Corneal Sensitivity Measurements Research Articles

Does the Belmonte air gas aesthesiometer deliver a true mechanical stimulus for corneal sensitivity measurement?

Purpose: Air gas aesthesiometry overcomes some of the limitations of the ‘gold standard’, CochetBonnet aesthesiometer. However, for truemechanical corneal sensitivitymeasurement, the airflow stimulus temperature of the aesthesiometer must equal corneal temperature at the corneal surface, to avoid additional response from temperature-sensitive nerves. The aim of this study was to record corneal surface temperature changes during the presentation of the air-stimulus with varying temperatures and pressures. Method: (a) Corneal surface temperaturewas recordedwith aid of an infrared camera (FLIR A310) on a total of 14 subjects (mean age 25.14±2.18 years; seven females) during the presentation of heated airflow stimuli at three temperatures: room temperature +10◦, +15◦ and +20 ◦C (duration 3s; 4mmdistance of exit-nozzle to cornea; airflow 60ml/min; room temperature 23-24 ◦C). (b) Subsequently, corneal temperaturemeasurements were repeated whilst varying the airflow rates and restricting the stimulus temperature to that which matched corneal temperature found in (a). Inclusion criteria were age<40, no contact lens wear, absence of ocular disease including dry eye, and no use of artificial tears. Repeated measures (ANOVA) and appropriate post hoc t-tests were applied. Results: A stimulus temperature of +15 ◦C induced the least change in corneal temperature. Consequently, corneal temperature changes were recorded when applying air stimuli of +15 ◦C with airflow rates of 30, 60, 80 and 100ml/min. Mean corneal temperature change was found to be: 0.00±0.07 ◦C with 30ml/min (p=1.000), +0.18±0.17 ◦C with 60ml/min (p=0.002), +0.32±0.13 ◦Cwith 80ml/min (p=0.000), and +0.43±0.10 ◦Cwith 100ml/min (p=0.000). Conclusions: Although stimulus temperature was set to produce no temperature change on the corneal surface, the need to vary stimulus-airflow to change stimulus intensity, produced a small, but statistically significant effect on corneal surface temperature. Consequently, this air stimulus may not be exclusively ‘mechanical’, exciting only Afibres sensitive to deformation, but may also have an additional response from the temperaturesensitive C fibres.

The impact of tear functions on visual outcome following keratoplasty in eyes with keratoconus

To investigate the impact of preoperative and postoperative tear functions on visual outcome and the recovery of visual function following keratoplasty in eyes with keratoconus. Twenty-five eyes of 25 consecutive patients (5 females, 20 males, mean age: 34.3 ± 15.8years (range: 19-70years) with keratoconus who underwent either penetrating keratoplasty (PKP) or deep anterior lamellar keratoplasty (DALK) were included in this prospective study. One patient who had a rejection episode during the follow-up period was excluded. All subjects underwent best corrected visual acuity (BCVA), corneal topography (refractive cylinder, surface regularity index: SRI and surface asymmetry index: SAI), Schirmer I test, tear film break-up time (BUT), corneal sensitivity, and fluorescein staining score measurements before as well as 1, 3, 6 and 12months after keratoplasty. The relation between the tear functions and the duration until the achievement of maximum BCVA was also evaluated. Linear regression analysis was performed to study the statistical significance of the correlations and the time wise change of each examined parameter. SRI, SAI, and BCVA significantly improved after keratoplasty. The postoperative corneal sensitivity was still significantly low even at 12months postoperatively. Postoperative BCVA at 3, 6months and maximum BCVA showed a significant linear negative correlation with the preoperative BUT (3months; r = -0.461, p = 0.036, 6months; r = -0.494, p = 0.023, maximum BCVA; r = -0.473, p = 0.030). The duration until the achievement of maximum BCVA showed a significant negative correlation with the preoperative Schirmer test (r = -0.429, p = 0.036). BCVA at 1 and 3months postoperatively showed significant linear negative correlations with BUT value at the respective periods (1month; r = -0.665, p = 0.0036, 3months; r = -0.580, p = 0.0059). Preoperative tear functions appeared to have an influence on postoperative BCVA and the duration of visual recovery in keratoconus patients undergoing keratoplasty. Postoperative tear film stability appears to play an important role for obtaining a better BCVA in the early postoperative period after keratoplasty.

Changes in Corneal Sensation and Ocular Surface in Patients With Asymmetrical Keratoconus

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.

Changes in the tear film and ocular surface after cataract surgery

To evaluate changes in corneal sensitivity, tear film function, and ocular surface stability in patients after cataract surgery. This hospital-based prospective randomized trial included 48 eyes from 30 patients who underwent phacoemulsification. Slit-lamp examination, Schirmer test 1 (ST1), and measurement of corneal sensitivity and tear film breakup time (BUT) were performed for all patients 1 day before and 1 day, 1 month, and 3 months after surgery. In addition, conjunctival impression cytology from the temporal region of the conjunctiva was simultaneously performed. Corneal sensitivity at the center and temporal incision sites had decreased significantly at 1 day postoperatively (P = .021, P < .001). However, the sensitivity had returned to almost the preoperative level 1 month postoperatively. The mean postoperative ST1 results were no different from preoperative values. On the other hand, BUT results had decreased significantly at 1 day postoperatively (P = .01) but had returned to almost the preoperative level 1 month postoperatively. Mean goblet cell density (GCD) had decreased significantly at 1 day, 1 month, and 3 months postoperatively (P < .001). In addition, decrease in GCD and cataract operative time were highly correlated (r² = 0.65). The decrease in GCD, which was correlated with operative time, had not recovered at 3 months after cataract surgery. Therefore, microscopic ocular surface damage during cataract surgery seems to be one of the pathogenic factors that cause ocular discomfort and dry eye syndrome after cataract surgery.

Morphological changes of corneal subepithelial nerve plexus in different types of herpetic keratitis

We investigated by in vivo confocal microscopy alterations in the subepithelial nerve plexus in different types of herpes simplex keratitis (HSK). Seventeen patients (seven women and ten men, mean age 63.9years) with a history of HSK were classified into three groups according to the classification of Herpetic Keratitis Infection Research Group. Slit-lamp examinations, corneal sensitivity measurements, and corneal in vivo confocal microscopy examinations [Rostock Corneal Module attached to the Heidelberg Retina Tomograph II (HRT II-RCM)] were performed. Among the 17 cases, three were classified as epithelial type, ten as stromal type, and four as endothelial type HSK. The average corneal sensitivities were 11.41±9.46mm in the affected eyes and 43.24±12.2mm in controls. Decreases in three parameters in the affected eyes (long nerve-fiber density, nerve-branch density, nerve thickness) were statistically significant compared with controls. Decreases in the three parameters were more remarkable in the epithelial and stromal types than in the endothelial type. The morphology of the corneal subepithelial nerve plexus may get gradually destroyed along with recurrent episodes of epithelial and stromal HSK. However, the destruction does not seem remarkable in the endothelial type of HSK, suggesting the possibility of a different route of virus recruitment in this type.

Ocular surface changes and corneal sensitivity in Keratoconus

AbstractPurpose This study aims to describe ocular surface, tear function, corneal nerve and sensitivity in patients with keratoconus.Methods Thirty‐one patients diagnosed as having asymmetrical KC (31 keratoconus eyes, and 31 subclinical keratoconus eyes) and 31 normal control subjects (one eye) were studied in a prospective, cross‐sectional study. The subjects underwent routine ophthalmic examinations, corneal topography, corneal sensitivity measurements, Schirmer test, conjunctival impression cytology, and tear osmolarity. Western blot analysis and Immunofluorescent staining with monoclonal antibodies for Class III β‐tubulin in corneas of keratoconus and normal were done.Results The mean corneal sensitivity and Schirmer test values were significantly lower in eyes of keratoconus and subclinical keratoconus compared with control. Conjunctiva of keratoconus and subclinical keratoconus had significantly higher grades of squamous metaplasia and goblet cell loss compared with normal. Corneal nerves were significantly decreased in eyes of keratoconus and subclinical keratoconus compared with control.Conclusion Whatever the keratoconus‐related factors might be, we found marked changes on the ocular surface that affected not only the corneal, but also the conjunctival epithelium. The loss or decreae of trophic effects of corneal nerves due to primary or secondary events with the progression of keratoconus may plays a role in the pathogenesis of the ocular surface change in keratoconus.

In Vivo Confocal Microscopic Evidence of Keratopathy in Patients with Pseudoexfoliation Syndrome

To measure the density of cells in different layers of the cornea and to determine whether morphologic changes of the subbasal corneal nerve plexus are present in eyes with the pseudoexfoliation (PEX) syndrome. Twenty-seven patients with unilateral PEX syndrome and 27 normal controls were investigated. All eyes underwent corneal sensitivity measurements with an esthesiometer and in vivo confocal microscopic study. Densities of the epithelial, stromal, and endothelial cells were measured. The density and tortuosity of the subbasal corneal nerve plexus were also evaluated. Eyes with PEX syndrome had significantly lower cell densities in the basal epithelium (P = 0.003), anterior stroma (P = 0.007), intermediate stroma (P = 0.009), posterior stroma (P = 0.012), and endothelium (P < 0.0001) than in the corresponding layers of normal eyes. PEX eyes also had lower subbasal nerve densities and greater tortuosity of the nerves than normal eyes. Fellow eyes of patients with PEX also had significantly lower densities of the basal epithelial and endothelial cells than the normal eyes. Corneal sensitivity was significantly decreased in PEX eyes, and this was significantly correlated with the decrease of basal epithelial cell and subbasal nerve densities. These results have shed light on understanding of the pathogenesis of decreased corneal sensitivity in eyes with PEX syndrome. PEX syndrome is probably a binocular condition for which keratopathy of the fellow eye also requires observation.

Assessing the sensory function of the ocular surface: Implications of use of a non-contact air jet aesthesiometer versus the Cochet–Bonnet aesthesiometer

Assessment of corneal sensory function is commonly carried out using the Cochet–Bonnet aesthesiometer. The limitations of this instrument have lead to development of newer instruments, such as the CRCERT–Belmonte aesthesiometer, which utilise a jet of air as their stimulus. Recent work, however, has demonstrated contradictory effects on ocular surface sensitivity when measured with different types of aesthesiometer. The purpose of the present study was to compare clinical measurements of corneal sensitivity obtained with the CRCERT–Belmonte and the Cochet–Bonnet aesthesiometers and to examine their stimulus characteristics in terms of force exerted. No association was found between central corneal sensitivity measured with the two aesthesiometers in a group of normal subjects. Sensitivity was measured to be lower with the Cochet–Bonnet aesthesiometer than with the CRCERT–Belmonte. Over half of the subjects could not be assessed with the standard Cochet–Bonnet filament and 11% could not be assessed with either filament, as their corneal sensitivity was outside of the range of the instrument. In contrast, all subjects were within the stimulus range of the CRCERT–Belmonte aesthesiometer. Corneal sensitivity measurements made with the non-contact CRCERT–Belmonte aesthesiometer and the Cochet–Bonnet aesthesiometer are not comparable. Due to dissimilarities in the composition of their stimuli, and thus mode of stimulation, it is possible that the two instruments measure different aspects of the neural response. The underestimation of corneal sensitivity by the Cochet–Bonnet aesthesiometer and its inability to measure sensitivity of some subjects at all are important considerations in the assessment of sensitivity loss. Subtle changes are unlikely to be detected with this instrument, particularly at higher sensitivity levels. The Cochet–Bonnet should therefore be used with caution and the 0.08mm diameter used as the filament of choice. Adoption of a non-contact aesthesiometer as standard for ocular sensitivity measurement should be considered. The non-contact instrument allows superior stimulus reproducibility and better control over stimulus characteristics, in addition to the ability for exploration of the response of all three types of neuro-receptors on the ocular surface.

Corneal nerve regeneration in neurotrophic keratopathy following autologous plasma therapy

AimsTo evaluate the effect of topical autologous plasma on nerve morphology in patients with neurotrophic keratopathy (NK) using the confocal microscope.MethodsEleven eyes of six patients with neurotrophic keratopathy were evaluated...

Alterations of the ocular surface epithelial MUC16 and goblet cell MUC5AC in patients with atopic keratoconjunctivitis

An increased understanding of the ocular surface at cellular level in the conjunctiva and the cornea may help explain the pathogenesis and the subsequent clinical appearance of atopic ocular allergies, which may be potentially blinding. To investigate the MUC16 and MUC5AC alterations, tear function and the ocular surface disorder in patients with atopic keratoconjunctivitis (AKC). Thirty-six eyes of 18 AKC patients as well as 28 eyes of 14 age- and sex-matched normal subjects were studied. The subjects underwent corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT), fluorescein and Rose-Bengal staining of the ocular surface, conjunctival impression cytology and brush cytology. Impression cytology samples underwent periodic acid schiff and immunohistochemical staining with MUC16 and MUC5AC antibodies. Brush cytology specimens underwent evaluation for inflammatory cell numbers and quantitative real-time polymerase chain reaction (PCR) for MUC16 and MUC5AC mRNA expression. The mean corneal sensitivity and BUT values were significantly lower in patients with AKC, compared with controls (P < 0.001). Brush cytology specimens from AKC patients revealed significantly higher numbers of inflammatory cells (P < 0.001). Specimens from patient eyes showed positive staining for MUC5AC and MUC16. MUC16 mRNA expression was significantly upregulated with significant downregulation of MUC5AC mRNA expression in eyes with AKC compared with the eyes of control subjects. Ocular surface inflammation, decline in corneal sensitivity, tear film instability, changes in conjunctival epithelial MUC5AC and MUC16 mRNA expressions were thought to be important in the pathogenesis of atopic ocular surface disease.

Corneal In Vivo Confocal Scanning Laser Microscopy in Patients with Atopic Keratoconjunctivitis

To elucidate the morphologic alterations of the cornea in atopic keratoconjunctivitis (AKC) using confocal microscopy (Heidelberg Retina Tomograph II-Rostock Cornea Module: HRT-II RCM). Prospective comparative study. We studied 21 right eyes of 21 AKC patients (11 males, 10 females; mean age, 26.3 years) as well as 19 right eyes of 19 normal subjects (12 males, 7 females; mean age, 28.4 years). All subjects underwent corneal sensitivity measurements, Schirmer test, tear film break-up time, fluorescein and Rose Bengal stainings, and HRT-II confocal laser scanning microscopy of the central cornea. The epithelial and endothelial cell densities of the central cornea, the density of subbasal long nerve fibers (LNFs) and total nerve branches (NBs) of the subbasal nerve plexus were calculated. The morphologic characteristics of the corneal nerves were studied. Correlation between nerve density, tear functions, and ocular surface examination parameters were investigated. The corneal sensitivity, tear stability and vital staining scores were significantly worse in eyes with AKC (P<0.01). Eyes with AKC showed a significantly lower density of basal epithelial cells, LNFs, and NBs compared with normal eyes. Nerve fiber abnormalities such as increased tortuosity, bifurcation abnormality, sharp deflections, and thickening of stromal nerves, as well as several inflammatory cells in close proximity of the subbasal and stromal nerve fibers were observed. The corneal disease in AKC was associated with significant alterations of the basal epithelium, and subbasal and stromal corneal nerves, which related to the changes in tear functions and corneal sensitivity. Confocal scanning laser microscopy was useful to study the pathological in vivo corneal changes in AKC.

The differences of tear function and ocular surface findings in patients with atopic keratoconjunctivitis and vernal keratoconjunctivitis

The pathogenesis of the ocular surface disease in atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC) has not been fully understood. We tried to clarify the differences in the ocular surface status in patients with AKC, VKC, and healthy control subjects. Twenty-four eyes of 12 AKC patients, 12 eyes of six VKC patients, and 20 eyes of 10 normal control subjects were studied. The subjects underwent corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT), vital staining of the ocular surface, conjunctival impression and brush cytology. Impression cytology samples underwent periodic acid Schiff staining for goblet cell density, squamous metaplasia grading, and immunohistochemical staining for MUC1, 2, 4, and 5AC. Brush cytology specimens underwent staining for inflammatory cell counting and Real Time PCR for MUC1, 2, 4, and 5AC mRNA expression. The mean BUT, corneal sensitivity, and conjunctival goblet cell density values in AKC patients were significantly lower compared with VKC patients and control subjects. The squamous metaplasia grades in eyes with AKC were significantly higher compared to eyes with VKC and controls. The inflammatory cell response in brush cytology specimens was different between patients with AKC and VKC. Eyes with AKC showed significantly higher MUC1, 2 and 4 and lower MUC5AC mRNA expression compared to eyes with VKC. Differences of the infiltrates, higher level of tear instability, lower corneal sensitivity, up-regulation of MUC1, 2, and 4, and down regulation of MUC5AC were important differential features of the ocular surface disease in AKC compared with VKC.

Alterations of the ocular surface epithelial mucins 1, 2, 4 and the tear functions in patients with atopic keratoconjunctivitis

An increased understanding of the ocular surface alterations at the cellular level in the conjunctiva and the cornea, may help explain the pathogenesis and the subsequent clinical appearance of atopic ocular allergies, which may be potentially blinding. To investigate MUC 1, 2 and 4 alterations, tear function and the ocular surface disorder in patients with atopic keratoconjunctivitis. Twenty-eight eyes of 14 atopic keratoconjunctivitis patients as well as 22 eyes of 11 age-and sex-matched normal subjects were studied. The subjects underwent corneal sensitivity measurements, Schirmer's test, tear film break-up time (BUT), fluorescein and Rose Bengal staining of the ocular surface, conjunctival impression cytology and brush cytology. Impression cytology samples underwent periodic acid-Schiff and immunohistochemical staining with MUC 1, 2 and 4 antibodies. Brush cytology specimens underwent evaluation for inflammatory cell numbers and quantitative real-time-PCR for MUC 1, 2 and 4 mRNA expression. Patient eyes with fluorescein and Rose Bengal scores greater than four points were regarded to have significant epithelial disease in this study. The mean corneal sensitivity and BUT values were significantly lower in atopic patients with significant epithelial disease, compared with patients with insignificant epithelial disease and controls (P < 0.01). Brush cytology specimens from patients with significant epithelial disease revealed significantly higher numbers of inflammatory cells (P < 0.01). Specimens from patient eyes showed positive staining for MUC 1, 2 and 4. MUC 1, 2 and 4 mRNA expressions were significantly higher in eyes with significant epithelial disease compared with eyes with insignificant epithelial disease and eyes of control subjects. Ocular surface inflammation, decline in corneal sensitivity, tear film instability, changes in conjunctival epithelial MUC 1, 2 and 4 mRNA expressions were thought to be important in the pathogenesis of atopic ocular surface disease.

Comparison of the effects of moxifloxacin (0.5%) and gatifloxacin (0.3%) ophthalmic solutions on corneal sensitivity

Purpose This study was designed to evaluate any changes in corneal sensitivity induced by the topical ophthalmic fluoroquinolone solutions moxifloxacin and gatifloxacin compared to placebo. Methods This contralateral, double masked, placebo controlled, three visit study enrolled healthy subjects with normal ocular health. Subjects were randomized to one of three treatment groups, which adhered to 10 days of QID dosing: moxifloxacin in one eye and placebo in the other, gatifloxacin in one eye and placebo in the other, or moxifloxacin in one eye and gatifloxacin in the other. Measurements of corneal sensitivity were recorded at baseline and at the two evaluatory visits (Day 7 and 14). A Cochet-Bonnet aesthesiometer was used to determine corneal sensitivity, as an indicator of any potential ocular neuropathic effects. Results Ninety two subjects completed the study. No significant differences in corneal sensitivity for moxifloxacin, gatifloxacin, or placebo-treated eyes were evident at Day 7 or Day 14 as compared to baseline. Similarly, there were no significant differences in corneal sensitivity measurements between the two fluoroquinolones. Conclusions Though peripheral neuropathies have been reported with use of systemic fluoroquinolones, this does not appear to be the case with ophthalmic fluoroquinolone formulations.

Atopic Ocular Surface Disease

To describe tear function, mucin alterations, and ocular surface disorder in patients with atopic diseases. Subjects underwent corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT) assay, and fluorescein and rose Bengal staining of the ocular surface. Conjunctival impression cytology and brush cytology were also conducted. Impression cytology samples underwent PAS and immunohistochemical staining for MUC5AC. Brush cytology specimens underwent evaluation for inflammatory cell expression and RT-PCR for MUC5AC mRNA expression. Differences related to tear function and ocular surface examination parameters among patients with and without corneal ulceration and healthy control subjects were studied. Mean corneal sensitivity and BUT values were significantly lower in atopic patients with corneal ulcers compared with patients without ulcers and controls (P<0.001). Brush cytology specimens from patients with corneal ulcers revealed significantly higher expression of inflammatory cells compared with patients without ulcers and controls (P<0.001). Impression cytology samples from eyes with corneal ulcers showed significant squamous metaplasia and reduction of goblet cell density compared with eyes without ulcers and control subjects. Specimens from eyes with corneal ulcers showed PAS (+) mucin pick up and did not stain positive for MUC5AC. MUC5AC mRNA expression was significantly lower in eyes with corneal ulcers compared with in eyes without ulcers and control subjects. Ocular surface inflammation, tear film instability, and decreased conjunctival MUC5AC mRNA expression are important in the pathogenesis of noninfectious corneal shield ulcers in atopic ocular surface disease.

Corneal mechanical sensitivity measurement using a staircase technique

To determine the repeatability of an unequal staircase technique (Garcia-Perez Staircase, GPS) to measure corneal mechanical threshold using the CRCERT-belmonte Aesthesiometer, and to compare this with a previously-reported psychophysical method (method of constant stimuli, MOCS). The GPS, utilising unequal ascending and descending steps, was used to obtain a threshold measurement from the mean of six response reversals. repeatability was determined for the GPS and MOCS methods (N = 14), and threshold results obtained with each method were compared (N = 10). The GPS (65.0 +/- 16.9 mL min(-1); CoR +/- 18.3 mL min(-1)) method was more repeatable than the MOCS (64.0 +/- 15.7 mL min(-1); CoR +/- 37.3 mL min(-1)) and the absolute values obtained with the two methods were not significantly different. Although each method gave equivalent threshold results, the GPS method was more repeatable and quicker to apply and hence should reduce the influence of patient fatigue and help to minimise possible carry-over effects.

Tear Function and Ocular Surface Alterations with Lactoferrin Treatment in Severe Dry Eyes

Purpose: To assess the changes in tear functions, ocular surface findings and dry eye symptomatology in severe dry eye patients with oral lactoferrin supplementation and compare the results with those of healthy control subjects. Methods:Fourteen eyes of 7 Sjogren’s syndrome patients( 4 males, 3 females; mean age:63.5 years) who had no improvement in tear functions and ocular surface vital staining scores after at least 8 weeks of conventional treatment with preservative free artificial tears, autologous serum eye drops and punctum plug applications as well as 10 eyes of 5 age and sex matched healthy control subjects were enrolled in this study. All subjects received lactoferrin supplement (270mg/day) for 2 months and underwent tear film lipid layer interferometry examinations with assessment of lipid layer thickness(DR–1, Kowa, Tokyo), Schirmer test–1, tear film break up time and corneal sensitivity measurements as well as ocular surface vital staining with fluorescein and Rose Bengal dyes before and after supplement therapy. Dry eye symptomatology was assessed with visual analog score scales. Results: There were no considerable changes in Schirmer test values before and 2 months after lactoferrin supplementation in all subjects. Pre treatment tear stability, interferometry dry eye grades and ocular surface staining scores fared worse in dry eye patients compared to controls. Tear stability, interferometry dry eye grades and ocular surface staining scores improved in all dry eyes with thickening of the tear film lipid layer(p<0.05). Lactoferrin supplementation was not associated with considerable thickening of the lipid layer in the control subjects. Dry eye symptomatology improved in all patients with significance. The need for artificial tear drops in the patients decreased from an average of 12 drops/day to a mean value of 5.5 drops / day within 2 months(p<0.05). Conclusions: Lactoferrin supplementation in severe dry eye patients is associated with improvement of dry eye symptoms, tear stability and vital staining scores owing to alterations in the tear film lipid layer.

Ocular Surface and MUC5AC Alterations in Atopic Patients with Corneal Shield Ulcers

Purpose: To describe MUC5AC alterations and the ocular surface disorder in atopic patients with or without corneal ulcers. Methods: Atopic patients' eyes were divided into two groups according to the presence and absence of corneal ulceration. The subjects underwent corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT), fluorescein and Rose Bengal staining of the ocular surface and conjunctival impression cytology and brush cytology. Impression cytology samples underwent PAS and immunohistochemical staining for MUC5AC. Brush cytology specimens underwent evaluation for inflammatory cell expression and quantitative real-time PCR for MUC5AC mRNA expression. The differences related to the tear function and ocular surface examination parameters between patients with and without corneal ulceration and healthy control subjects were studied. In addition, the differences of the study parameters related to ocular surface epithelial health and inflammatory status between patient eyes with atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC) were investigated. Results: The mean corneal sensitivity and BUT values were significantly lower in atopic patients with corneal ulcers, compared to patients without ulcers and controls (p < 0.001). Brush cytology specimens from patients with corneal ulcers revealed significantly higher expression of inflammatory cells compared to patients without ulcers and controls (p < 0.001). Impression cytology samples from eyes with corneal ulcers showed significant squamous metaplasia and reduction in goblet cell density compared to eyes without ulcers and eyes of control subjects. The mean squamous metaplasia grade was significantly higher in eyes with AKC compared to eyes with VKC (p < 0.02). The mean goblet cell density was significantly lower in eyes with AKC compared to eyes with VKC (p < 0.01). Specimens from eyes with corneal ulcers showed PAS positive mucin pickup and did not stain positive for MUC5AC. MUC5AC mRNA expression was significantly lower in eyes with corneal ulcers compared to eyes without ulcers and eyes of control subjects. MUC5AC mRNA expression was also significantly lower in eyes with AKC compared to eyes with VKC. Conclusions: Ocular surface inflammation, tear film instability, and decreased conjunctival MUC5AC mRNA expression were thought to be important in the pathogenesis of noninfectious corneal shield ulcers in atopic ocular surface disease.

Ocular surface changes with applanation contact lens and coupling fluid use after argon laser photocoagulation in noninsulin-dependent diabetes mellitus

Purpose To describe the effect of coupling solutions used during laser photocoagulation on the ocular surface of patients with noninsulin-dependent diabetes mellitus (NIDDM). Design A prospective case-controlled study. Methods Ninety-two eyes of 46 NIDDM patients with clinically significant macular edema, poor metabolic control of diabetes, and peripheral neuropathy and 100 eyes of 50 normal control subjects were studied. The patients' eyes were assigned to argon green focal/grid laser photocoagulation using an applanation contact lens and one of the coupling fluids; 2% methocel, Thilo-Tears Gel, 1.4% sodium hyaluronate, or 0.9% simple saline. The control subjects received time-matched three-mirror contact lens fundus examinations. All subjects underwent corneal sensitivity measurements, Schirmer test, tear film breakup time, and corneal fluorescein staining before as well as 3 and 8 days after the laser procedures and contact lens examinations. Patients with corneal problems persisting after 8 days were followed longer. Results Diabetic eyes assigned to 2% methocel and 1.4% sodium hyaluronate had significantly lower mean corneal sensitivities and break-up time values as well as significantly higher mean fluorescein staining scores at all examination points after laser photocoagulation. All diabetic eyes with aqueous deficiency assigned to 2% methocel and 1.4% sodium hyaluronate developed delayed corneal epithelial healing. Conclusion The use of viscous coupling solutions during applanation contact lens–aided laser procedures may be detrimental for the corneal epithelium in poorly controlled NIDDM patients with peripheral neuropathy and coexisting aqueous deficiency.

Tear function and ocular surface findings in premature and term babies

Objective To describe the ocular surface and tear function findings in premature and term babies. Design Prospective, case–control study. Participants Forty-eight eyes of 24 premature babies seen at the Department of Ophthalmology of Uludag University School of Medicine, Bursa, Turkey, from March 2002 through September 2002 and 50 eyes of 25 healthy term babies were studied. Intervention The subjects underwent routine ophthalmic examinations; corneal sensitivity measurements; Schirmer test with anesthesia, with and without nasal stimulation; primary Jones test; fluorescein staining of the ocular surface; and conjunctival impression cytology. Main outcome measures Premature and term babies were compared for corneal sensitivity, lacrimal drainage system patency, tear function and ocular surface staining parameters, goblet cell density, and squamous metaplasia grade. The relation of these parameters to the status of the ocular surface was also investigated. Results Mean corneal sensitivity scores were 45±5.0 mm and 55±4.5 mm in the premature and term babies, respectively ( P<0.001). Premature babies had a mean corneal fluorescein staining score of 1.5±0.25 points, compared with 0.22±0.28 points in the term babies ( P<0.001). The mean Schirmer test scores without and with stimulation were 1.5±2.5 mm and 4.15±2.5 mm in the premature babies, respectively, compared with 15±3.5 mm and 18.75±4.5 mm in the term babies. The intragroup and intergroup Schirmer test scores were statistically significant ( P<0.001). The primary Jones test was positive in 20.8% of the eyes in the premature babies, whereas it was positive in 84% of eyes in the term babies. The premature babies with positive primary Jones test results all had corneal epithelial defects or severe superficial punctuate keratopathy. Mean conjunctival impression cytology squamous metaplasia scores were 1.86±1.2 in the premature babies and 0.86±0.47 in the term babies ( P<0.001). Mean goblet cell densities were 393±484 cells/mm 2 and 739±503 cells/mm 2 in the premature and term babies, respectively ( P<0.001). Conclusion Decreased corneal sensitivity, reduced tearing, and lacrimal drainage patency are important determinants of ocular surface disease in premature infants. Premature newborns with low Schirmer test scores and a patent lacrimal system may experience corneal and conjunctival epithelial problems and should be carefully checked for the presence of dry eye complications.