Investigating the Utility of Near-Infrared Reflectance Imaging for Diabetic Retinopathy Screening.

BACKGROUND AND OBJECTIVE: We investigated the reliability of near-infrared reflectance (NIR) imaging as a method of assessing severity of diabetic retinopathy (DR). PATIENTS AND METHODS: One hundred ninety-five NIR images were reviewed by two graders for the number of hyporeflective foci, presence or absence of vascular abnormalities, and presumptive DR stage; these were correlated to fundus photography-defined DR stage. Interrater reliability was confirmed via one-way random effects model of intraclass correlation coefficients. Analysis of variance was used in subgroup analysis, receiver operating characteristic (ROC) curves were created to validate reliability of the model, and logistic regression was used to model foci and vascular abnormalities as predictors for moderate or worse disease. RESULTS: A statistically significant difference in mean number of hyporeflective foci was found between no DR and moderate non-proliferative DR (NPDR; P < 0.0001), no DR and severe NPDR (P < 0.001), no DR and proliferative DR (PDR; P < 0.0001), mild and moderate NPDR (P = 0.008), mild and severe NPDR (P < 0.001), and mild NPDR and PDR (P < 0.001). The area under the ROC curve was 0.849 (CI: 0.792 to 0.905). The threshold for detection of moderate NPDR or worse was 4.75 foci, with a sensitivity of 79.0% and a false positive rate of 20.0%. Multivariate logistic regression model incorporating hyporeflective foci with vascular abnormalities (odds ratio [OR] = 1.592, 95% CI: 1.381 to 1.835; P < 0.001) was able to accurately predict moderate disease or worse, just moderate disease (OR = 1.045, 95% CI: 1.003 to 1.089; P = 0.035), severe disease (OR = 1.050, 95% CI: 1.006 to 1.096; P = 0.027), and proliferative disease (OR = 1.050, 95% CI: 1.008 to 1.095; P = 0.018). CONCLUSIONS: NIR imaging may be an adjunct tool in screening for DR. [Ophthalmic Surg Lasers Imaging Retina 2024;55:318-325.].

Anomaly-guided weakly supervised lesion segmentation on retinal OCT images.

The availability of big data can transform the studies in biomedical research to generate greater scientific insights if expert labeling is available to facilitate supervised learning. However, data annotation can be labor-intensive and cost-prohibitive if pixel-level precision is required. Weakly supervised semantic segmentation (WSSS) with image-level labeling has emerged as a promising solution in medical imaging. However, most existing WSSS methods in the medical domain are designed for single-class segmentation per image, overlooking the complexities arising from the co-existence of multiple classes in a single image. Additionally, the multi-class WSSS methods from the natural image domain cannot produce comparable accuracy for medical images, given the challenge of substantial variation in lesion scales and occurrences. To address this issue, we propose a novel anomaly-guided mechanism (AGM) for multi-class segmentation in a single image on retinal optical coherence tomography (OCT) using only image-level labels. AGM leverages the anomaly detection and self-attention approach to integrate weak abnormal signals with global contextual information into the training process. Furthermore, we include an iterative refinement stage to guide the model to focus more on the potential lesions while suppressing less relevant regions. We validate the performance of our model with two public datasets and one challenging private dataset. Experimental results show that our approach achieves a new state-of-the-art performance in WSSS for lesion segmentation on OCT images.

PRIMARY CENTRAL NERVOUS SYSTEM AND VITREORETINAL LYMPHOMA MIMICKING VIRAL RETINITIS IN A YOUNG PATIENT.

BACKGROUND/PURPOSE: The purpose of this study was to report a young immunocompetent patient with primary central nervous system and vitreoretinal lymphoma initially presenting with peripheral retinitis. METHODS: This study is a case report. RESULTS: A 31-year-old woman presented with 20/60 vision in her left eye, vitreous haze, and peripheral retinal whitening. Intravitreal and oral antivirals were initiated for presumed acute retinal necrosis. Anterior chamber paracentesis was negative for viral nucleotide. Subretinal infiltrates developed, and vitreous biopsy was performed and interpreted as "negative except for rare yeast." Antifungal therapy was initiated. She developed multiple unilateral cranial neuropathies with multifocal areas of enhancement on neuroimaging. Lumbar puncture cytology was negative for neoplastic cells. After further worsening, aforementioned specimens were sent to a specialized ophthalmic pathology laboratory and the diagnosis revised to lymphoma of the diffuse B-cell type. Initial disease regression was seen after combined systemic and intraocular chemotherapy; unfortunately, the patient suffered a central nervous system recurrence and died from systemic complications 1 year later. CONCLUSION: There has been an increased incidence of primary central nervous system and vitreoretinal lymphoma in young patients. Although vitreous biopsy is the diagnostic gold standard for vitreoretinal lymphoma, a risk of false negative interpretation exists. A high index of suspicion and expert interpretation of pathology may be necessary to secure the correct diagnosis.

High Variation in Inner Retinal Reflectivity Predicts Poor Visual Outcome in Patients With Central Retinal Vein Occlusion: SCORE2 Report 21.

Purpose: To assess the association of a novel spectral domain optical coherence tomography biomarker with 6-month visual acuity in in the Study of COmparative Treatments for REtinal Vein Occlusion 2. Methods: Spectral domain optical coherence tomography volume scans were evaluated for inner retinal hyperreflectivity, quantified by optical intensity ratio (OIR) and OIR variation. Baseline visual acuity letter score (VALS), baseline OCT biomarkers, and month 1 OIR were correlated with VALS at month 6. Regression trees, a machine learning technique yielding readily interpretable models, were used to assess for variable interaction. Results: Only baseline VALS correlated positively with month 6 VALS in multivariate regression. Regression trees detected a novel functional and anatomical interaction in a subgroup. Among patients with a baseline VALS worse than 43, those with an OIR variation at month 1 of more than 0.09 had a mean of 13 fewer letters of vision at 6 months compared with patients with an OIR variation of 0.09 or less. Conclusions: Baseline VALS was the strongest predictor of month 6 VALS. Regression tree analysis detected an interaction effect, in which higher OIR variation at month 1 predicted worse 6-month VALS in patients with low VALS at baseline. OIR variation may serve as a predictor for poor visual outcome despite treatment of macular edema secondary to retinal vein occlusion in patients with poor vision at baseline. Translational Relevance: Pixel heterogeneity in three-dimensional OCT data may serve as measure of disruption of the retinal laminations, and this factor may carry visually prognostic value.

Follow-up Rates After Teleretinal Screening for Diabetic Retinopathy: Assessing Patient Barriers to Care.

Purpose: To study patient follow-up after they engage in a teleretinal screening program and to understand potential barriers to care. Methods: This was a retrospective analysis and a prospective study of telephone-based patient interviews of outpatients screened for diabetic retinopathy (DR) through a teleretinal referral system. Results: Of 2761 patients screened through a teleretinal referral program, 123 (4.5%) had moderate nonproliferative DR (NPDR), 83 (3.0%) had severe NPDR, and 31 (1.1%) had proliferative DR. Of the 114 patients with severe NPDR or worse, 67 (58.8%) saw an ophthalmologist within 3 months of referral. Eighty percent of interviewed patients reported they were not aware of the need for follow-up eye appointments. Conclusions: Of patients with severe retinopathy or worse, 58.8% presented for in-person evaluation and treatment within 3 months of screening. Although this result was negatively affected by factors related to the COVID-19 pandemic, key elements of patient education and improved referral strategies to facilitate in-person treatment are essential to improving follow-up after patients engage in telescreening.

Down-conversion of a single photon as a probe of many-body localization.

Decay of a particle into more particles is a ubiquitous phenomenon to interacting quantum systems, taking place in colliders, nuclear reactors or solids. In a nonlinear medium, even a single photon would decay by down-converting (splitting) into lower-frequency photons with the same total energy1, at a rate given by Fermi's golden rule. However, the energy-conservation condition cannot be matched precisely if the medium is finite and only supports quantized modes. In this case, the fate of the photon becomes the long-standing question of many-body localization, originally formulated as a gedanken experiment for the lifetime of a single Fermi-liquid quasiparticle confined to a quantum dot2. Here we implement such an experiment using a superconducting multimode cavity, the nonlinearity of which was tailored to strongly violate the photon-number conservation. The resulting interaction attempts to convert a single photon excitation into a shower of low-energy photons but fails owing to the many-body localization mechanism, which manifests as a striking spectral fine structure of multiparticle resonances at the standing-wave-mode frequencies of the cavity. Each resonance was identified as a many-body state of radiation composed of photons from a broad frequency range and not obeying Fermi's golden rule theory. Our result introduces a new platform to explore the fundamentals of many-body localization without having to control many atoms or qubits3-9.

Artificial Intelligence Algorithms in Diabetic Retinopathy Screening.

PURPOSE OF REVIEW: In this review, we focus on artificial intelligence (AI) algorithms for diabetic retinopathy (DR) screening and risk stratification and factors to consider when implementing AI algorithms in the clinic. RECENT FINDINGS: AI algorithms have been adopted, and have received regulatory approval, for automated detection of referable DR with clinically acceptable diagnostic performance. While these metrics are an important first step, performance metrics that go beyond measures of technical accuracy are needed to fully evaluate the impact of AI algorithm on patient outcomes. Recent advances in AI present an exciting opportunity to improve patient care. Using DR as an example, we have reviewed factors to consider in the implementation of AI algorithms in real-world clinical practice. These include real-world evaluation of safety, efficacy, and equity (bias); impact on patient outcomes; ethical, logistical, and regulatory factors.

Delayed Detection of Predominantly Pericentral Hydroxychloroquine Toxicity in a Dominican Patient.

Purpose: To describe delayed detection of pericentral hydroxychloroquine (HCQ) toxicity. Methods: 67-year-old Dominican woman with rheumatoid arthritis on HCQ presented for examination. Results: Spectral-domain optical coherence tomography (SD-OCT) demonstrated bilateral cystoid macular edema with parafoveal attenuation of the external limiting membrane (ELM) and the ellipsoid zone (EZ). ELM and EZ disruption was present in inferior macula. While subtle superior defects were present on 10-2 visual fields, superior pericentral defects were noted on 24-2 testing. Hyperautofluorescence along inferior arcades corresponded to SD-OCT and visual fields. Examination 2 years prior demonstrated nonspecific points of depression on 10-2 visual fields and normal central SD-OCT findings. EZ and ELM disruption was present in the perifoveal inferior macula. Conclusions: Early pericentral distribution of HCQ toxicity is not limited to Asian patients. Detecting pericentral HCQ toxicity involves reviewing entire macular cube on OCT. When OCT changes are suspected on parafoveal OCT B-scans, visual field testing with 24-2 may be more sensitive than 10-2.

Detecting retinal neurodegeneration in people with diabetes: Findings from the UK Biobank.

IMPORTANCE: Efforts are underway to incorporate retinal neurodegeneration in the diabetic retinopathy severity scale. However, there is no established measure to quantify diabetic retinal neurodegeneration (DRN). OBJECTIVE: We compared total retinal, macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness among participants with and without diabetes (DM) in a population-based cohort. DESIGN/SETTING/PARTICIPANTS: Cross-sectional analysis, using the UK Biobank data resource. Separate general linear mixed models (GLMM) were created using DM and glycated hemoglobin as predictor variables for retinal thickness. Sub-analyses included comparing thickness measurements for patients with no/mild diabetic retinopathy (DR) and evaluating factors associated with retinal thickness in participants with and without diabetes. Factors found to be significantly associated with DM or thickness were included in a multiple GLMM. EXPOSURE: Diagnosis of DM was determined via self-report of diagnosis, medication use, DM-related complications or glycated hemoglobin level of ≥ 6.5%. MAIN OUTCOMES AND MEASURES: Total retinal, mRNFL and GC-IPL thickness. RESULTS: 74,422 participants (69,985 with no DM; 4,437 with DM) were included. Median age was 59 years, 46% were men and 92% were white. Participants with DM had lower total retinal thickness (-4.57 µm, 95% CI: -5.00, -4.14; p<0.001), GC-IPL thickness (-1.73 µm, 95% CI: -1.86, -1.59; p<0.001) and mRNFL thickness (-0.68 µm, 95% CI: -0.81, -0.54; p<0.001) compared to those without DM. After adjusting for co-variates, in the GLMM, total retinal thickness was 1.99 um lower (95% CI: -2.47, -1.50; p<0.001) and GC-IPL was 1.02 µm lower (95% CI: -1.18, -0.87; p<0.001) among those with DM compared to without. mRNFL was no longer significantly different (p = 0.369). GC-IPL remained significantly lower, after adjusting for co-variates, among those with DM compared to those without DM when including only participants with no/mild DR (-0.80 µm, 95% CI: -0.98, -0.62; p<0.001). Total retinal thickness decreased 0.40 µm (95% CI: -0.61, -0.20; p<0.001), mRNFL thickness increased 0.20 µm (95% CI: 0.14, 0.27; p<0.001) and GC-IPL decreased 0.26 µm (95% CI: -0.33, -0.20; p<0.001) per unit increase in A1c after adjusting for co-variates. Among participants with diabetes, age, DR grade, ethnicity, body mass index, glaucoma, spherical equivalent, and visual acuity were significantly associated with GC-IPL thickness. CONCLUSION: GC-IPL was thinner among participants with DM, compared to without DM. This difference persisted after adjusting for confounding variables and when considering only those with no/mild DR. This confirms that GC-IPL thinning occurs early in DM and can serve as a useful marker of DRN.

A summary of eye-related visits to a tertiary emergency department.

Timely ophthalmologic consultation is important to ensure patients receive high quality ophthalmologic care in the Emergency Department (ED). Tele-ophthalmology may prove useful in safely and efficiently managing ED eye-related complaints. Prior to implementing such a solution, current consultation patterns must be understood. We aimed to assess case-mix acuity and consultation workflow patterns in the ophthalmology consult service at a tertiary emergency department in New York City. The medical records of patients with eye-related complaints who presented to the ED between January 1, 2015 and December 31, 2015 were reviewed. Visits were retrospectively assigned acuities and the ophthalmologic subspecialty involved in the case was recorded. The number of ophthalmologic consultations ordered and consultant response times were analyzed. Patients who were transferred to the ED for eye-related complaints were included. The ED received 1090 eye-related complaints in this period. 60% were retrospectively assigned low acuity, 27% were assigned medium acuity, and 13% were assigned high acuity. Ophthalmology was consulted on 19% of low, 18% of medium, and 48% of high acuity cases. 44% of complaints involved the anterior segment and 30% involved oculoplastics. 2/3 of transfer patients initially assigned high acuity were downgraded to low acuity upon examination. On average, the consult note was created and signed within 109 and 153 min, respectively, after consult order. ED consults are heavily weighted towards pathology of low-to-medium acuity affecting the anterior segment and ocular adnexa. Currently available tele-ophthalmology technology can potentially address a large volume of eye-related visits.

ATYPICAL CONGENITAL HYPERTROPHY OF THE RETINAL PIGMENT EPITHELIUM COMPLICATED BY PRESUMED RETINAL PIGMENT EPITHELIAL ADENOMA AND EXUDATIVE MACULOPATHY.

PURPOSE: To report a retinal pigment epithelium (RPE) tumor with exudative maculopathy, originating from an atypical RPE lesion presumed to represent congenital hypertrophy of the RPE or RPE hyperplasia. METHODS: Multimodal imaging including fundus autofluorescence, optical coherence tomography, fluorescein angiography, and optical coherence tomography angiography. RESULTS: A 76-year-old West African man noted visual acuity reduction to count fingers in the right eye and 20/400 in the left eye. Features of chronic glaucoma were noted. In addition, there was a fairly well-circumscribed darkly pigmented RPE lesion in the paramacular region in the right eye, measuring 4 mm in diameter and flat and consistent with atypical congenital hypertrophy of the RPE or RPE hyperplasia. On the posterior margin of this mass was an RPE tumor, presumed to represent RPE adenoma, producing exudative maculopathy and cystoid macular edema. Multimodal imaging was used to distinguish the RPE tumor from macular neovascularization. A similar atypical congenital hypertrophy of the RPE without retinopathy measuring 3.5mm in diameter was noted in the temporal macular region in the left eye. After six monthly doses of intravitreal bevacizumab (1.25 mg/0.05 mL) in the right eye, the maculopathy resolved and the RPE mass showed partial involution with visual acuity return to baseline 20/200. CONCLUSION: Congenital hypertrophy of the RPE and RPE hyperplasia can produce RPE adenoma with related exudative maculopathy. In this case, the maculopathy responded to bevacizumab.

PRESUMED FOVEAL BACILLARY LAYER DETACHMENT IN A PATIENT WITH TOXOPLASMOSIS CHORIORETINITIS AND PACHYCHOROID DISEASE.

PURPOSE: To report a detachment that apparently separated photoreceptor inner segment myoids from inner segment ellipsoids as a manifestation of toxoplasmosis chorioretinitis in a patient with pachychoroid spectrum disease. METHODS: Multimodal imaging including fundus photography, spectral domain and enhanced-depth imaging optical coherence tomography (OCT), indocyanine green angiography, and OCT angiography. RESULTS: A 33-year-old man with a history of toxoplasmosis chorioretinitis reported 1 week of decreased vision to 20/200 in his right eye. Examination of the right eye demonstrated mild vitritis with recurrent chorioretinitis inferior to the fovea and adjacent to a chorioretinal scar. A dome-shaped, foveal photoreceptor layer-splitting detachment was noted on OCT. Because degenerating cone photoreceptors are capable of shedding their inner segments, we inferred the location of the detachment at the level of the inner segment myoid and provided a histological example of such from an unrelated donor case. In addition, multimodal imaging revealed dilated choroidal veins (pachyvessels) with attenuation of the inner choroid in both eyes and asymptomatic findings of central serous chorioretinopathy in the left eye. After 1 month of antibiotic and steroid therapy, the chorioretinitis resolved, as did the detachment. Hyperreflective foci on the vitreoretinal interface were appreciated with en face OCT that appeared to aggregate throughout the course of therapy, induce inner retinal striae, and resolve without inducing epiretinal membrane formation. CONCLUSION: Patients with preexisting pachychoroid spectrum disease may manifest a more significant retinal fluid accumulation in the setting of superimposed chorioretinal inflammation. In this case of macular toxoplasmosis chorioretinitis, inflammation manifested as a retinal detachment at the level of photoreceptor inner segment myoids that we named as a bacillary layer detachment. In this case, inflammatory sequelae of toxoplasmosis reactivation responded well to oral and intravitreal therapy.

EVALUATION OF SEGMENTAL RETINAL ARTERITIS WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To describe the vascular anatomy and intraluminal flow characteristics of segmental retinal arteritis (SRA) using structural and angiographic optical coherence tomography (OCT). METHODS: Retrospective case series of consecutive patients presenting with SRA. All patients were evaluated at presentation with fundus photography, spectral domain OCT, and OCT angiography. One patient was imaged with dense B-scan OCT angiography. RESULTS: Three eyes of three male patients were evaluated. All examinations were consistent with reactivation of ocular toxoplasmosis with an area of active retinochoroiditis adjacent to a focal chorioretinal scar. Spectral domain OCT through areas of SRA noted on clinical examination demonstrated areas of hyperreflectivity circumscribing the affected vessel with a normoreflective lumen. Optical coherence tomography angiography and dense B-scan OCT angiography demonstrated narrowing of the intraluminal flow signal that correlated with areas of segmental hyperreflectivity on spectral domain OCT. Vascular sections proximal and distal to areas of SRA showed normal flow signal. CONCLUSION: Vessels with SRA demonstrated hyperreflectivity highlighting the vessel wall on spectral domain OCT. Optical coherence tomography angiography showed narrowing of the flow signal within these segments suggesting reduced lumen diameter. Coupling these finding with previous indocyanine green imaging findings in SRA, the collective data suggest the plaques are localized within the vessel wall to either the endothelium or the muscular tunica media without occlusion of the vessel lumen.

ASSESSING THE ABILITY OF PREOPERATIVE QUANTITATIVE SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS TO PREDICT VISUAL OUTCOME IN IDIOPATHIC MACULAR HOLE SURGERY.

PURPOSE: To determine which spectral domain optical coherence tomography biomarkers of idiopathic macular hole (MH) correlate with the postoperative best-corrected visual acuity (BCVA) in anatomically closed MH. METHODS: Retrospective analysis of spectral domain optical coherence tomography scans of 44 patients presenting with MH followed for a mean of 17 months. Widths of MH aperture, base, and ellipsoid zone disruption were calculated from presenting foveal spectral domain optical coherence tomography B-scans. Macular hole base area and ellipsoid zone disruption area were calculated through the custom in-house software. RESULTS: Poorer postoperative BCVA correlated with increased preoperative choroidal hypertransmission (r = 0.503, P = 0.0005), minimum diameter (r = 0.491, P = 0.0007), and base diameter (r = 0.319, P = 0.0348), but not with preoperative ellipsoid zone width (r = 0.199, P = 0.2001). Applying en-face analysis, the BCVA correlated weakly with preoperative ellipsoid zone loss area (r = 0.380, P = 0.013), but not with preoperative MH base area (r = 0.253, P = 0.1058). CONCLUSION: Increased MH minimum diameter, base diameter, base area, and choroidal hypertransmission are correlated with a poorer postoperative BCVA. Ellipsoid zone loss measurements were not consistently correlated with a BCVA. Choroidal hypertransmission width may be an easy-to-visualize predictive imaging biomarker in MH surgery.

Cost and Outcomes Analysis of Polypoidal Choroidal Vasculopathy (Aneurysmal Type 1 Neovascularization) Treatment Strategies.

Purpose: This work compares the relative cost utility of ranibizumab and aflibercept with and without verteporfin photodynamic therapy (vPDT) for the treatment of polypoidal choroidal vasculopathy. Methods: A retrospective cost and outcomes analysis of the PLANET (Efficacy and Safety of Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy) and EVEREST II (Efficacy and Safety of Ranibizumab With or Without Verteporfin Photodynamic Therapy for Polypoidal Choroidal Vasculopathy) studies was performed. Clinical utilization and outcomes were based on data from these clinical trials, and costs were obtained from Medicare fee schedules. Cost utility was derived from published visual outcomes and expressed as quality-adjusted life-years (QALYs). Cost per QALY and cost per line of vision gained for each treatment strategy (in US dollars) were assessed as the main outcome measure. Results: The 1-year facility (nonfacility) costs per QALY were $295,744.41 ($260,088.19), $209,574.09 ($182,831.77), $211,072.63 ($188,425.33), and $212,275.22 ($189,703.05) for ranibizumab as-needed monotherapy, ranibizumab as-needed with combination therapy, aflibercept monotherapy, and aflibercept with delayed vPDT combination therapy, respectively. Conclusions: Ranibizumab as-needed monotherapy was the least clinically effective and least cost efficient over 1 year. Ranibizumab as-needed with combination therapy, aflibercept monotherapy, and aflibercept with deferred vPDT combination therapy all had similar overall cost utility at 1 year. If bevacizumab were to be substituted for ranibizumab, the cost per QALY could be reduced by approximately a factor of 5, showing the benefit of bevacizumab for increasing the cost utility of polypoidal choroidal vasculopathy treatment.

Long-Term Multimodal Imaging of Solar Retinopathy.

This is a rare, multimodal imaging report spanning a decade of monitoring in a patient with chronic solar retinopathy showing the natural course of the disease. Spectral-domain optical coherence tomography (SD-OCT) showed mild widening of subfoveal loss of ellipsoid and interdigitation zones bilaterally, progressive retinal pigment epithelial thinning in the right eye, and hyperplasia in the left eye. Structural en face OCT showed subfoveal tissue loss bilaterally. There was no leakage on fluorescein angiography and OCT angiography (OCTA), and dense B-scan OCTA images were unremarkable. Microperimetry revealed bilateral decreased central sensitivity and eccentric fixation in the left eye. Vision remained stable throughout. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:388-392.].