Search

This study investigates the efficacy of predicting age-related macular degeneration (AMD) activity through deep neural networks (DNN) using a cross-instrument training dataset composed of Optical coherence tomography-angiography (OCTA) images from two different manufacturers. A retrospective cross-sectional study analyzed 2D vascular en-face OCTA images from Heidelberg Spectralis (1478 samples: 1102 training, 276 validation, 100 testing) and Optovue Solix (1003 samples: 754 training, 189 validation, 60 testing). OCTA scans were labeled based on clinical diagnoses and adjacent B-scan OCT fluid information, categorizing activity into normal, dry AMD, active wet AMD, and wet AMD in remission. Experiments explored cross-instrument disease classification using separate and combined datasets for training the DNN. Testing involved 100 Heidelberg and 60 Optovue samples. Training on Heidelberg data alone yielded 73% accuracy on Heidelberg images and 60% on Optovue images. Training on Optovue data alone resulted in 34% accuracy on Heidelberg and 85% on Optovue images. Combined training data from both instruments achieved 78% accuracy on Heidelberg and 76% on Optovue test sets. Results indicate that cross-instrument classifier training demonstrates high classification prediction accuracy, making cross-instrument training viable for future clinical applications. This implies that vascular morphology in OCTA can predict disease progression., (© 2024. The Author(s).)

Purpose: To quantify baseline and longitudinal structural changes post-cessation in patients with pentosan polysulfate sodium retinopathy., Methods: This is a retrospective cohort study. Retinal thickness and volume of choroidal and hyperreflective retinal pigment epithelium excrescences were manually segmented from optical coherence tomography volume scans. Baseline measurements were compared against age-matched control subjects. Longitudinal measurements were performed on patients with follow-up data., Results: Twenty-four eyes of 13 patients were included. At baseline, the mean total retinal thickness was lower in the pentosan polysulfate sodium retinopathy cohort than in age- and sex-matched control subjects (269.1 µ m vs. 290.2 µ m, P = 0.006). The median (range) of follow-up was 18.6 (4.1-34.7) months, with the mean last follow-up of 35.2 months after cessation. During the follow-up period, the thickness of the retina decreased significantly by 11.3 µ m (CI: 16.8, 5.8) ( P < 0.001), with an annual mean decrease of 6.70 µ m. However, the mean hyperreflective retinal pigment epithelium excrescence volume did not change significantly ( P = 0.140) over the follow-up period., Conclusion: After pentosan polysulfate sodium discontinuation, although retinal pigment epithelium excrescence volume do not change significantly, there continues to be a progressive long-term thinning of the retina, which continues at a rate greater than that associated with normal aging. Consequently, long-term follow-up is suggested to monitor patients with pentosan polysulfate sodium retinopathy.

Background and Objective: The purpose of this study was to analyze the safety and efficacy of combined intravitreal anti-vascular endothelial growth factor (anti-VEGF) and steroid therapeutic agents for resistant choroidal neovascularization (CNV). A retrospective observational clinical study was performed assessing anatomic and visual changes in a consecutive cohort of patients with refractory chronic wet age-related macular degeneration resistant to high-dose aflibercept therapy., Patients and Methods: Twelve eyes of 12 patients with unresponsive CNV despite aggressive monthly anti-VEGF (4-mg aflibercept [mean: 43.75 ± SD23.08]) were included. Combination consisted of simultaneous administration of anti-VEGF and corticosteroids. Study measures evaluated visual acuity, central retinal thickness (CRT), and intraocular pressure., Results: Paired tests revealed significant CRT reduction from the baseline at the 1-month (388.58 ± 89.31 versus 334.00 ± 92.88, P = 0.0117), 2-month (388.58 ± 89.31 versus 312.08 ± 75.61, P = 0.0185), and 3-month (388.53 ± 89.31 versus 304.56 ± 53.28, P = 0.046) visit. The Kaplan-Meier curve showed a median time of remission (no retinal fluid) of 70 days (95% CI 53, 147 days)., Conclusion: Combination treatment demonstrated clear anatomic improvement in eyes with anti-VEGF-resistant CNV. [ Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.] .

In this retrospective case series on neovascular age-related macular degeneration (nAMD), we aimed to improve Choroidal Neovascularization (CNV) visualization in Optical Coherence Tomography Angiography (OCTA) scans by addressing segmentation errors. Out of 198 eyes, 73 OCTA scans required manual segmentation correction. We compared uncorrected scans to those with minimal (2 corrections), moderate (10 corrections), and detailed (50 corrections) efforts targeting falsely segmented Bruch's Membrane (BM). Results showed that 55% of corrected OCTAs exhibited improved quality after manual correction. Notably, minimal correction (2 scans) already led to significant improvements, with additional corrections (10 or 50) not further enhancing expert grading. Reduced background noise and improved CNV identification were observed, with the most substantial improvement after two corrections compared to baseline uncorrected images. In conclusion, our approach of correcting segmentation errors effectively enhances image quality in OCTA scans of nAMD. This study demonstrates the efficacy of the method, with 55% of resegmented OCTA images exhibiting enhanced quality, leading to a notable increase in the proportion of high-quality images from 63 to 83%., (© 2024. The Author(s).)

Purpose: This study aimed to compare a new Artificial Intelligence (AI) method to conventional mathematical warping in accurately overlaying peripheral retinal vessels from two different imaging devices: confocal scanning laser ophthalmoscope (cSLO) wide-field images and SLO ultra-wide field images., Methods: Images were captured using the Heidelberg Spectralis 55-degree field-of-view and Optos ultra-wide field. The conventional mathematical warping was performed using Random Sample Consensus-Sample and Consensus sets (RANSAC-SC). This was compared to an AI alignment algorithm based on a one-way forward registration procedure consisting of full Convolutional Neural Networks (CNNs) with Outlier Rejection (OR CNN), as well as an iterative 3D camera pose optimization process (OR CNN + Distortion Correction [DC]). Images were provided in a checkerboard pattern, and peripheral vessels were graded in four quadrants based on alignment to the adjacent box., Results: A total of 660 boxes were analysed from 55 eyes. Dice scores were compared between the three methods (RANSAC-SC/OR CNN/OR CNN + DC): 0.3341/0.4665/4784 for fold 1-2 and 0.3315/0.4494/4596 for fold 2-1 in composite images. The images composed using the OR CNN + DC have a median rating of 4 (out of 5) versus 2 using RANSAC-SC. The odds of getting a higher grading level are 4.8 times higher using our OR CNN + DC than RANSAC-SC (p < 0.0001)., Conclusion: Peripheral retinal vessel alignment performed better using our AI algorithm than RANSAC-SC. This may help improve co-localizing retinal anatomy and pathology with our algorithm., (© 2023. The Author(s).)

Purpose: The authors hypothesize that optical coherence tomography angiography (OCTA)-visualized vascular morphology may be a predictor of choroidal neovascularization status in age-related macular degeneration (AMD). The authors thus evaluated the use of artificial intelligence (AI) to predict different stages of AMD disease based on OCTA en face 2D projections scans., Methods: Retrospective cross-sectional study based on collected 2D OCTA data from 310 high-resolution scans. Based on OCT B-scan fluid and clinical status, OCTA was classified as normal, dry AMD, wet AMD active, and wet AMD in remission with no signs of activity. Two human experts graded the same test set, and a consensus grading between two experts was used for the prediction of four categories., Results: The AI can achieve 80.36% accuracy on a four-category grading task with 2D OCTA projections. The sensitivity of prediction by AI was 0.7857 (active), 0.7142 (remission), 0.9286 (dry AMD), and 0.9286 (normal) and the specificity was 0.9524, 0.9524, 0.9286, and 0.9524, respectively. The sensitivity of prediction by human experts was 0.4286 active choroidal neovascularization, 0.2143 remission, 0.8571 dry AMD, and 0.8571 normal with specificity of 0.7619, 0.9286, 0.7857, and 0.9762, respectively. The overall AI classification prediction was significantly better than the human (odds ratio = 1.95, P = 0.0021)., Conclusion: These data show that choroidal neovascularization morphology can be used to predict disease activity by AI; longitudinal studies are needed to better understand the evolution of choroidal neovascularization and features that predict reactivation. Future studies will be able to evaluate the additional predicative value of OCTA on top of other imaging characteristics (i.e., fluid location on OCT B scans) to help predict response to treatment.

The Ultra-Wide-Field (UWF) retina images have attracted wide attentions in recent years in the study of retina. However, accurate registration between the UWF images and the other types of retina images could be challenging due to the distortion in the peripheral areas of an UWF image, which a 2D warping can not handle. In this paper, we propose a novel 3D distortion correction method which sets up a 3D projection model and optimizes a dense 3D retina mesh to correct the distortion in the UWF image. The corrected UWF image can then be accurately aligned to the target image using 2D alignment methods. The experimental results show that our proposed method outperforms the state-of-the-art method by 30%.

Age-related Macular Degeneration (AMD) is a degenerative eye disease that causes central vision loss. Optical Coherence Tomography Angiography (OCTA) is an emerging imaging modality that aids in the diagnosis of AMD by displaying the pathogenic vessels in the subretinal space. In this paper, we investigate the effectiveness of OCTA from the view of deep classifiers. To the best of our knowledge, this is the first study that solely uses OCTA for AMD stage grading. By developing a 2D classifier based on OCTA projections, we identify that segmentation errors in retinal layers significantly affect the accuracy of classification. To address this issue, we propose analyzing 3D OCTA volumes directly using a 2D convolutional neural network trained with additional projection supervision. Our experimental results show that we achieve over 80% accuracy on a four-stage grading task on both error-free and error-prone test sets, which is significantly higher than 60%, the accuracy of human experts. This demonstrates that OCTA provides sufficient information for AMD stage grading and the proposed 3D volume analyzer is more robust when dealing with OCTA data with segmentation errors.

Background: Retinitis pigmentosa (RP) represents a group of progressive, genetically heterogenous blinding diseases. Recently, relationships between measures of retinal function and structure are needed to help identify outcome measures or biomarkers for clinical trials. The ability to align retinal multimodal images, taken on different platforms, will allow better understanding of this relationship. We investigate the efficacy of artificial intelligence (AI) in overlaying different multimodal retinal images in RP patients., Methods: We overlayed infrared images from microperimetry on near-infra-red images from scanning laser ophthalmoscope and spectral domain optical coherence tomography in RP patients using manual alignment and AI. The AI adopted a two-step framework and was trained on a separate dataset. Manual alignment was performed using in-house software that allowed labelling of six key points located at vessel bifurcations. Manual overlay was considered successful if the distance between same key points on the overlayed images was ≤1/2°., Results: Fifty-seven eyes of 32 patients were included in the analysis. AI was significantly more accurate and successful in aligning images compared to manual alignment as confirmed by linear mixed-effects modelling (p < 0.001). A receiver operating characteristic analysis, used to compute the area under the curve of the AI (0.991) and manual (0.835) Dice coefficients in relation to their respective 'truth' values, found AI significantly more accurate in the overlay (p < 0.001)., Conclusion: AI was significantly more accurate than manual alignment in overlaying multimodal retinal imaging in RP patients and showed the potential to use AI algorithms for future multimodal clinical and research applications., (© 2023 Royal Australian and New Zealand College of Ophthalmologists.)

This cross-sectional study aimed to investigate the hypothesis that permanent capillary damage may underlie the long-term COVID-19 sequela by quantifying the retinal vessel integrity. Participants were divided into three subgroups; Normal controls who had not been affected by COVID-19, mild COVID-19 cases who received out-patient care, and severe COVID-19 cases requiring intensive care unit (ICU) admission and respiratory support. Patients with systemic conditions that may affect the retinal vasculature before the diagnosis of COVID-19 infection were excluded. Participants underwent comprehensive ophthalmologic examination and retinal imaging obtained from Spectral-Domain Optical Coherence Tomography (SD-OCT), and vessel density using OCT Angiography. Sixty-one eyes from 31 individuals were studied. Retinal volume was significantly decreased in the outer 3 mm of the macula in the severe COVID-19 group (p = 0.02). Total retinal vessel density was significantly lower in the severe COVID-19 group compared to the normal and mild COVID-19 groups (p = 0.004 and 0.0057, respectively). The intermediate and deep capillary plexuses in the severe COVID-19 group were significantly lower compared to other groups (p < 0.05). Retinal tissue and microvascular loss may be a biomarker of COVID-19 severity. Further monitoring of the retina in COVID-19-recovered patients may help further understand the COVID-19 sequela., (© 2023. The Author(s).)

Background and Objective: The purpose of this study was to evaluate the accuracy and the time to find a lesion, taken in different platforms, color fundus photographs and infrared scanning laser ophthalmoscope images, using the traditional side-by-side (SBS) colocalization technique to an artificial intelligence (AI)-assisted technique., Patients and Methods: Fifty-three pathological lesions were studied in 11 eyes. Images were aligned using SBS and AI overlaid methods. The location of each color fundus lesion on the corresponding infrared scanning laser ophthalmoscope image was analyzed twice, one time for each method, on different days, for two specialists, in random order. The outcomes for each method were measured and recorded by an independent observer., Results: The colocalization AI method was superior to the conventional in accuracy and time ( P < .001), with a mean time to colocalize 37% faster. The error rate using AI was 0% compared with 18% in SBS measurements., Conclusions: AI permitted a more accurate and faster colocalization of pathologic lesions than the conventional method. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:108-113.] .

Introduction: The aim of this study was to investigate retinal layer thickness and vessel density differences between patients with reticular pseudodrusen (RPD) and intermediate dry age-related macular degeneration (iAMD)., Methods: Participants included in the study were patients diagnosed by retinal specialists with RPD, iAMD, and both RPD and iAMD at our academic referral center, seen from May 2021 until February 2022. The central 3 mm retinal thickness was measured using spectral-domain optical coherence tomography (Heidelberg Spectralis HRA+OCT System; Heidelberg Engineering, Heidelberg, Germany). Individual retinal thickness measurements were obtained from the innermost layer (nerve fiber layer) until the outermost layer (retinal pigment epithelium [RPE]). Each thickness measurement was subdivided into nine Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. For the vessel density, OCT angiography from the Heidelberg Spectralis System was measured using proprietary third-party software (AngioTool; National Institutes of Health, National Cancer Institute, Bethesda, MD). Clinical and demographic characteristics were compared across the three groups (iAMD, RPD, iAMD and RPD) and analyzed with necessary adjustments. Linear mixed-effects models with necessary corrections were employed to compare continuous eye-level measurements between our three groups as well as in pairwise fashion using the R statistical programming software (R version 4.2.1)., Results: A total of 25 eyes of 17 patients with RPD, 20 eyes of 15 patients with iAMD, and 14 eyes of 9 patients with both iAMD and RPD were analyzed. Retinal thickness analysis identified that the superior inner (p = 0.028) and superior outer (p = 0.027) maculas of eyes with both iAMD and RPD were significantly thinner than those with iAMD alone. In eyes with RPD, the superior inner and superior outer RPE (p = 0.011 and p = 0.05, respectively), outer plexiform layer (p = 0.003 and p = 0.013, respectively), and inner nuclear layer (p = 0.034 and p = 0, respectively) were noted to be thinner compared to eyes with iAMD alone. In addition, the macular deep capillary plexus vessel density was significantly reduced in eyes with RPD compared to eyes with iAMD (p = 0.017)., Conclusion: Patients with RPD had inner retinal structural as well as vascular changes compared to iAMD patients. Inner retinal vascular attenuation should be investigated further to see if there is a causal association with retinal thinning., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Late-onset retinal degeneration (L-ORD) is an autosomal dominant macular dystrophy resulting from mutations in the gene CTRP5/C1QTNF5. A mouse model (Ctrp5 +/- ) for the most common S163R developed many features of human clinical disease. We generated a novel homozygous Ctrp5 gene knock-out (Ctrp5 -/- ) mouse model to further study the mechanism of L-ORD. The retinal morphology of these mice was evaluated by retinal imaging, light microscopy, and transmission electron microscopy (TEM) at 6, 11, and 18.5 mo. Expression of Ctrp5 was analyzed using immunostaining and qRT-PCR. The Ctrp5 -/- mice showed lack of both Ctrp5 transcript and protein. Presence of a significantly larger number of autofluorescent spots was observed in Ctrp5 -/- mice compared to the WT (P < 0.0001) at 19 mo. Increased RPE stress with vacuolization and thinning was observed as early as 6 mo in Ctrp5 -/- mice. Further, ultrastructural analyses revealed a progressive accumulation of basal laminar sub-RPE deposits in Ctrp5 -/- mice from 11 mo. The Ctrp5 -/- mice shared retinal and RPE pathology that matches with that previously described for Ctrp5 +/- mice suggesting that pathology in these mice results from the loss of functional CTRP5 and that the presence of CTRP5 is critical for normal RPE and retinal function., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Objective: To develop automated algorithms for the detection of posterior vitreous detachment (PVD) using OCT imaging., Design: Evaluation of a diagnostic test or technology., Subjects: Overall, 42 385 consecutive OCT images (865 volumetric OCT scans) obtained with Heidelberg Spectralis from 865 eyes from 464 patients at an academic retina clinic between October 2020 and December 2021 were retrospectively reviewed., Methods: We developed a customized computer vision algorithm based on image filtering and edge detection to detect the posterior vitreous cortex for the determination of PVD status. A second deep learning (DL) image classification model based on convolutional neural networks and ResNet-50 architecture was also trained to identify PVD status from OCT images. The training dataset consisted of 674 OCT volume scans (33 026 OCT images), while the validation testing set consisted of 73 OCT volume scans (3577 OCT images). Overall, 118 OCT volume scans (5782 OCT images) were used as a separate external testing dataset., Main Outcome Measures: Accuracy, sensitivity, specificity, F1-scores, and area under the receiver operator characteristic curves (AUROCs) were measured to assess the performance of the automated algorithms., Results: Both the customized computer vision algorithm and DL model results were largely in agreement with the PVD status labeled by trained graders. The DL approach achieved an accuracy of 90.7% and an F1-score of 0.932 with a sensitivity of 100% and a specificity of 74.5% for PVD detection from an OCT volume scan. The AUROC was 89% at the image level and 96% at the volume level for the DL model. The customized computer vision algorithm attained an accuracy of 89.5% and an F1-score of 0.912 with a sensitivity of 91.9% and a specificity of 86.1% on the same task., Conclusions: Both the computer vision algorithm and the DL model applied on OCT imaging enabled reliable detection of PVD status, demonstrating the potential for OCT-based automated PVD status classification to assist with vitreoretinal surgical planning., Financial Disclosures: Proprietary or commercial disclosure may be found after the references., (© 2022 Published by Elsevier Inc. on behalf of American Academy of Ophthalmology.)

We previously identified a homozygous G178R mutation in human ASRGL1 ( hASRGL1 ) through whole-exome analysis responsible for early onset retinal degeneration (RD) in patients with cone-rod dystrophy. The mutant G178R ASRGL1 expressed in Cos-7 cells showed altered localization, while the mutant ASRGL1 in E. coli lacked the autocatalytic activity needed to generate the active protein. To evaluate the effect of impaired ASRGL1 function on the retina in vivo, we generated a mouse model with c.578&#95;579insAGAAA (NM&#95;001083926.2) mutation ( Asrgl1 mut/mut ) through the CRISPR/Cas9 methodology. The expression of ASGRL1 and its asparaginase activity were undetectable in the retina of Asrgl1 mut/mut mice. The ophthalmic evaluation of Asrgl1 mut/mut mice showed a significant and progressive decrease in scotopic electroretinographic (ERG) response observed at an early age of 3 months followed by a decrease in photopic response around 5 months compared with age-matched wildtype mice. Immunostaining and RT-PCR analyses with rod and cone cell markers revealed a loss of cone outer segments and a significant decrease in the expression of Rhodopsin , Opn1sw , and Opn1mw at 3 months in Asrgl1 mut/mut mice compared with age-matched wildtype mice. Importantly, the retinal phenotype of Asrgl1 mut/mut mice is consistent with the phenotype observed in patients harboring the G178R mutation in ASRGL1 confirming a critical role of ASRGL1 in the retina and the contribution of ASRGL1 mutations in retinal degeneration.

Multi-modal retinal image registration plays an important role in the ophthalmological diagnosis process. The conventional methods lack robustness in aligning multi-modal images of various imaging qualities. Deep-learning methods have not been widely developed for this task, especially for the coarse-to-fine registration pipeline. To handle this task, we propose a two-step method based on deep convolutional networks, including a coarse alignment step and a fine alignment step. In the coarse alignment step, a global registration matrix is estimated by three sequentially connected networks for vessel segmentation, feature detection and description, and outlier rejection, respectively. In the fine alignment step, a deformable registration network is set up to find pixel-wise correspondence between a target image and a coarsely aligned image from the previous step to further improve the alignment accuracy. Particularly, an unsupervised learning framework is proposed to handle the difficulties of inconsistent modalities and lack of labeled training data for the fine alignment step. The proposed framework first changes multi-modal images into a same modality through modality transformers, and then adopts photometric consistency loss and smoothness loss to train the deformable registration network. The experimental results show that the proposed method achieves state-of-the-art results in Dice metrics and is more robust in challenging cases.

Comparing automated retinal layer segmentation using proprietary software (Heidelberg Spectralis HRA + OCT) and cross-platform Optical Coherence Tomography (OCT) segmentation software (Orion). Image segmentations of normal and diseased (iAMD, DME) eyes were performed using both softwares and then compared to the 'gold standard' of manual segmentation. A qualitative assessment and quantitative (layer volume) comparison of segmentations were performed. Segmented images from the two softwares were graded by two masked graders and in cases with difference, a senior retina specialist made a final independent decisive grading. Cross-platform software was significantly better than the proprietary software in the segmentation of NFL and INL layers in Normal eyes. It generated significantly better segmentation only for NFL in iAMD and for INL and OPL layers in DME eyes. In normal eyes, all retinal layer volumes calculated by the two softwares were moderate-strongly correlated except OUTLY. In iAMD eyes, GCIPL, INL, ONL, INLY, TRV layer volumes were moderate-strongly correlated between softwares. In eyes with DME, all layer volume values were moderate-strongly correlated between softwares. Cross-platform software can be used reliably in research settings to study the retinal layers as it compares well against manual segmentation and the commonly used proprietary software for both normal and diseased eyes., (© 2021. The Author(s).)

Multi-modal retinal image registration between 2D Ultra-Widefield (UWF) and narrow-angle (NA) images has not been well-studied, since most existing methods mainly focus on NA image alignment. The stereographic projection model used in UWF imaging causes strong distortions in peripheral areas, which leads to inferior alignment quality. We propose a distortion correction method that remaps the UWF images based on estimated camera view points of NA images. In addition, we set up a CNN-based registration pipeline for UWF and NA images, which consists of the distortion correction method and three networks for vessel segmentation, feature detection and matching, and outlier rejection. Experimental results on our collected dataset shows the effectiveness of the proposed pipeline and the distortion correction method.

Purpose: To determine structural predictors of treatment response in neovascular age-related macular degeneration analyzing optical coherence tomography (OCT)-related biomarkers., Methods: A retrospective review of patients undergoing treatment for neovascular age-related macular degeneration at a tertiary institute was performed at presentation. High-intensity regimen included eyes on long-term anti-vascular endothelial growth factor treatment with the inability to extend beyond a month without a relapse and needed double the dose of medication (n = 25). Low-intensity regimen had eyes that went into long-term remission after at least three injections and remained dry for more than a year until the last visit (n = 20). Multimodal imaging including fluorescein angiogram, OCT, and comprehensive ocular evaluation were done. Choroidal vascularity index, total choroidal area, luminal area, subfoveal choroidal thickness, choriocapillaris thickness and Haller and Sattler layer thickness were analyzed for statistical significance., Results: The groups had no significant difference at baseline in age, gender, incidence of reticular pseudodrusen, polypoidal choroidal vasculopathy feature on OCT, type of choroidal neovascular membrane, and geographic atrophy. Multinomial logistic regression revealed that thicker subfoveal choroidal thickness and larger total choroidal area were the significant predictors of poor response to anti-vascular endothelial growth factor treatment (E = 0.02; P = 0.02; E = 1.82; P = 0.0075)., Conclusion: Thicker subfoveal choroidal thickness and higher total choroidal area are useful variables to predict a poor treatment response.

Optical Coherence Tomography (OCT) is a powerful technique for non-invasive 3D imaging of biological tissues at high resolution that has revolutionized retinal imaging. A major challenge in OCT imaging is the motion artifacts introduced by involuntary eye movements. In this paper, we propose a convolutional neural network that learns to correct axial motion in OCT based on a single volumetric scan. The proposed method is able to correct large motion, while preserving the overall curvature of the retina. The experimental results show significant improvements in visual quality as well as overall error compared to the conventional methods in both normal and disease cases.

Background/aims: To evaluate the ability of optical coherence tomography angiography (OCTA) to identify the presence or absence of choroidal neovascularisation (CNV) and CNV activity in age-related macular degeneration (AMD)., Methods: Clinical parameters, fundus fluorescein angiogram and spectral-domain optical coherence tomography (SD-OCT) were used as the gold standard to determine disease activity. OCTA imaging was performed on the same day and was graded by two masked retina specialists for the presence or absence of CNV. Traditional multimodal imaging and OCTA findings were compared., Results: One hundred and fifty-two eyes of 106 patients with AMD were retrospectively reviewed. Of these, 59 eyes had wet AMD and 93 had dry AMD with high-risk drusen. OCTA had 85.4% and 79.3% specificity and sensitivity, respectively, in determining the presence or absence of CNV. OCTA was 69.5% accurate in determining active CNV. False positives and negatives were 21.6% and 8.0%, respectively., Conclusions: This study suggests that en-face OCTA images allow a moderate ability to identify CNV and that OCTA alone is weak at recognising active CNV requiring treatment in AMD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Lidocaine gel was suggested to be highly effective in providing anesthesia for intravitreal injections but adverse effects include a possibility of making sterilization of the conjunctiva difficult. Hence, we wished to determine the effect of using 0.5% proparacaine drops alone over the use of 3.5% lidocaine hydrochloride gel anesthesia during office-based intravitreal injections., Methodology: This was a case-control study in patients who came routinely to the clinic for antivascular endothelial growth factor injections. Eyes were treated with one of two anesthesia modalities. A total of 216 injections in 120 patients were reviewed. One group (N = 107) underwent anesthesia with 0.5% proparacaine drops, and the control group (N = 109) received 3.5% lidocaine gel. The pain perceived after injection was graded using the numerical rating scale, and score was immediately recorded by the "masked" injecting physician., Results: The mean pain score (±SD) for the proparacaine-only group versus gel group was 1.97 (±1.17) versus 1.76 (±0.92), P value = 0.3174. There was no statistical difference between the 2 groups., Conclusion: 3.5% lidocaine gel is not superior to 0.5% proparacaine drops as patients attained good pain control and excellent rates of overall satisfaction with proparacaine drops alone.

Purpose: To demonstrate whether pars plana vitrectomy (PPV) changes the progression of dry age-related macular degeneration (AMD) by assessing longitudinal changes in drusen volume over follow-up., Methods: Dry AMD patients who had undergone unilateral PPV for symptomatic vitreomacular disorders were evaluated for the progression of disease by spectral domain-optical coherence tomography (SD-OCT) features including drusen volume, development of geographic atrophy, or choroidal neovascularization during follow-up. Drusen volume was manually calculated using an image processing software (ImageJ, NIH) on raster SD-OCT scans. Mean change in drusen volume of surgery eyes was compared with values of the fellow eyes of the same subjects (control group)., Results: Among 183 eyes with both vitreoretinal disorder and dry AMD, 48 eyes of 24 patients met the inclusion criteria and were included. The mean drusen volume change during a mean of 25.49 ± 23.35 months of follow-up (range: 6.00-86.87 months) was 4.236.899 ± 20.488.913 μm 3 in the study eye and 7.796.357 ± 34.798.519 μm 3 in the fellow eye (p = 0.297). Best-corrected visual acuity (BCVA) significantly increased from 0.40 ± 0.18 logMAR (≈ 20/50 Snellen equivalent) to 0.32 ± 0.31 (≈ 20/41 Snellen equivalent) after surgery (p = 0.012) in the study group while BCVA remained stable in the control group (0.19 ± 0.34 logMAR [≈ 20/30 Snellen equivalent] at baseline and 0.20 ± 0.31 logMAR [≈ 20/31 Snellen equivalent], p = 0.432). Choroidal neovascularization developed in 1 vitrectomized eye (4.54%) and in 1 eye (4.54%) from the control group during follow-up., Conclusion: Vitrectomy did not seem to worsen dry AMD progression; even more visual acuity may improve despite a slight increase in drusen volume following surgery.

Multimodal retinal imaging plays an important role in ophthalmology. We propose a content-adaptive multimodal retinal image registration method in this paper that focuses on the globally coarse alignment and includes three weakly supervised neural networks for vessel segmentation, feature detection and description, and outlier rejection. We apply the proposed framework to register color fundus images with infrared reflectance and fluorescein angiography images, and compare it with several conventional and deep learning methods. Our proposed framework demonstrates a significant improvement in robustness and accuracy reflected by a higher success rate and Dice coefficient compared with other methods.

Purpose: The purpose of this study was to evaluate the ability to align two types of retinal images taken on different platforms; color fundus (CF) photographs and infrared scanning laser ophthalmoscope (IR SLO) images using mathematical warping and artificial intelligence (AI)., Methods: We collected 109 matched pairs of CF and IR SLO images. An AI algorithm utilizing two separate networks was developed. A style transfer network (STN) was used to segment vessel structures. A registration network was used to align the segmented images to each. Neither network used a ground truth dataset. A conventional image warping algorithm was used as a control. Software displayed image pairs as a 5 × 5 checkerboard grid composed of alternating subimages. This technique permitted vessel alignment determination by human observers and 5 masked graders evaluated alignment by the AI and conventional warping in 25 fields for each image., Results: Our new AI method was superior to conventional warping at generating vessel alignment as judged by masked human graders ( P < 0.0001). The average number of good/excellent matches increased from 90.5% to 94.4% with AI method., Conclusions: AI permitted a more accurate overlay of CF and IR SLO images than conventional mathematical warping. This is a first step toward developing an AI that could allow overlay of all types of fundus images by utilizing vascular landmarks., Translational Relevance: The ability to align and overlay imaging data from multiple instruments and manufacturers will permit better analysis of this complex data helping understand disease and predict treatment., Competing Interests: Disclosure: M. Cavichini, None; C. An, None; D.-U.G. Bartsch, None; M. Jhingan, None; M.J. Amador-Patarroyo, None; C.P. Long, None; J. Zhang, None; Y. Wang, None; A.X. Chan, None; S. Madala, None; T. Nguyen, None; W.R. Freeman, None, (Copyright 2020 The Authors.)

Purpose: Subretinal prostheses are a novel technology for restoring useful vision in patients with retinitis pigmentosa or age-related macular degeneration. We characterize the surgical implantation technique and functional time window of an acute rabbit eye model for testing of human subretinal prostheses., Methods: Retinal prostheses were implanted subretinally in 26 rabbits using a two-step technique. Fundus imaging, fluorescein fundus angiography, and optical coherence topography (OCT) were conducted postoperatively from days 1 to 21 to monitor prosthesis positioning and retinal anatomic changes., Results: Successful implantation and excellent retina apposition were achieved in 84.6% of the rabbits. OCTs showed the overlying retina at full thickness for the first 2 days after implantation. Histology confirmed intact inner layers of the overlying retina until day 3. Progressive atrophy of the overlying retina was revealed by repeated OCTs; approximately 40% of the retina thickness remained on postoperative days 5 and 6., Conclusions: The two-step implantation technique works well for the rabbit eye model with human prostheses. Rabbit retina may be used for acute electrophysiologic testing of a retinal prosthesis, but is unsuitable for chronic studies due to the merangiotic retina and its limited time window of validity., Translational Relevance: The improved efficacy in prosthesis surgery using this technique will circumvent the challenges in animal models that provide human-like features critical for the transition into human clinical trials., (Copyright 2019 The Authors.)

Purpose: To assess early retinal microvascular and functional changes in diabetic patients without clinical evidence of diabetic retinopathy with optical coherence tomography angiography and central visual analyzer., Methods: This was an observational case-control study of diabetic patients without diabetic retinopathy and nondiabetic controls. Patients underwent optical coherence tomography angiography imaging and visual acuity testing using the central visual analyzer. The foveal avascular zone area and the capillary density in the superficial and deep capillary plexuses were measured manually by a masked grader., Results: Sixty eyes from 35 diabetic patients were included in the study group, and 45 eyes from 31 nondiabetic patients were included in the control group. The foveal avascular zone area was not significantly different between the diabetic group and controls (both P > 0.05). The mean capillary density in the deep capillary plexus was significantly lower in diabetic eyes compared with control eyes (P = 0.04). The mean visual acuity in all central visual analyzer modules was significantly decreased in diabetic patients compared with controls (all P < 0.05)., Conclusion: Optical coherence tomography angiography was able to detect retinal microvascular changes in the deep capillary plexus, and the central visual analyzer showed signs of decreased visual acuity under conditions simulating suboptimal contrast and glare in diabetic patients without diabetic retinopathy.

Purpose: To evaluate depth of field, lateral resolution, and image quality of a heads-up 3D visualization system for vitreoretinal surgery using physician survey and optical measurement outcomes., Methods: Depth of field and lateral resolution were compared between the standard ocular viewing system and the digital 3D system at ×5, ×13, and ×18 magnification by 6 retinal surgeons. Optical techniques were used as well as a survey of surgeon impression. Surgeon impression surveys were performed after 6 weeks of surgical use of the device., Results: Physician questionnaire survey scores for depth of field at high magnification were better for the digital 3D system and equivalent for all other categories. Measured lateral resolution was 36.7 mm and 16.6 mm at ×5 magnification (P < 0.001), 14.3 mm and 6.4 mm at ×13 magnification (P < 0.001), and 9.8 mm and 4.2 mm (P < 0.001) at ×18 magnification for the digital 3D and oculars, respectively. Measured depth of field was 4.00 mm and 6.78 mm at ×5 magnification (P = 0.027), 0.72 mm and 0.86 mm at ×13 (P = 0.311), and 0.28 mm and 0.40 mm at ×18 magnification (P = 0.235) for the oculars and digital 3D, respectively., Conclusion: Lateral resolution of the digital 3D system was half that of the ocular viewing system and there was some improvement in depth of field with the digital system. Surgeon impression suggested that the digital system was superior when evaluating depth of field at high magnification.

Purpose: To compare retinal pathology visualization in multispectral scanning laser ophthalmoscope imaging between the Spectralis and Optos devices., Methods: This retrospective cross-sectional study included 42 eyes from 30 patients with age-related macular degeneration (19 eyes), diabetic retinopathy (10 eyes), and epiretinal membrane (13 eyes). All patients underwent retinal imaging with a color fundus camera (broad-spectrum white light), the Spectralis HRA-2 system (3-color monochromatic lasers), and the Optos P200 system (2-color monochromatic lasers). The Optos image was cropped to a similar size as the Spectralis image. Seven masked graders marked retinal pathologies in each image within a 5 × 5 grid that included the macula., Results: The average area with detected retinal pathology in all eyes was larger in the Spectralis images compared with Optos images (32.4% larger, P < 0.0001), mainly because of better visualization of epiretinal membrane and retinal hemorrhage. The average detection rate of age-related macular degeneration and diabetic retinopathy pathologies was similar across the three modalities, whereas epiretinal membrane detection rate was significantly higher in the Spectralis images., Conclusion: Spectralis tricolor multispectral scanning laser ophthalmoscope imaging had higher rate of pathology detection primarily because of better epiretinal membrane and retinal hemorrhage visualization compared with Optos bicolor multispectral scanning laser ophthalmoscope imaging.

Patients harboring homozygous c.498&#95;499insC mutations in MFRP demonstrate hyperopia, microphthalmia, retinitis pigmentosa, retinal pigment epithelial atrophy, variable degrees of foveal edema, and optic disc drusen. The disease phenotype is variable, however, with some patients maintaining good central vision and cone function till late in the disease. A knock-in mouse model with the c.498&#95;499insC mutation in Mfrp ( Mfrp KI/KI) was developed to understand the effects of these mutations in the retina. The model shares many of the features of human clinical disease, including reduced axial length, hyperopia, retinal degeneration, retinal pigment epithelial atrophy, and decreased electrophysiological responses. In addition, the eyes of these mice had a significantly greater refractive error ( p  < 0.01) when compared to age-matched wild-type control animals. Administration of recombinant adeno-associated virus-mediated Mfrp gene therapy significantly prevented thinning from retinal neurodegeneration ( p  < 0.005) and preserved retinal electrophysiology ( p  < 0.001) when treated eyes were compared to contralateral sham-treated control eyes. The Mfrp KI/KI mice will serve as a useful tool to model human disease and point to a potential gene therapeutic approach for patients with preserved vision and electrophysiological responses in MFRP -related retinopathy.

Purpose: To demonstrate factors related to the presence of subfoveal detachment (SD) secondary to epiretinal membrane (ERM) and to characterize the predictors for the resolution of SD after membrane peeling., Methods: A retrospective chart review was conducted for the patients who underwent pars plana vitrectomy for the idiopathic ERM peeling. Preoperative spectral domain optical coherence tomography characteristics of the eyes including central foveal thickness, foveal center point thickness, presence of intraretinal cyst, continuity of the membrane, area of the membrane within fovea (1 mm), and entire macula (6 mm) were evaluated to find the best predictors for the presence of SD. These predictors as well as perioperative parameters including use of internal tamponade and volume of SD were considered for time of resolution of SD., Results: Of 158 included eyes, 20.2% eyes (32 eyes) had SD, and the presence of SD was significantly related to involvement of the membrane within the macula. After surgery, SD completely resolved in 90.6% of eyes (29 eyes) at a median of 2.97 months (range: 0.03-12.0 months). The area of the membrane within fovea was the only significant predictor for time to resolution of SD (hazard ratio = 1.20, 95% confidence interval = 1.100-1.324, P = 0.021). A small percent of eyes showed some further changes including fluctuation (6.2%) or persistence (3.1%) of fluid., Conclusion: A larger extension of ERM over the macula is related to higher likelihood of the presence of SD. Time for resolution of subfoveal detachment does not seem to be affected by the preoperative and perioperative factors except the extent of membrane within 1,000 μm of the fovea.

Purpose: For more than 20 years, there has been an international, multidisciplinary effort to develop retinal prostheses to restore functional vision to patients blinded by retinal degeneration. We developed a novel subretinal prosthesis with 1512 optically addressed silicon nanowire photodiodes, which transduce incident light into an electrical stimulation of the remaining retinal circuitry. This study was conducted to evaluate the efficacy of optically driving the subretinal prosthesis to produce visual cortex activation via electrical stimulation of the retina., Methods: We measured electrically evoked potential responses (EEPs) in rabbit visual cortex in response to illumination of the subretinal nanowire prosthesis with pulsed 852-nm infrared (IR) light. We compared the EEP responses to visually evoked potential responses (VEPs) to pulsed 532-nm visible light (positive control) and pulsed 852-nm IR light (negative control)., Results: Activating the devices with IR light produced EEP responses with a significantly higher trough-to-peak amplitude (54.17 ± 33.4 μV) than IR light alone (24.07 ± 22.1 μV) or background cortical activity (23.22 ± 17.2 μV). EEP latencies were significantly faster than focal VEP latencies. Focal VEPs produced significantly higher amplitudes (94.88 ± 43.3 μV) than EEPs. We also demonstrated how an electrode placed on the cornea can be used as a noninvasive method to monitor the function of the implant., Conclusions: These results show that subretinal electrical stimulation with nanowire electrodes can elicit EEPs in the visual cortex, providing evidence for the viability of a subretinal nanowire prosthetic approach for vision restoration.

Purpose: Geographic atrophy (GA) is the sequelae of macular degeneration. Automated inner retinal analysis using optical coherence tomography is flawed because segmentation software is calibrated for normal eyes. The purpose of this study is to determine whether ganglion cell layer (GCL) volume is reduced in GA using manual analysis., Methods: Nineteen eyes with subfoveal GA and 22 controls were selected for morphometric analyses. Heidelberg scanning laser ophthalmoscope optical coherence tomography images of the optic nerve and macula were obtained, and the Viewing Module was used to manually calibrate retinal layer segmentation. Retinal layer volumes in the central 3-mm and surrounding 6-mm diameter were measured. Linear mixed models were used for statistics., Results: The GCL volume in the central 3 mm of the macula is less (P = 0.003), and the retinal nerve fiber layer volume is more (P = 0.02) in patients with GA when compared with controls. Ganglion cell layer volume positively correlated with outer nuclear layer volume (P = 0.020)., Conclusion: The patients with geographic atrophy have a small significant loss of the GCL. Ganglion cell death may precede axonal loss, and increased macular retinal nerve fiber layer volumes are not indicative of GCL volume. Residual ganglion cell stimulation by interneurons may enable vision in patients with GA.

Purpose: To characterize inner retinal damage in patients with dry age-related macular degeneration (AMD) using high-resolution spectral domain optical coherence tomography images., Methods: Sixty eyes of 60 patients with AMD were categorized using the Age-Related Eye Disease Study (AREDS) severity scale. Spectral domain optical coherence tomography images of these patients were quantified by manually correcting the segmentation of each retinal layer, including the retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer to ensure accurate delineation of layers. The mean ganglion cell complex thickness values (ganglion cell layer + inner plexiform layer + retinal nerve fiber layer) were compared with 30 eyes of 30 healthy subjects., Results: Ninety percent of eyes (81 eyes) required manual correction of segmentation. Compared with healthy subjects, mean ganglion cell complex thicknesses significantly decreased in more advanced dry AMD eyes, and this decrease was predominantly related to a change in inner plexiform layer thickness. There was no significant difference in thickness-related measurements between milder dry AMD (AREDS-2) eyes and healthy eyes (P > 0.05)., Conclusion: In patients with dry AMD, automatic optical coherence tomography segmentation algorithms may be erroneous. As the severity of dry AMD increases, the inner plexiform layer layer becomes thinned, suggesting that transsynaptic degeneration may be occurring, as the photoreceptor layer is affected by AMD.

Purpose: Our purpose was to compare the characteristics of the retinal and choroidal lesions including choroidal nevus, choroidal melanoma and congenital hypertrophy of the retina pigment epithelium using conventional color fundus photography (CFP) and multicolor imaging (MCI)., Methods: The paired images of patients with retinal or choroidal lesions were assessed for the visibility of lesion's border, halo and drusen using a grading scale (0-2). The area of the lesion was measured on both imaging modalities. The same grading was also done on the individual color channels of MCI for a further evaluation., Results: Thirty-three eyes of 33 patients were included. There were no significant differences in the mean border, drusen and halo visibility scores between the two imaging modalities (p = 0.12, p = 0.70, p = 0.35). However, the mean area of the lesion was significantly smaller on MCI than that on CFP (14.9±3.3 versus 18.7±3.4 mm 2 , p = 0.01)., Conclusion: The appearance of choroidal and/ or retinal lesions on MCI may be different than that on CFP. Though MCI can provide similar information with CFP for the features of retinal and/ or choroidal lesions including border, halo and drusen; the infrared light reflection on MCI underestimates the extent of the choroidal lesion by 33%.

Purpose: To compare the visualization of the epiretinal membrane (ERM) using multicolor imaging (MCI) (Heidelberg Engineering, Carlsbad, CA) and conventional white light flood color fundus photography (FP) (Topcon)., Methods: The paired images of patients with ERM who underwent same-day MCI and FP examinations were reviewed. Visibility of the ERM was graded using a scale (0: not visible, 1: barely visible, and 2: clearly visible) by masked readers, and surface folds were counted to quantify the membrane visibility for each method. Images from individual color channels in MCI (green, blue, and infrared) were also graded using the same method to further investigate MCI images., Results: Forty-eight eyes of 42 patients were included. The average ERM visibility score was 1.8 ± 0.37 for MCI and 1.01 ± 0.63 for FP (P < 0.001). The number of the surface folds detected per quadrant was signifi8cantly higher in MCI than that in FP (6.79 ± 3.32 vs. 2.85 ± 2.81, P < 0.001). The ERM was graded with similar scores on the two modalities in 43.8% of the eyes; in 56.2%, the ERM was better visualized on MCI than that on FP. Conventional FP failed to detect ERM in 11.4% of eyes when the mean central retinal thickness was <413 microns. Analysis of laser color reflectance revealed that green reflectance provided better detection of surface folds (5.54 ± 2.12) compared to blue reflectance (4.2 ± 2.34) and infrared reflectance (1.2 ± 0.9)., Conclusion: Multicolor scanning laser imaging provides superior ERM detection and delineation of surface folds than conventional FP, primarily due to the green channel present in the combination-pseudocolor image in MCI.

Purpose: Macular pigment, composed of lutein, zeaxanthin, and meso-zeaxanthin, is postulated to protect against age-related macular degeneration, likely because of filtering blue light and its antioxidant properties. Macular pigment optical density (MPOD) is reported to be associated with macular function evaluated by visual acuity and multifocal electroretinogram. Given the importance of macular pigment, reliable and accurate measurement methods are important. The main purpose of this study is to determine the reproducibility of MPOD measurement by two-wavelength autofluorescence method using scanning laser ophthalmoscopy., Methods: Sixty-eight eyes of 39 persons were enrolled in the study, including 11 normal eyes, 16 eyes with wet age-related macular degeneration, 16 eyes with dry age-related macular degeneration, 11 eyes with macular edema due to diabetic mellitus, branch retinal vein occlusion or macular telangiectasia, and 14 eyes with tractional maculopathy, including vitreomacular traction, epiretinal membrane, or macular hole. MPOD was measured with a two-wavelength (488 and 514 nm) autofluorescence method with the Spectralis HRA + OCT after pupil dilation. The measurement was repeated for each eye 10 minutes later. The analysis of variance and Bland-Altman plot were used to assess the reproducibility between the two measurements., Results: The mean MPOD at eccentricities of 1° and 2° was 0.36 ± 0.17 (range: 0.04-0.69) and 0.15 ± 0.08 (range: -0.03 to 0.35) for the first measurement and 0.35 ± 0.17 (range: 0.02-0.68) and 0.15 ± 0.08 (range: -0.01 to 0.33) for the second measurement, respectively. The difference between the 2 measurements was not statistically significant, and the Bland-Altman plot showed 7.4% and 5.9% points outside the 95% limits of agreement, indicating an overall excellent reproducibility. Similarly, there is no significant difference between the first and second measurements of MPOD volume within eccentricities of 1°, 2°, and 6° radius, and the Bland-Altman plot showed 8.8%, 2.9%, and 4.4% points outside the 95% limits of agreement, respectively. The data for the reproducibility did not differ significantly among the various disease and normal eyes., Conclusion: Under routine examination conditions with pupil dilation, MPOD measurement by two-wavelength autofluorescence method showed a high reproducibility.

Purpose: To compare the real-time visualization of vitreoretino-choroidal structures using full-depth imaging (FDI) spectral domain optical coherence tomography (SD-OCT) and swept-source (SS)-OCT., Methods: Foveal scans using both FDI SD-OCT (Heidelberg Spectralis) and SS-OCT (Topcon Deep Range Imaging-OCT-1) were obtained in 40 normal eyes, 40 eyes with macular pathologies, and 40 eyes with glaucoma. Full-depth imaging SD-OCT images were obtained by manually enhancing the vitreoretinal interface first and then the choroid while averaging each OCT B-scan 100 times. Swept-source-OCT images were obtained by averaging each B-scan 96 times. After masking and randomly mixing the original OCT images, two independent physicians graded visualization of the premacular bursa, interdigitation zone line, and chorioscleral boundary, and also sharpness of choroidal structures., Results: A real-time full-depth image of vitreoretino-choroidal structures was successfully achieved with FDI SD-OCT in 118 cases (98.3%) and with SS-OCT in 45 cases (37.5%, P < 0.001). Full-depth imaging SD-OCT imaging was superior to SS-OCT imaging in visualizing the anterior border of the premacular bursa in 109 eyes (90.8%), with average grading of 1.63 ± 0.53 for the FDI SD-OCT and 0.39 ± 0.52 for the SS-OCT (P < 0.001). Swept-source-OCT was similar to FDI SD-OCT in visualizing the chorioscleral boundary in 108 eyes (90.0%), with average grading of 1.81 ± 0.39 for the SS-OCT and 1.78 ± 0.38 for the FDI-OCT (P = 0.566). The visualization of the interdigitation zone line was identical in the 2 imaging instruments (P = 1.000). The sharpness of the choroidal structures was greater with SS-OCT than with FDI-OCT (P < 0.001)., Conclusion: Manual double-enhancing FDI technique using SD-OCT provided a good compromise between vitreous and retinochoroidal structures visualization in real time during scanning procedure. In contrast, SS-OCT imaged well details of choroidal sublayers. Appropriate OCT technology and software should be selected according to its application in clinical settings.

Aim: To characterise the presence of a hyperautofluorescent (HAF) ring associated with choroidal neovascularisation (CNV) complex in patients with wet age-related macular degeneration (AMD)., Methods: Fundus autofluorescence images and spectral-domain optical coherence tomography (OCT) scans from 362 eyes with wet AMD were reviewed. The presence and size of an HAF ring associated with the CNV complex was evaluated. A subgroup of 64 treatment-naive eyes with new-onset CNV was studied to analyse the relationship between pretreatment OCT characteristics and the presence of the HAF ring., Results: An HAF ring was present in 38% of the entire cohort of eyes and in 39% of treatment-naive eyes. The presence of the HAF ring was significantly correlated with the extent of baseline subretinal fluid (SRF) on OCT (p=0.0113), the number of antivascular endothelial growth factor (VEGF) injections (p=0.0439) and the number of treatment cycles (p=0.0154). Eyes with an HAF ring were more likely to have disruption of the ellipsoid zone line once the SRF was resolved compared with eyes without an HAF ring (p=0.0002). In multivariate analysis, the best predictors for HAF ring were the baseline area of SRF (p=0.0449) and the number of anti-VEGF treatments received (p=0.0568)., Conclusions: Nearly 40% of wet AMD eyes had an HAF ring. In treatment-naive eyes, the HAF ring had a significant association with SRF and was found as early as the baseline measurement and as long as 18 months after beginning treatment, persisting for up to 6 years after the initial diagnosis. Its association with baseline SRF and disruption of the ellipsoid zone line of the photoreceptors on OCT could indicate continuous stress on the outer retinal structures after exposure to prolonged SRF and/or transmitted autofluorescence from loss of the photoreceptors overlying the retinal pigment epithelium., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background and Objective: To evaluate the morphological and functional outcome of wet age-related macular degeneration (AMD) during antivascular endothelial growth factor therapy with bevacizumab using SLO microperimetry (SLO-MP) with eye tracking., Patients and Methods: First, reproducibility was tested over the choroidal neovascularization (CNV) in 21 eyes of 19 patients with wet AMD. Second, 21 eyes of 19 patients with active CNV were studied longitudinally during bevacizumab therapy. Best-corrected visual acuity, SLO-MP, spectral-domain optical coherence tomography and fluorescein angiography were performed., Results: There was good reproducibility with a concordance correlation coefficient of 0.85. In the longitudinal study, eyes with anatomical response demonstrated a significant increase of retinal sensitivity. Non-responders showed no change in SLO-MP. Retinal sensitivity at baseline had a significant predictive value for the change in retinal sensitivity during therapy with bevacizumab (P=.032)., Conclusion: SLO-MP is able to analyze retinal function overlying lesions in wet AMD and can be a useful tool to monitor therapy in patients with macular diseases., (Copyright 2015, SLACK Incorporated.)

Purpose: To use novel confocal scanning ophthalmoscopy technology to test hypothesis that HIV-seropositive patients without history of retinitis with a history of a low CD4 count are more likely to have damage to their retinal nerve fiber layer (RNFL) when compared to patients with high CD4 count. In addition, we compared optic disc morphologic changes with glaucoma., Design: Cross-sectional study., Participants and Controls: 171 patients were divided into four groups. The control group consisted of 40 eyes of 20 HIV-seronegative patients. The second group consisted of 80 eyes of 41 HIV-positive patients whose CD4 cell count never dropped below 100 (1.0 x 10(9)/L). The third group consisted of 44 eyes of 26 HIV-positive patients with a history of low CD4 counts <100. Fourth group consisted of 79 eyes of 79 patients with confirmed glaucoma who served as positive controls., Testing: Confocal scanning laser ophthalmoscopy was performed with the Heidelberg Retina Tomograph (HRT3) and data were analyzed with HRT3, software (Heyex version 1.5.10.0)., Main Outcome Measures: Disc area, cup area, cup volume, rim volume, mean cup depth, maximum cup depth, cup-to-disc ration, mean RNFL thickness, and RNFL cross-sectional area., Results: Analysis of the global optic nerve and cup parameters showed no difference in disk area among the four groups. There was also no difference in cup, rim volume, mean cup depth, or maximum cup depth among the first three groups but they were all different from glaucoma group. The RNFL was thinner in glaucoma and both HIV-positive groups compared to HIV-seronegative subjects. The cross sectional RNFL area was thinner in both high and low CD4 HIV-positive groups compared to HIV-seronegative group in the nasal and temporal/inferior sectors, respectively. Glaucoma group showed thinning in all sectors., Conclusions: HIV retinopathy results in retinal nerve fiber layer loss without structural optic nerve supportive tissue change. RNFL damage may occur early in HIV disease by mechanism different than in glaucoma.

Purpose: To determine the presence of structural changes in HIV retinae (i.e., photoreceptor density and retinal thickness in the macula) compared with age-matched HIV-negative controls., Methods: Cohort of patients with known HIV under CART (combination Antiretroviral Therapy) treatment were examined with a flood-illuminated retinal AO camera to assess the cone photoreceptor mosaic and spectral-domain optical coherence tomography (SD-OCT) to assess retinal layers and retinal thickness., Results: Twenty-four eyes of 12 patients (n = 6 HIV-positive and 6 HIV-negative) were imaged with the adaptive optics camera. In each of the regions of interest studied (nasal, temporal, superior, inferior), the HIV group had significantly less mean cone photoreceptor density compared with age-matched controls (difference range, 4,308-6,872 cones/mm2). A different subset of forty eyes of 20 patients (n = 10 HIV-positive and 10 HIV-negative) was included in the retinal thickness measurements and retinal layer segmentation with the SD-OCT. We observed significant thickening in HIV positive eyes in the total retinal thickness at the foveal center, and in each of the three horizontal B-scans (through the macular center, superior, and inferior to the fovea). We also noted that the inner retina (combined thickness from ILM through RNFL to GCL layer) was also significantly thickened in all the different locations scanned compared with HIV-negative controls., Conclusion: Our present study shows that the cone photoreceptor density is significantly reduced in HIV retinae compared with age-matched controls. HIV retinae also have increased macular retinal thickness that may be caused by inner retinal edema secondary to retinovascular disease in HIV. The interaction of photoreceptors with the aging RPE, as well as possible low-grade ocular inflammation causing diffuse inner retinal edema, may be the key to the progressive vision changes in HIV-positive patients without overt retinitis.

Purpose: A spontaneous frameshift mutation, c.3481delC, in the Crb1 gene is the underlying cause of dysplasia and retinal degeneration in rd8 mice. The rd8 mutation is found in C57BL/6N but not in C57BL/6J mouse sub-strains. The development of ocular pathology in single knockout Ccl2-/-, Cx3cr1-/- and in double knockout Ccl2-/-, Cx3cr1-/- mice raised on a C57BL/6 background has been reported to depend on the presence of a rd8 mutation. In this study, we investigated the influence of the rd8 mutation on the retinal pathology that we previously described in the late-onset retinal degeneration (L-ORD) mouse model with a heterozygous S163R mutation in the C1q-tumor necrosis factor-related protein-5Ctrp5+/- gene that was generated on a C57BL/6J background., Methods: Mouse lines carrying the Ctrp5 S163R and rd8 mutations (Ctrp5+/-;rd8/rd8), corresponding controls without the rd8 mutation (Ctrp5+/-;wt/wt), and wild-type mice with and without the rd8 mutation (Wtrd8/rd8 and Wtwt/wt, respectively) were generated by systematic breeding of mice in our L-ORD mouse colony. Genotyping the mice for the rd8 (del C at nt3481 in Crb1) and Ctrp5 S163R mutations was performed with allelic PCR or sequencing. Retinal morphology was studied with fundus imaging, histology, light microscopy, electron microscopy, and immunohistochemistry., Results: Genotype analysis of the mice in L-ORD mouse colony detected the rd8 mutation in the homozygous and heterozygous state. Fundus imaging of wild-type mice without the rd8 mutation (Wtwt/wt) revealed no autofluorescence (AF) spots up to 6-8 months and few AF spots at 21 months. However, the accumulation of AF lesions accelerated with age in the Ctrp5+/- mice that lack the rd8 mutation (Ctrp5+/-;wt/wt). The number of AF lesions was significantly increased (p<0.001), and they were small and uniformly distributed throughout the retina in the 21-month-old Ctrp5+/-;wt/wt mice when compared to the age-matched controls. Wild-type and Ctrp5+/- mice with the rd8 mutation (Wtrd8/rd8 and Ctrp5+/-;rd8/rd8, respectively) revealed an integrated retinal architecture with well-defined outer segments/inner segments (OS/IS), outer nuclear layer (ONL), outer plexiform layer (OPL), and inner nuclear layer (INL). The presence of pseudorosette structures reported in the rd8 mice between the ONL and the INL in the ventral quadrant of the retina was not observed in all genotypes studied. Further, the external limiting membrane was continuous in the Ctrp5+/-;rd8/rd8 and Wtrd8/rd8 mice. Evaluation of the retinal phenotype revealed that the Ctrp5+/-;wt/wt mice developed characteristic L-ORD pathology including age-dependent accumulation of AF spots, development of sub-retinal, sub-RPE, and basal laminar deposits, and Bruch's membrane abnormalities at older age, while these changes were not observed in the age-matched littermate WTwt/wt mice., Conclusions: The Wtrd8/rd8 and Ctrp5+/-;rd8/rd8 mice raised on C57BL/6J did not develop early onset retinal changes that are characteristic of the rd8 phenotype, supporting the hypothesis that manifestation of rd8-associated pathology depends on the genetic background. The retinal pathology observed in mice with the Ctrp5+/-;wt/wt genotype is consistent with the L-ORD phenotype observed in patients and with the phenotype we described previously. The lack of rd8-associated retinal pathology in the Ctrp5+/-;wt/wt mouse model raised on the C57BL/6J background and the development of the L-ORD phenotype in these mice in the presence and absence of the rd8 mutation suggests that the pathology observed in the Ctrp5+/-;wt/wt mice is primarily associated with the S163R mutation in the Ctrp5 gene.

Purpose: To compare laser photocoagulation plans for diabetic macular edema (DME) using fluorescein angiography (FA) versus optical coherence tomography (OCT) thickness map superimposed on the retina., Methods: Fourteen eyes with DME undergoing navigated laser photocoagulation with navigated photocoagulator had FA taken using the same instrument. Optical coherence tomography central retinal thickness map was imported to the photocoagulator and with same magnification aligned onto the retina. Three retina specialists placed laser spot marks separately on FA and OCT image in a masked fashion. The spots placed by each physician were compared between FA and OCT and among physicians. The area of dye leakage on FA and increased central retinal thickness on OCT of the same eye were also compared., Results: The average number of spots using FA and OCT template was 36.64 and 40.61, respectively (P = 0.0201). The average area of dye leakage was 7.45 mm, whereas the average area of increased central retinal thickness on OCT of the same eye was 10.92 mm (P = 0.013)., Conclusion: There is variability in the treatment planning for macular photocoagulation with a tendency to place more spots when guided by OCT than by FA. Integration of OCT map aligned to the retina may have an impact on treatment plan once such information is available.

Visual function abnormalities are common in people living with HIV disease (PLWH) without retinitis, even after improvement in immune status. Abnormalities such as reduced contrast sensitivity, altered color vision, peripheral visual field loss, and electrophysiological changes are related to a combination of retinal dysfunctions, involving inner and outer retinal structures. The standard protocol for testing vision performance in clinical practice is the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. However, this method poorly correlates with activities of daily living that require patients to assess visual stimuli in multiple light/contrast conditions, and with limited time. We utilized a novel interactive computer program (Central Vision Analyzer) to analyze vision performance in PLWH under a variety of light/contrast conditions that simulate stressful and real-world environments. The program tests vision in a time-dependent way that we believe better correlates with daily living activities than the non-timed ETDRS chart. We also aimed to correlate visual scores with retinal neuro-fiber layer thickness on optical coherence tomography. Here we show that visual acuity is more affected in PLWH in comparison to HIV-seronegative controls in varying contrast and luminance, especially if the nadir CD4+ T-cell count was lower than 100 cells/mm3. Visual impairment reflects the loss of retinal nerve fiber layer thickness especially of the temporal-inferior sector. In PLWH the ETDRS chart test led to better visual acuity compared to the Central Vision Analyzer equivalent test, likely because patients had indefinite time to guess the letters. This study confirms and strengthens the finding that visual function is affected in PLWH even in absence of retinitis, since we found that the HIV serostatus is the best predictor of visual loss. The Central Vision Analyzer may be useful in the diagnosis of subclinical HIV-associated visual loss in multiple light/contrast conditions, and may offer better understanding of this entity called "neuroretinal disorder".

Purpose: To compare the choroidal volume (CV) between emmetropic and highly myopic eyes, and to assess if the presence of myopic fundus abnormalities, myopic traction maculopathy, or choroidal neovascularization affects the CV., Methods: We retrospectively reviewed imaging studies of 98 eyes of 98 patients who underwent CV measurement on optical coherence tomography. We included 31 emmetropic eyes (Group 1), 36 highly myopic eyes without vitreoretinal or choroidal pathologies (Group 2), 21 highly myopic eyes with traction maculopathy (Group 3), and 10 highly myopic eyes with history of choroidal neovascularization (Group 3). Eyes with chorioretinal atrophy were excluded. Regression analysis was performed to evaluate the correlation between CV and multiple variables., Results: Choroidal volume was lower in Group 2 than in Group 1 (P < 0.001), and in Groups 3 and 4 than in Group 2 (P < 0.001 and P = 0.002, respectively). Age (P = 0.002), axial length (P < 0.001), sex (P = 0.047), staphyloma (P < 0.001), and myopic group (P = 0.05) were independent predictors for the final CV (R = 0.645). In highly myopic eyes, CV decreased by 0.32 mm for every 10 years and by 0.49 mm per millimeter of axial length., Conclusion: Choroidal thinning is present in highly myopic eyes compared with emmetropic eyes, and is related to age, axial length, sex, and staphyloma. However, myopic eyes with coexisting myopic traction maculopathy or history of choroidal neovascularization have more severe thinning, likely leading to insufficient metabolic supplementation for the macula.

Purpose: To evaluate the morphologic restoration of retinal anatomy after surgery for epiretinal membrane (ERM) peeling using spectral domain optical coherence tomography. Correlation of retinal structure with visual outcome., Design: Retrospective consecutive case series., Methods: Thirty-four consecutive eyes with ERM underwent surgery with 1 year follow-up examination. Spectral domain optical coherence tomography scans were analyzed preoperatively and 1, 3, 6, 9, and 12 months postoperative. Best-corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study charts was measured at each visit., Results: All eyes showed a significant improvement of BCVA after ERM peeling (P = 0.002). The time point of BCVA and retinal restoration seen on spectral domain optical coherence tomography occurred simultaneously and varied between individuals (occurrence of BCVA: mean, 4.82 months; retinal restoration: mean, 4.24 months). At 3 months, the retinal anatomical restoration rate was 70% and 88% at 6 months., Conclusion: Restoration of the retinal anatomical structure predominantly occurs within the first 3 months post-ERM peeling. An improvement of BCVA and anatomical retinal restoration after ERM removal varies in individuals. If retinal layers fully restore in their anatomical structure, BCVA improves at the same time point.