Clinical Research Of Corneal Neuropathy

PartⅠ Relation between Corneal Innervation with In Vivo Confocal Microscopy and Corneal Sensitivity with Contact Esthesiometry of the Normal Central Human CorneaPurpose:To investigate the corneal nerve density and the Langerhans cell (LC) density of normal central cornea in Chinese, and to evaluate whether they are correlated with mechanical corneal sensitivity.Methods:Twenty-four eyes of24healthy volunteers were recruited into1of the4age groups:aged20～29,30～39,40～49, or50years of age and older. All eyes were examined usingslit-lamp biomicroscopy, laser in vivo confocal microscopy (LSCM),and Cochet-Bonnet esthesiometer.Results:The mean corneal sensitivity of central, superior, inferior, nasal and temporal cornea were58.70±3.76mm,41.67±16.53mm,42.08±15.32mm,47.71±15.88mm,50.21±14.10mm respectively. The mean peripheral corneal sensitivity was47.77±9.51mm. The mean total corneal sensitivity was49.96±8.16mm. The difference between the central and superior (p=0.000), central and inferior (p=0.000), central and peripheral (p=0.012) was significant. No significant discrepancies were shown among different age groups or between genders (p>0.05). The mean corneal nerve densities (μm/frame) observed with LSCM were2442.09±653.05in total,2598.62±642.14in male, and2222.95±634.65in female (p=0.170). The mean LC densities (cell/mm2) were10.24±19.38in total,7.90±14.85for immature type and2.34±5.11for mature type. The mean LC densities in male and female were13.84±23.44and5.21±10.86respectively (p=0.292). There were no significant correlation among the corneal tactile sensitivities, the corneal nerve densities and the LC densities of central cornea.Conclusion:Compared with the previous studies conducted in other ethnicities, the level of the corneal tactile sensitivity and the corneal nerve density in Asian were the same as in theirs; while the LC density of central cornea and the percentage of eyes that exhibited LCs in this area were higher than those reported in previous surveys. No correlation among the corneal tactile sensitivities, the corneal nerve densities and the LC densities of central cornea were found. Part IIRelation between the Symptoms and the Corneal Innervation of Non-Sjogren’s Syndrome Dry Eye PatientsPurpose:To investigate the value of and the relation between symptoms, dry eye signs, mechanical corneal sensitivity, and corneal innervation of mild to medium non-Sjogren’s syndrome dry eye patients.Methods:Twenty-four eyes of24non-Sjogren’s syndrome dry eye patients, and twenty-four eyes of24age-and sex-matched healthy controls were recruited to the study. Ocular surface disease index (OSDI) questionnaire and visual analog scales (VAS) were used to assesssubjective symptoms.Hospital Anxiety and Depression Scale (HADS) was applied for psychological evaluation. All eyes were examined with slit-lamp biochemistry, Schirmer I test (Sit), tear breakup time (TBUT), corneal staining with fluorescein (FL) and laser in vivo confocal microscopy (LSCM). The mechanical corneal sensitivity was measuredusing Cochet-Bonnet esthesiometer.Results:OSDI and VAS scores were high in NSSDE patients, being5.83+3.23and1.79±0.38, compared with controls (p<0.001). Anxiety and depression scores of HADS in NSSDE patients were4.84±3.00and4.21±3.55, the same as those in controls (a=3.38±1.88, p(a)=0.189; d=4.5±2.72, p(d)=0.988). The mean SIt and TBUT value of NSSDE group were9.75±5.99mm and3.92±2.31sec, which were significantly lower than those of the control group, being14.26±8.18mm (p=0.036) and11.89±6.43sec (p=0.000). The mean corneal detection threshold was a little lower in patients than in controls (48.91±7.42mm vs.49.96±8.16mm, p=0.622). The nerve density of central cornea of NSSDE patients was higher than that of controls (2826.28±291.24μm/frame vs.2442.09±653.05μm/frame, p=0.030). The LC density of central cornea of NSSDE patients was higher than that of controls (33.43±39.80cell/mm2vs.10.24±19.38cell/mm2, p=0.014).72.73%NSSDE patients were found LCs in their central cornea, while only41.67%controls showed that. VAS scores were positively correlated with OSDI scores, corneal nerve densities and LC densities of central cornea (rho value were0.722, p<0.001;0.322, p=0.032;0.337, p=0.025respectively). TBUT was negatively correlated with VAS (rho=-0.613, p<0.001) and OSDI scores (rho=-0.600, p<0.001), SIt was positively correlated with TBUT (rho=0.342, p=0.019), and negatively correlated with HADd (rho=-0.330, p=0.033)。HADd was positively correlated with nerve densities of central cornea (rho=0.348, p=0.026).Conclusion:The corneal mechanical sensitivity in mild to medium NSSDE patients basically remained normal; while the nerve density and inflammation cells of central cornea increased with the severity of dry eye symptoms. Part IIISymptoms, Signs and Morphology of Corneal Innervation of Corneal NeuropathyPurpose:To characterize the symptoms, signs and corneal innervation of corneal neuropathy.Methods:Twenty-five eyes of25corneal neuropathy patients, twenty-four eyes of24age-and sex-matched non-Sjogren’s syndrome dry eye patients, and another twenty-four eyes of24healthy controls were recruited to the study. Ocular surface disease index (OSDI) questionnaire and visual analog scales (VAS) were used to assesssubjective symptoms.Hospital Anxiety and Depression Scale (HADS) was applied for psychological evaluation. All eyes were examined with slit-lamp biochemistry, Schirmer I test (SIt), tear breakup time (TBUT), corneal staining with fluorescein (FL) and laser in vivo confocal microscopy (LSCM). The mechanical corneal sensitivity was measuredusing Cochet-Bonnet esthesiometer.Results:The mean SIt of corneal neuropathy patients was (12.79±7.29mm), TBUT was11.90±3.67sec, and FL score was0.02±0.14, all of which were the same as those of controls (14.26±8.18mm;11.89±6.43sec;0.02±0.15; p>0.1), but lower than those of the NSSDE patients (9.75±5.99mm;3.92±2.31sec sec;0.42±0.97; p<0.001). There were no differences of the HADS scores among the three groups (p>0.05). The OSDI (38.67±19.51) and VAS scores (5.29±1.74) of corneal neuropathy were almost the same as those of NSSDE patients (29.80±15.83;4.77±1.79; p>0.05), but higher than those of controls (7.84±8.26;0.00; p<0.001). And OSDI was positively correlated with VAS (rho=0.458, p<0.01). The corneal sensitivity of neuropathy patients (56.43±4.51mm), higher than that of NSSDE patients (48.91±7.42mm) and controls (49.96±8.16mm)(p<0.001). The mean corneal nerve densities of neuropathy, NSSDE and controls were (u m/frame):3094.35±887.09,2668.36±534.59and2476.08±600.23respectively (p=0.011). The LC density of central cornea in neuropathy group was59.51±83.12cell/mm2, higher than that in NSSDE group (33.43±39.80, p>0.10) and in controls (10.24±19.38, p<0.01). In neuropathy patients, the LC densities of central cornea were positively correlated with OSDI scores (0.423, p=0.04).Conclusion:Corneal neuropathy could be identified and diagnosed through dry eye investigations. Though the causes and risk factors were unclear yet, patients with dry eye-like symptoms, increased corneal sensitivity and changes of corneal nerve morphology, and without signs of dryness, should be suspected of the morbidity.