Vincenzo Profazio

Performance of Tear Osmolarity Compared to Previous Diagnostic Tests for Dry Eye Diseases

Purpose: Tear osmolarity is considered a key point in dry eye disease (DED) and its measurement is the gold standard in dry eye diagnosis. Tear osmolarity was evaluated in dry eye (DE) patients vs. a control group to assess its diagnostic performance compared to clinical and laboratory tests performed in either clinical or research settings. Methods: Tear osmolarity was measured with the TearLab Osmolarity System (OcuSense) in 25 normal subjects and 105 DE patients (severity score 1–4, Dry Eye Workshop (DEWS)). The following tests were also performed: Ocular Surface Disease Index (OSDI) symptoms questionnaire, Schirmer I test, Tear Film Break Up Time (TFBUT), ferning test, lissamine green staining, tear clearance, corneal esthesiometry, and conjunctival cytology by scraping and imprint. Statistical evaluation was performed by unpaired Student’s t and Mann-Whitney tests, the Spearman’s ρ and the Pearson’s r correlation coefficients (significance p < 0.05); all variables were also analyzed for sensitivity, specificity, Receiver Operating Characteristics (ROC) curves, likelihood ratio LR+, and positive predictive value (PPV). Results: Tear osmolarity normal values were 296.5 ± 9.8 mOsm/L, increasing values were shown stepwise DE severity (mild to moderate to severe dry eye, respectively: 298.1 ± 10.6 vs. 306.7 ± 9.5 vs. 314.4 ± 10.1, p < 0.05). A progressive worsening occurred in all the parameters with DED severity increase. Tear osmolarity exhibited the larger correlation strength vs. tear clearance, TFBUT and clinical score, strength increased with DED severity, mainly to inflammatory score and corneal sensitivity. Tear osmolarity 305 mOsm/L was selected as cut-off value for dry eye, 309 mOsm/L for moderate dry eye, 318 mOsm/L for severe dry eye (Area-Under-the-Curve was 0.737, 0.759, and 0.711, respectively). Conclusions: Tear osmolarity can now be considered a test suitable to be performed in a clinical setting. It showed a good performance in dry eye diagnosis, higher than the other tests considered, mainly in severe dry eye. Tear osmolarity values should be interpreted as an indicator of DED evolutionary process to severity.

Eye discomfort and air pollution.

Discomfort eye syndrome (DES) comprises a series of ‘minor’ subjective symptoms in patients where no relevant clinical signs are observed suggesting ocular disease. Our study includes 100 DES patients, excluding video terminal users, selected from the First Aid Service of our Department over two peak periods in both winter and summer time. The Schirmer test I, ferning test, breakup time and conjunctival cytology (scraping and imprint) were performed and data were related to sex, age and air pollution indexes, recorded in the patients’ living zones. Our results demonstrate that: (i) the ocular surface cytology and the analysis of tear film changes provide significant information in those patients where no other clinical signs are evident; (ii) DES symptoms are more frequent in women than in men (ratio about 2:1), both with ages over 51 years; (iii) DES is significantly associated with ocular surface inflammation, as detected by cytological methods, and (iv) ocular surface subclinical inflammation and ocular dryness are related to high concentrations of atmospheric polluters, in both sexes.

Hyperosmolar Stress Upregulates HLA-DR Expression in Human Conjunctival Epithelium in Dry Eye Patients and In Vitro Models

PURPOSE To investigate the immune response of human conjunctival epithelium to hyperosmolar stress. METHODS Tear osmolarity was measured in 15 normal subjects and 25 dry eye (DE) patients; conjunctival imprint cytology samples were obtained at the nasal bulbar area. Subconfluent primary human conjunctival epithelial cells (pHCECs) and human conjunctival organ cultures (hCOCs), both cultured in iso-osmolar medium (305 mOsm/L), were exposed for 24 hours to media with progressively higher osmolarity, with or without the ion channel inhibitor ruthenium red (RuR). Human leukocyte antigen (HLA)-DR expression was evaluated by immunocytochemistry, on imprints from subjects, on primary human conjunctival epithelial cells, on formalin fixed-paraffin embedded hCOCs, and by RT-PCR. Statistical evaluation was performed by applying the unpaired Students t test, as well as Spearmans rho and Pearsons r correlation coefficients (significance P < 0.05). RESULTS HLA-DR expression increased in DE subjects with respect to control (% mean ± SD, respectively, 46.16 ± 7.2 vs. 7.48 ± 1.14, P < 0.0001) and exhibited significantly high correlations with tear osmolarity values (r = 0.614; P < 0.0001). In vitro experiments showed a progressive increase in HLA-DR expression as the osmolarity of the medium was increased from 6.75 ± 1.16 (% mean ± SD) in iso-osmolar-cultured cells to 9.96 ± 1.37 and 12.94 ± 4.04 in cells cultured in, respectively, 350 and 400 mOsm/L (P < 0.05). A stepwise progressive increase was also found in hCOCs. Results were confirmed by RT-PCR. Ruthenium red significantly reduced HLA-DR expression in hyperosmolar-cultured cells. CONCLUSIONS Data from complementary techniques demonstrate that extracellular hyperosmolarity induces HLA-DR overexpression in human conjunctival epithelial cells in both DE patients and in vitro cell culture models.

Dryness Symptoms, Diagnostic Protocol and Therapeutic Management: A Report on 1,200 Patients

Purpose: To report the diagnostic and therapeutic data obtained from 1,200 patients suffering from dry eye symptoms not due to Sjögren’s syndrome or other auto-immune diseases. Methods: Schirmer test I, ferning test, breakup time, vital dye staining, brush and imprint cytology were performed; data were grouped into diagnostic profiles, and the therapy was prescribed according to these. Results: Eight diagnostic profiles were identified. Dry eye was diagnosed in 57.1% of patients; the remaining 42.9% were found to suffer from eye discomfort or conjunctivitis of different aetiologies. Conclusions: Subjective symptoms of dryness can hide diseases other than dry eye; combined clinical and laboratory tests are requested to make a diagnosis. Our experience indicates that a therapy prescribed on the basis of diagnostic profiles provides relief in 79.1% of cases.

A Novel Scraping Cytology Score System (SCSS) Grades Inflammation in Dry Eye Patients

Purpose: We propose a conjunctival Scraping Cytology Scoring System (SCSS) as a reliable method to diagnose and score ocular surface inflammation in dry eye. Methods: Twenty normal subjects and 46 patients with dry eye of various severities were included in the study. Clinical signs were scored 1–4; an Ocular Surface Disease Index (OSDI) questionnaire was used to grade subjective symptoms. Concentrations of serum albumin and interleukin-6 (IL-6) in tears were evaluated. Scraped conjunctival cytology samples were processed and examined with light microscopy. The number of inflammatory cells was staged and sub-scores were assigned. SCSS resulted from their sum and ranged from 0–12. Statistical evaluation was performed by applying the unpaired Students t-test and the Spearmans correlation test (significance p < 0.05). SCSS was also analyzed for sensitivity, specificity, ROC curves, likelihood ratio LR+, positive (PPV) predictive value. Results: SCSS was positively correlated to clinical sign score, OSDI score, exudated serum albumin, and IL-6 in either control (Spearmans correlation test always p < 0.05) and in dry eye patients (respectively, p < 0.0001, p < 0.01, p < 0.05, and p < 0.0001). SCSS ≥ 4 was selected as the cut-off value for moderate dry eye (LR+ 10,9; PPV 22,5), SCSS ≥ 9 was selected as the cut-off value for severe dry eye (LR+ 15,6; PPV 26,2). Conclusions: SCSS can be applied in any trained laboratory. It is correlated with clinical signs and symptoms, and it shows a diagnostic performance to grade inflammation in dry eye, comparable to more expensive cytokine assay.

Efficacy of two-month treatment with Xiloial® eyedrops for discomfort from disposable soft contact lenses

Purpose: To evaluate the efficacy and tolerability of Xiloial® monodose eyedrops in the treatment of patients suffering from subjective symptoms of discomfort related to disposable soft contact lens (dSCL) wear. Methods: Fifteen (12 female, three male, medium age 39 ± 9 years) dSCL wearers were enrolled. Inclusion criteria were Ocular Surface Disease Index (ODSI) symptom questionnaire score >12, tear film break-up time (TFBUT) <10 sec, Schirmer test I >10 mm over five minutes, mild punctuate keratopathy, and conjunctival staining (Oxford grading ≤4). Monodose Xiloial eyedrops were administered three times daily for a two-month period. Patients were evaluated at enrollment, after three days of washout (baseline), and after one and two months of treatment, by OSDI score, Schirmer test I, TFBUT, ferning test, ocular surface damage (Oxford grade), and serum albumin in tears (index of passive exudation related to serum leakage). Results: At endpoint versus baseline, respectively, the mean ± standard deviation of all variables improved as follows: OSDI (8.5 ± 3 versus 20.2 ± 1.6); TFBUT (9.6 ± 1.1 versus 7.1 ± 1.0); Oxford grading (0.5 ± 0.1 versus 3.6 ± 0.8); ferning test (2 ± 1 versus 2.4 ± 0.5); and Schirmer test I (14.6 ± 1.1 versus 12 ± 2.1), with P < 0.05 for all variables (Friedman and Wilcoxon tests). Tolerability was high, with no adverse events noted. Conclusions: A two-month treatment with Xiloial showed good tolerance and appeared to reduce ocular surface damage and symptoms of discomfort.

One month use of Systane ® improves ocular surface parameters in subjects with moderate symptoms of ocular dryness

Objective To evaluate the efficacy of Systane® Lubricating Eye Drops in improving the symptoms of moderate ocular dryness. Methods Fifty subjects with moderate symptoms of ocular dryness were enrolled in this open label study. The mean age of subjects was 57.6 ± 15.4 years. To be eligible, subjects’ tear film break-up time (TFBUT) had to be <10 seconds, and subjects had to have at least one ocular discomfort symptom in addition to dryness. Saline was used for a washout period of 3–5 days. Subjects were re-examined, and those continuing to meet the inclusion criteria were dispensed Systane® and re-examined again after 28 days. At each visit, slitlamp examination was conducted, and ocular discomfort symptoms and TFBUT were evaluated. Subjects rated their overall satisfaction at baseline and on the last visit. Results No significant changes in TFBUT or ocular discomfort symptoms were observed after saline use, compared with screening visit. After 28 days of Systane® use there was statistically significant improvement of TFBUT (p = 0.0001) compared with baseline. Subjects experienced significant symptomatic relief for all 6 ocular discomfort symptoms at the endpoint visit. Conclusion Systane® effectively relieved the symptoms associated with moderate ocular dryness, with measurable improvement in objective TFBUT, subjective symptoms, and overall satisfaction.

Discomfort symptoms reduction and ocular surface parameters recovery with Artelac Rebalance treatment in mild-moderate dry eye.

Purpose To evaluate Artelac Rebalance® eyedrops’ efficacy in symptoms reduction, ocular surface parameters recovery, and tolerability in the treatment of mild to moderate dry eye. Methods Fifteen patients were enrolled. Inclusion criteria were Ocular Surface Disease Index (OSDI) score >16, tear film break-up time (TFBUT) <10 seconds, Schirmer test I >10 mm/5 min, and mild ocular surface damage (Oxford grading) ≤3. Artelac Rebalance® eyedrops were administered 3 times daily for 2 months. Patients were evaluated at enrollment, after 2 days of washout (baseline), and after 1 and 2 months of treatment. Parameters for ocular discomfort (OSDI score), tear film quality (Schirmer test I, TFBUT, tear osmolarity), ocular surface damage (fluorescein staining, conjunctival imprint cytology), and inflammation (scraping cytology and exuded serum albumin) were measured. Tolerability and satisfaction were assessed by validated questionnaires. Results At endpoint versus baseline, all variables showed a statistically significant improvement (paired Student t test, p<0.01 for all parameters) as follows: OSDI score (21.9 ± 10.6 vs 35.8 ± 12.2), TFBUT (6.5 ± 1.1 s vs 5.2 ± 2.3 s), Oxford grading of corneal and conjunctival damage (0.56 ± 0.50 vs 1.16 ± 0.37), tear osmolarity (294.6 ± 2.1 mOsm/L vs 303.1 ± 4.6 mOsm/L), conjunctival goblet cell density/mm2 (140.8 ± 43.3 cells/mm2 vs 115.1 ± 15.8 cells/mm2), scraping cytology score (2.9 ± 1.0 vs 4.2 ± 1.3), and percentage of serum albumin in tears (9.2% ± 4.8% vs 24.1% ± 10.8%). Tolerability and satisfaction were scored high, with no adverse events reported. Conclusions Application of Artelac Rebalance® eyedrops for 2 months in mild to moderate dry eye resulted in a reduction of ocular inflammation parameters, ocular surface damage, and subjective discomfort symptoms, with a parallel improvement in tear film quality (measured by TFBUT and osmolarity).