Browsing by Author "Grewal, Dilraj S"
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Item Open Access Choroidal Structural Analysis in Alzheimer's Disease, Mild Cognitive Impairment, and Cognitively Healthy Controls.(Am J Ophthalmol, 2020-10-08) Robbins, Cason B; Grewal, Dilraj S; Thompson, Atalie C; Powers, James H; Soundararajan, Srinath; Koo, Hui Yan; Yoon, Stephen P; Polascik, Bryce W; Liu, Andy; Agrawal, Rupesh; Fekrat, SharonPURPOSE: To assess choroidal structural parameters in symptomatic Alzheimer's disease (AD), mild cognitive impairment (MCI), and cognitively healthy controls. DESIGN: Prospective cross-sectional study. METHODS: Setting: Outpatient neurological disorders clinic. STUDY POPULATION: One hundred and twelve eyes of 67 individuals with AD, 143 eyes of 74 individuals with MCI, and 248 eyes of 137 controls. Individuals with diabetes, glaucoma, or retinal pathology were excluded. OBSERVATION PROCEDURE: High-definition EDI foveal scans were obtained using Zeiss Cirrus HD-5000 AngioPlex (Carl Zeiss Meditec, Dublin, CA). Subfoveal choroidal thickness (SFCT) was measured by two masked graders with a third adjudicator. Total choroidal area (TCA), luminal area (LA), and choroidal vascularity index (CVI) were calculated after image binarization. MAIN OUTCOME MEASURES: Association of choroidal parameters with AD, MCI, or controls using generalized estimating equations, adjusted for age and sex. RESULTS: After adjustment for age, sex, and visual acuity, TCA was significantly greater in AD (ß 2.73, p = 0.001) and MCI (ß 4.38, p < 0.001) compared to controls, LA was significantly greater in AD (ß 1.68, p = 0.001) and MCI (ß 2.69, p < 0.001) compared to controls, and CVI was significantly lower in MCI (ß -0.58, p = 0.002) compared to controls. SFCT was similar among AD, MCI, and controls on multivariable analysis (p > 0.05). CONCLUSIONS: TCA, LA, and CVI may differ between individuals with AD, MCI, and healthy cognition, whereas SFCT may not differ between these groups. TCA, LA, and CVI deserve further study in individuals along the Alzheimer's continuum.Item Open Access Convolutional neural network to identify symptomatic Alzheimer's disease using multimodal retinal imaging.(The British journal of ophthalmology, 2020-11-26) Wisely, C Ellis; Wang, Dong; Henao, Ricardo; Grewal, Dilraj S; Thompson, Atalie C; Robbins, Cason B; Yoon, Stephen P; Soundararajan, Srinath; Polascik, Bryce W; Burke, James R; Liu, Andy; Carin, Lawrence; Fekrat, SharonBACKGROUND/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.Item Open Access Intrasession Repeatability of OCT Angiography Parameters in Neurodegenerative Disease.(Ophthalmology science, 2023-06) Akrobetu, Dennis Y; Robbins, Cason B; Ma, Justin P; Soundararajan, Srinath; Quist, Michael S; Stinnett, Sandra S; Moore, Kathryn PL; Johnson, Kim G; Liu, Andy J; Grewal, Dilraj S; Fekrat, SharonPurpose
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.Item Open Access Repeatability of Peripapillary OCT Angiography in Neurodegenerative Disease.(Ophthalmology science, 2021-12) Ma, Justin P; Robbins, Cason B; Stinnett, Sandra S; Johnson, Kim G; Scott, Burton L; Grewal, Dilraj S; Fekrat, SharonPurpose
To assess the repeatability of peripapillary OCT angiography (OCTA) in those with Alzheimer disease (AD), mild cognitive impairment (MCI), Parkinson disease (PD), or normal cognition.Design
Cross-sectional.Participants
Patients with a clinical diagnosis of AD, MCI, PD, or normal cognition were imaged. Those with glaucoma, diabetes mellitus, vitreoretinal pathology, and poor-quality images were excluded.Methods
Each eligible eye of each participant underwent 2 OCTA 4.5 × 4.5-mm peripapillary scans in a single session using a Zeiss Cirrus HD-OCT 5000 with AngioPlex (Carl Zeiss Meditec). The Zeiss software (v11.0.0.29946) quantified measures of perfusion in the radial peripapillary capillary (RPC) plexus in 4 sectors (superior, nasal, inferior, temporal). The average of these sectors was calculated and reported.Main outcome measures
Radial peripapillary capillary plexus perfusion was quantified using 2 parameters: capillary perfusion density (CPD) and capillary flux index (CFI). Intraclass correlation coefficients (ICCs) were used to quantify repeatability. For subjects who had both eyes included, the average values of each scan pair were used to assess interocular symmetry of CPD and CFI.Results
Of 374 eyes, 46 were from participants who had AD, 85 were from participants who had MCI, 87 were from participants who had PD, and 156 were from participants who had normal cognition. Capillary perfusion density ICC in AD = 0.88 (95% confidence interval [CI], 0.79-0.93), MCI = 0.95 (0.92-0.96), PD = 0.91 (0.87-0.94), and controls = 0.90 (0.87-0.93). Capillary flux index ICC in AD = 0.82 (0.70-0.90), MCI = 0.87 (0.80-0.91), PD = 0.91 (0.87-0.94) and controls = 0.85 (0.79-0.89). There were no significant differences in interocular variation in average CPD and CFI in AD, MCI, or PD (all P > 0.05). Isolated interocular sectoral CPD differences were noted in AD (nasal, P = 0.049; temporal, P = 0.024), PD (nasal, P = 0.036), and controls (nasal, P = 0.016). Interocular differences in CFI in the superior sector in MCI (P = 0.028) and in average CFI for controls (P = 0.035) were observed.Conclusions
Peripapillary OCTA repeatability in AD, MCI, and PD is good-excellent and similar to those with normal cognition. Insignificant interocular asymmetry in peripapillary OCTA suggests neurodegeneration may proceed uniformly; future studies may reveal the appropriateness of single-eye imaging.Item Open Access Retinal and Choroidal Changes in Men Compared with Women with Alzheimer's Disease: A Case-Control Study.(Ophthalmology science, 2022-03) Mirzania, Delaram; Thompson, Atalie C; Robbins, Cason B; Soundararajan, Srinath; Lee, Jia Min; Agrawal, Rupesh; Liu, Andy J; Johnson, Kim G; Grewal, Dilraj S; Fekrat, SharonPurpose
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.Item Open Access Use of Letermovir as Salvage Therapy for Drug-resistant CMV Retinitis: A Case Series(Antimicrobial Agents and Chemotherapy) Turner, Nicholas; Strand, Andrew; Grewal, Dilraj S; Cox, Gary; Arif, Sana; Baker, Arthur W; Maziarz, Eileen K; Saullo, Jennifer H; Wolfe, Cameron RTreatment options for drug-resistant CMV are limited. Letermovir is a novel antiviral recently approved for CMV prophylaxis following hematopoietic cell transplantation, but efficacy in other settings is unknown. We recently used letermovir for salvage treatment in four solid organ transplant recipients with ganciclovir-resistant CMV retinitis. All patients improved clinically without known adverse drug events. However, three patients failed to maintain virologic suppression, including two patients who developed genotypically-confirmed resistance to letermovir while on therapy.