Shear-Thinning and Temperature-Dependent Viscosity Relationships of Contemporary Ocular Lubricants.

PURPOSE: To evaluate the shear viscosity of contemporary, commercially available ocular lubricants at various shear rates and temperatures and to derive relevant mathematical viscosity models that are impactful for prescribing and developing eye drops to treat dry eye disease. METHODS: The shear viscosity of 12 ocular lubricants was measured using a rheometer and a temperature-controlled bath at clinically relevant temperatures at which users may experience exposure to the drops (out of the refrigerator [4.3°C]; room temperature [24.6°C]; ocular surface temperature [34.5°C]). Three replicates for each sample at each temperature were obtained using a standard volume (0.5 mL) of each sample. The viscosity of each ocular lubricant was measured over the full range of shear rates allowed by the rheometer. RESULTS: The shear viscosity of the same ocular lubricant varied significantly among the three temperatures. In general, a higher temperature resulted in smaller viscosities than a lower temperature (an average of -48% relative change from 4.3°C to 24.6°C and -21% from 24.6°C to 34.5°C). At a constant temperature, the viscosity of an ocular lubricant over the studied shear rates can be well approximated by a power-law model. CONCLUSIONS: Rheological analysis revealed that the ocular lubricants exhibited shear-thinning behavior at the measured temperatures. Differences in the ocular lubricants' formulations and measured temperatures resulted in different viscosities. TRANSLATIONAL RELEVANCE: When prescribing eye drops, eye care professionals can select the optimal one for their patients by considering a variety of factors, including its rheological property at physiologically relevant shear rates and temperatures, which can improve residence time on the ocular surface, while ensuring appropriate comfort and vision. However, care must be taken when using the derived mathematical models in this study because the in vivo shear behavior of the ocular lubricants has not been examined and might show deviations from those reported when placed on the ocular surface.

Factors affecting central corneal thickness measurement agreement between Scheimpflug imaging and ultrasound pachymetry in keratoconus.

PURPOSE: To evaluate the agreement of central corneal thickness (CCT) measurement between Scheimpflug imaging and ultrasound (U/S) pachymetry in keratoconic eyes, and investigate factors that affect the agreement. METHODS: This post hoc analysis within a prospective, observational non-randomised study preformed at the Kensington Eye Institute, Toronto, Ontario, Canada, included crosslinking candidates with progressive keratoconus (KC). Main outcome measures were the agreement of CCT measurement between Scheimpflug imaging (Pentacam Oculus, Wetzlar, Germany) and U/S pachymetry (PachPen 24-5100, Accutome Inc., Malvern, Pennsylvania, USA), and factors that affect the agreement. RESULTS: A total of 794 keratoconic eyes of 456 subjects with a mean age of 27.6±8.0 years (69.7% males and 49.6% right eyes) were included. Agreement between devices was moderate (intraclass correlation coefficient: 74.9%, Bland-Altman limits of agreement: -48.5 µm to +62.5 µm). In a multivariable analysis, cone decentration (p<0.001, coefficient +10.13 [+6.73 to +13.53 95% CIs]) and Kmax (p<0.001, coefficient +0.68 [+0.46 to +0.90 95% CIs]) were significantly associated (both clinically and statistically) with the level of agreement between the devices; the discrepancy in CCT between the devices increased on average by 10.13 µm for every mm of cone decentration, and by 6.8 µm for every 10D of Kmax. Age, corneal astigmatism and spherical equivalent were statistically but not clinically significant factors affecting agreement. CONCLUSION: The agreement of CCT measurement between Scheimpflug imaging and U/S pachymetry in KC was moderate. To ensure the safety of crosslinking in keratoconic corneas, Scheimpflug and U/S CCT measurements should not be used interchangeably, especially in steep corneas and corneas with decentred cones.

Change in over-refraction after scleral lens settling on average corneas.

PURPOSE: The purpose of this study was to determine the change in over-refraction, if any, after a scleral lens settled on the eye for 6-8 h. METHODS: Sixteen patients of varying refractive errors and normal corneal curvatures (measured with Pentacam™ Oculus) were fitted with trial Mini-Scleral Design (MSD) scleral lenses (15.8 mm diameter) in one eye. The sagittal depths of the scleral lenses were selected by adding 350 µm to the corneal sagittal heights measured at a chord length of 15 mm with the Visante™ optical coherence tomographer (OCT) anterior segment scans and picking the closest available trial lens in the set. Initial measurements were taken 30 min after lens insertion and included an auto-refraction, subjective refraction, and best sphere refraction over the contact lens. Visual acuities and Visante™ OCT anterior segment scans were also taken. These measurements were repeated after 6-8 h of lens wear. RESULTS: Over the trial wearing period, the average change in the spherical component of the over-refraction was +0.06 D (S.D. 0.17) (p = 0.16). The average change in cylinder was +0.04 D (S.D. 0.19) (p = 0.33). The average absolute change in axis was 1.06° (S.D. 12.11) (p = 0.74). The average change in best sphere was +0.13 ± 0.30 D (p = 0.12). There was no significant change in visual acuity with the best sphere over-refraction over the 6-8 h wearing period. There was a significant change in central corneal clearance over the wearing period of 83 µm (S.D. 22) (p < 0.0001). CONCLUSION: Despite a significant change in the central corneal clearance due to thinning of the fluid reservoir as the scleral lens settled (an average decrease of 83 µm after wearing the lenses for 6-8 h), there was not a statistically significant change in the subjective over-refraction (sphere, cylinder, and axis) or best sphere or visual acuity. This study has confirmed that there is no link between reduction in central corneal clearance and change in over-refraction for average corneas.

In Vivo Imaging and Morphometry of the Human Pre-Descemet's Layer and Endothelium With Ultrahigh-Resolution Optical Coherence Tomography.

PURPOSE: To visualize in vivo and quantify the thickness of the posterior corneal layers: the acellular pre-Descemet's layer (PDL), Descemet's membrane (DM), and endothelium (END) in healthy subjects, using ultrahigh-resolution optical coherence tomography (UHR-OCT). METHODS: A research-grade, 800-nm UHR-OCT system with 0.95-µm axial resolution in corneal tissue was used to image in vivo the posterior cornea in healthy subjects. The system offers approximately 98 dB sensitivity for 680 µW optical power incident on the cornea and 34,000 A-scans/s image acquisition rate. This study comprised 20 healthy subjects, aged 20 to 60 years. The thickness of the PDL, DM, and END layers was measured both with a custom, automatic segmentation algorithm and manually. RESULTS: The boundaries and structure of the posterior corneal layers were clearly visible in the UHR-OCT images. The average thickness was measured to be 6.6 ± 1.4 µm (PDL), 10.4 ± 2.9 µm (DM), and 4.8 ± 0.4 µm (END), which agrees well with published data from ex vivo studies. Both the END and DM thickness showed minor spatial variations, whereas the PDL showed up to 2× thickness change for different locations on the same cross-sectional corneal image or over the entire imaged region of the cornea. CONCLUSIONS: Our data indicate that all three layers of the posterior cornea can be clearly visualized in vivo and their thicknesses measured precisely with UHR-OCT. Although the PDL thickness showed large spatial variations, the thickness of the DM and END layers was consistent over the entire imaged region of the cornea.

Osmotic pressure-adaptive responses in the eye tissues of rainbow smelt (Osmerus mordax).

PURPOSE: The rainbow smelt (Osmerus mordax), is a teleost fish, which avoids freezing by becoming virtually isosmotic with seawater. The effects that such massive changes in osmolarity have on both its visual system and its highly evolved and specialized circulation are not known. New knowledge about the osmotic adaptation of the rainbow smelt eye is highly relevant to the adaptation and survival of this species and to its ability to feed as a visual predator in the face of environmental pressures. Moreover, the molecular physiologic response of the smelt to osmotic stress might provide valuable insights into understanding and managing mammalian pathological hyperosmolarity conditions, such as diabetes. We undertook the present study to provide an initial assessment of gene expression in ocular vasculature during osmotic adaptation in rainbow smelt. METHODS: Immunohistochemistry with species cross reactive antibodies was used to assess blood vessel protein expression in paraffin sections. Western blotting was used to further verify antibody specificity for orthologs of mammalian blood vessel proteins in rainbow smelt. Thermal hysteresis and the analysis of glycerol concentrations in vitreous fluid were used to assess the physiologic adaptive properties of cold stressed eyes. RESULTS: Glycerol levels and osmotic pressure were significantly increased in the vitreal fluid of smelt maintained at <0.5 °C versus those maintained at 8-10 °C. Compared to the 8-10 °C adapted specimens, the rete mirabile blood vessels and connecting regions of the endothelial linings of the choroidal vessels of the <0.5 °C adapted specimens showed a higher expression level of Tubedown (Tbdn) protein, a marker of the endothelial transcellular permeability pathway. Expression of the zonula occludens protein ZO-1, a marker of the endothelial paracellular permeability pathway showed a reciprocal expression pattern and was downregulated in rete mirabile blood vessels and connecting regions in the endothelial linings of choroidal vessels in <0.5 °C adapted specimens. Smelt orthologs of the mammalian Tbdn and zoluna occludens protein 1 (ZO-1) proteins were also detected by western blotting using anti-mammalian antibodies raised against the same epitopes as those used for immunohistochemistry. CONCLUSIONS: This work provides the first evidence that molecules known to play a role in ocular vascular homeostasis are expressed and may be differentially regulated during anti-freezing cold adaptation in smelt eyes. We propose a hypothesis that in a state of cold-induced hyperosmolarity, changes in ZO-1 expression are associated with the passage of small solutes from the plasma space to ocular fluid, while changes in Tbdn expression regulate the passage of proteins between the ocular fluid and plasma space. This work also provides fundamental insight into the mechanisms underlying the adaptation of the blood-retinal barrier to metabolically relevant compounds such as glycerol.