Article

Ocular and optic nerve blood flow at normal and increased intraocular pressures in monkeys (Macaca Irus): a study with radioactively labeled microspheres including flow determinations in brain and some other tissues

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Abstract

The effects of moderate increments in the intraocular pressure on blood flow rates in the various tissues of the eye were studied in monkeys. Blood flow rates were determined with radioactively labelled microspheres, 15 μm in diam. One eye had its spontaneous intraocular pressure while the other eye had its pressure stabilized at a higher level. The mean values for the intraocular pressures in the two eyes were 13 and 41 cm H2O respectively. In eyes with spontaneous intraocular pressure mean blood flow through the retina, the iris, the ciliary body, and the choroid were 25, 17, 89, and 607 mg/min respectively. Blood flow through the ciliary processes was 222 and through the ciliary muscle 153 g/min/00 g tissue respectively. In eyes with increased intraocular pressure there were statistically significant reductions in blood flow through the choroid and through the prelaminar part of the optic nerve by 29 and 30% of the mean blood flow through control eyes respectively. The changes in blood flow through the retina, the iris, the ciliary processes and the ciliary muscle were not statistically significant. They ranged from a reduction by 8% to an increase by 19% in eyes with increased intraocular pressure. The results suggest that even moderate increments in intraocular pressure cause clear reductions in the blood flow through the choroid and through the prelaminar part of the optic nerve, while blood flow through the retina outside the optic disc and through the different parts of the anterior uvea is efficiently autoregulated. It is suggested that the susceptibility of the optic disc to increments in intraocular pressure is due to the deficient autoregulation of blood flow through the optic disc, which in turn might be explained by the choroidal origin of the optic disc vessels which interferes with normal autoregulatory mechanisms.

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... In the context of trans-scleral drug movement, where the drug penetrates all layers of the sclera and reaches the choroid, an additional dynamic barrier is presented. Choroidal blood flow is considerable; comparable only to, and in some cases exceeding, blood flow through the kidneys [54]. In common pharmacokinetic drug models for topical drug delivery, the choroid is usually regarded as a sink condition, in which the drug concentration is assumed to be zero [55]. ...
... Comparatively, the BRB o , comprised of the RPE, which rests upon the underlying Bruch membrane, separates the neural retina from the adjacent fenestrated choroidal capillaries. This capillary network is extensive, providing the retina with blood at a rate of 696±110 mg/min throughout the whole choroid [5,54]. Whilst systemically administered, neutral drug moieties up to 500 kDa freely enter the choroidal parenchyma through these fenestrations, entry through the BRBo is significantly limited based on the drug's physicochemical properties. ...
... This model, however, fails to consider the eye does not have homogenous attenuation throughout, rather the separate structures of the eye will attenuate the acoustic wave at different rates, and therefore heat at differing rates. The choroid, for instance, has an acoustic attenuation of 0.5 dB cm -1 MHz -1 (Table 5), but has the greatest vascular flow per gram of any body tissue, minimising the rate of heating expected in this tissue [54]. Comparatively, the lens, which has an appreciable mean thickness of 4-4.7 mm (increasing in thickness from 20-60 years), has a higher attenuation coefficient of 1.38 dB cm -1 MHz -1 (Table 5) [168,169]. ...
Article
Ultrasound has long been identified as a promising, non-invasive modality for improving ocular drug delivery across a range of indications. Yet, with 20 years of learnings behind us, clinical translation remains limited. To help address this, and in accordance with PRISMA guidelines, the various mechanisms of ultrasound-mediated ocular drug delivery have been appraised, ranging from first principles to emergent applications spanning both ex vivo and in vivo models. The heterogeneity of study methods precluded meta-analysis, however an extensive characterisation of the included studies allowed for semi-quantitative and qualitative assessments. Methods: In this review, we reflected on study quality of reporting, and risk of bias (RoB) using the latest Animal Research: Reporting of In Vivo Experiments (ARRIVE 2.0) guidelines, alongside the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) RoB tools. Literature studies from 2002 to 2022 were initially characterised according to methods of ultrasound application, ultrasound parameters applied, animal models employed, as well as safety and efficacy assessments. This exercise contributed to developing a comprehensive understanding of the current state of play within ultrasound-mediated ocular drug delivery. The results were then synthesised and processed into a guide to aid future study design, with the goal of improving the reliability of data, and to support efficient and timely translation to the clinic. Results: Key attributes identified as hindering translation included: poor reporting quality and high RoB, skewed use of animals unrepresentative of the human eye, and the over reliance of reductionist safety assessments. Ex vivo modelling studies were often unable to have comprehensive safety assessments performed on them, which are imperative to determining treatment safety, and represent a prerequisite for clinical translation. Conclusion: With the use of our synthesised guide, and a thorough understanding of the underlying physicochemical interactions between ultrasound and ocular biology provided herein, this review offers a firm foundation on which future studies should ideally be built, such that ultrasound-mediated ocular drug delivery can be translated from concept to the coalface where it can provide immense clinical benefit.
... While the central retinal artery provides the inner retina's blood supply, most of its oxygen demand (seven times greater than that of the brain per mass unit) is supplied by diffusion from the underlying choroid, which is the sole supply of the avascular fovea. The choroid has the highest rate of blood flow per weight of any tissue [43]. The choroid, because of its intense blood flow and the permeability of the Bruch's membrane (BM), has a major role in the thermoregulation of the macula. ...
... The Bruch's membrane is semi-permeable and this membrane is formed of glycated proteins such as heparin. The flow of the choroidal arteries is about 10 to 20 times higher than the flow of the retinal arteries [43,45], increasing the hydrostatic pressure in the retina. ...
Article
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Age-related macular degeneration (AMD) is both a poorly understood and devastating disease. Here, we analyze the physico-chemical forces at stake, including osmolarity, redox shift, and pressure due to inflammation. Hyperosmolarity plays a key role in diseases of the anterior segment of the eye such as glaucoma, cataracts or dry eyes, and corneal ulceration. However, its role in macular degeneration has been largely overlooked. Hyperosmolarity is responsible for metabolic shifts such as aerobic glycolysis which increases lactate secretion by Muller cells. Increased osmolarity will also cause neoangiogenesis and cell death. Because of its unique energetic demands, the macula is very sensitive to metabolic shifts. As a proof of concept, subretinal injection of drugs increasing hyperosmolarity such as polyethylene glycol causes neoangiogenesis and drusen-like structures in rodents. The link between AMD and hyperosmolarity is reinforced by the fact that treatments aiming to restore mitochondrial activity, such as lipoic acid and/or methylene blue, have been experimentally shown to be effective. We suggest that metabolic shift, inflammation, and hyperosmolarity are hallmarks in the pathogenesis and treatment of AMD.
... While the central retinal artery provides the inner retina's blood supply, most of its oxygen demand (seven times more important than that of the brain at constant weight) is supplied by diffusion from the underlying choroid, which is the sole supply of the avascular fovea. The choroid has the highest rate of blood flow per weight of any tissue [75]. The choroid, because of its intense blood flow and the permeability of the Bruch's membrane, has a major role in the thermoregulation of the macula. ...
... The Bruch's membrane is semi-permeable and this membrane is formed of glycated proteins such as heparin. The flow of the choroidal arteries is about 10 to 20 times more important than the flow of the retinal arteries [75,77], increasing the hydrostatic pressure in the retina. The two compartments of dialysis in the eye are the retinal pigment epithelium (RPE) and outer segments of the visual cells (OS) as the dialyzed sector animated by a centripetal flow, and secondary the choroid, which may be equated with a dialyzing bath driven by a centrifugal rather than counter flow. ...
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In our previous papers, we demonstrated that inflammation and aging are the common roots of cancer and Alzheimer’s disease (AD). In both diseases, there is an inhibition of the mitochondria. In cancer, the alkaline intracellular pH (pHi) is associated with cell proliferation; acidic pHi causes apoptosis in AD. This difference is because cancer feeds on chemically neutral glucose, while neurons feed on acidic lactic acid. Increased uptake of lactic acid is responsible for acidic pH and cell death. Similarly, to AD, inflammation is responsible for metabolic shifts in age-related macular degeneration (AMD). In AD, there is hyperosmolarity responsible for increased lactic secretion by glial cells. Increased lactic secretion will cause neo-angiogenesis and neural cell death. Drugs increasing hyperosmolarity (Polyethylene Glycol) cause neo-angiogenesis and drusen-like structures in rodents. The link between AMD and inflammation is reinforced by the fact that treatments aiming at restoring mitochondrial activity, such as lipoic acid and/or methylene blue, have been experimentally shown to be effective in each set of diseases. The role of osmolarity has been demonstrated in the pathologies of the anterior segment of the eye, such as dry eye, corneal ulceration, cataracts, and glaucoma. The role of increased osmolarity in age-related macular degeneration (AMD) has been largely overlooked. We herein suggest that metabolic shift, inflammation, and hyperosmolarity are key players in the pathogenesis of AMD.
... Volume SD-OCT scans (27 lines, automated retinal tracking, 16 scans averaged per line, good quality at least (29)(30)(31)(32)(33)(34) per the device specifications) were obtained on the Heidelberg Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Delaware, USA). Subjects without good-quality SD-OCT scans were removed. ...
... Previous research on SDDs has uncovered several findings that corroborate the perfusion hypothesis-mean choroidal thickness on SD-OCT has been found to be less in persons with SDDs and drusen compared with drusen alone, and CC flow deficits on SD-OCT angiography are more pronounced in those with SDDs compared with those with conventional drusen. [26][27][28] It is well known that the CC perfuses the RPE and photoreceptors 29 ; since photoreceptors have the highest ATP and oxygen demand in the eye 30 and the choroid has the highest rate of blood flow per unit weight of any tissue in the body, 31 it follows that photoreceptors would be highly sensitive to any disruption in choroidal blood supply. Moreover, our results show that the AMD subjects with HRVDs had higher odds of having SDDs compared with drusen only. ...
Article
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Purpose Subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are associated with systemic vascular diseases that compromise ocular perfusion. We demonstrate that SDDs are associated with decreased ellipsoid zone (EZ) thickness, further evidence of hypoxic damage. Methods Post hoc analysis of a cross-sectional study. 165 AMD subjects (aged 51–100; 61% women). Spectral-domain optical coherence tomography was obtained in both eyes. Masked readers assigned subjects to three groups: drusen only, SDD+drusen (SDD+D) and SDD only. EZ thickness was measured subfoveally and 2000 µm nasally, temporally, superiorly and inferiorly from the fovea. Univariate testing was performed using two-tailed t-tests with Bonferroni correction. Results The mean EZ thickness differences between the SDD+D and drusen-only groups were (in μm) 1.10, 0.67, 1.21, 1.10 and 0.50 at the foveal, nasal, temporal, superior and inferior locations, respectively (p=0.08 inferiorly, otherwise p≤0.01); between the SDD-only and drusen-only groups, the differences were 3.48, 2.48, 2.42, 2.08 and 1.42 (p≤0.0002). Differences in EZ thicknesses across all subjects and between groups were not significantly different based on gender, race or age. Conclusion Subjects with SDDs (±drusen) had thinner EZs than those with drusen only, and the inferior EZ was least affected. EZs were thinnest in SDD-only subjects. This thinning gradation is consistent with progressive destruction of highly oxygen-sensitive mitochondria in the EZ from hypoxia. These findings support the reduced ophthalmic perfusion hypothesis for the formation of SDDs secondary to high-risk systemic vasculopathy.
... AUC SIM refers to AUC obtained with an optimized set of parameters and AUC AE50% refers to AUC obtained by fret 0.05 [52] ficb 0.13 [52] Q AH (L/h) 6.39 9 10 -5 [54] Q VA (L/h) 2.28 9 10 -5 [55] Q BF (L/h) Q PtA -Q AH ? Q VA Calculated Q PtA (L/h) 1.02 9 10 -4 [54] PS cornea (L/h) 2.62 9 10 -8 [56,57] PS ret (L/h) 3.00 9 10 -6 [14,55] PS cho (L/h) 2.45 9 10 -6 [14,58,59] V AH (L) 1.29 9 10 -4 [58] V VH (L) 2.04 9 10 -4 [58] V lens (L) 1.00 9 10 -4 [58] V cornea (L) 4.36 9 10 -5 [58] ...
... AUC SIM refers to AUC obtained with an optimized set of parameters and AUC AE50% refers to AUC obtained by fret 0.05 [52] ficb 0.13 [52] Q AH (L/h) 6.39 9 10 -5 [54] Q VA (L/h) 2.28 9 10 -5 [55] Q BF (L/h) Q PtA -Q AH ? Q VA Calculated Q PtA (L/h) 1.02 9 10 -4 [54] PS cornea (L/h) 2.62 9 10 -8 [56,57] PS ret (L/h) 3.00 9 10 -6 [14,55] PS cho (L/h) 2.45 9 10 -6 [14,58,59] V AH (L) 1.29 9 10 -4 [58] V VH (L) 2.04 9 10 -4 [58] V lens (L) 1.00 9 10 -4 [58] V cornea (L) 4.36 9 10 -5 [58] ...
Article
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We have previously published a PBPK model comprising the ocular compartment to characterize the disposition of monoclonal antibodies (mAbs) in rabbits. While rabbits are commonly used preclinical species in ocular research, non-human primates (NHPs) have the most phylogenetic resemblance to humans including the presence of macula in the eyes as well as higher sequence homology. However, their use in ocular research is limited due to the strict ethical guidelines. Similarly, in humans the ocular samples cannot be collected except for the tapping of aqueous humor (AH). Therefore, we have translated this rabbit model to monkeys and human species using literature-reported datasets. Parameters describing the tissue volumes, physiological flows, and FcRn-binding were obtained from the literature, or estimated by fitting the model to the data. In the monkey model, the values for the rate of lysosomal degradation for antibodies (Kdeg), intraocular reflection coefficients (σaq, σret, σcho), bidirectional rate of fluid circulation between the vitreous chamber and the aqueous chamber (QVA), and permeability-surface area product of lens (PSlens) were estimated; and were found to be 31.5 h⁻¹, 0.7629, 0.6982, 0.9999, 1.64 × 10–5 L/h, and 4.62 × 10–7 L/h, respectively. The monkey model could capture the data in plasma, aqueous humor, vitreous humor and retina reasonably well with the predictions being within twofold of the observed values. For the human model, only the value of Kdeg was estimated to fit the model to the plasma pharmacokinetics (PK) of mAbs and was found to be 24.4 h⁻¹ (4.14%). The human model could also capture the ocular PK data reasonably well with the predictions being within two- to threefold of observed values for the plasma, aqueous and vitreous humor. Thus, the proposed framework can be used to characterize and predict the PK of mAbs in the eye of monkey and human species following systemic and intravitreal administration. The model can also facilitate the development of new antibody-based therapeutics for the treatment of ocular diseases as well as predict ocular toxicities of such molecules following systemic administration.
... Choroid is predominantly composed of blood vessels and is one of the tissues with the highest blood flow in the body. 33,34 Agrawal et al. 35 found that vascular area is a predominant segment influencing choroidal thickness in the normal population. The choroidal vessels can be differentiated into three layers: capillary plexus in the innermost layer, Sattler's layer with medium vessels in the middle, and Haller's layer with large vessels in the outer. ...
... The choroidal vessels can be differentiated into three layers: capillary plexus in the innermost layer, Sattler's layer with medium vessels in the middle, and Haller's layer with large vessels in the outer. 33 The ultra-widefield SS-OCTA used in this study allows wider non-invasive quantitative assessment of choroidal vascular indices in the different layers. Al-Sheikh et al. 36 and Su et al. 37 both reported that the area of flow deficit in the choriocapillaris increased in eyes with greater myopia; however, no significant difference in the vessel density of CCP was found among the different degrees of myopia in any grid in this study. ...
Article
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Purpose: To evaluate choroidal changes in young adults with myopia using ultra-widefield swept-source optical coherence tomography angiography (SS-OCTA). Methods: This study enrolled 105 eyes of 105 participants who underwent SS-OCTA imaging (24 mm × 20 mm) centered on the fovea. Eyes were categorized as low myopia, moderate myopia, or high myopia. Choroidal thickness, choroidal capillary plexus (CCP) vessel density, and choroidal Sattler's and Haller's layer (CSHL) vessel density were analyzed in nine grids using built-in angiography analysis software. Results: A significant decrease in choroidal thickness was found in most grids (P < 0.01) in high myopia. The CSHL vessel density also showed a significant decrease in most grids (P < 0.05) in high myopia. Choroidal thickness was negatively correlated with axial length in most grids (P < 0.05). Choroidal thinning was most evident in the macular grid (β = -22.55, P < 0.001). CSHL vessel density was negatively correlated with axial length in most grids (P < 0.05). Conclusions: Choroidal changes could be quantified using ultra-widefield SS-OCTA. Choroidal thinning with increasing axial length indicated regional differences in eyes with myopia, which were most evident in the macular area. Decreased CSHL vessel density with increasing axial length also indicated regional differences in eyes with myopia. Translational relevance: This study explored choroidal changes with a wider field of view than has been currently available.
... The blood flow in rabbit iris is 3.72 ml/h, and in the ciliary body, it is 4.91 ml/h (Nilsson and Alm, 2012). The corresponding values in monkeys are 1.02 ml/h and 5.34 ml/h, respectively (Alm and Bill, 1973). The iris-ciliary muscle vessels constitute the outer BAB (excluding the ciliary process vessels). ...
... The most probable path for the topical drugs to enter the posterior tissues is via the non-corneal route as described previously by Ahmed and Patton, (1985); Ahmed and Patton, (1987), that is, the drug permeates across the anterior sclera through the suprachoroidal space and reaches the choroidal tissue. The choroid is a vascular and connective tissue layer that consists primarily of large and highly fenestrated blood vessels, with the highest blood flow per unit weight compared to any other tissue in the body (Alm and Bill, 1973), being 62 ml/h in rabbits (Nilsson and Alm, 2012) and 43 ml/h in humans (Sebag et al., 1994). Therefore, most of the drug that enters Schematic representation of the non-productive conjunctival absorption of a drug (1) and the non-corneal absorption route with drug permeation through the conjunctiva and sclera, (2) reaching the iris-ciliary body, from the sclera to the choroid (3), only a small fraction may cross the RPE (retinal pigment epithelium) to penetrate the peripheral retina. ...
Article
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Topical ophthalmic instillation is an appealing strategy to deliver drugs to the back of the eye to treat retinal diseases such as neovascular age-related macular degeneration, diabetic retinopathy, retinal vein occlusion, and glaucomatous optic neuropathy. It has several advantages such as being non-invasive and user-friendly, e.g., allowing self-administration. However, the main obstacle has been how to achieve therapeutic drug concentrations in the retina due to the eye’s protective mechanisms, flows, and barriers. Less than 4% of the instilled drug dose enters the anterior chamber, and much less is expected to reach the posterior segment. It is crucial to understand a drug’s topical pharmacokinetics in humans and how one can extrapolate data from rabbits to humans. In this review, the available data on the retina and vitreous drug concentrations from pharmacokinetics studies conducted in human patients and rabbits have been compiled, together with the critical physiological factors to be considered for this route of administration. Improvements in the design of preclinical studies are suggested to increase their translatability to the treatment of human patients. Finally, the current status of clinical trials with topical ophthalmic formulations intended to treat the back of the eye is depicted. At present, no topical ophthalmic formulations to treat neovascular age-related macular degeneration or other retinal neurodegenerative illnesses have reached the market.
... Previously, inflammatory cytokines has been shown to induce the upregulation of early complement components in RPE (Chen et al., 2008;Juel et al., 2011;Faber et al., 2019). Given the potential high exposure of circulating cytokines in the highly perfused macular choriocapillaris (Alm and Bill, 1973), this could represent an early event in development of AMD. Thus, we sought to examine if inflammatory cytokines could mediate complement activation on the RPE cells. ...
... The high blood flow rate of the macular choriocapillaris results in a high RPE-exposure to circulating inflammatory mediators present in AMD (Alm and Bill, 1973). As such, alterations in levels of soluble mediators (Faber et al., 2015;Krogh Nielsen et al., 2019;Hong et al., 2011;Mo et al., 2010;Seddon et al., 2005;Liu et al., 2011) as well as alterations in levels and phenotypes of several leukocyte subsets Faber et al., 2013;Cousins, 2004;McLeod et al., 2016;Lechner et al., 2015) have been documented in AMD. ...
Article
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Age-related macular degeneration (AMD) has been associated with both complement activation and increased levels of circulating cytokines. Here, we sougth to investigate if cytokine-preexposure of retinal pigment epithelial (RPE) leads to increased complement activation and deposition of membrane attack complex (MAC). Primary human RPE and the ARPE19 cell line cultured in serum-free conditions were preexposed to 100 ng/ml interferon-gamma (IFNγ) and 20 ng/ml tumor necrosis factor-alpha (TNFα) for 48 h followed by exposure to diluted serum from healthy donors or complement factor B deficient (CFBd) serum for 70 min. Deposition of membrane attack complexes (MAC) was examined by use of a MAC-ELISA kit and by immunofluorescence. Eculizumab (anti-C5) was examined for its ability to prevent deposition of MAC on RPE cells exposed to serum. Lactatdehydrogenase (LDH) and thiazolyl blue tetrazolium bromide (MTT) assays were used to assess cellular metabolism and survival. MAC was deposited only on RPE preexposed to both IFNγ and TNFα. Lack of complement factor B or inhibition of C5 abrogated the MAC-deposition on RPE cells, while reconstitution of CFBd serum with CFB resulted in MAC-deposition. MAC-deposition resulted in RPE-release of LDH, but unaltered mitochondrial activity estimated by MTT. We conclude that preexposure of primary RPE and ARPE19 with inflammatory cytokines promoted alternative pathway activation of complement and deposition of MAC. This implies that circulating inflammatory mediators may increase susceptibility to local complement activation and MAC-deposition, which may represent an early event in the pathogenesis leading to AMD development.
... The choroid is a highly vascularized tissue in the eye that is affected by various systemic abnormalities affecting the blood vessels and is crucial to the physiology and pathogenesis of various ocular diseases [1]. As the only source of metabolic exchange in the avascular fovea, the choroid has the highest blood flow per unit weight of any human tissue [2]. ...
Article
BACKGROUND No study has investigated the change regularity between age and subfoveal choroidal thickness (SFCT) in proliferative diabetic retinopathy (PDR). AIM To investigate the relationship between the SFCT and age in Chinese patients with PDR. METHODS This was a cross-sectional retrospective study. The participants were hospitalized individuals with type 2 diabetes who underwent vitrectomy for PDR. Con-tralateral eyes that met the criteria were included in the study. All necessary laboratory tests were performed at the time of admission. Central macular thickness (CMT) and SFCT were two quantitative assessments made using enhanced depth imaging optical coherence tomography. CMT was measured automatically and SFCT was measured manually with digital calipers provided by the Heidelberg Eye Explorer software. RESULTS The final analysis included a total of 234 individuals with PDR. The average age was 55.60 years old ± 10.03 years old, and 57.69% of the population was male. Univariate analysis revealed a significant negative connection between age and SFCT in patients with PDR [β = -2.44, 95% confidence interval (95%CI): -3.46 to -1.42; P < 0.0001]. In the fully adjusted model, the correlation between SFCT and age remained steady (β = -1.68, 95%CI: -2.97 to -0.39; P = 0.0117). Spline smoothing showed that the relationship between SFCT and age in patients with PDR was non-linear, with an inflection point at 54 years of age. CONCLUSION Our findings suggest that age is a key determinant of choroidal thickness. The non-linear link between SFCT and age in PDR patients should be taken into account.
... The major portion of the blood from the ophthalmic artery, contributes to uveal circulation (85%) and only 2-5% goes to the retinal vasculature [3]. Due to the pronounced capillary network, the choroid has the largest blood volume in proportion to the perfunded tissue weight in the entire body with a blood flow volume of 18 ml/min/g tissue [4]). It also appears to have autoregulation [5], although this is far less effective than retinal autoregulation. ...
Article
Color vision testing can be used to detect subtle disturbances in retinal function, which can often occur before clinical symptoms and, for the ophthalmologist, before visible changes in the fundus of the eye in general vascular diseases. This makes it possible to carry out rapid and inexpensive early diagnosis by detecting acquired color vision disorders, which can prevent further damage by optimizing therapy. Here it is particularly important to work closely with general practitioners and internists. Such aspects should be given greater consideration in occupational medicine. In many areas of industry, high demands are placed on color vision. In areas such as the textile industry, the chemical paint industry, the food industry, the automotive industry (paints) and in painting companies, normal color perception is of fundamental importance. Color vision testing is an inexpensive and easy-to-perform examination method that can provide an early indication of acquired color vision deficiency under standardized conditions. In addition to the detection of a generalized microcirculatory disorder, this determination is also useful in occupational medicine in order to better determine suitability for certain occupational groups.
... The retinal vessels do not contain neural innervation, while the choroid is innervated directly by the autonomic nervous system (18,19). Both vasculatures have been found to have myogenic autoregulation to maintain BF over a range of ocular perfusion pressure (23, 24), although a lack of autoregulation in the choroid has also been reported (21,25), showing the need for further research (18,19). The exact vascular pathophysiology in glaucoma and the underlying molecular mechanisms in the retina and choroid remain uncertain, which would need to be studied in disease models. ...
Article
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Purpose Blood flow (BF) of the retinal and choroidal vasculatures can be quantitatively imaged using MRI. This study sought to improve methods of data acquisition and analysis for MRI of layer-specific retinal and choroidal BF and then applied this approach to detect reduced ocular BF in a well-established mouse model of glaucoma from both eyes. Methods Quantitative BF magnetic resonance imaging (MRI) was performed on glaucomatous DBA/2J and normal C57BL/6J mice. Arterial spin labeling MRI was applied to image retinal and choroidal BF using custom-made dual eye coils that could image both eyes during the same scan. Statistics using data from a single eye or two eyes were compared. BF values were calculated using two approaches. The BF rate per quantity of tissue was calculated as commonly done, and the peak BF values of the retinal and choroidal vasculatures were taken. Additionally, the BF rate per retinal surface area was calculated using a new analysis approach to attempt to reduce partial volume and variability by integrating BF over the retinal and choroidal depths. Results Ocular BF of both eyes could be imaged using the dual coil setup without effecting scan time. Intraocular pressure was significantly elevated in DBA/2J mice compared to C57BL/6J mice (P<0.01). Both retinal and choroidal BF were significantly decreased in DBA/2J mice in comparison to the age-matched normal C57BL/6J mice across all measurements ( P < 0.01). From simulations, the values from the integrated BF analysis method had less partial volume effect, and from in vivo scans, this analysis approach also improved power. Conclusion The dual eye coil setup allows bilateral eye data acquisition, increasing the amount of data acquired without increasing acquisition times in vivo . The reduced ocular BF found using the improved acquisition and analysis approaches replicated the results of previous studies on DBA/2J mice. The ocular hypertensive stress-induced BF reduction found within these mice may represent changes associated with glaucomatous progression.
... Despite the structural differences between the two microcirculatory systems, their regulatory mechanisms and importance to retinal function vary significantly. This variation is partially evidenced by the measurement of oxygen tension profiles (Wright et al., 2020), where it has been shown that the choroidal circulation receives the majority of ocular blood and oxygen supply (80-85%) but has the lowest oxygen consumption (Alm and Bill, 1973). However, when oxygen partial pressure near the photoreceptor (PR) layer of the outer retina is measured with microelectrodes, a significant drop is observed, aligning with the high oxygen and energy demands of this region for photon detection (Yu and Cringle, 2006). ...
Article
The retinal microcirculation system constitutes a unique terminal vessel bed of the systemic circulation, and its perfusion status is directly associated with the neural function of the retina. This vascular network, essential for nourishing various layers of the retina, comprises two primary microcirculation systems: the retinal microcirculation and the choroidal microcirculation, with each system supplying blood to distinct retinal layers and maintaining the associated neural function. The blood flow of those capillaries is regulated via different mechanisms. However, a range of internal and external factors can disrupt the normal architecture and blood flow within the retinal microcirculation, leading to several retinal pathologies, including diabetic retinopathy, macular edema, and vascular occlusions. Metabolic disturbances such as hyperglycemia, hypertension, and dyslipidemia are known to modify retinal microcirculation through various pathways. These alterations are observable in chronic metabolic conditions like diabetes, coronary artery disease, and cerebral microvascular disease due to advances in non-invasive or minimally invasive retinal imaging techniques. Thus, examination of the retinal microcirculation can provide insights into the progression of numerous chronic metabolic disorders. This review discusses the anatomy, physiology and pathophysiology of the retinal microvascular system, with a particular emphasis on the connections between retinal microcirculation and systemic circulation in both healthy states and in the context of prevalent chronic metabolic diseases.
... Vascular structures of the choroid can be classified into three layers from internal to external with the increase of luminal diameter. The innermost, middle, and outermost layers are the choriocapillaris (CC), Sattler's layer with medium vessels, and Haller's layer with large vessels, respectively (8). The choroidal vascularity index (CVI) has been applied to assess the vascular status of the choroid (9). ...
Article
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Aim The retinal and choroidal parameters were analyzed to understand the impairment of microcirculation of both retina and choroid in patients with diabetic retinopathy (DR). Methods Fifty-five treatment-naive non-proliferative diabetic retinopathy (NPDR) patients (75 eyes) with type 2 diabetes mellitus (T2DM), including 28 patients (36 eyes) with diabetic macular edema (DME) and 27 patients (39 eyes) without DME, and 25 healthy subjects (47 eyes) were enrolled in this study. The following parameters of DR patients with and without DME were evaluated: the foveal avascular zone area (FAZ-a), FAZ perimeter (FAZ-p), FAZ circularity index (FAZ-CI), total subfoveal choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), choriocapillaris flow area percentage, superficial capillary plexus (SCP), and deep capillary plexus (DCP). Results SCP, DCP, and the percentage of choriocapillaris flow area were significantly different between DR patients with and without DME. The DR patients presented lower LA, CVI, and FAZ-CI compared to those of healthy controls (all p < 0.05). The percentage of choriocapillaris flow area in DR patients with and without DME was significantly lower than that in healthy controls (p < 0.05). SCP and DCP were significantly correlated with FAZ-a and FAZ-p but presented insignificant associations with FAZ-CI. Conclusions Optical coherence tomography (OCT) and OCT angiography (OCTA) parameters, such as LA, CVI, FAZ-CI, and the percentage of choriocapillaris flow area, were reduced compared to those in controls, indicating that the microcirculations of the retina and choroid in the macular area were impaired in DR patients with DME and without DME.
... The pigmented appearance of the choroid is due to the presence of melanocytes that in healthy individuals are distributed throughout the stroma with the exception of the innermost choroid/choriocapillaris (Edwards and Lutty, 2021). The choroid has one of the highest blood flow rates per gram of any tissue (Alm and Bill, 1973;Bill and Sperber, 1990;Urs et al., 2018). This high blood flow is essential to provide at least 85% of the ...
... The choroid is a vascular structure located between the retina and the sclera and has the highest blood supply per unit tissue in the body. [4] It is mainly drained by the vortex veins, which subsequently drain into the superior and inferior ophthalmic veins. [5] Several color Doppler imaging studies have noted a reduction in superior ophthalmic vein flow rate in TED patients. ...
Article
Context This study adds to the existing body of literature on the role of optical coherence tomography (OCT) parameters in active thyroid eye disease (TED) among the Indian population. Purpose Comparison of choroidal vascularity index (CVI) and subfoveal choroidal thickness (SFCT) in active and inactive TED. Settings and Design An observational, cross-sectional analytical study conducted at a tertiary eye care hospital in North India that included patients with active and inactive TED. Methods Demographic details and clinical evaluation were performed for all TED patients. SFCT was determined with OCT by using the Cirrus linear measurement tool. CVI was calculated using Image J software. The SFCT and CVI measurements were compared between both groups. Statistical Analysis Used Comparison between active and inactive TED groups was done using Mann–Whitney U test for non-parametric data and Student t test for parametric data. Multivariate regression analysis was performed with SFCT and CVI as dependent variables. Results Sixty-two eyes of 31 patients were included. Thirteen eyes had active TED, and 49 eyes had inactive TED. SFCT was significantly lower in eyes with higher clinical activity score (CAS) and older age. No significant difference was found in CVI between active and inactive TED eyes. Conclusion SFCT was lower in eyes with higher CAS and older age. Our findings differ from previous studies, which showed a positive correlation between SFCT and CAS. There was no significant difference in CVI between active and inactive TED eyes.
... The choroidal vessels account for 85% of ocular blood flow and are supplied by the posterior ciliary branches of the ophthalmic artery [14]. The choroid consists of three layers: the choreocapillaris layer, Sattler's layer and Haller's layer, and is surrounded by connective tissue [15]. Systemic inflammatory diseases are known to affect the choroidal vasculature [16]. ...
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Purpose The purpose of the study was to investigate the parapapillary choroidal microvasculature in thyroid eye disease (TED) using optical coherence tomography angiography (OCTA). Methods Only one eye of each subject was included in the study. Patients with TED and controls were included in the study. Participants were divided into three groups: control, inactive TED (ITED) and active TED (ATED). OCTA scans of the optic discs were obtained in a 4.5 × 4.5-mm rectangular area. Radial peripapillary capillary (RPC) density and peripapillary retinal nerve fibre layer (pRNFL) thickness were automatically calculated by the device software. Parapapillary choroidal microvasculature (PPCMv) density was automatically calculated using MATLAB software. Results Forty-one patients with TED and 40 controls were included in the study. RPC density was significantly decreased in the ATED and dysthyroid optic neuropathy (DON) group compared to the controls and ITED group. There was significant increase in pRNFL in the ATED group. PPCMv density increased in the ATED group compared to the controls in whole ring area. The RPC density was significantly correlated with the TSHr Ab level (r < − 0.396, p < 0.001). Clinical activity score correlated positively with PPCMv density (r = 0.349, p = 0.001) but negatively with RPC density (r = − 0.321, p = 0.004). Conclusion Changes in peripapillary microvascular perfusion may play a role in the development of DON. As the severity of TED increases with clinical activity, so do the changes observed in peripapillary parameters. The decrease in RPC density may be due to compression caused by optic disc oedema, which may result in reduced blood flow. The increase in PPCMv density may be related to factors such as orbital congestion.
... 62 The choroid may be prone to arteriosclerotic processes to the same degree as other organs, specifically, considering the choroid an extremely vascular terminal organ associated with the largest flow per mm 3 in the body. 63 Here, we speculate that these choroidal vascular changes induced by age and cholesterol profile in patients with PDR can cause tissue ischemia. In the early stage, ischemia can be compensated for by the continuous expansion of choroidal vessels, leading to choroidal thickening. ...
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Introduction Extensive studies have studied the factors associated with subfoveal choroidal thickness (SFCT). However, studies of the association between lipid profile and SFCT in patients with proliferative diabetic retinopathy (PDR) in type 2 diabetes remain limited. Thus, we aimed to investigate the relationship between lipid profile and SFCT in patients with PDR. Materials and Methods This was a retrospective cross-sectional study. The included participants were inpatients who underwent vitrectomy for PDR with type 2 diabetes and contralateral eyes of PDR patients meeting the criteria. Multivariate linear regression analysis was used to determine the independent association between lipid profile and SFCT. Results A total of 131 participants with PDR were enrolled in the final analysis. The average age of the participants was 55.76 ± 9.88 years, and the average SFCT was 276.10 ± 92.92 μm. Multivariate linear regression model results showed that in the fully adjusted model, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) had a negative association with SFCT (β = −16.51, 95% CI: −29.57, −3.46; P = 0.0148; β = −42.65, 95% CI: −82.60, −2.70; P = 0.0390; β = −17.89, 95% CI: −33.24, −2.54; P = 0.0245, respectively), while triglyceride was not significantly associated with SFCT (β = 5.23, 95% CI: −18.57, 29.02; P = 0.6678). Furthermore, the results of stratified analysis showed that except for triglyceride, the trends of total cholesterol, HDL-C, LDL-C, and SFCT were consistent among different stratifications in participants. Conclusion The cholesterol profile had a significant negative association with SFCT in Chinese PDR patients, but triglyceride was not significantly associated with SFCT. This suggests that these systemic imbalances contribute to choroidal changes, and often coexist in diabetic patients.
... The choroid has one of the highest rates of blood flow in the body, reflecting its important role as a source of nutrients for the outer retina, which is one of the most metabolically demanding tissues of the body. 12 The choroid is thinnest at its anterior margin (i.e., at the ora serrata), where it transitions into the supraciliaris and vascular layer of the ciliary body. The choroid is thickest at the posterior pole, reflecting the high metabolic demands of the overlying macular region. ...
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The choroid is the richly vascular layer of the eye located between the sclera and Bruch's membrane. Early studies in animals, as well as more recent studies in humans, have demonstrated that the choroid is a dynamic, multifunctional structure, with its thickness directly and indirectly subject to modulation by a variety of physiologic and visual stimuli. In this review, the anatomy and function of the choroid are summarized and links between the choroid, eye growth regulation, and myopia, as demonstrated in animal models, discussed. Methods for quantifying choroidal thickness in the human eye and associated challenges are described, the literature examining choroidal changes in response to various visual stimuli and refractive error-related differences are summarized, and the potential implications of the latter for myopia are considered. This review also allowed for the reexamination of the hypothesis that short-term changes in choroidal thickness induced by pharmacologic, optical, or environmental stimuli are predictive of future long-term changes in axial elongation, and the speculation that short-term choroidal thickening can be used as a biomarker of treatment efficacy for myopia control therapies, with the general conclusion that current evidence is not sufficient.
... Some of the studies show that reducing stress can help to restore vision. In general, pressures of 20 -30 mm Hg usually cause damage over several years, but pressures of 40 -50 mm Hg can cause rapid visual loss and also precipitate retinovascular occlusion [12][13][14]. However, mindfulness-based stress reduction was associated with a significant decrease in IOP along with an improvement in optic nerve head perfusion and quality of life. ...
... Wybar [15], and Ring & Fujino [20] found no difference in the structure and density of the choriocapillaris in the macular region and other areas equidistant from the optic disc. Increased blood flow in the submacular choroid [49,50] simply seems to represent increased blood flow in the large number of arteries aggregated in the submacular choroid, and not necessarily through the choriocapillaris. Terminal arterioles supplying the macular choriocapillaris arise directly from all the temporal SPCAs and other large choroidal arteries lying in the submacular choroid, and are usually short, vertical and enter the choriocapillaris perpendicularly and abruptly, as compared to those going to the choriocapillaris in the peripheral [16,22]. ...
Article
The uveal vascular bed is the largest vascular system in the eye and has a role in supplying almost every tissue in the eyeball. This makes it the most important ocular vascular system. This is an up-to-date review of the literature of the entire uveal vascular bed in health based on detailed anatomy of the posterior ciliary arteries (PCAs), anterior ciliary arteries, cilioretinal arteries, and vortex veins. Although postmortem injection cast preparations gave us useful information on the morphology of the choroidal vascular bed; in vivo studies showed that they misled us for centuries about the in vivo situation. According to the postmortem cast studies, the uveal vascular bed has no segmental distribution, the uveal vessels anastomose freely with one another, there are inter-arterial and arteriovenous anastomoses in the choroid, and the choriocapillaris form a freely communicating and an uninterrupted vascular bed in the entire choroid.
... Unlike the ciliary arteries, the CRA is a terminal vessel. Animal studies have demonstrated that ciliary arteries transport a greater volume of blood than the retinal the blood flow (31,32). Therefore, the deep retina with its greater blood supply was less affected by ischemia than the superficial, which may account for the lack of significant correlation between the deep vascular densities and lacunes. ...
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Objective To detect fundus changes in patients with cerebral small vessel disease (CSVD) using optical coherence tomography angiography (OCTA) and to investigate the correlations between CSVD and fundus changes. Methods From January 2019 to January 2020, patients diagnosed with CSVD by magnetic resonance imaging (MRI) were enrolled in our study and received fundus examinations using OCTA. CSVD was defined as white matter hyperintensities, enlarged perivascular spaces, lacunes, or microbleeds on MRI. OCTA parameters included foveal avascular zone areas, retinal nerve fiber layer thickness, and capillary densities of the superficial retinal capillary plexuses, deep retinal capillary plexuses, and the radial peripapillary capillary network of the disc. Univariate and multivariate logistic regression analyses were performed to explore the correlation between CSVD and fundus changes. Results A total of 115 patients (40% male) were enrolled and analyzed, and the mean age was 65.11 ± 11.23 years. After multivariate logistic regression analysis, the radial peripapillary capillary network density was negatively correlated with severity of deep white matter lesions (OR: 0.909; 95% CI: 0.828–0.998; p = 0.046) and perivascular spaces (OR: 0.881; 95% CI: 0.779–0.995; p = 0.041). Parafoveal vessel densities of the superficial retinal capillary plexuses were independently correlated with lacunes (OR: 0.889; 95% CI: 0.817–0.967; p = 0.006). Conclusion OCTA parameters were correlated with CSVD, indicating that OCTA is a potential method for CSVD screening.
... Choroid is a high vascularized tissue situated between retina pigment epithelium and sclera. It has many functions, such as nourishing retina and monitor the IOP [15][16][17]. Especially, by changing its thickness to make retina reach to focus plane and transmit retinal-deprived signals to sclera, choroid was thought to regulate sclera extracellular matrix (ECM) remodeling and ocular growth during emmetropization period [18]. In different animal experiments, it has proved that imposed defocus can change choroidal thickness. ...
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Aims: This article aimed to assess the changes of subfoveal choroidal thickness (SFCT) in different follow-up durations for myopic children under the treatment of orthokeratology and give a reference for further studies. Method: Relevant publications were comprehensively retrieved through different databases, such as PubMed, Web of Science, Cochrane Library and Chinese database of Wan Fang and Wei Pu. Retrieval time was from the inception to February 2022. Standardized mean difference (SMD) and 95% confidence interval (95% CI) were selected as the effect for calculating and analyzing the changes of choroidal thickness in myopic children with orthokeratology. Result: A total of eight articles of 371 Patients (371 eyes) met our inclusion criteria. During the first month of wearing orthokeratology, choroidal thickness dramatically increased by 21.09 μ m (95%CI: 25.64, 16.7; P<0.00001). After the first month, it rose slightly, even became stable in next eleven months’ treatment (increased by 4.20 μm from the first month to the third month, 95%CI: 9.37, 0.9; P=0.11; increased by 3.99μm from the first month to the sixth month, 95%CI: 8.67, 0.6; P=0.09; increased by 2.99μm from the first month to the twelfth month, 95%CI: 7.76, 1.7; P=0.02). Conclusion: This meta-analysis demonstrated that in the first month with orthokeratology, choroidal thickness presented an obvious increase, after that it became stable or got a slightly rise for the longer following-up treatment.
... The middle layer of the eye between sclera and retina, the so-called choroid, is a densely vascularised tissue with one of the highest blood flow rates in the human body in relation to tissue weight. 1 Although the reason for this dense vascular supply is not fully understood, it is generally accepted that the choroid supplies the retinal photoreceptors with nutrients and oxygen and it is, therefore, of utmost relevance for proper photoreceptor function and hence vision. 2 It further serves as a heat sink, thus protecting the retina from thermal damage and is able to adjust the retinal focal plane by changing its thickness. 2 Furthermore, it represents the signaling tissue for scleral growth during emmetropisation 3 and also serves an exceptional position within the ocular immune defence. ...
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Background Choroidal vascular regulation is mediated by the autonomic nervous system in order to gain proper blood flow control. While the mechanisms behind this control are unknown, neuroregulatory peptides are involved in this process. To better understand choroidal function, we investigate the presence of urocortin-1 (UCN), a neuroregulatory peptide with vascular effects, in the human choroid and its possible intrinsic and extrinsic origin. Methods Human choroid and eye-related cranial ganglia (superior cervical ganglion- SCG, ciliary ganglion-CIL, pterygopalatine ganglion-PPG, trigeminal ganglion-TRI) were prepared for immunohistochemistry against UCN, protein–gene product 9.5 (PGP9.5), substance P (SP), tyrosine hydroxylase (TH) and vesicular acetylcholine transporter (VAChT). For documentation, confocal laser scanning microscopy was used. Results In choroidal stroma, UCN-immunoreactivity was present in nerve fibres, small cells and intrinsic choroidal neurons (ICN). Some UCN+ nerve fibres colocalised for VAChT, while others were VAChT. A similar situation was found with SP: some UCN+ nerve fibres showed colocalisation for SP, while others lacked SP. Colocalisation for UCN and TH was not observed. In eye-related cranial ganglia, only few cells in the SCG, PPG and TRI were UCN+, while many cells of the CIL displayed weak UCN immunoreactivity. Conclusion UCN is part of the choroidal innervation. UCN+/VAChT+ fibres could derive from the few cells of the PPG or cells of the CIL, if these indeed supply the choroid. UCN+/SP+ fibres might originate from ICN, or the few UCN+ cells detected in the TRI. Further studies are necessary to establish UCN function in the choroid and its implication for choroidal autonomic control.
... The retinal circulation and the choroidal circulation, both of which originate from the ophthalmic artery, are responsible for supplying oxygen and nutrition to the retina. Retinal circulation provides a low level of blood flow and a high level of oxygen extraction, contrary to that in choroidal circulation [96,97]. There is limited insufficient evidence of autonomic innervation in the intraocular branch of the central retinal artery (CRA) [98,99]. ...
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The autonomic nervous system (ANS) confers neural control of the entire body, mainly through the sympathetic and parasympathetic nerves. Several studies have observed that the physiological functions of the eye (pupil size, lens accommodation, ocular circulation, and intraocular pressure regulation) are precisely regulated by the ANS. Almost all parts of the eye have autonomic innervation for the regulation of local homeostasis through synergy and antagonism. With the advent of new research methods, novel anatomical characteristics and numerous physiological processes have been elucidated. Herein, we summarize the anatomical and physiological functions of the ANS in the eye within the context of its intrinsic connections. This review provides novel insights into ocular studies.
Article
The choroid is the thin, vasculature-filled layer of the eye situated between the sclera and the retina, where it serves the metabolic needs of the light-sensing photoreceptors in the retina. Illumination of the interior surface of the back of the eye (fundus) is a critical regulator of subretinal fluid homeostasis, which determines the overall shape of the eye, but it is also important for choroidal perfusion. Noted for having some of the highest blood flow rates in the body, the choroidal vasculature has been reported to lack intrinsic, intravascular pressure-induced (myogenic) autoregulatory mechanisms. Here, we ask how light directly regulates choroid perfusion and ocular fluid homeostasis, testing the hypothesis that light facilitates ocular fluid absorption by directly increasing choroid endothelial permeability and decreasing choroid perfusion. Utilizing ex vivo pressurized whole-choroid and whole-eye preparations from mice expressing cell-specific Ca ²⁺ indicators, we found that the choroidal vasculature has two intrinsically light-sensitive Ca ²⁺ -signaling mechanisms: One increases Ca ²⁺ -dependent production of nitric oxide in choroidal endothelial cells; the other promotes vasoconstriction through Ca ²⁺ elevation in vascular smooth muscle cells. In addition, we found that choroidal flow, or pressure, modulates endothelial and smooth muscle photosensitivity and trans-retinal absorption of fluid into the choroid. These results collectively suggest that the choroid vasculature exhibits an inverted form of autoregulatory control, where pressure- and light-induced mechanisms work in opposition to regulate blood flow and maintain fluid balance in response to changes in light and dark, aligning with the metabolic needs of photoreceptors.
Article
The pathogenic role of choriocapillaris blood flow in the progression of glaucomatous neurodegeneration has long been discussed in the literature. However, in vivo visualization of the deep microcirculatory structures in the peripapillary zone has remained challenging for a long time. Modern diagnostic methods, such as optical coherence tomography (OCT), particularly spectral domain OCT (SD-OCT), swept-source OCT (SS-OCT), and OCT angiography, now enable the visualization of deep ocular vessels, including the choriocapillaris layer, opening new possibilities for diagnosing and monitoring the progression of glaucoma. This review provides information on the anatomy of the choroid, the choriocapillaris layer, its role in the pathogenesis of glaucoma, as well as the latest methods of studying these structures using optical coherence tomography.
Article
Purposes: To determine the relationship between carotid artery stenosis (CAS) and the development of open-angle glaucoma (OAG) in the Taiwanese population. Methods: This retrospective cohort study was conducted using Chang Gung Research Database. Cox-proportional hazards model was applied to calculate the hazard ratio for OAG between CAS and the control cohort. Results: Among 19,590 CAS patients, 17,238 had mild CAS (<50%), 1,895 had moderate CAS (50-69%), and 457 had severe CAS (≥70%). The CAS cohort had a higher proportion of several comorbidities. After adjusting for comorbidities, no significant difference in OAG development was found between CAS and control cohorts. Matching for key comorbidities, no significant differences in OAG incidence were found between matched cohorts (P = .869). Subdividing the matched CAS cohort by stenosis severity: mild (<50%), moderate (50-69%), and severe (≥70%), a statistically significantly lower OAG risk was observed in patients with mild CAS stenosis (HR: 1.12, 95% CI = 1.03-1.21, P = .006). Kaplan-Meier analysis revealed reduced OAG incidence in CAS patients who underwent surgical intervention, compared to the control cohort (P <.001). Subgroup analysis revealed that patients in the mild CAS stenosis group, those who underwent surgical intervention exhibited a reduced OAG risk (HR: 0.29, 95% CI = 0.15-0.58, P = .001). Conclusions: No statistically significant differences in OAG risk were observed between patients with CAS and the control cohort. The severity of CAS appears to influence OAG risk, with surgical intervention potentially offering protective effects, particularly in patients with mild CAS stenosis (<50%), suggesting that enhanced ocular perfusion post-surgery may act as a protective factor against OAG development.
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Purpose: To examine the influence of subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI) on axial length (AL) elongation over a 2-year period in highly myopic children. Methods: In this is prospective, longitudinal, observational study, 163 participants (74%), who were 8 to 18 years of age with bilateral high myopia (sphere ≤ -6.0 D) and without pathologic myopia, completed follow-up visits over 2 years. All participants underwent baseline and follow-up ocular examinations, including swept-source optical coherence tomography (SS-OCT) and AL measurements. SFCT and CVI were derived from SS-OCT scans using a deep-learning-based program for choroidal structure assessment. Results: The mean age of the participants at baseline was 15.0 years (±2.3), with males constituting 47% of the cohort. An inverse relationship was observed between AL elongation and increases in baseline age, baseline SFCT, and CVI, as well as a decrease in baseline AL. Adjusting for other factors, every 10-µm increase in SFCT and each 1% increase in CVI were associated with decreases in AL elongation of 0.007 mm (95% confidence interval [CI], -0.013 to -0.002; P = 0.011) and 0.010 mm (95% CI, -0.019 to 0.000; P = 0.050), respectively. The incorporation of SFCT or CVI into predictive models improved discrimination over models using only age, gender, and baseline AL (both P < 0.05, likelihood ratio test). Conclusions: Our findings suggest a possible association between a thinner choroid and increased AL elongation over 2 years in children with high myopia, after adjusting for potential baseline risk factors such as age, gender, and initial AL.
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Background The choroid is crucial in myopia prevention and control research. This study aimed to investigate the effects of different lunch break postures and refractive errors on choroidal thickness (CT) and choroidal vascular volume (CVV). Methods Healthy adult participants underwent a 45-minute lunch break in three different postures on consecutive days: lying lunch break, sitting head-on-arms lunch break, and sitting no lunch break. SS-OCTA measured CT and CVV in the macula before and after each lunch break. Changes in CT were also evaluated across different refractive errors. Results Among 40 adults (80 eyes), the average CT change was 11.62µm for lying lunch break, significantly higher than sitting head-on-arms lunch break (2.60µm) and sitting no lunch break (1.39µm) (both p < 0.0001). Average CVV changes were 8.5µm³ for lying lunch break, 1.9µm³ for sitting head-on-arms lunch break, and 1.3µm³ for sitting no lunch break. CT changes strongly correlated with CVV changes (F1,2158 = 306.1, p < 0.0001). During sitting head-on-arms lunch break, CT decreased by 6.00 ± 14.17 µm in the emmetropia and low hyperopia group, significantly different from other groups (all p < 0.0001). Conclusions Lying down during lunch breaks is most conducive to choroidal thickening, driven by increased CVV. Sitting head-on-arms may lead to choroidal thinning in people with emmetropia or low hyperopia. When considering the development of myopia in children and adolescents, it is suggested that LLB may serve as a protective factor while sitting head-on-arms lunch break may act as a risk factor.
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Clinical relevance: Choroidal thickness measurement is gaining popularity in clinical practice and research as an early indicator of myopia progression. Understanding the influence of temperature on choroidal thickness changes will improve the reliability of the measures. Background: It has been suggested that environmental temperature may affect choroidal thickness and blood flow, with potential implications for ocular disease and refractive development. This study investigates the effect of changes in eyelid/ocular adnexa temperature on choroidal thickness. Methods: In a paired-eye study, 20 young, healthy subjects received a warm stimulus (heat pack) over one closed eye and simultaneously a cold stimulus (ice pack) over the other for 10 min. Eyelid temperatures were monitored with thermal probes, and optical coherence tomography scans of the retina and choroid were taken before and after heating and cooling, and then every 5 min during a 15-min recovery period. Retinal and choroidal thicknesses were measured across the macular region (6 mm), including the subfoveal (1 mm), parafoveal (1-3 mm), and perifoveal (3-5 mm) regions, and compared between the cooled and warmed eyes. Results: When the thermal stimuli were applied, eyelid surface temperatures changed predictably and remained significantly different (by approximately 10-15°C) between the eyes after 2 min (p < .001). Relative to the warmed eye, macular choroidal thickness in the cooled eye increased significantly after 10 min of treatment (p = .004). This choroidal thickening response occurred in the subfoveal, parafoveal, and perifoveal regions (all p < .05). Upon removal of the thermal stimuli, choroidal thickness rapidly returned to the baseline and was no longer different between the cooled and warmed eye (p = .641). Conclusion: Cooling the anterior eye by application of a cold stimulus directly onto the closed eyelid caused a small but significant increase in choroidal thickness relative to warming the anterior eye, demonstrating that the choroid can modulate its thickness rapidly and transiently in response to local temperature changes.
Article
Purpose: We hypothesized that contrast-enhanced ultrasound (CEUS) using a microbubble technique to quantify microvascular changes and Nakagami imaging for tissue characterization would provide a new approach for diagnosing and differentiating benign and malignant choroidal lesions. Methods: Five patients with choroidal melanoma (CM) and five patients with choroidal hemangioma (CH) were selected. Definity®, which contains perflutren microbubbles, was administered as a slow IV bolus (1 ml). CEUS was performed for 1 min postinjection of the contrast agent with ultrasound radiofrequency data acquired from 10 s to 60 s. The contrast value was calculated for the whole tumor region. A gradient magnitude method was used for each postcontrast frames with 1-second interval, and the time-averaged value in pixel intensity gradient of postinjection frames was estimated and reported. Based on the Nakagami statistical distribution model, two Nakagami parameters, m and Ω, where m (shape parameter), representing tissue heterogeneity, and Ω (scale parameter), representing the average energy of backscattered signals, were studied. Results: CEUS analysis showed that the time-averaged estimated contrast was significantly higher (p = 0.008) for CH compared to CM. Furthermore, the time-averaged contrast within the normal choroidal region was significantly higher than the choroidal tumor region for both CH and CM (p = 0.001 for CH cases and p < 0.0001 for CM cases). Nakagami analysis showed that the m estimates were significantly higher (p = 0.032) for CH (m = 0.61) than for CM (m = 0.28), indicating that CH is a more heterogeneous tumor than CM. The Ω estimates were significantly higher (p = 0.0019) for CH (Ω = 0.15) compared to CM (Ω = 0.03). These results may be due to the more vascular structures in CH compared to CM. Conclusions: Quantitative intensity-based perfusion analysis using CEUS and backscattering tissue analysis using Nakagami imaging can provide valuable insights to differentiate benign and malignant choroidal lesions.
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Melanocytes are dendritic cells localized in skin, eyes, hair follicles, ears, heart and central nervous system. They are characterized by the presence of melanosomes enriched in melanin which are responsible for skin, eye and hair pigmentation. They also have different functions in photoprotection, immunity and sound perception. Melanocyte dysfunction can cause pigmentary disorders, hearing and vision impairments or increased cancer susceptibility. This review focuses on the role of melanocytes in homeostasis and disease, before discussing their potential in regenerative medicine applications, such as for disease modeling, drug testing or therapy development using stem cell technologies, tissue engineering and extracellular vesicles.
Article
Aims: This study aimed to synthesize the variations in subfoveal choroidal thickness (SFCT) observed at different follow-up intervals in myopic children undergoing orthokeratology treatment. Materials and methods: Relevant articles were systematically retrieved from databases such as PubMed, EMBASE, Web of Science, and Cochrane Library. The retrieval period extended from the inception of these databases to November 2023. Means and standard deviations (SD) of baseline and post-treatment SFCT were selected as the results for analysis and calculation. Results: A total of eight articles involving 478 eyes fulfilled the inclusion criteria. At 1 month, 3 months, and 6 months intervals, the SFCT demonstrated significant increases by 16.74 μm (95% CI: 8.66, 24.82; p < 0.0001), 13.41 μm (95% CI: 4.36, 22.45; p = 0.004), and 17.57 μm (95% CI: 8.41, 26.73; p = 0.0002), respectively. Besides, children treated with orthokeratology exhibited a notably thicker change of SFCT in comparison with children with single-vision spectacles (SVL) (WMD = 13.50, 95% CI: 11.69, 15.13; p < 0.0001). Conclusion: Myopic children undergoing orthokeratology treatment experience a discernible increase in SFCT at 1 month, 3 months, and 6 months. Furthermore, compared to children utilizing SVL, those undergoing orthokeratology manifest a more pronounced thickening of SFCT.
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Glaucoma, a leading cause of irreversible blindness globally, primarily affects retinal ganglion cells (RGCs). This review dives into the anatomy of RGC subtypes, covering the different underlying theoretical mechanisms that lead to RGC susceptibility in glaucoma, including mechanical, vascular, excitotoxicity, and neurotrophic factor deficiency, as well as oxidative stress and inflammation. Furthermore, we examined numerous imaging methods and functional assessments to gain insight into RGC health. Finally, we investigated the current possible neuroprotective targets for RGCs that could help with future glaucoma research and management.
Chapter
Primary open-angle glaucoma (POAG) is a chronic neurodegenerative disease that may progress to the irreversible blindness. Unstable ocular blood flow is associated with a stronger patients’ reaction to psychological stress, which was described in patients with primary vascular dysregulation. Excessive activity of the sympathetic autonomic nervous system (ANS) may lead to both a blood supply violation of the nervous system and to a decrease in ocular perfusion pressure in the vessels of the optic nerve and choroid. It plays the crucial role in the pathogenesis of normal tension glaucoma. Systemic autonomic dysfunction may show a higher risk of glaucoma progression due to the stronger sensitivity of the optic nerve to fluctuations in intraocular pressure and intraocular perfusion pressure. Heart rate variability is a common tool for studying the autonomic modulation of the sympathovagal balance. As optic nerve head and retinal microcirculation is of great importance in glaucoma development and progression, it makes it reasonable to search for new methods of the vascular bed’s visualization for the early diagnosis and monitoring of glaucoma. New biomarkers of glaucoma progression including vascular parameters may improve glaucoma treatment and outcome in accordance with a goal of the predictive preventive personalized medicine (PPPM/3PM).
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Choroidal nevus is a benign melanocytic tumor that is often incidentally detected during ophthalmic examinations. It is typically located behind the equator of the eye and appears as a flat or slightly elevated lesion with indistinct borders. The shape of the nevus can be round or oval, and its color varies from brown to dark gray, depending on the amount of pigment present. Most nevi are asymptomatic. However, if choroidal neovascularization or serous retinal detachment develops, it can lead to a decrease in vision and become symptomatic. Fundus photography, B-mode ultrasonography, and optical coherence tomography are useful imaging techniques for clinical monitoring. Differential diagnosis between choroidal nevus and melanoma is important. Risk factors for the development of melanoma include a thickness greater than 2 mm, a basal diameter larger than 6 mm, the presence of lipofuscin pigment accumulation on the surface, proximity to the optic disc within 3 mm, serous retinal detachment, and visual impairment. These factors require further investigation.
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We examined the effect of reduced fluence (rf)-photodynamic therapy (PDT) of the macular area on the wide-field choroidal thickness in 20 eyes with central serous chorioretinopathy (CSC) and 20 age- and sex-matched control eyes. The choroidal thickness at the posterior pole was measured before and after rf-PDT, using a grid with inner and outer rings, each divided into superotemporal, inferotemporal, superonasal, and inferonasal quadrants, respectively, making up a total of nine subfields including the central 3 mm ring. Before treatment, all eyes showed wide-field choroidal thickening from the dilated vortex vein ampulla to the fovea, along the course of the vein. After rf-PDT of the macular area, the choroidal thickness significantly decreased, not only in the irradiated macular area but also outside the arcade vessels in all quadrants (p < 0.001 for all inner subfields; p = 0.035 and p = 0.024 for the outer superonasal and inferonasal subfields, respectively; p < 0.001 and p = 0.004 for the outer superotemporal and inferotemporal subfields, respectively). For control eyes, the choroidal thickness did not differ between the initial visit and follow-up 1.2 ± 0.7 months after the initial visit (p > 0.05 for all subfields). These findings provide new insights into the pathogenesis of CSC and explain the reasons for the effectiveness of rf-PDT for this condition.
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Blood cells trapped in stasis have been reported within the microcirculation, but their relevance to health and disease has not been established. In this study, we introduce an in vivo imaging approach that reveals the presence of a previously-unknown pool of erythrocytes in stasis, located within capillary segments of the central nervous system, and present in 100% of subjects imaged. These results provide a key insight that blood cells pause as they travel through the choroidal microvasculature, a vascular structure that boasts the highest blood flow of any tissue in the body. Demonstration of clinical utility using deep learning reveals that erythrocyte stasis is altered in glaucoma, indicating the possibility of more widespread changes in choroidal microvascular than previously realized. The ability to monitor the choroidal microvasculature at the single cell level may lead to novel strategies for tracking microvascular health in glaucoma, age-related macular degeneration, and other neurodegenerative diseases.
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This study investigated the effect of elevated intraocular pressure on the vascular conductivity in the distal segment of the optic nerve in the monkey. Both injection, followed by fixation and clearing, and fluorescein angiography in the living animal were used. The anatomic findings agreed with those previously reported, indicating that the papilla and distal optic nerve receive the majority of their blood supply from the posterior ciliary circulation and not the central retinal artery. Both latex injections and fluorescein angiography were done with the intraocular pressure elevated. It was demonstrated that elevated intraocular pressure compromises the small vessel structure of the distal optic nerve segment and it is hypothesized that this accounts for the glaucomatous disc changes seen in man.
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The vascular system of the optic nerve head was studied in eight species of primates. The Bushbaby had an unusual vascular supply, but all the others were quite similar to the human. There is overlapping arterial supply of the disk derived from the pial network on the optic nerve behind the globe, the short posterior ciliary arteries (not anastomatically joined to form a circle of Zinn-Haller), and the central retinal artery. These are connected anastomotically at the capillary level. Venous drainage is accomplished by at least two routes-the central retinal vein and the vortex veins.
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The capillary circulation in the posterior pole was studied by fluorescein angiography and silicone rubber injection in eight species of primates. Six of these were diurnal monkeys: marmoset, squirrel moneky, capuchin monkey, black spider monkey, African green monkey, and rhesus monkey. In these diurnal species, the retinas have both rods and cones, and there is a central region free of capillaries that corresponds to the fovea, just as in the human retina. In two nocturnal species, the bushbaby and the owl monkey, both of which lack a fovea, there is no central capillary-free zone.
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The retinal vascular system of the domestic cat was studied clinically, and by a variety of histological techniques. Fundus photographs and drawings were utilized to point out features of the retinal vasculature during life, and routine histology, electron microscopy, ink injections and digest preparations were used for in vitro study. While the present observations usually confirmed previous work on the retinal vascular system of the cat, a number of points of difference were noted. A comparison of the retinal capillaries with those of the choriocapillaris is provided. An arcuate arrangement of retinal arterioles was noted in cat, monkey and man, and is similar to that noted in other vascular beds. The retinal circulation of the cat was found to have many points of similarity with that of man.
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The anatomy and pathology of the choroidal vasculature in human eyes has been studied using intravascular injection techniques, conventional histologic cross sections, and flat preparations of the choroid. Interarterial anastomotic relationships are demonstrated as are the anatomic features of the choriocapillaris and vortex veins. The pathologic changes of ageing, hypertension, and glaucoma are observed. Round holes in Bruch's membrane at the posterior pole are regularly present in flat preparations from healthy adult eyes. It is suggested that these defects in Bruch's membrane contribute to the development of central serous retinopathy, detachment of the pigment epithelium, and disciform degeneration of the macula.
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