The causal mutation in ARR3 gene for high myopia and progressive color vision defect.

The ARR3 gene, also known as cone arrestin, belongs to the arrestin family and is expressed in cone cells, inactivating phosphorylated-opsins and preventing cone signals. Variants of ARR3 reportedly cause X-linked dominant female-limited early-onset (age < 7 years old) high myopia (< - 6D). Here, we reveal a new mutation (c.228T>A, p.Tyr76*) in ARR3 gene that can cause early-onset high myopia (eoHM) limited to female carriers. Protan/deutan color vision defects were also found in family members, affecting both genders. Using ten years of clinical follow-up data, we identified gradually worsening cone dysfunction/color vision as a key feature among affected individuals. We present a hypothesis that higher visual contrast due to the mosaic of mutated ARR3 expression in cones contributes to the development of myopia in female carriers.

RhoA/ROCK Signaling Regulates TGF-ß1-Induced Fibrotic Effects in Human Pterygium Fibroblasts through MRTF-A.

PURPOSE: The overexpression of transforming growth factor-beta1 (TGF-ß1) after surgical excision often leads to excessive fibrosis, indicating the recurrence of pterygium. The aims of the present in vitro study were to investigate the role of RhoA/ROCK signaling in regulating fibrotic effects of primary human pterygium fibroblasts (HPFs), as well as to explore the possible mechanisms of these effects. METHODS: Pterygium samples were obtained from surgery, and profibrotic activation was induced by TGF-ß1. Cell proliferation was detected by CCK-8 assay; cell migration was detected by wound healing assay; quantitative real-time PCR and Western blot were used to detect the effects of TGF-ß1 and the role of RhoA/ROCK signaling in the synthesis of alpha-smooth muscle actin (a-SMA), type I and III collagen (COL1 and COL3), and matrix metalloproteinase-9 (MMP9) in HPFs. The changes of signaling pathways were detected by Western blot; and pharmaceutical inhibition of RhoA/ROCK signaling and its downstream MRFT-A/SRF transcription pathway were used to assess their possible mechanism in HPFs fibrosis. RESULTS: ROCK inhibitor Y-27632 decreased TGF-ß1-induced cell proliferation and migration, reduced the TGF-ß1-induced expression of profibrotic markers in HPFs, and suppressed TGF-ß1-induced nuclear accumulation of Myocardin-related transcription factor A (MRTF-A) as well as accompanied elevation of F/G-actin ratio in HPFs. MRTF-A/Serum response factor (SRF) inhibitor CCG-100602 attenuated the TGF-ß1-induced α-SMA expression and reduced myofibroblast activation in HPFs. CONCLUSIONS: RhoA/ROCK signaling played a pivotal role in TGF-ß1-induced fibrosis and myofibroblast activation in HPFs at least in part by inactivating the downstream MRTF-A/SRF transcriptional pathway.

An accurate interactive segmentation and volume calculation of orbital soft tissue for orbital reconstruction after enucleation.

BACKGROUND: Accurate measurement and reconstruction of orbital soft tissue is important to diagnosis and treatment of orbital diseases. This study applied an interactive graph cut method to orbital soft tissue precise segmentation and calculation in computerized tomography (CT) images, and to estimate its application in orbital reconstruction. METHODS: The interactive graph cut method was introduced to segment extraocular muscle and intraorbital fat in CT images. Intra- and inter-observer variability of tissue volume measured by graph cut segmentation was validated. Accuracy and reliability of the method was accessed by comparing with manual delineation and commercial medical image software. Intraorbital structure of 10 patients after enucleation surgery was reconstructed based on graph cut segmentation and soft tissue volume were compared within two different surgical techniques. RESULTS: Both muscle and fat tissue segmentation results of graph cut method showed good consistency with ground truth in phantom data. There were no significant differences in muscle calculations between observers or segmental methods (p > 0.05). Graph cut results of fat tissue had coincidental variable trend with ground truth which could identify 0.1cm3 variation. The mean performance time of graph cut segmentation was significantly shorter than manual delineation and commercial software (p < 0.001). Jaccard similarity and Dice coefficient of graph cut method were 0.767 ± 0.045 and 0.836 ± 0.032 for human normal extraocular muscle segmentation. The measurements of fat tissue were significantly better in graph cut than those in commercial software (p < 0.05). Orbital soft tissue volume was decreased in post-enucleation orbit than that in normal orbit (p < 0.05). CONCLUSION: The graph cut method was validated to have good accuracy, reliability and efficiency in orbit soft tissue segmentation. It could discern minor volume changes of soft tissue. The interactive segmenting technique would be a valuable tool for dynamic analysis and prediction of therapeutic effect and orbital reconstruction.

Unilateral Levator Aponeurosis Excision for Marcus Gunn Syndrome and Risk Factors of Residual Jaw Winking.

PURPOSE: To investigate the association of ptosis, levator, and jaw winking in Marcus Gunn jaw-winking synkinesis (MGJWS), and the risk factor of preservation and outcomes of the unilateral levator excision and frontalis suspension. METHODS: Clinical features of MGJWS case series from 2011 to 2018 were retrospectively reviewed. Association between jaw winking and ptosis/levator function was statistically analyzed. The patients underwent unilateral levator excision and frontalis suspension using silicone rod or autogenous fascia lata. Clinical outcomes were evaluated in operated patients and the independent risk factors of residual jaw winking were investigated after a long follow-up. RESULTS: There were 42 MGJWS patients in 2011 to 2018, accounting for 2.87% of all congenital blepharoptosis. 80% of mild jaw winking was accompanied with mild ptosis and fair levator function, and moderate-to-severe jaw winking was often accompanied with moderate-to-severe ptosis and poor levator function (P < 0.05). Ptosis showed a strong association with excursion of jaw winking (R = 0.785, P < 0.01). Jaw winking was resolved in all 34 operated patients with good correction of ptosis. Severity of jaw winking is an independent risk factor for the residual synkinesis after surgery. Severe preoperative jaw winking had an 18.05 times increased risk of postoperative residual synkinesis compared with moderate jaw winking (P < 0.05). CONCLUSIONS: In MGJWS eyelid excursion of jaw winking has a direct correlation with ptosis and dysfunction of levator muscle. Unilateral levator aponeurosis excision and frontalis suspension is an efficient approach for MGJWS. Severe jaw winking is a risk factor of residual eyelid synkinesis after surgery.

Does rituximab improve clinical outcomes of patients with thyroid-associated ophthalmopathy? A systematic review and meta-analysis.

BACKGROUND: The current therapies of thyroid-associated ophthalmopathy (TAO) were still a challenging matter. In this study, we aimed to contrast the impact of before- after rituximab (RTX) therapy in the patients with TAO. METHODS: We searched the PubMed, EMBASE, and SCOPUS databases for articles published up to July 3, 2017. Fixed- or random-effects meta-analysis was used to provide pooled estimates of standard mean difference (SMD) both the primary outcome from clinical activity score (CAS), and secondary outcomes from thyrotropin receptor antibody (TRAb), proptosis, thyroid stimulating hormone (TSH), and interleukin-6 (IL-6) levels. In addition, the quality and each study was assessed using either the Newcastle Ottawa Scale (NOS) or the Cochrane Risk of Bias tool, and reliability of the meta-analytic result using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Of the 839 articles initially searched, 11 studies were finally eligible for inclusion. Subgroup analysis results showed that comparing with initial value, there was a decline in CAS at 1,3,6,12 month after RTX treatment, decreased TRAbs level at 6,12 month, proptosis improvement at least 1 month, unchanged IL-6 level at 6 month, decreased TSH level at 3 month but unchanged at 12 month. All included studies were classified as good quality. CONCLUSIONS: The pooled data suggested that the preliminary effects of RTX treatment on TAO might be promising. However, more large-sample and high-quality studies targeting RTX use during this disease and long-term surveillance of prognosis are urgently needed.

A new strategy to sustained release of ocular drugs by one-step drug-loaded microcapsule manufacturing in hydrogel punctal plugs.

PURPOSE: To design an injectable hyaluronate (HA)-based hydrogel system that contains drug-loaded microcapsules as resorbable plugs to deliver ocular drugs. METHODS: In-situ drug-loaded, core-shell-structured chitosan (CS)@HA microcapsules were fabricated via HA hydrosol collecting in electrospun bead-rich CS fibers under continuous stirring. An injectable and cytocompatible hydrogel system with different degrees of chemical crosslinking maintained viscoelastic and sustained drug release for a long-term period of time at body temperature in vitro. RESULTS: With the addition of adipic dihydrazide (ADH) or 1-Ethyl-3-(3-dimethyllaminopropyl) carbodiimide hydrochloride (EDCI), HA hydrosols transited from liquid to solid state at the gel point, with the G'/G″ ratio varying between 1.43 and 5.32 as a function of crosslinker concentration in the hydrogel phase. Ofloxacin (OFL) release from the mechanically mixed hydrosol system (CS-HA-A0-E0) and the micro-encapsulated hydrosol formulation (CS@HA-A0-E0) were respectively over 80% and 51% of the total drug load leaching out within 24 h. As for the drug-mixed hydrogel systems with low (CS-HA-A0.06-E0.15) and high (CS-HA-A0.06-E0.30) crosslinking density, the OFL release rate reached 38.5 and 46.6% respectively, while the micro-encapsulated hydrogel systems with low (CS@HA-A0.06-E0.15) and high (CS@HA-A0.6-E0.30) showed only (11.9 ± 2.7)% and (17.4 ± 3.5)% drug release respectively. CONCLUSIONS: A one-step in-situ drug-capsulizing method is developed to fabricate a resorbable hydrogel punctal plug with extended drug release. The chemistry of the crosslinking reaction involves the formation of highly biocompatible HA derivatives. Thus, the hydrogel can be used directly in the tear drainage canalicular system.

Exposure rate of unwrapped hydroxyapatite orbital implants in enucleation surgery.

OBJECTIVE: To document the long-term exposure rate of unwrapped coralline hydroxyapatite (HA) orbital implants and explore possible risk factors. DESIGN: This retrospective case series (May 2008-April 2013) reviewed the 234 patients with anophthalmia who underwent insertion of an unwrapped HA orbital implant by one of two different surgical closing techniques. RESULTS: Of the 234 cases, 151 underwent a rectus end-to-end suturing closure technique and 83 underwent a rectus orthotopic suturing closure technique. The time of follow-up ranged from 25 months to 69 months (mean 41.9 months). Implant exposure developed in 11 cases. Three in the rectus end-to-end suturing closure group (2.0%) and eight in the rectus orthotopic suturing closure group (9.6%). In the rectus end-to-end suturing technique, a crosswise fixation of vascularised rectus muscle tissue is formed across the front of the implant; in this group the incidence of implant exposure was reduced (OR=8.11, p=0.013). Prior ocular surgery was found to be a factor increasing the incidence of HA exposure (OR=2.73, p=0.032). CONCLUSIONS: The placement of an unwrapped HA orbital implant with rectus end-to-end suturing in enucleation surgery was associated with a low rate of exposure in most cases. The end-to-end suturing creates a joint-like structure over the HA sphere, protecting the Tenon's capsule and conjunctiva from its rough surface and reducing the risk of implant exposure. Prior ocular surgery may be another risk factor for HA exposure.

A primary study of poly(propylene fumarate)-2-hydroxyethyl methacrylate copolymer scaffolds for tarsal plate repair and reconstruction in rabbit eyelids.

Eyelid reconstruction includes anterior lamella reconstruction and posterior lamella reconstruction. As an important skeletal component of the posterior lamella, tarsal plates repair is the key issue for eyelid reconstruction. Presently, neither traditional surgery nor autograft/allograft has achieved satisfactory repair effects. Poly(propylene fumarate)-co-2-hydroxyethyl methacrylate (PPF-HEMA) networks with mass ratios of 1 : 0.5, 1 : 1 and 1 : 2 were synthesized and used as the tarsal substitute in this study. Their chemical compositions, swelling ability, and mechanical properties were characterized. Porous scaffolds were fabricated by a gelatin particle leaching method. The in vitro studies of cytotoxicity on human dermal fibroblasts (HDFs) and degradation demonstrated that PPF-HEMA scaffolds did not have noticeable cell cytotoxicity and their degradation rates correlated with the ratio of PPF to HEMA. The PPF-HEMA networks, with mass ratios of 1 : 1 and 1 : 2, and an ADM control were implanted in rabbits with tarsal plate defects for in vivo biocompatibility and degradation behavior evaluation. PPF-HEMA scaffolds provided satisfactory repair results with mild tissue response and biocompatibility to fibroblast growth and fibrous capsulation compared to the ADM control. The tissue compatible and biodegradable PPF-HEMA networks with elastic mechanical properties were proven to be a suitable candidate for tarsal repair.

[How to choose appropriate surgical approach in removal of the eyeball].

We often consult patients with non-functional eye caused by trauma, intraocular malignancy, absolute stage of glaucoma and other diseases who need to remove the eyeball in our clinical work. Eye removal is an irreversibly destructive procedure, which mainly include enucleation and evisceration. There are various surgical techniques which are still controversial. Both of the two procedures have their own advantages, disadvantages, indications and contraindications. The ophthalmologists should comprehensively consider the disease situations, medical conditions and the requirements of the patients when choosing appropriate surgical approach to remove the eyeball.