Association of Brain Volume and Retinal Thickness in the Early Stages of Alzheimer's Disease.

BACKGROUND: 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.

Prevalence Rates and Risk Factors for Primary Open Angle Glaucoma in the Middle East.

Glaucoma 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.

Craniofacial Trauma and Vascular Injury.

Cerebrovascular injury is a potentially devastating outcome following craniofacial trauma. Interventional radiologists play an important role in detecting, grading, and treating the different types of vascular injury. Computed tomography angiography plays a significant role in the detection of these injuries. Carotid-cavernous fistulas, extra-axial hematomas, pseudoaneurysms, and arterial lacerations are rare vessel injuries resulting from craniofacial trauma. If left untreated, these injuries can lead to vessel rupture and hemorrhage into surrounding areas. Acute management of these vessel injuries includes early identification with angiography and treatment with endovascular embolization. Endovascular therapy resolves vessel abnormalities and reduces the risk of vessel rupture and associated complications.

Can the Treatment of Normal-Pressure Hydrocephalus Induce Normal-Tension Glaucoma? A Narrative Review of a Current Knowledge.

Ventriculoperitoneal shunt placement is the most commonly used treatment of normal-pressure hydrocephalus (NPH). It has been hypothesized that normal-tension glaucoma (NTG) is caused by the treatment of NPH by using the shunt to reduce intracranial pressure (ICP). The aim of this study is to review the literature published regarding this hypothesis and to emphasize the need for neuro-ophthalmic follow-up for the concerned patients. The source literature was selected from the results of an online PubMed search, using the keywords "hydrocephalus glaucoma" and "normal-tension glaucoma shunt". One prospective study on adults, one prospective study on children, two retrospective studies on adults and children, two case reports, three review papers including medical hypotheses, and one prospective study on monkeys were identified. Hypothesis about the association between the treatment of NPH using the shunt to reduce ICP and the development of NTG were supported in all reviewed papers. This suggests that a safe lower limit of ICP for neurological patients, especially shunt-treated NPH patients, should be kept. Thus, we proposed to modify the paradigm of safe upper ICP threshold recommended in neurosurgery and neurology into the paradigm of safe ICP corridor applicable in neurology and ophthalmology, especially for shunt-treated hydrocephalic and glaucoma patients.

Etiology, pathogenesis and management of idiopathic intracranial hypertension, and role of optic canal size in asymmetric papilledema: A review.

Idiopathic intracranial hypertension (IIH) is characterized by raised intracranial pressure of unknown origin that primarily afflicts obese women of childbearing age. There are several treatment options, but currently there are none that are effective for the entire affected population. The lack of a universally effective treatment is related to an incomplete understanding of the etiology of the condition and the lack of a well-defined pathophysiological mechanism for the disease process. Classically, IIH has been thought of as a diagnosis of exclusion once radiographical imaging has ruled out all other causes of elevated intracranial pressure. Today, we know that imaging does capture subtle changes, and might provide keys to finally understand the pathogenesis of IIH so that a definitive treatment can be discovered or developed. Recently, advancements in radiography, optical coherence tomography, and electroretinography have shown promise for the future of IIH evaluation. A topic within IIH imaging that has recently sparked interest is the possibility that the severity of papilledema may have an association with the size of the optic canal. In this article, we also discuss the recent studies on the relationship between asymmetric papilledema and optic canal size.

Retinal oximetry in glaucoma: investigations and findings reviewed.

Abnormalities of the retinal blood supply have been widely implicated in primary open-angle glaucoma (POAG). Impaired blood supply to the retina and optic nerve head (ONH) may be a primary pathophysiologic mechanism contributing to POAG ('vascular hypothesis'). However, the decreased metabolic activity of atrophic tissue is itself known to induce both vascular changes and decreased blood flow due to reduced oxygen demand. Therefore, primary nonvascular factors could potentially induce glaucomatous atrophy, with subsequent secondary vascular pathology ('mechanical hypothesis'). Retinal oximetry holds great promise in the investigation of glaucoma pathogenesis, as it can provide useful data on retinal metabolic oxygen demand, especially when combined with measurements of retinal blood flow. This review surveys the research on retinal metabolism in POAG using spectroscopic retinal oximetry. The use of mathematical models in combination with oximetric data to investigate the role of retinal metabolism and oxygen supply in POAG is also discussed.

Optic disc haemorrhage and primary open-angle glaucoma: a clinical review.

Studies have confirmed that optic disc haemorrhage (ODH) is a significant risk factor for the development and progression of primary open-angle glaucoma (POAG). Various populations have differing risk factors for developing POAG. As such, a literature review was conducted examining seven studies published in India, China, Japan, Australia, Korea and the USA. The goal of this review was to better identify ODH risk factors and their relationship to development and progression of POAG. Ultimately, patients with ODH have a greater risk for developing POAG across all populations analysed in this review. However, some populations demonstrated additional risk factors for ODH, such as increasing age and female gender. Paradoxically, data from several studies show that people of African descent have a reduced risk of ODH despite having increased risk of open-angle glaucoma than their Caucasian counterparts. By parsing out the complex relations between ODH and open-angle glaucoma stratified by age, gender and race, we may gain a broader understanding of glaucoma pathogenesis and derive individualised treatment strategies.

Ocular blood flow as a clinical observation: Value, limitations and data analysis.

Alterations in ocular blood flow have been identified as important risk factors for the onset and progression of numerous diseases of the eye. In particular, several population-based and longitudinal-based studies have provided compelling evidence of hemodynamic biomarkers as independent risk factors for ocular disease throughout several different geographic regions. Despite this evidence, the relative contribution of blood flow to ocular physiology and pathology in synergy with other risk factors and comorbidities (e.g., age, gender, race, diabetes and hypertension) remains uncertain. There is currently no gold standard for assessing all relevant vascular beds in the eye, and the heterogeneous vascular biomarkers derived from multiple ocular imaging technologies are non-interchangeable and difficult to interpret as a whole. As a result of these disease complexities and imaging limitations, standard statistical methods often yield inconsistent results across studies and are unable to quantify or explain a patient's overall risk for ocular disease. Combining mathematical modeling with artificial intelligence holds great promise for advancing data analysis in ophthalmology and enabling individualized risk assessment from diverse, multi-input clinical and demographic biomarkers. Mechanism-driven mathematical modeling makes virtual laboratories available to investigate pathogenic mechanisms, advance diagnostic ability and improve disease management. Artificial intelligence provides a novel method for utilizing a vast amount of data from a wide range of patient types to diagnose and monitor ocular disease. This article reviews the state of the art and major unanswered questions related to ocular vascular anatomy and physiology, ocular imaging techniques, clinical findings in glaucoma and other eye diseases, and mechanistic modeling predictions, while laying a path for integrating clinical observations with mathematical models and artificial intelligence. Viable alternatives for integrated data analysis are proposed that aim to overcome the limitations of standard statistical approaches and enable individually tailored precision medicine in ophthalmology.

Risk Factors for Open-angle Glaucoma in Persons of Latin American Descent.

PURPOSE: The aim of this paper is to concisely summarize what is currently known about OAG among persons of LAD in the United States for the purpose of improving individualized care and highlighting areas requiring further study. MATERIALS AND METHODS: Review of relevant literature was performed through PubMed and Google Scholar from October 1978 through November 11, 2019. RESULTS: As the Latin American population grows within the United States, it is predicted that by 2050, men of LAD will make up the largest demographic group with OAG. Persons of LAD experience a greater increase in OAG prevalence per decade of life compared with persons of African descent and may have unique risk factors. In particular, those with African ancestry and hypertension are at greater risk of elevated intraocular pressure (IOP). Maximum IOP, variability in IOP, and diabetes are also important considerations. Unique anatomic and physiological characteristics such as scleral tensile strain, longer axial length, thin corneas, and corneal hysteresis may play a role in this population's unique risk for the development and progression of OAG. CONCLUSIONS: OAG represents a growing concern among persons of LAD in the United States; however, information on specific risk factors in this population currently remains limited. Studies should be designed to investigate the LAD population and their respective structural, vascular, and social risk factors for the development and progression of OAG to assist clinicians in improving outcomes for this growing population.

The Influence of Translaminar Pressure Gradient and Intracranial Pressure in Glaucoma: A Review.

The current evidence associating intracranial pressure (ICP) with glaucoma, the translaminar pressure gradient hypothesis, and anatomic factors likely affecting the relationship between ICP and retrolaminar tissue pressure including the size of the optic canal and lamina cribrosa thickness are reviewed. In addition, the evidence of diurnal and positional variation on the translaminar pressure gradient, effects of glaucoma medications, evidence of ICP helping to maintain cerebrospinal fluid flow in the optic nerve to prevent glaucomatous damage, and the effect of intraocular pressure variation in glaucoma are also reviewed. We find that while low ICP is associated with glaucoma disease in most studies, evidence is mixed on how closely ICP matches retrolaminar tissue pressure, and it appears the relationship is affected by the size of the optic canal, thickness of the lamina cribrosa, and lymphatic outflow from the optic nerve. Future studies can likely strengthen associations by measuring and controlling for some of these factors.

Review of non-invasive intracranial pressure measurement techniques for ophthalmology applications.

Assessment and monitoring of intracranial pressure (ICP) are important in the management of traumatic brain injury and other cerebral pathologies. In the eye, ICP elevation and depression both correlate with optic neuropathies, the former because of papilledema and the latter related to glaucoma. While the relationship between ICP elevation and papilledema is well established, the relationship between low ICP and glaucoma is still poorly understood. So far, ICP monitoring is performed invasively, but this entails risks including infection, spurring the study of non-invasive alternatives. We review 11 methods of non-invasive estimation of ICP including correlation to optic nerve sheath diameter, intraocular pressure, ophthalmodynamometry and two-depth transcranial Doppler of the ophthalmic artery. While none of these methods can fully replace invasive techniques, certain measures show great potential for specific applications. Although only used in small studies to date, a MRI based method known as MR-ICP, appears to be the best non-invasive technique for estimating ICP, with two-depth transcranial ultrasound and ophthalmodynamometry showing potential as well.

Ocular changes in traumatic brain injury: A review.

Traumatic brain injury is represented by a penetrating or non-penetrating head injury, which causes disruption in the normal functioning of the brain. Traumatic brain injury has been an ardently debated topic of discussion due to its prevalence in media centric persons such as military personnel and athletes. Current assessments for traumatic brain injury have looked at vestibulo-ocular and vascular parameters to aid in diagnosis. Innovations in non-invasive ophthalmic imaging have allowed for the visualization of specific tissue structure/function relationships in a variety of ophthalmic and neurodegenerative diseases. As the eye and brain share significant embryological and physiological pathways, ocular imaging modalities may provide a novel and impactful tool in advancing assessment of traumatic brain injury. Herein, we examined the available literature and data on visual fields, mean retinal nerve fiber layer thickness, retinal ganglion cell layer thickness, and cerebral blood flow following traumatic brain injury. This review of published individual and population-based studies was performed in order to explore the feasibility and importance of considering ocular imaging biomarkers following traumatic brain injury.

Circadian Rhythm and Glaucoma: What do We Know?

PURPOSE: The current understanding of circadian regulation disorders and their involvement in glaucoma pathophysiology are poorly understood, yet they may have a substantial impact on the onset and progression of glaucoma. Herein, we review and summarize all the available literature on circadian rhythm disorder and glaucoma to uncover the impact on glaucoma risk, and we highlight future research and potential novel targets for glaucoma management. MATERIALS AND METHODS: A review of the relevant literature was performed through PubMed through August 1, 2019. RESULTS: Within a normal circadian rhythm, intraocular pressure (IOP) peaks at night, whereas blood pressure (BP) troughs at night. High nocturnal IOP coupled with low nocturnal systemic BP results in low ocular perfusion pressure and potential for unobserved damage to retinal tissues and the optic nerve. Circadian-related melatonin and sleep disorders also result in changes in IOP and ocular perfusion pressure that lead to the progression of glaucoma. In addition, impaired perception of light input due to glaucoma can subsequently lead to abnormal serum levels of melatonin, resulting in circadian rhythm misalignment. This disruption of the circadian rhythm also contributes to sleep and mood disorders, common in individuals with glaucoma. As regards treatment, glaucoma medications that lower nocturnal IOP without influencing nocturnal BP or diminishing circadian variation seem most effective. CONCLUSIONS: Glaucoma progression is influenced by multiple physiological factors regulated by the circadian rhythm. Progression of the disease may also cause physiological changes that lead to circadian-related issues. Further research is warranted on the diurnal cycle, melatonin-mediated processes, and their influence on glaucoma management.

Management of Glaucoma in Pregnancy.

Management of glaucoma during pregnancy represents a challenge for the physician. Important disease and patients' health decisions begin even before conception and continue throughout pregnancy and breastfeeding. The data on this topic is limited due to ethical and legal constraints and challenges of conducting large, prospective, and randomized clinical trials on this patient population. Our review suggests that individually, intraocular pressure is lower in a pregnant woman when compared with a nonpregnant woman. Importantly, the medical management of glaucoma during pregnancy poses special challenges due to the possibility of adverse effects of medications on the fetus and newborn. Laser trabeculoplasty and traditional filtration surgery, and minimally invasive glaucoma surgery, represent nondrug management options. Thus, managing glaucoma in pregnancy is a delicate balance between treatment to prevent damage to the optic nerve in the mother and avoidance of interventions potentially harmful to the fetus. This literature review of published individual and population-based studies was performed to explore current knowledge and guidelines in the management of glaucoma in pregnancy.

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.

Lutein Complex Supplementation Increases Ocular Blood Flow Biomarkers in Healthy Subjects.

Introduction: To investigate the effects of a lutein complex supplementation on ocular blood flow in healthy subjects. Materials and Methods: Sixteen healthy female patients (mean age 36.8 ± 12.1 years) were enrolled in this randomized, placebo-controlled, double-blinded, two-period crossover study. Subjects received daily an oral dose of the lutein with synergistic phytochemicals complex (lutein (10 mg), ascorbic acid (500 mg), tocopherols (364 mg), carnosic acid (2.5 mg), zeaxanthin (2 mg), copper (2 mg), with synergistic effects in reducing pro-inflammatory mediators and cytokines when administered together in combination) and placebo during administration periods. Measurements were taken before and after three-week supplementation periods, with crossover visits separated by a three-week washout period. Data analysis included blood pressure, heart rate, intraocular pressure, visual acuity, contrast sensitivity detection, ocular perfusion pressure, confocal scanning laser Doppler imaging of retinal capillary blood flow, and Doppler imaging of the retrobulbar blood vessels. Results: Lutein complex supplementation produced a statistically significant increase in mean superior retinal capillary blood flow, measured in arbitrary units (60, p = 0.0466) and a decrease in the percentage of avascular area in the superior (-0.029, p = 0.0491) and inferior (-0.023, p = 0.0477) retina, as well as reduced systolic (-4.06, p = 0.0295) and diastolic (-3.69, p = 0.0441) blood pressure measured in mmHg from baseline. Data comparison between the two supplement groups revealed a significant decrease in systemic diastolic blood pressure (change from pre- to post-treatment with lutein supplement (mean (SE)): -3.69 (1.68); change from pre- to post-treatment with placebo: 0.31 (2.57); p = 0.0357) and a significant increase in the peak systolic velocity (measured in cm/sec) in the central retinal artery (change from pre- to post-treatment with lutein supplement: 0.36 (0.19); change from pre- to post-treatment with placebo: -0.33 (0.21); p = 0.0384) with lutein complex supplement; data analyses from the placebo group were all non-significant. Discussion: In healthy participants, oral administration of a lutein phytochemicals complex for three weeks produced increased ocular blood flow biomarkers within retinal vascular beds and reduced diastolic blood pressure compared to placebo.

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.

Neurothekeoma of the eyelid: a case report.

The purpose of this article is to describe a rare benign tumor of nerve sheath origin arising from the eyelid in an elderly male. Local excision was done and histopathological examination revealed a neurothekeoma. Six months later the patient was doing well with no recurrence. The case was unique in that the patient was an elderly male while neurothekeoma is commonly seen on the face of young adults, especially females.