Korean J Ophthalmol.  2017 Apr;31(2):115-122. 10.3341/kjo.2017.31.2.115.

Efficacy and Safety of Intravitreal Dexamethasone Implants for Treatment of Refractory Diabetic Macular Edema

• Unsal E
• Eltutar K
• Sultan P
• Erkul SO
• Osmanbasoglu OA

• KMID: 2373467
• DOI: http://doi.org/10.3341/kjo.2017.31.2.115

Abstract

PURPOSE
To evaluate the safety and efficacy of intravitreal dexamethasone (IVD) implants in eyes with diabetic macular edema that did not respond to previous treatment.
METHODS
We included 46 eyes of 46 patients in this retrospective study. Each month, we recorded patient visual acuity with logarithm of the minimum angle of resolution using the Early Treatment Diabetic Retinopathy Study chart, central macular thickness measurements with optical coherence tomography, intraocular pressure (IOP), and posttreatment complication occurrence.
RESULTS
The mean follow-up time was 8.95 ± 1.33 months (range, 6 to 12). Best-corrected visual acuity improved significantly in the first 4 months after IVD, but no statistically significant change was observed over the following 2 months. Although a statistically significant decrease in central macular thickness was observed in the first 3 months, the change was not statistically significant in the following 3 months. There was a statistically significant increase in IOP in the first 2 months, but no statistically significant change was observed in the following months. IOP was controlled with medication in all patients with elevated IOP. Of the 26 phakic patients, two had cataracts requiring surgery.
CONCLUSIONS
Cases of refractory diabetic macular edema that did not respond to previous treatment, such as anti-vascular endothelial growth factor injections and laser photocoagulation, exhibited improvements in visual acuity and decreases in retinal thickness after IVD implantation. Both functional and anatomical effects were observed in the first 3 months after injection. Repeat injections and frequent examination might be required for continued improvement. Side effects, such as cataracts and elevation of IOP, may require medical or surgical treatment.

Keyword

Diabetic macular edema; Intravitreal dexamethasone implants

MeSH Terms

Cataract
Dexamethasone*
Diabetic Retinopathy
Endothelial Growth Factors
Follow-Up Studies
Humans
Intraocular Pressure
Light Coagulation
Macular Edema*
Retinaldehyde
Retrospective Studies
Tomography, Optical Coherence
Visual Acuity
Dexamethasone
Endothelial Growth Factors
Retinaldehyde

Figure

• 

  Fig. 1 Mean BCVA, CMT, and IOP at study onset and during follow-up. (A) Mean BCVA (logMAR), (B) mean CMT, (C) mean IOP before and after treatment. BCVA = best-corrected visual acuity; logMAR = logarithm of the minimum angle of resolution; Preop = preoperative; CMT = central macular thickness; IOP = intraocular pressure.

Reference

1. Williams GA. Diabetic macular edema. In : Bandello F, Querques G, editors. ESASO course series. Vol. 1. Medical retina. Basel: Karger;2012. p. 99–104.

2. Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XV: the long-term incidence of macular edema. Ophthalmology. 1995; 102:7–16.

3. Photocoagulation for diabetic macular edema: Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol. 1985; 103:1796–1806.

4. Adamis AP. Is diabetic retinopathy an inflammatory disease? Br J Ophthalmol. 2002; 86:363–365.

5. Grant MB, Afzal A, Spoerri P, et al. The role of growth factors in the pathogenesis of diabetic retinopathy. Expert Opin Investig Drugs. 2004; 13:1275–1293.

6. Nguyen QD, Shah SM, Van Anden E, et al. Supplemental oxygen improves diabetic macular edema: a pilot study. Invest Ophthalmol Vis Sci. 2004; 45:617–624.

7. Nauck M, Karakiulakis G, Perruchoud AP, et al. Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells. Eur J Pharmacol. 1998; 341:309–315.

8. Heiss JD, Papavassiliou E, Merrill MJ, et al. Mechanism of dexamethasone suppression of brain tumor-associated vascular permeability in rats: involvement of the glucocorticoid receptor and vascular permeability factor. J Clin Invest. 1996; 98:1400–1408.

9. McGhee CN. Pharmacokinetics of ophthalmic corticosteroids. Br J Ophthalmol. 1992; 76:681–684.

10. Parke DW 3rd, Sisk RA, Houston SK, Murray TG. Ocular hypertension after intravitreal triamcinolone with vitrectomy and phacoemulsification. Clin Ophthalmol. 2012; 6:925–931.

11. Massin P, Audren F, Haouchine B, et al. Intravitreal triamcinolone acetonide for diabetic diffuse macular edema: preliminary results of a prospective controlled trial. Ophthalmology. 2004; 111:218–224.

12. Park CH, Jaffe GJ, Fekrat S. Intravitreal triamcinolone acetonide in eyes with cystoid macular edema associated with central retinal vein occlusion. Am J Ophthalmol. 2003; 136:419–425.

13. Edelman JL, Lutz D, Castro MR. Corticosteroids inhibit VEGF-induced vascular leakage in a rabbit model of blood-retinal and blood-aqueous barrier breakdown. Exp Eye Res. 2005; 80:249–258.

14. Haller JA, Bandello F, Belfort R Jr, et al. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology. 2010; 117:1134–1146.

15. Goldfein A. Adrenocorticosteroids and adrenocortical antagonists. In : Katzung BG, editor. Basic and clinical pharmacology. 6th ed. London: Prentice Hall;1995. p. 592–607.

16. Chang-Lin JE, Attar M, Acheampong AA, et al. Pharmacokinetics and pharmacodynamics of a sustained-release dexamethasone intravitreal implant. Invest Ophthalmol Vis Sci. 2011; 52:80–86.

17. Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012; 35:556–564.

18. Bhagat N, Grigorian RA, Tutela A, Zarbin MA. Diabetic macular edema: pathogenesis and treatment. Surv Ophthalmol. 2009; 54:1–32.

19. American Diabetes Association. Standards of medical care in diabetes--2009. Diabetes Care. 2009; 32:Suppl 1. S13–S61.

20. Brown DM, Nguyen QD, Marcus DM, et al. Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials. RISE and RIDE. Ophthalmology. 2013; 120:2013–2022.

21. Gillies MC, Sutter FK, Simpson JM, et al. Intravitreal triamcinolone for refractory diabetic macular edema: two-year results of a double-masked, placebo-controlled, randomized clinical trial. Ophthalmology. 2006; 113:1533–1538.

22. Jonas JB, Degenring R, Kreissig I, Akkoyun I. Safety of intravitreal high-dose reinjections of triamcinolone acetonide. Am J Ophthalmol. 2004; 138:1054–1055.

23. Thakur A, Kadam R, Kompella UB. Trabecular meshwork and lens partitioning of corticosteroids: implications for elevated intraocular pressure and cataracts. Arch Ophthalmol. 2011; 129:914–920.

24. Boyer DS, Yoon YH, Belfort R Jr, et al. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology. 2014; 121:1904–1914.

25. Zucchiatti I, Lattanzio R, Querques G, et al. Intravitreal dexamethasone implant in patients with persistent diabetic macular edema. Ophthalmologica. 2012; 228:117–122.

26. Scaramuzzi M, Querques G, Spina CL, et al. Repeated intravitreal dexamethasone implant (Ozurdex) for diabetic macular edema. Retina. 2015; 35:1216–1222.

27. Dutra Medeiros M, Postorino M, Navarro R, et al. Dexamethasone intravitreal implant for treatment of patients with persistent diabetic macular edema. Ophthalmologica. 2014; 231:141–146.

28. Callanan DG, Gupta S, Boyer DS, et al. Dexamethasone intravitreal implant in combination with laser photocoagulation for the treatment of diffuse diabetic macular edema. Ophthalmology. 2013; 120:1843–1851.

29. 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.

30. Rishi P, Rishi E, Kuniyal L, Mathur G. Short-term results of intravitreal dexamethasone implant (OZURDEX(®)) in treatment of recalcitrant diabetic macular edema: a case series. Oman J Ophthalmol. 2012; 5:79–82.

31. Badala F. The treatment of branch retinal vein occlusion with bevacizumab. Curr Opin Ophthalmol. 2008; 19:234–238.