Early Proteomic Characteristics and Changes in the Optic Nerve Head, Optic Nerve, and Retina in a Rat Model of Ocular Hypertension.

The pathogenesis of glaucoma is still unknown. There are few studies on the dynamic change of tissue-specific and time-specific molecular pathophysiology caused by ocular hypertension (OHT). This study aimed to identify the early proteomic alterations in the retina, optic nerve head (ONH), and optic nerve (ON). After establishing a rat model of OHT, we harvested the tissues from control and glaucomatous eyes and analyzed the changes in protein expression using a multiplexed quantitative proteomics approach (TMT-MS3). Our study identified 6403 proteins after 1-day OHT and 4399 proteins after 7-days OHT in the retina, 5493 proteins after 1-day OHT and 4544 proteins after 7-days OHT in ONH, and 5455 proteins after 1-day OHT and 3835 proteins after 7-days OHT in the ON. Of these, 560 and 489 differential proteins were identified on day 1 and 7 after OHT in the retina, 428 and 761 differential proteins were identified on day 1 and 7 after OHT in the ONH, and 257 and 205 differential proteins on days 1 and 7 after OHT in the ON. Computational analysis on day 1 and 7 of OHT revealed that alpha-2 macroglobulin was upregulated across two time points and three tissues stably. The differentially expressed proteins between day 1 and 7 after OHT in the retina, ONH, and ON were associated with glutathione metabolism, mitochondrial dysfunction/oxidative phosphorylation, oxidative stress, microtubule, and crystallin. And the most significant change in retina are crystallins. We validated this proteomic result with the Western blot of crystallin proteins and found that upregulated on day 1 but recovered on day 7 after OHT, which are promising as therapeutic targets. These findings provide insights into the time- and region-order mechanisms that are specifically affected in the retina, ONH, and ON in response to elevated IOP during the early stages.

Phacoemulsification combined with Kahook Dual Blade Goniotomy versus with Trabectome in the treatment of open angle glaucoma.

PURPOSE: To compare the surgical effectiveness and safety of phacoemulsification combined with KDB (Phaco-KDB) and with Trabectome (Phaco-Trabectome) at 6 months follow-up in patients with open-angle glaucoma (OAG) METHODS: This comparative case series was conducted at Beijing Tongren Hospital, including patients diagnosed with OAG who underwent Phaco-KDB from November 2021 to April 2022 and Phaco-Trabectome from April 2017 to December 2017. Surgical success was defined as an IOP reduction ≥ 20% or a postoperative IOP ≤ 21 mmHg. Kaplan-Meier methods were used to calculate cumulative rates of success among groups RESULTS: A total of 35 eyes from 29 patients were included in the analysis. At 6-month, Both groups exhibited a significant reduction in IOP and the number of IOP-lowering medications compared to preoperative (P=0.01 and P<0.01, respectively). There were no significant differences among groups in terms of reducing IOP and the number of IOP-lowering medications (all P values<0.05). In the Phaco-KDB and Phaco-Trabectome groups, 53.8% and 45.0% of patients achieved an IOP reduction of ≥ 20%, while 92.3% and 85% achieved a mean IOP ≤ 21 mmHg 6 months after surgery. The incidence of IOP spike was 20%, and 3 eyes (8.6%) needed further surgery to control the IOP CONCLUSIONS: Both Phaco-KDB and Phaco-Trabectome demonstrate a significant reduction in IOP and the number of IOP-lowering medications. Phaco-Trabectome appears to provide a more predictable postoperative course in the early postoperative period compared to Phaco-KDB, and the postoperative mean IOP is lower in Phaco-KDB compared to Phaco-Trabectome, despite not being statistically significant.

The impact of different postures on acute intraocular pressure and accommodation responses during reading.

INTRODUCTION: To investigate the effects of different reading postures on intraocular pressure (IOP) and near-work-induced transient myopia (NITM) in children with myopia. METHODS: Sixty myopic children were instructed to read a book text placed at 33 cm for 30 min with two different reading postures: head bowed and head upright postures. The participants' IOP and NITM were assessed using a rebound tonometer and an open-field autorefractor. The measurement of IOP was conducted prior to reading, during reading sessions (at 5, 10, 20, and 30-min intervals), and after a 5-min recovery period. RESULTS: For the head bowed posture, the mean baseline IOP was 16.13 ± 2.47 mmHg. A significant rise in IOP was observed after 5 min of reading (17.17 ± 2.97 mmHg; +1.03 ± 2.29 mmHg; p = 0.014). Subsequent measurements revealed a further increase after 20 min (17.87 ± 2.90 mmHg; +1.73 ± 2.58 mmHg; p < 0.001), which continued to persist even after 30 min of reading (17.57 ± 3.46 mmHg; +1.43 ± 2.66 mmHg; p = 0.002). The IOP at different time points measured in the head upright posture did not show any significant difference in comparison to the baseline measurement (all p = 1.000). Compared to reading with the head upright, reading with the head bowed resulted in a greater increase in IOP at each time point (p < 0.05). Furthermore, the NITM was higher for reading with the head bowed than for reading with head upright at 30 min (-0.24 ± 0.53 D vs. -0.12 ± 0.47 D, p = 0.038). CONCLUSION: Reading in a head bowed position resulted in greater increases in IOP and NITM compared to reading in a head upright posture.

Long-term outcomes of anti-vascular endothelial growth factor therapy with and without posterior scleral reinforcement on myopic maculopathy in myopic choroidal neovascularization eyes.

BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapy is used for myopic choroidal neovascularization (mCNV). Patchy chorioretinal atrophy (pCRA) enlargement has been reported in mCNV cases associated with vision loss. Our aim was to compare the long-term effectiveness of anti-VEGF therapy alone versus anti-VEGF followed by posterior scleral reinforcement (PSR) in controlling myopic maculopathy in mCNV eyes. METHODS: We performed a retrospective review of the medical records of 95 high myopia patients (refractive error ≥ 6.00 diopters, axial length ≥ 26.0 mm) with mCNV. Patients were treated with anti-VEGF alone (group A) or anti-VEGF followed by PSR (group B). The following data were collected: refractive error, best corrected visual acuity (BCVA), ophthalmic fundus examination, ocular coherence tomography and ocular biometry at 12 and 24 months pre- and postoperatively. The primary outcomes were changes in pCRA and BCVA. RESULTS: In 26 eyes of 24 patients, the mean pCRA size significantly increased from baseline (0.88 ± 1.69 mm2) to 12 months (1.57 ± 2.32 mm2, t = 3.249, P = 0.003) and 24 months (2.17 ± 2.79 mm2, t = 3.965, P = 0.001) postoperatively. The increase in perilesional pCRA in group B (n = 12) was 98.2% and 94.2% smaller than that in group A (n = 14) at 12 and 24 months (Beta 0.57 [95% CI 0.01, 191 1.13], P = 0.048). In group B, 7 eyes (58.3%) gained more than 2 lines of BCVA compared with only 4 eyes (28.6%) in group A at 24 months. CONCLUSION: Anti-VEGF therapy followed by PSR achieved better outcomes than anti-VEGF therapy alone in controlling the development of myopic maculopathy in mCNV and may constitute a better treatment option by securing a better long-term VA outcome.

Zonular instability-associated morphologic features in eyes with primary angle closure disease using the swept-source anterior segment - optical coherence tomography system.

BACKGROUND: This study aims to investigate the morphologic features of the crystalline lens in Primary Angle Closure Disease (PACD) patients with zonular instability during cataract surgery using the swept-source CASIA 2 Anterior Segment-Optical Coherence Tomography (AS-OCT) system. METHODS: A total of 398 eyes (125 PACD eyes with zonular instability, 133 PACD eyes with zonular stability, and 140 cataract patient controls) of 398 patients who underwent cataract surgery combined or not glaucoma surgery between January 2021 and January 2023 were enrolled. The crystalline lens parameters were measured by CASIA2 AS-OCT. Then, logistic regression was performed to evaluate the risk factors associated with zonular instability. RESULTS: The results revealed that PACD eyes had a more anterior lens equator position, a steeper anterior curvature of lens, shorter Axial Length (AL), shallower Anterior Chamber Distance (ACD), higher Lens Vault (LV) and thicker Lens Thickness (LT), when compared to eyes in the cataract control group. Furthermore, PACD eyes in the zonular instability group had steeper front R, front Rs and Front Rf, flatter back Rf, thicker lens anterior part thickness, higher lens anterior-to-posterior part thickness ratios, shallower ACD, and greater LV, when compared to PACD eyes with zonular stability. The logistic regression analysis, which was adjusted for age and gender, revealed that zonular instability was positively correlated with anterior part thickness, lens anterior-to-posterior part thickness ratio, and LV, but was negatively correlated with lens anterior radius and ACD. CONCLUSION: Steeper anterior curvature, increased lens anterior part thickness, higher anterior-to-posterior part thickness ratio, shallower ACD, and greater LV are the anatomic features of PACD eyes associated with zonular instability.

Separation of astragaloside IV from Astragalus membranaceus based on high-speed countercurrent chromatography in continuous injection mode.

INTRODUCTION: Astragaloside IV (AS-IV) is an index for the quality evaluation of the traditional Chinese medicine Astragalus and an important material basis for Astragalus to exert its medicinal effects, and it is difficult to obtain a single AS-IV by ordinary separation methods. OBJECTIVE: To find a new isolation method that can prepare AS-IV quickly and efficiently. METHODOLOGY: AS-IV was isolated from Astragalus membranaceus extract by high-speed countercurrent chromatography using a two-phase solvent system consisting of ethyl acetate/n-butanol/water (4.2:0.8:5, v/v) at a speed of 950 rpm at a flow rate of 2 mL/min using one of the high-speed countercurrent chromatographic sequential injection models developed during the previous study. RESULTS: Compared with the common countercurrent chromatographic separation, this separation method increased the injection volume and yield by 4-fold and 4.47-fold, respectively, with only about 1.2-fold increase in solvent consumption and separation time, and the purity was basically not reduced, and 55.9 mg of AS-IV, with a purity of 96.95%, was finally prepared from 400 mg of the crude extract in 240 min. CONCLUSION: The continuous injection mode of high-speed countercurrent chromatography was able to successfully prepare a large amount of AS-IV with high purity at one time.

Retrocorneal membrane interception enhanced penetrating canaloplasty for patients with open angle glaucoma secondary to ICE syndrome.

INTRODUCTION: To assess the efficacy and safety of retrocorneal membrane interception (RMI)-enhanced penetrating canaloplasty in glaucoma secondary to iridocorneal endothelial syndrome (GS-ICE) with open angle or small peripheral anterior synechiae (PAS). METHODS: A series of 13 patients (13 eyes) with GS-ICE and uncontrolled intraocular pressure (IOP) underwent RMI-enhanced penetrating canaloplasty from March 2019 to October 2020. The patients were followed up at one week, 1 month, 3 months, 6 months, and 12 months, postoperatively. The main outcome measure was surgical success, which was defined as an IOP ≤ 18 mmHg or ≤ 21 mmHg, with glaucoma medications (qualified success), or without glaucoma medications (complete success). Secondary outcome measures were IOP, medication usage, and surgical complications. RESULTS: Among the 13 GS-ICE eyes, 12 (92%) achieved qualified success and 10 (77%) achieved complete success at 12 months postoperatively. The mean IOP decreased from 36.41 ± 8.92 mmHg on 3.0 (IQR 0.5) medications before surgery to 17.09 ± 7.71 mmHg (p = 0.0004) on 0.0 (IQR 0.5) medications (p = 0.0004) at 12 months after surgery. Transient hypotony (38%) and hyphema (38%) were the most common complications. CONCLUSIONS: RMI-enhanced penetrating canaloplasty appears effective and safe in treating GS-ICE with open angle or small PAS up to one year of follow up.

Mechanosensitive channel Piezo1 is an essential regulator in cell cycle progression of optic nerve head astrocytes.

Optic nerve head (ONH) astrocytes provide structural and metabolic support to neuronal axons in developmental, physiological, and pathological progression. Mechanosensitive properties of astrocytes allow them to sense and respond to mechanical cues from the local environment. We confirmed that ONH astrocytes express the mechanosensitive ion channel Piezo1 in vivo. By manipulating Piezo1 knockdown or overexpression in vitro, we found that Piezo1 is necessary but insufficient for ONH astrocyte proliferation. Loss of Piezo1 can lead to cell cycle arrest at G0/G1 phase, a possible mechanism involving decreased yes-associated protein (YAP) nuclear localization and downregulation of YAP-target cell cycle-associated factors, including cyclin D1 and c-Myc. Gene ontology enrichment analysis of differential expression genes from RNA-seq data indicates that the absence of Piezo1 affects biological processes involving cell division. Our results demonstrate that Piezo1 is an essential regulator in cell cycle progression in ONH astrocytes.

Outdoor time influences VIPR2 polymorphism rs2071623 to regulate axial length in Han Chinese children.

Clinical relevance: Identification of individuals with a higher risk of developing refractive error under specific gene and environmental backgrounds, especially myopia, could enable more personalized myopic control advice for patients. Background: Refractive error is a common disease that affects visual quality and ocular health worldwide. Its mechanisms have not been elaborated, although both genes and the environment are known to contribute to the process. Interactions between genes and the environment have been shown to exert effects on the onset of refractive error, especially myopia. Axial length elongation is the main characteristic of myopia development and could indicate the severity of myopia. Thus, the purpose of the study was to investigate the interaction between environmental factors and genetic markers of VIPR2 and their impact on spherical equivalence and axial length in a population of Han Chinese children. Methods: A total of 1825 children aged 13~15 years in the Anyang Childhood Eye Study (ACES) were measured for cycloplegic autorefraction, axial length, and height. Saliva DNA was extracted for genotyping three single-nucleotide polymorphisms (SNPs) in the candidate gene (VIPR2). The median outdoor time (2 h/day) was used to categorize children into high and low exposure groups, respectively. Genetic quality control and linear and logistic regressions were performed. Generalized multifactor dimensional reduction (GMDR) was used to investigate gene-environment interactions. Results: There were 1391 children who passed genetic quality control. Rs2071623 of VIPR2 was associated with axial length (T allele, ß=-0.11 se=0.04 p=0.006), while SNP nominally interacted with outdoor time (T allele, ß=-0.17 se=0.08 p=0.029). Rs2071623 in children with high outdoor exposure had a significant interaction effect on axial length (p=0.0007, ß=-0.19 se=0.056) compared to children with low outdoor exposure. GMDR further suggested the existence of an interaction effect between outdoor time and rs2071623. Conclusions: Rs2071623 within VIPR2 could interact with outdoor time in Han Chinese children. More outdoor exposure could enhance the protective effect of the T allele on axial elongation.

Correlation between spherical equivalent and biometry parameters in adult Cynomolgus macaque.

PURPOSE: To characterize the distribution of refractive and ocular biometry parameters and analyze the effect factors of the refractive status in cynomolgus monkey colonies. METHODS: A Population-based cross-sectional study was conducted in adult cynomolgus macaque colonies. Animals were anesthetized with Zoletil 50. Intraocular pressure was measured using the Icare tonometer. Cycloplegic refraction (three drops of 1% tropicamide) and corneal radius of curvature (CRC) were measured using an autorefractor. The spherical equivalent (SE) was calculated. Biometric measurements, including the anterior chamber depth (ACD), lens thickness (LT), and axial length (AL), were obtained by A-scan ultrasonography. The AL-to-CR ratio (AL/CRC) was calculated. Central corneal thickness (CCT) and choroidal thickness (ChT) were measured using the Heidelberg Spectralis HRA OCT. Multiple regression analysis was performed to explore the association between refraction and ocular biometry. RESULTS: Among 263 cynomolgus monkeys (aged 5-26 years), which consisted of 520 eyes, 29.42% had hyperopia, 27.12% had emmetropia, 33.27% had mild-to-moderate myopia and 10.19% had high myopia. The mean SE was -1.27 ± 3.44 Diopters (D). The mean CRC, CCT, AL, and ChT was 5.70 ± 0.22 mm, 454.30 ± 32.40 µm, 18.76 ± 0.89 mm and 188.96 ± 38.19 µm, respectively. The LT was the thickest in the hyperopic eyes. CRC was the lowest, and CCT was the thickest in high myopic eyes. AL increased, while ChT decreased as SE decreased. For the SE variance, AL alone explained 40.5%; age, AL, and CRC together explained 57.5%. CONCLUSIONS: The refractive characteristics and biometry parameters of cynomolgus monkeys are highly comparable to those of humans. AL, CRC, and ChT showed the similar variation tendency in cynomolguses when compared to humans. Cynomolgus monkeys with naturally-occurring refractive errors may be a good animal model for refractive studies.

Human Pro370Leu Mutant Myocilin Induces the Phenotype of Open-Angle Glaucoma in Transgenic Mice.

To investigate the characteristics of mutation myocilin proteins and glaucoma pathological phenotype in transgenic mice with full-length human Pro370Leu mutant myocilin gene (Tg-MYOCP370L). Tg-MYOCP370L mice were established using the CRISPR/Cas9 system. Long-term intraocular pressure (IOP) was measured, myocilin protein expressions in anterior chamber angle, retina, optic nerve tissues and aqueous humor were detected by western blot. RBPMS, myocilin, Iba-1 and GFAP expression were visualized by immunofluorescence. H&E staining was applied to assess the ocular angle and retinal morphology. Aqueous humor dynamics were visualized by Gadolinium magnetic resonance imaging (Gd-MRI). TUNEL assay was used to evaluate the specific cell apoptosis in trabecular meshwork and retina. Optomotor and electroretinography tests were employed to evaluate the visual function in Tg-MYOCP370L and wild-type (WT) mice. Homozygous myocilin mutation at position 503 (C > T) was identified by PCR and sequencing in Tg-MYOCP370L mice. Myocilin protein expression was overexpressed in eye tissues of Tg-MYOCP370L mice with reduced myocilin secretion in aqueous humor. H&E staining showed normal histological morphology of anterior chamber angle whereas decreased thickness and nuclei in ganglion cell layer were found (P < 0.05). Gd signals were significantly increased in the anterior chamber of Tg-MYOCP370L compared with WT eyes (P < 0.05). IOP was elevated in Tg-MYOCP370L mice starting at 5 months of age, with significant RGC loss (P < 0.05). Upregulation of caspase-3 and caspase-9 expressions and increased TUNEL-positive cells were found in eyes of Tg-MYOCP370L mice. Excessive activation of retinal glial cells and impaired visual function were detected in Tg-MYOCP370L mice. Tg-MYOCP370L mice can induce the phenotype of open-angle glaucoma, featured as IOP elevation, activated retinal glial cells, loss of RGCs and impaired visual function. These pathologic changes may arise from the abnormal mutant myocilin protein accumulation in the trabecular meshwork and injured aqueous humor drainage. Therefore, Tg-MYOCP370L mice model can serve as an effective animal model for glaucoma research, especially for glaucoma-associated myocilin mutation studies.

Pigment dispersion syndrome and pigmentary glaucoma: overview and racial disparities.

Pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG) are two stages within the same ophthalmic disease spectrum, which are known to be affected by race. The prevalence of PDS is underestimated, largely due to its minor clinical symptoms. Although the prevalence of PG is low, the visual impairment associated with PG is extremely severe. The prevalence of PDS-PG is four or more times higher in Caucasians than in Blacks or Asians, and the "classic" PDS in Caucasians has long been used as a benchmark diagnostic criterion. Following extensive research focused on African Americans and Asians, the standard for diagnosing PDS-PG was refined. At the same time, the pathogenesis of PDS is not the same in different races. Hence, the effectiveness of preventive treatment and the need for treatment may not be equivalent in different races. The rate of conversion of PDS to PG is nearly 1/3 in Caucasians and higher in blacks and Asians, requiring more aggressive treatment and monitoring. We systematically searched a PubMed database from inception to March 2022 to provide an overview of research progress in various aspects of PDS-PG. Specifically, this paper considers the effects of race on disease prevalence, clinical manifestation, diagnostic criteria, disease mechanism, hereditary traits, treatment, and prevention to provide an accurate and comprehensive guide for the diagnosis and treatment of PDS-PG in various races.

Comparison of the retinal microvasculature between compressive and glaucomatous optic neuropathy.

PURPOSE: To compare the patterns of retinal microvasculature change in the peripapillary and macular region between compressive optic neuropathy (CON) and glaucomatous optic neuropathy (GON), and to assess the ability of optical coherence tomography angiography (OCTA) in differentiating the two conditions. METHODS: This cross-sectional study included 108 participants (108 eyes), 36 with CON, 36 with GON, and 36 healthy controls. The CON and GON eyes were matched by the average peripapillary retinal nerve fiber layer (pRNFL) thickness (1:1). Optical coherence tomography (OCT) and OCTA were performed to compare the structural and vascular change of the peripapillary and macular region between groups. RESULTS: Both CON and GON eyes showed more severe structural and vascular damage than the control eyes. The CON eyes had lower pRNFL thickness than the GON eyes in the temporal and nasal quadrants, and thicker pRNFL thickness in the inferior quadrant. The average GCC thickness did not differ between the two groups. The peripapillary vessel density of the CON group was significantly higher in the inferior sectors than that of the GON group. In the macular region, the CON group had significantly higher vessel density in the whole image, the temporal sector in parafovea region, and the temporal, superior, and inferior sectors in perifovea region. CONCLUSION: To a similar degree of structural damage, CON had less retinal vascular impairment than GON, especially in the macular region, and the significance of the finding needs further evaluation.

Effect of refractive status on retinal nerve fiber layer thickness in Chinese Population.

PURPOSE: To evaluate the relationship between retinal nerve fiber layer (RNFL) thickness and other related parameters measured by spectral-domain optical coherence tomography and the refractive error of eyes. METHODS: A total of 5394 subjects were enrolled in this population-based cohort study, who were divided into three groups by refractive state after they underwent a standardized ophthalmic examination: emmetropia (the absolute value should range from 0 to 0.5 D), low-moderate myopia (the absolute value of myopic error should range from 0.5 to 6 D), and high myopia (the absolute value of myopic error should be over than 6 D). R 3.6.1 software was adopted for statistical analysis. RESULTS: Two thousand five hundred fifty-two subjects (4548 eyes) were collected in this study, with an average age of 53.14 ± 10.64 years. There were significant differences among groups in average central corneal curvature, spherical equivalent, and axial length (P < 0.001). The measurements of average retinal nerve fiber layer (RNFL) were 113.95 ± 10.62 µm, 112.97 ± 11.59 µm, and 101.88 ± 15.67 µm, respectively, in the emmetropia, low-moderate, and high myopia groups (P < 0.001). Meanwhile, there was a decreasing trend of cup area, cup volume, disc area, and rim area in the high myopia group compared with the emmetropia group (P < 0.001). CONCLUSION: The measurements of RNFL thickness vary greatly with refractive error, and this study indicated that it is of great significance for the accurate diagnosis of glaucoma to establish an individualized RNFL thickness database.

Serum antiretinal antibodies and cytokine profiling in autoimmune retinopathy and their association with clinical outcomes.

PURPOSE: Autoimmune retinopathy (AIR) is a group of autoimmune retinal diseases that can cause blindness. The purpose of this study is to investigate the profiles of serum antiretinal antibodies (ARAs) and cytokines and their association with disease diagnosis as well as clinical features in AIR. METHODS: The patients with presumed para (p) and non-paraneoplastic (np) AIR diagnosis, the patients with retinitis pigmentosa and bilateral uveitis as disease controls, and healthy subjects were prospectively enrolled. Western blotting and Luminex multiple cytokine assay/enzyme linked immunosorbent assay were used to determine the presence of serum ARAs and the concentration of cytokines, respectively. Kruskal-Wallis or chi square test was applied to compare the profiles of ARA and cytokines among various groups. The multilevel mixed-effect regression was used to investigate the association of ARA or cytokines with clinical features. RESULTS: No significant difference in the band number and subtypes of serum ARAs was found between AIR patients and their controls. AIR patients had higher concentration of serum IFN-ɤ, CXCL9, or CXCL10 than non-AIR controls. A positive correlation was found between increased number of ARAs and elevated TNF-α in np-AIR patients. Elevated pro-inflammatory cytokines or ARA subtypes (antibody against recoverin and α-enolase) were associated with worse retinal functions or anatomy, including visual acuity, visual field, ERG parameters, and central retinal thickness. CONCLUSIONS: The data of our study demonstrate that detection of serum ARAs has limited value in the diagnosis of AIR. Th1-type cytokines/chemokines or specific ARA subtypes are associated with pathogenesis and disease severity of the AIR.

Effect of low-dose atropine eyedrops on pupil metrics: results after half a year of treatment and cessation.

PURPOSE: To evaluate the effect of low-dose atropine eyedrops on pupil metrics. METHODS: This study was based on a randomized, double-masked, placebo-controlled, and cross-over trial in mainland China. In phase 1, subjects received 0.01% atropine or placebo once nightly. After 1 year, the atropine group switched to placebo (atropine-placebo group), and the placebo group switched to atropine (placebo-atropine group). Ocular parameters were measured at the crossover time point (at the 12th month) and the 18th month. RESULTS: Of 105 subjects who completed the study, 48 and 57 children were allocated into the atropine-placebo and placebo-atropine groups, respectively. After cessation, the photopic pupil diameter (PD) and mesopic PD both decreased (- 0.46 ± 0.47 mm, P < 0.001; - 0.30 ± 0.74 mm, P = 0.008), and the constriction ratio (CR, %) increased (4.39 ± 7.54, P < 0.001) compared with values at the crossover time point of the atropine-placebo group; pupil metrics of the atropine-placebo group had no difference from the values at the crossover time point of the placebo-atropine group. After 6 months of treatment, the photopic PD and the mesopic PD increased (0.54 ± 0.67 mm, P < 0.001; 0.53 ± 0.89 mm, P < 0.001), the CR (%) decreased (- 2.53 ± 8.64, P < 0.001) compared with values at the crossover time point of the placebo-atropine group. There was no significant relationship between pupil metrics and myopia progression during 0.01% atropine treatment. CONCLUSION: Pupil metrics and the CR could return to pre-atropine levels after cessation. Pupil metrics had no significant effect on myopia progression during treatment.

Impact of primary glaucoma on health-related quality of life in China: the handan eye study.

BACKGROUND: We assessed health-related quality of life (HRQOL) and its determinants among rural glaucoma participants compared to age-matched normal controls in the population-based Handan Eye Study (HES), in rural Yongnian County, northern China. METHODS: We enrolled 99 adults with glaucoma (mean age 63.0 ± 11.0 years), including primary open-angle glaucoma (POAG, n = 67) and primary angle-closure glaucoma (PACG, n = 32) and 102 controls (mean age 58.5 ± 5.3 years) with normal visual acuity and visual field and no history of glaucoma. Results of ophthalmic examinations and socioeconomic data were recorded. HRQOL was measured using the EQ-5D (converted to utility valves, UVs), and visual function (VF) and vision-related quality of life (VRQOL) were evaluated using the visual function-quality of life (VF-QOL) instrument. PRIMARY AND SECONDARY OUTCOME MEASURES: EQ-5D and VF-QOL scores. RESULTS: The mean UVs, VF, and VRQOL scores for glaucoma cases were 0.98 ± 0.04, 87.9 ± 15.2, and 95.5 ± 12.8, respectively, significantly worse than VF (94.4 ± 4.4) and VRQOL (100.0 ± 0.0) among controls, even after adjusting for age, gender, educational level, and family income (P = 0.015, P = 0.033). UVs were significantly lower among glaucoma participants with impaired VRQOL (55.4 ± 11.5) compared to those with normal VRQOL scores (99.1 ± 2.8) (UVs: 0.92 ± 0.08 vs. 0.99 ± 0.03, P = 0.036), also after adjustment for age and family income (P = 0.006). Participants with PACG had significantly lower VF and VRQOL scores compared to POAG (77.8 ± 21.4 vs. 92.9 ± 6.8, P < 0.001; 89.0 ± 18.1 vs. 98.7 ± 7.5, P < 0.001). CONCLUSION: Participants with glaucoma have worse visual function and related quality of life compared to age-matched normal population controls. Participants with PACG have lower VF and VRQOL compared to those with POAG. UVs can be used for cost-effectiveness research and to support public health strategies for glaucoma in rural China.

Design, methodology, and preliminary results of the non-human primates eye study.

PURPOSE: To describe the normative profile of ophthalmic parameters in a healthy cynomolgus monkey colony, and to identify the characteristic of the spontaneous ocular disease non-human primates (NHP) models. METHODS: The NHP eye study was a cross-sectional on-site ocular examination with about 1,000 macaques held in Guangdong Province, southeastern China. The NHPs (Macaca fascicularis, cynomolgus) in this study included middle-aged individuals with a high prevalence of the ocular disease. The NHP eye study (NHPES) performed the information including systematic data and ocular data. Ocular examination included measurement of intraocular pressure (IOP), anterior segment- optical coherence tomography (OCT), slit-lamp examination, fundus photography, autorefraction, electroretinography, etc. Ocular diseases included measurement of refractive error, anisometropia, cataract, pterygium, etc. RESULTS: A total of 1148 subjects were included and completed the ocular examination. The average age was 16.4 ± 4.93 years. Compared to the male participants, the females in the NHPES had shorter axial length and the mean Average retinal nerve fiber layer (RNFL) thickness (except for the nasal quadrants). The mean IOP, anterior chamber depth, lens thickness, axial length, central corneal thickness, choroid thickness and other parameters were similar in each group. CONCLUSION: The NHPES is a unique and high-quality study, this is the first large macaque monkey cohort study focusing on ocular assessment along with comprehensive evaluation. Results from the NHPES will provide important information about the normal range of ophthalmic measurements in NHP.

iPSCs-Based Therapy for Trabecular Meshwork.

The trabecular meshwork (TM) of the eye serves as an essential tissue in controlling aqueous humor (AH) outflow and intraocular pressure (IOP) homeostasis. However, dysfunctional TM cells and/or decreased TM cellularity is become a critical pathogenic cause for primary open-angle glaucoma (POAG). Consequently, it is particularly valuable to investigate TM characteristics, which, in turn, facilitates the development of new treatments for POAG. Since 2006, the advancement in induced pluripotent stem cells (iPSCs) provides a new tool to (1) model the TM in vitro and (2) regenerate degenerative TM in POAG. In this context, we first summarize the current approaches to induce the differentiation of TM-like cells from iPSCs and compare iPSC-derived TM models to the conventional in vitro TM models. The efficacy of iPSC-derived TM cells for TM regeneration in POAG models is also discussed. Through these approaches, iPSCs are becoming essential tools in glaucoma modeling and for developing personalized treatments for TM regeneration.

Discovery of Clinical Manifestations in Spontaneous Glaucoma Suspect Nonhuman Primates.

INTRODUCTION: The primary aim of this study was to assess the longitudinal changes in retinal nerve fiber layer (RNFL) thickness and relative ONH parameters using spectral-domain optical coherence tomography (SD-OCT) in the living eyes of nonhuman primates with spontaneous glaucoma. METHODS: Totally 9 macaque subjects underwent a standard fundus photo and OCT examination, including 3 adult monkeys with stable elevated intraocular pressure (IOP) as the glaucoma suspect group and 6 normal IOP monkeys as the control group. Each eye of primates with IOP measurement was repeated three times. OCT measurements recorded RNFL, Bruch's membrane opening (BMO) minimum rim width (MRW). The follow-up scan of glaucomatous subjects was undergone in 10 months. RESULTS: The mean ages of glaucoma and healthy subjects are 19.33 ± 0.33 and 20.5 ± 1.46 years. Elevated IOP was achieved in three nonhuman primate eyes with an average increase of 10 mm Hg over the study period. Elevated IOP was associated with decreased RNFL thickness in all the regions and decreased RNFL phase retardation in the superior and inferior regions. When averaged over the entire retinal area, only the whole RNFL and temporal regions showed a significant decrease. The mean IPL thicknesses are 87.17 ± 2.15 µm in glaucomatous and 93.33 ± 1.51 µm in healthy eyes (p = 0.03). Lamina cribrosa parameters are measured from the OCT images and showed significant differences between glaucoma primates and normal primates. CONCLUSIONS: Of the measured parameters, decreased RNFL and MRW were correlated with glaucomatous damage. Natural glaucoma primate can be a natural glaucoma model which is closer to glaucoma in humans.