Subbasal Nerve Tortuosity Research Articles

Evaluation of Corneal Alterations After Short-Term Silicone Hydrogel Contact Lens Use by Confocal Microscopy.

To evaluate the corneal subbasal nerve morphology, corneal sensitivity, and anterior segment alterations in short-term silicone hydrogel contact lens (SiHCL) users by confocal microscopy. The study included 25 right eyes of 25 male volunteers aged 25-30 years who had never used SiHCLs before. ocular surface disease index (OSDI), tear break-up time, Schirmer test, tear meniscus area, strip meniscometry tube, corneal sensitivity, and corneal subbasal nerve morphology were evaluated before and after 1 month of CL use. OSDI was 10.6±1.1 before CL use and 17.2±1.2 after 1 month of CL use (p<0.01). Schirmer test distance was 16.3±2.3 mm before and 14.3±1.9 mm after 1 month of CL use (p>0.05). Tear film break-up time was 7.1±0.4 s before and 6.2±0.3 s after CL use (p>0.05). The tear meniscus area was 0.026±0.002 mm2 before and 0.024±0.001 mm2 after 1 month of CL use (p>0.05). Strip meniscometry tube results were 5.4±0.9 mm before and 4.9±0.8 mm after 1 month of CL use (p>0.05). Corneal sensitivity values were 3.2±0.4 mm before and 2.95±0.3 mm after 1 month of CL use (p>0.05). Dendritic cell density evaluated by confocal microscopy was 14.84±3.1 cells/mm2 before and 32.57±4.2 cells/mm2 after 1 month of CL use (p<0.01). Subbasal nerve tortuosity was 0.92±0.2 before and 1.03±0.2 after 1 month of CL use (p>0.05). Subbasal nerve density was measured as 4726±310 pixels/frame before and 4570±272 pixels/frame after 1 month of CL use (p>0.05). After a month of SiHCL use, no significant changes were observed in tear secretion, corneal sensitivity, tear meniscus volume, subbasal corneal nerve density, reflectivity, or tortuosity, while a significant increase was found in OSDI and dendritic cell density.

Discrepancy between NTG and POAG with corneal nerves in CCM.

To investigate the morphological features of corneal subbasal nerve plexus (CSNP) in normal-tension glaucoma (NTG) and primary open-angle glaucoma (POAG). Thirty-four eyes with NTG (16 untreated), 23 eyes with POAG (11 untreated) and 31 eyes of healthy subjects were recruited. CSNP were assessed by corneal confocal microscopy (CCM) and peripapillary retinal nerve fibre layer (RNFL) was measured with optical coherence tomography (OCT). CCM parameters including corneal subbasal nerve fibre length (FL), corneal subbasal nerve branch number (BN), corneal subbasal nerve width (NW), corneal subbasal nerve reflectivity (NR), total and local corneal subbasal nerve tortuosity (NT) was compared across all groups, as well as between the topical medication treated and the nontreated patients. The newly diagnosed NTG patients had the longest FL (3619.15 ± 501.55), most BN (21.02 ± 5.90), thinnest corneal subbasal nerve width (3.04 ± 0.82), corneal subbasal nerve lowest reflectivity (140.43 ± 10.24) and the corneal subbasal nerves were most bending (1.09 ± 0.06) and tortuous (123.36 ± 7.82) compared with untreated POAG patients and controls. Untreated POAG had similar CSNP to controls. The treated glaucoma patients had longer FL and more BN than the nontreated but with no significant difference. FL and BN had correlations with RNFL thickness in untreated NTG patients, and NR and NW had correlations with RNFL thickness in untreated POAG patients. NT had no correlations with RNFL thickness. The NTG group had different CSNP characteristics from the POAG group and controls, while the latter two shared more morphological features. The CCM parameters except NT had associations with the RNFL thickness in glaucoma patients.

The effects of systemic aromatase inhibitors on meibomian glands and corneal structure.

To evaluate the ocular surface, meibomian glands and corneal structural changes using in vivo confocal microscopy (IVCM) in patients receiving aromatase inhibitor (AI) therapy due to the breast cancer. This prospective observational study included 13 patients undergoing AI therapy. The patients were evaluated before the treatment, at 3- and 6-month timepoints of AI therapy. To examine the ocular surface and tear film, corneal sensitivity (CS) measurement with Cochet-Bonnet Aesthesiometer, tear film break-up time (TBUT), lissamine green (LG) staining, Schirmer I test with anaesthesia (ST) and the ocular-surface disease index (OSDI) questionnaire were performed consecutively. Corneal cell densities and sub-basal nerve plexus were evaluated with IVCM (ConfoScan 4, Nidek, Japan). Finally, quantitative MG drop-out assessment was made using infrared meibography. Shapiro Wilk, Friedman's and Post-hoc Dunn tests were used for the statistical analysis. TBUT, ST scores, basal epithelium, anterior and posterior keratocytes and endothelial cell densities, long and total sub-basal nerve densities were found to be decreased (p < 0.001, p = 0.023, p < 0.001, p = 0.01, p = 0.002, p = 0.004, p < 0.001, p < 0.001), and meiboscore, CS, OSDI scores and sub-basal nerve tortuosity values were increased (p < 0.001, p = 0.015, p = 0.001, p = 0.004) during the treatment. Endothelial pleomorphism rates were lower at the 3- and 6-month timepoints compared to before the treatment (p = 0.04). This study showed that aromatase inhibitor therapy causes deteriorations in many of the ocular-surface parameters and corneal structural changes in relation with the duration of treatment. These patients should be observed during the therapy in terms of the ocular-surface side effects.

Quantification of Increased Corneal Subbasal Nerve Tortuosity in Dry Eye Disease and Its Correlation With Clinical Parameters.

PurposeThis study quantified corneal subbasal nerve tortuosity in dry eye disease (DED) and investigated its correlation with clinical parameters by proposing an aggregated measure of tortuosity (Tagg).MethodsThe sample consisted of 26 eyes of patients with DED and 23 eyes of healthy volunteers, which represented separately the dry eye group and the control group. Clinical evaluation of DED and in vivo confocal microscopy analysis of the central cornea were performed. Tagg incorporated six metrics of tortuosity. Corneal subbasal nerve images of subjects and a validation data set were analyzed using Tagg. Spearman's rank correlation was performed on Tagg and clinical parameters.ResultsTagg was validated using 1501 corneal nerve images. Tagg was higher in patients with DED than in healthy volunteers (P < 0.001). Tagg was positively correlated with the ocular surface disease index (r = 0.418, P = 0.003) and negatively correlated with tear breakup time (r = −0.398, P = 0.007). There was no correlation between Tagg and visual analog scale scores, corneal fluorescein staining scores, or the Schirmer I test.ConclusionsTagg was validated for quantification of corneal subbasal nerve tortuosity and was higher in patients with DED than in healthy volunteers. A higher Tagg may be linked to ocular discomfort, visual function disturbance, and tear film instability.Translational RelevanceCorneal subbasal nerve tortuosity is a potential biomarker for corneal neurobiology in DED.

Objective analysis of corneal subbasal nerve tortuosity and its changes in patients with dry eye and diabetes

Objective To construct an objective analysis system of corneal nerve tortuosity and detect the changes of corneal subbasal nerve tortuosity in patients with dry eye and diabetes. Methods Grade Ⅰ to Ⅳ nerve tortuosity were evaluated and 80 photos of each grade were randomly chosen from the in vivo confocal microscopy library.Nerve fibers were extracted, segmented and then analyzed by 6 tortuosity related parameters including L_C, Seg_L_C_mean, Cur_mean, Specific_p, ICM and SCC_mean.After verifying the validaty of parameters above, a cross-sectional study was conducted.Subjects were collected from June, 2018 to February, 2019 in Peking University Third Hospital, and were divided into healthy control group (28 persons 56 eyes), dry eye without diabetes group (28 patients 56 eyes), diabetes without dry eye group(24 patients 48 eyes), diabetes with dry eye group (23 patients 46 eyes). Basic and dry eye information includes sex, age, ocular surface disease index (OSDI), tear film break-up time (TBUT), Schirmer Ⅰ test (SⅠt) and corneal fluorescence staining (CFS) score.Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) were detected in diabetic patients.Cochet-Bonnet examination (C-BE) was detected to evaluate corneal sensation and 2 corneal subbasal nerve photos of each eye were selected for effective tortuosity and density related parameters analysis.Data was analyzed by SPSS and diagnostic test were perfomed by MedCalc.This study followed the Declaration of Helsinki.This study protocol was approved by Ethic Committee of Peking University Third Hospital(No.IR6761-M2017354). Written informed consent was obtained from each subject prior to entering study cohort. Results L_C, Seg_L_C_mean, Cur_mean, Specific_p, ICM and SCC_mean increased as the nerve tortuosity increased from Grade Ⅰ to Grade Ⅳ, with an overall significance among 4 groups (F=39.100, 36.367, 57.743, 4.043, 6.818, 33.493; all at P<0.01). Among the above 6 parameters, Cur_mean and L_C of any two groups were of significant difference (all at P<0.01). Twenty three to twenty eight persons were enrolled in each group of the cross-sectional study.Sex and age were comparable among 4 groups.Diagnostic criteria were met in dry eye and diabetes.Corneal sensation parameter C-BE decreased in diabetes without dry eye group and diabetes with dry eye group compared with healthy control group(all at AdjP<0.05), other than in dry eye without diabetes group (AdjP≥0.05). Nerve density of diabetes without dry eye group and diabetes with dry eye group was lower compared with healthy control group(all at P<0.001), while no significant difference between dry eye without diabetes group and healthy control group(P≥0.05). Among the effective parameters of tortuosity, L_C, Cur_mean, Seg_L_C_mean and SCC_mean of dry eye without diabetes group, diabetes without dry eye group, diabetes with dry eye group were higher compared with healthy control group(all at P<0.05). Diagnostic tests of tortuosity related parameters all showed an area under curve (AUC) from 0.5 to 0.7. Conclusions L_C and Cur_mean can be used to analyze corneal nerve curvature more reliably.Compared with normal volunteers, patients of dry eye or diabetes show higher corneal subbasal nerve tortuosity. Key words: Corneal subbasal nerve; Tortuosity; Dry eye; Diabetes

Corneal confocal microscopy and dry eye findings in contact lens discomfort patients

To evaluate the corneal confocal microscopy and dry eye findings in patients with contact lens discomfort. The study included 3 groups of participants: Contact lens wearers using silicone hydrogel soft contact lenses who are symptomatic (CLD, n=15) or asymptomatic (ACL, n=11) and non-wearers as controls (n=14). Duration of contact lens wear, Ocular Surface Disease Index (OSDI) questionnaire responses, fluorescein tear break-uptime (FBUT), and corneal confocal microscopy findings were recorded. Mean age was 25.7±8.2 years and male/female ratio was 7/33. Demographic findings were similar regarding the groups. CLD patients had a longer lens use history than ACL (median 5 vs 2 years, p<0.001). OSDI scores were higher in CLD group than ACL or controls (p<0.001, p=0.002). FBUT was significantly lowest in CLD group, compared to controls and ACL (p<0.001, p=0.039). FBUT was also lower in ACL patients compared to controls (p=0.036). There was no difference between basal epithelium cell counts between all 3 groups. Anterior stromal activated keratocyte numbers were similar between contact lens using groups but was lower in controls (p=0.005). However, dendritiform cells in the sub-basal nerve layer were higher in CLD group compared to controls but similar to ACL (p<0.001, p=0.058). Graded sub-basal nerve tortuosity was more prominent in CLD group than the ACL (p=0.014). Patients with CLD had been wearing contact lenses for longer than those without symptoms. OSDI and FBUT scores were worse in CLD patients. In contact lens discomfort patients, there were increased dendritiform cells, indicating intensified inflammatory status of the cornea.

Long term safety and tolerability of Tafluprost 0.0015% vs Timolol 0.1% preservative-free in ocular hypertensive and in primary open-angle glaucoma patients: a cross sectional study

BackgroundThe effects of preservatives of antiglaucoma medications on corneal surface and tear function have been widely shown in literature; it’s not the same as regards the active compounds themselves. The purpose of our study was to compare Ocular Surface Disease (OSD) signs and symptoms of Tafluprost 0.0015% versus preservative free (PF) Timolol 0.1% eyedrops in ocular hypertensive (OH) and in primary open-angle glaucoma (POAG) patients.MethodsA cross-sectional study included patients in monotherapy for at least 36 months with Tafluprost 0.0015% (27) or PF Timolol 0.1% (24) and 20 healthy age and sex-matched volunteers. All subjects underwent clinical tests (Schirmer I and break-up time), in vivo confocal microscopy (IVCM) and were surveyed using Ocular Surface Disease Index (OSDI) and Glaucoma Symptoms Scale (GSS) questionnaires. The groups were compared with ANOVA, Kruskal-Wallis test, t-test, Mann-Whitney test and Bonferroni’s adjustment of p-values.ResultsNo significant differences were found in questionnaires scores, clinical tests, IVCM variables between therapy groups. Tafluprost 0.0015% group showed significantly higher OSDI score, basal epithelial cells density, stromal reflectivity, sub-basal nerves tortuosity (p = 0.0000, 0.037, 0.006, 0.0000) and less GSS score, number of sub-basal nerves (p = 0.0000, 0.037) than controls but similar clinical tests results (p > 0.05). PF Timolol group had significantly higher OSDI score, basal epithelial cells density, stromal reflectivity and sub-basal nerve tortuosity (p = 0.000, 0.014, 0.008, 0.002), less GSS score, BUT and number of sub-basal nerves (p = 0.0000, 0.026, 0.003) than controls.ConclusionsCompared to PF Timolol 0.1%, Tafluprost 0.0015% showed similar safety with regards to tear function and corneal status and a similar tolerability profile. Both therapy groups show some alterations in corneal microstructure but no side effects on tear function except for an increased tear instability in PF Timolol 0.1% group. Ophtalmologists should be aware that even PF formulations may lead to a mild ocular surface impairment.

Two-Dimensional Plane for Multi-Scale Quantification of Corneal Subbasal Nerve Tortuosity.

PurposeTo assess the performance of a novel system for automated tortuosity estimation and interpretation.MethodsA supervised strategy (driven by observers' grading) was employed to automatically identify the combination of tortuosity measures (i.e., tortuosity representation) leading to the best agreement with the observers. We investigated 18 tortuosity measures including curvature and density of inflection points, computed at multiple spatial scales. To leverage tortuosity interpretation, we propose the tortuosity plane (TP) onto which each image is mapped. Experiments were carried out on 140 images of subbasal nerve plexus of the central cornea, covering four levels of tortuosity. Three experienced observers graded each image independently.ResultsThe best tortuosity representation was the combination of mean curvature at spatial scales 2 and 5. These tortuosity measures were the axes of the proposed TP (interpretation). The system for tortuosity estimation revealed strong agreement with the observers on a global and per-level basis. The agreement with each observer (Spearman's correlation) was statistically significant (αs = 0.05, P < 0.0001) and higher than that of at least one of the other observers in two out of three cases (ρOUR = 0.7594 versus ρObs3 = 0.7225; ρOUR = 0.8880 versus ρObs1 = 0.8017, ρObs3 = 0.7315). Based on paired-sample t-tests, these improvements were significant (P < 0.001).ConclusionsOur automated system stratifies images by four tortuosity levels (discrete scale) matching or exceeding the accuracy of experienced observers. Of importance, the TP allows the assessment of tortuosity on a two-dimensional continuous scale, thus leading to a finer discrimination among images.

Focused Tortuosity Definitions Based on Expert Clinical Assessment of Corneal Subbasal Nerves.

We examined agreement among experts in the assessment of corneal subbasal nerve tortuosity. Images of corneal subbasal nerves were obtained from investigators at seven sites (Auckland, Boston, Linköping, Manchester, Oslo, Rostock, and Sydney) using laser-scanning in vivo confocal microscopy. A set of 30 images was assembled and ordered by increasing tortuosity by 10 expert graders from the seven sites. In a first experiment, graders assessed tortuosity without a specific definition and performed grading three times, with at least 1 week between sessions. In a second experiment, graders assessed the same image set using four focused tortuosity definitions. Intersession and intergrader repeatability for the experiments were determined using the Spearman rank correlation. Expert graders without a specific tortuosity definition had high intersession (Spearman correlation coefficient 0.80), but poor intergrader (0.62) repeatability. Specific definitions improved intergrader repeatability to 0.79. In particular, tortuosity defined by frequent small-amplitude directional changes (short range tortuosity) or by infrequent large-amplitude directional changes (long range tortuosity), indicated largely independent measures and resulted in improved repeatability across the graders. A further refinement, grading only the most tortuous nerve in a given image, improved the average correlation of a given grader's ordering of images with the group average to 0.86 to 0.90. Definitions of tortuosity specifying short or long-range tortuosity and considering only the most tortuous nerve in an image improved the agreement in tortuosity grading among a group of expert observers. These definitions could improve accuracy and consistency in quantifying subbasal nerve tortuosity in clinical studies.

Ocular Surface Alterations and In Vivo Confocal Microscopic Features of Corneas in Patients With Newly Diagnosed Graves' Disease.

To evaluate the ocular surface characteristics and corneal microstructure in patients with newly diagnosed Graves disease (GD) with no evidence of active thyroid eye disease (TED). Eighty eyes of 40 patients with newly diagnosed GD and 40 age-matched control subjects were recruited in this cross-sectional study. All participants underwent ocular surface tests in the order of tear break-up time (BUT), lissamine green (LG) staining, Schirmer I test with anesthesia, and ocular surface disease index (OSDI) questionnaire. Basal epithelial cell, keratocyte, and endothelial cell densities and subbasal nerves were evaluated using in vivo confocal microscopy (IVCM). Independent sample t test, χ test, and Mann-Whitney U test were used for statistical analysis. Patients with GD had higher OSDI (5.9 ± 6.6 vs. 1.7 ± 2.4, respectively, P ≤ 0.001) and LG staining scores (0.5 ± 0.6 vs. 0.2 ± 0.4, respectively, P = 0.003), and lower BUT scores (7.3 ± 2.5 vs. 9.9 ± 1.7, respectively, P < 0.001) compared with those of control subjects. Patients with GD had lower mean basal epithelial cell density (3928 ± 657 cells/mm² vs. 4771 ± 622 cells/mm², respectively) and total subbasal nerve density (958 ± 394 cells/mm² vs. 1416 ± 744 cells/mm², respectively) and higher subbasal nerve tortuosity (2.7 ± 0.8 vs. 1.6 ± 0.6, respectively) compared with those of control subjects (P < 0.001). There was a statistically significant negative correlation between the duration of symptoms of hyperthyroidism and BUT (rho = -0.273, P = 0.014) and a positive correlation between LG staining scores (rho = 0.329, P = 0.003). A significant reduction in BUT (rho = -0.238, P = 0.003) and epithelial cell density (rho = -0.174, P = 0.029) and an increase in OSDI scores (rho = 0.328, P = 0.003) were found with increasing exophthalmometry measurements. Ocular surface alterations begin early in the course of Graves disease before the onset of overt TED.

Corneal nerve structure and function after long-term wear of fluid-filled scleral lens.

The aim of this study was to determine whether long-term wear of a fluid-filled scleral lens alters basal tear production, corneal sensation, corneal nerve density, and corneal nerve morphology in 2 disease categories. Patients recruited from the Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) treatment program at the Weill Cornell Medical College were categorized into 2 groups: distorted corneas (DC) or ocular surface disease (OSD). We measured tear production, central corneal sensation, subbasal nerve density and tortuosity, and stromal nerve thickness before and after long-term wear of the prosthetic device used in PROSE treatment, defined as at least 60 days of wear for a minimum of 8 hours a day. Twenty patients were included in the study. After long-term wear of the prosthetic device, tear production decreased in patients with DC (21.2 ± 8.5 to 10.4 ± 4.6 mm; P < 0.0001) but did not change in patients with OSD (7.5 ± 5.2 to 8.7 ± 7.2 mm; P = 0.71). Corneal sensation increased in the DC group (45.6 ± 9.2 to 55.0 ± 5.6 mm; P < 0.05). There was no significant change in sensation in patients with OSD (45.0 ± 8.7 to 49.1 ± 14.8 mm; P = 0.37). Subbasal nerve density, subbasal nerve tortuosity, and stromal nerve thickness remained unchanged in both DC and OSD groups after long-term wear (P > 0.05). Patients with DC had significantly reduced basal tear production and increased corneal sensation after long-term wear of the scleral lens, but patients with OSD did not show any changes in tear production or corneal sensation.

The Relationship between Subbasal Nerve Morphology and Corneal Sensation in Ocular Surface Disease

The purpose of this study was to evaluate the relationship between the in vivo confocal microscopic (IVCM) morphology of subbasal corneal nerves and corneal sensitivity in patients with ocular surface disease. Ten healthy volunteers (control group), 12 patients with dry eye (dry-eye group), and 14 patients treated with IOP-lowering topical medications (glaucoma group) were included. Central corneal sensation was measured using the contact Cochet-Bonnet esthesiometer. IVCM of the cornea was performed and the following subbasal corneal nerves parameters were analyzed: density, number, width, number of beadings, number of branching, tortuosity, and reflectivity. One eye of each subject was included in the study. Corneal sensitivity was significantly decreased in dry-eye and glaucoma patients compared with controls. The density and number of subbasal corneal nerves were also significantly decreased in dry eye and glaucoma patients compared with controls. There was no difference in terms of subbasal nerve width, number of beadings, tortuosity, reflectivity, and number of branching between the dry-eye, the glaucoma, and the control groups. In all subjects, corneal sensitivity correlated positively with the density and number of subbasal nerves; however, in the dry-eye group, corneal sensitivity correlated with the density and the number of nerves, whereas in the glaucoma group, corneal sensitivity correlated only with the tortuosity of subbasal nerves. The relationship between corneal sensation and subbasal nerve morphology, as evaluated with IVCM, depends on the pathophysiological mechanism of ocular surface disease.

In vivo confocal microscopy study of climatic droplet keratopathy

Sir, Climatic droplet keratopathy (CDK) is a corneal degenerative disease characterized by its progressive opacity because of accumulation of globular deposits in Bowman's layer (BL) and anterior stroma (AS), as well as abnormal corneal sensitivity.1, 2 We report herein for the first time the study of three patients each with different grades of CDK using in vivo confocal microscopy (iVCM), a technique that has allowed the measurement of normal and pathological corneal components.3, 4, 5 Table 1, Figures 1 and ​and22 summarize the corneal abnormalities found in these patients. Cochet-Bonnet aesthesiometry (CBA) demonstrated a decrease of the mechanical sensitivity of the cornea in eyes with grade II and III CDK. Grade I CDK was characterized by incipient changes in the BL and AS but normal sub-basal and stromal nerve plexus. Grade II CDK showed hyper-reflectivity and globular non-reflective deposits in the BL and AS. In grade III, the AS showed fibrosis with increment of diffused hyper-reflective deposits and large non-reflective deposits. Concomitant to these changes, there was an increased number of dendritic cells (DC) at the peripheral cornea and limbus, but their role in the progression of CDK needs further studies. No abnormalities were found in the rest of the stroma and endothelium.​endothelium. Figure 1 In vivo confocal laser scanning microscopy images. BL: (a) Grade 1: dot-like hyper-reflective deposits in the central cornea. (b) Grade 2: increased density of the deposits. (c) Grade 3: confluent hyper-reflective deposits. Sub-basal nerves: (d) Grade ... Figure 2 In vivo confocal laser scanning microscopy images. Deposits at the peripheral cornea: (a) Grade 1: reflective punctiform or dot-like deposits. (b) Grade 2: hyper-reflective punctate and homogeneous round globular non-reflective deposits. (c) Grade 3: ... Table 1 Abnormalities found in corneas of CDK eyes according to biomicroscopic grade of the disease Although we were unable to study sub-epithelial nerves because they occupied the same area of the deposits in CDK, we found that the early changes in CDK did not affect the sub-basal and stromal nerves, but the progression of the disease lead to a significant density decrease of sub-basal nerves, and some structural changes in stromal nerves, such as uneven thickness and irregular configuration, that might be responsible for corneal hyposensitivity found in advanced stages of CDK. In a recent study, Patel et al5 showed that sub-basal nerve tortuosity but not mean total sub-basal nerve density varied with age in normal individuals. The loss of corneal sensation could not be attributed to the age of our patients as we have previously found in a case–control study that corneal sensation was related to CDK grades and not to the age of individuals.2

Changes in corneal parameters at confocal microscopy in treated glaucoma patients

Background:The purpose of this study was to evaluate corneal parameters in treated glaucoma patients, nontreated glaucoma patients, and normal subjects using confocal microscopy.Methods:Forty patients with primary open-angle glaucoma and 22 untreated controls underwent confocal microscopy of the cornea using the Heidelberg retinal tomograph cornea module. The glaucoma group was divided into two subgroups, ie, patients on medical treatment for at least two years before inclusion (with beta-blockers or prostaglandin analogs) and nontreated glaucoma patients. The following corneal parameters were evaluated: endothelial cell density and number, reflectivity, and tortuosity of sub-basal nerves. For reflectivity and tortuosity, a dedicated grading scale ranging from 0 to 4 was used. Differences between treatments were also evaluated in the treated glaucoma group.Results:Number of fibers and reflectivity of the sub-basal plexus were significantly lower in glaucoma patients as compared with controls (2.5 ± 0.7 versus 2.9 ± 0.9, P = 0.006, and 2.3 ± 0.8 versus 2.7 ± 0.9, P = 0.04, respectively), whereas tortuosity was significantly higher (2.6 ± 1 versus 2.0 ± 0.8, P = 0.007). Endothelial cell density (measured as cells per mm2) was lower in the glaucoma group comparing treated patients with nontreated patients (2826 ± 285 versus 3124 ± 272, P = 0.0003). Comparing treated patients with nontreated patients, relevant differences were found in number (2.3 ± 0.7 versus 2.8 ± 0.8, P = 0.004), tortuosity (2.8 ± 1 versus 2.2 ± 0.8, P = 0.004), and reflectivity (2.2 ± 0.8 versus 2.6 ± 0.8, P = 0.04). No differences in corneal parameters were found between beta-blockers and prostaglandin analogs.Conclusion:This study shows that differences in corneal parameters between glaucoma patients and controls may be due to the medical treatments used for glaucoma. These data should be taken into consideration in long-standing medical glaucoma treatment and in potential candidates for surgery.

Tear Dynamics and Corneal Confocal Microscopy of Subjects with Mild Self-Reported Office Dry Eye

To investigate changes in tear dynamics and corneal microstructure in mild self-reported office dry eye. Prospective laboratory investigation. Twenty healthy office workers, 20 office workers with mild self-reported dry eye, and 20 office workers with moderate to severe dry eye as determined by the Ocular Surface Disease Index (OSDI). Real-time anterior segment optical coherence tomography was used to obtain upper (UTMV), lower (LTMV), tear meniscus volumes. The total tear meniscus volume (TTMV) was the sum of the UTMV and LTMV. This was followed by measurement of noninvasive tear breakup time (NITBUT), fluorescein tear breakup time (FTBUT), fluorescein staining, Schirmer I test, and in vivo confocal microscopy of cornea. Upper tear meniscus volume, LTMV, TTMV, NITBUT, fluorescein tear FTBUT, fluorescein staining, Schirmer I test, and in vivo confocal microscopy of cornea. There were no significant differences in UTMV and LTMV between the control and mild self-reported dry eye groups (P>0.05). These values in the moderate to severe dry eye group were significantly lower than those in the control and mild dry eye groups (P<0.01). Both mild and moderate to severe office dry eye groups had decreased NITBUT (P<0.05 each) and FTBUT (P<0.01 each) compared with controls. On the basis of receiver operating characteristic curves, the cutoff value for abnormal FTBUT was 3.3 seconds, yielding good diagnostic accuracy with a sensitivity of 0.75 and specificity of 0.80. For NITBUT, when the cutoff time was 9.7 seconds, the sensitivity was 0.90 and specificity was 0.50. The moderate to severe office dry eye group had decreased Schirmer I test values and increased subbasal nerve tortuosity compared with the mild office dry eye and control groups (P<0.05 each). Both the mild dry eye and moderate to severe dry eye groups had decreased cell densities in superficial, intermediate, and basal epithelial layers compared with the controls (P<0.05 each). Although the quantity of tears in patients with mild self-reported office dry eye was not decreased, ocular surface damage was present.

Corneal Sensitivity and Slit Scanning In Vivo Confocal Microscopy of the Subbasal Nerve Plexus of the Normal Central and Peripheral Human Cornea

To determine the subbasal nerve density and tortuosity at 5 corneal locations and to investigate whether these microstructural observations correlate with corneal sensitivity. Sixty eyes of 60 normal human subjects were recruited into 1 of 3 age groups, group 1: aged <35 years, group 2: aged 35-50 years, and group 3: aged >50 years. All eyes were examined using slit-lamp biomicroscopy, noncontact corneal esthesiometry, and slit scanning in vivo confocal microscopy. The mean subbasal nerve density and the mean corneal sensitivity were greatest centrally (14,731 +/- 6056 microm/mm and 0.38 +/- 0.21 millibars, respectively) and lowest in the nasal mid periphery (7850 +/- 4947 microm/mm and 0.49 +/- 0.25 millibars, respectively). The mean subbasal nerve tortuosity coefficient was greatest in the temporal mid periphery (27.3 +/- 6.4) and lowest in the superior mid periphery (19.3 +/- 14.1). There was no significant difference in mean total subbasal nerve density between age groups. However, corneal sensation (P = 0.001) and subbasal nerve tortuosity (P = 0.004) demonstrated significant differences between age groups. Subbasal nerve density only showed significant correlations with corneal sensitivity threshold in the temporal cornea and with subbasal nerve tortuosity in the inferior and nasal cornea. However, these correlations were weak. This study quantitatively analyzes living human corneal nerve structure and an aspect of nerve function. There is no strong correlation between subbasal nerve density and corneal sensation. This study provides useful baseline data for the normal living human cornea at central and mid-peripheral locations.

Comparative in vivo high‐resolution confocal microscopy of corneal epithelium, sub‐basal nerves and stromal cells in mice with and without dry eye after photorefractive keratectomy

The present study compares, using a new-generation high-resolution in vivo confocal microscope, the epithelial morphology, sub-basal nerves and stroma in two groups of mice: one exposed to normal conditions (NC) and the other to a desiccating environment (DE), following photorefractive keratectomy (PRK) with mechanical epithelial scraping. Twenty-four 4- to 8-week-old female Balb/C mice were used in this study. Twenty mice underwent bilateral corneal epithelial scraping using an electric brush prior to PRK. Then, the mice were divided in two groups: 10 mice were placed in NC. The other 10 mice were exposed to a DE for 2 weeks. Four mice served as controls. Corneas were analysed in vivo using the Rostock Cornea Module of the Heidelberg retina tomograph II. For all eyes, 20 confocal microscopic images of each layer, that is, the superficial and basal corneal epithelium, Bowman's layer, anterior and posterior stroma and the endothelium, were recorded. Epithelial and stromal cell densities and sub-basal and stromal nerves were measured and compared. There was a higher density of superficial epithelial cells in the DE group (693 +/- 148 cells/mm(2) in NC group and 443 +/- 128 cells/mm(2) in DE group; Mann-Whitney U-test; P = 0.05). Higher number of basal cells were observed in the DE group. Its density was 986 +/- 198 cells/mm(2) in NC and 1598 +/- 280 cells/mm(2) in DE group (Mann-Whitney U-test; P < 0.05). Significantly higher number of reflective structures were noted within the stroma without clearly visible nuclei in the DE group compared with the NC eyes. Additionally, higher number of beads, nerve sprouts and higher tortuosity of sub-basal nerves were observed in the DE group. No difference was observed in the endothelial cell density between the groups. Exposure of corneas to a DE after PRK with previous mechanical epithelial scraping increases epithelial turnover and is associated with a higher number of reflective structures in the stroma. Additionally increased nerve beading, nerve sprouts and tortuosity of sub-basal nerves were observed in the DE group, possibly directed to repair the alterations observed at the epithelial level.