Effect of Scleral Contact Lens Size and Duration of Wear on Intraocular Pressure.

OBJECTIVE: To evaluate the effects of scleral lens size and the duration of wear on intraocular pressure (IOP) during lens wear. METHODS: Healthy adults were recruited for this prospective and randomized study. Intraocular pressure measurements were performed using a pneumotonometer. A block randomization was used to assign the order of scleral lens diameter of either 15.6 mm or 18.0 mm for 5-hr bilateral wear over a course of two visits. Scleral IOP (sIOP) was measured during the predetermined intervals, 1.25 hr apart, during the 5-hr scleral lens wear. Corneal IOP (cIOP) was measured before and after the scleral lens wear. The primary outcome measure was the mean change in sIOP from prelens insertion baseline. RESULTS: Corneal IOP unchanged after scleral lens removal compared with the baseline measurements ( P =0.878). Smaller and larger lenses introduced significantly higher sIOP at 2.5 hr after lens insertion with the mean (95% CI) increase of 1.16 (0.54, 1.78) mm Hg and 1.37 (0.76, 1.99) mm Hg, respectively. There was no difference in IOP change between the smaller and larger diameter lenses ( P =0.590). CONCLUSIONS: Well-fitted scleral lenses do not result in clinically significant changes in intraocular pressure during 5-hr lens wear in young and healthy individuals.

How do cardiovascular risk factors correlate with post-stroke cognitive function: Directly or indirectly through stroke severity?

Objectives: Cognitive impairment may affect one-third of stroke survivors. Cardiovascular risk factors and stroke severity were known to be associated with cognitive function after stroke. However, it is unclear whether cardiovascular risk factors directly affect cognition after stroke, indirectly affect cognition by changing stroke severity, or both. Moreover, the effect of a combination of hypertension and diabetes mellitus was conflicting. We aimed to investigate the multiple direct and indirect associations and inspire potential intervention strategies. Materials and methods: From February 2020 to January 2021, 350 individuals received cognitive tests within 7 days after incident stroke. Cognitive tests were performed using the Chinese version of the Mini-Mental State Examination (MMSE). A moderated mediation model was constructed to test the indirect associations between cardiovascular and demographic risk factors and cognition mediated through stroke severity, the direct associations between risk factors and cognition, and the moderating effects of hypertension and diabetes. Results: Age (estimate, -0.112), atrial fibrillation (estimate, -4.092), and stroke severity (estimate, -1.994) were directly associated with lower cognitive function after stroke. Vascular disease (estimate, 1.951) and male sex (estimate, 2.502) were directly associated with better cognition after stroke. Higher education level was associated with better cognition directly (estimate, 1.341) and indirectly (estimate, 0.227) through stroke severity. The combination of hypertension decreased the magnitude of the negative association between atrial fibrillation and cognition (estimate, from -4.092 to -3.580). Conclusion: This is the first Chinese study exploring the moderated and mediating associations between cardiovascular risk factors, stroke severity, and cognitive function after stroke. Age, female sex, and atrial fibrillation were directly associated with lower cognition after stroke. The combination of hypertension might have a positive effect on cognition.

Corneal Health during Three Months of Scleral Lens Wear.

SIGNIFICANCE: This study evaluated the effects scleral lens wear has on corneal health using fluorometry and in vivo confocal microscopy. No subclinical changes on healthy corneas of young subjects were observed during 3 months of scleral lens wear. PURPOSE: This study aimed to evaluate the effects 3 months of scleral lens wear has on the corneal epithelial barrier function, dendritic cell density, and nerve fiber morphology. METHODS: Twenty-seven neophytes (mean [standard deviation] age, 21.4 [3.9] years) wore scleral lenses of a fluorosilicone acrylate material bilaterally (97 Dk, 15.6 to 16.0-mm diameter) for 3 months without overnight wear. Subjects were randomized to use either Addipak (n = 12) or PuriLens Plus (n = 15) during lens insertion. Measurements of corneal epithelial permeability to fluorescein were performed with automated scanning fluorophotometer (Fluorotron Master; Ocumetrics, Mountain View, CA) on the central cornea of the right eye and the temporal corneal periphery of the left eye. Images of the distributions of corneal nerve fibers and dendritic cells and nerve fibers were captured in vivo with a confocal laser scanning microscope (Heidelberg Retina Tomograph, Rostock Cornea Module; Heidelberg Engineering, Heidelberg, Germany) on the central and inferior peripheral cornea of the left eye. Corneal measurements and imaging were performed at baseline and after 1 and 3 months of lens wear. RESULTS: The corneal permeability values in natural log, dendritic cell densities, and nerve fiber morphology did not significantly change from baseline to 1 and 3 months of lens wear, for both central and peripheral corneal regions (P > .05). Dendritic cell density at the inferior cornea was higher than the central cornea throughout the study (P < .001). No relationships were observed between each outcome measurements and the saline solution groups (P > .05). CONCLUSIONS: Scleral lens wear for 3 months on healthy cornea of young subjects did not affect corneal epithelial barrier function, nerve fiber, and dendritic cell densities. Buffered and nonbuffered saline solutions impacted the corneal health in similar ways.

Effects of scleral-lens oxygen transmissibility on corneal thickness: A pilot study.

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.

Tear dynamics under scleral lenses.

PURPOSE: To evaluate post-lens tear dynamics at two different time points during scleral lens wear in two cohorts with 10 neophytes each. METHODS: All subjects wore bilaterally scleral lenses for 5 h on 3 separate visits. Post-lens tear exchange was measured using Out-in method, which required 5 µL of 2% FITC-Dextran instilled on the bulbar conjunctiva during lens wear. Time taken to observe the first sign of fluorescence in post-lens tear reservoir was recorded with a stopwatch. Out-in measurements were collected at 5-hour post-lens insertion in Group 1 and compared with those obtained at 20 min of lens wear in Group 2. Tear dynamics under the lens was observed in Group 2 with fluorogram using a modified slit-lamp technique (Tan et al., 2018) to monitor post-lens fluorescence intensity and with high-resolution spectral domain optical coherence tomography (ENVISU 2300; Bioptigen Inc.) to measure post-lens tear thickness (PoLTT) over 5 h of lens wear. RESULTS: 60% of subjects in Group 1 achieved Out-in times less than 5 min at 5-hour post-lens insertion, compared with 67% of subjects at 20-min lens wear (Tan et al., 2018). Using qualitative analysis on 60 series of data in Group 2 to compare the changes in fluorescence intensity and PoLTT with respect to lens-wearing time, 27% was due to lens settling, 13% was due to tear exchange and mixing while 60% indicated tear dynamics under scleral lenses was due to a combination of tear exchange, mixing, and lens settling. CONCLUSION: Tear flow into tear reservoir under a scleral lens on subjects with healthy cornea occurred at 20 min and 5 h after lens insertion. After 5 h of lens wear, roughly one third of the subjects had no tear flow into post-lens reservoir, as the observed decline in post-lens tear fluorescence was predominately due to lens settling.

Effects of corneoscleral topography on soft contact lens performance: A pilot study.

To quantify corneoscleral junction (CSJ) topography in soft contact lens (SCL) wearers, and assess the association between the CSJ and SCL performance and subjective comfort, forty-four adapted SCL wearers (16 Asians, 16 Caucasians, 12 Latinos) were recruited for the present study. Corneal topography was taken with a Medmont E300 (Medmont International, Pty Ltd.). CSJ images were taken with a commercial OCT (Bioptigen, Inc.). Our published CSJ image analysis technique was used to describe the geometric properties of the CSJ using the sum of squared orthogonalized residuals (SSRo). Multivariable mixed effects models were employed to examine associations between SSRo and subject demographics, ocular characteristics, SCL fit and performance, and comfort. The SSRo was significantly related to quadrant (p < 0.001), ethnicity (p = 0.014), and horizontal corneal shape factor (p = 0.044). The nasal quadrant had the largest SSRo, indicating the steepest CSJ profile and/or the most irregular CSJ surface, followed by the inferior quadrant. The superior and temporal quadrants had the smallest SSRo, indicating relatively flat and even CSJ topography. Caucasians had the steepest and/or most irregular CSJ compared with Latinos and Asians. Less inferior-superior heterogeneity in the SSRo was associated with greater comfort after 6 h of lens wear. The SSRo was proved to be a useful tool to quantify CSJ geometry in SCL wearers. Significant differences in the SSRo were found among quadrants and ethnic groups. Better subjective comfort after 6 h of SCL wear was associated with a smaller difference in the SSRo between the superior and inferior quadrants.

Effects of Scleral-lens Tear Clearance on Corneal Edema and Post-lens Tear Dynamics: A Pilot Study.

SIGNIFICANCE: The present study with small-diameter scleral lenses (SLs) revealed that post-lens tear thickness (PoLTT) was significantly associated with post-lens tear mixing, but not with central corneal edema, after short-term SL wear. PURPOSE: The aim of this study was to investigate the influence of SL tear clearance (PoLTT) on central corneal thickness and post-lens tear dynamics during 5-hour lens wear. METHODS: Neophytes with no active ocular disease were fitted bilaterally with SLs (hofocon A; 15.6-mm diameter; ~438-µm thickness; 97 Dk; 1.44 refractive index) with various initial PoLTT values ranging from 74 to 543 µm. Central corneal thickness and PoLTT were measured using optical coherence tomography during lens wear. Tear mixing was assessed using fluorogram and "out-in" method. RESULTS: The mean central corneal edema after 5-hour lens wear was 1.51% (95% confidence interval, 1.26 to 1.76%; P < .001), reached its peak at 2-hour post-lens insertion (1.65% [95% confidence interval, 1.45 to 1.85%]), and was independent of PoLTT. The fastest fluorescence decay of the post-lens tear film was observed superiorly. The fluorescence decay rate increased from center to periphery in all quadrants except superiorly. An inverse relationship was found between PoLTT and fluorescence decay rate at both 20-minute and 5-hour wear after lens insertion (P < .05). Excluding observations with out-in time exceeding 5 minutes, we found a direct relationship between PoLTT at 20 minutes after lens insertion and out-in time (P = .047). The % change in the PoLTT after 5-hour wear was greater with a thinner initial tear clearance than those with a thicker one (P = .034). CONCLUSIONS: Within our study parameters, a thinner PoLTT under a small-diameter SL was associated with faster PoLTT mixing. However, there was no relationship between PoLTT and central corneal thickness during 5-hour SL wear.

Alzheimer's disease: amyloid-based pathogenesis and potential therapies.

Alzheimer's disease is one of the most severe neurodegenerative diseases among elderly people. Different pathogenic factors for Alzheimer's disease have been posited and studied in recent decades, but no effective treatment has been found, necessitating further studies. In this Viewpoint article, we assess studies on the mechanisms underlying the accumulation of amyloid (Aß) peptide and the formation of Aß oligomers because their accumulation in amyloid plaques in brain tissue has become a well-studied hallmark of Alzheimer's disease. We focus on the production of Aß and its impact on the function of synapses and neural circuits, and also discuss the clinical prospects for amyloid-targeted therapies.

Effects of Lens-Care Solutions on Hydrogel Lens Performance.

SIGNIFICANCE: Lens care multipurpose solutions (MPSs) can have varying effects on contact lens (CL) surface properties and the corneal epithelium. PURPOSE: The aim of this study was to investigate the short-term effects of newer MPS on CL comfort and dryness, prelens tear-film stability, and ocular-surface health. In vitro study was also performed to assess the effect of MPSs on CL surface properties. METHODS: Acuvue 2 CLs were soaked in control solution, Clear Care (CC), or test solutions: PureMoist, Biotrue, RevitaLens (RL), or saline solution (SS). Over four visits, subjects were exposed to control solution in one eye and to test solution in the contralateral eye for 2 hours using presoaked CLs. Contact lens comfort and dryness, ocular-surface health assessment, prelens noninvasive tear breakup time, and corneal epithelial permeability measured with fluorometry were assessed. Captive-sessile bubble technique evaluated CL wettability and viscous drag in vitro. RESULTS: At 10 minutes, mean comfort ± SD with PureMoist (76 ± 22) was lower than CC (86 ± 15, P = .02), Biotrue (92 ± 9, P < .005), RL (90 ± 13, P < .005), and SS (90 ± 14, P < .005). No other difference in comfort or dryness was noted. RevitaLens was associated with greater corneal epithelial permeability than CC (P = .020) and increased corneal staining compared with all MPSs (P < .005 for all). RevitaLens was also associated with longer prelens noninvasive tear breakup than CC (P < .005). In vitro results agreed with clinical findings of tear-film stability as RL reduced viscous drag. Contact lens surface wettability was enhanced by all MPSs in comparison to SS. CONCLUSIONS: Differences of MPSs on the ocular surface were found in vivo and in vitro. RL caused the greatest corneal epithelium disruption but also associated with higher tear-film stability. The effect of MPSs on CL surface properties in vitro seems to reflect how MPSs altered prelens tear stability.

Directional Optical Coherence Tomography Reveals Reliable Outer Nuclear Layer Measurements.

PURPOSE: Directional Optical Coherence Tomography (D-OCT) is a method used to optically segment and identify the outer nuclear layer (ONL) in vivo. The purpose of this study was to determine the repeatability and reproducibility of D-OCT ONL thickness measurements in healthy eyes. METHODS: Sixteen healthy eyes of sixteen subjects were imaged using the Cirrus SD-OCT. The OCT beam entry position was varied horizontally and vertically through the pupil, and cross-sectional images were obtained at baseline and 1-month follow-up by two observers. Detailed segmentation was performed to quantify the thickness of ONL without the inclusion of overlying Henle Fiber Layer. Inter-observer, intra-observer, and inter-visit variability was evaluated using Bland-Altman and coefficient of variation analysis for each category. RESULTS: All 16 eyes were successfully imaged, registered, and segmented. The maximum mean (SD) inter-operator difference was 2.6 (4.8) µm. The maximum mean (SD) intra-operator difference was 2.4 (5.3) µm. There was no statistically significant difference in ONL measurements detected between baseline and follow-up (p > 0.05). The mean (SD) differences measured across visits by one operator varied from -1.6 (3.1) to 1.1 (6.1) µm. The mean (SD) coefficient of variance (CV%) for all sectors with horizontal orientation was 9.1% (2.3%), 10.1% (2.5%), and 8.6% (2.3%) for inter-observer, intra-observer, and inter-visit, respectively. The mean (SD) coefficient of variance (CV%) for all sectors with vertical orientation was 8.3% (1.8%), 6.9% (1.4%), and 8.3% (2.1%) for inter-observer, intra-observer, and inter-visit, respectively. The majority of the variation of paired repeated measurements originated from between-subject variance. The within-subject variance accounted for less than 1% of the total variability. CONCLUSIONS: ONL thickness measurements can be quantified with good repeatability and reproducibility using D-OCT. Identifying the magnitude of D-OCT variability among normal subjects will allow for improved development of future clinical studies that quantitatively track the progression of macular pathology.

Increased corneal epithelial permeability after overnight sleep.

PURPOSE: To investigate factors of ethnicity, sex, age, and diurnal variation on human corneal epithelial permeability. METHODS: Data of corneal epithelial permeability to sodium fluorescein (Pdc) were collected from 374 noncontact lens wearers at various times after awakening throughout the day. Mixed-effect models were developed to investigate the association between Pdc and factors of interest, including time awake (TA), age, sex, ethnicity, and interactions of these factors. RESULTS: Two models evaluated the "Pdc recovery period" from awakening to 2 hours (Model 1) and the "Pdc plateau" period after TA of 2 hours (Model 2). In Model 1, Pdc declined significantly with length of awake time (P = 0.000), and showed higher Pdc with males (P = 0.098), although this sex difference was not observed after 2 hours (Model 2). Both models showed significantly higher Pdc in Asians than in non-Asians (P = 0.000) and increased Pdc with age (P = 0.048, P = 0.001). CONCLUSIONS: Baseline corneal epithelial barrier function increases after overnight sleep and varies significantly by ethnicity and age.

Diurnal Pattern of Tear Osmolarity and Its Relationship to Corneal Thickness and Deswelling.

PURPOSE: To identify the diurnal variations of tear osmolarity (TO) and its relationship with central corneal thickness (CCT) and corneal deswelling over a 14-hour period. METHODS: TO and CCT were measured using the TearLab Osmometer and Bioptigen spectral domain optical coherence tomography, respectively, on 38 healthy neophytes (mean age, 21.5 ± 2.2 years). TO and CCT were measured at bedtime (baseline), upon awakening, 20 minutes, 40 minutes, 1 hour, 2 hours, 4 hours, and 8 hours after awakening. Deswelling rate was estimated and expressed as percent recovery per hour (PRPH). Mixed-effect linear regression models describe the relationships among TO, CCT, and PRPH. RESULTS: The tear film upon wakening (264 ± 14 mOsm/L) was hypoosmotic compared with baseline (297 ± 15 mOsm/L, P < 0.001). TO (in mOsm/L) at 20 minutes, 40 minutes, 1 hour, 2 hours, 4 hours, and 8 hours were 287 ± 10, 292 ± 16, 293 ± 12, 292 ± 10, 289 ± 10, and 286 ± 10, respectively. CCT (mean ± SD) at baseline was 552.2 ± 35.9 µm and increased to 572.0 ± 38.7 µm after sleep. CCT returned to baseline thickness 4 hours after awakening (P < 0.000) and remained stable throughout the day. A small but statistically significant association was found between higher TO and lower CCT (P < 0.0001) and between lower baseline TO and higher PRPH (faster deswelling; P < 0.0001). CONCLUSIONS: The diurnal pattern of TO has been established. The association of TO with corneal thickness and deswelling suggests that the tear film tonicity may be partly responsible for corneal hydration control; however, the effect may not be of clinical significance in a normal study cohort.

Short-term effects of overnight orthokeratology on corneal epithelial permeability and biomechanical properties.

PURPOSE: To investigate the effects of 30 nights of overnight orthokeratology (OOK) on corneal epithelial permeability (Pdc) and corneal biomechanical properties. METHODS: BE Retainer and Paragon CRT lenses were used. Visits were scheduled approximately 4 hours after awakening at baseline and after 1, 5, 10, 14, and 30 days of treatment. Pdc was measured at baseline and at day 30, whereas corneal biomechanical properties and visual acuities (VAs) were measured at all visits. RESULTS: Thirty-nine neophytes and soft contact lens wearers completed the study. There was no difference in Pdc between baseline (ln[Pdc] [95% confidence interval (CI)] = -2.65 [-2.80 to -2.50]) and day 30 (ln[Pdc][CI] = -2.68 [-2.85 to -2.50]) (P = 0.88). Corneal hysteresis (CH) and corneal resistance factor (CRF) reduced significantly from baseline (CH [CI] = 10.89 [10.59-11.19] mm Hg and CRF [CI] = 10.35 [9.99-10.72] mm Hg) to day 30 (CH [CI] = 10.59 [10.31-10.87] mm Hg and CRF [CI] = 9.58 [9.26-9.89] mm Hg) (P = 0.001 for CH and P < 0.001 for CRF). Posttreatment VA did not reach baseline targets, and the difference was worse with low-contrast letters. Asian individuals (n = 18) had significantly worse VA than non-Asian individuals (n = 21) under most conditions through day 5, and the difference extended through day 14 with low-contrast letters under mesopic conditions. The percentage of participants who achieved 20/20 uncorrected was 17% Asian and 40% non-Asian individuals after day 1 and reached 69% Asian and 83% non-Asian individuals at day 30. CONCLUSIONS: Thirty nights of OOK did not alter Pdc when measured 4 hours after awakening. OOK caused CH and CRF to decrease, but the changes were not clinically significant compared with diseased and postsurgical cases. Asian individuals, who had lower baseline CH in this study, responded slower to OOK based on early uncorrected VA and overrefraction measurements.

Objective quantification of fluorescence intensity on the corneal surface using a modified slit-lamp technique.

OBJECTIVES: To improve the digital quantification of fluorescence intensity of sodium fluorescein instilled on corneal surface by modifying a slit lamp hardware and performing computerized processing of captured digital images. METHODS: The optics of a slit lamp were modified to remove corneal Purkinje reflection and to expand the illuminated area on the cornea, followed by postexperiment image processing to minimize the influence of uneven illumination. To demonstrate the feasibility and reliability of this new technique, we applied it to objective grading of corneal staining with sodium fluorescein. The results of computerized grading were compared with the results obtained using standard subjective grading of corneal staining. Objective digital grades, staining area, and staining pixel with manually and automatically defined threshold (SP-M and SP-A) were calculated for both original and processed images. Standard subjective grades of the original images were performed by 13 trained observers using National Eye Institute (NEI), Efron, and CCLRU grading scales. A series of linear regression analyses were performed to investigate the correlation between objective and subjective grades. RESULTS: Digital grades of the captured images were correlated significantly with subjective grades. After minimization of the artifact caused by the nonuniform illumination, correlations between digital and subjective grading were mostly strengthened. In some cases, digital grading of corneal staining was more sensitive than subjective grading methods when differentiating subtle differences of corneal staining. CONCLUSIONS: Modifications performed on commercial slit-lamp hardware and the proposed digital image-processing technique have improved the quality of captured images for semiautomated quantification of fluorescein intensity on the cornea.