Mitochondrial dysfunctions are detrimental to organ metabolism. The cornea, transparent outmost layer of the eye, is prone to environmental aggressions, such as UV light, and therefore dependent on adequate mitochondrial function. While several reports have linked corneal defects to mitochondrial dysfunction, the impact of OPA1 mutation, known to induce such dysfunction, has never been studied in this context. We used the mouse line carrying OPA1delTTAG mutation to investigate its impact on corneal biology. To our surprise, neither the tear film composition nor the corneal epithelial transcriptomic signature were altered upon OPA1 mutation. However, when analyzing the corneal innervation, we discovered an undersensitivity of the cornea upon the mutation, but an increased innervation volume at 3 months. Furthermore, the fibre identity changed with a decrease of the SP + axons. Finally, we demonstrated that the innervation regeneration was less efficient and less functional in OPA1+/- corneas. Altogether, our study describes the resilience of the corneal epithelial biology, reflecting the mitohormesis induced by the OPA1 mutation, and the adaptation of the corneal innervation to maintain its functionality despite its morphogenesis defects. These findings will participate to a better understanding of the mitochondrial dysfunction on peripheral innervation.

This study explores the impact of electrostatic interactions and hydrogen bonding on tear film stability, a crucial factor for ocular surface health. While mucosal and meibomian layers have been extensively studied, the role of electrolytes in the aqueous phase remains unclear. Dry eye syndrome, characterized by insufficient tear quantity or quality, is associated with hyperosmolality, making electrolyte composition an important factor that might impact tear stability. Using a model buffer solution on a silica glass dome, we simulated physiologically relevant tear film conditions. Sodium chloride alone induced premature dewetting through salt crystal nucleation. In contrast, trace amounts of solutes with hydroxyl groups (sodium phosphate dibasic, potassium phosphate monobasic, and glucose) exhibited intriguing phenomena: quasi-stable films, solutal Marangoni-driven fluid influx increasing film thickness, and viscous fingering due to Saffman-Taylor instability. These observations are rationalized by the association of salt solutions with increased surface tension and the propensity of hydroxyl-group-containing solutes to engage in significant hydrogen bonding, altering local viscosity. This creates a viscosity contrast between the bulk buffer solution and the film region. Moreover, these solutes shield the glass dome, counteracting sodium chloride crystallization. These insights not only advance our understanding of tear film mechanics but also pave the way for predictive diagnostics in dry eye syndrome, offering a robust platform for personalized medical interventions based on individual tear film composition.

OBJECTIVE: To evaluate the diagnostic performance of corneal and conjunctival staining, and lid wiper epitheliopathy (LWE) in detecting dry eye disease, as defined by the global consensus Tear Film and Ocular Surface Society Dry Eye Workshop II (TFOS DEWS II) criteria.
METHODS: A total of 2066 community residents (1285 females; mean ± SD age, 40 ± 19 years) were recruited in an investigator-masked, prospective registry-based, diagnostic accuracy study. Dry eye symptomology and ocular surface parameters were assessed in a single clinical session. The Sjögren\'s International Collaborative Clinical Alliance (SICCA) corneal and conjunctival staining scoring and Korb lid wiper epitheliopathy (LWE) grading were evaluated by an independent masked assessor.
RESULTS: Overall, 807 (39 %) participants fulfilled the TFOS DEWS II criteria for dry eye disease, of which 178 (9 %) participants were classified as moderate-to-severe disease. The discriminative abilities of superior and inferior LWE (C-statistics, 0.724 and 0.712, respectively) were greater than corneal and conjunctival staining (C-statistics, 0.573 and 0.627, respectively). The Youden-optimal diagnostic cut-offs for the SICCA corneal and conjunctival staining scores were both ≥1, and the optimal thresholds for the Korb superior and inferior LWE grades were both ≥1. LWE was more commonly detected in both mild-to-moderate and moderate-to-severe dry eye disease, and demonstrated more consistent correlation with other ocular surface parameters across a broader range of disease severity.
CONCLUSIONS: LWE demonstrates superior diagnostic performance relative to corneal and conjunctival staining. These findings would support the routine incorporation of LWE evaluation as part of the diagnostic workup of dry eye disease.

Background/Objectives: Modern life is inconceivable without visual display terminal (VDT) work, including smartphones, computers, and games for both children and adults. VDT work under air conditioning and low humidity poses a high risk of dry eye and digital eye strain. Methods: Thirty-one participants were randomly divided into two groups using a desktop humidifier with photocatalytic technology, namely the \"with mist\" (humidifier) group and \"without mist\" (control) group. Participants performed VDT tasks using the humidifier with or without mist for 1 h. Ocular subjective symptoms and objective tear film parameters were assessed before, immediately after, and 1.5 h after the VDT task with or without mist. (Registry ID: UMIN000054379) Results: Ocular symptom scores improved significantly in the humidifier group immediately after the VDT task and up to 1.5 h later compared to before the task (p < 0.001, =0.006, respectively). Immediately after the VDT task, tear meniscus height was significantly higher and non-invasive breakup time was significantly longer in the humidifier group than in the control group (p < 0.001, =0.040, respectively). Plugging of the meibomian gland orifices was significantly reduced only in the humidifier group immediately after the VDT task compared to before the VDT task and remained significantly reduced up to 1.5 h later (p = 0.004, 0.016, respectively). Conclusions: The use of the photocatalytic desktop humidifier during VDT task resulted in significant improvements in the tear film parameters and subjective symptoms. The photocatalytic desktop humidifier could be effective in alleviating dry eye and eye strain in computer users in a modern office environment.

The aim of this study is to report the clinical outcomes of oral supplementation with curcumin-phospholipid in addition to hyaluronic acid-based tear substitute for the management of dry eye disease (DED). Patients with a diagnosis of DED confirmed by pathological values of both NIKBUT <10 s. and OSDI Questionnaire score > 12 were included. Patients were randomized to receive 2 different treatments: 0.25% hyaluronic acid-based tear substitute 3 time daily (Group 1) or as above plus curcumin-phosphatidylcholine complex tablets once a day (Group 2). Patients were evaluated at baseline (T0) and after 90 days of treatment (T1) by means of Keratograph for the measurement of NIKBUT, TMH, meibomian gland dropout and bulbar redness. Overall, data from 90 eyes of 45 patients were included. Group 1 consisted of 48 eyes of 24 patients, while group 2 included 42 eyes of 21 patients. When comparing median values of both groups at T0, no statistically significant differences were found for all parameters; instead for T1, statistically significant differences were found for redness and OSDI compared to Group 1. In group 1, a statistically significant reduction after the treatment was detected for Nikbut average and OSDI questionnaire; while in group 2, a statistically significant reduction after treatment was recorded for Nikbut average, bulbar redness and OSDI questionnaire. The addition of an oral supplement containing curcumin-phospholipid may help in a greater improvement of bulbar redness and subjective ocular symptoms compared to the treatment with tear substitutes alone for the management of DED.

The combination of keratoconus (KC) with signs of dry eye disease (DES) has been described in numerous scientific publications. At the same time, there is a relationship between KC stage and an increase in the severity of DES symptoms, however, there is still no common understanding of the severity of xerotic process depending on the clinical course of keratectasia.
OBJECTIVE: This study assesses the changes in the state of the precorneal tear film in KC relative to the stages of the disease.
METHODS: The study included 50 patients (100 eyes) with bilateral non-operated KC from subclinical to stage IV. The following methods were used for a comprehensive assessment of the condition of the tear film: biomicroscopy of the anterior segment of the eye using vital dyes, functional tests (Norn, Schirmer, Jones tests), tearscopy of the lipid layer of the tear film with software processing of the results, OCT-meniscometry, as well as filling out the OSDI questionnaire by patients.
RESULTS: The following significant changes were revealed as the KC stage progressed: an increase in the area of staining of the ocular surface with vital dyes, a decrease in the results of the Norn functional test and OCT-meniscometry, an increase in the areas of smaller thickness of lipids and areas of their complete absence according to tearscopy, as well as an increase in scores of the OSDI questionnaire.
CONCLUSIONS: A comprehensive assessment of the condition of the tear film in KC indicates the relationship and the strengthening of the signs of DES as keratectasia progresses, and can be considered as justification for the need to prescribe tear replacement and reparative therapy that improves the condition of the ocular surface and stabilizes the precorneal tear film.
На сегодняшний день сочетание кератоконуса (КК) с признаками синдрома «сухого глаза» (ССГ) описано в ряде многочисленных научных публикаций. При этом прослеживается взаимосвязь между увеличением стадии КК и усилением симптомокомплекса ССГ, однако до сих пор нет единого понимания выраженности ксеротического процесса в зависимости от клинического течения кератэктазии.
UNASSIGNED: Оценка изменения состояния прекорнеальной слезной пленки при КК относительно стадий данного заболевания.
UNASSIGNED: Обследовано 50 пациентов (100 глаз) с билатеральным неоперированным КК от субклинической до IV стадии. Для комплексной оценки состояния слезной пленки включены такие методы, как биомикроскопия переднего отрезка глаза с применением витальных красителей, функциональные пробы (пробы Норна, Ширмера, Джонеса), тиаскопия с программной обработкой результатов липидного слоя слезной пленки, ОКТ-менискометрия, а также заполнение пациентами опросника OSDI.
UNASSIGNED: По мере выраженности клинической стадии КК были выявлены следующие значимые изменения: увеличение зон прокрашивания глазной поверхности витальными красителями, снижение результатов функциональной пробы Норна и ОКТ-менискометрии, увеличение площади зон с меньшей толщиной липидов и зон их полного отсутствия по данным тиаскопии, а также увеличение количества баллов по опроснику OSDI.
UNASSIGNED: Комплексная оценка состояния слезной пленки при КК свидетельствует о взаимосвязи и усилении признаков ССГ по мере увеличения стадии кератэктазии и является обоснованием необходимости назначения слезозаместительной и репаративной терапии, способствующей улучшению состояния глазной поверхности и стабилизации прекорнеальной слезной пленки.

OBJECTIVE: The primary aim of this study is to evaluate the repeatability of noninvasive break-up time (NIBUT) measurement by keratograph when it is determined from one, two or three partial measurements, and to recommend a suitable methodology for practice. Another goal is to verify that repeated measurements do not affect the measured value.
METHODS: Thirty-eight healthy volunteers (30 women and 8 men) aged between 19 and 50 years old were included in the study, in which only one eye of each volunteer was measured. The study was designed as a prospective one. Each subject adapted to the local conditions of the laboratory for 15 minutes and subsequently underwent two series of NIBUT measurements (test, retest) on an OCULUS 3 Keratograph. The minimum time interval between the two series was 10 minutes, in which each series contained three partial measurements approximately 3 three measurements in the given series. Repeatability was assessed by a Bland-Altman analysis and expressed as a repeatability coefficient. In every case, only the time of the first break-up of the tear film was monitored.
RESULTS: The statistical analysis did not show statistically significant differences both between partial measurements of NIBUT in the individual series (p = 0.92, p = 0.81) and when comparing all six measurements (p = 0.95). The mean values of the partial measurements ranged from 13.6 s to 14.4 s. The repeatability coefficients were found to be 15.0 s, 12.1 s and 10.0 s for methodologies A, B and C, respectively. A supplementary analysis for 12 eyes with low NIBUT (< 10 s) showed statistically significantly better repeatability in this group, with coefficients of 7.0 s (methodology A), 6.0 s (B) and 4.6 s (C).
CONCLUSIONS: Determination of NIBUT from three consecutive measurements (with a sufficient interval of ideally a few minutes) significantly improves repeatability. Such repeated NIBUT measurements do not have a significant effect on the measured value. The mentioned methodology for measuring NIBUT on a keratograph can be recommended for use in practice.

OBJECTIVE: To investigate ocular surface disorders and tear function changes in patients with acne vulgaris and explore the potential relationship between acne vulgaris and dry eye.
METHODS: This cross-sectional study included right eyes of 53 patients with acne vulgaris and 54 healthy controls. The participants completed the Ocular Surface Disease Index (OSDI) questionnaire. The following ocular surface-related parameters were measured: tear meniscus height (TMH), noninvasive tear breakup time (NIBUT), Schirmer I test (SIT), lipid layer thickness (LLT) score of the tear film, meibum score, meibomian gland orifice obstruction score, the ratio of meibomian gland loss, conjunctival hyperemia score, and corneal fluorescein staining (CFS) score.
RESULTS: The stability of the tear film decreased in acne vulgaris patients. In the acne group, the TMH and NIBUT were lower, whereas the OSDI, meibum score, meibomian gland orifice obstruction score, ratio of meibomian gland loss, and conjunctival hyperemia score were higher compared with controls (P<0.05). There were no significant differences in the CFS score, SIT, or LLT score between the groups (P>0.05). In two dry eye groups, the TMH, NIBUT, and LLT score were lower in the acne with dry eye (acne-DE) group, and the meibum score, meibomian gland orifice obstruction score, ratio of meibomian gland loss and conjunctival hyperemia score in the acne-DE group were higher (P<0.05). There were no significant differences between OSDI, SIT, and CFS score (P>0.05).
CONCLUSIONS: Patients with moderate-to-severe acne vulgaris are more likely to experience dry eye than those without acne vulgaris. Reduced tear film stability and meibomian gland structure dysfunction are more pronounced in patients with moderate-to-severe acne and dry eye.

Diabetic retinopathy (DR) remains the leading cause of blindness in the working-age population. Its progression causes gradual damage to corneal nerves, resulting in decreased corneal sensitivity (CS) and disruption of anterior-eye-surface homeostasis, which is clinically manifested by increased ocular discomfort and dry eye disease (DED). This study included 52 DR patients and 52 sex- and age-matched controls. Ocular Surface Disease Index (OSDI) survey, tear film-related parameters, CS, and in vivo corneal confocal microscopy (IVCM) of the subbasal plexus were performed. Furthermore, all patients underwent tear sampling for neurotrophin and cytokine analysis. OSDI scores were greater in DR patients than in controls (p = 0.00020). No differences in the Schirmer test score, noninvasive tear film-break-up time (NIBUT), tear meniscus or interferometry values, bulbar redness, severity of blepharitis or meibomian gland loss were found. In the DR group, both the CS (p < 0.001), and the scotopic pupil diameter (p = 0.00008) decreased. IVCM revealed reduced corneal nerve parameters in DR patients. The stage of DR was positively correlated with the OSDI (Rs = +0.51, 95% CI: + 0.35-+0.64, p < 0.001) and negatively correlated with IVCM corneal nerve parameters and scotopic pupillometry (Rs = -0.26, 95% CI: -0.44--0.06, p = 0.0097). We found negative correlations between the OSDI and IVCM corneal innervation parameters. The DR group showed lower tear film-brain-derived neurotrophic factor (BDNF) levels (p = 0.0001) and no differences in nerve growth factor (NGF)-β, neurotrophin (NT)-4, vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-4, IL-5, IL-6, or IL-12 concentrations. Tumor necrosis factor (TNF)-α, IL-2, IL-8, IL-10, granulocyte macrophage colony-stimulating factor (GM-CSF), and interferon (IFN)-γ levels were decreased among patients with DR. Corneal innervation defects have a direct impact on patients\' subjective feelings. The evolution of DR appears to be associated with corneal nerve alterations, emphasizing the importance of IVCM.

Dry eye disease is a common clinical problem encountered by ophthalmologists worldwide. Interest in this entity has increased in recent years due to the consequences it has on the ocular surface after any surface procedure. With changing times, several new factors have come to light that can influence this disease. The effect of the COVID-19 pandemic has also been greatly felt, with a range of causes, starting from increased screen work to inflammatory processes, exacerbating the condition in many. With changes in the concepts of the etiopathogenesis of the disease, a paradigm shift has taken place in the approaches to treatment. More researchers are in favor of a new tear film-oriented approach that tries to localize the disease to a single component in the tear film. Innovation of newer techniques for the treatment of meibomian gland disease has also made its foray into clinical ophthalmology. Newer drug formulations and molecules are underway to better treat the inflammatory component of the disease. Many other receptors and targets for the treatment of dry eyes are being researched. This review hopes to provide a succinct, narrative summary of the relevant research on dry eye disease to date to increase awareness about the nature and future course of this disease and its management.