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.

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.

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.

Artificial intelligence in dementia.

PURPOSE OF REVIEW: Artificial intelligence tools are being rapidly integrated into clinical environments and may soon be incorporated into dementia diagnostic paradigms. A comprehensive review of emerging trends will allow physicians and other healthcare providers to better anticipate and understand these powerful tools. RECENT FINDINGS: Machine learning models that utilize cerebral biomarkers are demonstrably effective for dementia identification and prediction; however, cerebral biomarkers are relatively expensive and not widely available. As eye images harbor several ophthalmic biomarkers that mirror the state of the brain and can be clinically observed with routine imaging, eye-based machine learning models are an emerging area, with efficacy comparable with cerebral-based machine learning models. Emerging machine learning architectures like recurrent, convolutional, and partially pretrained neural networks have proven to be promising frontiers for feature extraction and classification with ocular biomarkers. SUMMARY: Machine learning models that can accurately distinguish those with symptomatic Alzheimer's dementia from those with mild cognitive impairment and normal cognition as well as predict progressive disease using relatively inexpensive and accessible ocular imaging inputs are impactful tools for the diagnosis and risk stratification of Alzheimer's dementia continuum. If these machine learning models can be incorporated into clinical care, they may simplify diagnostic efforts. Recent advancements in ocular-based machine learning efforts are promising steps forward.

CLINICAL CHARACTERISTICS AND VISUAL OUTCOMES IN ENDOPHTHALMITIS AFTER KERATOPROSTHESIS IMPLANTATION.

PURPOSE: To describe the presentation, microbiology, management, and prognosis of eyes with endophthalmitis after Boston keratoprosthesis implantation. METHODS: Retrospective case series with history, diagnostics, management, and outcomes data in endophthalmitis after keratoprosthesis implantation presenting to a tertiary center between 2009 and 2020. RESULTS: Of 137 keratoprosthesis-implanted eyes, 7 eyes of 7 patients (5%) developed endophthalmitis. On presentation, 6 (86%) reported decreased visual acuity, and only 1 (14%) reported pain. Peripheral corneal ulcers were present in 2 eyes (29%). Seidel testing was negative in all cases. Six eyes (86%) had retroprosthetic membranes. One (14%) underwent initial pars plana vitrectomy with mechanical vitreous biopsy, whereas 6 (86%) received a needle vitreous tap-half of which were dry. Organisms were isolated after vitreous tap in two eyes: Streptococcus intermedius and Mycobacterium abscessus. The mean visual acuity preendophthalmitis, at presentation, and at 6 months were 20/267, 20/5,944, and 20/734, respectively. The visual acuity improved 9.08 ± 11.78 Early Treatment Diabetic Retinopathy Study lines from presentation to 6 months. Six-month visual acuity was correlated with preendophthalmitis visual acuity (r = 0.92, P = 0.003) but not presenting visual acuity (P = 0.838). CONCLUSION: Visual acuity at 6 months is correlated with preendophthalmitis visual acuity, not presenting visual acuity. Endophthalmitis should be considered in the differential diagnosis of painless intraocular inflammation any time after keratoprosthesis implantation, even if Seidel negative.

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.

USE OF THE ISCHEMIC INDEX ON WIDEFIELD FLUORESCEIN ANGIOGRAPHY TO CHARACTERIZE A CENTRAL RETINAL VEIN OCCLUSION AS ISCHEMIC OR NONISCHEMIC.

PURPOSE: To understand the relationship between baseline ischemic index (IsI) values on ultra-widefield fluorescein angiography and classification as ischemic central retinal vein occlusion (CRVO). METHODS: Single-center retrospective cohort study of CRVO patients imaged using ultra-widefield fluorescein angiography from which IsI values were calculated. An ischemic CRVO was defined as those eyes with an afferent pupillary defect and counting fingers acuity or worse or neovascularization during the first year of follow-up. Logistic regression was performed to characterize the relation between the IsI and clinical outcomes. RESULTS: Sixty eyes of 60 treatment-naive CRVO patients with baseline ultra-widefield fluorescein angiography and ≥1 year of follow-up were identified. Those with an IsI ≥35% were significantly more likely to have an ischemic CRVO during the first year of follow-up than those with an IsI <35% (83.3 vs. 13.9%, odds ratio 111, P < 0.0001). Baseline and final logarithm of the minimum angle of resolution acuity were worse in eyes with an IsI ≥35% (1.18 vs. 0.46, P < 0.001 and 1.26 vs. 0.45, P < 0.001, respectively) despite similar baseline and final central subfield thickness (P = 0.1-0.23). CONCLUSION: A baseline IsI of ≥35% on ultra-widefield fluorescein angiography in eyes with treatment-naive CRVO was sensitive (90%) and specific (92.5%) for classification as an ischemic CRVO during the first year of follow-up.

CENTRAL RETINAL VEIN OCCLUSION IN YOUNG INDIVIDUALS: A Comparison of Risk Factors and Clinical Outcomes.

PURPOSE: To compare the presentation and outcomes of patients younger than 50 years versus patients aged 50 years and older with central retinal vein occlusion (CRVO). METHODS: This single-center retrospective study included patients with CRVO presenting between January 2009 and July 2016. Charts were reviewed and data were abstracted. Presenting and final clinical parameters, treatment burden, and predisposing factors for CRVO were compared between the two groups. RESULTS: Thirty-six patients younger than 50 years and 233 patients aged 50 years and older at the time of CRVO onset were included. At presentation, younger patients had better visual acuity than older patients (20/80 vs. 20/224, P = 0.001) and a lower incidence of cystoid macular edema (54 vs. 79%, P = 0.001). Twenty-one of 36 (58%) younger patients had at least one identifiable nontraditional risk factor for CRVO. At final follow-up, younger patients received fewer total intravitreal injections (3.8 ± 5.8 at 34.2 months) compared with older patients (6.5 ± 8.8, at 37.6 months, P = 0.03) and had better final acuity (20/85 vs. 20/289, P = 0.004, respectively). CONCLUSION: Younger patients had better baseline and final acuities, a lower incidence of cystoid macular edema at presentation, and received fewer intravitreal injections than older patients. Workup for etiology of CRVO in younger patients may reveal nontraditional risk factors for CRVO.

AMBULATORY BLOOD PRESSURE PATTERNS IN PATIENTS WITH RETINAL VEIN OCCLUSION.

PURPOSE: Failure of blood pressure (BP) to dip during sleep (nondipper pattern) is associated with cardiovascular disease and stroke. The prevalence and degree of nondipping and masked hypertension in patients with retinal vein occlusion (RVO), which is associated with stroke, has not been previously examined. METHODS: We measured clinic and 24-hour ambulatory BPs in 22 patients with RVO and 20 control participants without known eye disease matched by age and sex. Mean BP dipping, defined as the ratio of difference in mean awake and sleep systolic BPs to mean awake systolic BP, and masked and nocturnal hypertension were compared between groups. RESULTS: Mean 24-hour ambulatory BP was 144/79 mmHg among those with RVO and 136/77 mmHg among controls. Patients with RVO had an almost 2-fold higher prevalence of nondipping pattern (80.8% [95% confidence interval, 52.8-94.1] vs. 50.4% [95% confidence interval, 26.1-74.5]; P = 0.008). Average sleep systolic BP dip in patients with RVO was 6.1% versus 11.9% in controls (P = 0.004). More patients with RVO had masked hypertension by ambulatory BPs than controls (71% vs. 50%), but this difference was not statistically significant. CONCLUSION: Our data suggest an association between RVO and nondipper BP pattern. Ambulatory BP monitoring may be useful in the evaluation of patients with RVO by identifying those who may benefit from more aggressive BP control.

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.

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 aqueous concentrations, plasma concentrations, and 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.

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.

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.

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.].

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.

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.

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.

Preclinical evaluation and intraoperative human retinal imaging with a high-resolution microscope-integrated spectral domain optical coherence tomography device.

PURPOSE: The authors have recently developed a high-resolution microscope-integrated spectral domain optical coherence tomography (MIOCT) device designed to enable OCT acquisition simultaneous with surgical maneuvers. The purpose of this report is to describe translation of this device from preclinical testing into human intraoperative imaging. METHODS: Before human imaging, surgical conditions were fully simulated for extensive preclinical MIOCT evaluation in a custom model eye system. Microscope-integrated spectral domain OCT images were then acquired in normal human volunteers and during vitreoretinal surgery in patients who consented to participate in a prospective institutional review board-approved study. Microscope-integrated spectral domain OCT images were obtained before and at pauses in surgical maneuvers and were compared based on predetermined diagnostic criteria to images obtained with a high-resolution spectral domain research handheld OCT system (HHOCT; Bioptigen, Inc) at the same time point. Cohorts of five consecutive patients were imaged. Successful end points were predefined, including ≥80% correlation in identification of pathology between MIOCT and HHOCT in ≥80% of the patients. RESULTS: Microscope-integrated spectral domain OCT was favorably evaluated by study surgeons and scrub nurses, all of whom responded that they would consider participating in human intraoperative imaging trials. The preclinical evaluation identified significant improvements that were made before MIOCT use during human surgery. The MIOCT transition into clinical human research was smooth. Microscope-integrated spectral domain OCT imaging in normal human volunteers demonstrated high resolution comparable to tabletop scanners. In the operating room, after an initial learning curve, surgeons successfully acquired human macular MIOCT images before and after surgical maneuvers. Microscope-integrated spectral domain OCT imaging confirmed preoperative diagnoses, such as full-thickness macular hole and vitreomacular traction, and demonstrated postsurgical changes in retinal morphology. Two cohorts of five patients were imaged. In the second cohort, the predefined end points were exceeded with ≥80% correlation between microscope-mounted OCT and HHOCT imaging in 100% of the patients. CONCLUSION: This report describes high-resolution MIOCT imaging using the prototype device in human eyes during vitreoretinal surgery, with successful achievement of predefined end points for imaging. Further refinements and investigations will be directed toward fully integrating MIOCT with vitreoretinal and other ocular surgery to image surgical maneuvers in real time.