Applications of topical immunomodulators enhance clinical signs of vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC): a meta-analysis.

PURPOSE: This meta-analysis aimed to review the safety and efficacy of topical cyclosporine A (CsA) and topical tacrolimus in allergic eye disease. METHODS: A systematic search identified thirteen studies and a total of 445 patients for inclusion, making this the largest meta-analysis published on the subject. The current review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). RESULTS: Thirteen randomized control trials were included in the meta-analysis. Eleven studies used CsA as the treatment, and two used Tacrolimus. In total, 445 participants were included, of whom 76.6% were male. The mean age of participants across the included studies was 14 years. All studies reported clinical signs as evaluated by an examining clinician. Signs were usually assessed by anatomical region, with the most common regions being the conjunctiva and the cornea, and the most common signs assessed were hyperemia and papillae. Three studies accounted for more than 50% of the meta-analysis's weight. Effect size (d) ranged from - 2.37 to - 0.03, negative values favoring immunomodulators. Fixed Effect Meta-Analysis returned an SMD of - 0.81 (95% CI [- 0.98, - 0.65]). However, there was significant heterogeneity (I2 = 61%, Qw = 30.76) in the outcome measure (P = 0.0021); therefore, a random-effect meta-analysis was also completed in which the pooled SMD was - 0.98 (95% CI [- 1.26, - 0.69], τ2 = 0.16). CONCLUSIONS: This study affirms the current scientific community's stance that immunomodulators effectively treat clinical signs, including blepharitis, conjunctival hyperemia, edema, papillae, and corneal damage in severe ocular allergic disease.

Efficient Adsorptive Removal of Methylene Blue Dye from Aqueous Solution Using Eragrostis Teff Biomass-Derived Nitrogen and Phosphorus-Codoped Carbon Quantum Dots.

Carbon quantum dots have a great application potential in environmental protection via adsorption technology due to their large specific surface area and negative zeta potential. In this work, nitrogen and phosphorus-codoped carbon quantum dots (NP-CQDs) with a large specific surface area and negative zeta potential were successfully synthesized by a single-step hydrothermal synthesis. Batch adsorption studies were utilized to assess the adsorbent's capacity to remove common methylene blue (MB) dye contaminants from an aqueous solution. The experiment showed that MB dye could be removed in 30 min under optimum experimental conditions, with a removal efficiency of 93.73%. The adsorbent's large surface area of 526.063 m2/g and negative zeta potential of -12.3 mV contribute to the high removal efficiency. The Freundlich isotherm model fits the adsorption process well at 298 K, with R2 and n values of 0.99678 and 4.564, respectively, indicating its applicability. A kinetic study demonstrated that the pseudo-second-order model, rather than the pseudo-first-order model, is more suited to represent the process of MB dye adsorption onto NP-CQDs. This research established a simple and cost-effective method for developing a highly efficient NP-CQD adsorbent for organic dye degradation by adsorption.

Neurotrophic keratitis: inflammatory pathogenesis and novel therapies.

PURPOSE OF REVIEW: Neurotrophic keratitis is a rare degenerative disease characterized by decrease or absence of corneal sensation. Neurotrophic keratitis varies from mild forms with mild epitheliopathy to severe manifestations such as corneal ulceration, melting and perforation that can lead to irreversible visual loss. The cause of neurotrophic keratitis comprises a long list of diseases, medications, congenital or genetic conditions as well as trauma. The mechanism of neurotrophic keratitis is complex and multifactorial and its understanding is crucial to better address the treatment strategies. We aimed to review neurotrophic keratitis pathology, mechanisms and management. RECENT FINDINGS: Corneal nerves are critical for the homeostasis of a healthy ocular surface. The lack of nerve-derived neuromediators and corneal-released neuropeptides, neuro-trophins and neurotrophic factors in neurotrophic keratitis leads to a decrease in trophic supply to corneal cells in addition to a decrease in afferent signaling to the brain. This results in pathological tear secretion, decreased blinking rate, corneal healing along with ocular surface and corneal inflammation. Lately, nerve growth factor in special gained emphasis as a treatment strategy targeting the disease mechanism rather than its manifestations. Other therapies, including surgical interventions, are in the pipeline of neurotrophic keratitis management. However, there are still no proper therapeutic guidelines and neurotrophic keratitis treatment remains challenging. SUMMARY: Neurotrophic keratitis may have a devastating outcome and treatment is still challenging. Understanding the disease pathology may assist in the development of new treatment strategies. Prompt disease recognition and immediate intervention are key factors to promote corneal healing and avoid further deterioration.

Ocular surface inflammation and ectatic corneal disorders.

PURPOSE OF REVIEW: Inflammatory mediators are a focus of recent corneal ectasia (CE) research and are a profound, modifiable contributor to CE in general and keratoconus (KC) in particular, opening a path to explore new methods of control. As advanced imaging technology and expanded population screening allow for earlier detection, the possibility of early intervention can profoundly change the prognosis of CE. RECENT FINDINGS: Significant increases in the inflammatory mediators and immune components have been observed in the cornea, tear fluid, and blood of ectasia patients, while inflammation dampeners such as vitamin D and their receptors are reduced. Atopy and allergy have a strong association with KC, known to increase itch factors and stimulate eye rubbing, a risk factor in ectasia pathogenesis. Management of atopy or allergic conditions and topical anti-inflammatories has helped stabilize CE disease. SUMMARY: Strategies such as monitoring inflammatory factors and using immune or inflammatory modulators, including managing subclinical inflammation, may be clinically beneficial in stabilizing the disease and improving outcomes. The detected factors are biomarkers, but as yet unproven to be sensitive or specific enough to be considered biomarkers for early detection of CE. The establishment of such biomarkers could improve the therapeutic outcome.

Prevalence and clinical characteristics of vernal keratoconjunctivitis in sub-Saharan Africa.

PURPOSE OF REVIEW: Vernal keratoconjunctivitis (VKC) is a chronic bilateral allergic inflammatory disease of the conjunctiva and cornea that affects children and young adults, especially in sub-Saharan Africa. A limbal form (tropical endemic limbo conjunctivitis) is thought to be more common in the tropics where research on this vision-impairing condition is scanty. We sought to review current literature from sub-Saharan Africa, with a focus on the prevalence of VKC and its clinical presentation. RECENT FINDINGS: There is a variable prevalence of VKC in SSA, up to 32.9% of children, especially in male individuals less than 5 years old, and has been diagnosed in a 4-month-old baby. Associated factors include exposure to dust, personal and family history of atopy, Vitamin D3 deficiency and HIV. The mixed form of VKC is the most frequent form seen and conjunctival pigmentation might be an early diagnostic sign. SUMMARY: Childhood screening programs for VKC should be established to reduce the morbidity, decreased quality of life and school absenteeism that is seen in these patients. VKC-related research should be encouraged in this milieu to bring to light the particularities of VKC in SSA.

Outcome indicators for cross linking in pediatric keratoconus.

Purpose: To evaluate the predictive factors for successful corneal collagen cross-linking (CXL) in pediatric patients with Keratoconus (KC). Methods: This retrospective study was conducted using a prospectively built database. Patients (18 years old or younger) underwent CXL for KC between 2007 and 2017, with a 1-year follow-up period or longer. The outcomes included changes in Kmax (delta [Δ] Kmax = Kmaxlast - Kmaxpre) and LogMAR visual acuity (ΔLogMAR = LogMARlast - LogMARpre).The effects of CXL type (accelerated or non-accelerated), demographics (age, sex, background of ocular allergy, ethnicity), preoperative LogMAR visual acuity, maximal corneal power (Kmax), pachymetry (CCTpre), refractive cylinder, and follow-up (FU) time on the outcomes were analyzed. Results: One hundred thirty-one eyes of 110 children were included (mean age, 16 ± 2 years; range, 10-18 years). Kmax and LogMAR improved from baseline to last visit: from 53.81 D ± 6.39 D to 52.31 D ± 6.06 D (p < 0.001) and from 0.27 ± 0.23 LogMAR units to 0.23 ± 0.19 LogMAR units (p = 0.005), respectively. A negative ΔKmax (meaning corneal flattening) was associated with a long FU, low CCTpre, high Kmaxpre, high LogMARpre, and non-accelerated CXL on univariate analysis. High Kmaxpre and non-accelerated CXL were associated with negative ΔKmax in the multivariate analysis.A negative ΔLogMAR (meaning vision improvement) was associated with a high LogMARpre in univariate analysis. Conclusion: CXL is an effective treatment option in pediatric patients with KC. Our results showed that the non-accelerated treatment was more effective than the accelerated treatment. Corneas with advanced disease had a greater effect on CXL.

Corneal complications of rheumatoid arthritis.

PURPOSE OF REVIEW: Rheumatoid arthritis (RA) is an autoimmune disease that primarily affects the joints. Extra-articular manifestations (EAMs) are common and may affect up to 40.6% of patients. Ocular EAM can occur in 39% of the patients. The cornea is involved by different pathogenic mechanisms and corneal disease varies from mild symptoms to severe corneal ulceration and melting with visual loss. Severe corneal involvement is associated with increased mortality in RA patients. We aimed to review the prevalence, mechanisms, management and overall impact of corneal involvement in RA patients. RECENT FINDINGS: Corneal involvement is frequent among RA patients. With the wider use of systemic immunosuppression, in particular the disease-modifying antirheumatic drugs (DMARDs), and with improvement of surgical techniques, spontaneous and surgery-related corneal ulceration and melting is becoming less common. However, RA patients are still at risk and should be carefully managed. SUMMARY: RA-related corneal complications are associated with a decreased quality of life and poor ocular and systemic prognosis. Prompt recognition and a multidisciplinary approach involving topical ophthalmic management and systemic immunosuppression are the key factors to maintain ocular integrity and avoid a lethal outcome.

Neurostimulation for dry eye disease.

PURPOSE OF REVIEW: To review the neuroanatomy and physiology of the basal and reflex tearing and present the available and developing therapies using the concept of neurostimulation in dry eye disease (DED). RECENT FINDINGS: The most prevalent current DED treatments seek to supplement low tear volume and tear components or reduce inflammation. Neurostimulation is a unique approach gaining momentum in recent years, geared toward increasing the production of all basal tear components by stimulating the nerves responsible for producing the various tear components. The neuroanatomy of the lacrimal unit provides several possible access points to stimulate tear production through two arms of the sensory trigeminal nerves. Modes of stimulation include chemical or energy in electrical or magnetic form. Research thus far has shown that neurostimulation can achieve lacrimal, goblet cell, and meibomian gland stimulation. Subjectively it improves symptoms of DED. Clinically, neurostimulation has improved the signs and symptoms of DED by increasing basal tear production and tear volume. SUMMARY: Neurostimulation using electrical, mechanical, or chemical means is a novel concept to increase tear production and was demonstrated to be an effective, safe, and well-tolerated method for managing DED.

Predicting factors for the efficacy of cross-linking for keratoconus.

PURPOSE: To evaluate predictors for success in corneal crosslinking (CXL) for keratoconus in a large cohort and extended follow-up. DESIGN: A retrospective study based on a prospectively built database. METHODS: Participants underwent CXL for keratoconus from 2007 to 2018. Statistical analysis was performed for patients with at least 1-year follow-up. We analyzed effects of CXL type (Epithelium-on or Epithelium-off and Accelerated (9mW/cm2@10min) or Standard (3mW/cm2@30min)) and pre-operative factors including age, gender, baseline LogMAR visual acuity (LogMARpre), maximal corneal power (Kmaxpre), pachymetry, refractive and topographic cylinders, spherical equivalent (SEpre), mean corneal power (MeanK) and follow-up time on outcome measures. The outcome measures were the final change of Kmax (Delta Kmax) and the final change in LogMAR visual acuity (Delta LogMAR). A more negative Delta Kmax or Delta LogMAR represents a favorable effect of crosslinking. RESULTS: 517 eyes had Kmax results, and 385 eyes had LogMAR results with more than one year follow-up. These eyes were included in the study. The mean follow-up time was 2.29 years. Mean Kmax decreased from 54.07±5.99 diopters to 52.84±5.66 diopters (p<0.001), and Mean LogMAR decreased from 0.28±0.20 to 0.25±0.21 (p<0.001). Non-accelerated epithelium-off CXL resulted in greater flattening of Kmax when compared with other protocols. Visual acuity improvement was similar when comparing different CXL protocols. Multivariate analysis showed four factors associated with negative Delta Kmax: high Kmaxpre, high SEpre, high MeanKpre, and non-accelerated procedure. Multivariate analysis showed three factors associated with negative Delta LogMAR: high LogMARpre, high SEpre, and Low MeanKpre. After excluding corneas with Kmaxpre >65 D or Pachymetry<400 microns, multivariate analysis showed that high Kmaxpre, high SEpre, and non-accelerated CXL were associated with negative Delta Kmax while high LogMARpre and high SEpre were associated with negative Delta LogMAR. CONCLUSION: CXL for keratoconus is a highly effective treatment, as evident by its effects on the outcome measures: Delta Kmax and Delta LogMAR. CXL was more successful in eyes with high Kmaxpre, high SEpre, and high LogMARpre, which express disease severity. The non-accelerated epithelium-off protocol was associated with greater flattening of corneal curvature but did not show a better effect on visual acuity as compared to the other CXL protocols.

Vernal keratoconjunctivitis and keratoconus.

PURPOSE OF REVIEW: Vernal keratoconjunctivitis (VKC) is a severe allergic inflammatory disease affecting the conjunctiva in children and young adults. Keratoconus (KC) is a progressive corneal disease characterized by thinning of the corneal stroma, increased and asymmetric corneal curvature, with a potential for significant visual deterioration and is one of the most common corneal complications of VKC. We aimed to review the association of these two diseases, with focus on the mechanisms, prevalence, natural history and treatment strategies of KC associated with VKC. RECENT FINDINGS: KC is a common complication of VKC. KC prevalence can be as high as 26.8% among VKC patients, whereas abnormal corneal topography may appear in up to 71% of them. It is more severe and progresses faster in the setting of VKC (P < 0.05), with remarkable visual deterioration and with an increased need for keratoplasty. Crosslinking treatment and corneal transplantation appear to be as effective for KC patients with VKC as compared to the patients without VKC. However, postoperative complications are higher in patients with VKC and demand close monitoring, tight control of local inflammation and prompt awareness with consequent restrain of eye rubbing. SUMMARY: Patients with VKC should be closely monitored for KC. Prompt recognition of VKC and KC allows tight control of KC pathogenesis mechanisms, timely management of KC progression and preservation of vision and quality of life of young patients.

Quadrant Asymmetric Design Contact Lens for Visual Rehabilitation after Eye Trauma.

The purpose of this case report is to demonstrate the efficacy of an asymmetric peripheral design scleral contact lens in a case of highly irregular corneal-scleral pattern due to trauma. A 63-year-old patient was involved in a jeep accident which caused a partial-thickness penetrating injury to the peripheral cornea of his left eye. The subsequent corneal irregularity extended beyond the limbus into the sclera which made it difficult to stabilize a contact lens. A quadrant specific peripheral curve (quadrant asymmetric periphery) scleral contact lens successfully resulted in improved comfort and visual acuity. This is the first known published case to use this lens design to correct a post-trauma irregular cornea-scleral relationship. Quadrant asymmetric periphery scleral contact lenses can be effective in cases of severe irregular corneal-scleral patterns.

Serological and hematological characteristics of Sjogren's syndrome and dry eye syndrome patients using a novel immune serology technique.

OBJECTIVES: To compare hematologic and serological parameters among patients with Sjogren's syndrome (SS), dry eye syndrome (DES) and controls, and validate a novel multiplex-serology method for identifying auto-antibodies in these populations. METHODS: In a clinic-based case-control study a total of 422 participants were recruited, including 91 with SS, 120 DES, and 211 controls (age and sex frequency-matched). We measured blood counts, anti-nuclear-antibodies (ANA), anti-SSA/SSB, anti-ribonucleoprotein (RNP), anti-double-stranded-DNA (DS-DNA), and rheumatoid factor (RF) using the "Immunodot" qualitative-ELISA assay. Immunoglobulins, C3 and C4 were measured by immune-fluorescence. Autoantibodies were also quantified with a newly-developed method using glutathione-S-transferase fusion proteins of SSA/Ro 52 and 60kD and SSB/La (multiplex-serology), measuring median fluorescence intensity (MFI). RESULTS: Among DES patients, only 2% (95%CI: 0.36-6.3) had positive immune serology. SS patients had lower lymphocyte, hemoglobin and C3 levels but higher prevalence of RF, ANA, anti-SSA/B and higher IgG and MFI levels, compared to DES and controls (P<0.001). Presence of anti-SSA/Ro-52kD was associated with SS [odds ratio (OR) = 2.05, 95% confidence interval (CI): 1.46-2.88]. Anti-SSB/La was inversely associated with DES (OR = 0.81, 95%CI: 0.65-1.00) compared to controls. Positivity to RF (adjusted for age, gender and ethnicity OR = 5.03, 95%CI: 1.78-14.21), ANA (OR = 14.75, 95%CI: 4.09-53.17), or combination of anti-SSA/B (OR = 20.97, 95%CI: 4.60-95.54) were more likely in SS compared to DES. The novel multiplex-serology method correctly identified anti-SSA/B autoantibodies by ELISA among SS, DES patients and controls (sensitivity = 1.0, negative-predictive-value = 1.0). CONCLUSIONS: Serologic parameters distinguish SS from DES patients and controls. A newly-developed multiplex-serology technique may be useful to detect autoantibodies in large epidemiologic studies.

Ocular allergic contact dermatitis from topical drugs.

PURPOSE OF REVIEW: Ocular allergic contact dermatitis is a common yet challenging and frequently misdiagnosed condition. Inappropriate or delayed treatment can contribute to a variety of clinical symptoms such as tearing and itching with signs such as ptosis and cicatricial ectropion, resulting in deterioration of disease, for which the topical medication was originally prescribed to resolve. RECENT FINDINGS: Understanding previously unrecognized pathogenic mechanisms involving ocular contact dermatitis has driven new approaches to control the inflammatory process by neutralizing inflammatory mediators and their receptors. SUMMARY: Early diagnosis and removing the antagonizing substance is crucial to manage ocular contact dermatitis. Steroid therapy is usually required to reduce symptoms. As ocular allergic dermatitis often develops in patients using drugs for chronic conditions that necessitate chronic application, it may be difficult at times to discontinue or replace the offending agent.

Chemokines in allergic conjunctivitis.

PURPOSE OF REVIEW: Chemokines are a large group of low molecular weight cytokines that attract and activate leukocytes throughout the body and therefore have a key role in the framework of late-phase allergic responses. The purpose of this article is to provide an overview of the main chemokines involved in allergic conjunctivitis, their primary functions and their physiological roles, and therapies targeted at chemokines and their receptors for ocular allergic diseases. RECENT FINDINGS: In recent years, there have been considerable advances in the understanding of ocular pathophysiology of ocular surface inflammatory diseases including both allergic eye diseases and dry eye syndrome. Several therapies being developed for dry eye inflammation are recognized as possible therapies for ocular allergic diseases as there are often common chemokines involved in both disease spectra. SUMMARY: Chemokines represent an integral part of the late-phase cascade of ocular allergic inflammation. A deep understanding of specific chemokines and their interactions will help in targeting therapies to effectively manage ocular clinical findings and symptoms of allergic eye disease.

Ophthalmology practice during the COVID-19 pandemic.

OBJECTIVE: To present an established practice protocol for safe and effective hospital-setting ophthalmic practice during the coronavirus disease 2019 (COVID-19) pandemic. METHODS AND ANALYSIS: Literature was reviewed to identify articles relevant to COVID-19 pandemic and ophthalmology. The following keywords were used: COVID-19, SARS-CoV-2 and telemedicine, combined with eye, ophthalmology, conjunctivitis and tears. Data were extracted from the identified manuscripts and discussed among subspecialists to obtain consensus evidence-based practice. RESULTS: A protocol for ophthalmic practice in the era of COVID-19 pandemic was established. The protocol covered patient screening, clinic flow, required personal protective equipment and modifications of ophthalmic equipment for improved safety. CONCLUSION: Important literature emerged with respect to the practice of ophthalmology in the era of COVID-19. An evidence-based ophthalmic practice protocol was established and should be modified in the future to accommodate new insights on the COVID-19 pandemic.

Pathogenesis and complications of chronic eye rubbing in ocular allergy.

PURPOSE OF REVIEW: To review the updated literature regarding eye rubbing complications and its association with ocular allergy disorders. RECENT FINDINGS: Atopy and ocular allergy disorders, mainly vernal keratoconjunctivitis (VKC), are strongly associated with rubbing-related complications, most probably via itching and watery eye sensations that trigger the habit of chronic eye rubbing. Vigorous and prolonged rubbing may lead to establishment of corneal remodeling and ectatic disorders, such as keratoconus. Keratoconus development in rubbed eyes can be caused by mechanical mechanisms of corneal thinning and its loss of rigidity, by elevated temperature of the epithelium during rubbing, by increased intraocular pressure (IOP) because of distending forces, and by inflammatory molecules that may serve as a causal mediator between eye rubbing and keratoconus. Other eye rubbing complications include acute hydrops and perforation, IOP spikes, iris prolapse and iridoschisis rupture of lens capsule and IOL dislocation, and even posterior segment disorders, such as glaucomatous optic neuropathy, retinal detachment and extrusion of implanted silicone oil in the eye. SUMMARY: Chronic eye rubbing in allergic eye diseases can lead to progression of keratoconus, and to other rare anterior and posterior segment complications. Strategies eliminating eye rubbing and its consequences are vital, mainly among at-risk populations, such as young children and individuals with allergic ocular disorders or corneal transplants.

Topical tacrolimus for allergic eye diseases.

PURPOSE OF REVIEW: The spectrum of allergic eye diseases includes a variety of conditions, each characterized by complex immunopathologies.Antiallergic drugs, such as antihistamines and mast cell stabilizers, are often insufficient without concomitant topical corticosteroid treatment. The chronic course of the more severe allergic eye diseases, such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC), limits the treatment with topical corticosteroids to short courses. In addition, topical corticosteroid treatment puts patients at high risk of developing severe ocular complications, particularly during childhood when VKC most frequently occurs.The immunopathology of chronic diseases, such as VKC and AKC, involves predominantly T lymphocytes, and as such, immunomodulators that inhibit T-cell activation seem to be the appropriate treatment for these chronic diseases. In the past years, there is an increased incidence of managing chronic allergic eye diseases with the immunomodulator tacrolimus. The current review presents an update of the recent clinical experience with topical tacrolimus for the management of chronic allergic eye diseases. RECENT FINDINGS: Topical tacrolimus significantly improves the symptoms and signs of the various forms of chronic allergic eye disease. Recent studies also demonstrate the efficacy of low concentrations of topical tacrolimus for VKC.Early medical treatment with topical tacrolimus can also prevent the development of serious ocular complications of VKC, such as shield ulcers or limbal stem cell deficiency. SUMMARY: Topical tacrolimus has significantly changed the management approaches in severe and chronic allergic eye diseases and has minimized the need for topical corticosteroids.

SNP variations in IL10, TNFα and TNFAIP3 genes in patients with dry eye syndrome and Sjogren's syndrome.

BACKGROUND: Cytokines are known to be key players in dry eye syndrome (DES) and Sjogren's syndrome (SS) pathogenesis. In this study we compared single nucleotide polymorphism (SNP) variations in genes encoding cytokine levels among SS and DES patients in Israel. METHODS: We recruited 180 subjects, 82 with SS and 98 with DES. Using a candidate gene approach and allele-specific PCR technique for genotyping, proportions of risk alleles in Tumor Necrosis Factor α (TNFα) (rs1800629), IinterLeukin-10 (IL-10) (rs1800896) and TNFAIP3 (rs2230926) SNPs were compared between study groups. RESULTS: Allelic distribution was found very similar to Caucasian (CEU - Utah residents with Northern and Western European roots) population distributions in these SNPs. While none of the SNPs' variants were significantly associated with SS or DES in a recessive model, in an additive model the TNFα G risk allele was found higher among SS patients compared to DES (Homozygote-G: 84.2% vs. 70.8%; Heterozygote: 26.9% vs. 11.2%, respectively, p = 0.02). After adjustment for age, gender and ethnicity, these variants weren't associated with SS. Genetic scoring reveals that SS patients are more likely to present variants of all three SNPs than DES subjects. CONCLUSIONS: This is the first study evaluating these SNP variations among both patients with DES and patients with SS. We found the allelic distribution in each SNP to be very similar to that found in healthy Caucasian populations presented in the HapMap project. We found the TNFα allele significantly associated with DES for homozygotes, and associated with SS for heterozygotes in the additive model.

[TOPICAL ANTI-INFLAMMATORY AGENTS FOR DRY EYE DISEASE].

INTRODUCTION: Dry eye disease (dry eye) is a multifactorial disorder of the ocular surface. Dry eye is one of the most frequent ocular disorders, affecting 5% to 50% of the entire population at all ages. Evidence suggests that inflammation and hyperosmolarity are considered core mechanisms in the development of dry eye. Dry eye is accompanied by changes in tear composition including enhanced hyperosmolarity and secretion of pro-inflammatory mediators such as cytokines, chemokines, matrix metalloproteinases (MMPs) and adhesion molecules. All these factors may act as mediators of tissue damage leading to lysis of cell membranes and tight junctions in epithelial cells. Eventually these processes lead to corneal and conjunctival epithelial cells death as well as conjunctival goblet cell dysfunction and death. Anti-inflammatory agents for dry eye include corticosteroids, immunomodulator agents and essential fatty acids. Recently, an integrin lymphocyte function-associated antigen-1 (LFA-1) antagonist, lifitegrast ophthalmic solution (Xiidra) was approved in the USA for the treatment of dry eye. Lifitegrast blocks the binding of intercellular adhesion molecule-1 (ICAM-1) to LFA-1. The following review attempts to present a current update of the available anti-inflammatory agents for dry eye disease.

Shared Medical and Environmental Risk Factors in Dry Eye Syndrome, Sjogren's Syndrome, and B-Cell Non-Hodgkin Lymphoma: A Case-Control Study.

OBJECTIVES: To assess whether there are shared exposures associated with Sjogren's syndrome (SS), dry eye syndrome (DES), and B-cell non-Hodgkin lymphoma (B-NHL), in order to determine whether they are etiologically related. METHODS: In a clinic-based case-control study, 702 participants (91 SS, 120 DES, 211 (age and sex frequency-matched) controls, and 280 B-NHL cases) were recruited and interviewed regarding exposures, medical history, and family history. RESULTS: Female predominance was noted in SS (ratio 9.2 : 1). Eye dryness was severest in SS compared to DES and controls (P < 0.001). Compared to controls, alcohol consumption was inversely associated with NHL, DES, and SS (odds ratio (OR) = 0.47, 95% confidence interval (CI): 0.31-0.71; OR = 0.54, 95% CI: 0.33-0.88; and OR = 0.26, 95% CI: 0.14-0.49, respectively), while a previous history of infection requiring hospitalization was positively associated with all three conditions: NHL (OR = 1.92; 95% CI: 1.23-2.99), DES (OR = 3.29; 95% CI: 1.97-5.47), and SS (OR = 4.74; 95% CI: 2.66-8.44). NHL patients were more likely to report first-degree relatives with hematologic cancer, while having first-degree relatives with an autoimmune disease (AID) was associated with SS (OR = 5.25; 95% CI: 2.59-10.63) and DES (OR = 3.55; 95% CI: 1.83-6.91) compared to controls. CONCLUSIONS: Some exposures are associated with all three conditions (such as an inverse association with alcohol consumption and a positive association with serious past infection), while a family history of AID appears to be shared by DES and SS, but not NHL subjects. Shared risk factors for all three conditions indicate possible mutual etiological pathways.