Diagnostic Utility of Swept-Source OCT-Based Biometry and Fundus Photographs Compared to Spectral Domain OCT in Center-Involving Diabetic Macular Edema.

PURPOSE: This study was aimed to evaluate the agreement between the swept-source optical coherence tomography (SS-OCT)-based biometry, fundus photographs, and their combination, in comparison to the gold standard spectral-domain optical coherence tomography (SD-OCT) for the detection of center-involving diabetic macular edema (CI-DME). METHODS: We conducted a retrospective cross-sectional study involving 55 subjects (78 eyes) diagnosed with diabetic macular edema (DME) detected clinically and on SD-OCT (Carl Zeiss Meditec AG). Post-mydriatic 45-degree color fundus photograph (Crystal-Vue NFC-700), 1 mm macular scan obtained from SS-OCT-based biometry (IOL-Master 700), and macula cube scan obtained from SD-OCT was used to detect and grade DME into CI-DME and NCI-DME. RESULTS: Our findings revealed that SS-OCT-based biometry was noted to have a high sensitivity of 1 (0.94-1.00) and a specificity of 0.63 (0.31-0.89) in detecting CI-DME compared to the gold standard (SD-OCT). When combined with data from fundus photographs, specificity decreased to 0.32 (0.15-0.53). Fundus photographs alone exhibited a low sensitivity of 0.52 (0.38-0.64) and a specificity of 0.45 (0.16-0.76) in CI-DME detection. CONCLUSION: In conclusion, SS-OCT-based biometry can be used as an effective tool for the detection of CI-DME in diabetic patients undergoing cataract surgery and can serve as a screening tool in centers without SD-OCT facilities.

Diabetic Macular Edema (DME); Center Involving Diabetic Macular Edema (CI-DME); Non-Center Involving Diabetic Macular Edema (NCI-DME); Swept-Source Optical Coherence Tomography (SS-OCT); Spectral-Domain Optical Coherence Tomography (SD-OCT); Anti-Vascular Endothelial Growth Factor (Anti-VEGF); Central Retinal Thickness (CRT); Intra Retinal Fluid (IRF); Sub Retinal Fluid (SRF); Diabetic Retinopathy (DR); Non Proliferative Diabetic Retinopathy (NPDR); Proliferative Diabetic Retinopathy (PDR); Best Corrected Visual Acuity (BCVA); Glycosylated hemoglobin (HbA1c); Mean Spherical Error (MSE); Standard Deviation (SD); Positive Predictive value (PPV); Predictive value (PPV); Negative predictive value (NPV); Area under the Curve (AUC).

Atypical phacolytic glaucoma diagnosed by biometry and anterior segment optical coherence tomography (OCT) in a patient with CMV anterior uveitis.

PURPOSE: To report a case of phacolytic glaucoma with atypical presentation in a patient which was diagnosed with biometry swept source optical coherence tomography (SS-OCT) and anterior segment spectral domain OCT (SD-OCT). METHODS: A 56-year-old male with a history of cytomegalovirus (CMV) chronic anterior uveitis in the right eye presented with a white cataract, minimal anterior chamber reaction and intraocular pressure (IOP) of 56 mmHg. Visual acuity was light perception. The anterior chamber was deep, without evidence of macroscopically visible capsular rupture. A surgical intervention was necessitated with the puzzle being whether to proceed with a trabeculectomy or a combined phaco-trabeculectomy. After a routine preoperative assessment with intraocular lens Master700, the disintegration of the natural lens was noticed. Anterior segment Spectralis OCT confirmed a lamellar separation of the anterior one third of the lens, resembling a poultaceous material. After an uneventful phacoemulsification, visual acuity was 6/6, IOP was well-controlled on maximum topical antiglaucoma treatment and no CMV recurrence was observed. RESULTS: The diagnosis of phacolytic glaucoma was established with the aid of current imaging OCT systems. Both OCT images were suggestive of a phacolytic nature of our case, despite the fact that the clinical presentation was not in concordance with such a typical case. In view of our findings the decision was to proceed with cataract extraction alone. CONCLUSION: This is the first time that we image and document the phacolytic nature of a natural lens. Our patient did not have the typical clinical presentation and was differentially diagnosed with biometry SS-OCT and confirmed by anterior segment SD-OCT.

Rediscovering Age-Related Macular Degeneration with Swept-Source OCT Imaging: The 2022 Charles L. Schepens, MD, Lecture.

PURPOSE: Swept-source OCT angiography (SS-OCTA) scans of eyes with age-related macular degeneration (AMD) were used to replace color, autofluorescence, infrared reflectance, and dye-based fundus angiographic imaging for the diagnosis and staging of AMD. Through the use of different algorithms with the SS-OCTA scans, both structural and angiographic information can be viewed and assessed using both cross sectional and en face imaging strategies. DESIGN: Presented at the 2022 Charles L. Schepens, MD, Lecture at the American Academy of Ophthalmology Retina Subspecialty Day, Chicago, Illinois, on September 30, 2022. PARTICIPANTS: Patients with AMD. METHODS: Review of published literature and ongoing clinical research using SS-OCTA imaging in AMD. MAIN OUTCOME MEASURES: Swept-source OCT angiography imaging of AMD at different stages of disease progression. RESULTS: Volumetric SS-OCTA dense raster scans were used to diagnose and stage both exudative and nonexudative AMD. In eyes with nonexudative AMD, a single SS-OCTA scan was used to detect and measure structural features in the macula such as the area and volume of both typical soft drusen and calcified drusen, the presence and location of hyperreflective foci, the presence of reticular pseudodrusen, also known as subretinal drusenoid deposits, the thickness of the outer retinal layer, the presence and thickness of basal laminar deposits, the presence and area of persistent choroidal hypertransmission defects, and the presence of treatment-naïve nonexudative macular neovascularization. In eyes with exudative AMD, the same SS-OCTA scan pattern was used to detect and measure the presence of macular fluid, the presence and type of macular neovascularization, and the response of exudation to treatment with vascular endothelial growth factor inhibitors. In addition, the same scan pattern was used to quantitate choriocapillaris (CC) perfusion, CC thickness, choroidal thickness, and the vascularity of the choroid. CONCLUSIONS: Compared with using several different instruments to perform multimodal imaging, a single SS-OCTA scan provides a convenient, comfortable, and comprehensive approach for obtaining qualitative and quantitative anatomic and angiographic information to monitor the onset, progression, and response to therapies in both nonexudative and exudative AMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Spectral-Domain and Swept-Source OCT Angiographic Scans Yield Similar Drusen Measurements When Processed with the Same Algorithm.

Purpose: An algorithm developed to obtain drusen area and volume measurements using swept-source OCT angiography (SS-OCTA) scans was tested on spectral-domain OCT angiography (SD-OCTA) scans. Design: Retrospective study. Participants: Forty pairs of scans from 27 eyes with intermediate age-related macular degeneration and drusen. Methods: Patients underwent both SD-OCTA and SS-OCTA imaging at the same visit using the 6 mm × 6 mm OCTA scan patterns. Using the same algorithm, we obtained drusen area and volume measurements within both 3 mm and 5 mm fovea-centered circles. Paired 2-sample t-tests were performed along with Pearson's correlation tests. Main Outcome Measures: Mean square root (sqrt) drusen area and cube root (cbrt) drusen volume within the 3 mm and 5 mm fovea-centered circles. Results: Mean sqrt drusen area values from SD-OCTA and SS-OCTA scans were 1.57 (standard deviation [SD] 0.57) mm and 1.49 (SD 0.58) mm in the 3 mm circle and 1.88 (SD 0.59) mm and 1.76 (SD 0.58) mm in the 5 mm circle, respectively. Mean cbrt drusen volume measurements were 0.54 (SD 0.19) mm and 0.51 (SD 0.20) mm in the 3 mm circle, and 0.60 (SD 0.17) mm and 0.57 (SD 0.17) mm in the 5 mm circle. Small differences in area and volume measurements were found (all P < 0.001); however, the correlations between the instruments were strong (all coefficients > 0.97; all P < 0.001). Conclusions: An algorithm originally developed for SS-OCTA scans performs well when used to obtain drusen volume and area measurements from SD-OCTA scans; thus, a separate SD-OCT structural scan is unnecessary to obtain measurements of drusen. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Hyperreflective Material Boundary Remodeling in Neovascular Age-Related Macular Degeneration: A Post Hoc Analysis of the AVENUE Trial.

OBJECTIVE: To describe the spatial and temporal characteristics of hyperreflective material (HRM) on spectral-domain OCT (SD-OCT) in neovascular age-related macular degeneration (nAMD) during antiangiogenic treatment and explore associations with best-corrected visual acuity (BCVA) and macular atrophy (MA). DESIGN: Retrospective regrading of SD-OCT-images from the multicenter, randomized controlled AVENUE trial (NCT02484690, conducted from August 2015 to September 2017). PARTICIPANTS: Treatment-naive nAMD patients enrolled from 50 sites in the US. METHODS: Retrospective regrading and secondary analysis. MAIN OUTCOME MEASURES: Spectral-domain OCT images from 207 study eyes that fit criteria for the present analysis were graded for HRM features, its evolution, and associated hypertransmission into choroid (HTC), a proxy for MA. The appearance of a well-defined hyperreflective inner boundary that separated persistent HRM from the neurosensory retina continuous with the adjacent retinal pigment epithelium layer was defined as hyperreflective material boundary remodeling (HRM-BR). Patterns of HRM composition/evolution were defined as follows: (1) no subretinal HRM at baseline, (2) fully resolved, (3) persistent with complete HRM-BR, or (4) partial/absent HRM-BR. Associations of HRM patterns with BCVA and HTC were analyzed. Predictive factors for complete HRM-BR were explored. RESULTS: Of 207 included eyes, subretinal HRM was present in 159 (76.8%) at baseline and persisted until month 9 in 118 (57.0%) eyes. Of these 118 eyes, 44.9% developed complete HRM-BR and had similar BCVA outcomes by month 9 compared with no/fully resolved subretinal HRM. Partial/absent HRM-BR had a strong negative association with BCVA outcome (-6.1 ETDRS letters; P = 0.016) and a higher frequency of intralesional HTC (69.2%) compared with eyes with complete HRM-BR (20.8%) at month 9. Older age (odds ratio [OR], 0.96; P = 0.054) and presence of intralesional HTC (OR, 0.06; P = 0.010) at baseline were associated with lower odds of complete HRM-BR at month 9. CONCLUSIONS: In nAMD eyes under antiangiogenic treatment, complete HRM-BR occurred frequently and was associated with better BCVA than when HRM-BR was only partial/absent. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Retinal Nerve Fiber Layer Imaging with Two Different Spectral Domain Optical Coherence Tomographs: Normative Data for Romanian Children.

The purpose of this study is to analyze and compare pediatric normative data for the retinal nerve fiber layer of Romanian children using two different spectral domain optical coherence tomographs. Due to different scanning speeds and axial and transverse resolution, the results of the measurements of scans cannot be transposed. A total of 140 healthy children aged 4 to 18 were enrolled in the study. Overall, 140 eyes were scanned with a Spectralis SD-OCT (Heidelberg Technology), and the other 140 eyes were imaged with a Copernicus REVO SOCT (Optopol Technology (Zawiercie, Poland)). The mean global RNFL thickness and average RNFL thickness for the four quadrants were measured and compared. The average peripapillary RNFL thickness measured with the Spectralis was 104.03 ± 11.42 (range 81 to 126 µm), while the one measured with the Revo 80 was 127.05 ± 15.6 (range 111.43-158.28). The RNFL thickness measurements taken with the Spectralis in the superior, inferior, nasal, and temporal quadrants were 132 ±19.1, 133.5 ± 21.77, 74 ± 16.48, and 73 ± 11.95 µm, respectively, while those taken with the Revo 80 were 144.44 ± 9.25, 144.86 ±23.12, 96.49 ± 19.41, and 77 ± 11.4 µm, respectively. Multivariate analysis showed that the average RNFL thickness was not influenced by gender or eye laterality and was negatively correlated with age when we used the Spectralis device. This study provides normative data for SD-OCT peripapillary RNFL in healthy Romanian children for two different tomographs. These data help the clinician evaluate and interpret the results of optical coherence tomography for a child, taking into consideration all the technical and individual parameters.

Quantitative and Qualitative Assessments of Retinal Structure with Variable A-Scan Rate Spectralis OCT: Insights into IPL Multilaminarity.

The aim of this study was to evaluate the qualitative and quantitative differences between 20 and 85 kHz A-scan rate optical coherence tomography (OCT) images acquired by spectral domain OCT. The study included 60 healthy subjects analyzed with horizontal linear scans with a variable A-scan rate (SHIFT technology, Heidelberg Engineering, Heidelberg, Germany). The retinal thickness measurement of each retinal layer was performed in three different positions (subfoveal, nasal, and temporal). The qualitative assessment was performed by two independent observers who rated every image with a score ranging from 1 ("sufficient") to 3 ("excellent") on the basis of three parameters: visualization of the vitreo-retinal interface, characterization of the retinal layers, and visualization of the sclero-choroidal interface. No statistically significant differences in terms of retinal layer thickness between the two A-scan rate scans were observed (p > 0.05). The coefficient of variation of the retinal thickness values was lower in the 20 kHz group (25.8% versus 30.1% with the 85 kHz). The 20 kHz images showed a higher quality index for both observers. An inner plexiform layer (IPL) multilaminarity was detected in 78.3% of patients from the 20 kHz group and in 40% of patients from the 85 kHz group (p < 0.05).

Validation of an Automated Artificial Intelligence Algorithm for the Quantification of Major OCT Parameters in Diabetic Macular Edema.

Artificial intelligence (AI) and deep learning (DL)-based systems have gained wide interest in macular disorders, including diabetic macular edema (DME). This paper aims to validate an AI algorithm for identifying and quantifying different major optical coherence tomography (OCT) biomarkers in DME eyes by comparing the algorithm to human expert manual examination. Intraretinal (IRF) and subretinal fluid (SRF) detection and volumes, external limiting-membrane (ELM) and ellipsoid zone (EZ) integrity, and hyperreflective retina foci (HRF) quantification were analyzed. Three-hundred three DME eyes were included. The mean central subfield thickness was 386.5 ± 130.2 µm. IRF was present in all eyes and confirmed by AI software. The agreement (kappa value) (95% confidence interval) for SRF presence and ELM and EZ interruption were 0.831 (0.738-0.924), 0.934 (0.886-0.982), and 0.936 (0.894-0.977), respectively. The accuracy of the automatic quantification of IRF, SRF, ELM, and EZ ranged between 94.7% and 95.7%, while accuracy of quality parameters ranged between 99.0% (OCT layer segmentation) and 100.0% (fovea centering). The Intraclass Correlation Coefficient between clinical and automated HRF count was excellent (0.97). This AI algorithm provides a reliable and reproducible assessment of the most relevant OCT biomarkers in DME. It may allow clinicians to routinely identify and quantify these parameters, offering an objective way of diagnosing and following DME eyes.

Macular Telangiectasia Type 2: A Classification System Using MultiModal Imaging MacTel Project Report Number 10.

Purpose: To develop a severity classification for macular telangiectasia type 2 (MacTel) disease using multimodal imaging. Design: An algorithm was used on data from a prospective natural history study of MacTel for classification development. Subjects: A total of 1733 participants enrolled in an international natural history study of MacTel. Methods: The Classification and Regression Trees (CART), a predictive nonparametric algorithm used in machine learning, analyzed the features of the multimodal imaging important for the development of a classification, including reading center gradings of the following digital images: stereoscopic color and red-free fundus photographs, fluorescein angiographic images, fundus autofluorescence images, and spectral-domain (SD)-OCT images. Regression models that used least square method created a decision tree using features of the ocular images into different categories of disease severity. Main Outcome Measures: The primary target of interest for the algorithm development by CART was the change in best-corrected visual acuity (BCVA) at baseline for the right and left eyes. These analyses using the algorithm were repeated for the BCVA obtained at the last study visit of the natural history study for the right and left eyes. Results: The CART analyses demonstrated 3 important features from the multimodal imaging for the classification: OCT hyper-reflectivity, pigment, and ellipsoid zone loss. By combining these 3 features (as absent, present, noncentral involvement, and central involvement of the macula), a 7-step scale was created, ranging from excellent to poor visual acuity. At grade 0, 3 features are not present. At the most severe grade, pigment and exudative neovascularization are present. To further validate the classification, using the Generalized Estimating Equation regression models, analyses for the annual relative risk of progression over a period of 5 years for vision loss and for progression along the scale were performed. Conclusions: This analysis using the data from current imaging modalities in participants followed in the MacTel natural history study informed a classification for MacTel disease severity featuring variables from SD-OCT. This classification is designed to provide better communications to other clinicians, researchers, and patients. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Association of an Objective Structural and Functional Reference Standard for Glaucoma with Quality of Life Outcomes.

PURPOSE: To compare self-reported quality-of-life (QoL) outcomes of patients diagnosed as normal, glaucoma suspect, and glaucoma based on an objective reference standard for glaucomatous optic neuropathy (GON). DESIGN: Cross-sectional study. PARTICIPANTS: 1884 eyes of 1019 patients were included in the study. METHODS: The data was sourced from the Duke Glaucoma Registry. Eyes were classified according to the presence and topographic correspondence of functional and structural damage, as assessed by parameters from standard automated perimetry (SAP) and spectral-domain OCT (SD-OCT). The objective diagnosis of the worse eye was used to define patient-level diagnosis. To assess QoL in the diagnostic groups, 14 unidimensional vision-related items of the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) were used to assess QoL in the diagnostic groups. Association between NEI VFQ-25 Rasch-calibrated scores and diagnostic groups was assessed through multivariable regression that controlled for confounding demographic and socioeconomic variables such as age, sex, race, income, marriage status, insurance status, and highest education level. MAIN OUTCOME MEASURES: NEI VFQ-25 Rasch scores compared with objective criteria diagnosis based on SAP mean deviation (MD) and SD-OCT retinal nerve fiber layer (RNFL) thickness. RESULTS: Overall, eyes classified as normal, glaucoma suspect, and glaucoma had decreasing mean scores in SAP MD (0.2 ± 1.0 dB, -0.9 ± 2.4 dB, -6.2 ± 7.0 dB, respectively; P < 0.001) and SD-OCT RNFL thickness (97.8 ± 9.5 µm, 89.0 ± 13.1 µm, 64.5 ± 12.8 µm, respectively; P < 0.001). The mean Rasch-calibrated NEI VFQ-25 score was significantly different among normal, suspect, and glaucoma groups (82.9 ± 13.0, 78.2 ± 14.8, and 72.6 ± 16.2, respectively; P < 0.001). When adjusted for confounding socioeconomic variables, glaucoma patients had significantly worse QoL than those classified as normal (ß = -6.8 Rasch score units; P < 0.001). CONCLUSION: A glaucoma diagnosis, based on an objective reference standard for GON, was significantly associated with worse Rasch-adjusted scores of QoL. Utilization of such objective criteria may provide clinically relevant metrics with potential to improve comparability of research findings and validation of newly proposed diagnostic tools. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Assessment of the Classification of Age-Related Macular Degeneration Severity from the Northern Ireland Sensory Ageing Study Using a Measure of Dark Adaptation.

Purpose: To assess the differences in rod-mediated dark adaptation (RMDA) between different grades of age-related macular degeneration (AMD) severity using an OCT-based criterion compared with those of AMD severity using the Beckman color fundus photography (CFP)-based classification and to assess the association between the presence of subretinal drusenoid deposits (SDDs) and RMDA at different grades of AMD severity using an OCT-based classification. Design: Cross-sectional study. Participants: Participants from the Northern Ireland Sensory Ageing study (Queen's University Belfast). Methods: Complete RMDA (rod-intercept time [RIT]) data, CFP, and spectral-domain OCT images were extracted. Participants were stratified into 4 Beckman groups (omitting late-stage AMD) and 3 OCT-based groups. The presence and stage of SDDs were identified using OCT. Main Outcome Measures: Rod-intercept time data (age-corrected). Results: Data from 459 participants (median [interquartile range] age, 65 [59-71] years) were stratified by both the classifications. Subretinal drusenoid deposits were detected in 109 eyes. The median (interquartile range) RMDA for the Beckman classification (Beckman 0-3, with 3 being intermediate age-related macular degeneration [iAMD]) groups was 6.0 (4.5-8.7), 6.6 (4.7-10.5), 5.7 (4.4-7.4), and 13.2 (6-21.1) minutes, respectively. OCT classifications OCT0-OCT2 yielded different median (interquartile range) values: 5.8 (4.5-8.5), 8.4 (5.2-13.3), and 11.1 (5.3-20.1) minutes, respectively. After correcting for age, eyes in Beckman 3 (iAMD) had statistically significantly worse RMDA than eyes in the other Beckman groups (P ≤ 0.005 for all), with no statistically significant differences between the other Beckman groups. Similarly, after age correction, eyes in OCT2 had worse RMDA than eyes in OCT0 (P ≤ 0.001) and OCT1 (P < 0.01); however, there was no statistically significant difference between eyes in OCT0 and eyes in OCT1 (P = 0.195). The presence of SDDs was associated with worse RMDA in OCT2 (P < 0.01) but not in OCT1 (P = 0.285). Conclusions: Eyes with a structural definition of iAMD have delayed RMDA, regardless of whether a CFP- or OCT-based criterion is used. In this study, after correcting for age, the RMDA did not differ between groups of eyes defined to have early AMD or normal aging, regardless of the classification. The presence of SDDs has some effect on RMDA at different grades of AMD severity.

Retinal Thickness and Morphology Changes on OCT in Youth with Type 2 Diabetes: Findings from the TODAY Study.

Objective: To evaluate changes in retinal thickness and morphology using OCT in youth with type 2 diabetes (T2D) and to identify systemic biomarkers correlating with these changes. Design: Retrospective subgroup analysis of a prospective study. Participants: Participants who underwent OCT imaging in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) trial and its follow-up study TODAY2. Methods: In 2010-2011 (TODAY) and 2017-2018 (TODAY2), 6 × 6-mm macular volume OCT scans were acquired, segmented, and analyzed to generate total retinal thickness, inner retinal thickness, and outer retinal thickness. The main retinal morphologies graded were intraretinal cystoid spaces, subretinal fluid, and posterior vitreous detachment (PVD). Main Outcome Measures: Changes in total and individual retinal layer thickness and development of abnormal vitreomacular morphology between TODAY and TODAY2. Results: Participants had a mean age of 17.9 ± 2.4 years and glycated hemoglobin (HbA1c) of 8.2 ± 2.8% in TODAY and a mean age of 25.0 ± 2.4 years and mean HbA1c of 9.5 ± 2.8% in TODAY2. Longitudinally between assessments, there were overall decreases in outer retinal thickness from 167.2 ± 11.5 microns to 158.4 ± 12.8 microns (P < 0.001) and in photoreceptor thickness from 30.3 ± 2.9 microns to 29.8 ± 4.1 microns (P = 0.04) in the central subfield, while in the inner subfield, we noted a decrease in outer retinal thickness from 150.5 ± 10.1 microns to 144.9 ± 10.5 microns (P < 0.001) and an increase in inner retinal thickness from 136.9 ± 11.5 microns to 137.4 ± 12.6 microns (P = 0.01). Multivariate analysis showed that in the center subfield, HbA1c increases were associated with increases in total retinal thickness (r: 0.67, P = 0.001), whereas fasting glucose was positively correlated with inner retinal thickness (r: 0.02, P = 0.02). In the inner subfield, both systolic (r: -0.22, P < 0.001) and diastolic (r: -0.22, P = 0.003) blood pressures were negatively correlated with total retinal thickness. There was an increase in PVD (18.9%) and cystoid spaces (4.2%). Conclusions: Youth with T2D develop retinal thickness changes on OCT, including increases in total retinal and inner retinal thickness in the center subfield that correlate with HbA1c and fasting glucose, respectively. Taken together with the increased prevalence of abnormal vitreomacular morphology in this cohort at risk, these findings emphasize the importance of controlling risk factors to prevent the development of sight-threatening retinal complications.

Cotransplantation of Limbal Epithelial and Stromal Cells for Ocular Surface Reconstruction.

Purpose: To propose an improved stem cell-based strategy for limbal stem cell deficiency (LSCD) treatment. Design: Experimental randomized or parallel-group animal study. Subjects: Fifty adult male New Zealand white rabbits. Methods: Human limbal stem/progenitor cells (LSCs) and limbal stromal stem/progenitor cells (LSSCs) were cultured in serum-free conditions and further differentiated into corneal epithelial cells and keratocytes, respectively. All cell types were characterized with lineage-specific markers. Gene expression analysis was performed to identify the potential function of LSSCs in corneal regeneration. Two LSCD models of rabbits for transplantations were used: transplantation performed at the time of limbal and corneal epithelial excision (LSCD model) and transplantation performed after clinical signs were induced in an LSCD model (pLSCD model). The pLSCD model better mimics the pathologic changes and symptoms of human LSCD. Rabbit models received LSC or LSC plus LSSC treatment. Corneal epithelial defects, neovascularization, and opacity were assessed every 3 weeks for 24 weeks. ZsGreen-labeled LSSCs were used for short-term tracking in vivo. Main Outcome Measures: Rates of corneal epithelial defect area, corneal neovascularization and opacity scores, graft survival rate, and immunofluorescence staining of specific markers. Results: Both LSC transplantation and LSC plus LSSC cotransplantation effectively repaired the corneal surface in the LSCD model. These 2 strategies showed no significant differences in terms of graft survival rate or epithelial repair. However, corneal opacity was observed in the LSC group (in 3 of 8 rabbits), but not in the LSC plus LSSC group. Notably, when treating LSCD rabbits with distinguishable stromal opacification and neovascularization, cotransplantation of LSCs and LSSCs exhibited significantly better therapeutic effects than transplantation of LSCs alone, with graft survival rates of 87.5% and 37.5%, respectively. The implanted LSSCs could differentiate into keratocytes during the wound-healing process. RNA sequencing analysis showed that the stromal cells produced not only a collagen-rich extracellular matrix to facilitate reconstruction of the lamellar structure, but also niche factors that accelerated epithelial cell growth and inhibited angiogenesis and inflammation. Conclusions: These findings highlight the support of stromal cells in niche homeostasis and tissue regeneration, providing LSC plus LSSC cotransplantation as a new treatment strategy for corneal blindness.

The APOE E4 Allele Is Associated with Faster Rates of Neuroretinal Thinning in a Prospective Cohort Study of Suspect and Early Glaucoma.

Purpose: To investigate the association between the apolipoprotein E (APOE) E4 dementia-risk allele and prospective longitudinal retinal thinning in a cohort study of suspect and early manifest glaucoma. Design: Retrospective analysis of prospective cohort data. Participants: This study included all available eyes from participants recruited to the Progression Risk of Glaucoma: Relevant SNPs [single nucleotide polymorphisms] with Significant Association (PROGRESSA) study with genotyping data from which APOE genotypes could be determined. Methods: Apolipoprotein E alleles and genotypes were determined in PROGRESSA, and their distributions were compared with an age-matched and ancestrally matched normative cohort, the Blue Mountains Eye Study. Structural parameters of neuroretinal atrophy measured using spectral-domain OCT were compared within the PROGRESSA cohort on the basis of APOE E4 allele status. Main Outcome Measures: Longitudinal rates of thinning in the macular ganglion cell-inner plexiform layer (mGCIPL) complex and the peripapillary retinal nerve fiber layer (pRNFL). Results: Rates of mGCIPL complex thinning were faster in participants harboring ≥1 copies of the APOE E4 allele (ß = -0.13 µm/year; P ≤0.001). This finding was strongest in eyes affected by normal-tension glaucoma (NTG; ß = -0.20 µm/year; P = 0.003). Apolipoprotein E E4 allele carriers were also more likely to be lost to follow-up (P = 0.01) and to demonstrate a thinner average mGCIPL complex (70.9 µm vs. 71.9 µm; P = 0.011) and pRNFL (77.6 µm vs. 79.2 µm; P = 0.045) after a minimum of 3 years of monitoring. Conclusions: The APOE E4 allele was associated with faster rates of mCGIPL complex thinning, particularly in eyes with NTG. These results suggest that the APOE E4 allele may be a risk factor for retinal ganglion cell degeneration in glaucoma.

Longitudinal Evaluation of Visual Function Impairments in Early and Intermediate Age-Related Macular Degeneration Patients.

Purpose: To evaluate visual function (VF) changes in early and intermediate age-related macular degeneration (eAMD and iAMD) over 24 months. Design: Prospective, observational natural history study. Participants: Participants were enrolled at the Duke Eye Center. Methods: A total of 101 subjects (33 with eAMD, 47 with iAMD, and 21 normal controls) were recruited. Visual function (VF) tests included best-corrected visual acuity (BCVA), low- luminance visual acuity (LLVA), microperimetry (MP), cone contrast tests (CCTs), and dark adaptation (DA). Mixed-effect model repeated measures based on absolute values and change from baseline identified VF tests differentiating AMD from controls and revealing longitudinal VF decline when controlling for covariates (baseline value, age, coronary artery disease, dry eye, and phakic status). Nine AMD genetic risk variants, combinations of these (genetic burden score), reticular pseudodrusen (RPD), and hyperreflective foci (HRF) were tested as predictors of diagnosis and VF performance. Main Outcome Measures: Longitudinal changes in VF metrics over 24 months. Results: A total of 70 subjects completed the 2-year visit (22 with eAMD, 31 with iAMD, and 17 controls). Percent reduced threshold (PRT) on MP and CCT red significantly distinguished iAMD versus controls after 12 and 24 months, respectively. Cone contrast test red, PRT, and absolute threshold (AT) on MP showed significant longitudinal deterioration of VF in iAMD versus baseline at 12 months and onward, however, with a reduced rate of worsening. The DA data confirmed a preexisting functional deficit in iAMD at baseline and revealed an increasing proportion of poorly performing iAMD subjects in DA over the study period. None of the other VF measures showed consistent significant changes among the normal, early, and intermediate groups or over time. The genetic burden score was significantly associated with AMD diagnosis (relative risk for iAMD = 1.64, P < 0.01) and DA (r = 0.42, P = 0.00005). Reticular pseudodrusen and HRF showed moderate associations with DA and weak to moderate associations with MP variables. Conclusions: In iAMD, MP variables, CCT red, and DA revealed slow and nonlinear functional decline over 24 months. A structure-function relationship in eAMD and iAMD stages was demonstrated among HRF, RPD, and DA, possibly modified by genetic risk factors. These structural and functional features represent potential end points for clinical trials in iAMD.

Microstructural changes of photoreceptor layers detected by ultrahigh-resolution SD-OCT in patients with autosomal recessive bestrophinopathy.

Purpose: To determine the changes in the microstructures of the photoreceptors in patients with autosomal recessive bestrophinopathy (ARB) by ultrahigh-resolution spectral-domain optical coherence tomography (UHR-SD-OCT). Methods: Five eyes of 4 patients with ARB were studied. Cross-sectional images of the fovea were recorded by the UHR-SD-OCT system with a depth resolution of <2.0 µm. Results: The UHR-SD-OCT images revealed changes in the outer retinal structures that were dependent on the severity of the photoreceptor atrophy. There was an increase in the reflectivity and appearance of small hyperreflective dots (HRDs) in the outer segments, followed by an irregularity and decrease in the length of the outer segments, then a disruption of the ellipsoid zone (EZ) band, and appearance of large HRDs corresponding to the segmented ellipsoids. Finally, there was a disappearance of the large HRDs followed by a localized thinning of the outer nuclear layer and appearance of hyperreflective foci above the region of the disrupted EZ. Conclusions: UHR-SD-OCT can record images that show detailed changes of the microstructures of the photoreceptors at different stages of ARB. These observations should help in determining the mechanisms involved in retinal pathology and should provide important information on the effectiveness of treatments.

Corneal and corneal epithelial thickness distribution characteristics in healthy North Indian eyes using spectral domain optical coherence tomography.

Purpose: To determine the pattern of corneal thickness and epithelial thickness distribution in healthy North Indian eyes by using spectral domain optical coherence tomography (SD-OCT). Methods: The observational study measured total corneal and epithelial thickness in the central 2 mm zone and eight sectors each in paracentral 2-5 mm (ring 1) and midperipheral 5-7 mm (ring 2) zones on SD-OCT. Results: The study included 67 eyes of 67 subjects with a male:female ratio of 32:35 and mean age of 25.04 ± 4.54 years. The mean central corneal and epithelial thicknesses were 505.97 ± 30.12 µm and 60.48 ± 8.37 µm, respectively. The epithelium of inferior and infero-nasal sectors in ring 1 and inferior sector in ring 2 was significantly thicker than the radially opposite sectors of the respective rings (P = 0.001; P = 0.01 and P = 0.02, respectively). Sector-wise analysis did not reveal any significant correlation between the total corneal thickness and epithelial thickness (all P > 0.05) except in the outer superior sector where there was a weak positive correlation (r = 0.28, P = 0.02). Central epithelial thickness in males (60.59 ± 9.28 µm) and females (60.37 ± 7.58 µm) was comparable (P = 0.91). Pachymetry was thinnest in the inferior, inferonasal, and inferotemporal sectors in 44.79% of eyes (n = 30), while thinnest epithelium was seen in the superior, superonasal, and superotemporal quadrants in 50.75% of eyes (n = 34). Conclusion: The epithelial thickness distribution in this sample of topographically normal healthy North Indian eyes was nonuniform and independent of the underlying corneal thickness. Epithelium was thinner in the superior cornea, whereas total corneal thickness was minimum in the inferior part.

Imaging of Classic Dalén Fuchs Nodules in Sympathetic Ophthalmia With Spectral Domain OCT.

Sympathetic ophthalmia (SO) is a rare, severe condition that typically presents as bilateral diffuse granulomatous uveitis secondary to trauma in one eye. The variability of symptoms requires that diagnosis depends heavily on the correlation of these symptoms with relevant imaging. Visualisation of characteristic nodules seen between the Bruchs membrane and the retinal pigment epithelium, and the presence of Dalén Fuchs nodules, can be diagnostic when coupled with the clinical findings. This report discusses the use of spectral domain optical coherence tomography (OCT) to indicate the presence of Dalén Fuchs nodules, which have previously not been identified on OCT in a confirmed case of SO.

Role of spectral domain optical coherence tomography in the diagnosis and prognosis of papilledema.

PURPOSE: The study of papilledema with a novel noninvasive technique such as spectral domain-optical coherence tomography (SD-OCT) provides minute and detailed cross-sectional changes thus giving an insight into the application of biomechanical principles and pathophysiology of disc edema. METHODS: We measured average retinal nerve fiber layer (RNFL) thickness and the retinal pigment epithelium/Bruch's membrane (RPE/BM) angle at the temporal and nasal borders of the neural canal opening (NCO) in 30 eyes with papilledema, 30 eyes with papillitis, and 80 control eyes. The inward angulation was considered as positive and the outward as negative. Follow-up was done at 1, 2, 3, and 6 months. The main outcome measures are the average RNFL thickness and the RPE/BM angle. RESULTS: 29 eyes (96.6%) with papilledema had a positive RPE/BM angle (+8.11 ± 3.13). 29 eyes (96.6%) with papillitis had a negative RPE/BM angle (-1.04 ± 3.27). On follow-up at 1 month, both RNFL thickness (P = 0.01) and RPE-BM angle (P = 0.001) reduced significantly in eyes with papilledema; in eyes with papillitis, there was a significant reduction in the RNFL thickness (P = 0.02), but not in the RPE-BM angle (P > 0.05). RNFL thickness in papilledema cases normalized at 3 months whereas RPE/BM normalized at 6 months of follow-up. To detect papilledema, OCT has a sensitivity of 96.66% and specificity of 99.09% on both nasal and temporal sides. CONCLUSION: After appropriate treatment, the RPE/BM angle in papilledema decreased much later than the RNFL thickness. Hence, the RPE/BM angle in papilledema (positive) can be used to differentiate it from papillitis (negative) and also to monitor the activity of the disease.