Hyperreflective Retinal Spots Research Articles

Optical coherence tomography as retinal imaging biomarker of neuroinflammation/neurodegeneration in systemic disorders in adults and children.

The retina and the optic nerve are considered extensions of the central nervous system (CNS) and thus can serve as the window for evaluation of CNS disorders. Spectral domain optical coherence tomography (OCT) allows for detailed evaluation of the retina and the optic nerve. OCT can non-invasively document changes in single retina layer thickness and structure due to neuronal and retinal glial cells (RGC) modifications in systemic and local inflammatory and neurodegenerative diseases. These can include evaluation of retinal nerve fibre layer and ganglion cell complex, hyper-reflective retinal spots (HRS, sign of activated microglial cells in the retina), subfoveal neuroretinal detachment, disorganization of the inner retinal layers (DRIL), thickness and integrity of the outer retinal layers and choroidal thickness. This review paper will report the most recent data on the use of OCT as a non invasive imaging biomarker for evaluation of the most common systemic neuroinflammatory and neurodegenerative/neurocognitive disorders in the adults and in paediatric population. In the adult population the main focus will be on diabetes mellitus, multiple sclerosis, optic neuromyelitis, neuromyelitis optica spectrum disorders, longitudinal extensive transverse myelitis, Alzheimer and Parkinson diseases, Amyotrophic lateral sclerosis, Huntington’s disease and schizophrenia. In the paediatric population, demyelinating diseases, lysosomal storage diseases, Nieman Pick type C disease, hypoxic ischaemic encephalopathy, human immunodeficiency virus, leukodystrophies spinocerebellar ataxia will be addressed.

Serum Iba-1, GLUT5, and TSPO in Patients With Diabetic Retinopathy: New Biomarkers for Early Retinal Neurovascular Alterations? A Pilot Study.

PurposeThis study explored the possibility of highlighting early retinal neurovascular alterations of diabetic retinopathy (DR) by monitoring in DR patients the serum levels of microglial biomarkers ionized calcium-binding adapter molecule 1 (Iba-1), glucose transporter 5 (GLUT5), and translocator protein (TSPO), along with serum changes of the endothelial dysfunction marker arginase-1.MethodsSerum markers were determined by enzyme-linked immunosorbent assay in 50 patients: 12 non-diabetic subjects, 14 diabetic patients without DR, 13 patients with non-proliferative DR (NPDR), and 11 patients with proliferative DR (PDR). The results were correlated with hyperreflective retinal spots (HRS), observed with optical coherence tomography (OCT).ResultsAlthough HRS were absent in diabetic patients without DR, NPDR patients showed an average of 4 ± 1 HRS, whereas the highest presence was detected in PDR patients, with 8 ± 1 HRS (P < 0.01 vs. NPDR). HRS were positively correlated (P < 0.01) with serum levels of arginase-1 (r = 0.91), Iba-1 (r = 0.96), GLUT5 (r = 0.94), and TSPO (r = 0.88). Moreover, serum proinflammatory cytokines and chemokines showed a positive correlation (P < 0.01) with HRS number and the serum markers analyzed.ConclusionsSerum markers of microglial activation positively correlate with retinal HRS in NPDR and PDR patients.Translational RelevanceThese data corroborate the possibility of highlighting early retinal neurovascular changes due to diabetes by monitoring circulating microglial markers.

A Comparison of Hyper-Reflective Retinal Spot Counts in Optical Coherence Tomography Images from Glaucomatous and Healthy Eyes.

Purpose: To compare the number of hyper-reflective retinal spots (HRS) in optical coherence tomography (OCT) images of healthy controls and patients affected with primary open angle glaucoma (POAG). Methods: Thirty patients affected with POAG and 34 healthy controls were recruited and underwent raster OCT examination of the macular region. Among the acquired B-scans, the one with the lowest foveal thickness was selected, and a central area of 3000 μm was defined (region of interest, ROI), in order to identify HRS. HRS were defined as small point-like hyper-reflective elements, detectable at the visual inspection of the OCT image. HRS were independently counted by two investigators in the ROI of each OCT scan. Results: Inter-rater agreement for HRS counting was good to excellent (ICC = 0.96, 95% CI: 0.83–0.99). More HRS were found in the OCT images from glaucoma patients, in comparison with healthy controls (average value: 90.5 ± 13.02 and 74.72 ± 11.35, for glaucoma and healthy subjects, respectively; p < 0.01). Significant correlations between the average number of HRS and visual field mean deviation (MD, p = 0.01) and pattern standard deviation (PSD, p < 0.01) were found. Conclusions: OCT images from glaucoma patients showed a higher number of HRS when compared with healthy controls. As HRS have been hypothesized to be a sign of neuroinflammation, these results may support the role of neuroinflammation in glaucoma etiopathogenesis.

NATURAL COURSE OF VITREOMACULAR TRACTION IN EYES WITH DIABETIC RETINOPATHY AND FACTORS ASSOCIATED WITH SPONTANEOUS RELEASE.

The aim of this study was to determine the natural course of vitreomacular traction (VMT) in patients with diabetic retinopathy and to evaluate the factors associated with VMT relief. Seventy-four eyes of 65 patients with VMT accompanying diabetic retinopathy were evaluated retrospectively. The presence of intravitreal injection and the presence of panretinal photocoagulation were obtained from the medical records of the patients. Spontaneous release of VMT, the horizontal length of vitreomacular traction, the presence of hyperreflective retinal spots, the presence of the epiretinal membrane, and the grade of VMT were evaluated from the spectral-domain optical coherence tomography images. Factors associated with the spontaneous release of VMT were evaluated by logistic regression analysis. Spontaneous release was observed in 28 eyes (37.8%). The horizontal length of VMT was lower in the release of the VMT group compared with the persistent VMT group (P = 0.03). The persistent VMT group had a higher rate of hyperreflective retinal spots and epiretinal membrane compared with the release of the VMT group (respectively; P = 0.003 and P = 0.031). No statistically significant difference was observed between the release of VMT and persistent VMT groups in terms of intravitreal injection and panretinal photocoagulation treatment (respectively; P = 0.938 and P = 0.36). The absence of hyperreflective retinal spots was the most important prognostic factor for the spontaneous release of VMT (P = 0.029). Spontaneous release of VMT observed higher rates of patients without hyperreflective retinal spots, epiretinal membrane, and patients with lower horizontal length of VMT.

Subthreshold Micropulse Laser in Diabetic Macular Edema: 1-Year Improvement in OCT/OCT-Angiography Biomarkers

PurposeThe aim of this study was to evaluate 1-year quantitative changes in specific inflammatory parameters on optical coherence tomography (OCT) / optical coherence tomography angiography (OCTA) in diabetic macular edema (DME) treated with subthreshold micropulse laser (SMPL).MethodsThirty-seven patients / eyes with previously treatment-naïve DME treated with SMPL were prospectively evaluated at 3, 6, and 12 months. Fifteen fellow eyes with only microaneurysms (MAS) not eligible for treatment were controls. Evaluated OCT / OCTA parameters included: central macular thickness (CMT); hyper-reflective retinal spots (HRS); disorganization of inner retinal layers (DRILs); MA in the superficial / deep capillary plexuses (SCP/DCP); cysts in the area at the SCP / DCP; and macular perfusion parameters (MATLAB, version 2017b).ResultsIn the treated group, mean best corrected visual acuity (BCVA) progressively increased from 69.4 ± 12.0 to 76.0 ± 9.1 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (P < 0.001) at 12 months; HRS decreased from baseline (80.75 ± 20.41) at 3 (73.81 ± 17.1, P = 0.002), 6 (69.16 ± 16.48, P < 0.0001), and 12 months (66.29 ± 18.53, P < 0.0001). MA decreased at 3 months in the DCP (P = 0.015), at 6 and 12 months in both plexuses (P ≤ 0.0007). BCVA, HRS, and MA remained stable in the controls during all follow-ups. DRIL was present in 18 of 37 patients at baseline and progressively decreased from 557.0 ± 238.7 to 387.1 ± 282.1 μm (P = 0.01). The area of cyst decreased both in the SCP (P = 0.03) and the DCP (P = 0.02). CMT and perfusion parameters did not change.ConclusionsSMPL reduced the number of HRS (sign of activated microglia cells in the retina), MA, DRIL extension, and the area of cysts. Further studies are needed to confirm these preliminary data on the anti-inflammatory effect of SMPL, and to explore the mechanism of action.Translational RelevanceThe follow-up of OCT/OCTA noninvasive biomarkers offers a unique insight in the mechanism of laser action, suggesting an anti-inflammatory effect of SMPL.

Profile of non-responder and late responder patients treated for diabetic macular edema: systemic and ocular factors.

Diabetic macular edema (DME) treatment represents a challenge for the ophthalmologists, and several aspects of real treatment expectancy are still being discussed and not yet fully elucidated. A univocal definition of responsiveness to treatment has not been reached. How the clinicians can evaluate the therapeutic success? The evaluation of systemic and ocular factors should help in this complex management. The age influences the long-term outcomes, and the role of glycemic control is confounded by contrasting correlations between hemoglobin glycated A1c and DME. Long-term treatment success is influenced by baseline best-corrected visual acuity (BCVA), central macular thickness (CMT) and early BCVA response. Also baseline diabetic retinopathy severity scale score is useful to evaluate the chances of improvement before and during treatments. The time-switching was influenced by early BCVA response, however considering a delayed response in a percentage of patients. Several structural optical coherence tomography (OCT) findings could predict long-term success, as the presence of serous retinal detachment, hyperreflective retinal spots, the disruption of external limiting membrane and ellipsoid zone, the disorganization of inner retinal layers and continued increase in CMT were considered predictors of poor response to treatment. Foveal avascular zone enlargement, high number of microaneurysms (Mas), lower vessel density (VD) in deep capillary plexus and lower parafoveal VD in superficial capillary plexus were considered as OCT angiography biomarkers of poor responsiveness. The aim of this review is to report the factors that could influence the response to treatment of DME patients.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY CHANGES AFTER SUBTHRESHOLD MICROPULSE YELLOW LASER IN DIABETIC MACULAR EDEMA.

To assess changes on optical coherence tomography (OCT) angiography in diabetic macular edema (DME) treated with subthreshold micropulse yellow laser (SMPL) over a period of 6 months. Thirty-five eyes (35 consecutive patients) with treatment-naive DME prospectively underwent (at baseline, 3 and 6 months) best-corrected visual acuity, swept-source OCT angiography/OCT, and fundus autofluorescence. Following parameters were evaluated on OCT angiography in the superficial capillary plexus (SCP) and deep capillary plexus (DCP): the area of foveal avascular zone, number of microaneurysms (MA), area of cysts, and presence of capillary network alterations. Microaneurysm change was also evaluated in 15 fellow eyes, not needing treatment over 6 months. Vessel and perfusion densities were evaluated in the SCP, DCP, and choriocapillaris, with image J. Retina thickness, number of hyperreflective retinal spots, and external limiting membrane integrity were evaluated on OCT. All measurements were performed by two masked graders, independently. All patients had diabetes mellitus Type 2 (mean age, 69.4 ± 10.9 years; duration of diabetes mellitus, 15.7 ± 8.7 years; and HbA1c 7.7 ± 1.2%). Mean best-corrected visual acuity at baseline was 69.7 ± 12.0 letters ETDRS, 72.7 ± 10.7 at 3 months (gain 3.1 ± 4.3, P = 0.0049) and 74.3 ± 9.5 at 6 months (gain 4.6 ± 7.2, P < 0.0001). Foveal avascular zone area decreased in the DCP at 6 months (P = 0.01). Area of cysts decreased in the SCP at 3 months and 6 months (P = 0.038; P = 0.049), and in the DCP at 6 months (P = 0.0071). Number of MA decreased at 6 months in the SCP (P = 0.0007) and at 3 months and 6 months in the DCP (P = 0.048; P < 0.0001) in treated eyes. No significant change in number of MA was found in nontreated eyes. There was no statistically significant change in any other OCT angiography/OCT parameter. Subthreshold micropulse yellow laser induces more pronounced changes in the DCP than in the SCP in DME. These changes occurred as early as 3 months after treatment. The evaluation of specific parameters in the DCP may help in determining treatment response.

Diabetic macular edema with neuroretinal detachment: OCT and OCT-angiography biomarkers of treatment response to anti-VEGF and steroids.

To assess and compare early changes in neuroinflammatory and vascular parameters in diabetic macular edema (DME) with subfoveal neuroretinal detachment (SND) after treatment with intravitreal dexamethasone (DEX-I) and ranibizumab (IVR). Thirty-three eyes (33 patients) with treatment naïve DME with SND were retrospectively evaluated at baseline and 2months after DEX-I (15 eyes) and 1month after 3 monthly IVR injections (18 eyes). Inclusion criteria were: complete eye examination, good quality OCT and OCT-A images. OCT parameters included: central macular thickness (CMT); number of hyper-reflective retinal spots (HRS) in inner, outer (IR, OR) and full retina; choroidal thickness (CT), extent of disorganization of inner retinal layers (DRIL), outer retina integrity (OR). On OCT-A: foveal avascular zone (FAZ) parameters in the superficial capillary plexus (SCP); cysts area and perfusion density (PD) in SCP and deep capillary plexus (DCP) and flow voids (FV) in choriocapillaris. FAZ was analyzed using ImageJ, perfusion parameters and FV using MATLAB. BCVA increased equally after both treatments (13.0 ± 10.0 ETDRS letters, p < 0.0001). There was a similar decrease (p < 0.05) in: height of SND, cysts area at SCP, central and mean CT, increase in FAZ perimeter and OR integrity, after both treatments. A greater decrease in DEX-I versus IVR group was found in: CMT (- 38.7% vs. - 22.2%, p = 0.012), HRS number in IR (- 29.2% vs. - 14.0%, p = 0.05) and full retina (- 24.7% vs. - 8.0%, p = 0.03), DRIL extension (- 62.0% vs. - 24%, p = 0.008), cysts area at DCP (- 68.7% vs. - 26.1%, p = 0.03), FAZ-CI (- 19.1% vs. - 8.3%, p = 0.02), PD at DCP (- 27.5% vs. + 4.9%, p = 0.02). FV did not change. More pronounced changes in specific inflammatory parameters in the inner retina are documented after steroid versus anti-VEGF treatment. These include reduction in HRS number, DRIL extension, CMT, cysts area at DCP. These data may help in further study of noninvasive imaging biomarkers for better evaluation of treatment response.

This issue of ACTA

This issue of ACTA

Dexamethasone for unresponsive diabetic macular oedema: optical coherence tomography biomarkers.

To analyse the effects of intravitreal dexamethasone implant (DEX) in patients with diabetic macular oedema (DME) unresponsive to ranibizumab treatment, in relation to the inflammatory optical coherence tomography (OCT) retinal features, subfoveal neuroretinal detachment (SND) and hyperreflective retinal spots (HRS). Patients with DME poorly responsive to three injections of ranibizumab were treated with DEX. Best-corrected visual acuity (BCVA) and central macula thickness (CMT, measured by Spectralis SD-OCT) were assessed at baseline and at 1, 3, and 6months. Overall, 44 eyes were included in the study. In the whole group, mean BCVA (baseline 51.5±8.3 letters) increased significantly at 1month (to 56.9±8.8 letters; Tukey HSD p=0.017) and was 55.5±8.8 letters at 3months (Tukey HSD p=0.128). Central macula thickness (CMT) reduced significantly at 1 and 3months (417±149μm and 469±128μm, respectively, both Tukey HSD p<0.001 versus baseline). Subgroup analysis showed a significant BCVA increase at 1month in eyes with SND+HRS (from 51.2±9.2 to 58.2±9.0, p=0.029), and a trend to BCVA increase in eyes with HRS (from 52.3±6.4 to 56.8±7.9, p=0.080), with a significant CMT decrease in both groups (p<0.001). No changes of either parameter were found in eyes without SND and HRS. Spectral domain OCT is useful in identifying some inflammatory features in DME. Among DME eyes 'poorly responsive' to ranibizumab, those with SND and HRS responded better to DEX implants than those without these features.

Early retinal and choroidal OCT and OCT angiography signs of inflammation after uncomplicated cataract surgery

PurposeTo evaluate, by means of optical coherence tomography (OCT) and OCT angiography (OCTA), early retinal, choroidal and macular perfusion changes induced by a local inflammatory reaction secondary to uncomplicated cataract...

This issue of ACTA

The cover illustration shows a prolene thread inserted into Schlemm′s canal as reported by Grieshaber et al. in this issue of Acta. Klemp et al. in Copenhagen describe exudative retinal detachment, cataract formation and melanocytic tumours as the characteristic ocular findings in uveal melanocytic proliferation. Campos et al. in Portugal consider the role of the choroid in diabetic macular oedema and how OCT studies of the choroid advance this field of research. Jørstad et al. in Oslo found positive results with aflibercept in AMD eyes which were resistant to ranibizumab and bevacizumab injections. Many eyes required more than bimonthly aflibercept injections. Vujosevic et al. in Italy emphasize inflammatory biomarkers in diabetic macular oedema such as hyperreflective retinal spots, subfoveal neuroretinal detachment and increased foveal autofluorescence. These biomarkers improved with dexamethasone treatment. Subhi and Lykke Sørensen in Denmark correlated systemic leucocyte activity with onset and size of neovascular lesions in AMD. They suggest that inflammation plays a role in the pathophysiology. Sauer et al. in Germany used fluorescence lifetime imaging to map pigment distribution and evaluate its role in macular hole formation. Hamoudi et al. in Denmark found no difference in corneal endothelial density between combined and separated phacoemulsification and vitrectomy for epiretinal membrane. Makdoumi et al. in Sweden and the USA used blue light and riboflavin to kill resistant staphylococci and suggest this approach may work in corneal infections. Margulis et al. in the Netherlands, Spain and Denmark examined use of nonsteroidal anti-inflammatory eye drops. These were used with cataract surgery and for allergic conjunctivitis. Pärssinen and Kauppinen in Finland found astigmatism to increase with myopia. Corneal astigmatism predominates. Grieshaber et al. in South Africa and Switzerland recommend the Stegmann Schlemm′s canal expander to lower intraocular pressure in patients with moderate to advanced open angle glaucoma. Quérat and Chen in Sweden recommend ICARE® self-tonometry. Day-to-day variations are seen in most patients. Mrowicka et al. in Poland propose that insufficient antioxidant capacity may play a role in age related macular degeneration. This hypothesis is based on study of enzymes and genes related to antioxidant activity. Pilat et al. in UK used hand-held OCT to image anterior segment dysgenesis in children. The following articles are published electronically only and are accessible on www.actaophtalmologica.com, where you can also access the printed articles. Nitta et al. in Japan report an increase in retinal oximetry readings in retinal venules following glaucoma surgery and lowering of intraocular pressure. Tanito et al. in Japan recommend microhook trabeculotomy in glaucoma patients. It lowers IOP and reduces need for glaucoma medications. Mansouri and Shaarawy in the USA and Switzerland fond similar outcomes with scanning laser trabeculoplasty and selective laser trabeculoplasty. Lanza et al. in Italy used light backscattering with in vivo corneal confocal microscopy to evaluate changes in corneal layers in patients with Sjögren syndrome and dry eyes. Shimada et al. in Japan found reduced anterior chamber bacterial contamination with either 0.025% povidone-iodine or 0.0025% polyvinyl alcohol iodine irrigation of ocular surface. Peiretti et al. in Italy, the Netherlands, Saudi Arabia and the USA examined retinal folds following retinal detachment repair. This was not influenced by use of heavy liquids in surgery or postoperative positioning. Chan et al. in Hong Kong, Singapore and UK seek ways to measure and control emulsification of intraocular silicone oil. Kang et al. in Korea measured greater choroidal thickness in eyes with vitreoretinal traction. This was reversed following epiretinal membrane surgery and release of the traction. Jonas et al. in India and Germany found myopic retinopathy to be rare in rural India. It was associated with open angle glaucoma. Carreño et al. in Spain, USA and UK measured several inflammatory cytokines in tear fluid in uveitis patients. Bray et al. in UK suggest that portable electronic vision enhancement systems are cost-effective to improve near vision. However, it may not provide cost-effective improvement in quality of life. Babeau et al. in France comment on an article on using adaptive optics for screening chloroquine retinopathy. Parrovano et al. in Italy used OCT angiography to monitor reduction in neovascular lesions. Van Asten et al. in the Netherlands found positive outcomes with aflibercept in AMD patients unresponsive to bevacizumab. Lytvynchuk in Ukraine surgically removed a retinal branch artery embolus. Dimopoulos et al. in Germany used autologous thrombocyte serum for macular hole surgery. Grewal et al. in USA used intraoperative OCT to guide placement of Argus II retinal prosthesis. Huynh et al. in the USA found no benefit from dilated fundus examination in patients with spontaneous subconjunctival haemorrhage. Qu-Knafo et al. in France suggest that eyes with DME and serous retinal detachment may show greater improvement with ranibizumab than eyes without serous detachment. I hope you are enjoying a pleasant summer and Acta fits into your summer reading schedule.

Diabetic Macular Edema With and Without Subfoveal Neuroretinal Detachment: Two Different Morphologic and Functional Entities

To assess specific morphologic and functional characteristics in eyes with diabetic macular edema (DME) with subfoveal neuroretinal detachment (SND+) vs DME without SND (SND-). Cross-sectional, prospective, comparative case series. Seventy-two patients (72 eyes: 22 eyes SND+ and 50 eyes SND-) with treatment-naïve, center-involving DME were evaluated. Data gathering included fundus color photographs, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), best-corrected visual acuity (BCVA), and microperimetry. The following parameters were evaluated with SD-OCT: central macular thickness (CMT [including SND]); central retinal thickness (CRT [excluding SND]); choroidal thickness (CT); nasal and temporal retinal thickness (RT) at 500μm and 1500μm from the fovea; the number of hyperreflective retinal spots (HRS) in the central 3000μm; and the presence of SND and integrity of the external limiting membrane (ELM). Retinal sensitivity (RS) was evaluated within 4 degrees and 12 degrees of the fovea. Correlation among CT, RS, and HRS in patients with and without SND was determined. CMT (P= .032), temporal RT at 1500μm (P= .03), mean CT (P= .009), and mean number of HRS (P= .0001) were all higher in SND+ vs SND- eyes. CRT, BCVA, HbA1c, and prevalence of systemic arterial hypertension were not different between the 2 groups. RS within 4 degrees (P= .002) and 12 degrees (P= .015) was lower in SND+ vs SND- eyes. SND correlated significantly with disruption of the ELM (54.55% vs 24%, P= .01) and lower RS. A direct correlation was found between the number of HRS, presence of SND, CT, and RS within 12 degrees in SND- eyes, and an inverse correlation was found between CT and RS within 12degrees in SND+ eyes. These data may improve characterization of DME in eyes with SND. DME with SND correlates with greater CT, more HRS, disruption of the ELM, and significant macular functional impairment (RS decrease) vs SND-.

HYPERREFLECTIVE RETINAL SPOTS IN NORMAL AND DIABETIC EYES: B-Scan and En Face Spectral Domain Optical Coherence Tomography Evaluation.

To evaluate hyperreflective retinal spots (HRS), in normal subjects and diabetic patients without and with macular edema (diabetic macular edema, DME), on linear B-scans and corresponding en face image of spectral-domain optical coherence tomography. Retrospective evaluation of images of 54 eyes/subjects (16 normal subjects, 19 diabetic patients without DME, and 19 with DME). On horizontal B-scan spectral-domain optical coherence tomography, passing through the center of the fovea, the following characteristics of HRS were evaluated: location (inner retina or outer retina), size (≤30 or >30 μm), reflectivity (similar to nerve fiber layer or to retinal pigment epithelium-Bruch complex), and presence or absence of back shadowing. On en face spectral-domain optical coherence tomography, the following patterns were evaluated: 1) isolated HRS (not corresponding to any visible lesion); 2) HRS corresponding to a segment of retinal capillary or microaneurysm wall; and 3) HRS corresponding to hard exudate. All gradings were performed twice by two graders in a masked fashion. Size ≤30 μm, reflectivity similar to nerve fiber layer, and absence of back shadowing were associated with absence of vessels or any other lesion on en face image (P = 0.0001 for all). Size >30 μm, reflectivity similar to retinal pigment epithelium-Bruch complex, presence of back shadowing, and location in the outer retina were all associated with presence of hard exudate on en face imaging (P < 0.0001 for all). Multiple logistic regression analysis showed that HRS present in the inner retina (P < 0.0001), size >30 μm (P = 0.0029), and presence of back shadowing (P < 0.0001) are directly associated with presence of microaneurysms on en face image. Intragrader and intergrader repeatability were excellent for all evaluations. Hyperreflective retinal spots ≤30 μm, reflectivity similar to nerve fiber layer, and absence of back shadowing may represent activated microglial cells; HRS >30 μm, reflectivity similar to retinal pigment epithelium-Bruch complex, presence of back shadowing, and location in the outer retina may represent hard exudate; HRS >30 μm, presence of back shadowing, and location in the inner retina may represent microaneurysms. These hypotheses may be tested in further studies.

Imaging retinal inflammatory biomarkers after intravitreal steroid and anti-VEGF treatment in diabetic macular oedema.

To evaluate changes of specific retinal imaging biomarkers [intraretinal hyper-reflective retinal spots: HRS ; subfoveal neuroretinal detachment: SND; and increased foveal autofluorescence: IFAF after intravitreal steroid or anti-vascular endothelial growth factor treatment in diabetic macular oedema (DME)] as possible indicators of retinal inflammatory condition. Retrospective analysis of images and clinical charts of 49 eyes (49 patients) with DME treated with intravitreal dexamethasone (dexamethasone, 23 eyes) or intravitreal ranibizumab (ranibizumab, 26 eyes). All patients had fundus colour photograph, spectral domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF), best-corrected visual acuity (BCVA) and microperimetry recorded before and 1month after the end of treatment. Central macular thickness (CMT), number of HRS and presence of SND were evaluated by SD OCT. Fundus autofluorescence images were evaluated for area of (IFAF). Retinal sensitivity within 4° and 12° from fovea was quantified by microperimetry. Changes in morphologic and functional parameters were assessed, and correlation was performed by Pearson's correlation. Best-corrected visual acuity and CMT improved in all patients, (p<0.05, for both groups). Mean number of HRS decreased after both treatments (p<0.0001). Subfoveal neuroretinal detachment resolved in 85.7% dexamethasone-treated eyes (p=0.014) and in 50% ranibizumab-treated eyes (p=0.025). Mean IFAF area decreased in both groups, (p<0.0001, for both). A significantly higher decrease in CMT was observed in dexamethasone- versus ranibizumab-treated eyes, (p=0.032). In dexamethasone group, higher number of HRS at baseline and larger IFAF were correlated with higher increase in retinal sensitivity; eyes with SND at baseline had major decrease in CMT versus those without SND, (p=0.003). Higher number of HRS, larger area of IFAF and presence of SND may indicate a prevalent inflammatory condition in DME with specific response to targeted treatment.