Understanding Vernal Keratoconjunctivitis: Beyond Allergic Mechanisms

Vernal keratoconjunctivitis (VKC) is a chronic, recurrent, inflammatory disease of the cornea and conjunctiva mostly affecting boys in prepubertal age. VKC recurrence is characterized by intense symptoms of itching, redness, and photophobia associated with corneal damage, impairment of visual function, and quality of life. The pathogenesis of VKC has not yet been completely understood, and it is still controversial. In fact, VKC is considered an ocular allergic disease due to the involvement of immunoglobulin E, eosinophils, and mast cells, and of a lymphocyte T-helper type 2 reaction. However, approximately half of VKC patients have negative allergological history and testing, suggesting that other pathogenic mechanisms participate in VKC development and severity. Specifically, evidence suggests that genetic, endocrine, neuronal factors and an imbalance of innate immunity are involved in the pathogenesis of VKC. The purpose of this review is to summarize evidence on the pathogenic role of innate immunity, neuroimmune reaction, and hormonal changes in VKC. Increasing understanding of the pathogenic mechanisms behind VKC may lead to the identification of novel biomarkers for diagnosis and/or potential therapeutic targets in order to improve the management of this challenging condition.

Simultaneously Monitoring Whole Corneal Injury with Corneal Optical Density and Thickness in Patients Undergoing Cataract Surgery

To pursue the least corneal implication during cataract surgery, this study aimed to monitor corneal wound injury after cataract surgery with a novel method. The prospective cohort study involved thirty-two patients, who were assessed by a Scheimpflug tomography AxL® (Oculus GmbH, Wetzlar, Germany) via the following two kinds of indices: whole corneal optical density (COD) and corneal thickness (CT), two weeks before and one month after cataract surgery. The results of the COD revealed that corneal annuli 0.0–2.0 mm and 2.0–6.0 mm, and the average and maximal values at the incisional site significantly increased postoperatively. Also, the anterior and central stroma of 0.0–2.0 mm, and all three depths of 2.0–6.0 mm, increased remarkably after the operation. For the CT, all ranges of diameters plus incisional sites showed significant increases postoperatively. Furthermore, we analyzed the differences (delta) of COD and CT between pre- and post-operation, and found significant correlations between the delta of COD and the delta of CT, regarding annuli 0.0–2.0 mm, 2.0–6.0 mm, and 6.0–10.0 mm, but no correlation at the incisional site, with either average density or maximal density, was detected. We concluded that whole COD and CT, especially at the central zones of the cornea (annulus < 6 mm), are both valuable parameters in the assessment of corneal damage post-cataract surgery, and are independent indices at the incisional site.

Comparison of Pregabalin and Placebo Effects in Treating Eye Pain Following Cataract Surgery by Phacoemulsification Method

Cataract surgery sometimes is associated with adverse effects, such as dryness, burning, and patient discomfort. This study evaluates the treatment of dry eye syndrome and pain caused by corneal damage following cataract surgery with pregabalin compared to placebo. In our double-blind clinical trial, a total of 60 cases were divided into two groups. The pain score was assessed by the Numeric Rating Scale (NRS), and the impact of pain and dryness on the patient's performance was evaluated by the Brief Pain Inventory (BPI). The patient's pain score was evaluated postoperatively and followed for six weeks after the procedure. After the sixth week of the study, NRS, BPI, and photophobia in the pregabalin group were significantly different from the placebo group. Pregabalin can significantly reduce chronic and resistant eye pain after cataract surgery.

Integrin αv and Vitronectin Prime Macrophage-Related Inflammation and Contribute the Development of Dry Eye Disease

Cell signaling mediated by the αv integrin plays a pivotal role in macrophage activation in various inflammatory processes, but its involvement in the pathogenesis of dry eye disease (DED) remains unclear. In a murine model of DED, we found increased αv integrin expression in ocular surface macrophages. The αv integrins inhibitor c(RGDfK) ameliorated the corneal damage caused by DED, suggesting a pathogenic role for αv integrin. Because tear hyperosmolarity induces ocular inflammation in DED, a hyperosmolar culture of murine bone marrow-derived macrophages (BMDMs) is used to reproduce inflammation in vitro. However, the expression of proinflammatory cytokine mRNA was minimal, even though αv integrin was induced. In searching for components that are involved in αv integrin-mediated inflammation but that are missing from the culture model, we showed that the levels of vitronectin (VTN), a binding ligand of αv integrins, were increased in the tear fluid and conjunctival stroma of DED animals. The addition of VTN prominently enhanced hyperosmolarity-induced inflammation in BMDMs. Mechanistically, we showed that VTN/αv integrins mediated NF-κB activation to induce inflammatory gene expression in the BMDMs. Our findings indicate that interaction the of VTN with αv integrins is a crucial step in the inflammatory process in DED and suggests a novel therapeutic target.

Corneal Healing and Recovery of Ocular Crystallinity with a Dichloromethane Extract of Sedum dendroideum D.C. in a Novel Murine Model of Ocular Pterygium

Pterygium is a corneal alteration that can cause visual impairment, which has been traditionally treated with the sap of Sedum dendroideum D.C. The pharmacological effect of a dichloromethane extract of S. dendroideum was demonstrated and implemented in a pterygium model on the healing process of corneal damage caused by phorbol esters. In mice of the ICR strain, a corneal lesion was caused by intravitreal injection of tetradecanoylphorbol acetate (TPA). The evolution of the corneal scarring process was monitored with vehicle, dexamethasone, and dichloromethane extract of S. dendroideum treatments by daily ophthalmic administration for fifteen days. The lesions were evaluated in situ with highlighted images of fluorescence of the lesions. Following treatment levels in eyeballs of IL-1α, TNF-α, and IL-10 cytokines were measured. The effective dose of TPA to produce a pterygium-like lesion was determined. The follow-up of the evolution of the scarring process allowed us to define that the treatment with S. dendroideum improved the experimental pterygium and had an immunomodulatory effect by decreasing TNF-α, IL-1α, and maintaining the level of IL-10 expression, without difference with respect to the healthy control. Traditional medical use of S. dendroideum sap to treat pterygium is fully justified by its compound composition.

Serp-1 change globally Promotes Corneal Wound Healing by Facilitating Re-epithelialization and Inhibiting Fibrosis and Angiogenesis

Purpose: Chemical corneal injuries carry a high morbidity and commonly lead to visual impairment. Here, we investigate the role of Serp-1, a serine protease inhibitor, in corneal wound healing.Methods: An alkaline-induced corneal injury was induced in 14 mice. Following injury, five mice received daily topical saline application while nine mice received Serp-1 100 μL topically combined with a daily subcutaneous injection of 100 ng/gram body weight of Serp-1. Corneal damage was monitored daily through fluorescein staining and imaging. Cross sectional corneal H&amp;E staining were obtained. CD31 was used as marker for neovascularization.Results: Serp-1 facilitates corneal wound healing by reducing fibrosis and neovascularization while mitigating inflammatory cell infiltration with no noticeable harm related to its application.Conclusions: Serp-1 effectively mitigates inflammation, decreases fibrosis, and reduce neovascularization in a murine model of corneal injury without affecting other organs.Translational Relavence: Our study provides preclinical data for topical application of Serp-1 to treat corneal wounds.

Bilateral Severe Corneal Ulcer in a Patient with Lung Adenocarcinoma Treated with Gefitinib

We describe the case of Gefitinib-related bilateral corneal perforation. An 86-year-old female patient had bilateral painless and progressive vision loss due to neurotrophic corneal ulcer, following a 2-month treatment with Gefitinib, a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for metastatic adenocarcinoma of the lung with confirmed EGFR gene mutation. She had no signs of ocular infection, inflammation, or lid problems to account for the development of corneal damage. Neurotrophic ulcer evolved into a frank perforation in one eye and an impending perforation on the other eye. EGFR inhibitors have been associated with dry eye, epithelial erosions, ulcerative keratitis, and corneal edema. However, to the best of our knowledge, this is the first case of bilateral severe corneal ulcer due to Gefitinib. The patient went on to have bilateral corneal graft surgery. This case aims to raise awareness among ophthalmologists and oncologists of the association between EGFR inhibitors, corneal neurotrophic ulcers, and possible evolution in corneal perforation.

DESCRIPTION OF MOTHER AND CHARACTERISTICS OF MOTHER WHO HAVE A BABY AGE 6-11 MONTHS ABOUT VITAMIN A IN PAMEKARAN VILLAGE

One indicator of the success of development in the health sector can be seen from the level of maternal and infant mortality rates. One cause of death in infants and toddlers is neurological diseases including eye disease. Around the world among preschoolers there are an estimated 6-7 million cases of xerophthalmia each year, approximately 10% of them suffer from corneal damage. Among those who suffered corneal damage 60% died within one year, 25% became blind and 50-60% were half blind. This is caused due to lack of vitamin A in a child's body. To combat VAD in Indonesia, especially in infants (6-59 months) the Indonesian Ministry of Health has collaborated with Helen Keller Indonesia (IPR) by administering high doses of vitamin A capsules to infants, toddlers and postpartum mothers. This study aims to determine the description of the attitude of mothers who have babies 6-11 months about vitamin A in Pamekaran village (conducted in April-June 2019). The design used is descriptive research. With the data obtained through the collection of questionnaire data from mothers who have babies 6-11 months. Data is presented in the form of frequency distribution with univariate analysis. With a population of 445 people, and a total sample of 82 people with a simple random sampling technique. The results showed that more than half of respondents had negative attitudes namely 61%. Characteristics of mothers who have babies aged 6-11 months are half aged 21-35 years which is as much as 68.3%, more than half are high school educated at 73.2% and more than half are multipara at 70.7%. Thus it can be concluded that more than half of the respondents have negative attitudes, aged 21-35 years, multigravida and high school graduates. Therefore it is expected that health workers will further enhance IEC about vitamin A and also more vigorously sweeping or giving vitamin A door-to-door.

Infectious keratoconjunctivitis in red deer (Cervus elaphus) in Poland – A case report

Infectious keratoconjunctivitis (IKC) has not been observed in European deer (Cervus elaphus). Our case concerned two red deer bulls in a natural environment, which had orientation disorders and/or circle movement. A detailed post-mortem examination of one of the bulls revealed extensive conjunctivitis in both eyes, clouding and ulceration of the cornea. There were no lesions in the other organs, particularly in the central nervous system (CNS). The histopathological examination of the eyeballs showed corneal epithelium erosions and vascularisation and an inflammatory infiltration of the stroma. Descemet’s membrane was found to be disrupted and the corneal stroma was fused with the iris. The remaining structure of the eye did not show any lesions. Furthermore, the polymerase chain reaction analysis for OvHV-1, BHV-1, BHV-5, CapHV-1, CcHV-1, and EHV-1 showed negative results. In the agar culture, only single bacteria were present. There were no Thelazia spp. worms in the conjunctival sac, but numerous Lipoptena cervi flies were present on the skin in the eye region and on the corneal surface. The findings of our case study and those reported in the literature suggest that IKC is a polyetiological disease, where the composition of the pathogenic agents may differ from case to case. The present study suggests that the mechanical irritation of L. cervi parasites could be a contributing factor to the corneal damage, infection and chronic inflammation resulting in a loss of vision in red deer.