Number Of Hyperreflective Foci Research Articles

Aflibercept combined with triamcinolone acetonide in the treatment of diabetic macular edema: optical coherence tomography and optical coherence tomography angiography.

To analyze the relationship between optical coherence tomography (OCT) and OCT angiography (OCTA) imaging in patients with diabetic macular edema (DME) who are treated with a combination of aflibercept and triamcinolone acetonide (TA). A total of 76 eyes newly diagnosed DME were included in this study. They were randomly assigned to receive either aflibercept or a combination of aflibercept and TA. Injections once a month for a total of three injections. Central macular thickness (CMT), number of hyperreflective foci (HRF), height of subretinal fluid (SRF), and area of foveal avascular zone (FAZ) were evaluated using OCT and OCTA at baseline and after each monthly treatment. Both groups showed improvement in best corrected visual acuity (BCVA) and reduction in macular edema after treatment, and the difference in BCVA between the two groups was statistically significant after each treatment (P<0.05). The difference in CMT between the two groups was statistically significant after the first two injections (P<0.01), but not after the third injection (P=0.875). The number of HRF (1mo: 7.41±8.25 vs 10.86±7.22, P=0.027; 2mo: 5.33±6.13 vs 9.12±8.61, P=0.034; 3mo: 3.58±3.00 vs 6.37±5.97, P=0.007) and height of SRF (1mo: 82.39±39.12 vs 105.77±42.26 µm, P=0.011; 2mo: 36.84±10.02 vs 83.59±37.78 µm, P<0.01; 3mo: 11.57±3.29 vs 45.43±12.60 µm, P<0.01) in combined group were statistically significant less than aflibercept group after each injection, while the area of FAZ showed no significant change before and after treatment in both groups. The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and SRF. However, both aflibercept and combination therapy show no significant change in the area of FAZ.

Optical Coherence Tomography-Based Grading of Diabetic Macular Edema Is Associated with Systemic Inflammatory Indices and Imaging Biomarkers

Introduction: Objectives of the study were to investigate the correlation between optical coherence tomography (OCT)-based grading of diabetic macular edema (DME) and systemic inflammatory indices, imaging biomarkers, and early anti-vascular endothelial growth factor (VEGF) treatment response. Methods: A total of 111 eyes from 111 patients with DME treated with intravitreous anti-VEGF therapy for 3 consecutive months every month were enrolled in this retrospective study. According to a protocol termed “TCED,” DME was divided into early, advanced, severe, and atrophic stages. The best-corrected visual acuity (BCVA), subretinal fluid (SRF), and the number of hyperreflective foci (HRF) in the whole retinal layers were analyzed at baseline and 3 months after the first injection. Peripheral blood inflammatory indices were calculated, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet (PLT)-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and C-reactive protein (CRP). Statistical analysis was performed to compare the visual and anatomical results and evaluate HRF and SRF in different stages of DME before and after treatment. Results: There were significant differences in systemic inflammatory indices among the four groups, including NLR, PLR, MLR, SII, and CRP (all p < 0.05). The CRP, NLR, PLR, MLR, and SII were significantly higher in the atrophic stage compared to the advanced stage (all p < 0.05). Conversely, the CRP, NLR, PLR, MLR, and SII were significantly lower in the advanced stage compared to the early stage (all p < 0.05). Except for the atrophic stage, BCVA and central retinal thickness (CRT) were significantly improved after treatment in early, advanced and severe stages (all p < 0.05), especially in the severe stage. The decline in the proportion of SRF and HRF ≥20 was the most significant in the advanced stage after anti-VEGF treatment (p < 0.001, p = 0.016), but not in the early and severe stages (all p > 0.05). Conclusion: Systemic inflammatory indices and the decline in the proportion of SRF and HRF ≥20 were closely associated with different stages of DME based on “TCED.” Meanwhile, the “TCED” grading system can predict visual and anatomical prognosis of DME after anti-VEGF treatment, which may be a biomarker for identifying risk stratification and management of DME.

Changes of optical coherence tomographic hyperreflective foci in rhegmatogenous retinal detachment patients after successful surgery

PurposeTo assess the changes of hyperreflective foci (HRF) in rhegmatogenous retinal detachment (RRD) patients after successful reattachment surgery. MethodsTwenty-nine macula-off RRD eyes with successful reattachment surgery were retrospectively analyzed. Optical coherence tomography (OCT) was used to image macular regions and measure HRF in outer retina and inner retina at 0.5, 1, 3, 6, 12 months after surgery. The relationships between HRF and photoreceptor layer status, visual outcomes were evaluated. ResultsAfter retinal reattachment, HRF mainly distributed at the location where external limiting membrane (ELM) or inner and outer segment (IS/OS) line was disrupted. The HRF numbers in outer and inner retina were greater in eyes with discontinuous IS/OS line than eyes with continuous IS/OS line (all p<0.05). In the outer retina, HRF increased in the initial three months after retinal reattachment, and then decreased gradually after 3 months (p<0.05). The HRF number in the outer retina at postoperative 0.5 months was associated with favorable visual outcomes at 6 and 12 months (r=-0.487, p =0.025; r=-0.626, p=0.005, respectively), nevertheless, the HRF number at 3 months was correlated with poor visual results at 6 and 12 months (r=0.441, p =0.017; r=0.477, p=0.019, respectively). ConclusionHRF mainly occurred near the site where ELM or IS/OS line was injured after retinal reattachment. In the outer retina, the number of HRF gradually increased in the first 3 months and then gradually decreased. The early appearance of HRF in the outer retina was associated with a good visual prognosis, while the late appearance may suggest a less favorable visual outcome.

En-face optical coherence tomography hyperreflective foci of choriocapillaris in central serous chorioretinopathy

The purpose of this study is to evaluate choroidal hyperreflective foci (HRF) changes in central serous chorioretinopathy (CSC) on en-face optical coherence tomography (OCT). Retrospective analysis of 42 patients with unilateral CSC (84 eyes, including fellow eyes for controls) and 42 age- and sex-matched controls. With 4.5 × 4.5 mm macular scans, structural en-face OCT choriocapillaris (CC) slabs were used to calculate the density and number of HRF in acute CSC eyes with serous retinal detachment (SRD), resolved CSC eyes without SRD, unaffected fellow eyes, control eyes, and 1-year follow-up eyes. Based on the 2-disc diameter (3000 μm), the en-face OCT scan was divided into foveal and perifoveal lesion and analyzed to consider the impact of SRF in HRF measurement. Regression analyses were performed on the several factors with HRF number and density in the acute and resolved CSC eyes. The perifoveal density and number of CC HRF was significantly lower in the resolved CSC eyes when compared to the acute CSC eyes (P = 0.002, both), fellow eyes (P = 0.042/density, 0.028/number), and controls (P = 0.021/density, P = 0.003/number). There was no significant difference between the acute CSC eyes, fellow eyes, controls, and 1-year follow-up eyes. As subfoveal choroidal thickness decreased and choroidal vascularity (CVI) increased, the perifoveal density and number of HRF was measured higher with a significant correlation in univariate regression analysis of the acute and resolved CSC eyes (all, P < 0.05). The authors hypothesized that stromal edema induced by choroidal congestion and hyperpermeability has the greatest influence on HRF measurement, possibly affected by inflammatory cells and materials extravasation.

Correlation between hyperreflective foci and visual function testing in eyes with intermediate age-related macular degeneration

BackgroundTo investigate the relationship between intraretinal hyperreflective foci (HRF) and visual function in intermediate age-related macular degeneration (iAMD).MethodsRetrospective, cross-sectional study. iAMD patients underwent spectral domain optical coherence tomography (SD-OCT) imaging and vision function testing: normal luminance best corrected visual acuity (VA), low luminance VA (LLVA), quantitative contrast sensitivity function (qCSF), low luminance qCSF (LLqCSF), and mesopic microperimetry. Each OCT volume was graded for the presence and number of HRF. Each HRF was graded for: separation from the retinal pigment epithelium (RPE), above drusen, and shadowing. Central drusen volume was calculated by the built-in functionality of the commercial OCT software after manual segmentation of the RPE and Bruch’s membrane.ResultsHRF group: 11 eyes; 9 patients; mean age 75.7 years. No-HRF group: 11 eyes; 10 patients; mean age 74.8 years. In linear mixed effect model adjusting for cube-root transformed drusen volume, HRF group showed statistically significant worse VA, LLVA, LLqCSF, and microperimetry. HRF group showed worse cone function, as measured by our pre-defined multicomponent endpoint, incorporating LLVA, LLqCSF and microperimetry (p = 0.018). For eyes with HRF, # of HRF did not correlate with any functional measures; however, % of HRF separated from RPE and # of HRF that created shadowing were statistically associated with low luminance deficit (LLD).ConclusionsThe association between the presence of HRF and worse cone visual function supports the hypothesis that eyes with HRF have more advanced disease.

Optical Coherence Tomography Biomarkers in Predicting Treatment Outcomes of Diabetic Macular Edema after Ranibizumab Injections

Background and Objectives: The identification of possible biomarkers that can predict treatment response among DME eyes is important for the individualization of treatment plans. We investigated optical coherence tomography (OCT)-based biomarkers that may predict the one-year real-life outcomes among diabetic macular edema (DME) eyes following treatment by intravitreal ranibizumab (IVR) injections. Materials and Methods: A total of 65 eyes from 35 treatment-naïve patients with DME treated with ranibizumab injection were recruited. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), intraocular pressure (IOP), and OCT scans were retrospectively recorded at baseline before treatment and at 3 months, 6 months, and 12 months after treatment. The OCT scans were evaluated for biomarkers of interest, which included central retinal thickness (CRT), amount and locations of hyperreflective foci (HRF), subretinal fluid (SRF), intraretinal cysts (IRC), large outer nuclear layer cyst (LONLC), ellipsoid zone disruption (EZD), disorganization of retinal inner layers (DRIL), hard exudates (HE), epiretinal membrane (ERM), and vitreomacular interface (VMI). Correlations between these OCT biomarkers and outcome measures (visual and structural) were statistically analyzed. Results: A total of 65 eyes from 35 patients with DME were enrolled. The mean age was 64.2 ± 10.9 years old. Significant improvement in terms of mean BCVA (p < 0.005) and mean CRT was seen at final follow-up compared to baseline. The biomarkers of DRIL, LONLC, and SRF were found to be predictive for at least 50 μm CRT reduction after treatment (with odds ratio of 8.69, 8.5, and 17.58, respectively). The biomarkers of IRC, LONLC, and SRF were predictive for significant improvement in terms of BCVA and CRT after treatment. Finally, the number of HRF was predictive for both BCVA improvement and a CRT reduction of less than 100 μm after treatment. No serious complications were reported during the study. Conclusion: Our study demonstrated the utility of OCT biomarkers as therapeutic predictors of ranibizumab treatment among DME eyes.

Association between Aqueous Humor Cytokines and Structural Characteristics Based on Optical Coherence Tomography in Patients with Diabetic Macular Edema.

To investigate the relationship between aqueous humor cytokines and structural characteristics based on optical coherence tomography (OCT) in patients with diabetic macular edema (DME). Forty eyes of 28 patients with DME diagnosed in the Affiliated Eye Hospital of Wenzhou Medical University at Hangzhou were included. All patients collected aqueous humor during anti-VEGF treatment, and the IL-6, IL-8, IL-10, VEGF, VCAM-1, ICAM-1, TGF-β1, FGF, and MCP-1 concentrations were detected. OCT examination was performed before anti-VEGF treatment and 1 month after anti-VEGF operation. Central macular thickness (CMT), macular volume (MV), choroidal thickness (CT), and the number of hyperreflective foci (HRF) were obtained for analysis. Each eye was determined whether there is subretinal effusion (SRD), cystoid macular edema (CME), and diffuse retinal thickening (DRT). The levels of IL-6 and FGF in DME patients with SRD were significantly higher than those without SRD (all P < 0.05). The level of VEGF in DME patients with CME was significantly higher than that in DME patients without CME (P = 0.005); IL-6, TGF-β1, and MCP-1 were significantly higher in DME patients with DRT than that without DRT (all P < 0.05). There was no significant correlation between aqueous humor cytokines and retinal thickness and retinal volume. However, the thinner the CT, the higher the level of aqueous humor cytokines IL-6 (r = -0.313, P = 0.049) and FGF (r = -0.361, P = 0.022). A multivariate linear regression analysis showed that IL-6 was significantly correlated with CT (P = 0.002) and SRD (P = 0.017), FGF was also significantly correlated with CT (P = 0.002) and SRD (P = 0.005), and TGF-β1 was correlated with triglycerides (P = 0.030) and HRF (P = 0.021). DME patients with significant macular cystoid edema changes may be related to high VEGF concentrations and thin CT; meanwhile, the presence of SRD or a high number of HRF on OCT macular scans in DME patients may indicate high levels of intraocular inflammatory factors. Thus, OCT morphology characteristics to some extent reflect intraocular inflammatory factors and VEGF levels and may guide treatment alternatives.

A Prospective Randomized Study Comparing 27-Gauge Vitrectomy to 23-Gauge Vitrectomy for Epiretinal Membranes and Full-Thickness Macular Holes.

To compare the surgical and clinical outcomes of 27-gauge vitrectomy and 23-gauge vitrectomy. We conducted a single-center, prospective, randomized study. Fifty-three patients affected by vitreoretinal interface disorders (epiretinal membranes and macular holes) were randomly scheduled to undergo 27-gauge (28 patients) or 23-gauge (25 patients) pars plana vitrectomy. The presence of any potential factor of increased baseline inflammation or eye anatomy influencing the surgery was criteria for exclusion. The time of surgery, postoperative intraocular pressure (IOP), state of sclerotomy wounds, rate of complications, postoperative pain, and indicators of inflammation were studied. We also introduced a new parameter to compare intraocular inflammation after surgery, given by the change in the number of intraretinal hyperreflective foci (HRF). The 27-gauge vitrectomy was 1.28 min longer than 23-gauge vitrectomy (P < 0.05). The day after surgery, the mean IOP value was significantly higher in the 27-gauge group (16.12 mmHg versus 13.04 mmHg in the 23-gauge group,P < 0.05), but this difference disappeared in successive follow-ups and the sclerotomy wounds closed after 2 weeks in the both groups. The rate of postoperative hypotony did not significantly differ in the two groups (10.71% in the 27-gauge group and 8% in the 23-gauge group the day after the surgery,P = 0.94). Less postoperative eye redness was seen in 27-gauge eyes (value 1 on the scale) compared to 23-gauge (value 2 on the scale) (P < 0.05), but there was no significant difference in intraocular inflammation (cells, Tyndall, and number of HRF,P > 0.05 for all). The 27-gauge vitrectomy may have better outcomes in terms of IOP maintenance and cause less redness after the surgery but with a slightly prolonged surgery time and no other differences under other parameters (inflammation, rate of complications, postoperative pain, visual gain, and closure of the sclerotomy wounds).

Photoreceptor outer segment layer thinning as a biomarker in acute central serous chorioretinopathy.

The photoreceptor outer segment (PROS) layer demonstrates focal thinning above the fluorescein leakage in acute central serous chorioretinopathy (CSC); however, the nature of this phenomenon is not known. To study the relationship between the PROS layer and thickness of the outer retinal layers above the fluorescein leakage in newly diagnosed acute CSC. Single-center retrospective study. All participants received multimodal imaging, including fluorescein angiography and optical coherence tomography. Thickness of PROS, outer nuclear layer (ONL), and ONL-outer plexiform layer (OPL) complex was measured above the leakage and outside the leakage within the area of neurosensory detachment. The number of intraretinal hyperreflective foci of the outer retina was counted. The correlation between PROS thickness and ONL, OPL-ONL complex thickness, and the number of intraretinal hyperreflective foci was calculated. Fifty eyes of 48 patients (38 males and 10 females, 43.8 ± 10.6 years) with a mean symptom duration of 1.4 ± 1.3 months were included. PROS thickness above the fluorescein leakage showed a statistically significant correlation with ONL thickness, OPL-ONL complex thickness, and the number of hyperreflective foci in the outer retina, 0.57, 0.60, and -0.46, respectively (p < 0.001). Measuring the extent of PROS thinning above the leakage in newly diagnosed CSC allowed to predict self-resolution of subretinal fluid. The greatest linear dimension of PROS thinning showed an area under the receiver operating curve (ROC) curve of 0.98. The cases without PROS thinning had the fastest resolution of subretinal fluid. PROS thinning above the fluorescein leakage in acute CSC is associated with thinning of the outer retinal layers and reveals mild outer retinal atrophy. The absence of PROS thinning predicts faster resolution of CSC.

Optical coherence tomography biomarkers as predictors of transition to chronic central serous chorioretinopathy after retinal laser photocoagulation.

To explore the optical coherence tomography (OCT) biomarkers to predict the transition to chronic central serous chorioretinopathy (cCSC) after retinal laser photocoagulation. Patients enrolled in this study were from a 12-week clinical trial comparing the efficacy and safety of subthreshold micropulse laser (SML) with threshold conventional laser (TCL) for CSC and had extended follow-up for more than 1 year. They were divided into two groups, transited to cCSC group (cCSC group) and did not transited to cCSC group (non-cCSC group) according to fundus examination at the extended follow-up. Collect the best-corrected visual acuity (BCVA) and OCT characteristics of patients at baseline and 12 weeks after laser treatment. Twenty-seven patients were enrolled (42.6 ± 7.7 years old), and duration of follow-up was 178.9 ± 88.8 (57.0-312.0) weeks. Nine patients (33.3%) were assigned to cCSC group, and the other 18 patients (66.7%) were assigned to the non-cCSC group. Twelve weeks after the laser treatment, subretinal fluid (SRF) of 15 patients (83.3%) in non-cCSC group and 5 patients (55.6%) in cCSC group absorbed completely; the height of SRF had statistical difference between two groups (p = 0.035); rough RPE was less common in cCSC group (p = 0.030); hyper reflective mass (HRM) was more common in cCSC group (p = 0.024); more number of hyper reflective foci (HRF) in outer segment of photoreceptor layer were detected in cCSC group (p = 0.035). From baseline to 12 weeks after laser treatment, the number of HRF in outer segment photoreceptor layer did not change significantly in cCSC group (p = 0.665) but decreased significantly in non-cCSC group (p = 0.000). A total of five patients suffered binocular CSC, three of them in the non-cCSC group occurred later than the other two in the cCSC group (129.9-278.3 weeks vs 96.1-114.9 weeks after baseline). SRF, rough RPE, HRM, and number of HRF in outer segment photoreceptor layer 12 weeks after laser treatment, and change in the number of HRF in outer segment photoreceptor layer from baseline to 12 weeks after laser treatment may predict the transition to cCSC.

The Efficacy of Anti-VEGF Therapy for Putative or Visible CNV in Central Serous Chorioretinopathy by Optical Coherence Tomography Angiography.

Purpose To investigate the effect and underlying mechanism of intravitreal antivascular endothelial growth factor (VEGF) in patients with putative or visible choroidal neovascularization (CNV) secondary to central serous chorioretinopathy (CSCR) with optical coherence tomography angiography (OCTA). Methods In a retrospective cohort study, 16 eyes of 15 treatment-naïve CSCR patients were included and divided into two groups: a putative CNV group with nonhomogenous hyperreflectivity in the slab of choriocapillaris and a visible CNV group with obvious tangled vascular network in the slab of choriocapillaris in OCTA. Patients were recorded with best-corrected visual acuity (BCVA). The parameters, evaluated by OCTA, included central macular thickness (CMT), the height of subretinal fluid (SRF), the number of hyperreflective foci (HRF), and the area of putative or visible CNV. Results Compared with the baseline, visual acuity was improved significantly at the last follow-up, and CMT and the height of SRF were decreased significantly (P < 0.0001). The number of HRF was also declined in the outer retina and the choriocapillaris layer (P=0.0343). Although the visible CNV area in the eyes represented virtually unchanged during anti-VEGF treatment (P=0.4015), the area of putative CNV displayed an obvious reduction (P=0.0081). Conclusion Anti-VEGF is effective in treating CSCR coexisting putative or visible CNV. Early initiation of anti-VEGF therapy benefits CSCR patients with putative CNV detected by OCTA. Translational relevance nonhomogenous hyperreflectivity in the choriocapillaris layer in OCTA indicates putative CNV in patients with CSCR, implying early treatment with anti-VEGF.

OCT-Based Biomarkers are Associated with Systemic Inflammation in Patients with Treatment-Naïve Diabetic Macular Edema.

Diabetic macular edema (DME) is one of the major sight-threatening complications of diabetic retinopathy, which is associated with retinal inflammation. However, it is still unknown whether DME is associated with systemic inflammation. The study aimed to investigate the association between systemic inflammatory and optical coherence tomography (OCT) biomarkers in patients with treatment-naïve center-involving diabetic macular edema (DME) and to further explore the role of systemic inflammation in DME. Medical records including clinical characteristics and ophthalmic examinations were collected from patients with treatment-naïve center-involving DME. Systemic inflammation markers including systemic immune-inflammatory index (SII), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were calculated. OCT biomarkers, including intraretinal cyst (IRC) size, disorganization of retinal inner layers (DRIL), external limiting membrane (ELM)/ellipsoid zone (EZ) integrity, retinal hyperreflective foci (HRF), subretinal fluid (SRF) and vitreomacular (VM) status were evaluated manually. Correlation analysis and multivariable linear regression models were used to investigate the relationship between systemic inflammatory markers and OCT biomarkers. A total of 82 patients with treatment-naïve center-involving DME were included. The number of HRF on OCT was correlated with SII, NLR, and PLR and positively associated with SII (p < 0.001) in both univariate and multivariate linear regression analyses. The differences remained largely the same during subgroup analysis controlling DM duration, SRF, and ELM/EZ integrity. No significant association was observed between other OCT biomarkers and blood inflammatory markers. Retinal HRF in diabetic macular edema is associated with blood inflammatory markers, which supports the theory of HRF's inflammatory nature and emphasizes the important role of inflammation in DME. SII may be a potential marker for DME treatment decisions.

Anti-VEGF reduces inflammatory features in macular edema secondary to retinal vein occlusion.

To investigate the anti-inflammatory effect of intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) in patients with macular edema secondary to retinal vein occlusion (RVO-ME). Twenty-eight eyes from twenty-eight treatment-naïve patients (14 males and 14 females) with RVO-ME were included in this retrospective study. The retinal vein occlusion (RVO) was comprised of both central retinal vein occlusion (CRVO, n=14) and branch retinal vein occlusion (BRVO, n=14). Intravitreal injection of anti-VEGF reagents were administered monthly for three consecutive months, in which 18 patients were injected with ranibizumab and 10 patients were injected with conbercept. All eyes were imaged with optical coherence tomography angiography (OCTA) at baseline and 1wk after monthly intravitreal anti-VEGF injection. The visual acuity (VA), central macular thickness (CMT), the number of hyperreflective foci (HRF) recognized as an inflammatory sign in OCT images, and non-perfusion area (NPA), were compared before and after anti-VEGF treatments. The mean interval between baseline and follow-up was 29.4±0.79 (range, 27-48)d. Compared with the baseline, the VA improved (logMAR 1.5±0.1 vs 0.8±0.1, P<0.05) and CMT decreased (460±34.0 µm vs 268.8±12.0 µm, P<0.05), significantly, after anti-VEGF treatment. The number of HRF was decreased significantly (76.5±4.8 vs 47.8±4.3, P<0.05) after anti-VEGF treatment. Anti-VEGF therapy is effective in treating RVO-ME. The mechanisms for the decreased HRF and the reduction of NPA by anti-VEGF therapy merits further exploration.

Hyperreflective Foci in Diabetic Macular Edema with Subretinal Fluid: Association with Visual Outcomes after Anti-VEGF Treatment

Introduction: Objectives of the study were to describe the hyperreflective foci (HRF) on optical coherence tomography angiography in diabetic macular edema (DME) with subretinal fluid (SRF) and explore the association of HRF in the outer retina with photoreceptor integrity and visual outcomes after anti-vascular endothelial growth factor (anti-VEGF) treatment. Methods: We retrospectively reviewed 46 eyes (36 patients) with DME treated with anti-VEGF drugs. The following parameters, including best-corrected visual acuity (BCVA), central macular thickness (CMT), the height of SRF, the number of HRF in the superficial capillary plexus, deep capillary plexus, and the outer retina, as well as the integrity of external limiting membrane (ELM) and ellipsoid zone (EZ), were evaluated and compared between the baseline and after 2 monthly injections of anti-VEGF drugs. The relationship between the HRF in the outer retina and the integrity of ELM and EZ, as well as BCVA, was analyzed. Results: BCVA was significantly improved in DME after anti-VEGF treatment; however, for the subgroup of DME patients with SRF, visual acuity remained unchanged after anti-VEGF treatment (p < 0.05 vs. p = 0.375). The number of HRF (p < 0.05), CMT (p < 0.001), and SRF height (p < 0.001) were significantly reduced, accompanied with partial restoration of ELM and EZ integrity after anti-VEGF injection. The HRF in the outer retina was correlated with the final ELM (p = 0.036) and EZ (p = 0.004) status. The final BCVA was significantly better in eyes with intact ELM (p = 0.002) and EZ at final visit (p < 0.001). Conclusion: The number of HRF in outer retina was negatively associated with the microstructural restoration of ELM and EZ, as well as the visual outcome in DME patients with SRF after anti-VEGF treatment.

Morphological parameters predicting subthreshold micropulse laser effectiveness in central serous chorioretinopathy.

The purpose of this prospective study was to predict the effectiveness of subthreshold micropulse laser (SML) based on morphological parameters in patients with central serous chorioretinopathy (CSC). Thirty-one patients were examined at presentation, 3months, and 6months after the disease onset. In patients with persistent subretinal fluid (SRF) at 3months, SML was performed. The following morphological parameters were observed just before treatment: central retinal thickness (CRT), maximal SRF, choroidal thickness (CT), pigment epithelial detachment (PED) height and width, number of hyperreflective foci (HF) at fovea and leakage site, secondary choroidal neovascularization (CNV), and severity of retinal pigment epithelium (RPE) alterations using multimodal imaging. Good response was associated with lower SRF (p = 0.038), narrower PED (p = 0.078), and decreasing number of HF at fovea (difHFf) (p = 0.016) just before the treatment. From a bivariate and multivariate point of view, the two groups differed significantly in the pair (SRF, PED width) (p = 0.048) and in the triple (SRF, PED width, difHFf) (p = 0.026). Lower SRF, narrower PED, and decreasing HF could be associated with good response to SML in CSC patients.

Hyperreflective Foci and Subretinal Fluid Are Potential Imaging Biomarkers to Evaluate Anti-VEGF Effect in Diabetic Macular Edema.

Purpose: The aim was to investigate the effect and underlying mechanism of anti-vascular endothelial growth factor (anti-VEGF) in diabetic macular edema (DME) by optical coherence tomography angiography (OCTA).Methods: Twenty-five eyes in 18 treatment-naïve patients with DME were included. All eyes were imaged by OCTA at baseline and 1 week after monthly intravitreal aflibercept injection (IAI). Visual acuity was measured as best corrected visual acuity (BCVA). Additional parameters were evaluated by OCTA, including central macular thickness (CMT), the number of hyperreflective foci (HRF), foveal avascular zone (FAZ), vessel density (VD) in the deep capillary plexus (DCP), the en-face area of cystoid edema in DCP segmentation, and subretinal fluid (SRF) height.Results: The mean time between baseline and final follow-up by OCTA was 79.24 ± 38.15 (range, 28–163) days. Compared with baseline, BCVA was increased significantly after the 3rd IAI, while CMT was decreased significantly from the 1st IAI. SRF height and the area of cystoid edema in DCP segmentation were decreased significantly after the 2nd IAI compared with baseline. The number of HRF was decreased significantly after the 1st IAI (8.87 ± 9.38) compared with baseline (11.22 ± 10.63). However, FAZ’s area and perimeter as well as VD in DCP showed no significant changes post-treatment.Conclusion: Anti-VEGF is effective in treating DME, improving visual acuity and decreasing macular edema. The decreased HRF indicates anti-inflammatory effects of aflibercept to deactivate retinal microglia/macrophages. The decreased cystoid edema and SRF height indicated improved drainage function of Müller glial cells and retinal pigment epithelium after IAI.

[Treatment response to Conbercept of different types of diabetic macular edema classified based on optical coherence tomography].

To compare different types of diabetic macular edema (DME) classified based on optical coherence tomography (OCT) for their responses to Conbercept injection and analyze the factors that affect the treatment responses. We retrospectively analyzed the clinical data of 65 patients (76 eyes) with DME diagnosed and treated with intravitreal injection of Conbercept (1+PRN) in our hospital from February, 2019 to February, 2021. According to OCT findings, DME in these patients was classified into cystic macular edema (CME; 28 eyes), serous retinal detachment (SRD; 33 eyes), and diffuse retinal thickening (DRT; 15 eyes). The best corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured before and at 3 months after the first treatment. The baseline OCT characteristics of different types of DME were compared, and the correlation of these OCT characteristics with the treatment response to Conbercept was analyzed. All the patients showed significant improvement of the BCVA 3 months after the treatment (P < 0.05). For all the 3 types of DME, the CRT at 3 months after the first treatment was significantly reduced as compared to the baseline (P < 0.05). The number of hyperreflective foci (HF) in the outer retina and the proportion of ellipsoid zone (EZ) interruption were the greatest in SRD group (P < 0.05). The baseline outer retinal HF was significantly correlated with the baseline CRT, CRT changes and CRT after treatment (all P < 0.05). The patients with baseline outer limiting membrane (ELM)/ EZ disruption had poorer baseline BCVA, greater baseline CRT, greater variation of CRT and poorer BCVA at 3 months after treatment (all P < 0.05). For all the 3 types of DME, treatment with intravitreal injection of Conbercept can significantly improve the BCVA and CRT of the patients. DME of the SRD type has the best morphological response to Conbercept, while the DRT type has a relatively poor response. A greater number of HF at baseline may indicate a better morphological response to Conbercept treatment, and baseline ELM/EZ disruption may suggest a poor visual prognosis at 3 months after treatment.

Optical Coherence Tomography Angiography Characteristics Serve as Retinal Vein Occlusion Therapeutic Biomarkers for Dexamethasone Intravitreal Implant.

Background Retinal vein occlusion (RVO) is the second most common vision-threatening retinal vascular disease. Intravitreal dexamethasone implant has been applied to treat macular edema secondary to RVO (RVO-ME). However, the alteration of morphologic features detected with optical coherence tomography angiography (OCTA) has not been fully studied in RVO-ME patients before and after the treatment. Objective This study is aimed at identifying potential therapeutic targets in RVO with integrative bioinformatic analysis and compares the OCTA characteristics alterations in patients with RVO-ME receiving injection of dexamethasone intravitreal implant. Methods Bioinformatic analysis was analyzed in GSE101398 dataset from the Gene Expression Omnibus database. Multiple functional enrichment analyses were performed, and protein-protein interaction network was constructed to visualize the key node genes. Eleven eyes with RVO-ME were examined with OCTA before and after intravitreal dexamethasone implant. The OCTA parameters, including macular thickness, vessel density, foveal avascular zone parameters, the number of hyperreflective foci (HRF), area of cystoid edema, and subretinal fluid (SRF), were compared. The correlation was analyzed between best-corrected visual acuity (BCVA) and OCTA parameters. Results A total of 79 differentially expressed genes were identified. Functional enrichment analyses revealed the enriched inflammatory events in RVO. In RVO-ME, Pearson correlation revealed that baseline BCVA was positively correlated with the area of SRF and central macular thickness, while no correlation was detected between baseline BCVA and HRF number or the area of cystoid edema. The visual acuity improved, and the central macular thickness was decreased after intravitreal dexamethasone implant injection. Besides, the number of HRF, the area of cystoid edema, and SRF were significantly alleviated after dexamethasone intravitreal injection. Conclusion Retinal inflammation plays a crucial role in RVO pathogenesis. The imaging biomarkers of RVO including Müller glial intracellular edema, and retinal pigment epithelium dysfunction, could be assessed in OCTA and attenuated by intravitreal dexamethasone implant effectively.

Prediction of anti‐VEGF efficacy in diabetic macular oedema using intraocular cytokines and macular optical coherence tomography

In eyes with diabetic macular oedema (DME), aqueous humour (AH) cytokine levels before and after anti-vascular endothelial growth factor (VEGF) treatment were compared and correlated with optical coherence tomography structural parameters. This prospective study included 56 control patients with cataracts and 83 patients with DME manifesting as diffuse retinal thickening (DRT), cystoid macular oedema and serous retinal detachment (SRD). AH samples were obtained before intravitreal injection of anti-VEGF or cataract surgery. VEGF, interleukin (IL)-6, IL-8, IL-10, interferon-inducible protein 10 (IP-10) and monocyte chemotactic protein 1 (MCP-1) levels were measured by multiplex bead assay. AH cytokine levels, central macular thickness (CMT), number of hyper-reflective foci (HF), continuity of external limiting membrane and ellipsoid zone (EZ) and best-corrected visual acuity were evaluated. In SRD, IL-6 and MCP-1 levels and HF were increased (all p < 0.05) compared to DRT. At baseline, the number of HF was correlated with VEGF, IL-6, IL-8, IP-10 and MCP-1 (all p < 0.05). Eyes sensitive to anti-VEGF treatment had high baseline levels of VEGF, MCP-1, HF and many EZ disruptions (all p < 0.05). DME patients with normal VEGF levels but with high levels of IL-8, IP-10 and MCP-1 (all p < 0.05) had little change in CMT after anti-VEGF treatment (p = 0.678). AH concentrations of some inflammatory cytokines in DME were differentially expressed among the three DME morphologies. HF was associated with VEGF and other inflammatory cytokine levels. Multiple HF at baseline predicted a significant decrease in CMT, and eyes with normal VEGF but increased inflammatory cytokines may be insensitive to anti-VEGF treatment.

Hyperreflective foci in predicting the treatment outcomes of diabetic macular oedema after anti-vascular endothelial growth factor therapy

This retrospective study evaluated the association of hyperreflective foci (HRF) with treatment response in diabetic macular oedema (DME) after anti-vascular endothelial growth factor (VEGF) therapy. The medical records, including of ophthalmologic examinations and optical coherence tomography (OCT) images, of 106 patients with DME treated with either intravitreal ranibizumab or aflibercept were reviewed. The correlations between best-corrected visual acuity (BCVA) changes and HRF along with other OCT biomarkers were analysed. The mean logMAR BCVA improved from 0.696 to 0.461 after an average of 6.2 injections in 1 year under real-world conditions. Greater visual-acuity gain was noted in patients with a greater number of HRF in the outer retina at baseline (p = 0.037), along with other factors such as poor baseline vision (p < 0.001), absence of epiretinal membrane (p = 0.048), and presence of subretinal fluid at baseline (p = 0.001). The number of HRF after treatment was correlated with the presence of hard exudate (p < 0.001) and baseline haemoglobin A1C (p = 0.001). Patients with proliferative diabetic retinopathy had greater HRF reduction after treatment (p = 0.018). The number of HRF in the outer retina, in addition to other baseline OCT biomarkers, could be used to predict the treatment response in DME after anti-VEGF treatment.