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.].

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.

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.

The effect of a brief, unplanned treatment delay on neovascular age-related macular degeneration patients: a retrospective cohort study.

Non-compliance to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy can result in increased disease activity in neovascular age-related macular degeneration (nAMD). Our study aims to determine effects of unplanned delay in anti-VEGF injection treatment for nAMD. This retrospective observational study included patients with delays in receiving intravitreal injections for nAMD treatment from March to May 2020 by at least 21 days. Baseline demographic and clinical characteristics, visual acuity (VA), central macular thickness (CMT) measured on optical coherence tomography (OCT), and duration of delayed treatment were analyzed for 3 time points, the pre-delay visit (v1) and post-delay visits (v2 and v3). Data were compared to age-matched controls treated for nAMD in 2019 without delay. Demographic characteristics were compared using two-sample t-tests for continuous variables and Pearson's chi-square tests for categorical variables. For the two primary outcomes of interest, VA and CMT, means and standard deviations were reported for each combination of group and time. Each outcome was modeled using a linear mixed model with the group, time and group-time interaction as fixed effects. A total of 69 patients (99 eyes) in the treatment delay group and 44 patients (69 eyes) in the control group were identified. Statistically significant differences between control and delayed groups were detected for VA (difference in mean logMAR = 0.16; 95% CI 0.06, 0.27; p = 0.002) and CMT (difference in mean CMT = 29; 95% CI 12, 47; p = 0.001) at v2. No differences were detected for v1 and v3 time points for both outcomes. An unplanned delay in intravitreal injection treatment for nAMD resulted in an increase in CMT and worsening of VA compared to controls observed at v2. At v3, CMT and VA recovered to near v1 levels. This study demonstrates that a one-time, brief interruption in treatment for nAMD results in reversible, temporary worsening.

Retinal and Choroidal Changes in Men Compared with Women with Alzheimer's Disease: A Case-Control Study.

Purpose: To evaluate differences in the retinal microvasculature and structure and choroidal structure among men and women with Alzheimer's disease (AD) compared with age-matched cognitively normal male and female controls. Design: Case-control study of participants ≥ 50 years of age. Participants: A total of 202 eyes of 139 subjects (101 cases and 101 controls). Methods: All participants and controls underwent OCT and OCT angiography (OCTA), and parameters of subjects with AD were compared with those of cognitively normal controls. Main Outcome Measures: The foveal avascular zone (FAZ) area, vessel density (VD), and perfusion density (PD) in the superficial capillary plexus within the 3- and 6-mm circle and ring using Early Treatment Diabetic Retinopathy Study (ETDRS) grid overlay on OCTA; central subfield thickness (CST), retinal nerve fiber layer (RNFL) thickness, ganglion cell-inner plexiform layer (GCIPL) thickness, and choroidal vascularity index (CVI) on OCT. Results: No significant sex differences in VD or PD were found in the AD or control cohorts; however, there were greater differences in VD and PD among AD female participants than AD male participants compared with their respective controls. The CST and FAZ area were not different between male and female AD participants. Among controls, men had a thicker CST (P < 0.001) and smaller FAZ area (P = 0.003) compared with women. The RNFL thickness, GCIPL thickness, and CVI were similar among male and female AD participants and controls. Conclusions: There may be a loss of the physiologic sex-related differences in retinal structure and microvasculature in those with AD compared with controls. Further studies are needed to elucidate the pathophysiological basis for these findings.

ASSESSMENT OF RETINAL MICROVASCULAR ALTERATIONS IN INDIVIDUALS WITH AMNESTIC AND NONAMNESTIC MILD COGNITIVE IMPAIRMENT USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To assess retinal microvascular alterations in individuals with amnestic mild cognitive impairment (MCI) and nonamnestic MCI. METHODS: One hundred twelve eyes of 59 amnestic MCI participants, 32 eyes of 17 nonamnestic MCI participants, and 111 eyes of 56 controls with normal cognition were included. Optical coherence tomography angiography vessel density and perfusion density in the Early Treatment Diabetic Retinopathy Study 3-mm circle and ring were assessed. Retinal thickness parameters including retinal nerve fiber layer thickness, ganglion cell-inner plexiform layer thickness, central subfield thickness, and subfoveal choroidal thickness were also analyzed. Multivariable generalized estimating equations were used for statistical analysis. RESULTS: Perfusion density in the 3-mm inner ring was significantly lower in amnestic MCI patients when compared with nonamnestic MCI participants (0.29 ± 0.03 vs. 0.34 ± 0.09, P = 0.025) and controls with normal cognition (0.29 ± 0.03 vs. 0.39 ± 0.02, P < 0.001), after adjustment for age and sex as covariates. Vessel density, retinal nerve fiber layer thickness, ganglion cell-inner plexiform layer thickness, central subfield thickness, and subfoveal choroidal thickness did not differ among or between diagnostic groups. CONCLUSION: Perfusion density was significantly reduced in individuals with amnestic MCI, compared with those with nonamnestic MCI and controls with normal cognition.

Longitudinal Analysis of the Retina and Choroid in Cognitively Normal Individuals at Higher Genetic Risk of Alzheimer Disease.

PURPOSE: To assess the baseline differences and longitudinal rate of change in retinal and choroidal imaging parameters between apolipoprotein ε4 (APOE ε4) carriers and noncarriers with normal cognition. DESIGN: Prospective study. SUBJECTS: Four hundred thirteen eyes of 218 individuals with normal cognition aged ≥ 55 years with known APOE status (98 APOE ε4 carriers and 120 noncarriers). The exclusion criteria included diabetes mellitus, uncontrolled hypertension, glaucoma, and vitreoretinal or neurodegenerative disease. METHODS: OCT and OCT angiography (OCTA) were performed at baseline and 2 years (Zeiss Cirrus HD-OCT 5000 with AngioPlex; Zeiss Meditec). The groups were compared using sex- and age-adjusted generalized estimating equations. MAIN OUTCOME MEASURES: OCT parameters: retinal nerve fiber layer thickness, macular ganglion cell-inner plexiform layer thickness, central subfield thickness (CST), and choroidal vascularity index. OCT angiography parameters: foveal avascular zone area, perfusion density (PD), vessel density, peripapillary capillary PD (CPD), and capillary flux index (CFI). The rate of change per year was calculated. RESULTS: At the baseline, the APOE ε4 carriers had lower CST (P = 0.018), PD in the 6-mm ETDRS circle (P = 0.049), and temporal CFI (P = 0.047). Seventy-one APOE ε4 carriers and 78 noncarriers returned at 2 years; at follow-up, the 6-mm ETDRS circle (P = 0.05) and outer ring (P = 0.049) showed lower PD in the APOE ε4 carriers, with no differences in the rates of change between the groups (all P > 0.05). CONCLUSIONS: There was exploratory evidence of differences in the CST, PD, and peripapillary CFI between the APOE ε4 carriers and noncarriers with normal cognition. Larger and longer-term studies may help further elucidate the potential prognostic value of these findings.

Management Patterns and Outcomes for Intravitreal Injection-Related Endophthalmitis.

Purpose: This work describes the clinical management and outcomes in cases of presumed infectious endophthalmitis following intravitreal injection at a tertiary academic medical center. Methods: A retrospective review took place of eyes that presented to the Duke Eye Center over a 9-year period and were diagnosed with intravitreal injection-related endophthalmitis. Clinical presentation, management, microbiologic yield, visual outcomes, and complications were abstracted from medical records. Results: Of 23 eyes diagnosed with postinjection endophthalmitis, 52.2% underwent anterior chamber tap (33.3% of which first underwent dry needle vitreous tap), 47.8% underwent needle vitreous tap, 17.4% underwent neither, and none underwent pars plana vitrectomy (PPV) for initial management. Subsequent PPV was performed in 6 eyes (26.1%). Mean visual acuity (VA) improved by 50 Early Treatment Diabetic Retinopathy Study letters at 6 months. Eyes that underwent initial anterior chamber tap had worse presenting VA than those that did not (P = .01). Eyes undergoing subsequent PPV had worse VA at presentation (P = .02) and at 6 months (P < .001). Eyes presenting with VA of hand motion (20/8000) or worse were more likely to undergo subsequent PPV (P = .02). Conclusions: Eyes with intravitreal injection-related endophthalmitis presenting with VA of hand motion or worse were more likely to undergo subsequent PPV. Future studies with larger cohorts may reveal whether earlier vitrectomy should be considered in these patients.

Convolutional neural network to identify symptomatic Alzheimer's disease using multimodal retinal imaging.

BACKGROUND/AIMS: To develop a convolutional neural network (CNN) to detect symptomatic Alzheimer's disease (AD) using a combination of multimodal retinal images and patient data. METHODS: Colour maps of ganglion cell-inner plexiform layer (GC-IPL) thickness, superficial capillary plexus (SCP) optical coherence tomography angiography (OCTA) images, and ultra-widefield (UWF) colour and fundus autofluorescence (FAF) scanning laser ophthalmoscopy images were captured in individuals with AD or healthy cognition. A CNN to predict AD diagnosis was developed using multimodal retinal images, OCT and OCTA quantitative data, and patient data. RESULTS: 284 eyes of 159 subjects (222 eyes from 123 cognitively healthy subjects and 62 eyes from 36 subjects with AD) were used to develop the model. Area under the receiving operating characteristic curve (AUC) values for predicted probability of AD for the independent test set varied by input used: UWF colour AUC 0.450 (95% CI 0.282, 0.592), OCTA SCP 0.582 (95% CI 0.440, 0.724), UWF FAF 0.618 (95% CI 0.462, 0.773), GC-IPL maps 0.809 (95% CI 0.700, 0.919). A model incorporating all images, quantitative data and patient data (AUC 0.836 (CI 0.729, 0.943)) performed similarly to models only incorporating all images (AUC 0.829 (95% CI 0.719, 0.939)). GC-IPL maps, quantitative data and patient data AUC 0.841 (95% CI 0.739, 0.943). CONCLUSION: Our CNN used multimodal retinal images to successfully predict diagnosis of symptomatic AD in an independent test set. GC-IPL maps were the most useful single inputs for prediction. Models including only images performed similarly to models also including quantitative data and patient data.

Identifying Peripapillary Radial Capillary Plexus Alterations in Parkinson's Disease Using OCT Angiography.

PURPOSE: To compare radial peripapillary capillary (RPC) plexus vascular parameters and retinal nerve fiber layer (RNFL) thickness between those with Parkinson's disease (PD) and controls. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: A total of 151 eyes of 81 PD participants and 514 eyes of 266 controls. METHODS: Participants underwent OCT angiography (OCTA) imaging using the Zeiss Cirrus HD-5000 AngioPlex (Carl Zeiss AG). Capillary perfusion density (CPD) and capillary flux index (CFI) were assessed using a 4.5 × 4.5-mm peripapillary scan, and RNFL thickness was assessed using a 200 × 200-µm optic nerve cube OCT scan. Hoehn and Yahr clinical staging for PD was determined by an experienced movement disorders specialist. Generalized estimating equations adjusted for age and sex were used for analysis. MAIN OUTCOME MEASURES: Differences in RNFL thickness, CPD, and CFI as assessed using multivariable generalized estimating equations between individuals with PD and controls. RESULTS: After adjustment for age and sex, average CPD (0.446% ± 0.018% vs. 0.439% ± 0.017%, P < 0.001) and CFI (0.434 ± 0.031 vs. 0.426 ± 0.036, P = 0.008) were significantly higher in PD eyes. Average RNFL thickness was similar between groups (PD 89.71 ± 10.45 µm vs. control 88.20 ± 10.33 µm, P = 0.19). Significant correlations between Hoehn and Yahr stage and OCTA parameters were not observed. The OCTA parameters were not significantly different between eyes of the same patient. CONCLUSIONS: Increased peripapillary microvascular density and flux were detected in a large cohort of individuals with PD compared with controls after adjusting for age and sex; however, RNFL thickness was similar between groups. Peripapillary OCTA parameters may not correlate with the severity of PD. OCTA may serve as a noninvasive method to identify novel biomarkers for the early diagnosis of PD; as such, this methodology deserves further investigation.

Assessing the Retinal Microvasculature in Individuals With Early and Late-Onset Alzheimer's Disease.

BACKGROUND AND OBJECTIVE: To evaluate retinal microvascular changes in early and late-onset Alzheimer's disease (AD). PATIENTS AND METHODS: Eighty-six eyes of 50 late-onset AD participants, 27 eyes of 15 early onset AD participants, and 111 eyes of 57 cognitively normal controls were included. Optical coherence tomography angiography (OCTA) vessel density (VD) and perfusion density (PD) in Early Treatment Diabetic Retinopathy Study 3-mm and 6-mm circles and rings were assessed. RESULTS: There was decreased PD in early onset AD 3-mm circle (P = .026) and ring (P = .026) versus controls as well as in late-onset AD 3-mm circle (P = .023) and ring (P = .023) versus controls. There was decreased VD in late-onset AD 3-mm circle (P = .012) and ring (P = .006). No parameters differed between early and late-onset AD (P > .05). CONCLUSIONS: AD eyes exhibited decreased retinal microvascular density compared to controls. Retinal parameters may not differ between early onset AD and late-onset AD after adjusting for age. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:336-344.].

Characterization of Retinal Microvascular and Choroidal Structural Changes in Parkinson Disease.

Importance: Noninvasive retinal imaging may detect structural changes associated with Parkinson disease (PD) and may represent a novel biomarker for disease detection. Objective: To characterize alterations in the structure and microvasculature of the retina and choroid in eyes of individuals with PD and compare them with eyes of age- and sex-matched cognitively healthy control individuals using optical coherence tomography (OCT) and OCT angiography (OCTA). Design, Setting, and Participants: This cross-sectional study was conducted at the Duke Neurological Disorders Clinic in Durham, North Carolina. Individuals aged 50 years or older with a diagnosis of PD were eligible for inclusion and underwent an evaluation and diagnosis confirmation before enrollment. Control individuals aged 50 years or older and without subjective cognitive dysfunction, a history of tremor, or evidence of motor dysfunction consistent with parkinsonism were solicited from the clinic or the Duke Alzheimer's Disease Prevention Registry. Individuals with diabetes, glaucoma, retinal pathology, other dementias, and corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity worse than 20/40 Snellen were excluded. Data were analyzed between January 1, 2020, and March 30, 2020. Exposures: All participants underwent OCT and OCTA imaging. Main Outcomes and Measures: Generalized estimating equation analysis was used to characterize the association between imaging parameters and PD diagnosis. Superficial capillary plexus vessel density (VD) and perfusion density (PFD) were assessed within the ETDRS 6 × 6-mm circle, 6 × 6-mm inner ring, and 6 × 6-mm outer ring, as was the foveal avascular zone area. Peripapillary retinal nerve fiber layer thickness, macular ganglion cell-inner plexiform layer thickness, central subfield thickness, subfoveal choroidal thickness, total choroidal area, luminal area, and choroidal vascularity index (CVI) were measured. Results: A total of 124 eyes of 69 participants with PD (39 men [56.5%]; mean [SD] age, 71.7 [7.0] years) and 248 eyes of 137 control participants (77 men [56.2%]; mean [SD] age, 70.9 [6.7] years) were analyzed. In the 6 × 6-mm ETDRS circle, VD (ß coefficient = 0.37; 95% CI, 0.04-0.71; P = .03) and PFD (ß coefficient = 0.009; 95% CI, 0.0003-0.018; P = .04) were lower in eyes of participants with PD. In the inner ring of the 6 × 6-mm ETDRS circle, VD (ß coefficient = 0.61; 95% CI, 0.20-1.02; P = .003) and PFD (ß coefficient = 0.015; 95% CI, 0.005-0.026; P = .004) were lower in eyes of participants with PD. Total choroidal area (ß coefficient = -1.74 units2; 95% CI, -3.12 to -0.37 units2; P = .01) and luminal area (ß coefficient = -1.02 units2; 95% CI, -1.86 to -0.18 units2; P = .02) were greater, but CVI was lower (ß coefficient = 0.5%; 95% CI, 0.2%-0.8%; P < .001) in eyes of individuals with PD. Conclusions and Relevance: This study found that individuals with PD had decreased retinal VD and PFD as well as choroidal structural changes compared with age- and sex-matched control participants. Given the observed population differences in these noninvasive retinal biomarkers, further research into their clinical utility in PD is needed.

Choroidal Structural Analysis in Alzheimer Disease, Mild Cognitive Impairment, and Cognitively Healthy Controls.

PURPOSE: To assess choroidal structural parameters in symptomatic Alzheimer disease (AD), mild cognitive impairment (MCI), and cognitively healthy control subjects. DESIGN: Prospective cross-sectional study. METHODS: This study took place in an outpatient neurological disorders clinic. Participants included 67 patients (112 eyes) with AD, 74 patients (143 eyes) with MCI, and 137 (248 eyes) control subjects. Subjects with diabetes, glaucoma, or retinal pathology were excluded. High-definition enhanced depth imaging foveal scans were obtained using Zeiss Cirrus HD-5000 AngioPlex. Subfoveal choroidal thickness (SFCT) was measured by 2 masked graders with a third adjudicator. Total choroidal area (TCA), luminal area (LA), and the choroidal vascularity index (CVI) were calculated after image binarization. Association of choroidal parameters with AD, MCI, or control subjects was assessed using multivariable generalized estimating equations, adjusted for age, sex, and visual acuity. RESULTS: After adjustment for age, sex, and visual acuity, TCA was significantly greater in patients with AD (ß = 2.73; p = .001) and MCI (ß = 4.38; p < .001) compared with control subjects. LA was significantly greater in patients with AD (ß = 1.68; p = .001) and MCI (ß = 2.69; p < .001) compared with control subjects, and CVI was significantly lower in patients with MCI (ß = -0.58; p = .002) compared with control subjects. SFCT was similar among patients with AD and MCI and control subjects on multivariable analysis (p > .05). CONCLUSIONS: TCA, LA, and CVI may differ between patients with AD, MCI, and healthy cognition, whereas SFCT may not differ among these groups. TCA, LA, and CVI deserve further study in subjects on the Alzheimer continuum.