Atopic Keratoconjunctivitis: Pathophysiology, Clinic, and Potential New Therapeutic Concepts. / Atopische Keratokonjunktivitis: Pathophysiologie, Klinik und potenzielle neue Therapiekonzepte.

Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease with a bipolar age distribution in childhood, adolescence and middle adulthood. Up to 50% of AD patients show ocular involvement, which can be potentially sight threatening. Clinically, the majority of cases present with atopic blepharo(kerato)conjunctivitis or atopic keratoconjunctivitis (AKC); other clinical variants from this group of inflammatory ocular surface diseases are keratoconjunctivitis vernalis in childhood and adolescence and allergic conjunctivitis. In addition to the aforementioned blepharitis, keratitis and conjunctivitis, AD is also associated with eyelid involvement with subsequent eyelid malposition, limbal insufficiency with the development of pseudopterygia, (chronic) cicatrizing conjunctivitis with symblephara formation and fornix shortening, as well as ocular surface malignancies such as conjunctival intraepithelial neoplasia (CIN) and squamous cell carcinoma. In addition, an association with AD or AKC has been described for keratoconus. Whereas the therapy of AD in dermatology has made revolutionary advances in recent years through the use of biologicals, the primary use of these biologicals in ophthalmological complications is still very hesitant. Treatment here is often provided using topical steroids and calcineurin inhibitors. The following article summarises recent developments in basic and clinical dermatological research and discusses them in the context of current concepts for ophthalmological therapy.

Allergy and Dry Eye Disease.

Ocular allergy (OA) and dry eye disease (DED) are the most common ocular surface disorders with a potential severe impact on the patient's quality of life. OA and DED may coexist and have a significant clinical overlap. Therefore, clinical features commonly believed to be distinctive of OA or DED may be sometimes insufficient for a differential diagnosis. Alterations of the tear film, epithelial barrier, and corneal innervation are described in OA and can pave the way to DED. Conversely, DED may facilitate or worsen allergic reactions in predisposed (atopic) patients. For these reasons, OA and DED should be considered as reciprocal predisposing conditions that share ocular surface inflammation as a common background.

Pediatric Keratoconus: Topographic, Biomechanical and Aberrometric Characteristics.

PURPOSE: This study sought to evaluate the demographic profile, clinical features, topographic features, and biomechanical and aberrometric characteristics in pediatric keratoconus (KC). DESIGN: Cross-sectional study. METHODS: Pediatric KC cases <18 years of age were evaluated at a tertiary hospital. Main outcome measurements were demographic profile, clinical features, visual acuity, corneal topography, aberrometry, and biomechanical and confocal microscopy findings. RESULTS: A total of 116 eyes of 62 consecutive patients were recruited with a mean ± age of 14.7 ± 2.77 years (range: 8-18 years); 46 of 62 (88%) were males; 57 of 62 cases (92%) had bilateral disease; 53 of 116 eyes (46%) had progressive KC; and 9 of 116 eyes (8%) had acute hydrops. Systemic associations were found in 6 of 62 patients (9.7%) and ocular associations in 77 of 116 eyes (66.3%); 68 of 116 eyes (58.6%) had associated vernal keratoconjunctivitis (VKC). Among eyes with VKC, 29 of 68 eyes (46%) were in stage IV KC, versus 25% of eyes with no VKC (P = .004). The mean ± SD refractive spherical equivalent was -4.72 ± 3.32 diopters (D), and refractive astigmatism was 3.69 ± 3.09 D. The mean values of maximum keratometry, thinnest pachymetry, and corneal higher-order aberrations were 60.89 ± 10.9 D, 396.05 ± 95.03 µm, and 1.18 ± 1.2 µm, respectively. Values of corneal hysteresis and corneal resistance factor correlated with the stage of KC (r = -0.26; P = .007). CONCLUSIONS: Pediatric KC was commonly associated with VKC in this cohort. Eyes with VKC had more severe KC than those without VKC. Nearly half of the patients presented with progressive disease. Corneal biomechanical changes correlated well with stage of KC in this pediatric age group.

The spectrum of allergic ocular diseases.

OBJECTIVE: The purpose of this article is to review the pathophysiologic mechanisms, differential diagnosis, evaluation, and treatment of the various manifestations of ocular allergy, with an especial focus on immunoglobulin E (IgE)-mediated disease. DATA SOURCES: A PubMed search was performed to include articles, using the search terms ocular allergy and allergic conjunctivitis. STUDY SELECTIONS: Recent and relevant human studies in the English language pertaining to our topic of study were selected. Animal studies pertaining to pathophysiology of ocular allergy were also reviewed. We focused on clinical trials, practice guidelines, reviews, and systematic reviews. In addition, case reports were reviewed if they described rare clinical presentations, disease mechanisms, or novel therapies. RESULTS: Ocular allergy encompasses both IgE- and non-IgE-mediated disease, and the clinical severity may range from mild to sight-threatening inflammation. A comprehensive treatment regimen including education, lifestyle measures, topical therapies, and even systemic interventions may be necessary for the effective management of ocular allergies, tailored according to symptom severity. CONCLUSION: Ocular allergy is frequently encountered by allergists and eye-care specialists, and despite progressively increasing incidence, it often remains underdiagnosed and, hence, untreated.

Small airways in children with allergic rhinoconjunctivitis: the potential role of a multicomponent nutraceutical.

Allergic rhinitis and asthma are closely linked. A progression from rhinitis to overt asthma is common. FEF25-75 is a spirometry parameter that could reflect small airways patency and could reliably predict early bronchial involvement in allergic rhinitis patients. MEF50 very strongly correlates with FEF25-75. The aim of this study was to evaluate possible spirometry change in two groups of children suffering from AR over time. The first group took a course of a nutraceutical (Lertal®) before the observation (active group, AG); a second one was considered as control (control group, CG). The children were visited at baseline, at the end of the nutraceutical course, and after 1 year. FEV1, FVC, and MEF50 were the primary outcomes. After one year, children in AG had significantly higher MEF50 than CG children (p=0.009). In conclusion, the present study showed that a course with a multicomponent nutraceutical could prevent the MEF50 decline in children with allergic rhinoconjunctivitis.

Allergic rhinoconjunctivitis: pathophysiological mechanism and new therapeutic approach.

Allergic rhinoconjunctivitis (AR) is the most common IgE-mediated disease. A type2 immune response is involved in AR pathogenesis. Allergic inflammation is characterized by eosinophilic infiltrate and mediators release. AR treatment is usually based on medication prescription, including antihistamines and intranasal corticosteroids. However, medications may be prescribed for long periods and sometimes may be scarcely effective, thus aggressive strategy should be used. Therefore, complementary medicine is becoming attractive for patients at present. Nutraceuticals represent interesting therapeutic options in clinical practice. In this regard, a new compound has been designed containing Vitamin D3, Perilla extract, and quercetin.

Pollen-Food Allergy Syndrome: A not so Rare Disease in Childhood.

Seasonal allergic rhinoconjunctivitis (SAR) affects millions of people worldwide, particularly in childhood and adolescence. Pollen food allergy syndrome (PFAS) is a common adverse reaction occurring few minutes after the consumption of vegetable foods in patients with pollen-induced SAR. PFAS has rarely been investigated in the pediatric population, as it has been mainly examined as an adult disease. Recent studies suggested that PFAS might be more frequent in childhood than previously recognized. The present review aims to give an overview of the epidemiology, pathophysiology, diagnosis, management and prognosis of PFAS in children with SAR-induced by pollens.

Safety and Efficacy of Supratarsal Triamcinolone for Treatment of Vernal Keratoconjunctivitis in Ireland.

PURPOSE: To describe the clinical features, risk factors, and treatment outcomes after supratarsal injection of triamcinolone for vernal keratoconjunctivitis (VKC). METHODS: A retrospective review of all patients treated with supratarsal triamcinolone for VKC between February 2002 and May 2017 at the Royal Victoria Eye and Ear Hospital and Our Lady's Children Hospital Crumlin, Dublin, Ireland, was performed. RESULTS: Twenty-five patients, 46 eyes, and 145 injections were included for analysis. The mean age at first injection was 9.1 ± 5.7 years. Ninety-six percent of the patients were male. A seasonal variation was noted, with 59 injections (41%) of triamcinolone administered for acute and refractive cases of VKC in the summer compared with 35 (24%), 35 (24%), and 16 (11%) in the spring, autumn, and winter months, respectively. The most common presenting complaint was red eye, which was seen in all cases. Hay fever (64%) was the most common associated systemic disease. Each eye required, on average, 3.2 injections (range 1-9 injections), and the mean duration from the onset of symptoms to final treatment was 3.03 years (range 0-7.9 years). The mean presenting and final visual acuities were 0.33 and 0.11 logarithm of the minimum angle of resolution, respectively (P < 0.0001). During our study period, no patient experienced intraocular pressure rise requiring treatment, development of lenticular opacity, or ptosis after supratarsal injection of triamcinolone. CONCLUSIONS: In this case series, supratarsal triamcinolone was used in cases of VKC in which topical medications had failed to control the disease process. All patients reported improvement after treatment. There were no cases of intraocular pressure rise, lenticular opacity, or ptosis development after treatment.

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.

The histaminergic control of the iridal vascular tone in rats and its influencing by topical administration of olopatadine and ranitidine.

Objective. We evaluated the histamine's role in regulating the iris vasomotricity in rats, using as a research tool topical olopatadine, a selective H1 blocker, which is indicated for the treatment of allergic conjunctivitis and ranitidine, a selective H2 blocker mainly used for the treatment of peptic ulcer disease. Methods. Two groups of six Wistar rats anesthetized with ketamine 200 mg/kg body weight were used. They received distilled water in conjunctival instillations, initially and after 5 minutes, olopatadine 2.5 mmol/ l for the first group, respectively ranitidine 2.5 mmol/ l for the second group. The changes of the iris arteriolar and venular diameters were recorded. Results. Both olopatadine and ranitidine produced statistically significant iridal arteriolar vasoconstriction and ranitidine determined statistically significant venuloconstriction, while distilled water did not produce any statistically significant effect. Conclusions. There is a vasodilator histaminergic tone exerted through the histaminergic H1 and H2 receptors in the iris arterioles and, respectively, through the H2 receptors in the iridal venules. Olopatadine, a topical H1 antagonist used in the treatment of ocular allergies, may interfere with the humoral regulation of the iris arteriolar tone. Ranitidine, an H2 antagonist, decreased the diameter of the iris arterioles and venules, when administered topically in rats.

Mini-monoka stenting for patients with perennial allergic conjunctivitis.

Purpose: To assess the effectiveness of mini-monoka (MM) stenting in treating patients with perennial allergic conjunctivitis (PAC) and punctal stenosis. Methods: A retrospective case analysis was performed on 20 patients (40 eyes) who suffered from PAC with punctal stenosis who underwent MM (FCI Ophthalmics, Pembroke, MA, USA) stenting. Results: Nineteen patients (95%) were females, with an age range of 19-66 years (average 40.6 ± 25.4 years). All 20 patients (100% of eyes) had signs of PAC and punctal stenosis. All 20 patients (40 eyes) had received previous topical treatment including steroids. Nineteen patients (95% of eyes) had significant improvement in their allergy symptoms (tearing and conjunctival inflammation) following MM stenting. Conclusions: Stenosis of the punctum may play a role in the relapsing symptoms in PAC. MM stenting is a simple, safe, effective, and relatively non-invasive treatment option for the management of PAC in the presence of punctal stenosis.

Ocular involvement in atopic disease: a review.

PURPOSE OF REVIEW: To provide a review of the potential sight-threatening sequelae associated with ocular involvement of atopic disease and to discuss the management of this chronic condition. RECENT FINDINGS: There has been a recognition that atopic keratoconjunctivitis (AKC) is a chronic, inflammatory and potentially blinding disease. Recent efforts have focused on steroid sparing, systemic T cell and calcineurin inhibitor medications for the treatment of severe disease. SUMMARY: Ocular involvement in atopic disease can have a variety of clinical manifestations. Progressive disease can be vision threatening, especially in younger patients. Prompt and effective treatment through a multidisciplinary approach, including ophthalmology, allergy and immunology and dermatology, can permit stability of the disease.

Ocular allergy as a risk factor for dry eye in adults and children.

PURPOSE OF REVIEW: To provide an overview of the pathogenic mechanisms underlying the correlation between ocular allergy and dry eye disease (DED), highlighting how the first condition may be a risk factor for the second one. RECENT FINDINGS: Recent advances in our comprehension of the pathogenesis of ocular allergy and DED allow identifying several pathways of interaction between these two conditions. A growing body of evidence supports the role of ocular allergy as a risk factor for DED. Ocular allergy, particularly the severe forms of keratoconjunctivitis, can impact on different key mechanisms of the DED vicious cycle, including tear film instability, ocular surface inflammation and damage, and neurosensory abnormalities. SUMMARY: Ocular allergy and DED are two common, relevant, symptomatic, not mutually exclusive conditions affecting the ocular surface. They share some clinical and biochemical features. To better understand the complex interactions between these two conditions, it's essential to consider the very wide spectrum of clinical conditions included in the term ocular allergy and the still largely unexplored peculiarities of the pediatric ocular surface physio-pathology and DED.

The burden of allergic rhinitis and allergic rhinoconjunctivitis on adolescents: A literature review.

OBJECTIVE: To evaluate the literature regarding the burden of allergic rhinitis (AR) and allergic rhinoconjunctivitis (ARC) in adolescents (aged 10-19 years). DATA SOURCES: Searches were performed in MEDLINE, Embase, Health Technology Assessment Database, and National Health Service Economic Evaluation Database for studies that evaluated concepts of symptoms, quality of life (QOL), daily activities, sleep, examination performance, school absenteeism and presenteeism, and treatment burden in adolescents with AR or ARC. STUDY SELECTIONS: English-language journal articles indexed in the last 15 years describing noninterventional, population-based studies. Records were assessed by 2 independent reviewers. RESULTS: A total of 27 articles were identified; outcomes evaluated were symptoms (n = 6 studies), QOL (n = 9), daily activities (n = 5), emotional aspects (n = 3), sleep (n = 6), education (n = 7), and treatment burden (n = 2). AR symptoms rated most bothersome were rhinorrhea, nasal congestion, and itchy eyes. QOL was worse in adolescents with AR vs controls regardless of QOL instrument used. Nasal symptoms and nasal obstruction were more likely to be associated with poor QOL in adolescents than in adults or younger children, respectively. Daily functioning and sleep were also negatively affected by AR. In addition, a detrimental effect on absenteeism, school productivity, and academic performance was reported. CONCLUSION: Although AR and ARC are sometimes perceived as trivial conditions, this review indicates that their effect on adolescent life is negative and far-reaching. It is critical that clinicians gain a greater understanding of the unique burden of AR and ARC in adolescents to ensure they receive prompt and appropriate care and treatment to improve clinical and academic outcomes.

Atopic keratoconjunctivitis: A diagnostic dilemma-a case report.

RATIONALE: Atopic keratoconjunctivitis (AKC) remains a difficult diagnosis despite advances in imaging technologies. This is a case study of the diagnostic and treatment course for a patient with AKC. PATIENT CONCERNS: A 15-year-old male complained of progressively increasing pain, redness, watering and blurred vision in the right eye. The medical history showed that the patient suffered from itching on the hands, knees, neck and the eye skin one year before the onset of initial symptoms in the affected eye. DIAGNOSES: A final diagnosis of stage III AKC with atopic dermatitis (AD) was reached. INTERVENTIONS: The patient was used 0.1% tacrolimus eye drops and 0.3% gatifloxacin eye gel after antimicrobial susceptibility test was performed. In the presence of AD, 0.1% mometasone furoate cream and 0.03% tacrolimus ointment were applied twice daily. OUTCOMES: One month after starting treatment, the conjunctivitis and corneal ulcer rapidly improved along with reduced lid papillae. Macular grade corneal opacity was noticed with minimal thinning. The AD also rapidly improved. At the end of two months patient was asymptomatic with a significant improvement in his quality of life. LESSONS: Proper diagnosis of AKC especially when associated with dermatological signs along with management of AD in conjunction with dermatologist is necessary to prevent corneal involvement which can cause permanent visual disability is of utmost importance. We also noticed that topical tacrolimus is a good option for the treatment of severe AKC with AD along with systemic immunosupressants.

Lack of effect of Timothy grass pollen sublingual immunotherapy tablet on birch pollen-induced allergic rhinoconjunctivitis in an environmental exposure unit.

BACKGROUND: Timothy grass pollen allergen extract tablets (Grastek) are standardized sublingual immunotherapy tablets (SLIT-T) approved for the treatment of grass pollen-induced allergic rhinitis (AR) and conjunctivitis. Many grass allergic patients are also cosensitized to birch pollen. Whether Timothy grass SLIT-T can confer symptomatic benefits for birch pollen-induced AR symptoms is unknown. OBJECTIVE: To evaluate the treatment effect of Timothy grass SLIT-T for birch pollen-induced AR in participants sensitized to both grass and birch pollen using an environmental exposure unit (EEU). METHODS: This study was a phase 4, randomized, double-blind, placebo-controlled, parallel-group study that enrolled participants aged 18 to 65 years allergic to both timothy grass and birch pollen. After a baseline EEU birch pollen challenge, in which a minimum total nasal symptom score (TNSS) of 6 of 12 was required for enrollment, participants were randomized to receive Timothy grass SLIT-T or placebo taken once daily for 4 months. No confirmatory grass pollen challenge was performed. The primary end point was the change in TNSS averaged from assessments from hours 2 to 5 during the posttreatment birch pollen challenge compared with baseline. The secondary and exploratory end points included temporally identical changes in total ocular symptom score (TOSS), total rhinoconjunctivitis symptom score (TRSS), and individual symptom scores. RESULTS: The difference in TNSS reduction after 4 months of therapy between the Timothy grass SLIT-T and placebo group was not significant (P = .83). Reductions in TOSS (P = .19) and TRSS (P = .67) were also comparable between groups. Findings between groups for individual symptom scores were similar (all P > .40), except for watery eyes, in which symptom reduction was slightly better in the placebo arm (P = .01). Timothy grass SLIT-T was well tolerated, and no serious adverse effects occurred. CONCLUSION: A bystander effect of grass SLIT-T on birch pollen-induced AR symptoms was not detected. Symptomatic benefits of grass SLIT-T are likely allergen specific. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02394600.

Comparative Evaluation of Tacrolimus Versus Interferon Alpha-2b Eye Drops in the Treatment of Vernal Keratoconjunctivitis: A Randomized, Double-Masked Study.

PURPOSE: Vernal keratoconjunctivitis (VKC) is a bilateral, chronic, external ocular inflammatory disorder that mainly affects patients in their first or second decade. This study was designed to compare tacrolimus and interferon alpha-2b (IFN alpha-2b) eye drops in the treatment of VKC. METHODS: In this randomized, double-masked clinical trial, 40 consecutive patients with VKC were sent to a referral eye hospital in a tropical region southeast of Iran. Patients were randomly assigned to receive either 0.005% tacrolimus or IFN alpha-2b (1,000,000 units/cc). Chi-square and t tests were used for comparison of outcomes between both groups. RESULTS: Mean ± SD age was 11.1 ± 5.2 years. Thirty-one patients (77.5%) were male. The mean duration of disease was 3.4 ± 2.9 years. In this study, the signs and symptoms were significantly reduced in patients after treatment in both groups (P = 0.0001). In the tacrolimus group, all patients responded to treatment whereas only one subject in the IFN group failed to respond (P = 0.99). Side effects in both groups were mild and tolerable. CONCLUSIONS: This study indicated that both 0.005% tacrolimus and IFN alpha-2b are effective and appear to be safe in treatment of recalcitrant VKC.

Effect of Allergic Diseases on Keratoconus Severity.

PURPOSE: To investigate the association between keratoconus (KC) and allergic diseases. METHODS: In a prospective age- and sex-matched case--control study clinical data of 885 KC patients and 1526 controls were evaluated regarding the presence of various allergic diseases. Severity of KC and ophthalmic parameters of KC patients were compared between KC patients with and without allergic diseases. RESULTS: The prevalence of allergic diseases was significantly higher in KC patients. KC patients with vernal keratoconjunctivitis (VKC) or allergic conjunctivitis (AC) had significantly thinner and steeper corneas in comparison with non-allergic KC patients. Only VKC and AC were significantly associated with KC severity. CONCLUSIONS: Patients with VKC or AC were at increased risk of KC. They had more severe KC and should be closely followed up and intensively treated.

Increasing Comorbidities Suggest that Atopic Dermatitis Is a Systemic Disorder.

Atopic dermatitis comorbidities extend well beyond the march to allergic conditions (food allergy, asthma, allergic rhinitis, allergic conjunctivitis, and eosinophilic esophagitis), suggesting both cutaneous and systemic immune activation. In reviewing atopic dermatitis comorbidities, Councilors of the International Eczema Council found a strong pattern of immune activation in peripheral blood and the propensity to both skin and systemic infections. Associations with cardiovascular, neuropsychiatric, and malignant diseases were increasingly reported, but confirmation of their link with atopic dermatitis requires longitudinal studies. Given the possibility of atopic dermatitis-related systemic immune activation, future investigations of new interventions should concurrently examine the impact on these comorbidities.