Optical Coherence Tomography Biomarkers Research Articles

The impact of laboratory findings and optical coherence tomography biomarkers on response to intravitreal anti-VEGF treatment in patients with retinal vein occlusion.

To investigate potential laboratory and imaging biomarkers as treatment response predictors to intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents in patients with retinal vein occlusion (RVO). Participants in this prospective study were 53 patients with treatment naïve macular edema secondary to RVO, treated with intravitreal anti-VEGF agents and followed-up for 12months. At baseline, all participants underwent best-corrected visual acuity measurement, dilated fundoscopy, optical coherence tomography and fluorescein angiography (FFA), while full blood count and biochemical analysis of various parameters was also performed. At month 12, treatment response was examined and classified as "favorable" or "non-response". Potential associations between laboratory/imaging biomarkers and treatment response were assessed. Univariate analysis showed that "favorable" response at month 12 after initiation of anti-VEGF treatment was correlated with baseline central subfield thickness (CST) < 464μm (p < 0.001), absence of subretinal fluid (p = 0.004), absence of hyperreflective foci (HF) (p = 0.004), intact ellipsoid zone (EZ) and external limiting membrane (ELM) (p < 0.001 and p = 0.001, respectively), absence of epiretinal membrane (ERM) (p = 0.020) and absence of macular ischemia on FFA (p < 0.001), while increased monocytes-to-lymphocytes ratio was also associated with "favorable" treatment response (p = 0.010). All other laboratory parameters did not reach statistical significance. However, at the multivariate analysis, EZ and ELM status, HF, macular ischemia and monocytes-to-lymphocytes ratio were found to be independent predictors of treatment response. Intact EZ and ELM, absence of HF, absence of macular ischemia and increased monocytes-to-lymphocytes ratio at baseline can predict "favorable" treatment response in patients with treatment naïve macular edema secondary to RVO.

Optical coherence tomography biomarkers in patients with macular edema secondary to retinal vein occlusion treated with dexamethasone implant

PurposeTo evaluate the impact of optical coherence tomography (OCT) biomarkers on intravitreal dexamethasone (DEX) implant clinical outcomes in patients with macular edema secondary to retinal vein occlusion (RVO-ME).MethodsRetrospective study conducted on a cohort of patients with RVO-ME, either naïve or previously treated, who underwent treatment with DEX implant and had a follow-up of 6 months. Anatomic success was defined as a central retinal thickness (CRT) < 250 μm or a relative reduction of CRT ≥10% from baseline. The primary endpoint was the mean change in CRT from baseline to month-6. Secondary end-points included changes in BCVA, the impact of baseline OCT biomarkers on functional and anatomic outcomes; and the impact of treatment on the different OCT biomarkers. OCT biomarkers associated with functional and anatomic outcomes were estimated using a logistic regression model.ResultsFifty-seven eyes were included in the study. Baseline CRT was significantly decreased from 567.6 ± 226.2 μm to 326.9 ± 141.0 μm at month-6 (p < 0.0001). Baseline BCVA was significantly lower in the eyes with disrupted external limiting membrane (ELM) (mean 40.3 ± 21.3 letters) than in those with non-disrupted (mean 68.6 ± 10.7 letters) or partially-disrupted ELM (mean 59.6 ± 13.2 letters), p = 0.0001 and p = 0.0011, respectively. Baseline BCVA was significantly lower in eyes with > 20 hyperreflective foci (HRF) than in those with < 10 HRF (p = 0.0388). The eyes with disorganization of the retinal inner layers (DRIL) had lower baseline BCVA than those without DRIL (Hodges-Lehmann median difference: − 12.0 letters, 95% CI: − 25.0 to − 5.0 letters, p = 0.0042). At month-6, 26 (45.6%); 24 (42.1%), and 20 (35.1%) eyes achieved a BCVA improvement ≥5, ≥10, and ≥ 15 letters respectively. Forty (70.2%) eyes were classified as anatomic success at month-6. Logistic regression analysis found none factor significantly associated with success in the multivariate analysis.ConclusionsThe results of this study suggested a positive impact of DEX on CRT and BCVA in eyes with RVO-ME. No OCT-biomarkers were identified as predictors of clinical-outcomes. Additionally, presence of DRIL, presence of HRF (> 20), or disrupted ELM were significantly associated with worse baseline BCVA.

Diagnostic Reliability of Optical Coherence Tomography Biomarkers for Postsurgical Success in Visual Acuity in Patients with Idiopathic Epiretinal Membranes.

Several optical coherence tomography (OCT) biomarkers for postsurgical success in patients with idiopathic epiretinal membranes (iERMs) have been described in single predictor analyses. The aim of this study was to assess the reliability of diagnosis of OCT biomarkers and to calculate their impact on postsurgical visual acuity by applying multiple regression analysis. This retrospective study included patients scheduled for pars plana vitrectomy with membrane peeling for iERMs. Presurgical OCT scans were analyzed for the presence of OCT biomarkers by two reviewers. Intra- and interobserver reliability was calculated with the Kuder-Richardson 20 test. Among the 136 patients included, intra-/interobserver reliability of the OCT biomarkers was 0.89/0.70 for ectopic inner foveal layer (EIFL), 0.82/0.53 for disorganization of retinal inner layer (DRIL), 0.93/0.89 for intraretinal cystoid changes, 0.84/0.78 for alterations of the ellipsoid zone, 0.84/0.72 for cotton ball sign, 0.68/0.58 for hyperreflective foci, 0.55/0.47 for epimacular membrane rips (EMM-rips), and 0.87/0.60 for retinal contraction. Only DRIL and central subfield macular thickness (CMT) were significant predictors for BCVA 3 months after surgery in a multiple regression analysis. Intraobserver reliability of OCT biomarkers was higher than interobserver reliability, reflecting both clinical and grading experience with respect to OCT biomarker evaluation. DRIL and CMT were shown to be significant predictors in a multiple regression analysis, with potential for negative influence on final BCVA after vitrectomy with membrane peeling for iERMs.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY BIOMARKERS OF RETINAL HYPERPERMEABILITY AND CHOROIDAL INFLAMMATION AS PREDICTORS OF SHORT-TERM FUNCTIONAL AND ANATOMICAL OUTCOMES IN EYES WITH DIABETIC MACULAR EDEMA TREATED WITH INTRAVITREAL BEVACIZUMAB

Purpose: To assess spectral domain optical coherence tomography biomarkers of short-term outcomes in eyes with diabetic macular edema treated with intravitreal bevacizumab. Methods: In a prospective interventional case series, 66 eyes with diabetic macular edema underwent 3 monthly intravitreal bevacizumab injections. Best-corrected visual acuity measurement and spectral domain optical coherence tomography were performed at baseline and at 3 months. Multivariate regression analysis was performed to investigate the baseline spectral domain optical coherence tomography parameters as predictors of functional and anatomical outcomes. Results: Patients with diabetic nephropathy had greater subfoveal choroidal thickness (300.8 ± 35.54 vs. 253.0 ± 50.07 µm, P &lt; 0.01) and were more likely to have subretinal fluid (r = 0.26, P = 0.03) at baseline. Multivariate analysis showed that the extent of external limiting membrane disruption (P = 0.03) and the extent of disorganization of retinal inner layers (P = 0.03) at baseline were predictors of best-corrected visual acuity at 3 months, whereas the extent of disorganization of retinal inner layers (P = 0.04) and duration of diabetes mellitus (P = 0.03) were predictors of central subfield thickness at 3 months. Conclusion: External limiting membrane disruption and disorganization of retinal inner layers, as the spectral domain optical coherence tomography biomarkers of retinal hyperpermeability, can predict short-term outcomes in diabetic macular edema eyes treated with intravitreal bevacizumab.

Changes of Optical Coherence Tomography Biomarkers in Macular Edema Secondary to Retinal Vein Occlusion After Anti-VEGF and Anti-Inflammatory Therapies.

PurposeThis study aimed to assess the short-term changes of macular microstructures following anti-VEGF and anti-inflammatory therapies in patients with macular edema secondary to retinal vein occlusion (RVO-ME).Patients and MethodsIn this retrospective study, 70 eyes of 70 patients with RVO-ME were divided into the anti-VEGF (Group A, 35 eyes) and anti-inflammatory (Group B, 35 eyes) treatment groups. All patients underwent best-corrected visual acuity (BCVA) assessment, intraocular pressure (IOP) assessment, slit lamp, fundus fluorescein angiography (FA), scanning laser ophthalmoscopy (SLO), and spectral-domain optical coherence tomography (SD-OCT). Group A received intravitreal injection of 0.05 mL anti-VEGF antibodies (Lucentis® or Aflibercept®) monthly for 3 consecutive months, while Group B received 0.7 mg dexamethasone (Ozurdex®) single intravitreal injection. BCVA and SD-OCT biomarkers were recorded at baseline and 3 months after the first injection. Changes of BCVA and SD-OCT biomarkers following these treatments were compared between the two groups.ResultsBCVA and SD-OCT biomarkers, except choroidal thickness, in both groups were significantly improved after treatment (all P < 0.01). At 3 months, the height of serous retinal detachment (SRD) was markedly lower (P = 0.006), with significantly less hyperreflective dots (HRD, P = 0.037) in Group B compared with Group A. Other SD-OCT biomarkers and BCVA were not significantly different between the two groups (all P > 0.05).ConclusionAnti-VEGF and anti-inflammatory therapies are both effective in RVO-ME, with improvement in BCVA and SD-OCT biomarkers. Anti-inflammatory therapy may be more effective than anti-VEGF therapy in SRD and HRD resolution.

Semi-Automated Quantification of Retinal and Choroidal Biomarkers in Retinal Vascular Diseases: Agreement of Spectral-Domain Optical Coherence Tomography with and without Enhanced Depth Imaging Mode.

Background: We compared with and without enhanced depth imaging mode (EDI) in semi-automated quantification of retinal and choroidal biomarkers in optical coherence tomography (OCT) in patients with diabetic retinopathy (DR) or retinal vein occlusion (RVO) complicated by macular edema. We chose to study three OCT biomarkers: the numbers of hyperreflective foci (HF), the ellipsoid zone reflectivity ratio (EZR) and the choroidal vascularity index (CVI), all known to be correlated with visual acuity changes or treatment outcomes. Methods: In a single examination, one eye of each patient (n = 60; diabetic retinopathy: n = 27, retinal vein occlusion: n = 33) underwent macular 870 nm spectral domain-OCT (SD-OCT) B-scans without and with EDI mode. Semi-automated quantification of HF, EZR and CVI was applied according to preexisting published protocols. Paired Student’s t-test or Wilcoxon rank-sum test was used to test for differences in subgroups. Intraclass correlation coefficient (ICC) and Bland–Altman plots were applied to describe the agreement between quantification in EDI and conventional OCT mode. The effect of macular edema on semi-automated quantification was evaluated. Results: For the entire cohort, quantification of all three biomarkers was not significantly different in SD-OCT scans with and without EDI mode (p > 0.05). ICC was 0.78, 0.90 and 0.80 for HF, EZR and CVI. The presence of macular edema led to significant differences in the quantification of hyperreflective foci (without EDI: 80.00 ± 33.70, with EDI: 92.08 ± 38.11; mean difference: 12.09, p = 0.03), but not in the quantification of EZR and CVI (p > 0.05). Conclusion: Quantification of EZR and CVI was comparable whether or not EDI mode was used. In conclusion, both retinal and choroidal biomarkers can be quantified from one single 870 nm SD-OCT EDI image.

Investigation of Correlations Between Optical Coherence Tomography Biomarkers and Visual Acuity in X-Linked Retinoschisis.

PurposeTo investigate the imaging biomarkers of spectral-domain optical coherence tomography (SD-OCT) and their correlations with age and best-corrected visual acuity (BCVA) in patients with X-linked retinoschisis (XLRS).MethodsOCT images of 72 eyes of 39 patients with confirmed XLRS were obtained to assess imaging biomarkers, including but not limited to the automatic evaluation of foveal thickness, central subfield thickness (CST), macular volume, and the manual measurement of area of macular schisis cavity (AMS). Correlations between age/BCVA and all OCT parameters were computed as well.ResultsIn this study, median age was 10.5 (8–12) years old and median BCVA was 0.90 (0.70–1.00) logarithm of the minimum angle of resolution. Macular retinoschisis was found in all affected eyes, with peripheral retinoschisis (PRS) in 34 (47.2%) eyes. Cystic cavities most frequently affected inner nuclear layer (100%) in the macula. Ellipsoid zone (EZ) defects occurred in 53 (73.6%) eyes. As for correlation, BCVA was significantly correlated with several OCT parameters, including CST, AMS, EZ defect, PRS and vitreomacular adhesion, whereas no correlation was found between age and any OCT parameter.ConclusionExplicable OCT imaging biomarkers such as CST, AMS, and photoreceptor defects were identified and may serve as reference parameters or potential regions of interest for future observational and interventional research design and result interpretation.

Risk Classification for Progression to Subfoveal Geographic Atrophy in Dry Age-Related Macular Degeneration Using Machine Learning-Enabled Outer Retinal Feature Extraction.

To evaluate the utility of spectral-domain optical coherence tomography biomarkers to predict the development of subfoveal geographic atrophy (sfGA). This was a retrospective cohort analysis including 137 individuals with dry age-related macular degeneration without sfGA with 5 years of follow-up. Multiple spectral-domain optical coherence tomography quantitative metrics were generated, including ellipsoid zone (EZ) integrity and subretinal pigment epithelium (sub-RPE) compartment features. Reduced mean EZ-RPE central subfield thickness and increased sub-RPE compartment thickness were significantly different between sfGA convertors and nonconvertors at baseline in both 2-year and 5-year sfGA risk assessment. Longitudinal change assessment showed a significantly higher degradation of EZ integrity in sfGA convertors. The predictive performance of a machine learning classification model based on 5-year and 2-year risk conversion to sfGA demonstrated an area under the receiver operating characteristic curve of 0.92 ± 0.06 and 0.96 ± 0.04, respectively. Quantitative outer retinal and sub-RPE feature assessment using a machine learning-enabled retinal segmentation platform provides multiple parameters that are associated with progression to sfGA. [Ophthalmic Surg Lasers Imaging. 2022;53:31-39.].

FOVEAL MÜLLER CELL CONE AS A PROGNOSTIC OPTICAL COHERENCE TOMOGRAPHY BIOMARKER FOR INITIAL RESPONSE TO ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN CYSTOID DIABETIC MACULAR EDEMA.

To investigate the effect of the foveal Müller cell cone structure on the anatomical and functional response to intravitreal bevacizumab treatment in patients with diabetic macular edema. In 93 treatment-naive eyes with center-involved cystic type diabetic macular edema, spectral-domain optical coherence tomography scans of baseline were retrospectively evaluated to determine the foveal Müller cell cone structure and prognostic features including length of disorganization in the retinal inner layers and ellipsoid zone disruption. The area and circularity of the foveal avascular zone of the superficial and deep capillary plexus 1 month after intravitreal bevacizumab treatment were evaluated using optical coherence tomography angiography. Destruction of the foveal Müller cell cone structure and a large foveal avascular zone in the deep capillary plexus (mm2) correlated strongly with a poor anatomical response (CST > 250 µm) at 1 month after first intravitreal bevacizumab (Exp [B] = 29.444, P = 0.002 and Exp [B] = 12.419, P = 0.013, respectively). A destroyed Müller cell cone structure (P = 0.008) and length of ellipsoid zone disruption (P < 0.001) at baseline were associated with poor visual acuity at 1 month after the first intravitreal bevacizumab. The foveal Müller cell cone structure correlates with the response to initial antivascular endothelial growth factor treatment.

Significance of Hyperreflective Foci as an Optical Coherence Tomography Biomarker in Retinal Diseases: Characterization and Clinical Implications.

Hyperreflective foci (HRF) is a term coined to depict hyperreflective dots or roundish lesions within retinal layers visualized through optical coherence tomography (OCT). Histopathological correlates of HRF are not univocal, spacing from migrating retinal pigment epithelium cells, lipid-laden macrophages, microglial cells, and extravasated proteinaceous or lipid material. Despite this, HRF can be considered OCT biomarkers for disease progression, treatment response, and prognosis in several retinal diseases, including diabetic macular edema, age-related macular degeneration (AMD), retinal vascular occlusions, and inherited retinal dystrophies. The structural features and topographic location of HRF guide the interpretation of their significance in different pathological conditions. The presence of HRF less than 30 μm with reflectivity comparable to the retinal nerve fiber layer in the absence of posterior shadowing in diabetic macular edema indicates an inflammatory phenotype with a better response to steroidal treatment. In AMD, HRF overlying drusen are associated with the development of macular neovascularization, while parafoveal drusen and HRF predispose to macular atrophy. Thus, HRF can be considered a key biomarker in several common retinal diseases. Their recognition and critical interpretation via multimodal imaging are vital to support clinical strategies and management.

Real-life outcomes of intravitreal ranibizumab, aflibercept, and dexamethasone implant administrations in patients with treatment-naïve diabetic macular edema.

PURPOSE:To investigate optical coherence tomography (OCT) biomarker data on visual recovery in treatment-naïve diabetic macular edema (DME) and follow the results of intravitreal ranibizumab (RNB), aflibercept (AFL), and dexamethasone (DEX) implant administration within the 1st year of the pro re nata treatment regimen.METHODS:One hundred and twenty eyes of 102 patients were enrolled in the study. The patients medical records were analyzed retrospectively. Best-corrected visual acuity (BCVA), central macular thickness (CMT), type of DME, presence of subretinal fluid, number and localization of hyperreflective dots, vitreomacular interface disorders, disorganization of the retinal inner layer (DRIL), inner segment/outer segment (IS/OS) junction-external limiting membrane (ELM) status, intraretinal cyst diameter and localization, and subfoveal choroidal thickness were examined in all patients.RESULTS:A statistically significant increase in BCVA and a decrease in CMT were detected in all treatment groups. When cases were evaluated in terms of BCVA before and after treatment, statistically significant differences were observed in the RNB and AFL groups at 1 and 4 months and in the DEX group during the 1st year. In terms of OCT biomarkers, visual recovery was obtained in cases of intact IS/OS-ELM and non-DRIL patients. In the serous macular detachment group, more visual gain was achieved with the RNB (1 and 4 months) and AFL (1, 4, and 6 months) agents compared to the DEX implant. On the other hand, in the group with cystoid macular edema, more visual gain was achieved with RNB compared to the DEX implant in all months, but more visual gain was achieved only in the 1st month with AFL administration.CONCLUSION:Significant improvement was achieved for both BCVA and CMT in all treatment groups. We expect that OCT-based prognostic factors will become more important in the treatment of DME and will be determining factors in the choice of treatment.

Temporal variation of optical coherence tomography biomarkers as predictors of anti-VEGF treatment outcomes in diabetic macular edema.

To report a longitudinal analysis of specific optical coherence tomography (OCT) features in eyes with diabetic macular edema (DME) treated with anti-VEGF. A total of 133 eyes of 103 consecutive patients with center-involving DME were included in the study. The eyes were treated between August 2008 and April 2019 with three monthly intravitreal anti-VEGF injections, either with or without prompt or deferred laser, followed by pro re nata (PRN) re-treatment. The following OCT biomarkers were evaluated: subfoveal neuroretinal detachment (SND) (defined as present (SND+) or absent (SND-)), hyperreflective retinal foci (HRF) number (defined as: absent/few(HRF-) or moderate/many (HRF+)), external limiting membrane (ELM) integrity, central macular thickness (CMT), and central retinal thickness (CRT). Changes in SND status and in the number of HRF were evaluated at each DME recurrence throughout the follow-up(FU) period. Mutual correlation among OCT biomarkers and their relationship with visual and anatomic outcomes were assessed both at baseline and over the FU period. The mean FU was 71.2 months (SD 28.4; min. 12-max. 111). At baseline, the prevalence of SRD+ was 27.8% and a high number of HRF were detected in 41.4% of the eyes. A significant reduction in the number of HRF, CMT, CRT, and in the prevalence of SND was recorded in the post-loading phase (p-value <0.0001). In DME recurrences, the presence of SND+ and HRF+ was significantly more frequent in eyes with baseline SND+ and HRF+ compared to eyes presenting baseline SND- and HRF- (p-value <0.0001). No role of SND (p-value: 0.926) and HRF (p-value: 0.281) as baseline predictors of visual and anatomic outcomes was demonstrated, while a worse visual outcome was significantly correlated with a higher incidence of relapsing SND+ (p-value <0.0001) and HRF+ (p-value <0.0028) throughout the FU period. In this study, SND and HRF were frequently present in DME recurrences with the same pattern exhibited at baseline, suggesting that these OCT biomarkers may characterize a specific pattern of DME that repeats over time. Moreover, the results suggested that the persistence and recurrence of SND and HRF may account for a decrease in visual function more than the baseline prevalence of these biomarkers. Further studies are required to confirm these findings.

Ellipsoid Zone Integrity and Visual Acuity Changes during Diabetic Macular Edema Therapy: A Longitudinal Study.

Purpose Ellipsoid zone (EZ) integrity is identified as a potential biomarker for therapy surveillance and outcome prediction of visual acuity (VA). However, only a few studies report long-term results of over 1 year of clinical and anatomical changes in patients with diabetic macular edema (DME). This study is aimed at describing the long-term VA and anatomical outcomes in spectral domain optical coherence tomography (OCT) (relative ellipsoid zone reflectivity ratio, central macular thickness, and volume) in patients with DME treated with antivascular endothelial growth factor (anti-VEGF) therapy. Furthermore, we studied the correlation between EZ integrity and changes in visual acuity. Methods 71 eyes of 71 patients were included in this retrospective study. Clinical characteristics were reviewed yearly. OCT data were assessed at baseline and after 1, 3, and 5 years. EZ parameters were quantified automatically. OCT parameters and visual outcome were correlated and analyzed in multivariable regression models. Results EZ reflectivity ratio correlated with functional outcome in DME patients from baseline to fifth year at all time points (for all p < 0.05). EZ reflectivity improved the most in the first year of treatment (0.68 to 0.75; p < 0.05) and declined gradually until year 5 of therapy (0.71; compared to baseline p > 0.05). Similarly, best VA was achieved after 1 year (0.40 logarithm of the minimum angle of resolution (logMAR) to 0.28 logMAR; p < 0.001) and declined gradually until year 5. Final VA in year 5 was comparable to baseline (0.45 logMAR, compared to baseline p > 0.05). Together with baseline VA, baseline EZ parameters did predict VA outcome after 1 year (p < 0.05). Concordantly, VA and EZ parameters from year 1 were associated with VA outcome in year 2. Conclusion This study described the long-term course of EZ changes during anti-VEGF treatment in DME patients. In addition, our results underlined the potential of EZ parameters as novel OCT biomarkers for prediction of VA outcomes during therapy.

NATURAL HISTORY AND PREDICTORS OF VISION LOSS IN EYES WITH DIABETIC MACULAR EDEMA AND GOOD INITIAL VISUAL ACUITY.

To identify clinical and anatomic factor-associated vision loss in eyes with treatment-naïve diabetic macular edema and good initial visual acuity. Retrospective cohort study after long-term history of eyes with untreated center-involving diabetic macular edema and baseline visual acuity ≥ 20/25 seen at the University of California, Davis Eye Center between March 2007 and March 2018. We collected characteristics including diabetes type, hemoglobin A1c, presence of visual symptoms, visual acuity, and diabetic retinopathy severity; and spectral-domain optical coherence tomography biomarkers including central subfield thickness, intraretinal cyst size, intraretinal hyperreflective foci, disorganization of retinal inner layers, and outer layer disruptions to determine factors associated with vision loss as defined by DRCR Protocol V as threshold for initiating aflibercept therapy. Fifty-six eyes (48 patients) with untreated diabetic macular edema and mean baseline visual acuity of logMAR 0.05 ± 0.05 (Snellen 20/22) were followed for an average of 5.1 ± 3.3 years, with a median time to vision loss of 465 days (15 months). Older age (hazard ratio [HR] 1.04/year, P = 0.0195) and eyes with severe NPDR (HR 3.0, P = 0.0353) or proliferative diabetic retinopathy (HR 7.7, P = 0.0008) had a higher risk of a vision loss event. None of the spectral-domain optical coherence tomography biomarkers were associated with vision loss except central subfield thickness (HR 0.98, P = 0.0470) and cyst diameter (HR 1.0, P = 0.0094). In eyes with diabetic macular edema and good initial vision, those with older age and worse diabetic retinopathy severity should be monitored closely for prompt treatment initiation when vision loss occurs.

Long-Term Visual Outcomes and Morphologic Biomarkers of Vision Loss in Eyes With Diabetic Macular Edema Treated With Anti-VEGF Therapy

To analyze the morphological characteristics and long-term visual outcomes in eyes with diabetic retinopathy (DR) and diabetic macular edema (DME) treated with anti-vascular endothelial growth factor (anti-VEGF) therapy. Retrospective clinical cohort study. Patients with a long-term follow-up and evidence of resolved DME in at least 1 visit (study visit) after 5 years of follow-up after the initiation of anti-VEGF therapy were included. At the study visit, structural optical coherence tomography (OCT) scans were reviewed for qualitative features reflecting a distress of the neuroretina or retinal pigment epithelium (RPE). A quantitative topographical assessment of the inner and outer retinal thicknesses was also provided. A total of 61 eyes (50 patients) were included and were divided into 2 subgroups according to visual acuity (VA) at the study visit, yielding a group of 24 eyes with a VA <20/40 ("poor/intermediate vision" group), and 37 eyes with a VA ≥20/40 ("good vision" group). The external limiting membrane (ELM) and RPE bands were more frequently disrupted or absent in the poor/intermediate vision group (P=.003 and P=.019). Similarly, disorganization of retinal inner layers was more prevalent in the poor/intermediate vision group (P=.013). The foveal and parafoveal outer retinal thicknesses were reduced in eyes with poor/intermediate vision (P=.022 and P=.044). Multivariate stepwise linear regression analysis demonstrated that VA was associated with appearances of the RPE and ELM (P < .0001 and P=.048), foveal and parafoveal outer retinal thicknesses (P=.046 and P=.035). Modifications in the outer retina and RPE represent OCT biomarkers of long-term visual outcomes in eyes with DME treated with anti-VEGF.

Optical Coherence Tomography Biomarkers Predicting Visual Acuity Change after Intravitreal Bevacizumab Injections for Macular Edema Secondary to Branch Retinal Vein Occlusion

Purpose: This study aimed to identify baseline optical coherence tomography (OCT) factors in branch retinal vein occlusion (BRVO) that predict response to bevacizumab injections. Methods: It is a retrospective case series of consecutive patients that underwent OCT at diagnosis, and the central macular thickness (CMT), extent of disorganized retinal inner layers, and outer retinal layers including external limiting membrane, ellipsoid zone (EZ), and cone outer segment tips (COST) were measured. Patients received 3 consecutive monthly injections of bevacizumab followed by pro re nata treatment. The main outcome measure was improvement in best-corrected visual acuity (BCVA) after 1 year. Results are expressed as mean ± SD, and p value <0.05 was considered statistically significant. Results: Overall, 66 eyes of 66 patients, with an average age of 68.5 ± 11.4 years, were included. The mean BCVA improved significantly from 0.68 logMAR at baseline to 0.50 logMAR at 1 year (p < 0.001). Baseline logMAR BCVA (r = 0.41, p < 0.001) and CMT (r = 0.23, p = 0.04) were associated with improvement while EZ (r = −0.24, p = 0.05) and COST (r = −0.32, p = 0.01) disruption with deterioration in BCVA. Conclusion: In patients with naïve BRVO treated with bevacizumab, BCVA improvement at 1 year can be predicted from baseline BCVA, CMT, extent of COST disruption, and EZ disruption.

Fundus autofluorescence and optical coherence tomography biomarkers associated with the progression of geographic atrophy secondary to age-related macular degeneration.

To investigate the impact of qualitatively graded and deep learning quantified imaging biomarkers on growth of geographic atrophy (GA) secondary to age-related macular degeneration. This prospective study included 1062 visits of 181 eyes of 100 patients with GA. Spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) images were acquired at each visit. Hyperreflective foci (HRF) were quantitatively assessed in SD-OCT volumes using a validated deep learning algorithm. FAF images were graded for FAF patterns, subretinal drusenoid deposits (SDD), GA lesion configuration and atrophy enlargement. Linear mixed models were calculated to investigate associations between all parameters and GA progression. FAF patterns were significantly associated with GA progression (p < 0.001). SDD was associated with faster GA growth (p = 0.005). Eyes with higher HRF concentrations showed a trend towards faster GA progression (p = 0.072) and revealed a significant impact on GA enlargement in interaction with FAF patterns (p = 0.01). The fellow eye status had no significant effect on lesion enlargement (p > 0.05). The diffuse-trickling FAF pattern exhibited significantly higher HRF concentrations than any other pattern (p < 0.001). Among a wide range of investigated biomarkers, SDD and FAF patterns, particularly in interaction with HRF, significantly impact GA progression. Fully automated quantification of retinal imaging biomarkers such as HRF is both reliable and merited as HRF are indicators of retinal pigment epithelium dysmorphia, a central pathogenetic mechanism in GA. Identifying disease markers using the combination of FAF and SD-OCT is of high prognostic value and facilitates individualized patient management in a clinical setting.

OCT Biomarkers in Neovascular Age-Related Macular Degeneration: A Narrative Review

Age-related macular degeneration (AMD) is the leading cause of legal blindness in elderly people. Neovascular AMD (nAMD) is responsible for the majority of cases of severe visual loss in eyes with AMD. Optical coherence tomography (OCT) is the most widely used technology for the diagnosis and follow-up of nAMD patients, which is widely used to study and guide the clinical approach, as well as to predict and evaluate treatment response. The aim of this review is to describe and analyze various structural OCT-based biomarkers, which have practical value during both initial assessment and treatment follow-up of nAMD patients. While central retinal thickness has been the most common and one of the first OCT identified biomarkers, today, other qualitative and quantitative biomarkers provide novel insight into disease activity and offer superior prognostic value and better guidance for tailored therapeutic management. The key importance of retinal fluid compartmentalization (intraretinal fluid, subretinal fluid, and subretinal pigment epithelium (RPE) fluid) will be discussed firstly. In the second part, the structural alterations of different retinal layers in various stages of the disease (photoreceptors layer integrity, hyperreflective dots, outer retinal tubulations, subretinal hyperreflective material, and retinal pigment epithelial tears) will be analyzed in detail. The last part of the review will focus on how alterations of the vitreoretinal interface (vitreomacular adhesion and traction) and of the choroid (sub-RPE hyperreflective columns, prechoroidal clefts, choroidal caverns, choroidal thickness and choroidal volume, and choroidal vascular index) interact with nAMD progression. OCT technology is evolving very quickly, and new retinal biomarkers are continuously described. This up-to-date review article provides a comprehensive description on how structural OCT-based biomarkers provide a valuable tool to monitor the progression of the disease and the treatment response in nAMD patients. Thus, in this perspective, clinicians will be able to allocate hospital resources in the best possible way and tailor treatment to the individual patient's needs.

Challenges in Diabetic Macular Edema Management: An Expert Consensus Report.

PurposeThis paper aimed to present daily-practice recommendations for the management of diabetic macular edema (DME) patients based on available scientific evidence and the clinical experience of the consensus panel.MethodsA group of Spanish retina experts agreed to discuss different aspects related with the clinical management of DME patients.ResultsPanel was mainly focused on therapeutic objectives in DME management; definition terms; and role of biomarkers as prognostic and predictive factors to intravitreal treatment response. The panel recommends to start DME treatment as soon as possible in those eyes with a visual acuity less than 20/25 (always according to the retina unit capacity). Naïve patient was defined, in a strict manner, as a patient who, up to that moment, had never received any treatment. A refractory DME patient may be defined as the one who did not achieve a complete resolution of the disease, regardless of the treatment administered. Different optical coherence tomography biomarkers, such as disorganization of the retinal inner layers, hyperreflective dots, and cysts, have been identified as prognostic factors.ConclusionThis document has sought to lay down a set of recommendations and to identify key issues that may be useful for the daily management of DME patients.

Optical Coherence Tomography Biomarkers in Diabetic Macular Edema

Biomarkers are defined as measurable objective indicators that can be used to assess normal physiological process, pathological process and/or tissue response to pharmacological therapeutic agents. In this review article, we address the most notable structural changes encountered in DME patients and their impact on treatment planning and outcomes.