Efficacy of moxidectin, using various dose regimens, against JYD-34, a macrocyclic lactone resistant isolate of Dirofilaria immitis.

BACKGROUND: Macrocyclic lactones (MLs) are the only class of drugs currently commercially available that are effective for preventing heartworm disease. The data presented in this article provide information on the efficacy of oral moxidectin against JYD-34, a known ML-resistant Dirofilaria immitis isolate, when dogs are treated under various dosing regimens. METHODS: Fifty-two purpose-bred Beagle dogs were used in five laboratory studies. All dogs were inoculated with 50 D. immitis third-stage larvae (L3) (JYD-34 isolate) 30 days prior to the first treatment. Dogs were randomized to treatment (four to five animals in each group) with one, three, or five monthly doses of oral moxidectin ranging from 6 to 100 µg/kg body weight. In each study, control dogs were not treated. Five to 6 months after L3 inoculation, dogs were euthanized, and adult worms were counted to evaluate efficacy of the dosing regimens. RESULTS: Adult heartworms were recovered from all control dogs, with an overall geometric mean of 29.7 worms (range 15.2 to 38.0, individual counts ranged from 8 to 51). Five monthly doses of 6 µg/kg provided 83.3% and 90.2%, efficacy, and the same number of monthly doses of 9 µg/kg demonstrated 98.8% and 94.1% efficacy. Three monthly doses of 30 and 50 µg/kg demonstrated 97.9% and 99.0% efficacy, respectively, while a single dose of 100 µg/kg demonstrated 91.1% efficacy. CONCLUSIONS: Five monthly doses of 9 µg/kg provided similar or only marginally lower efficacy against JYD-34, a known ML-resistant isolate, compared to substantially higher doses administered for 3 months. This underscores the importance of duration of exposure to moxidectin when facing ML-resistant isolates. Repeated administration of lower doses of moxidectin are an alternative to higher doses in the prevention of heartworm disease associated with less susceptible or resistant isolates.

Safety of an oral combination of moxidectin, afoxolaner, and pyrantel pamoate in dogs.

NexGard®PLUS (moxidectin, afoxolaner, and pyrantel pamoate), is an oral combination product for dogs indicated for the prevention of heartworm disease, the treatment and prevention of flea and tick infestations, and the treatment of gastro-intestinal nematode infections. The safety of this product in dogs was evaluated in three studies. Study #1 was a margin-of-safety study conducted in puppies, dosed six times at 28-day intervals at 1X, 3X, or 5X multiples of the maximum exposure dose (equivalent to 24 µg/kg moxidectin, 5 mg/kg afoxolaner, and 10 mg/kg pyrantel). In Study #2, the product was administered to ABCB1-deficient collie dogs at a 1X dose twice at a 28-day interval, and at a 3X or 5X dose once. Study #3 evaluated the safety of the product at 1X and 3X doses administered three times at 4-week intervals, to dogs harboring adult Dirofilaria immitis. In the three studies, the safety was evaluated on the basis of multiple clinical observations and physical examinations, including a complete assessment of toxicity to macrocyclic lactones, and on comprehensive clinical and anatomical pathology evaluations in Study #1. No clinically significant combination product-related effects were observed in any of the three studies. No signs of macrocyclic lactone toxicity were observed in the ABCB1-deficient collie dogs. Some mild and self-resolving instances of emesis or diarrhea were occasionally observed in the 3X and 5X dosed dogs. NexGard® PLUS was demonstrated to be safe following multiple administrations in puppies, in ABCB1-deficient collie dogs, and in microfilaremic dogs infected with adult D. immitis.

Efficacy of an oral combination of moxidectin, afoxolaner, and pyrantel pamoate for the prevention of heartworm disease in dogs.

Dirofilaria immitis, the mosquito-borne agent of dirofilariosis, a chronic and sometimes fatal cardiopulmonary canine disease, is endemic in most warm and temperate regions in the world. The efficacy of an oral endectoparasiticide product (test product or TP) combining moxidectin, afoxolaner, and pyrantel pamoate was evaluated for the prevention of heartworm disease in dogs, in two laboratory and one field studies. In each laboratory study, 20 D. immitis-naïve beagle dogs were experimentally infected with D. immitis. Ten control dogs were sham-treated, and ten dogs were administered the TP targeting the minimum effective dose, six times monthly and starting 30 days post infection. At necropsy seven months after inoculations, no heartworms were found in any of the TP treated dog, whereas 19 to 42 live heartworms were found in the control dogs. In each study, treatment efficacy was 100% and the difference between treated and untreated groups was highly significant (p < 0.0001). A field study was conducted through the full transmission season in several heartworm-endemic regions of the United States. One hundred and twenty client-owned dogs that were negative for D. immitis at enrollment were administered twelve monthly oral doses of the TP at label dose. Blood tests for D. immitis antigen and modified Knott's tests for microfilariae remained negative through the full duration of the study, demonstrating that all dogs were protected from heartworm infection during the full transmission season. These studies demonstrated that TP administered monthly for at least six doses is effective at preventing dirofilariosis.

Differentially Expressed Tear Proteins in Sjögren's Syndrome Keratoconjunctivitis Sicca.

Purpose: The purpose of this study was to determine if there are significant differences in the concentrations of tear proteins in Sjögren's syndrome keratoconjunctivitis sicca (SS KCS) compared to healthy controls. Methods: Tear samples were collected with unmarked Schirmer strips from 15 patients with SS KCS and 21 healthy controls. Tear protein was eluted and the concentration measured. Inflammatory mediators were assayed with a Raybiotech L-507 glass slide array and normalized by strip wetting length. All patients underwent an ocular surface exam to evaluate tear break-up time (TBUT), corneal fluorescein (CF) staining, and conjunctival (CJ) staining. The symptom assessment questionnaire in dry eye (SANDE) scores were collected for all patients. Results: Two hundred fifty-three of the 507 tear proteins analyzed were significantly different in patients with SS compared to controls. Two hundred forty-one if the proteins were upregulated and 12 were downregulated. One hundred eighty-one differentially expressed proteins were significantly correlated with all four clinical parameters: TBUT, CF staining, CJ staining, and SANDE score. Conclusions: These findings indicate that hundreds of factors can be assayed in tear proteins collected from a Schirmer strip. The results suggest tear protein concentrations are altered in patients with SS KCS compared to controls. The upregulated tear proteins correlated with clinical measures of dry eye symptoms and disease severity. Translational Relevance: Tear proteins could serve as important biomarkers for studying pathogenesis and in clinical diagnosis and management of SS KCS.

Trends in Residency Academic Productivity of Ophthalmic Plastic and Reconstructive Surgery Fellows Between 2012 and 2019.

PURPOSE: To characterize research productivity of ophthalmic plastic and reconstructive surgery (OPRS) fellows during residency. METHODS: A database was compiled of OPRS fellows listed on the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) Annual Fall Scientific Symposium program books who began their fellowship between 2012 and 2019. PubMed was searched for all publications published between July 1st of the year they began residency and September 30th of the year they began fellowship training. Bibliometric variables captured for each fellow included: the number of publications, first-author publications, and ophthalmology-related publications. RESULTS: A total of 197 OPRS fellows who began their fellowship training between 2012 and 2019 published a mean (± SD) of 2.42 ± 2.80 publications, 1.43 ± 1.85 first-author publications, and 2.33 ± 2.74 ophthalmology-related publications during residency. Linear regression revealed that the number of publications ( P < 0.001), first-author publications ( P < 0.001), and ophthalmology-related publications ( P < 0.001) that OPRS fellows published during residency have all significantly increased over the time assessed. CONCLUSIONS: The academic productivity of OPRS fellows during residency was quantified through bibliometric analysis to establish a national benchmark for the benefit of both prospective applicants and program directors. Residency research output of OPRS fellows has significantly increased between 2012 and 2019. Since ASOPRS program requirements necessitate academic productivity and thesis completion, publication records and involvement in research become valuable considerations when evaluating fellowship applicants. The knowledge of what accepted fellows have published provides the opportunity to make historical comparisons and may prove useful in the evaluation of the competitiveness of a given year's applicant pool.

Efficacy of eprinomectin topical solution and eprinomectin extended-release injection treatments against developing larval and adult Chabertia ovina and Oesophagostomum venulosum - two less common cattle nematode parasites.

The efficacy of the topical and injection formulations of eprinomectin (0.5 % w/v topical solution, EPRINEX®; 5 % w/v extended-release injection, LONGRANGE®; Boehringer Ingelheim) against larval and adult stages of the rare bovine large intestine nematodes Chabertia ovina and Oesophagostomum venulosum was evaluated in one Good Clinical Practice study compliant to World Association for the Advancement of Veterinary Parasitology and International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products anthelmintic guidelines. Forty nematode naïve induced infected Brown Swiss calves were allocated into five groups of eight completely at random. Inoculation with isolates obtained in Germany was staggered so that the parasites of the two species were, when the treatments were administered, concurrently fourth-stage larval or adult nematodes, respectively. One group served as untreated control, two groups each received eprinomectin 0.5 % w/v topical solution or eprinomectin 5 % w/v extended-release injection per product label. Animals were necropsied at one and the same day (corresponding to six weeks or two weeks after administration of treatments against fourth-stage larval or adult nematodes) for parasite recovery and count. Both C. ovina (range, 39-604) and O. venulosum (range, 3-23) were recovered from all eight controls while among the 32 calves which were administered topical solution or extended-release injection eprinomectin, only a single C. ovina specimen was isolated from one animal which received the injection product when the nematodes were adult. Eprinomectin treatments were > 99.9 % effective against fourth-stage larval or adult C. ovina and O. venulosum nematodes (p 0.001 at α = 0.05). All animals accepted the treatments well. No adverse events or other health problems were observed in the study animals.

Eprinomectin 5% w/v extended-release injection for the treatment of larval and/or adult Bunostomum phlebotomum, Haemonchus contortus, H. placei, Nematodirus helvetianus, Oesophagostomum radiatum, and Trichostrongylus colubriformis infections in cattle.

In an effort to generate data for regulatory purposes on the therapeutic efficacy of eprinomectin 5% w/v extended-release injection (Eprinomectin ERI) (LongRange®, Boehringer Ingelheim) against infections of immature and adult stages of some nematode species (or stages) which are generally less common or predominantly seen in younger cattle, nine studies (minimum two per parasite and stage) were conducted in the USA and Germany. A total of 218 young cattle were included in seven experimentally induced infection studies (180 animals) and two studies with naturally acquired nematode infections (38 animals), which were compliant with WAAVP and VICH guidelines. In each study, cattle were randomly assigned into groups which received 1 mL per 50 kg body weight of either saline (controls) or Eprinomectin ERI (equivalent to 1 mg eprinomectin per kg body weight) via subcutaneous injection when the parasites were developing fourth-stage larval (L4) or adult nematodes. Following necropsy and parasite recovery, percentage efficacy was calculated based on the comparison of geometric mean nematode counts of the Eprinomectin ERI- vs. the saline-treated animals. Eprinomectin ERI-treated cattle had significantly (p < 0.05) lower counts of each species and stage of nematodes than the controls. Eprinomectin ERI treatment was demonstrated to be efficacious (> 90%) against L4 and adult Bunostomum phlebotomum and Nematodirus helvetianus; against L4 Haemonchus placei, Oesophagostomum radiatum, and Trichostrongylus colubriformis; and against adult H. contortus. Percentage efficacy against L4 H. contortus was variable (69.6 to 100%). All treatments were well accepted, and no treatment-related health problems were observed in any study.

Naturally acquired ovine-adapted nematode infections in young cattle and their treatment with eprinomectin 5% w/v extended-release injection.

The objective of this controlled study was to determine the anthelmintic efficacy of eprinomectin 5% w/v extended-release injection (Eprinomectin ERI; LONGRANGE®, Boehringer Ingelheim Animal Health) against primarily ovine-adapted gastrointestinal strongylid nematode (GIN) parasites in naturally infected young cattle. Eighteen calves which grazed on a sheep-dominated mixed sheep-cattle farm were randomly allocated into two equal groups (saline [control] or Eprinomectin ERI, administered each at 1 mL/50 kg body weight once subcutaneously), treated and euthanized 14 days thereafter for a differential GIN count. Ten species of strongylid nematodes were recovered from the control calves (ovine-adapted Haemonchus contortus, Teladorsagia circumcincta, Trichostrongylus colubriformis, Cooperia curticei, Nematodirus battus, Chabertia ovina; bovine-adapted Ostertagia ostertagi, Cooperia oncophora, Nematodirus helvetianus; 'generalist' Trichostrongylus axei). Adult GIN counts ranged from 1,540 to 5,244 for the control calves and from zero to 110 for the Eprinomectin ERI-treated calves. Accepting the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products anthelmintic guidelines criteria on adequacy of infections to be demonstrated in the control animals, this study showed that Ch. ovina, C. curticei, H. contortus, N. battus, T. axei, and T. colubriformis were reduced significantly (p < 0.0001) by ≥ 98.7% in the animals treated with Eprinomectin ERI. In conclusion, Eprinomectin ERI treatment was efficacious against a range of ovine-adapted nematode parasites in naturally infected young cattle.

A Bibliometric Analysis of Ophthalmology Resident Research Productivity in the United States.

Background The extent and impact of ophthalmology resident scholarly output is not well known. The authors aim to quantify scholarly activity of ophthalmology residents during residency and assess what factors may be associated with greater research productivity of these residents. Material and Methods Ophthalmology residents who graduated in 2021 were identified from their respective program Web sites. Bibliometric data published by these residents between the beginning of their postgraduate year 2 (July 1, 2018) until 3 months after graduation (September 30, 2021) were captured through searches via PubMed, Scopus, and Google Scholar. The association of the following factors with greater research productivity numbers was analyzed: residency tier, medical school rank, sex, doctorate degree, type of medical degree, and international medical graduate status. Results We found 418 ophthalmology residents from 98 residency programs. These residents published a mean (±standard deviation [SD]) number of 2.68 ± 3.81 peer-reviewed publications, 2.39 ± 3.40 ophthalmology-related publications, and 1.18 ± 1.96 first-author publications each. The mean (±SD) Hirsch index (h-index) for this cohort was 0.79 ± 1.17. Upon multivariate analysis, we discovered significant correlations between both residency tier and medical school rank and all bibliometric variables assessed. Pairwise comparisons revealed that residents from higher tier programs had greater research productivity numbers than those from lower tier programs. Conclusion We obtained bibliometric standards for ophthalmology residents on a national scale. Residents who graduated from higher-ranked residency programs and medical schools possessed higher h-indices and published more peer-reviewed publications, ophthalmology-related articles, and first-author publications.

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.

Characteristics of Branch Retinal Vein Occlusion in African American Patients.

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.].

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.].

Repeatability of Peripapillary Optical Coherence Tomography Angiography Parameters in Older Adults.

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 ß coefficient -0.00172, P < .001; average CFI ß 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.

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.

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.

Association of OCT Angiography Parameters With Age in Cognitively Healthy Older Adults.

BACKGROUND AND OBJECTIVE: To evaluate the association of changes in retinal anatomy and microvasculature 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.].

Eyes With Acute, Treatment-Naïve CRVO and Foveal Intraretinal Hemorrhage: Characteristics and Outcomes.

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.].

Correlation of OCTA and Volumetric MRI in Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUD AND OBJECTIVE: To evaluate the relationship between retinal microvascular parameters on optical coherence tomography angiography (OCTA) and neurodegenerative changes assessed by measurement of brain volume on volumetric magnetic resonance imaging (MRI) in Alzheimer's disease (AD) and mild cognitive impairment (MCI). PATIENTS AND METHODS: Sixteen subjects with AD and MCI underwent OCTA imaging (3 mm × 3 mm and 6 mm × 6 mm scans) and volumetric brain MRI imaging with automated volumetric segmentation and quantification. Spearman's correlation (ρ) was performed between forebrain parenchyma, cortical gray matter, inferolateral ventricle (ILV), lateral ventricle (LV), and hippocampus (HP) MRI volumes and vessel density (VD), along with perfusion density (PD) for the 6-mm circle, 6-mm ring, 3-mm circle, and 3-mm ring Early Treatment Diabetic Retinopathy Study regions of the superficial capillary plexus. RESULTS: Thirty eyes of 16 patients (seven MCI and nine AD) with good-quality OCTA images were analyzed. ILV volume inversely correlated with the VD in the 6-mm circle (ρ = -0 .565, P = .028) and 3-mm ring (ρ = -0.569, P = .027) and PD in the 3-mm ring (ρ = -0.605, P = .0169). Forebrain, cortical gray matter, LV, and HP volumes did not significantly correlate with either VD or PD (P > .05). CONCLUSIONS: In this pilot investigation, the authors found a significant correlation between reduction in the superficial capillary plexus VD and PD on OCTA and expansion of the ILV in MCI and AD. This relationship between the retinal microvasculature and cerebral volumetric changes deserves further investigation. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:709-718.].