Aqueous and Plasma Levels of Phosphorylated Tau 181 in Individuals with Normal Cognition.

Background: Plasma and cerebrospinal fluid (CSF) levels of p-tau181 have been associated with Alzheimer's disease (AD). The retina and vitreous have shown measurable quantities of phosphorylated tau 181 (p-tau181). The aqueous humor, which can be collected during cataract surgery, may have measurable concentrations of p-tau181. Objective: To determine whether p-tau181 is detectable in the aqueous humor and if so, whether it is associated with other measures that might be consistent with AD such as higher plasma p-tau181 concentration and lower Montreal Cognitive Assessment (MoCA-BLIND version 7.1) score. Methods: Aqueous humor samples, blood samples, and MoCA-BLIND scores were collected from patients who did not carry a clinical diagnosis of cognitive impairment at the time of cataract surgery. Aqueous p-tau181 concentrations and plasma p-tau181 concentrations were then measured using ultra-sensitive single-molecule assay ELISA technology. A rank-transformed mixed-effects multivariate regression model was used to determine associations between MoCA-BLIND scores. Results: 16 eyes of 16 participants were enrolled with an average age of 71.6. Average MoCA-BLIND score was 20.6/22, average aqueous p-tau181 concentration was 6.4 pg/mL, and average plasma p-tau181 concentration was 3.1 pg/mL. Higher plasma p-tau181 was significantly associated with higher aqueous p-tau181 (p = 0.02). Aqueous p-tau181 and plasma p-tau181 were negatively associated with MoCA-BLIND scores (p = 0.005 and p = 0.001 respectively) in these patients. Conclusions: Aqueous p-tau181 is positively correlated with plasma p-tau181 and is negatively correlated with MoCA-BLIND scores. Further study in individuals with mild cognitive impairment or AD characterized by cerebrospinal fluid and volumetric MRI metrics may yield further insights.

Analysis of the Retinal and Choroidal Vasculature Using Ultrawidefield Fundus Imaging in Mild Cognitive Impairment and Normal Cognition.

Purpose: To utilize ultrawidefield (UWF) imaging to evaluate retinal and choroidal vasculature and structure in individuals with mild cognitive impairment (MCI) compared with that of controls with normal cognition. Design: Prospective cross sectional study. Participants: One hundred thirty-one eyes of 82 MCI patients and 230 eyes of 133 cognitively normal participants from the Eye Multimodal Imaging in Neurodegenerative Disease Study. Methods: A scanning laser ophthalmoscope (California, Optos Inc) was used to obtain UWF fundus color images. Images were analyzed with the Vasculature Assessment Platform for Images of the Retina UWF (VAMPIRE-UWF 2.0, Universities of Edinburgh and Dundee) software. Main outcome measures: Imaging parameters included vessel width gradient, vessel width intercept, large vessel choroidal vascular density, vessel tortuosity, and vessel fractal dimension. Results: Both retinal artery and vein width gradients were less negative in MCI patients compared with controls, demonstrating decreased rates of vessel thinning at the periphery (P < 0.001; P = 0.027). Retinal artery and vein width intercepts, a metric that extrapolates the width of the vessel at the center of the optic disc, were smaller in MCI patients compared with that of controls (P < 0.001; P = 0.017). The large vessel choroidal vascular density, which quantifies the vascular area versus the total choroidal area, was greater in MCI patients compared with controls (P = 0.025). Conclusions: When compared with controls with normal cognition, MCI patients had thinner retinal vasculature manifested in both the retinal arteries and the veins. In MCI, these thinner arteries and veins attenuated at a lower rate when traveling toward the periphery. MCI patients also had increased choroidal vascular density. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Longitudinal Retinal and Choroidal Image Analysis in a Set of Monozygotic Twins.

We analyzed multimodal retinal and choroidal imaging, including optical coherence tomography (OCT) and OCT angiography (OCTA), to assess differences and characterize variations in the retinal and choroidal structure and microvasculature between healthy monozygotic twins without ocular or systemic pathology over a five-year period. Retinal imaging of both subjects revealed normal age-related changes. There was up to an 11% difference in OCT and OCTA variables within the subjects, both at baseline and at five years, and there was up to an 18% difference in OCT and OCTA parameters between the subjects for both time points. Larger changes in subfoveal choroidal thickness and foveal avascular zone area were observed. Our observations suggest that the parafoveal superficial capillary plexus, choroidal vascularity index, central subfield thickness, retinal nerve fiber layer thickness, and ganglion cell-inner plexiform layer thickness may be more heavily influenced by genetic, rather than environmental, factors. In contrast, subfoveal choroidal thickness and the foveal avascular zone area may be more heavily influenced by environmental factors. The environmental impact on retinal and choroidal structure and microvasculature is increasingly important to characterize, as such imaging parameters are being explored as potential biomarkers of systemic disease. These differences, as seen in these identical twin subjects, may be important considerations in supporting the security of biometric identifiers.

Incidence, risk factors, and treatment of retroprosthetic membranes following Boston keratoprosthesis eyes and the impact of glaucoma surgery.

PURPOSE: To assess incidence, risk factors, and treatment of retroprosthetic membrane (RPM) formation in eyes following Boston keratoprosthesis (Kpro) implantation and their correlation with glaucoma drainage device placement (GDD). METHODS: A retrospective review was performed on eyes that underwent Kpro type I or II implantation between 2005 and 2020 at a tertiary academic center. Multiple variables were collected including preoperative characteristics, presence of RPM, management of RPM, and outcomes including corrected visual acuity (VA). A Fischer's exact test was used to evaluate the significance of risk factors of RPM formation and an odds ratio was calculated for each possible risk factor. A Mann-Whitney U test was used to evaluate comparisons between outcomes and qualitative analyses. RESULTS: Of the 87 eyes identified, 37 (43%) developed an RPM within an average of 1.5 years (range, 31 days-7.5 years) following Kpro implantation. Mean follow-up duration was 4.3 years. Eyes that developed RPM had significantly worse preoperative VA compared to those that did not (logMAR 2.55 vs. 2.28, p = 0.022). The mean number of prior penetrating keratoplasty procedures trended higher in eyes that developed RPM (2.46 vs. 2.18, p = 0.44) but was not significant. GDD placement after Kpro implantation was associated with an increased risk of RPM formation (RR = 1.69 p = 0.026). Of the 37 eyes that developed an RPM following Kpro, 17 (47%) were treated with Nd:YAG laser, and four of those 17 (21%) also underwent pars plana vitrectomy (PPV). Seven of 37 eyes (19%) underwent PPV without Nd:YAG. Comparisons between RPM occurrence and final VA were not significant. CONCLUSIONS: The incidence of RPM formation following Kpro implantation was 43%. Eyes that developed RPM had significantly worse preoperative VA. GDD placement after Kpro implantation increased the risk of developing RPM. Final VA and occurrence of RPM were not significantly different between the Nd:YAG and PPV treatment groups.

Peripapillary Optical Coherence Tomography Angiography in Alzheimer's Disease, Mild Cognitive Impairment, and Normal Cognition.

OBJECTIVE: This study aimed to identify peripapillary microvascular changes in Alzheimer's disease (AD) and mild cognitive impairment (MCI). PATIENTS AND METHODS: In this prospective study, 66 eyes of 36 subjects with AD, 119 eyes of 63 with MCI, and 513 eyes of 265 controls with normal cognition were enrolled. Peripapillary capillary perfusion density (CPD), capillary flux index (CFI), and retinal nerve fiber layer (RNFL) thickness were determined. RESULTS: Average CPD differed significantly between all three groups (P = 0.001), being significantly greater in AD vs controls (0.446 ± 0.015 vs 0.439 ± 0.017, P = 0.001) and MCI vs controls (0.443 ± 0.020 vs 0.439 ± 0.017, P = 0.007) but not AD vs MCI (P = 0.69). CFI and average RNFL thickness did not significantly differ among groups (all P > 0.05). CONCLUSION: Peripapillary CPD is increased in eyes with AD or MCI compared to controls despite similar RNFL thickness. [Ophthalmic Surg Lasers Imaging Retina 2024;55:78-84.].

Ultra-Widefield Imaging of the Retinal Macrovasculature in Parkinson Disease Versus Controls With Normal Cognition Using Alpha-Shapes Analysis.

Purpose: To investigate retinal vascular characteristics using ultra-widefield (UWF) scanning laser ophthalmoscopy in Parkinson disease (PD). Methods: Individuals with an expert-confirmed clinical diagnosis of PD and controls with normal cognition without PD underwent Optos California UWF imaging. Patients with diabetes, uncontrolled hypertension, glaucoma, dementia, other movement disorders, or known retinal or optic nerve pathology were excluded. Images were analyzed using Vasculature Assessment and Measurement Platform for Images of the Retina (VAMPIRE-UWF) software, which describes retinal vessel width gradient and tortuosity, provides vascular network fractal dimensions, and conducts alpha-shape analysis to further characterize vascular morphology (complexity, Opαmin; spread, OpA). Results: In the PD cohort, 53 eyes of 38 subjects were assessed; in the control cohort, 51 eyes of 33 subjects were assessed. Eyes with PD had more tortuous retinal arteries in the superotemporal quadrant (P = 0.043). In eyes with PD, alpha-shape analysis revealed decreased OpA, indicating less retinal vasculature spread compared to controls (P = 0.032). Opαmin was decreased in PD (P = 0.044), suggesting increased vascular network complexity. No differences were observed in fractal dimension in any region of interest. Conclusions: This pilot study suggests that retinal vasculature assessment on UWF images using alpha-shape analysis reveals differences in retinal vascular network spread and complexity in PD and may be a more sensitive metric compared to fractal dimension. Translational Relevance: Retinal vasculature assessment using these novel methods may be useful in understanding ocular manifestations of PD and the development of retinal biomarkers.

Differences in Retinal and Choroidal Microvasculature and Structure in Dementia With Lewy Bodies Compared With Normal Cognition.

Purpose: To evaluate the retinal and choroidal microvasculature and structure in individuals with dementia with Lewy bodies (DLB) compared with controls with normal cognition using optical coherence tomography (OCT) and OCT angiography (OCTA). Methods: An institutional review board-approved cross-sectional comparison of patients with DLB and cognitively normal controls was performed. The Cirrus HD-OCT 5000 with AngioPlex (Carl Zeiss Meditec) was used to obtain OCT and OCTA images. Results: Thirty-four eyes of 18 patients with DLB and 85 eyes of 48 cognitively normal patients were analyzed. The average capillary perfusion density (CPD) was higher in the DLB group than in the control group (P = .005). The average capillary flux index (CFI) and ganglion cell inner-plexiform layer (GC-IPL) thickness were lower in the DLB group than in the control group (P = .016 and P = .040, respectively). Conclusions: Patients with DLB had an increased peripapillary CPD, decreased peripapillary CFI, and attenuated GC-IPL thickness compared with those with normal cognition.

Acute, Treatment-Naïve Branch Retinal Vein Occlusion in Younger Individuals: Risk Factors and Clinical Outcomes.

Purpose: To compare the risk factors and clinical outcomes in patients younger than 50 years with acute, treatment-naïve branch retinal vein occlusion (BRVO) with outcomes in patients 50 years or older. Methods: Patients diagnosed with acute, treatment-naïve BRVO at Duke Eye Center over a 9.5-year period who had BRVO with onset 3 months or less before presentation, BRVO with macular involvement, and 12 months or more of follow-up were included. Demographic data, presenting clinical features, risk factors, treatment patterns, and clinical outcomes were extracted during a retrospective review of medical records. Results: Of 302 patients identified, 23 were younger than 50 years (younger group) and 279 were 50 years or older (older group). Compared with older patients, younger patients had similar rates of hypertension (P = .275), diabetes mellitus (P = 1.000), smokers (P = .787), and open-angle glaucoma (P = .628). The younger group had a lower rate of hyperlipidemia than the older group (35% vs 59%) (P = .028). The 2 groups had similar presenting logMAR visual acuities (VAs) in the BRVO eye (P = .131). At the final follow-up, younger patients had significantly better logMAR VA in the BRVO-affected eye than older patients (mean 0.51 ± 0.65 vs 1.01 ± 1.20) (P = .016). The 2 groups had similar treatment burdens at 1 year (P = .516) and at the final follow-up (P = .782). Conclusions: Younger patients with acute, treatment-naïve BRVO have similar risk factors and treatment patterns as older patients, except for a lower rate of hyperlipidemia. Younger patients with BRVO may have similar presenting VA as older BRVO patients but better final VA, suggesting that age may be a potential prognostic factor.

Characterizing differences in retinal and choroidal microvasculature and structure in individuals with Huntington's Disease compared to healthy controls: A cross-sectional prospective study.

OBJECTIVE: To characterize retinal and choroidal microvascular and structural changes in patients who are gene positive for mutant huntingtin protein (mHtt) with symptoms of Huntington's Disease (HD). METHODS: This study is a cross-sectional comparison of patients who are gene positive for mHtt and exhibit symptoms of HD, either motor manifest or prodromal (HD group), and cognitively normal individuals without a family history of HD (control group). HD patients were diagnosed by Duke movement disorder neurologists based on the Unified Huntington's Disease Rating Scale (UHDRS). Fovea and optic nerve centered OCT and OCTA images were captured using Zeiss Cirrus HD-5000 with AngioPlex. Outcome metrics included central subfield thickness (CST), peripapillary retinal nerve fiber layer (pRNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, and choroidal vascularity index (CVI) on OCT, and foveal avascular zone (FAZ) area, vessel density (VD), perfusion density (PD), capillary perfusion density (CPD), and capillary flux index (CFI) on OCTA. Generalized estimating equation (GEE) models were used to account for inter-eye correlation. RESULTS: Forty-four eyes of 23 patients in the HD group and 77 eyes of 39 patients in the control group were analyzed. Average GCIPL thickness and FAZ area were decreased in the HD group compared to controls (p = 0.001, p < 0.001). No other imaging metrics were significantly different between groups. CONCLUSIONS: Patients in the HD group had decreased GCIPL thickness and smaller FAZ area, highlighting the potential use of retinal biomarkers in detecting neurodegenerative changes in HD.

IMPLICATIONS OF COMPLETE POSTERIOR VITREOUS DETACHMENT IN EYES WITH CENTRAL RETINAL VEIN OCCLUSION.

BACKGROUND/PURPOSE: To evaluate the status of the posterior vitreous hyaloid on presenting optical coherence tomography images of the macula and its relationship to clinical characteristics, treatment patterns, and outcomes in eyes with central retinal vein occlusion. METHODS: This is a retrospective longitudinal cohort study of consecutive patients with acute, treatment-naive central retinal vein occlusion diagnosed between 2009 and 2021 who had at least 12 months of follow-up. Clinical characteristics, treatment patterns, and outcomes were analyzed between eyes stratified based on the presence or absence of a complete posterior vitreous detachment (PVD) on optical coherence tomography at presentation. RESULTS: Of 102 acute, treatment-naive central retinal vein occlusions identified, 52 (51%) had complete PVD at presentation and 50 (49%) did not. Central subfield thickness was significantly lower in those with complete PVD (12 months: 284.9 ± 122.9 µ m vs. 426.8 ± 286.4 µ m, P < 0.001; last follow-up: 278 ± 127.9 vs. 372.8 ± 191.0 µ m, P = 0.022). One-year intravitreal injection burden was significantly less for those with a complete PVD than those without (5.1 ± 3.6 injections vs. 6.7 ± 3.3 injections, P = 0.013). CONCLUSION: Central retinal vein occlusion with complete PVD on presentation had significantly lower central subfield thickness and 1-year injection burden. Assessment of the vitreomacular interface in central retinal vein occlusion may serve as a prognostic imaging biomarker.

Asymmetric Purtscher-Like Retinopathy Caused by a Hypertensive Emergency and Undiagnosed Type 2 Diabetes.

Purpose: To report a case of Purtscher-like retinopathy (PLR) in the setting of a hypertensive emergency and undiagnosed type 2 diabetes mellitus (DM). Methods: A case was analyzed. Results: A 29-year-old, obese, hypertensive man presented with a 10-day history of progressive vision loss in the left eye with no history of trauma. The visual acuity was 20/25 OD and hand motions OS. A fundus examination showed dilated, tortuous veins; dot-blot and flame hemorrhaging; numerous cotton-wool spots; and polygonal areas of retinal whitening consistent with Purtscher flecken in the right eye and a vitreous hemorrhage in the left eye. The blood pressure was 226/125 mm Hg, and the hemoglobin A1c was 11.6%. The patient's presentation was concerning for a hypertensive emergency and type 2 DM as the etiology for the ocular findings. Conclusions: The presence of one condition in association with PLR does not exclude the presence of another concurrent etiology.

ENDOGENOUS ENDOPHTHALMITIS ASSOCIATED WITH INJECTION DRUG USE COMPARED WITH OTHER ETIOLOGIES.

PURPOSE: To compare features of endogenous endophthalmitis associated with injection drug use (IDU) to endogenous endophthalmitis from other etiologies. METHODS: The authors retrospectively collected data on patients with endogenous endophthalmitis due to IDU or other causes from three academic tertiary care centers over a six-year period. Differences in presenting characteristics, culture results, treatment, and visual acuity were compared between groups. RESULTS: Thirty-eight patients (34%) had IDU-associated endogenous endophthalmitis while 75 patients (67%) had endogenous endophthalmitis from other causes. Compared with patients in the non-IDU group, IDU patients were significantly younger, more frequently male, had longer duration of symptoms at diagnosis, and were less likely to have bilateral disease ( P < 0.05 for all). Injection drug use patients were less likely to have a systemic infection source identified (29% vs. 71%, P < 0.001) or have positive cultures (47% vs. 80%, P < 0.001). The IDU group was less likely to be admitted to the hospital (71% vs. 92%, P = 0.005) and less likely to receive treatment with intravenous antimicrobials (55% vs. 83%, P = 0.003). Visual acuity did not significantly differ between groups. CONCLUSION: Endophthalmitis related to IDU presents in younger patients with less comorbidities and frequently without positive cultures or an identifiable systemic source; therefore, a high index of suspicion is needed to identify this disease.

Convolutional Neural Network-Based Automated Quality Assessment of OCT and OCT Angiography Image Maps in Individuals With Neurodegenerative Disease.

Purpose: To train and test convolutional neural networks (CNNs) to automate quality assessment of optical coherence tomography (OCT) and OCT angiography (OCTA) images in patients with neurodegenerative disease. Methods: Patients with neurodegenerative disease were enrolled in the Duke Eye Multimodal Imaging in Neurodegenerative Disease Study. Image inputs were ganglion cell-inner plexiform layer (GC-IPL) thickness maps and fovea-centered 6-mm × 6-mm OCTA scans of the superficial capillary plexus (SCP). Two trained graders manually labeled all images for quality (good versus poor). Interrater reliability (IRR) of manual quality assessment was calculated for a subset of each image type. Images were split into train, validation, and test sets in a 70%/15%/15% split. An AlexNet-based CNN was trained using these labels and evaluated with area under the receiver operating characteristic (AUC) and summaries of the confusion matrix. Results: A total of 1465 GC-IPL thickness maps (1217 good and 248 poor quality) and 2689 OCTA scans of the SCP (1797 good and 892 poor quality) served as model inputs. The IRR of quality assessment agreement by two graders was 97% and 90% for the GC-IPL maps and OCTA scans, respectively. The AlexNet-based CNNs trained to assess quality of the GC-IPL images and OCTA scans achieved AUCs of 0.990 and 0.832, respectively. Conclusions: CNNs can be trained to accurately differentiate good- from poor-quality GC-IPL thickness maps and OCTA scans of the macular SCP. Translational Relevance: Since good-quality retinal images are critical for the accurate assessment of microvasculature and structure, incorporating an automated image quality sorter may obviate the need for manual image review.

Longitudinal Assessment of the Choroidal Vascularity Index in Eyes with Branch Retinal Vein Occlusion-Associated Cystoid Macular Edema.

INTRODUCTION: Cystoid macular edema (CME) is the most common cause of central vision loss in eyes with branch retinal vein occlusion (BRVO eyes). In recent literature, choroidal vascularity index (CVI) has been proposed to be an enhanced depth imaging optical coherence tomography (EDI-OCT) metric that may help characterize choroidal vascular changes in the setting of retinal ischemia, and potentially prognose visual outcomes and treatment patterns for patients with BRVO-related CME. This study sought to further characterize choroidal vascular changes in BRVO by comparing the CVI, subfoveal choroidal thickness (SFCT), and central subfield thickness (CST) in BRVO eyes with CME compared to unaffected fellow eyes. METHODS: This was a retrospective cohort study. Subjects included treatment-naïve BRVO eyes with CME diagnosed within 3 months of onset of symptoms and unaffected fellow eyes. EDI-OCT images were collected at baseline and at the 12-month follow-up visit. CVI, SFCT, and CST were measured. Demographics, treatment patterns, and best-corrected visual acuity (VA) were abstracted. Median CVI, SFCT, CST, and VA were compared between the two cohorts. Longitudinal relationships between these variables were analyzed. RESULTS: A total of 52 treatment-naïve eyes with BRVO and CME and 48 unaffected fellow eyes were identified. Baseline CVI was lower in eyes with BRVO than in fellow eyes (64.7% vs. 66.4%, P = 0.003). At 12 months, there was no difference in CVI between BRVO eyes and fellow eyes (65.7% vs 65.8%, P = 0.536). In BRVO eyes, there was a strong correlation between reduced CST and improved VA over the 12-month study period (r = 0.671, P < 0.001). CONCLUSION: There are differences in CVI in treatment-naïve BRVO eyes with CME at presentation compared to fellow eyes, but these differences resolve over time. Anatomic changes in macular thickness in BRVO eyes with CME may be correlated with VA outcomes.

Our study evaluated a novel ocular optical coherence tomography imaging metric, the choroidal vascularity index, in eyes that developed cystoid macular edema, a condition which can significantly impair acuity of central vision, after being diagnosed with branch retinal vein occlusion. In each patient, we compared the choroidal vascularity index in eyes that developed treatment-naïve, newly diagnosed branch retinal vein occlusion with cystoid macular edema to the non-diseased fellow eye. We made comparisons at the time of diagnosis (baseline) and at the 12-month follow up, and analyzed changes over time. We found that at the baseline visit, branch retinal vein occlusion eyes with cystoid macular edema had a significantly lower choroidal vascularity index than their unaffected fellow eyes, but that the differences between eyes resolved by the 12-month follow-up visit. Our findings suggest that choroidal vascularity may be compromised in the acute phase of branch retinal vein occlusion, but that this phenomenon resolves over time. Future research should further evaluate whether imaging characteristics of choroidal vascularity may be associated with changes in anatomic and visual outcomes in retinal diseases.

Intrasession Repeatability of OCT Angiography Parameters in Neurodegenerative Disease.

Purpose: To assess the intrasession repeatability of macular OCT angiography (OCTA) parameters in Alzheimer's disease (AD), mild cognitive impairment (MCI), Parkinson's disease (PD), and normal cognition (NC). Design: Cross sectional study. Subjects: Patients with a clinical diagnosis of AD, PD, MCI, or NC were imaged. Images with poor quality and of those with diabetes mellitus, glaucoma, or vitreoretinal disease were excluded from analysis. Methods Intervention or Testing: All participants were imaged using the Zeiss Cirrus HD-5000 with AngioPlex (Carl Zeiss Meditec, Software Version 11.0.0.29946) and repeat OCTA images were obtained for both eyes. Perfusion density (PFD), vessel density (VD), and Foveal avascular zone (FAZ) area were measured from 3 × 3 mm and 6 × 6 mm OCTA images centered on the fovea using an ETDRS grid overlay. Main Outcome Measures: Intraclass correlation coefficients were used to quantify repeatability of PFD, VD, and FAZ area measurements obtained from imaging. Results: 3 × 3 mm scans of 22 AD, 40 MCI, 21 PD, and 26 NC participants and 6 × 6 mm scans of 29 AD, 44 MCI, 29 PD, and 30 NC participants were analyzed. Repeatability values ranged from 0.64 (0.49-0.82) for 6 × 6 mm PFD in AD participants to 0.87 (0.67-0.92) for 3 × 3 mm PFD in AD participants. No significant differences were observed in repeatability between NC participants and those with neurodegenerative disease. Conclusions: Overall, similar OCTA repeatability was observed between NC participants and those with neurodegeneration. Regardless of diagnostic group, macular OCTA metrics demonstrated moderate to good repeatability. Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

Retinal Vascular Changes in Alzheimer's Dementia and Mild Cognitive Impairment: A Pilot Study Using Ultra-Widefield Imaging.

Purpose: Retinal microvascular abnormalities measured on retinal images are a potential source of prognostic biomarkers of vascular changes in the neurodegenerating brain. We assessed the presence of these abnormalities in Alzheimer's dementia and mild cognitive impairment (MCI) using ultra-widefield (UWF) retinal imaging. Methods: UWF images from 103 participants (28 with Alzheimer's dementia, 30 with MCI, and 45 with normal cognition) underwent analysis to quantify measures of retinal vascular branching complexity, width, and tortuosity. Results: Participants with Alzheimer's dementia displayed increased vessel branching in the midperipheral retina and increased arteriolar thinning. Participants with MCI displayed increased rates of arteriolar and venular thinning and a trend for decreased vessel branching. Conclusions: Statistically significant differences in the retinal vasculature in peripheral regions of the retina were observed among the distinct cognitive stages. However, larger studies are required to establish the clinical importance of our findings. UWF imaging may be a promising modality to assess a larger view of the retinal vasculature to uncover retinal changes in Alzheimer's disease. Translational Relevance: This pilot work reports an investigation into which retinal vasculature measurements may be useful surrogate measures of cognitive decline, as well as technical developments (e.g., measurement standardization), that are first required to establish their recommended use and translational potential.

Resident Vitreoretinal Procedure Volume: Effect of Intravitreal Injections, Region, Program Size, and Vitreoretinal Fellowship and Veterans Affairs Affiliation.

Purpose To analyze resident vitreoretinal procedure volume across Accreditation Council of Graduate Medical Education (ACGME) accredited ophthalmology residency programs. We assessed the effect of the increase in intravitreal injections (IVI), geographic region, program size, and Veterans Affairs (VA) and vitreoretinal fellowship affiliation on vitreoretinal procedures. Methods A request was sent to all residency programs in 2018 for their graduating residents' ACGME case logs. Vitreoretinal procedures were defined by ACGME case log categories and included vitreoretinal surgery, peripheral retinal lasers, and IVI. Procedures were categorized by Current Procedural Terminology (CPT) code. Programs were studied by geographic region, program size, and by VA and vitreoretinal fellowship affiliation. Results A total of 38 of 115 (33.0%) programs responded, and 167 residents logged 32,860 vitreoretinal procedures. The median number of retina procedures per resident was 146 (range 36-729). Programs with a vitreoretinal fellowship had a higher average number of vitreoretinal procedures per resident (208.3 vs. 125.0; p = 0.002), but there was no difference between the average number of non-IVI vitreoretinal procedures (60.0 vs. 64.2; p = 0.32). For IVI, VA affiliation (146.6 vs. 71.1; p = 0.02) and vitreoretinal fellowship (149.4 vs. 60.8; p < 0.001) were associated with a greater number. More IVI strongly correlated with a larger total volume of retinal procedures ( r = 0.98), and there was no difference across programs for total retinal procedures when IVI was removed. Conclusions The presence of a vitreoretinal fellowship at a residency program had a positive effect on resident total vitreoretinal case volume, but their residents performed more IVI. Programs without vitreoretinal fellowships completed on average more non-IVI procedures.

Longitudinal Analysis of Retinal Microvascular and Choroidal Imaging Parameters in Parkinson's Disease Compared with Controls.

Purpose: To quantify rate of change of retinal microvascular and choroidal structural parameters in subjects with Parkinson's disease (PD) compared with controls using OCT and OCT angiography (OCTA). Design: Prospective longitudinal study. Participants: Seventy-four eyes of 40 participants with PD and 149 eyes of 78 control individuals from the Eye Multimodal Imaging in Neurodegenerative Disease database. Methods: Subjects underwent OCT and OCTA imaging at 2 time points approximately 12 months apart. Main Outcome Measures: Imaging parameters included central subfield thickness, ganglion cell-inner plexiform layer (GC-IPL) thickness, peripapillary retinal nerve fiber layer thickness, choroidal vascularity index, superficial capillary plexus perfusion density (PFD), vessel density (VD), and foveal avascular zone area. Results: Participants with PD had greater rate of yearly decrease in GC-IPL (PD = -0.403µm, control = + 0.128 µm; P = 0.01), greater yearly decline in PFD in the 3 × 3 mm ETDRS circle (PD = -0.016, control = + 0.002; P < 0.001) and ring (PD = -0.016, control = + 0.002; P < 0.001); 6 × 6 mm ETDRS circle (PD = -0.021, control = 0.00; P = 0.001), and outer ring (PD = -0.022, control = 0.00; P = 0.001). Participants with PD had greater rate of yearly decline in VD in 3 × 3 mm circle (PD = -0.939/mm, control = + 0.006/mm; P < 0.001) and ring (PD = -0.942/mm, control = + 0.013/mm; P < 0.001); 6 × 6 mm circle (PD = -0.72/mm, control = -0.054/mm; P = 0.006), and outer ring (PD = -0.746/mm, control = -0.054/mm; P = 0.005). When stratified by PD severity based on Hoehn and Yahr stage, faster rates of decline were seen in Hoehn and Yahr stages 3 to 4 in the 3 × 3 mm circle PFD and VD as well as 3 × 3 mm ring VD. Conclusions: Individuals with PD experience more rapid loss of retinal microvasculature quantified on OCTA and more rapid thinning of the GC-IPL than controls. There may be more rapid loss in patients with greater disease severity. Financial Disclosures: The author(s) have no proprietary or commercial interest in any materials discussed in this article.