Browsing by Author "Oddone, Francesco"
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Item Asian Race and Primary Open-Angle Glaucoma: Where Do We Stand?(MDPI, 2022-04-28) Belamkar, Aditya; Harris, Alon; Oddone, Francesco; Verticchio Vercellin, Alice; Fabczak-Kubicka, Anna; Siesky, Brent; Ophthalmology, School of MedicinePrimary open-angle glaucoma (POAG) is an optic neuropathy characterized by irreversible retinal ganglion cell damage and visual field loss. The global POAG prevalence is estimated to be 3.05%, and near term is expected to significantly rise, especially within aging Asian populations. Primary angle-closure glaucoma disproportionately affects Asians, with up to four times greater prevalence of normal-tension glaucoma reported compared with high-tension glaucoma. Estimates for overall POAG prevalence in Asian populations vary, with Chinese and Indian populations representing the majority of future cases. Structural characteristics associated with glaucoma progression including the optic nerve head, retina, and cornea are distinct in Asians, serving as intermediates between African and European descent populations. Patterns in IOP suggest some similarities between races, with a significant inverse relationship between age and IOP only in Asian populations. Genetic differences have been suggested to play a role in these differences, however, a clear genetic pattern is yet to be established. POAG pathogenesis differs between Asians and other ethnicities, and it may differ within the broad classification of the Asian race. Greater awareness and further research are needed to improve treatment plans and outcomes for the increasingly high prevalence of normal tension glaucoma within aging Asian populations.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 Diagnostic Capability of OCTA-Derived Macular Biomarkers for Early to Moderate Primary Open Angle Glaucom(MDPI, 2024-07-18) Verticchio Vercellin, Alice; Harris, Alon; Oddone, Francesco; Carnevale, Carmela; Siesky, Brent A.; Arciero, Julia; Fry, Brendan; Eckert, George; Sidoti, Paul A.; Antman, Gal; Alabi, Denise; Coleman-Belin, Janet C.; Pasquale, Louis R.; Mathematical Sciences, School of ScienceBackground/Objectives: To investigate macular vascular biomarkers for the detection of primary open-angle glaucoma (POAG). Methods: A total of 56 POAG patients and 94 non-glaucomatous controls underwent optical coherence tomography angiography (OCTA) assessment of macular vessel density (VD) in the superficial (SCP), and deep (DCP) capillary plexus, foveal avascular zone (FAZ) area, perimeter, VD, choriocapillaris and outer retina flow area. POAG patients were classified for severity based on the Glaucoma Staging System 2 of Brusini. ANCOVA comparisons adjusted for age, sex, race, hypertension, diabetes, and areas under the receiver operating characteristic curves (AUCs) for POAG/control differentiation were compared using the DeLong method. Results: Global, hemispheric, and quadrant SCP VD was significantly lower in POAG patients in the whole image, parafovea, and perifovea (p < 0.001). No significant differences were found between POAG and controls for DCP VD, FAZ parameters, and the retinal and choriocapillaris flow area (p > 0.05). SCP VD in the whole image and perifovea were significantly lower in POAG patients in stage 2 than stage 0 (p < 0.001). The AUCs of SCP VD in the whole image (0.86) and perifovea (0.84) were significantly higher than the AUCs of all DCP VD (p < 0.05), FAZ parameters (p < 0.001), and retinal (p < 0.001) and choriocapillaris flow areas (p < 0.05). Whole image SCP VD was similar to the AUC of the global retinal nerve fiber layer (RNFL) (AUC = 0.89, p = 0.53) and ganglion cell complex (GCC) thickness (AUC = 0.83, p = 0.42). Conclusions: SCP VD is lower with increasing functional damage in POAG patients. The AUC for SCP VD was similar to RNFL and GCC using clinical diagnosis as the reference standard.Item Disease progression pathways of wet AMD: opportunities for new target discovery(Taylor & Francis, 2022) Wolf, Amber T.; Harris, Alon; Oddone, Francesco; Siesky, Brent; Verticchio Vercellin, Alice; Ciulla, Thomas A.; Ophthalmology, School of MedicineIntroduction: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among people age 60 years or older in developed countries. Current standard-of-care anti-vascular endothelial growth factor (VEGF) therapy, which inhibits angiogenesis and vascular permeability, has been shown to stabilize choroidal neovascularization and increase visual acuity in neovascular AMD. However, therapeutic limitations of anti-VEGF therapy include limited durability with consequent need for frequent intravitreal injections, and a ceiling of efficacy. Current strategies under investigation include targeting VEGF-C and VEGF-D, integrins, tyrosine kinase receptors, and the Tie2/angiopoietin-2 pathway. A literature search was conducted through November 30, 2021 on PubMed, Medline, Google Scholar, and associated digital platforms with the following keywords: wet macular degeneration, age-related macular degeneration, therapy, VEGF-A, VEGF-C, VEGF-D, integrins, Tie2/Ang2, and tyrosine kinase inhibitors. Areas covered: The authors provide a comprehensive review of AMD disease pathways and mechanisms involved in wet AMD as well as novel targets for future therapies. Expert opinion: With novel targets and advancements in drug delivery, there is potential to address treatment burden and to improve outcomes for patients afflicted with neovascular AMD.Item 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.Item Heterogeneity of Ocular Hemodynamic Biomarkers among Open Angle Glaucoma Patients of African and European Descent(MDPI, 2023-02-06) Siesky, Brent; Harris, Alon; Verticchio Vercellin, Alice; Arciero, Julia; Fry, Brendan; Eckert, George; Guidoboni, Giovanna; Oddone, Francesco; Antman, Gal; Mathematical Sciences, School of ScienceThis study investigated the heterogeneity of ocular hemodynamic biomarkers in early open angle glaucoma (OAG) patients and healthy controls of African (AD) and European descent (ED). Sixty OAG patients (38 ED, 22 AD) and 65 healthy controls (47 ED, 18 AD) participated in a prospective, cross-sectional study assessing: intraocular pressure (IOP), blood pressure (BP), ocular perfusion pressure (OPP), visual field (VF) and vascular densities (VD) via optical coherence tomography angiography (OCTA). Comparisons between outcomes were adjusted for age, diabetes status and BP. VF, IOP, BP and OPP were not significantly different between OAG subgroups or controls. Multiple VD biomarkers were significantly lower in OAG patients of ED (p < 0.05) while central macular VD was lower in OAG patients of AD vs. OAG patients of ED (p = 0.024). Macular and parafoveal thickness were significantly lower in AD OAG patients compared to those of ED (p = 0.006–0.049). OAG patients of AD had a negative correlation between IOP and VF index (r = −0.86) while ED patients had a slightly positive relationship (r = 0.26); difference between groups (p < 0.001). Age-adjusted OCTA biomarkers exhibit significant variation in early OAG patients of AD and ED.Item Physiology-Enhanced Data Analytics to Evaluate the Effect of Altitude on Intraocular Pressure and Ocular Hemodynamics(MDPI, 2022) Verticchio Vercellin, Alice; Harris, Alon; Belamkar, Aditya; Zukerman, Ryan; Carichino, Lucia; Szopos, Marcela; Siesky, Brent; Quaranta, Luciano; Bruttini, Carlo; Oddone, Francesco; Riva, Ivano; Guidoboni, Giovanna; Ophthalmology, School of MedicineAltitude affects intraocular pressure (IOP); however, the underlying mechanisms involved and its relationship with ocular hemodynamics remain unknown. Herein, a validated mathematical modeling approach was used for a physiology-enhanced (pe-) analysis of the Mont Blanc study (MBS), estimating the effects of altitude on IOP, blood pressure (BP), and retinal hemodynamics. In the MBS, IOP and BP were measured in 33 healthy volunteers at 77 and 3466 m above sea level. Pe-retinal hemodynamics analysis predicted a statistically significant increase (p < 0.001) in the model predicted blood flow and pressure within the retinal vasculature following increases in systemic BP with altitude measured in the MBS. Decreased IOP with altitude led to a non-monotonic behavior of the model predicted retinal vascular resistances, with significant decreases in the resistance of the central retinal artery (p < 0.001) and retinal venules (p = 0.003) and a non-significant increase in the resistance in the central retinal vein (p = 0.253). Pe-aqueous humor analysis showed that a decrease in osmotic pressure difference (OPD) may underlie the difference in IOP measured at different altitudes in the MBS. Our analysis suggests that venules bear the significant portion of the IOP pressure load within the ocular vasculature, and that OPD plays an important role in regulating IOP with changes in altitude.Item Prevalence Rates and Risk Factors for Primary Open Angle Glaucoma in the Middle East(Knowledge E, 2021-10-25) Torabi, Rana; Harris, Alon; Siesky, Brent; Zukerman, Ryan; Oddone, Francesco; Mathew, Sunu; Januleviciene, Ingrida; Verticchio Vercellin, Alice C.; Ophthalmology, School of MedicineGlaucoma is a multifactorial disease and a leading cause of irreversible blindness worldwide. Current data has demonstrated the approximate distribution of primary open-angle glaucoma (POAG) in patients of European, African, Hispanic, and Eastern Asian descent. However, a significant gap in the literature exists regarding the prevalence of POAG in Middle Eastern (ME) populations. Current studies estimate ME POAG prevalence based on a European model. Herein we screened 65 total publications on ME prevalence of POAG and specific risk factors using keywords: “glaucoma”, “prevalence”, “incidence”, “risk factor”, “Middle East”, “Mideast”, “Persian”, “Far East”, as well as searching by individual ME countries through PubMed, Embase, Ovid, Scopus, and Trip searches with additional reference list searches from relevant articles published up to and including March 1, 2021. Fifty qualifying records were included after 15 studies identified with low statistical power, confounding co-morbid ophthalmic diseases, and funding bias were excluded. Studies of ME glaucoma risk factors that identify chromosomes, familial trend, age/gender, socioeconomic status, lifestyle, intraocular pressure, vascular influences, optic disc hemorrhage, cup-to-disc ratio, blood pressure, obstructive sleep apnea, and diabetes mellitus were included in this systematic review. We conclude that the prevalence of POAG in the ME is likely higher than the prevalence rate that European models suggest, with ME specific risk factors likely playing a role. However, these findings are severely limited by the paucity of population-level data in the ME. Well-designed, longitudinal population-based studies with rigorous inclusion and exclusion criteria are ultimately needed to accurately assess the epidemiology and specific mechanistic risk factors of glaucoma in ME populations.Item Sustained release glaucoma therapies: Novel modalities for overcoming key treatment barriers associated with topical medications(Taylor & Francis, 2022) Belamkar, Aditya; Harris, Alon; Zukerman, Ryan; Siesky, Brent; Oddone, Francesco; Verticchio Vercellin, Alice; Ciulla, Thomas A.; Ophthalmology, School of MedicineGlaucoma is a progressive optic neuropathy and a leading cause of irreversible blindness. The disease has conventionally been characterized by an elevated intraocular pressure (IOP); however, recent research has built the consensus that glaucoma is not only dependent on IOP but rather represents a multifactorial optic neuropathy. Although many risk factors have been identified ranging from demographics to co-morbidities to ocular structural predispositions, IOP is currently the only modifiable risk factor, most often treated by topical IOP-lowering medications. However, topical hypotensive regimens are prone to non-adherence and are largely inefficient, leading to disease progression in spite of treatment. As a result, several companies are developing sustained release (SR) drug delivery systems as alternatives to topical delivery to potentially overcome these barriers. Currently, Bimatoprost SR (DurystaTM) from Allergan plc is the only FDA-approved SR therapy for POAG. Other SR therapies under investigation include: bimatoprost ocular ring (Allergan) (ClinicalTrials.gov identifier: NCT01915940), iDose® (Glaukos Corporation) (NCT03519386), ENV515 (Envisia Therapeutics) (NCT02371746), OTX-TP (Ocular Therapeutix) (NCT02914509), OTX-TIC (Ocular Therapeutix) (NCT04060144), and latanoprost free acid SR (PolyActiva) (NCT04060758). Additionally, a wide variety of technologies for SR therapeutics are under investigation including ocular surface drug delivery systems such as contact lenses and nanotechnology. While challenges remain for SR drug delivery technology in POAG management, this technology may shift treatment paradigms and dramatically improve outcomes.Item Topical carbonic anhydrase inhibitors and glaucoma in 2021: where do we stand?(BMJ Publishing, 2022) Stoner, Ari; Harris, Alon; Oddone, Francesco; Belamkar, Aditya; Verticchio Vercellin, Alice Chandra; Shin, Joshua; Januleviciene, Ingrida; Siesky, Brent; Ophthalmology, School of MedicineCarbonic anhydrase inhibitors (CAIs) have been used for many decades in the treatment of glaucoma. Systemic CAIs were an early treatment option to lower intraocular pressure by reducing aqueous humour production; however, frequent side effects including polyuria and paresthesia contributed to the eventual development of topical CAIs. As topical drug development evolved over time, prostaglandin analogues and beta-blockers have become the gold standard of glaucoma therapies. Although prescribed less often than other classes of topical glaucoma therapies, topical CAIs continue to be used in combination therapies with beta-blockers and alpha agonists. Topical CAIs have also been demonstrated to alter biomarkers of ocular haemodynamics, which have relevance in glaucoma. The purpose of this review is to review and summarise the current state of topical CAI prescribing trends, known efficacy and suggested mechanisms and potential influence on ocular haemodynamics for the future of glaucoma management.