Dimethyl itaconate inhibits antigen-specific Th17 cell responses and autoimmune inflammation via modulating NRF2/STAT3 signaling.

Pathogenic Th17 cells play a crucial role in autoimmune diseases like uveitis and its animal model, experimental autoimmune uveitis (EAU). Dimethyl itaconate (DMI) possesses potent anti-inflammatory effects. However, there is still a lack of knowledge about the role of DMI in regulating pathogenic Th17 cells and EAU. Here, we reported that intraperitoneal administration of DMI significantly inhibited the severity of EAU via selectively suppressing Th17 cell responses. In vitro antigen stimulation studies revealed that DMI dramatically decreased the frequencies and function of antigen-specific Th17, but not Th1, cells. Moreover, DMI hampered the differentiation of naive CD4+ T cells toward pathogenic Th17 cells. DMI-treated DCs produced less IL-1ß, IL-6, and IL-23, and displayed an impaired ability to stimulate antigen-specific Th17 activation. Mechanistically, DMI activated the NRF2/HO-1 pathway and suppressed STAT3 signaling, which subsequently restrains p-STAT3 nuclear translocation, leading to decreased pathogenic Th17 cell responses. Thus, we have identified an important role for DMI in regulating pathogenic Th17 cells, supporting DMI as a promising therapy in Th17 cell-driven autoimmune diseases including uveitis.

Myopia Control Effect of Repeated Low-Level Red-Light Therapy Combined with Orthokeratology: A Multicenter Randomized Controlled Trial.

PURPOSE: To investigate the efficacy and safety of repeated low-level red-light (RLRL) therapy combined with orthokeratology among children who, despite undergoing orthokeratology, exhibited an axial elongation of at least 0.50 mm over 1 year. DESIGN: Multicenter, randomized, parallel-group, single-blind clinical trial (ClinicaTrials.gov identifier, NCT04722874). PARTICIPANTS: Eligible children were 8-13 years of age with a cycloplegic spherical equivalent refraction of -1.00 to -5.00 diopters at the initial orthokeratology fitting examination and had annual axial length (AL) elongation of ≥0.50 mm despite undergoing orthokeratology. Forty-eight children were enrolled from March 2021 through January 2022, and the final follow-up was completed in March 2023. METHODS: Children were assigned randomly to the RLRL therapy combined with orthokeratology (RCO) group or to the orthokeratology group in a 2:1 ratio. The orthokeratology group wore orthokeratology lenses for at least 8 hours per night, whereas the RCO group received daily RLRL therapy twice daily for 3 minutes in addition to orthokeratology. MAIN OUTCOME MEASURES: The primary outcome was AL change measured at 12 months relative to baseline. The primary analysis was conducted in children who received the assigned intervention and completed at least 1 follow-up after randomization using the modified intention-to-treat principle. RESULTS: Forty-seven children (97.9%) were included in the analysis (30 in the RCO group and 17 in the orthokeratology group). The mean axial elongation rate before the trial was 0.60 mm/year and 0.61 mm/year in the RCO and orthokeratology groups, respectively. After 12 months, the adjusted mean AL changes were -0.02 mm (95% confidence interval [CI], -0.08 to +0.03 mm) in the RCO group and 0.27 mm (95% CI, 0.19-0.34 mm) in the orthokeratology group. The adjusted mean difference in AL change was -0.29 mm (95% CI, -0.44 to -0.14 mm) between the groups. The percentage of children achieving an uncorrected visual acuity of more than 20/25 was similar in the RCO (64.3%) and orthokeratology (65.5%) groups (P = 0.937). CONCLUSIONS: Combining RLRL therapy with orthokeratology may offer a promising approach to optimize axial elongation control among children with myopia. This approach also potentially allows children to achieve satisfactory visual acuity, reducing daytime dependence on corrective eyewear. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

INOS ablation promotes corneal wound healing via activation of Akt signaling.

Corneal injury leads to impaired normal structure of the cornea. Improving the wound healing process in epithelial cells significantly contributes to ocular damage treatments. Here, we aimed to investigate the potential mechanisms of nitric oxide (NO) and its mediator, inducible nitric oxide synthase (iNOS), in the process of corneal wound healing. We established a corneal injury model of iNOS-/- mice, and treated human corneal epithelial cell lines (HCE-2) with the iNOS inhibitor L-INL, with or without NO replenishment by supplying sodium nitroferricyanide dihydrate (SNP). Our findings showed that inhibition of NO/iNOS accelerated corneal repair, enhanced uPAR (a receptor protein indicating the migration ability), and improved epithelial cell migration. Furthermore, NO/iNOS ablation activated Akt phosphorylation, reduced neutrophil marker protein MPO expression, and downregulated the transcription of inflammation cytokines CXCL-1, CXCL-2, IL-1ß, IL-6, and TNF-α. However, the protective effects of NO/iNOS inhibition are significantly reduced by NO replenishment when treated with SNP. Therefore, we confirmed that inhibiting NO/iNOS improved the corneal wound healing by facilitating epithelial cell migration and reducing inflammatory reactions, which might be related to the activation of the Akt signaling pathway.

AS101 regulates the Teff/Treg balance to alleviate rabbit autoimmune dacryoadenitis through modulating NFATc2.

Sjögren's syndrome (SS) dry eye can cause ocular surface inflammation and lacrimal gland (LG) damage, leading to discomfort and potential vision problems. The existing treatment options for SS dry eye are currently constrained. We investigated the possible therapeutic effect and the underlying mechanism of AS101 in autoimmune dry eye. AS101 was injected subconjunctivally into a rabbit model of autoimmune dacryoadenitis and its therapeutic effects were determined by evaluating clinical and histological scores. The expressions of effector T cells (Teff)/regulatory T cells (Treg)-related transcription factors and cytokines, inflammation mediators, and transcription factor NFATc2 were measured by quantitative real-time PCR and/or Western blot both in vivo and in vitro. Additionally, the role of NFATc2 in the immunomodulatory effects of AS101 on T cells was explored by co-culturing activated peripheral blood lymphocytes (PBLs) transfected with NFATc2 overexpression lentiviral plasmid with AS101. AS101 treatment potently ameliorated the clinical severity and reduced the inflammation of LG. Further investigation revealed that AS101 treatment led to decreased expression of Th1-related genes (T-bet and IFN-γ) and Th17-related genes (RORC, IL-17A, IL-17F, and GM-CSF) and increased expression of Treg-related gene Foxp3 in vivo and in vitro. Meanwhile, AS101 suppressed the expression of TNF-α, IL-1ß, IL-23, IL-6, MMP-2, and MMP-9. Mechanistically, AS101 downregulated the expression of NFATc2 in inflamed LGs. Overexpression of NFATc2 in activated PBLs partially blunted the effect of AS101 on Teff suppression and Treg promotion. In conclusion, AS101 is a potential regulator of Teff/Treg cell balance and could be an effective treatment agent for SS dry eye.

METTL3 inhibits autoreactive Th17 cell responses in experimental autoimmune uveitis via stabilizing ASH1L mRNA.

Methyltransferase like 3 (METTL3), a primary N6-methyladenosine (m6A) methyltransferase, has been implicated in various biological and pathological processes including immune responses. However, the functions and mechanisms of METTL3 in pathogenic T helper (Th)17 cells are poorly understood. Here we found significantly decreased METTL3 expression along with reduced m6A levels in eyeballs and T cells of experimental autoimmune uveitis (EAU). Overexpression of METTL3 ameliorated the development of EAU and suppressed pathogenic Th17 cell responses in vivo and in vitro. Mechanistically, METTL3 promoted the expression of absent, small, or homeotic-like 1 (ASH1L) via enhancing its stability in a YT521-B homology domain containing 2 (YTHDC2)-dependent manner, which further decreased the expression of IL-17 and IL-23 receptor (IL-23R), resulting in reduced pathogenic Th17 responses. Together, our data reveal a pivotal role of METTL3 in regulating pathogenic Th17 responses, which may contribute to human uveitis therapy.

Mettl3 induced miR-338-3p expression in dendritic cells promotes antigen-specific Th17 cell response via regulation of Dusp16.

Pathogenic Th17 cells are critical drivers of multiple autoimmune diseases, including uveitis and its animal model, experimental autoimmune uveitis (EAU). However, how innate immune signals modulate pathogenic Th17 responses remains largely unknown. Here, we showed that miR-338-3p endowed dendritic cells (DCs) with an increased ability to activate interphotoreceptor retinoid-binding protein (IRBP)1-20 -specific Th17 cells by promoting the production of IL-6, IL-1ß, and IL-23. In vivo administration of LV-miR-338-infected DCs promoted pathogenic Th17 responses and exacerbated EAU development. Mechanistically, dual-specificity phosphatase 16 (Dusp16) was a molecular target of miR-338-3p. miR-338-3p repressed Dusp16 and therefore strengthened the mitogen-activated protein kinase (MAPK) p38 signaling, resulting in increased production of Th17-polarizing cytokines and subsequent pathogenic Th17 responses. In addition, methyltransferase like 3 (Mettl3), a key m6A methyltransferase, mediated the upregulation of miR-338-3p in activated DCs. Together, our findings identify a vital role for Mettl3/miR-338-3p/Dusp16/p38 signaling in DCs-driven pathogenic Th17 responses and suggest a potential therapeutic avenue for uveitis and other Th17 cell-related autoimmune disorders.

Relative corneal refractive power shift and inter-eye differential axial growth in children with myopic anisometropia treated with bilateral orthokeratology.

PURPOSE: To investigate the relationship between relative corneal refractive power shift (RCRPS) and axial length growth (ALG) in bilateral myopic anisometropes treated with orthokeratology. METHODS: A total of 102 children with myopic anisometropia in this prospective interventional study were randomly assigned to the spectacle group and orthokeratology group. Axial length (AL) and corneal topography was measured at baseline and the 12-month follow-up visit. ALG was defined as the difference between the two measurements, and RCRPS profiles were calculated from two axial maps obtained. RESULTS: In the orthokeratology group, the ALG in the more myopic eye (0.06 ± 0.15 mm) was significantly smaller than that in the less myopic eye (0.15 ± 0.15 mm, p < 0.001), and the interocular difference in AL significantly decreased following 1-year treatment, from 0.47 ± 0.32 to 0.38 ± 0.28 mm (p < 0.001). However, in the spectacle group, the ALG was similar between the two eyes, and the interocular difference in AL did not change significantly over one year (all p > 0.05). The interocular difference in ALG in the orthokeratology group was significantly correlated with the interocular difference in RCRPS (dRCRPS, ß=-0.003, p < 0.001) and the interocular difference in baseline AL (ß=-0.1179, p < 0.001), with R2 being 0.6197. CONCLUSION: Orthokeratology was effective in decreasing the magnitude of anisometropia. The interocular variation in RCRPS is an important factor accounting for the reduction of interocular ALG difference in anisomyopic children post-orthokeratology. These results provide insight into establishing eye-specific myopia control guidelines during orthokeratology treatment for myopic anisometropes.

Relationship between the structure and microcirculation of the optic disc region and myopic traction maculopathy in highly myopic eyes.

PURPOSE: To explore the characteristics and influencing factors structural and microcirculatory of optic disc and peripapillary tissue in eyes with myopia traction maculopathy (MTM). METHODS: There were 100 eyes from 77 patients in this study. We used 1:1 matching axial length in myopic eyes. Patients were divided into two groups according to the presence or absence of MTM. Fundus structure parameters were obtained by swept source optical coherence tomography (SS-OCT), and the optic disc microcirculation parameters were obtained by OCT angiography (OCTA). RESULTS: MTM group were older (P = 0.001) and had poorer Best-corrected Visual Acuity (BCVA) (P = 0.011), the optic disc-fovea distance (DFD) was longer (P < 0.019), optic disc tilt was greater (P < 0.001), area of peripapillary atrophy (PPA) was larger (P < 0.001), and PPA/optical disc area (ONH) was higher (P < 0.001). The peripapillary scleral thickness (PST) was lower in the MTM group (P < 0.001). The mean peripapillary choroidal thickness (PCT) (P < 0.001) and PCT in the 10 orientations were significantly lower in the MTM group than in the NMTM group (all P < 0.01). Vascular density in the nasosuperior (NS) region of the optic disc was significantly lower in the MTM group (P = 0.037). The generalized estimating equation suggested that PPA area (P = 0.028), mean PCT (P = 0.008), superior PCT (P = 0.027), inferonasal PCT (P = 0.040), temporoinferior PCT (P = 0.013), and PST (P = 0.046) correlated with MTM. Age, axial length, optic disc tilt, PPA area, mean PCT, and optic disc central zone (0-2 mm) vascular density (all P < 0.05) were significantly correlated with PST. CONCLUSIONS: The enlarged PPA area and thinner PCT and PST in eyes with MTM are more significant. Lower PST in high myopia was related to abnormalities of PCT and microcirculation. TRIAL REGISTRATION: Clinical Trial Registration number: ChiCTR2100046590.

Morphological characteristics of the foveal avascular zone in pathological myopia and its relationship with macular structure and microcirculation.

PURPOSE: To explore the characteristics of macular structure, microcirculation, and foveal avascular zone (FAZ) morphology in pathological myopia and to research the associations between these factors and pathological myopia. METHODS: This is a cross-sectional study. The study included 103 eyes with non-high myopia and 206 eyes with high myopia (139 with simple high myopia and 67 with pathological myopia). Macular structural and microcirculation parameters were determined using optical coherence tomography angiography (OCTA). The FAZ morphological parameters were measured manually using Image J software. Correlations between pathological myopia and various factors were analyzed. RESULTS: Patients with pathological myopia had a thinner retinal thickness (RT) and choroidal thickness (CT) and a lower retinal superficial vascular density (SVD), retinal deep vascular complex density (DVD), choriocapillaris perfusion area (CCPA), and choroidal vascularity index (CVI) (all P < 0.05). Patients with pathological myopia had a larger FAZ area, perimeter, major axis, minor axis, acircularity index (AI), and lower circularity index (CI) (all P < 0.01). The axial length (AL), the major axis of the superficial FAZ, CI, and AI were significantly correlated with myopia severity (all P < 0.05). CONCLUSIONS: Patients with pathological myopia exhibited worse macular microcirculation and thinner macular retina and choroid. The FAZ in pathological myopia was larger and more irregular. The AL, CI, and AI were significantly associated with myopia severity. Thus, CI and AI might serve as new indicators for monitoring the progression of myopia. Further investigations should be performed. TRIAL REGISTRATION: Clinical Trials.gov Identifier: ChiCTR2100046590.

IMPACTS OF POSTERIOR STAPHYLOMA ON PARAPAPILLARY MICROVASCULATURE AND ATROPHY IN HIGH MYOPIC EYES: A MATCHED COHORT STUDY WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: We aimed to evaluate the impacts of the different types of posterior staphyloma (PS) in high myopia on parapapillary microvasculature and parapapillary atrophy (PPA, i.e., γ-zone and δ-zone) with optical coherence tomography angiography. METHODS: This cross-sectional study included 152 high myopic eyes (152 participants) with γ-zone. After matching, high myopic eyes were stratified into PS (n = 33) and non-PS (n = 33) groups. PS types, parapapillary microvasculature characteristics, the prevalence of non-juxtapapillary microvasculature dropout (NJ-MvD), the longest radial width from the optic disc edge to retinal pigment epithelium atrophy edge (PPA-w), γ-zone, and δ-zone with changes in visual field and best-corrected visual acuity (BCVA) were evaluated and analyzed. RESULTS: According to Curtin's classification, we identified five types of PS included: primary types I, II, III, and compound types VII, and IX. Eyes with type II showed a higher optic disc tilted ratio and larger PPA-w compared to other primary PS. Subjects with type IX were the oldest. Eyes with types VII and IX had wider γ-zone and δ-zone, worse visual field outcomes, poorer BCVA, and a higher incidence of NJ-MvD compared to primary PS. Choroidal and intrascleral vessels were associated with NJ-MvD and were located near or connected to the circle of Zinn-Haller. CONCLUSIONS: Eyes with high myopia and PS show wider PPA, affecting the γ-zone and δ-zone, and are at a higher risk of developing NJ-MvD. Specifically, eyes with PS types VII and IX are more susceptible to visual field damage and decreased BCVA. These results highlight the importance of impact of PS on PPM and PPA in high myopia.

Retinal and choroidal structure and vascularity in Chinese emmetropic and myopic children.

PURPOSE: This study evaluated the structural features of the retinal and choroidal regions and their correlations with ocular biometric and vascular parameters in Chinese children using optical coherence tomography angiography (OCTA). METHODS: A total of 159 children, 6-13 years of age, were included in this prospective study. The sample consisted of 55 emmetropes (spherical equivalent ≤ +0.75 and > -0.50 D), 53 low-moderate myopes (≤ -0.50 to > -6.00 D) and 51 high myopes without pathological changes (≤ -6.00 D). Optical coherence biometry was used to measure axial length (AL) and anterior segment parameters. Swept-source optical coherence tomography/OCTA was used to assess the macular structures and vascular characteristics in a 6 × 6 mm region centred on the macula. RESULTS: In a comprehensive analysis adjusting for age, sex, AL, macular blood perfusion, intraocular pressure and anterior segment parameters, retinal thickness (RT) showed a significant positive association with deep retinal vascular density and superficial retinal vascular density in the foveal area, but not with AL. Moreover, RT exhibited a significant negative association with AL in the parafoveal and perifoveal regions. Further, a significant positive correlation was observed between choroidal thickness and both choroidal vascular volume and choriocapillaris perfusion area, along with a negative correlation with AL across the entire macular region. CONCLUSIONS: This study showed that the thickness of retina and choroid in Chinese children was not only associated with AL but also showed dynamic properties such as the blood perfusion of the retina and choroid, particularly in the foveal area.

Evaluating the microcirculation of the dome-shaped macula and its complications in adults with highly myopic eyes by swept-source optical coherence tomography angiography.

PURPOSE: The aim of this study was to investigate the microcirculatory characteristics of the dome-shaped macula (DSM), its complications in highly myopic eyes and to explore the factors associated with a DSM. METHODS: This cross-sectional case-control study included a total of 98 subjects (98 eyes): 49 eyes with DSM and 49 eyes without DSM. The axial length (AL) of the myopic eyes was matched 1:1 to eliminate the effect of AL differences on the results. Choroidal (CT) and scleral thickness (ST) and other structural parameters were assessed by swept-source optical coherence tomography (SS-OCT). OCT angiography was used to measure microcirculatory parameters in highly myopic eyes. RESULTS: Subjects with DSM had thinner subfoveal choroidal thickness (46.01 ± 13.25 vs. 81.62 ± 48.26 µm; p < 0.001), thicker subfoveal scleral thickness (SFST; 331.93 ± 79.87 vs. 238.74 ± 70.96 µm; p < 0.001) and thinner foveal CT (66.86 ± 24.65 vs. 107.85 ± 52.65 µm; p < 0.001) compared to subjects without DSM. The foveal choroidal perfusion area (0.72 ± 0.04 vs. 0.76 ± 0.04 mm2; p < 0.001) and foveal choroidal vascularity index (0.15 ± 0.04 vs. 0.33 ± 0.14; p < 0.001) were significantly lower in eyes with DSM. Retinoschisis (81.6% vs. 38.8%; p < 0.001) was more common in eyes with DSM. Eyes with horizontal DSM had worse best-corrected logMAR visual acuity than eyes with round DSM (0.34 ± 0.22 vs. 0.23 ± 0.22; p = 0.03). DSM height (98.95 ± 65.17 vs. 104.63 ± 44.62 µm; p = 0.05) was lower in the horizontal DSM. SFST (OR = 1.06, p = 0.04) and foveal choroidal vascularity index (OR = 0.711, p = 0.02) were significantly associated with DSM. DSM width (p < 0.001), foveal choroidal perfusion area (p = 0.01), foveal choriocapillaris perfusion area (p = 0.02) and parafoveal choroidal vascularity index (p = 0.03) were the most significantly associated factors with DSM height. CONCLUSIONS: The microcirculatory characteristics of eyes with DSM differed from those without DSM. Microcirculatory abnormalities were significantly associated with a DSM. The height of the DSM was associated with decreased blood perfusion.

Refraction and ocular biometric parameters of preschool children in the Beijing whole childhood eye study: the first-year report.

BACKGROUND: Prevention of myopia should begin before school age. However, few population-based cohort studies have investigated refractive status in preschool children with cycloplegia. This study aimed to investigate the post-COVID-19 refraction and ocular biometric parameters of preschool children in Beijing Tongzhou District. METHODS: A population-based cohort study of kindergarten children in Tongzhou District, Beijing, commenced in November 2021. The present study reports data from the first year of the aforementioned population-based study. We selected children aged 3-6 years from nine kindergartens. Biometric parameters, including axial length (AL), anterior chamber depth (ACD), and corneal radius of curvature (CR), were collected before cycloplegia. Cycloplegic refraction was also measured. The spherical equivalent (SE), lens power (LP), and AL-to-CR ratio were calculated. Multiple linear regression analysis was used to analyse the correlation between refraction and ocular biometric parameters. RESULTS: A total of 1,505 children completed the examination, and a mean SE of 1.24 ± 0.91 D was found. The overall prevalence of myopia was 1.93%. The mean AL, ACD, CR, LP, and AL-to-CR ratio were 22.24 ± 0.70 mm, 3.28 ± 0.26 mm, 7.77 ± 0.26 mm, 26.01 ± 1.56 D, and 2.86 ± 0.07, respectively. Longer AL, deeper ACD, larger AL-to-CR ratio, and lower LP were associated with older age; the CR was not significantly different among different ages. In the multiple linear regression analysis, after adjusting for sex and age, the model that included AL, CR, and LP explained 87% of the SE variation. No differences were observed in the prevalence of myopia or the SE in this particular age range. CONCLUSION: The findings of this study suggest that a large proportion of preschool children in Beijing are mildly hyperopic, with a considerably low prevalence of myopia. In preschool children, refractive development was found to present mild hyperopia rather than emmetropia or myopia, a phenomenon that is characteristic of this age range.

Association between whole-grain intake and myopia in chinese children: a cross-sectional epidemiological study.

BACKGROUND: Nutritional status influences the growth and development of the eyes. However, there are few studies on the association between diet, especially whole grains (WG) consumption, and myopia. The study aimed to evaluate the association between WG intake and myopia prevalence among primary school-age children in China. METHODS: This cross-sectional epidemiological study conducted between November 2019 and December 2019 included 586 children, aged 6-12 years, attending primary school in Binhai district, Tianjin, China. Ophthalmologic examinations and optometric cycloplegic refraction measurements were conducted. Information was collected on known risks and protective factors for myopia and the consumption of WGs, vegetables, and fruits. This association between the probability of myopia and the proportion of WG consumption (WG proportion was calculated as the mean intake from WG sources divided by total grain intake), adjusted for protective and risk factors, was analysed using crude and multivariable logistic regression. RESULTS: Among the study participants, 226/586 (38.57%) children had myopia in at least one eye. WG intake was inversely correlated with the prevalence of myopia. Furthermore, in the multivariate analysis, WG intake of > 50% was identified as a protective factor against myopia after subsequent adjustment for children's age, sex, parental myopia, near-work activity, screen time, reading and writing habits, visual fatigue, outdoor time, and classroom light environment (all P < 0.05). CONCLUSION: WG intake (> 50%) was an independent protective factor against myopia. Modifying the form of grains consumed (whole versus refined) could be one of the targets of future public health measures.

The relationship between baseline axial length and axial elongation in myopic children undergoing orthokeratology.

PURPOSE: To investigate the correlation between the baseline axial length (AL) and axial elongation in myopes undergoing orthokeratology (ortho-k). METHODS: This was a retrospective study. During the 1-year follow-up, 1176 children (aged 8-14 years) were included and divided into an ortho-k group (n = 588) and a single-vision spectacle group (n = 588). The ortho-k group participants (8-11 years of age) who completed the 3-year follow-up (n = 150) were further divided into three subgroups stratified by their baseline AL: subgroup 1 (AL < 24.5 mm), subgroup 2 (24.5 ≤ AL < 26 mm) and subgroup 3 (AL ≥ 26 mm). AL was measured at baseline and during the annual visit. RESULTS: The ortho-k group exhibited slower 1-year axial elongation (39% reduction) than the spectacle group. The 1-year axial elongation was negatively correlated with initial age in both groups. A negative association between 1-year axial elongation and baseline AL was observed in the ortho-k group but not in the spectacle group. However, this relationship only existed in ortho-k participants 8-11 years of age. For the younger ortho-k participants who completed the 3-year follow-up, the annual axial elongation was significantly higher in subgroup 1 for the first and second years but not in the third year compared with subgroups 2 and 3. CONCLUSION: Axial elongation was negatively correlated with baseline AL in the ortho-k group. Children aged 8-11 years with longer baseline AL (≥24.5 mm) demonstrated slower annual axial elongation during the first 2 years of ortho-k treatment, which may provide insight into establishing individual guidelines for controlling myopia using ortho-k in children with different baseline characteristics.

Short-term Changes in Epithelial and Optical Redistribution Induced by Different Orthokeratology Designs.

OBJECTIVES: This study aimed to investigate corneal epithelial and topographic changes caused by two commercial myopia orthokeratology (ortho-k) designs. METHODS: Twenty-six subjects fitted with vision shape treatment (VST) lenses and 30 subjects fitted with corneal reshaping therapy (CRT) lenses were reviewed 1 day, 1 week, and 1 month after lens initiation. A spectral-domain optical coherence tomography system was used to create epithelial maps that were in turn used to determine the average epithelial thickness of each zone and the diameter of treatment zone. By measuring the topographic tangential differential map, the treatment zone diameter and the power and width of the high convex zone (HCZ) were obtained. All epithelial thicknesses and topographic corneal variations recorded were analyzed. RESULTS: At the central zone, the epithelial thickness changes (△ET) decreased significantly after 1 day of ortho-k in two groups. At 2- to 9-mm peripheral zone, ortho-k increased △ET until 1 week in the VST group, whereas it kept increasing in the CRT group after 1 week. At 1 month, the central △ET is -9.51±2.38 mm in the VST group, which was comparable to -8.72±3.43 mm in the CRT group. The nasal HCZ power and the △ET of nasal and inferior nasal were significantly larger in the CRT group. A positive correlation was found between the HCZ power and △ET generated by VST-type lenses inferiorly and temporally. For the CRT group, a positive correlation was found between inferior HCZ power and △ET. CONCLUSIONS: At the early stage of ortho-k, epithelial thickness and topography change quickly and simultaneously. Epithelial changes were in line with corneal topography reshaping. Epithelial and optical remodelling were affected by different lens types.

Characteristics of the ocular surface in neurotrophic keratitis induced by trigeminal nerve injury following neurosurgery.

PURPOSE: To analyse and quantify ocular surface parameters in patients with unilateral neurotrophic keratitis (NK) induced by trigeminal nerve injury post-neurosurgery. METHODS: The study included 26 unilateral NK patients who had undergone neurosurgery, and 20 matched normal controls. Demographic and clinical characteristics of all participants were collected and analysed. Slit-lamp examination, Cochet-Bonnet aesthesiometry, Keratograph 5 M, and LipiView interferometer were performed on both eyes of 17 mild NK patients. For nine moderate/severe NK patients, sub-basal nerve density was measured by in vivo confocal microscopy. RESULTS: Of the 26 patients, nine had acoustic neuroma, nine had trigeminal neuralgia, and eight had neoplasms. Facial nerve paralysis was observed in one of the 17 mild NK eyes (5.9%) and seven of the nine moderate/severe NK eyes (77.8%). Compared to contralateral and normal control eyes, 26 NK eyes showed significantly reduced sensitivity in five corneal regions (P < 0.05). Corneal sensitivity in moderate/severe NK eyes was significantly lower than in mild NK eyes (P < 0.05). Moderate/severe NK eyes had poor visual acuity, and their sub-basal nerve density was lower than that of the controls. The onset of the moderate/severe NK was from 0.5 to 24 months (median [Q1, Q3], 1 [0.5, 2.5] months) after neurosurgery. For the mild NK eyes, the number of total blinks, the first non-invasive tear breakup time (NITBUT) and average NITBUT were significantly lower than contralateral and normal control eyes (P < 0.05), and the number of partial blinks and partial blinking rate were significantly higher than the other two control groups (P < 0.05). CONCLUSIONS: Patients with NK induced by trigeminal nerve injury following neurosurgery had decreased corneal sensitivity to various degrees accompanied by increased partial blinks and shortened NITBUT. The severity of NK is related to the severity of the corneal sensory impairment. Facial nerve paralysis can worsen the clinical progression of NK. Trial registration Chinese Clinical Trial Registry (ChiCTR2100044068, Date of Registration: March 9, 2021).

Posterior scleral reinforcement for the treatment of myopic traction maculopathy.

BACKGROUND: This study aimed to investigate the clinical effectiveness of posterior scleral reinforcement(PSR) for the treatment of myopic traction maculopathy (MTM). METHODS: This was a prospective study of 32 eyes from 20 patients with MTM treated with PSR using genipin-cross-linked donor sclera. The length of the scleral strip used for the surgery was designed to be 1.5-times the axial length of the eye, whereas its width was 0.4-times the axial length of the eye. The optical coherence tomography images, spherical equivalent of refractive error, axial length, best corrected visual acuity, electroretinogram findings, and intraocular pressure of the patients were assessed postoperatively. RESULTS: The mean duration of follow-up was 17.80 ± 8.74 months. The differences between the spherical equivalent of refractive error, best corrected visual acuity, axial length, and electroretinogram findings recorded preoperatively and those measured postoperatively were statistically significant (p < 0.05). The final reduction in axial length was 1.64 ± 0.85 mm. At the end of the follow-up, optical coherence tomography showed essential foveal reattachment in 30 eyes (93.75%), partial reattachment in two eyes (6.25%), and closure of macular holes in seven eyes (77.78%). No retinal detachment, vitreous haemorrhage, or other serious complications occurred following the surgery. CONCLUSIONS: Posterior scleral reinforcement with genipin-cross-linked sclera showed safe and effective outcomes for the treatment of MTM during a follow-up period of at least one year. TRIAL REGISTRATION: 11\12\2018, ChiCTR1800020012 .

The treatment zone decentration and corneal refractive profile changes in children undergoing orthokeratology treatment.

BACKGROUND: To confirm the association between treatment-zone (TZ) decentration and axial length growth (ALG) in children who underwent orthokeratology; and to explore the association between TZ decentration and relative corneal refractive power (RCRP) profile, which was known to be significantly associated with ALG retardation. METHODS: Four hundred myopic children of age 12 years participated in the study, with 200 wearing orthokeratology lenses and the other 200 wearing single-vision spectacle as the controls. Cycloplegic refraction was performed at baseline. Axial length was measured at baseline and 12 months after initial lens wear, and ALG was defined as the difference. In the ortho-k group, TZ decentration and the RCRP map were calculated from the topography map obtained at the 12-month visit. RCRP were summed within various chord radii from the cornea center, and the association to TZ decentration, spherical equivalent (SE), ALG were analyzed with linear regressions. RESULTS: Compared to the controls, children wearing orthokeratology lenses had significantly smaller ALG over 1 year (0.1 ± 0.15 mm vs. 0.32 ± 0.17 mm, p < 0.001). ALG was significantly and negatively associated with summed RCRP within the central cornea of 2 mm in radius. The mean TZ decentration was 0.62 ± 0.25 mm, and the mean direction was 214.26 ± 7.39 degrees. ALG was negatively associated with the TZ decentration magnitude (p < 0.01), but not the direction (p = 0.905). TZ decentration caused an asymmetrical distribution of the RCRP with the nasal side plus power shifting towards the corneal center. For chord radius ranging 1-2 mm, the association between TZ decentration and the summed RCRP were significant, and the proportion of variance accountable increased with chord radius. For chord radius beyond 1.5 mm, the association between baseline spherical equivalent (SE) and summed RCRP was significant. The portion of variance accountable by SE increased and peaked in 2.5 mm chord radius. CONCLUSIONS: A larger TZ decentration was associated with a larger summed RCRP in the central cornea. It may be one of the possible reasons why TZ decentration is beneficial to retarding myopia progression.

Assessment of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in patients with high myopia.

BACKGROUND: Previous reports have suggested that inflammation levels play a crucial role in the pathogenesis of high myopia (HM). This study aimed to investigate the relationship between HM and systemic inflammation using the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). METHODS: Overall, 100 age- and sex-matched participants were recruited for the study, including 50 participants each in the non-HM (NHM) and HM groups. Ocular examinations and blood tests were performed. The NLR and PLR values were calculated from complete blood counts. Receiver operating characteristic (ROC) curves and optimal cut-off values were used to determine the optimal values of the NLR and PLR to distinguish between the HM and NHM groups. RESULTS: The values of NLR and PLR were significantly elevated in the HM group compared with those in the NHM group (P < 0.001 and P = 0.010, respectively). Axial length (AL) was significantly correlated with the NLR (r = 0.367, P < 0.001) and PLR (r = 0.262, P = 0.009). In the ROC analysis, the NLR value to distinguish between the HM and NHM groups was 0.728; the best cut-off value was 2.68, with 76% sensitivity and 62% specificity. The PLR value to distinguish between the HM and NHM groups was 0.650; the best cut-off value was 139.69, with 52% sensitivity and 76% specificity. CONCLUSION: The findings of this study indicate that the development of HM may be associated with systemic inflammation measured using the NLR and PLR. TRIAL REGISTRATION: The study was registered on December 28, 2021 ( http://www.chictr.org.cn ; ChiCTR2100054834).