Santosh Khanal

Dry Eye Diagnosis

PURPOSE To determine the most effective objective tests, applied singly or in combination in the diagnosis of dry eye disease. METHODS Two groups of subjects--41 with dry eye and 32 with no ocular surface disease--had symptoms, tear film quality, evaporation, tear turnover rate (TTR), volume and osmolarity, and meibomian gland dropout score assessed. RESULTS The subjects with dry eye had TTR, tear evaporation, and osmolarity significantly different from that of healthy normal subjects. Cutoff values between the groups were determined from distribution curves for each aspect of tear physiology, and the effectiveness of the cutoff was determined from receiver operator characteristic (ROC) curves. Values of 12%/min for TTR, 33 g/m(-2)/h for evaporation, and 317 mOsmol/L for osmolarity were found to give sensitivities, specificities, and overall accuracies of 80%, 72%, and 77%; 51%, 96%, and 67%; and 78, 78%, and 79%, respectively when applied singly as diagnostic criteria in dry eye. In combination, they yielded sensitivities, specificities, and overall accuracy of 100%, 66%, and 86% (in parallel) and 38%, 100%, and 63% (in series), respectively. Discriminant function analysis incorporating these three factors in an equation allowed diagnosis with a sensitivity of 93%, specificity of 88%, and overall accuracy of 89%. CONCLUSIONS Tear osmolarity is the best single test for the diagnosis of dry eye, whereas a battery of tests employing a weighted comparison of TTR, evaporation, and osmolarity measurements derived from discriminant function analysis is the most effective.

Assessment of Tear Film Dynamics: Quantification Approach

The dynamics of the tear film are reviewed with specific reference to the biophysical aspects: distribution, turnover and elimination through evaporation, drainage, and absorption. The review concentrates on quantitative assessments and is confined to aspects of the dynamics that can be fully and directly measured. The techniques of fluorophotometry, fluorescein clearance, lacrimal scintigraphy, evaporimetry and osmometry are described. Reports in the literature for values of tear turnover (flow), evaporation and osmolarity for normal and dry eyes are collated. Indices of tear film dynamics based on these measurements, including tear function index, total tear flow, and osmolarity, are discussed in relation to their potential in the differential diagnosis of dry eye and new referent values for the disease suggested. The limitations of derivation and application of these indices are discussed.

Changes in corneal sensitivity and tear physiology after phacoemulsification.

Purpose:  To identify any changes in corneal sensitivity and tear physiology after phacoemulsification and to evaluate the effectiveness of the use of ophthalmic lubricants.

Effect of an oil-in-water emulsion on the tear physiology of patients with mild to moderate dry eye.

Purpose: To determine the effect of an oil-in-water emulsion eye drop compared with a conventional dry eye supplement (hypromellose) on tear physiology in dry eye. Methods: A randomized parallel, longitudinal, and investigator-masked study of the efficacy of 1.25% castor oil emulsion and 0.32% hypromellose solution was carried out. A total of 53 patients with mild to moderate dry eye (27 in emulsion group and 26 in hypromellose group) were recruited for the study. Patients were enrolled if they reported at least 2 symptoms on a McMonnies Dry Eye Questionnaire together with 1 of the following screening tests: noninvasive tear breakup time (5-10 seconds) and Schirmer test without anesthesia (2-5 mm in 5 minutes). Patients were instructed to use the test solutions 3 times a day for 30 days. Tear production, evaporation, lipid layer structure, and osmolality were measured before and 30 days after use of the drops. Results: A statistically significant decrease was seen after 1 month in tear evaporation rates with both emulsion (7.25 ± 5.43 g/m2/h) and hypromellose (2.02 ± 4.75 g/m2/h). However, the decrease with emulsion was significantly greater than with hypromellose (P < 0.001). Lipid layer structure improved from day 1 to day 30 of the study with the emulsion but not with the hypermellose. No significant changes were seen in tear production and osmolality with either of the drops. Conclusions: The oil-water emulsion was more effective in reducing tear evaporation than hypromellose after repeated application over a 1-month period. This finding signifies the potential of the emulsion in the management of evaporative dry eye.

Tear physiology of aqueous deficiency and evaporative dry eye

Purpose. To determine the differences in tear physiology between aqueous deficiency dry eye (ADDE) and evaporative dry eye (EDE), and evaluate their utility in diagnosis. Methods. Fifty-six dry eye patients were classified into 30 ADDE and 26 EDE according to the recently published Dry Eye Workshop criteria. A range of tear physiology measures comprising of tear evaporation, turnover rate (TTR), distribution, volume and osmolarity, and meibomian gland dropout were measured in these patients. The effectiveness of the tests, singly and in combinations, in differentiating between the dry eye subtypes was evaluated by retrospective allocation into groups and by Receiver Operative Characteristics (ROC) curve analysis. Results. Statistically significant differences were seen for TTR and tear evaporation (with lower values for ADDE) between ADDE and EDE, but no significant differences were seen for tear osmolarity, volume, distribution, and meibomian gland dropout scores. Differentiation of ADDE and EDE by a cut-off value of 11%/min for TTR was found to have a sensitivity of 86%, specificity of 75%, positive predictive value 89%, negative predictive value 69%, and overall accuracy 83%. The area under the curve on the ROC curve was 0.83. For tear evaporation, a cut-off of 60 g/m2h was found to have a sensitivity of 77%, specificity of 55%, positive predictive value 38%, negative predictive value 80%, and overall accuracy 58% in subtype differentiation. The area under the curve was 0.59 on the ROC curve. The distribution curve of the evaporation rates for ADDE and EDE, showed an overlap coefficient of 0.76 indicating that tear evaporation is within a similar range in these two dry eye subtypes. Conclusions. Tear turnover is significantly lower in ADDE than EDE, but there is considerable overlap of tear evaporation between the two dry eye subtypes. Tear osmolarity and turn over tests can be conducted sequentially to effectively diagnose dry eye and its subtypes.

Tear physiology in dry eye associated with chronic GVHD

The purpose of this study was to compare tear physiology characteristics of chronic GVHD (cGVHD)-associated dry eye to dry eye caused by Sjogren’s syndrome (SS), a extreme form of aqueous-deficient dry eye, and meibomian gland dysfunction (MGD), the major cause of evaporative dry eye. Tear turnover rate, evaporation and osmolarity along with meibomian gland dropout and lipid layer interferometric patterns were assessed in the right eyes of 12 patients with dry eye associated with cGVHD, 12 age-matched patients with SS and 12 age-sex matched subjects with MGD. In cGVHD, the decrease in tear turnover rate was similar (P=0.33), but the number of non-functioning meibomian glands was significantly higher (P<0.01) than in SS. Tear evaporation rate in cGVHD dry eye was found to be similar to that in MGD (P=0.36) and significantly higher than in SS (P<0.01). The lipid layer was most unstable in cGVHD compared with other groups. There was no variation in tear volume across all groups. Although statistical significance was not detected, the mean tear osmolarity (333.51±14.67mOsm/L) was highest in cGVHD. Major aspects of tear physiology were severely impaired in cGVHD-associated dry eye.

Effect of artificial tears on tear stress test.

Purpose. To determine the effect of two artificial tears of different viscosities in the relief of environmental dry eye induced with a novel tear stress test (TST). Methods. A novel TST was developed and validated. The following four test conditions were evaluated in 12 healthy normal subjects in a cross-over and subject masked study; unprotected (no test solution used), relief (test solution instilled just after application of TST), immediate protection (test solution instilled just before application of TST), and chronic protection (1 week prophylactic use of the solution). The test solutions were Cellumed, with high viscosity, and Refresh Contacts, with low viscosity. Low contrast visual acuity, symptoms with analogue scales (symptom scoring), non-invasive tear break-up time, and tear evaporation were measured before (prestress) and 2 min after (poststress) application of TST. Two weeks of washout period was allowed after first test solution. Results. In unprotected test condition, there was no significant difference between pre- and poststress visual acuity (p = 0.102), tear evaporation (p = 0.530), and non-invasive tear break-up time (p = 0.878), however, poststress total symptom score was significantly higher than prestress (p = 0.002). No significant differences were seen between pre- and post-total symptom score at relief (p = 0.241 for Cellumed and 0.114 for Refresh Contacts) and immediate protection (p = 0.890 for Cellumed and 0.136 for Refresh Contacts) for both test solutions, whereas postsymptoms total score was significantly higher than prestress at chronic protection (p = 0.003 for both). No significant differences were seen in the effect of the two solutions in all test conditions. Conclusions. There is an increase in dry eye symptomatology after ocular stress. The use of artificial tears just before or after ocular stress is helpful in relieving resultant symptoms in normals.