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Year : 2019  |  Volume : 67  |  Issue : 11  |  Page : 1855-1856

Commentary: Hyperreflective dots - An imaging biomarker of inflammation?

Post Graduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication22-Oct-2019

Correspondence Address:
Dr. Aniruddha Agarwal
Advanced Eye Center, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh - 160 012
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_1250_19

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How to cite this article:
Agarwal A. Commentary: Hyperreflective dots - An imaging biomarker of inflammation?. Indian J Ophthalmol 2019;67:1855-6

How to cite this URL:
Agarwal A. Commentary: Hyperreflective dots - An imaging biomarker of inflammation?. Indian J Ophthalmol [serial online] 2019 [cited 2020 Aug 3];67:1855-6. Available from: http://www.ijo.in/text.asp?2019/67/11/1855/269604

Today, with the advancement of optical coherence tomography (OCT) technology, small punctate lesions measuring only a few microns can be easily detected. The study by Hanumunthadu et al.[1] have presented their astute findings of hyperreflective dots (HRDs) in eyes with central serous chorioretinopathy (CSC) and have renewed our interest in this novel and enigmatic observation. A brief reappraisal of the historical literature related to HRDs will help us understand the finer nuances of this entity.

HRDs (or hyperreflective foci) were described using OCT in 2009 by Coscas et al.[2] who reported their presence in neovascular age-related macular degeneration (AMD). These HRDs were noted in all retinal layers, especially around fluid accumulation in intraretinal cystoid spaces. At the same time, Bolz et al.[3] in 2009 showed HRDs in patients with diabetic macular edema (DME). Similar to the observations by Coscas et al., they observed HRDs in all the retinal layers and found them to be unrelated to microaneurysms (on slit-lamp biomicroscopy and fundus photography). While these studies could not determine the significance of HRDs, they generated a great interest among retina and uveitis specialists in determining the cause and significance of these findings. Subsequently, several authors observed HRD in other conditions such as retinal vein occlusions (RVOs),[4] CSC,[5] and Coats disease,[6] among others.

We now know that HRDs are typically described as well-circumscribed punctate lesions (approximately 20–40 μm in diameter) of equal or higher reflectivity than the retinal pigment epithelium.[7] There are a number of theories regarding the etiopathogenesis of HRDs. In the absence of a direct histopathological correlation, only indirect associations can be drawn. We rely on the conclusions drawn by various authors from OCT scans and other imaging tools such as infrared imaging.[2],[4],[7],[8] Certain authors such as Bolz et al.[3] have postulated that these foci may represent small intraretinal protein and/or lipid deposits which may be precursors of hard exudates. However, since then, there have been studies which differentiated HRD from lipid exudates based on their morphology.[7],[8],[9] In addition, HRDs show rapid resolution and reduction in the number following therapies such as antivascular growth factor agents (anti-VEGF) and corticosteroids, which is inconsistent with intraretinal lipid. These studies hypothesize that HRDs could represent activated glial cells (the primary immune cells in the retina) which migrate and secrete proinflammatory mediators.[10]

The study by Chatziralli et al.[11] tested the hypothesis that HRDs can independently predict visual outcome in patients with macular edema due to various causes. On the same lines, Coscas et al.[8] evaluated the prognostic value of HRDs in eyes with neovascular AMD. These studies showed that higher number of HRDs were significantly associated with suboptimal gains in visual acuity with standard anti-VEGF therapies. Nonresponders to anti-VEGF therapy were found to have high number of HRD on OCT scans. These findings, coupled with the popular hypothesis that HRDs are inflammatory in origin, led authors such as Hwang et al.[7] and Coscas et al.[8] to believe that anti-inflammatory therapies such as intravitreal dexamethasone implants may have a greater role in eyes with high number of HRDs.

In the context of CSC, Ojima et al.[5] in 2007 observed punctate areas of intense reflectivity (which today we recognize as HRDs) more frequently with chronic CSC compared with acute cases. Since there are very few articles in the literature that describe HRDs in CSC,[5],[12],[13] it is not clear whether the pathogenesis of HRDs in CSC is similar to AMD, DME, and RVO, among other conditions. The study by Hanumunthadu, et al.[1] further helps us understand that alterations such as increased choroidal thickness, higher neurosensory detachment, and chronicity of the disease may result in development of HRD. However, questions still remain – are HRDs formed as a result of inflammation across the entire spectrum of retinal pathologies ranging from AMD, to DME, and CSC? Thus far, we do not have data from cytokine or interleukin analysis from intraocular fluids in eyes with HRD to demonstrate higher levels of proinflammatory mediators compared with control subjects (with no or few HRDs). We also recognize that the theory of microglial migration and proliferation does not have a direct histological correlation. Could the increased choroidal hyperpermeability in CSC directly impact the immune cell migration? The location of HRDs within the retinal layers may also have prognostic significance, but this has not been addressed satisfactorily thus far. Based on the evidence (direct and indirect) in the literature, retina specialists world over may be more inclined toward treating patients with HRD on OCT using corticosteroids. Whether this approach will truly impact the outcomes of our patients remains to be evaluated conclusively.

  References Top

Hanumunthadu D, Matet A, Rasheed MA, Goud A, Vuppurabina KK, Chhablani J. Evaluation of choroidal hyperreflective dots in acute and chronic central serous chorioretinopathy. Indian J Ophthalmol 2019;67:1850-4.  Back to cited text no. 1
  [Full text]  
Coscas G, Coscas F, Vismara S, Zourdani A, Li Calzi CI. Clinical features and natural history of AMD. In: Coscas G, Coscas F, Vismara S, Zourdani A, Li Calzi CI, editors. Optical Coherence Tomography in Age-Related Macular Degeneration. Germany: Springer, Heidelberg; 2009. p. 171-4.  Back to cited text no. 2
Bolz M, Schmidt-Erfurth U, Deak G, Mylonas G, Kriechbaum K, Scholda C. Optical coherence tomographic hyperreflective foci: A morphologic sign of lipid extravasation in diabetic macular edema. Ophthalmology 2009;116:914-20.  Back to cited text no. 3
Gelman SK, Freund KB, Shah VP, Sarraf D. The pearl necklace sign: a novel spectral domain optical coherence tomography finding in exudative macular disease. Retina 2014;34:2088-95.  Back to cited text no. 4
Ojima Y, Hangai M, Sasahara M, Gotoh N, Inoue R, Yasuno Y, et al. Three-dimensional imaging of the foveal photoreceptor layer in central serous chorioretinopathy using high-speed optical coherence tomography. Ophthalmology 2007;114:2197-207.  Back to cited text no. 5
Ong SS, Cummings TJ, Vajzovic L, Mruthyunjaya P, Toth CA. Comparison of optical coherence tomography with fundus photographs, fluorescein angiography, and histopathologic analysis in assessing Coats disease. JAMA Ophthalmol 2018. doi: 10.1001/jamaophthalmol. 2018.5654.  Back to cited text no. 6
Hwang HS, Chae JB, Kim JY, Kim DY. Association between hyperreflective dots on spectral-domain optical coherence tomography in macular edema and response to treatment. Invest Ophthalmol Vis Sci 2017;58:5958-67.  Back to cited text no. 7
Coscas G, De Benedetto U, Coscas F, Li Calzi CI, Vismara S, Roudot-Thoraval F, et al. Hyperreflective dots: A new spectral-domain optical coherence tomography entity for follow-up and prognosis in exudative age-related macular degeneration. Ophthalmologica 2013;229:32-7.  Back to cited text no. 8
Vujosevic S, Bini S, Midena G, Berton M, Pilotto E, Midena E. Hyperreflective intraretinal spots in diabetics without and with nonproliferative diabetic retinopathy: An in vivo study using spectral domain OCT. J Diabetes Res 2013;2013:491835. doi: 10.1155/2013/491835.  Back to cited text no. 9
Zeng H, Green WR, Tso MOM. Microglial activation in human diabetic retinopathy. Arch Ophthalmol 2008;126:227-32.  Back to cited text no. 10
Chatziralli IP, Sergentanis TN, Sivaprasad S. Hyperreflective foci as an independent visual outcome predictor in macular edema due to retinal vascular diseases treated with intravitreal dexamethasone or ranibizumab. Retina 2016;36:2319-28.  Back to cited text no. 11
Ambiya V, Goud A, Rasheed MA, Gangakhedkar S, Vupparaboina KK, Chhablani J. Retinal and choroidal changes in steroid-associated central serous chorioretinopathy. Int J Retina Vitreous 2018;4. doi: 10.1186/s40942-018-0115-1.  Back to cited text no. 12
Vogel RN, Langlo CS, Scoles D, Carroll J, Weinberg DV, Kim JE. High- resolution imaging of intraretinal structures in active and resolved central serous chorioretinopathy. Invest Ophthalmol Vis Sci 2017;58:42-9.  Back to cited text no. 13


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