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Vitreoretinal surgery is an essential approach to treat proliferative diabetic vitreopathy, retinal detachment, retinal tear, ocular trauma, and macular holes. The removal of the natural vitreous and the replacement with substitutes are critical steps for retina reattachment. Vitreous substitutes including silicone oil (SiO), air, sulfur hexafluoride (SF 6 ), and perfluoropropane (C 3 F 8 ), have been widely applied in clinical practice. However, these substitutes are reported to cause complications such as emulsification, high intraocular pressure, and lens opacification. Polymeric hydrogels are a kind of material with favorable physical, mechanical properties, and adaptable biocompatibility, thus being highly expected to be ideal vitreous substitutes. Despite years of research, very few polymeric hydrogels can be applied practically in the vitreous cavity. In this review, we focus on the development of polymeric natural-based hydrogels and synthetic hydrogels. Particularly, we pay attention to recent advances in the novel stimuli-response and self-assembly supramolecular hydrogels. Characterized by easy injectability and long residence time, this kind of hydrogel becomes the potentially promising candidates for ideal vitreous substitutes. Finally, we evaluate the current challenges and provide the future directions of vitreous substitutes., (© 2021 IOP Publishing Ltd.)

Research on the vitreous humor and development of hydrogel vitreous substitutes have gained a rapid increase in interest within the past two decades. However, the properties of the vitreous humor and vitreous substitutes have yet to be consolidated. In this paper, the mechanical properties of the vitreous humor and hydrogel vitreous substitutes were systematically reviewed. The number of publications on the vitreous humor and vitreous substitutes over the years, as well as their respective testing conditions and testing techniques were analyzed. The mechanical properties of the human vitreous were found to be most similar to the vitreous of pigs and rabbits. The storage and loss moduli of the hydrogel vitreous substitutes developed were found to be orders of magnitude higher in comparison to the native human vitreous. However, the reported modulus for human vitreous, which was most commonly tested in vitro , has been hypothesized to be different in vivo . Future studies should focus on testing the mechanical properties of the vitreous in situ or in vivo . In addition to its mechanical properties, the vitreous humor has other biotransport mechanisms and biochemical functions that establish a redox balance and maintain an oxygen gradient inside the vitreous chamber to protect intraocular tissues from oxidative damage. Biomimetic hydrogel vitreous substitutes have the potential to provide ophthalmologists with additional avenues for treating and controlling vitreoretinal diseases while preventing complications after vitrectomy. Due to the proximity and interconnectedness of the vitreous humor to other ocular tissues, particularly the lens and the retina, more interest has been placed on understanding the properties of the vitreous humor in recent years. A better understanding of the properties of the vitreous humor will aid in improving the design of biomimetic vitreous substitutes and enhancing intravitreal biotransport.

Purpose: To investigate changes in intraocular pressure (IOP) and axial length (AL) on the ascent to high altitude from Beijing to Lhasa., Patients and Methods: Twenty volunteers (17 men, 3 women) who had been sent to work in Lhasa, Tibet for more than 6 months were enrolled. One of their journeys from Beijing to Lhasa was chosen as the time for the examination. IOP, AL, corneal curvature (K), and blood pressure (BP) were measured in Beijing (altitude 43 m) and Lhasa (altitude 3658 m). Their first examination was conducted at least 1 day before arriving in Lhasa and the second examination after they had stayed in Lhasa for 7 days. The data from the highland and lowland examinations were analyzed with a paired-sample T test and Pearson's correlation coefficient was calculated for the association between IOP and average BP., Results: The mean IOP was 12.65±2.34 mmHg in Beijing and 14.85±3.1 mmHg in Lhasa. The mean AL was 24.61±1.50mm in Beijing, and 24.98±1.45 mm in Lhasa. The IOP and AL showed a significant elevation in highland compared with lowland (P<0.05). The mean K was 43.58±2.25 D in Beijing and 43.56±2.21 D in Lhasa and no significant difference was found in this study (P>0.05). A positive correlation between variance of IOP and ACD was found (r = 0.475, P<0.05) and no correlation between IOP and average BP was noted., Conclusions: High altitude may lead to a small but significant change in IOP and axial length. However, the shape of the corneal surface was not influenced by the hypobaric and hypoxic conditions., Competing Interests: The authors have declared that no competing interests exit.

Purpose: To study a prototype of an ultrasound-based vitrector, and to try to understand the physical phenomena underlying this new technology., Methods: We tested the ultrasound-based vitrector prototype (UV) (ultrasonically-driven handpiece obtained from a modified version of the Alcon CONSTELLATION Vision System [Alcon]) using an automatic experimental setup. Balanced saline solution (BSS) and vitreous (from fresh postmortem enucleated porcine eyes) flow rates were analyzed using three different tips., Results: In general, BSS solution flow rates increased with increasing aspiration levels and decreased when we used % US power. Vitreous flow rates were influenced by aspiration levels, % US power, and ultrasound-related phenomena: cavitation phenomenon and "jet streaming.", Conclusion: Ultrasound-based vitrectomy may represent an important alternative to traditional vitrectomy. Such a tool, capable of liquefying and excising the vitreous body using ultrasound, could overcome all the limits of the guillotine-based technique (GV). Knowledge of the physical phenomena underlying ultrasound-based technology is a necessary prerequisite for further development of this new technology.

Objective: To identify associations between anthropometric indicators (height, weight and body mass index (BMI)) and both refraction and ocular biometrics in Chinese schoolchildren in Tianjin, China., Design: Cross-sectional study., Participants: A total of 482 (86.07%) students (6-15 years old) with no history of ocular or systemic pathologies were enrolled in this study., Methodology: Height and weight were measured using standardised protocols. Ocular biometrics (axial length (AL), vitreous chamber depth (VCD) and corneal curvature (CC)) were measured by a low-coherence optical reflectometry device. Cycloplegic refraction was measured using autorefraction. The AL/CC ratio and spherical equivalent refraction (SER) were calculated. Myopia was defined as SER ≤-0.50 dioptres (D). Multiple linear regression analysis was performed to explore the associations between anthropometric indicators (height, weight and BMI) and both refraction and ocular biometrics., Results: The overall prevalence of myopia was 71.16%. Overall, only height was associated with ALs, VCDs, AL/CC ratios and refractions after controlling for age, gender, parental myopia, family income, reading and writing distance and time spent outdoors. Furthermore, age-specific results demonstrated that height and weight were independently associated with refraction in participants aged 6-8 years and 9-11 years participants. Higher heights in schoolchildren were associated with longer ALs (regression coefficient b =+0.25 for each 10 cm difference in height, p<0.01), deeper VCDs ( b =+0.23, p<0.01), higher AL/CC ratios ( b =+0.04, p<0.01) and more negative refractions ( b =-0.48, p<0.01). Heavier weights were also associated with longer ALs (+0.29 mm, p<0.01), deeper VCDs (+0.29 mm, p<0.01), higher AL/CC ratios (+0.04, p<0.01) and more negative refractions (-0.48 D, p<0.01)., Conclusions: Height and weight remained independently related to refraction and various ocular biometrics during the early adolescent growth period after adequately controlling for covariates, which could support the idea that a shared mechanism may regulate the coordinated growth of body and eye size in children., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To characterize the biophysical properties of an artificial vitreous body substitute (VBS), which consists of a biocompatible, cross-linked, hyaluronic acid (HA)-based hydrogel, by analysing the VBS's influence on intraocular pressure (IOP) and retinal integrity in distinct ex vivo eye models in order to evaluate the its potential for in vivo biocompatibility testing., Methods: Pig eyes were obtained immediately postmortem, and VBS was injected after core-vitrectomy. IOP was followed for 24 h (n = 5). VBS influence on retinal integrity was investigated using isolated bovine retinas superfused with an oxygen saturated nutrient solution. An electroretinogram (ERG) was recorded on explanted bovine retinae using silver/silver chloride electrodes; after application of VBS for 2 min, a washout period of 70 min was employed. The percentage of a-and b-wave reduction at the end of the washout phase was compared to baseline values (n = 5). Data were calculated throughout as the mean and the standard deviation. qRT-PCR (Bax/Bcl-2-ratio, GFAP- and PGP9.5-levels) or western blot analysis was used to test for toxicity of Princess Volume after 24 h (and β-3 tubulin with GAPDH as a control gene). Significance was estimated by Student´s t-test; p ≤0.05 was considered to be statistically significant., Results: The IOP increased non-significantly by 10% after 24 h. Short-term biocompatibility testing using isolated superfused bovine retinas showed neither significant reductions of the b-wave nor the a-wave amplitudes (b-wave reduction 14.2%, p>0.05; a-wave reduction 23.9%, p>0.05). qRT-PCR and western blot analysis did not reveal significant toxicity after 24 h., Conclusions: The manufactured HA-based hydrogel showed highly favourable biophysical characteristics in the explored ex vivo models, justifying in vivo studies enabling the assessment of biocompatibility., Competing Interests: Parts of the experiments were financed by Croma Pharma GmbH, Austria. CH and CR are employed by Croma Pharma GmbH. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

One of the main ocular diseases is age-related macular degeneration, actually treated with antibodies injections into the eye. This problem has been faced by computational approaches, taking into account either the influence of the tissues surrounding the vitreous, or the saccades. The aim of this work is to propose a combined fluid dynamic model of the vitreous chamber that analyses the impact of the saccades on the fluid dynamic mechanisms. The ocular vitreous humor was modeled considering liquefaction occurring in presence of age-related macular degeneration. We identified two kinds of boundary conditions, one related to the physiological environment outside the chamber, and one related to the saccades. The scleral hydraulic conductivity was evaluated by means of experimental permeability tests. An exponential decay was used to describe the trend of the scleral hydraulic conductivity with the acting pressure drop. The streamline analysis shows two main stagnant regions on the equatorial plane and peculiar fluid dynamics in absence of saccades. This study demonstrates the major role played by the saccades in determining the fluid dynamic mechanisms inside the vitreous chamber of the eye and represents a powerful tool to investigate vitreous dynamics and its relation to clinical issues.

The intravitreal delivery of therapeutic agents promises major benefits in the field of ocular medicine. Traditional delivery methods rely on the random, passive diffusion of molecules, which do not allow for the rapid delivery of a concentrated cargo to a defined region at the posterior pole of the eye. The use of particles promises targeted delivery but faces the challenge that most tissues including the vitreous have a tight macromolecular matrix that acts as a barrier and prevents its penetration. Here, we demonstrate novel intravitreal delivery microvehicles-slippery micropropellers-that can be actively propelled through the vitreous humor to reach the retina. The propulsion is achieved by helical magnetic micropropellers that have a liquid layer coating to minimize adhesion to the surrounding biopolymeric network. The submicrometer diameter of the propellers enables the penetration of the biopolymeric network and the propulsion through the porcine vitreous body of the eye over centimeter distances. Clinical optical coherence tomography is used to monitor the movement of the propellers and confirm their arrival on the retina near the optic disc. Overcoming the adhesion forces and actively navigating a swarm of micropropellers in the dense vitreous humor promise practical applications in ophthalmology.

Purpose: To investigate real-time intraocular pressure (IOP) during small incision lenticule extraction (SMILE) in rabbit eyes for myopia correction., Methods: During SMILE, real-time IOP was measured in the vitreous cavity of rabbit eyes with an optic fiber pressure sensor (OFPS). Two groups (n = 6 for each) underwent surgery, one group for a -2.00 diopter (D) refractive spherical correction and the other for a -6.00 D correction., Results: During surgery, the IOP increased once the glass contact attached to the cornea (Pre-suction), and peaked 83.94 mmHg (SD ± 23.87 mmHg) for the -2.00 D group and 89.17 mmHg (SD ± 22.66 mmHg) for the -6.00 D group, both average values were less than 110 mmHg when suction was initiated to fix the glass contact onto the cornea (Suction on). It then fell to 74.81 mmHg (SD ± 20.64 mmHg) and 76.94 mmHg (SD ± 27.43 mmHg), respectively, and remained stable during lenticule creation (Cutting). After suction stopped (Suction off), IOP fell steeply. During lenticule separation/extraction, the change in IOP was 32.26 mmHg (SD ± 2.91 mmHg). Notably, the average duration of elevated IOP during the surgery was 166.05 s (no longer than 3 min)., Conclusions: The IOP fluctuations in the vitreous cavity using an OFPS in a rabbit model during SMILE showed that real-time IOP significantly was increased during Pre-suction, Suction on, Cutting, Suction off, and lenticule separation/extraction compared to baseline IOP, although, peaked at Suction on. Neither the degree of myopic correction nor central corneal thickness significantly affected these changes in IOP.

Purpose of present study is to evaluate whether the Pre-Macular Bursa (PMB) modifies Wall Shear Stress (WSS) at the retinal surface during saccadic movements. We created a mathematical model consisting of 25,000 grid cells and simulated a horizontal saccade spanning 50° in 0.17s, both in absence and in presence of the PMB. Wall Shear Stress SS was computed throughout the retinal surface and the posterior pole was divided into 3 Zones comprising 400 nodes each: Zone 1 (radius 3.5 mm; 0°-17°) corresponding to the PMB area; Zone 2 (concentric annular area 5 mm in radius; 22°) and Zone 3 (concentric annular area 5.5 mm; 28°). The PMB reduced WSS significantly at the macula and increased it in the immediate surroundings. Average WSS in Zone 1 was 1.53 ± 1.01 (max 4.23 Pa) with PMB Vs 6.94 ± 9.23 (max 35.83 Pa) without. Zone 2 WSS was 9.39 ± 10.33 (max 48.36 Pa) with PMB Vs 6.95 ± 9.40 (max 38.60 Pa) without Zone 3 WSS was 8.41 ± 10.03 (max 43.16 Pa) with PMB Vs 6.88 ± 9.42 (max 39.43 Pa) without (p < 0.001 in all cases). The PMB significantly reduces WSS over the retinal surface underlying the bursa region; conversely, WSS slightly increases it in the immediate neighboring areas., (Copyright © 2018. Published by Elsevier Ltd.)

Post-mortem measurements were made of the body temperature of dogs. The aim of the study was to evaluate and verify a reliable mathematical model that can be used to establish the time elapsed since the death of a dog during the initial post-mortem period at room temperature, using the eye (vitreous body), internal organs (heart, liver, kidney and lung), and rectum as sites for temperature measurement. The measurements were performed at six points in the body using an electronic thermometer in conjunction with a temperature probe. The method of temperature measurement is simple and does not cause perceptible macroscopic changes or disfigure the carcass. Multiple regression analysis was shown to be suitable for estimating the time elapsed from death to the discovery of the body for a period up to 12h post-mortem. The proposed multiple regression equation using body weight and the temperature at a specific site reduces manipulation of the carcass to a minimum and thus reduces error in establishing the time of death. The multiple regression model makes it possible to precisely estimate the time elapsed since the death of the animal., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: The murine double minute (MDM)2 is a critical negative regulator of the p53 tumor suppressor, and MDM2 SNP309G is associated with a higher risk of proliferative vitreoretinopathy (PVR); in addition, the MDM2 T309G created using clustered regularly interspaced short palindromic repeats (CRISPR)/associated endonuclease (Cas)9 enhances normal rabbit vitreous-induced expression of MDM2 and survival of primary human retinal pigment epithelial (hRPE) cells in vitro. The goal of this study was to determine whether this MDM2 T309G contributes to the development of experimental PVR., Methods: hRPE cells expressing MDM2 T309G or T309T only were treated with vitreous from human PVR donors (HV). The expression of MDM2 and p53 in the treated cells was examined by Western blot. The in vitro vitreous-induced cellular responses, such as contraction were assessed, and PVR was induced by intravitreal injection of the hRPE cells with MDM2 T309G or T309T only into rabbit eyes., Results: Western blot analyses indicated that treatment of hRPE cells with HV led to a significant increase (1.7 ± 0.2-fold) in the expression of MDM2 and a significant decrease in p53 in the cells expressing MDM2 T309G compared with those with MDM2 T309T. In addition, HV promoted contraction of the hRPE cells expressing MDM2 T309G significantly more than those with MDM2 T309T only. Furthermore, MDM2 T309G in the hRPE cells enhanced the development of PVR in a rabbit model., Conclusions: The MDM2 SNP309 in RPE cells enhances their potential of PVR pathogenesis.

Purpose: In humans, vitrectomy is associated with development of nuclear cataracts. Iron catalyzes free radical formation causing oxidative damage, which is implicated in cataract formation. This study was designed to determine if vitreous humor, which can initiate differentiation of lens epithelial cells, would have an effect on iron-handling proteins., Methods: Cultured canine lens epithelial cells were treated with collected canine vitreous humor. Lysates of treated and control cells were separated by SDS-PAGE. Ferritin H- and L-chains, transferrin receptor 1, and aquaporin 0 were immunodetected and quantitated with specific antibodies. Morphologic changes in treated cells were assessed., Results: Treatment of lens epithelial cells with a 33% (vol/vol) solution of vitreous humor changed the morphology of lens cells and induced expression of aquaporin 0, a marker of fiber cell differentiation that was undetectable in control cells. Treatment did not modify the size of iron-handling proteins but significantly increased content of ferritin from 2.9- to 8.8-fold over control and decreased levels of transferrin receptor by 37% to 59%., Conclusions: Vitreous humor may significantly limit iron uptake by transferrin/transferrin receptor pathway, and by increasing ferritin levels could profoundly increase the iron-storage capacity of ferritin in lens cells. Vitreous humor may play a significant protective role against iron-catalyzed oxidative damage of lens epithelial cells and therefore in the formation of cataracts.

Objetive: To determine whether vitrectomised eyes have a higher lens optical density, when measured with a Scheimpflug camera, compared to non-vitrectomised eyes., Method: The peak and linear Scheimpflug optical density (DOS), and area of both eyes were measured in a sample size of 81 vitrectomised phakic patients. A comparison was made between the DOS of the vitrectomised eye lens and the contralateral non-vitrectomised eye using the Student-t test., Results: A significantly higher linear DOS and area was obtained in the 81 vitrectomised phakic eyes when compared to the non-vitrectomised eyes (P<.001). The peak DOS is not significantly increased in respect to non-vitrectomised eyes (P=.59)., Conclusions: The lens DOS in vitrectomised eyes is higher than in non-vitrectomised eyes. The importance of the vitreous in the maintenance of lens transparency is emphasised., (Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

In rhegmatogenous retinal detachment (RRD), scattered RPE cells from the basement membrane into the vitreous cavity undergo an epithelial mesenchymal transition (EMT) and form the intraocular fibrous membrane in response to vitreous fluid. We investigated whether exposure to vitreous samples was associated with EMT-associated signals and mesenchymal characters. Human vitreous samples were collected from patients with RRD, epiretinal membrane (ERM), or macular hole (MH). We evaluated the effects of vitreous on ARPE-19 cells in suspension cultures using poly 2-hydroxyethyl methacrylate-coated dishes and three-dimensional (3D) Matrigel cultures. We found that exposure to vitreous samples did not induce morphological changes or accelerate wound closure in monolayers. Several samples showed increased phosphorylation of Smad2 and nuclear translocation of nuclear factor-κB. Mechanical stress triggered an elevation of phosphorylation levels in Smad2. In addition, exposure to vitreous fluid increased the phosphorylation of p38 mitogen-activated protein kinase in cell suspension cultures after mechanical stress. Moreover, ARPE-19 cells showed a stellate invasive phenotype in 3D Matrigel cultures with vitreous samples. In this study, we demonstrated that mechanical stress and vitreous were associated with EMT-associated signals and invasive phenotypes in 3D cultures but not in monolayers. These results have important implications for the role of vitreous humor in the induction of EMT and intraocular fibrosis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: To elucidate the dynamic accommodative movements of the lens capsule, posterior lens and the strand that attaches to the posterior vitreous zonule insertion zone and posterior lens equator (PVZ INS-LE), and their age-related changes., Methods: Twelve human subjects (ages 19-65 years) and 12 rhesus monkeys (ages 6-27 years) were studied. Accommodation was induced pharmacologically (humans) or by central electrical stimulation (monkeys). Ultrasound biomicroscopy was used to image intraocular structures in both species. Surgical procedures and contrast agents were utilized in the monkey eyes to elucidate function and allow visualization of the intraocular accommodative structures., Results: Human: The posterior pole of the lens moves posteriorly during accommodation in proportion to accommodative amplitude and ciliary muscle movement. Monkey: Similar accommodative movements of the posterior lens pole were seen in the monkey eyes. Following extracapsular lens extraction (ECLE), the central capsule bows backward during accommodation in proportion to accommodative amplitude and ciliary muscle movement, while the peripheral capsule moves forward. During accommodation the ciliary muscle moved forward by ~1.0 mm, pulling forward the vitreous zonule and the PVZ INS-LE structure. During the accommodative response the PVZ INS-LE structure moved forward when the lens was intact and when the lens substance and capsule were removed. In both the monkey and the human eyes these movements declined with age., Conclusions: The accommodative shape change of the central capsule may be due to the elastic properties of the capsule itself. For these capsule/lens accommodative posterior movements to occur, the vitreous face must either allow for it or facilitate it. The PVZ INS-LE structure may act as a 'strut' to the posterior lens equator (pushing the lens equator forward) and thereby facilitate accommodative forward lens equator movement and lens thickening. The age-related posterior restriction of the ciliary muscle, vitreous zonule and the PVZ-INS LE structure dampens the accommodative lens shape change. Future descriptions of the accommodative mechanism, and approaches to presbyopia therapy, may need to incorporate these findings., (© 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.)

The vitreous, the vasculature of the retina, macular pigments, phototransduction, retinal pigment epithelium, Bruch's membrane and the extracellular matrix, all play an important role in the normal function of the retina as well as in diseases. Understanding the pathophysiology allows us to target treatment. As ocular angiogenesis, immunity and inflammation are covered elsewhere, those subjects will not be discussed in this chapter., (© 2016 S. Karger AG, Basel.)

Objective: The aim of this study was to compare sonoelastographic findings in the retina-choroid-sclera (RCS) complex and vitreous in glaucomatous and healthy eyes., Methods: For this cross-sectional comparative study, 20 patients with primary open-angle glaucoma and 20 healthy volunteers were recruited. Ultrasound elastography measurements were taken with a sonographic scanner of the RCS complex, anterior vitreous (AV), posterior vitreous (PV), retrobulbar fat tissue (RFT), optic disc (OD) and optic nerve (ON) in each eye., Results: The elasticity index of the RCS complex, RFT, OD, ON, AV and PV was similar in both groups (p  >  0.05), although the AV/PV strain ratio in the group of patients with glaucoma was significantly higher (p  =  0.04)., Conclusion: Glaucoma increases the AV/PV strain ratio. In providing reproducible and consistent values, the real-time elastography (RTE) technique may be helpful in elucidating the mechanisms of glaucoma in some aspects., Advances in Knowledge: This study can help to evaluate the elasticity of the RCS complex and vitreous in glaucomatous eyes with RTE.

Purpose: To evaluate the influence of vitreomacular attachment on outcomes after intravitreal aflibercept for neovascular age-related macular degeneration., Methods: In a prospective case series, eyes with neovascular age-related macular degeneration were treated with intravitreal aflibercept, given as 3 consecutive monthly injections, followed by further injection every 2 months. Spectral domain optical coherence tomography images were reviewed at each visit to determine the attachment of the posterior hyaloid. Best-corrected visual acuity and retinal thickness were also recorded. Outcomes at Months 2 and 6 were compared between the eyes with persistent vitreomacular attachment (Stage 1) and those with posterior vitreous detachment (Stages 2 or 3 PVD) at baseline., Results: At baseline, 30 eyes had Stage 1 PVD and 63 eyes had either Stage 2 or 3 PVD. Although there was a trend for both greater visual acuity gains and reductions in retinal thickness for the eyes with Stages 2 or 3 PVD, this failed to reach significance. Baseline visual acuity and age were negatively associated with visual acuity change, and baseline retinal thickness alone was associated with retinal thickness change., Conclusion: Visual acuity, retinal thickness, and age at the baseline examination, but not PVD status, are associated with functional and anatomical outcomes after intravitreal aflibercept for neovascular age-related macular degeneration.

Vitrectomy is a standard ophthalmic procedure to remove the vitreous body from the eye. The biomechanics of the vitreous affects its duration (by changing the removal rate) and the mechanical forces transmitted via the vitreous on the surrounding tissues during the procedure. Biomechanical characterization of the vitreous is essential for optimizing the design and control of instruments that operate within the vitreous for improved precision, safety, and efficacy. The measurements are carried out using a magnetic microprobe inserted into the vitreous, a method known as magnetic microrheology. The location of the probe is tracked by a microscope/camera while magnetic forces are exerted wirelessly by applied magnetic fields. In this work, in vitro artificial vitreous, ex vivo human vitreous and ex vivo porcine vitreous were characterized. In addition, in vivo rabbit measurements were performed using a suturelessly injected probe. Measurements indicate that viscoelasticity parameters of the ex vivo human vitreous are an order of magnitude different from those of the ex vivo porcine vitreous. The in vivo intra-operative measurements show typical viscoelastic behavior of the vitreous with a lower compliance than the ex vivo measurements. The results of the magnetic microrheology measurements were validated with those obtained by a standard atomic force microscopy (AFM) method and in vitro artificial vitreous. This method allows minimally-invasive characterization of localized mechanical properties of the vitreous in vitro, ex vivo, and in vivo. A better understanding of the characteristics of the vitreous can lead to improvements in treatments concerning vitreal manipulation such as vitrectomy.

The purpose of this study is to determine baseline vitreous humor temperature during a combined phacoemulsification and pars plana vitrectomy (PPV) procedure; to determine what is the temperature variation during phacoemulsification; and to compare vitreous temperature to sublingual temperature. The methods used are prospective, interventional and comparative study. Patients with a diagnosis of cataract and vitreous hemorrhage, programed for a combined procedure of phacoemulsification and PPV, were included. Patients were excluded if posterior capsular rupture existed during the anterior segment procedure. A thermoprobe was inserted through a PPV trocar. Measurement of the vitreous temperature was obtained at baseline and throughout phacoemulsification, at the end of every surgical step, and every 5 min. Sublingual temperature was measured with the same probe at the end of the surgery. Room temperature was registered. Seventeen eyes of 17 patients were included. Mean sublingual temperature was 36.5 °C (standard deviation [σ] 0.26 °C). Mean total vitreous temperature was 31.47 °C (σ 2.1 °C). Mean baseline vitreous temperature was 33.04 °C (σ 0.99 °C). Comparison of sublingual temperature with baseline vitreous temperature resulted in a significant difference (t test P < 0.000. 95 % confidence interval 2.93-3.98). Temperature measured by surgical step and surgical time presented a significant decrease in temperature from baseline (Kruskal-Wallis P < 0.000, P = 0.003, respectively). Vitreous humor is significantly hypothermic when compared to sublingual temperature. Vitreous temperature decreases significantly during phacoemulsification.

Purpose: Our aim was to evaluate the ultrasound (US) elastography of ocular and periocular structures in high myopia., Methods: There were 20 eyes of 20 high myopic patients in the study group, whereas there were 20 eyes of 20 age- and sex-matched healthy participants in the control group. The eyes in the study group had myopia greater than -5.0 diopters and had axial length (AL) greater than 25.0 mm. The US elastography measurements were performed with the LOGİQ E9 Ultrasound Elastography. The elastography values of anterior vitreous, posterior vitreous (PV), retina-choroid-sclera complex (RCS), and retrobulbar fat tissue (RF) were measured in each eye., Results: Anterior vitreous US elastography values were similar in both groups (p = 0.17), whereas PV is more elastic in high myopic eyes (p = 0.01). There was a moderate negative correlation between AL and RCS/RF elastography ratio (r = -0.35, p = 0.03) and a positive correlation between refractive error and RCS/RF elastography ratio (r = 0.36, p = 0.02)., Conclusions: High myopia is associated with more elastic PV. Elasticity of posterior RCS increases as the AL increases.

Multiple rheological studies have characterized the dynamic material properties of adult vitreous, but no studies have investigated vitreous properties in the immature eye. In this study, premature, infant and adult ovine vitreous specimens were tested in shear to identify differences in dynamic moduli with age. Significant inertial artifact and rapid degradation of the vitreous ex vivo hindered the ability to accurately collect dynamic data through standard oscillation protocols. Therefore, dynamic moduli were calculated by converting relaxation spectrum data to the retardation spectrum, resulting in the calculation of the storage (G') and loss (G") moduli from the first few milliseconds of creep testing when tissue degradation and inertia is minimal. The technique was validated against two synthetic materials that span the viscoelastic spectrum. G' and G" of the primarily viscous synthetic material (polystyrene, tanδ=0.61) and G' of the primarily elastic material (agar, tanδ=0.06) were not significantly different than those calculated from dynamic oscillatory testing (p<0.05). G" of agar was overestimated (4-39%) with the interconversion technique due to creep ringing. Ovine vitreous was primarily viscous (tanδ=1.31), so this technique was used to evaluate changes in dynamic moduli with age. G' and G" for adult vitreous was 2-4 times and 1.5-2 times lower, respectively, than infant vitreous, corresponding to the structural breakdown of the vitreous with age. The dynamic moduli of premature vitreous was lower than infant and adult, likely due to premature development of the vitreal structure. These data suggest that significant differences exist between the viscoelastic response of infant and adult vitreous, and computational models of the pediatric eye will require appropriate age and rate material properties of vitreous., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: The purpose of the present study was to investigate the profile of posterior precortical vitreous pocket (PPVP) in children using spectral-domain optical coherence tomography (OCT) and to compare the profile with that of adults., Materials and Methods: In this retrospective comparative study, the height at the fovea and the horizontal diameter of PPVP in healthy children and adults in the upright position were measured based on OCT (Spectralis, Heidelberg Engineering GmbH, Heidelberg, Germany) images. PPVP diameter was divided into nasal length and temporal length based on the center of the fovea. The proportion of temporal length to the entire horizontal diameter was calculated as temporal length/horizontal diameter of PPVP. The association of age with the height and the proportion of temporal length to the entire horizontal diameter were evaluated in each group. The two values were also compared between the two groups., Results: Sixty-three eyes of 63 children (mean age: 6.9 ± 1.8 years) and 44 eyes of 44 young adults (mean age: 32.1 ± 5.3 years) were included. The height of PPVP at the fovea was 355.3 ± 80.3 µm in children and 367.8 ± 75.6 µm in adults. The proportion of temporal length to the entire horizontal diameter was 0.45 ± 0.05 and 0.50 ± 0.03. The proportion was significantly greater in adults than in children (p < 0.001), whereas the height (p = 0.349) was not different between the two groups. In children, there was a positive association between the age and the proportion of temporal length to the entire horizontal diameter (p = 0.001)., Conclusion: The results suggest a progressive temporal extension of PPVP during childhood.

We applied a metabolomic approach to monitor the modifications occurring in goat vitreous humor (VH) metabolite composition at different times (0, 6, 12, 18, and 24 hours) after death. The (1)H-NMR analysis of the VH samples was performed for the simultaneous determination of several metabolites (i.e., the metabolite profile) representative of the VH status at different times. Spectral data were analyzed by Principal Component Analysis (PCA) and by Orthogonal Projection to Latent Structures (OPLS) regression technique. PCA and OPLS suggested that different spectral regions were involved in time-related changes. The major time-related compositional changes, here detected, were the increase of lactate, hypoxanthine, alanine, total glutathione, choline/phosphocholine, creatine, and myo-inositol and the decrease of glucose and 3-hydroxybutyrate. We attempted a speculative interpretation of the biological mechanisms underlying these changes. These results show that multivariate statistical approach, based on (1)H NMR metabolite profiling, is a powerful tool for detecting ongoing differences in VH composition and may be applied to investigate several physiological and pathological conditions.

Purpose: Vitreous liquefaction and subsequent posterior vitreous detachment can lead to several sight-threatening diseases, including retinal detachment, macular hole and macular traction syndrome, nuclear cataracts, and possibly, open-angle glaucoma. In this study, we tested the ability of three novel synthetic chondroitin sulfate proteoglycan mimics to preserve the structure and physical properties of enzymatically-degraded bovine vitreous., Methods: Chondroitin sulfate proteoglycan mimics, designed to bind to type II collagen, hyaluronic acid, or both, were applied to trypsin- or collagenase-treated bovine vitreous in situ and in vitro. Rheology and liquefaction tests were performed to determine the physical properties of the vitreous, while Western blots were used to detect the presence and degradation of soluble collagen II (α1). Deep-etch electron microscopy (DEEM) identified the ultrastructure of mimic-treated and untreated enzyme-degraded bovine vitreous., Results: Proteoglycan mimics preserved the physical properties of trypsin-degraded bovine vitreous and protected against vitreous liquefaction. Although the collagen-binding mimic maintained the physical properties of collagenase-treated vitreous, liquefaction still occurred. Western blots indicated that the mimic provided only marginal protective ability against soluble collagen degradation. Deep-etch electron microscopy, however, showed increased density and isotropy of microstructural components in mimic-treated vitreous, supporting the initial result that vitreous structure was preserved., Conclusions: Proteoglycan mimics preserved bovine vitreous physical properties after enzymatic degradation. These compounds may be useful in delaying or preventing the pathological effects of age-related, or enzymatically-induced, degradation of the vitreous body., (Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.)

Proliferative vitreoretinopathy (PVR) remains one of the most common causes of failed retinal detachment (RD) surgery. Many histological and clinical studies have highlighted the chain of events leading to PVR: cellular migration into the vitreous cavity, cellular differentiation, myofibroblast proliferation and activation, synthesis of extracellular matrix proteins, then contraction of preretinal tissues. The development of PVR can be explained schematically by cellular exposure to growth factors and cytokines (particularly retinal pigment epithelial cells and glial cells), in the context of break-down of the blood-retinal barrier (inflammation, choroidal detachment, iatrogenic effect of cryotherapy and surgery) and of cellular contact with the vitreous. Although the pathophysiology of PVR is now better understood, its severity remains an issue. A systematic search for preoperative PVR risk factors allows the most suitable therapeutic option to be chosen., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Purpose: To describe enhanced vitreous imaging for visualization of anatomic features and microstructures within the posterior vitreous and vitreoretinal interface in healthy eyes using swept-source optical coherence tomography (SS-OCT). The study hypothesis was that long-wavelength, high-speed, volumetric SS-OCT with software registration motion correction and vitreous window display or high-dynamic-range (HDR) display improves detection sensitivity of posterior vitreous and vitreoretinal features compared to standard OCT logarithmic scale display., Design: Observational prospective cross-sectional study., Methods: Multiple wide-field three-dimensional SS-OCT scans (500×500A-scans over 12×12 mm2) were obtained using a prototype instrument in 22 eyes of 22 healthy volunteers. A registration motion-correction algorithm was applied to compensate motion and generate a single volumetric dataset. Each volumetric dataset was displayed in three forms: (1) standard logarithmic scale display, enhanced vitreous imaging using (2) vitreous window display and (3) HDR display. Each dataset was reviewed independently by three readers to identify features of the posterior vitreous and vitreoretinal interface. Detection sensitivities for these features were measured for each display method., Results: Features observed included the bursa premacularis (BPM), area of Martegiani, Cloquet's/BPM septum, Bergmeister papilla, posterior cortical vitreous (hyaloid) detachment, papillomacular hyaloid detachment, hyaloid attachment to retinal vessel(s), and granular opacities within vitreous cortex, Cloquet's canal, and BPM. The detection sensitivity for these features was 75.0% (95%CI: 67.8%-81.1%) using standard logarithmic scale display, 80.6% (95%CI: 73.8%-86.0%) using HDR display, and 91.9% (95%CI: 86.6%-95.2%) using vitreous window display., Conclusions: SS-OCT provides non-invasive, volumetric and measurable in vivo visualization of the anatomic microstructural features of the posterior vitreous and vitreoretinal interface. The vitreous window display provides the highest sensitivity for posterior vitreous and vitreoretinal interface analysis when compared to HDR and standard OCT logarithmic scale display. Enhanced vitreous imaging with SS-OCT may help assess the natural history and treatment response in vitreoretinal interface diseases.

Proliferative vitreoretinopathy (PVR) is a blinding disorder that occurs in eyes with rhegmatogenous retinal detachment and in eyes that have recently undergone retinal detachment surgery. There are presently no treatment strategies to reduce the risk of developing PVR in eyes with retinal detachment, and surgical intervention is the only option for eyes with retinal detachment and established PVR. Given the poor visual outcome associated with the surgical treatment of PVR, considerable work has been done to identify pharmacologic agents that could antagonize the PVR process. Intensive efforts to identify molecular determinants of PVR implicate vitreal growth factors. A surprise that emerged in the course of testing the 'growth factor hypothesis' of PVR was the existence of a functional relationship amongst growth factors that engage platelet-derived growth factor (PDGF) receptor α (PDGFRα), a receptor tyrosine kinase that is key to pathogenesis of experimental PVR. Vascular endothelial cell growth factor A (VEGF), which is best known for its ability to activate VEGF receptors (VEGFRs) and induce permeability and/or angiogenesis, enables activation of PDGFRα by a wide spectrum of vitreal growth factors outside of the PDGF family (non-PDGFs) in a way that triggers signaling events that potently enhance the viability of cells displaced into vitreous. Targeting these growth factors or signaling events effectively neutralizes the bioactivity of PVR vitreous and prevents PVR in a number of preclinical models. In this review, we discuss recent conceptual advances in understanding the role of growth factors in PVR, and consider the tangible treatment strategies for clinical application., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Histones are DNA-binding proteins and are involved in chromatin remodeling and regulation of gene expression. Histones can be released after tissue injuries, and the extracellular histones cause cellular damage and organ dysfunction. Regardless of their clinical significance, the role and relevance of histones in ocular diseases are unknown. We studied the role of histones in eyes with retinal detachment (RD). Vitreous samples were collected during vitrectomy, and the concentration of histone H3 was measured by enzyme-linked immunosorbent assay. The location of the histones and related molecules was examined in a rat RD model. The release of histones and their effects on rat retinal progenitor cells R28 and ARPE-19 were evaluated in vitro. In addition, the protective role of the vitreous body against histones was tested. The intravitreal concentration of histones was higher in eyes with RD (mean, 30.9 ± 9.8 ng/ml) than in control eyes (below the limit of detection, P<0.05). In the rat RD model, histone H3 was observed on the outer side of the detached retina and was associated with photoreceptor death. Histone H3 was released from cultured R28 by oxidative stress. Histones at a concentration 10 μg/ml induced the production of interleukin-8 in ARPE-19 cells (2.5-fold increase, P<0.05) that was mediated through the ERK1/2- and p38 MAPK-dependent pathways and Toll-like receptor 4. Histones were toxic to cells at concentrations of ≥ 20 μg/ml. Vitreous body or hyaluronan decreased toxicity of histones by inhibiting diffusion of histones. These results indicate that histones are released from retinas with RD and may modulate the subretinal microenvironment by functioning as damage-associated molecular pattern molecules, thereby inducing proinflammatory cytokines or cell toxicity. In addition, the important role of the vitreous body and hyaluronan in protecting the retina from these toxic effects is suggested.

This work aimed to consider the hazardous side effect of eye floaters treatment with Q-switched Nd:YAG laser on the protein and viscoelastic properties of the vitreous humor, and evaluate the protective role of vitamin C against laser photo disruption. Five groups of New Zealand rabbits were divided as follows: control group for (n = 3) without any treatment, the second group (n = 9) treated with Q-switched Nd:YAG laser energy of 5 mJ × 100 pulse delivered to the anterior, middle, and posterior vitreous, respectively (n = 3 for each). The third group (n = 9) received a daily dose of 25 mg/kg body weight vitamin C for 2 weeks, and then treated with laser as the previous group. The fourth group (n = 9) treated with 10 mJ 9 50 pulse delivered to the anterior, middle, and posterior vitreous, respectively (n = 3 rabbits each). The fifth group (n = 9) received a daily dose of 25 mg/kg body weight vitamin C for 2 weeks, and then treated with laser as the previous group. After 2 weeks of laser treatment, the protein content, refractive index (RI), and the rheological properties of vitreous humor, such as consistency, shear stress, and viscosity, were determined. The results showed that, the anterior vitreous group exposed to of 5 mJ × 100 pulse and/or supplemented with vitamin C, showed no obvious change. Furthermore, all other treated groups especially for mid-vitreous and posterior vitreous humor showed increase in the protein content, RI and the viscosity of vitreous humor. The flow index remained below unity indicating the non-Newtonian behavior of the vitreous humor. Application of Q-switched Nd:YAG laser should be restricted to the anterior vitreous humor to prevent the deleterious effect of laser on the gel state of the vitreous humor.

We discuss some aspects of the fluid dynamics of vitreous substitutes in the vitreous chamber, focussing on the flow induced by rotations of the eye bulb. We use simple, yet not trivial, theoretical models to highlight mechanical concepts that are relevant to understand the dynamics of vitreous substitutes and also to identify ideal properties for vitreous replacement fluids. We first recall results by previous authors, showing that the maximum shear stress on the retina grows with increasing viscosity of the fluid up to a saturation value. We then investigate how the wall shear stress changes if a thin layer of aqueous humour is present in the vitreous chamber, separating the retina from the vitreous replacement fluid. The theoretical predictions show that the existence of a thin layer of aqueous is sufficient to substantially decrease the shear stress on the retina. We finally discuss a theoretical model that predicts the stability conditions of the interface between the aqueous and a vitreous substitute. We discuss the implications of this model to understand the mechanisms leading to the formation of emulsion in the vitreous chamber, showing that instability of the interface is possible in a range of parameters relevant for the human eye.

This paper presents a fully functionally integrated 1024-channel mixed-mode and mixed-voltage system-on-a-chip (SoC) for epi-retinal and neural prostheses. Taking an AC input, an integrated power telemetry circuits is capable of generating multiple DC voltages with a voltage conversion efficiency of 83% at a load of 100 mW without external diodes or separate power integrated circuits, reducing the form factor of the prosthetic device. A wireless DPSK receiver with a novel noise reduction scheme supports a data rate of 2 Mb/s at a bit-error-rate of 2 ×10⁻⁷. The 1024-channel stimulator array meets an output compliance voltage of ±10 V and provides flexible stimulation waveforms. Through chip-clustering, the stimulator array can be further expanded to 4096 channels. This SoC is designed and fabricated in TSMC 0.18 μm high-voltage 32 V CMOS process and occupies a chip area of 5.7 mm × 6.6 mm. Using this SoC, a retinal implant bench-top test system is set up with real-time visual verification. In-vitro experiment conducted in artificial vitreous humor is designed and set-up to investigate stimulation waveforms for better visual resolution. In our in-vivo experiment, a hind-limb paralyzed rat with spinal cord transection and implanted chronic epidural electrodes has been shown to regain stepping and standing abilities using stimulus provided by the SoC.

Background: The vitreous has been shown to induce epithelial-mesenchymal transdifferentiation because it induces fibroblast-like morphology, enhanced migration and invasion in retinal pigment epithelial cells in proliferative vitreoretinopathy. Rac1 is the principal mediator of cell migration. In the current study, the relationship between Rac1 and cell migration, and invasion in vitreous-transformed retinal pigment epithelial cells was investigated using NSC23766, a specific inhibitor of Rac guanosine-5'-triphosphatase activity, and the involvement of a Rac1 guanosine-5'-triphosphatase-dependent pathway was detected., Design: One-way design with multiple levels and repeated measurement design., Participants and Samples: The vitreous humor was collected from 20 healthy donor eyes and the retinal pigment epithelial cells were obtained from 9 healthy donor eyes., Methods: Human low-passage retinal pigment epithelial cells were treated with normal medium or 25% vitreous medium. Rac1 activity was measured using a pull-down assay. The cytotoxicity of NSC23766 was measured using the trypan blue dye exclusion test. Cell migration was measured using a wound healing assay. Cell invasion was determined using a transwell invasion assay. Protein expression of Rac1 and phosphorylation of LIM kinase 1 and cofilin were detected by Western blot analysis., Main Outcome Measures: Cell migration, invasion, Rac1 activity and phosphorylation of LIM kinase 1 and cofilin., Results: Rac1guanosine-5'-triphosphatase was activated in vitreous-transformed retinal pigment epithelial cells. A Rac inhibitor suppressed vitreous-induced migration and invasion in retinal pigment epithelial cells. Cofilin phosphorylation was activated by vitreous treatment but blocked by NSC23766., Conclusions: Rac1 mediates vitreous-transformed retinal pigment epithelial cells' plasticity of mesenchymal movement via Rac1 guanosine-5'-triphosphatase-dependent pathways that modulate LIM kinase 1 and cofilin activity. Rac inhibition may be considered a novel treatment for proliferative vitreoretinopathy., (© 2013 The Authors. Clinical and Experimental Ophthalmology © 2013 Royal Australian and New Zealand College of Ophthalmologists.)

Polyethylene glycol (PEG) is a short-term (41 days) potential vitreous substitute and is too short for an ideal vitreous substitute. Previously, a foldable capsular vitreous body (FCVB) was designed to mimic vitreous function. The aim of this study is to evaluate whether PEG injected into FCVB can serve as a long-term vitreous substitute. In vitro study, a concentration of 5% (w/v) PEG sols showed natural-like mechanical and optical properties in terms of pH, density, light transmittance, refractive index, interfacial tension, viscosity, rheology, and cytotoxicity. Then in vivo tests, 30 rabbits received standard pars plana vitrectomy, of which 12 eyes were implanted with PEG injected into FCVB, nine eyes were injected with PEG sols alone, and nine others were injected with balance salt solution as control. A clinical evaluation of the anterior segment, fundus, and intraocular pressure was measured pre- and postoperatively up to 180 days, which showed that FCVBs had good retina supporting function, except for a higher incidence of cataracts. Gross pathology, hematoxylin and eosin, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining analysis also showed that FCVBs had good biocompatibility, and that all quadrants of the capsular wall fitted well with the retina. This study demonstrated that PEG injected into FCVB can serve as a long-term vitreous substitute and has potential clinical use., (Copyright © 2013 Wiley Periodicals, Inc.)

The biomechanical properties of Müller glial cells may have importance in understanding the retinal tissue alterations after retinal surgery with removal of the inner limiting membrane and during the ontogenetic development, respectively. Here, we compared the viscoelastic properties of Müller cells from man and monkey as well as from different postnatal developmental stages of the rat. We determined the complex Young's modulus E = E' + iE″ in a defined range of deforming frequencies (30, 100, and 200 Hz) using a scanning force microscope, where the real part E' reflects the elastic property (energy storage or elastic stiffness) and the imaginary part E″ reflects the viscous property (energy dissipation) of the cells. The viscoelastic properties were similar in Müller cells from man, monkey, and rat. In general, the elastic behavior dominated over the viscous behavior (E' > E″). The inner process of the Müller cell was the softest region, the soma the stiffest (Einnerprocess(')Eglia(')). These relations were also observed during the postnatal development of the rat. It is concluded that, generally, retinal cells display mechanics of elastic solids. In addition, the data indicate that the rodent retina is a reliable model to investigate retinal mechanics and tissue alterations after retinal surgery. During retinal development, neuronal branching and synaptogenesis might be particularly stimulated by the viscoelastic properties of Müller cell processes in the inner plexiform layer., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the morphologic features of posterior precortical vitreous pockets (PPVPs) with positional changes using spectral domain optical coherence tomography., Methods: The authors measured the distance between the fovea and anterior PPVP border on spectral domain optical coherence tomography scans in both eyes of 20 consecutive individuals and compared the differences with changes in position from sitting to supine., Results: A PPVP was identified in both eyes of 14 individuals (70%). In the vertical scan, the superior portion of the pocket was larger than the inferior portion in all 28 eyes when the participants were sitting. The mean distances between the fovea and the anterior PPVPs that border in the right and left eyes, respectively, were 477.6 ± 40.7 μm and 497.1 ± 31.8 μm when the participants were sitting and 665.6 ± 51.6 μm and 750.5 ± 48.2 μm when the participants were supine. The differences between the 2 positions were significant (P < 0.005)., Conclusion: The superior portion of the PPVPs enlarged when the participants were sitting. The anterior border of the pocket moved anteriorly when the participants were supine.

Biological fluids fulfill key functionalities such as hydrating, protecting, and nourishing cells and tissues in various organ systems. They are capable of these versatile tasks owing to their distinct structural and viscoelastic properties. Characterizing the viscoelastic properties of bio-fluids is of pivotal importance for monitoring the development of certain pathologies as well as engineering synthetic replacements. Laser Speckle Rheology (LSR) is a novel optical technology that enables mechanical evaluation of tissue. In LSR, a coherent laser beam illuminates the tissue and temporal speckle intensity fluctuations are analyzed to evaluate mechanical properties. The rate of temporal speckle fluctuations is, however, influenced by both optical and mechanical properties of tissue. Therefore, in this paper, we develop and validate an approach to estimate and compensate for the contributions of light scattering to speckle dynamics and demonstrate the capability of LSR for the accurate extraction of viscoelastic moduli in phantom samples and biological fluids of varying optical and mechanical properties.

To investigate refractive and axial responses to the shift of focal plane resulting from the interchange of two monochromatic lights separately corresponding to the peak wavelengths of the cones absorption spectrum in retina, fifty 2-week-old pigmented guinea pigs were randomly assigned to five groups based on the mode of illumination: short-wavelength light (SL), middle-wavelength light (ML) and broad-band white light (BL) for 20 weeks, SL for 10 weeks followed by ML for 10 weeks (STM), as well as ML for 10 weeks followed by SL for 10 weeks (MTS). Biometric and refractive measurements were then performed every 2 weeks. After 10 weeks, SL and STM groups became more hyperopic and had less vitreous elongation than BL group. However, ML and MTS groups became more myopic and had more vitreous elongation. After interchange of the monochromatic light, the refractive error decreased rapidly by about 1.93D and the vitreous length increased by 0.14 mm in STM group from 10 to 12 weeks. After that, there were no significant intergroup differences between STM and BL groups. The interchange from ML to SL quickly increased the refractive error by about 1.53D and decreased the vitreous length by about 0.13 mm in MTS group after two weeks. At this time, there were also no significant intergroup differences between MTS and BL groups. The guinea pig eye can accurately detect the shift in focal plane caused by interchange of two monochromatic lights and rapidly generate refractive and axial responses. However, an excessive compensation was induced. Some properties of photoreceptors or retina may be changed by the monochromatic light to influence the following refractive development.

During retinal surgical treatment often the gel-like vitreous humor is replaced by aqueous substitutes. A two-dimensional computational model is developed for simulating transpupillary thermotherapy (TTT) process in a human eye under post-retinal treatment. The model accounts for natural convection in vitreous humor and the choroidal blood perfusion. Time dependent and steady state forms of Pennes bio heat transfer and the natural convection governing energy equations are solved using finite volume formulation. The results for steady state and at the end of 60 s of the laser irradiated TTT process show that flow in vitreous humor is significant. The velocity contours indicate strong natural convection on the upper half of the vitreous chamber. Compared with the stationary vitreous case, the peak temperature in retina during TTT, drops by 15 K and 12.5 K due to natural convection flow in the vitreous humor under steady and transient states, respectively. The choroidal blood perfusion also reduces the peak retinal temperature by 6 K and 1.5 K in steady state and transient cases, respectively. The vitreous humor convection enhances heat transfer in the regions adjacent to the laser spot. The temperature rise and the associated thermal damage in the neighboring regions resulting from the flow of vitreous humor is presented., (Copyright © 2013 John Wiley & Sons, Ltd.)

In this study, the distributions of intravitreal injected drugs in post-vitrectomy human eyes, which are subjected to periodic saccade movements, are investigated. The computational model for the vitreous cavity of human eye is a sphere with one side truncated by the eye lens. A dynamic mesh technique was used to model the eye motion and the unsteady 3-D forms of continuity; Navier-Stokes and concentration transport of drug equations were solved numerically. The numerical model was validated earlier for the vitreous liquid flow field. The predicted drug concentration for idealized geometry was compared with the available analytic solution and excellent agreement was observed. The validated computer model was then used to simulate a real vitreous cavity filled with Balanced Salt Solution or aqueous humor as a vitreous substitute in order to obtain distribution of drugs in the post-vitrectomy eyes or liquefied vitreous. Additionally, effects of locations of drug injection, drug diffusion coefficients and saccade amplitude on the drug distribution and its uniformity were investigated. Although the earlier findings in the literature reported a day or a week as a needed time for drug uniform distribution in the vitreous substitutes, the present work depicts that saccade movements augment the transport of the drug in a way that the uniformity of the drug distribution can be achieved in a matter of minutes. Furthermore, in a vitreous cavity subjected to the saccade movements, the diffusion coefficient of drugs does not significantly affect their distribution after a few minutes. Even the injection location does not matter as uniform distribution is achieved after some time.

Intravitreal drug delivery is a commonly used treatment for several retinal diseases. The objective of this research is to characterize and quantify the role of the vitreous humor motion, induced by saccadic movements, on drug transport processes in the vitreous chamber. A Perspex model of the human vitreous chamber was created, and filled with a purely viscous fluid, representing eyes with a liquefied vitreous humor or those containing viscous tamponade fluids. Periodic movements were applied to the model and the resulting three-dimensional (3D) flow fields were measured. Drug delivery within the vitreous chamber was investigated by calculating particle trajectories using integration over time of the experimental velocity fields. The motion of the vitreous humor generated by saccadic eye movements is intrinsically 3D. Advective mass transport largely overcomes molecular diffusive transport and is significantly anisotropic, leading to a much faster drug dispersion than in the case of stationary vitreous humor. Disregarding the effects of vitreous humor motion due to eye movements when predicting the efficiency of drug delivery treatments leads to significant underestimation of the drug transport coefficients, and this, in turn, will lead to significantly erroneous predictions of the concentration levels on the retina.

Purpose: To identify and quantify sources of error on refractive assessment using exact ray tracing., Methods: The Liou-Brennan eye model was used as a starting point and its parameters were varied individually within a physiological range. The contribution of each parameter to refractive error was assessed using linear regression curve fits and Gaussian error propagation analysis. A MonteCarlo analysis quantified the limits of refractive assessment given by current biometric measurements., Results: Vitreous and aqueous refractive indices are the elements that influence refractive error the most, with a 1% change of each parameter contributing to a refractive error variation of +1.60 and -1.30 diopters (D), respectively. In the phakic eye, axial length measurements taken by ultrasound (vitreous chamber depth, lens thickness, and anterior chamber depth [ACD]) were the most sensitive to biometric errors, with a contribution to the refractive error of 62.7%, 14.2%, and 10.7%, respectively. In the pseudophakic eye, vitreous chamber depth showed the highest contribution at 53.7%, followed by postoperative ACD at 35.7%. When optic measurements were considered, postoperative ACD was the most important contributor, followed by anterior corneal surface and its asphericity. A MonteCarlo simulation showed that current limits of refractive assessment are 0.26 and 0.28 D for the phakic and pseudophakic eye, respectively., Conclusions: The most relevant optical elements either do not have available measurement instruments or the existing instruments still need to improve their accuracy. Ray tracing can be used as an optical assessment technique, and may be the correct path for future personalized refractive assessment., (Copyright 2013, SLACK Incorporated.)

Physically transparent cornea, lens, and vitreous body are not transparent from histophysiological viewpoint and hence, cannot directly transmit light to the retina. The lens forms from two primordia in the course of the eye development: ectodermal (for capsular epithelium) and neuroglia (for lenticular stroma). These data suggest that the neuroglia migrating from the internal leaflet of the ocular goblet is a source of stromal fibroblasts of the corneal proper substance and also presents the fibroblast differons in the human ocular vitreous body and in the lenticular posterior pole. The common source in the development of the stroma of the transparent structures of the eye is explained and confirmed by the fact that the cornea, lens, vitreous body, and the retinal and brain neuroglia contain special proteins common for all these structures, crystallins. The structural relationship and origin of fibroblasts of the transparent ocular media underlie the identical functions of crystallin production; the physical and chemical characteristics of crystallins prevent the diffusion of light and cumulate it in one direction. In addition, our data on the neuroglial origin of the lenticular stroma suggest that the lenticular cells can act as Muller's glia, regulating the transformed energy flow. Hence, the fibers and stromal cells of the cornea, lens, vitreous body, and retinal glia can serve as components of the universal conduction system perceiving light, transforming it into another type of energy (presumably into electromagnetic waves or some motor pulse), and only then sending it to the photosensor cells. As a result, we have one-way light conduction due to stromal cells of transparent eye structures and inability of the retina to identify these cells. We therefore conclude that the cells located in front of the retina are invisible for the photoreceptors, because they conduct stimulation being not transparent in the physical sense, but just physiologically. We see only what this unique conduction system allows us to see.

The vitreous is a complex structure whose composition and appearance change with age. Anomalous adhesions between the posterior vitreous face and the retinal surface are the cause of numerous vitreoretinal complications, while the presence of an intact posterior hyaloid provides a scaffold for vascular growth and anteroposterior traction. This review summarizes what is known about the biochemistry of the vitreous, the process of posterior vitreous detachment (PVD) development, and the available clinical approaches to examining the vitreous and its interface. A pooled analysis of studies looking at the presence of a complete, partial or absent PVD in a number of macular and retinal diseases allows us to establish odds ratios for these various states. From this emerge both protective and disease-associated states in conditions such as proliferative diabetic retinopathy, macular edema, and age-related macular degeneration. With the emergence of pharmacological means to separate the posterior hyaloid, a better understanding of the possible role of the vitreous in tractional syndromes is required., (Copyright © 2013 S. Karger AG, Basel.)

The goal of this work was to compare human temperature decay curves generated from execution of a COMSOL Multiphysics(®) finite element software model with that of experimental postmortem temperature decay curves. Experiments were performed in 10 human cadavers. The postmortem temperature was continuously measured in human eyeballs and rectums from c. 3 h up to 15 h postmortem. Model-generated curves reflected experimental curves for 10 cases with coefficients of determination ranging from 0.9448 to 0.9953. From modeling efforts, normalized temperature decay curves were generated to aid first responders to estimate time of death within the early postmortem period of 0-24 h. This proposed model has advantages over other models in that it is applied to the human eyeball, where temperature plateau effects are minimal to nonexistent. Nevertheless, the proposed model can be adjusted to compensate for any temperature plateau effects that do exist. It also can take account of antemortem hyperthermia conditions that are known to have occurred. The current model only applies to natural environmental conditions, with no forced convection, no direct sunlight, immersion in water, or other unusual conditions., (© 2012 American Academy of Forensic Sciences.)