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Item Characterizing and quantifying the temporal relationship between structural and functional change in glaucoma(Public Library of Science, 2021-04-01) Chu, Fang-I; Racette, Lyne; Ophthalmology, School of MedicinePurpose: To characterize and quantify the temporal relationship between structural and functional change in glaucoma. Methods: 120 eyes of 120 patients with ocular hypertension or primary open-angle glaucoma were selected from the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study. Patients had 11 visits, separated by at least 3 months over 5 to 10 years. Each visit had rim area (RA) and mean sensitivity (MS) measurements taken within a 30-day period. The structure-function (SF) relationship was summarized using conventional and modified cross-correlation functions (CCFs), which identified the strongest absolute and positive correlation, respectively. Patients were categorized in one of the following three groups: RA and MS evolved simultaneously (lag = 0), RA preceded MS (lag<0), and MS preceded RA (lag>0). Lagging regression analysis was used to examine the variations of the SF relationship within groups. Results: The number of participants, mean visit lag, and mean correlation (standard deviation) were, for the conventional and modified CCFs, respectively: lag = 0 [16, 0, 0.53 (0.10) and 16, 0, 0.46 (0.11)]; lag<0 [50, -2.94, 0.51 (0.11) and 55, -3.45, 0.44 (0.12)], and lag>0 [54, 3.35, 0.53 (0.13) and 49, 3.78, 0.45 (0.12)]. A significant difference of the visit lag relation within groups was identified using lagging regression analysis (p<0.0001). Conclusions: The strongest relationship between structure and function was obtained at different visit lags in different patients. This finding also suggests that the SF relationship should be addressed at the subject level when using both measurements jointly to model glaucoma progression.Item Choroidal Thickness and Primary Open-Angle Glaucoma—A Narrative Review(MDPI, 2022-02-23) Verticchio Vercellin, Alice; Harris, Alon; Stone, Ari M.; Oddone, Francesco; Mendoza, Kristen Ann; Siesky, Brent; Ophthalmology, School of MedicineThe choroid provides the majority of blood flow to the ocular tissues and structures that facilitate the processes of retinal metabolism responsible for vision. Specifically, the choriocapillaris provides a structural network of small blood vessels that supplies the retinal ganglion cells and deep ocular tissues. Similar to retinal nerve fiber layer thickness, choroidal thickness (CT) has been suggested to represent a quantifiable health biomarker for choroidal tissues. Glaucoma is a disease with vascular contributions in its onset and progression. Despite its importance in maintaining ocular structure and vascular functionality, clinical assessments of choroidal tissues have been historically challenged by the inaccessibility of CT biomarker targets. The development of optical coherence tomography angiography and enhanced depth imaging created a framework for assessing CT and investigating its relationship to glaucomatous optic neuropathy onset and progression. Pilot studies on CT in glaucoma are conflicting—with those both in support of, and against, its clinical utility. Complicating the data are highly customized analysis methods, small sample sizes, heterogeneous patient groups, and a lack of properly designed controlled studies with CT as a primary outcome. Herein, we review the available data on CT and critically discuss its potential relevance and limitations in glaucoma disease management.Item Comparison of Intraocular Pressure, Blood Pressure, Ocular Perfusion Pressure and Blood Flow Fluctuations During Dorzolamide Versus Timolol Add-On Therapy in Prostaglandin Analogue Treated Glaucoma Subjects(MDPI, 2012-03-21) Januleviciene, Ingrida; Siaudvytyte, Lina; Diliene, Vaida; Barsauskaite, Ruta; Paulaviciute-Baikstiene, Daiva; Siesky, Brent; Harris, Alon; Ophthalmology, School of MedicineObjective: To compare the effects of dorzolamide and timolol add-on therapy in open-angle glaucoma (OAG) patients previously treated with prostaglandin analogue (Pg), by evaluating fluctuations in the intraocular (IOP), blood (BP), ocular perfusion pressures (OPP) and retrobulbar blood flow (RBF) parameters. Methods: 35 OAG patients (35 eyes), 31 women (88.6%) age 63.3 (8.9) years were evaluated in a 3 month randomized, cross-over, single-masked study. During the experiments BP, heart rate, IOP and OPP were assessed 4 times per day (8-12-16-20 h). RBF was measured twice per day (8-20 h) using Color Doppler imaging in the ophthalmic (OA), central retinal (CRA), nasal (nSPCA) and temporal (tSPCA) posterior ciliary arteries. In each vessel, peak systolic velocity (PSV) and end-diastolic velocity (EDV) were assessed and vascular resistance (RI) calculated. Results: Both add-on therapies lowered IOP in a statistically significant manner from 15.7 ± 2.4 mmHg at latanoprost baseline to 14.9 ± 2.2 mmHg using dorzolamide (p < 0.001) and 14.2 ± 1.9 mmHg using timolol (p < 0.001). The IOP lowering effect was statistically significant at 20 h, favoring timolol as compared to dorzolamide (1.4 ± 2.4 vs. 0.2 ± 2.1 mmHg), (p < 0.05). Dorzolamide add-on therapy showed smaller IOP (2.0 ± 1.4), SPP (13.3 ± 7.9), systolic BP (13.5 ± 8.7) and diastolic BP (8.4 ± 5.4) fluctuations as compared to both latanoprost baseline or timolol add-on therapies. Higher difference between morning and evening BP was correlated to decreased evening CRA EDV in the timolol group (c = -0.41; p = 0.01). With increased MAP in the morning or evening hours, we found increased evening OA RI in timolol add-on group (c = 0.400, p = 0.02; c = 0.513, p = 0.002 accordingly). Higher MAP fluctuations were related to impaired RBF parameters during evening hours-decreased CRA EDV (c = -0.408; p = 0.01), increased CRA RI (c = 0.576; p < 0.001) and tSPCA RI (c = 0.356; p = 0.04) in the dorzolamide group and increased nSPCA RI (c = 0.351; p = 0.04) in the timolol add-on group. OPP fluctuations correlated with increased nSPCA RI (c = 0.453; p = 0.006) in the timolol group. OPP fluctuations were not related to IOP fluctuations in both add-on therapies (p < 0.05). Conclusions: Both dorzolamide and timolol add-on therapies lowered IOP in a statistically significant fashion dorzolamide add-on therapy showed lower fluctuations in IOP, SPP and BP. Higher variability of daytime OPP led to impaired RBF parameters in the evening.Item Evaluation of Cerebrospinal Fluid Pressure by a Formula and Its Role in the Pathogenesis of Glaucoma(Hindawi, 2019-11) Landi, Laura; Casciaro, Federica; Telani, Serena; Traverso, Carlo E.; Harris, Alon; Verticchio Vercellin, Alice C.; Saint, Lauren; Iester, Michele; Ophthalmology, School of MedicineItem Glaucoma Treatment Outcomes in Open-Angle Glaucoma Patients of African Descent(World Scientific, 2022) Siesky, Brent; Harris, Alon; Belamkar, Aditya; Zukerman, Ryan; Horn, Avery; Verticchio Vercellin, Alice; Mendoza, Kristen Ann V.; Sidoti, Paul A.; Oddone, Francesco; Ophthalmology, School of MedicineOpen angle glaucoma (OAG), characterized by structural changes to the optic nerve head and retinal nerve fiber layer, is a progressive multifactorial optic neuropathy and leading cause of irreversible blindness globally. Currently intraocular pressure is the only modifiable risk factor; however, others have been identified including genetics and race. Importantly, OAG is much more prevalent in persons of African descent (AD) compared to those of European descent (ED). OAG patients of AD are also known to have a more severe course of the disease, a finding potentially explained by structural and/or vascular differences within eye tissues. In addition, disparities in treatment outcomes have been identified in OAG patients of AD. Specifically, prostaglandin analogues have been suggested to be more effective in patients of AD than in those ED, while beta-adrenergic receptors have been suggested to be less effective, although the evidence is inconsistent. Being of AD has also been identified as a risk factor for trabeculectomy failure while laser trabeculoplasty, has been conversely found to be very effective in lowering IOP in patients of AD. Alternative surgical options including Ex-Press shunt implantation, viscocanalostomy, and canaloplasty are promising in equivalence but require further research to properly evaluate disparity in outcomes. In addition to treatment outcomes, social disparities affecting clinical care also exist for persons of AD in the form of reduced adherence, access, and choice. Overall, data suggests the need for properly designed prospective trials with AD populations as a primary focus to identify the potential mechanisms driving disparities in treatment and address overall potential bias in glaucoma management.