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To assess choroidal structural parameters in symptomatic Alzheimer disease (AD), mild cognitive impairment (MCI), and cognitively healthy control subjects.Prospective cross-sectional study.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.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).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.

BACKGROUND AND OBJECTIVES: To describe the presentation, management, and clinical outcomes of branch retinal vein occlusion (BRVO) in African American patients compared to patients of other racial or ethnic backgrounds. PATIENTS AND METHODS: This retrospective cohort study included eyes diagnosed with BRVO and macular edema at a tertiary referral center. Presenting features, treatment, and outcomes were compared based on racial or ethnic backgrounds. RESULTS: The study included 285 eyes: 21.8% African American, 78.2% other. African American patients were more likely to have comorbid diabetes ( P = .012), open-angle glaucoma ( P < .001), and to present with subretinal fluid ( P = .049); multivariate analysis showed race and ethnicity alone may not fully explain presenting subretinal fluid (odds ratio = 2.807; 95% CI, 0.997 to 7.903; P = .051). There was no difference in other comparisons of clinical outcomes or treatment burden, including visual acuity, duration, or treatment method. CONCLUSIONS: Despite significant differences at presentation, the management and outcomes of BRVO did not differ significantly between African American patients and patients of other racial and ethnic backgrounds. [ Ophthalmic Surg Lasers Imaging Retina. 2021;52:492–497.]

BACKGROUND AND OBJECTIVE: To compare outcomes in eyes with central retinal vein occlusion (CRVO) presenting with (group 1) or without (group 2) fovea-involving intraretinal hemorrhage (IRH). PATIENTS AND METHODS: Retrospective review of patients diagnosed with acute, treatment-naïve CRVO between January 2009 and July 2016. RESULTS: One hundred fifteen (39.8%) of 289 CRVO eyes had fovea-involving IRH. At baseline, eyes in group 1 had significantly worse visual acuity (VA) (1.2 ± 0.10 logMAR vs. 0.9 ± 0.06 logMAR; P = .001) and greater central subfield thickness (CST) (610.4 μm ± 35.9 μm vs. 435.0 μm + 21.6 μm; P < .001) than eyes in group 2. Final visual outcomes were comparable between groups (1.24 ± 0.09 logMAR vs. 1.02 ± 0.08 logMAR; P = .08). Group 1 received a significantly greater number of intravitreal anti-vascular endothelial growth factor injections during the first year (7.80 ± 0.40 vs. 5.20 ± 0.40; P = .001). CONCLUSIONS: Although treatment-naïve eyes with acute CRVO and fovea-involving IRH had worse VA and greater CST at presentation, the final VA was comparable to eyes without such a hemorrhage. Eyes with foveal IRH had a greater treatment burden in the first 12 months. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:752–759.]

BACKGROUND AND OBJECTIVE: To compare risk factors in patients with a central retinal vein occlusion (CRVO) in the first eye and a subsequent retinal vein occlusion (RVO) in the fellow eye versus those with only unilateral CRVO. PATIENTS AND METHODS: Records of patients who presented to the Duke Eye Center with unilateral CRVO were evaluated. Logistic regression models were performed to identify potential covariates of subsequent development of RVO in the fellow eye. RESULTS: Of the 287 patients with CRVO in one eye, 31 (10.8%) developed an RVO in the fellow eye during a mean ± standard deviation follow-up of 36.7 months ± 38.86 months. The conversion rate of unilateral-to-bilateral RVO was 3.4% per year. Several comorbidities were observed to be unique to 25.8% of patients with bilateral RVO. Patients who used oral pentoxifylline ( P = .008) or those who had an ischemic CRVO in the first eye ( P = .001) were less likely to develop an RVO in the fellow eye. CONCLUSION: This information may be used to develop a predictive model to assess the risk of developing bilateral RVO in patients with unilateral CRVO. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:444–449.]

Purpose:The purpose of this article is to evaluate the effect of systemic medications and glycemic control on the visual outcome and treatment burden in patients with diabetes and branch retinal vein occlusion (BRVO).Methods:A retrospective review was performed for patients with diabetes diagnosed with a BRVO at an academic eye center from 2009 to 2017. The use of select antihypertensives, antiplatelet agents, anticoagulants, and hypoglycemics was reviewed. Data on visual acuity (VA), central subfield thickness (CST), treatment course, and hemoglobin (Hb)A1c were obtained throughout follow-up.Results:A total of 121 eyes met criteria with a median follow-up duration of 19.4 months. The mean baseline logarithm of the minimum angle of resolution (logMAR) VA was 0.56 (Snellen equivalent, 20/72) and mean final logMAR VA was 0.5 (20/63). At final follow-up, aspirin 325 mg was associated with 4.8 fewer injections (n = 13, P = .04), insulin was associated with 3.6 more injections (n = 26, P = .04), warfarin was associated with a 79 µm increase in CST ( P = .02), and a 1% increase in HbA1c was associated with 0.86 more injections ( P < .01).Conclusions:The VA outcome of BRVO in diabetics may be worse than that of BRVO in nondiabetics. Worse diabetic control was associated with a higher treatment burden. High-dose aspirin was associated with fewer injections.

BACKGROUND AND OBJECTIVE: To assess the impact of the disorganization of retinal inner layers (DRIL) on visual acuity (VA) and its correlation with ischemic index (IsI) on ultra-widefield fluorescein angiography (UWFFA) in eyes with acute, treatment-naïve branch retinal vein occlusion (BRVO). PATIENTS AND METHODS: Retrospective, longitudinal study of BRVO eyes with 1 year of follow-up or more. Area of intraretinal cysts, DRIL length, extent of disruption of external limiting membrane (ELM), and ellipsoid zone (EZ) were graded on the central 1,000 μm of foveal optical coherence tomography (OCT) scan. Baseline IsI was calculated on UWFFA. RESULTS: Thirty eyes of 30 patients with a mean follow-up of 25.4 months ± 11.0 months were evaluated. At baseline, 50% had DRIL (mean 443.1 μm ± 460.4 μm). DRIL length at baseline was predictive of worse VA at 12 months ( P = .029), and DRIL length at 12 months was predictive of worse final VA( P = .011). In multivariate analyses, DRIL length was associated with final VA ( P = .008) after controlling for other OCT parameters. There was no association between baseline IsI on UWFFA and DRIL. CONCLUSIONS: DRIL served as an independent OCT biomarker predictive of worse VA during a period of 2 years in acute, treatment-naïve BRVO. Development of DRIL was influenced by presence of CME, intraretinal cyst area, and extent of ELM and EZ disruption, but not by severity of baseline IsI. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:354–364.]

Purpose Evaluate and compare the retinal microvasculature in the superficial capillary plexus (SCP) in Alzheimer’s disease (AD), mild cognitive impairment (MCI), and cognitively intact controls using OCT angiography. OCT parameters were also compared. Design Cross-sectional study. Participants Seventy eyes from 39 AD participants, 72 eyes from 37 MCI participants, and 254 eyes from 133 control participants were enrolled. Methods Participants were imaged using Zeiss Cirrus HD-5000 with AngioPlex (Carl Zeiss Meditec, Dublin, CA) and underwent cognitive evaluation with Mini-Mental State Examination. Main Outcome Measures Vessel density (VD) and perfusion density (PD) in the SCP within the Early Treatment Diabetic Retinopathy Study 6-mm circle, 3-mm circle, and 3-mm ring were compared between groups. Foveal avascular zone (FAZ) area, central subfield thickness (CST), macular ganglion cell-inner plexiform layer (GC-IPL) thickness, and peripapillary retinal nerve fiber layer (RNFL) thickness were also compared. Results Alzheimer’s participants showed significantly decreased SCP VD and PD in the 3-mm ring (P = 0.001 and P = 0.002, respectively) and 3-mm circle (P = 0.003 and P = 0.004, respectively) and decreased SCP VD in the 6-mm circle (P = 0.047) compared with MCI and significantly decreased SCP VD and PD in the 3-mm ring (P = 0.008 and P = 0.004, respectively) and 3-mm circle (P = 0.015 and P = 0.009, respectively) and SCP PD in the 6-mm circle (P = 0.033) when compared with cognitively intact controls. There was no difference in SCP VD or PD between MCI and controls (P > 0.05). FAZ area and CST did not differ significantly between groups (P > 0.05). Alzheimer’s participants showed significantly decreased GC-IPL thickness over the inferior (P = 0.032) and inferonasal (P = 0.025) sectors compared with MCI and significantly decreased GC-IPL thickness over the entire (P = 0.012), superonasal (P = 0.041), inferior (P = 0.004), and inferonasal (P = 0.006) sectors compared to controls. MCI participants showed significantly decreased temporal RNFL thickness (P = 0.04) compared with controls. Conclusions Alzheimer’s participants showed significantly reduced macular VD, PD, and GC-IPL thickness compared with MCI and controls. Changes in the retinal microvasculature may mirror small vessel cerebrovascular changes in AD.

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.]

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 (β coefficient = 0.37; 95% CI, 0.04-0.71;P = .03) and PFD (β 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 (β coefficient = 0.61; 95% CI, 0.20-1.02;P = .003) and PFD (β coefficient = 0.015; 95% CI, 0.005-0.026;P = .004) were lower in eyes of participants with PD. Total choroidal area (β coefficient = –1.74 units2; 95% CI, −3.12 to −0.37 units2;P = .01) and luminal area (β coefficient = –1.02 units2; 95% CI, −1.86 to −0.18 units2;P = .02) were greater, but CVI was lower (β coefficient = 0.5%; 95% CI, 0.2%-0.8%;P 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.

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.Prospective, cross-sectional study.A total of 151 eyes of 81 PD participants and 514 eyes of 266 controls.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.Differences in RNFL thickness, CPD, and CFI as assessed using multivariable generalized estimating equations between individuals with PD and controls.After adjustment for age and sex, average CPD (0.446% ± 0.018% vs. 0.439% ± 0.017%, P0.001) 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.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.

Purpose: This work assesses the intrasession repeatability of capillary perfusion density (CPD) and capillary flux index (CFI) measurements on peripapillary optical coherence tomography angiography (OCTA) in healthy eyes of older adults. Methods: In this cross-sectional study, healthy volunteers aged 50 years or older underwent 4.5 × 4.5 mm OCTA imaging centered on the optic nerve head using Zeiss Cirrus HD-5000 AngioPlex (Carl Zeiss Meditec). Two consecutive images were acquired in the same eye during a single study session. CPD and CFI were assessed using AngioPlex Software (version 11.0.0.29946) for the radial peripapillary capillary plexus (average over whole scan area) and 4 quadrants (superior, inferior, temporal, and nasal). CPD and CFI repeatability was assessed by intraclass correlation (ICC), mean interocular differences using 2-tailed t test, and association with age using generalized estimating equations. Results: A total of 150 images were acquired from 75 eyes of 47 patients. For CPD, ICC results ranged from 0.7160 (nasal CPD) to 0.9218 (average CPD). For CFI, ICC results ranged from 0.6167 (temporal CFI) to 0.8976 (inferior CFI). Temporal CFI was significantly different between right and left eyes of the same patient ( P = .03). CPD and CFI decreased with age in all analyses (average CPD β coefficient –0.00172, P < .001; average CFI β coefficient −0.00278, P < .001). Conclusions: Moderate to good repeatability was observed for most peripapillary OCTA metrics; temporal measurements were least repeatable for CPD and CFI. Peripapillary CPD and CFI decrease with age even beyond the fifth decade in healthy older adults.

Background/AimsTo develop a convolutional neural network (CNN) to detect symptomatic Alzheimer’s disease (AD) using a combination of multimodal retinal images and patient data.MethodsColour 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.Results284 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).ConclusionOur 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.

BACKGROUND AND OBJECTIVE: To evaluate the association of changes in retinal anatomy and micro-vasculature with age and sex in cognitively healthy older adults. PATIENTS AND METHODS: Cross-sectional study of cognitively healthy subjects aged 50 years and older who underwent optical coherence tomography angiography (OCTA) to estimate the association between age and sex with ganglion cell layer-inner plexiform layer (GC-IPL); central subfield thickness (CST); subfoveal choroidal thickness (CT); foveal avascular zone (FAZ) size; and superficial (SCP), deep (DCP), and whole capillary plexus (WCP) vessel density (VD) and perfusion density (PD) measured in the ETDRS 3-mm and 6-mm circle and rings. RESULTS: Among 141 older adults (72.9% female; median age: 69 years), 282 eyes were imaged. Females had a greater CT, GC-IPL thickness, and FAZ size and a lower CST than males. After controlling for sex, both CT ( P = .001) and GC-IPL thickness ( P < .001) decreased with age, whereas FAZ size and CST did not. There was a reduction in VD and PD in SCP, DCP, and WCP with age in the 3-mm circle, 3-mm ring, and 6-mm circle (all P < .05). CONCLUSIONS: There is a significant reduction in both VD and PD, as well as decreased choroidal and GC-IPL thickness associated with aging, even beyond the fifth decade, in cognitively healthy adults. [ Ophthalmic Surg Lasers Imaging Retina . 2020;51:706–714.]

Purpose: To report an unusual case of bilateral recurrent full-thickness macular holes (FTMH) in both eyes of a single patient over a 15-year period, with a total of 3 FTMH in the right eye and 2 in the left eye. Each FTMH was successfully treated with vitreous surgery, resulting in hole closure and visual acuity improvement. Observations: During the previous 15 years, a 59-year-old female developed a total of 3 FTMH in the right eye and 2 FTMH in the left eye. The initial FTMH in each eye was surgically closed with pars plana vitrectomy (PPV), epiretinal membrane (ERM) peeling, 14% C3F8 gas placement, and face down positioning. Subsequent recurrences of FTMH, 2 in the right and 1 in the left, were surgically closed with PPV and ERM peeling and/or indocyanine green-assisted internal limiting membrane peeling, 14% C3F8 gas placement, and face down positioning. Seven years following the last FTMH surgical closure, the patient's best-corrected visual acuity was 20/50 in the right eye and 20/32 in the left eye with no FTMH in either eye. Conclusions and importance: This case illustrates that a rare individual may have more than one recurrent FTMH in both eyes. Final visual outcome can be favorable following closure of more than one recurrent FTMH. Keywords: Macular hole, Recurrent macular hole, Reopening macular hole, Vitrectomy, Internal limiting membrane peel, Optical coherence tomography