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Open Access Publications from the University of California

Scholarly Works (17 results)

  • Article
  • Peer Reviewed
UC Berkeley Previously Published Works (2021)
    • Thesis
    • Peer Reviewed
    UC Berkeley Electronic Theses and Dissertations (2022)

    There are numerous types of contact-lens materials and designs available for lens wearers today. Regardless of whether the lens is mass produced or customized to an individual patient, oxygen and ion transport across the contact lens is critical to ensure that contact-lens wear is safe and comfortable for the lens wearers. High oxygen-permeable contact lenses allow enough oxygen supply from the environment to the cornea to avoid corneal hypoxia-induced edema. Meanwhile, high ion-permeable contact lenses allow the tear-film between the contact lens and the ocular surface (i.e., post-lens tear film) to be thick enough to avoid lens adherence to the ocular surface. However, high ion-permeable contact lenses could potentially result in post-lens tear-film hyperosmolarity to activate corneal nociceptors and cause discomfort. Effect of contact-lens ion transmissibility (strictly salt transmissibility) on post-lens tear-film hyperosmolarity has not been investigated. Aims of this dissertation is to quantify the effects of contact-lens salt transport properties on post-lens tear-film hyperosmolarity and to quantify central-to-peripheral corneal edema during wear of various types of contact lenses that have yet to be investigated for hypoxic safety. To quantify central-to-peripheral corneal edema for wear of various contact lenses, one-dimensional metabolic-edema model is initially developed to determine central corneal edema for scleral-lens wear. The model utilizes metabolic kinetics and diffusion to determine accurate concentrations of aerobic and anerobic metabolic species. Change in concentrations of metabolic species due to corneal hypoxia affects the hydraulic pressure and, therefore, the corneal thickness. The severity of corneal hypoxia is dependent on the adjustable lens oxygen transmissibility and the post-lens tear-film thickness. Model results show excellent agreement with the clinical corneal edema measurements made from subjects wearing scleral lenses with various lens oxygen transmissibilities and post-lens tear-film thicknesses. Central corneal edema due to wear of scleral lenses made of silicone-acrylate based materials is clinically insignificant while being awake. However, scleral-lens wear during sleep will cause clinically significant swelling and should be avoided. The one-dimensional metabolic-edema model is expanded to two dimensions by incorporating central-to-peripheral cornea and contact lens. Alongside, metabolic support from the limbus is incorporated at the peripheral cornea to accurately model non-central corneal edema. Central-to-peripheral corneal edema is determined for wear of soft contact, scleral, and component embedded contact lenses and is rigorously compared with available clinical data to ensure the accuracy of the metabolic-edema model. Results show that supply of bicarbonate ions and oxygen and removal of lactate ions by the limbal blood supply reduces corneal edema at the midperiphery and the periphery. Due to the limbal metabolic support, central corneal edema measured clinically is a good standard for assessing hypoxic safety for wear of scleral and soft contact lenses despite the variance in lens oxygen transmissibility throughout the lens and higher oxygen demand at the non-central cornea than the central cornea. For component embedded contact lenses, central-to-peripheral corneal edema must be accounted to ensure the hypoxic safety of lens wear. To minimize corneal edema, low oxygen permeable embedments are advised to be embedded in the lens periphery. Post-lens tear-film osmolarity during contact-lens wear has not been measured clinically because the tear film is microns thick and because the tear film is covered by the contact lens that prevents direct probe interaction. To understand the osmolarity of the post-lens tear film, theoretical osmolarity models are developed to predict spatially-averaged and localized post-lens tear-film osmolarities during wear of soft contact lenses with varying salt diffusivity, lens thickness, and salt partition coefficients. Lenses made of acrylate materials are not studied because those hard lenses are practically ion impermeable compared to those of soft contact lenses. Spatially-averaged osmolarity of post-lens tear film is determined by quantifying the transport of salt and water across the contact lens between the pre-lens and the post-lens tear films. The model also incorporates tear production and evaporation rates, tear mixing, and tear produced from the cornea and the bulbar conjunctiva to accurately model the lens-wear osmotic behavior. Meanwhile, localized post-lens tear-film osmolarity due to tear break-up areas on the pre-lens tear film is determined by developing a 2-dimensional model that allows localized hyperosmotic regions to be formed on the pre-lens tear film. Results show that soft-contact-lens wear can protect the cornea from both localized and spatially-averaged hyperosmolarity when the lens-salt diffusivity is low. Realistic ranges of salt partition coefficient and lens thickness for existing soft contact lenses do not have meaningful impact on the post-lens tear-film osmolarity. Conversion of localized post-lens tear-film hyperosmolarity spike values to pain scores based on a previously conducted clinical study suggests that soft-contact-lens wear can mitigate osmolarity-induced discomfort. Understanding salt and oxygen transports across contact lenses allow development of safe and comfortable novel contact lenses. Theoretical models in this dissertation allow optimization of future lens designs to minimize hyperosmolarity and hypoxia for safe and comfortable lens wear.

      Cover page: Effects of Oxygen and Salt Transport Across Contact Lenses on Lens-Wear Safety and Comfort
      • Article
      • Peer Reviewed
      UC Berkeley Previously Published Works (2020)
        • Article
        • Peer Reviewed
        UC Berkeley Previously Published Works (2022)

        Purpose

        With active investigation underway for embedded-circuit contact lenses, safe oxygen supply of these novel lenses remains a question. Central-to-peripheral corneal edema for healthy eyes during wear of soft contact (SCL) and scleral lenses (SL) with embedding components is assessed.

        Methods

        Various 2-dimensional (2D) designs of SL and SCL with embedded components are constructed on Comsol Multiphysics 5.5. Local corneal swelling associated with the designed lenses is determined by a recently developed 2D metabolic-swelling model. Settled central post-lens tear-film thicknesses (PoLTFs) are set at 400 μm and 3 μm for SL and SCL designs, respectively. Each lens design has an axisymmetric central and an axisymmetric peripheral embedment. Oxygen permeability (Dk) of the lens and the embedments ranges from 0 to 200 Barrer. Dimensions and location of the embedments are varied to assess optimal-design configurations to minimize central-to-peripheral corneal edema.

        Results

        By adjusting oxygen Dk of the central embedment, the peripheral embedment, or the lens matrix polymer, corneal swelling is reduced by up to 2.5 %, 1.5 %, or 1.4 % of the baseline corneal thickness, respectively, while keeping all other parameters constant. A decrease in PoLTF thickness from 400 μm to 3 μm decreases corneal edema by up to 1.8 % of the baseline corneal thickness. Shifting the peripheral embedment farther out towards the periphery and towards the anterior lens surface reduces peak edema by up to 1.3 % and 0.6 % of the baseline corneal thickness, respectively.

        Conclusions

        To minimize central-to-peripheral corneal edema, embedments should be placed anteriorly and far into the periphery to allow maximal limbal metabolic support and oxygen transport in the polar direction (i.e., the θ-direction in spherical coordinates). High-oxygen transmissibility for all components and thinner PoLTF thickness are recommended to minimize corneal edema. Depending on design specifications, less than 1 % swelling over the entire cornea is achievable even with oxygen-impermeable embedments.
          Cover page: Central-to-peripheral corneal edema during wear of embedded-component contact lenses
          • Article
          • Peer Reviewed
          UC Berkeley Previously Published Works (2020)

          Purpose

          To assess the influence of limbal metabolic support on corneal edema during scleral-lens (SL) and soft-contact-lens (SCL) wear for healthy lens wearers.

          Methods

          A two-dimensional (2D) model of the cornea and sclera was designed on Comsol Multiphysics 5.4 along with SL and SCL architectures to mimic lens-wear induced hypoxia. The cornea is suffused with oxygen and metabolites from the limbus and aqueous humor. Air oxygen is supplied from and carbon dioxide is expelled to the atmosphere. Lens-oxygen permeability (Dk) was adjusted to investigate lens-wear safety against edema in different wear conditions. The 2D concentrations of oxygen, carbon dioxide, bicarbonate, lactate, sodium, chloride, glucose, and pH are quantified. Central-to-peripheral swelling of the cornea is determined by the change in stromal hydration caused by changing metabolite concentrations at the endothelium during hypoxia.

          Results

          The metabolic model assesses central-to-peripheral corneal swelling with different types of lenses, and oxygen Dks. Limbal metabolic support reduces edema from the periphery to approximately 1 mm away from the central cornea. Despite thicker lens designs, the peripheral cornea exhibits practically zero swelling due to limbal metabolic support.

          Conclusions

          The metabolic model accurately predicts central-to-peripheral corneal edema with various contact-lens designs, post-lens tear-film thicknesses, and lens oxygen Dk values. Despite the thicker periphery of most contact-lens designs, lactate and bicarbonate support from the limbus significantly reduces peripheral and mid-peripheral corneal edema, whereas oxygen has a lesser effect.

          Translational relevance

          By utilizing metabolic kinetics, we provide a 2D computational tool to predict oxygenation safety across the entire cornea with various types and designs of contact lenses.
            Cover page: Limbal Metabolic Support Reduces Peripheral Corneal Edema with Contact-Lens Wear
            • Article
            • Peer Reviewed
            UC Berkeley Previously Published Works (2019)
              Cover page: Repeatability of Modified Schirmer Strip Wetted Lengths and Basal Tear Production Rates
              • Multimedia
              • Peer Reviewed
              UC Berkeley Previously Published Works (2017)
              • 1 supplemental PDF
              • Article
              • Peer Reviewed
              UC Berkeley Previously Published Works (2022)
              Hyperosmotic tear stimulates human corneal nerve endings, activates ocular immune response, and elicits dry-eye symptoms. A soft contact lens (SCL) covers the cornea preventing it from experiencing direct tear evaporation and the resulting blink-periodic salinity increases. For the cornea to experience hyperosmolarity due to tear evaporation, salt must transport across the SCL to the post-lens tear film (PoLTF) bathing the cornea. Consequently, limited salt transport across a SCL potentially protects the ocular surface from hyperosmotic tear. In addition, despite lens-wear discomfort sharing common sensations to dry eye, no correlation is available between measured tear hyperosmolarity and SCL-wear discomfort. Lack of documentation is likely because clinical measurements of tear osmolarity during lens wear do not interrogate the tear osmolarity of the PoLTF that actually overlays the cornea. Rather, tear osmolarity is clinically measured in the tear meniscus. For the first time, we mathematically quantify tear osmolarity in the PoLTF and show that it differs significantly from the clinically measured tear-meniscus osmolarity. We show further that aqueous-deficient dry eye and evaporative dry eye both exacerbate the hyperosmolarity of the PoLTF. Nevertheless, depending on lens salt-transport properties (i.e., diffusivity, partition coefficient, and thickness), a SCL can indeed protect against corneal hyperosmolarity by reducing PoLTF salinity to below that of the ocular surface during no-lens wear. Importantly, PoLTF osmolarity for dry-eye patients can be reduced to that of normal eyes with no-lens wear provided that the lens exhibits a low lens-salt diffusivity. Infrequent blinking increases PoLTF osmolarity consistent with lens-wear discomfort. Judicious design of SCL material salt-transport properties can ameliorate corneal hyperosmolarity. Our results confirm the importance of PoLTF osmolarity during SCL wear and indicate a possible relation between PoLTF osmolarity and contact-lens discomfort.
                Cover page: Protection against corneal hyperosmolarity with soft-contact-lens wear
                • Article
                • Peer Reviewed
                UC Berkeley Previously Published Works (2019)

                Purpose

                To investigate the effect of various oxygen transmissibilities (Dk/t) of scleral lenses and corneal thickness recovery time from overnight eye closure with patching on corneal edema during 5 h lens wear.

                Methods

                Scleral lenses (hofocon A, 15.6 mm diameter) were worn bilaterally with three different Dks (100, 140, and 160 Barrer). Central and peripheral corneal thickness (CCT and PCT) were measured using optical coherence tomography. Four subjects were randomly selected for one additional visit and asked to patch one eye before night sleeping. The patch was not removed until lens insertion to avoid corneal deswelling. Then CCT of both eyes was measured.

                Results

                Ten neophytes with healthy eyes participated in the study. Mean [95% CI] Dk/t of the study lenses was 32.0 [29.2, 34.7] hBarrer/cm. Mean [95% CI] CCT immediately upon lens insertion and after 5 h of lens wear were 532.4 [520.3, 544.5] μm and 538.7 [526.5, 551.0] μm, respectively. Mean [95% CI] percentage change (%Δ) in CCT was 1.2% [0.9%, 1.5%], 1.2% [0.9%, 1.4%], and 0.8% [0.6%, 1.1%] for CCT, nasal PCT, and temporal PCT, respectively. There was an inverse relationship between temporal Dk/t and %ΔPCT (p < 0.05) while Dk/t was not found significantly associated with either CCT or nasal PCT. The patched eyes maintained a relatively stable CCT and showed progressive deswelling, starting and ending with 2.8% and 0.6%, respectively. In contrast, the unpatched eyes swelled, starting with nearly 0% and ending with 0.7% with a maximum swelling of 1.8%.

                Conclusion

                There was limited amount of corneal edema induced by short-term scleral lens wear with lens Dk/t ranging from 21 to 47 hBarrer/cm and lenses with lower lens Dk/t did not induce significantly higher corneal swelling. Scleral lens insertion soon after overnight eye closure with patching did not introduce additional swelling for young and healthy eyes.
                  Cover page: Effects of scleral-lens oxygen transmissibility on corneal thickness: A pilot study
                  • Article
                  • Peer Reviewed
                  UC Berkeley Previously Published Works (2018)

                  Purpose

                  To evaluate the safety of scleral-lens designs, we model and clinically assess central corneal edema induced by scleral-lens wear for healthy subjects.

                  Materials and methods

                  Central corneal swelling during scleral-lens wear is measured using optical coherence tomography (OCT). Transport resistances are modeled for oxygen diffusion through the scleral lens and post-lens tear-film (PoLTF), and into the cornea. Oxygen deficiency in the cornea activates anaerobic metabolic reactions that induce corneal edema. Oxygen permeability, carbon-dioxide permeability, settled-lens PoLTF thickness, and scleral-lens thickness are varied in the calculations to mimic different lens fits.

                  Results

                  Transport modeling predicts that for open eyes, increasing PoLTF thickness from 50 to 400 µm increases central corneal swelling by approximately 1-1.5% when oxygen transmissibility (Dk/L) is greater than 10 hBarrer/cm (i.e., hectoBarrer/cm). Although swelling is larger for oxygen Dk/L < 10 hBarrer/cm, PoLTF thickness has minimal impact in this range. For open eye, oxygen transmissibility of the lens plays a significant role in corneal edema, but is negligible when oxygen Dk/L is > 40 hBarrer/cm. For closed eye, central corneal swelling is greater than 5% for an oxygen Dk/L range of 0-100 hBarrer/cm with typical lens-fitting parameters. For carbon-dioxide transmissibilities increasing from 50 to 250 hBarrer/cm and with a fixed oxygen Dk/L of 25 hBarrer/cm, calculated swelling diminishes by an additional 0.5%. Comparison of model calculations to clinical-swelling data is within the error range of the clinical measurements.

                  Conclusions

                  Oxygen/metabolite transport calculations for open-eye scleral-lens wear show that typical PoLTF thicknesses fitted by clinicians (i.e., PoLTF thicknesses < 400 µm) with modern scleral lenses (i.e., oxygen Dk/L > 25 hBarrer/cm) produce corneal swelling of less than 2% in agreement with experiment. Therefore, scleral lenses prescribed today evoke less than physiological hypoxic swelling (i.e., less than 4%) for healthy corneas during open-eye. Closed-eye wear, however, appears clinically unsafe.
                    Cover page: Central Corneal Edema with Scleral-Lens Wear
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