Refractory diffuse clinically significant macular edema is a special entity of diabetic macular edema (DME) that is difficult to treat, with limited role for laser in management. Vitrectomy has been shown to be effective in improving these cases, particularly those with taught hyaloids and vitreomacular traction (VMT).1,2 This is explained by its mechanisms of removing anterioposterior as well as tangential traction, removing VEGF and other vasopermeable factors, potentially increasing macular microcirculation, and improving retinal and vitreous oxygenation. Vitrectomy has also shown a potential role in managing DME without macular treatment.3-7
Despite reports in the literature, some cases still do not do well, and combining treatment modalities might be a better option.
Intravitreal Implant Delivery
The role of intravitreal steroids in the management of macular edema is well established, showing good short-term outcomes; however, recurrence of edema and increase in intraocular pressure (IOP) occurs in approximately 30% of cases, along with lens changes, risk of multiple injections, and finding poor prognosis if significant hyaloidal traction is present.8 We also know that effect of combining intravitreal steroid with vitrectomy is temporary due to the high clearance rate of a vitrectomized eye compared with a nonvitrectomized eye.
One solution to this fast clearance may be the use of extended-release intravitreal implants. The CHAMPLAIN study showed that treatment with the dexamethasone intravitreal implant (Ozurdex, Allergen Inc.) led to statistically significant improvements in both vision and vascular leakage from DME in difficult-to-treat vitrectomized eyes.9 This concept was also supported by Chang Lin et al,10 showing similar pharmacokinetics after implantation in vitrectomized and nonvitrectomized eyes, suggesting a potential role for extended-release steroid combined with vitrectomy in managing these difficult-to-treat cases. Extended-release steroids do have issues, however, including IOP increase and cataract formation.
Suprachoroidal delivery has a therapeutic effect similar to that of the intravitreal route, with extended half-life (no washout, longer absorption time) and less incidence of IOP increase. Olsen et al11 demonstrated in a pig model that the suprachoroidal space could serve as a reservoir for sustained-release formulations, establishing a steep concentration gradient for drug diffusion into the retina and choroid. They also showed a high local drug concentration in the choroid and retina in the macular region for at least 4 months. Rizzo and colleagues12 showed resolution of massive subfoveal hard exudates in cases of DME unresponsive to multiple intravitreal injections using a combination of bevacizumab and triamcinolone administrated to the submacular suprachoroidal space.
Vitrectomy Combined With Suprachoroidal Steroid Delivery
We have used the technique described below to treat different cases of refractory DME (watch the video by scanning the QR code here, or by following the quicklink). In this technique, we perform a classic 3-port pars plana vitrectomy with hyaloid removal and internal limiting membrane peeling in cases of evident traction on optical coherence tomography (OCT), followed by a 2-mm sclerotomy incision that is 3 to 4 mm behind and parallel to the limbus at the 12 o'clock position. The sclerotomy exposes the choroid. The choroid is separated from the sclera by a viscoelastic dissection bubble. We then introduce a specially designed suprachoroidal catheter (El Rayes catheter, MedOne Surgical), primed with preservative-free triamcinolone acetate (Figure 1). The catheter has 2 arms: 1 connected to the machine light source and the other connected to an injection syringe carrying the drug. SUPPLEMENTAL VIDEO
The 400-μm catheter is threaded into the suprachoroidal space under direct visualization through the microscope to reach the submacular area in the suprachoroidal space. The light spot at the tip marks the target tissue. We then inject 8 mg under direct visualization (Figure 2). We then remove the catheter and close the sclerotomy.
We have used this technique in 38 patients with improvement in macular edema clinically as well as on OCT in all of them, even eyes with subretinal hard exudates. We have noticed immediate improvement in retinal thickness as early as 48 hours postoperative, compared with vitrectomy alone (Figure 3). We have seen IOP elevation only in 1 eye, and this was transient and was controlled medically. OCT improvement was stable over 4 to 5 month follow-up. There was a gradual increase in retinal thickness on OCT that was noted in 5 eyes. No thickness measurements reached 50% of the preoperative thickness.
Other than the patients in our trial, we have used escalating doses of triamcinolone up to 12 mg with the same therapeutic effect and no increase in IOP. Even extrafoveal injection (around the arcades) had a therapeutic effect (watch the video by scanning the QR code here, or by following the quicklink). SUPPLEMENTAL VIDEO
Suprachoroidal Delivery Alone for Nontraction Refractory DME
Recently, we started using suprachoroidal delivery without vitrectomy for nontraction refractory DME. We use the catheter and a chandelier light (no vitrectomy infusion and tapping the anterior chamber) and have found this to have a therapeutic effect over 5 months of follow-up.
Suprachoroidal steroid delivery augments the therapeutic role of vitrectomy in retinal edema. It also has demonstrated a possible role as a sustained-release approach in nonvitrectomized eyes with no traction. Delivery through the suprachoroidal space acts as a slow-release reservoir and avoids the anterior chamber side effects of glaucoma and cataract when using intravitreal steroids. It also obviates washout and increases the duration of drug activity in a cost-effective approach as an adjunct to vitrectomy or as monotherapy for macular edema.
More study is needed to compare suprachoroidal steroid delivery as monotherapy for macular edema with catheterization and delivery under chandelier light to other modes of treatment. In my opinion, however, suprachoroidal drug delivery is a viable option and may also be used in the future with newer drugs still in the development pipeline.
Ehab N. El Rayes, MD, PhD, is a Professor of Ophthalmology in the Retina Department, Institute of Ophthalmology in Cairo, Egypt. Dr. El Rayes states that he is a consultant to MedOne Inc., is the patent holder of the suprachoroidal catheter and cannula for suprachoroidal buckling and drug delivery, and has received lecture fees from Novartis and travel support from Alcon. He states that he has no financial interests in relation to the content of this article. Dr. El Rayes may be reached at email@example.com.
- Diabetic Retinopathy Clinical Research Network Writing Committee. Haller JA, Qin H, Apte RS, et al. Vitrectomy outcomes in eyes with diabetic macular edema and vitreomacular traction. Ophthalmology. 2010;117:1087-1093 e1083.
- Lewis H , Abrams GW, Blumenkranz MS Campo RV . Vitrectomy for diabetic macular traction and edema associated with posterior hyaloids traction. Ophthalmology. 1992;99:753-759.
- Schweitzer KV, Eneh A , Gale J. Practice patterns of connection vitreoretinal specialists in diabetic macular edema treatment . Can J Ophthalmology. 2011;46:227-231.
- Sakamoto A, Nishjima K, Kita M, Oh H , Tsujikawa A, Yoshimura N. Association between foveal photoreceptors statues and visual acuity after resolution of diabetic macular edema by pars plana vitrectomy. Graefes Arch Clin Exp Ophthalmology. 2009;247:1325-1330.
- Doi N, Sakamoto T, Sonoda Y, et al. Comparative study of vitrectomy versus intravitreous triamcinolone for diabetic macular edema on randomized paired eyes . Grafes Arch Clin Exp Ophthalmology. 2012;250:71-78.
- Chhabiani JK, Kim LS, Cheng L, Kozak I, Freeman W. External limiting membrane as a predictor of visual improvement in diabetic macular edema after pars plane vitrectomy. Graefes Arch Clin Exp Ophthalmology. 2012;250:1415-1420.
- Hartlay KL , Smiddy WE, Flyn HW, Murray TG. Pars plana vitrectomy with internal limiting membrane peeling for diabetic macular edema. Retina. 2008:28:410-419.
- Chin HS, Park TS , Moon YS, Oh H . Difference of clearance of intravitreal triamcinolone acetonide between vitrectomized and non vitrectomized eye. Retina. 2005:25(5):556-560
- Boyer DS, Faher D, Gupta S, et al; Ozurdex CHAMPLAIN Study Group. Dexamethasone intravitreal implant for treatment of diabetic macular edema in vitrectomized patients. Retina. 2011;31(5):915-923.
- Chang Lin J , Burke JA, Peng Q , et al . Pharmacokinetic of a sustained released dexamethasone intravitreal implant in vitrectomized and nonvitrectomized eyes. Invest Ophthalmology Vis Sci. 2011;52(7)4605-4604.
- Olsen TW, Ferg X, Wabner K, et al . Cannulation of the supra choroidal space a novel drug delivery methodology to the posterior segment. Am J Ophthalmol. 2006;142:777-787.
- Rizzo S, Ebert FG, Bartolo ED, et al. Suprachoroidal drug infusion for the treatment of severe subfoveal hard exudate. Retina. 2012;32:766-784.