RobOCTNet: Robotics and Deep Learning for Referable Posterior Segment Pathology Detection in an Emergency Department Population.

Purpose: To evaluate the diagnostic performance of a robotically aligned optical coherence tomography (RAOCT) system coupled with a deep learning model in detecting referable posterior segment pathology in OCT images of emergency department patients. Methods: A deep learning model, RobOCTNet, was trained and internally tested to classify OCT images as referable versus non-referable for ophthalmology consultation. For external testing, emergency department patients with signs or symptoms warranting evaluation of the posterior segment were imaged with RAOCT. RobOCTNet was used to classify the images. Model performance was evaluated against a reference standard based on clinical diagnosis and retina specialist OCT review. Results: We included 90,250 OCT images for training and 1489 images for internal testing. RobOCTNet achieved an area under the curve (AUC) of 1.00 (95% confidence interval [CI], 0.99-1.00) for detection of referable posterior segment pathology in the internal test set. For external testing, RAOCT was used to image 72 eyes of 38 emergency department patients. In this set, RobOCTNet had an AUC of 0.91 (95% CI, 0.82-0.97), a sensitivity of 95% (95% CI, 87%-100%), and a specificity of 76% (95% CI, 62%-91%). The model's performance was comparable to two human experts' performance. Conclusions: A robotically aligned OCT coupled with a deep learning model demonstrated high diagnostic performance in detecting referable posterior segment pathology in a cohort of emergency department patients. Translational Relevance: Robotically aligned OCT coupled with a deep learning model may have the potential to improve emergency department patient triage for ophthalmology referral.

Update on Retinal Drug Toxicities.

PURPOSE OF REVIEW: This review aims to provide an update on the clinical presentations and diagnostic findings of drug-induced retinal toxicities. RECENT FINDINGS: Several newly FDA-approved medications have been associated with acute retinal toxicities, including brolucizumab, MEK inhibitors, ulixertinib, and FGFR inhibitors. Additionally, as previously believed-to-be well-tolerated medications, such as pentosan sulfate sodium, anti-retroviral therapies, and certain intraoperative ocular medications, are used more frequently or for longer periods of time, associated toxic retinopathies and inflammatory reactions have been reported. Finally, advances in ocular imaging have revealed novel findings in hydroxychloroquine and tamoxifen maculopathies. SUMMARY: Discovery of new medications, increased frequency of use, and longer-term use have led to increased reports of retinal toxicities. Advances in retinal imaging have allowed for earlier detection of subclinical changes associated with these medications, which may help prevent progression of disease. However, more research is needed to determine the point at which vision loss becomes irreversible. Risks and benefits must be assessed prior to discontinuation of the offending, but potentially lifesaving, therapy.

An Evaluation of the Microvasculature of Macular Nodules in Coats Disease Using Optical Coherence Tomography Angiography: A Report of 3 Cases.

Purpose: This work aimed to examine the microvasculature of macular fibrosis in Coats disease. Methods: Three boys (aged 3, 4, and 6 years) with Coats disease (stages 2B to 3A2) and macular fibrotic nodules were imaged using optical coherence tomography angiography (OCTA) on the Spectralis spectral-domain OCT tabletop and investigational portable Spectralis Flex module (version 6.9, Heidelberg Engineering). Results: In 2 eyes, a neovascular complex was observed in the avascular slab on OCTA. This neovascular complex had vessels connected to diving vessels from the superficial vascular complex that traveled through the deep vascular complex to the avascular complex. In the third eye, no neovascular complex was observed on OCTA at presentation, but on subsequent examinations fluorescein leakage was observed and cross-sectional OCTA further confirmed the presence of angiographic flow in the nodule. Conclusions: OCTA demonstrates the presence of type 3 neovascularization in fibrotic nodules in Coats disease.

Clinicopathologic correlation of aniridia: Optical coherence tomography angiography and histopathologic observations.

PURPOSE: To describe optical coherence tomography angiography (OCTA) findings in a patient with aniridia and correlate with representative histopathology. OBSERVATIONS: OCTA images of the macula of a pediatric aniridic patient, who has nystagmus and impaired vision bilaterally, demonstrate a complete absence of the foveal avascular zone (FAZ) in both the superficial and deep vascular complexes (SVC and DVC). In addition, larger superficial blood vessels were found to be abnormally diving from the SVC into the DVC. Similarly, immunofluorescence with confocal microscopy imaging of a retinal histopathology specimen from a 2 month old aniridic patient demonstrated larger vessels diving in the same manner. CONCLUSIONS AND IMPORTANCE: This study highlights the clinical, imaging and histopathologic findings of aniridia. Supine OCTA imaging, performed during examination under anesthesia, allowed for visualization of retinal microvasculature in eyes with nystagmus. The histopathology images helped validate OCTA findings that, with further investigation, may lead to new information about the development of abnormal retinal microvasculature.

Appearance of pediatric choroidal neovascular membranes on optical coherence tomography angiography.

PURPOSE: Compared with fluorescein angiography (FA), the gold standard for diagnosing choroidal neovascularization (CNV) activity, optical coherence tomography angiography (OCTA) is non-invasive without risks associated with fluorescein dye use, and may be especially advantageous in the diagnosis and monitoring of children with CNV. METHODS: Eight eyes from eight patients aged 12 months to 18 years were imaged with the investigational Spectralis OCTA (version 6.9, Heidelberg Engineering, Heidelberg, Germany) and the RTVue XR Avanti (Optovue Inc., Fremont, CA, USA). Two patients were imaged during examination under anesthesia while six patients were imaged in the clinic. Demographic information, ocular characteristics, treatment history, and imaging studies (color photos, fluorescein angiography, OCT) were collected and reviewed. RESULTS: Three eyes had active CNV while five had quiescent CNV at the time of imaging. CNV was idiopathic or secondary to trauma, retinal vascular dysgenesis versus retinopathy of prematurity, pigmentary retinopathy, Best vitelliform macular dystrophy, panuveitis, morning glory disc anomaly, and optic disc drusen. OCTA of two active CNV demonstrated presence of a main trunk with multiple fine capillaries, vessel loops, and anastomoses. OCTA was repeated after treatment for two CNV and demonstrated a decrease in size with loss of fine capillaries, vessel loops, and anastomoses. For the third active CNV, OCTA verified flow in the CNV complex despite the uncertainty of FA hyperfluorescence in the setting of grossly abnormal retinal vasculature. The five quiescent CNV all lacked fine capillaries, vessel loops, and anastomoses on OCTA. CONCLUSION: OCTA demonstrates morphological differences between active and quiescent pediatric CNV.

Assessment of Macular Microvasculature in Healthy Eyes of Infants and Children Using OCT Angiography.

PURPOSE: To assess macular vasculature in healthy infants and children using OCT angiography (OCTA). DESIGN: Prospective cross-sectional study. PARTICIPANTS: One hundred thirty-five normal maculae of 89 healthy infants and children (mean age, 8.5±5.3 years; range, 9 weeks-17 years) treated at the Duke University Eye Center. METHODS: We imaged 135 maculae of 89 pediatric patients using the standard Spectralis tabletop and investigational Spectralis with Flex module devices, both equipped with investigational OCTA software (Heidelberg Engineering, Heidelberg, Germany). OCT angiography images of the superficial vascular complex (SVC) and deep vascular complex (DVC) were analyzed for foveal avascular zone (FAZ) area and superficial and deep vessel density. We assessed effects of age, gender, race, axial length (AL), and central subfield thickness on FAZ and vessel density. Patients with both eyes imaged were assessed for agreement between the FAZ and vessel densities of the left and right eyes. MAIN OUTCOME MEASURES: The FAZ area, as well as vessel area density (VAD) and vessel length density (VLD) in the SVC and DVC. RESULTS: The FAZ varied significantly with race; white patients showed a significantly smaller FAZ than black patients (mean difference, 0.11 mm2; P = 0.004). The FAZ did not vary with age, gender, or AL (P > 0.05). In the SVC, VAD and VLD varied significantly with age (P < 0.001) and AL (R2 = 0.46; P < 0.001) but not gender (P > 0.05). The SVC VLD was significantly different between races and ethnicities (P = 0.037), but VAD was not (P < 0.05). In the DVC, VAD and VLD also varied significantly with age (P < 0.001) and AL (R2 = 0.46; P < 0.001) but not gender or race (P > 0.05). There was excellent agreement between the right and left eyes for FAZ (intraclass correlation [ICC], 0.97), SVC VLD (ICC, 1.00), and DVC VLD (ICC, 1.00). CONCLUSIONS: Quantitative studies of pediatric perifoveal vasculature should consider age, race, and AL. In eyes with unilateral disease, the perifoveal vasculature in the unaffected eye may be used as a control comparison because there is excellent agreement between eyes.

Macular Microvascular Findings in Familial Exudative Vitreoretinopathy on Optical Coherence Tomography Angiography.

BACKGROUND AND OBJECTIVE: To describe depth-resolved macular microvasculature abnormalities in patients with familial exudative vitreoretinopathy (FEVR) using optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: Twenty-two eyes (11 eyes of six patients with FEVR and 11 control eyes) were imaged with OCTA. Graders qualitatively analyzed the OCTA images of the superficial and deep vascular complexes for abnormal vascular features and compared to fluorescein angiography (FA). RESULTS: Seven of 11 eyes with FEVR displayed abnormal macular vascular findings. Abnormalities in the superficial vascular complex included dilation, disorganization, straightening, heterogeneous vessel density, and curls/loops. In the deep vascular complex, abnormalities included areas of decreased density, disorganization, curls/loops, and "end bulbs." Except for dragging and straightening of the vessels, none of these macular features were visible on FA. CONCLUSION: OCTA revealed marked macular abnormalities in eyes with FEVR that have not been previously observed with FA alone, suggesting this is more than a disease of the retinal periphery and involves macular and deep retinal vasculature abnormalities. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:322-329.].

Longitudinal Study of Visual Function in Dry Age-Related Macular Degeneration at 12 Months.

PURPOSE: To report the 1-year progression of visual impairment on psychophysical tests of visual function in patients with early and intermediate age-related macular degeneration (AMD). DESIGN: Prospective, observational study. PARTICIPANTS: Patients with early and intermediate AMD were enrolled from the existing population at the Duke Eye Center, and healthy age-matched control participants were recruited from family members or friends of the AMD patients and from the Duke Optometry and Comprehensive Eye Clinics. METHODS: Patients and control participants recruited during the baseline study were assessed at both 6 and 12 months after the initial study visit. Measurements of visual function included best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), low-luminance deficit (LLD), microperimetry percent-reduced threshold (PRT), microperimetry average threshold (AT), and cone contrast tests (CCTs). MAIN OUTCOME MEASURES: Changes in BCVA, LLVA, LLD, microperimetry PRT, microperimetry AT, and CCT results from baseline to 6 months and to 12 months were assessed. RESULTS: Eighty-five patients completed the 12-month examination (19 control participants, 27 early AMD patients, and 39 intermediate AMD patients). Longitudinal analysis detected significant changes from baseline within each group in microperimetry PRT and AT and in the intermediate AMD group only for BCVA and CCT results (P < 0.05). CONCLUSIONS: Microperimetry and CCT are able to detect functional changes resulting from progression of dry AMD within a period as short as 12 months. These functional markers may be useful end points in future clinical trials that assess the effect of potential treatments for AMD.

Hyperreflective Vitreous Opacities on Optical Coherence Tomography in a Patient With Bilateral Retinoblastoma.

An investigational, portable spectral-domain optical coherence tomography (SD-OCT) unit revealed small hyperreflective opacities in both eyes of a patient with bilateral retinoblastoma. There was no evidence of vitreous seeding on ophthalmoscopy of either eye. Although the opacities may initially raise concern for potential vitreous seeding, this report suggests alternate potential etiologies for such opacities, which were also seen on imaging of a cohort of normal eyes in pediatric patients. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:50-52.].

Microvascular Features of Treated Retinoblastoma Tumors in Children Assessed Using OCTA.

BACKGROUND AND OBJECTIVE: To describe the microvascular features of treated, clinically regressed, or reactivated retinoblastoma lesions using an investigational portable optical coherence tomography angiography (OCTA) system. PATIENTS AND METHODS: Single-center, prospective, cross-sectional, consecutive case-series of children with previously treated retinoblastoma who underwent portable OCTA of posterior retinoblastoma lesions. RESULTS: Eight tumors from seven eyes of five children with retinoblastoma were included. Tumors with types 1 (calcified remnant, n = 3), 2 (non-calcified remnant, n = 1), and 3 (both calcified and noncalcified remnants, n = 1) regression revealed persistent intrinsic superficial vasculature on OCTA (five of five lesions; 100%). Lesions with type 4 regression (atrophic scar, n = 2) had complete vascular flow voids in the involved retina and underlying choriocapillaris. A reactivated tumor (n = 1) showed a distinct area of vascularity with prominent feeder/draining vessels. CONCLUSIONS: OCTA revealed that significant vascularity exists in inactive retinoblastoma lesions. Dilated feeder vessels may suggest continued disease activity. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:43-49.].

Orbital arteriovenous fistula presenting with choroidal pulsations on optical coherence tomography.

PURPOSE: To describe a case of orbital arteriovenous fistula diagnosed based on choroidal pulsations on optical coherence tomography (OCT). OBSERVATIONS: A 69-year-old female originally referred for evaluation of macular degeneration. During acquisition of OCT images, choroidal pulsations of the right eye were noted on the B-scan on the instrument display. The pulsations were not noted on gross or funduscopic examination. Fluorescein angiography was unremarkable. Indocyanine green angiography revealed engorged choroidal vasculature in the right eye. OCT angiography revealed relative tortuosity and dilation of the superficial and deep vascular complexes respectively. B-scan ultrasonography revealed orbital pulsations on the right. MRI imaging of the brain and orbits was unremarkable. Findings were attributed to a low-flow orbital arteriovenous fistula. The patient subsequently developed mild stasis retinopathy for which anti-VEGF therapy was initiated. CONCLUSIONS AND IMPORTANCE: Arteriovenous fistulas of the brain and orbit classically present with gross pulsatile proptosis among other clinical features. Low flow orbital fistulas may present with subtle choroidal pulsations only detectable on OCT.

Characterization of Corneal Donor Tissue Lesions by Anterior Segment Optical Coherence Tomography Compared With Eye Bank Technician Slit-Lamp Examination.

PURPOSE: To compare anterior segment spectral-domain optical coherence tomography (OCT) with eye bank technician slit-lamp examination (SLE) in characterizing lesions in donor corneas. METHODS: Twenty-nine donor corneas identified by eye bank technicians to have opacities or lesions potentially representing pathologic findings affecting the stroma were evaluated through the use of technician SLE, SLE photography, and OCT. Technicians were tasked with describing the lesion, estimating the lesion depth, and photographing their SLE findings. A masked grader evaluated the OCT images and measured the lesion depth using customized software. The lesions identified on OCT were then compared with those identified on SLE. RESULTS: A total of 37 lesions were detected on SLE; 25 of the 37 lesions identified on SLE were matched to a lesion on OCT. SLE and OCT depth measurements were statistically significantly different (P = 0.0042, mean difference 4.8% ± 6.5%), and OCT graded lesions as slightly deeper. Of the 12 out of the 37 lesions that were noted on SLE (but not identified on OCT), these included 2 central and paracentral anterior stromal lesions (OCT showed loose epithelium), 5 peripheral anterior stromal lesions, and 5 corneas with LASIK. CONCLUSIONS: Our study highlights both advantages and limitations of OCT compared with technician SLE in the evaluation of donor corneal tissue. Although OCT may miss some peripheral lesions and LASIK scars that are identifiable on SLE, OCT's depth resolution is helpful in differentiating whether shallow anterior opacities actually extend deeper into the stroma or are confined superficially to the epithelium.

Volumetric Measurement of Subretinal Blebs Using Microscope-Integrated Optical Coherence Tomography.

PURPOSE: We advance studies of subretinal treatments by developing a microscope-integrated optical coherence tomography (MIOCT) image-based method for measuring the volume of therapeutics delivered into the subretinal space. METHODS: A MIOCT image-based volume measurement method was developed and assessed for accuracy and reproducibility by imaging an object of known size in model eyes. This method then was applied to subretinal blebs created by injection of diluted triamcinolone. Bleb volumes obtained from MIOCT were compared to the intended injection volume and the surgeon's estimation of leakage. RESULTS: Validation of the image-based volume measurement method showed accuracy to ±1.0 µL (6.0% of measured volume) with no statistically significant variation under different imaging settings. When this method was applied to subretinal blebs, four of 11 blebs without surgeon-observed leakage yielded a mean volume of 32 ± 12.5 µL, in contrast to the intended 50 µL volume injected from the delivery device. This constituted a mean difference of -18 µL (mean percent error, 36 ± 25%). For all 11 blebs, the surgeon's estimations of leakage were significantly different from and showed no correlation with the volume loss based on image-based volume measurements (P < 0.001, paired t-test; intraclass correlation = 0). CONCLUSIONS: We validated an accurate and reproducible method for measuring subretinal volumes using MIOCT. Use of this method revealed that the intended volume might not be delivered into the subretinal space. MIOCT can allow for accurate assessment of subretinal dose delivered, which may have therapeutic implications in evaluating the efficacy and toxicity of subretinal therapies. TRANSLATIONAL RELEVANCE: Use of MIOCT can provide feedback on the accuracy of subretinal injection volumes delivered.