To evaluate the short-term efficacy and safety of ultrasound cycloplasty (UCP) procedure in Chinese patients with angle-closure glaucoma (ACG), and the mechanisms of its intraocular pressure (IOP) lowering effects.

Fifty-six patients (56 eyes) diagnosed with primary and/or secondary ACG were enrolled in this prospective study. Visual acuity, IOP, slit-lamp examinations, structural parameters of anterior segments including anterior chamber depth (ACD), pupillary diameter (PD), anterior chamber area (ACAr), anterior chamber angle (ACAn), and side effects were evaluated. Seven rhesus macaques (Macaca Mulatta) were used for the analyses of IOP lowering effects, including inflammatory reactions, pathohistological evaluation, scanning electron microscopy (SEM), and aqueous outflow pathway via 1% basic fuchsin perfusion.

Fifty six eyes of 24 male and 32 female patients with an average age of 58.93±15.97 years old were recruited in primary and secondary ACG affected 31 and 25 eyes, respectively. Clinically, the mean IOP was 17.89±7.93 mm Hg (n=53, 53.63% reduction, P<0.001) at 1wk and 22.47±12.00 mm Hg at 12mo (n=16, 18.67% reduction, P<0.01) after UCP, compared to the baseline of 39.08±14.75 mm Hg (n=56). Postoperative tolerance was favorable in 94.64% of cases, with visual acuity unchanged or improved in 96.43% of patients. Mild and transient inflammatory reactions were observed post UCP. UBM analysis revealed statistically significant changes in anterior chamber parameters: increased ACD (n=22, P<0.05), enlarged PD (n=22, P<0.05), expanded ACAr (n=16, P<0.01), and widened ACAn (n=19, P<0.05) compared to preoperative measurements. As in normal monkey eyes, IOP was also reduced upon UCP. Mild inflammatory reactions were seen 1-7d post treatment. Hematoxylin and Eosin (H&E) staining showed enlarged spaces among ciliary muscle bundles. Ciliary process stromal edema was evident, but significant loss of two layers of ciliary epitheliums was not seen. SEM confirmed ciliary muscle fibers concentrated. Fuchsin anterior chamber perfusion showed the whole ciliary body staining in UCP group, but only surface staining in controls.

UCP is efficient and safe to lower the IOP of patients with ACG. Changed anterior chamber structure and increased aqueous humour outflow via uveoscleral pathway may significantly attribute to IOP lowering effects of UCP.

To explore the phenotype and genotype of Weill-Marchesani syndrome (WMS) in a Chinese family and review related literature.

Three WMS patients and other unaffected individuals in this family with a history of consanguineous marriage were included in this study. Medical history, comprehensive ophthalmic examinations, and systemic evaluation, as well as whole exome and Sanger sequencing of specific genomic regions, were performed.

The three affected siblings presented with short stature, brachydactyly and ocular disorders, including very shallow anterior chamber, high myopia, microspherophakia lens subluxation with stretched zonules and glaucoma. Genetic analysis verified a homozygous missense mutation (c.2983C>T: p. Arg995Trp) in ADAMTS17, which was correlated with the diseases in this family, indicating an autosomal recessive inherited manner of WMS. This review aims to summarize the mutation sites of WMS genes, so as to prevent the disease and better guide clinical diagnosis and treatment.

A novel homozygous missense variant of ADAMTS17 is identified in a WMS family with a history of consanguineous marriage. Our study expands the range of mutations associated with WMS and deepens our understanding of pathology in disease associated with ADAMTS17 variants.

To evaluate the potential of two trabecular meshwork (TM)-specific promoters, Chitinase 3-like 1 (Ch3L1) and matrix gla protein (MGP), for improving specificity and safety in glaucoma gene therapy based on self-complementary AAV2 (scAAV2) vector technologies.

An scAAV2 vector with C3 transferase (C3) as the reporter gene (scAAV2-C3) was selected. The scAAV2-C3 vectors were driven by Ch3L1 (scAAV2-Ch3L1-C3), MGP (scAAV2-MGP-C3), enhanced MGP (scAAV2-eMGP-C3) and cytomegalovirus (scAAV2-CMV-C3), respectively. The cultured primary human TM cells were treated with each vector at different multiplicities of infections. Changes in cell morphology were observed by phase contrast microscopy. Actin stress fibers and Rho GTPases/Rho-associated protein kinase pathway-related molecules were assessed by immunofluorescence staining, real-time quantitative polymerase chain reaction and Western blot. Each vector was injected intracamerally into the one eye of each rat at low and high doses respectively. In vivo green fluorescence was visualized by a Micron Ⅲ Retinal Imaging Microscope. Intraocular pressure (IOP) was monitored using a rebound tonometer. Ocular responses were evaluated by slit-lamp microscopy. Ocular histopathology analysis was examined by hematoxylin and eosin staining.

In TM cell culture studies, the vector-mediated C3 expression induced morphologic changes, disruption of actin cytoskeleton and reduction of fibronectin expression in TM cells by inhibiting the Rho GTPases/Rho-associated protein kinase signaling pathway. At the same dose, these changes were significant in TM cells treated with scAAV2-CMV-C3 or scAAV2-Ch3L1-C3, but not in cells treated with scAAV2-eMGP-C3 or scAAV2-MGP-C3. At low-injected dose, the IOP was significantly decreased in the scAAV2-Ch3L1-C3-injected eyes but not in scAAV2-MGP-C3-injected and scAAV2-eMGP-C3-injected eyes. At high-injected dose, significant IOP reduction was observed in the scAAV2-eMGP-C3-injected eyes but not in scAAV2-MGP-C3-injected eyes. Similar to scAAV2-CMV-C3, scAAV2-Ch3L1-C3 vector showed efficient transduction both in the TM and corneal endothelium. In anterior segment tissues of scAAV2-eMGP-C3-injected eyes, no obvious morphological changes were found except for the TM. Inflammation was absent.

In scAAV2-transduced TM cells, the promoter-driven efficiency of Ch3L1 is close to that of cytomegalovirus, but obviously higher than that of MGP. In the anterior chamber of rat eye, the transgene expression pattern of scAAV2 vector is presumably affected by MGP promoter, but not by Ch3L1 promoter. These findings would provide a useful reference for improvement of specificity and safety in glaucoma gene therapy using scAAV2 vector.