Vascular imaging findings in retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a vascular disease among preterm infants involving incomplete or abnormal retinal vascularization and is a leading cause of preventable blindness globally. Measurements of ocular blood flow originating from a variety of imaging modalities, including colour Doppler imaging (CDI), fluorescein angiography (FA) and ocular coherence tomography angiography (OCTA), have been associated with changes in ROP patients. Herein, we discuss and summarize the relevant current literature on vascular imaging and ROP reviewed through December 2022. Differences in vascular imaging parameters between ROP patients and healthy controls are reviewed and summarized. The available data identify significantly increased peak systolic velocity (PSV) in the central retinal artery and ophthalmic artery as measured by CDI, increased vascular tortuosity as measured by FA, smaller foveal avascular zone (FAZ) as measured by FA and OCTA, and increased foveal vessel density (VD) and reduced parafoveal VD as measured by OCTA in ROP patients compared with controls. None of the above findings appear to reliably correlate with visual acuity. The studies currently available, however, are inconclusive and lack robust longitudinal data. Vascular imaging demonstrates the potential to aid in the diagnosis, management and monitoring of ROP, alongside retinal examination via indirect ophthalmoscopy and fundus photography.

Ocular blood flow biomarkers may predict long-term glaucoma progression.

BACKGROUND/AIM: To examine the relationship between baseline blood flow biomarkers and long-term open-angle glaucoma (OAG) progression. METHODS: 112 patients with early to moderate OAG (mean age 64.9±11.0 years; 68 female) were evaluated at baseline and every 6 months from 2008 to 2013. Biomarkers of retinal capillary blood flow were assessed by Heidelberg retinal flowmetry. Functional disease progression was monitored via Humphrey visual field examinations, defined as two consecutive visits with a mean deviation decrease ≥2 decibels and/or Advanced Glaucoma Intervention Study score increase ≥2 compared with baseline. Structural progression was monitored with optical coherence tomography and Heidelberg retinal tomograph, defined as two consecutive visits with retinal nerve fibre layer thickness decrease ≥8% and/or horizontal or vertical cup/disk ratio increase ≥0.2 compared with baseline. Mixed-model analysis of covariance was used to test for significant change from baseline to 5-year follow-up. Times to functional and structural progression were analysed using Cox proportional hazards models. RESULTS: Lower HRF retinal capillary blood flow in the superior retina was significantly associated with structural progression (p=0.0009). CONCLUSION: In our OAG sample, baseline lower retinal capillary perfusion in the superior retina was predictive of structural progression after 5 years. TRIAL REGISTRATION NUMBER: NCT01145911.

Dry eye disease and blinking behaviors: A narrative review of methodologies for measuring blink dynamics and inducing blink response.

Dry eye disease (DED) is a leading cause of ophthalmology clinical encounters with prevalence ranging from 8.7% to 64% in various populations. Blinking is an endogenous process to refresh the tear film, clear debris and maintain quality vision. Altered blinking behavior is a common feature of DED and is implicated in the pathology of the disease. However, lack of a comprehensive review on the relationship between altered blinking behavior and DED is notable in the literature. Blinking behavior may be an effect of DED due to an unstable tear film sensitizing a motor response or be its cause due to destabilization of the tear film in conditions such as benign essential blepharospasm. In this comprehensive review, we summarize the current models and theories of tear film dynamics and blinking behavior to better understand their connection to DED and introduce contemporary technologies and measurement tools used in the evaluation and induction of blinking behavior. We also describe future directions of research to better understand the relationship between DED and blinking and explore therapies that address the abnormal blinking component of DED.

Progress in the pharmacotherapy of uveitis: the art of personalized care.

INTRODUCTION: Uveitis is a heterogeneous group of inflammatory intraocular disorders that can lead to blindness, but prompt diagnosis and management can improve visual outcomes and reduce treatment burden. AREAS COVERED: In this review, the authors provide an overview of commonly used treatments for the management of noninfectious uveitis. EXPERT OPINION: Initially, the treatment of noninfectious uveitis was limited to corticosteroids, which have a broad range of adverse ocular and systemic effects. Now new delivery and therapeutic options, such as biological response modulators, represent novel yet exciting additions to this armory and have the potential to alter the course of treatment as well as prognostic outcomes for uveitis patients. Further research is needed to evaluate the efficacy of this novel class of immunomodulators in uveitis therapy.

The 'Fault' Lies in the Choroid: Peripapillary Intrachoroidal Cavitation Presenting with Progressive Vision Loss.

A 55-year-old male was referred to the Neuro-ophthalmology clinic due to gradual onset, progressive vision loss. On fundus examination a subtle yellow-orange peripapillary lesion was detected in the left eye. Optical coherence tomography with radial scanning illustrated retinal nerve fibre layer thinning as well as an area of intrachoroidal cavitation that corresponded to the lesion. Visual field testing showed a left inferior arcuate defect. Magnetic resonance imaging of the brain and orbit, and laboratory testing was unremarkable. Clinical examination, imaging, and testing were consistent with peripapillary intrachoroidal cavitation (PICC). Follow-up with serial visual field testing showed mild progression of the field defect. While PICC is not well understood in the literature, studies have reported associated risk factors including pathological myopia, older age, increased ocular axial length, chorioretinal atrophy, and vascular abnormalities. Importantly, glaucoma-like visual field defects as well as structural changes have been noticed in a high proportion of patients with PICC. While these alterations are evident, the pathogenic relationship between them is yet to be uncovered. Treatment with anti-glaucoma medications has been suggested, however, the evidence remains scarce for its true benefits. Care providers must be aware of the presentation of a yellow-orange peripapillary lesion with an associated visual field defect to accurately diagnose and manage this condition.

Asian Race and Primary Open-Angle Glaucoma: Where Do We Stand?

Primary 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.

Glaucoma Treatment Outcomes in Open Angle Glaucoma Patients of African Descent.

Open angle glaucoma (OAG), characterized by structural changes to the optic nerve head and retinal nerve fiber layer, is a progressive multifactorial optic neuropathy and a 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 with 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. 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 intraocular pressure in patients of AD. Alternative surgical options, including Ex-Press shunt implantation, viscocanalostomy, and canaloplasty are promising in equivalence but require further research to evaluate disparity in outcome properly. In addition to treatment outcomes, social disparities affecting clinical care also exist for AD persons in the form of reduced adherence, access, and choice. Overall, data suggest 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.

Sustained release glaucoma therapies: Novel modalities for overcoming key treatment barriers associated with topical medications.

Glaucoma 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.

Clinical implications of retinal oximetry in retinal vein occlusion: a review.

PURPOSE: To review retinal vein occlusion (RVO) and its relationship with retinal oxygen saturation via automated retinal oximetry in eyes with RVO. METHODS: A literature review was performed in PubMed and Medline until October 2021 utilizing specific keywords and cross-matched reference lists. RESULTS: This review found RVO to be associated with risk factors including age, hypertension, cardiovascular and metabolic conditions, male gender, and glaucoma. These may be attributed to a breakdown of regulatory processes in the retina. Retinal venous oxygen saturation (SvO2 ) and arteriovenous difference in eyes with central RVO have been found to be reduced and elevated, respectively. The literature indicates variable and contradictory findings in regard to branch RVO and retinal oxygenation. Additionally, ischaemic eyes have been found to have elevated retinal arterial oxygen saturation; however, the literature reports variable results regarding SvO2 levels. Medications have been suggested to increase SvO2 in RVO eyes, which may represent an important mechanism for disease management. Ranibizumab is currently the most studied drug for retinal oxygenation in RVO and has been suggested to increase SvO2 in RVO eyes. In comparison, dexamethasone was found to decrease SvO2 . CONCLUSION: The current literature on retinal oxygenation in ischaemic subtypes of RVO and in drug therapies is minimal, and further work is required to expand upon our understanding of how ischaemia and drugs influence retinal oxygenation and clinical outcomes.

Topical carbonic anhydrase inhibitors and glaucoma in 2021: where do we stand?

Carbonic 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.

Physiology-Enhanced Data Analytics to Evaluate the Effect of Altitude on Intraocular Pressure and Ocular Hemodynamics.

Altitude 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.

Incidence of Dementia in Patients With Open-angle Glaucoma: A Population-based Study.

PRECIS: In this population-based study of 509 open-angle glaucoma (OAG) patients over a 36-year period, we identified a decreased rate of developing dementia compared with the rate in the general population. PURPOSE: The aim was to determine the incidence of dementia and Alzheimer disease (AD) among patients with OAG. PATIENTS AND METHODS: Retrospective, population-based cohort study. All residents of Olmsted County, Minnesota (≥40 y) who were diagnosed with OAG between January 1, 1965 and December 31, 2000, were eligible for inclusion in this study. A total of 509 patients were included over the 36-year period. The cumulative probability of developing dementia was calculated and compared with the population risk of dementia. RESULTS: Of the 509 patients included, 300 (58.9%) were female, the median age was 67.5 years, and 278 patients (54.6%) had primary OAG. Other subgroups were pseudoexfoliation in 15.1%, treated ocular hypertension in 14.1%, normal tension glaucoma in 10.6%, and pigmentary glaucoma in 5.5% of the patients. Respectively, 118 (23.0%) and 99 (19.4%) patients developed dementia and AD. The 10-year cumulative probability of developing dementia and AD was 12.0% and 9.9%, with a 95% confidence interval of 9.3%-15.3% and 7.5%-13%, respectively. The observed 10-year incidence of dementia and AD were significantly lower than the expected population incidence (19.0% and 19.0%; P<0.001). Older age at diagnosis of glaucoma was a strong predictor for the development of dementia by multivariate analysis (hazard ratio: 3.31, 95% confidence interval: 2.61-4.20, P<0.001). CONCLUSION: The risk of developing dementia or AD was decreased in OAG patients compared with the general population. OAG with onset at a later age may present as a different etiopathogenetic entity compared with onset at a younger age, and represent the optic nerve findings of generalized neurodegenerative processes.

Vascular dysfunction in retinitis pigmentosa.

The relationship between ocular haemodynamics and retinitis pigmentosa (RP) has not been fully understood. Reductions in blood flow have been established in RP patients by a variety of studies; however, questions have yet to be answered regarding the role of vascular dysfunction in photoreceptors (PR) degeneration, the causes of vascular dysfunction in RP, as well as the diagnostic, prognostic and perhaps therapeutic potential of measuring ocular haemodynamics in RP patients. While significant evidence supports the theory that vascular dysfunction is associated with but not the cause of PR death in retinitis pigmentosa, evidence suggests that vascular abnormalities in the foveal and parafoveal regions may exacerbate cone cell loss. Additional evidence demonstrates that vascular dysfunction likely results from changes in metabolic demand due to death of PR cells in the retina. Detection and monitoring of ocular blood flow, retinal oxygen saturation, endothelin-1 levels and vascular structural abnormalities could provide diagnostic, prognostic and therapeutic potential for patients with RP.

Effects of Sex Hormones on Ocular Blood Flow and Intraocular Pressure in Primary Open-angle Glaucoma: A Review.

Primary open-angle glaucoma (POAG) is a multifactorial optic neuropathy characterized by progressive retinal ganglion cell death and visual field loss. Some speculate that sex plays a role in the risk of developing POAG and that the physiological differences between men and women may be attributed to the variable effects of sex hormones on intraocular pressure, ocular blood flow, and/or neuroprotection. Estrogen, in the form of premenopausal status, pregnancy, and postmenopausal hormone therapy is associated with an increase in ocular blood flow, decrease in intraocular pressure and neuroprotective properties. The vasodilation caused by estrogen and its effects on aqueous humor outflow may contribute. In contrast, although testosterone may have known effects in the cardiovascular and cerebrovascular systems, there is no consensus as to its effects in ocular health or POAG. With a better understanding of sex hormones in POAG, sex hormone-derived preventative and therapeutic considerations in disease management may provide for improved sex-specific patient care.