Browsing by Author "WuDunn, Darrell"
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Item The acute and chronic effects of intravitreal anti-vascular endothelial growth factor injections on intraocular pressure: A review(Elsevier, 2017) Bracha, Peter; Moore, Nicholas A.; Ciulla, Thomas A.; WuDunn, Darrell; Cantor, Louis B.; Department of Ophthalmology, School of MedicineThe acute and chronic effects of repeated intravitreal antivascular endothelial growth factor (VEGF) injections on intraocular pressure have not been fully characterized, and the development of sustained ocular hypertension could adversely affect patients who are at risk of glaucomatous optic neuropathy. As expected, volume-driven, acute ocular hypertension immediately follows intravitreal injection, but this pressure elevation is generally transient and well tolerated. Several medications have been investigated to limit acute ocular hypertension following anti-VEGF therapy, but the benefits of pretreatment are not conclusive. Chronic, sustained ocular hypertension, distinct from the short-term acute ocular hypertension after each injection, has also been associated with repeated intravitreal anti-VEGF injections. Risk factors for chronic ocular hypertension include the total number of injections, a greater frequency of injection, and preexisting glaucoma. Proposed mechanisms for chronic ocular hypertension include microparticle obstruction, toxic or inflammatory effects on trabecular meshwork, as well as alterations in outflow facility by anti-VEGF agents. Although limiting anti-VEGF therapy could minimize the risk of both acute and chronic ocular hypertension, foregoing anti-VEGF therapy risks progression of various macular diseases with resulting permanent central vision loss. While definitive evidence of damage to the retinal nerve fiber layer is lacking, patients receiving repeated injections should be monitored for ocular hypertension and patients in whom sustained ocular hypertension subsequently developed should be periodically monitored for glaucomatous changes with optic nerve optical coherence tomography and static visual fields.Item Association of Brain Volume and Retinal Thickness in the Early Stages of Alzheimer’s Disease(IOS Press, 2023) Mathew, Sunu; WuDunn, Darrell; Mackay, Devin D.; Vosmeier, Aaron; Tallman, Eileen F.; Deardorff, Rachael; Harris, Alon; Farlow, Martin R.; Brosch, Jared R.; Gao, Sujuan; Apostolova, Liana G.; Saykin, Andrew J.; Risacher, Shannon L.; Radiology and Imaging Sciences, School of MedicineBackground: The eye has been considered a 'window to the brain,' and several neurological diseases including neurodegenerative conditions like Alzheimer's disease (AD) also show changes in the retina. Objective: To investigate retinal nerve fiber layer (RNFL) thickness and its association with brain volume via magnetic resonance imaging (MRI) in older adults with subjective or objective cognitive decline. Methods: 75 participants underwent ophthalmological and neurological evaluation including optical coherence tomography and MRI (28 cognitively normal subjects, 26 with subjective cognitive decline, 17 patients diagnosed with mild cognitive impairment, and 4 with AD). Differences in demographics, thickness of RNFL, and brain volume were assessed using ANCOVA, while partial Pearson correlations, covaried for age and sex, were used to compare thickness of the peripapillary RNFL with brain volumes, with p < 0.05 considered statistically significant. Results: Mean RNFL thickness was significantly correlated with brain volumes, including global volume (right eye r = 0.235 p = 0.046, left eye r = 0.244, p = 0.037), temporal lobe (right eye r = 0.242 p = 0.039, left eye r = 0.290, p = 0.013), hippocampal (right eye r = 0.320 p = 0.005, left eye r = 0.306, p = 0.008), amygdala (left eye r = 0.332, p = 0.004), and occipital lobe (right eye r = 0.264 p = 0.024) volumes. Conclusion: RNFL thickness in both eyes was positively associated with brain volumes in subjects with subjective and objective cognitive decline. The RNFL, however, did not correlate with the disease, but the small sample number makes it important to conduct larger studies. RNFL thickness may be a useful non-invasive and inexpensive tool for detection of brain neurodegeneration and may assist with diagnosis and monitoring of progression and treatment in AD.Item Differences in Ocular Blood Flow Between People of African and European Descent With Healthy Eyes(Lippincott, Williams, and Wilkins, 2016-09) Kaskan, Betül; Ramezani, Koosha; Harris, Alon; Siesky, Brent; Olinde, Carine; WuDunn, Darrell; Eikenberry, Jennifer; Tobe, Leslie A.; Racette, Lyne; Department of Ophthalmology, IU School of MedicinePurpose: To investigate differences in ocular blood flow between people of African descent (AD) and European descent (ED) with healthy eyes. Materials and Methods: Retrobulbar and retinal capillary blood flow was assessed in 1 eye of 58 participants (24 AD, 34 ED) with healthy eyes with systemic blood pressure lower than 140/90. Retrobulbar blood flow was measured in the ophthalmic artery (OA), central retinal artery (CRA), nasal posterior ciliary artery (NPCA) and temporal posterior ciliary artery (TPCA). Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI) were assessed. Retinal capillary blood flow was assessed using mean retinal flow and avascular space defined as the percent of area measured with no blood flow. Groups were compared using t tests and Pearson correlations were compared using Fisher r-to-z transformation. Results: Compared with people of ED, people of AD had significantly lower EDV in the NPCA (P=0.01), and higher RI in the CRA (P=0.04) and TPCA (P=0.01). No significant differences were observed in mean retinal capillary flow or avascular area. In the CRA, a significant negative correlation was observed between pattern standard deviation and peak systolic velocity (P=0.02) in the AD group and this correlation was significantly different from that observed in the ED group (P=0.01). A significant correlation was also observed between pattern standard deviation and EDV (0.04) in the AD group. Conclusions: This study suggests that retrobulbar blood flow is lower in healthy eyes in persons of AD compared with ED. This may provide a mechanism through which people of AD are at increased risk for ophthalmic diseases such as glaucoma.Item The Effect of Molecular Weight on Passage of Proteins Through the Blood-Aqueous Barrier(ARVO, 2019-04) Ragg, Susanne; Key, Melissa; Rankin, Fernanda; WuDunn, Darrell; Biostatistics, School of Public HealthPurpose: To determine the effect of molecular weight (MW) on the concentration of plasma-derived proteins in aqueous humor and to estimate the plasma-derived and eye-derived fractions for each protein. Methods: Aqueous humor and plasma samples were obtained during cataract surgery on an institutional review board–approved protocol. Protein concentrations were determined by ELISA and quantitative antibody microarrays. A total of 93 proteins were studied, with most proteins analyzed using 27 to 116 aqueous and 6 to 30 plasma samples. Results: Plasma proteins without evidence of intraocular expression by sequence tags were used to fit a logarithmic model relating aqueous-plasma ratio (AH:PL) to MW. The log(AH:PL) appears to be well predicted by the log(MW) (P < 0.0001), with smaller proteins such as cystatin C (13 kDa) having a higher AH:PL (1:6) than larger proteins such as albumin (66 kDa, 1:300) and complement component 5 (188 kDa, 1:2500). The logarithmic model was used to calculate the eye-derived intraocular fraction (IOF) for each protein. Based on the IOF, 66 proteins could be categorized as plasma-derived (IOF<20), whereas 10 proteins were primarily derived from eye tissue (IOF >80), and 17 proteins had contribution from both plasma and eye tissue (IOF 20–80). Conclusions: Protein concentration of plasma-derived proteins in aqueous is nonlinearly dependent on MW in favor of smaller proteins. Our study demonstrates that for proper interpretation of results, proteomic studies evaluating changes in aqueous humor protein levels should take into account the plasma and eye-derived fractions.Item Gender Differences in Case Volume Among Ophthalmology Residents(American Medical Association, 2019-07-18) Gong, Dan; Winn, Bryan J.; Beal, Casey J.; Blomquist, Preston H.; Chen, Royce W.; Culican, Susan M.; Dagi Glass, Lora R.; Domeracki, Gary F.; Goshe, Jeffrey M.; Jones, Jeremy K.; Khouri, Albert S.; Legault, Gary L.; Martin, Timothy J.; Mitchell, Kelly T.; Naseri, Ayman; Oetting, Thomas A.; Olson, Joshua H.; Pettey, Jeff H.; Reinoso, Maria A.; Reynolds, Andrew L.; Siatkowski, R. Michael; SooHoo, Jeffrey R.; Sun, Grace; Syed, Misha F.; Tao, Jeremiah P.; Taravati, Parisa; WuDunn, Darrell; Al-Aswad, Lama A.; Ophthalmology, School of MedicineQuestion Do differences in cataract surgery and total procedural volume exist between US male and female residents during ophthalmology residency training? Findings This analysis of the case logs of 1271 ophthalmology residents from 24 US ophthalmology residency programs estimates that female residents performed 7.8 to 22.2 fewer cataract operations and 36.0 to 80.2 fewer total procedures compared with their male counterparts from 2005 to 2017, and the gap widened during this period for total procedural volume. Meaning The current state of surgical training in ophthalmology residency programs deserves further study to ensure that male and female residents have equivalent training experiences. Go to: Abstract Importance Although almost equal numbers of male and female medical students enter into ophthalmology residency programs, whether they have similar surgical experiences during training is unclear. Objective To determine differences for cataract surgery and total procedural volume between male and female residents during ophthalmology residency. Design, Setting, Participants This retrospective, longitudinal analysis of resident case logs from 24 US ophthalmology residency programs spanned July 2005 to June 2017. A total of 1271 residents were included. Data were analyzed from August 12, 2017, through April 4, 2018. Main Outcomes and Measures Variables analyzed included mean volumes of cataract surgery and total procedures, resident gender, and maternity or paternity leave status. Results Among the 1271 residents included in the analysis (815 men [64.1%]), being female was associated with performing fewer cataract operations and total procedures. Male residents performed a mean (SD) of 176.7 (66.2) cataract operations, and female residents performed a mean (SD) of 161.7 (56.2) (mean difference, −15.0 [95% CI, −22.2 to −7.8]; P < .001); men performed a mean (SD) of 509.4 (208.6) total procedures and women performed a mean (SD) of 451.3 (158.8) (mean difference, −58.1 [95% CI, −80.2 to −36.0]; P < .001). Eighty-five of 815 male residents (10.4%) and 71 of 456 female residents (15.6%) took parental leave. Male residents who took paternity leave performed a mean of 27.5 (95% CI, 13.3 to 41.6; P < .001) more cataract operations compared with men who did not take leave, but female residents who took maternity leave performed similar numbers of operations as women who did not take leave (mean difference, −2.0 [95% CI, −18.0 to 14.0]; P = .81). From 2005 to 2017, each additional year was associated with a 5.5 (95% CI, 4.4 to 6.7; P < .001) increase in cataract volume and 24.4 (95% CI, 20.9 to 27.8; P < .001) increase in total procedural volume. This increase was not different between genders for cataract procedure volume (β = −1.6 [95% CI, −3.7 to 0.4]; P = .11) but was different for total procedural volume such that the increase in total procedural volume over time for men was greater than that for women (β = −8.0 [95% CI, −14.0 to −2.1]; P = .008). Conclusions and Relevance Female residents performed 7.8 to 22.2 fewer cataract operations and 36.0 to 80.2 fewer total procedures compared with their male counterparts from 2005 to 2017, a finding that warrants further exploration to ensure that residents have equivalent surgical training experiences during residency regardless of gender. However, this study included a limited number of programs (24 of 119 [20.2%]). Future research including all ophthalmology residency programs may minimize the selection bias issues present in this study.Item Racial differences in correlations between optic nerve head morphology and ocular blood flow in healthy eyes(Office of the Vice Chancellor for Research, 2016-04-08) Ramezani, Koosha; Harris, Alon; Siesky, Brent A; Olinde, Carine; WuDunn, Darrell; Kaskan, Betül; Eikenberry, Jennifer; Tobe, Leslie A.; Racette, LynePurpose: To assess differences in the relationship between optic nerve head (ONH) morphology and ocular blood flow between persons of African descent (AD) and European descent (ED) with healthy eyes. Methods: 46 participants (20 AD, 26 ED) with normal fundoscopic exam and intraocular pressure were included. Each participant was assessed for disc area (DA), rim area (RA), linear cup to disc ratio (CDR), mean retinal nerve fiber layer (RNFL) thickness by Heidelberg retina tomograph. Retrobulbar blood flow was assessed by color Doppler imaging in the ophthalmic (OA), central retinal (CRA), nasal short posterior ciliary (NPCA) and temporal short posterior ciliary (TPCA) arteries. Peak systolic velocity (PSV), end diastolic velocity (EDV) and the resistive index (RI) were assessed in each artery. Mean retinal capillary blood flow and % of the area with no blood flow in both hemifields were measured with Heidelberg retinal flowmeter. Correlations between ONH morphology and ocular blood flow were derived using Pearson correlations. Differences between the correlations in the AD and ED groups were assessed using the Fisher r-to-z transformation method. Results: Age, gender, IOP and blood pressure were not significantly different between groups. Significant differences in correlations were observed between groups in the CRA. In this artery, PSV and DA were positively correlated in AD (r=0.43) and negatively correlated in ED (r=-0.35) (Δr=0.78; p=0.01). A similar finding was observed for PSV and RA (AD: r=0.39; ED: r=-0.22; Δr=0.61; p=0.04). Significant negative correlations between RI and CDR were observed in all arteries in the ED group (r coefficients range=-0.48 to -0.39), but not in the AD group (r coefficients range=-0.14 to 0.17). No significant differences were observed in the correlations of ONH morphology and capillary blood flow. Conclusion: ONH morphology and ocular blood flow relationship was significantly different in the healthy eyes of AD compared to ED.Item Visual contrast sensitivity is associated with the presence of cerebral amyloid and tau deposition(Oxford University Press, 2020) Risacher, Shannon L; WuDunn, Darrell; Tallman, Eileen F.; West, John D.; Gao, Sujuan; Farlow, Martin R.; Brosch, Jared R.; Apostolova, Liana G.; Saykin, Andrew J.; Radiology and Imaging Sciences, School of MedicineVisual deficits are common in neurodegenerative diseases including Alzheimer’s disease. We sought to determine the association between visual contrast sensitivity and neuroimaging measures of Alzheimer’s disease-related pathophysiology, including cerebral amyloid and tau deposition and neurodegeneration. A total of 74 participants (7 Alzheimer’s disease, 16 mild cognitive impairment, 20 subjective cognitive decline, 31 cognitively normal older adults) underwent the frequency doubling technology 24-2 examination, a structural MRI scan and amyloid PET imaging for the assessment of visual contrast sensitivity. Of these participants, 46 participants (2 Alzheimer’s disease, 9 mild cognitive impairment, 12 subjective cognitive decline, 23 cognitively normal older adults) also underwent tau PET imaging with [18F]flortaucipir. The relationships between visual contrast sensitivity and cerebral amyloid and tau, as well as neurodegeneration, were assessed using partial Pearson correlations, covaried for age, sex and race and ethnicity. Voxel-wise associations were also evaluated for amyloid and tau. The ability of visual contrast sensitivity to predict amyloid and tau positivity were assessed using forward conditional logistic regression and receiver operating curve analysis. All analyses first were done in the full sample and then in the non-demented at-risk individuals (subjective cognitive decline and mild cognitive impairment) only. Significant associations between visual contrast sensitivity and regional amyloid and tau deposition were observed across the full sample and within subjective cognitive decline and mild cognitive impairment only. Voxel-wise analysis demonstrated strong associations of visual contrast sensitivity with amyloid and tau, primarily in temporal, parietal and occipital brain regions. Finally, visual contrast sensitivity accurately predicted amyloid and tau positivity. Alterations in visual contrast sensitivity were related to cerebral deposition of amyloid and tau, suggesting that this measure may be a good biomarker for detecting Alzheimer’s disease-related pathophysiology. Future studies in larger patient samples are needed, but these findings support the power of these measures of visual contrast sensitivity as a potential novel, inexpensive and easy-to-administer biomarker for Alzheimer’s disease-related pathology in older adults at risk for cognitive decline.