Optical Coherence Tomography Volume Scans Research Articles

COMPLETE RETINAL PIGMENT EPITHELIAL AND OUTER RETINAL ATROPHY IN AGE-RELATED MACULAR DEGENERATION: A Longitudinal Evaluation.

There is a need for robust earlier biomarkers of atrophic age-related macular degeneration that could act as surrogate endpoints for geographic atrophy (GA) in early interventional trials. This study sought to examine the risk of progression of complete retinal pigment epithelium and outer retinal atrophy (cRORA) to the traditional atrophic endpoint of GA on color fundus photography. This study also compared the risk of progression for cRORA to that associated with the specific optical coherence tomography features that define nascent GA (nGA), a strong predictor of GA development. One hundred forty participants with bilateral large drusen at baseline underwent optical coherence tomography imaging and color fundus photography at 6-month intervals for up to 36 months. Optical coherence tomography volume scans were graded for the presence of cRORA and nGA, and color fundus photographs were graded for the presence of GA. The association and rate of progression to GA for cRORA and nGA were examined. Both cRORA and nGA were significantly associated with GA development (adjusted hazard ratio, 65.7 and 76.8 respectively; both P < 0.001). The probability of progression of cRORA to GA over 24 months (26%) was significantly lower than the probability of progression of nGA (38%; P = 0.039). This study confirmed that cRORA was a significant risk factor for developing GA, although its rate of progression was slightly lower compared with nGA. While requiring replication in future studies, these findings suggest that the specific features of photoreceptor degeneration used to define nGA appear important when assessing the risk of progression.

Deep Learning-Facilitated Study of the Rate of Change in Photoreceptor Outer Segment Metrics in RPGR-Related X-Linked Retinitis Pigmentosa.

The aim of this retrospective cohort study was to obtain three-dimensional (3D) photoreceptor outer segment (OS) metrics measurements with the assistance of a deep learning model (DLM) and to evaluate the longitudinal change in OS metrics and associated factors in retinitis pigmentosa GTPase regulator (RPGR) X-linked retinitis pigmentosa (XLRP). The study included 34 male patients with RPGR-associated XLRP who had preserved ellipsoid zone (EZ) within their spectral-domain optical coherence tomography volume scans and an approximate 2-year or longer follow-up. Volume scans were segmented using a DLM with manual correction for EZ and apical retinal pigment epithelium (RPE). OS metrics were measured from 3D EZ-RPE layers of volume scans. Linear mixed-effects models were used to calculate the rate of change in OS metrics and the associated factors, including baseline age, baseline OS metrics, and follow-up duration. The mean (standard deviation) of progression rates were -0.28 (0.43) µm/y, -0.73 (0.61) mm2/y, and -0.014 (0.012) mm3/y for OS thickness, EZ area, and OS volume, respectively. In multivariable analysis, the progression rates of EZ area and OS volume were strongly associated with their baseline values, with faster decline in eyes with larger baseline values (P ≤ 0.003), and nonlinearly associated with the baseline age (P ≤ 0.003). OS thickness decline was not associated with its baseline value (P = 0.32). These results provide evidence to support using OS metrics as biomarkers to assess the progression of XLRP and as the outcome measures of clinical trials. Given that their progression rates are dependent on their baseline values, the baseline EZ area and OS volume should be considered in the design and statistical analysis of future clinical trials. Deep learning may provide a useful tool to reduce the burden of human graders to analyze OCT scan images and to facilitate the assessment of disease progression and treatment trials for retinitis pigmentosa.

Investigating the associations of macular edema in retinitis pigmentosa

Macular edema (ME), the accumulation of intraretinal fluid in the macula, is a common sight affecting sequelae of retinitis pigmentosa (RP). However, it is unclear why some patients develop ME, and others do not. This study aims to identify associations between clinical-genetic factors in RP with ME. Patients with clinically confirmed RP cases were identified from the inherited retinal disease database at a large tertiary referral academic center. Demographic and genetic testing findings were noted. Additionally, optical coherence tomography volume scans were graded using a validated grading system. One hundred and six patients (73.1%) were found to have ME in at least one eye (OD = 88, mean = 37.9%, OS = 98, mean = 31.7%). Structurally, the presence of epiretinal membrane (ERM) (p < 0.007) and vitreo-macular traction (VMT) (p < 0.003) were significantly associated with ME. Additionally, X-linked (p < 0.032) and autosomal dominant inheritance (p < 0.039) demonstrated a significant association with ME, with RP1 (p < 0.045) and EYS (p < 0.017) pathogenic variants also significantly associated with ME. This study, in a large cohort of RP patients, confirms previous retinal structural associations for ME in RP and identifies potential new genetic associations.

Relative Ellipsoid Zone Reflectivity in Macular Telangiectasia Type 2.

The relative ellipsoid zone reflectivity (rEZR) has been proposed as an innovative biomarker for photoreceptor integrity. This study evaluates the rEZR in macular telangiectasia type 2 (MacTel) eyes of different disease stages. The mean rEZR (ratio ellipsoid zone [EZ]/external limiting membrane [ELM] reflectivity [arbitrary units {AUs}], grey level range = 0-1) was analyzed for an entire spectral domain optical coherence tomography volume scan (global) and for each subfield of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid (topographic) in patients with MacTel and controls. MacTel disease severity was classified according to Gass and Blodi. Linear mixed-model analysis of 145 eyes of 74 patients and 50 eyes of 25 controls revealed globally lower, yet not statistically significant, rEZR values in MacTel eyes. Topographically, most pronounced decreases were found in stages 3 and 4/5 for the temporal inner (coefficient estimates [CEs] = -25.4 [-38.2; -12.6] and -34.1 [-48.7; -19.6] AU, both: P < 0.001), the inferior inner (-29.9 [-44.6; -15.6] and -35.3 [-52.1; -18.5] AU, both: P < 0.001), the nasal inner (-21.5 [-35.52; -7.4] and -31.6 [-47.6; -15.6] AU, P = 0,003 and P < 0.001), and in the superior inner subfield of stage 4/5 (-25.0 [-42.0; -7.9] AU, P = 0.004). The rEZR showed association with disease severity and the predilection area of MacTel. Given the current understanding of the pathophysiological concept of MacTel, these findings underscore the value of the rEZR as a potential novel biomarker for outer retinal integrity. Longitudinal studies are demanded to better characterize its value as a biomarker for early photoreceptor alterations and disease progression in MacTel.

High Variation in Inner Retinal Reflectivity Predicts Poor Visual Outcome in Patients With Central Retinal Vein Occlusion: SCORE2 Report 21.

To assess the association of a novel spectral domain optical coherence tomography biomarker with 6-month visual acuity in in the Study of COmparative Treatments for REtinal Vein Occlusion 2. Spectral domain optical coherence tomography volume scans were evaluated for inner retinal hyperreflectivity, quantified by optical intensity ratio (OIR) and OIR variation. Baseline visual acuity letter score (VALS), baseline OCT biomarkers, and month 1 OIR were correlated with VALS at month 6. Regression trees, a machine learning technique yielding readily interpretable models, were used to assess for variable interaction. Only baseline VALS correlated positively with month 6 VALS in multivariate regression. Regression trees detected a novel functional and anatomical interaction in a subgroup. Among patients with a baseline VALS worse than 43, those with an OIR variation at month 1 of more than 0.09 had a mean of 13 fewer letters of vision at 6 months compared with patients with an OIR variation of 0.09 or less. Baseline VALS was the strongest predictor of month 6 VALS. Regression tree analysis detected an interaction effect, in which higher OIR variation at month 1 predicted worse 6-month VALS in patients with low VALS at baseline. OIR variation may serve as a predictor for poor visual outcome despite treatment of macular edema secondary to retinal vein occlusion in patients with poor vision at baseline. Pixel heterogeneity in three-dimensional OCT data may serve as measure of disruption of the retinal laminations, and this factor may carry visually prognostic value.

447 Characterization of the human iridocorneal angle in vivo using a custom design goniolens with OCT gonioscopy

OBJECTIVES/GOALS: The trabecular meshwork (TM) and Schlemm’s canal (SC), located within the iridocorneal angle (ICA), form the main outflow pathway and a major target for glaucoma treatments. We characterized the human ICA in vivo with Optical Coherence Tomography (OCT) imaging using a customized goniolens and a commercial OCT device (Heidelberg Spectralis). METHODS/STUDY POPULATION: Imaging these structures is difficult due to the optical limitations of imaging through the cornea at high angles. Therefore, a clinical gonioscopy lens was modified with a 12mm plano-convex lens placed on its anterior surface to focus light on the ICA structures, and capture returning light. Each subjects’ eye was anesthetized with 1 drop of Proparacaine 0.5%. The goniolens was coupled to the eye with gonio-gel and it was held by a 3D adjustable mount. OCT volume scans were acquired on 10 healthy subjects. The linear polarization of the OCT was rotated with a half-waveplate to measure dependence of the ICA landmarks on polarization orientation. RESULTS/ANTICIPATED RESULTS: The TM was seen in 9 of 10 subjects. Polarization rotation modified the brightness of the band of extracanalicular limbal lamina (BELL) and corneoscleral bands due to the birefringent nature of the collagenous structures, increasing the contrast of SC. SC width was 99 ± 20µm varying in size over space, including a subject with SC narrowing in the inferior-temporal quadrant. DISCUSSION/SIGNIFICANCE: This clinically suitable gonioscopic OCT approach has successfully been used to image the human ICA in 3D in vivo, providing detailed characterization of the TM and SC as well as enhancing their contrast against their birefringent backgrounds by rotating the polarization of the imaging beam.

OCTA Biomarker Search in Patients with nAMD: Influence of Retinal Fluid on Time-Dependent Biomarker Response

Purpose Previous studies have identified a link between optical coherence tomography (OCT)-derived and OCT angiography (OCTA)-based parameters in patients with neovascular AMD (nAMD); the latter may serve as direct biomarkers for macular neovascularization (MNV) activity. The aim of this study was to assess the individual influence of retinal thickness (RT) as well as intra- and sub-retinal fluid (IRF, SRF) presence on the treatment response over time as assessed by previously identified OCTA-derived MNV vascular parameters. Methods During the first 3 months of anti-VEGF therapy patients were prospectively followed. RT, SRF and IRF were determined from SSOCT/A (PlexElite, Zeiss) images and using the semi-automated AngioTool software, vessel area (VA), total vessel length (TVL), total number of junctions (TNJ), junction density (JD), vessel density (VD) as well as MNV area were exported. IRF and SRF were identified manually on OCT volume scans .The associations between RT, IRF, and SRF and SSOCTA vascular parameters were analyzed using linear mixed models. Results 31 eyes of 31 patients with treatment-naïve and OCTA-positive nAMD MNV were included in this analysis. VA, TVL, TNJ, and MNV area show a statistically significant change over time in response to anti-VEGF treatment, even after correcting for the presence of SRF, IRF, or RT (all p < 0.05). This is not the case for JD and VD (both p > 0.05). Conclusions OCTA-based parameters VA, TVL, TNJ, and MNVarea show a strong response to anti-VEGF therapy over time, independent of the presence of IRF, SRF or RT. We conclude that the above listed OCTA parameters could contribute to our understanding of MNV biology and to guide individualized treatment in the future. Trial registry The authors confirm that all ongoing and related trials are registered. ClinicalTrials.gov Number: NCT02521142

AI-based clinical assessment of optic nerve head robustness superseding biomechanical testing

Background/aimsTo use artificial intelligence (AI) to: (1) exploit biomechanical knowledge of the optic nerve head (ONH) from a relatively large population; (2) assess ONH robustness (ie, sensitivity of the ONH...

Facilitating glaucoma diagnosis with intereye neuroretinal rim asymmetry analysis using spectral-domain optical coherence tomography.

To determine whether intereye asymmetry of a three-dimensional neuroretinal rim parameter, the minimum distance band, is useful in differentiating normal eyes from those with open-angle glaucoma. This is a cross-sectional study of 28 normal subjects and 33 glaucoma subjects. Subjects underwent spectral domain optical coherence tomography imaging of both eyes. From high-density raster scans of the optic nerve head, a custom-designed segmentation algorithm calculated mean minimum distance band neuroretinal rim thickness globally, for four quadrants, and for four sectors. Intereye minimum distance band thickness asymmetry was calculated as the absolute difference in minimum distance band thickness values between the right and left eyes. Increasing global minimum distance band thickness asymmetry was not associated with increasing age or increasing refractive error asymmetry. Glaucoma patients had thinner mean neuroretinal rim thickness values compared to normal patients (209.0 μm vs 306.0 μm [P < 0.001]). Glaucoma subjects had greater intereye thickness asymmetry compared to normal subjects for the global region (51.9 μm vs 17.6 μm [P < 0.001]) as well as for all quadrants and all sectors. For detecting glaucoma, a thickness asymmetry value >28.3 μm in the inferior quadrant yielded the greatest sum of sensitivity (87.9%) and specificity (75.0%). Globally, thickness asymmetry >30.7 μm yielded the greatest sum of sensitivity (66.7%) and specificity (89.3%). This study indicates that intereye neuroretinal rim minimum distance band asymmetry measurements, using high-density spectral domain optical coherence tomography volume scans, may be an objective and quantitative tool for assessing patients suspected of open-angle glaucoma.

Optic disc drusen in patients diagnosed with normal tension glaucoma.

To investigate the prevalence of optic disc drusen (ODD) and optic nerve head (ONH) morphology in patients diagnosed with normal tension glaucoma (NTG). In this prospective cross-sectional study, we included patients diagnosed with NTG from two glaucoma units. In both eyes, dense enhanced depth imaging optical coherence tomography volume scans of the ONH by means of standardized scanning guidelines were performed to examine for presence of ODD, and radial ONH scans were used for investigating parameters such as scleral canal diameter, cup/disc ratio and cup depth. We found ODD in 7 (3.6%) of 195 eyes, in 6 (6.1%) out of 98 patients diagnosed with NTG. The ODD were not ophthalmoscopically visible in five out of six patients. Eyes with ODD had lower cup/disc ratio, 0.44±0.4 (p=0.040), and less-prominent cup depth, 236.6±204.4μm (p=0.041) compared to eyes without ODD, 0.81±0.2 and 437.8±139.1μm, respectively. We found no significant difference in scleral canal diameter between the eyes without (1602.8±193μm) and those with ODD (1492±123.4μm, p=0.057). The prevalence of ODD in patients diagnosed with NTG is substantially higher than in the background population. A low cup/disc ratio correlates with ODD presence. Therefore, due to the challenges associated with NTG diagnosis, we recommend examining the deep layers of the ONH in NTG patients with a cup/disc ratio lower than 0.5 to avoid misdiagnosing ODD as NTG.

Visual Outcomes and Optical Coherence Tomography Biomarkers of Vision Improvement in Patients With Leber Hereditary Optic Neuropathy Treated With Idebenone

To assess the relationship of demographics, clinical characteristics and structural optical coherence tomography (OCT) findings to long-term visual outcomes in patients with Leber hereditary optic neuropathy (LHON) treated with idebenone. Retrospective, interventional, noncomparative clinical cohort study. In this study, a total of 17 participants (34 eyes) with LHON treated with idebenone therapy within 1 year after disease onset and 2 years (24 months) of regular follow-ups were retrospectively enrolled. At baseline, structural OCT volume scans of the macula and optic nerve were reviewed to measure metrics reflecting neuronal loss (ie, macular ganglion cell and inner plexiform layer [GC-IPL] and peripapillary retinal nerve fiber layer [RNFL] thicknesses). Stepwise multiple regression analyses were computed to assess associations between final best-corrected visual acuity (BCVA) at 2 years and change in BCVA from baseline at 2 years as dependent variables with demographics, clinical characteristics, and OCT metrics at baseline (visit before the initiation of treatment). The BCVA was 1.6±0.8 logMAR (Snellen VA of ∼20/800) at baseline (visit before the initiation of treatment) and 1.0±0.7 logMAR (Snellen VA of 20/200) at the 2-year follow-up visit (P < .0001). Mean±SD change in BCVA from baseline at 2 years was -51.9%±35.9%. In multivariable analysis, the strongest associations with final BCVA were with baseline BCVA (P=.012), superior macular GC-IPL thickness (P=.044), superotemporal macular GC-IPL thickness (P=.010), and inferotemporal macular GC-IPL thickness (P=.015). Similarly, the strongest associations with delta BCVA were with superior macular GC-IPL thickness (P=.045), superotemporal macular GC-IPL thickness (P=.047), and inferotemporal macular GC-IPL thickness (P=.030). We identified OCT biomarkers associated with long-term (ie, 2-year) visual outcomes in patients with LHON treated with idebenone therapy in the first year after disease onset. Thinning of the GC-IPL in the superior and temporal parafoveal regions was associated with worse long-term visual outcomes in these patients.

Characteristics of intermediate age-related macular degeneration with hyperreflective foci

Hyperreflective foci (HRF) are the findings observed in optical coherence tomography (OCT) in several retinal diseases and are believed to be associated with the increased risk of atrophy in eyes with age-related macular degeneration (AMD). In this study, we investigated the clinical and genetic characteristics of intermediate AMD with HRF. We reviewed the medical charts for 155 patients with intermediate AMD, in whom macular neovascularization (MNV) was observed in the contralateral eye. The presence or absence of an HRF was evaluated using a spectral-domain OCT volume scan spanning the macular region. Patients were followed longitudinally for at least 12 months, and the maximum follow-up period was 60 months. Genotyping of ARMS2 A69S and CFH I62V was performed in all participants. Of the 155 patients (mean age: 77.8 ± 7.6 years, male/female: 103/52), HRF was observed in 53 eyes (34.2%) and was significantly associated with type-3 MNV (p = 1.0 × 10−5) in the contralateral eye, pseudodrusen (p = 5.0 × 10−4), thinner subfoveal choroidal thickness (p = 0.013), and risk of ARMS2 A69S (p = 0.023). During follow-up (40.8 ± 17.5), 38 eyes (24.5%) developed advanced AMD. The mean time to the onset of advanced AMD was 29.8 ± 12.9 months in eyes with intermediate AMD. HRF was associated with MNV (p = 1.0 × 10−3), but not with atrophy.

Optical Coherence Tomography Biomarkers for Conversion to Exudative Neovascular Age-related Macular Degeneration

To identify optical coherence tomography (OCT) biomarkers, including thin and thick double-layer sign (DLS) for the progression from intermediate AMD (iAMD) to exudative macular neovascularization (MNV) over 24 months. Retrospective cohort study. Setting: Retina consultants of Texas. 458 eyes of 458 subjects with iAMD in at least 1 eye with 24 months of follow-up data. The following biomarkers were assessed at baseline: high central drusen volume (≥0.03 mm3), intraretinal hyper-reflective foci (IHRF), subretinal drusenoid deposits, hyporeflective drusen cores, thick DLS, thin DLS, and central choroidal thickness. A binary logistic regression was computed to investigate the association between baseline OCT covariates and the conversion to exudative MNV within 24 months. In addition, fellow eye status was also included in the model. During follow-up, 18.1% (83 of 458) of eyes with iAMD progressed to exudative MNV. Thick DLS, IHRF, and fellow eye exudative MNV were found to be independent predictors for the development of exudative MNV within 2 years. The baseline frequencies, odds ratios, 95% confidence intervals, and P values for these biomarkers were as follows: thick DLS (9.6%, 4.339, 2.178-8.644; P < .001), IHRF (36.0%, 2.340, 1.396-3.922; P=0.001), and fellow eye exudative MNV (35.8%, 1.694, 1.012-2.837; P=.045). Thick DLS, IHRF, and fellow eye exudative MNV were associated with an increased risk of progression from iAMD to exudative MNV. These biomarkers, which are readily identified by the review of OCT volume scans, may aid in risk prognostication for patients and for identifying patients for early intervention trials.

OCT Macular Volume as a Predictor of Vascular Leakage in Uveitis.

IntroductionThis study aimed to evaluate the optical coherence tomography (OCT) macular volume as a marker for active vascular leakage in patients with intermediate and pan uveitis.MethodsIn this single-center prospective longitudinal study, patients were included under three criteria: diagnosed with noninfectious intermediate or pan uveitis; presented vascular leakage at their initial visit; and were imaged with concurrent wide-field fluorescein angiography (FA) and OCT. A scoring system was employed to measure vascular leakage. OCT volume scans were performed on the patients to produce the corresponding thickness map. The central subfield thickness (CST) and macular volume (MV) were calculated. CST is defined as the average thickness within the 1-mm fovea circle, while MV includes the 3-mm and 6-mm circles on the thickness map. Mixed-effects models were applied to analyze the correlation between each patient’s OCT and FA imaging results.ResultsA total of 72 patients (115 eyes) were included. The median follow-up time was 11 months (interquartile range 1.8–16.1 months). A total of 679 observations across all time points were analyzed. Both CST and MV were found to be positively associated with the leakage scores (p < 0.001). In the mixed-effects models, MV in the 6-mm circle presented the strongest correlation with leakage scores, which explained 57% of the variation in leakage (p < 0.001). MV in the 3-mm circle and CST explained 45.8% and 39.5%, respectively.ConclusionCST and MV in both the 6-mm and the 3-mm circles demonstrated significant correlations with angiographic inflammatory activity. Among those imaging parameters, MV in the 6-mm circle has the highest correlation. The study results suggest that this parameter can be considered a quantitative and non-invasive alternative to FA for monitoring vasculitic inflammation in uveitis.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40123-022-00558-z.

Predicting treat-and-extend outcomes and treatment intervals in neovascular age-related macular degeneration from retinal optical coherence tomography using artificial intelligence.

PurposeTo predict visual outcomes and treatment needs in a treat & extend (T&E) regimen in neovascular age-related macular degeneration (nAMD) using a machine learning model based on quantitative optical coherence tomography (OCT) imaging biomarkers.Materials and methodsStudy eyes of 270 treatment-naïve subjects, randomized to receiving ranibizumab therapy in the T&E arm of a randomized clinical trial were considered. OCT volume scans were processed at baseline and at the first follow-up visit 4 weeks later. Automated image segmentation was performed, where intraretinal (IRF), subretinal (SRF) fluid, pigment epithelial detachment (PED), hyperreflective foci, and the photoreceptor layer were delineated using a convolutional neural network (CNN). A set of respective quantitative imaging biomarkers were computed across an Early Treatment Diabetic Retinopathy Study (ETDRS) grid to describe the retinal pathomorphology spatially and its change after the first injection. Lastly, using the computed set of OCT features and available clinical and demographic information, predictive models of outcomes and retreatment intervals were built using machine learning and their performance evaluated with a 10-fold cross-validation.ResultsData of 228 evaluable patients were included, as some had missing scans or were lost to follow-up. Of those patients, 55% reached and maintained long (8, 10, 12 weeks) and another 45% stayed at short (4, 6 weeks) treatment intervals. This provides further evidence for a high disease activity in a major proportion of patients. The model predicted the extendable treatment interval group with an AUROC of 0.71, and the visual outcome with an AUROC of up to 0.87 when utilizing both, clinical and imaging features. The volume of SRF and the volume of IRF, remaining at the first follow-up visit, were found to be the most important predictive markers for treatment intervals and visual outcomes, respectively, supporting the important role of quantitative fluid parameters on OCT.ConclusionThe proposed Artificial intelligence (AI) methodology was able to predict visual outcomes and retreatment intervals of a T&E regimen from a single injection. The result of this study is an urgently needed step toward AI-supported management of patients with active and progressive nAMD.

Reproducibility of Neuroretinal Rim Measurements Obtained from High-Density Spectral Domain Optical Coherence Tomography Volume Scans.

PurposeTo compare the reproducibility of two-dimensional (2D) peripapillary retinal nerve fiber layer (RNFL) thickness and three-dimensional (3D) neuroretinal rim measurements using spectral domain optical coherence tomography (SDOCT) in normal and glaucoma subjects.MethodsOne eye per subject for 27 normal and 40 glaucoma subjects underwent repeat SDOCT RNFL thickness scans and optic nerve volume scans on the same day. From the volume scan, custom software calculated five neuroretinal rim parameters: 3D minimum distance band (MDB) thickness, 3D MDB area, 3D rim volume, 2D rim area, and 2D rim thickness. Within-subject variance (Sw), coefficient of variation (CV), and intraclass correlation coefficient (ICC) were analyzed.ResultsMDB thickness and RNFL thickness have similar reproducibility among normal and glaucoma subjects (eg, global MDB thickness CVs of 2.4% and 3.6%, and global RNFL thickness CVs of 1.3% and 2.2%; P > 0.05 for both comparisons). Reproducibility of MDB thickness was lower in glaucoma patients for the superior and inferior quadrants compared to normal subjects (CVs of 9.6% versus 3.4% and 6.9% versus 2.7%; P < 0.05, respectively). There were no statistically significant differences between both groups for RNFL thickness in the four quadrants. For both patient groups and for all regions, MDB thickness had the lowest CVs among all five neuroretinal rim parameters (eg, global MDB thickness CVs of 2.4% and 3.6% versus 3.0% and 18.9% for the other four neuroretinal rim parameters).ConclusionGlobal MDB and global RNFL thickness are similarly reproducible among normal and glaucoma subjects, though MDB thickness for the superior and inferior quadrants is less reproducible among glaucoma subjects.

Intracorneal Ring Segment Implantation Results in Corneal Mechanical Strengthening Visualized With Optical Coherence Elastography.

To quantify the mechanical impact of intracorneal ring segment (ICRS) implantation of different dimensions in an ex vivo eye model. A total of 30 enucleated porcine eyes were assigned to ICRS implantation (thickness: 300 µm, angle: 120°, 210°, or 325°), tunnel creation only, or virgin control groups. For mechanical evaluation, each globe was mounted on a customized holder and intraocular pressure (IOP) was increased in steps of 0.5 mm Hg from 15 to 17 mm Hg, simulating physiologic diurnal IOP fluctuations. At each step, an optical coherence tomography volume scan was recorded. Deformations between subsequent scans and the locally induced axial strains were analyzed using a vector-based phase difference method. The effective E-modulus was derived from the overall induced strain as a measure of global mechanical impact. ICRS implantation increased the effective E-modulus from 146 and 163 kPa in virgin and tunnel-only eyes to 149, 192, and 330 kPa in eyes that received a 5-mm optical zone ICRS with 120°, 210°, and 325° arc length, respectively; and to 209 kPa in a 6-mm optical zone ICRS with 325° arc length. The most consistent effect was a shift toward positive strains in the posterior stroma by 0.1% to 0.46% (factor 1.15 to 2.15) after ICRS surgery. ICRS implantation reduces the overall tissue strain under the load of the IOP and provokes posterior tissue relaxation. This effect is more prominent the longer the arc length and the smaller the optical zone of the ICRS is. ICRS have not only a geometrical, but also a mechanical impact on corneal tissue. This behavior might have clinical implications when ICRS implantation is performed in biomechanically weakened keratoconic corneas. [J Refract Surg. 2022;38(7):459-464.].

Corneal Strain Induced by Intracorneal Ring Segment Implantation Visualized With Optical Coherence Elastography.

To record the axial strain field in the cornea directly after creating a stromal tunnel and implanting an intracorneal ring segment (ICRS). Freshly enucleated porcine eyes were obtained and assigned to either ICRS implantation, tunnel creation only, or virgin control groups. Immediately after manual tunnel creation and ICRS positioning, the entire eye globe was mounted on a customized holder and intraocular pressure (IOP) was adjusted to 15 mm Hg. Then, IOP was inreased to 20 mm Hg, in steps of 1 mm Hg. At each step, an optical coherence tomography volume scan was recorded. Displacements between subsequent scans were retrieved using a vector-based phase difference method. The induced corneal strain direction was determined by taking the axial gradient. In addition, corneal surface was detected and sagittal curvature maps computed. Corneal tissue presented a localized compressive strain in the direct vicinity of the stromal tunnel, which was independent of IOP change. The central and peripheral (exterior to the ICRS) cornea demonstrated compressive strains on IOP increase, and tensile strains on IOP decrease. ICRS implantation induced an annular-shaped tensile strain at its inner border, particularly during IOP increase. The compressive strains close to the tunnel remained after ICRS implantation. Corneal curvature changes were concentrated on regions where strain was induced. ICRS implantation induces localized strains in the regions subjected to refractive changes, suggesting that corneal strain and curvature are directly related. Studying corneal strain in response to surgical intervention may provide new insights on underlying working principles. [J Refract Surg. 2022;38(3):210-216.].

Photoreceptor degeneration in ABCA4-associated retinopathy and its genetic correlates.

BACKGROUNDOutcome measures sensitive to disease progression are needed for ATP-binding cassette, sub-family A, member 4–associated (ABCA4-associated) retinopathy. We aimed to quantify ellipsoid zone (EZ) loss and photoreceptor degeneration beyond EZ-loss in ABCA4-associated retinopathy and investigate associations between photoreceptor degeneration, genotype, and age.METHODSWe analyzed 132 eyes from 66 patients (of 67 enrolled) with molecularly confirmed ABCA4-associated retinopathy from a prospective natural history study with a median [IQR] follow-up of 4.2 years [3.1, 5.1]. Longitudinal spectral-domain optical coherence tomography volume scans (37 B-scans, 30° × 15°) were segmented using a deep learning (DL) approach. For genotype-phenotype analysis, a model of ABCA4 variants was applied with the age of criterion EZ-loss (6.25 mm2) as the dependent variable.RESULTSPatients exhibited an average (square-root-transformed) EZ-loss progression rate of [95% CI] 0.09 mm/y [0.06, 0.11]. Outer nuclear layer (ONL) thinning extended beyond the area of EZ-loss. The average distance from the EZ-loss boundary to normalization of ONL thickness (to ±2 z score units) was 3.20° [2.53, 3.87]. Inner segment (IS) and outer segment (OS) thinning was less pronounced, with an average distance from the EZ-loss boundary to layer thickness normalization of 1.20° [0.91, 1.48] for the IS and 0.60° [0.49, 0.72] for the OS. An additive model of allele severity explained 52.7% of variability in the age of criterion EZ-loss.CONCLUSIONPatients with ABCA4-associated retinopathy exhibited significant alterations of photoreceptors outside of EZ-loss. DL-based analysis of photoreceptor laminae may help monitor disease progression and estimate the severity of ABCA4 variants.TRIAL REGISTRATIONClinicalTrials.gov identifier: NCT01736293.FUNDINGNational Eye Institute Intramural Research Program and German Research Foundation grant PF950/1-1.

Semi-Automated Extraction of Lens Fragments via a Surgical Robot Using Semantic Segmentation of OCT Images with Deep Learning - Experimental Results in ex vivo Animal Model.

The overarching goal of this work is to demonstrate the feasibility of using optical coherence tomography (OCT) to guide a robotic system to extract lens fragments from ex vivo pig eyes. A convolutional neural network (CNN) was developed to semantically segment four intraocular structures (lens material, capsule, cornea, and iris) from OCT images. The neural network was trained on images from ten pig eyes, validated on images from eight different eyes, and tested on images from another ten eyes. This segmentation algorithm was incorporated into the Intraocular Robotic Interventional Surgical System (IRISS) to realize semi-automated detection and extraction of lens material. To demonstrate the system, the semi-automated detection and extraction task was performed on seven separate ex vivo pig eyes. The developed neural network exhibited 78.20% for the validation set and 83.89% for the test set in mean intersection over union metrics. Successful implementation and efficacy of the developed method were confirmed by comparing the preoperative and postoperative OCT volume scans from the seven experiments.