Corneal Parameters Research Articles

Hydro-implantation versus Visco-implantation of Intraocular Lenses and Fluid Load Effect on Corneal Endothelial Cells after Uneventful Phacoemulsification

AIM: The purpose of the study was to study the effect of implantation method and fluid load (aspiration time, aspiration volume) on corneal endothelium in uneventful phacoemulsification surgeries. METHODS: This study was a prospective and interventional study involved 77 eyes, 50−81 years, divided into three groups according to implantation method (on Saline, Healon, or Methylcellulose). Specular microscope analysis of corneal endothelial parameters: Cell density (CD), central corneal thickness (CCT), coefficient of variation (CV), and Hexagonality (HEX) were done before and 3 months after surgery. RESULTS: A total of 77 eyes with cataracts were studied, and there was a significant increase in CCT and CV with a decrease in CD and HEX in all three groups. On comparing the same parameters between the three groups, there were insignificant differences regarding CCT and HEX changes. Although there was a significant change in CD, the highest loss was in the Healon group (median −0.138), followed by the Saline group (median −0.118), and the lowest was in the Methyl group (median −0.075). There was a significant change in CV, showing the highest increase in the Healon group (median 0.16129) followed by the Saline group (median 0.13307) and the lowest in the Methyl group (median 0.1266). There was a non-significant change in all corneal parameters among cases in each group with different aspiration volumes and times. CONCLUSION: Endothelial cell loss was lowest with Methyl followed by saline, and highest with Healon implantation. Fluidics had an insignificant effect in the three groups. Saline implantation was comparable to Healon, with an insignificant difference in CD loss.

Evaluation of Dynamic Corneal Response Parameters and the Biomechanical E-Staging After Accelerated Corneal Cross-Linking in Keratoconus.

This study evaluated the biomechanical E-staging in progressive keratoconus (KC) corneas before and after epithelium-off accelerated corneal cross-linking (CXL, 9mW/cm2, 10min, 5.4J/cm2). German university-based retrospective longitudinal cohort study. The biomechanical E-staging for ectatic corneal diseases was applied retrospectively on 49 progressive KC corneas of 41 patients who underwent CXL. Main outcome parameters included the Corvis Biomechanical Factor (CBiF, the linearized Corvis Biomechanical Index), the biomechanical E-staging (E1 to E4 result of dividing the CBiF value range into 5 groups), maximal anterior keratometry (Kmax), anterior radius of curvature (ARC), and thinnest corneal thickness (TCT). They were evaluated at 2.1±2.0 months preoperatively (n=49 corneas, 41 patients) and postoperatively after 5.4±1.4, 11.3±1.8, and 23.4±1.6 months. The CBiF decreased (5.1±0.5 | 5.0±0.5, P=0.0338) and the E-staging increased significantly (2.4±0.9 | 2.6±0.8, P=0.0035) from preoperatively to the first postoperative follow-up. The difference was not significant after 11 months and there were same values after 23 months. Kmax, ARC, and TCT slightly decreased (Kmax: 56.9±6.3, 54.3±5.1, 56.2±6.6, 54.0±5.2; ARC: 49.8±3.5, 48.9±3.2, 50.8±5.6, 49.0±3.7; TCT: 470±34, 454±36, 459±35, 466±39; preoperatively and 5, 11, and 23 months postoperatively). A postoperatively decreased TCT was associated with an increased E-stage, whereas an equal or increased TCT measurement after CXL was associated with equal or lower E-staging results. The biomechanical E-staging in KC corneas is influenced by TCT measurements and increases within the first postoperative months after CXL. On the long term, it indicates a postoperative KC stabilization, with comparable E-values to preoperatively at 11 and 23 months after CXL.

Corneal epithelial dendritic cells, tear neuropeptides and corneal nerves continue to be affected more than 12 months after LASIK.

LASIK causes corneal nerve damage and may affect the neuro-immune crosstalk. This study examined the effects of LASIK on corneal epithelial dendritic cells (CEDC) density and morphology and explored their relationships with corneal nerves and tear neuropeptides. A grading system was developed to assess CEDC morphology. Intra- and inter-observer repeatability of the CEDC morphology grading system was established using kappa (κ). In vivo confocal microscope images of the central cornea were captured from 20 participants who had undergone LASIK 12-16 months earlier and 20 controls (age 18-32 years, 55%F). CEDC density was counted manually, and CEDC morphology was assessed using a new grading system. CEDC sub-types (contacting nerves [CEDCc] and not contacting nerves [CEDCnc]) were also assessed. Differences in CEDC density and morphology were examined using mixed models and chi-squared test. Relationships between CEDC and corneal nerve parameters and tear substance P were explored using Spearman's correlation. Excellent intra- and inter-observer repeatability was demonstrated for the grading system (κ=0.82-0.97). In post-LASIK participants, CEDC density was lower compared with controls (5 [0-34] vs. 21 [7-77] cells/mm2 ; p= 0.01), and the proportion of CEDC with thick dendrites was higher (55%-73% vs. 11%-21%, p< 0.003). Higher tear substance P levels were associated with higher CEDC density (rho=0.48, p= 0.003). Fewer nerve interconnections were observed in participants in whom CEDC had dendrites (p= 0.03). CEDC sub-types followed a similar pattern to CEDC. The findings suggest that CEDC may remain altered more than 12 months post-LASIK. The association with substance P suggests a role for CEDC in corneal neurogenic inflammation.

Age- and gender-related characteristics of astigmatism in a myopic population.

PurposeTo explore age- and gender-related differences of refractive and corneal astigmatism in myopic patients looking for refractive surgery.DesignA retrospective cross-sectional study.Materials and methodsThe medical files of candidates looking for corneal refractive surgery between 2019 and 2021 were reviewed, demographic and refractive parameters including age, gender, refractive status, and corneal parameters were analyzed.ResultsA total of 1,417 eyes of 1,417 patients (453 males and 964 females) were included. Males had thicker cornea than females, while females had steeper cornea than males, there was no gender-related difference in refractive and corneal astigmatism depending on patients’ age. There was no difference in refractive astigmatism among different age group from 18 to 50 years, while corneal astigmatism had a shift from with-the rule (WTR) to against-the-rule (ATR) with increasing age. Age, central corneal thickness (CCT), sphere, refractive astigmatism (RA), and corneal curvature (Km) were correlated with corneal astigmatism (CA) (standardized coefficients of are 0.006, p = 0.011 for age, −0.001, p = 0.004 for CCT, and −0.027, p < 0.001 for sphere, 0.61, p < 0.001 for RA, −0.05, p < 0.001 for corneal curvature).ConclusionRefractive astigmatism is stable until the age of 50 years in myopic patients looking for refractive surgery, while corneal astigmatism showed a shift from WTR to ATR with advancing age. Age, CCT, sphere, refractive astigmatism and corneal curvature (Km) were correlated with corneal astigmatism.

Implementation of corneal confocal microscopy for screening and early detection of diabetic neuropathy in primary care alongside retinopathy screening: Results from a feasibility study.

ObjectiveScreening for diabetic peripheral neuropathy (DPN) is essential for early detection and timely intervention. Quantitative assessment of small nerve fiber damage is key to the early diagnosis and assessment of its progression. Corneal confocal microscopy (CCM) is a non-invasive, in-vivo diagnostic technique that provides an accurate surrogate biomarker for small-fiber neuropathy. In this novel study for the first time, we introduced CCM to primary care as a screening tool for DPN alongside retinopathy screening to assess the level of neuropathy in this novel cohort.Research design and methods450 consecutive subjects with type 1 or type 2 diabetes attending for annual eye screening in primary care optometry settings underwent assessment with CCM to establish the prevalence of sub-clinical diabetic peripheral neuropathy. Subjects underwent assessment for neurological and ocular symptoms of diabetes and a history of diabetic foot disease, neuropathy and diabetic retinopathy (DR).ResultsCCM examination was completed successfully in 427 (94.9%) subjects, 22% of whom had neuropathy according to Diabetic Neuropathy Symptom (DNS) score. The prevalence of sub-clinical neuropathy as defined by abnormal corneal nerve fiber length (CNFL) was 12.9%. In the subjects with a short duration of type 2 diabetes, 9.2% had abnormal CNFL. CCM showed significant abnormalities in corneal nerve parameters in this cohort of subjects with reduction of corneal nerve fiber density (CNFD, p<0.001), CNFL (p<0.001) and corneal nerve branch density (CNBD, p<0.001) compared to healthy subjects. In subjects who had no evidence of DR (67% of all subjects), 12.0% had abnormal CNFL.ConclusionsCCM may be a sensitive biomarker for early detection and screening of DPN in primary care alongside retinopathy screening.

Assessment of corneal biomechanics in anisometropia using Scheimpflug technology.

Purpose: To investigate the relationship between corneal biomechanical and ocular biometric parameters, and to explore biomechanical asymmetry between anisometropic eyes using the corneal visualization Scheimpflug technology device (Corvis ST). Methods: 180 anisometropic participants were included. Participants were divided into low (1.00≤△Spherical equivalent (SE) < 2.00D), moderate (2.00D≤△SE < 3.00D) and high (△SE ≥ 3.00D) anisometropic groups. Axial length (AL), keratometry, anterior chamber depth (ACD) and corneal biomechanical parameters were assessed using the OA-2000 biometer, Pentacam HR and Corvis ST, respectively. Results: The mean age of participants was 16.09 ± 5.64 years. Stress-Strain Index (SSI) was positively correlated with SE (r = 0.501, p < 0.001) and negatively correlated with AL (r = -0.436, p < 0.001). Some other Corvis ST parameters had weak correlation with SE or AL. Corneal biomechanical parameters except for time of first applanation (A1T), length of second applanation (A2L), deformation amplitude (DA), first applanation stiffness parameter (SPA1) and ambrosia relational thickness-horizontal (ARTh) were correlated with ametropic parameters (SE or AL) in multiple regression analyses. A1T, velocity of first applanation (A1V), time of second applanation (A2T), A2L, velocity of second applanation (A2V), corneal curvature radius at highest concavity (HCR), peak distance (PD), DA, deformation amplitude ratio max (2mm) (DAR), SPA1, integrated radius (IR), and SSI showed significant differences between fellow eyes (p < 0.05). There was no significant difference in asymmetry of corneal biomechanics among the three groups (p > 0.05). Asymmetry of some biomechanical parameters had weak correlation with asymmetry of mean corneal curvatures and ACD. However, asymmetry of corneal biomechanical parameters was not correlated with asymmetry of SE or AL (p > 0.05). Conclusion: More myopic eyes had weaker biomechanical properties than the contralateral eye in anisometropia. However, a certain linear relationship between anisometropia and biomechanical asymmetry was not found.

Corneal Biomechanical Changes after Corneal Cross-Linking in Patients with Keratoconus.

To evaluate the changes in biomechanical properties of the cornea using the Corvis ST device after the treatment of keratoconus patients with ultraviolet-A/riboflavin corneal cross-linking (CXL). Thirty-seven eyes from 37 consecutive patients with progressive keratoconus were included in this prospective observational case series. Corneal biomechanical parameters including the length of the applanated cornea (L1 and L2), corneal movement velocity during applanation (V1 and V2) at the moment of the first and second applanation, deformation amplitude (DA), distance between bending points of the cornea points of the cornea (PD), and concave radius of curvature (R) at the point of the highest concavity were recorded using the Corvis ST at baseline, 3 months, and 1 year after CXL. The mean age of the patients was 23.27 years (range, 19-31 years). Among CorVis ST corneal biomechanical parameters, L1, DA, PD, and R at the point of the highest concavity did not change significantly. The length of the applanated cornea at the moment of second applanation (L2) showed a significant change 3 months after CXL, but no significant difference was found between the 3-month and 1-year values of this parameter. Corneal movement velocity during applanation (V1 and V2) did not change 3 months after doing CXL, but the changes in these parameters were significant 1 year after CXL. Although the CorVis ST device may detect changes in some biomechanical properties of cornea after the treatment of keratoconus patients with CXL, many parameters remain unchanged, and this device cannot readily be used to find the effects of CXL.

Agreement between 2 SS-OCT biometry devices.

To assess the agreement between 2 swept-source optical coherence tomography biometry devices, Anterion and IOLMaster 700. Tertiary referral center, Brisbane, Australia. Prospective comparative study. Bland-Altman analysis was used to assess agreement between devices for flat (K1), steep (K2), and mean (Km) keratometry for anterior, posterior, and total cornea, lens thickness (LT), anterior chamber depth (ACD), central corneal thickness (CCT), white to white (WTW), and axial length (AL). Generalized estimating equations were used to control for within-patient between-eye correlations. Interdevice differences were considered clinically significant if they were likely to alter the spherical refractive outcome by 0.25 diopter (D) or more. 159 eyes of 91 patients (41 male, 50 female) were included. Statistically significant differences were found for K1, K2, and Km for anterior, posterior, and total cornea. When the Anterion was compared with the IOLMaster 700, the mean differences were as follows: anterior K1: -0.17 D, anterior K2: -0.18 D, anterior Km: -0.17 D, posterior K1: -0.38 D, posterior K2: -0.36 D, posterior Km: -0.37 D, total K1: -0.65 D, total K2: -0.82 D, and total Km: -0.74 D. The difference in posterior and total K metrics was clinically significant. Statistically significant differences were noted for LT: 0.159 mm, CCT: -0.004 mm, ACD: 0.054 mm, and WTW: -0.152 mm, although these were not found to be clinically significant. There was no significant difference between devices for AL. This study found statistically and clinically significant differences for both posterior and total keratometry between the Anterion and the IOLMaster 700. Posterior and total corneal parameters cannot be considered interchangeable between devices.

Change Patterns in Corneal Intrinsic Aberrations and Nerve Density after Cataract Surgery in Patients with Dry Eye Disease.

This study aimed to evaluate the change patterns in corneal intrinsic aberrations and nerve density after cataract surgery in dry eye disease. The preoperative, 1- and 3-month postoperative dry eye-related parameters were obtained by the Oculus keratograph and the ocular surface disease index questionnaire. The corneal intrinsic aberrations were measured using the Pentacam HR system. In vivo confocal microscopy was performed to observe the vortical and peripheral corneal nerves. An artificial intelligence technique run by the deep learning model generated the corneal nerve parameters. Corneal aberrations on the anterior and total corneal surfaces were significantly increased at 1 month compared with the baseline (p < 0.05) but gradually returned to the baseline by 3 months (p > 0.05). However, the change in posterior corneal aberration lasted up to 3 months (p < 0.05). There was a significant decrease in the corneal vortical nerve maximum length and average density after the operation (p < 0.05), and this damage lasted approximately 3 months. The corneal vortical nerve maximum length and average density were negatively correlated with the anterior corneal surface aberrations before and 1 month after the operation (correlation coefficients, CC = −0.26, −0.25, −0.28; all p < 0.05). Corneal vortex provided a unique site to observe long-term corneal nerve injury related to eye dryness. The continuous damage to the corneal vortical nerve may be due to the continuous dry eye state.

Association between systemic omega-3 polyunsaturated fatty acid levels, and corneal nerve structure and function

BackgroundOmega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have anti-inflammatory and neuroprotective properties. This study sought to determine the relationship between corneal parameters and systemic omega-3 fatty acid levels.MethodsForty-seven participants with no/mild peripheral neuropathy (26 with diabetes and 21 without) underwent comprehensive ocular surface and systemic PUFA assessments. Corneal anatomical parameters were assessed using in vivo confocal microscopy. Corneal sensitivity was measured using non-contact esthesiometry. Relationships between systemic PUFA levels and corneal parameters were evaluated with multiple linear regression, adjusted for age, sex, neuropathy symptom score, and presence of diabetes and dry eye disease. The relationship between corneal nerve fibre length (CNFL) and corneal sensitivity threshold was evaluated.ResultsThe median Omega-3 Index, a measure of erythrocyte EPA and DHA, was 5.21% (interquartile range: 4.44–5.94%) in the study population. Mean ( ± SD) CNFL was 13.53 ± 3.37 mm/mm2. Multiple linear regression showed that Omega-3 Index (β = 0.33; p = 0.02), age (β = −0.46; p = 0.001) and diabetes (β = −0.30; p = 0.03) were independently associated with CNFL (R2 = 0.39, p = 0.002). In a separate model, DHA (β = 0.32; p = 0.027) and age (β = −0.41; p = 0.003) were associated with CNFL (R2 = 0.37, p = 0.003). Neither systemic EPA nor omega-6 fatty acid levels correlated with CNFL. There was no association between PUFA levels and corneal sensitivity or corneal immune cell density. A negative correlation was found between CNFL and corneal sensation thresholds to a cooled stimulus in diabetes participants, in the central (ρ = −0.50; p = 0.009) and peripheral (ρ = −0.50; p = 0.01) cornea.ConclusionsA positive relationship between the systemic Omega-3 Index and corneal nerve parameters suggests omega-3 PUFA intake may influence corneal nerve architecture.

To Achieve a Bullseye: Factors Related to Corneal Refractive Therapy Orthokeratology Lens Toricity.

This retrospective study investigated the toricity of dual-axis corneal refractive therapy (CRT) orthokeratology lenses and corneal parameters, including flat keratometry (FK), flat eccentricity (e), steep e, corneal astigmatism, and the difference in elevation at 8 mm chord length. We analyzed the right eyes of 143 adolescent patients who underwent ocular examinations, subjective refraction, and corneal topography before CRT lens fitting by trial lens evaluation. After orthokeratology treatment, all patients underwent a topography map with an intact plus power ring and decentration of <1 mm. The mean patient age was 10.7 ± 2.2 years old; 33% were male. The lens toricity range was 25–100 µm. Multiple linear regression analysis showed significant associations between CRT lens toricity and corneal astigmatism (β = 10.913, t = 3.012, p = 0.003) and the difference in elevation at 8 mm chord length (β = 0.681, t = 4.049, p < 0.001); no association was found between CRT lens toricity and FK, flat e, or steep e (all p > 0.05). Corneal astigmatism was positively associated with difference in elevation at 8 mm chord length (r = 0.743, p < 0.001, Pearson’s correlation), and corneal astigmatism and the difference in elevation at 8 mm chord length were positively associated with CRT lens toricity (r = 0.657 and r = 0.643, respectively; both p < 0.01, Spearman’s correlation). These results suggest that difference in elevation at 8 mm chord length can be used to conveniently estimate CRT lens toricity in clinical practice, using the equation Y (CRT lens toricity) = 1.02X (difference in elevation at 8 mm chord length) + 20.3.

Corneal densitometry in bilateral keratoconus patients with unilateral corneal Vogt's striae: a contralateral eye study.

To investigate corneal densitometry and correlations with corneal morphological parameters in patients with bilateral keratoconus (KC) with unilateral Vogt's striae. This prospective contralateral study enrolled 112 patients (224 eyes) with evident KC characteristics (corneal topography with asymmetric bow-tie pattern, inferior steepening), and at least one KC sign (conical protrusion of the cornea at the apex, corneal stromal thinning, Fleischer ring, Vogt's striae) on slit-lamp examination. Corneal densitometry and morphological parameters were measured using Pentacam HR. The mean age was 23.93 ± 6.81years. Fifty-two (23.22%), 111 (49.55%), and 61 (27.23%) eyes were in mild, moderate, and severe groups, respectively. Corneal densitometry values of the anterior 0-2mm and 2-6mm, intermediate 0-2mm and 2-6mm, posterior 2-6mm, and total cornea 2-6mm were significantly higher in eyes with Vogt's striae (P < 0.05), whereas those of the anterior 6-10mm, posterior 0-2mm, and total cornea 6-10mm were significantly lower in eyes with Vogt's striae (P < 0.05). Anterior 0-2mm and total cornea 2-6mm corneal densitometry values were positively correlated with anterior K1 (A-K1), K2 (A-K2), Km (A-Km), Kmax (A-Kmax), anterior corneal elevation, and posterior corneal elevation (P < 0.05), and negatively correlated with central corneal thickness and thinnest corneal thickness in eyes with Vogt's striae (P < 0.05). A-K2, A-Km, and A-Kmax were significantly correlated with the densitometry values of the anterior 0-2mm and intermediate 0-2mm in eyes without Vogt's striae (P < 0.05). Vogt's striae mainly occur on the anterior and intermediate layers during KC progression.

Best indices of dual Scheimpflug/Placido tomographer for keratoconus detection.

To evaluate the accuracy of different corneal parameters in detecting keratoconus using a dual Scheimpflug/Placido system (Sirius, CSO, Italy). Sixty-eight eyes of 68 keratoconus patients and 77 eyes of 77 normal subjects were prospectively assessed in a diagnostic test study. The mean differences of the corneal parameters were compared using the independent t-test. The accuracy of curvature, elevation, pachymetry, and aberrometry indices, aqueous depth, and corneal volume in 10mm was evaluated using the area under the curve (AUC), and the DeLong method was used for the comparison of AUCs. Multiple tests in a parallel manner and multiple logistic regression analysis were applied to determine the best predictor indices. All indices except aqueous depth and corneal volume were significantly different between the two groups (P < 0.001). Back keratoconus vertex (KVb) and front Baiocchi-Calossi-Versaci index (BCVf) had the highest sensitivity (for both 98.53%) followed by front symmetry index (SIf) (96.12%) and thinnest point of the cornea (88.24%) in elevation, aberrometry, curvature, and pachymetry parameters, respectively. The highest diagnostic ability was observed in KVb (AUC 0.993) and BCVf index (AUC 0.992) (DeLong > 0.05). Multiple test analysis showed a combination of indices with the highest accuracy that was similar to the performance of each one individually, and keratoconus was diagnosed correctly in 98.5% of the cases (R2 = 93%). The parameters extracted from Sirius can differentiate keratoconus from normal corneas with high accuracy without the need for complex computational algorithms. Elevation-based and combined aberrometry indices had the highest diagnostic power.

Corneal endothelium, retinal nerve fiber layer, ganglion cell complex, and perimetry measurements in normal eyes and those with primary open-angle glaucoma.

Corneal endothelial cell (CEC) loss in glaucoma can be attributed to the direct compressive effect of elevated intraocular pressure. Herein, we aimed to evaluate specular microscopic changes in CEC count and morphology in correlation to retinal nerve fiber layer (RNFL) changes detected by spectral-domain optical coherence tomography (SD-OCT) in early and advanced primary open-angle glaucoma (POAG). This descriptive-analytical study involved patients with medically controlled POAG versus non-glaucomatous patients of the same age group. Specular microscopy, visual field testing, and SD-OCT of the RNFL and macular ganglion cell complex (GCC) were performed. Eyes with POAG were further subcategorized into early and advanced stages. The study included 130 eyes of 130 participants; 70 were eyes with POAG (40 eyes with early-stage POAG, 30 eyes with advanced-stage POAG), and 60 were healthy eyes. The groups were comparable regarding mean age and sex. No significant difference was found in corneal parameters between healthy eyes, eyes with early POAG, and eyes with advanced POAG (all P > 0.05). In eyes with early-stage POAG, a significant negative correlation was found between the coefficient of variation (CV) and superior RNFL thickness (r = - 0.5; P = 0.018), and between the percentage of hexagonal cells (hexagonality) and vertical cup-to-disc ratio (r = - 0.43; P = 0.035). A significant positive correlation was found between hexagonality and superior as well as inferior RNFL thickness (r = + 0.53; P = 0.008 and r = + 0.50; P = 0.015, respectively). However, in the advanced glaucomatous eyes, no significant correlation was found between RNFL thickness and CEC parameters. CEC parameters were not affected in eyes with early or advanced POAG compared with healthy eyes, despite a significant thinning of RNFL and macular GCC. In eyes with early-stage POAG, a significant correlation was found between morphological characteristics of CECs, such as CV and hexagonality, with superior and inferior RNFL thickness in the optic nerve head on SD-OCT images. Future longitudinal studies with larger sample sizes are needed to verify our results.

Descemet Membrane Endothelial Keratoplasty-Induced Refractive Shift and Descemet Membrane Endothelial Keratoplasty-Induced Intraocular Lens Calculation Error.

The aim of this study was to determine the mechanisms leading to the refractive shift and intraocular lens calculation error induced by Descemet membrane endothelial keratoplasty (DMEK), using ocular biometry and corneal elevation tomography data. This is a retrospective, monocentric cohort study. Eyes which underwent uncomplicated DMEK surgery with available pre-DMEK and post-DMEK Scheimpflug rotating camera data (Pentacam, Oculus, Wetzlar, Germany) were considered for inclusion with an age-matched control group of healthy corneas. Cataract surgery data were collected for triple-DMEK cases. DMEK-induced refractive shift (DIRS) and intraocular lens calculation error (DICE) were calculated. Pearson r correlation coefficient was calculated between each corneal parameter variation and both DIRS and DICE. DIRS was calculable for 49 eyes from 43 patients. It was 30.61% neutral, 53.06% hyperopic (36.73% > 1D), and 16.32% myopic (6.12% > 1 D). DICE was calculable for 30 eyes of 26 patients: It was 46.67% neutral, 40.00% hyperopic (10.00% > 1D), and 13.33% myopic (3.33% > 1D). DIRS and DICE were mainly associated with variations in PRC/ARC ratio, anterior average radii of curvature (ARC), posterior average radii of curvature (PRC), and posterior Q. Our results suggest that ARC variations, PRC/ARC ratio variations, PRC variations, and posterior Q variations are the most influential parameters for both DIRS and DICE. We suggest that a distinction between those different phenomenons, both currently described as "hyperopic shift" in the literature, should be made by researchers and clinicians.

Is Corneal Subbasal Nerve Loss Associated With Meibomian Gland Loss in Inactive Mild and Moderate-to-Severe Graves' Ophthalmopathy?

To evaluate meibomian gland and subbasal nerve plexus parameters in Graves' Ophthalmopathy (GO) and association of meibomian gland loss with corneal subbasal nerve plexus loss. Fifty-two eyes of 52 mild and moderate-to-severe GO patients and 32 eyes of 32 healthy controls were enrolled. The meibomian gland dropout area (MGDA) and meibography scores were evaluated using noncontact meibography. In vivo confocal microscopy of corneal subbasal nerve plexus were conducted. ACCMetrics was used to obtain corneal parameters. Compared with healthy subjects, GO patients had worse upper and lower eyelid MGDA ( p < 0.001, for all) and upper, lower and total meibography scores ( p < 0.001, p = 0.001, and p < 0.001, respectively). Eyelid margin scores were worse in the GO group ( p < 0.001) and showed correlation with all noncontact meibography parameters ( p < 0.001 for all). All corneal subbasal nerve parameters were significantly lower in the GO group compared with the controls ( p < 0.05 for all). Subbasal nerve parameters of GO patients did not reveal a correlation with MGDA and meibography scores but showed correlations with ocular surface disease index score and Schirmer I test (r = -0.304; p = 0.042 and r = 0.336; p = 0.021, respectively). Meibomian gland and corneal nerve loss could be observed even in the inactive phase and mild GO. The lack of a correlation between meibomian gland loss and subbasal nerve loss suggests that meibomian gland loss is not a significant additional component in the pathogenesis of subbasal nerve damage in GO. Furthermore, our study revealed new evidence regarding the use of eyelid margin score to represent meibomian gland loss in GO.

Influence of Specialty Contact Lens Wear on Posterior Corneal Tomography in Keratoconus Subjects.

To evaluate the effect of specialty contact lens (CL) wear on posterior corneal tomography in keratoconus subjects. Patients with keratoconus who were wearing specialty CL were included in this retrospective cohort study. Tomographic parameters were evaluated with Scheimpflug imaging (Pentacam HR) before lens fitting and immediately after removal of CLs worn habitually for a period of several months. Subjects were divided into groups, according to type of lens (corneal, scleral, and hybrid) and keratoconus severity based on Belin/Ambrosio D (BAD-D) score, for further analysis. Thirty-four eyes of 34 subjects diagnosed with keratoconus were included. Mean duration of habitual CL wear was 7.0±0.3 months. For the entire cohort, a small increase in flat keratometric reading at the anterior corneal surface (K1F; P =0.032) and at the posterior surface (K1B; P =0.041) was found. In the corneal CL group (10 eyes; 29.4%), flattening of the anterior corneal curvature was detected (K max ; P =0.015). An increase in K1B value was seen in the scleral CL group (15 eyes; 44.1%) ( P =0.03). Combined topometric indices showed a small but significant difference in the entire cohort ( P <0.05) and in the subgroups of corneal CL wear and of moderate keratoconus (BAD-D score≥7). Various types of specialty CLs exert a differential influence on corneal parameters. A small steepening of keratometry at the posterior surface (K1B) was observed in the scleral lens group. Although corneal lens wear flattens the anterior cornea (K max ), it does not significantly alter the posterior corneal surface.

Tear film substance P in patients treated with neurotoxic chemotherapy

Neurotoxic chemotherapy has been shown to be associated with reduced corneal nerves and ocular surface discomfort. Substance P is a neuropeptide expressed by sensory nerves including those in the densely innervated cornea. It is involved in both pain signaling and the regulation of epithelial and neural health. While its levels in tear fluids have been used as a neuropathic biomarker in diabetes, investigations of tear concentrations of substance P in chemotherapy-induced peripheral neuropathy have not been explored. The current cross-sectional study assessed substance P expression in tears of patients following neurotoxic chemotherapy treatment. Patients treated with paclitaxel (n = 35) or oxaliplatin (n = 30) 3–24 months prior to assessment were recruited along with healthy controls (n = 25). Flush tear collection, in-vivo corneal confocal microscopy and neurotoxicity assessments were also conducted. Enzyme-linked immunosorbent assays were used to measure substance P concentrations in collected tears, while total protein content (TPC) was measured with the bicinchoninic acid method (BCA). General linear models were used for statistical analysis. Substance P concentration was reduced in paclitaxel-treated patients [Median (Interquartile range, IQR): 1.11 (0.20–2.24) ng/ml)] compared to the oxaliplatin group [4.28 (1.01–10.73) ng/ml, p = 0.02]. Substance P expressed as a proportion of TPC was also lower in the paclitaxel group [0.00006 (0.00001–0.00010) %] compared to the oxaliplatin group [0.00018 (0.00008–0.00040) %, p = 0.005]. Substance P concentration and its percentage in TPC were also reduced in the paclitaxel group when compared to healthy controls [4.61 (1.35–18.51) ng/ml, p = 0.02; 0.00020 (0.00006–0.00060) %, p = 0.04, respectively]. Higher cumulative dose of paclitaxel was correlated with a reduction in substance P concentrations (r = −0.40, p = 0.037), however no associations were found with corneal nerve parameters or neuropathy severity (p > 0.05). While these findings show evidence for the dysregulation of tear film substance P following paclitaxel treatment, longitudinal studies should be conducted to investigate how substance P levels in tears change during treatment.

Reproducibility and Reliability of Subbasal Corneal Nerve Parameters of the Inferior Whorl in the Neurotoxic and Healthy Cornea.

The aim of this study was to investigate the reliability of subbasal corneal nerve plexus parameters of the inferior whorl compared with the central cornea with in vivo corneal confocal microscopy and to investigate the impact of inferior whorl pattern complexity on reproducibility. Subbasal corneal nerves of healthy controls (n = 10) and patients with chemotherapy-induced peripheral neuropathy (n = 10) were imaged with a laser scanning confocal microscope. Two masked, experienced observers and the original image taker were tasked with selecting representative images of the central cornea and inferior whorl for each participant. This was conducted on 2 occasions 1 week apart. Corneal nerve fiber length (CNFL) and fractal dimension (CNFrD) [central cornea: CNFL and CNFrD; inferior whorl region: inferior whorl length (IWL) and inferior whorl fractal dimension (IWFrD)] were analyzed. Intraclass correlation coefficient (ICC) was analyzed for interobserver and intraobserver reliability. Inferior whorl complexity was classified according to the ease of identification of the center point of convergence. Interobserver ICC was 0.992 for CNFL, 0.994 for CNFrD, 0.980 for IWL, and 0.954 for IWFrD. When analyzed by inferior whorl complexity, the interobserver reliability was similar for simple (0.987 for IWL; 0.960 for IWFrD) and complex patterns (0.967 for IWL; 0.949 for IWFrD). However, intraobserver ICC were reduced for complex (IWL 0.841-0.970; IWFrD 0.830-0.955) compared with simple patterns (IWL 0.931-0.970; IWFrD 0.921-0.969). Although the overall interobserver reliability was excellent for the central corneal and inferior whorl parameters, there was lower intraobserver reliability for the inferior whorl parameters for complex morphological patterns. To improve reliability, more sophisticated wide-field imaging of the inferior whorl may be needed.

The Utility of Oral Vitamin B1 and Mecobalamin to Improve Corneal Nerves in Dry Eye Disease: An In Vivo Confocal Microscopy Study.

Our purpose is to demonstrate the changes in cornea nerve parameters and symptoms and signs in dry eye disease (DED) patients after oral vitamin B1 and mecobalamin treatment. In this randomized double-blind controlled trial, DED patients were randomly assigned to either the treatment group (oral vitamin B1 and mecobalamin, artificial tears) or the control group (artificial tears). Corneal nerve parameters via in vivo confocal microscopy (IVCM), DED symptoms, and signs were assessed at baseline and 1 and 3 months post-treatment. In total, 398 eyes from 199 patients were included. In the treatment group, there were significant improvements in corneal nerve length, width, and neuromas, the sign of conjunctival congestion score (CCS), symptoms of dryness, pain, photophobia, blurred vision, total symptom score, and OSDI (OSDI) at 1/3 months post-treatment (all p < 0.05). Patients who received vitamin B1 and mecobalamin showed greater improvement in CCS, dryness scores at 1 month (p < 0.05), corneal fluorescein staining (CFS) (p = 0.012), photophobia (p = 0.032), total symptom scores (p = 0.041), and OSDI (p = 0.029) at 3 months. Greater continuous improvement in CFS (p = 0.045), dryness (p = 0.033), blurred vision (p = 0.031) and total symptom scores (p = 0.023) was demonstrated at 3 months than at 1 month post-treatment in the treatment group. We found that oral vitamin B1 and mecobalamin can improve corneal nerve length, width, reflectivity and the number of neuromas in IVCM, thereby repairing epithelial cells and alleviating some ocular symptoms. Thus, vitamin B1 and mecobalamin are potential treatment options for patients with DED.