Eye and Vision最新文献

Background: Thyroid eye disease (TED) is a vision-threatening autoimmune disorder. Orbital tissue fibrosis leading to intractable complications remains a troublesome issue in TED management. Exploration of novel therapeutic targets and agents to ameliorate tissue fibrosis is crucial for TED. Recent work suggests that Ca²⁺ signaling participates in tissue fibrosis. However, whether an alteration of Ca²⁺ signaling has a role in fibrogenesis during TED remains unclear. In this study, we aimed to investigate the role of Ca²⁺ signaling in the fibrogenesis process during TED and the potential therapeutic effects of a highly selective inhibitor of the L-type calcium channel (LTCC), nimodipine, through a TGF-β1 induced in vitro TED model.

Methods: Primary culture of orbital fibroblasts (OFs) were established from orbital adipose connective tissues of patients with TED and healthy control donors. Real-time quantitative polymerase chain reaction (RT-qPCR) and RNA sequencing were used to assess the genes expression associated with LTCC in OFs. Flow cytometry, RT-qPCR, 5-ethynyl-2'-deoxyuridine (EdU) proliferation assay, wound healing assay and Western blot (WB) were used to assess the intracellular Ca²⁺ response on TGF-β1 stimulation, and to evaluate the potential therapeutic effects of nimodipine in the TGF-β1 induced in vitro TED model. The roles of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and signal transducer and activator of transcription 1 (STAT1) in fibrogenesis during TED were determined by immunohistochemistry, WB, flow cytometry and co-immunoprecipitation assay. Selective inhibitors were used to explore the downstream signaling pathways.

Results: LTCC inhibitor nimodipine blocked the TGF-β1 induced intracellular Ca²⁺ response and further reduced the expression of alpha-smooth muscle actin (α-SMA), collagen type I alpha 1 (Col1A1) and collagen type I alpha 2 (Col1A2) in OFs. Besides, nimodipine inhibited cell proliferation and migration of OFs. Moreover, our results provided evidence that activation of the CaMKII/STAT1 signaling pathway was involved in fibrogenesis during TED, and nimodipine inhibited the pro-fibrotic functions of OFs by down-regulating the CaMKII/STAT1 signaling pathway.

Conclusions: TGF-β1 induces an LTCC-mediated Ca²⁺ response, followed by activation of CaMKII/STAT1 signaling pathway, which promotes the pro-fibrotic functions of OFs and participates in fibrogenesis during TED. Nimodipine exerts potent anti-fibrotic benefits in vitro by suppressing the CaMKII/STAT1 signaling pathway. Our work deepens our understanding of the fibrogenesis process during TED and provides potential therapeutic targets and alternative candidate for TED.

Background: The primary objective of this investigation was to compare the nominal central ablation depth with the achieved central corneal stromal ablation depth after StreamLight transepithelial photorefractive keratectomy (tPRK) for myopia with WaveLight® laser by Alcon Laboratories, TX, USA.

Methods: This ambispective study encompassed a retrospective analysis of 40 eyes who underwent treatment for myopia and astigmatism, followed by a prospective examination conducted 6-9 months postoperatively. Pre- and postoperative Avanti spectral-domain optical coherence tomography (SD-OCT; Optovue Inc., CA, USA) provided stromal and epithelial thickness maps. The difference between pre- and postoperative central stromal thicknesses at the corneal vertex was used to calculate the achieved stromal thickness ablation depth. This value was then compared with the corresponding central nominal depth on the laser ablation planning map.

Results: A total of 40 eyes (OD/OS:18/22) of 40 patients (31.4 ± 9.2 years) were available for evaluation. The mean treated spherical equivalent was - 2.98 ± 1.46 D. The mean nominal and achieved central stromal ablation depths were 51.22 µm and 59.67 μm, respectively, showing a mean stromal excessive ablation of 16.50%. The mean pre- and postoperative central epithelial thicknesses were 53.74 μm and 59.31 μm, respectively, showing a mean postoperative thickness increase of 10.46%. This increase in the epithelial thickness rendered the mean postoperative pachymetry reduction to 54.11 μm, only 2.33% greater than the mean nominal ablation depth.

Conclusions: The study revealed a central stromal ablation 16.50% greater than the nominal ablation depth. This excessive stromal removal was largely compensated for by the increase in epithelial thickness, resulting in a mean difference between the nominal ablation depth and the achieved central corneal pachymetry reduction of only 2.33%. This significant excessive central stromal ablation must be taken into consideration in the calculation of the residual stromal thickness.

Background: The value of quantitatively analyzing peripapillary capillary volume (PPCV) distribution was explored in normal and diabetic retinopathy (DR) eyes using dense B-scan optical coherence tomography angiography (DB OCTA).

Methods: This was a cross-sectional observational study followed by prospective follow-up for those with DR, which enrolled 101 healthy subjects and 140 DR patients. Dense, automatic, real-time (DART) volume scans of DB OCTA were performed using a Spectralis HRA + OCT2. ImageJ and MATLAB were used to process and calculate PPCV distribution detected by DB OCTA.

Results: In normal subjects, PPCV distribution were significantly correlated with the age and quadrant location (all P < 0.001). The PPCV distribution in each quadrant was significantly lower in severe nonproliferative DR patients than in normal subjects in all age groups (all P < 0.05, t-test). Compared to normal subjects, the PPCV distribution improved significantly in the pan-retinal photocoagulation treatment and surgery groups (all P < 0.001). No significant variation was observed in the anti-VEGF treatment group and normal subjects (P > 0.05). The PPCV distribution is significantly correlated with post-treatment best-corrected visual acuity in both the pan-retinal photocoagulation treatment and surgery groups (all P < 0.003) but not in the anti-VEGF treatment group (P = 0.940).

Conclusions: Quantitative assessment of PPCV distribution using DB OCTA is valuable in prognosis evaluation of DR with pan-retinal photocoagulation and surgery.

Background: The objective of this study is to illustrate the changes in the choroidal vasculature in individuals with diffuse chorioretinal atrophy (DCA, early-stage myopic maculopathy) and investigate the association between them.

Methods: This study included 1418 highly myopic eyes from 720 participants aged 18 - 60 years from the Wenzhou High Myopia Cohort Study. These participants underwent comprehensive ophthalmic assessments. Myopic maculopathy classification followed the Meta-PM system, with pathological myopia defined as myopic maculopathy of DCA or severer. Eyes with myopic maculopathy categorized as no macular lesions (C0), tessellated fundus (C1), and DCA (C2) were enrolled in the analysis. Choroidal images were obtained from swept-source optical coherence tomography (SS-OCT), and the images were processed with a deep learning-based automatic segmentation algorithm and the Niblack auto-local threshold algorithm.

Results: DCA was detected in 247 eyes (17.4%). In comparison to eyes with C0, those with C2 exhibited significant reductions in choroidal thickness (ChT), luminal area (LA), and stromal area (SA) across all evaluated regions (all P < 0.001). An increase in choroidal vascular index (CVI) was observed in all regions, except for the nasal perifoveal (N2) and inferior perifoveal (I2) regions (all P < 0.01). Multivariable logistic regression analysis revealed a negative association between the presence of DCA and increases in choroidal LA and SA (odds ratio ≤ 0.099, P < 0.001). Multivariable linear regression analysis showed that the mean deviation of the visual field test was positively associated with LA and SA at the vertical meridian (B = 1.512, P < 0.001 for LA; B = 1.956, P < 0.001 for SA). Furthermore, the receiver operating characteristic curve analyses showed the optimal ChT to diagnose pathological myopia was 82.4 µm in the N2 region, the LA was 0.076 mm² and the SA was 0.049 mm², with area under the curves of 0.916, 0.908, and 0.895, respectively.

Conclusions: The results of this study indicated that both the presence of DCA and visual function impairment were associated with reductions in choroidal perfusion and stromal components. Moreover, we established threshold values for choroidal parameters in diagnosing pathological myopia, offering valuable references for clinical diagnosis and management.

Background: Atropine, specifically 0.05% eyedrops, has proven effective in slowing myopia progression. This study aims to investigate peripheral refraction (PR) characteristics in myopic children treated with 0.05% atropine eyedrops at different frequencies.

Methods: One hundred thirty-eight myopic children completed this one-year prospective study, randomly assigned to once daily (7/7), twice per week (2/7), or once per week (1/7) groups. Spherical equivalent (SE) and axial length (AL) were measured. PR was assessed using a custom-made Hartmann-Shack wavefront peripheral sensor, covering a visual field of horizontal 60° and vertical 36°. Relative peripheral refraction (RPR) was calculated by subtracting central from peripheral measurements.

Results: After one year, SE increased more significantly in the 1/7 group compared to the 7/7 group (P < 0.001) and 2/7 group (P = 0.004); AL elongation was also greater in the 1/7 group compared to the 7/7 group (P < 0.001). In comparison with higher frequency groups, 1/7 group exhibited more myopic PR in the fovea and its vertical superior, inferior, and nasal retina; and less myopic RPR in the periphery retina after one-year (P < 0.05). Additionally, RPR in the 7/7 group demonstrated myopic shift across the entire retina, the 2/7 group in temporal and inferior retina, while the 1/7 group showed a hyperopic shift in the superior retina (P < 0.05). Moreover, myopic shift of RPR in the temporal retina is related to less myopia progression, notably in the 7/7 group (P < 0.05).

Conclusions: Atropine inhibits myopia progression in a frequency-dependent manner. The once-daily group showed the slowest myopia progression but exhibited more myopic shifts in RPR. Additionally, RPR in the temporal retina was related to myopia progression in all groups.

Trial registration: Chinese Clinical Trial Registry, ChiCTR2100043506. Registered 21 February 2021, https://www.chictr.org.cn/showproj.html?proj=122214.

Background: Acute retinal necrosis (ARN) is a relatively rare but highly damaging and potentially sight-threatening type of uveitis caused by infection with the human herpesvirus. Without timely diagnosis and appropriate treatment, ARN can lead to severe vision loss. We aimed to develop a deep learning framework to distinguish ARN from other types of intermediate, posterior, and panuveitis using ultra-widefield color fundus photography (UWFCFP).

Methods: We conducted a two-center retrospective discovery and validation study to develop and validate a deep learning model called DeepDrARN for automatic uveitis detection and differentiation of ARN from other uveitis types using 11,508 UWFCFPs from 1,112 participants. Model performance was evaluated with the area under the receiver operating characteristic curve (AUROC), the area under the precision and recall curves (AUPR), sensitivity and specificity, and compared with seven ophthalmologists.

Results: DeepDrARN for uveitis screening achieved an AUROC of 0.996 (95% CI: 0.994-0.999) in the internal validation cohort and demonstrated good generalizability with an AUROC of 0.973 (95% CI: 0.956-0.990) in the external validation cohort. DeepDrARN also demonstrated excellent predictive ability in distinguishing ARN from other types of uveitis with AUROCs of 0.960 (95% CI: 0.943-0.977) and 0.971 (95% CI: 0.956-0.986) in the internal and external validation cohorts. DeepDrARN was also tested in the differentiation of ARN, non-ARN uveitis (NAU) and normal subjects, with sensitivities of 88.9% and 78.7% and specificities of 93.8% and 89.1% in the internal and external validation cohorts, respectively. The performance of DeepDrARN is comparable to that of ophthalmologists and even exceeds the average accuracy of seven ophthalmologists, showing an improvement of 6.57% in uveitis screening and 11.14% in ARN identification.

Conclusions: Our study demonstrates the feasibility of deep learning algorithms in enabling early detection, reducing treatment delays, and improving outcomes for ARN patients.

Background: To identify longitudinal changes in each retinal layer thickness in central retinal vein occlusion (CRVO) patients with resolved macular edema (ME).

Methods: In this retrospective observational study, CRVO patients without a recurrence of ME for more than 3 years and normal controls were enrolled. Each retinal layer thickness of the parafoveal area, including ganglion cell complex (GCC), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), photoreceptor layer (PRL), and retinal pigment epithelium (RPE) was measured. After the resolution of ME, three more examinations with a 1-year interval were analyzed.

Results: A total of 98 eyes were enrolled, 50 eyes for the control group and 48 eyes for the CRVO group. The baseline GCC thickness was 114.2 ± 15.6 μm and 104.2 ± 25.4 μm in the control and CRVO groups, respectively, which was significantly different (P = 0.022). The thicknesses of other layers including INL, OPL, ONL, PRL, and RPE were not significantly different at baseline. The reduction rate of GCC, INL, OPL, and ONL was - 3.92, - 1.33, - 0.91, and - 2.31 μm/year in the CRVO group, whereas no significant reductions were observed in the control group. Best-corrected visual acuity was significantly associated with changes in the GCC, OPL, and ONL in the CRVO group.

Conclusions: In patients with CRVO, even in the absence of recurrent ME, retinal damage progresses over time, evidenced by thinning of the inner retina and outer retina including OPL and ONL. These changes may be associated with alterations in visual function.