How does ocular graft-versus-host disease fit under the dry eye umbrella? A review.

Graft-versus-host disease (GVHD) is a systemic disease that can affect multiple organs as a consequence of an allogeneic haematopoietic stem cell transplant. One organ system that is often affected in GVHD is the eyes. Ocular GVHD (oGVHD) may involve various structures within the eye including the lacrimal glands, eyelids, conjunctiva, cornea, and nasolacrimal ducts, and is a source of morbidity in patients with GVHD. Common presenting features of GVHD overlap with dry eye disease (DED), including decreased tear production, epithelial disruption, and Meibomian gland dysfunction (MGD). In this review, we aim to compare oGVHD and DED to better understand the similarities and differences between the conditions, with a focus on pathophysiology, risk factors, clinical features, and treatments.

Prevalence and Risk Factors of Dry Eye Disease in the South of Palestine.

Background: The prevalence of dry eye disease (DED) is rising globally and needs to be urgently addressed by medical professionals because it lowers patients' quality of life. There are as yet no available data in the literature about the prevalence of and risk factors for DED in the Gaza Strip, a gap that the present study seeks to address. Methods: A cross-sectional study was carried out between March and August 2022 in Gaza governorates using a proportional stratified sampling technique. Only Gazan individuals ≥ 18 years old and able to follow the instructions were included. The Ocular Surface Disease Index (OSDI) questionnaire, which has previously been translated into Arabic and validated, was applied to evaluate DED symptoms. Subjective clinical tests for DED conducted were tear meniscus height (TMH), meibomian gland dysfunctions (MGDs), Marx line (ML), conjunctival Lissamine green staining (LGS), tear film break-up time test (TBUT), corneal fluorescein staining (CFS) and Schirmer II tear test (STT). DED was defined based on an Arab-OSDI score ≥ 13 and at least one positive clinical sign. Results: A total of 426 participants were assessed from four areas (North Gaza Strip, 82; Gaza City, 147; Mid-Zone Gaza Strip, 62; South Gaza Strip, 135). The prevalence of DED in the present study was 31.5% (95% CI: 27.1, 36.1). Age > 50 years old (odds ratio [OR] = 10.45; 95% CI: 2.95, 37.05; P < 0.001), female gender (OR = 3.24; 95% CI: 1.40, 7.52, P = 0.006), menopause or pregnancy (OR = 2.59; 95% CI: 1.25, 5.35; P = 0.03) and pharmacotherapy (artificial tears; OR = 9.91; 95% CI: 2.77, 35.46; P < 0.001) were each associated with DED symptoms. South Gaza Strip (OR = 0.04; 95% CI: 0.01, 0.12; P < 0.001), unemployed (OR = 11.67; 95% CI: 1.43, 95.44; P = 0.02), non-consumption of caffeine (OR = 0.40; 95% CI: 0.19, 0.88; P = 0.02) and TMH < 0.2 (OR = 1.80; 95% CI: 1.02, 3.19; P = 0.04) were associated with TBUT < 5 s. LGS was associated with those > 50 years old (OR = 2.70; 95% CI: 1.38, 5.28; P = 0.004), previous refractive or ocular surface surgeries (OR = 2.97; 95% CI: 1.34, 6.59; P = 0.008) and CFS ≥ 1 (OR = 1.91; 95% CI: 1.07, 3.44; P = 0.03). Conclusion: Various aspects of DED were linked with different risk factors, suggesting that DED subtypes have different underlying pathophysiologies.

Tear 1H Nuclear Magnetic Resonance-Based Metabolomics Application to the Molecular Diagnosis of Aqueous Tear Deficiency and Meibomian Gland Dysfunction.

PURPOSE: Meibomian gland dysfunction (MGD) is a major cause of signs and symptoms related to dry eyes (DE) and eyelid inflammation. We investigated the composition of human tears by metabolomic approaches in patients with aqueous tear deficiency and MGD. METHODS: Participants in this prospective, case-control pilot study were split into patients with aqueous tear deficiency and MGD (DE-MGD [n = 15]) and healthy controls (CG; n = 20). Personal interviews, ocular surface disease index (OSDI), and ophthalmic examinations were performed. Reflex tears collected by capillarity were processed to 1H nuclear magnetic resonance (NMR) spectroscopy and quantitative data analysis to identify molecules by spectra comparison to library entries of purified standards and/or unknown entities. Statistical analyses were made by the SPSS 22.0 program. RESULTS: Chemometric analysis and 1H NMR spectra comparison revealed the presence of 60 metabolites in tears. Differentiating features were evident in the NMR spectra of the 2 clinical groups, characterized by significant upregulation of phenylalanine, glycerol, and isoleucine, and downregulation of glycoproteins, leucine, and -CH3 lipids, as compared to the CG. The 1H NMR metabolomic analyses of human tears confirmed the applicability of this platform with high predictive accuracy/reliability. CONCLUSIONS: Our key distinctive findings support that DE-MGD induces tear metabolomics profile changes. Metabolites contributing to a higher separation from the CG can presumably be used, in the foreseeable future, as DE-MGD biomarkers for better managing the diagnosis and therapy of this disease.

Punctate fluorescein staining scores in dogs with or without aqueous tear deficiency.

OBJECTIVE: To compare the superficial punctate fluorescein staining in dogs with and without aqueous tear deficiency. PROCEDURES: An eye from each client-owned dogs presented to Triangle Animal Eye Clinic between January and December 2018 underwent tear and ocular surface tests, which included the Schirmer tear test (STT), phenol red thread test (PRT), and strip meniscometry tube tear test (SMT). Punctate fluorescein staining of the cornea (PFS-C) and the upper palpebral conjunctiva (PFS-UPC) were also performed. Fifty-seven dogs with STT results of <15 mm/min had aqueous tear deficiency (AD); 31 dogs had <10 mm/min and 26 dogs had ≥10 mm/min. The 162 dogs with STT results of ≥15 mm/min did not have AD. The test results of the groups were compared using Kruskal-Wallis and Steel-Dwass multiple comparison tests. RESULTS: Two hundred and nineteen eyes from 219 dogs were enrolled in this study. The PRT and SMT results, presented as mean ± SD, were significantly lower in the AD group than in the non-AD group (PRT: 29.5 ± 8.1 vs 36.9 ± 5.6 mm/15 s; SMT: 6.2 ± 3.8 vs 10.8 ± 2.8 mm/5 s). The PFS scores were significantly higher in the AD group than in the non-AD group (PFS-C: 4.4 ± 0.7 and 3.7 ± 0.8; PFS-UPC: 2.3 ± 0.5 and 1.7 ± 0.5). CONCLUSIONS: These results suggest that aqueous tear deficiency is not only reflected by PRT and SMT but also PFS-C and PFS-UPC.

Acupuncture promotes tear secretion by up-regulating VIP/cAMP/PKA/AQP5 signaling in guinea pigs with aqueous tear deficiency dry eye. / 基于VIP/cAMP/PKA/AQP5信号通路探讨针刺治疗水液缺乏型干眼的作用机制.

OBJECTIVES: To observe the effect of acupuncture on the ocular surface symptoms and the protein expression of vasoactive intestinal peptide (VIP) / cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) / aquaporin 5(AQP5) signaling pathway in lacrimal gland tissue of aqueous tear deficiency (ATD) type dry eye model, so as to investigate its mechanism underlying improvement of ATD. METHODS: British shorthair guinea pigs were randomly divided into blank control, model, acupuncture, sham-acupuncture and medication group, with 8 guinea pigs in each group. The ATD model was established by subcutaneous injection of scopolamine hydrobromide (0.6 mg/dose, 4 times/d for 10 days). For guinea pigs of the acupuncture group, filiform needles were inserted into bilateral "Jingming"(BL1), "Cuanzhu"(BL2), "Sizhukong"(TE23), "Taiyang"(EX-HN5), and "Tongziliao"(GB1) for 15 min. For guinea pigs of the sham-acupuncture group, a blunt filiform needle was used to repeatedly prick (not pierce) the skin of the same acupoints mentioned above. The treatment in the above two groups was conducted once daily for 14 days. The guinea pigs in the medication group received administration of sodium hyaluronate eye drops in both eyes, three times a day for 14 days. The objective tests of tear film break-up time (BUT), corneal fluorescein staining score (FLS) and phenol red thread (PRT) test were conducted before and after modeling and after the intervention. After the intervention, the lacrimal index (weight of lacrimal gland/body weight) was calculated. Histopathological changes of the lacrimal gland were observed after H.E. staining. The expression of AQP5 in the lacrimal gland were detected by immunofluorescence, and the contents of VIP and AQP5 in the lacrimal gland were measured by ELISA, the protein expression levels of VIP, cAMP, PKA, p-PKA and AQP5 in the lacrimal gland were detected by Western blot. RESULTS: In comparison with the blank control group, the PRT, BUT, lacrimal index, AQP5 immunoactivity, contents of VIP and AQP5, and protein expression levels of VIP, cAMP, PKA, p-PKA and AQP5 were significantly decreased(P<0.01, P<0.05), and FLS was obviously increased (P<0.01) in the model group . Compared to the model group, the PRT, BUT, lacrimal index, AQP5 immunoactivity, contents of VIP and AQP5, and expression levels of VIP and AQP5 in both acupuncture and medication groups, and the expression levels of cAMP, PKA, p-PKA in the acupuncture group were considerably increased (P<0.01, P<0.05), while the FLS was markedly decreased in both acupuncture and medication groups (P<0.01, P<0.05). Compared with the medication group, the acupuncture group had increased PRT (P<0.05). CONCLUSIONS: Acupuncture intervention is effective in reducing ocular surface damage and promoting tear secretion in guinea pigs with ATD, which may be related to its function in activating VIP/cAMP/PKA signaling, and promoting the expression of AQP5 in the lacrimal gland.

Beyond dry eye: how co-morbidities influence disease phenotype in dry eye disease.

Dry Eye Disease (DED) is a complex and multifactorial disorder of tear homoeostasis that results in pain, visual disturbance, and ocular surface damage. It is highly prevalent around the world and is associated with many co-morbidities that may contribute to or exacerbate symptoms and signs of disease and affect disease phenotype. However, DED is not one disease and can manifest with a variety of symptoms and/or signs. In this review, we discuss relationships between various co-morbidities and DED phenotypes. For example, individuals with immune mediated diseases, like Sjögren's Syndrome and Graft versus Host Disease, often present with aqueous tear deficiency (ADDE) in the setting of lacrimal gland dysfunction. Individuals with disorders that affect the periocular skin, like rosacea and seborrhoeic dermatitis, often present with evaporative dry eye (EDE) in the setting of eyelid and/or meibomian gland abnormalities. Individuals with pain related disorders, such as chronic pain syndrome and migraine, often present with ocular pain out of proportion to tear film abnormalities, often with accompanying corneal nerve hypersensitivity. Individuals with diabetes mellitus often present with an epitheliopathy in the setting of decreased sensation (neurotrophic keratitis). While not absolute, understanding relationships between co-morbidities and DED phenotypes can help tailor a therapeutic plan to the individual patient.

Metagenomic Analysis Reveals the Heterogeneity of Conjunctival Microbiota Dysbiosis in Dry Eye Disease.

Background: Dry eye disease (DED) is a multifactorial inflammatory disease of the ocular surface. It is hypothesized that dysbiosis of the conjunctival microbiota contributes to the development of DED. However, species-level compositions of the conjunctival microbiota in DED and the potential dysbiosis involving microorganisms other than bacteria remain largely uncharacterized. Methods: We collected conjunctival impression samples from a cohort of 95 individuals, including 47 patients with DED and 48 healthy subjects. We examined the conjunctival microbiota of these samples using shotgun metagenomic sequencing and analyzed microbial dysbiosis in DED at the species level. Results: The conjunctival microbiota in DED exhibited a decreased α-diversity and an increased inter-individual variation. The α-diversity of female patients with DED was higher than that of male patients. Despite a decreased prevalence in DED, 23 microbial species were identified to show abnormally high abundance in DED samples positive for the species. Among these species, a fungal species Malassezia globosa was enriched female patients. In addition, distinct patterns of associations with disease status were observed for different species of the same genus. For DED subtypes, Staphylococcus aureus and S. capitis were associated with meibomian gland dysfunction (MGD), whereas S. hominis was enriched in patients solely with aqueous tear deficiency (ATD). The microbiota of patients with a mixed type of diagnosis was more similar to MGD patients than ATD patients. Conclusion: We demonstrated that the conjunctival microbiota dysbiosis in DED is characterized by significant heterogeneity. Microbial signatures may offer novel insights into the complicated etiology of DED and potentially promote the development of personalized treatment for DED in the future.

Characterising the ocular surface and tear film in a population-based birth cohort of 45-year old New Zealand men and women.

PURPOSE: To assess the prevalence of dry eye disease, aqueous tear deficiency, meibomian gland dysfunction, and asymptomatic ocular surface disease in a population-based cohort of 45-year-old New Zealand men and women. METHODS: This cross-sectional study of 885 participants (442 females, 443 males) was based on a population-representative birth cohort of individuals born between April 1 1972 and March 31 1973 in Dunedin, New Zealand (the Dunedin Multidisciplinary Health and Developmental Study). Participants were assessed at 45 years of age, and dry eye symptomology, ocular surface characteristics, and tear film quality were evaluated for each participant within a single clinical session. The diagnosis of dry eye disease was made according to the validated rapid non-invasive dry eye assessment algorithm. RESULTS: Clinical dry eye signs were present in 402 (45%) participants, of which 78 (9%) participants fulfilled the diagnostic criteria for dry eye disease, and 322 (37%) had asymptomatic ocular surface disease. Among participants with dry eye disease, 22 (2%) exhibited aqueous tear deficiency, and 65 (7%) had meibomian gland dysfunction. Females were more likely to be affected by dry eye disease, meibomian gland dysfunction, and asymptomatic ocular surface disease (all p < 0.05). CONCLUSIONS: Clinical dry eye signs were present in almost half of this population-based cohort of 45-year-old New Zealanders, although only 9% of participants fulfilled the diagnostic criteria for dry eye disease. The high prevalence of asymptomatic ocular surface disease presents an opportunity for preventative public health intervention.

Diagnostic tests in dry eye.

INTRODUCTION: Dry Eye (DE) is a multifactorial condition with a variable clinical presentation. This highly prevalent disease has multiple symptoms and signs that often do not correlate with one another. As such, the diagnosis of DE can be challenging to make, and a systematic approach must be taken. AREAS COVERED: We review the different methods commonly utilized to evaluate a patient complaining of DE symptoms. Included in this review are clinical examination techniques, point of care tests, and imaging techniques. EXPERT OPINION: DE is an umbrella term that encompasses different etiologies and pathophysiological mechanisms. The current definition recognizes tear instability, high osmolarity, inflammation, and neuro-sensory dysfunction as causative entities. The approach to DE begins with a systematic assessment of symptoms and signs, evaluating for both nociceptive and neuropathic sources of symptoms. Future research is needed to develop tests that assess neurosensory status in DE and couple point of care tests with therapeutic algorithms.

Comparison of two methods for establishing rat dry eye model: lacrimal gland extirpation and lacrimal gland injection of botulinum toxin A / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:The dry eye model of rat was induced either by lacrimal gland extirpation or injection of botulinum toxin A into lacrimal gland. The clinical manifestations, pathological features and cytokine changes of these two models were compared, then we discussed their advantages, disadvantages and applicable scope.<p>METHODS:Thirty healthy 8-week-old male Brown Norway rats were randomly assigned into three groups equally. The left eye of group A was blank group, group B was the left lacrimal gland extirpation model, the left tear gland of group C was injected with botulinum toxin A. We compared the data of Schirmer I test, tear break-up time(BUT), and the corneal fluoresceince staining scores at different times(1d before experiment, 3d, 7d, 14d, 28d, and 42d after the surgical process). We observed pathological changes of conjunctiva, cornea and lacrimal gland at 42d, and we used real-time polymerase chain reaction to analyze interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)and epithelial growth factor(EGF).<p>RESULTS:At the 3d, compared with group A, the tear secretion of both group B and group C were continuous decrease(<i>P</i><0.05). At the 7d, compared with group A, the BUT of both group B and group C began to decreased(<i>P</i><0.05), and the corneal epithelial staining scores of both group B and group C began to significantly increase(<i>P</i><0.05). There was no statistical difference in the above clinical data between group B and group C(<i>P></i>0.05). The corneal epithelial cells in group A was set as normal morphology, while the corneal epithelial cells in group B and group C showed filamentous separation of surface cells to varying degrees, and the number of conjunctival goblet cells was decreased. The lacrimal gland of group C was obviously atrophic. In conjunctival and corneal tissues, the expression of EGF, TNF-α and IL-6 were significantly increased in group B and group C, which was statistically significant compared with group A(<i>P</i><0.05). The expression of EGF and TNF-α didn't altered significantly between group B and group C(<i>P</i>>0.05), however, the expression of IL-6 in group B was much higher than that in group C(<i>P</i><0.05).<p>CONCLUSION:In this study, we proved that both lacrimal gland extirpation and lacrimal gland injection botulinum toxin A could construct a stable aqueous tear deficiency dry eye rat model. The appropriate animal model should be selected according to the experimental design and research purpose.

P2Y2 receptor agonists for the treatment of dry eye disease: a review.

Recent advances in the understanding of dry eye disease (DED) have revealed previously unexplored targets for drug therapy. One of these drugs is diquafosol, a uridine nucleotide analog that is an agonist of the P2Y2 receptor. Several randomized controlled trials have demonstrated that the application of topical diquafosol significantly improves objective markers of DED such as corneal and conjunctival fluorescein staining and, in some studies, tear film break-up time and Schirmer test scores. However, this has been accompanied by only partial improvement in patient symptoms. Although evidence from the literature is still relatively limited, early studies have suggested that diquafosol has a role in the management of DED. Additional studies would be helpful to delineate how different subgroups of DED respond to diquafosol. The therapeutic combination of diquafosol with other topical agents also warrants further investigation.