Dry eye disease (DED) can arise from a variety of factors, including inflammation, meibomian gland dysfunction (MGD), and neurosensory abnormalities. Individuals with DED may exhibit a range of clinical signs, including tear instability, reduced tear production, and epithelial disruption, that are driven by different pathophysiological contributors. Those affected often report a spectrum of pain and visual symptoms that can impact physical and mental aspects of health, placing an overall burden on an individual’s well-being. This cumulative impact of DED on an individual’s activities and on society underscores the importance of finding diverse and effective management strategies. Such management strategies necessitate an understanding of the underlying pathophysiological mechanisms that contribute to DED in the individual patient. Presently, the majority of approved therapies for DED address T cell-mediated inflammation, with their tolerability and effectiveness varying across different studies. However, there is an emergence of treatments that target additional aspects of the disease, including novel inflammatory pathways, abnormalities of the eyelid margin, and neuronal function. These developments may allow for a more nuanced and precise management strategy for DED. This review highlights the recent pharmacological advancements in DED therapy in the United States. It discusses the mechanisms of action of these new treatments, presents key findings from clinical trials, discusses their current stage of development, and explores their potential applicability to different sub-types of DED. By providing a comprehensive overview of products in development, this review aims to contribute valuable insights to the ongoing efforts in enhancing the therapeutic options available to individuals suffering from DED.

Background/aims To investigate relationships between dry eye (DE) disease and sleep quality, with a focus on which aspects of sleep most closely relate to DE. Methods 141 veterans (mean age: 56±5) seen at the Miami Veterans Affairs eye clinic filled out questionnaires to quantify the severity of DE symptoms (5-Item Dry Eye Questionnaire (DEQ-5) and Ocular Surface Disease Index (OSDI)) and ocular pain (Numerical Rating Scale (NRS) and Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-E)). All individuals also underwent an ocular surface examination. Aspects of sleep quality were assessed using the Pittsburgh Sleep Quality Index (PSQI). DE metrics were examined by PSQI scores and subscores. Results Most participants (76%) reported mild or greater DE symptoms (DEQ-5 ≥6). Overall, ocular symptoms were more related to sleep metrics than signs. The strongest DE symptom association was between the OSDI and sleep disturbances (PSQI subscore 5, r=0.49, p<0.0005). For DE signs, ocular surface inflammation and meibum quality were related to subjective sleep quality (PSQI subscore 1, r=0.29, p=0.03, for both). On linear regression analyses, most ocular symptom questionnaires remained associated with sleep disturbances (PSQI subscore 5: NRS (r=0.52, p<0.0005), DEQ-5 (r=0.36, p<0.0005), and OSDI (r=0.31, p<0.0005)). For DE signs, ocular surface inflammation and meibum quality remained associated with subjective sleep quality (r=0.26, p=0.01; r=0.46, p<0.0005, respectively). Conclusion DE symptom and ocular pain intensity were closely related to sleep metrics, most strongly to sleep disturbances. Relationships were weaker for DE signs, with subjective sleep quality relating to inflammation and meibum quality.

The goal of the study was to examine whether a genetic polymorphism in tumor necrosis factor receptor 1 (TNFR1) gene impacted the dry eye disease (DED) phenotype and response to anti-inflammatory therapy. The prospective study included 328 individuals with various dry eye (DE) symptoms and signs recruited from the Miami Veterans Hospital eye clinic between October 2013 and October 2017. The population underwent genetic profiling for a polymorphism within the TNFR1 gene (rs1800693 [TT, TC, CC]). The study examined the genotype distribution and relationships between the genotype, phenotype, and response to anti-inflammatory therapy. The mean age of the population was 61.7 ± 9.8 years. Here, 92% self-identified as male, 44% as White, and 21% as Hispanic; 13% (n = 42) of individuals had a CC genotype. DED symptoms and signs were similar across the three genotype groups. Thirty individuals (four with CC) were subsequently treated with an anti-inflammatory agent. There was a non-significant trend for individuals with CC genotype to have a partial or complete symptomatic response to treatment compared with the other two groups (100% for CC vs. 40% for TT and 36.4% for TC, p = 0.22). In conclusion, the presence of homozygosity of minor allele C (CC genotype) in a single nucleotide polymorphism (SNP) within TNFR1 was noted in a minority of individuals with various aspects of DED, but did not impact the DED phenotype. Our findings suggest that the current phenotyping strategies for DED are insufficient to identify underlying disease contributors, including potential genetic contributors.

Background/aims To examine demographic and clinical factors associated with ocular pain 1 day after refractive surgery. Methods Prospective study of individuals undergoing refractive surgery. Participants rated their ocular pain on a 0–10 numerical rating scale (NRS) presurgery and 1 day after surgery. Presurgery, participants completed questionnaires on demographics, comorbidities, medications and dry eye and ocular pain symptoms; and an anaesthetised Schirmer test was performed. Acute ocular pain 1 day after surgery was defined as an NRS score of worst pain since surgery ≥3 and this group was compared with individuals with NRS scores<3. Results 251 individuals underwent refractive surgery (89% laser-assisted in situ keratomileusis, n=222; 11% PRK, n=29). Mean age was 35±8 years (range 19 to 60); 60% (n=150) self-identified as female, 80% (n=203) as White, and 36% (n=89) as Hispanic. Thirteen (5%) individuals reported ocular pain (NRS ≥3) prior to surgery and 67% (n=168) reported ocular pain 1 day after surgery (nine individuals had pain at both time points). Factors that were associated with pain 1 day after surgery included Hispanic ethnicity (adjusted relative risk (aRR) 1.42, 95% CI 1.21 to 1.68, p<0.001) and the presence of eye pain presurgery (aRR 1.10, 95% CI 1.02 to 1.18, p=0.02). Conclusion A majority of individuals report moderate or greater pain within 24 hours of refractive surgery. Hispanic ethnicity and eye pain prior to surgery were associated with self-reported acute postsurgical pain.

Dry eye disease is an umbrella term that includes a variety of symptoms and signs. A link between diabetes mellitus and dry eye disease exists, but the associated phenotype needs further examination. Thus, our aim was to determine how diabetes mellitus relates to the dry eye disease phenotype. A prospective, cross-sectional study was conducted at the Miami Veteran Affairs Medical Center ophthalmology clinic between October 2013 and September 2019. Participants included a volunteer sample of 366 South Florida veterans with one or more symptoms or signs of dry eye disease [Dry Eye Questionnaire-5 ≥ 6 OR tear break-up time ≤ 5 OR Schirmer’s test score ≤ 5 OR corneal fluorescein staining ≥ 2]. Participants were divided into three groups: (1) individuals without diabetes mellitus (controls); (2) individuals with diabetes mellitus but without end-organ complications; and (3) individuals with diabetes mellitus and end-organ complications. Dry eye metrics were compared across groups. The main outcome measures included ocular symptom questionnaires [e.g., 5-item Dry Eye Questionnaire, Ocular Surface Disease Index, and ocular pain assessment] and clinical parameters obtained from an ocular surface evaluation. A total of 366 individuals were included (mean age 59 ± 6 years; 89% males; 39% White; 11% diabetes mellitus and end-organ complications; 15% diabetes mellitus but without end-organ complications). Individuals with diabetes mellitus and end-organ complications had lower symptom scores on the dry eye disease and pain-specific questionnaires compared to individuals with diabetes mellitus but without end-organ complications and controls (Ocular Surface Disease Index: 42.1 ± 24.5 vs. 38.9 ± 25.1 vs. 23.6 ± 16.2; p < 0.001; numerical rating scale of ocular pain intensity: 4.9 ± 3.2 vs. 4.3 ± 2.7 vs. 3.5 ± 2.7; p = 0.02). Eyelid laxity was also more severe in the group with diabetes mellitus and end-organ complications (0.69 ± 0.64 vs. 0.73 ± 0.72 vs. 1.08 ± 0.77; p = 0.004) compared to the two other groups. The diabetic dry eye disease phenotype is driven by signs more so than by symptoms, with anatomic eyelid abnormalities being more frequent in individuals with diabetes mellitus and end-organ complications. Given this, ocular surface abnormalities in individuals with DM may be missed if screened by symptoms alone. As such, individuals with DM should undergo a slit lamp examination for signs of ocular surface disease, including anatomic abnormalities.