Mohs micrographic surgery challenges and new technologies to optimize care of cutaneous malignancies of the ear.

Cutaneous malignancies affecting the ear, exacerbated by extensive ultraviolet (UV) exposure, pose intricate challenges owing to the organ's complex anatomy. This article investigates how the anatomy contributes to late-stage diagnoses and ensuing complexities in surgical interventions. Mohs Micrographic Surgery (MMS), acknowledged as the gold standard for treating most cutaneous malignancies of the ear, ensures superior margin control and cure rates. However, the ear's intricacy necessitates careful consideration of tissue availability and aesthetic outcomes. The manuscript explores new technologies like Reflectance Confocal Microscopy (RCM), Optical Coherence Tomography (OCT), High-Frequency, High-Resolution Ultrasound (HFHRUS), and Raman spectroscopy (RS). These technologies hold the promise of enhancing diagnostic accuracy and providing real-time visualization of excised tissue, thereby improving tumor margin assessments. Dermoscopy continues to be a valuable non-invasive tool for identifying malignant lesions. Staining methods in Mohs surgery are discussed, emphasizing hematoxylin and eosin (H&E) as the gold standard for evaluating tumor margins. Toluidine blue is explored for potential applications in assessing basal cell carcinomas (BCC), and immunohistochemical staining is considered for detecting proteins associated with specific malignancies. As MMS and imaging technologies advance, a thorough evaluation of their practicality, cost-effectiveness, and benefits becomes essential for enhancing surgical outcomes and patient care. The potential synergy of artificial intelligence with these innovations holds promise in revolutionizing tumor detection and improving the efficacy of cutaneous malignancy treatments.

Biomarker evidence of early vision and rod energy-linked pathophysiology benefits from very low dose DMSO in 5xFAD mice.

Here, we test whether early visual and OCT rod energy-linked biomarkers indicating pathophysiology in nicotinamide nucleotide transhydrogenase (Nnt)-null 5xFAD mice also occur in Nnt-intact 5xFAD mice and whether these biomarkers can be pharmacologically treated. Four-month-old wild-type or 5xFAD C57BL/6 substrains with either a null (B6J) Nnt or intact Nnt gene (B6NTac) and 5xFAD B6J mice treated for one month with either R-carvedilol + vehicle or only vehicle (0.01% DMSO) were studied. The contrast sensitivity (CS), external limiting membrane-retinal pigment epithelium (ELM-RPE) thickness (a proxy for low pH-triggered water removal), profile shape of the hyperreflective band just posterior to the ELM (i.e., the mitochondrial configuration within photoreceptors per aspect ratio [MCP/AR]), and retinal laminar thickness were measured. Both wild-type substrains showed similar visual performance indices and dark-evoked ELM-RPE contraction. The lack of a light-dark change in B6NTac MCP/AR, unlike in B6J mice, is consistent with relatively greater mitochondrial efficiency. 5xFAD B6J mice, but not 5xFAD B6NTac mice, showed lower-than-WT CS. Light-adapted 5xFAD substrains both showed abnormal ELM-RPE contraction and greater-than-WT MCP/AR contraction. The inner retina and superior outer retina were thinner. Treating 5xFAD B6J mice with R-carvedilol + DMSO or DMSO alone corrected CS and ELM-RPE contraction but not supernormal MCP/AR contraction or laminar thinning. These results provide biomarker evidence for prodromal photoreceptor mitochondrial dysfunction/oxidative stress/oxidative damage, which is unrelated to visual performance, as well as the presence of the Nnt gene. This pathophysiology is druggable in 5xFAD mice.

Influencing Factors on Pupillary Light Responses as a Biomarker for Local Retinal Function in a Large Normative Cohort.

Purpose: Investigating influencing factors on the pupillary light response (PLR) as a biomarker for local retinal function by providing epidemiological data of a large normative collective and to establish a normative database for the evaluation of chromatic pupil campimetry (CPC). Methods: Demographic and ophthalmologic characteristics were captured and PLR parameters of 150 healthy participants (94 women) aged 18 to 79 years (median = 46 years) were measured with L-cone- and rod-favoring CPC protocols. Linear-mixed effects models were performed to determine factors influencing the PLR and optical coherence tomography (OCT) data were correlated with the pupillary function volume. Results: Relative maximal constriction amplitude (relMCA) and latency under L-cone- and rod-favoring stimulation were statistically significantly affected by the stimulus eccentricity (P < 0.0001, respectively). Iris color and gender did not affect relMCA or latency significantly; visual hemifield, season, and daytime showed only minor influence under few stimulus conditions. Age had a statistically significant effect on latency under rod-specific stimulation with a latency prolongation ≥60 years. Under photopic and scotopic conditions, baseline pupil diameter declined significantly with increasing age (P < 0.0001, respectively). Pupillary function volume and OCT data were not correlated relevantly. Conclusions: Stimulus eccentricity had the most relevant impact on relMCA and latency of the PLR during L-cone- and rod-favoring stimulation. Latency is prolonged ≥60 years under scotopic conditions. Considering the large study collective, a representative normative database for relMCA and latency as valid readout parameters for L-cone- and rod-favoring stimulation could be established. This further validates the usability of the PLR in CPC as a biomarker for local retinal function.

Assessment of retinal and choroidal microvasculature in night shift medical workers by OCT angiography.

This study evaluated retinal and choroidal microvascular changes in night shift medical workers and its correlation with melatonin level. Night shift medical workers (group A, 25 workers) and non-night shift workers (group B, 25 workers) were recruited. The images of macula and optic nerve head were obtained by swept-source OCT-angiography. Vessel density of retina, choriocapillaris (CC), choriocapillaris flow deficit (CC FD), choroidal thickness (CT) and choroidal vascularity index (CVI) were measured. 6-sulfatoxymelatonin concentration was analyzed from the morning urine. CC FD and CVI were significantly decreased and CT was significantly increased in group A (all P < 0.05). 6-sulfatoxymelatonin concentration was significantly lower in group A (P < 0.05), which was significantly positively correlated with CC FD size (r = 0.318, P = 0.024) and CVI of the most regions (maximum r-value was 0.482, P < 0.001), and was significantly negatively associated with CT of all regions (maximum r-value was - 0.477, P < 0.001). In night shift medical workers, the reduction of melatonin was significantly correlated with CT thickening, CVI reduction and CC FD reduction, which suggested that they might have a higher risk of eye diseases. CC FD could be a sensitive and accurate indicator to reflect CC perfusion.

Choroidalyzer: An Open-Source, End-to-End Pipeline for Choroidal Analysis in Optical Coherence Tomography.

Purpose: To develop Choroidalyzer, an open-source, end-to-end pipeline for segmenting the choroid region, vessels, and fovea, and deriving choroidal thickness, area, and vascular index. Methods: We used 5600 OCT B-scans (233 subjects, six systemic disease cohorts, three device types, two manufacturers). To generate region and vessel ground-truths, we used state-of-the-art automatic methods following manual correction of inaccurate segmentations, with foveal positions manually annotated. We trained a U-Net deep learning model to detect the region, vessels, and fovea to calculate choroid thickness, area, and vascular index in a fovea-centered region of interest. We analyzed segmentation agreement (AUC, Dice) and choroid metrics agreement (Pearson, Spearman, mean absolute error [MAE]) in internal and external test sets. We compared Choroidalyzer to two manual graders on a small subset of external test images and examined cases of high error. Results: Choroidalyzer took 0.299 seconds per image on a standard laptop and achieved excellent region (Dice: internal 0.9789, external 0.9749), very good vessel segmentation performance (Dice: internal 0.8817, external 0.8703), and excellent fovea location prediction (MAE: internal 3.9 pixels, external 3.4 pixels). For thickness, area, and vascular index, Pearson correlations were 0.9754, 0.9815, and 0.8285 (internal)/0.9831, 0.9779, 0.7948 (external), respectively (all P < 0.0001). Choroidalyzer's agreement with graders was comparable to the intergrader agreement across all metrics. Conclusions: Choroidalyzer is an open-source, end-to-end pipeline that accurately segments the choroid and reliably extracts thickness, area, and vascular index. Especially choroidal vessel segmentation is a difficult and subjective task, and fully automatic methods like Choroidalyzer could provide objectivity and standardization.

Epithelial and stromal thickness profile and lens decentration in myopic orthokeratology / Perfil de espesor epitelial y estromal y descentrado del cristalino en ortoqueratología miope

Purpose: To study topographic epithelial and total corneal thickness changes in myopic subjects undergoing successful orthokeratology treatment in connection with the objective assessment of contact lens decentration. Methods: A prospective-observational and non-randomized study in 32 Caucasian myopic eyes undergoing Ortho-k for 3 months. Total, epithelial, and stromal thicknesses were studied before and after Ortho-k treatment, using optical coherence tomography with anterior segment application software. Central, paracentral, and mid-peripheral values are taken along 8 semi-meridians. Results: The central average total corneal thickness was 4.72 ± 1.04 μm thinner after Ortho-K. The paracentral corneal thickness showed no significant changes (p = 0.137), while the mid-peripheral corneal thickness was increased by 3.25 ± 1.6 μm associating this increase exclusively to the epithelial plot (p<0.001). When lens centration was assessed, a lens fitting decentration less than 1.0 mm was found for the whole sample, predominantly horizontal-temporal (87.5%) and vertical-inferior (50%) decentring. Corneal topographical analysis revealed a horizontal and vertical epithelial thickness asymmetric change profile with paracentral temporal thinnest values, and mid-peripheral nasal thickest values. Conclusions: The present study found a central corneal thinning induced by Ortho-k lenses in subjects with moderate myopia, only associated with a change in epithelial thickness, as well as mid-peripheral thickening, that seems to be mainly epithelial in origin. The authors also found a tendency of contact lens decentration toward temporal and inferior areas conditioning an asymmetric epithelial redistribution pattern.(AU)

Influence of static and dynamic ocular aberrations on full-field optical coherence tomography for in vivo high-resolution retinal imaging.

Under spatially incoherent illumination, time-domain full-field optical coherence tomography (FFOCT) offers the possibility to achieve in vivo retinal imaging at cellular resolution over a wide field of view. Such performance is possible, albeit there is the presence of ocular aberrations even without the use of classical adaptive optics. While the effect of aberrations in FFOCT has been debated these past years, mostly on low-order and static aberrations, we present, for the first time to our knowledge, a method enabling a quantitative study of the effect of statistically representative static and dynamic ocular aberrations on FFOCT image metrics, such as SNR, resolution, and image similarity. While we show that ocular aberrations can decrease FFOCT SNR and resolution by up to 14 dB and fivefold, we take advantage of such quantification to discuss different possible compromises between performance gain and adaptive optics complexity and speed, to optimize both sensor-based and sensorless FFOCT high-resolution retinal imaging.

A case of choroidal neovascularization as a first manifestaion of systemic lupus erythematosus.

BACKGROUND: To report a rare occurrence of pigment epitheliopathy associated with choroidal neovasculization as a first manifestation of systemic lupus erythematosus. CASE PRESENTATION: A 54-year-old female, with no prior medical history, sought a second opinion due to sudden drop in vision in her right eye to 20/80. Slit lamp examination was normal. Fundus examination revealed the presence of a subretinal hemorrhage in the macular area. Fundus imaging including optical coherence tomography and fluorescein angiography showed multifocal retinal pigment epitheliopathy associated with choroidal neovascularization (CNV). The patient had received an intravitreal injection of Bevacizumab 2 weeks ago. It was decided to complete the loading dose regimen with two additional Bevacizumab injections, and the first injection was done 2 weeks after her presentation. Two weeks later, the patient reported a rash on her cheeks, painful joints, and purpura. Systemic workup revealed positive ANA, anti-cardiolipin antibodies, and decreased complement levels, with negative anti-histone antibodies. This led to the diagnosis of systemic lupus erythematosus (SLE) based on the "Systemic Lupus International Collaborating Clinics" criteria. The patient was treated with 50 mg of prednisolone which was then tapered. 1 month after the third injection, an showed a total resolution of the sub-retinal fluid with an improvement of vision to 20/20. No recurrence was observed during follow-up. CONCLUSION: Based on the findings from the fundus exam and imaging, systemic symptoms and the blood work-up, we postulate that the pigment epitheliopathy associated with choroidal neovascularization was related to the vaso-occlusive disease at the level of the choroid that can be part of SLE vasculopathy. To our knowledge, this represents the first case in which pigment epitheliopathy and CNV were the primary manifestations of SLE.

Ixabepilone related angiographically silent macular edema.

INTRODUCTION: We present a single-eyed case with a previous diagnosis of breast cancer who had intraretinal cystoid changes associated with the systemic administration of ixabepilone in her only seeing eye. To our best knowledge, this is the first reported case describing this phenomenon related to the ixabepilone administration. CASE DESCRIPTION: A 54-year-old woman with a history of breast cancer was examined due to visual deterioration in her only good left eye. The patient had undergone cataract surgery and lens implantation in her right eye following a childhood accident, but subsequently had developed a refractory glaucoma and lost her right vision. Six cycles of 40 mg/m2 systemic ixabepilone (3-hly intravenous infusion once every 3 weeks) had been administered within the past six months. Her visual decline started two weeks following the last treatment session. She was offered intravitreal anti-vascular endothelial growth factor injection elsewhere. Fluorescein angiogram showed no dye leakage whereas spectral-domain optical coherence tomography demonstrated parafoveal intraretinal cystoid changes. En-face optical coherence tomography revealed petaloid type roundish hyporeflective areas at the level of superficial and deep vascular plexus. Ixabepilone-associated cystoid maculopathy was suspected as she received only ixabepilone for the chemotherapy in the last six months. We thus recommended her not to continue ixabepilone therapy. Ten weeks after the ixabepilone cessation, intraretinal cystoid changes had resolved completely. CONCLUSION: Angiographically silent intraretinal cystoid changes may develop in association with the use of ixabepilone. Referral to an ophthalmologist should be considered for the patients experiencing visual complaints as ixabepilone cessation may lead to visual improvement and avoid unnecessary treatment.

The prone position in COVID-19 impacts the thickness of peripapillary retinal nerve fiber layers and macular ganglion cell layers.

The prone position reduces mortality in severe cases of COVID-19 with acute respiratory distress syndrome. However, visual loss and changes to the peripapillary retinal nerve fiber layer (p-RNFL) and the macular ganglion cell layer and inner plexiform layer (m-GCIPL) have occurred in patients undergoing surgery in the prone position. Moreover, COVID-19-related eye problems have been reported. This study compared the p-RNFL and m-GCIPL thicknesses of COVID-19 patients who were placed in the prone position with patients who were not. This prospective longitudinal and case-control study investigated 15 COVID-19 patients placed in the prone position (the "Prone Group"), 23 COVID-19 patients not in the prone position (the "Non-Prone Group"), and 23 healthy, non-COVID individuals without ocular disease or systemic conditions (the "Control Group"). The p-RNFL and m-GCIPL thicknesses of the COVID-19 patients were measured at 1, 3, and 6 months and compared within and between groups. The result showed that the Prone and Non-Prone Groups had no significant differences in their p-RNFL thicknesses at the 3 follow-ups. However, the m-GCIPL analysis revealed significant differences in the inferior sector of the Non-Prone Group between months 1 and 3 (mean difference, 0.74 µm; P = 0.009). The p-RNFL analysis showed a significantly greater thickness at 6 months for the superior sector of the Non-Prone Group (131.61 ± 12.08 µm) than for the Prone Group (118.87 ± 18.21 µm; P = 0.039). The m-GCIPL analysis revealed that the inferior sector was significantly thinner in the Non-Prone Group than in the Control Group (at 1 month 80.57 ± 4.60 versus 83.87 ± 5.43 µm; P = 0.031 and at 6 months 80.48 ± 3.96 versus 83.87 ± 5.43 µm; P = 0.044). In conclusion, the prone position in COVID-19 patients can lead to early loss of p-RNFL thickness due to rising intraocular pressure, which is independent of the timing of prone positioning. Consequently, there is no increase in COVID-19 patients' morbidity burden.

Does collagen cross linking have any effect on retinal circulation in patients with keratoconus? An optical coherence tomography angiography (OCTA) study.

BACKGROUND: We aimed to employ Optical Coherence Tomography Angiography (OCTA) to comprehensively assess changes in the optic nerve head (ONH) and macular perfusion before and after the Corneal Collagen Cross-Linking (CCL) procedure in patients with keratoconus. METHODS: A total of 22 keratoconus patient's candidate for CCL procedures were included based on specific criteria, with meticulous exclusion criteria in place to minimize potential confounders. Participants underwent OCTA assessments of the ONH and macula using the Spectralis OCT (Heidelberg) before CCL, as well as at 1- and 3-months post-CCL. MATLAB software was utilized for image analysis. RESULTS: The mean age of the participants was 20.09 ± 6.11, including 59% male, and the mean intraocular pressure (IOP) before the surgery was 13.59 ± 2.85 mmHg. Peripapillary Retinal nerve fiber layer (ppRNFL) thickness and overall retinal thickness remained stable post-CCL. However, significant alterations were observed in macular vessel density, emphasizing regional variations in vascular response. For macular large vessel density (LVD), both superficial and deep vascular complex (SVC and DVC) demonstrated significant differences between before surgery and the 3 months post-surgery follow-up (p < 0.001 and p = 0.002, respectively). Optic nerve head markers demonstrated relative stability, except for changes in avascular complex density, which was 49.2 ± 2.2% before the surgery and decrease to 47.6 ± 1.7% three months after the operation (P-value = 0.005). CONCLUSION: While CCL appears to maintain the integrity of certain ocular structures, alterations in macular perfusion post-CCL suggest potential effects on retinal blood supply. Long-term monitoring is crucial to understand the implications of these changes, particularly in the context of conditions such as diabetes.

[Preliminary clinical observation and analysis of structural changes of optic nerve head in glaucoma patients after visual training].

Objective: To investigate the effect of virtual reality visual training on remodeling optic nerve structures of glaucoma patients and analyze the influencing factors of visual training effect. Methods: A prospective non-randomized controlled trial was conducted. Glaucoma patients who presented to the Department of Ophthalmology, Beijing Shijitan Hospital between October 2021 and October 2022 were collected and divided into the training group or the control group according to their intentions. The training group accepted 3 months of visual training, while the control group did not. Optical coherence tomography was used to examine the disc edge area, cup volume, disc area, cup-to-disc ratio, and other parameters of the optic disc of both eyes of the patients at enrollment and after 3 months, and the changes of each parameter in the two groups were analyzed. Multivariate analysis was performed in the training group to investigate the effects of sex, age, visual field index, and mean defect on visual disc structure changes during visual training. Results: A total of 53 glaucoma patients (101 eyes) were included in the final analysis, among which the training group consisted of 27 cases (51 eyes), with 19 males and 8 females, and the age range was 48.0 (40.0, 61.0) years old. The control group comprised 26 cases (50 eyes), with 26 males and 11 females, and the age range was 54.0 (38.0, 63.0) years old. Compared with the control group, the deviation of cup volume was -0.006(-0.050, 0.015)mm3 (P<0.05), and the deviation of disc edge area was 0.00(-0.04, 0.05)mm2 (P<0. 05)in the visual training group after 3 months of visual training. The gender (OR=4.217, 95%CI=1.188-14.966) may be the influence factor of rim area. While,the mean defect (OR=1.526, 95%CI=0.245-9.491) was not that influential on rim area change. Conclusions: Visual training can increase the disc area and decrease the optic cup volume of the optic nerve in glaucoma patients. The rim area may be increased more easily after visual training in male glaucoma patients.

Artificial neural network for enhancing signal-to-noise ratio and contrast in photothermal optical coherence tomography.

Optical coherence tomography (OCT) is a medical imaging method that generates micron-resolution 3D volumetric images of tissues in-vivo. Photothermal (PT)-OCT is a functional extension of OCT with the potential to provide depth-resolved molecular information complementary to the OCT structural images. PT-OCT typically requires long acquisition times to measure small fluctuations in the OCT phase signal. Here, we use machine learning with a neural network to infer the amplitude of the photothermal phase modulation from a short signal trace, trained in a supervised fashion with the ground truth signal obtained by conventional reconstruction of the PT-OCT signal from a longer acquisition trace. Results from phantom and tissue studies show that the developed network improves signal to noise ratio (SNR) and contrast, enabling PT-OCT imaging with short acquisition times and without any hardware modification to the PT-OCT system. The developed network removes one of the key barriers in translation of PT-OCT (i.e., long acquisition time) to the clinic.

Glaucoma detection using non-perfused areas in OCTA.

Multiple ophthalmic diseases lead to decreased capillary perfusion that can be visualized using optical coherence tomography angiography images. To quantify the decrease in perfusion, past studies have often used the vessel density, which is the percentage of vessel pixels in the image. However, this method is often not sensitive enough to detect subtle changes in early pathology. More recent methods are based on quantifying non-perfused or intercapillary areas between the vessels. These methods rely upon the accuracy of vessel segmentation, which is a challenging task and therefore a limiting factor for reliability. Intercapillary areas computed from perfusion-distance measures are less sensitive to errors in the vessel segmentation since the distance to the next vessel is only slightly changing if gaps are present in the segmentation. We present a novel method for distinguishing between glaucoma patients and healthy controls based on features computed from the probability density function of these perfusion-distance areas. The proposed approach is evaluated on different capillary plexuses and outperforms previously proposed methods that use handcrafted features for classification. Moreover the results of the proposed method are in the same range as the ones of convolutional neural networks trained on the raw input images and is therefore a computationally efficient, simple to implement and explainable alternative to deep learning-based approaches.

Intraoperative quantitative crystalline lens nuclear opacities analysis based on crystalline lenSx platform.

PURPOSE: The main objective is to quantify the lens nuclear opacity using spectral-domain optical coherence tomography (SD-OCT) and to evaluate its association with Lens Opacities Classification System III (LOCS-III) system, lens thickness (LT), and surgical parameters. The secondary objective is to assess the diagnostic model performance for hard nuclear cataract. METHODS: This study included 70 eyes of 57 adults with cataract, with 49 (70%) and 21 (30%) in training and validation cohort, respectively. Correlations of the average nuclear density (AND) /maximum nuclear density (MND) with LOCS-III scores, LT, and surgical parameters were analyzed. Univariate and multivariate logistic regression analysis, receiver operating characteristic curves and calibration curves were performed for the diagnostic of hard nuclear cataract. RESULTS: The pre-operative uncorrected distance visual acuity (UDVA), intraocular pressure (IOP), mean axial length (AL), and LT were 1.20 ± 0.47 log MAR, 15.50 ± 2.87 mmHg, 27.34 ± 3.77 mm and 4.32 ± 0.45 mm, respectively. The average nuclear opalescence (NO) and nuclear colour (NC) scores were 3.61 ± 0.94 and 3.50 ± 0.91 (ranging from 1.00 to 6.90), respectively. The average AND and MND were 137.94 ± 17.01 and 230.01 ± 8.91, respectively. NC and NO scores both significantly correlated with the AND (rNC = 0.733, p = 0.000; rNO = 0.755, p = 0.000) and MND (rNC = 0.643, p = 0.000; rNO = 0.634, p = 0.000). In the training cohort, the area under the curve (AUC) of the model was 0.769 (P < 0.001, 95%CI 0.620-0.919), which had a good degree of differentiation (Fig. 2a). The calibration curve showed good agreement between predicted and actual probability. CONCLUSION: The nuclear density measurement on SD-OCT images can serve as an objective and reliable indicator for quantifying nuclear density.

Follow-up report of fundus findings of tuberous sclerosis-associated retinal astrocytoma of two siblings.

A late adolescent with tuberous sclerosis (TS) presented with reduced vision in one eye to our tertiary care university hospital 4 years ago. Fundus examination revealed multiple retinal astrocytic hamartomas (RAHs) in both eyes. His younger sibling, who also had TS, was found to have RAH on retinal screening. The swept-source optical coherence tomography (SS-OCT) findings were typical of RAH. We further noted that some of the RAH lesions showed segmental whitening of the outer walls of the arterioles, which traversed through them. The segmental whitening may suggest the enveloping of normal retinal vessels by the tumour. En-face and B-scan SS-OCT angiography of patients with TS showed vascularity within the tumour. The vessels within the tumour appeared to be in continuity with the retinal vasculature. Both siblings were reviewed annually. At the end of 4 years, there was no change in visual acuity, tumour size, number, vascularity and behaviour.

Quantifying Putative Retinal Gliosis in Preclinical Alzheimer's Disease.

Purpose: Neuroinflammation plays a significant role in the pathology of Alzheimer's disease (AD). Mouse models of AD and postmortem biopsy of patients with AD reveal retinal glial activation comparable to central nervous system immunoreactivity. We hypothesized that the surface area of putative retinal gliosis observed in vivo using en face optical coherence tomography (OCT) imaging will be larger in patients with preclinical AD versus controls. Methods: The Spectralis II instrument was used to acquire macular centered 20 × 20 and 30 × 25-degrees spectral domain OCT images of 76 participants (132 eyes). A cohort of 22 patients with preclinical AD (40 eyes, mean age = 69 years, range = 60-80 years) and 20 control participants (32 eyes, mean age = 66 years, range = 58-82 years, P = 0.11) were included for the assessment of difference in surface area of putative retinal gliosis and retinal nerve fiber layer (RNFL) thickness. The surface area of putative retinal gliosis and RNFL thickness for the nine sectors of the Early Treatment Diabetic Retinopathy Study (ETDRS) map were compared between groups using generalized linear mixed models. Results: The surface area of putative retinal gliosis was significantly greater in the preclinical AD group (0.97 ± 0.55 mm2) compared to controls (0.68 ± 0.40 mm2); F(1,70) = 4.41, P = 0.039; Cohen's d = 0.61. There was no significant difference between groups for RNFL thickness in the 9 ETDRS sectors, P > 0.05. Conclusions: Our analysis shows greater putative retinal gliosis in preclinical AD compared to controls. This demonstrates putative retinal gliosis as a potential biomarker for AD-related neuroinflammation.

Integrating Machine Learning and Traditional Survival Analysis to Identify Key Predictors of Foveal Involvement in Geographic Atrophy.

Purpose: The purpose of this study was to investigate the incidence of foveal involvement in geographic atrophy (GA) secondary to age-related macular degeneration (AMD), using machine learning to assess the importance of risk factors. Methods: Retrospective, longitudinal cohort study. Patients diagnosed with foveal-sparing GA, having GA size ≥ 0.049 mm² and follow-up ≥ 6 months, were included. Baseline GA area, distance from the fovea, and perilesional patterns were measured using fundus autofluorescence. Optical coherence tomography assessed foveal involvement, structural biomarkers, and outer retinal layers thickness. Onset of foveal involvement was recorded. Foveal survival rates were estimated using Kaplan-Meier curves. Hazard ratios (HRs) were assessed with mixed model Cox regression. Variable Importance (VIMP) was ranked with Random Survival Forests (RSF), with higher scores indicating greater predictive significance. Results: One hundred sixty-seven eyes (115 patients, average age = 75.8 ± 9.47 years) with mean follow-up of 50 ± 29 months, were included in this study. Median foveal survival time was 45 months (95% confidence interval [CI] = 38-55). Incidences of foveal involvement were 26% at 24 months and 67% at 60 months. Risk factors were GA proximity to the fovea (HR = 0.97 per 10-µm increase, 95% CI = 0.96-0.98), worse baseline visual acuity (HR = 1.37 per 0.1 LogMAR increase, 95% CI = 1.21-1.53), and thinner outer nuclear layer (HR = 0.59 per 10-µm increase, 95% CI = 0.46-0.74). RSF analysis confirmed these as main predictors (VIMP = 16.7, P = 0.002; VIMP = 6.2, P = 0.003; and VIMP = 3.4, P = 0.01). Lesser baseline GA area (HR = 1.09 per 1-mm2 increase, 95% CI = 1.01-1.16) and presence of a double layer sign (HR = 0.42, 95% CI = 0.20-0.88) were protective but less influential. Conclusions: This study identifies anatomic and functional factors impacting the risk of foveal involvement in GA. These findings may help identify at-risk patients, enabling tailored preventive strategies.