Spectral-domain Optical Coherence Tomography Scans Research Articles

Prognostic impact of hyperreflective foci in nonsyndromic retinitis pigmentosa.

To evaluate the prognostic impact of hyperreflective foci (HRF) on spectral-domain optical coherence tomography (SD-OCT) in nonsyndromic retinitis pigmentosa (RP). Retrospective, single-center cohort study including genetically-tested RP patients with a minimum follow-up of 24 months. Clinical data including demographics, genetic results and best-corrected visual acuity (BCVA) at baseline and follow-up were collected. Horizontal and vertical SD-OCT scans were analyzed by 2 independent graders. Outer nuclear layer (ONL) thickness and ellipsoid zone (EZ) width were manually measured in horizontal and vertical scans. HRF were classified according to location: outer retinal layers within the central 3mm (central-HRF), outer retinal layers beyond the central 3mm (perifoveal-HRF), and choroid (choroidal-HRF). Central macular thickness (CMT), central point thickness (CPT) and choroidal thickness (CT) at baseline and follow-up were also recorded. A total of 175 eyes from 94 RP patients (47.9% female, mean age 50.7±15.5 years) were included, with a mean follow-up of 29.24±7.17 months. Mean ETDRS (early treatment diabetic retinopathy study) BCVA decreased from 61.09±23.54 to 56.09±26.65 (p=0.082). At baseline, 72 eyes (41.1%) showed central-HRF, 110 eyes (62.9%) had perifoveal-HRF and 149 eyes (85.1%) exhibited choroidal-HRF. Central-HRF and perifoveal-HRF were associated with worse final BCVA, as well as greater BCVA deterioration (all p<0.0029). Only central-HRF were associated with a worse final CMT (p<0.001). Shorter EZ widths were associated with all types of HRF (p<0.05). Perifoveal and choroidal-HRF predicted smaller final EZ areas (p<0.01). HRF are highly prevalent in RP patients and appear to have a negative prognostic impact in visual function and EZ area.

Internal Carotid Artery Stenosis and Ipsilateral Subretinal Drusenoid Deposits.

Subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are strongly associated with vasculopathies such as myocardial infarction and ischemic stroke. This study evaluates ischemic stroke subjects for SDDs to determine whether ocular hypoperfusion from internal carotid artery (ICA) stenosis is associated with ipsilateral SDDs. A cross-sectional study at Mount Sinai Hospital recruited 39 subjects with ischemic stroke (aged 52-90; 18 women, 21 men); 28 completed all study procedures. Computed tomography (CT) of the head and neck evaluated 54/56 ICAs for stenosis criteria: none (n = 33), mild (n = 12), moderate (n = 3), severe (n = 3), and complete (n = 3). Spectral-domain optical coherence tomography (SD-OCT) scans were read to consensus by two masked graders for soft drusen, SDDs and choroidal thickness (CTh; choroidal thinning = CTh < 250µm). Univariate testing was done with Fisher's exact test. Multivariate logistic regression models tested age, gender, and ICA stenosis as covariates. Moderate or more ICA stenosis (≥50%-69%) was significantly associated with ipsilateral choroidal thinning (P = 0.021) and ipsilateral SDDs (P = 0.005); the latter were present distal to six of nine stenosed ICAs versus five of 33 normal ICAs. Mild ICA stenosis (≥1%-49%) was not significantly associated with ipsilateral SDDs. Multivariate regression found that older age (P = 0.015) and moderate or more ICA stenosis (P = 0.011) remained significant independent risks for ipsilateral SDDs. At least moderate ICA stenosis (≥50%-69%) is strongly associated with ipsilateral SDDs and choroidal thinning, supporting downstream ophthalmic artery and choroidal hypoperfusion from ICA stenosis as the mechanism for SDD formation. SDDs may thus serve as sensitive biomarkers for ischemic stroke and other vascular diseases.

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.

Iron overload and chelation modulates bisretinoid levels in the retina

AimIron dysregulation in conjunction with other disease processes may exacerbate retinal degeneration. We employed models of iron overload and iron chelation to explore the interactions between iron-catalyzed oxidation and photoreactive bisretinoid lipofuscin.MethodsThe mice were injected intravitreally with ferric ammonium citrate (FAC) or were treated using the iron chelator deferiprone (DFP) from birth to 2 months of age. Short-wavelength fundus autofluorescence (SW-AF) and spectral-domain optical coherence tomography (SD-OCT) scans were acquired. The bisretinoid levels were quantified using ultra performance liquid chromatography (UPLC) and in vivo through quantitative fundus autofluorescence (qAF). In histologic sections, the photoreceptor cell viability was assessed by measuring the thickness of the outer nuclear layer (ONL).ResultsThe levels of bisretinoids, all-trans-retinal dimers, and A2PE were significantly increased in the FAC-injected eyes of C57BL/6J mice. Seven days after FAC injection, hyperautofluorescent foci were visible in fundus autofluorescence (488 nm) images, and in SD-OCT scans, aberrant hyperreflectivity was present in the outer retina and ONL thinning was observed. In FAC-injected Abca4–/– mice with pronounced RPE bisretinoid lipofuscin accumulation, the hyperautofluorescent puncta were more abundant than in the wild-type mice, and the extent of ONL thinning was greater. Conversely, the intravitreal injection of FAC in Mertk–/– mice led to a more modest increase in A2PE after 2 days. In contrast to the effect of iron accumulation, chelation with DFP resulted in significantly increased levels of A2E and A2-GPE and qAF due to the reduced iron-catalyzed oxidation of bisretinoids. In Mertk–/– mice, the A2E level was significantly lower and the ONL area was smaller than in DFP-treated mice. DFP chelation did not impair the visual cycle in BALB/cJ mice.ConclusionIron accumulation was associated with progressive impairment in photoreceptor cells that was associated with the increased formation of a bisretinoid species known to form in photoreceptor outer segments as a precursor to A2E. Additionally, disease features such as the development of hyperautofluorescence puncta in fundus AF images, hyperreflectivity in the outer retina of SD-OCT scans, and ONL thinning were more pronounced when iron was delivered to Abca4–/– mice with a greater propensity for bisretinoid formation. Higher bisretinoid levels and enhanced qAF are indicative of lesser bisretinoid loss due to oxidation.

Deep-learning-based automated measurement of outer retinal layer thickness for use in the assessment of age-related macular degeneration, applicable to both swept-source and spectral-domain OCT imaging.

Effective biomarkers are required for assessing the progression of age-related macular degeneration (AMD), a prevalent and progressive eye disease. This paper presents a deep learning-based automated algorithm, applicable to both swept-source OCT (SS-OCT) and spectral-domain OCT (SD-OCT) scans, for measuring outer retinal layer (ORL) thickness as a surrogate biomarker for outer retinal degeneration, e.g., photoreceptor disruption, to assess AMD progression. The algorithm was developed based on a modified TransUNet model with clinically annotated retinal features manifested in the progression of AMD. The algorithm demonstrates a high accuracy with an intersection of union (IoU) of 0.9698 in the testing dataset for segmenting ORL using both SS-OCT and SD-OCT datasets. The robustness and applicability of the algorithm are indicated by strong correlation (r = 0.9551, P < 0.0001 in the central-fovea 3 mm-circle, and r = 0.9442, P < 0.0001 in the 5 mm-circle) and agreement (the mean bias = 0.5440 um in the 3-mm circle, and 1.392 um in the 5-mm circle) of the ORL thickness measurements between SS-OCT and SD-OCT scans. Comparative analysis reveals significant differences (P < 0.0001) in ORL thickness among 80 normal eyes, 30 intermediate AMD eyes with reticular pseudodrusen, 49 intermediate AMD eyes with drusen, and 40 late AMD eyes with geographic atrophy, highlighting its potential as an independent biomarker for predicting AMD progression. The findings provide valuable insights into the ORL alterations associated with different stages of AMD and emphasize the potential of ORL thickness as a sensitive indicator of AMD severity and progression.

Identification of Choroidal Vascular Abnormalities in Patients with Hereditary Hemorrhagic Telangiectasia (HHT)

Purpose: To evaluate the frequency of ocular imaging in patients with HHT at a large academic medical institution; characterize the choroidal vascular changes on indocyanine green angiography (ICGA) and optical coherence tomography (OCT); and explore the relationship of these ocular features with HHT genotypes and systemic manifestations. Methods: Retrospective review of patients with HHT who were seen in the Mayo Clinic ophthalmology department between 2011 to 2021. Results: Of the 71 patients with HHT identified, 7 (10%) individuals had qualifying imaging defined as radial or raster spectral-domain OCT scans and/or ICGA. 4 (57%) patients had enlarged choroidal vessels detected on OCT and/or ICGA. 3 (43%) patients had retinal telangiectasias. Patients with choroidal changes (mean age 67 years) had the endoglin gene mutation, gastrointestinal arteriovenous malformations (AVM), and facial and mucocutaneous telangiectasias. In contrast, patients without choroidal changes (mean age 45 years) included the activin A receptor type-like kinase 1 gene mutation. Conclusion: Only a small proportion of patients with HHT undergo ophthalmic imaging at our institution. The presence of choroidal abnormalities is associated with the endoglin gene mutation, older age, corroborating retinal vascular changes, and increased systemic manifestations.

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.].

Association between Oral Active-Matrix Metalloproteinase-8 Levels and Subretinal Fibrosis among Wet Age-Related Macular Degeneration Patients

Purpose Periodontitis causes low-grade systemic inflammation and has been associated with elevated active-matrix metalloproteinase (aMMP-8) levels, blood-ocular barrier breakdown and a risk of wet age-related macular degeneration. To assess the association between aMMP-8 levels and macular status among patients with wet age-related macular degeneration (AMD). Methods Patients on anti-VEGF treatment for wet AMD were enrolled for oral aMMP-8 rinse test in Mehiläinen Private Hospital, Helsinki, Finland. Macular status was examined from spectral-domain optical coherence tomography (SD-OCT) scans by a medical retina specialist and aMMP-8 levels were analyzed with chairside point-of-care oral rinse (PerioSafe®) test and real-time quantitated by a dentist using the ORALyzer®- reader with a 10 ng/ml cut-off for aMMP-8 activity. Results Elevated aMMP-8 levels were found in 10 out of 32 patients. Age, gender, anti-VEGF (bevacizumab or aflibercept) distribution, cumulative number of anti-VEGF injections and treatment interval were comparable between patients with aMMP-8 levels below and above the point-of-care level. Macular status differed in regard to aMMP-8 activity; among patients with aMMP-8 levels below the point-of-care subretinal fibrosis was found in 6 out of 22 eyes, whereas among patients with aMMP-8 levels above the point-of-care subretinal fibrosis was found in 8 out of 10 eyes (p = 0.005). Respectively, the mean thickness of subretinal fibrosis at fovea was 19.5 ± 44.1 and 92.3 ± 78.3 µm (p = 0.018). No differences were found in the presence and in the area of geographic atrophy, or fluid distribution, whereas thicknesses of serous pigment epithelial detachment (65.5 ± 99.5 and 12.9 ± 27.9 µm, p = 0.038) and neuroretina (204.2 ± 57.8 µm and 143.0 ± 43.7 µm, p = 0.006) were greater in the eyes of patients with physiological aMMP-8 levels compared to those with elevated aMMP-8 levels. Conclusion Elevated aMMP-8 levels may account for subretinal fibrosis formation in wet AMD.

Longitudinal structure-function analysis of molecularly-confirmed CYP4V2 Bietti Crystalline Dystrophy

ObjectivesBietti Crystalline Dystrophy (BCD) is an autosomal recessive progressive retinal disease caused by mutations in CYP4V2. We have characterised the natural history including structural and functional measures to identify potential outcome metrics for future clinical trials.MethodsMolecularly-confirmed BCD patients with biallelic variants in CYP4V2 were retrospectively identified from Moorfields Eye Hospital (UK). Clinical details including results of molecular genetic testing, best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (OCT) scans were extracted. From OCT scans, ellipsoid zone (EZ) measures, foveal thickness of the whole retina, outer retina and choroid were measured. Age-related changes of clinical parameters were assessed with linear mixed models.ResultsTwenty-eight BCD patients were identified, with median age at baseline of 37 years (interquartile range [IQR]: 30–49.5). Median follow-up was 7.7 years (IQR: 3.4–14.5). Most patients (41.7%) showed chorioretinal atrophy at baseline. All OCT parameters showed significant age-related loss (p < 0.05), with EZ measures and choroidal thickness displaying the most rapid degeneration (2.3–3.3% per year vs 0.6–1.5% per year). Median BCVA was 0.2 LogMAR (IQR: 0–0.5) at baseline and showed small age-related loss ( + 0.016 LogMAR per year, p = 0.0019). Patients exhibited substantial phenotypic variability.ConclusionsBCD presents between age 25 and 40, and slowly progresses to an advanced chorioretinal atrophy and vision loss by age 60. BCVA may be preserved until late, and is seemingly poorly representative of disease progression. OCT parameters capturing EZ and choroid changes may afford more suitable trial outcome measures.

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.

Detection and Classification of Diabetic Macular Edema with a Desktop-Based Code-Free Machine Learning Tool.

To evaluate the effectiveness of the Lobe application, a machine learning (ML) tool that can be used on a personal computer without requiring coding expertise, in the recognition and classification of diabetic macular edema (DME) in spectral-domain optical coherence tomography (SD-OCT) scans. A total of 695 cross-sectional SD-OCT images from 336 patients with DME and 200 OCT images of 200 healthy controls were included. Images with DME were classified into three main types: diffuse retinal edema (DRE), cystoid macular edema (CME), and cystoid macular degeneration (CMD). To develop the ML model, we used the desktop-based code-free Lobe application, which includes a pre-trained ResNet-50 V2 convolutional neural network and is available free of charge. The performance of the trained model in recognizing and classifying DME was evaluated with 41 DRE, 28 CMD, 70 CME, and 40 normal SD-OCT images that were not used in the training. The developed model showed 99.28% sensitivity and 100% specificity for class-independent detection of DME. Sensitivity and specificity by labels were 87.80% and 98.57% for DRE, 96.43% and 99.29% for CME, and 95.71% and 95.41% for CMD, respectively. To our knowledge, this is the first evaluation of the effectiveness of Lobe with ophthalmological images, and the results indicate that it can be used with high efficiency in the recognition and classification of DME from SD-OCT images by ophthalmologists without coding expertise.

The Double Layer Sign Is Highly Predictive of Progression to Exudation in Age-Related Macular Degeneration

The presences of a double layer sign (DLS) and a shallow irregular retinal pigment epithelium (RPE) elevation (SIRE) were investigated using spectral domain-OCT (SD-OCT) imaging to determine their ability to predict progression to exudative macular neovascularization (eMNV) in the unaffected fellow eyes (study eye) of participants with age-related macular degeneration (AMD) with newly diagnosed unilateral eMNV. Retrospective, reanalysis of SD-OCT scans of study eyes from the Early Detection of Neovascular AMD (EDNA) study with 3 years follow-up (FU). The EDNA study repository of SD-OCT scans was assessed for inclusion. Cases with incomplete data sets, low quality scans, or exhibiting other pathology were excluded, which resulted in 459 eligible cases. Spectral domain-OCT volume scans of study eyes were graded for irregular elevation of the RPE (IE), with length, and height measurements made on the most affected B-scan. Eyes with heterogeneous reflectivity within the IE were classified as exhibiting the DLS. Eyes with DLS where the length of separation between RPE and Bruch's membrane was ≥ 1000 μm in length and < 100 μm in height were subclassified as SIRE. Hazard of progression to eMNV for DLS and SIRE. Of the 459 eyes, 268 had IE, of which 101 were DLS-like and 51 also fulfilled criteria for SIRE. Over the 3 years FU period, 104 (23%) eyes progressed to eMNV. After an FU of 18 months, a significantly higher proportion of study eyes (P < 0.001) with IE, DLS, and SIRE developed eMNV compared with those without these features (IE: 17% vs. no IE 6.3%; DLS: 23% vs. no DLS 9.9%; SIRE: 22% vs. no SIRE 11%). In the adjusted Cox regression models, a significantly greater hazard of progression (P < 0.001) was associated with the presence of IE (adjusted hazard ratio [HR], 3.01; 95% confidence interval [CI], 1.88-4.82), DLS (adjusted HR, 3.41; 95% CI, 2.26-5.14), or SIRE (adjusted HR, 2.83; 95% CI, 1.68-4.75). The DLS is a highly sensitive predictor of progression to eMNV, and the use of SIRE does not improve predictability. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Evaluating the Effects of C3 Inhibition on Geographic Atrophy Progression from Deep-Learning OCT Quantification: A Split-Person Study.

To evaluate the effect pegcetacoplan, a C3 and C3b inhibitor, on the rate of progression of geographic atrophy (GA) as assessed by spectral domain optical coherence tomography (SD-OCT) using a split-person study design and deep-learning quantification. A post hoc analysis of phase 2 FILLY trial data comparing study (treated monthly, treated every other month and sham-treated) and fellow (untreated) eyes in a split-person study design was performed. This analysis included 288 eyes from 144 patients with bilateral GA from the FILLY phase 2 trial (Clinical Trials identifier: NCT02503332). Only patients with bilateral GA and without evidence of choroidal neovascularisation in either eye were included. Patient study eyes were treated with sham injections or with pegcetacoplan monthly (PM) or every other month (PEOM) for 12months. SD-OCT scans of study and fellow eyes taken at baseline and 12months were used for the analysis. The main outcomes were the annual change in the area of retinal pigment epithelial and outer retinal atrophy (RORA), its constituent features (photoreceptor degeneration [PRD], retinal pigment epithelium [RPE] loss, hypertransmission) and intact macula as compared to the untreated fellow eye. Annual GA growth was reduced in eyes treated with PM versus untreated fellow eyes for OCT features, including RORA (study eye 0.792 vs. fellow eye 1.13 mm2; P = 0.003), PRD (0.739 vs. 1.23 mm2; P = 0.015), RPE-loss (0.789 vs. 1.17 mm2; P = 0.007) and intact macula (- 0.735 vs. - 1.29 mm2; P = 0.011). Similar (but not statistically significant) trends were observed with the PEOM treatment or when GA was quantified with fundus autofluorescence (FAF). The sham treatment demonstrated no effect. Pearson correlation coefficients showed concordance in the enlargement rate of GA between the study and fellow eyes in the sham (R = 0.64) and PEOM (R = 0.68) groups, but not in the PM group (R = 0.21). Pegcetacoplan-treated eyes demonstrated a reduction in spatial GA progression compared to their untreated counterparts. This effect was more evident on OCT than with FAF. Clinical Trials identifier: NCT02503332.

The Choroidal Vascularity Index Versus Optical Coherence Tomography Angiography in the Evaluation of the Choroid with a Focus on Age-Related Macular Degeneration.

The choroid is the most vascularized structure of the eye and it is fundamental for the trophism of the outer retina. Its proper functioning and homeostasis represent key points in maintaining normal retinal physiology. Choroidal alterations may be implicated in the development and progression of numerous pathologies; therefore, in-depth studies using imaging techniques can be of crucial relevance to understanding the pathophysiology of retinal-choroidal diseases. The advent of spectral-domain optical coherence tomography (SDOCT) has enabled the non-invasive study of the choroid in vivo and the most recent development, optical coherence tomography angiography (OCTA), allows for the high-resolution visualization of the choriocapillaris and the choroid in regard to vascularization. The choroidal vascularity index (CVI) is a new parameter calculated on SDOCT scans and is defined as the ratio of the luminal area to the total choroidal area. In this review, a study of the choroid using OCTA and CVI will be evaluated in depth and the pros and cons of these two methods will be analyzed, with a particular focus on age-related macular degeneration.

Rate of Retinal Nerve Fiber Layer Thinning in Glaucomatous Eyes with Optic Disc and Parapapillary Deep-Layer Microvasculature Loss.

Microvasculature dropout in the parapapillary choroidal layer was a more important biomarker of glaucomatous nerve fiber layer thinning when it presented with deep-layer microvasculature of the optic disc rather than when it presents by itself. To characterize open-angle glaucoma (OAG) eyes with optic nerve head (ONH) deep-layer microvasculature dropout (MvD-D) and parapapillary choroidal layer microvasculature dropout (MvD-P) and compare their retinal nerve fiber layer (RNFL) thinning rate. This study included 122 OAG eyes that underwent ≥5 serial spectral-domain optical coherence tomography (OCT) scans during a mean follow-up of 5.4 years. Swept-source OCT angiography (SS-OCTA) was used to evaluate MvD-P and MvD-D. Subjects were classified into three groups according to the presence of MvD-P and MvD-D: (1) no dropout (n=37); (2) solely MvD-P (n=40), and (3) both MvD-P and MvD-D (n=45). The RNFL thinning rate was compared among the three groups, and the associated factors were assessed by Cox proportional hazard analysis. RNFL thinning rates were highest in the group with both MvD-P and MvD-D, followed by the group with solely MvD-P and finally by the no dropout group (-0.24 vs. -0.65 vs. -1.20μm/year, P<0.001). Thinner central corneal thickness (hazard ratio [HR]=0.990, P=0.003), presence of disc hemorrhage (HR=1.802, P=0.035), and coexistence of MvD-P and MvD-D (HR=2.941, P<0.001) were the factors associated with RNFL thinning. The coexistence of MvD-P and MvD-D was associated with faster RNFL thinning than MvD-P alone or no dropout, which suggested that observing the optic disc deep microvasculature along with parapapillary choroidal layer using SS-OCTA may be clinically relevant in monitoring glaucoma progression.

Exudation in Patients With Neovascular Age-Related Macular Degeneration Treated With the Port Delivery System or Monthly Injections

To evaluate for the presence, severity, and type of exudation at each study visit for a subgroup of patients with neovascular age-related macular degeneration from the Archway and Portal trials. Retrospective analysis of prospectively obtained data. Spectral-domain optical coherence tomography scans from each study visit of 44 patients from the Port Delivery System (PDS) arm and 32 patients from the monthly injection arm of Archway were evaluated, and composites of horizontal scans through the fovea were created. Each composite was graded for the presence, type, and severity of exudation and impact on best-corrected visual acuity. After PDS implantation, 20 of 44 eyes (45%) never showed any exudation in the fovea, 2 (5%) never showed exudation in the fovea but had several missed visits, whereas 15 (34%), 3 (7%), and 4 (9%) showed mild, moderate, or severe exudation at 1 or more study visits, respectively. When exudation was present, it was most commonly subretinal fluid (50%). Of 32 patients randomized to monthly injections, 15 (47%) had no exudation in the fovea during monthly injections or after PDS implantation. Fluctuation of exudation in the fovea over time was seen in some patients after PDS implantation or during monthly injections with little or no identifiable impact on best-corrected visual acuity. In the 7 eyes with moderate or severe exudation in the fovea after PDS implantation, final vision was good in 5 (20/25 in 3, 20/40 in 1, and 20/50 in 1) and 2 had reduced vision from submacular hemorrhage. The PDS provides excellent control of exudation in the fovea in patients with neovascular age-related macular degeneration, and when exudation occurs, it often resolves without a negative impact on vision.

Diagnostic Performance of Adding the Optic Nerve Region Assessed by Optical Coherence Tomography to the Diagnostic Criteria for MS.

The optic nerve has been recommended as an additional region for demonstrating dissemination in space (DIS) in diagnostic criteria for multiple sclerosis (MS). To investigate whether adding the optic nerve region as determined by optical coherence tomography (OCT) as part of the DIS criteria improves the 2017 diagnostic criteria. From a prospective observational study, we included patients with a first demyelinating event who had complete information to assess DIS and a spectral-domain OCT scan obtained within 180 days. Modified DIS criteria (DIS+OCT) were constructed by adding the optic nerve to the current DIS regions based on validated thresholds for OCT inter-eye differences. Time to second clinical attack was the primary endpoint. We analyzed 267 MS patients (mean age 31.3 years [SD 8.1], 69% female) during a median observation period of 59 months (range: 13 - 98).Adding the optic nerve as a fifth region improved the diagnostic performance by increasing accuracy (DIS+OCT 81.2% vs. DIS 65.6%,) and sensitivity (DIS+OCT 84.2% vs. DIS 77.9%) without lowering specificity (DIS+OCT 52.2% vs. DIS 52.2%).Fulfilling DIS+OCT criteria (≥2 of 5 DIS+OCT regions involved) indicated a similar risk of a second clinical attack (HR 3.6, CI 1.4 - 14.5) compared to a 2.5-fold increased risk when fulfilling DIS criteria (HR 2.5, CI 1.2 - 11.8).When the analysis was conducted according to topography of the first demyelinating event, DIS+OCT criteria performed similarly in both optic neuritis and non-optic neuritis. Addition of the optic nerve, assessed by OCT, as a fifth region in the current DIS criteria improves diagnostic performance by increasing sensitivity without lowering specificity. This study provides Class II evidence that adding the optic nerve as determined by optical coherence tomography (OCT) as a fifth dissemination in space (DIS) criterion to the 2017 McDonald criteria improves diagnostic accuracy.

A Workflow to Quantitatively Determine Age-Related Macular Degeneration Lesion-Specific Variations in Fundus Autofluorescence.

Fundus autofluorescence (FAF) imaging allows the noninvasive mapping of intrinsic fluorophores of the ocular fundus, particularly the retinal pigment epithelium (RPE), now quantifiable with the advent of confocal scanning laser ophthalmoscopy-based quantitative autofluorescence (QAF). QAF has been shown to be generally decreased at the posterior pole in age-related macular degeneration (AMD). The relationship between QAF and various AMD lesions (drusen, subretinal drusenoid deposits) is still unclear. This paper describes a workflow to determine lesion-specific QAF in AMD. A multimodal in vivo imaging approach is used, including but not limited to spectral domain optical coherence tomography (SD-OCT) macular volume scanning and QAF. Using customized FIJI plug-ins, the corresponding QAF image is aligned with the near-infrared image from the SD-OCT scan (characteristic landmarks; i.e., vessel bifurcations). The foveola and the edge of the optic nerve head are marked in the OCT images (and transferred to the registered QAF image) for accurate positioning of the analysis grids. AMD-specific lesions can then be marked on individual OCT BScans or the QAF image itself. Normative QAF maps are created to account for the varying mean and standard deviation of QAF values throughout the fundus (QAF images from a representative AMD group were averaged to build normative standard retinal QAF AMD maps). The plug-ins record the X and Y coordinates, z-score (a numerical measurement that describes the QAF value in relation to the mean of AF maps in terms of standard deviation from the mean), mean intensity value, standard deviation, and number of pixels marked. The tools also determine z-scores from the border zone of marked lesions.This workflow and the analysis tools will improve the understanding of the pathophysiology and clinical AF image interpretation in AMD.

Choroidal lesions in varicella zoster virus uveitis

To evaluate choroidal lesions with spectral domain optical coherence tomography (SD-OCT) scan in varicella zoster virus (VZV) uveitis.VZV-uveitis cases which underwent OCT scan for choroidal lesions were studied. SD-OCT scan passing through these lesions was studied in detail. Subfoveal choroidal thickness (SFCT) during active and resolved stages was studied. Angiogaphic features were studied where available.Thirteen out of 15 cases had same-sided herpes zoster ophthalmicus skin rashes. All except three patients had old or active kerato-uveitis. All eyes demonstrated clear vitreous and a single or multiple hypopigmented orangish-yellow choroidal lesions. The number of lesions remained unchanged during the follow-up on clinical examination. SD-OCT over lesions (n = 11) showed choroidal thinning (n = 5), hyporeflective choroidal elevation during active inflammation (n = 3), transmission effects (n = 4), and ellipsoid zone disruption (n = 7). The mean change in SFCT (n = 9) after resolution of the inflammation was 26.3 μm (range: 3-90 μm). Fundus fluorescein angiography showed iso-fluorescence over lesions in all (n = 5), but indocyanine green angiography (n = 3) showed hypofluorescence at lesions. Mean follow-up was 1.38 years (range: 3 months-7 years). De-novo appearance of choroidal lesion during the first relapse of VZV-uveitis was captured in one case.VZV-uveitis can cause focal or multifocal hypopigmented choroidal lesions with thickening or scarring of choroidal tissue, depending on the disease activity.

Addition of optic nerve involvement to dissemination in space criteria for multiple sclerosis – the value of optical coherence tomography (S46.009)

Addition of optic nerve involvement to dissemination in space criteria for multiple sclerosis – the value of optical coherence tomography (S46.009)