Hyperreflective foci (HF), detected in the retina of diabetic patients, suggest the presence of microglial activation and migration, while controversies still remain for the origin of HF to be precursors of hard exudates. We investigated the presence of HF and their association with dyslipidemia in serous retinal detachment (SRD)-type diabetic macular edema (DME).
Forty-two eyes in 42 patients with diabetic retinopathy (DR) and 22 eyes in 22 patients with branch retinal vascular occlusion (BRVO) showing macular edema were included in this study. The medical records and OCT findings were retrospectively reviewed in patients with SRD-type DME and compared with those with BRVO. The mean number of HF, the mean choroidal thickness, and lipid profiles were analyzed and compared between groups.
The mean number of HF was significantly higher in DR group compared to BRVO group. Significant correlation of HF was noted with triglycerides (r = 0.523, P = 0.002). Triglycerides were significantly associated with HF by linear regression (β = 0.012, 95% CI 0.001–0.024, P = 0.034) and remained significantly associated by multiple linear regression (β = 0.014, 95% CI 0.003–0.025, P = 0.014).
HF on OCT of DME patients could be indicative of activated microglia. HF are associated with dyslipidemia, especially high triglycerides, suggesting inflammatory reaction from dyslipidemia in diabetic retina.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Bandello F, Lattanzio R, Zucchiatti I, Del Turco C (2013) Pathophysiology and treatment of diabetic retinopathy. Acta Diabetol 50:1–20
Kim JT, Lee DH, Joe SG, Kim JG, Yoon YH (2013) Changes in choroidal thickness in relation to the severity of retinopathy and macular edema in type 2 diabetic patients. Investig Ophthalmol Vis Sci 54:3378–3384
Otani T, Kishi S, Maruyama Y (1999) Patterns of diabetic macular edema with optical coherence tomography. Am J Ophthalmol 127:688–693
Sonoda S, Sakamoto T, Shirasawa M, Yamashita T, Otsuka H, Terasaki H (2013) Correlation between reflectivity of subretinal fluid in OCT images and concentration of intravitreal VEGF in eyes with diabetic macular edema. Investig Ophthalmol Vis Sci 54:5367–5374
Sonoda S, Sakamoto T, Yamashita T, Shirasawa M, Otsuka H, Sonoda Y (2014) Retinal morphologic changes and concentrations of cytokines in eyes with diabetic macular edema. Retina 34:741–748
Daruich A, Matet A, Moulin A et al (2018) Mechanisms of macular edema: beyond the surface. Prog Retin Eye Res 63:20–68
Omri S, Behar-Cohen F, de Kozak Y et al (2011) Microglia/macrophages migrate through retinal epithelium barrier by a transcellular route in diabetic retinopathy: role of PKCzeta in the Goto Kakizaki rat model. Am J Pathol 179:942–953
Bolz M, Schmidt-Erfurth U, Deak G, Mylonas G, Kriechbaum K, Scholda C (2009) Optical coherence tomographic hyperreflective foci: a morphologic sign of lipid extravasation in diabetic macular edema. Ophthalmology 116:914–920
Vujosevic S, Bini S, Midena G, Berton M, Pilotto E, Midena E (2013) Hyperreflective intraretinal spots in diabetics without and with nonproliferative diabetic retinopathy: an in vivo study using spectral domain OCT. J Diabetes Res 2013:491835
Vujosevic S, Torresin T, Bini S et al (2017) Imaging retinal inflammatory biomarkers after intravitreal steroid and anti-VEGF treatment in diabetic macular oedema. Acta Ophthalmol 95:464–471
Jaulim A, Ahmed B, Khanam T, Chatziralli IP (2013) Branch retinal vein occlusion: epidemiology, pathogenesis, risk factors, clinical features, diagnosis, and complications. An update of the literature. Retina 33:901–910
Noma H, Mimura T, Yasuda K, Shimura M (2014) Role of inflammation in diabetic macular edema. Ophthalmologica 232:127–135
Zhang W, Liu H, Al-Shabrawey M, Caldwell RW, Caldwell RB (2011) Inflammation and diabetic retinal microvascular complications. J Cardiovasc Dis Res 2:96–103
Chung YR, Park SW, Choi SY et al (2017) Association of statin use and hypertriglyceridemia with diabetic macular edema in patients with type 2 diabetes and diabetic retinopathy. Cardiovasc Diabetol 16:4
Das R, Kerr R, Chakravarthy U, Hogg RE (2015) Dyslipidemia and diabetic macular edema: a systematic review and meta-analysis. Ophthalmology 122:1820–1827
Kang JW, Chung H, Chan Kim H (2016) Correlation of optical coherence tomographic hyperreflective foci with visual outcomes in different patterns of diabetic macular edema. Retina 36:1630–1639
Das A, McGuire PG, Rangasamy S (2015) Diabetic macular edema: pathophysiology and novel therapeutic targets. Ophthalmology 122:1375–1394
Klaassen I, Van Noorden CJ, Schlingemann RO (2013) Molecular basis of the inner blood-retinal barrier and its breakdown in diabetic macular edema and other pathological conditions. Prog Retin Eye Res 34:19–48
Checchin D, Sennlaub F, Levavasseur E, Leduc M, Chemtob S (2006) Potential role of microglia in retinal blood vessel formation. Investig Ophthalmol Vis Sci 47:3595–3602
Altmann C, Schmidt MHH (2018) The role of microglia in diabetic retinopathy: Inflammation, microvasculature defects and neurodegeneration. Int J Mol Sci 19:110
Chen L, Yang P, Kijlstra A (2002) Distribution, markers, and functions of retinal microglia. Ocul Immunol Inflamm 10:27–39
Jo DH, Yun JH, Cho CS, Kim JH, Kim JH, Cho CH (2019) Interaction between microglia and retinal pigment epithelial cells determines the integrity of outer blood-retinal barrier in diabetic retinopathy. Glia 2019:321–331
Vujosevic S, Torresin T, Berton M, Bini S, Convento E, Midena E (2017) Diabetic macular edema with and without subfoveal neuroretinal detachment: two different morphologic and functional entities. Am J Ophthalmol 181:149–155
Gallego-Pinazo R, Dolz-Marco R, Pardo-Lopez D et al (2013) Ranibizumab for serous macular detachment in branch retinal vein occlusions. Graefes Arch Clin Exp Ophthalmol 251:9–14
Lee WJ, Kang MH, Seong M, Cho HY (2012) Comparison of aqueous concentrations of angiogenic and inflammatory cytokines in diabetic macular oedema and macular oedema due to branch retinal vein occlusion. Br J Ophthalmol 96:1426–1430
Lee H, Jang H, Choi YA, Kim HC, Chung H (2018) Association between soluble CD14 in the aqueous humor and hyperreflective foci on optical coherence tomography in patients with diabetic macular edema. Invest Ophthalmol Vis Sci 59:715–721
Vujosevic S, Toma C, Villani E et al (2019) Diabetic macular edema with neuroretinal detachment: OCT and OCT-angiography biomarkers of treatment response to anti-VEGF and steroids. Acta Diabetol. https://doi.org/10.1007/s00592-019-01424-4
Choi MY, Jee D, Kwon JW (2019) Characteristics of diabetic macular edema patients refractory to anti-VEGF treatments and a dexamethasone implant. PLoS ONE 14:e0222364
Kim KT, Kim DY, Chae JB (2019) Association between hyperreflective foci on spectral-domain optical coherence tomography and early recurrence of diabetic macular edema after intravitreal dexamethasone implantation. J Ophthalmol 2019:3459164
Christenbury JG, Folgar FA, O'Connell RV, Chiu SJ, Farsiu S, Toth CA (2013) Progression of intermediate age-related macular degeneration with proliferation and inner retinal migration of hyperreflective foci. Ophthalmology 120:1038–1045
Nassisi M, Lei J, Abdelfattah NS et al (2019) OCT risk factors for development of late age-related macular degeneration in the fellow eyes of patients enrolled in the HARBOR study. Ophthalmology 126:1667–1674
Nassisi M, Fan W, Shi Y et al (2018) Quantity of intraretinal hyperreflective foci in patients with intermediate age-related macular degeneration correlates with 1-year progression. Investig Ophthalmol Vis Sci 59:3431–3439
Ho J, Witkin AJ, Liu J et al (2011) Documentation of intraretinal retinal pigment epithelium migration via high-speed ultrahigh-resolution optical coherence tomography. Ophthalmology 118:687–693
Saha S, Nassisi M, Wang M et al (2019) Automated detection and classification of early AMD biomarkers using deep learning. Sci Rep 9:10990
Hammer SS, Busik JV (2017) The role of dyslipidemia in diabetic retinopathy. Vision Res 139:228–236
Davoudi S, Papavasileiou E, Roohipoor R et al (2016) Optical coherence tomography characteristics of macular edema and hard exudates and their association with lipid serum levels in type 2 diabetes. Retina 36:1622–1629
De Benedetto U, Sacconi R, Pierro L, Lattanzio R, Bandello F (2015) Optical coherence tomographic hyperreflective foci in early stages of diabetic retinopathy. Retina 35:449–453
Rübsam A, Parikh S, Fort PE (2018) Role of inflammation in diabetic retinopathy. Int J Mol Sci 19:942
Graeber MB, Li W, Rodriguez ML (2011) Role of microglia in CNS inflammation. FEBS Lett 585:3798–3805
Tang J, Kern TS (2011) Inflammation in diabetic retinopathy. Prog Retin Eye Res 30:343–358
This study was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1D1A1A02018439).
Conflict of interest
The authors declare that they have no conflict of interest.
Human and animal rights
This study was approved by the Institutional Review Board of Ajou University Hospital, Suwon, Korea (IRB No.: MED-MDB-18-481) and complied with the Declaration of Helsinki.
For this type of study, no informed consent is required.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This article belongs to the topical collection Eye Complications of Diabetes, managed by Giuseppe Querques.
About this article
Cite this article
Chung, YR., Lee, S.Y., Kim, Y.H. et al. Hyperreflective foci in diabetic macular edema with serous retinal detachment: association with dyslipidemia. Acta Diabetol 57, 861–866 (2020). https://doi.org/10.1007/s00592-020-01495-8
- Diabetic macular edema
- Hyperreflective foci