IL-33-induced keratoconjunctivitis is mediated by group 2 innate lymphoid cells in mice.

BACKGROUND: Interleukin-33 (IL-33) is involved in type 2 innate immunity by inducing type 2 cytokines, such as IL-5 and IL-13, through the activation of group 2 innate lymphoid cells (ILC2s) or T helper 2 (Th2) cells. We previously reported that mice overexpressing IL-33 (IL-33Tg) in the cornea and conjunctiva spontaneously develop atopic keratoconjunctivitis-like inflammation. Despite previous studies, it is not fully understood what types of immune cells contribute to the disease process of IL-33-induced keratoconjunctivitis. METHODS: To defect Th2 cells, IL-33Tg mice were crossed with Rag2KO mice. To defect ILC2s, IL-33Tg mice received bone marrow transplantations from B6.C3(Cg)-Rorasg/J mice that lacked ILC2. Immunostaining techniques were used to determine where ILC2 is distributed in the cornea and conjunctiva. We analyzed the transcriptomes of ILC2 from the conjunctiva by using single-cell RNA-seq analysis. To investigate whether tacrolimus reduces type 2 cytokine production by ILC2, ILC2 was cultured with tacrolimus, and the percentage of cytokine-producing ILC2 was examined. To investigate whether tacrolimus can inhibit IL-33-induced keratoconjunctivitis in vivo, IL-33Tg mice were treated with tacrolimus eye drops. RESULTS: ILC2 infiltrated the conjunctival epithelium and subepithelial tissue. Keratoconjunctivitis developed spontaneously in Rag2KO/IL-33Tg mice, but keratoconjunctivitis was abolished in IL-33Tg mice lacking ILC2. ILC2 was not a uniform cluster but a heterogeneous cluster. Tacrolimus inhibited cytokine production from ILC2s in vitro, and tacrolimus eye drops inhibited keratoconjunctivitis in IL-33Tg mice in vivo. CONCLUSIONS: ILC2 plays a pivotal role in IL-33-induced keratoconjunctivitis in mice.

Case Report: Two Cases of Keratoconjunctivitis Tied to Sargassum Algae Emanations.

Since 2011, considerable amounts of Sargassum algae regularly end up on beaches in the Gulf of Mexico, the Caribbean, and in the French overseas departments. We report observations of two bilateral keratoconjunctivitis associated with important functional symptomatology. There was a conjunctival hyperemia and superficial punctate keratitis. The ocular impairment would repeat at every algae ashore landing. Clinical examination, history, and time line of symptomatology onset allowed us to eliminate the classic etiologies of bilateral keratoconjunctivitis and to suggest an irritant toxic origin tied to hydrogen sulfide. This is the first description of ocular impairment tied to Sargassum algae decomposition. Their decomposition, through H2S emission, can be at the origin of bilateral keratoconjunctivitis. Ocular impairment is often at the forefront of complaints made by individuals exposed to H2S.

Dupilumab-induced ocular surface disease (DIOSD) in patients with atopic dermatitis: clinical presentation, risk factors for development and outcomes of treatment with tacrolimus ointment.

AIM: To identify risk factors for the development of dupilumab-induced ocular surface disease (DIOSD) in adult patients with atopic dermatitis (AD) and describe outcomes of treatment. METHODS: A retrospective institutional cohort study performed at the Rabin Medical Center, Petach Tikva, Israel. Adult patients with AD who received dupilumab from March 2018 to June 2019 were included. Demographics, AD severity scores, blood IgE levels, previous atopic keratoconjunctivitis (AKC), dermatological response to dupilumab, ophthalmological evaluation and treatment were noted. Univariate and multivariate analyses were used to identify risk factors for DIOSD. RESULTS: Sixteen of 37 patients who were included in the study (43%) had new or exacerbated symptoms of ocular surface disease starting at 2 weeks following the first treatment. Three patients reported transient dry eye sensation which lasted 2 weeks; nine patients reported chronic dry eye sensation, and four patients (25%) had marked blepharoconjunctivitis. The presence of severe AD was the strongest predictor of DIOSD. Not a single patient with moderate AD had DIOSD. In multivariate analysis, prior AKC was a risk factor for DIOSD (R2=15.78, OR=23.28, p=0.005) while a family history of atopy was protective of DIOSD (R2=6.22, OR=0.13, p=0.05). All four patients with blepharoconjunctivitis had resolution of signs, and symptoms within days of starting periocular 0.03%-0.1% tacrolimus ointment. CONCLUSIONS: DIOSD is common in patients with AD receiving dupilumab. While most cases are mild, some patients can develop blepharoconjunctivitis which responds well to tacrolimus ointment. AD severity, and previous AKC are risk factors for DIOSD.

Toxic Keratoconjunctivitis.

Toxic keratoconjunctivitis (TK) is an underrecognized complication of ophthalmic drug use and various environmental or occupational exposures. A detailed history and clinical examination are important to identify the offending agent(s). Common drug-related causes of TK include preservatives in ophthalmic medications, topical antimicrobials, and topical anesthetics. Alternatives to benzalkonium chloride as well as preservative-free formulations should be considered in patients requiring long-term topical medication. More advanced cases of TK may require preservative-free topical steroids and/or antibiotics, and occasionally surgical intervention. Early recognition and appropriate management of TK may help prevent permanent ocular and visual damage.

Ocular toxicity by seeds of Annona squamosa (custard apple).

Custard apple seeds have been used in native medicine from time immemorial for the management of head lice and skin exfoliation. We report six consecutive patients who developed toxic keratoconjunctivitis within 6-12 h of ocular exposure to custard apple seeds. The use of topical steroid worsens the toxicity and predisposes to the development of microbial keratitis in such cases. Patients showed a good response to primary treatment with topical fortified antibiotics and lubricants. This case series highlights the need to educate the patients regarding the potential toxic effects of the custard seeds and the treating physicians about possible deleterious effects on using topical steroid.

Prevention of cytarabine-induced kerato-conjunctivitis by eye rinse in patients receiving high-dose cytarabine and total body irradiation as a conditioning for hematopoietic stem cell transplantation.

We previously reported a high incidence of kerato-conjunctivitis in patients receiving high-dose cytarabine following total body irradiation (TBI) as a conditioning for hematopoietic stem cell transplantation (HSCT) even on prophylaxis with topical corticosteroid. This study aimed to evaluate whether addition of eye rinse, which was designed to remove cytarabine from ocular surface, further reduces the incidence of kerato-conjunctivitis in the same setting. Seventy-six patients receiving cytarabine at a dose of 3 g/m(2) every 12 h for 4 days after receiving TBI (12 Gy) as conditioning for HSCT were evaluated. All patients received betamethasone sodium phosphate eye drops. Twenty-three patients were further instructed to rinse their eyes with sterile saline every 10-15 min during and for two additional hours after the completion of each cytarabine infusion. Among 23 patients with eye rinse, Grades 2-3 and 1-3 kerato-conjunctivitis were observed in 4 (17.4%) and 5 patients (21.7%), respectively. These incidences were significantly lower than those [35 (66.0%) and 41 (77.4%)] observed in 53 patients without eye rinse (P < 0.001 and P < 0.00001, respectively). These results strongly suggest that eye rinse effectively reduces the incidence and severity of cytarabine-induced kerato-conjunctivitis in HSCT recipients who receive high-dose cytarabine following TBI.

Prophylactic treatment for cytosine arabinoside-induced keratoconjunctivitis.

High-dose cytosine arabinoside (Ara-C) is known to cause keratoconjunctivitis in a large proportion of patients. Topical steroids are a popular choice of prophylactic treatment. The objective of this survey was to evaluate the type, dose, frequency and duration of drops used in all centres (n = 117) participating in the acute myeloid leukaemia trial 15 (AML 15), and to assess adherence to the trial protocol prescribed guidelines. All centres used prophylactic treatment; however, the dose of Ara-C at which it was initiated varied from 100 to 6000 mg/m(2)/day. All centres used some form of steroid prophylaxis with prednisolone 0.5% being the most commonly used (98/117), but only 6 of the 117 centres initiated treatment at doses recommended in the trial protocol. Ten centres used lubricants in addition to steroids. No centre reported the use of non-steroidal anti-inflammatory drops. The duration of treatment ranged from 2 days prior to commencing Ara-C to 28 days post-treatment. Twenty-two centres reported complications of which preservative allergy was the commonest. There is a large variation in prophylactic treatment practice in the UK. Clear guidance on the use of prophylaxis and further studies are required to ascertain the most effective prophylactic treatment and regimen.

[Ocular findings in hepatitis C patients treated with interferon]. / Zmiany w narzadzie wzroku u chorych z przewleklym zapaleniem watroby typu C leczonych interferonem.

The pathology of the liver is associated with many disorders including the eye. We described ocular changes following hepatitis C. The most common ophthalmic findings in hepatitis C patients treated with interferon--involve keratoconjunctivitis, scleritis, dry eye syndrome, uveitis, retinopathy, retinal hemorrhages, anterior ischemic optic neuropathy, retinal vascular changes and macular oedema, as well as electroretinogram, visual field and OCT abnormalities.

Conjunctival impression cytology for the diagnosis, follow-up, and treatment in a patient with severe keratoconjunctivitis caused by alkali injury.

PURPOSE: To report a case of severe keratoconjunctivitis after chemical exposure that was treated by a conjunctival-limbal autograft transplantation according to conjunctival impression cytology (CIC) results. METHODS: A 48-year-old woman was diagnosed with a severe keratoconjunctivitis developed after exposure to a mixture of abrasive cleaning agents. Based on CIC results, decision to perform a limbal-conjunctival autotransplantation from the contralateral eye was taken after conventional topical treatment failed to improve symptoms. Polyethersulfone papers were used to take samples from the superior and inferior bulbar conjunctiva of affected and contralateral eyes, and Periodic acid Schiff's (PAS) staining was used to reveal the status of goblet cell (GC) population of the conjunctiva. RESULTS: Tearing, burning sensation, keratitis, squamous metaplasia, and GC improved noticeably, as observed by CIC, after autotransplantation. CONCLUSIONS: CIC helped on the diagnosis, treatment decision, and follow-up of a patient severely affected by alkali exposure by checking the status of GC in the conjunctiva. Limbal-conjunctival autotransplantation decision was taken and performed consequently, and a significant improvement was observed through a follow-up by CIC.

Conjunctival and corneal reactions in rabbits following short- and repeated exposure to preservative-free tafluprost, commercially available latanoprost and 0.02% benzalkonium chloride.

AIM: To compare the conjunctival and corneal reactions of commercially available solution of latanoprost (Xalatan) and preservative-free (PF) tafluprost in rabbits. METHODS: The rabbits received 50 microl of phosphate-buffered saline (PBS), PF-tafluprost 0.0015%, latanoprost 0.005% or benzalkonium chloride (BAK) 0.02%; all solutions were applied at 5 min intervals for a total of 15 times. The ocular surface toxicity was investigated using slit-lamp biomicroscopy examination, flow cytometry (FCM) and on imprints for CD45 and tumour necrosis factor-receptor 1 (TNFR1) conjunctival impression cytology (CIC) and corneal in vivo confocal microscopy (IVCM). Standard immunohistology also assessed inflammatory/apoptotic cells. RESULTS: Clinical observation and IVCM images showed the highest ocular surface toxicity with latanoprost and BAK, while PF-tafluprost and PBS eyes presented almost normal corneoconjunctival aspects. FCM showed a higher expression of CD45+ and TNFR1+ in latanoprost- or BAK-instilled groups, compared with PF-tafluprost and PBS groups. Latanoprost induced fewer positive cells for inflammatory marker expressions in CIC specimens compared with BAK-alone, both of which were higher than with PF-tafluprost or PBS. Immunohistology showed the same tendency of toxic ranking. CONCLUSION: The authors confirm that rabbit corneoconjunctival surfaces presented a better tolerance when treated with PF-tafluprost compared with commercially available latanoprost or BAK solution.

Reduced efficacy of topical corticosteroid in preventing cytarabine-induced kerato-conjunctivitis in patients receiving high-dose cytarabine and total body irradiation for allogeneic hematopoietic stem cell transplantation.

This study aimed to retrospectively evaluate the incidence of kerato-conjunctivitis in patients receiving TBI followed by high-dose cytarabine, and to clarify how effectively topical corticosteroid eye drops prevent kerato-conjunctivitis in these patients. Fifty-three patients who received cytarabine at a dose of 3 g/m2 every 12 h for 4 days after receiving TBI (12 Gy) as a conditioning for allogeneic hematopoietic stem cell transplantation (HSCT) were evaluated. For the prophylaxis of kerato-conjunctivitis, all patients received betamethasone sodium phosphate eye drops every 6 h, starting 1 day before the first dose of cytarabine and continuing until 1 day after the last dose of cytarabine or the complete resolution of ocular symptoms. For grading of kerato-conjuncitivitis, the National Cancer Institute-Common Toxicity Criteria were used. Among the 53 patients, the grades of kerato-conjunctivitis were grade 0 in 13 patients, grade 1 in 6 patients (11.3%), grade 2 in 10 patients (18.9%) and grade 3 in 25 patients (47.2%). These results strongly suggest that topical corticosteroid eye drops could not effectively prevent the development of cytarabine-induced kerato-conjunctivitis in HSCT recipients who receive high-dose cytarabine following TBI. Further investigation into a more effective prophylaxis for cytarabine-induced kerato-conjunctivitis in this setting is required.

Camphor-related self-inflicted keratoconjunctivitis complicating delusions of parasitosis.

PURPOSE: To report a case of camphor-related self-inflicted keratoconjunctivitis secondary to delusions of parasitosis. METHODS: A 61-year-old man with delusions of parasitosis suffered from camphor-related self-inflicted ocular trauma that manifested with corneal epithelial defects and secondary anterior chamber reaction. Two episodes of exacerbation of the ocular conditions related to the use of camphor occurred. The left eye had secondary infection with Sternotrophomonas maltophilia and Staphylococcus aureus in the second episode of exacerbation. RESULTS: The right eye recovered well with the treatment of topical lubricants and corticosteroids and had best-corrected visual acuity (BCVA) of 20/25. The infection of the left eye led to corneal perforation, necessitating penetrating keratoplasty; BCVA was hand motions because of a mature cataract. Olanzapine therapy for 1 month to decrease the delusions of parasitosis and 24-hour watch to prevent the use of camphor led to the resolution of self-inflicted keratoconjunctivitis in the patient. CONCLUSIONS: Delusions of parasitosis may lead to vision-threatening self-inflicted ocular trauma. This may be the first case report of pure camphor-related self-inflicted toxic keratoconjunctivitis.