Impact of Diabetic Peripheral Neuropathy on Corneal Sensitivity and Ocular Surface

Understanding the Dual Dilemma of Dry Eye and Glaucoma: An International Review.

To determine whether tear osmolarity contributes to the assessment of the ocular surface in soft contact lens (CL) wearers. Prospective, case-control series in 44 CL wearers (28 tolerant and 16 intolerant) and 34 healthy subjects. Every patient underwent a thorough ophthalmic examination with a tear osmolarity test (TearLab System), conjunctival impression cytology and meibomian lipid sampling. Symptoms, break-up time (BUT), tear osmolarity, conjunctival expression of HLA-DR and meibomian fatty acid composition were evaluated. Tear osmolarity did not differ between controls and CL wearers (p= 0.23). Flow cytometry results expressed in antibody-binding capacity (ABC) units and percentage of positive cells revealed a significant difference between the intolerant CL wearer group and the control group (p< 0.0001). Comparisons between tolerant and intolerant CL wearers showed only a significant difference for mean fluorescence levels expressed in ABC units (p< 0.0001). The BUT was significantly shorter in intolerant and tolerant CL wearers subjects than in healthy subjects (p< 0.0001), whereas there was no significant difference in meibomian fatty acid composition (p= 0.99) between the two groups. Contact lens wear is responsible for ocular surface alterations whose patterns are very similar to those reported in early dry-eye syndrome. However, tear osmolarity was not modified in these selected CL wearers. The yield of tear osmolarity with TearLab™ in assessing ocular surface disorders in CL wearers deserves further investigation.

Comparison of Ocular Surface Disease Index and Tear Osmolarity as Markers of Ocular Surface Dysfunction in Video Terminal Display Workers

To explore the relationship between dry eye disease and type 1 diabetes mellitus (DM) and also to identify whether diabetic peripheral neuropathy (DPN) was a significant predictor for the development of dry eye disease. This prospective cross sectional study involved patients with type 1 DM and aged- and sex-matched healthy controls. All of the participants underwent dry eye tests including meibomian gland function. Based on neurologic examination and electromyography findings, diabetic patients were grouped as DPN + and DPN-. All findings were compared and predictive factors for dry eye disease were identified. Of the 97 patients with type 1 DM, 42 (43.3%) were diagnosed as DPN. In patients with DM, there was a significant increase in the ocular surface disease index, corneal surface staining, eyelid margin abnormality and meibomian gland dysfunction and a significant decrease in tear break-up time and Schirmer's I test (p < 0.05). Measurements of dry eye tests were more severe with the presence of DPN (p < 0.05). Age of the patients, duration of DM and HbA1c level were significantly correlated with ocular surface and meibomian gland dysfunction parameters (p < 0.05). Age of the patients (p < 0.001), duration of DM (p = 0.001), HbA1c level (p = 0.036) and presence of DPN (p < 0.001) were found to be the independent and significant predictors of dry eye disease. Type 1 DM was found to be significantly associated with ocular surface abnormalities including meibomian gland dysfunction. Furthermore, age of the patients, duration of DM, HbA1c level and presence of DPN were predictive factors of dry eye disease in type 1 DM.

PurposeTo analyse clinical signs and symptoms of ocular surface disease in patients with diabetes mellitus (DM), based on severity of diabetic peripheral neuropathy (DPN).MethodsThis cross-sectional study included participants who were...

Obstructive Sleep Apnea Syndrome (OSAS) is a common sleep disorder involving recurrent upper airway obstruction during sleep, leading to intermittent hypoxia, oxidative stress, and systemic inflammation. Although OSAS has been linked to several ocular disorders, its specific impact on ocular surface health, particularly in relation to dry eye disease (DED) and corneal sensitivity, is not fully understood. This study aimed to assess how OSAS severity influences dry eye parameters and corneal sensitivity, and to explore associations with systemic and demographic factors. In this cross-sectional study, 174 patients diagnosed with OSAS via overnight polysomnography were divided into normal-mild OSAS and moderate-severe OSAS groups. Ocular surface assessments included non-invasive tear break-up time (NIBUT), Schirmer II test (ST), Ocular Surface Disease Index (OSDI), and corneal sensitivity measured in five corneal regions using a Cochet-Bonnet esthesiometer. Statistical analyses involved group comparisons, correlation assessments, and multivariable linear regression to identify predictors of dry eye parameters. Moderate-severe OSAS (AHI ≥ 15; n = 85) patients were older, had higher BMI, and lower minimum oxygen saturation (p < 0.001). No significant differences were observed between groups in NIBUT, ST, or regional corneal sensitivity. Interestingly, OSDI scores were lower in the moderate-severe group, nearing statistical significance (p = 0.055). ST was positively correlated with corneal sensitivity (r = 0.22-0.26), whereas OSDI was negatively correlated (r = - 0.14- - 0.18). Regression analyses identified age and smoking as significant predictors of NIBUT, and gender and oxygen saturation as predictors of OSDI. Although OSAS severity did not significantly affect objective dry eye measures or corneal sensitivity, subtle associations between tear production and corneal nerve function suggest possible subclinical ocular changes. Routine eye evaluations may benefit OSAS patients, especially those with risk factors like aging, smoking, and hypoxemia.

PurposeTo determine the prevalence of dry eye disease (DED) in patients scheduled for cataract surgery in a Norwegian eye clinic.Patients and Methods218 patients scheduled for cataract surgery were examined for DED in one randomly selected eye and questioned regarding symptoms and risk factors. Patients were diagnosed with DED if they fulfilled the DEWS II criteria with symptom score >12/100 with Ocular Surface Disease Index (OSDI) questionnaire, and the presence of any of the three signs: tear osmolarity >307 mOsm/L in either eye or a difference in osmolarity between the two eyes of >8 mOsm/L, corneal fluorescein staining (CSF) ≥ grade 2 and non-invasive tear film breakup time (NIKBUT) of <10 seconds. Additional tests were the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire, tear meniscus height (TMH), Schirmer 1, tear film thickness (TFT), corneal sensitivity and meibography (meiboscore). Dry eye test outcomes were correlated with risk factors for DED.ResultsThe prevalence of DED was 55.5% according to the DEWS II criteria. The abnormal osmolarity percentage was 66.5, while 29.8% had shortened NIKBUT and 19.7% exhibited CFS ≥2. 57% had Schirmer 1 ≤ 10 mm/5 min, and 81.1% had a meiboscore of ≥1. 71.2% of subjects scored positive for DED symptoms using the OSDI questionnaire and 69.3% using SPEED. Logistic regression analysis showed that higher age correlated with a lower OSDI symptom score, reduced corneal sensitivity and increased meibomian gland atrophy. Female sex was associated with higher odds of having DED, abnormal NIKBUT and abnormal CFS. Ocular tests for DED did not correlate with OSDI symptom scores when assessed with Spearman`s rank analysis.ConclusionThe prevalence of DED in an elderly Norwegian population scheduled for cataract surgery is high and associated with female sex. There was a lack of correlation between signs and symptoms of DED.

Ocular surface disease (OSD), one of the major side-effects of long-term use of antiglaucoma drugs, is thought to develop secondary to reduced tear production, corneal epithelial damage, decreased number of subbasal nerves and corneal sensitivity, reduced number of goblet cells and damage to the mucous layer of the tear film resulting in tear film instability (Pisella et al. 2002). OSD in elderly is also associated with several conditions including conjunctivochalasis (CCh), a frequently overlooked ocular surface problem of the ageing population characterized by looseness and redundancy of inferior bulbar conjunctiva between the globe and the eyelid, which causes OSD symptoms by inducing tear film instability, delayed tear clearance and ocular surface inflammation (Liu 1986; Di Pascuale et al. 2004). The aim of this study was to evaluate whether the effect of CCh on ocular surface parameters differs according to the type of topical antiglaucoma medication in primary open-angle glaucoma patients. A total of 190 eyes of 190 subjects with or without CCh were included in this prospective study. Participants were divided into three groups: Group I was composed of patients treated with prostaglandin (PG) analogues (n = 46); Group II was composed of patients treated with beta-adrenergic antagonists (n = 45); Group III (control group) was composed of healthy subjects (n = 99). The subjects were categorized into two subgroups according to the presence or the absence of CCh. The tear break-up time (BUT), lissamine green (LG) staining and Schirmer test were performed and ocular surface disease index (OSDI) questionnaire scores were noted for each subject. Mann–Whitney U test, Kruskal–Wallis test and one-way anova were used for statistical analysis. All ocular surface parameters were found worse in each group with CCh. Patients with CCh in Group I had significantly lower Schirmer test values and higher LG grading and OSDI scores than those of patients with CCh in Group II and Group III (p < 0.05; Table 1). Ocular surface parameters of patients with grade 2 CCh were significantly different than those of grade 1 CCh in all groups (p < 0.05). Both beta-blockers and PG analogues increase the inflammatory marker expression and decrease MUC5AC-related mucin production in epithelial cells compared with normal subjects (Pisella et al. 2004). These factors may be crucial in development of ocular surface changes in patients without CCh who are on PG analogue therapy or beta-adrenergic antagonists. In addition, it is also known that preservatives have adverse effects on ocular surface (Pisella et al. 2002). Thus, we cannot rule out BAK as a co-pathogenic factor for the observed ocular surface alterations detected in our study. We found that ocular surface parameters were adversely affected in the presence of CCh in medically treated glaucoma patients compared with healthy control subjects. In addition, grade 2 CCh had evidence of more profound alterations in ocular surface testing than those of grade 1 CCh in both glaucoma patients and control subjects. Patients who were on PG analogue therapy and had coexistent CCh showed evidence of a more severe ocular surface disease compared with patients who were on beta-adrenergic antagonists. This could be due to the contribution of both PG use and CCh separately to ocular surface disease, as both PG use and CCh are known to be associated with ocular surface inflammation (Fodor et al. 2012). In conclusion, long-term monotherapy with topical antiglaucoma therapy is associated with OSD in patients with and without CCh. The severity of CCh is associated with both objective and subjective alterations. It seems reasonable to evaluate and follow-up glaucoma patients treated with a long-term antiglaucoma drug for the presence of CCh and the ocular surface disease.

To describe tear function, ocular surface changes, and corneal sensitivity in patients with asymmetrical keratoconus (KC). Thirty-one patients with asymmetrical KC (31 KC and 31 subclinical KC eyes) and 30 control subjects (1 eye in each subject) were enrolled in this prospective, case-control study. The patients and control subjects underwent ocular surface examinations including corneal sensitivity measurements, the Schirmer test using topical anesthesia, tear osmolarity test, and conjunctival impression cytology. Mean corneal sensitivity and Schirmer test values were significantly lower in the KC and subclinical KC eyes compared with the control eyes. The conjunctiva of KC and subclinical KC eyes showed significantly higher grades of squamous metaplasia and goblet cell loss compared with the control group. However, no significant difference in tear osmolarity was found among the groups. The corneal sensitivity and ocular surface changes were significant in the subclinical KC and KC eyes compared with the control subjects. Ocular surface disease in KC was characterized by tear deficiency disorder and abnormal impression cytology results. However, no significant difference in tear osmolarity was found among the groups. The decrease in corneal sensitivity and ocular surface change may be associated with the pathogenesis of ocular surface changes in KC and the progression of the disease.

PurposeTo evaluate the short-term changes in ocular surface measures and tear inflammatory mediators after femtosecond lenticule extraction (FLEx) and small-incision lenticule extraction (SMILE) procedures.MethodsEighteen subjects (18 eyes) underwent FLEx and 23 subjects (23 eyes) underwent SMILE in this single-center and prospective study. Central corneal sensitivity, Schirmer I test (SIT), noninvasive tear breakup time (NI-TBUT), tear meniscus height, corneal fluorescein (FL) staining, and ocular surface disease index (OSDI) were assessed in all patients. Concentrations of interleukin-1α (IL-1α), tumor necrosis factor-α (TNF-α), nerve growth factor (NGF), interferon-γ (IFN-γ), transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) in collected tears were measured by multiplex antibody microarray.ResultsCentral corneal sensitivity was reduced in both groups, but the scores in the SMILE group were higher than those in the FLEx group at all time points postoperatively (P<0.01). Lower FL scores and longer NI-BUT were observed in the SMILE group 1 week after surgery (P<0.05). OSDI scores in both groups increased rapidly at 1 day and 1 week postoperatively, then returned to their preoperative levels within 1 month (P<0.05). There were no significant differences in SIT or tear meniscus height between the two groups. Lower and faster recovery of tear NGF, TGF-β1 and IL-1α concentration were found in the SMILE group compared to the FLEx group postoperatively. No significant difference was found in tear TNF-α, IFN-γ and MMP-9 for either group before or after surgery. Tear NGF, TGF-β1 and IL-1α show a correlation with ocular surface changes after FLEx or SMILE surgery.ConclusionSMILE has superiority over FLEx in early ocular surface changes and NGF, TGF-β1 and IL-1α may contribute to the process of ocular surface recovery.Trial RegistrationClinicalTrials.gov NCT02540785

To investigate the relationships of dry eye symptoms and corneal and conjunctival sensitivity to pneumatic stimulation, tear film stability, and clinical ocular surface characteristics in symptomatic and asymptomatic subjects. Ninety-seven subjects were enrolled and grouped by a questionnaire-based single score for symptoms of ocular dryness (none to trace, non-dry group; mild to severe, symptomatic group); 43 were symptomatic and 54 were non-dry. Corneal (K) and conjunctival (C) sensitivities were measured with a computer-controlled Belmonte pneumatic (room temperature) stimulus. Symptoms were assessed according to the Ocular Surface Disease Index (OSDI). Ocular surface staining with fluorescein (FL) and lissamine green (LG), noninvasive tear film break-up time (NIBUT), and the phenol red thread test (PRT) were assessed. The symptomatic group showed lower K and C thresholds (P < 0.01), greater corneal FL and conjunctival LG staining, and shorter NIBUT than did the non-dry eye group (all others P < 0.05). The OSDI scores were higher in the symptomatic group (P < 0.001). K and C thresholds and NIBUT were inversely correlated with the OSDI and corneal and conjunctival staining (all P < 0.05). The K and C threshold and NIBUT (all P < 0.01) correlated positively. Step-wise multiple regression analysis showed that ocular surface sensitivity and NIBUT were significant predictors of the OSDI. Ocular irritation assessed with the OSDI is associated with ocular surface hyperesthesia to cooling, corneal epitheliopathy, and tear film instability. Although cause and effect are unclear, the analysis showed that altered corneal and conjunctival sensory processing and tear film attributes are essential aspects of what characterizes dry eye.

Low serum nerve growth factor (NGF) levels have been reported in patients with diabetic peripheral neuropathy (DPN), but the role of NGF in the development of neuropathy is unclear. Thus, we investigated the associations of serum NGF level and NGF receptor activity with the presence and severity of DPN. One hundred and thirty-six patients with Type 2 diabetes were included in this cross-sectional study. Serum NGF levels were measured by ELISA. Expressions of NGF receptors (TrkA and p75(NTR)) were measured by immunohistochemical staining. The presence and severity of DPN were assessed by neuropathy disability score (NDS) and by corneal nerve fibre length (cNFL) and nerve branch density (cNBD) using in vivo confocal microscopy. Patients with DPN had higher serum NGF levels (56-451 pg/ml) than patients without DPN (4-54 pg/ml). However, in DPN patients, serum NGF was negatively associated with neuropathy severity (mild 222 +/- 64 pg/ml; moderate 114 +/- 17 pg/ml; severe 89 +/- 20 pg/ml). This negative association was consistent in all severity indices (NDS, P < 0.001; cNFL, P < 0.001; cNBD P = 0.010) even after adjustment for age, sex, diabetes duration, insulin use, fasting glucose and glycated haemoglobin. Although NGF receptor activities had significantly (P < 0.05) negative associations with the presence and severity of neuropathy, these associations were not significant when adjusted for other factors. Serum NGF level was positively associated with the presence of DPN but negatively associated with neuropathy severity in DPN patients. The change in serum NGF might be a consequence of, rather than a contributor to, the early development of DPN.

To detect and analyze the changes on ocular surface and tear function in type II diabetic patients with proliferative diabetic retinopathy (PDR), an advanced stage of diabetic retinopathy (DR), using conventional ophthalmic tests and the high-resolution laser scanning confocal microscopy. Fifty-eight patients with type II diabetes were selected. Based on the diagnostic criteria and stage classification of DR, the patients were divided into the non-DR (NDR) group and the PDR group. Thirty-six patients with cataract but no other ocular and systemic disease were included as non-diabetic controls. All the patients were subjected to the conventional clinical tests of corneal sensitivity, Schirmer I Test, and corneal fluorescein staining. The non-invasive tear film break-up time (NIBUT) and tear interferometry were conducted by a Tearscope Plus. The morphology of corneal epithelia and nerve fibers was examined using the high-resolution confocal microscopy. The NDR group exhibited significantly declined corneal sensitivity and Schirmer I test value, as compared to the non-diabetic controls (P< 0.001). The PDR group showed significantly reduced corneal sensitivity, Schirmer I test value, and NIBUT in comparison to the non-diabetic controls (P < 0.001). Corneal fluorescein staining revealed the progressively injured corneal epithelia in the PDR patients. Moreover, significant decrease in the corneal epithelial density and morphological abnormalities in the corneal epithelia and nerve fibers were also observed in the PDR patients. Ocular surface changes, including blunted corneal sensitivity, reduced tear secretion, tear film dysfunction, progressive loss of corneal epithelia and degeneration of nerve fibers, are common in type II diabetic patients, particularly in the diabetic patients with PDR. The corneal sensitivity, fluorescein staining scores, and the density of corneal epithelial cells and nerve fibers in the diabetic patients correlate with the duration of diabetes. Therefore, ocular surface of the patients with PDR should be examined regularly by conventional approaches and confocal microscopy to facilitate early diagnosis and treatment of keratopathy.

Purpose:To investigate age- and sex-related differences in tear film parameters of normal Indian population and study interparametric relationships.MethodsHealthy subjects with no ocular disease (median ocular surface disease index = 0) were subjected to an automated evaluation of tear meniscus height (TMH), non-invasive tear breakup time (NIBUT) using Keratograph 5M (OCULUS GmbH, Wetzlar, Germany), and tear osmolarity using the TearLab Osmolarity System (TearLab Corporation, California, USA). A mixed-effects model with random intercepts at the patient level was used to evaluate the relationships between explanatory (age, gender, and tear osmolarity) and outcome variables (TMH and NIBUT).ResultsA total of 237 subjects (474 eyes; 150 males) were enrolled with a mean age of 40 ± 17 years (range, 10-78 years). The mean values (± standard deviation) of TMH, NIBUT, and tear osmolarity were 0.34 ± 0.07 mm, 10.95 ± 2.02 s and 289.0 ± 5.8 mOsm/L, respectively. Age had a significant positive relationship with TMH (p < 0.0001; 0.002 mm/year; r = 0.12), but there was no effect on NIBUT (p = 0.26) and tear osmolarity (p = 0.27). There were no sex-based differences in tear film parameters. Interparametric relationship revealed no significant association between TMH and NIBUT (p = 0.12) or tear osmolarity and TMH (p = 0.83) or tear osmolarity and NIBUT values (p = 0.48).ConclusionsIn a normal Indian population, TMH is weakly affected by age and is independent of sex, NIBUT, and tear osmolarity. Tear breakup time and osmolarity show no significant age- and sex-related variation.

Dry eye in Parkinson's disease (PD) has been studied, but meibomian gland dysfunction (MGD) has not yet been assessed using meibography, and corneal sensitivity data remain limited. The aims of this study were to analyze ocular surface parameters in newly diagnosed PD patients, evaluate MGD using meibography and corneal sensitivity using esthesiometry, and compare with the control group. This cross-sectional clinical study included 44 newly diagnosed PD patients and a control group of 44 age- and gender-matched healthy individuals. Clinical staging of PD patients was performed according to the modified Hoehn-Yahr Scale. Patients with early stages such as stages 1, 1.5, and 2 were included in the study. Ocular surface disease index (OSDI) questionnaire, Schirmer test, tear meniscus height (TMH), noninvasive tear breakup time (NITBUT), meibography staging, degree of conjunctival redness using Keratograph 5 M (Oculus, Wetzlar, Germany), and corneal sensitivity measurements using Cochet-Bonnet esthesiometer (Cochet-Bonnet, Luneau, France) were performed in the patient and control groups. The Schirmer test, TMH, NITBUT, and corneal sensitivity results were significantly lower in the PD group than in the control group (P < 0.001, P = 0.028, P < 0.001, and P < 0.001, respectively). Meanwhile, the OSDI score, degree of conjunctival redness, and total meiboscore results were significantly higher in the PD group than in the control group (P < 0.001, P < 0.001, and P < 0.001, respectively). There were significant differences in meibomian gland morphology, tear parameters, and corneal sensitivity between newly diagnosed treatment-naive PD patients and healthy individuals. These patients should be monitored for early ocular surface damage and MGD.