This report provides an evidence-based review of current strategies to manage dry eye disease (DED). First-line management focuses on methods to replenish, conserve, and stimulate the tear film, with an emphasis on ocular supplements, which remain the cornerstone of DED treatment. Meibomian gland dysfunction, a primary contributor to DED, is typically treated with warm compresses and a wide variety of in-office treatments, including device-driven technologies to warm the eyelids, intense pulsed light therapy, low-level light therapy, and other new and emerging technologies. Lid hygiene treatments include lid wipes, anti-Demodex therapies, blepharoexfoliation, and topical antibiotics. DED caused by certain etiological drivers can benefit from anti-inflammatory therapies, including topical and oral corticosteroids, T-cell immunomodulatory drugs, and a wide variety of pharmacological agents, in addition to biologic tear substitutes such as autologous serum and platelet-rich plasma. Emerging therapies, such as neuromodulation via nasal neurostimulation and novel pharmacological treatments, offer potential future options. Advanced options, including amniotic membrane grafts and complex surgical methods, provide options for severe or refractory cases. Lifestyle modifications, including optimized blinking, dietary supplementation, and environmental adjustments, play a crucial role in long-term management. Patient education and adherence to treatment regimens remain essential for sustained symptom relief. The TFOS DEWS III prescribing algorithm provides an evidence-based framework to offer guidance to clinicians in selecting relevant interventions based on disease etiology that aim to provide targeted management of the relevant DED subtype(s) that an individual is experiencing.

Purpose.: To investigate the expression of CXCL9, -10, -11, and CXCR3 in the tear film and ocular surface of patients with dry eye syndrome. Methods.: Thirty-three patients with dry eye (16 with and 17 without Sjögren's syndrome) and 15 control subjects were recruited. The concentrations of CXCL9, -10, and -11 in tears were measured with enzyme-linked immunosorbent assays. The correlation between chemokine levels and tear film and ocular surface parameters was analyzed. The expression of CXCL9, -10, -11, and CXCR3 in the conjunctiva was evaluated by using immunohistochemistry. Flow cytometry was performed to count CXCR3⁺ cells and CXCR3⁺CD4⁺ cells in the conjunctiva. Results.: The concentrations of CXCL9, -10, and -11 were 1,148 ± 1,088, 24,338 ± 8,706, and 853 ± 334 pg/mL, in the patients with dry eye, and 272 ± 269 (P = 0.01), 18,149 ± 5,266 (P = 0.02), and 486 ± 175 (P < 0.01) pg/mL in the control subjects, respectively. The concentrations significantly increased in tears of the patients with Sjögren's syndrome compared with those of the patients with non-Sjögren's dry eye (P < 0.05). CXCL10 levels correlated significantly with basal tear secretion, and CXCL11 levels correlated significantly with basal tear secretion, tear clearance rate, keratoepitheliopathy score, and goblet cell density (P < 0.05). Staining for CXCL9, -10, -11, and CXCR3 increased in patients with dry eye, especially in the patients with Sjögren's syndrome. Flow cytometry demonstrated an increased number of CXCR3⁺ and CXCR3⁺CD4⁺ cells in all the patients with dry eye. Conclusions.: Expression of CXCL9, -10, -11, and CXCR3 increased in the tear film and ocular surface of patients with dry eye syndrome, especially in those with Sjögren's syndrome. CXCL11 levels correlated significantly with various tear film and ocular surface parameters. (ClinicalTrials.gov number, NCT00991679.)

Purpose: To investigate the expression of lipid peroxidation markers in the tear film and ocular surface and their correlation with disease severity in patients with dry eye disease. Methods: The concentrations of hexanoyl-lysine (HEL), 4-hydroxy-2-nonenal (HNE), and malondialdehyde (MDA) were measured with enzyme-linked immunosorbent assays in tears obtained from 44 patients with non-Sjogren syndrome dry eye and 33 control subjects. The correlations between the marker levels and the tear film and ocular surface parameters, including tear film break-up time (BUT), Schirmer tear value, tear clearance rate, keratoepitheliopathy scores, corneal sensitivity, conjunctival goblet cell density, and symptom score, were analyzed. The expression of the lipid peroxidation markers HEL, 4-HNE, and MDA in the conjunctiva was evaluated using immunohistochemistry. Results: The concentrations of HEL, 4-HNE, and MDA were 279.84 ± 69.98 nmol/L, 0.02 ± 0.01 μg/mL, and 3.80 ± 1.05 pmol/mg in control subjects and 283.21 ± 89.67 nmol/L (p = 0.97), 0.20 ± 0.03 μg/mL (p < 0.01), and 13.32 ± 4.03 pmol/mg (p < 0.01) in dry eye patients. 4-HNE and MDA levels significantly correlated with BUT, Schirmer tear value, tear clearance rate, keratoepitheliopathy scores, conjunctival goblet cell density, and symptom score (p < 0.05), whereas HEL levels did not correlate with these parameters. Staining intensities for 4-HNE and MDA increased in dry eye patients. Conclusions: The expression of late lipid peroxidation markers, 4-HNE and MDA, increases in the tear film and ocular surface of patients with dry eye. The levels correlate with various tear film and ocular surface parameters and may reflect the severity of dry eye disease.

To investigate the influences of smartphone use on ocular symptoms, status of the tear film, and oxidative stress indices in the tears and at the ocular surface. Eighty healthy volunteers were enrolled in the study. Subjective symptoms and asthenopia were evaluated using the ocular surface disease index (OSDI), visual analogue scale (VAS), and computer vision syndrome (CVS) score before and after smartphone or computer display (control) use. The status of the tear film was evaluated using fluorescein film break-up time (FBUT), non-invasive keratograph break up time (NIKBUT), Schirmer score, keratoepitheliopathy (KEP), and tear meniscus height (TMH). Oxidative stress markers in the tear film including hexanoyl lysine (HEL), 4-hydroxy-2-nonenal (4-HNE), malondialdehyde (MDA), and 8-oxo-2’-deoxyguanosine (8-OHdG) in the tear film were measured using ELISA. Reactive oxygen species (ROS) at the ocular surface were measured through 2’,7’-dichloro-dihydrofluorescein diacetate. All measurements were conducted at baseline, and after use for 1 and 4 h. All parameters showed no significant group-wise differences at baseline. Scores of OSDI, VAS, fatigue, burning sensation, and dryness showed significant increases after 1 and 4 h of smartphone use compared with those at baseline (all P < 0.05). The smartphone group showed higher OSDI, fatigue, burning, and dryness scores than the control group at 4 h. Smartphone use showed significantly decreased FBUT and NIBUT at 4 h than those at baseline (P < 0.01). In the smartphone group, the concentration of HEL significantly increased at 4 h compared with that at baseline and 1 h (P < 0.01). Both groups showed increased ROS with higher value in the smartphone group versus the control group at 4 h (P < 0.01). Smartphone use could not only aggravate subjective symptom indices such as the OSDI, VAS, and CVS but also induce tear film instability and oxidative stress indices in the tears and at the ocular surface.

Purpose.: To investigate the effects of visible light on human corneal epithelial cells and the impact of natural antioxidants on oxidative stress produced by overexposure to light. Methods.: Light-emitting diodes with various wavelengths (410–830 nm) were used to irradiate human corneal epithelial cells, and cell viability was assessed. The production of reactive oxygen species (ROS) was analyzed using 2′,7′-dichlorodihydrofluorescein diacetate (DCF-DA). Ethyl alcohol (EtOH) extracts were prepared from mixtures of medicinal plants. After application of the EtOH extracts, the free radical scavenging activity was measured using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The induction of antioxidant enzymes including heme oxygenase-1 (HO-1), peroxiredoxin-1 (Prx-1), catalase (CAT), and superoxide dismutase-2 (SOD-2) by the extracts was evaluated by reverse transcription-polymerase chain reaction and Western blotting. The ability of the extracts to inhibit ROS was also analyzed using DCF-DA. Results.: The viability of corneal epithelial cells was diminished after irradiation of blue light (above 10 J at 410 nm and 50 J at 480 nm). Reactive oxygen species production was induced by irradiation at 410 and 480 nm at doses of 5 J/cm² and higher. Ethyl alcohol extracts had potent radical scavenging activity. Application of the extracts not only increased the expression of HO-1, Prx-1, CAT, and SOD-2, but it also attenuated the ROS production induced by blue light in a dose-dependent manner. Conclusions.: Overexposure to blue light (410–480 nm) may have a harmful effect on human corneal epithelial cells compared with other visible light wavelengths. Medicinal plant extracts can have potent protective effects on blue light–induced oxidative stress.

Purpose.: To investigate the severity and duration of desiccating stress-induced dry eye disease between mice with and without a genetic predisposition to spontaneous autoimmunity. Methods.: Experimental dry eye was induced in 12- to 16-week-old wild-type C57BL/6 and autoimmune NOD.B10.H2 ^b mice by subcutaneous injection of scopolamine with exposure to an air draft for 10 days. Tear volume and corneal smoothness were measured at baseline, 5 and 10 days after desiccating stress, and 3, 7, 14, and 28 days after the removal of desiccating stress. Periodic acid-Schiff staining and immunohistochemistry were performed to evaluate the densities of conjunctival goblet cells and CD4⁺ T cells in each group. Interleukin (IL)-1β and IL-6 concentrations in conjunctival tissues were measured by multiplex immunobead assay. Results.: Signs of experimental dry eye were noted at 5 and 10 days after desiccating stress in both strains. After the removal of desiccating stress, in C57BL/6 mice, tear production and corneal smoothness improved at 3 and 7 days, respectively, and conjunctival goblet cells and CD4⁺ T-cell densities and cytokine levels returned to baseline levels at 14 days. In contrast, in NOD.B10.H2 ^b mice, none of the parameters recovered to baseline levels during a period of 28 days after the removal of desiccating stress. Conclusions.: After the removal of desiccating stress in experimental dry eye, tear volume and ocular surface parameters recovered within 2 weeks in C57BL/6 mice, whereas they remained unchanged in NOD mice. In contrast to autoimmune mice, experimental dry eye can be reversed after the elimination of desiccating stress in nonsusceptible mice.