INVESTIGATING MICROANGIOPATHY USING SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH SUSAC SYNDROME.

PURPOSE: To determine whether optical coherence tomography angiography is of diagnostic utility for Susac syndrome (SuS) by quantifying microvascular retinal changes. METHODS: We enrolled 18 eyes of 9 healthy controls and 18 eyes of 9 patients with chronic SuS (12 had previous branch retinal artery occlusions and 6 were clinically unaffected). Images of the fovea were taken using an optical coherence tomography angiography system. Analysis included vessel density, fractal dimension, vessel diameter, and measurements of the foveal avascular zone (area, eccentricity, acircularity index, and axis ratio) in deep and superficial retinal layers. RESULTS: Skeleton density and inner ring vessel density were significantly lower in patients with SuS (skeleton density: Susac 0.11 ± 0.01 vs. controls 0.12 ± 0.01, P = 0.027. VD: SuS 0.39 ± 0.04 vs. controls 0.42 ± 0.02, P = 0.041). Eccentricity and axis ratio were significantly higher in patients with SuS (EC: Susac 0.61 ± 0.11, controls 0.51 ± 0.10, P = 0.003; axis ratio: Susac 1.57 ± 0.28, controls 1.39 ± 0.11, P = 0.005). SuS eyes (affected and unaffected) had poorer outcomes of the remaining vascular parameters compared with controls (P > 0.05). CONCLUSION: Optical coherence tomography angiography identified chronic microvascular changes in the eyes of patients with chronic SuS. Even clinically unaffected SuS eyes showed poorer vascular parameters. Although further research is needed, this noninvasive imaging modality seems to have the potential to serve as a valuable additive diagnostic tool.

EN FACE OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF INNER RETINAL DIMPLES AFTER INTERNAL LIMITING MEMBRANE PEELING FOR FULL-THICKNESS MACULAR HOLES.

PURPOSE: To quantitatively and qualitatively evaluate the microvascular and structural abnormalities associated with inner retinal dimpling after internal limiting membrane peeling for full-thickness macular holes using sequential en face optical coherence tomography (OCT) and OCT angiography. METHODS: Thirteen eyes of 13 patients with idiopathic full-thickness macular holes were enrolled in the study. Patients were treated with pars plana vitrectomy, internal limiting membrane peeling, and gas tamponade. Subjects were evaluated preoperatively and at postoperative Months 1, 3, and 6. At each visit, patients underwent a comprehensive ophthalmologic examination, en face OCT and OCT angiography. The morphology and number and proportionate area of inner retinal dimples were analyzed. Vessel density of the superficial vascular complex at all visits was also measured. RESULTS: Inner retinal dimples were identified 1 month after surgery in all cases. The number and proportionate area of inner retinal dimples significantly increased over the follow-up period (P = 0.05). Preoperative vessel density of the superficial vascular complex was 17.9 ± 1.9 and did not change significantly over the follow-up period (P = 0.15). CONCLUSION: Inner retinal dimples are identified with en face OCT as early as the first month after internal limiting membrane peeling for idiopathic full-thickness macular holes and progressively increase in number and proportionate area in the subsequent 3 to 6 months after surgery. This may be the result of progressive deturgescence of the nerve fiber layer in the postoperative period.

Three-Dimensional Printing of a Transconjunctival Vitrectomy Trocar-Cannula System.

PURPOSE: The aim of this paper was to study the feasibility of manufacturing a customizable trocar-cannula system for vitreoretinal surgery utilizing commercially available three-dimensional (3D) printing technology. METHODS: A digital model of a trocar-cannula system for vitreoretinal surgery was created using computer-aided design (CAD) software and printed utilizing a laser-sintering 3D printer in modified ABS thermoplastic material. The trocar-cannula prototypes were tested in pig eyes. RESULTS: A customizable digital model was created using commercially available CAD software. Three trocar-cannulas were printed. The smallest cannulas that could be printed had dimensions between 21 and 22G. The trocar-cannulas were inserted in pig eyes after performing sclerotomies with a commercially available 20G MVR blade. One cannula broke during insertion. CONCLUSIONS: This study demonstrates the feasibility of printing a transconjunctival vitrectomy trocar-cannula system with commercially available 3D print technology. The 3D printer and build material used resulted in trocar-cannulas with functional limitations including a minimum size achievable and mechanical resistance.

Treatment outcomes of PCR-positive acute retinal necrosis.

BACKGROUND: Acute retinal necrosis (ARN) is a progressive necrotizing retinitis caused by viral infection. Optimal management strategies have not been established for this detrimental disease. Previous literature published suggests that Varicella-zoster virus (VZV) and Herpes simplex virus-1 (HSV1) are the most common promoters of acute retinal necrosis (ARN). AIMS: The purpose of our study was to investigate the viral distribution, demographic, and treatment outcomes of ARN. METHODS: A retrospective chart review evaluated data from PCR-positive ARN patients diagnosed between 2009 and 2018. RESULTS: Analysis of fourteen eyes from 12 patients found CMV and VZV as the commonest causes of ARN. Patients on 1 g of valacyclovir three times a day (V1T) had worse vision between first and final visits (mean difference of 1.25 ± 0.65, n = 2) compared with patients treated with 2 g of valacyclovir three times a day (V2T), or 900 mg twice a day of valganciclovir (V9B) (mean difference of - 0.067 ± 0.13, n = 6, and 0.067 ± 0.067, n = 6, respectively). Both V1T patients developed retinal detachments (RD). Both CMV patients treated with intravitreal triamcinolone developed ARN, elevated IOP, and one developed multiple RD. CONCLUSIONS: Our review found increased incidence of CMV-positive ARN. Patients with zone 1 disease had worse initial visual acuity. Moreover, patients had more favorable outcomes with V2T and V9B compared to V1T. CMV-positive patients clinically worsened after intravitreal steroid injections, further underscoring the value of a PCR diagnosis to tailor the patients' treatment plan accordingly.

Retinal capillary perfusion heterogeneity in diabetic retinopathy detected by optical coherence tomography angiography.

BACKGROUND: Diabetic retinopathy (DR) is a leading cause of blindness and involves retinal capillary damage, microaneurysms, and altered blood flow regulation. Optical coherence tomography angiography (OCTA) is a non-invasive way of visualizing retinal vasculature but has not been used extensively to study blood flow heterogeneity. The purpose of this study is to detect and quantify blood flow heterogeneity utilizing en-face swept source OCTA in patients with DR. METHODS: This is a prospective clinical study which examined patients with either type 1 or 2 diabetes mellitus. Each included eye was graded clinically as no DR, mild DR, or moderate-severe DR. Ten consecutive en face 6 × 6 mm foveal SS-OCTA images were obtained from each eye using a PLEX Elite 9000 (Zeiss Meditec, Dublin, CA). Built-in fixation-tracking, follow-up functions were utilized to reduce motion artifacts and ensure same location imaging in sequential frames. Images of the superficial and deep vascular complexes (SVC and DVC) were arranged in temporal stacks of 10 and registered to a reference frame for segmentation using a deep neural network. The vessel segmentation was then masked onto each stack to calculate the pixel intensity coefficient of variance (PICoV) and map the spatiotemporal perfusion heterogeneity of each stack. RESULTS: Twenty-nine eyes were included: 7 controls, 7 diabetics with no DR, 8 mild DR, and 7 moderate-severe DR. The PICoV correlated significantly and positively with DR severity. In patients with DR, the perfusion heterogeneity was higher in the temporal half of the macula, particularly in areas of capillary dropout. PICoV also correlates as expected with the established OCTA metrics of perfusion density and vessel density. CONCLUSION: PICoV is a novel way to analyze OCTA imaging and quantify perfusion heterogeneity. Retinal capillary perfusion heterogeneity in both the SVC and DVC increased with DR severity. This may be related to the loss of retinal capillary perfusion autoregulation in diabetic retinopathy.

Relationship between automated choroidal thickness measurements and retinal sensitivity using microperimetry in patients with myopia and different stages of myopic maculopathy.

PURPOSE: To assess the relationship between macular choroidal thickness (CT) measurements and retinal sensitivity (RS) in eyes with myopia and different stages of myopic maculopathy. METHODS: A masked, cross-sectional, and consecutive study involving patients with emmetropia/myopia (control group) and high myopia (HM) eyes. Automated choroidal thickness (CT) and manual outer retinal layer (ORL) thickness were acquired using swept-source optical coherence tomography, while retinal sensitivity (RS) assessed by microperimetry (MP3) in all regions of the macular Early Treatment Diabetic Retinopathy Study (ETDRS) grid. Comparisons were made between groups, and correlations were performed among these measurements, demographic and ocular parameters and myopic maculopathy classification. RESULTS: A total of 37 (74 eyes) patients were included in the study. The mean age was 39 ± 13 years, and 28 patients (76%) were female. HM eyes exhibited inferior best-corrected visual acuity and a more advanced myopic maculopathy classification compared to the control group. The mean macular CT were 255 and 179 µm in the control and HM eyes (P < 0.001), respectively. In the HM eyes, superior ETDRS region presented the greatest values. Mean RS in control and HM groups was 28 and 24 dB (P = 0.001), respectively. Inner temporal followed by superior, were the regions of higher RS. Mean ORL thickness was 83 and 79 µm (P < 0.001), in the control and HM groups, respectively. The inner temporal ETDRS region presented the thickest measure. CT correlated significantly with RS (r = 0.41, P < 0.001) and ORL thickness, (r = 0.58, P < 0.001), which also correlated with RS (r = 0.40, P < 0.001). Spherical equivalent, axial length and myopic maculopathy stage were the parameters that most correlated with CT, RS and ORL thickness. For every 100 µm increase in thickening of CT there was an average increase of 3.4 µm in ORL thickness and 2.7 dB in RS. Myopic maculopathy classification demonstrated influence only with CT. CONCLUSION: Myopia degree is related to ORL and choroidal thinning and deterioration of retinal sensitivity in some ETDRS regions of the macula. Choroidal thinning is associated to with a decline of retinal sensitivity, thinning of ORL, and worsening of myopic maculopathy classification, so new treatments are necessary to prevent myopia progression.

Ciliary body lymphangiogenesis in uveal melanoma with and without extraocular extension.

PURPOSE: To determine whether peritumoral ciliary body lymphatics are found in uveal melanoma in the absence of extraocular extension. DESIGN: Consecutive case series from 1999 to 2005. PARTICIPANTS: Thirty-two uveal melanoma cases involving the ciliary body from the Ophthalmic Pathology Laboratory, University of Toronto, of which 23 showed no extraocular extension. METHODS: All immunofluorescence studies and quantitative analyses were performed in a masked fashion. Sections were immunostained for the presence of lymphatic endothelium using podoplanin (D2-40 antibody) and blood vessel endothelium using CD34. MAIN OUTCOME MEASURES: Identification and quantification of D2-40-positive lymphatic vessels in the ciliary body. RESULTS: In every case (n = 32), D2-40-positive lymphatics were detected in the peritumoral ciliary body. Lymphatic signal was significantly increased in the peritumoral ciliary body compared with the nonperitumoral ciliary body (P < 0.0001). There was no difference in lymphatic signal between cases with and without extraocular extension (P > 0.05). Lymphatics were not detected within the tumors. CONCLUSIONS: Peritumoral lymphangiogenesis was present in the ciliary body in uveal melanomas with and without extraocular extension, and as such, the presence of peritumoral lymphatics is not recommended as a prognostic marker in uveal melanoma.

Long-term assessment of internal limiting membrane peeling for full-thickness macular hole using en face adaptive optics and conventional optical coherence tomography.

OBJECTIVE: To evaluate the long-term structural and microvascular retinal effects of internal limiting membrane peeling for full-thickness macular hole (FTMH) using en face adaptive optics optical coherence tomography (AO-OCT), conventional OCT, and OCT angiography (OCTA). DESIGN: Interventional case series. PARTICIPANTS: Patients with FTMH treated with vitrectomy, internal limiting membrane peeling, and gas tamponade. METHODS: Eleven eyes with FTMH that had at least 12 months of postoperative follow-up were enrolled in the study. En face AO-OCT was used to image the superficial retina in the peeled and nonpeeled areas. En face structural OCT was performed to image the inner retinal dimples (IRDs), macular thickness, and retinal nerve fibre layer (RNFL). En face OCTA was used to examine the integrity of the peripapillary nerve fibre layer (NFL) plexus. RESULTS: AO-OCT showed RFNL wrapping around the IRDs, and no obvious peripapillary NFL plexus dropout was seen with OCTA. Scattered hyper-reflective dots were observed on the surface of the peeled retina in all patients imaged with AO-OCT. No significant differences were found in IRD number (91.5 ± 24.4 versus 77.2 ± 14.7; P = 2.07), IRD proportionate area (8.36 ± 3.34 versus 7.53 ± 2.60; P = 0.159), or macular thickness between the 6- and 12-month (or greater) postoperative visits. CONCLUSION: IRDs do not to progress beyond 6 months postoperatively, and no obvious damage to RFNL and peripapillary NFL plexus was detected. Hyper-reflective dots on the surface of the retina suggestive of possible Müller cell reactive gliosis were identified with AO-OCT.

ADAPTIVE OPTICS OPTICAL COHERENCE TOMOGRAPHY IN A CASE OF ACUTE ZONAL OCCULT OUTER RETINOPATHY.

PURPOSE: To report a case of acute zonal occult outer retinopathy in which adaptive optics (AO) facilitated visualization of abnormal photoreceptors previously thought to be in an area of normal retina on conventional optical coherence tomography (OCT). METHODS: Case report. RESULTS: A 51-year-old woman presents with 11-month history of photopsias and scotoma in the temporal visual field of her left eye. Ocular imaging including fluorescein angiography, fundus autofluorescence and OCT suggested the diagnosis of acute zonal occult outer retinopathy in the left eye. Adaptive optics optical coherence tomography (AO-OCT) revealed photoreceptor abnormalities not previously identified in conventional OCT, in areas apparently normal on multimodal imaging. On enface and cross-sectional AO-OCT, round and evenly spaced hyperreflectivity corresponding to normal cone mosaic (Pattern 1) was adjacent to unevenly and disrupted cone hyperreflectivity (Pattern 2) and areas with hyporeflectivity or no cone reflectivity (Pattern 3). Cross-sectional AO-OCT of Patterns 2 and 3 also revealed attenuation of ellipsoid zone with loss of interdigitation zone. CONCLUSION: Adaptive optics OCT documented cone photoreceptors in finer details than conventional OCT and revealed early changes in a patient with acute zonal occult outer retinopathy, in an area of the retina thought to be normal on conventional multimodal imaging. These findings may provide important insight into pathogenesis and progression of the disease.

Clinical explainable differential diagnosis of polypoidal choroidal vasculopathy and age-related macular degeneration using deep learning.

BACKGROUND: This study aims to achieve an automatic differential diagnosis between two types of retinal pathologies with similar pathological features - Polypoidal choroidal vasculopathy (PCV) and wet age-related macular degeneration (AMD) from volumetric optical coherence tomography (OCT) images, and identify clinically-relevant pathological features, using an explainable deep-learning-based framework. METHODS: This is a retrospective study with data from a cross-sectional cohort. The OCT volume of 73 eyes from 59 patients was included in this study. Disease differentiation was achieved through single-B-scan-based classification followed by a volumetric probability prediction aggregation step. We compared different labeling strategies with and without identifying pathological B-scans within each OCT volume. Clinical interpretability was achieved through normalized aggregation of B-scan-based saliency maps followed by maximum-intensity-projection onto the en face plane. We derived the PCV score from the proposed differential diagnosis framework with different labeling strategies. The en face projection of saliency map was validated with the pathologies identified in Indocyanine green angiography (ICGA). RESULTS: Model trained with both labeling strategies achieved similar level differentiation power (>90%), with good correspondence between pathological features detected from the projected en face saliency map and ICGA. CONCLUSIONS: This study demonstrated the potential clinical application of non-invasive differential diagnosis using AI-driven OCT-based analysis, with minimal requirement of labeling efforts, along with clinical explainability achieved through automatically detected disease-related pathologies.

CONVERSION OF FOCAL CHOROIDAL EXCAVATION WITH THE ONSET OF CENTRAL SEROUS CHORIORETINOPATHY: REPORT OF 2 CASES AND REVIEW OF THE LITERATURE.

PURPOSE: To describe two cases of focal choroidal excavation (FCE) conversion in patients with central serous chorioretinopathy. METHODS: Case report and literature review of cases of FCE conversion. RESULTS: A 35-year-old asymptomatic pregnant patient was found to have conforming FCE on spectral domain optical coherence tomography of the right eye during hydroxychloroquine screening. Three months later, she presented with decreased vision in the right eye and subretinal fluid in both eyes secondary to central serous chorioretinopathy. Spectral domain optical coherence tomography revealed that her FCE had changed to nonconforming type. A 40-year-old male patient was found to have nonconforming FCE and subretinal fluid in his right eye on spectral domain optical coherence tomography. On follow-up, spectral domain optical coherence tomography demonstrated resolution of subretinal fluid and conversion of nonconforming FCE to conforming type. Literature review showed that most cases of FCE remain stable over time. Conversion from nonconforming FCE to conforming type has been described after photodynamic therapy or anti-vascular endothelial growth factor therapy. Conversion from conforming to nonconforming type has been described in 2 cases that developed subretinal fluid in the setting of acute central serous chorioretinopathy. CONCLUSION: Our cases and literature review suggest that nonconforming FCE is the result of persistent subretinal fluid. Further studies are necessary to determine whether symptomatic nonconforming SRF needs treatment to reduce subretinal fluid.

Investigation of the Peripapillary Choriocapillaris in Normal Tension Glaucoma, Primary Open-angle Glaucoma, and Control Eyes.

PRECIS: The peripapillary choriocapillaris (CC) was observed to be significantly impaired in normal tension glaucoma (NTG) subjects compared with normal controls using optical coherence tomography angiography (OCTA). PURPOSE: The aim was to quantitatively evaluate the peripapillary CC in NTG, primary open-angle glaucoma (POAG), and control eyes using OCTA. MATERIALS AND METHODS: Ninety eyes (30 controls, 30 NTG, and 30 POAG) from 73 patients were imaged using the Zeiss Plex Elite 9000. Five repeat 3×3 mm OCTA scans were acquired both nasally and temporally to the optic disc and subsequently averaged. Four CC flow deficit (FD) measures were calculated using the fuzzy C-means approach: FD density (FDD), mean FD size (MFDS), FD number (FDN), and FD area (FDA). RESULTS: Temporal NTG CC parameters were associated with visual field index and mean deviation (P<0.05). The control group showed a significantly lower nasal FDD (nasal: 3.79±1.26%, temporal: 4.48±1.73%, P=0.03), FDN (nasal: 156.43±38.44, temporal: 178.40±45.68, P=0.02), and FDA (nasal: 0.22±0.08, temporal: 0.26±0.10, P=0.03) when compared with temporal optic disc. The NTG group showed a significantly higher FDD (NTG: 5.04±2.38%, control: 3.79±1.26%, P=0.03), FDN (NTG: 185.90±56.66, control: 156.43±38.44, P=0.04), and FDA (NTG: 0.30±0.14 mm2, control: 0.22±0.08 mm2, P=0.03) nasal to the optic disc compared with controls. CONCLUSIONS: Association between CC parameters and glaucoma severity in NTG, but not POAG subjects, suggests vascular abnormalities may be a potential factor in the multifactorial process of glaucoma damage in NTG patients.

Subconjunctival lidocaine before laser treatment: a randomized trial.

PURPOSE: The aim of the study was to determine whether subconjunctival anesthesia is effective at reducing pain associated with laser retinopexy. DESIGN: This was a single-center, prospective, patient-masked, randomized, controlled trial. PARTICIPANTS: In the primary study group, 65 patients were recruited. Thirty-two patients (32 eyes) received anesthetic injection, and 33 patients (33 eyes) received the sham injection. The crossover study group consisted of 28 patients (56 eyes). METHODS: Between February 2008 and April 2008, all patients who were consecutively booked to undergo panretinal photocoagulation (PRP) or peripheral laser retinopexy (PLR) were invited to participate in the study. Patients were randomized to receive subconjunctival lidocaine injection or a sham injection before their intended laser retinal treatment. These patients were defined as our primary study group. Patients who required a second laser treatment received the opposite injection in a masked fashion before laser retinal treatment. These patients were defined as our crossover group. Patients in both the primary study group and the crossover group were masked to the treatment given. After the laser treatment, patients completed a pain questionnaire. MAIN OUTCOME MEASURES: The primary outcome was incidence of pain. The secondary outcome was severity of pain. RESULTS: Primary study group: In the anesthetic treatment group, 19 patients (59%) experienced pain compared with 32 patients (97%) in the sham treatment group (P<0.001). Among the patients who did experience pain, the average pain score was 3.6 in the anesthetic treatment group and 4.1 in the sham treatment group (P=0.55). Crossover study group: In the anesthetic treatment group, 12 patients (43%) experienced pain compared with 28 patients (100%) in the sham treatment group (P<0.001). In patients who did experience pain, the average pain score was 3.3 in the anesthetic treatment group and 4.6 in the sham treatment group. Twenty patients (71%) preferred anesthetic to sham treatments, 1 patient (4%) preferred sham over anesthetic, and 7 patients (25%) thought both laser treatments were the same. CONCLUSIONS: Subconjunctival 2% lidocaine significantly reduces the incidence of pain in patients who receive PRP or PLR.

SPONTANEOUS IMPROVEMENT OF SYPHILIS CHORIORETINITIS: CASE REPORT AND REVIEW OF THE LITERATURE.

PURPOSE: To describe a case of spontaneous improvement of syphilis chorioretinitis and review the literature. METHODS: Case report and literature review of cases with untreated syphilis chorioretinitis. RESULTS: A 58-year-old man presented to the emergency department with counting fingers vision, normal fundus, and disruption of the outer retinal layers on optical coherence tomography of the right eye. Examination by a retina specialist 3 weeks later revealed visual acuity of 20/50 and partial restoration of outer retinal layers on optical coherence tomography. Workup showed positive serology for syphilis and human immunodeficiency virus. Treatment with intravenous penicillin resulted in further vision improvement. Literature review showed six cases of spontaneous improvement of syphilis chorioretinitis. CONCLUSION: Spontaneous improvement of syphilis chorioretinitis is possible. Clinicians should keep a high index of suspicion and consider syphilis chorioretinitis in diseases that affect the outer retina even with spontaneous improvement.

Evaluating Signs of Microangiopathy Secondary to Diabetes in Different Areas of the Retina with Swept Source OCTA.

Purpose: The purpose of this study was to compare perfusion parameters of the parafovea with scans outside the parafovea to find an area most susceptible to changes secondary to diabetic retinopathy (DR). Methods: Patients with different DR severity levels as well as controls were included in this cross-sectional clinical trial. Seven standardized 3 × 3 mm areas were recorded with Swept Source Optical Coherence Tomography Angiography: one centered on the fovea, three were temporal to the fovea, and three nasally to the optic disc. The capillary perfusion density (PD) of the superficial capillary complex (SCC) and deep capillary complex (DCC) as well as the fractal dimension (FD) were generated. Statistical analyses were done with R software. Results: One hundred ninety-two eyes (33 controls, 51 no-DR, 41 mild DR, 37 moderate/severe DR, and 30 proliferative DR), of which 105 patients with diabetes and 25 healthy controls were included (59 ± 15 years; 62 women). Mean PD of the DCC was significantly less in patients without DR (parafovea = 0.48 ± 0.03; temporal = 0.48 ± 0.02; and nasal = 0.48 ± 0.03) compared to controls (parafovea = 0.49 ± 0.02; temporal = 0.50 ± 0.02; and nasal = 0.50 ± 0.03). With increasing DR severity, PD and FD of the SCC and DCC further decreased. Conclusions: Capillary perfusion of the retina is affected early by diabetes. PD of the DCC was significantly reduced in patients with diabetes who did not have any clinical signs of DR. The capillary network outside the parafovea was more susceptible to capillary perfusion deficits compared to the capillaries close to the fovea. Trial Registration: clinicaltrial.gov, NCT03765112, https://clinicaltrials.gov/ct2/show/NCT03765112?term=NCT03765112&rank=1.

Ensemble Deep Learning for Diabetic Retinopathy Detection Using Optical Coherence Tomography Angiography.

Purpose: To evaluate the role of ensemble learning techniques with deep learning in classifying diabetic retinopathy (DR) in optical coherence tomography angiography (OCTA) images and their corresponding co-registered structural images. Methods: A total of 463 volumes from 380 eyes were acquired using the 3 × 3-mm OCTA protocol on the Zeiss Plex Elite system. Enface images of the superficial and deep capillary plexus were exported from both the optical coherence tomography and OCTA data. Component neural networks were constructed using single data-types and fine-tuned using VGG19, ResNet50, and DenseNet architectures pretrained on ImageNet weights. These networks were then ensembled using majority soft voting and stacking techniques. Results were compared with a classifier using manually engineered features. Class activation maps (CAMs) were created using the original CAM algorithm and Grad-CAM. Results: The networks trained with the VGG19 architecture outperformed the networks trained on deeper architectures. Ensemble networks constructed using the four fine-tuned VGG19 architectures achieved accuracies of 0.92 and 0.90 for the majority soft voting and stacking methods respectively. Both ensemble methods outperformed the highest single data-type network and the network trained on hand-crafted features. Grad-CAM was shown to more accurately highlight areas of disease. Conclusions: Ensemble learning increases the predictive accuracy of CNNs for classifying referable DR on OCTA datasets. Translational Relevance: Because the diagnostic accuracy of OCTA images is shown to be greater than the manually extracted features currently used in the literature, the proposed methods may be beneficial toward developing clinically valuable solutions for DR diagnoses.

Microvasculature Segmentation and Intercapillary Area Quantification of the Deep Vascular Complex Using Transfer Learning.

Purpose: Optical coherence tomography angiography (OCT-A) permits visualization of the changes to the retinal circulation due to diabetic retinopathy (DR), a microvascular complication of diabetes. We demonstrate accurate segmentation of the vascular morphology for the superficial capillary plexus (SCP) and deep vascular complex (DVC) using a convolutional neural network (CNN) for quantitative analysis. Methods: The main CNN training dataset consisted of retinal OCT-A with a 6 × 6-mm field of view (FOV), acquired using a Zeiss PlexElite. Multiple-volume acquisition and averaging enhanced the vasculature contrast used for constructing the ground truth for neural network training. We used transfer learning from a CNN trained on smaller FOVs of the SCP acquired using different OCT instruments. Quantitative analysis of perfusion was performed on the resulting automated vasculature segmentations in representative patients with DR. Results: The automated segmentations of the OCT-A images maintained the distinct morphologies of the SCP and DVC. The network segmented the SCP with an accuracy and Dice index of 0.8599 and 0.8618, respectively, and 0.7986 and 0.8139, respectively, for the DVC. The inter-rater comparisons for the SCP had an accuracy and Dice index of 0.8300 and 0.6700, respectively, and 0.6874 and 0.7416, respectively, for the DVC. Conclusions: Transfer learning reduces the amount of manually annotated images required while producing high-quality automatic segmentations of the SCP and DVC that exceed inter-rater comparisons. The resulting intercapillary area quantification provides a tool for in-depth clinical analysis of retinal perfusion. Translational Relevance: Accurate retinal microvasculature segmentation with the CNN results in improved perfusion analysis in diabetic retinopathy.

PARANEOPLASTIC VITELLIFORM MACULOPATHY ASSOCIATED WITH METASTATIC MELANOMA.

PURPOSE: To report a case of paraneoplastic vitelliform maculopathy in a patient with metastatic melanoma of unknown primary site. METHODS: Case report. Main outcome measures include funduscopic examination, fluorescein angiography, fundus autofluorescence, and spectral domain optical coherence tomography. RESULTS: A 44-year-old man with a known history of metastatic melanoma was referred for ophthalmic evaluation because of bilateral vision loss. Funduscopic examination was remarkable for vitelliform maculopathy that was confirmed with fundus autofluorescence and spectral domain optical coherence tomography. CONCLUSION: We describe a rare case of paraneoplastic vitelliform maculopathy. There are many etiologies of acquired vitelliform retinal lesions in the retina. Multimodal retinal imaging, including fundus autofluorescence and spectral domain optical coherence tomography, can be best used to identify these lesions. A history of systemic metastatic melanoma should be ruled out in patients with vitelliform maculopathy.

Automated identification of cone photoreceptors in adaptive optics optical coherence tomography images using transfer learning.

Automated measurements of the human cone mosaic requires the identification of individual cone photoreceptors. The current gold standard, manual labeling, is a tedious process and can not be done in a clinically useful timeframe. As such, we present an automated algorithm for identifying cone photoreceptors in adaptive optics optical coherence tomography (AO-OCT) images. Our approach fine-tunes a pre-trained convolutional neural network originally trained on AO scanning laser ophthalmoscope (AO-SLO) images, to work on previously unseen data from a different imaging modality. On average, the automated method correctly identified 94% of manually labeled cones when compared to manual raters, from twenty different AO-OCT images acquired from five normal subjects. Voronoi analysis confirmed the general hexagonal-packing structure of the cone mosaic as well as the general cone density variability across portions of the retina. The consistency of our measurements demonstrates the high reliability and practical utility of having an automated solution to this problem.