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.

Background—It is recognized that inflammation is an underlying cause of dry eye disease (DED), with cytokine release involved. We systematically reviewed literature with meta-analyses to quantitatively summarize the levels of tear cytokines in DED. Methods—The PubMed, Embase, Web of Science, Ovid, Cochrane, and Scopus databases were reviewed until September 2019, and original articles investigating tear cytokines in DED patients were included. Differences of cytokines levels of DED patients and controls were summarized by standardized mean differences (SMD) using a random effects model. Study quality was assessed by applying Newcastle-Ottawa-Scale and the GRADE quality score. Methods of analytical procedures were included as covariate. Results—Thirteen articles investigating 342 DED patients and 205 healthy controls were included in the meta-analysis. The overall methodological quality of these studies was moderate. Systematic review of the selected articles revealed that DED patients had higher tear levels of interleukin (IL)-1β, IL-6, chemokine IL-8, IL-10, interferon-γ, IFN-γ, and tumor necrosis factor-α, TNF-α as compared to controls. Evidence was less strong for IL-2 and IL-17A. Conclusions—Data show that levels of tear cytokines in DED and control display a great variability, and further studies of higher quality enrolling a higher number of subjects are needed, to define a cut-off value.

Neurotrophic keratitis (NK) is a degenerative corneal disease caused by damage of trigeminal corneal innervation, which leads to spontaneous epithelial breakdown and corneal ulceration. The impairment of corneal sensory innervation causes the reduction of both protective reflexes and trophic neuromodulators that are essential for the vitality, metabolism, and wound healing of ocular surface tissues. A wide range of ocular and systemic conditions, including herpetic keratitis, ocular chemical burns, corneal surgery, diabetes, multiple sclerosis, and neurosurgical procedures, can cause NK by damaging trigeminal innervation. Diagnosis of NK requires careful investigation of any ocular and systemic condition associated with the disease, complete ocular surface examination, and quantitative measurement of corneal sensitivity. The clinical stages of NK range from corneal epithelial alterations (stage 1) to persistent epithelial defect (stage 2) and ulcer (stage 3), which may progress to corneal perforation. Management of NK is based on clinical severity, and the aim of the therapy is to halt the progression of corneal damage and promote epithelial healing. Although several medical and surgical treatments have been proposed, no therapies are currently available to restore corneal sensitivity, and thus, NK remains difficult and challenging to treat. The purpose of this review is to summarize available evidence on the pathogenesis, diagnosis, and treatment of NK. Novel medical and surgical therapies including the topical administration of nerve growth factor and corneal neurotization are also described.

Purpose: To assess whether omega-3 fatty acid (FA) supplementation is more efficacious than placebo in amelioration of signs and symptoms of dry eye disease. Methods: We performed a systematic literature search in PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. We included randomized clinical trials comparing omega-3 FA supplementation with placebo in patients with dry eye disease. The outcome measures were dry eye symptoms, breakup time (BUT), Schirmer test, and corneal fluorescein staining. The pooled effect sizes were estimated using a random-effects model. Heterogeneity was evaluated using the Q and I² tests. Sensitivity analysis and assessment of publication bias were performed. Meta-regression was performed to evaluate the source of heterogeneity. Results: Seventeen randomized clinical trials involving 3363 patients were included. Compared with placebo, omega-3 FA supplementation decreased dry eye symptoms [standardized difference in mean values (SDM) = 0.968; 95% confidence interval (CI) 0.554–1.383; P < 0.001] and corneal fluorescein staining (SDM = 0.517; 95% CI, 0.043–0.991; P = 0.032), whereas it increased the BUT (SDM = 0.905; 95% CI, 0.564–1.246; P < 0.001) and Schirmer test values (SDM = 0.905; 95% CI, 0.564–1.246; P < 0.001). No evidence of publication bias was observed, and sensitivity analyses indicated the robustness of results obtained. Meta-regression analysis showed a higher improvement of dry eye symptoms and BUT in studies conducted in India. Conclusions: This meta-analysis provides evidence that omega-3 FA supplementation significantly improves dry eye symptoms and signs in patients with dry eye disease. Therefore, our findings indicate that omega-3 FA supplementation may be an effective treatment for dry eye disease.