Vitreous Humor Rheology After Nd:YAG Laser Photo Disruption

Abdelkawi, Salwa Ahmed; Abdel-Salam, A. M.; Ghoniem, Dina Fouad; Ghaly, Sally K.

doi:10.1007/s12013-013-9706-5

Cited by 18 publications

(12 citation statements)

References 22 publications

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“…While the composition and nature of vitreous humor has been the subject of considerable investigation,13,37–40 there is no consensus on whether or how these factors influence drug distribution, nor are there robust data on interspecies differences in many aspects of vitreous composition. Indeed, while rabbit vitreous frequently is stated to be “more viscous” than that of other species (human, monkey), a conclusion that gross physical appearances of dissected vitreous supports, there is considerable debate in the field regarding how to most appropriately characterize the rheologic and mechanical properties of the vitreous 13,37,38,41,42. In existing ocular models, vitreous humor has been described alternately as a porous medium (e.g., Missel14), or a homogeneous viscous fluid (e.g., Schmitt19).…”

Section: Discussionmentioning

confidence: 99%

Influence of Charge, Hydrophobicity, and Size on Vitreous Pharmacokinetics of Large Molecules

Crowell¹,

Wang²,

Famili³

et al. 2019

Trans. Vis. Sci. Tech.

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PurposeDevelopment of therapeutics for retinal disease with improved durability is hampered by inadequate understanding of pharmacokinetic (PK) drivers following intravitreal injection. Previous work shows that hydrodynamic radius is correlated with vitreal half-life over the range of 3 to 7 nm, and that charge and hydrophobicity influence systemic clearance. Better understanding the molecular attributes affecting vitreal elimination half-life enables improved design of therapeutics and enhances clinical translatability.MethodsImpacts of charge and hydrophobicity on vitreal PK in the rabbit were systematically assessed using antibody and antibody fragment (Fab) variant series, including ranibizumab, altered through amino acid changes in hypervariable regions of the light chain. The impact of molecule size on vitreal PK was assessed in the rabbit, nonhuman primate, and human for a range of molecules (1–45 nm, net charge −1324 to +22.9 in rabbit), including published and internal data.ResultsNo correlation was observed between vitreal PK and charge or hydrophobicity. Equivalent rabbit vitreal PK was observed for ranibizumab and its variants with isoelectric points (pI) in the range of 6.8 to 10.2, and hydrophobicities of the variable domain unit (FvHI) between 1009 and 1296; additional variant series had vitreal PK similarly unaffected by pI (5.4–10.2) and FvHI (1004–1358). Strong correlations were observed between vitreal half-life and hydrodynamic radius for preclinical species (R2 = 0.8794–0.9366).ConclusionsDiffusive properties of soluble large molecules, as quantified by hydrodynamic radius, make a key contribution to vitreal elimination, whereas differences in charge or hydrophobicity make minor or negligible contributions.Translational RelevanceThese results support estimation of vitreal elimination rates based on molecular size in relevant preclinical species and humans.

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Section: Discussionmentioning

confidence: 99%

Influence of Charge, Hydrophobicity, and Size on Vitreous Pharmacokinetics of Large Molecules

Crowell¹,

Wang²,

Famili³

et al. 2019

Trans. Vis. Sci. Tech.

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“…Only by using pulse durations in the nanosecond-range and focusing the radiation, these laser systems can generate optical breakdowns, accompanied by generating cavitation bubbles. Contradictory statements have been made about the rheology of corpus vitreum in the literature: Whereas Krauss et al found no essential changes of the vitreous body 23 after Q-switch Nd:YAG laser irradiation, Abdelkawi et al could determine clear effects on vitreous body rheology (e.g., a change in protein content, refractive index, viscosity and consistency) 24 , 25 .…”

Section: Discussionmentioning

confidence: 99%

“…Despite the fact that the vitreous body exhibits rheological properties like a non-Newtonian fluid 23 – 25 , values of the viscosity are not clearly defined in the literature. Some data are given as dynamic viscosity adopted to Newton’s law as a Newtonian fluid, given in Eq.…”

Section: Discussionmentioning

confidence: 99%

A promising approach in laser vitrectomy executed by plasma-mediated removal of vitreous body via a diode-pumped Q-switched Nd:YAG laser

Uthoff

Oravecz

Kuehnl

et al. 2020

Sci Rep

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To examine the applicability of plasma-mediated vitreous body removal, a diode-pumped Q-switched Neodymium:YAG laser was used for a possible application in eye surgery/vitrectomy. On a total of 1500 porcine vitreous bodies, removal rates were evaluated by comparing different LaserVit-tip designs (Mark I/II Gauge 19 and Mark III Gauge 22). The Nd:YAG laser, operating at a wavelength of 1064 nm and a pulse duration of 4 ns, was utilized for vitreous body removal with respective settings of 2, 3 and 4 mJ and pulse repetition rates (cut rates) from 5 to 25 Hz (300–1500 /min) in 5 Hz-steps as well as for 100 Hz (6000 cuts/min). The exposure times were selected at 10, 20, 40 and 60 s, respectively. Comparative measurements were carried out with mechanical cutters (Gauge 20 and Gauge 23), applying a fixed cut rate of 800 /min (13.33 Hz) at identical exposure times. The LaserVit-tips showed successful vitreous body removal for all laser settings and exposure times (Mark I: 6.2 g/min, Mark II: 8.2 g/min at 1500 cuts/min and 3 mJ, Mark II: 10.1 g/min, Mark III: 3.6 g/min at 6000 cuts/min at 3 mJ). Similar tip-dimensions (Gauge 22laser and Gauge 23cutter) showed comparable removal rates of 3.6 g/minlaser and 1.3 g/mincutter with settings of 6000 cuts/min at 3 mJ (laser) and 800 cuts/min for the mechanical cutter. A diode-pumped Q-switched Nd:YAG laser can successfully and gently remove vitreous body. The efficiency of the laser was comparable to that of mechanical cutters in terms of quantity of material removed per time unit.

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“…50 Floaters are reported to have various compositions and sizes. 51 It is possible that part of the hyaloid vessel that breaks down at birth results in fragments that are also part of the floaters. 52 In adults, floaters are most likely caused by PVD but in adolescence, floaters most likely result from myopic vitreopathy.…”

Section: Diseases Associated With Liquefactionmentioning

confidence: 99%

“…A proposed treatment for floaters is focusing a laser onto the floater to disrupt the collagen strands of floaters. 51 A treatment proven effective is performing a vitrectomy. 50 Macular hole formation results from the VH pulling away from the retina and causing the macula to tear.…”

Section: Diseases Associated With Liquefactionmentioning

confidence: 99%

The regional distribution and molecular interactions of phospholipids and glucose in mammalian vitreous humors.

Schnepf¹

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The vitreous humor (VH) is located in between the lens and the retina. It is composed of 98% water, hyaluronan (HA), collagen, proteins, phospholipids (PLs), and other metabolites. With aging, the VH undergoes liquefaction, a process that causes the gel-like structure of the VH to turn into a liquid and can lead to serious ocular diseases, including retinal detachment, vitreal detachment, and macular hole formation. The liquefaction process is expedited in diabetic VHs. This project focuses on understanding the molecular changes that lead to liquefaction and the reasons for which this process is accelerated with diabetes. Matrix-assisted laser desorption ionization/mass spectrometry (MALDI/MS) and nuclear magnetic resonance (NMR) spectroscopy were applied for in vitro, ex situ, and model studies of VHs to identify and quantify several components of the VH network and explore their interactions. In-vitro and ex-situ methods were optimized and conducted on porcine and human VHs. The mammalian species produced similar compositional trends. MALDI/MS showed that PLs were most abundant in the posterior region (closest to the retina) followed by the anterior (closest to the lens) and then the central regions. Diabetic and non-diabetic VHs regional distribution of glucose was compared. Glucose was vi present in significant higher levels (three-fold) in diabetic VHs compared to non-diabetic ones of similar age. The levels of glucose in the diabetic VH were highest in the posterior followed by the anterior and central regions. This trend follows that observed for the PLs. Model studies were performed to explore the interaction(s) of vitreal components and hyaluronan (HA) using MALDI/MS and NMR. The studies indicate interactions between both the headgroups of PLs and the carboxylate groups of HA as well as that between the acyl tails on PC with the hydrophobic regions of HA. Such interactions are proposed to disrupt the H-bonding network of HA and contribute to liquefaction of the VH. Future studies will focus on age-dependent studies of human VHs as well as the analysis of fresh human VHs following vitrectomy surgery. vii

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Vitreous Humor Rheology After Nd:YAG Laser Photo Disruption

Cited by 18 publications

References 22 publications

Influence of Charge, Hydrophobicity, and Size on Vitreous Pharmacokinetics of Large Molecules

Influence of Charge, Hydrophobicity, and Size on Vitreous Pharmacokinetics of Large Molecules

A promising approach in laser vitrectomy executed by plasma-mediated removal of vitreous body via a diode-pumped Q-switched Nd:YAG laser

The regional distribution and molecular interactions of phospholipids and glucose in mammalian vitreous humors.

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