Behavior of SD-OCT Detectable Hyperreflective Foci in Diabetic Macular Edema Patients after Therapy with Anti-VEGF Agents and Dexamethasone Implants

Abstract

Purpose. Diabetic macular edema (DME) is the most common cause of blindness in the working-age population. Spectral-domain optical coherence tomography (SD-OCT) allows detection and monitoring of the edema and a detailed analysis of the retinal structure. Hyperreflective foci (HF) are small, circumscribed lesions on OCT, and their origin is yet to be determined. Our study was aimed to shed light on HF pathophysiology, by analyzing their number and location in DME patients at baseline and after therapy. Methods. A prospective, observational study on 59 eyes of 51 DME patients who were treated with antivascular endothelial growth factor (VEGF) therapy (VEGF group, n = 40 eyes) or dexamethasone implant (DEX group, n = 19 ). HF and hard exudates (HE) were discriminated by their appearance on fundus photographs and their size on OCT. Quantity and location of HF and HE were analyzed at baseline and after therapy. Results. DME decreased in 75% of patients in the VEGF (455.5 μm vs. 380.8 μm, p = 0.02 ) and in 95% of patients in the DEX group (471.6 μm vs. 381.9 μm, p = 0.007 ). The number of foci decreased in 62.5% of patients after anti-VEGF (130.6 vs. 111.1, p = 0.07 ) and in 68% of patients after dexamethasone injection ((123.4 vs. 94.9, p = 0.02 ) 5.1). A subgroup of 15% of eyes, all treated with anti-VEGF, showed accumulation of larger HF in outer retinal layers to visible HE during DME resolution, whereas smaller HF, found in all retinal layers, remained unchanged. There was a trend towards a dynamic shift of the foci from inner to outer retinal layers. Conclusion. The dynamic rearrangement of the small HF and their slightly greater reduction after anti-inflammatory therapy suggest inflammatory cells as their origin, whereas larger HF in the outer retinal layers correspond to microexudates. Furthermore, we found a more favourable outcome in patients with HF after treatment with dexamethasone implants compared to anti-VEGF agents.

Prognostic Imaging Biomarkers in Diabetic Macular Edema Eyes Treated with Intravitreal Dexamethasone Implant

“…Our results agree with other studies [ 4 , 30 , 31 ] in which a better morphological response to intravitreal anti-VEGF and steroids was associated with the presence of HRF. In addition, a greater HRF reduction after DEXi compared with anti-VEGF treatment has been documented [ 28 , 32 , 33 ], confirming the HRF as a biomarker of inflammatory DME pattern [ 4 , 5 , 34 ].…”

The Presence of Hyperreflective Foci Reflects Vascular, Morphologic and Metabolic Alterations in Retinitis Pigmentosa

“…In the SD-OCT scan they are seen as tiny dense particles in the outer- and inner retinal layers with greater reflectivity than the retinal pigment epithelium (RPE). Their prevalence has been related to the progression of atrophy in age-related macular degeneration [ 44 ], to the activity of diabetic retinopathy [ 45 , 46 , 47 ], macular telangiectasia type 2 (MacTel) [ 48 ] or Morbus Coats [ 49 ], but also to the extent of ischemia in retinal vein occlusion [ 50 ], to the progression of degeneration in RP [ 38 , 39 , 40 , 41 ], as well as to the progression of atrophy in Stargardt disease [ 51 , 52 ].…”

“…Some studies suppose that the HRF represents an inflammatory component like microglia or migrated RPE and/or the extravasation of lipoproteins following the breakdown of the blood-retinal barrier [ 53 , 54 ]. It has been shown that HRF foci are also a predictive marker of the final visual outcome in diseases like retinal vein occlusion [ 50 ], diabetic retinopathy [ 46 ], polypoidal choroidal vasculopathy [ 55 ], neovascular age-related macular degeneration [ 55 ], but also in degenerative diseases like RP [ 38 , 39 , 40 , 41 ].…”

Efficacy and safety profile of intravitreal dexamethasone implant versus antivascular endothelial growth factor treatment in diabetic macular edema: a systematic review and meta-analysis

“…The 0.7 mg intravitreal DEX implant Ozurdex® (Allergan, Inc.) was designed to deliver medication to the retina and could maintain the drug concentration in the vitreous body for up to 6 months 3 . Several research groups thereafter initiated head-to-head clinical trials to compare the efficacy of anti-VEGF therapy and Ozurdex therapy 14 – 58 . BEVORDEX, the first RCT to assess this, reported that Ozurdex therapy was not inferior to anti-VEGF therapy in terms of visual acuity (VA) changes and that it led to superior anatomical outcomes compared with anti-VEGF therapy at the primary endpoint 35 .…”