Shield ulcer in keratoconus in the absence of atopic or vernal kerato-conjunctivitis

Purpose: To describe MUC5AC alterations and the ocular surface disorder in atopic patients with or without corneal ulcers. Methods: Atopic patients' eyes were divided into two groups according to the presence and absence of corneal ulceration. The subjects underwent corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT), fluorescein and Rose Bengal staining of the ocular surface and conjunctival impression cytology and brush cytology. Impression cytology samples underwent PAS and immunohistochemical staining for MUC5AC. Brush cytology specimens underwent evaluation for inflammatory cell expression and quantitative real-time PCR for MUC5AC mRNA expression. The differences related to the tear function and ocular surface examination parameters between patients with and without corneal ulceration and healthy control subjects were studied. In addition, the differences of the study parameters related to ocular surface epithelial health and inflammatory status between patient eyes with atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC) were investigated. Results: The mean corneal sensitivity and BUT values were significantly lower in atopic patients with corneal ulcers, compared to patients without ulcers and controls (p < 0.001). Brush cytology specimens from patients with corneal ulcers revealed significantly higher expression of inflammatory cells compared to patients without ulcers and controls (p < 0.001). Impression cytology samples from eyes with corneal ulcers showed significant squamous metaplasia and reduction in goblet cell density compared to eyes without ulcers and eyes of control subjects. The mean squamous metaplasia grade was significantly higher in eyes with AKC compared to eyes with VKC (p < 0.02). The mean goblet cell density was significantly lower in eyes with AKC compared to eyes with VKC (p < 0.01). Specimens from eyes with corneal ulcers showed PAS positive mucin pickup and did not stain positive for MUC5AC. MUC5AC mRNA expression was significantly lower in eyes with corneal ulcers compared to eyes without ulcers and eyes of control subjects. MUC5AC mRNA expression was also significantly lower in eyes with AKC compared to eyes with VKC. Conclusions: Ocular surface inflammation, tear film instability, and decreased conjunctival MUC5AC mRNA expression were thought to be important in the pathogenesis of noninfectious corneal shield ulcers in atopic ocular surface disease.

The objective of this study is to evaluate the practical usefulness of a scoring system using the 5-5-5 exacerbation grading scale for allergic conjunctivitis disease (ACD). Subjects were 103 patients with ACD including 40 patients with vernal keratoconjunctivitis (VKC), 20 patients with atopic keratoconjunctivitis (AKC), and 43 patients with allergic conjunctivitis (AC). The 5-5-5 exacerbation grading scale consists of the following 3 graded groups of clinical observations: the 100-point-grade group (100 points for each observation) includes active giant papillae, gelatinous infiltrates of the limbus, exfoliative epithelial keratopathy, shield ulcer and papillary proliferation at lower palpebral conjunctiva; the 10-point-grade group (10 points for each observation) includes blepharitis, papillary proliferation with velvety appearance, Horner-Trantas spots, edema of bulbal conjunctiva, and superficial punctate keratopathy; and the 1-point-grade group (1 point for each observation) includes papillae at upper palpebral conjunctiva, follicular lesion at lower palpebral conjunctiva, hyperemia of palpebral conjunctiva, hyperemia of bulbal conjunctiva, and lacrimal effusion. The total points in each grade group were determined as the severity score of the 5-5-5 exacerbation grading scale. The median severity scores of the 5-5-5 exacerbation grading scale in VKC, AKC and AC were 243 (range: 12-444), 32.5 (11-344), and 13 (2-33), respectively. The severity score of each ACD disease type was significantly different (P < 0.001, Kruskal-Wallis test). The severity of each type of ACD was classified as severe, moderate, or mild according to the severity score. The 5-5-5 exacerbation grading scale is a useful clinical tool for grading the severity of each type of ACD.

Tear and serum soluble leukocyte activation markers in conjunctival allergic diseases

Vernal keratoconjunctivitis (VKC) is a rare yet severe form of allergic conjunctivitis predominantly affecting children, mainly boys, with a global prevalence and a higher incidence in certain geographical regions. The disease is characterized by seasonal exacerbations. VKC presents with ocular surface inflammation leading to various distressing symptoms such as itching, redness, mucous discharge, and pain. The disease primarily manifests bilaterally, though it may initially appear unilaterally. If left untreated, VKC can result in corneal complications, including shield ulcers and vision impairment, affecting daily activities and psychosocial well-being, especially in children. The diagnosis of VKC involves identifying key clinical findings on the ocular surface such as Tranta dots, giant papillae, or shield ulcers. Management follows a stepwise approach, including anti-allergic eye drops, steroid eye drops, and topical medications like cyclosporine, which may take up to 3months to show efficacy. Allergic sensitization, often to inhaled allergens like pollen and house dust mites, is associated with VKC in half of the cases. Understanding and managing these allergies through measures such as avoidance, sensitization control, and co-treatment of associated conditions like asthma and rhinoconjunctivitis are essential in VKC management. Atopic keratoconjunctivitis (AKC), a related condition associated with atopic dermatitis and asthma, shares similarities with VKC but typically affects young adults. However, there is an observed spectrum between the two diseases, indicating similar treatment strategies for both. VKC treatment requires a patient-centered approach, involving informed and supported parents, considering economic factors due to costly eye drops, and ensuring accessibility and practicality of treatment, especially in children. A multidisciplinary team collaboration, including ophthalmologists, pediatricians, and dermatologists, optimizes patient care. The rewarding aspect of VKC treatment lies in witnessing children regain their quality of life, overcome vision challenges, and thrive in their daily activities. In conclusion, understanding VKC, its associated allergies, and employing a comprehensive, patient-centered approach are crucial in managing this challenging condition, particularly in children, to enhance their vision and overall well-being.

Acquisition of Vernal and Atopic Keratoconjunctivitis After Bone Marrow Transplantation

Collyres de ciclosporine : étude d’une cohorte de patients de 2009 à 2013

To evaluate the effectiveness and safety of a novel cyclosporine 0.1% aqueous ophthalmic solution in a large population with vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC). A prospective observational postmarketing study was initiated in Japan. A total of 594 patients with VKC or AKC were started on this drug within 1 year after market launch (January 2006) and completed a 6-month follow-up. These patients were observed clinically, and subjective ocular symptoms (itching, discharge, tearing, photophobia, foreign body sensation, and pain), objective signs (hyperemia, swelling, follicle, papillae, and giant papillae for the tarsal conjunctiva; hyperemia and edema for the bulbar conjunctiva; Trantas dots and swelling for the limbus; and corneal involvement), and adverse events were recorded. All scores for symptoms and signs significantly decreased from Month 1 through Month 6 of treatment in both VKC and AKC. Median total symptom scores at baseline, Month 1, and Month 6 were 6, 2, and 1, respectively, for VKC, and 7, 3, and 2, respectively, for AKC. Similarly, median total sign scores were 12, 7, and 5, respectively, for VKC, and 14, 10, and 7, respectively, for AKC. The percentage of patients able to complete topical cyclosporine 0.1% therapy within 6 months due to alleviation of symptoms was higher for VKC (44.4%) than for AKC (21.9%). In both VKC and AKC, approximately 30% of steroid users were able to discontinue topical steroids. Adverse drug reactions (ADRs) were found in 12.0% of patients, and the most common ADR was eye irritation (4.4%). Infectious corneal complications were observed in five AKC patients, including two cases of bacterial corneal ulcer and three cases of herpetic keratitis; all of these patients were concomitantly using topical steroids. Topical cyclosporine 0.1% is an effective and safe treatment for VKC and AKC.

Atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC) are severe and potentially sight-threatening allergic eye diseases characterised by chronic inflammation of the ocular surface. Both topical and systemic treatments are used. This Cochrane Review focuses on systemic treatments. To assess the effects of systemic treatments (including corticosteroids, NSAIDS, immunomodulators, and monoclonal antibodies), alone or in combination, compared to placebo or other systemic or topical treatment, for severe AKC and VKCin children and young people up to the age of 16 years. We searched CENTRAL, Ovid MEDLINE, Ovid Embase, the ISRCTN registry, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). There were no restrictions to language or year of publication. We last searched the electronic databases on 17 February 2020. We searched for randomised controlled trials (RCTs) that involved systemic treatments in children aged up to 16 years with a clinical diagnosis of AKC or VKC. We planned to include studies that evaluated a single systemic medication versus placebo, and studies that compared two or multiple active treatments. We used standard methods expected by Cochrane. No trial met the inclusion criteria of this Cochrane Review. No RCTs have been carried out on this topic. There is currently no evidence from randomised controlled trials regardingthe safety and efficacy of systemic treatments for VKC and AKC. Trials are required to test efficacy and safety of current and future treatments. Outcome measures need to be developed which can capture both objective clinical and patient-reported aspects of the condition and treatments.

The usefulness of measuring tear periostin for the diagnosis and management of ocular allergic diseases

Vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) are complex and rare diseases. Thus, their diagnosis and treatment are often achallenge. Discussion on the epidemiology, new pathogenetic concepts, interesting clinical findings, diagnostic possibilities and new treatment options and their side effects in severe ocular allergies. Analysis of the presentation of VKC in the internet. Evaluation of recent review articles, original publications, and case reports on the topics of VKC and AKC over the past 5years. Ocular allergies have significantly increased over the last decades. Recent concepts discussed in the pathogenesis of VKC and AKC are the role of the local and gut microbiome as well as the influence of neuroinflammation. Keratoconus is significantly more common in patients with VKC and AKC compared to the normal population. It is associated with faster progression and a more severe course of disease. Aconjunctival provocation test is only rarely necessary in the diagnosis of allergic conjunctivitis. Treatment of atopic dermatitis with dupilumab, an interleukin 4 receptor alpha (IL-4Ra) antagonist, can cause ocular side effects. Unfortunately, information available on the internet for patients and parents on the topic of VKC is sometimes dangerously incorrect. From the abovementioned new pathogenetic concepts, preventive and personalized treatment options could be developed in the future. Keratoconus in AKC/VKC must be recognized and treated early. Official guidelines are now available for astandardized conjunctival provocation test in the diagnosis of allergic conjunctivitis. The unwanted ocular side effects of dupilumab are often difficult to discriminate from the actual underlying AKC and respond well to anti-inflammatory treatment. Patients with VKC must be informed about the incorrect information on the internet regarding their disease.

Giant papillae (GP) in patients with vernal keratoconjunctivitis (VKC) refractory to clinical treatment may cause serious corneal complications, such as shield ulcer. We propose a surgical treatment--resection of GP--in conjunction with free autologous conjunctival graft to treat severe cases of VKC with GP. Six eyes of five patients with VKC, characterized by GP and shield ulcer refractory to clinical treatment, underwent surgical resection of GP associated with free autologous conjunctival graft. No recurrence of GP over the graft was observed during follow-up intervals ranging from 9 months to 27 months. Corneal shield ulcers healed during the first week after treatment and did not recur. Patients with refractory VKC and GP associated with corneal shield ulcer may benefit from resection of GP and autologous conjunctival graft.

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. 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. Topical tacrolimus has significantly changed the management approaches in severe and chronic allergic eye diseases and has minimized the need for topical corticosteroids.

Background and importanceTacrolimus is an immunosuppressant with many potential uses in ophthalmic diseases. It is an inhibitor of calcineurin phosphatases, which suppress the first phase of T cell activation and...

Patients with atopic eczema frequently experience colonization with Staphylococcus aureus that is directly correlated with the eczema severity. We hypothesized that S. aureus-secreted enterotoxins (SE) are involved in the pathophysiology of atopic keratoconjunctivitis (AKC). A total of 45 subjects (18 with AKC, nine vernal keratoconjunctivitis (VKC), eight seasonal allergic conjunctivitis (SAC), and ten healthy volunteers) were enrolled. Slit lamp examinations, including fluorescein staining, were performed. Scraped samples were collected from the upper tarsal conjunctiva, lower conjunctival sacs, and the skin around the eyelid margins. Superantigen (SAg) genes were detected using polymerase chain reaction (PCR). Among 45 cases, S. aureus was detected significantly more in AKC patients than VKC patients (P = 0.026), SAC patients (P = 0.0003), and healthy volunteers (P = 0.0001). SAg genes were detected in 11 patients. SEB (2/11), SEG (8/11), and SEI (8/11) were detected, but no other SE. There was a significant difference in SE detection between AKC and SAC patients (P = 0.03). In severe types of ocular allergic disease such as AKC and VKC (N = 27), SE was detected in six of ten patients with corneal ulcers and two of 17 patients without corneal ulcers. SE was detected in significantly more patients with corneal ulcers (P = 0.025). In patients with AKC, S. aureus and SE were detected more frequently compared with other patients and healthy volunteers, especially in association with corneal ulceration suggesting a role of SE. So far, it is unknown whether SE leads to tissue damage of the cornea by initiating an immune response or has direct toxic effects.

The pathogenesis of the ocular surface disease in atopic keratoconjunctivitis (AKC) and vernal keratoconjunctivitis (VKC) has not been fully understood. We tried to clarify the differences in the ocular surface status in patients with AKC, VKC, and healthy control subjects. Twenty-four eyes of 12 AKC patients, 12 eyes of six VKC patients, and 20 eyes of 10 normal control subjects were studied. The subjects underwent corneal sensitivity measurements, Schirmer test, tear film break-up time (BUT), vital staining of the ocular surface, conjunctival impression and brush cytology. Impression cytology samples underwent periodic acid Schiff staining for goblet cell density, squamous metaplasia grading, and immunohistochemical staining for MUC1, 2, 4, and 5AC. Brush cytology specimens underwent staining for inflammatory cell counting and Real Time PCR for MUC1, 2, 4, and 5AC mRNA expression. The mean BUT, corneal sensitivity, and conjunctival goblet cell density values in AKC patients were significantly lower compared with VKC patients and control subjects. The squamous metaplasia grades in eyes with AKC were significantly higher compared to eyes with VKC and controls. The inflammatory cell response in brush cytology specimens was different between patients with AKC and VKC. Eyes with AKC showed significantly higher MUC1, 2 and 4 and lower MUC5AC mRNA expression compared to eyes with VKC. Differences of the infiltrates, higher level of tear instability, lower corneal sensitivity, up-regulation of MUC1, 2, and 4, and down regulation of MUC5AC were important differential features of the ocular surface disease in AKC compared with VKC.