Dataset Information

Eye Pain Caused by Epithelial Damage in the Central Cornea in Aqueous-Deficient Dry Eye.

ABSTRACT: In this study, the severity of eye pain (EP) and associated objective findings were evaluated in aqueous-deficient dry eye (ADDE) patients using PainVision^®, a quantitative pain-measuring device. This study involved 53 eyes of 53 ADDE patients (6 males and 47 females; mean age: 64.4 ± 13.4 [mean ± SD] years). Of those, 18 eyes of 18 patients underwent punctal occlusion, and EP and objective findings in those patients were evaluated before and after treatment. In all patients, the severity of EP as measured by PainVision^® was assessed using the Pain Degree (PD). The median PD for the 53 patients was 30.6 µA/µA (interquartile range, 16.9-93.2), and the nasal and central corneal staining score and the upper lid-wiper epitheliopathy score were significantly correlated with PD (R = 0.33, 0.33, and 0.28, respectively) (all: p < 0.05). Using the least squares method, the central corneal staining score most significantly affected PD. In the 18 cases that underwent punctal occlusion, PD was significantly reduced (median PD: 24.8 to 7.1 µA/µA; p < 0.0001). Using the least squares method, the central corneal staining score and tear meniscus radius were significantly more influential as factors contributing to PD before and after treatment, and central corneal epithelial damage was the factor most associated with ADDE-related EP.

SUBMITTER: Yoshikawa Y

PROVIDER: S-EPMC10802830 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Eye Pain Caused by Epithelial Damage in the Central Cornea in Aqueous-Deficient Dry Eye.

Yoshikawa Yamato Y Yokoi Norihiko N Kusada Natsuki N Kato Hiroaki H Sakai Rieko R Komuro Aoi A Sonomura Yukiko Y Sotozono Chie C

Diagnostics (Basel, Switzerland) 20231222 1

In this study, the severity of eye pain (EP) and associated objective findings were evaluated in aqueous-deficient dry eye (ADDE) patients using PainVision<sup>®</sup>, a quantitative pain-measuring device. This study involved 53 eyes of 53 ADDE patients (6 males and 47 females; mean age: 64.4 ± 13.4 [mean ± SD] years). Of those, 18 eyes of 18 patients underwent punctal occlusion, and EP and objective findings in those patients were evaluated before and after treatment. In all patients, the seve ...[more]

PMID: 38201339

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Project description:PurposeDespite advances in orbital radiotherapy (XRT), a significant proportion of patients develop ophthalmic complication like dry eye syndrome (DES). The study evaluates the prevalence of aqueous deficient DES (ADDE) and lacrimal gland (LG) changes through histologic evaluation and ex-vivo expansion potential postorbital XRT.MethodsWith the approval of the institutional review board, medical records of patients who underwent orbital XRT as management protocol were reviewed for evidence of ADDE using DEWS (Dry Eye Workshop) 2007 criteria (n = 51). HuLG was harvested from three of these patients who underwent subsequent orbital exenteration and used for histological studies/ex-vivo culture.ResultsADDE was noted in 47.07% of the patients, status postorbital XRT, with a prediction of nearly 50% developing it within 0.5 to 2.9 years. ADDE severity was grade 2 (18%), grade 3 (14%), and grade 4 (17%). Other comorbidities were radiation retinopathy (33.4%), radiation-induced cataract (24.9%), and radiation keratopathy (20.8%). Multivariate and univariate analysis showed that fraction of radiation and dose of radiation/fraction were significant risk factors; male gender and young age were protective factors. The post-XRT exenterated HuLG showed near-total effacement of histoarchitecture with intra/periductal and intra/interlobular fibrosis, loss of acini, and reduced secretory activity. The potential of the LG to expand and grow in culture was impaired with loss of stem cells as compared to normal HuLG.ConclusionThis study documents that orbital-XRT is associated with morphological and functional loss of lacrimal function in nearly 50% of the patients with a prediction of two-third developing ADDE by the end of 5 years.Translational relevanceThe study provides objective clinical evidence for DES development due to architectural/functional damage to the LG postorbital XRT. Based on recent findings that the LG can be cultured in-vitro, with preservation of stem cells and secretory potential, it would be logical to harvest a portion of LG before radiation, and expand and transplant it to rescue the damaged gland if indicated.

Project description:Oxidative stress may cause ocular surface damage during the development of dry eye. Mammalian cells have defense systems against oxidative stress. A central regulator of the stress response is nuclear factor-erythroid 2-related factor 2 (NFE2L2). NFE2L2 is activated by the novel triterpenoid RS9 (a biotransformation compound of RTA 402). The purpose of this study was to assess the efficacy of RS9 against dry eye using in vitro and in vivo models. Bioactivity was estimated by the induction of mRNAs for two NFE2L2-targeted genes: NQO1 (prevents radical species) and GCLC (glutathione synthesis), using a corneal epithelial cell line (HCE-T). Protection against oxidation and cell damage was tested in vitro by culturing cells under hyperosmotic stress or by the addition of menadione, a generator of reactive oxygen species (ROS). Dry eye in vivo was induced by the injection of scopolamine into rats. Then, 930 nM of RS9 was applied to both eyes for 2 weeks. Oxidative stress was measured by the accumulation of 8-hydroxy-2'-deoxyguanosine (8-OHdG). Corneal wound healing was measured by scoring for superficial punctate keratitis (SPK). Corneal epithelial cell densities were evaluated histologically. RS9 and RTA 402 induced the expression of NQO1 and GCLC mRNAs in HCE-T cells. And both compounds suppressed hyperosmotic-ROS generation and menadione induced cellular damage. However RS9 had a stronger protective effect than RTA 402. Ocular instillation of RS9 also significantly upregulated the expression of Nqo1 mRNA in the corneal epithelium. Accumulation of 8-OHdG, increase of SPK scores and decrement of basal cell density were observed in corneal epithelium from scopolamine-injected rats. These changes were significantly ameliorated by the topical administration of RS9. RS9 induced Nfe2l2 activation and Nfe2l2-targeted genes, reduced oxidation, and ameliorated symptoms of dry eye using in vitro and in vivo models. Thus, RS9 might be a potent candidate agent against dry eye disease.

Dataset Information

Eye Pain Caused by Epithelial Damage in the Central Cornea in Aqueous-Deficient Dry Eye.

Publications

Eye Pain Caused by Epithelial Damage in the Central Cornea in Aqueous-Deficient Dry Eye.

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