Machine learning and optical coherence tomography-derived radiomics analysis to predict persistent diabetic macular edema in patients undergoing anti-VEGF intravitreal therapy.

BACKGROUND: Diabetic macular edema (DME) is a leading cause of vision loss in patients with diabetes. This study aimed to develop and evaluate an OCT-omics prediction model for assessing anti-vascular endothelial growth factor (VEGF) treatment response in patients with DME. METHODS: A retrospective analysis of 113 eyes from 82 patients with DME was conducted. Comprehensive feature engineering was applied to clinical and optical coherence tomography (OCT) data. Logistic regression, support vector machine (SVM), and backpropagation neural network (BPNN) classifiers were trained using a training set of 79 eyes, and evaluated on a test set of 34 eyes. Clinical implications of the OCT-omics prediction model were assessed by decision curve analysis. Performance metrics (sensitivity, specificity, F1 score, and AUC) were calculated. RESULTS: The logistic, SVM, and BPNN classifiers demonstrated robust discriminative abilities in both the training and test sets. In the training set, the logistic classifier achieved a sensitivity of 0.904, specificity of 0.741, F1 score of 0.887, and AUC of 0.910. The SVM classifier showed a sensitivity of 0.923, specificity of 0.667, F1 score of 0.881, and AUC of 0.897. The BPNN classifier exhibited a sensitivity of 0.962, specificity of 0.926, F1 score of 0.962, and AUC of 0.982. Similar discriminative capabilities were maintained in the test set. The OCT-omics scores were significantly higher in the non-persistent DME group than in the persistent DME group (p < 0.001). OCT-omics scores were also positively correlated with the rate of decline in central subfield thickness after treatment (Pearson's R = 0.44, p < 0.001). CONCLUSION: The developed OCT-omics model accurately assesses anti-VEGF treatment response in DME patients. The model's robust performance and clinical implications highlight its utility as a non-invasive tool for personalized treatment prediction and retinal pathology assessment.

Chemically induced cone degeneration in the 13-lined ground squirrel.

Animal models of retinal degeneration are critical for understanding disease and testing potential therapies. Inducing degeneration commonly involves the administration of chemicals that kill photoreceptors by disrupting metabolic pathways, signaling pathways, or protein synthesis. While chemically induced degeneration has been demonstrated in a variety of animals (mice, rats, rabbits, felines, 13-lined ground squirrels (13-LGS), pigs, chicks), few studies have used noninvasive high-resolution retinal imaging to monitor the in vivo cellular effects. Here, we used longitudinal scanning light ophthalmoscopy (SLO), optical coherence tomography, and adaptive optics SLO imaging in the euthermic, cone-dominant 13-LGS (46 animals, 52 eyes) to examine retinal structure following intravitreal injections of chemicals, which were previously shown to induce photoreceptor degeneration, throughout the active season of 2019 and 2020. We found that iodoacetic acid induced severe pan-retinal damage in all but one eye, which received the lowest concentration. While sodium nitroprusside successfully induced degeneration of the outer retinal layers, the results were variable, and damage was also observed in 50% of contralateral control eyes. Adenosine triphosphate and tunicamycin induced outer retinal specific damage with varying results, while eyes injected with thapsigargin did not show signs of degeneration. Given the variability of damage we observed, follow-up studies examining the possible physiological origins of this variability are critical. These additional studies should further advance the utility of chemically induced photoreceptor degeneration models in the cone-dominant 13-LGS.

Role of noninvasive ocular imaging as a biomarker in peripheral artery disease (PAD): A systematic review.

This study aimed to review the current literature exploring the utility of noninvasive ocular imaging for the diagnosis of peripheral artery disease (PAD). Our search was conducted in early April 2022 and included the databases Medline, Scopus, Embase, Cochrane, and others. Five articles were included in the final review. Of the five studies that used ocular imaging in PAD, two studies used retinal color fundus photography, one used optical coherence tomography (OCT), and two used optical coherence tomography angiography (OCTA) to assess the ocular changes in PAD. PAD was associated with both structural and functional changes in the retina. Structural alterations around the optic disc and temporal retinal vascular arcades were seen in color fundus photography of patients with PAD compared to healthy individuals. The presence of retinal hemorrhages, exudates, and microaneurysms in color fundus photography was associated with an increased future risk of PAD, especially the severe form of the disease. The retinal nerve fiber layer (RNFL) was significantly thinner in the nasal quadrant in patients with PAD compared to age-matched healthy individuals in OCT. Similarly, the choroidal thickness in the subfoveal region was significantly thinner in patients with PAD compared to controls. Patients with PAD also had a significant reduction in the retinal and choroidal circulation in OCTA compared to healthy controls. As PAD causes thinning and ischemic changes in retinal vessels, examination of the retinal vessels using retinal imaging techniques can provide useful information about early microvascular damage in PAD. Ocular imaging could potentially serve as a biomarker for PAD. PROSPERO ID: CRD42022310637.

Repeatability and reproducibility of quantitative OCT angiography measurements from table-top and portable Flex Spectralis devices.

PURPOSE: The recent development of a portable investigational handheld OCT-angiography (OCTA) device has allowed for expansion of imaging into the operating room (OR) in addition to standard in-clinic imaging. The aim of this study was to assess intravisit repeatability and intervisit reproducibility of retinal microvasculature measures and central retinal thickness for in-clinic table-top and portable OR compatible OCTA devices. METHODS: Repeated 10 × 10 OCTA images were acquired in 20 healthy adult participants on two separate visit days using Spectralis spectral-domain OCTA table-top and investigational armature suspended Flex systems. Intravisit and intervisit intraclass correlation coefficients and average absolute percent difference were calculated for quantitative microvasculature measures and CRT. RESULTS: 120 OCTA images were acquired from 20 subjects (n = 20, mean age 26.7 ± 1.61 years, range 24-30 years) with both devices across two separate imaging days. FAZ and CRT measurements had near complete intravisit and intervisit agreement with ICCs between .97 and 1 for both table-top (FAZ ICC .97, .97; CRT ICC .98-1, .98-.99) and Flex (FAZ ICC .97, .95; CRT ICC .99-1, .98-.99) devices. Vessel density measures demonstrated greater variance with only fair to strong agreement (ICC .32-.75) and average absolute percent differences ranging from 2.96 to 6.63%. CONCLUSION: FAZ and CRT measures for both devices demonstrated high repeatability and reproducibility; retinal vessel density measures demonstrated less. Differences of less than 7% for retinal microvasculature measurements across time and devices are most likely attributable to expectable variance between repeat scans.

Macular dystrophy in Kabuki syndrome due to de novo KMT2D variants: refining the phenotype with multimodal imaging and follow-up over 10 years: insight into pathophysiology.

BACKGROUND: Kabuki Syndrome is a rare and genetically heterogenous condition with both ophthalmic and systemic complications and typical facial features. We detail the macular phenotype in two unrelated patients with Kabuki syndrome due to de novo nonsense variants in KMT2D, one novel. A follow-up of 10 years is reported. Pathogenicity of both de novo nonsense variants is analyzed. METHODS: Four eyes of two young patients were studied by full clinical examination, kinetic perimetry, short wavelength autofluorescence, full field (ff) ERGs, and spectral-domain optical coherence tomography (SD-OCT). One patient had adaptive optic (AO) imaging. Whole exome sequencing was performed in both patients. RESULTS: Both patients had de novo nonsense variants in KMTD2. One patient had c.14843C>G; p. (Ser4948ter) novel variant and the second c.11119C>T; p. (Arg3707ter). Both had a stable Snellen visual acuity of 0.2-0.3. The retinal multimodal imaging demonstrated abnormalities at the fovea in both eyes: hyperreflectivity to blue light and a well-delimited gap-disruption of ellipsoid and interdigitation layer on OCT. The dark area on AO imaging is presumed to be absent for, or with structural change to photoreceptors. The ff ERGs and kinetic visual fields were normal. The foveal findings remained stable over several years. CONCLUSION: Kabuki syndrome-related maculopathy is a distinct loss of photoreceptors at the fovea as shown by multimodal imaging including, for the first time, AO imaging. This report adds to the literature of only one case with maculopathy with two additional macular dystrophies in patients with Kabuki syndrome. Although underestimated, these cases further raise awareness of the potential impact of retinal manifestations of Kabuki syndrome not only among ophthalmologists but also other healthcare professionals involved in the care of patients with this multisystem disorder.

Parkinson's Disease: What Can Retinal Imaging Tell Us?

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia. While the diagnosis of PD primarily relies on clinical assessments and neurological examination, there has been growing interest in exploring non-invasive imaging techniques to aid in early detection and monitoring of the disease. In recent years, retinal imaging has emerged as a promising tool for studying PD due to the close anatomical and functional similarities between the retina and the brain. Retinal imaging methods, such as spectral domain optical coherence tomography and optical coherence tomography angiography, enable non-intrusive visualization and measurement of retinal structures and blood vessels. These techniques hold the promise of capturing alterations in retinal structure and function that could potentially mirror the underlying pathological mechanisms in PD. This review article aims to provide an overview of the current understanding of retinal changes in PD and the potential utility of retinal imaging as a diagnostic and monitoring tool.

Associations of inner retinal layers with risk of incident dementia: An individual participant data analysis of four prospective cohort studies.

INTRODUCTION: Our main objective was to investigate whether retinal neurodegeneration, estimated from lower thickness of inner retinal layers, was associated with incident all-cause dementia and Alzheimer's disease (AD). METHODS: We performed an individual participant data meta-analysis using unpublished data from four prospective cohort studies with a total of 69,955 participants (n = 1087 cases of incident all-cause dementia; n = 520 cases incident AD; follow-up time median [interquartile range] 11.3 [8.8-11.5] years). RESULTS: General baseline characteristics of the study population were mean (standard deviation) age, 58.1 (8.8) years; 47% women. After adjustment, lower baseline macular retinal nerve fiber layer thickness was significantly associated with a 10% and 11% higher incidence of all-cause dementia and AD, respectively. Lower baseline macular ganglion cell-inner plexiform layer thickness was not significantly associated with these outcomes. DISCUSSION: These findings suggest that retinal neurodegeneration precedes the onset of clinical dementia. Retinal imaging tools may be informative biomarkers for the study of the early pathophysiology of dementia.

Thinner inner retinal layers are associated with lower cognitive performance, lower brain volume, and altered white matter network structure-The Maastricht Study.

INTRODUCTION: The retina may provide non-invasive, scalable biomarkers for monitoring cerebral neurodegeneration. METHODS: We used cross-sectional data from The Maastricht study (n = 3436; mean age 59.3 years; 48% men; and 21% with type 2 diabetes [the latter oversampled by design]). We evaluated associations of retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer thicknesses with cognitive performance and magnetic resonance imaging indices (global grey and white matter volume, hippocampal volume, whole brain node degree, global efficiency, clustering coefficient, and local efficiency). RESULTS: After adjustment, lower thicknesses of most inner retinal layers were significantly associated with worse cognitive performance, lower grey and white matter volume, lower hippocampal volume, and worse brain white matter network structure assessed from lower whole brain node degree, lower global efficiency, higher clustering coefficient, and higher local efficiency. DISCUSSION: The retina may provide biomarkers that are informative of cerebral neurodegenerative changes in the pathobiology of dementia.

Smartphone Eye Examination: Artificial Intelligence and Telemedicine.

Background: The current medical scenario is closely linked to recent progress in telecommunications, photodocumentation, and artificial intelligence (AI). Smartphone eye examination may represent a promising tool in the technological spectrum, with special interest for primary health care services. Obtaining fundus imaging with this technique has improved and democratized the teaching of fundoscopy, but in particular, it contributes greatly to screening diseases with high rates of blindness. Eye examination using smartphones essentially represents a cheap and safe method, thus contributing to public policies on population screening. This review aims to provide an update on the use of this resource and its future prospects, especially as a screening and ophthalmic diagnostic tool. Methods: In this review, we surveyed major published advances in retinal and anterior segment analysis using AI. We performed an electronic search on the Medical Literature Analysis and Retrieval System Online (MEDLINE), EMBASE, and Cochrane Library for published literature without a deadline. We included studies that compared the diagnostic accuracy of smartphone ophthalmoscopy for detecting prevalent diseases with an accurate or commonly employed reference standard. Results: There are few databases with complete metadata, providing demographic data, and few databases with sufficient images involving current or new therapies. It should be taken into consideration that these are databases containing images captured using different systems and formats, with information often being excluded without essential detailing of the reasons for exclusion, which further distances them from real-life conditions. The safety, portability, low cost, and reproducibility of smartphone eye images are discussed in several studies, with encouraging results. Conclusions: The high level of agreement between conventional and a smartphone method shows a powerful arsenal for screening and early diagnosis of the main causes of blindness, such as cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration. In addition to streamlining the medical workflow and bringing benefits for public health policies, smartphone eye examination can make safe and quality assessment available to the population.

Unveiling Drivers of Retinal Degeneration in RCS Rats: Functional, Morphological, and Molecular Insights.

Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, significantly contribute to adult blindness. The Royal College of Surgeons (RCS) rat is a well-established disease model for studying these dystrophies; however, molecular investigations remain limited. We conducted a comprehensive analysis of retinal degeneration in RCS rats, including an immunodeficient RCS (iRCS) sub-strain, using ocular coherence tomography, electroretinography, histology, and molecular dissection using transcriptomics and immunofluorescence. No significant differences in retinal degeneration progression were observed between the iRCS and immunocompetent RCS rats, suggesting a minimal role of adaptive immune responses in disease. Transcriptomic alterations were primarily in inflammatory signaling pathways, characterized by the strong upregulation of Tnfa, an inflammatory signaling molecule, and Nox1, a contributor to reactive oxygen species (ROS) generation. Additionally, a notable decrease in Alox15 expression was observed, pointing to a possible reduction in anti-inflammatory and pro-resolving lipid mediators. These findings were corroborated by immunostaining, which demonstrated increased photoreceptor lipid peroxidation (4HNE) and photoreceptor citrullination (CitH3) during retinal degeneration. Our work enhances the understanding of molecular changes associated with retinal degeneration in RCS rats and offers potential therapeutic targets within inflammatory and oxidative stress pathways for confirmatory research and development.

Imaging characterization of the fellow eye in patients with unilateral polypoidal choroidal vasculopathy.

INTRODUCTION: New insights on polypoidal choroidal vasculopathy (PCV) have shed light regarding its pathophysiology and associations. However, PCV characterization is still incomplete in Caucasians, which is due to presumed lower prevalence in this population. Features typically associated with AMD such as drusen, retinal pigmentary changes or atrophy are seen in PCV, as precursors and in the fellow eye. Pachychoroid spectrum, predisposing to PCV, also presents with chronic changes in the retinal pigment epithelium (RPE), such as drusen-like deposits (DLD), and in the choroid. The purpose of this study is to perform a multimodal imaging characterization of unaffected fellow eyes in a sample of Caucasian patients with unilateral PCV. METHODS: Multicenter retrospective cohort study with a sample of 55 unaffected fellow eyes from patients diagnosed with unilateral PCV confirmed by indocyanine green angiography. The sample was characterized in the baseline by color fundus photography, spectral domain optical coherence tomography (SD-OCT), fluorescein angiography and indocyanine green angiography. Morphological characteristics of both the retina and the choroid were evaluated. The SD-OCT of the last follow-up visit was also evaluated in order to exclude evolution to PCV or choroidal neovascularization. All images captured underwent evaluation by two independent graders. Informed consent was obtained from all participants. RESULTS: Fifty-five patients (median age, 74 ± 15 years) were included. After 15.5 ± 6.4 months of follow-up, only one developed disease (1.9%). Soft and/or hard drusen were present in 60% and pachydrusen in 23.6%. Pachychoroid signs were present in 47.2%, the double-layer sign in 36.4%, disruption of the RPE changes in 16.4% and RPE atrophy in 10.9%. ICGA revealed choroidal vascular dilation in 63.6% and punctiform hyperfluorescence in 52.7%. Branching vascular networks were identified in only 1.9% of cases. CONCLUSION: The identification of pachychoroid signs in the OCT and ICGA were present in over half of the cases and the presence of the double-layer sign in more than a third provide crucial insights for enhanced characterization of this pathology and deeper understanding of its pathogenesis. These findings contribute significantly to the current knowledge, offering valuable markers to discern various phases of the pathology's progression.

Validation of a deep-learning-based retinal biomarker (Reti-CVD) in the prediction of cardiovascular disease: data from UK Biobank.

BACKGROUND: Currently in the United Kingdom, cardiovascular disease (CVD) risk assessment is based on the QRISK3 score, in which 10% 10-year CVD risk indicates clinical intervention. However, this benchmark has limited efficacy in clinical practice and the need for a more simple, non-invasive risk stratification tool is necessary. Retinal photography is becoming increasingly acceptable as a non-invasive imaging tool for CVD. Previously, we developed a novel CVD risk stratification system based on retinal photographs predicting future CVD risk. This study aims to further validate our biomarker, Reti-CVD, (1) to detect risk group of ≥ 10% in 10-year CVD risk and (2) enhance risk assessment in individuals with QRISK3 of 7.5-10% (termed as borderline-QRISK3 group) using the UK Biobank. METHODS: Reti-CVD scores were calculated and stratified into three risk groups based on optimized cut-off values from the UK Biobank. We used Cox proportional-hazards models to evaluate the ability of Reti-CVD to predict CVD events in the general population. C-statistics was used to assess the prognostic value of adding Reti-CVD to QRISK3 in borderline-QRISK3 group and three vulnerable subgroups. RESULTS: Among 48,260 participants with no history of CVD, 6.3% had CVD events during the 11-year follow-up. Reti-CVD was associated with an increased risk of CVD (adjusted hazard ratio [HR] 1.41; 95% confidence interval [CI], 1.30-1.52) with a 13.1% (95% CI, 11.7-14.6%) 10-year CVD risk in Reti-CVD-high-risk group. The 10-year CVD risk of the borderline-QRISK3 group was greater than 10% in Reti-CVD-high-risk group (11.5% in non-statin cohort [n = 45,473], 11.5% in stage 1 hypertension cohort [n = 11,966], and 14.2% in middle-aged cohort [n = 38,941]). C statistics increased by 0.014 (0.010-0.017) in non-statin cohort, 0.013 (0.007-0.019) in stage 1 hypertension cohort, and 0.023 (0.018-0.029) in middle-aged cohort for CVD event prediction after adding Reti-CVD to QRISK3. CONCLUSIONS: Reti-CVD has the potential to identify individuals with ≥ 10% 10-year CVD risk who are likely to benefit from earlier preventative CVD interventions. For borderline-QRISK3 individuals with 10-year CVD risk between 7.5 and 10%, Reti-CVD could be used as a risk enhancer tool to help improve discernment accuracy, especially in adult groups that may be pre-disposed to CVD.

Wide-Field Three-Dimensional Depth-Invariant Cellular-Resolution Imaging of the Human Retina.

Three-dimensional (3D) cellular-resolution imaging of the living human retina over a large field of view will bring a great impact in clinical ophthalmology, potentially finding new biomarkers for early diagnosis and improving the pathophysiological understanding of ocular diseases. While hardware-based and computational adaptive optics (AO) optical coherence tomography (OCT) have been developed to achieve cellular-resolution retinal imaging, these approaches support limited 3D imaging fields, and their high cost and intrinsic hardware complexity limit their practical utility. Here, this work demonstrates 3D depth-invariant cellular-resolution imaging of the living human retina over a 3 × 3 mm field of view using the first intrinsically phase-stable multi-MHz retinal swept-source OCT and novel computational defocus and aberration correction methods. Single-acquisition imaging of photoreceptor cells, retinal nerve fiber layer, and retinal capillaries is presented across unprecedented imaging fields. By providing wide-field 3D cellular-resolution imaging in the human retina using a standard point-scan architecture routinely used in the clinic, this platform proposes a strategy for expanded utilization of high-resolution retinal imaging in both research and clinical settings.

L-arginine and aged garlic extract for the prevention of migraine: a study protocol for a randomised, double-blind, placebo-controlled, phase-II trial (LARGE trial).

BACKGROUND: Migraine is a common and distressing neurological condition characterised by recurrent throbbing headaches, nausea and heightened sensitivity to light and sound. Accumulating evidence suggests that cerebral arteries dilate during migraine, causing distal microvessels to constrict, which could activate nociceptors and cause onset of headache pain. If so, preventing or attenuating chronic microvascular constriction, and promoting a dilatory phenotype, may reduce frequency and/or severity of migraines. The primary aim of the L-Arginine and Aged Garlic Extract (LARGE) trial is to investigate whether oral treatment with dietary nutraceuticals, L-arginine and aged garlic extract (AGE), both systemic vasodilatory agents, will alleviate migraine frequency, duration and severity in adults with chronic frequent episodic migraines. METHODS: The study is a randomised double-blind placebo-controlled phase-II single-site clinical trial conducted in Perth, Australia. The target sample is to recruit 240 participants diagnosed with chronic frequent episodic migraines between 18 and 80 years of age. Participants will be randomised to one of four treatment groups for 14 weeks (placebo induction for 2 weeks, followed by 12 weeks on one of the respective treatment arms): placebo, L-arginine, AGE, or a combination of L-arginine and AGE. The doses of L-arginine and AGE are 1.5 g and 1 g daily, respectively. The primary outcome is to assess migraine response using change in migraine frequency and intensity between baseline and 12 weeks. Secondary outcomes include the impact of L-arginine and/or AGE on photosensitivity, retinal vessel changes, and blood biomarker concentrations of vascular tone, following a 12-week intervention. DISCUSSION: The protocol describes the oral administration of 2 nutraceutical-based interventions as possible prophylactic treatments for chronic frequent episodic migraines, with potential for direct clinical translation of outcomes. Potential limitations of the study include the fixed-dose design of each treatment arm and that in vivo neuroimaging methods, such as magnetic resonance imaging (MRI), will not be conducted to determine putative cerebro-vasodilatory changes to coincide with the outcome measures. Dose-response studies may be indicated. TRIAL REGISTRATION: The trial was retrospectively registered with the Australian New Zealand Clinical Trials Registry ACTRN12621001476820 (Universal Trial Number: U1111-1268-1117) on 04/08/2021. This is protocol version 1, submitted on 25/11/2022.

Retinopathy of prematurity detection: a retrospective quality improvement project before-after implementation of retinal digital imaging for screening.

Screening of retinopathy of prematurity (ROP) was modified in a level-3 neonatal intensive care unit by the introduction of a wide-field retinal imaging. The aim of this study was to evaluate whether retinopathy of prematurity (ROP) diagnosis was improved or not compared to previously used binocular indirect ophthalmoscopy (BIO). This was a retrospective, uncontrolled, quality improvement project. Records of consecutive premature newborns screened for ROP over two 1-year periods were reviewed. Systemic factors potentially influencing the occurrence of ROP were investigated using uni- and multivariable linear regression followed by stepwise forward regression. ROP screening was performed by ophthalmologists using BIO in 2014, and digital wide-field retinal imaging (Panocam™ pro) in 2019. Records of N = 297 patients were analyzed (N = 159 in 2014 and N = 138 in 2019). The proportion of ROP diagnosed at any stage, over the total number of neonates screened, was significantly higher in 2019 (n = 46/138, 33.1%) compared to 2014 (n = 11/159, 6.9%) (p < 0.0001). Most neonates presented with mild forms of ROP during both 1-year periods analyzed. After adjustment for all parameters influencing ROP occurrence, the variables contributing independently to the diagnosis of any stage of ROP were birth weight (p = 0.002), duration of mechanical ventilation (p = 0.028) and wide-field fundus camera-assisted screening (p < 0.001). CONCLUSION: After adjusting for many recognized systemic factors influencing the development of ROP, screening by wide-field digital retinal imaging was independently associated with higher ROP detection. WHAT IS KNOWN: • No consensus has been reached to replace binocular indirect ophthalmoscopy by retinal imaging for ROP screening. • Diagnostic accuracy and high sensitivity and specificity has been reported for wide-field digital imaging. WHAT IS NEW: • The introduction of wide-field imaging for ROP screening in at level-3 reference center was independently associated to higher ROP detection.

Comparison of 2-Field and 5-Field Mydriatic Handheld Retinal Imaging in a Community-Based Diabetic Retinopathy Screening Program.

INTRODUCTION: The purpose of this study was to compare 2-field (2F) and 5-field (5F) mydriatic handheld retinal imaging for the assessment of diabetic retinopathy (DR) severity in a community-based DR screening program (DRSP). METHODS: This was a prospective, cross-sectional diagnostic study, evaluating images of 805 eyes from 407 consecutive patients with diabetes acquired from a community-based DRSP. Mydriatic standardized 5F imaging (macula, disc, superior, inferior, temporal) with handheld retinal camera was performed. 2F (disc, macula), and 5F images were independently assessed using the International DR classification at a centralized reading center. Simple (K) and weighted (Kw) kappa statistics were calculated for DR. Sensitivity and specificity for referable DR ([refDR] moderate nonproliferative DR [NPDR] or worse) and vision-threatening DR ([vtDR] severe NPDR or worse) for 2F compared to 5F imaging were calculated. RESULTS: Distribution of DR severity by 2F/5F images (%): no DR 66.0/61.7, mild NPDR 10.7/14.4, moderate NPDR 7.9/8.1, severe NPDR 3.3/5.6, proliferative DR 5.6/4.6, ungradable 6.5/5.6. Exact agreement of DR grading between 2F and 5F was 81.7%, within 1-step 97.1% (K = 0.64, Kw = 0.78). Sensitivity/specificity for 2F compared 5F was refDR 0.80/0.97, vtDR 0.73/0.98. The ungradable images rate with 2F was 16.1% higher than with 5F (6.5 vs. 5.6%, p < 0.001). CONCLUSIONS: Mydriatic 2F and 5F handheld imaging have substantial agreement in assessing severity of DR. However, the use of mydriatic 2F handheld imaging only meets the minimum standards for sensitivity and specificity for refDR but not for vtDR. When using handheld cameras, the addition of peripheral fields in 5F imaging further refines the referral approach by decreasing ungradable rate and increasing sensitivity for vtDR.

Comparison of Diabetic Retinopathy Lesions Identified Using Ultrawide Field Imaging and Optical Coherence Tomography Angiography.

INTRODUCTION: Optical coherence tomography (OCT) angiography (OCTA) has the potential to influence the diagnosis and management of diabetic eye disease. This study aims to determine the correlation between diabetic retinopathy (DR) findings on ultrawide field (UWF) color photography (UWF-CP), UWF fluorescein angiography (UWF-FA), and OCTA. METHODS: This is a cross-sectional, prospective study. One hundred and fourteen eyes from 57 patients with diabetes underwent mydriatic UWF-CP, UWF-FA, and OCTA. DR severity was assessed. Ischemic areas were identified on UWF-FA using ImageJ and the nonperfusion index (NPI) was calculated. Diabetic macular edema (DME) was assessed using OCT. Superficial capillary plexus vessel density (VD), vessel perfusion (VP), and foveal avascular zone (FAZ) area were automatically measured on OCTA. Pearson correlation coefficient between the imaging modalities was determined. RESULTS: Forty-five eyes were excluded due to non-DR findings or prior laser photocoagulation; 69 eyes were analyzed. DR severity was associated with larger NPI (r = 0.55944, p < 0.0001) even after distinguishing between cones (Cone Nonperfusion Index [CPI]: r = 0.55617, p < 0.0001) and rods (Rod Nonperfusion Index [RPI]: r = 0.55285, p < 0.0001). In eyes with nonproliferative DR (NPDR), NPI is correlated with DME (r = 0.51156, p = 0.0017) and central subfield thickness (CST) (r = 0.67496, p < 0.0001). UWF-FA macular nonperfusion correlated with NPI (r = 0.42899, p = 0.0101), CPI (r = 0.50028, p = 0.0022), and RPI (r = 0.49027, p = 0.0028). Central VD and VP correlated with the DME presence (r = 0.52456, p < 0.0001; r = 0.51952, p < 0.0001) and CST (r = 0.50133, p < 0.0001; r = 0.48731, p < 0.0001). Central VD and VP were correlated with macular nonperfusion (r = 0.44503, p = 0.0065; r = 0.44239, p = 0.0069) in eyes with NPDR. Larger FAZ was correlated with decreased central VD (r = -0.60089, p = 0.0001) and decreased central VP (r = -0.59224, p = 0.0001). CONCLUSION: UWF-CP, UWF-FA, and OCTA findings provide relevant clinical information on diabetic eyes. Nonperfusion on UWF-FA is correlated with DR severity and DME. OCTA metrics of the superficial capillary plexus correlate with the incidence of DME and macular ischemia.

Multimodal Retinal Imaging in Patients with Diabetes Mellitus and Association with Cerebrovascular Disease.

INTRODUCTION: This study aimed to evaluate the association between macular optical coherence tomography angiography (OCT-A) metrics, characteristics of ultrawide field (UWF) imaging, and cerebrovascular disease in patients with diabetes mellitus (DM) with different stages of diabetic retinopathy (DR). METHODS: 516 eyes of 258 DM patients were enrolled in two centers (Milan and Belfast). UWF color fundus photos (CFPs) were obtained with Optos California (Optos, PLC) and graded for both DR severity and predominantly peripheral lesions presence (>50% of CFP lesions) by two independent graders. OCT-A (3 × 3 mm), available in 252 eyes of 136 patients, was used to determine perimeter, area, and circularity index of the foveal avascular zone and vessel density (VD); perfusion density (PD); fractal dimension on superficial, intermediate (ICP), and deep capillary plexuses; flow voids (FVs) in the choriocapillaris. RESULTS: Out of 516 eyes, 108 eyes (20.9%) had no DR, and 6 eyes were not gradable. The remaining 402 eyes were as follows: 10.3% (53) had mild nonproliferative DR (NPDR), 38.2% (197) had moderate NPDR, 11.8% (61) had severe NPDR, and 17.6% (91) had proliferative DR. A worse DR stage was associated with a history of stroke (p = 0.044). Logistic regression analysis after taking into account sex, type of DM, age, DM duration, and OCT-A variables found that PD and VD on ICP were significantly associated with presence of stroke and DR severity. CONCLUSION: OCT-A metrics show an association with the presence of cerebrovascular complications, providing potentially useful parameters to estimate vascular risk in patients with DM.

Comparisons of Handheld Retinal Imaging with Optical Coherence Tomography for the Identification of Macular Pathology in Patients with Diabetes.

INTRODUCTION: Handheld retinal imaging cameras are relatively inexpensive and highly portable devices that have the potential to significantly expand diabetic retinopathy (DR) screening, allowing a much broader population to be evaluated. However, it is essential to evaluate if these devices can accurately identify vision-threatening macular diseases if DR screening programs will rely on these instruments. Thus, the purpose of this study was to evaluate the detection of diabetic macular pathology using monoscopic macula-centered images using mydriatic handheld retinal imaging compared with spectral domain optical coherence tomography (SDOCT). METHODS: Mydriatic 40°-60° macula-centered images taken with 3 handheld retinal imaging devices (Aurora [AU], SmartScope [SS], RetinaVue 700 [RV]) were compared with the Cirrus 6000 SDOCT taken during the same visit. Images were evaluated for the presence of diabetic macular edema (DME) on monoscopic fundus photographs adapted from Early Treatment Diabetic Retinopathy Study (ETDRS) definitions (no DME, noncenter-involved DME [non-ciDME], and center-involved DME [ciDME]). Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for each device with SDOCT as gold standard. RESULTS: Severity by ETDRS photos: no DR 33.3%, mild NPDR 20.4%, moderate 14.2%, severe 11.6%, proliferative 20.4%, and ungradable for DR 0%; no DME 83.1%, non-ciDME 4.9%, ciDME 12.0%, and ungradable for DME 0%. Gradable images by SDOCT (N = 217, 96.4%) showed no DME in 75.6%, non-ciDME in 9.8%, and ciDME in 11.1%. The ungradable rate for images (poor visualization in >50% of the macula) was AU: 0.9%, SS: 4.4%, and RV: 6.2%. For DME, sensitivity and specificity were similar across devices (0.5-0.64, 0.93-0.97). For nondiabetic macular pathology (ERM, pigment epithelial detachment, traction retinal detachment) across all devices, sensitivity was low to moderate (0.2-0.5) but highly specific (0.93-1.00). CONCLUSIONS: Compared to SDOCT, handheld macular imaging attained high specificity but low sensitivity in identifying macular pathology. This suggests the importance of SDOCT evaluation for patients suspected to have DME on fundus photography, leading to more appropriate referral refinement.

Pushing Retinal Imaging Forward: Innovations and Their Clinical Meaning - The 2022 Ophthalmologica Lecture.

Retinal imaging has greatly expanded our understanding of various pathological conditions. This article presents a summary of the key points covered during the 2022 Ophthalmologica Lecture held at the Euretina Congress in Hamburg. The first part of the article focuses on the use of optical coherence tomography angiography to examine and comprehend the choroid in age-related macular degeneration (AMD). Subsequently, we delve into the discussion of the "postreceptor neuronal loss" theory in AMD, which was studied using en face structural optical coherence tomography (OCT). Following that, we explore pertinent findings obtained through cross-sectional OCT in retinal and optic nerve diseases, such as AMD, diabetic macular edema, pathologic myopia, central serous chorioretinopathy, and Leber's hereditary optic neuropathy.