Spectral-domain Optical Coherence Tomography Features Research Articles

Optical coherence tomography features in vitreoretinal lymphoma compared with non-infectious uveitis

BackgroundVitreoretinal lymphoma (VRL) is a rare intraocular malignancy that poses a diagnostic challenge due to the non-specific clinical presentation that resembles uveitis. The use of spectral domain optical coherence tomography (SD-OCT) has emerged as a valuable imaging tool to characterize VRL. Therefore, we sought to determine the specific OCT features in VRL compared to the uveitides.MethodsRetrospective chart review of patients who were seen at Mayo Clinic from January 1, 2010 through December 31, 2022.The medical records and SD-OCT images at time of initial presentation were reviewed in patients with biopsy-proven VRL, intermediate uveitis, or biopsy-confirmed sarcoid posterior uveitis. Patients with VRL or similar uveitides including intermediate uveitis or sarcoid posterior uveitis were included.ResultsThere were 95 eyes of 56 patients in the VRL group and 86 eyes of 45 patients in the uveitis group, of whom 15 (33.3%) were diagnosed with intermediate uveitis and 30 (66.7%) with sarcoid chorioretinitis. The SD-OCT features more commonly seen at initial presentation in VRL patients (vs. uveitis) included preretinal deposits (31.6% vs. 9.3%, p = 0.002), intraretinal infiltrates (34% vs. 3.5%, p < 0.001), inner retinal hyperreflective spots (15.8% vs. 0%, p < 0.001), outer retinal atrophy (22.1% vs. 2.3%, p < 0.001), subretinal focal deposits (21.1% vs. 4.7%, p = 0.001), retinal pigmented epithelium (RPE) changes (49.5% vs. 3.5%, p < 0.001), and sub-RPE deposits (34.7% vs. 0%, p < 0.001). Features more frequently seen in uveitis included epiretinal membrane (ERM) (82.6% vs. 44.2%, p < 0.001), central macular thickening (95.3% vs. 51.6%, p < 0.001), cystoid macular edema (36% vs. 11.7%, p < 0.001), subretinal fluid (16.3% vs 6.4%, p = 0.04), and subfoveal fluid (16.3% vs. 3.2%, p = 0.003). Multivariate regression analysis controlling for age and sex showed absence of ERM (OR 0.14 [0.04,0.41], p < 0.001) and absence of central macular thickening (OR 0.03 [0,0.15], p = 0.02) were associated with VRL as opposed to uveitis.ConclusionOCT features most predictive of VRL (vs. uveitis) included absence of ERM and central macular thickening.

In vivo cone-photoreceptor density comparison between eyes with subretinal drusenoid deposits and healthy eyes using high magnification imaging.

To compare photoreceptor density automated quantification in eyes with subretinal drusenoid deposits (SDD) and healthy controls using Heidelberg Spectralis High Magnification Module (HMM) imaging. Twelve eyes of 6 patients with intermediate AMD, presenting with SDD were included, as well as twelve eyes of healthy controls. Individual dot SDD within the central 30° retina were examined with infrared confocal laser ophthalmoscopy, HMM, and spectral-domain optical coherence tomography (SD-OCT). Photoreceptor density analysis was performed on the best-quality image using the ImageJ Foci Picker plugin, after the removal of SDD from the HMM image. Correlations were made between the HMM quantified photoreceptor density, SD-OCT characteristics, stage, and number of SDD. Mean age was 75.17 ± 2.51years in the SDD group (3 males, 3 females) versus 73.17 ± 3.15years in the healthy control group (p = 0.2). Defects in the overlying ellipsoid zone were present on SD-OCT in 8/12 (66.66%) eyes. The mean ± standard deviation foci detected (i.e., cone photoreceptors) was 7123.75 ± 3683.32foci/mm2 in the SDD group versus 13,253 ± 3331.00foci/mm2 in the healthy control group (p = 0.0003). The number of SDD was associated with a reduction in foci density, p = 0.0055, r = - 0.7622. The decreased cone density in eyes with SDD may correlate with a decrease in retinal function in intermediate AMD eyes independent of neovascular complications or outer retinal pigment epithelial atrophy.

Deep learning-based algorithm for the detection of idiopathic full thickness macular holes in spectral domain optical coherence tomography

BackgroundAutomated identification of spectral domain optical coherence tomography (SD-OCT) features can improve retina clinic workflow efficiency as they are able to detect pathologic findings. The purpose of this study was to test a deep learning (DL)-based algorithm for the identification of Idiopathic Full Thickness Macular Hole (IFTMH) features and stages of severity in SD-OCT B-scans.MethodsIn this cross-sectional study, subjects solely diagnosed with either IFTMH or Posterior Vitreous Detachment (PVD) were identified excluding secondary causes of macular holes, any concurrent maculopathies, or incomplete records. SD-OCT scans (512 × 128) from all subjects were acquired with CIRRUS™ HD-OCT (ZEISS, Dublin, CA) and reviewed for quality. In order to establish a ground truth classification, each SD-OCT B-scan was labeled by two trained graders and adjudicated by a retina specialist when applicable. Two test sets were built based on different gold-standard classification methods. The sensitivity, specificity and accuracy of the algorithm to identify IFTMH features in SD-OCT B-scans were determined. Spearman’s correlation was run to examine if the algorithm’s probability score was associated with the severity stages of IFTMH.ResultsSix hundred and one SD-OCT cube scans from 601 subjects (299 with IFTMH and 302 with PVD) were used. A total of 76,928 individual SD-OCT B-scans were labeled gradable by the algorithm and yielded an accuracy of 88.5% (test set 1, 33,024 B-scans) and 91.4% (test set 2, 43,904 B-scans) in identifying SD-OCT features of IFTMHs. A Spearman’s correlation coefficient of 0.15 was achieved between the algorithm’s probability score and the stages of the 299 (47 [15.7%] stage 2, 56 [18.7%] stage 3 and 196 [65.6%] stage 4) IFTMHs cubes studied.ConclusionsThe DL-based algorithm was able to accurately detect IFTMHs features on individual SD-OCT B-scans in both test sets. However, there was a low correlation between the algorithm’s probability score and IFTMH severity stages. The algorithm may serve as a clinical decision support tool that assists with the identification of IFTMHs. Further training is necessary for the algorithm to identify stages of IFTMHs.

Closure Grading and Visual Outcome in Patients with Large Idiopathic Macular Holes: A Spectral-Domain Optical Coherence Tomography Observation

Introduction: So far, there has been no closure grade system synthesizing morphological and microstructural features for large idiopathic macular holes (IMHs) treated by vitrectomy and internal limiting membrane (ILM) peeling. This study aimed to propose a concise one and explore its relevance with visual acuity and the related preoperative factors. Methods: Consecutive patients with large IMHs (minimum diameter >400 μm), undergoing vitrectomy and ILM peeling, obtaining primary closure and regularly followed-up were enrolled. Preoperative clinical charts and spectral-domain optical coherence tomography (SD-OCT) parameters were reviewed. SD-OCT images and best corrected visual acuity (BCVA) were assessed at 1, 4, and 10 months postoperatively. SD-OCT features at last visit were categorized by BCVA significance, and preoperative risk factors were analyzed. Results: Sixty-eight eyes from 64 patients were enrolled. The 10-month postoperative SD-OCT images were categorized into closure grade 1, 2, and 3 with successively decreased BCVA (p < 0.001). During early follow-up, part of grades 2 and 3 could evolve into the upper grade, respectively, but grade 3 could never evolve into grade 1 and exhibited the least satisfactory long-term BCVA. Binary logistic regression showed that large minimum linear diameter (MLD) was a risk factor for grade 3 occurrence (p < 0.001), with a cutoff value of 625.5 μm from the receiver operating characteristic curve for MLD predicting grade 3 occurrence (p = 0.001). Conclusion: Long-term closure status of large IMHs could be categorized into three grades with BCVA significance. Large horizontal MLD is a risk factor for occurrence of grade 3 closure with unsatisfactory visual recovery.

A Deep-Learning Algorithm to Predict Short-Term Progression to Geographic Atrophy on Spectral-Domain Optical Coherence Tomography

The identification of patients at risk of progressing from intermediate age-related macular degeneration (iAMD) to geographic atrophy (GA) is essential for clinical trials aimed at preventing disease progression. DeepGAze is a fully automated and accurate convolutional neural network-based deep learning algorithm for predicting progression from iAMD to GA within 1 year from spectral-domain optical coherence tomography (SD-OCT) scans. To develop a deep-learning algorithm based on volumetric SD-OCT scans to predict the progression from iAMD to GA during the year following the scan. This retrospective cohort study included participants with iAMD at baseline and who either progressed or did not progress to GA within the subsequent 13 months. Participants were included from centers in 4 US states. Data set 1 included patients from the Age-Related Eye Disease Study 2 AREDS2 (Ancillary Spectral-Domain Optical Coherence Tomography) A2A study (July 2008 to August 2015). Data sets 2 and 3 included patients with imaging taken in routine clinical care at a tertiary referral center and associated satellites between January 2013 and January 2023. The stored imaging data were retrieved for the purpose of this study from July 1, 2022, to February 1, 2023. Data were analyzed from May 2021 to July 2023. A position-aware convolutional neural network with proactive pseudointervention was trained and cross-validated on Bioptigen SD-OCT volumes (data set 1) and validated on 2 external data sets comprising Heidelberg Spectralis SD-OCT scans (data sets 2 and 3). Prediction of progression to GA within 13 months was evaluated with area under the receiver-operator characteristic curves (AUROC) as well as area under the precision-recall curve (AUPRC), sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. The study included a total of 417 patients: 316 in data set 1 (mean [SD] age, 74 [8]; 185 [59%] female), 53 in data set 2, (mean [SD] age, 83 [8]; 32 [60%] female), and 48 in data set 3 (mean [SD] age, 81 [8]; 32 [67%] female). The AUROC for prediction of progression from iAMD to GA within 1 year was 0.94 (95% CI, 0.92-0.95; AUPRC, 0.90 [95% CI, 0.85-0.95]; sensitivity, 0.88 [95% CI, 0.84-0.92]; specificity, 0.90 [95% CI, 0.87-0.92]) for data set 1. The addition of expert-annotated SD-OCT features to the model resulted in no improvement compared to the fully autonomous model (AUROC, 0.95; 95% CI, 0.92-0.95; P = .19). On an independent validation data set (data set 2), the model predicted progression to GA with an AUROC of 0.94 (95% CI, 0.91-0.96; AUPRC, 0.92 [0.89-0.94]; sensitivity, 0.91 [95% CI, 0.74-0.98]; specificity, 0.80 [95% CI, 0.63-0.91]). At a high-specificity operating point, simulated clinical trial recruitment was enriched for patients progressing to GA within 1 year by 8.3- to 20.7-fold (data sets 2 and 3). The fully automated, position-aware deep-learning algorithm assessed in this study successfully predicted progression from iAMD to GA over a clinically meaningful time frame. The ability to predict imminent GA progression could facilitate clinical trials aimed at preventing the condition and could guide clinical decision-making regarding screening frequency or treatment initiation.

Clinical features of idiopathic epiretinal membrane in children and the factors influencing postoperative visual acuity.

To describe the characteristics and surgical outcomes of idiopathic epiretinal membrane (iERM) in children and to determine the factors associated with postoperative visual acuity (VA). We retrospectively reviewed the medical records of 17 patients with iERM (age, < 18years) who had undergone ERM surgery from 2009 to 2021. Spectral-domain optical coherence tomography features were documented. The eyes with iERMs involving the fovea were assigned to the localized and diffused groups depending on the morphological description of the membrane. Multiple linear regression analysis was used to explore the factors associated with the final VA. The mean age was 9.2 ± 3.8years. The mean follow-up period was 38.9 ± 45.4months. After surgery, the central foveal thickness and the best-corrected VA (BCVA) improved significantly (all, P < 0.05). Fourteen eyes with iERMs showed involvement of the foveal area (localized group, six eyes; diffused group, eight eyes). There were no significant differences in the preoperative BCVA between the two groups (P = 0.064). However, the final BCVA was better in the diffused group than in the localized group (P = 0.043). Multiple regression analysis indicated that the localized membrane (P = 0.042) and lower preoperative BCVA (P = 0.043) were factors associated with a worse final VA in pediatric iERMs. Surgical removal of ERM showed a high anatomical and functional success rate in children. In pediatric patients with iERMs involving the fovea, a good VA was more common when the membrane was diffused than when it was localized.

Spectral-domain optical coherence tomography biomarkers in vitreoretinal lymphoma.

Although early detection is critical, diagnosing vitreoretinal lymphoma (VRL) remains difficult. We sought to assess the potential diagnostic value of spectral-domain optical coherence tomography (SD-OCT) in VRL. We reviewed the clinical records and pre-treatment SD-OCT images of biopsy-confirmed VRL and uveitis patients, with primary involvement of the sub-retinal pigment epithelium (RPE) and the outer retina, including acute syphilitic posterior placoid chorioretinitis (ASPPC), chronic stage sympathetic ophthalmitis (SO), and idiopathic multifocal choroiditis (MFC). We included 45 eyes of 45 VRL patients and 40 eyes of 40 uveitis patients (17 ASPPC eyes, eight chronic SO eyes, and 15 MFC eyes). On SD-OCT, lymphoma cell infiltration was observed in various retinal layers, most commonly in the sub-RPE (80%) and sub-retinal space (62%). Highly sensitive features for VRL as compared to uveitis included vitreous cells (93%), focal hyper-reflective sub-retinal infiltration (51%), and diffuse RPE elevations (56%). The features strongly specific for VRL included preretinal deposits (92.5%), intra-retinal infiltration (except the incomplete vertical hyper-reflective type, 100%), banded hyper-reflective sub-retinal infiltration (90%), and confluent RPE detachments (100%). We identified an approach to VRL diagnosis based on these SD-OCT findings: (1) two highly sensitive features plus one strongly specific feature; or (2) one highly sensitive feature plus two strongly specific features, demonstrated a sensitivity of 80% and specificity of 95% for VRL. The SD-OCT may enable the detection of detailed lymphoma infiltration characteristics and provide significant supplemental value for VRL diagnosis, particularly when combining highly sensitive and specific VRL-associated SD-OCT features.

Spectral-domain optical coherence tomography characteristics of cystic retinal tuft

ObjectiveTo investigate the characteristics of cystic retinal tufts (CRTs) with 55° widefield spectral-domain optical coherence tomography.MethodsThis was a retrospective study. All subjects underwent a complete ocular examination, ultra-widefield (UWF) pseudocolor fundus photography and Spectral domain optical coherence tomography (SD-OCT) with a 55° widefield lens. The SD-OCT characteristics were analyzed in subjects with CRT.ResultsTwenty-six eyes of 25 subjects were scanned and 29 CRTs were analyzed for SD-OCT characteristics. On SD-OCT images, the CRTs exhibited hyperreflective irregular elevated lesions with internal hyporeflective cystoid cavities. Normal layers of the neuroepithelium could not be distinguished. The mean diameter of CRTs was 1022 microns (range, 117–3711 microns; standard deviation, 815 microns). There was vitreoretinal traction at the apex of CRTs. Among them, retinal tears in 24.14% (7/29), suspected retinal tears in 27.59% (8/29), and shallow neuroepithelium detachment in 31.03% (9/29).ConclusionsThe widefield SD-OCT imaging can provide detailed cross-sectional anatomic information of CRT and may guide clinical treatment.

Automatic quantification of retinal photoreceptor integrity to predict persistent disease activity in neovascular age-related macular degeneration using deep learning.

Using deep learning (DL)-based technique, we identify risk factors and create a prediction model for refractory neovascular age-related macular degeneration (nAMD) characterized by persistent disease activity (PDA) in spectral domain optical coherence tomography (SD-OCT) images. A total of 671 typical B-scans were collected from 186 eyes of 186 patients with nAMD. Spectral domain optical coherence tomography images were analyzed using a classification convolutional neural network (CNN) and a fully convolutional network (FCN) algorithm to extract six features involved in nAMD, including ellipsoid zone (EZ), external limiting membrane (ELM), intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelium detachment (PED), and subretinal hyperreflective material (SHRM). Random forest models were probed to predict 1-year disease activity (stable, PDA, and cured) based on the quantitative features computed from automated segmentation and evaluated with cross-validation. The algorithm to segment six SD-OCT features achieved the mean accuracy of 0.930 (95% CI: 0.916-0.943), dice coefficients of 0.873 (95% CI: 0.847-0.899), a sensitivity of 0.873 (95% CI: 0.844-0.910), and a specificity of 0.922 (95% CI: 0.905-0.940). The six-metric model including EZ and ELM achieved the optimal performance to predict 1-year disease activity, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.980, the accuracy of 0.930, the sensitivity of 0.920, and the specificity of 0.962. The integrity of EZ and ELM significantly improved the performance of the six-metric model than that of the four-metric model. The prediction model reveals the potential to predict PDA in nAMD eyes. The integrity of EZ and ELM constituted the strongest predictive factor for PDA in nAMD eyes in real-world clinical practice. The results of this study are a significant step toward image-guided prediction of long-term disease activity in the management of nAMD and highlight the importance of the automatic identification of photoreceptor layers.

Spectral domain OCT features in type 2 macular telangiectasia (type 2 MacTel): its relevance with clinical staging and visual acuity

BackgroundTo report spectral domain optical coherence tomography (SDOCT) imaging findings in type 2 macular telangiectasia (MacTel) and correlate them with clinical stages and visual acuity.MethodsThis retrospective, cross-sectional study included type 2 MacTel cases who underwent SDOCT imaging with Spectralis machine. Macular SDOCT images were analysed. Imaging features were tested for correlation with different clinicals stages and visual acuity.Results212 eyes of 108 type 2 MacTel patients were included. Hyperreflective middle retinal layer (87%) was the most frequently detected abnormality. This was followed by inner retinal cavities (49%), outward bending of inner retinal layers (35%), retinal pigment clumps (35%) and foveal contour irregularity (31%). Hyperreflective middle retinal layers (p < 0.001), inner (p = 0.032) and outer retinal (p = 0.002) cavities and internal limiting membrane drape (p = 0.031) were associated with poor vision in non-proliferative group and presence of retinal pigment clumps (p = 0.002), subretinal fluid (p = 0.037) and foveal contour irregularity (p < 0.001) were associated with poor vision in proliferative group.ConclusionThe described SDOCT features are practical for the diagnosis and staging in type 2 MacTel. Presence of hyperreflective middle retinal layers, hyporeflective inner and outer retinal cavities and internal limiting membrane drape were associated with poor vision in the non-proliferative group while retinal pigment clumps and subretinal neovascular membrane were associated with proliferative group and poor vision. Further long-term studies are required to describe the progressive and sequential changes on SDOCT.

Posterior segment findings by spectral-domain optical coherence tomography and clinical associations in active toxoplasmic retinochoroiditis

Toxoplasmic retinochoroiditis is a common, potentially blinding parasitic infection. We sought to define the spectrum and frequency of signs of active toxoplasmic retinochoroiditis by spectral domain optical coherence tomography (SD-OCT), and to identify clinical associations. Ninety eyes of 90 individuals presenting consecutively to a tertiary referral uveitis service with active toxoplasmic retinochoroiditis and gradable SD-OCT scans were evaluated prospectively. SD-OCT features were collated, and associations with lesion location, primary versus recurrent episode, serological status, human immunodeficiency virus infection and best-corrected Snellen visual acuity were explored. Active toxoplasmic retinochoroiditis presented with thickened (65%) and hyperreflective (61%) retina, choroidal thickening (55%) and hyporeflectivity (61%), hyperreflective vitreous dots (80%) and deposits (36%), and posterior hyaloid thickening (35%) on SD-OCT. Most signs occurred with similar frequency across clinical groups. Retinal hyporeflectivity (17%) was significantly associated with a visual acuity of 20/200 or worse at resolution. Our observations demonstrate that active toxoplasmic retinochoroiditis has diverse SD-OCT signs and that none are universally present. Retinal hyporeflectivity—suggesting liquefactive necrosis—predicts poor visual outcome.

Predictive value of the characteristics of intraretinal cystoid spaces on early response to antivascular endothelial growth factor treatment in patients with cystoid diabetic macular edema.

To evaluate whether baseline spectral-domain optical coherence tomography characteristics of intraretinal cystoid spaces predict visual outcomes in patients receiving intravitreal antivascular endothelial growth factor injection therapy (bevacizumab 1.25mg/0.05ml) for diabetic cystoid macular edema. The relationship between the properties of the cystoid spaces before injection and anatomic and functional results after injection were investigated in patients who received three consecutive intravitreal bevacizumab injections for cystoid macular edema. The best-corrected visual acuity for functional success and central subfield thickness for anatomical success were evaluated. The relationship of the location of the cystoid spaces with the integrity of photoreceptors and inner retinal layers was also evaluated. In 36 eyes of 36 patients, the mean best-corrected visual acuity significantly improved (p=0.002), and mean central subfield thickness decreased after injections (p=0.003). The improvement in best-corrected visual acuity was limited in eyes with outer nuclear layer cysts (p=0.045). Intracystic reflectivity was higher in eyes that poor best-corrected visual acuity than in eyes with successful visual outcomes (p=0.028). The disrupted ellipsoid zone was present in 13 (59.0%) of 22 eyes with outer nuclear layer cysts, whereas in only 1 of 14 eyes (7.1%) without outer nuclear layer cysts (p=0.009). Disorganization of retinal inner layers was present in 15 of 22 (68.1%) eyes with outer nuclear layer cysts, whereas only 2 of 14 (14.2%) without outer nuclear layer cysts had disorganization of retinal inner layers (p=0.013). Characteristics of intraretinal cystoid spaces may predict prognosis in patients with diabetic cystoid macular edema, and visual gain may be limited in the eyes with outer nuclear layer cysts.

Sex variation of central serous chorioretinopathy by spectral domain optical coherence tomography

Purpose The aim of this study was to compare the spectral domain optical coherence tomography (SD-OCT) characteristics of central serous chorioretinopathy (CSR) between male and female patients.Patients and methods This is a retrospective study that included 39 patients of both sexes diagnosed as CSR during the period between January 2018 and May 2020. The analyzed data included patients’ age, duration of symptoms, and the SD-OCT measurable parameters in the male and female patient groups. The SD-OCT parameters included central total retinal thickness, central sensory retinal thickness, vertical distance of subfoveal subretinal fluid, horizontal distance of subfoveal subretinal fluid, and the presence of subretinal deposits. These parameters were compared and statistically analyzed between the two groups.Results The study included 24 male patients and 15 female patients. The mean age was 35.33±9.88 years in the male group and 41.53±8.28 years in the female group (P=0.05). In the male group, central total retinal thickness, central sensory retinal thickness, vertical distance of subfoveal subretinal fluid, and horizontal distance of subfoveal subretinal fluid were 448±93 μm, 182±34 μm, 305±53 μm, and 3.07±0.63 mm, respectively, while in the female group, they were 346±127 μm (P=0.006), 178±34 μm (P=0.73), 244±61 μm (P=0.002), and 2.34±0.67 mm (P=0.001), respectively. The percentage of patients having subretinal deposit was significantly more in the male group than in the female group (P=0.003).Conclusions There was a statistically significant difference in SD-OCT characteristics of CSR between male and female patients. Further studies are needed regarding the persistence of these OCT differences after treatment of CSR.

Interspecies Correlations between Human and Mouse NR2E3-Associated Recessive Disease.

NR2E3-associated recessive disease in humans is historically defined by congenital night blinding retinopathy, characterized by an initial increase in short-wavelength (S)-cone sensitivity and progressive loss of rod and cone function. The retinal degeneration 7 (rd7) murine model, harboring a recessive mutation in the mouse ortholog of NR2E3, has been a well-studied disease model and recently evaluated as a therapeutic model for NR2E3-associated retinal degenerations. This study aims to draw parallels between human and mouse NR2E3-related disease through examination of spectral domain optical coherence tomography (SD-OCT) imaging between different stage of human disease and its murine counterpart. We propose that SD-OCT is a useful non-invasive diagnostic tool to compare human clinical dystrophy presentation with that of the rd7 mouse and make inference that may be of therapeutically relevance. Additionally, a longitudinal assessment of rd7 disease progression, utilizing available clinical data from our patients as well as extensive retrospective analysis of visual acuity data from published cases of human NR2E3-related disease, was curated to identify further valuable correlates between human and mouse Nr2e3 disease. Results of this study validate the slow progression of NR2E3-associated disease in humans and the rd7 mice and identify SD-OCT characteristics in patients at or near the vascular arcades that correlate well with the whorls and rosettes that are seen also in the rd7 mouse and point to imaging features that appear to be associated with better preserved S-cone mediated retinal function. The correlation of histological findings between rd7 mice and human imaging provides a solid foundation for diagnostic use of pathophysiological and prognostic information to further define characteristics and a relevant timeline for therapeutic intervention in the field of NR2E3-associated retinopathies.

Local Anatomic Precursors to New-Onset Geographic Atrophy in Age-Related Macular Degeneration as Defined on OCT

In macula-wide analyses, spectral-domain (SD) optical coherence tomography (OCT) features including drusen volume, hyperreflective foci, and OCT-reflective drusen substructures independently predict geographic atrophy (GA) onset secondary to age-related macular degeneration (AMD). We sought to identify SD OCT features in the location of new GA before its onset. Retrospective study. Age-Related Eye Disease Study 2 Ancillary SD OCT Study participants. We analyzed longitudinally captured SD OCT images and color photographs from 488 eyes of 488 participants with intermediate AMD at baseline. Sixty-two eyes with sufficient image quality demonstrated new-onset GA on color photographs during study years 2 through 7. The area of new-onset GA and one size-matched control region in the same eye were segmented separately, and corresponding spatial volumes on registered SD OCT images at the GA incident year and at 2, 3, and 4 years previously were defined. Differences in SD OCT features between paired precursor regions were evaluated through matched-pairs analyses. Localized SD OCT features 2 years before GA onset. Compared with paired control regions, GA precursor regions at 2, 3, and 4 years before (n= 54, 33, and 25, respectively) showed greater drusen volume (P= 0.01, P= 0.003, and P= 0.003, respectively). At 2 and 3 years before GA onset, they were associated with the presence of hypertransmission (P < 0.001 and P= 0.03, respectively), hyperreflective foci (P < 0.001 and P= 0.045, respectively), OCT-reflective drusen substructures (P= 0.004 and P= 0.03, respectively), and loss or disruption of the photoreceptor zone, ellipsoid zone, and retinal pigment epithelium (RPE, P < 0.001 and P= 0.005-0.045, respectively). At 4 years before GA onset, precursor regions were associated with photoreceptor zone thinning (P= 0.007) and interdigitation zone loss (P= 0.045). Evolution to GA is heralded by early local photoreceptor changes and drusen accumulation, detectable4 years before GA onset. These precede other anatomic heralds such as RPE changes and drusen substructure emergence detectable1 to 2 years before GA. This study thus identified earlier end points for GA as potential therapeutic targets in clinical trials.

Gene expression analysis identifies two distinct molecular clusters of idiopatic epiretinal membranes

Idiopathic epiretinal membranes (ERMs) are fibrocellular membranes containing extracellular matrix proteins and epiretinal cells of retinal and extraretinal origin. iERMs lead to decreased visual acuity and their pathogenesis has not been completely defined. Aim of this study was to provide a molecular characterization of iERMs by gene expression analysis. To this purpose, 56 iERMs obtained by pars plana vitrectomy were analyzed for the expression levels of genes encoding biomarkers of the cellular and molecular events occurring in iERMs. RT-qPCR analysis showed significant differences in the levels of cell population, extracellular matrix and cytokine/growth factor biomarkers among the iERMs investigated. Hierarchical clustering of RT-qPCR data identified two distinct iERM clusters, Cluster B samples representing transcriptionally “activated” iERMs when compared to transcriptionally “quiescent” Cluster A specimens. Further, Cluster B could be subdivided in two subgroups, Cluster B1 iERMs, characterized by a marked glial cell activation, and Cluster B2 samples characterized by a more pro-fibrotic phenotype. Preoperative decimal best-corrected visual acuity and post-surgery inner segment/outer grading values were higher in Cluster A patients, that showed a prevalence of fovea-attached type iERMs with near-normal inner retina, than in Cluster B patients, that presented more severe clinical and spectral domain optical coherence tomography (SD-OCT) features. In conclusion, this molecular characterization has identified two major clusters of iERM specimens with distinct transcriptional activities that reflect different clinical and SD-OCT features of iERM patients. This retrospective work paves the way to prospective whole-genome transcriptomic studies to allow a molecular classification of iERMs and for the identification of molecular signature(s) of prognostic and therapeutic significance.

Changes of retinal structure after systemic immunosuppressive treatment in eyes with Vogt-Koyanagi-Harada disease

Objective: To assess structural changes in retina after systemic immunosuppressive treatment in Vogt-Koyanagi-Harada (VKH) disease using spectral-domain optical coherence tomography (SD-OCT). Methods: The clinical data of 17 VKH cases (34 eyes) who consecutively attended the Beijing Tongren Hospital between December 2015 and December 2019 were retrospectively reviewed. All the patients had acute or subacute onset, and underwent high-dose systemic corticosteroid and/or immunosuppressive treatment, with a followed-up time of at least 6 months. At the end of follow-up, the intraocular inflammation was controlled, and oral prednisone was withdrawn or being adjusted to less than 10 mg/day. The SD-OCT features of the included eyes were analyzed before treatment, 1 week, 1 month and 3 months after treatment, and at the last visit. Results: A total of 17 cases (34 eyes; 6 males and 11 females) were included, with an age of (42.2±10.6) years, and were followed up for (9.4±3.3) months. At 1 week after initiating treatment, the percentage of the eyes with extensive/multiple or multifocal retinal detachment in the macular region, membranous structures and intraretinal cysts, and undulations and bumps of retinal pigment epithelium (RPE) decreased (5.9% vs 100%, 2.9% vs 47.1%, 5.9% vs 70.6%, 11.8% vs 58.8%, respectively, all P<0.001). There was statistical significant difference of the percentage of ellipsoid zone and external limiting membrane (ELM) disruptions before treatment, at 3 months and the last visit (100% vs 35.3%, 64.7% vs 52.9%, 41.2% vs 26.5%, respectively, all P<0.001). At the last visit, there were statistical significant differences of the best corrected vision acuity (BCVA) between the intact ellipsoid zone group (20 eyes) and the discontinuous group (14 eyes), as well as between the intact ELM group (25 eyes) and the discontinuous group (9 eyes), respectively [0 (0, 0.05) vs 0.10 (0.03, 0.33) (log MAR), P=0.004; 0 (0, 0.07) vs 0.22 (0.05, 0.40) (log MAR), P=0.005]. Conclusions: The edema of choroid and retina subsided obviously at 1 week after initiating treatment. The extent of damage and recovery ability of ellipsoid zone and ELM were different before treatment, at 3 months and the last visit. At the last visit, the outer retinal layers failed to recover completely in some patients, and were related to the BCVA.

SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY FEATURES OF VITREORETINAL LYMPHOMA IN 55 EYES.

To evaluate spectral domain optical coherence tomography (SD-OCT) features of vitreoretinal lymphoma (VRL). Review of records and SD-OCT images of vitreoretinal lymphoma evaluated at Ocular Oncology Service, Wills Eye Hospital between July 1, 2000, and April 1, 2019. There were 55 eyes of 32 patients included. At presentation, SD-OCT features included vitreous opacities (n = 36, 65%), preretinal deposits (n = 7, 13%), intraretinal deposits (n = 8, 15%), subretinal deposits (n = 20, 36%), retinal pigment epithelium abnormalities (n = 35, 64%), and subretinal pigment epithelium deposits (n = 35, 64%). Of 36 eyes with observed tumor progression, comparison (initial visit vs. time of progression) revealed more intraretinal deposits (17% vs. 50%, P = 0.005) at progression. Of 15 eyes with tumor recurrence, comparison (initial visit vs. time of recurrence) revealed more intraretinal deposits (7% vs. 47%, P = 0.04) at recurrence. At last visit, 39 eyes demonstrated tumor regression. By comparison (initial presentation vs. regression), there were less frequent vitreous opacities (67% vs. 0%, P < 0.001), intraretinal deposits (15% vs. 0%, P = 0.03), subretinal deposits (36% vs. 0%, P < 0.001), and subretinal pigment epithelium deposits (69% vs. 21%, P < 0.001) at regression. Using SD-OCT in patients with vitreoretinal lymphoma, local tumor regression correlated with a reduction in vitreous opacities, intraretinal deposits, subretinal deposits, and subretinal pigment epithelium deposits. SD-OCT is useful in judging vitreoretinal lymphoma response to therapy.

Association of Clinical and Genetic Heterogeneity With BEST1 Sequence Variations

Detailed phenotypic information on the spectrum of fundus abnormalities and clinical variability of all phenotypes associated with sequence variations in BEST1 is limited. To report a detailed phenotypic and genetic analysis of a patient cohort with sequence variations in BEST1. This retrospective case series took place at the Oxford Eye Hospital in Oxford, UK. Thirty-six patients from a single center with disease-causing sequence variations in BEST1 from 25 different families were analyzed. Data were collected from November 2017 to June 2018, and analysis began April 2018. Results of ocular phenotyping and genetic testing using targeted next-generation sequencing to identify BEST1 sequence variations. Thirty-six patients from 25 families with disease-causing sequence variations in BEST1 were included. Of 36 patients, 20 (55.6%) were female. Three distinct clinical phenotypes were identified: autosomal recessive bestrophinopathy (ARB), best vitelliform macular dystrophy (BVMD), and adult-onset vitelliform macular dystrophy. The ARB phenotype group comprised 18 patients from 9 families with age in years at symptom onset ranging from less than 10 to 40s. All patients showed a common phenotype of fundus autofluorescence abnormalities, and spectral-domain optical coherence tomography features were similar in all patients with schitic and cystoid changes. A phenotype of a beaten metallic retinal appearance extending from the mid periphery to the far periphery was identified in 8 patients. Four patients from 1 family with ARB were previously reported to have autosomal recessive retinitis pigmentosa but were reclassified as having ARB as part of this study. The BVMD phenotype group comprised 16 patients from 14 families with age at symptom onset ranging from less than 10 to 70s. Fundus features were localized to the macula and consistent with the stage of BVMD. In the adult-onset vitelliform macular dystrophy phenotype group, the age in years at symptom onset varied from 50s to 70s in 2 patients from 2 families. Fundus features included small vitelliform lesions. Where available, electro-oculogram results demonstrated a reduced or absent light rise in all patients with ARB and BVMD. Genetic testing identified 22 variants in BEST1. These findings support the notion that ARB, BVMD, and adult-onset vitelliform macular dystrophy are clinically distinct and recognizable phenotypes and suggest that the association of autosomal recessive retinitis pigmentosa with sequence variations in BEST1 should be rereviewed.

Baseline SD-OCT characteristics of diabetic macular oedema patterns can predict morphological features and timing of recurrence in patients treated with dexamethasone intravitreal implants

AimsTo evaluate the timing and spectral-domain optical coherence tomography (SD-OCT) features of diabetic macular oedema (DME) recurrence according to baseline OCT patterns in patients treated with dexamethasone implant (DEX-I).MethodsThis is a retrospective observational study (72 eyes/65 patients). Best-corrected visual acuity, timing of DME recurrence, and SD-OCT pattern [intraretinal cysts (IRC), IRC plus subretinal fluid (mixed), external limiting membrane (ELM), ellipsoid (IS/OS) layer integrity] were assessed at baseline and monthly until first DME recurrence.ResultsForty-two (58.3%) and 30 (41.6%) DME eyes had an IRC and mixed DME pattern at baseline, respectively. Twenty-four out of thirty mixed eyes (80%) relapsed without subretinal fluid. At baseline, mixed eyes showed similar changes in ELM and IS/OS (60 and 76.6% of eyes, respectively) versus IRC eyes (42.8 and 80.9% of eyes). After DME recurrence, more mixed eyes at baseline showed ELM and IS/OS changes (63.3 and 86.6%) than IRC eyes (50 and 76.2%). 33.3% of mixed eyes had DME recurrence at ≥ 6 months from first DEX-I implant versus 19% of IRC eyes.ConclusionsMixed DME eyes were treated with DEX-I relapse later and more frequently without subretinal fluid than IRC eyes. SD-OCT characteristics of different DME patterns at baseline can predict morphological features and timing of DME recurrence.