Unique presentation of congenital cataract concurrent with microcornea, microphthalmia plus posterior capsule defect in monozygotic twins caused by a novel GJA8 mutation

Ikervis has been marketed as a dry eye product with less tolerance issues than other forms of topical ciclosporin (predominantly due to vehicle differences) and effective as a once daily dose (reducing instillation frequency and associated discomfort) [4]. In our study, Ikervis was tolerated in the majority of these DED patients with reasonable treatment duration (mean 11 months). However, local ocular irritation led to intolerance of treatment in a small number of patients (7.7%). It has been suggested that concurrent use of topical steroids during the initiation of topical ciclosporin use can improve tolerance by reducing local ocular side effects [5]. This appeared to be the experience for most of our patients, but was not universal, reflecting the severity and complexity of DED. The SANSIKA and SICCANOVE studies suggested that initial ocular irritation decreased with longterm Ikervis use [2, 3, 6, 7]. Our small study provides real-world experience data regarding the use, persistence and tolerability of topical Ikervis outside the controlled confines of these key clinical trials.

Congenital cataracts are the most common diseases which account for 10-30% of blindness in children [1]. Multiple genetic mutations contribute to the progression of this genetically heterogeneous and complex disease. Among the reported causative congenital cataract mutations, approximately one quarter are connexin genes, including Connexin 46 which is encoded by GJA3 and Connexin 50 which is encoded by GJA8 [2].
In this study, we encountered four generations of a Chinese family with bilateral congenital cataracts at the Eye Hospital of Wenzhou Medical University. Among the four affected  To investigate the causative mutation in this family, we first performed whole exome sequencing on DNA from subject IV-1 ( Fig. 2A) and identified a novel missense mutation, c. T133C, in GJA8. Sanger sequencing confirmed that the mutation co-segregated with all affected individuals and was not observed in the unaffected family member or in 100 unrelated controls (Fig. 2B). The mutation resulted in a missense amino-acid change, tryptophan to arginine, which was absent in dbSNP137, 1000 G, ESP6500 and ExAC databases. The arginine residue at position 45 is highly conserved across species and isoforms (Fig. 2C). Moreover, p. W45R is predicted to be pathogenic by SIFT (score 0.00 out of 1.00, "damaging"), Polyphen-2 (score 0.999 out of 1.000, "probably damaging") and Mutation Taster (score 0.00 out of 1.00, "damaging"). Based on the above evidences, we can determine that the novel mutation (c.133 T > C, p.W45R) in GJA8 is the pathogenic mutation in this family.
In conclusion, our study identifies a novel missense mutation in GJA8 in a Chinese family with congenital cataracts using WES, thereby expanding the existing spectrum of GJA8 mutations.

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Conflict of interest The authors declare that they have no conflict of interest.
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/. The incidence of unexplained central vision loss immediately following removal of silicone oil (ROSO) has been reported at between 3.3% [1] and 5.9% [2], but may be considerably higher in certain retinal detachment subgroups. For example, the rate of ROSO maculopathy after macula-on giant retinal tear (GRT) repair was reported as high as 50% [1] in this journal, perhaps suggesting maculaon GRTs (Fig 1), or indeed any macula-on retinal detachment, are uniquely susceptible to ROSO maculopathy.
Perfluorocarbon heavy liquid (PFCL) as a short-term post-operative tamponade agent in GRT repair is a safe and effective alternative to silicone oil (SiO) or gas. This technique, first described by Bottoni [3] and subsequently by others [4][5][6][7], is used to manage all GRT detachments at the Royal Victorian Eye and Ear Hospital. PFCL remains in the eye for approximately 14 days, before exchange with fluid, air or gas. To investigate whether removal of short-term PFCL tamponade resulted in a lower rate of unexplained vision loss than ROSO in macula-on GRT detachments, we performed a consecutive retrospective review of all maculaon GRT repairs between 19 August 2007 and 12 December 2016. Best-corrected visual acuity (VA) was recorded at initial presentation, and 3 months following PFCL removal. The outcome of the procedure was determined at 3 months.
Statistical analysis was performed using a paired student's ttest assuming equal variance (alpha = 0.05).
A total of 25 eyes in 24 patients (mean age 57 years; range 39-79 years) comprising 4 female patients (16.7%) and 20 male patients (83.3%) were included in the study cohort ( Table 1). The mean (range) duration of PFCL tamponade was 14.6 days, (10-28 days) before removal and exchange either with 20 or 25% SF6 gas (n = 13, 52%), air (n = 7, 28%) or balanced salt solution (n = 5, 20%). The mean baseline VA was 76 letters. The mean VA 3 months post- Repositioning of the fold is facilitated by intra-operative perfluorocarbon liquid (PFCL) tamponade. Intra-or post-operative slippage can occur when the PFCL is exchanged for gas or, more rarely, silicone oil. An effective alternative is short-term post-operative tamponade with PFCL, which minimises the risk of retinal slippage