Jr, Blumenkranz MS, Gillies M, Heier J, et al. Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results. Ophthalmology. 2011;118:2453–60. doi: 10.1016/j.ophtha.2011.05.014.
    1. Capone A, Jr, Singer MA, Dodwell DG, Dreyer RF, Oh KT, Roth DB, et al. Efficacy and safety of two or more dexamethasone intravitrial implant injections for the treatment of macular edema related to retinal vein occulsion (SHASTA study) Retina. 2014;34:342–51. doi: 10.1097/IAE.0b013e318297f842.
    1. Querques L, Querques G, Lattanzio R, Gigante SR, Del Turco C, Corradetti G, et al. Repeated intravitreal dexamethasone implant (Ozurdex®) for retinal vein occlusion. Ophthalmologica. 2013;229:21–5. doi: 10.1159/000342160.
    1. Joshi L, Yaganti S, Gemenetzi M, Lightman S, Lindfield D, Liolios V, et al. Dexamethasone implants in retinal vein occlusion: 12-month clinical effectiveness using repeat injections as-needed. Br J Ophthalmol. 2013;97:1040–4. doi: 10.1136/bjophthalmol-2013-303207.
    1. Day S, Acquah K, Mruthyunjaya P, Grossman DS, Lee PP, Sloan FA. Ocular complications after anti-vascular endothelial growth factor therapy in Medicare patients with age-related macular degeneration. Am J Ophthalmol. 2011;152:266–72. doi: 10.1016/j.ajo.2011.01.053.
    1. Mansour AM, Shahin M, Kofoed PK, Parodi MB, Shami M, Schwartz SG, et al. Insight into 144 patients with ocular vascular events during VEGF antagonist injections. Clin Ophthalmol. 2012;6:343–63. doi: 10.2147/OPTH.S29075.
    1. Aref AA. Management of immediate and sustained intraocular pressure rise associated with intravitreal antivascular endothelial growth factor injection therapy. Curr Opin Ophthalmol. 2012;23:105–10. doi: 10.1097/ICU.0b013e32834ff41d.
    1. Good TJ, Kimura AE, Mandava N, Kahook MY. Sustained elevation of intraocular pressure after intravitreal injections of anti-VEGF agents. Br J Ophthalmol. 2011;95:1111–4. doi: 10.1136/bjo.2010.180729.
    1. Mathalone N, Arodi-Golan A, Sar S, Wolfson Y, Shalem M, Lavi I, et al. Sustained elevation of intraocular pressure after intravitreal injections of bevacizumab in eyes with neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol. 2012;250:1435–40. doi: 10.1007/s00417-012-1981-0.
    1. Singh RS, Kim JE. Ocular hypertension following intravitreal anti-vascular endothelial growth factor agents. Drugs Aging. 2012;29:949–56. doi: 10.1007/s40266-012-0031-2.
    1. Skalicky SE, Ho I, Agar A, Bank A. Glaucoma filtration surgery following sustained elevation of intraocular pressure secondary to intravitreal anti-VEGF injections. Ophthalmic Surg Lasers Imaging. 2012;43:328–34. doi: 10.3928/15428877-20120618-01.
    1. Tseng JJ, Vance SK, Della Torre KE, Mendonca LS, Cooney MJ, Klancnik JM, et al. Sustained increased intraocular pressure related to intravitreal antivascular endothelial growth factor therapy for neovascular age-related macular degeneration. J Glaucoma. 2012;21:241–7. doi: 10.1097/IJG.0b013e31820d7d19.
    1. Kiddee W, Trope GE, Sheng L, Beltran-Agullo L, Smith M, Strungaru MH, et al. Intraocular pressure monitoring post intravitreal steroids: a systematic review. Surv Ophthalmol. 2013;58:291–310. doi: 10.1016/j.survophthal.2012.08.003.
    1. Nehme A, Lobenhofer EK, Stamer WD, Edelman JL. Glucocorticoids with different chemical structures but similar glucocorticoid receptor potency regulate subsets of common and unique genes in human trabecular meshwork cells. BMC Med Genomics. 2009;2:58. doi: 10.1186/1755-8794-2-58.
    1. Thakur A, Kadam R, Kompella UB. Trabecular meshwork and lens partitioning of corticosteroids: implications for elevated intraocular pressure and cataracts. Arch Ophthalmol. 2011;129:914–20. doi: 10.1001/archophthalmol.2011.39.

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