Dry eye disease is a chronic ocular surface disorder of multifactorial origin, characterized by a loss of tear film homeostasis and associated with a range of ocular discomfort symptoms. Growing evidence underscores a significant bidirectional relationship between dry eye and depression: individuals with dry eye disease exhibit a higher prevalence of depressive disorders, and conversely, those diagnosed with depression demonstrate an increased susceptibility to developing dry eye. This interplay is mediated through several pathophysiological pathways, such as chronic inflammation, cerebral functional alterations, gut microbiome dysregulation, and sleep disturbances, which may collectively sustain a vicious cycle. The use of antidepressant therapy introduces further complexity, exerting heterogeneous effects on dry eye—some agents may offer symptomatic relief, whereas others can aggravate ocular surface impairment. The mechanisms responsible for these differential outcomes remain incompletely elucidated and merit further investigation. This review systematically consolidates epidemiological data on the dry eye-depression link, examines potential shared pathological mechanisms, and evaluates current therapeutic options. We propose an integrated management approach that combines conventional dry eye treatments, such as traditional Chinese medicine, electroacupuncture, physical activity and antidepressants—a multimodal strategy that may yield synergistic benefits in alleviating both ocular and affective symptoms, thereby improving overall quality of life. Moving forward, research should focus on deciphering the underlying mechanistic pathways and facilitating the translation of these insights into clinical practice to inform targeted, combined treatment regimens for patients with dry eye and depression.

Objective:To evaluate the effect of short-term topical administration of atropine eye drops with various concentrations and frequencies on eye safety in children.Methods:A double-blind randomized controlled trial was conducted.Sevevty-two children with ametropia or pre-myopia (72 eyes) were enrolled in Tianjin Medical University Eye Hospital from December 2020 to January 2022.The subjects were randomly divided into 0.01% atropine group, 0.02% atropine group and 0.04% atropine group according to a random number table, with 24 cases (24 eyes) in each group.Automatic refraction with an automatic computer optometry device, subjective refraction with a phoropter, intraocular pressure with a non-contact tonometer, axial length by optical biometrics, the amplitude of accommodation (AMP) by the push-up method, pupil diameter with pupilometer, near visual acuity at 33 cm with a standard logarithmic visual acuity chart, tear evaluation with Keratograph 5M and Ocular Surface Disease Index (OSDI) questionnaire survey were performed among all subjects.One drop of 0.01%, 0.02%, and 0.04% atropine was administrated to the study eye according to grouping, and the pupil diameter was measured every 10 minutes until the pupil did not enlarge three times, then the data after a single treatment of the three groups were recorded.After one-week application of the corresponding concentration of atropine eye drops once at night, the data after one-week treatment were recorded.For the next week, the application frequency of 0.01% and 0.02% atropine groups changed to once daily in the morning and evening, and 0.04% atropine group maintained once at night, then the data after two-week treatment were recorded.Data of the right eyes were analyzed.The changes in pupil diameter, AMP and other eye parameters before and after atropine eye drops of the three groups were compared.This study adhered to the Declaration of Helsinki and the study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (No.2020KY[L]-51). All subjects and their guardians were fully informed of the method and purpose of this study before entering the cohort.Written informed consent was obtained from guardians.Results:Pupil diameters of 0.01%, 0.02% and 0.04% atropine groups were (5.59±0.48), (5.35±0.76) and (5.65±0.43)mm before treatment respectively, (7.00±0.68), (7.17±0.58) and (8.40±1.71)mm after a single treatment, (6.67±0.62), (6.56±0.65) and (7.60±0.69)mm after one-week treatment, (6.96±0.49), (7.04±0.53) and (7.60±0.36)mm after two-week treatment.There were significant differences in pupil diameter at different time points after treatment among the three groups ( Fgroup=9.430, P<0.001; Ftime=156.620, P<0.001). The AMP of 0.01%, 0.02% and 0.04% atropine groups were (12.94±3.02), (13.25±2.81) and (13.42±2.60)D before treatment respectively, (11.62±2.61), (11.53±2.06) and (9.64±1.93)D after a single treatment, (11.14±2.61), (11.33±2.33) and (8.30±1.18)D after one-week treatment, (9.99±1.81), (8.72±1.25) and (8.76±2.12)D after two-week treatment.There was no significant difference in the AMP among the three groups ( Fgroup=2.800, P=0.063). In the three groups, the AMP at different time points after treatment were significantly lower than that before treatment ( Ftime=61.400, P<0.001). There was no difference in spherical equivalent refraction, intraocular pressure, near visual acuity, axial length, first none-invasive tear break-up time, average none-invasive tear break-up time, tear meniscus height and OSDI score among the three groups ( Fgroup=0.030, 0.630, 1.420, 0.580, 0.140, 0.120, 0.340, 0.142; all at P>0.05). There were significant differences in spherical equivalent refraction, intraocular pressure, first none-invasive tear break-up time, average none-invasive tear break-up time, tear meniscus height and OSDI score at different time points between before and after medication among the three groups ( Ftime=12.560, 4.730, 4.720, 5.220, 3.720; all at P<0.05). Conclusions:Varying pupil dilation and AMP reduction occur after the use of different concentrations of atropine and are more severe at higher concentrations.Increased administration frequency of atropine is associated with more pupil dilation and AMP reduction, but there is no intolerable adverse effect.