Disorganization Of Retinal Inner Layers Research Articles

Intensive Glycemic Management Is Associated With Reduced Retinal Structure Abnormalities on Ocular Coherence Tomography in the DCCT/EDIC Study.

To investigate quantitative and qualitative changes in retinal structure using optical coherence tomography (OCT) and their associations with systemic or other risk factors in individuals with type 1 diabetes (T1D). In the Epidemiology of Diabetes Interventions and Complications (EDIC) study, OCT images were obtained during study years 25-28 (2019-2022) in 937 participants; 54% and 46% were from the original intensive (INT) and conventional (CONV) glycemic management treatment groups, respectively. Average age for participants was 61 years old, diabetes duration 39 years, and HbA1c 7.6%. Participants originally in the CONV group were more likely to have disorganization of retinal inner layers (DRIL) (CONV 27.3% vs. INT 18.7%; P = 0.0003), intraretinal fluid (CONV 24.4% vs. INT 19.2%; P = 0.0222), and intraretinal cysts (CONV 20.8% vs. INT 16.6%; P = 0.0471). In multivariable models, sex, age, smoking, mean updated systolic blood pressure, and history of "clinically significant" macular edema (CSME) and of anti-VEGF treatment were independently associated with changes in central subfield thickness, while HbA1c, BMI, and history of CSME and of ocular surgery were associated with DRIL. Visual acuity (VA) decline was associated with significant thinning of all retinal subfields except for the central and inner nasal subfields. Early intensive glycemic management in T1D is associated with a decreased risk of DRIL. This important morphological abnormality was associated with a history of macular edema, a history of ocular surgery, and worse VA. This study reveals benefits of intensive glycemic management on the retina beyond features detected by fundus photographs and ophthalmoscopy.

Enhancing Diabetic Macular Edema Treatment Outcomes: Exploring the ESASO Classification and Structural OCT Biomarkers.

This study assessed the European School of Advanced Studies in Ophthalmology (ESASO) classification's prognostic value for diabetic macular edema (DME) in predicting intravitreal therapy outcomes. In this retrospective, multicenter study, patients aged > 50years with type 1 or 2 diabetes and DME received intravitreal antivascular endothelial growth factor (anti-VEGF) agents (ranibizumab, bevacizumab, and aflibercept) or steroids (dexamethasone). The primary outcome was visual acuity (VA) change post-treatment, termed as functional response, measured 4-6weeks post-third anti-VEGF or 12-16weeks post-steroid injection, stratified by initial DME stage. Of the 560 eyes studied (62% male, mean age 66.7years), 31% were classified as stage 1 (early), 50% stage 2 (advanced), 17% stage 3 (severe), and 2% stage 4 (atrophic). Visual acuity (VA; decimal) improved by 0.12-0.15 decimals in stages 1-2 but only 0.03 decimal in stage 3 (all p < 0.0001) and 0.01 in stage 4 (p = 0.38). Even in eyes with low baseline VA ≤ 0.3, improvements were significant only in stages 1 and 2 (0.12 and 0.17 decimals, respectively). Central subfield thickness (CST) improvement was greatest in stage 3 (-229µm, 37.6%, p < 0.0001), but uncorrelated with VA gains, unlike stages 1 and 2 (respectively: -142µm, 27.4%; - 5µm, 12%; both p < 0.0001). Stage 4 showed no significant CST change. Baseline disorganization of retinal inner layers and focal damage of the ellipsoid zone/external limiting membrane did not influence VA improvement in stages 1 and 2. Treatment patterns varied, with 61% receiving anti-VEGF and 39% dexamethasone, influenced by DME stage, with no significant differences between therapeutic agents. The ESASO classification, which views the retina as a neurovascular unit and integrates multiple biomarkers, surpasses single biomarkers in predicting visual outcomes. Significant functional improvement occurred only in stages 1 and 2, suggesting reversible damage, whereas stages 3 and 4 likely reflect irreversible damage.

Correlation between retinal sensitivity assessed by microperimetry and structural abnormalities on optical coherence tomography after successful epiretinal membrane surgery

BackgroundTo verify the correlation between retinal sensitivity (RS) assessed by the microperimetry (MP) and optical coherence tomography (OCT) parameters measured in eyes submitted to pars-plana vitrectomy (PPV) for idiopathic epiretinal membrane (ERM) treatment.Methods43 patients underwent PPV. Best-corrected visual acuity (BCVA) and OCT imaging were acquired preoperatively and 6 months after surgery. The RS values were recorded 6 months after the surgery. Total macular thickness (TMT) measurements and OCT-evaluated structural findings were also analyzed. The MP examination tested 44 points, with direct topographic correspondence with the OCT-ETDRS map. Correlations between BCVA, RS, and OCT parameters were assessed.ResultsTMT measurements in patients were significantly thicker preoperatively and reduced after surgery. All patients demonstrated BCVA improvements after surgery. The RS parameters after surgery were significantly lower in patients. For OCT structural analyses, patients with lower RS at the fovea correlated with the preexisting disorganization of retinal inner layers (DRIL). In addition, lower RS values were associated with DRIL, outer retinal changes (ORC), and intraretinal microcysts after surgery.ConclusionsThe RS values after surgery were significantly lower when compared to controls. The DRIL presence before and after surgery, and microcysts and ORC after surgery were related to worse visual outcomes.

Clinical and optical coherence tomography biomarkers as prognostic factors in dexamethasone intravitreal implant for diabetic macular edema.

Aim of the study was to evaluate the efficacy of dexamethasone (DEX) 0.7 mg intravitreal implant in patients with diabetic macular edema (DME) and serous retinal detachment (SRD), and to study the prognostic factors on a follow up of 12 months. Forty eyes of twenty- six patients with centre involving DME and SRD, who underwent DEX implant, were enrolled. Best-corrected visual acuity (BCVA), Swept source OCT imaging and intraocular pressure were evaluated. Central macular thickness (CMT), vitreomacular adhesion (VMA), disorganization of retinal inner layers (DRILs), hyperreflective dots (HRD), SRD and ellipsoid zone (EZ) disruption were included in the analysis at baseline and 12 months after implant. According to our parametric analysis, at 12 months, BVCA improvement from 48.6 ± 23.4 letters to 53.3 ± 24.5 letters was statistically significant (p = 0.04), CMT decreased from 460 ± 99.52 μm to 322.9 ± 117 μm. The presence at baseline of VMA (p = 0.01), EZ disruption (p = 0.03) and DRILs (p = 0.04), were associated with poor BCVA improvement at the end of follow-up. In conclusion, OCT biomarkers can be considered significant prognostic factors for treatment outcome in patients with DME undergoing DEX intravitreal implant.

OCT Biomarkers Predicting Recurrence of Macular Edema Secondary to Branch Retinal Vein Occlusion

Purpose: We evaluated factors predicting the recurrence of macular edema in patients with branch retinal vein occlusion using optical coherence tomography (OCT).Methods: This study enrolled 55 patients diagnosed with branch retinal vein occlusion who presented to the outpatient clinic between March 2022 and March 2023. A retrospective analysis categorized patients into non-recurrence and recurrence groups. Data on visual acuity, spherical equivalent, intraocular pressure, number of injections, and follow-up duration were collected from medical records. OCT images were obtained before and 6 months after intravitreal injection to measure and analyze central retinal thickness, subfoveal choroidal thickness, and disorganization of retinal inner layers.Results: No statistically significant difference was observed in the central retinal thickness change before and after treatment between the groups. Although no significant differences were observed in visual acuity between the two groups before treatment, significant improvement in visual acuity was observed in the non-recurrence group after 6 months of treatment. The non-recurrence group was younger compared to the recurrence group; moreover, the intraocular pressure in non-recurrence patients decreased significantly during the 6-month treatment period. In addition, a decrease in subfoveal choroidal thickness before and after treatment, the difference in subfoveal choroidal thickness between the affected eye and the fellow eye before treatment, and the reduction in disorganization of retinal inner layers before and after treatment were associated with a favorable prognosis without recurrence.Conclusions: Changes in subfoveal choroidal thickness before and after treatment, variations in subfoveal choroidal thickness between the affected and fellow eyes before treatment, and the degree of disorganization of retinal inner layers exhibited significant associations with the recurrence of macular edema. This is significant because it allows for predictions based on baseline OCT images.

The role of optical coherence tomography biomarkers in predicting the outcome of epiretinal membrane removal surgery

Epiretinal membrane (ERM) is a common condition that can cause visual impairment. ERM removal surgery is an effective treatment option, but predicting postoperative visual outcomes is challenging. Imaging modalities, particularly optical coherence tomography (OCT), have emerged as valuable tools for preoperative evaluation and predicting surgical outcomes. This presentation focuses on the role of preoperative OCT biomarkers in estimating postoperative vision improvement after ERM removal surgery. Such biomarkers include the disorganization of retinal inner layers (DRIL), the presence of ectopic inner foveal layer (EIFL), the cotton ball sign, the cone outer segment tips (COST) line, the photoreceptor outer segment (PROS) length, the inner retina irregularity index, and the presence of posterior vitreous detachment (PVD).DRIL refers to the abnormal appearance of the inner retinal layers on OCT, and has been found to be associated with poorer postoperative visual outcomes in ERM removal surgery. Significant EIFL has also been associated with poorer visual outcomes after surgery. The cotton ball sign, which appears as a hyper‐reflective area in the inner nuclear layer, has been found to be associated with increased difficulty in ERM removal and poorer visual outcomes. These biomarkers suggest that a greater degree of retinal disorganization and irregularity may lead to more challenging surgeries and poorer visual outcomes.In contrast, the presence of intact COST line and normal PROS length have been associated with better visual function. PVD, which represents separation of the vitreous from the retina, has been shown to be associated with less surgical trauma and better postoperative outcomes. The inner retina irregularity index, which measures the extent of disorganization of the inner retinal layers, has also been found to correlate with the changes in metamorphopsia and quality of vision after surgery.These biomarkers have the potential to improve the accuracy of preoperative evaluation and prediction of surgical outcomes in ERM removal surgery. By identifying patients with a greater degree of retinal disorganization and irregularity, we can anticipate more challenging surgeries and poorer visual outcomes. Conversely, patients with minimal COST line defects, normal PROS length and full PVD may have better postoperative visual outcomes.In summary, preoperative OCT findings can help predict postoperative visual outcomes in ERM removal surgery. The use of imaging modalities and specific biomarkers can provide useful insight in management decisions, case selection, and timing of surgery.

Rationale and Design of VOYAGER: Long-term Outcomes of Faricimab and Port Delivery System with Ranibizumab for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema in Clinical Practice

PurposeTo describe the rationale and design of the VOYAGER (NCT05476926) study, which aims to investigate the safety and effectiveness of faricimab and the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) in routine clinical practice. VOYAGER also aims to understand drivers of real-word treatment outcomes by gaining novel insight into the intersection of treatment regimens, treatment decisions, anatomic outcomes and vision. DesignPrimary data collection, noninterventional, prospective, multinational, multicenter real-world study. ParticipantsAt least 5000 patients initiating or continuing faricimab or PDS for nAMD or DME across 500 sites in 31 countries. MethodsManagement will be per usual care, with no mandated schedule visits or imaging protocol requirements. Using robust methodologies, relevant clinical and ophthalmic data, including visual acuity (VA), and data on treatment clinical setting/regimens/philosophies, presence of anatomical features and safety events will be collected. Routinely collected fundus images will be uploaded to the proprietary Imaging Platform for analysis. An innovative investigator interface will graphically display the patient treatment journey with the aim of optimizing treatment decisions. Main Outcome MeasuresThe primary endpoint is VA change from baseline at 12 months per study cohort (faricimab in nAMD and in DME, PDS in nAMD). Secondary endpoints include VA change over time and according to treatment regimens (fixed, treat-and-extend, pro re nata, other) and number. Exploratory endpoints include VA change in relation to presence/location of anatomical features that impact vision (fluid, central subfield thickness, fibrosis, atrophy, subretinal hyperreflective material, diabetic retinopathy severity, disorganization of retinal inner layers) and according to treatment regimen/philosophies. The impact of regional and practice differences on outcomes will be assessed as will safety (ocular and nonocular adverse events). ResultsRecruitment commenced in November 2022 and will continue until late 2027 allowing for up to 5-years of follow-up. Exploratory interim analyses are planned annually. ConclusionsVOYAGER is an innovative real-world study of retinal diseases that will assess effectiveness and safety of faricimab and PDS in nAMD and DME and identify clinician- and disease-related factors driving treatment outcomes in clinical practices globally to help optimize vision outcomes for patients.

Clinical Utility of Spectral-Domain Optical Coherence Tomography Marker Disorganization of Retinal Inner Layers in Diabetic Retinopathy.

Disorganization of retinal inner layers (DRIL) is a potential spectral-domain optical coherence tomography (SD-OCT) imaging biomarker with clinical utility in diabetic retinopathy (DR). A cross-sectional study was conducted at a large academic center. The cohort was composed of 1,175 patients with type 2 diabetes with and without retinopathy on initial examination between September 2009 and January 2019 (n = 2,083 eyes). DR risk and progression factors were obtained from the medical record. Trained graders masked to patients' clinical histories evaluated SD-OCT scans for DRIL. Of 2,083 eyes, 28.1% (n = 585) demonstrated presence of DRIL with high interrater reliability (K = 0.88, 95% CI 0.86-0.90). DRIL was associated with worse visual acuity (VA) (P < 0.001) and DR severity (P < 0.0001). Insulin users had more severe DR (P < 0.0001). DR-related factors, race (Black, White) and sex (male) were significantly associated with DRIL (P < 0.05). DRIL was strongly associated with DR severity and worse VA, supporting its utility as an unfavorable prognostic indicator. [Ophthalmic Surg Lasers Imaging Retina 2023;54:692-700.].

Oct biomarkers for early prognosis in diabetic macular edema treatment with ranibizumab.

Diabetic macular edema is the main cause of vision loss in patients with diabetic retinopathy. In this work, we aimed to assess the role of Optical Coherence Tomography (OCT) biomarkers in patients treated with ranibizumab. A prospective study enrolling 46 eyes with DME under ranibizumab intravitreal therapy with 12 months of follow-up. The primary endpoint was to assess the association between OCT biomarkers at baseline and the type of treatment response. Good responders, compared with partial/non responders, had lower number of inner nuclear layer cysts (INLc) at baseline, (26.5% vs 73.5%, p = 0.035) and presented, at 12 months of follow-up, lower percentage of disorganization of retinal inner layers (12.0% vs 88.0%, p = 0.001), lower disruption of outer plexiform layer (8.7% vs 91.3%, p < 0.001) and lower outer nuclear layer cysts (17.4% vs 82.6%, p = 0.013). At the end of follow-up, it was observed a higher frequency of inner nuclear layer cysts in patients with higher glycated haemoglobin (p = 0.028). This study showed the value and importance of OCT parameters, such as absence of INLc, as a prognostic therapeutic response. A normalization of the macular anatomy with ranibizumab is more likely to happen in early complete responders. The association between INLc and higher glycated haemoglobin levels showed the importance of systemic metabolic control in systemic diabetic manifestations. Clinicaltrials.gov NCT04387604.

Fuzzy Logic-Based System for Identifying the Severity of Diabetic Macular Edema from OCT B-Scan Images Using DRIL, HRF, and Cystoids.

Diabetic Macular Edema (DME) is a severe ocular complication commonly found in patients with diabetes. The condition can precipitate a significant drop in VA and, in extreme cases, may result in irreversible vision loss. Optical Coherence Tomography (OCT), a technique that yields high-resolution retinal images, is often employed by clinicians to assess the extent of DME in patients. However, the manual interpretation of OCT B-scan images for DME identification and severity grading can be error-prone, with false negatives potentially resulting in serious repercussions. In this paper, we investigate an Artificial Intelligence (AI) driven system that offers an end-to-end automated model, designed to accurately determine DME severity using OCT B-Scan images. This model operates by extracting specific biomarkers such as Disorganization of Retinal Inner Layers (DRIL), Hyper Reflective Foci (HRF), and cystoids from the OCT image, which are then utilized to ascertain DME severity. The rules guiding the fuzzy logic engine are derived from contemporary research in the field of DME and its association with various biomarkers evident in the OCT image. The proposed model demonstrates high efficacy, identifying images with DRIL with 93.3% accuracy and successfully segmenting HRF and cystoids from OCT images with dice similarity coefficients of 91.30% and 95.07% respectively. This study presents a comprehensive system capable of accurately grading DME severity using OCT B-scan images, serving as a potentially invaluable tool in the clinical assessment and treatment of DME.

Association of OCT biomarkers and visual impairment in patients with diabetic macular oedema with vitreomacular adhesion.

To analyse the distribution of spectral domain optical coherence tomography (SD-OCT) biomarkers in different types of vitreomacular adhesion (VMA) associated visual impairment in diabetic macular oedema. A total of 317 eyes of 202 patients were enrolled. Cases were divided into two groups focal VMA and broad VMA and subjects with no VMA were enrolled as controls. A grading platform was used for evaluating the morphology of diabetic macular oedema (DME), using good-quality SD-OCT images. Grading was done for VMA and the biomarkers. Best corrected visual acuity (BCVA), central retinal thickness (CRT) and central subfield thickness (CSFT) was also recorded. The CRT (p = <0.001) and CSFT (p = <0.001) values were statistically significant between the groups. Except for Inner Nuclear Layer Cysts (p = <0.001), absence of Bridging Tissue that is composed of muller cell fibers and bipolar cells (p<0.001), and Hyper Reflective Dots (HRD) in cyst (p = 0.006) there were no significant differences in the distribution of OCT biomarkers among the 3 groups (focal VMA, broad VMA and no VMA). Only Disorganization of Retinal Inner Layers (DRIL) (p = 0.044) showed significant association with vision impairment in all the 3 groups. The distribution of OCT biomarkers was similar across all eyes of cases and controls. However, they were more likely to be associated with visual impairment in the presence of VMA than no VMA.

Deep Learning Algorithm Detects Presence of Disorganization of Retinal Inner Layers (DRIL)-An Early Imaging Biomarker in Diabetic Retinopathy.

To develop and train a deep learning-based algorithm for detecting disorganization of retinal inner layers (DRIL) on optical coherence tomography (OCT) to screen a cohort of patients with diabetic retinopathy (DR). In this cross-sectional study, subjects over age 18, with ICD-9/10 diagnoses of type 2 diabetes with and without retinopathy and Cirrus HD-OCT imaging performed between January 2009 to September 2019 were included in this study. After inclusion and exclusion criteria were applied, a final total of 664 patients (5992 B-scans from 1201 eyes) were included for analysis. Five-line horizontal raster scans from Cirrus HD-OCT were obtained from the shared electronic health record. Two trained graders evaluated scans for presence of DRIL. A third physician grader arbitrated any disagreements. Of 5992 B-scans analyzed, 1397 scans (∼30%) demonstrated presence of DRIL. Graded scans were used to label training data for the convolution neural network (CNN) development and training. On a single CPU system, the best performing CNN training took ∼35 mins. Labeled data were divided 90:10 for internal training/validation and external testing purpose. With this training, our deep learning network was able to predict the presence of DRIL in new OCT scans with a high accuracy of 88.3%, specificity of 90.0%, sensitivity of 82.9%, and Matthews correlation coefficient of 0.7. The present study demonstrates that a deep learning-based OCT classification algorithm can be used for rapid automated identification of DRIL. This developed tool can assist in screening for DRIL in both research and clinical decision-making settings. A deep learning algorithm can detect disorganization of retinal inner layers in OCT scans.

Evaluation of the efficacy of anti-vascular endothelial growth factors in diabetic macular edema with retinal inner and outer layers disorganization.

This study aims to compare the effectiveness of treatment between anti-vascular endothelial growth factor (anti-VEGF) agents in diabetic macular edema (DME) patients with disorganization of retinal inner layers (DRIL). Epiretinal membrane, serous macular detachment, ellipsoid zone (EZ) disorder, external limiting membrane (ELM) disorder, and hyperreflective foci were also examined. Patients treated for DME and also had DRIL were included in the study. The study design was retrospective and cross-sectional. The complete ophthalmologic records and imaging were scanned at the beginning, 3rd-month, 6th-month, and 12th-month follow-up, and the treatments administered were recorded. Anti-VEGF agents administered to the patients were examined in three groups: bevacizumab, ranibizumab, and aflibercept. A total of 141 eyes of 100 patients were included in our study. One hundred and fifteen eyes (81.6%) had a BCVA of 0, 5, or less at the beginning. There was no statistically significant difference between the three groups regarding initial BCVA and CMT and the change in BCVA and CMT at the beginning and the 12th month (p > 0.05). There was a negative correlation between EZ and ELM disorders in patients and the change in BCVA at 12months (r: 0.45 p < 0.001, r: 0.32 p < 0.001, respectively). The number of injections over five was positively correlated with the change in CMT but not with BCVA (r: - 2.35 p = 0.005 and r: 0.147 p = 0.082, respectively). No statistically significant difference was found between anti-VEGF agents when treating DME patients with DRIL. In addition, we have shown that anatomically better results were obtained in those who had five or more injections, although not in terms of BCVA.

Caspase-9 inhibition confers stronger neuronal and vascular protection compared to VEGF neutralization in a mouse model of retinal vein occlusion.

Retinal vein occlusion (RVO) is a sight-threatening condition typically treated with intravitreal injection of vascular endothelial growth factor (VEGF) antagonists. Treatment response to anti-VEGF therapies is highly variable, with poor visual outcomes and treatment response in patients with significant retinal nonperfusion following RVO. Recently, caspase-9 has been identified as a potent regulator of edema, gliosis, and neuronal dysfunction during acute retinal hypoxia. The purpose of this study was to compare the therapeutic effect of caspase-9 inhibition against VEGF-neutralization in an established mouse model of RVO. Adult male C57Bl/6 J mice were randomized to induction of RVO and treatment with either vehicle, intravitreal injection of anti-VEGF antibody, topical administration of a selective caspase-9 inhibitor (Pen1-XBir3), or a combination therapy. Animals were followed on days 1, 2, and 8 after RVO with fundus retinal imaging, and with optical coherence tomography (OCT) to capture retinal swelling, capillary nonperfusion (measured by disorganization of retinal inner layers, DRIL), hyperreflective foci (HRF), and retinal atrophy. Focal electroretinography (ERG) measurements were performed on day 7. Histology was performed on retinal sections from day 8. Both VEGF neutralization and caspase-9 inhibition showed significant retinal protection from RVO compared to vehicle treatment arm. Retinal reperfusion of occluded veins was accelerated in eyes receiving caspase-9 inhibitor, but not significantly different from vehicle in the anti-VEGF group. Retinal edema was suppressed in all treatment groups, with approximately 2-fold greater edema reduction with caspase-9 inhibition compared to VEGF neutralization. HRF were reduced similarly across all treatment groups compared to vehicle. Retinal detachment was reduced only in eyes treated with caspase-9 inhibitor monotherapy. Caspase-9 inhibition reduced retinal atrophy and preserved ERG response; VEGF neutralization did not prevent neurodegeneration following RVO. Caspase-9 inhibition confers stronger neuronal and vascular protection compared to VEGF neutralization in the mouse laser-induced model of RVO.

Pathological Neurovascular Unit Mapping onto Multimodal Imaging in Diabetic Macular Edema.

Diabetic retinopathy is a form of diabetic microangiopathy, and vascular hyperpermeability in the macula leads to retinal thickening and concomitant reduction of visual acuity in diabetic macular edema (DME). In this review, we discuss multimodal fundus imaging, comparing the pathogenesis and interventions. Clinicians diagnose DME using two major criteria, clinically significant macular edema by fundus examination and center-involving diabetic macular edema using optical coherence tomography (OCT), to determine the appropriate treatment. In addition to fundus photography, fluorescein angiography (FA) is a classical modality to evaluate morphological and functional changes in retinal capillaries, e.g., microaneurysms, capillary nonperfusion, and fluorescein leakage. Recently, optical coherence tomography angiography (OCTA) has allowed us to evaluate the three-dimensional structure of the retinal vasculature and newly demonstrated that lamellar capillary nonperfusion in the deep layer is associated with retinal edema. The clinical application of OCT has accelerated our understanding of various neuronal damages in DME. Retinal thickness measured by OCT enables us to quantitatively assess therapeutic effects. Sectional OCT images depict the deformation of neural tissues, e.g., cystoid macular edema, serous retinal detachment, and sponge-like retinal swelling. The disorganization of retinal inner layers (DRIL) and foveal photoreceptor damage, biomarkers of neurodegeneration, are associated with visual impairment. Fundus autofluorescence derives from the retinal pigment epithelium (RPE) and its qualitative and quantitative changes suggest that the RPE damage contributes to the neuronal changes in DME. These clinical findings on multimodal imaging help to elucidate the pathology in the neurovascular units and lead to the next generation of clinical and translational research in DME.

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.

Effects of disorganization of retinal inner layers for Idiopathic epiretinal membrane surgery: the surgical status and prognosis

BackgroundTo compare the surgical status in idiopathic epiretinal membrane (IERM) patients with or without disorganization of retinal inner layers (DRIL) and to correlate with optical coherence tomography angiography (OCTA) and clinical data.MethodsIn 74 eyes from 74 patients with IERM treated by surgery with 12-month follow-up. According to the superficial hemorrhage, the patients were divided into group A (no macular bleeding), group B (macular parafoveal bleeding) and group C (macular foveal bleeding). Optical coherence tomography (OCT) were evaluated for presence of DRIL,central retina thickness and integrity of the inner/outer segment layer recorded at baseline and at 1, 3, 6, and 12 months postoperatively and best-corrected visual acuity (BCVA) was recorded simultaneously. OCTA was conducted at 12 months postoperatively. Main outcome measures is correlation between DRIL and superficial hemorrhage in membrane peeling,and BCVA and OCTA outcomes postoperatively.ResultsThe rate of DRIL and BCVA had statistically significant differences between the three groups at the time points(baseline and 1, 3, 6, and 12 months after surgery), respectively (P < 0.001 for all). FD-300 value (P = 0.001)and DCP in all parafoveal regions (superior: P = 0.001; inferior: P = 0.002;Nasal: P = 0.014;Tempo: P = 0.004) in eyes with DRIL were lower than those without DRIL.There was a linear regression relationship between FD-300 and postoperative BCVA (P = 0.011).ConclusionIERM Patients with DRIL have more intraoperative adverse events and limited benefits from surgery which should be considered in the decision whether to perform mebrane peeling.OCT-A provides more detailed vascular information that extends our understanding of persistent DRIL.

OCT outcomes as biomarkers for disease status, visual function, and prognosis in diabetic macular edema

PurposeTo evaluate disorganization of retinal inner layers (DRIL), as detected on spectral-domain optical coherence tomography (OCT) images, as a biomarker for diabetic macular edema (DME) activity, visual function, and prognosis in eyes with DME. DesignLongitudinal prospective. MethodsPost hoc correlation analyses were performed on data from a phase 2 clinical trial. Seventy-one eyes of 71 patients with treatment-naive DME received either suprachoroidally administered CLS-TA (proprietary formulation of a triamcinolone acetonide injectable suspension) combined with intravitreal aflibercept or intravitreal aflibercept with a sham suprachoroidal injection procedure. DRIL area, maximum horizontal extent of DRIL, ellipsoid zone (EZ) integrity, and the presence and location of subretinal (SRF) and intraretinal fluid (IRF) were evaluated at baseline and week 24 by certified reading centre graders. ResultsAt baseline, the area and maximum horizontal extent of DRIL were negatively correlated with best-corrected visual acuity (BCVA; r = –0.25, p = 0.05 and r = –0.32, p =0.01, respectively). Mean baseline BCVA progressively worsened with each ordinal drop in EZ integrity, improved with the presence of SRF, and was invariant to the presence of IRF. DRIL area and maximum extent were significantly decreased at week 24 (–3.0 mm2 [p < 0.001] and –775.8 mm [p < 0.001], respectively. At week 24, decreases in the area and maximum horizontal extent of DRIL were positively correlated with increases in BCVA (r = –0.40, p = 0.003 and r = –0.30, p = 0.04). Improvements in BCVA at week 24 were no different between patients showing improvement in EZ, SRF, or IRF and those showing no improvement or worsening from baseline. ConclusionsDRIL area and DRIL maximum horizontal extent were demonstrated to be novel biomarkers for macular edema status, visual function, and prognosis in eyes with treatment-naive DME.

Predictors of As-Needed Ranibizumab Injection Frequency in Patients With Macular Edema Following Retinal Vein Occlusion

To evaluate spectral-domain optical coherence tomography (SD-OCT) biomarkers associated with ranibizumab injection frequency after 7 monthly doses in the prospective, multicenter SHORE study for macular edema due to retinal vein occlusion (RVO). Prospective phase IV clinical trial data. Post hoc analysis of 95 patients who received 7 monthly doses of ranibizumab followed by either pro re nata (PRN) or nonrandomized monthly injections from months 7-15 in eyes with macular edema secondary to RVO. Baseline SD-OCT biomarkers assessed include central subfield thickness (CST), epiretinal membrane presence, intraretinal and subretinal fluid, hyperreflective foci, disorganization of retinal inner layers (DRIL), and disruption of the external limiting membrane, ellipsoid zone, or interdigitation zone. Univariate and multivariable regression analyses evaluated the association between SD-OCT biomarkers and ranibizumab injection frequency. Mean age of patients was 65.3 (SD, 12.7) years. Overall, 57.9% had BRVO/HRVO and 42.1% of eyes had CRVO. Mean BCVA improved (+17.5 [SD, 1.2] Early Treatment of Diabetic Retinopathy Study [ETDRS] letters) during the 7-month fixed dosing period, remaining stable from baseline (+20.1 [SD, 1.5] ETDRS letters) during the PRN phase from months 7-15. The mean number of PRN injections was 4.32 (SD, 2.35). On multivariate regression, greater baseline DRIL (β=0.021, P=.0275) and higher CST at month 3 (β=0.01, P < .001) were associated with a higher total number of PRN injections. Greater baseline DRIL and higher CST at 3 months after starting ranibizumab treatment are associated with more frequent ranibizumab injections in PRN-treated patients with macular edema due to RVO.

Morphological Characteristics of Foveal Pit Base and Its Impact on Visual Acuity in Macular Pseudoholes

Introduction: To investigate the characteristics of macular pseudoholes (MPHs) with different foveal profiles and their impact on preoperative and postoperative visual acuity (VA). Methods: A retrospective review of 47 eyes from 46 consecutive patients with MPH who had undergone vitrectomy was conducted. The MPHs were classified into u-shape and v-shape according to the morphological description of the foveola base. The best-corrected visual acuity (BCVA), central foveal point thickness, parafoveal thickness, parafoveal inner and outer retinal thickness, stretched lamellar cleavage, microcystic macular edema (MME), disorganization of retinal inner layers (DRIL), and the integrity of outer retinal layers were recorded. Results: The eyes in the v-shaped group (n = 31) had lower BCVA, thicker retinal thickness, more intraretinal cleavage, MME, and DRIL than the u-shaped (n = 16) group (all p < 0.05). Multiple regression analysis revealed that the morphology of the foveola base was significantly related to the preoperative BCVA (p = 0.025). The VA was significantly improved in both groups, and the improvement was greater in the v-shaped group (p = 0.024). No significant difference was found in the postoperative BCVA between the two groups (all p > 0.05). Conclusion: The v-shape, reflecting the stretch in the foveola, had a significant impact on preoperative BCVA. However, the VA was improved after surgery whatever their initial foveal profile.