Corneal Sensitivity Threshold Research Articles

Remission of corneal and peripheral neuropathy after bariatric surgery in people with diabetes

PurposeDiabetic peripheral neuropathy can be detected using non-invasive in vivo confocal microscopy of the cornea (IVCM) and such abnormalities may precede the development of clinical neuropathy. The current study aimed to assess any progression or remission of corneal and peripheral neuropathy in patients with type 2 diabetes undergoing bariatric surgery. MethodsPeople with known type 2 diabetes for at least five years and listed for bariatric surgery were recruited. Participants were assessed before, and 12, 26, and 52 weeks following bariatric surgery. IVCM and corneal sensitivity measurements were performed. A modified total neuropathy score (mTNS) was obtained from neuropathy questionnaire, clinical assessment and biothesiometry. ResultsTwenty-nine participants (M:F, 11:18) with mean BMI of 44.7 ± 6.4 kg/m2, and 11 ± 7.6 years duration of diabetes, were assessed. Corneal sub-basal nerve fibre length (CNFL), displayed an increase from a baseline mean of 12.20 ± 1.00 to 17.48 ± 0.92 mm/mm2 at 52 weeks (p < 0.0001). Corneal sensitivity threshold displayed a decrease over time, thus corneal sensitivity improved, falling from a mean of 1.11 ±0 .15 to 0.62 ± 0.11 (mBAR) (p < 0.0001). Clinical neuropathy scores demonstrated significant improvements from baseline, displaying a decrease in average mTNS score from 3.29 ± 0.68 to 0.76 ± 0.30 (p < 0.0001). A significant inverse relationship was shown between CNFL and sensitivity (β coefficient = −0.047, p < 0.001), and CNFL and mTNS (β coefficient = −0.178, p < 0.001). ConclusionBariatric surgery led to an improvement in metabolic control of diabetes and weight loss, along with improvement in corneal nerve microstructure, corneal sensitivity, and neuropathic symptoms, suggesting a reversal of both small and large fibre neuropathy.

Predictive performance of corneal and lid margin sensitivity for dry eye disease: An investigator-masked, prospective, prognostic accuracy study

PurposeTo evaluate the prognostic ability of non-contact esthesiometry corneal and lid margin sensitivity measurements in detecting symptoms and signs of dry eye disease, as defined by the global consensus TFOS DEWS II criteria. MethodsA total of 87 community residents (58 females; mean ± SD age, 53 ± 16 years) were recruited in an investigator-masked, prospective, prognostic accuracy study. Dry eye symptomology, tear film parameters, and ocular surface characteristics were evaluated in a single clinical session, and non-contact esthesiometry corneal and lid margin sensitivity measurements performed by an independent masked assessor. ResultsOverall, 49 (56%) participants fulfilled the TFOS DEWS II criteria for dry eye disease, while 57 (66%) exhibited clinical symptoms, and 67 (77%) had positive signs. The prognostic abilities of corneal and lid margin sensitivity measurements were significantly greater than chance for the detection dry eye signs (both p ≤ 0.03), but not for symptoms or overall disease diagnosis (all p > 0.10). The Youden-optimal prognostic cut-offs for corneal and lid margin sensitivity thresholds were both ≥0.8 mbar for the detection of clinical dry eye signs. Lid margin sensitivity demonstrated marginally higher predictive performance than corneal sensitivity (C-statistic, 0.688 versus 0.658), and was significantly correlated with tear film stability, corneal, conjunctival and lid wiper staining (all p < 0.05). ConclusionsCorneal and lid margin sensitivity demonstrated moderate prognostic utility for detecting clinical dry eye signs. Future research is warranted to investigate the utility of incorporating non-contact esthesiometry in the workup for dry eye disease and neurotrophic keratopathy.

Clinical application of the Swiss Liquid Jet Aesthesiometer for corneal sensitivity measurement

ABSTRACT Clinical relevance Corneal sensitivity represents an important indicator for corneal health, its innervation and hence also for ocular disease. It is therefore of great interest from a clinical and research perspective to quantify ocular surface sensation. Background The aim of this prospective cross-sectional cohort study was to clinically test the within-day and day-to-day repeatability of the new Swiss Liquid Jet Aesthesiometer, employing small droplets of isotonic saline solution for repeatability, and correlate with the Cochet–Bonnet aesthesiometer in a cohort of participants of two different age groups, based on participant feedback (psychophysical method). Methods Participants were recruited from two equally, large age groups: group A (18–30 years) and group B (50–70 years). The inclusion criteria were healthy eyes, Ocular Surface Disease Index (OSDI) ≤ 13, and no contact lens wear. Mechanical corneal sensitivity threshold measurements with means of liquid jet and Cochet–Bonnet methods were carried out twice during two visits (a total of four measurements), with a stimulus temperature equal to or slightly above the ocular surface temperature. Results Ninety participants completed the study (n = 45 per age group, average age in group A: 24.2 ± 2.94 years, group B: 58.5 ± 5.71 years). The coefficient of repeatability for the liquid jet method was 2.56 dB within visits and 3.61 between visits. For the Cochet–Bonnet method, it was 2.27 dB within visits and 4.42 dB between visits (Bland Altman with bootstrap analysis). Moderate correlation was observed between the liquid jet and the Cochet–Bonnet method (r = 0.540, p < .001, robust linear regression). Conclusions Swiss liquid jet aesthesiometry offers a new examiner independent method for corneal sensitivity measurement with acceptable repeatability and moderate correlation with the Cochet–Bonnet aesthesiometer. It offers a large stimulus pressure range of 100–1500 mbar and a precision of 1 mbar. Stimulus intensity can be tuned more precisely and much smaller sensitivity fluctuations may be potentially detected.

Age-Related Changes in Corneal Sensitivity.

The aim of this prospective cross-sectional cohort study was to clinically test whether corneal sensation decreases with age, based on subject feedback (psychophysical method), and whether it correlates with general pain perception. Subjects were recruited from 2 equally large age groups: group A (18-30 years) and group B (50-70 years; n = 45 per group). The inclusion criteria were healthy eyes, Ocular Surface Disease Index ≤13, and no contact lens wear. Corneal sensitivity threshold (CST) measurements were performed twice during each of the 2 visits, with the aid of the new Swiss liquid jet esthesiometer for corneal sensitivity (SLACS) and Cochet-Bonnet (CB) esthesiometer. A general pain sensitivity score was obtained from all participants. Ninety subjects completed the study (n = 45 per age group, average age in group A: 24.2 ± 2.94 years, group B: 58.5 ± 5.71 years). Statistically higher CSTs for age group B were only observed for SLACS (mean difference: 1.58 dB, P < 0.001). No correlation was observed between the pain score and the CSTs obtained with either esthesiometry method (r = 0.11, P = 0.25 for liquid jet and r=-0.076, P = 0.61 CB). A statistically significant decrease in corneal sensitivity was observed for the older age group with SLACS in this study, with CB however only a trend in the same direction was noted. General pain perception was not found to correlate with ocular surface sensation.

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.

Klinischer Vergleich eines neu entwickelten Prototyps zur Messung der Hornhautsensibilität zum aktuellen Goldstandard

Purpose. The aim of the study was to test a newly developed prototype for corneal sensitivity measurement (liquid jet (LJ) with saline as stimulus) for repeatability and correlation with the Cochet-Bonnet esthesiometer (CB). This is an excerpt of a master thesis, which was part of a larger study Material and Methods. Corneal sensitivity thresholds (CST) were determined for 30 subjects, in a clinical trial with 30 subjects, with each device on two separate dates (with inter- vals of at least one day and a maximum of fourteen days). In addition, the pain sensitivity questionnaire (PSQ) was applied to determine any possible correlation with corneal sensitivity. Results. Similar standard deviations of the CSTs for LJ and CB were obtained (LJ (M ± SD): 24.3 ± 2.0 dB; CB (M ± SD): 20.0 ± 2.0 dB). No statistically significant difference in CST was found between the two visits for LJ (mean differen- ce: -0.063 dB, p = 0.78), however there was a statistically significant difference for CB (mean difference: -0.641 dB, p = 0.003). LJ CSTs correlated moderately positively with CB CSTs and PSQ (LJ-CB: r = 0.476, p &lt; 0.001; LJ-PSQ: r = 0.437, p &lt; 0.001). Conclusion. LJ offers a significantly larger stimulus bandwidth than CB. Better reproducibility was observed for LJ, while correlation between the results for the two instruments was good. Significant moderate positive correlation was found between LJ CSTs and general pain sensitivity. Keywords esthesiometry, Cochet-Bonnet, Liquid Jet, prototype, PSQ

CLINICAL PECULIARITIES OF BACTERIAL KERATITIS IN TYPE 1 DIABETIC PATIENTS

The purpose was to define the clinical peculiarities of bacterial keratitis in patients with type 1 diabetes mellitus (DM1) at visit 1. &#x0D; Methods. We retrospectively reviewed the results of 62 DM1 patients (62 eyes) with bacterial keratitis and 43 nondiabetic patients (43 eyes) with bacterial keratitis of the control group who were referred for visit 1 (before administering the treatment). Research methods were as follows: visual acuity, tonometry, slit-lamp biomicroscopy of anterior and posterior eye segments, bacteriological studies, fluorescein dye test, anterior eye OCT and non-contact corneal esthesiometry. &#x0D; Results. Compared to nondiabetic, DM1 patients with bacterial keratitis showed higher degree of inflammatory reaction in the anterior chamber of the eye at visit 1 (p&lt;0.05) as well as 28.8% lower mean corneal sensitivity threshold (p&lt;0.05). At visit 1, the degree of decreasing of corneal sensitivity in DM1 patients with bacterial keratitis was higher than in control group (p&lt;0.05). Localization of bacterial keratitis, the degree of pericorneal injection, corneal ulcer defect size and depth, corneal infiltration as well as edema of the corneal tissue surrounding the ulcer did not depend on the presence of diabetes mellitus (р&gt;0,05) at visit 1.&#x0D; Conclusions. There are clinical peculiarities of bacterial keratitis in patients with type 1 diabetes mellitus at visit 1.

FEATURES OF THE DYNAMICS OF THE I DEGREE OF SEVERETY BACTERIAL KERATITES IN DIABETIC PATIENTS

Summary. Diabetes mellitus (DM) is a risk factor for severe bacterial keratitis, which often leads to complications.&#x0D; The aim was to identify the features of the dynamics of the I degree of severity bacterial keratitis in diabetic patients.&#x0D; Materials and methods. The results of treatment of 15 patients with type 1 DM and bacterial keratitis of the I degree of severity (main group) and 20 patients with bacterial keratitis of the I degree of severity without DM (control group) were analyzed. The severity of bacterial keratitis was determined according to our proposed scheme with a total score of ≤ 14. All patients were treated with instillations of ofloxacin, antiseptics, antioxidants, reparents, artificial tears, mydriatics, systemic anti-inflammatory therapy. In addition to standard, ophthalmic examination methods included bacteriological examination, fluorescein test, OCT of the anterior segment of the eye, non-contact corneal esthesiometry.&#x0D; Results and discussion. In diabetic patients with bacterial keratitis of the I degree of severity the degree of inflammatory reaction in the anterior chamber of the eye and the average threshold of corneal sensitivity at all airflow temperatures at the first visit exceeded the indicators of controls (p&lt;0.05). The degree of the average corneal sensitivity threshold decrease throughout the observation, the degree of pericorneal injection, the size of the corneal ulcer, the depth of corneal infiltration from the 3rd day of observation, the depth of corneal ulcer and corneal edema from the 7th day exceeded indicators of controls (p&lt;0.05).&#x0D; Conclusions. Diabetic patients have features of the dynamics of the I degree of severity bacterial keratitis, which lead to prolongation of the disease and worsening of its consequences.

Bacterial Keratitis in Type 1 Diabetic Patients: Course and Consequences

<i>The purpose</i> was to define the peculiarities of the course and consequences of bacterial keratitis in patients with type 1 diabetes mellitus (DM1) depending on the stage of its severity. <i>Methods.</i> 34 DM1 patients (34 eyes) with bacterial keratitis whose initial bacteriological examination revealed pathogen sensitivity to the antibiotic ofloxacin participated in this study. All patients were treated topically with ofloxacin, antiseptics, repairing agents, antioxidants, mydriatics, artificial tears and systemically with anti-inflammatory agents. Patients were divided into two groups according to the severity of bacterial keratitis at the first visit. Research methods were as follows: visual acuity, tonometry, slit-lamp biomicroscopy of anterior and posterior eye segments, fluorescein dye test, non-contact corneal esthesiometry, anterior eye OCT and bacteriological studies. <i>Results.</i> Compared to the stage I, DM1 patients with stage II severity bacterial keratitis showed higher degree of pericorneal injection, larger and deeper corneal ulcer defect, deeper corneal infiltration and edema, higher mean corneal sensitivity threshold at all time point of the study, p<0.05. DM1 patients with stage II severity bacterial keratitis were more prone for longer duration of the disease and worse consequences. Therefore, on day 24 in 33.3% diabetic patients with stage II severity bacterial keratitis corneal ulcer was not found to be healed.<i> Conclusions.</i> Course and consequences of bacterial keratitis in type 1 diabetes mellitus patients depend on the stage of severity of bacterial keratitis.

Чутливість рогівки у хворих на бактеріальний кератит залежно від наявності цукрового діабету

The aim. To identify the features of corneal sensitivity of the sick and the fellow eye in bacterial keratitis patients with or without diabetes mellitus. Materials and methods. The analysis was performed on the basis of survey data of 62 type 1 diabetes patients with bacterial keratitis and 43 nondiabetic control patients with bacterial keratitis. The examination was performed at the first visit. In addition to standard ophthalmic examination, the patients underwent fluorescein test, OCT of the anterior segment of the eye, non-contact corneal aesthesiometry. Results and discussion. The average corneal sensitivity threshold in diabetic patients with bacterial keratitis at the first visit at all air flow temperatures exceeded the corresponding indicators in nondiabetic patients of the control group: by 33.5% at an air temperature of 5 °C, by 30.6% at 15 °C, by 28.8% at 20 °C, by 27% at 30 °C, and by 26.1% at 40 °C (p&lt;0.05). The average corneal sensitivity threshold at a temperature of 20 °C in the fellow eye in diabetic patients with bacterial keratitis exceeded that in nondiabetic patients with bacterial keratitis of the control group by 32.9 % (p&lt;0.05). Conclusions. Corneal sensitivity of the sick and fellow eye in patients with bacterial keratitis depends on the presence of diabetes mellitus. The average threshold of corneal sensitivity of the sick and fellow eye in diabetic patients with bacterial keratitis at the first visit exceeds the corresponding values in nondiabetic patients with bacterial keratitis. Keywords: diabetes mellitus, bacterial keratitis, corneal sensitivity.

Precision, agreement and utility of a contemporary non‐contact corneal aesthesiometer

BackgroundThe measurement of corneal sensitivity threshold is important for several ocular surface diseases. The current study assesses the precision, agreement and utility of corneal sensitivity threshold measurement using a new, purpose‐built non‐contact corneal aesthesiometer.MethodsA new instrument and an established non‐contact corneal aesthesiometer device was used to measure the corneal sensitivity threshold on the right eye of 40 healthy human participants. Exclusion criteria included: corneal pathology, previous ocular surgery, ocular trauma, contact lens wear, diabetes or peripheral neuropathy. A forced‐response, double‐staircase method was used to obtain corneal sensitivity threshold from the mean of three readings per participant, for each non‐contact corneal aesthesiometer. Screen demarcations relative to the corneal limbus facilitated alignment with the new device. Repeatability of the new instrument was tested three consecutive times on the same day. Intra‐observer and inter‐observer reproducibility and agreement were determined using one‐way analysis of variance or analysis of variance and Bland–Altman analysis, respectively.ResultsForty eyes of 40 participants were assessed (15:25 M:F, 30.5 ± 11.4-years). The new instrument demonstrated good repeatability (p = 0.47). There was no difference in the mean corneal sensitivity threshold between the new (0.60 ± 0.36-mbar) and established (0.60 ± 0.34-mbar) aesthesiometers (p = 0.92). Utilising the new instrument, inter‐observer reproducibility (on a different subset of 10 participants) yielded thresholds of 0.41 ± 0.16-mbar and 0.42 ± 0.13-mbar (p = 0.88) for the two observers. Bland–Altman analysis confirmed good intra and inter‐observer agreement. Screen demarcations relative to the limbus, enabled easier corneal alignment.ConclusionThe new non‐contact corneal aesthesiometer confirmed very good repeatability and reproducibility, as well as good agreement with the long‐established instrument. Overall, this contemporary approach enables accurate and precise assessment of corneal sensitivity and thus, corneal nerve function, in normal and diseased cornea.

Changes in corneal innervation and pain responses in fungal keratitis

To characterize changes in the cornea nerve and pain responses in fungal keratitis (FK). A retrospective analysis of in vivo confocal microscopy images of 11 FK corneas was performed, and the results were compared with those for 11 normal corneas. Subbasal corneal nerves were analyzed for total nerve number, main nerve trunk number, branching patterns and tortuosity. C57BL/6 mice were infected with Aspergillus fumigatus. Disease severity was determined through clinical scoring and slit lamp photography. Corneas were harvested at 1, 3, 5, and 7d post infection (p.i.) and assessed for β III tubulin. Corneal mechanical sensitivity thresholds were detected by von Frey test. β-endorphin (β-EP) and µ receptor protein expression was detected through Western blotting. Total nerve number, main nerve trunk number, and nerve branching were significantly lower in FK patients than in controls, but tortuosity was not significantly different. In infected mice, subbasal nerve density decreased from 1d p.i., reaching a minimum at 5d p.i. Clinical scores rose at 1d p.i., peaked at 3d p.i., and decreased at 5d p.i. Mechanical sensitivity thresholds showed the same trends. β-EP and µ receptor protein expression increased after infection. Corneal nerve density is lower in FK patients and Aspergillus fumigatus-infected mice than in controls. Pain sensitivity decreases with postinfection corneal ulcer aggravation. β-EP and µ receptor proteins are both upregulated in infected mouse corneas.

Changes of tear film and corneal sensitivity after femtosecond laser-assisted cataract extraction surgery

Objective To compare the changes of tear film and corneal sensitivity between femtosecond laser-assisted cataract surgery and microincisional phacoemulsification surgery. Methods A prospective cohort study was performed.Fifty-three eyes of 53 patients with age-related cataract were included in Wuhan Aier Eye Hospital from March to July 2015.The patients were divided into femtosecond laser group and microincisional group.The 26 eyes in the femtosecond laser group received femtosecond laser-assisted cataract surgery, and 27 eyes in the microincisional group received 2.2 mm microincisional phacoemulsification surgery.The patients were followed-up for 3 months.The data of corneal sensitivity, Schirmer test values, non-invasive tear film break-up time (NIBUT) and subjective score for dryness were collected in 7 days, 1 month and 3 months after surgery, and these results were compared between the two groups.This study was approved by Ethic Committee of Wuhan Aier Ophthalmology Hospital, and written informed consent was obtained from each patient prior to surgery. Results The operations were finished smoothly in all the eyes.In preoperative and 7 days, 1 month, 3 months after operation, the upper corneal sensitivity threshold and NIBUT between the two groups appeared a first reduction and a subsequent rise, the same phenomenon occurred in Schirmer test of the microincisional group and the subjective scores for dryness of the femtosecond laser group with statistically significant differences in the overall comparison (all at P 0.05). The dry eye scores increased gradually with the time expand after operation in the microincisional group, the difference was statistically significant (P<0.05). In postoperative 3 months, these parameters were restored preoperative values.However, the dry eye scores in the microincisional group were still higher than that before operation, and the difference was statistically significant (P<0.05). Conclusions Compared with the 2.2 mm microincisional phacoemulsification surgery, femtosecond laser-assisted cataract surgery brings less disturbance to lacrimal secretion, slight symptoms of dry eye and more comfortable sensation. Key words: Femtosecond laser/therapy use; Cataract/surgery; Tear film; Dry eye; Corneal sensuousness; Prospective study

The Effect of Tear Supplementation with 0.15% Preservative-Free Zinc-Hyaluronate on Ocular Surface Sensations in Patients with Dry Eye.

To evaluate the effect of tear supplementation with preservative free 0.15% zinc-hyaluronate on ocular surface sensations and corneal sensitivity in dry eye patients. Ocular surface sensations were assessed using the ocular surface disease index (OSDI) questionnaire and by recording ocular sensations during forced blinking in parallel with noninvasive tear film breakup time measurement in 20 eyes of 20 dry eye patients. Corneal sensitivity thresholds to selective stimulation of corneal mechano-, thermal- and chemical receptors were measured using the Belmonte gas esthesiometer. All baseline measurements were repeated after 1 month of treatment with 0.15% zinc-hyaluronate. After 1 month, a significant decrease in mean OSDI score (from 35.66 ± 12.36 to 15.03 ± 11.22; P < 0.001) and a significant improvement in tear film breakup time (from 3.83 ± 0.80 to 8.67 ± 4.50 s; P < 0.001) was observed compared to baseline. Sensory responses during the interblink period also significantly decreased after 1 month (P < 0.004). Corneal sensitivity thresholds to mechanical stimulation (90.61 ± 20.35 vs. 103.92 ± 17.97 mL/min; P < 0.025) and chemical stimulation (33.21 ± 0.51 vs. 33.58% ± 0.44% CO2; P < 0.025) significantly increased after 1 month, however sensitivity thresholds to thermal stimulation remained unchanged compared to baseline (P > 0.05). Prolonged use of 0.15% zinc-hyaluronate results in an improvement of tear film stability and a decrease of dry eye complaints. The decrease in corneal mechano-and polymodal receptor excitability suggests that zinc-hyaluronate helps to recover normal corneal sensitivity, and thus might have a beneficial additional effect on reducing ocular surface complaints in dry eye patients.

Assessment of Corneal Sensation, Innervation and Retinal Nerve Fiber Layer in Patients Treated with Multiple Intravitreal Ranibizumab Injections.

PurposeTo evaluate the effects of repeated intravitreal ranibizumab injections on corneal sensitivity, corneal sub-basal nerve plexus (SBNP) and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with neovascular age-related macular degeneration (AMD).MethodsSixty-six eyes of 33 patients who had received unilateral repeated intravitreal ranibizumab injections (0.5 mg/0.05 ml) for the treatment of AMD and 25 eyes of 25 healthy subjects were included in the study. Central corneal sensation was measured using the contact Cochet-Bonnet esthesiometer. The laser scanning in vivo corneal confocal microscope was used to determine corneal SBNP parameters. The peripapillary RNFL thickness was assessed with spectral-domain optical coherence tomography. Data obtained from the ranibizumab-injected eyes were compared with those of the fellow non-treated eyes and the eyes of the healthy control subjects.ResultsThe mean number of ranibizumab injections per eye was 8.9±5.0 (range 3–20). There were no statistically significant differences in the central corneal sensitivity threshold and corneal SBNP parameters between the ranibizumab-injected eyes and the fellow untreated eyes or between those with neovascular AMD and the healthy control group (P>0.05 for all). The average peripapillary RNFL thickness of the treated eyes did not differ significantly to the fellow eyes (P = 0.237), and the eyes of healthy control subjects (P = 0.918). There were no significant correlations between the number of ranibizumab injections and any of the study parameters.ConclusionsMultiple intravitreal injections of ranibizumab seem to have no harmful effects on corneal sensitivity, innervation and peripapillary RNFL thickness in patients with AMD.

Observation of Influence of Cataract Surgery on the Ocular Surface

IntroductionTo evaluate meibomian gland function, changes of lacrimal tears and ocular surface parameters and tear inflammatory mediators following cataract surgery.Methods48 eyes of 34 patients who underwent uncomplicated phacoemulsification were involved and divided into 2 groups with those who had preexisting dry-eye before cataract surgery and those who did not. Ocular symptom score, Schirmer I test, tear film break-up time (TBUT), corneal sensitivity threshold, corneal staining, inflammatory cytokine activities, lid margin abnormalities, meibum expressibility, meibum quality and meibomian gland imaging were evaluated preoperatively, at 1 day, 1 and 2 months postoperatively.ResultsOcular symptom scores were worse at 1 and 2 months postoperatively but, TBUT, corneal staining score and corneal sensitivity threshold showed gradual improvements at 1 month and 2 months postoperatively (p<0.05, respectively). Interestingly there were statistically significant improvements in TBUT, corneal staining score and corneal sensitivity threshold at 1 month postoperatively when topical eye drops were used compared to the period without topical therapy which is the months 2 postoperatively. There were statistically significant decreases in IL-1β, IL-6, IL-8, MCP-1, TNF-α and IFN-γ concentrations at 1 and 2 months postoperatively. Lid margin abnormalities, meibum quality and expressibility scores increased significantly (p < 0.05, respectively) at postoperative period. Compared with the no dry eye group, dry eye group revealed significantly higher ocular symptom scores, lower TBUT, higher lid margin abnormalities, meibum quality and expressibility scores after cataract surgery. There were significant correlations between IL-6 and parameters of dry eye, and between MGD parameters and ocular symptom scores.ConclusionsOur study revealed that meibomian gland function is influenced after cataract surgery accompanying structural changes and these were correlated with increased ocular symptom scores. Therefore, it could elucidate the development of dry eye related to cataract surgery.

Corneal Sensitivity and Inflammatory Biomarkers in Contact Lens Discomfort.

The aim of this study was to analyze whether symptoms of discomfort in hydrogel contact lens (HCL) wearers were associated with changes in corneal sensitivity or levels of tear inflammatory mediators. Sixty-six subjects were included: 47 HCL wearers, further divided into 24 symptomatic and 23 asymptomatic wearers by the Contact Lens Dry Eye Questionnaire short form and 19 non-contact lens wearers. At least 24 h after HCL removal, we obtained scores from the Ocular Surface Disease Index and mechanical, hot, and cold corneal thresholds using a Belmonte esthesiometer. We collected 4 μl of tears with a capillary micropipette and measured levels of 12 inflammatory markers using a bead-based array: epidermal growth factor, fractalkine, interleukin-10 (IL-10), IL-1β, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-8, monocyte chemoattractant protein 1, tumor necrosis factor-α, and matrix metalloproteinase 9. There were no significant differences between groups in corneal sensitivity thresholds and levels of tear molecules. The following significant correlations were found in the total sample pooled: Ocular Surface Disease Index correlated with mechanical threshold (p < 0.01; rho = -0.324) and epidermal growth factor (p < 0.01, rho = -0.330), and mechanical threshold correlated with heat threshold (p < 0.01, rho = -0.321). Twenty-four hours after HCL removal, symptoms of discomfort in HCL wearers are not related to changes in corneal sensitivity or tear inflammatory mediator levels. This might indicate either that HCL wear has no effect on these parameters or that ocular surfaces recover from HCL-caused effects during the first hours after HCL removal. However, there were correlations for associations between symptoms, corneal sensitivity, and some molecules in tears.

Relationship between Corneal Sensation, Blinking, and Tear Film Quality.

To examine the possible role of corneal sensitivity and tear film quality in triggering a blink by investigating the relationship between blink rate, central corneal sensitivity threshold (CST), ocular surface temperature (OST), tear meniscus height (TMH), tear film quality (noninvasive tear break-up time [NIBUT]), and tear film lipid pattern under normal conditions. Forty-two volunteers (average age, 27.76 ± 5.36 years; 11 males) with good ocular health (Ocular Surface Disease Index, <15.0) were recruited for this cross-sectional cohort study. Blink rate, CST (noncontact corneal air gas aesthesiometry, NCCA), minimum and maximum OST in the central and inferior cornea between blinks (thermal infrared camera), TMH, NIBUT, and lipid pattern of the tear film (Keeler Tearscope Plus) were recorded on the right eye only. Median blink rate was 11 blinks/min (interquartile range [IR], 6.95 to 17.05), CST was 0.35 mbars (IR, 0.30 to 0.40), minimum OST in the central cornea was 35.15°C (IR, 34.58 to 35.50), and NIBUT was 34.55 s (IR, 12.45 to 53.80). Moderate but statistically significant correlations were observed between CST and NIBUT (r = 0.535, p < 0.001), CST and blink rate (r = -0.398, p < 0.001), lipid pattern and OST (r = 0.556, p < 0.001), and between CST and OST (r = 0.371, p = 0.008). The correlations between blink rate and NIBUT (r = -0.696, p < 0.001) and between OST and NIBUT (r = 0.639, p < 0.001; Spearman test) achieved higher significance; this was highlighted by the linear regression model where NIBUT and minimum central and inferior OST were identified as significant predictor variables. There is strong evidence for significant interactions between corneal sensitivity, NIBUT, OST, and blink frequency, emphasizing that ocular surface conditions represent a possible important trigger for the initiation of a blink. However, the mechanisms involved in the initiation of a blink are complex, with local ocular sensory input as only one trigger, along with other external influences and internal factors under cortical control.

Effect of Platelet-Rich Plasma in Nerve Regeneration After LASIK

To investigate the effect of topical eye application of platelet-rich plasma (E-PRP) on the recovery of corneal sensitivity after LASIK and the anatomical recovery of the sub-basal corneal plexus as studied by confocal microscopy. This was a randomized, consecutive, controlled, prospective and masked study on 108 myopic eyes receiving LASIK. The main variables of the study were the increase in corneal sensitivity (Cochet-Bonet aesthesiometer; Luneau, Paris, France) and the aspect of the sub-basal nerve plexus (confocal microscope). Additionally, a biomicroscopic study of the epithelial status of the cornea and a subjective questionnaire were completed. Each eye of each patient was assigned to one of two groups: 54 eyes treated with balanced saline solution and 54 fellow eyes receiving PRP drops for 3 months. No significant differences were detected when the corneal sensitivity thresholds were compared at any postoperative visit in both groups (P > .05 for all comparisons). Almost identical sub-basal fiber densities were estimated for both groups before LASIK (t test, P = .66). However, the type and severity of staining detected during the slit-lamp examinations at the first and third month postoperatively were significantly less evident in the E-PRP treatment group (Wilcoxon test, P < .05). PRP drops have beneficial effects for promoting epithelial status after LASIK but have no positive effect on recovery of corneal sensitivity, probably due to the limited bioavailability of growth factors in corneal stroma when the substance is topically administered.

Characterization by Belmonte's Gas Esthesiometer of Mechanical, Chemical, and Thermal Corneal Sensitivity Thresholds in a Normal Population

We used a prototype gas esthesiometer to measure corneal threshold sensitivity values for mechanical, chemical, and thermal stimuli. We also evaluated the reproducibility of the esthesiometer measurements, the influence of previous corneal symptoms, and the safety of this technique. Forty healthy subjects participated in the study. Mechanical, chemical, and thermal (hot and cold) thresholds were determined at the center of the cornea using a prototype Belmonte's gas esthesiometer. To determine reproducibility of the results, the sensitivity thresholds were measured for each eye on 2 days. Corneal fluorescein staining and bulbar hyperemia after completion of the tests were analyzed. There were no differences for any sensitivity threshold between eyes or between the first and second esthesiometries. The reproducibilities of mechanical and hot thresholds were higher than for chemical and cold thresholds. Men had significantly higher chemical intensity thresholds than did women (men: 23.50 ± 5.10; women: 10.20 ± 2.16, P = 0.021). There were no alterations of the ocular surface after completion of the measurements. Mechanical, chemical, and thermal corneal sensitivity thresholds in the central cornea have been established in healthy men and women of different age groups. The use of the Belmonte gas esthesiometer is safe and reproducible, with the highest reproducibility in determining mechanical and hot thresholds.