Age-related differences in corneal nerve regeneration after SMILE and the mechanism revealed by metabolomics

Li, Min; Liu, Lin; Shi, Yuehui; Sun, Li; Ma, Xiaoli; Zou, Jun

doi:10.1016/j.exer.2021.108665

Cited by 10 publications

(14 citation statements)

References 43 publications

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“…In particular, elderly participants had significantly lower CNFD and CNFL compared with nonelderly participants. Aging exerts detrimental effects on corneal nerves; it is associated with dysregulated inflammatory processes and changes in metabolites that alter corneal homeostasis, 17 impair nerve protection and regeneration, 33 and reduce the regenerative capacity of nerves, eventually leading to a decrease in corneal nerve fiber parameters. 33 Substance P, one of the most abundant neuromediators in the cornea involved in the maintenance of normal corneal nerve morphology, is expressed in high levels by corneal nerves.…”

Section: Discussionmentioning

confidence: 99%

“…Aging exerts detrimental effects on corneal nerves; it is associated with dysregulated inflammatory processes and changes in metabolites that alter corneal homeostasis, 17 impair nerve protection and regeneration, 33 and reduce the regenerative capacity of nerves, eventually leading to a decrease in corneal nerve fiber parameters. 33 Substance P, one of the most abundant neuromediators in the cornea involved in the maintenance of normal corneal nerve morphology, is expressed in high levels by corneal nerves. It promotes corneal nerve regeneration, 34 and its expression decreases with advancing age, which parallels the decrease in corneal nerve density.…”

Section: Discussionmentioning

confidence: 99%

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Impact of Age on the Characteristics of Corneal Nerves and Corneal Epithelial Cells in Healthy Adults

Chin,

Liu,

Lee

et al. 2023

Cornea

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Purpose: The aim of this study was to investigate age-related changes in corneal nerves and corneal epithelial cell parameters and to establish age-adjusted reference values. Methods: A total of 7025 corneal nerve images and 4215 corneal epithelial images obtained using in vivo confocal microscopy from 281 eyes of 143 healthy participants were included. Seven corneal nerve parameters and 3 corneal epithelial cell parameters were quantified using 2 automatic analytic software and analyzed across 6 age groups ranging from 21 to 80 years. Results: There was a declining trend in all 7 nerve parameters with advancing age. In particular, corneal nerve fiber length and corneal nerve fiber density demonstrated a significant decrease in subjects aged 65 years or older compared with subjects younger than 65 years (10.8 ± 2.6 mm/mm2 vs. 9.9 ± 2.0 mm/mm2, P = 0.011 in corneal nerve fiber length; 15.8 ± 5.2 fibers/mm2 vs. 14.4 ± 4.3 fibers/mm2, P = 0.046 in corneal nerve fiber density), whereas corneal nerve fractal dimension demonstrated a borderline significant decrease (P = 0.057). Similarly, there was a general declining trend in all epithelial cell parameters with advancing age. Corneal epithelial cell circularity was significantly lower in subjects aged 65 years and older as compared to subjects younger than 65 years (0.722 ± 0.021 μm2 vs. 0.714 ± 0.021 μm2; P = 0.011). Conclusions: Advancing age results in reduced corneal nerve metrics and alteration of corneal cell morphology. Aging effects should be considered when evaluating patients with corneal neuropathy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Impact of Age on the Characteristics of Corneal Nerves and Corneal Epithelial Cells in Healthy Adults

Chin,

Liu,

Lee

et al. 2023

Cornea

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“…A lipidomic study has shown modifications of the tear film lipid layer after refractive surgery, and this is likely to have effects on its physiological function [ 69 ]. A study correlated metabolomic profiles of lenticules derived from corneas undergoing SMILE with the rate of postoperative corneal nerve recovery [ 13 ]. The study reported that corneal nerve fiber length and corneal nerve fiber density recovered to the preoperative level within 1 year in the 18–30 age group, but those in the 31–40 and 41–50 age groups remained less than that before surgery.…”

Section: Refractive Surgerymentioning

confidence: 99%

“…The analysis of metabolites from tears or aqueous humor has been used to reveal biomarkers of several ocular diseases such as predicting glaucoma progression [ 8 ], with greater sensitivity and specificity than the analysis of plasma or serum [ 9 ]. Several corneal diseases or conditions, including dry eye disease [ 10 ], keratoconus [ 11 ], Sjogren’s syndrome [ 12 ], refractive surgery [ 13 ], prolonged contact lens wear [ 14 ], and diabetic corneas [ 15 ], have been reported to have significant metabolomic alterations in tears or corneas. Metabolomics has therefore been applied in the studies of corneal diseases to potentially identify new biomarkers or elucidate the disease mechanisms ( Figure 1 ).…”

Section: Introductionmentioning

confidence: 99%

Metabolomics in Corneal Diseases: A Narrative Review from Clinical Aspects

et al. 2023

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Corneal pathologies may have subtle manifestations in the initial stages, delaying diagnosis and timely treatment. This can lead to irreversible visual loss. Metabolomics is a rapidly developing field that allows the study of metabolites in a system, providing a complementary tool in the early diagnosis and management of corneal diseases. Early identification of biomarkers is key to prevent disease progression. The advancement of nuclear magnetic resonance and mass spectrometry allows the identification of new biomarkers in the analysis of tear, cornea, and aqueous humor. Novel perspectives on disease mechanisms are identified, which provide vital information for potential targeted therapies in the future. Current treatments are analyzed at a molecular level to offer further information regarding their efficacy. In this article, we provide a comprehensive review of the metabolomic studies undertaken in the cornea and various pathologies such as dry eye disease, Sjogren’s syndrome, keratoconus, post-refractive surgery, contact lens wearers, and diabetic corneas. Lastly, we discuss the exciting future that metabolomics plays in cornea research.

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“…This finding is supported by Min et al and Primavera et al, who also reported age as a contributing factor delaying corneal recovery when investigating nerve regeneration and refractive outcomes, respectively. 34,35 However, to the best of the authors' knowledge, our study is the first to examine the effect of age on various epithelial-related complications. Other studies have reported older age as a significant risk factor for intraoperative epithelial-related complications during LASIK, likely secondary to basement membrane changes that damage the adhesive connections with hemidesmosomes in the corneal epithelium.…”

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confidence: 95%

Incidence and Management of Epithelial-Related Complications After SMILE

Moshirfar,

Zhang,

Pandya

et al. 2023

OPTH

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To investigate the incidence and management of only epithelial-related complications following small incision lenticule extraction (SMILE). Patients and Methods: A retrospective, single-site study analyzed patients who underwent SMILE at Hoopes Vision Clinic in Draper, Utah, from June 2017 to February 2023. Demographic data and preoperative parameters were reviewed. Postoperatively, patients were assessed for visual acuity and complications at different time points. Statistical analyses were conducted between the control and complication groups. Results: Four hundred and thirty-two eyes of 220 patients received SMILE. Postoperative epithelial-related complications were indicated in 68 (15.7%) eyes, including anterior basement membrane (ABM) changes (five [1.2%]) eyes), epithelial ingrowth (nine [2.1%] eyes), erosion (two [0.5%] eyes), rough epithelium (18 [4.2%] eyes), epithelial defect (12 [2.8%] eyes), diffuse lamellar keratitis (DLK) secondary to epitheliopathy (two [0.5%] eyes), microstriae secondary to epitheliopathy (four [0.9%] eyes), interface debris (21 [4.9%] eyes), and incisional fibrosis (one [0.2%] eye). There was a statistically significant difference in age, with older patients more likely to develop epitheliopathy postoperatively (P = 0.001). Additionally, patients with epithelial-related complications were more likely to receive photorefractive keratectomy (PRK) enhancement after SMILE than the control (P = 0.001). However, there was no statistical difference in uncorrected distance visual acuity (UDVA) better than 20/20 and corrected distance visual acuity (CDVA) between the complications group and the control at the last postoperative visit (P = 0.974 and 0.310, respectively). There was no statistically significant difference in the safety and efficacy indices between the complications and control group (P = 0.281 and 0.617, respectively). Conclusion: In our study, epithelial-related complications were more prevalent in older patients and predisposed patients to require PRK enhancements after recovery from SMILE. Despite the incidence of epithelial-related complications, visual prognoses were favorable and achieved through various management strategies.

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Age-related differences in corneal nerve regeneration after SMILE and the mechanism revealed by metabolomics

Cited by 10 publications

References 43 publications

Impact of Age on the Characteristics of Corneal Nerves and Corneal Epithelial Cells in Healthy Adults

Impact of Age on the Characteristics of Corneal Nerves and Corneal Epithelial Cells in Healthy Adults

Metabolomics in Corneal Diseases: A Narrative Review from Clinical Aspects

Incidence and Management of Epithelial-Related Complications After SMILE

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