Two or more dexamethasone intravitreal implants in treatment-naïve patients with macular edema due to retinal vein occlusion: subgroup analysis of a retrospective chart review study

Pravin U Dugel, Antonio Capone Jr, Michael A Singer, Richard F Dreyer, David G Dodwell, Daniel B Roth, Rui Shi, John G Walt, Lanita C Scott, David A Hollander, SHASTA Study Group, Pravin U Dugel, Antonio Capone Jr, Michael A Singer, 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 biodegradable, sustained-release implant that releases dexamethasone for up to 6 months. We evaluated the efficacy and safety of DEX implant in the treatment of macular edema secondary to retinal vein occlusion (RVO) in treatment-naïve patients.

Methods: A multicenter, retrospective, open-label chart review study investigated the efficacy and safety of DEX implant treatment in 289 patients with macular edema secondary to branch or central RVO (BRVO, CRVO) who received ≥2 treatments with DEX implant in the study eye. Concomitant adjunctive RVO treatments were permitted. Data collected from the time of the first implant (baseline) to 3-6 months after the last implant included best-corrected visual acuity (BCVA) and central retinal thickness measured with optical coherence tomography. In this subgroup analysis, we evaluated outcomes in patients who had received no previous treatment for RVO complications.

Results: Thirty-nine patients were treatment-naïve at the time of their first DEX implant (18 BRVO, 21 CRVO). Before the initial DEX implant, the mean duration of macular edema in treatment-naïve patients was 4.9 months, mean central retinal thickness was 550 μm, and mean Early Treatment Diabetic Retinopathy Study BCVA was 8.5 lines (20/125 Snellen). Treatment-naïve patients received a mean of 2.9 implants, either as monotherapy (n = 12) or with adjunctive RVO treatments (n = 27). The mean interval between implants was 177 days. After the first through sixth implants, mean changes from baseline BCVA ranged from +3.0 - +8.0 lines, and mean decreases from baseline central retinal thickness ranged from 241-459 μm. BCVA improved in both BRVO and CRVO and in both phakic and pseudophakic eyes. Overall, 83.8 % of treatment-naïve patients gained ≥2 lines in BCVA, 70.3 % gained ≥3 lines in BCVA, and 56.4 % achieved central retinal thickness ≤250 μm. The most common adverse event was increased intraocular pressure. Fifteen treatment-naïve patients had intraocular pressure ≥25 mm Hg; none required laser or incisional glaucoma surgery.

Conclusion: Treatment with 2 or more DEX implants had a favorable safety profile and improved visual acuity and anatomic outcomes when used, either alone or with adjunctive RVO therapy, as initial treatment for RVO-associated macular edema.

Trial registration: ClinicalTrials.gov NCT01411696 , registered on August 5, 2011.

Figures

Fig. 1
Fig. 1
Mean change in best-corrected visual acuity (BCVA) from baseline after each dexamethasone intravitreal implant (DEX implant). Results are shown for patients with retinal vein occlusion who were treatment-naïve at the time of the first DEX implant treatment. a All treatment-naïve patients. b Treatment-naïve patients diagnosed with branch or central retinal vein occlusion (BRVO, CRVO). Numbers in parentheses indicate number (n) of patients included in analysis (all patients with available data). Error bars, standard deviation. *P ≤ 0.034 vs baseline
Fig. 2
Fig. 2
Mean change in best-corrected visual acuity from baseline after each dexamethasone intravitreal implant (DEX implant). Results are shown in phakic and pseudophakic eyes with retinal vein occlusion that were treatment-naïve at the time of the first DEX implant treatment. No pseudophakic eyes received >4 DEX implant treatments. Numbers in parentheses indicate number (n) of patients included in analysis (all patients with available data). *P ≤ 0.020 vs baseline
Fig. 3
Fig. 3
Gain of at least 2 or 3 lines in best-corrected visual acuity. The percentage of treatment-naïve patients with retinal vein occlusion who gained at least 2 or 3 lines in best-corrected visual acuity from baseline after each dexamethasone intravitreal implant (DEX implant) is shown. Numbers in parentheses indicate number (n) of patients included in analysis (all patients with available data)
Fig. 4
Fig. 4
Mean change in central retinal thickness from baseline after each dexamethasone intravitreal implant (DEX implant). Results are shown for patients with retinal vein occlusion who were treatment-naïve at the time of the first DEX implant treatment. Numbers in parentheses indicate number (n) of patients included in analysis (all patients with available data). Error bars, standard deviation. *P ≤ 0.004 vs baseline

References

    1. Rehak M, Wiedemann P. Retinal vein thrombosis: pathogenesis and management. J Thromb Haemost. 2010;8:1886–94. doi: 10.1111/j.1538-7836.2010.03909.x.
    1. Coscas G, Loewenstein A, Augustin A, Bandello F, Battaglia Parodi M, Lanzetta P, Monés J, de Smet M, Soubrane G, Staurenghi G. Management of retinal vein occlusion—consensus document. Ophthalmologica. 2011;226:4–28. doi: 10.1159/000327391.
    1. Sohn HJ, Han DH, Kim IT, Oh IK, Kim KH, Lee DY, Nam DH. Changes in aqueous concentrations of various cytokines after intravitreal triamcinolone versus bevacizumab for diabetic macular edema. Am J Ophthalmol. 2011;152:686–94. doi: 10.1016/j.ajo.2011.03.033.
    1. Saraiya NV, Goldstein DA. Dexamethasone for ocular inflammation. Expert Opin Pharmacother. 2011;12:1127–31. doi: 10.1517/14656566.2011.571209.
    1. Shim SH, Hah JH, Hwang SY, Heo DS, Sung MW. Dexamethasone treatment inhibits VEGF production via suppression of STAT3 in a head and neck cancer cell line. Oncol Rep. 2010;23:1139–43.
    1. Greenberger S, Boscolo E, Adini I, Mulliken JB, Bischoff J. Corticosteroid suppression of VEGF-A in infantile hemangioma-derived stem cells. N Engl J Med. 2010;362:1005–13. doi: 10.1056/NEJMoa0903036.
    1. Chang-Lin JE, Attar M, Acheampong AA, Robinson MR, Whitcup SM, Kuppermann BD, Welty D. 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, Loewenstein A, Yoon YH, Jacques ML, Jiao J, Li XY, Whitcup SM, OZURDEX GENEVA Study Group 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. Haller JA, Bandello F, Belfort R, Jr, Blumenkranz MS, Gillies M, Heier J, Loewenstein A, Yoon YH, Jiao J, Li XY, Whitcup SM, Ozurdex GENEVA Study Group 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, Walt JG, Scott LC, Hollander DA. Efficacy and safety of two or more dexamethasone intravitreal implant injections for treatment of macular edema related to retinal vein occlusion (SHASTA study) Retina. 2014;34:342–51. doi: 10.1097/IAE.0b013e318297f842.
    1. Yeh WS, Haller JA, Lanzetta P, Kuppermann BD, Wong TY, Mitchell P, Whitcup SM, Kowalski JW. Effect of the duration of macular edema on clinical outcomes in retinal vein occlusion treated with dexamethasone intravitreal implant. Ophthalmology. 2012;119:1190–98. doi: 10.1016/j.ophtha.2011.12.028.
    1. Bhisitkul RB, Campochiaro PA, Shapiro H, Rubio RG. Predictive value in retinal vein occlusions of early versus late or incomplete ranibizumab response defined by optical coherence tomography. Ophthalmology. 2013;120:1057–63. doi: 10.1016/j.ophtha.2012.11.011.
    1. Campochiaro PA, Heier JS, Feiner L, Gray S, Saroj N, Rundle AC, Murahashi WY, Rubio RG, BRAVO Investigators 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. Brown DM, Campochiaro PA, Singh RP, Li Z, Gray S, Saroj N, Rundle AC, Rubio RG, Murahashi WY, CRUISE Investigators 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. Querques L, Querques G, Lattanzio R, Gigante SR, Del Turco C, Corradetti G, Cascavilla ML, Bandello F. Repeated intravitreal dexamethasone implant (Ozurdex®) for retinal vein occlusion. Ophthalmologica. 2013;229:21–5. doi: 10.1159/000342160.
    1. Matonti F, Hoffart L, Baeteman C, Denis D. Repeated treatment for macular edema in vein occlusion by intravitreal implant of dexamethasone. Case Rep Ophthalmol. 2012;3:339–42. doi: 10.1159/000343643.
    1. Kiddee W, Trope GE, Sheng L, Beltran-Agullo L, Smith M, Strungaru MH, Baath J, Buys YM. Intraocular pressure monitoring post intravitreal steroids: a systematic review. Surv Ophthalmol. 2013;58:291–310. doi: 10.1016/j.survophthal.2012.08.003.
    1. Jain N, Stinnett SS, Jaffe GJ. Prospective study of a fluocinolone acetonide implant for chronic macular edema from central retinal vein occlusion: thirty-six-month results. Ophthalmology. 2012;119:132–7. doi: 10.1016/j.ophtha.2011.06.019.
    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.
    1. Nehmé 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. 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. Lucentis® (ranibizumab injection) Intravitreal Injection Prescribing Information. Revised 02/2013.
    1. Maggio E, Polito A, Deiro AP, Benetti E, Pertile G. Intravitreal dexamethason implant (Ozurdex) for macular edema secondary to retinal vein occlusion: a comparative study between recent onset and chronic edema. IOVS 2013;54:ARVO E-Abstract 2824.
    1. Forte R, Cennamo GL, Finelli ML, de Crecchio G. Comparison of time domain Stratus OCT and spectral domain SLO/OCT for assessment of macular thickness and volume. Eye (Lond) 2009;23:2071–8. doi: 10.1038/eye.2008.363.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi