Hypoxic corneal changes following 8 hours of scleral contact lens wear

- Purpose To examine the change in corneal thickness and posterior curvature following 8 hours of miniscleral contact lens wear. - Methods Scheimpflug imaging (Pentacam HR, Oculus) was captured before, and immediately following, 8 hours of miniscleral contact lens wear for 15 young (mean age 22 ± 3 years), healthy participants with normal corneae. Natural diurnal variations were considered by measuring baseline corneal changes obtained on a separate control day without contact lens wear. - Results Over the central 6 mm of the cornea, a small, but highly statistically significant amount of edema was observed following 8 hours of miniscleral lens wear, after accounting for normal diurnal fluctuations (mean ± standard deviation percentage swelling 1.70 ± 0.98%, p < 0.0001). Posterior corneal topography remained stable following lens wear (-0.01 ± 0.07 mm steepening over the central 6 mm, p = 0.60). The magnitude of posterior corneal topographical changes following lens wear did not correlate with the extent of lens-related corneal edema (r = -0.16, p = 0.57). Similarly, the initial central corneal vault (maximum post-lens tear layer depth) was not associated with corneal swelling following lens removal (r = 0.27, p = 0.33). - Conclusions While a small amount of corneal swelling was induced following 8 hours of miniscleral lens wear (on average <2%), modern high Dk miniscleral contact lenses that vault the cornea do not induce clinically significant corneal edema or hypoxic related posterior corneal curvature changes during short-term wear. Longer-term studies of compromised eyes (e.g. corneal ectasia) are still required to inform the optimum lens and fitting characteristics for safe scleral lens wear to minimize corneal hypoxia.

The influence of a novel simulated learning environment upon student clinical subjective refraction performance: A pilot study

Background: Optometry students are taught the process of subjective refraction through lectures and laboratory based practicals before progressing to supervised clinical practice. Simulated learning environments (SLEs) are an emerging technology that are used in a range of health disciplines, however, there is limited evidence regarding the effectiveness of clinical simulators as an educational tool. Methods: Forty optometry students (20 fourth year and 20 fifth year) were assessed twice by a qualified optometrist (two examinations separated by 4-8 weeks) while completing a monocular non-cycloplegic subjective refraction on the same patient with an unknown refractive error simulated using contact lenses. Half of the students were granted access to an online SLE, The Brien Holden Vision Institute (BHVI®) Virtual Refractor, and the remaining students formed a control group. The primary outcome measures at each visit were; accuracy of the clinical refraction compared to a qualified optometrist and relative to the Optometry Council of Australia and New Zealand (OCANZ) subjective refraction examination criteria. Secondary measures of interest included descriptors of student SLE engagement, student self-reported confidence levels and correlations between performance in the simulated and real world clinical environment. Results: Eighty percent of students in the intervention group interacted with the SLE (for an average of 100 minutes); however, there was no correlation between measures of student engagement with the BHVI® Virtual Refractor and speed or accuracy of clinical subjective refractions. Fifth year students were typically more confident and refracted more accurately and quickly than fourth year students. A year group by experimental group interaction (p = 0.03) was observed for accuracy of the spherical component of refraction, and post hoc analysis revealed that less experienced students exhibited greater gains in clinical accuracy following exposure to the SLE intervention. Conclusions: Short-term exposure to a SLE can positively influence clinical subjective refraction outcomes for less experienced optometry students and may be of benefit in increasing the skills of novice refractionists to levels appropriate for commencing supervised clinical interactions.

Role of Basement Membrane and Extracellular Matrix Proteins in the Adhesion and Spreading of Immortalized Human Corneal Epithelial Cells

The repair of corneal wounds requires both epithelial cell adhesion and migration. Basement membrane (BM) and extracellular matrix (ECM) proteins function in these processes via integrin and non-integrin receptors. We have studied the adhesion, spreading and migration of immortalized human corneal epithelial (HCE) cells and their interactions with the laminins (Lms), fibronectins and tenascins produced. Human corneal BM expresses Lms-332 and -511, while Lm-111 was not found in these experiments. HCE cells produced both processed and unprocessed Lm-332, whereas neither Lm-111 nor Lm-511 was produced. Because HCE cells did not produce Lm-511, although it was present in corneal BM, we suggest that Lm-511 is produced by stromal keratocytes. The adhesion of HCE cells to Lms-111, -332 and -511 was studied first by determining the receptor composition of HCE cells and then by using quantitative cell adhesion assays. Immunofluorescence studies revealed the presence of integrin α2, α3, α6, β1 and β4 subunits. Among the non-integrin receptors, Lutheran (Lu) was found on adhering HCE cells. The cells adhered via integrin α3β1 to both purified human Lms-332 and -511 as well as to endogenous Lm-332. However, only integrin β1 subunit functioned in HCE cell adhesion to mouse Lm-111. The adhesion of HCE cells to Lm-511 was also mediated by Lu. Since Lm-511 did not induce Lu into focal adhesions in HCE cells, we suggest that Lm-511 serves as an ECM ligand enabling cell motility. HCE cells produced extradomain-A fibronectin, oncofetal fibronectin and tenascin-C (Tn-C), which are also found during corneal wound healing. Monoclonal antibodies (MAbs) against integrins α5β1 and αvβ6 as well as the arginine-glycine-aspartic acid (RGD) peptide inhibited the adhesion of HCE cells to fibronectin. Although the cells did not adhere to Tn-C, they adhered to the fibronectin/Tn-C coat and were then more efficiently inhibited by the function-blocking MAbs and RGD peptide. During the early adhesion, HCE cells codeposited Lm-332 and the large subunit of tenascin-C (Tn-CL) beneath the cells via the Golgi apparatus and microtubules. Integrin β4 subunit, which is a hemidesmosomal component, did not mediate the early adhesion of HCE cells to Lm-332 or Lm-332/Tn-C. Based on these results, we suggest that the adhesion of HCE cells is initiated by Lm-332 and modulated by Tn-CL, as it has been reported to prevent the assembly of hemidesmosomes. Thereby, Tn-CL functions in the motility of HCE cells during wound healing. The different distribution of processed and unprocessed Lm-332 in adhering, spreading and migrating HCE cells suggests a distinct role for these isoforms. We conclude that the processed Lm-332 functions in cell adhesion, whereas the unprocessed Lm-332 participates in cell spreading and migration.

The inferior whorl for detecting diabetic peripheral neuropathy using corneal confocal microscopy

PURPOSE: In vivo corneal confocal microscopy (CCM) is increasingly used as a surrogate endpoint in studies of diabetic polyneuropathy (DPN). However, it is not clear whether imaging the central cornea provides optimal diagnostic utility for DPN. Therefore, we compared nerve morphology in the central cornea and the inferior whorl, a more distal and densely innervated area located inferior and nasal to the central cornea. METHODS: A total of 53 subjects with type 1/type 2 diabetes and 15 age-matched control subjects underwent detailed assessment of neuropathic symptoms (NPS), deficits (neuropathy disability score [NDS]), quantitative sensory testing (vibration perception threshold [VPT], cold and warm threshold [CT/WT], and cold- and heat-induced pain [CIP/HIP]), and electrophysiology (sural and peroneal nerve conduction velocity [SSNCV/PMNCV], and sural and peroneal nerve amplitude [SSNA/PMNA]) to diagnose patients with (DPN+) and without (DPN-) neuropathy. Corneal nerve fiber density (CNFD) and length (CNFL) in the central cornea, and inferior whorl length (IWL) were quantified. RESULTS: Comparing control subjects to DPN- and DPN+ patients, there was a significant increase in NDS (0 vs. 2.6 ± 2.3 vs. 3.3 ± 2.7, P < 0.01), VPT (V; 5.4 ± 3.0 vs. 10.6 ± 10.3 vs. 17.7 ± 11.8, P < 0.01), WT (°C; 37.7 ± 3.5 vs. 39.1 ± 5.1 vs. 41.7 ± 4.7, P < 0.05), and a significant decrease in SSNCV (m/s; 50.2 ± 5.4 vs. 48.4 ± 5.0 vs. 39.5 ± 10.6, P < 0.05), CNFD (fibers/mm2; 37.8 ± 4.9 vs. 29.7 ± 7.7 vs. 27.1 ± 9.9, P < 0.01), CNFL (mm/mm2; 27.5 ± 3.6 vs. 24.4 ± 7.8 vs. 20.7 ± 7.1, P < 0.01), and IWL (mm/mm2; 35.1 ± 6.5 vs. 26.2 ± 10.5 vs. 23.6 ± 11.4, P < 0.05). For the diagnosis of DPN, CNFD, CNFL, and IWL achieved an area under the curve (AUC) of 0.75, 0.74, and 0.70, respectively, and a combination of IWL-CNFD achieved an AUC of 0.76. CONCLUSIONS: The parameters of CNFD, CNFL, and IWL have a comparable ability to diagnose patients with DPN. However, IWL detects an abnormality even in patients without DPN. Combining IWL with CNFD may improve the diagnostic performance of CCM.

Peripheral refraction in 7- and 14-year-old children in central China: The Anyang Childhood Eye Study

Purpose: To determine the distribution of peripheral refraction, including astigmatism, in 7- and 14-year-old Chinese children. Methods: 2134 7-year-old and 1780 14-year-old children were measured with cycloplegic central and horizontal peripheral refraction (15° and 30° at temporal and nasal visual fields). Results: 7- and 14-year-old children included 9 and 594, respectively, with moderate and high myopia (≤−3.0 D), 259 and 831 with low myopia (−2.99 to −0.5 D), 1207 and 305 with emmetropia (−0.49 to +1.0 D), and 659 and 50 with hyperopia (>1.0 D), respectively. Myopic children had relative peripheral hyperopia while hyperopic and emmetropic children had relative peripheral myopia, with greater changes in relative peripheral refraction occurring in the nasal than the temporal visual field. The older group had the greater relative peripheral hyperopia and higher peripheral J180. Both age groups showed positive slopes of J45 across the visual field, with greater slopes in the older group. Conclusions: Myopic children in mainland China have relative peripheral hyperopia while hyperopic and emmetropic children have relative peripheral myopia. Significant differences exist between 7- and 14-year-old children, with the latter showing more relative peripheral hyperopia, greater rate of change in J45 across the visual field, and higher peripheral J180.

Paraxial schematic eye models for 7- and 14-year-old Chinese children

Purpose.: To develop three-surface paraxial schematic eyes with different ages and sexes based on data for 7- and 14-year-old Chinese children from the Anyang Childhood Eye Study. Methods.: Six sets of paraxial schematic eyes, including 7-year-old eyes, 7-year-old male eyes, 7-year-old female eyes, 14-year-old eyes, 14-year-old male eyes, and 14-year-old female eyes, were developed. Both refraction-dependent and emmetropic eye models were developed, with the former using linear dependence of ocular parameters on refraction. Results.: A total of 2059 grade 1 children (boys 58%) and 1536 grade 8 children (boys 49%) were included, with mean age of 7.1 ± 0.4 and 13.7 ± 0.5 years, respectively. Changes in these schematic eyes with aging are increased anterior chamber depth, decreased lens thickness, increased vitreous chamber depth, increased axial length, and decreased lens equivalent power. Male schematic eyes have deeper anterior chamber depth, longer vitreous chamber depth, longer axial length, and lower lens equivalent power than female schematic eyes. Changes in the schematic eyes with positive increase in refraction are decreased anterior chamber depth, increased lens thickness, decreased vitreous chamber depth, decreased axial length, increased corneal radius of curvature, and increased lens power. In general, the emmetropic schematic eyes have biometric parameters similar to those arising from regression fits for the refraction-dependent schematic eyes. Conclusions.: The paraxial schematic eyes of Chinese children may be useful for myopia research and for facilitating comparison with other children with the same or different racial backgrounds and living in different places.

Lens shape and refractive index distribution in type 1 diabetes

Purpose: To compare lens dimensions and refractive index distributions in type 1 diabetes and age-matched control groups. Methods: There were 17 participants with type 1 diabetes, consisting of two subgroups (7 young [23 ± 4 years] and 10 older [54 ± 4 years] participants), with 23 controls (13 young, 24 ± 4 years; 10 older, 55 ± 4 years). For each participant, one eye was tested with relaxed accommodation. A 3T clinical magnetic resonance imaging scanner was used to image the eye, employing a multiple spin echo (MSE) sequence to determine lens dimensions and refractive index profiles along the equatorial and axial directions. Results: The diabetes group had significantly smaller lens equatorial diameters and larger lens axial thicknesses than the control group (diameter mean ± 95% confidence interval [CI]: diabetes group 8.65 ± 0.26 mm, control group 9.42 ± 0.18 mm; axial thickness: diabetes group 4.33 ± 0.30 mm, control group 3.80 ± 0.14 mm). These differences were also significant within each age group. The older group had significantly greater axial thickness than the young group (older group 4.35 ± 0.26 mm, young group 3.70 ± 0.25 mm). Center refractive indices of diabetes and control groups were not significantly different. There were some statistically significant differences between the refractive index fitting parameters of young and older groups, but not between diabetes and control groups of the same age. Conclusions: Smaller lens diameters occurred in the diabetes groups than in the age-matched control groups. Differences in refractive index distribution between persons with and without diabetes are too small to have important effects on instruments measuring axial thickness.

Relative peripheral hyperopia does not predict development and progression of myopia in children

Purpose To test the hypothesis that relative peripheral hyperopia predicts development and progression of myopia. Methods Refraction along the horizontal visual field was measured under cycloplegia at visual field angles of 0°, ±15°, and ±30° at baseline, 1 and 2 years in over 1700 initially 7-year-old Chinese children, and at baseline and 1 year in over 1000 initially 14-year olds. One refraction classification for central refraction was “nonmyopia, myopia” (nM, M), consisting of nM greater than −0.50 diopters (D; spherical equivalent) and M less than or equal to −0.50 D. A second classification was “hyperopia, emmetropia, low myopia, and moderate/high myopia” (H, E, LM, MM) with H greater than or equal to +1.00 D, E, −0.49 to +0.99 D, LM, −2.99 to −0.50 D, and MM less than or equal to −3.00 D. Subclassifications were made on the basis of development and progression of myopia over the 2 years. Changes in central refraction over time were determined for different groups, and relative peripheral refraction over time was compared between different subgroups. Results Simple linear regression of central refraction as a function of relative peripheral refraction did not predict myopia progression as relative peripheral refraction became more hyperopic: relative peripheral hyperopia and relative peripheral myopia predicted significant myopia progression for 0% and 35% of group/visual field angle combinations, respectively. Subgroups who developed myopia did not have more initial relative peripheral hyperopia than subgroups who did not develop myopia. Conclusions Relative peripheral hyperopia does not predict development nor progression of myopia in children. This calls into question the efficacy of treatments that aim to slow progression of myopia in children by “treating” relative peripheral hyperopia.

Morphological changes in the conjunctiva, episclera and sclera following short-term miniscleral contact lens wear in rigid lens neophytes

PURPOSE To quantify the influence of short-term wear of miniscleral contact lenses on the morphology of the corneo-scleral limbus, the conjunctiva, episclera and sclera. METHODS OCT images of the anterior eye were captured before, immediately following 3h of wear and then 3h after removal of a miniscleral contact lens for 10 young (27±5 years) healthy participants (neophyte rigid lens wearers). The region of analysis encompassed 1mm anterior, to 3.5mm posterior to the scleral spur. Natural diurnal variations in thickness were measured on a separate day and compensated for in subsequent analyses. RESULTS Following 3h of lens wear, statistically significant tissue thinning was observed across all quadrants, with a mean decrease in thickness of -24.1±3.6μm (p<0.001), which diminished, but did not return to baseline 3h after lens removal (-16.9±1.9μm, p<0.001). The largest tissue compression was observed in the superior quadrant (-49.9±8.5μm, p<0.01) and in the annular zone 1.5mm from the scleral spur (-48.2±5.7μm), corresponding to the approximate edge of the lens landing zone. Compression of the conjunctiva/episclera accounted for about 70% of the changes. CONCLUSIONS Optimal fitting miniscleral contact lenses worn for three hours resulted in significant tissue compression in young healthy eyes, with the greatest thinning observed superiorly, potentially due to the additional force of the eyelid, with a partial recovery of compression 3h after lens removal. Most of the morphological changes occur in the conjunctiva/episclera layers.

In response: UV–vis light transmittance through tinted contact lenses and the effect of color on values

In the study, we used the Agilent 8453 spectrophotometer (which is equipped with a limiting aperture that restricts the light beam to the central 5 mm of the contact lens), to measure the transmittance of various coloured contact lenses including the one Day Acuvue define manufactured by Johnson and Johnson which the authors represent. We measured the instrument baseline before the transmittance spectra of lenses were tested. The values of lens transmittances were thus the difference between baseline and lens measurement at each time. The transmittance measurements were obtained at 0.5 nm intervals, from 200 to 700 nm after a soak in saline to remove the influence of any surface active agents within the packaging products. The technique used in our study was not very different from how other research studies [2], [3], [4], [5] and [6] have measured the spectra transmittances of contact lenses...

Tissue thickness calculation in ocular optical coherence tomography

Thickness measurements derived from optical coherence tomography (OCT) images of the eye are a fundamental clinical and research metric, since they provide valuable information regarding the eye’s anatomical and physiological characteristics, and can assist in the diagnosis and monitoring of numerous ocular conditions. Despite the importance of these measurements, limited attention has been given to the methods used to estimate thickness in OCT images of the eye. Most current studies employing OCT use an axial thickness metric, but there is evidence that axial thickness measures may be biased by tilt and curvature of the image. In this paper, standard axial thickness calculations are compared with a variety of alternative metrics for estimating tissue thickness. These methods were tested on a data set of wide-field chorio-retinal OCT scans (field of view (FOV) 60° x 25°) to examine their performance across a wide region of interest and to demonstrate the potential effect of curvature of the posterior segment of the eye on the thickness estimates. Similarly, the effect of image tilt was systematically examined with the same range of proposed metrics. The results demonstrate that image tilt and curvature of the posterior segment can affect axial tissue thickness calculations, while alternative metrics, which are not biased by these effects, should be considered. This study demonstrates the need to consider alternative methods to calculate tissue thickness in order to avoid measurement error due to image tilt and curvature.

Light exposure and eye growth in childhood

PURPOSE The purpose of this study was to examine the relationship between objectively measured ambient light exposure and longitudinal changes in axial eye growth in childhood. METHODS A total of 101 children (41 myopes and 60 nonmyopes), 10 to 15 years of age participated in this prospective longitudinal observational study. Axial eye growth was determined from measurements of ocular optical biometry collected at four study visits over an 18-month period. Each child’s mean daily light exposure was derived from two periods (each 14 days long) of objective light exposure measurements from a wrist-worn light sensor. RESULTS Over the 18-month study period, a modest but statistically significant association between greater average daily light exposure and slower axial eye growth was observed (P ¼ 0.047). Other significant predictors of axial eye growth in this population included children’s refractive error group (P < 0.001), sex (P < 0.01), and age (P < 0.001). Categorized according to their objectively measured average daily light exposure and adjusting for potential confounders (age, sex, baseline axial length, parental myopia, nearwork, and physical activity), children experiencing low average daily light exposure (mean daily light exposure: 459 6 117 lux, annual eye growth: 0.13 mm/y) exhibited significantly greater eye growth than children experiencing moderate (842 6 109 lux, 0.060 mm/y), and high (1455 6 317 lux, 0.065 mm/y) average daily light exposure levels (P ¼ 0.01). CONCLUSIONS In this population of children, greater daily light exposure was associated with less axial eye growth over an 18-month period. These findings support the role of light exposure in the documented association between time spent outdoors and childhood myopia.

Longitudinal changes in choroidal thickness and eye growth in childhood

PURPOSE To examine longitudinal changes in choroidal thickness and axial length in a population of children with a range of refractive errors. METHODS One hundred and one children (41 myopes and 60 nonmyopes) aged 10 to 15 years participated in this prospective, observational longitudinal study. For each child, 6-month measures of choroidal thickness (using enhanced depth imaging optical coherence tomography) and axial ocular biometry were collected four times over an 18-month period. Linear mixed-models were used to examine the longitudinal changes in choroidal thickness and the relationship between changes in choroidal thickness and axial eye growth over the study period. RESULTS A significant group mean increase in subfoveal choroidal thickness was observed over 18 months (mean increase 13 6 22 lm, P < 0.001). Myopic children exhibited significantly thinner choroids compared with nonmyopic children (P < 0.001), although there was no significant time by refractive group interaction (P ¼ 0.46), indicating similar changes in choroidal thickness over time in myopes and nonmyopes. However, a significant association between the change in choroidal thickness and the change in axial length over time was found (P < 0.001, β = −0.14). Children showing faster axial eye growth exhibited significantly less choroidal thickening over time compared with children showing slower axial eye growth. CONCLUSIONS A significant increase in choroidal thickness occurs over an 18-month period in normal 10- to 15-year-old children. Children undergoing faster axial eye growth exhibited less thickening and, in some cases, a thinning of the choroid. These findings support a potential role for the choroid in the mechanisms regulating eye growth in childhood.

Thickness metrics in posterior segment optical coherence tomography

To develop and compare a set of metrics for calculating tissue thickness in wide-field OCT data.