Search

To evaluate the intra- and interdevice repeatability of microperimetry (MP) assessments in patients with diabetic macular edema (DME) two consecutive MP testings (45 fovea-centered stimuli, 4-2 staircase strategy) were performed using MP3 (NIDEK, Aichi, Japan) and MAIA (CenterVue, Padova, Italy), respectively. Intraretinal fluid (IRF) and ellipsoid zone (EZ) thickness were automatically segmented by published deep learning algorithms. Hard exudates (HEs) were annotated semi-automatically and disorganization of retinal inner layers (DRIL) was segmented manually. Point-to-point registration of MP stimuli to corresponding spectral-domain OCT (Spectralis, Heidelberg Engineering, Germany) locations was performed for both devices. Repeatability was assessed overall and in areas of disease-specific OCT biomarkers using Bland-Altmann coefficients of repeatability (CoR). A total of 3600 microperimetry stimuli were tested in 20 eyes with DME. Global CoR was high using both devices (MP3: ± 6.55 dB, MAIA: ± 7.69 dB). Higher retest variances were observed in stimuli with IRF (MP3: CoR ± 7.4 dB vs. ± 6.0 dB, p = 0.001, MAIA: CoR ± 9.2dB vs. ± 6.8 dB, p = 0.002) and DRIL on MP3 (CoR ± 6.9 dB vs. ± 3.2 dB, p < 0.001) compared to stimuli without. Repeatabilities were reduced in areas with thinner EZ layers (both p < 0.05). Fixation (Fuji classification) was relatively unstable independent of device and run. These findings emphasize taking higher caution using MP in patients with DME., (© 2024. The Author(s).)

Purpose: Given the similarities between the retinal and coronary microvasculature, the retina holds promising potential to serve as a non-invasive screening tool for coronary artery disease (CAD). We aimed to develop novel inner ellipse-based metrics and discern whether foveal avascular zone (FAZ) alterations can serve as indicators for CAD presence and severity., Methods: Patients admitted to the Department of Cardiology who underwent coronary angiography were included. This resulted in an inclusion of 212 patients, of which 73 had no CAD. During the same visit, 6 × 6-mm (nominal size) fovea-centered optical coherence tomography angiography images of both eyes were acquired. The Gensini score (GS) was utilized to quantify CAD severity. Six known FAZ shape metrics were assessed and three novel biomarkers based on the inner ellipse were defined: absolute inner ellipse difference, Hausdorff distance, and Chamfer distance., Results: Eight out of nine metrics showed significant associations with the GS in the left eye. However, significant differences across three CAD severity groups were only demonstrated by the novel metrics. Utilizing the Chamfer distance, age, and sex, patients with and without CAD could be distinguished with an average area under the curve (AUC) of 0.89 (95% confidence interval [CI], 0.84-0.95). Moreover, three CAD severity groups could be discerned with a macro average AUC of 0.77 (95% CI, 0.72-0.84)., Conclusions: A comprehensive assessment of FAZ shape descriptors was performed, and a strong association with CAD was found. The inner ellipse-based biomarkers especially demonstrated high predictive abilities for CAD presence and severity.

We present improvements on the adaptive optics (AO) correction method using a pyramid wavefront sensor (P-WFS) and introduce a novel approach for closed-loop focus shifting in retinal imaging. The method's efficacy is validated through in vivo adaptive optics optical coherence tomography (AO-OCT) imaging in both, healthy individuals and patients with diabetic retinopathy. In both study groups, a stable focusing on the anterior retinal layers is achieved. We further report on an improvement in AO loop speed that can be used to expand the imaging area of AO-OCT in the slow scanning direction, largely independent of the eye's isoplanatic patch. Our representative AO-OCT data reveal microstructural details of the neurosensory retina such as vessel walls and microglia cells that are visualized in single volume data and over an extended field of view. The excellent performance of the P-WFS based AO-OCT imaging in patients suggests good clinical applicability of this technology., Competing Interests: The named authors have no conflict of interest, financial or otherwise., (© 2024 The Author(s).)

Objective: To investigate the localization, distribution, and type of central microaneurysms (MAs) and their relationship with retinal vascular alterations in patients with retinal vein occlusion (RVO)., Methods: In this cross-sectional study, ultra-widefield color fundus photography (UWF-CF), standard and single-capture 65° widefield (WF) optical coherence tomography angiography (OCTA) were performed in consecutive patients with RVO treated at the Department of Ophthalmology and Optometry, Medical University of Vienna. UWF-CF, en face and B-Scans in 6 mm × 6 mm OCTA were examined for detection of MAs. Nonperfusion areas (NPA) and collateral vessels (CV) were evaluated on WF-OCTA, ghost vessels (GV), and tortuous vessels (TV) on UWF-CF., Results: One-hundred-and-twelve patients were included in the study, and data from 59 eyes of 59 patients with disease duration longer than 3 months, good image quality, and without relevant ocular comorbidities were eligible for statistical analysis. Fifty-six of 59 (94.9%) patients were previously treated with anti-vascular endothelial growth factor agents for macular edema, 31 of 59 (52.5%) patients presented with MAs in the central 6 mm and 60 MAs were found in total using multimodal imaging. There was no statistically significant difference in the greatest diameter of fluid-associated versus non-fluid-associated MAs (p = 0.53). Eyes with MAs were associated with CV, TV, and GV (χ 2 -test; p < 0.001, p = 0.0498, and p = 0.001). Median NPA was 27.3 mm 2 (quartiles 1.3-62.8 mm 2 ) in eyes with MAs and 0 mm 2 (quartiles 0-36.2 mm 2 ) in eyes without MAs (Mann-Whitney-U-test; p = 0.018)., Conclusion: MAs were associated with extensive NPA, the presence of CV, GV, and TV. There was no correlation between the diameter of the MA and the adjacent intraretinal fluid in our predominantly pretreated RVO study patients., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To compare detection rates of microaneurysms (MAs) on high-speed megahertz optical coherence tomography angiography (MHz-OCTA), fluorescein angiography (FA) and colour fundus photography (CF) in patients with diabetic retinopathy (DR)., Methods: For this exploratory cross-sectional study, MHz-OCTA data were acquired with a swept-source OCT prototype (A-scan rate: 1.7 MHz), and FA and CF imaging was performed using Optos® California. MA count was manually evaluated on en face MHz-OCTA/FA/CF images within an extended ETDRS grid. Detectability of MAs visible on FA images was evaluated on corresponding MHz-OCTA and CF images. MA distribution and leakage were correlated with detectability on OCTA and CF imaging., Results: 47 eyes with severe DR (n = 12) and proliferative DR (n = 35) were included. MHz-OCTA and CF imaging detected on average 56% and 36% of MAs, respectively. MHz-OCTA detection rate was significantly higher than CF (p < 0.01). The combination of MHz-OCTA and CF leads to an increased detection rate of 70%. There was no statistically significant association between leakage and MA detectability on OCTA (p = 0.13). For CF, the odds of detecting leaking MAs were significantly lower than non-leaking MAs (p = 0.012). Using MHz-OCTA, detection of MAs outside the ETDRS grid was less likely than MAs located within the ETDRS grid (outer ring, p < 0.01; inner ring, p = 0.028). No statistically significant difference between rings was observed for CF measurements., Conclusions: More MAs were detected on MHz-OCTA than on CF imaging. Detection rate was lower for MAs located outside the macular region with MHz-OCTA and for leaking MAs with CF imaging. Combining both non-invasive modalities can improve MA detection., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Diabetes mellitus is a chronic disease the microvascular complications of which include diabetic retinopathy and maculopathy. Diabetic macular edema, proliferative diabetic retinopathy, and diabetic macular ischemia pose a threat to visual acuity. Artificial intelligence can play an increasingly more important role in making the diagnosis and the treatment regimen of maculopathies in everyday clinical practice in the future. It can be used to automatically detect and quantify pathological parameters of the retina. The aim is to improve patient care in the clinical routine using so-called clinical decision support systems with personalized treatment algorithms. This review article outlines the current research regarding new biomarkers in diabetic maculopathy using optical coherence tomography (OCT) and OCT angiography (OCT-A)., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

The fovea of the human retina, a specialization for acute and color vision, features a high concentration of cone photoreceptors. A pit on the inner retinal aspect is created by the centrifugal migration of post-receptoral neurons. Foveal cells are specified early in fetal life, but the fovea reaches its final configuration postnatally. Pre-term birth retards migration resulting in a small pit, a small avascular zone, and nearly continuous inner retinal layers. To explore the involvement of Müller glia, we used serial-section electron microscopic reconstructions to examine the morphology and neural contacts of Müller glia contacting a single foveal cone in a 28-year-old male organ donor born at 28 weeks of gestation. A small non-descript foveal avascular zone contained massed glial processes that included a novel class of 'inner' Müller glia. Similar to classic 'outer' Müller glia that span the retina, inner Müller glia have bodies in the inner nuclear layer (INL). These cells are densely packed with intermediate filaments and insert processes between neurons. Unlike 'outer' Müller glia, 'inner' Müller glia do not reach the external limiting membrane but instead terminate at the outer plexiform layer. One completely reconstructed inner cell ensheathed cone pedicles and a cone-driven circuit of midget bipolar and ganglion cells. Inner Müller glia outnumber foveal cones by 1.8-fold in the outer nuclear layer (221,448 vs. 123,026 cells/mm 2 ). Cell bodies of inner Müller glia outnumber those of outer Müller glia by 1.7-fold in the INL (41,872 vs. 24,631 cells/ mm 2 ). Müller glia account for 95 and 80% of the volume of the foveal floor and Henle fiber layer, respectively. Determining whether inner cells are anomalies solely resulting from retarded lateral migration of inner retinal neurons in pre-term birth requires further research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kar, Singireddy, Kim, Packer, Schalek, Cao, Sloan, Pollreisz, Dacey and Curcio.)

Purpose: To evaluate microvascular intereye differences in diabetic patients with same-stage diabetic retinopathy (DR) in both eyes as assessed using optical coherence tomography angiography (OCTA)., Methods: In this cross-sectional study, fovea-centered swept-source 6 × 6 mm OCTA scans were acquired using a 200 kHz OCTA device. Vessel density (VD) and fractal dimension were calculated on binarized, vessel-segmented images in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). Foveal avascular zone (FAZ) area (FAZA) and perimeter (FAZP) was measured and FAZ circularity (FAZC) calculated. Absolute difference (δabs) and asymmetry index between eyes was assessed and compared across DR stages. Differences of VD, FD, and FAZ parameters between left and right eye were evaluated using linear mixed models., Results: A total of 336 eyes of 168 diabetic patients without DR and with DR stages ranging from mild nonproliferative to proliferative DR were included for analysis. The intereye comparison revealed significantly lower VD in the SCP (estimate [95% CI] = -0.009 [-0.01; -0.006], P < 0.01), as well as a significantly lower FD in the SCP (-0.007 [-0.009; -0.005], P < 0.01) of the left compared to the right eye. FAZC of the left compared to the right eye was lower in eyes without DR, moderate DR, and PDR (P < 0.05). FAZ δabs and asymmetry index were higher in more advanced disease stages (P < 0.05)., Conclusions: OCTA metrics provide important information on the retinal microvasculature in systemic diseases such as DR. Our results reveal a significant intereye difference with lower VD and FD in the SCP as well as higher FAZ impairment of the left compared to the right eye.

Purpose: To evaluate the proportion, predictors, and outcomes of patients with neovascular age-related macular degeneration (nAMD) treated with a high burden of VEGF inhibitor intravitreal (IVT) injections after 2 years in routine clinical practice., Design: Retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! Project, of patients treated in European centers., Participants: Treatment-naïve eyes (1 eye per patient) starting VEGF inhibitors for nAMD from January 2017 to March 2020 with 24 months of follow-up. We analyzed the following 3 treatment-burden groups defined by the mean interval of the 3 closest injections to the 24-month visit: (1) those with a high-treatment burden had injection intervals ≤ 42 days, (2) those with a low-treatment burden had injection intervals between 43 and 83 days; and (3) those with tolerable treatment burden had injection intervals between 84 and 365 days., Methods: Multinomial regression was used to evaluate baseline risk predictors of patients requiring a high-treatment burden., Main Outcome Measures: The proportion of patients that experienced a high-treatment burden at 2 years and its predictors., Results: We identified 2038 eligible patients completing 2 years of treatment (2038/3943 patients [60%]) with a median (quartile 1, quartile 3) of 13 (10, 17) injections. The proportion of patients with a high-treatment burden was 25% (516 patients) at 2 years. Younger patients (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.96-0.99; P < 0.01) were more likely to have high-treatment burden, whereas eyes with type 3 choroidal neovascular lesions at baseline were significantly less likely (OR, 0.26; 95% CI, 0.13-0.52; P < 0.01). Regarding type of fluid, patients with subretinal fluid only at baseline (OR, 3.85; 95% CI, 1.34-11.01; P = 0.01) and persistent active intraretinal (OR, 1.56; 95% CI, 1.18-2.06; P < 0.01) or subretinal fluid only (OR, 2.21; 95% CI, 1.52-3.21; P < 0.01) after the loading phase had a higher risk of high treatment burden at 2 years., Conclusions: High treatment burden is a common issue in routine clinical practice in Europe, with a quarter of patients requiring injections of conventional VEGF inhibitors every 6 weeks at 2 years and 40% discontinuing treatment within 2 years., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the visualization capabilities of high-speed swept-source optical coherence tomography (SS-OCT) in cataract surgery., Methods: Cataract surgery was simulated in wet labs with ex vivo porcine eyes. Each phase of the surgery was visualized with a novel surgical microscope-integrated SS-OCT with a variable imaging speed of over 1 million A-scans per second. It was designed to provide four-dimensional (4D) live-volumetric videos, live B-scans, and volume capture scans., Results: Four-dimensional videos, B-scans, and volume capture scans of corneal incision, ophthalmic viscosurgical device injection, capsulorrhexis, phacoemulsification, intraocular lens (IOL) injection, and position of unfolded IOL in the capsular bag were recorded. The flexibility of the SS-OCT system allowed us to tailor the scanning parameters to meet the specific demands of dynamic surgical steps and static pauses. The entire length of the eye was recorded in a single scan, and unfolding of the IOL was visualized dynamically., Conclusions: The presented novel visualization method for fast ophthalmic surgical microscope-integrated intraoperative OCT imaging in cataract surgery allowed the visualization of all major steps of the procedure by achieving large imaging depths covering the entire eye and high acquisition speeds enabling live volumetric 4D-OCT imaging. This promising technology may become an integral part of routine and advanced robotic-assisted cataract surgery in the future., Translational Relevance: We demonstrate the visualization capabilities of a cutting edge swept-source OCT system integrated into an ophthalmic surgical microscope during cataract surgery.

Aim: To assess the detection rate of retinal neovascularisation (NV) in eyes with proliferative diabetic retinopathy (PDR) using widefield optical coherence tomography angiography (WF-OCTA) in comparison to ultrawidefield fluorescein angiography (UWF-FA)., Methods: Single-capture 65°-WF-OCTA-imaging was performed in patients with NV at the disc or elsewhere (NVE) detected on UWF-FA using a modified PlexElite system and B-scans were examined for blood flow signals breaching the internal limiting membrane. Sensitivity of WF-OCTA and UWF colour fundus (UWF-CF) photography for correct diagnosis of PDR was determined and interdevice agreement (Fleiss' κ) between WF-OCTA and UWF-FA for detection of NV in the total gradable area and each retinal quadrant was evaluated., Results: Fifty-nine eyes of 41 patients with PDR detected on UWF-FA were included. Sensitivity of detecting PDR on WF-OCTA scans was 0.95 in contrast to 0.78 on UWF-CF images. Agreement in detecting NVE between WF-OCTA and UWF-FA was high in the superotemporal (κ=0.98) and inferotemporal (κ=0.94) and weak in the superonasal (κ=0.24) and inferonasal quadrants (κ=0.42). On UWF-FA, 63% of NVEs (n=153) were located in the temporal quadrants with 93% (n=142) of them being detected on WF-OCTA scans., Conclusion: The high reliability of non-invasive WF-OCTA imaging in detecting PDR can improve clinical examination with the potential to replace FA as a single diagnostic tool., Competing Interests: Competing interests: Research was funded by European Commisson H2020 programme initiated by the Photonics Public Private Partnership (MOON number 732969). UMS-E is a scientific consultant for Genentech, Heidelberg, Kodiak, Novartis, RetinSight, and Roche; and provides contract research for the Medical University of Vienna for Apellis, Genentech and Kodiak. SS is an advisory board member at Bayer, Roche and Novartis. AP is a scientific consultant for Bayer, Roche, Novartis and Oertli Instruments and received financial support by Roche. MN and ThS are consultants for Carl Zeiss Meditec. WD and RL are consultants for and received financial support by Carl Zeiss Meditec. TiS is an employee at Carl Zeiss Meditec Inc. The following athors have no financial disclosures: HS, JI, AS, IS., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Despite the centrality of the retinal pigment epithelium (RPE) in vision and retinopathy our picture of RPE morphology is incomplete. With a volumetric reconstruction of human RPE ultrastructure, we aim to characterize major membranous features including apical processes and their interactions with photoreceptor outer segments, basolateral infoldings, and the distribution of intracellular organelles., Methods: A parafoveal retinal sample was acquired from a 21-year-old male organ donor. With serial block-face scanning electron microscopy, a tissue volume from the inner-outer segment junction to basal RPE was captured. Surface membranes and complete internal ultrastructure of an individual RPE cell were achieved with a combination of manual and automated segmentation methods., Results: In one RPE cell, apical processes constitute 69% of the total cell surface area, through a dense network of over 3000 terminal branches. Single processes contact several photoreceptors. Basolateral infoldings facing the choriocapillaris resemble elongated filopodia and comprise 22% of the cell surface area. Membranous tubules and sacs of endoplasmic reticulum represent 20% of the cell body volume. A dense basal layer of mitochondria extends apically to partly overlap electron-dense pigment granules. Pores in the nuclear envelope form a distinct pattern of rows aligned with chromatin., Conclusions: Specialized membranes at the apical and basal side of the RPE cell body involved in intercellular uptake and transport represent over 90% of the total surface area. Together with the polarized distribution of organelles within the cell body, these findings are relevant for retinal clinical imaging, therapeutic approaches, and disease pathomechanisms.

Purpose: To evaluate the association of microvascular lesions on ultrawidefield (UWF) color fundus (CF) images with retinal nonperfusion (RNP) up to the midperiphery on single-capture widefield (WF) OCT angiography (OCTA) in patients with diabetic retinopathy (DR)., Design: Cross-sectional study., Subjects: Seventy-five eyes of 50 patients with mild to severe nonproliferative DR (NPDR) and proliferative DR (PDR) were included in this analysis., Methods: ETDRS level and presence of predominantly peripheral lesions (PPLs) were assessed on UWF-CF images acquired with a Zeiss Clarus 700. Single-capture 65°-WF-OCTA was performed using a PlexElite prototype (Carl Zeiss Meditec, Inc.). A custom grid consisting of a central ETDRS grid extended by 2 rings reaching up to the midperiphery was overlaid to subdivide retinal areas visible on WF-OCTA en face images. Retinal nonperfusion was measured in each area and in total. Nonperfusion index (NPI) was calculated from total RNP. On UWF-CF images, the number of microaneurysms, hemorrhages, neovascularizations, and areas with intraretinal microvascular abnormalities (IRMAs) were evaluated using the same grid., Main Outcome Measures: Association of diabetic lesions with RNP was calculated using Spearman correlations (r s )., Results: Median RNP on WF-OCTA was 0 mm 2 (0-0.9), 4.9 mm 2 (1.9-5.4), 23.4 mm 2 (17.8-37), and 68.4 mm 2 (40.8-91.7) in mild, moderate, and severe NPDR and PDR, respectively. We found a statistically significant correlation (P < 0.01) of overall RNP (r s  = 0.96,) and NPI (r s  = 0.97) on WF-OCTA with ETDRS level. Number of grid-fields affected by IRMAs on CF images was highly associated with NPI (r s  = 0.86, P < 0.01). Intraretinal microvascular abnormalities and RNPs had similar topographic distributions with high correlations in affected areas. Eyes with PPLs (n = 43 eyes, 57%) on CF images had a significantly higher NPI (P = 0.014) than eyes without PPLs., Conclusion: The combination of UWF-CF imaging and single-capture WF-OCTA allows precise and noninvasive analysis of the retinal vasculature up to the midperiphery in patients with DR. The presence and extent of IRMAs on CF images may serve as an indicator for underlying RNP, which is more pronounced in eyes with PPLs., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

To compare retinal microvascular perfusion between the eyes of hypertensive patients with and without chronic kidney disease (CKD), the vessel density (VD) and fractal dimension (FD) of the superficial (SVP) and deep retinal vascular plexus (DVP) were analyzed on 6 × 6 mm fovea-centered optical coherence tomography angiography (OCTA) images of patients with hypertension. The retina was divided into an inner ring (IR) and outer ring (OR) according to the Early Treatment of Diabetic Retinopathy Study grid. The glomerular filtration rate (GFR) was determined and CKD was diagnosed (GFR < 60 mL/min/1.73 m 2 ). Ninety-six eyes from 52 patients with hypertension were included in this analysis. Twenty patients ( n = 37 eyes) were diagnosed with CKD. The mean age was 69 ± 11.7 years and 60.4 ± 9.2 years in the CKD group and in the control group, respectively. The univariate model revealed a significant difference in VD between patients without and with CKD in the superficial IR (0.36 ± 0.03 vs. 0.34 ± 0.04, p = 0.03), the superficial OR (0.35 ± 0.02 vs. 0.33 ± 0.04, p = 0.02), the deep OR (0.24 ± 0.01 vs. 0.23 ± 0.02, p = 0.003), and the FD in the SVP (1.87 ± 0.01 vs. 1.86 ± 0.02, p = 0.02) and DVP (1.83 ± 0.01 vs. 1.82 ± 0.01, p = 0.006). After adjusting for age and sex, these differences did not remain statistically significant. Similar results were observed for the FD in the SVP and DVP. In our cohort, patients with hypertension and CKD did not differ from patients without CKD in regard to microvascular perfusion status in the macular area as assessed using OCTA.

Diabetic retinopathy (DR), a pathologic change of the human retinal vasculature, is the leading cause of blindness in working-age adults with diabetes mellitus. Optical coherence tomography angiography (OCTA), a functional extension of optical coherence tomography, has shown potential as a tool for early diagnosis of DR through its ability to visualize the retinal vasculature in all spatial dimensions. Previously introduced deep learning-based classifiers were able to support the detection of DR in OCTA images, but require expert labeling at the pixel level, a labor-intensive and expensive process. We present a multiple instance learning-based network, MIL-ResNet,14 that is capable of detecting biomarkers in an OCTA dataset with high accuracy, without the need for annotations other than the information whether a scan is from a diabetic patient or not. The dataset we used for this study was acquired with a diagnostic ultra-widefield swept-source OCT device with a MHz A-scan rate. We were able to show that our proposed method outperforms previous state-of-the-art networks for this classification task, ResNet14 and VGG16. In addition, our network pays special attention to clinically relevant biomarkers and is robust against adversarial attacks. Therefore, we believe that it could serve as a powerful diagnostic decision support tool for clinical ophthalmic screening., (© 2023. The Author(s).)

The Old World macaque monkey and New World common marmoset provide fundamental models for human visual processing, yet the human ancestral lineage diverged from these monkey lineages over 25 Mya. We therefore asked whether fine-scale synaptic wiring in the nervous system is preserved across these three primate families, despite long periods of independent evolution. We applied connectomic electron microscopy to the specialized foveal retina where circuits for highest acuity and color vision reside. Synaptic motifs arising from the cone photoreceptor type sensitive to short (S) wavelengths and associated with "blue-yellow" (S-ON and S-OFF) color-coding circuitry were reconstructed. We found that distinctive circuitry arises from S cones for each of the three species. The S cones contacted neighboring L and M (long- and middle-wavelength sensitive) cones in humans, but such contacts were rare or absent in macaques and marmosets. We discovered a major S-OFF pathway in the human retina and established its absence in marmosets. Further, the S-ON and S-OFF chromatic pathways make excitatory-type synaptic contacts with L and M cone types in humans, but not in macaques or marmosets. Our results predict that early-stage chromatic signals are distinct in the human retina and imply that solving the human connectome at the nanoscale level of synaptic wiring will be critical for fully understanding the neural basis of human color vision.

Background: At the Department of Ophthalmology and Optometry at the MUV surgical method (scleral buckling, vitrectomy, combined vitrectomy/scleral buckling) and timing (daytime, nighttime) for the treatment of primary rhegmatogenous retinal detachment (RRD) changed continuously in the years 2004 to 2012. This study aims to evaluate changes in surgical strategies over time including their impact on functional and anatomical outcomes., Methods: Retrospective evaluation of patients operated on primary RRD between the years 2004 and 2012. Baseline demographic data, month 3 best-corrected visual acuity (BCVA), surgical method, single success surgery, surgical timing, and intraoperative complications were analyzed., Results: Overall, 812 eyes of 812 patients with a mean (±SD) age of 58.1 ± 13.3 years were included. A total of 413 (51%) patients presented with macula-on and 359 (44%) with macula-off RRD. Month 3 BCVA increased over time, both in macula-on or macula-off groups ( p < 0.001). The rate of complete retinal reattachment 3 months postoperatively increased significantly from 65% in 2004 to 83% in 2012 in both groups. Scleral buckling surgeries decreased continuously from 95% to 16% with an appropriate increase in vitrectomies as well as a decrease in surgeries during nighttime (68% in 2004, 6% in 2012) with equal or better visual and functional outcomes., Conclusion: Our data showed that improving functional and single-success surgery outcomes in patients operated on for primary RRD. In the years 2004 to 2012, surgical techniques shifted from scleral buckling to primary vitrectomy and were increasingly scheduled during the daytime.

Diabetes mellitus can cause diabetic retinopathy, diabetic macular edema, optic neuropathy, cataract or dysfunction of the eye muscles. The incidence of these disorders correlates with disease duration and quality of metabolic control. Regular ophthalmological examinations are needed to prevent sight-threatening advanced stages of diabetic eye diseases., (© 2022. The Author(s).)

Comparison of two ultra-widefield (UWF) color-fundus (CF) imaging devices in diabetic patients for visualization of retinal periphery and detection of early microvascular lesions. The total gradable areas (TGA) seen on non-mydriatic CF-images of two UWF-imaging devices (Optos Daytona P200T; Zeiss Clarus 700) were compared and differences in projected area measured. Retinal periphery outside the 7 standard fields (7SF) was divided into: F3 temporal, F4 superotemporal, F5 inferotemporal, F6 superonasal, F7 inferonasal. DR stage was evaluated in the 7SF and the TGA on images of both devices and compared using Cohens κ. 67 eyes of 67 patients (52.5 ± 15.3 years) were analysed. DR stages in the 7SF were no (n = 36 Optos, n = 35 Clarus), mild (n = 16 Optos, n = 17 Clarus), and moderate DR (n = 15). Optos depicted significantly more area in F3 (median [interquartile range]; 2.41% [1.06-4.11] vs 0% [0-0], P < 0.001) and Clarus in F7 (3.29% [0-7.69] vs 0% [0-3.27], P = 0.002). In 4 eyes DR-stage was higher using Optos due to peripheral lesions not seen on the Clarus. Interrater reliability of DR-stage on both devices was almost perfect in the 7SF (κ = 0.975) and the TGA (κ = 0.855). Reliability in detecting signs of early DR is high on both devices. Clarus allowed for better visualization of the inferonasal field, Optos of the temporal field., (© 2022. The Author(s).)

Purpose: To evaluate neuroretinal integrity in different subtypes of optical coherence tomography (OCT)-graded partial-thickness macular holes., Methods: Fovea-centred SD-OCT images (Cirrus, Carl Zeiss Meditec AG; Spectralis, Heidelberg Engineering GmbH) and visual acuity (VA) acquired at every visit were analysed by two retina specialists retrospectively in 71 eyes of 65 patients. Partial-thickness macular holes were classified as lamellar macular hole (LMH), epiretinal membrane foveoschisis (ERMF) or macular pseudohole (MPH)., Results: Lamellar macular hole, ERMF and MPH were diagnosed in 33 (47%), 31 (43%) and 7 (10%) eyes with a VA of 0.18 ± 0.25, 0.15 ± 0.2, and 0.06 ± 0.08 (p = 0.323), respectively. Median follow-up time was 11 (interquartile range 4-32.5), 10 (interquartile range 5-18) and 19 (interquartile range 8-24) months in LMH, ERMF and MPH. In all subgroups, VA remained stable during the follow-up (p = 0.652, p = 0.915 and p = 1.000). Epiretinal proliferations (EP) were present in 12 LMH and 3 ERMF. At baseline, eyes with EP had significantly worse VA (p < 0.001), wider foveal cavities (p = 0.007) and thinner foveal floors (p < 0.001) compared with eyes without EP. Twelve out of 15 eyes with EP showed exudative cystoid spaces. Among all 71 eyes, 51 remained morphologically and functionally stable during follow-up., Conclusion: In our study cohort, EP are associated with worse VA and advanced neuroretinal tissue loss presenting with wider foveal cavities and thinner foveal floors. During the follow-up period, VA remained stable in all entities of partial-thickness macular holes., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Aim: To prospectively monitor subclinical changes in capillary perfusion and retinal layer thickness in patients with type 2 diabetes and early diabetic retinal disease over 2 years., Methods: In this longitudinal study we performed biannual retinal vascular imaging using optical coherence tomography angiography (RTVue) to analyse the foveal avascular zone (FAZ) area, perimeter, acircularity index (AI) and parafoveal superficial/deep vessel density (VD). Spectral-domain optical coherence tomography (Spectralis) was used to measure the thickness of nine macular layers and the peripapillary nerve fibre layer., Results: Among 117 eyes (58 left) of 59 patients (21 female), 105 had no diabetic retinopathy (DR), 6 mild and 6 moderate non-proliferative DR at baseline. We found DR progression in 13 eyes at year 2. The FAZ area (+0.008±0.002 mm 2 /year, p<0.0001), perimeter (+0.036±0.010 mm/year, p=0.006) and AI (+0.005±0.002/year, p=0.0280) increased significantly. A pronounced decrease was found in the superficial (-1.425±0.290%/year, p<0.0001) but not the deep VD. Inner neuroretinal loss was confined to the ganglion cell (-0.539±0.150 µm/year, p=0.0004) and the inner plexiform layer (-0.361±0.127 µm/year, p=0.0045). In the outer retina, we observed a statistically significant decrease in thickness in the outer plexiform, photoreceptor layer and pigment epithelium of -0.921±0.161 µm/year, -0.325±0.139 µm/year and -0.385±0.084 µm/year, respectively., Conclusion: Subclinical signs of microangiopathy and neurodegeneration appear in parallel and are highly progressive even in the earliest stages of diabetic retinal disease. Trial registration number EudraCT20156000239634., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Comparison of diabetic retinopathy (DR) severity between autonomous Artificial Intelligence (AI)-based outputs from an FDA-approved screening system and human retina specialists' gradings from ultra-widefield (UWF) colour images., Methods: Asymptomatic diabetics without a previous diagnosis of DR were included in this prospective observational pilot study. Patients were imaged with autonomous AI (IDx-DR, Digital Diagnostics). For each eye, two 45° colour fundus images were analysed by a secure server-based AI algorithm. UWF colour fundus imaging was performed using Optomap (Daytona, Optos). The International Clinical DR severity score was assessed both on a 7-field area projection (7F-mask) according to the early treatment diabetic retinopathy study (ETDRS) and on the total gradable area (UWF full-field) up to the far periphery on UWF images., Results: Of 54 patients included (n = 107 eyes), 32 were type 2 diabetics (11 females). Mean BCVA was 0.99 ± 0.25. Autonomous AI diagnosed 16 patients as negative, 28 for moderate DR and 10 for having a vision-threatening disease (severe DR, proliferative DR, diabetic macular oedema). Based on the 7F-mask grading with the eye with the worse grading defining the DR stage 23 patients were negative for DR, 11 showed mild, 19 moderate and 1 severe DR. When UWF full-field was analysed, 20 patients were negative for DR, while the number of mild, moderate and severe DR patients were 12, 21, and 1, respectively., Conclusions: The autonomous AI-based DR examination demonstrates sufficient accuracy in diagnosing asymptomatic non-proliferative diabetic patients with referable DR even compared to UWF imaging evaluated by human experts offering a suitable method for DR screening., (© 2022. The Author(s).)

In this retrospective study the morphological response of teleangiectatic capillaries (TCs) to focal laser treatment and the functional and morphological outcome after Indocyanine green angiography (ICGA)-guided laser therapy was evaluated. TCs in eyes with diabetic macular edema (DME) were treated with laser therapy. The immediate and subsequent reaction of the TCs lumina to direct photocoagulation was monitored with customized OCT single scans. Additionally, patients were treated with intravitreal anti-VEGF as needed. 12 eyes of 9 patients with treatment naive (6 eyes) and pretreated (6 eyes) DME were followed-up for a mean of 24 months (± 8.1SD). Best-corrected visual acuity improved from 0.25 logMar (± 0.2SD) to 0.12 (± 0.10SD; p = 0.06) at each patient's last visit. During laser treatment a darkening of the TCs lumina was achieved in 91.3% of lesions. All these lesions fully resolved, whereas TCs, which showed no darkening of their lumen in OCT persisted and required re-treatment with laser. Additional anti-VEGF injections were indicated in only one eye (8.3%). The darkening of the TCs lumina visible in OCT might provide an image-biomarker that indicates successful coagulation of aneurysmatic lesions. Consequently, a significant functional and morphological improvement with need for anti-VEGF treatment in only one eye, was achieved.Information concerning the registration of the trial: date of registration: 11th of december, 2019. Trial registration number: 107/2019., (© 2022. The Author(s).)

Purpose: Cardiovascular disease and foremost coronary heart disease (CHD) are the worldwide leading causes of death. The aim of this study was to use non-invasive, multimodel retinal imaging to define microvascular features in patients with and without coronary angiography (CA)-confirmed CHD., Methods: In this prospective, cross-sectional pilot study we included adult patients who presented to a tertiary referral center for elective CA due to suspected CHD. All patients underwent widefield fundus photography for retinopathy grading. Optical coherence tomography angiography was used to measure vessel density (VD) of the individual capillary plexuses in 6 × 6-mm macular volume scans. Adaptive optics imaging was performed to assess the first-order arteriolar lumen diameter (LD), total diameter (TD), wall-to-lumen ratio (WLR), and wall cross-section area, as well as to qualitatively describe vessel morphology., Results: Of the included 45 patients (13 females; 65 ± 10 years old), 27 were confirmed with CHD in elective CA. The most prevalent retinal vascular pathologies were arteriovenous nickings, focal arterial narrowings, and microaneurysms. VD in the superficial capillary plexus, deep capillary plexus, and choriocapillaris was lower in CHD patients, although the odds ratios were not significantly different from 1 (P = 0.06-0.92). Median arterial LD, TD, and WLR values were 98.3 µm (interquartile range [IQR] = 13.0), 122.9 µm (IQR = 17.6), and 0.26 µm (IQR = 0.07), respectively, with a trend toward a higher WLR in CHD patients., Conclusions: In a cardiovascular risk population, high-resolution quantitative and qualitative microvascular phenotyping in the retina may provide valuable subclinical indicators for coronary artery impairment, although larger clinical trials are needed., Translational Relevance: Subclinical retinal microvascular changes may serve as non-invasive, cost-effective biomarkers for risk stratification of patients with CHD.

Purpose: The purpose of this study was to assess density and morphology of cone photoreceptors (PRs) and corresponding retinal sensitivity in ischemic compared to nonischemic retinal capillary areas of diabetic eyes using adaptive optics optical coherence tomography (AO-OCT) and microperimetry (MP)., Methods: In this cross-sectional, observational study five eyes of four patients (2 eyes with proliferative diabetic retinopathy (DR) and 3 eyes moderate nonproliferative DR) were included. PR morphology and density was manually assessed in AO-OCT en face images both at the axial position of the inner-segment outer segment (IS/OS) and cone outer segment tips (COSTs). Retinal sensitivity was determined by fundus-controlled microperimetry in corresponding areas (MP-3, Nidek)., Results: In AO-OCT, areas affected by capillary nonperfusion showed severe alterations of cone PR morphology at IS/OS and COST compared to areas with intact capillary perfusion (84% and 87% vs. 9% and 8% of area affected for IS/OS and COST, respectively). Mean reduction of PR signal density in affected areas compared to those with intact superficial capillary plexus (SCP) and deep capillary plexus (DCP) perfusion of similar eccentricity was -38% at the level of IS/OS (P = 0.01) and -39% at the level of COST (P = 0.01). Mean retinal sensitivity was 10.8 ± 5.4 in areas affected by DCP nonperfusion and 28.2 ± 1.5 outside these areas (P < 0.001)., Conclusions: Cone PR morphology and signal density are severely altered in areas of capillary nonperfusion. These structural changes are accompanied by a severe reduction of retinal sensitivity, indicating the importance of preventing impaired capillary circulation in patients with DR.

The pyramid wavefront sensor (P-WFS) has replaced the Shack-Hartmann (SH-) WFS as the sensor of choice for high-performance adaptive optics (AO) systems in astronomy. Many advantages of the P-WFS, such as its adjustable pupil sampling and superior sensitivity, are potentially of great benefit for AO-supported imaging in ophthalmology as well. However, so far no high quality ophthalmic AO imaging was achieved using this novel sensor. Usually, a P-WFS requires modulation and high precision optics that lead to high complexity and costs of the sensor. These factors limit the competitiveness of the P-WFS with respect to other WFS devices for AO correction in visual science. Here, we present a cost-effective realization of AO correction with a non-modulated P-WFS based on standard components and apply this technique to human retinal in vivo imaging using optical coherence tomography (OCT). P-WFS based high quality AO imaging was successfully performed in 5 healthy subjects and smallest retinal cells such as central foveal cone photoreceptors are visualized. The robustness and versatility of the sensor is demonstrated in the model eye under various conditions and in vivo by high-resolution imaging of other structures in the retina using standard and extended fields of view. As a quality benchmark, the performance of conventional SH-WFS based AO was used and successfully met. This work may trigger a paradigm shift with respect to the wavefront sensor of choice for AO in ophthalmic imaging., Competing Interests: The authors declare no conflicts of interest., (Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.)

Purpose: To prospectively investigate the development of quantitative autofluorescence (qAF) during progression from intermediate to late age-related macular degeneration (AMD)., Methods: Quantitative autofluorescence images from patients with intermediate AMD were acquired every three months with a Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany) using a built-in autofluorescence reference. The association between changes in longitudinal qAF and progression toward late AMD was assessed using Cox regression models with time-dependent covariates., Results: One hundred and twenty-one eyes of 71 patients were included, and 653 qAF images were acquired. Twenty-one eyes of 17 patients converted to late AMD (median follow-up: 21 months; 12 eyes: atrophic AMD; nine eyes: neovascular AMD). The converting patients' mean age was 74.6 ± 4.4 years. Eleven eyes in the converting group (52.4%) were pseudophakic. The presence of an intraocular lens did not affect the qAF regression slopes (P > 0.05). The median change for atrophic AMD was -2.34 qAF units/3 months and 0.78 qAF units/3 months for neovascular AMD. A stronger decline in qAF was significantly associated with an increased risk of developing atrophic AMD (hazard ratio = 1.022, P < 0.001). This association, however, was not present in the group progressing toward neovascular AMD (hazard ratio = 1.001, P = 0.875)., Conclusion: The qAF signal declines with progression to atrophy, contrary to developing neovascularization. Quantitative autofluorescence may allow identification of patients at risk of progressing to late AMD and benefits individualized patient care in intermediate AMD.

Purpose: To study birefringence of the peripapillary retinal nerve fiber layer (RNFL) of diabetic eyes with no clinical signs of diabetic retinopathy (DR) or mild to moderate DR stages using spectral-domain polarization-sensitive (PS) optical coherence tomography (OCT)., Methods: In this observational pilot study, circular PS-OCT scans centered on the optic nerve head were recorded in prospectively recruited diabetic and age-matched healthy eyes. From averaged circumpapillary intensity and retardation tomograms plots of RNFL birefringence were obtained by a linear fit of retardation versus depth within the RNFL tissue for each A-scan position and mean birefringence values for RNFL calculated. Spectral-domain OCT imaging (Heidelberg Engineering) was performed to assess peripapillary RNFL thickness and macular ganglion cell complex (GCC)., Results: Out of 70 eyes of 43 diabetic patients (mean ± SD age: 50.86 ± 15.71) 36 showed no signs of DR, 17 mild and 17 moderate nonproliferative DR with no diabetic macular edema. Thirty-four eyes of 34 healthy subjects (53.21 ± 13.88 years) served as controls. Compared with healthy controls (0.143° ± 0.014°/µm) mean total birefringence of peripapillary RNFL was significantly reduced in subclinical diabetic eyes (0.131° ± 0.014°/µm; P = 0.0033), as well as in mild to moderate DR stages (0.125° ± 0.018°/µm, P < 0.0001) with borderline statistically significant differences between diabetic patients (P = 0.0049). Mean birefringence values were significantly lower in inferior compared with superior RNFL sectors (P < 0.0001) of diabetic eyes with no such difference detected in the healthy control group., Conclusions: We identified evidence of early neuroretinal alteration in diabetic eyes through reduced peripapillary RNFL birefringence assessed by PS-OCT occurring before appearance of clinical microvascular lesions or GCC alterations.

Purpose: To assess the influence of the SARS-CoV-2 lockdown in spring on frequency, severity and quality of care of rhegmatogeneous retinal detachments (RRD) in a tertiary referral center in Vienna, Austria., Methods: Single center, consecutive case series with historical controls. Patients presenting with primary RRD during the first Austrian SARS-CoV-2 lockdown (March 16th-May 3rd 2020) and a corresponding control group consisting of the same time period of the preceding 3 years., Results: The mean number of patients with RD in the reference group (RG) was 22 (± 1) and in the lockdown group (LG) 15. Median total delay, defined as onset of symptoms until surgery, in the RG was 5 (lower quartile: 3.0; upper quartile: 8.0) compared to 7 (3.0; 12.0) days in the LG, (p = 0.740). During the lockdown 67% of patients were referred from an external ophthalmologist compared to 52% in the RG, (p = 0.395). 34% of patients in the RG presented with an attached macula compared to 33% in the LG (p = 0.597). PVR was present in 49% of cases in the RG compared to 73% in the LG. Single surgery success (SSS) rates were lower in the LG (73.3%) compared to the RG (85.3%), (p = 0.275)., Conclusion: Patients with RRD during the SARS-CoV-2 lockdown presented and were treated within acceptable time limits, showed the same macula-on ratios but a higher PVR rate and a tendency towards worse SSS rates compared to the time period of the preceding 3 years., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Ursula Schmidt-Erfurth has received lecture fees from Alcon, Bayer Healthcare, Novartis, Regeneron, and Pfizer and consulting fees from Alcon, Bayer Healthcare, and Novartis. Andreas Pollreisz has received consulting fees from Oertli Instruments. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: To assess and compare safety and effectiveness between 23-gauge and 25-gauge vitrectomy systems for the treatment of common vitreoretinal diseases in non-vitrectomized eyes., Methods: Retrospective evaluation of patients who underwent pars plana vitrectomy from April 2018 to December 2019 at the Department of Ophthalmology and Optometry at the Medical University of Vienna (MUV) for the following indications: macular epiretinal membrane, macular hole, macular lamellar hole, vitreous hemorrhage, vitreous opacities, vitreomacular traction syndrome and macular edema., Results: 201 eyes of 195 patients that underwent 23-gauge (n = 105 eyes) or 25-gauge (n = 96 eyes) vitrectomy were included in this study. The mean best-corrected visual acuity (BCVA) improved at 1-3 months postoperatively and beyond 3 months in both gauge groups. Risk of any complication within 1 month postoperatively was lower in the 25-gauge group, but the difference was statistically not significant (HR [95% CI]: 0.95 [0.53; 1.70], p = 0.85). Intraocular pressure less than 5 mmHg was observed in 2 eyes (2%) in the 23-gauge group at the first postoperative day. Intraocular pressure elevation over 25 mmHg occurred in 5 eyes (2 eyes, 2%, in 23-gauge and 3 eyes, 3%, in 25-gauge group) at postoperative day 1, between 7 and 28 days in 5 cases (2 eyes, 2%, in 23-gauge and 3 eyes, 3%, in 25-gauge group), and in 2 eyes (2%) of the 23-gauge group at postoperative day 145 and 61, respectively. Retinal detachment occurred in 1 eye (1%) in the 23-gauge and in 3 eyes (3%) in the 25-gauge group. We did not observe any cases of endophthalmitis., Conclusion: Results in terms of safety, surgical success and visual outcomes for the treatment of common vitreoretinal surgery indications seem to be comparable between 23-gauge and 25-gauge vitrectomy systems, indicating that the two gauge systems can be used equally in the clinical routine., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: consultant at Oertli Instruments (Andreas Pollreisz).This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Purpose: To identify the changes in distinct vascular parameters of choroidal neovascularization (CNV) in eyes with treatment-naïve neovascular age-related macular degeneration (nAMD) during the primary response to anti-VEGF therapy using aflibercept., Methods: Patients were prospectively followed during the first 3 months according to a standardized protocol with mandatory visits at days 7 and 14 after each anti-VEGF treatment up to day 90. Fourteen eyes were seen in addition at days 1 and 3 post-initial injection. Aflibercept was administered at baseline (BL), day 30 and 60. 6 × 6mm SSOCTA (PlexElite, Zeiss) images were acquired. Using the semi-automated AngioTool, CNV area, vessel area, vessel density (VD), the number of junctions, junctions density, total vessel length, average vessel length, total number of endpoints and lacunarity were assessed., Results: Thirty-two consecutive patients presenting with treatment-naïve, SSOCTA-positive CNV lesions were included. Close follow-up showed a characteristic neovascular response curve with a dynamic decrease in lesion size within days and a reactive increase following 2 weeks after initial treatment. An undulating pattern was seen for all neovascular parameters except for vascular density, with variable statistical significance. Due to a flattening of the therapeutic response as early as after the second treatment, CNV lesion size and most of the related parameters had an increase in activity above baseline values at the end of the loading phase. Lesion size was the leading feature of reactivation by a mean increase of 19.3% after three monthly aflibercept injections. Subgroup analysis based on lesion size revealed a significant correlation between best-corrected visual acuity and quantitative change in lesion size over time, but not baseline size., Conclusions: Using SSOCTA, a morphologic neovascular response pattern can be identified in anti-VEGF treatment of CNV. A synchronized early decrease and consecutive reactivation in a large spectrum of neovascular biomarkers including size and internal structure are visualized in a qualitative and quantitative manner. SSOCTA analyses allow new insights in CNV morphology changes and therapeutic response., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To evaluate the change in the fovea's postoperative location after successful pars plana vitrectomy with combined epiretinal and internal limiting membrane peeling in patients with idiopathic epiretinal membranes (iERMs)., Methods: In this prospective study 32 eyes of 32 patients with iERMs were followed from baseline before until 3 months after surgery. Study measures included 4-m Early Treatment Diabetic Retinopathy Study best-corrected visual acuity, enhanced-depth imaging-optical coherence tomography, and intraoperative fundus photographs. Foveal movement was assessed by measuring the change in the papillofoveal distance (∆PFD)., Results: Mean ∆PFD in the study eye was -124 µm (±138) and -272 µm (±213) one day and 3 months after surgery, respectively. Mean ∆PFD after 3 months was greater in the study than in the fellow eye (P < 0.001). ∆PFD at Month 3 did not correlate with the internal limiting membrane area peeled (P = 0.78)., Conclusion: Foveal movement starts immediately after surgery and causes a statistically significant reduction in PFD after uneventful macular pucker surgery. ∆PFD correlates statistically significantly with baseline best-corrected visual acuity and baseline central retinal thickness. The internal limiting membrane peeling size had no significant effect on the amount of postoperative foveal dislocation.

Purpose: To refine estimates of macular soft drusen abundance in eyes with age-related macular degeneration (AMD) and evaluate hypotheses about drusen biogenesis, we investigated topographic distribution and growth rates of drusen by optical coherence tomography (OCT). We compared results to retinal features with similar topographies (cone density and macular pigment) in healthy eyes., Methods: In a prospective study, distribution and growth rates of soft drusen in eyes with AMD were identified by human observers in OCT volumes and analyzed with computer-assistance. Published histologic data for macular cone densities (n = 12 eyes) and in vivo macular pigment optical density (MPOD) measurements in older adults with unremarkable maculae (n = 31; 62 paired eyes, averaged) were revisited. All values were normalized to Early Treatment Diabetic Retinopathy Study (ETDRS) subfield areas., Results: Sixty-two eyes of 44 patients were imaged for periods up to 78 months. Soft drusen volume per unit volume at baseline is 24.6-fold and 2.3-fold higher in the central ETDRS subfield than in outer and inner rings, respectively, and grows most prominently there. Corresponding ratios (central versus inner and central versus outer) for cone density in donor eyes is 13.3-fold and 5.1-fold and for MPOD, 24.6 and 23.9-fold, and 3.6 and 3.6-fold., Conclusions: Normalized soft drusen volume in AMD eyes as assessed by OCT is ≥ 20-fold higher in central ETDRS subfields than in outer rings, paralleling MPOD distribution in healthy eyes. Data on drusen volume support this metric for AMD risk assessment and clinical trial outcome measure. Alignment of different data modalities support the ETDRS grid for standardizing retinal topography in mechanistic studies of drusen biogenesis.

Purpose: To assess the signal composition of cone photoreceptors three-dimensionally in healthy retinas using adaptive optics optical coherence tomography (AO-OCT)., Methods: Study population. Twenty healthy eyes of ten subjects (age 23 to 67). Procedures. After routine ophthalmological assessments, eyes were examined using AO-OCT. Three-dimensional volumes were acquired at 2.5° and 6.5° foveal eccentricity in four main meridians (superior, nasal, inferior, temporal). Cone densities and signal compositions were investigated in four different planes: the cone inner segment outer segment junction (IS/OS), the cone outer segment combined with the IS/OS (ISOS+), the cone outer segment tips (COST) and full en-face plane (FEF) combining signals from all mentioned cone layers. Additionally, reliability of a simple semi-automated approach for assessment of cone density was tested. Main outcome measures. Cone density of IS/OS, IS/OS+, COST and FEF. Qualitative depiction and composition of each cone layer. Inter-rater agreement of cone density measurements., Results: Mean overall cone density at all eccentricities was highest at the FEF plane (21.160/mm2), followed by COST (20.450/mm2), IS/OS+ (19.920/mm2) and IS/OS (19.530/mm2). The different meridians and eccentricities had a significant impact on cone density, with lower eccentricity resulting in higher cone densities (p≤.001), which were highest at the nasal, then temporal, then inferior and then superior meridian. Depiction of the cone mosaic differed between all 4 layers regarding signal size and packing density. Therefore, different cone layers showed evident but not complete signal overlap. Using the semi-automated technique for counting of cone signals achieved high inter-rater reliability (ICC > .99)., Conclusions: In healthy individuals qualitative and quantitative changes in cone signals are found not only in different eccentricities and meridians, but also within different photoreceptor layers. The variation between cone planes has to be considered when assessing the integrity of cone photoreceptors in healthy and diseased eyes using adaptive optics technology., Competing Interests: The authors have declared that no competing interests exist.

Background: To prospectively investigate retinal vascular changes in patients undergoing epiretinal membrane (ERM) and internal limiting membrane (ILM) peeling using swept source optical coherence tomography angiography (SSOCTA)., Methods: Consecutive patients were grouped based on ERM severity and followed using SSOCTA up to month 3 after surgical intervention. Superficial and deep foveal avascular zone (s/dFAZ) as well as foveal and parafoveal vessel density (VD) were correlated with ERM severity and visual acuity. Differences between groups were evaluated., Results: Significant correlations were found between ERM severity and baseline sFAZ, dFAZ and best corrected visual acuity (BCVA), central retinal subfield thickness (CST) and ΔCST (r = -0.52, r = -0.43, r = -0.42, r = 0.58, r = 0.39; all p<0.05). Vascular flow parameters did not correlate with age, peeling size, pseudophakia or CST, but correlated with intraretinal cysts presence. No associations of BCVA with any of the OCTA parameters across time were found. Significant differences between ERM severity groups 1 and 2 were found for sFAZ at baseline (p = 0.005) and at the 3-month follow-up (p = 0.014), and for dFAZ at baseline (p = 0.017). Superficial foveal and parafoveal VD were not significantly different between groups (all p>0.05)., Conclusions: This study clearly shows that ERM severity based on ERM staging has to be taken into account when undertaking studies in patients with idiopathic ERM using SSOCTA. Further, specific changes in the superficial and deep retinal vasculature in eyes undergoing ERM and ILM peeling were found. However, the clinical usefulness and prognostic value for post-surgical treatment BCVA of the SSOCTA-derived variables (sFAZ and dFAZ area, as well as foveal and parafoveal VD) used remains questionable., Competing Interests: The authors have declared that no competing interests exist.

An adaptive optics optical coherence tomography (AO-OCT) system is used to assess sixty healthy eyes of thirty subjects (age 22 to 75) to evaluate how the outer retinal layers, foveal eccentricity and age effect the mean cone density. The cone mosaics of different retinal planes (the cone inner segment outer segment junction (IS/OS), the cone outer segment combined with the IS/OS (ISOS+), the cone outer segment tips (COST), and the full en-face plane (FEF)) at four main meridians (superior, nasal, inferior, temporal) and para- and perifoveal eccentricities (ecc 2.5° and 6.5°) were analyzed quantitatively. The mean overall cone density was 19,892/mm 2 at ecc 2.5° and 13,323/mm 2 at ecc 6.5°. A significant impact on cone density was found for eccentricity (up to 6,700/mm 2 between ecc 2.5° and 6.5°), meridian (up to 3,700/mm 2 between nasal and superior meridian) and layer (up to 1,400/mm 2 between FEF and IS/OS). Age showed only a weak negative effect. These factors as well as inter-individual variability have to be taken into account when comparing cone density measurements between healthy and pathologically changed eyes, as their combined effect on density can easily exceed several thousand cones per mm 2 even in parafoveal regions.

Purpose: To evaluate the characteristics and morphological alterations in central retinal ischemia caused by diabetic retinopathy (DR) or retinal vein occlusion (RVO) as seen in optical coherence tomography angiography (OCTA) and their relationship to visual acuity., Methods: Swept-source optical coherence tomography (SSOCT) and OCTA (Topcon, Triton) data of patients with central involving retinal ischemia were analyzed in this cross-sectional study. The following parameters were evaluated: vessel parameters, foveal avascular zone (FAZ), intraretinal cysts (IRC), microaneurysms (MA), vascular collaterals in the superficial (SCP) and deep plexuses (DCP), hyperreflective foci (HRF), epiretinal membrane (ERM), external limiting membrane (ELM) and ellipsoid zone (EZ) disruption, as well as the disorganization of retinal inner layers (DRIL). Best-corrected visual acuity (BCVA), age, gender, disease duration and ocular history were also recorded., Results: 44 eyes of 44 patients (22 with RVO, 22 with DR) were analyzed. The mean age was 60.55 ± 11.38 years and mean BCVA 0.86 ± 0.36 (Snellen, 6m). No significant difference was found between DR subgroups (non proliferative vs. proliferative). Between RVO subgroups (CRVO vs. BRVO) a significant difference was found in term of collateral vessel of the DCP (p = 0.014). A pooled DR and RVO group were created and compared. Significantly more MAs (p = 0.007) and ERM (p = 0.007) were found in the DR group. Statistically significant negative correlation was demonstrated between FAZ and BCVA (p = 0.45) when analyzing all patients with retinal ischemia., Conclusion: This study has shown that the best predictor of visual outcome in center involved ischemic diseases is the size of FAZ. Besides the presence of MAs and ERM, all other OCT and OCTA parameters were present in a similar extent in DR and RVO group despite the completely different disease origins. Our results suggest that as soon as retinal ischemia in the macular region is present, it has a similar appearance and visual outcome independently of the underlying disease., Competing Interests: The authors have declared that no competing interest exist in relation to this work.

Background: The aim of our study was to investigate a possible association between macular perfusion status and retinal ischemia and leakage up to far peripheral retinal areas in eyes with early to advanced stages of diabetic retinopathy (DR)., Methods: In a retrospective, cross sectional analysis ultrawide field (UWF) color fundus photos (Optos, Optomap California) were graded for DR severity. Foveal avascular zone (FAZ) and vessel density from the superficial (SCP) and deep capillary plexus (DCP) were assessed on optical coherence tomography angiography (OCTA) scans (Topcon, DRI-OCT Triton). UWF angiography images were used to quantify leakage/ischemic index and number of microaneurysms (MA). Age, gender, disease duration, type of diabetes, HbA1C, hypertension, complications of diabetes and ocular history were recorded. Univariate mixed models and Spearman correlation analysis were used for statistical testing., Results: 24 eyes of 17 laser-naive diabetic patients with different stages of DR were analyzed. The mean age was 59.56 ± 8.46 years and the mean disease duration 19.65 ± 12.25 years. No statistically significant associations between FAZ size, macular vessel density of SCP/DCP and peripheral retinal ischemia, leakage and MA number were demonstrated. Higher stages of DR were associated with ischemic index (estimate [95% CI]: 13.04 [1.5; 24.5], p = 0.033) and MA count (estimate [95% CI]: 43.7 [15.6; 71.8], p = 0.01), but no association with leakage index was observed. Only weak correlations between DR severity and anamnestic data were found., Conclusion: Retinal ischemic index and the amount of MAs assessed on UWFA up to peripheral areas are indicators of DR severity but not related to microvascular perfusion status in the macular region. Significance and timely sequence of macular vessel density in DR progression may need to be re-evaluated in future studies.

Purpose: To compare area measurements between swept source optical coherence tomography angiography (SSOCTA), fluorescein angiography (FA), and indocyanine green angiography (ICGA) after applying a novel deep-learning-assisted algorithm for accurate image registration., Methods: We applied an algorithm for the segmentation of blood vessels in FA, ICGA, and SSOCTA images of 24 eyes with treatment-naive neovascular age-related macular degeneration. We trained a model based on U-Net and Mask R-CNN for each imaging modality using vessel annotations and junctions to estimate scaling, translation, and rotation. For fine-tuning of the registration, vessels and the elastix framework were used. Area, perimeter, and circularity measurements were performed manually using ImageJ., Results: Choroidal neovascularization lesion size, perimeter, and circularity delineations showed no significant difference between SSOCTA and ICGA (all P > 0.05). Choroidal neovascularization area showed excellent correlation between SSOCTA and ICGA (r = 0.992) and a Bland-Altman bias of -0.10 ± 0.24 mm. There was no significant difference in foveal avascular zone size between SSOCTA and FA (P = 0.96) and an extremely small bias of 0.0004 ± 0.04 mm and excellent correlation (r = 0.933). Foveal avascular zone perimeter was not significantly different, but foveal avascular zone circularity was significantly different (P = 0.047), indicating that some small cavities or gaps may be missed leading to higher circularity values representing a more round-shaped foveal avascular zone in FA., Conclusion: We found no statistically significant differences between SSOCTA and FA and ICGA area measurements in patients with treatment-naive neovascular age-related macular degeneration after applying a deep-learning-assisted approach for image registration. These findings encourage a paradigm shift to using SSOCTA as a first-line diagnostic tool in neovascular age-related macular degeneration.

Purpose: The impact of peripheral retinal lesions (PL) visualized with ultra-wide-field imaging on diabetic retinopathy (DR) remains unclear. The purpose of this study was to assess the presence of PL and their association with macular microvasculopathy, metabolic dysfunction, and neurodegeneration in patients with Type II diabetes and early retinal disease., Methods: Forty-five degree color fundus (Topcon) and 200° ultra-wide-field images (Optos) were assessed for the presence and severity of DR. Lesions anterior to the 45° were considered peripheral. The foveal avascular zone area, perimeter and acircularity index, and foveal full-retina and parafoveal superficial/deep complex vessel density were evaluated with RTVue optical coherence tomography angiography. Vessel oxygen saturation was measured with oximetry. Peripapillary retinal nerve fiber and individual macular retinal layer thicknesses were measured with Spectralis optical coherence tomography., Results: Among the 161 eyes (80 left eyes) of 81 patients (34 female), 64 (39.8%) showed higher levels of DR on ultra-wide-field than on 45° fundus images (P < 0.0001). PL were identified in 97 eyes (60.3%) and in 59 among 115 eyes without central signs of DR. No significant correlation to biomarkers of central microvascular disease (foveal avascular zone/vessel density variables), oxygen saturation, and retinal layer thickness was found., Conclusion: Ultra-wide-field imaging helps to detect more eyes with early DR due to the detection of PL, which appear independently of biomarkers of macular microvascular impairment, metabolic function, and neuropathy in eyes without central signs of DR. These results suggest that the evaluation of the retinal periphery may become crucial in DR screening if PL are proven to influence disease outcomes.

The retinal nerve fiber layer (RNFL) is a fibrous tissue that shows form birefringence. This optical tissue property is related to the microstructure of the nerve fiber axons that carry electrical signals from the retina to the brain. Ocular diseases that are known to cause neurologic changes, like glaucoma or diabetic retinopathy (DR), might alter the birefringence of the RNFL, which could be used for diagnostic purposes. In this pilot study, we used a state-of-the-art polarization sensitive optical coherence tomography (PS-OCT) system with an integrated retinal tracker to analyze the RNFL birefringence in patients with glaucoma, DR, and in age-matched healthy controls. We recorded 3D PS-OCT raster scans of the optic nerve head area and high-quality averaged circumpapillary PS-OCT scans, from which RNFL thickness, retardation and birefringence were derived. The precision of birefringence measurements was 0.005°/µm. As compared to healthy controls, glaucoma patients showed a slightly reduced birefringence (0.129 vs. 0.135°/µm), although not statistically significant. The DR patients, however, showed a stronger reduction of RNFL birefringence (0.103 vs. 0.135°/µm) which was highly significant. This result might open new avenues into early diagnosis of DR and related neurologic changes., Competing Interests: The authors declare no conflicts of interest., (Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.)

Purpose: To assess geographic atrophy (GA) using a multimodal imaging approach, focusing on alterations at the level of the retinal pigment epithelium (RPE) and the choriocapillaris (CC) layers, by lesion demarcation, and assessment of morphological alterations within the atrophic area and in the transition zone., Methods: Fifty-seven eyes of 34 patients with atrophic age-related macular degeneration (AMD) were included in this prospective, observational, cross-sectional study. Multimodal imaging using wide-field polarization-sensitive optical coherence tomography (PS-OCT), optical coherence tomography angiography (OCT-A) and fundus autofluorescence (FAF) was performed. The images were overlaid and used to analyse and compare alterations in the retina and the CC., Results: Mean atrophic lesion size was 8.15 mm 2 (range: 2.23-17.23 mm 2 ). In 52 of 57 eyes (91%), OCT-A displayed focal hypodense areas at the CC level in the transition zone of GA, as well as increased focal depolarizing material (e.g. melanin-containing structures) showed in PS-OCT en face depolarizing material maps. These regions of increased depolarizing material at the transition zone corresponded to the hypodense areas on OCT-A scans. All 57 eyes presented with abnormal FAF patterns at the transition zone. All 57 eyes showed distinct alterations of CC flow pattern architecture. Six eyes (11%) demonstrated reduced and three eyes (5%) a complete loss of CC flow pattern architecture across the entire area of GA, while 48 of 57 eyes (84%) presented with irregular mixed patterns of different focal alterations of CC flow architecture within the area of GA. Reduced CC patterns exceeding GA lesion margins into the transitional zone were found in all eyes., Conclusions: Optical coherence tomography angiography images revealed different degrees of flow impairment within the atrophic lesion area and its transition zone. Alterations in RPE morphology and tissue integrity resulting in accumulation of depolarizing material, such as melanin, could result in misinterpretation of OCT-A imaging in areas in the shadow of depolarizing material. These changes seem to be partially independent from autofluorescence altering processes., (© 2020 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To investigate geographic atrophy (GA) progression using quantitative autofluorescence (qAF) in eyes with solitary GA., Methods: Forty-three eyes of 26 patients (age 79.7 ± 7.2 years; 28 women; 16 pseudophakic) underwent spectral-domain optical coherence tomography and qAF imaging at baseline and after 12 months. The junctional zone (AJZ) and a nonaffected 300-µm-wide control area (AC) were delineated on spectral-domain optical coherence tomography scans and transferred to the qAF image. Linear mixed models were calculated to investigate the association between GA progression and qAF, age, and baseline GA area. Mixed model analyses of variance were used to investigate differences in qAF between areas., Results: Quantitative autofluorescence of the three inferior sections of both the AJZ (P = 0.028; P = 0.014 and P = 0.032) and the AC (P = 0.043; P = 0.02 and P = 0.028) were significantly associated with GA progression after 12 months. However, qAF measurements were not associated with GA progression in the overall model (P > 0.05). Mean qAF was significantly lower in the AJZ and growth area (AG12) than in the AC (both P ≤ 0.001)., Conclusion: The authors report a statistically significant association between GA growth area and qAF measurements at specific retinal locations and a significant difference in qAF between the GA border and unaffected areas outside the lesion. Quantitative autofluorescence measurements may be limitedly useful for predicting GA progression.

Using adaptive optics optical coherence tomography, human photoreceptors and retinal pigment epithelium (RPE) cells are typically visualized on a small field of view of ∼1° to 2°. In addition, volume averaging is required for visualizing the RPE cell mosaic. To increase the imaging area, we introduce a lens based spectral domain AO-OCT system that shows low aberrations within an extended imaging area of 4°×4° while maintaining a high (theoretical) transverse resolution (at >7 mm pupil diameter) in the order of 2 µm. A new concept for wavefront sensing is introduced that uses light mainly originating from the RPE layer and yields images of the RPE cell mosaic in a single volume acquisition. The capability of the instrument for in vivo imaging is demonstrated by visualizing various cell structures within the posterior retinal layers over an extended field of view., Competing Interests: The authors declare no conflicts of interest., (Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.)

Purpose: To quantify organelles impacting imaging in the cell body and intact apical processes of human retinal pigment epithelium (RPE), including melanosomes, lipofuscin-melanolipofuscin (LM), mitochondria, and nuclei., Methods: A normal perifovea of a 21-year-old white male was preserved after rapid organ recovery. An aligned image stack was generated using serial block-face scanning electron microscopy and was annotated by expert readers (TrakEM, ImageJ). Acquired measures included cell body and nuclear volume (n = 17); organelle count in apical processes (n = 17) and cell bodies (n = 8); distance of cell body organelles along a normalized apical-basal axis (n = 8); and dimensions of organelle-bounding boxes in apical processes in selected subsamples of cell bodies and apical processes., Results: In 2661 sections through 17 cells, apical processes contained 65 ± 24 melanosomes in mononucleate (n = 15) and 131 ± 28 in binucleate cells (n = 2). Cell bodies contained 681 ± 153 LM and 734 ± 170 mitochondria. LM was excluded from the basal quartile, and mitochondria from the apical quartile. Lengths of melanosomes, LM, and mitochondria, respectively were 2305 ± 528, 1320 ± 574, and 1195 ± 294 nm. The ratio of cell body to nucleus volume was 4.6 ± 0.4. LM and mitochondria covered 75% and 63%, respectively, of the retinal imaging plane., Conclusions: Among RPE signal sources for optical coherence tomography, LM and mitochondria are the most numerous reflective cell body organelles. These and our published data show that most melanosomes are in apical processes. Overlapping LM and previously mitochondria cushions may support multiple reflective bands in cell bodies. This atlas of subcellular reflectivity sources can inform development of advanced optical coherence tomography technologies.

Purpose: To investigate the impact of subretinal drusenoid deposits (SDD) and photoreceptor integrity on global and local geographic atrophy (GA) progression., Methods: Eighty-three eyes of 49 patients, aged 50 years and older with GA secondary to age-related macular degeneration (AMD), were prospectively included in this study. Participants underwent spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) imaging at baseline and after 12 months. The junctional zone and presence of SDD were delineated on SD-OCT and FAF images. Linear mixed models were calculated to investigate the association between GA progression and the junctional zone area, baseline GA area, age, global and local presence of SDD and unifocal versus multifocal lesions., Results: The area of the junctional zone was significantly associated with the progression of GA, both globally and locally (all P < 0.001). SDD were associated with faster growth in the overall model (P = 0.039), as well as in the superior-temporal (P = 0.005) and temporal (P = 0.002) sections. Faster progression was associated with GA baseline area (P < 0.001). No difference was found between unifocal and multifocal lesions (P > 0.05). Age did not have an effect on GA progression (P > 0.05)., Conclusions: Photoreceptor integrity and SDD are useful for predicting global and local growth in GA. Investigation of the junctional zone is merited because this area is destined to become atrophic. Photoreceptor loss visible on SD-OCT might lead to new structural outcome measurements visible before irreversible loss of retinal pigment epithelium occurs.

Purpose: To determine the effect of intravitreal ranibizumab and a dexamethasone implant on aqueous humour cytokine, protein and enzyme levels and to correlate findings to morphologic and functional changes., Methods: In a prospective, randomized, controlled, double-blind study, patients with clinically significant diabetic macular oedema (CSME) were randomly allocated to receive either monthly intravitreal injections of ranibizumab (Lucentis, Novartis Pharma) or a single dexamethasone implant (Ozurdex, Pharm-Allergan) at baseline (BL). Aqueous humour samples were collected at BL and weeks 2, 8 and 20., Results: The study included 18 eyes of 18 patients. In the dexamethasone implant group, soluble intercellular adhesion molecule 1 (sICAM-1) (weeks 2 and 8), CXCL9/monokine induced by gamma interferon (MIG) (weeks 2 and 8), soluble vascular cell adhesion protein 1 (sVCAM-1) (weeks 2 and 8) and monocyte chemo-attractant protein 1 (MCP-1) (week 2) levels were significantly decreased compared with baseline. In the ranibizumab group, placental growth factor (PIGF) (week 2) and vascular endothelial growth factor (VEGF) (week 2 and 8) levels were significantly decreased compared with baseline. No significant changes in central retinal thickness (CRT) or Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) were observed in the Ozurdex group at any time-points. ETDRS scores significantly increased at week 20 (84.88 ± 8.88 letters) compared with baseline (74.78 ± 14.85 letters), and the CRT decreased significantly at week 4 (381.00 ± 114.64 μm) compared with baseline (440 ± 144 μm) in the Lucentis group., Conclusion: The dexamethasone implant affected the aqueous cytokines and proteins MCP-1, sICAM-1, sVCAM-1 and MIG, whereas ranibizumab treatments reduced VEGF and PIGF levels. Morphological changes may diverge from cytokine changes. Results may indicate a rationale for a combination therapy for CSME using both agents, the dexamethasone implant and repeatedly administered ranibizumab injections., (© 2019 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Purpose: Limited information is available on morphologic and functional regeneration of photoreceptors after retinal detachment (RD) surgery. This observational clinical study compared morphologic and functional changes of cones after vitrectomy for macula-off retinal detachment., Design: Prospective, fellow-eye comparative case series., Methods: StudyPopulation: Five eyes after vitrectomy with gas for macula-off retinal detachment (retinal detachment eyes, RDE) and 5 healthy fellow eyes (HFE) of 5 patients (mean age 59.8 years, macula-off duration 0.5 days to 5.5 days). ObservationProcedures: Eyes were examined with adaptive-optics optical coherence tomography (AO-OCT), spectral-domain OCT (SDOCT), and microperimetry (MP) at 6 (baseline, BL) and 56 weeks (follow-up, FUP) after 23 gauge pars plana vitrectomy and SF6 gas tamponade. Eight corresponding regions at foveal eccentricities of 2.5° (ecc 2.5°) and 6.5° (ecc 6.5°) were analyzed in every eye. AO-OCT en face images and SD-OCT B-scans were graded regarding irregularity and loss of photoreceptor signals ranging from none to severe changes. The number of detectable cones at height of the inner-outer segment junction (IS/OS) and cone outer segment tips (COST) was counted manually in AO-OCT images. MP with a custom grid was used to assess retinal sensitivity at these locations. MainOutcomeMeasures: Cone density, cone pattern regularity and signal attenuation, retinal sensitivity., Results: In comparison to HFE, RDE showed highly irregular cone patterns in AO-OCT and irregular outer retinal bands in SDOCT. Despite significant improvement of cone pattern regularity compared to BL (P < .001), 63% of AO images showed remaining cone pattern irregularity and 45.5% of SDOCT B-scans showed severe signal reduction at FUP. In HFE, mean cone density retrieved from IS/OS and COST remained around 20,000/mm 2 (ecc 2.5°) and 16,000/mm 2 (ecc 6.5°) at BL and FUP. Cone density of RDE was significantly reduced and ranged between 200/mm 2 and 15,600/mm 2 (P < .001) at BL. Despite improvement at FUP (P < .001), mean cone density at IS/OS and COST was still lower compared to HFE and ranged between 7790 and 9555 cones/mm 2 (P < .001). Mean retinal sensitivity of all measured locations remained 18 dB in HFE and was significantly lower in RDE, with 14.30 dB at BL and 14.64 dB at FUP. Both SDOCT grading and microperimetry sensitivity showed strong correlation with AO-OCT grading and cone density (rho values > 0.750)., Conclusions: The combination of AO-OCT, SDOCT, and microperimetry is a powerful tool to capture cone regeneration after vitreoretinal surgery. Our study shows that cone morphology and function improve within 56 weeks after RD surgery but structural and functional impairment is still present., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To investigate the short-time effect of intravitreal injections (IVI) of the vascular endothelial growth factor inhibitors ranibizumab and aflibercept on retinal arterial and venous oxygen saturation (SO2a and SO2v), arteriovenous oxygen saturation difference (AVD) and vessel diameter (VDa and VDv) in patients with diabetic macular oedema (DME) and patients with choroidal neovascularization (CNV) due to age-related macular degeneration., Methods: Uncontrolled prospective observational study in 100 eyes. Retinal vessel oxygen saturation and diameters were assessed using a retinal oximeter before and minutes after IVI of ranibizumab or aflibercept., Results: 40 eyes with CNV and 34 eyes with DME were included in the analysis. At baseline, SO2a and SO2v were significantly higher in DME (p = 0.043 and p = 0.009, respectively). After IVI, SO2a significantly decreased in CNV and DME eyes by 2.6% (p = 0.016) and 4.6% (p = 0.002) and SO2v decreased by 14.0% (p = 0.004) and 12.4% (p = 0.017), respectively. However, a significant increase in AVD was only found in CNV (15.7%, p = 0.001). VDa decreased significantly only in DME by 5.7% (p = 0.010). No medication-specific disease effect was found and vice versa., Conclusions: The observed changes can be interpreted as signs of increased metabolic demand during the physiological stress after an IVI. The abnormal arterial constriction and the abolished increase in AVD seen only in eyes with DME indicate an impairment of vascular autoregulation and oxygen distribution and a reduced neuroretinal metabolism in the diabetic retina with a significant impact on inner retinal oxygen consumption shortly after IVI., (© 2019 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)