A novel compound heterozygous PEX1 variant in Heimler syndrome.

Heimler syndrome (HS) is a rare autosomal recessive hereditary disease that is caused by biallelic variants in peroxisomal biogenic factor 1 gene (PEX1), peroxisomal biogenic factor 6 gene (PEX6) or peroxisomal biogenic factor 26 gene (PEX26), resulting in intracellular peroxisomal dysfunction (PBDs). We report a patient with HS with a new compound heterozygous PEX1 variant. Exon sequencing was used to screen pathologic variants in the patient. Retinal characteristics and serum metabolome alterations were evaluated. Scanning laser ophthalmoscope showed a large area of retinal choroidal atrophy at the posterior pole of the retina, with scattered patchy subretinal pigmentation. Optical coherence tomography showed fovea atrophy accompanied by retinal retinoschisis in the right eye and macular retinoschisis and edema in the left eye. The electroretinogram showed obviously reduced amplitudes of a-waves and b-waves under photopic and scotopic conditions in both eyes. Visual field tests showed a reduced central visual field in both eyes. Exon sequencing identified the compound heterozygous variant including c.2966T > C and c.1670+1G > T of the PEX1 gene, with the latter being novel. Nontargeted determination of total lipid metabolites and targeted determination of medium- and long-chain fatty acids in the serum of the patient and his healthy sibling were tested. This study identified a new compound heterozygous PEX1 variant, expanding our understanding of phenotypes in HS.

The molecular genetics of anterior segment dysgenesis.

Anterior segment dysgenesis is a severe developmental eye disorder that leads to blindness in children. The exact mechanisms underlying this condition remain elusive. Recently, an increasing amount of studies have focused on genes and signal transduction pathways that affect anterior segment dysgenesis;these factors include transcription factors, developmental regulators, extracellular matrix genes, membrane-related proteins, cytoskeleton proteins and other associated genes. To date, dozens of gene variants have been found to cause anterior segment dysgenesis. However, there is still a lack of effective treatments. With a broader and deeper understanding of the molecular mechanisms underlying anterior segment development in the future, gene editing technology and stem cell technology may be new treatments for anterior segment dysgenesis. Further studies on the mechanisms of how different genes influence the onset and progression of anterior segment dysgenesis are still needed.

Latest progress in the study of nanoparticle-based delivery of the CRISPR/Cas9 system.

The CRISPR/Cas9 system has been harnessed to cleave a targeted DNA fragment via its Cas nuclease activity under the direction of guide RNA for rendering gene insertions, deletions, and point mutations in basic research and clinical applications. There are a number of vehicles, including lipofectamine, viruses, and nanoparticles, that can deliver the CRISPR/Cas9 system, but all these methods face numerous challenges during their application in life science contexts. Here, we focus on the delivery of CRISPR/Cas9 via nanoparticles because this method has shown great advantages in terms of safety, simplicity and flexibility.

Peroxidasin is essential for eye development in the mouse.

Mutations in Peroxidasin (PXDN) cause severe inherited eye disorders in humans, such as congenital cataract, corneal opacity and developmental glaucoma. The role of peroxidasin during eye development is poorly understood. Here, we describe the first Pxdn mouse mutant which was induced by ENU (N-ethyl-N-nitrosourea) and led to a recessive phenotype. Sequence analysis of cDNA revealed a T3816A mutation resulting in a premature stop codon (Cys1272X) in the peroxidase domain. This mutation causes severe anterior segment dysgenesis and microphthalmia resembling the manifestations in patients with PXDN mutations. The proliferation and differentiation of the lens is disrupted in association with aberrant expression of transcription factor genes (Pax6 and Foxe3) in mutant eyes. Additionally, Pxdn is involved in the consolidation of the basement membrane and lens epithelium adhesion in the ocular lens. Lens material including γ-crystallin is extruded into the anterior and posterior chamber due to local loss of structural integrity of the lens capsule as a secondary damage to the anterior segment development leading to congenital ocular inflammation. Moreover, Pxdn mutants exhibited an early-onset glaucoma and progressive retinal dysgenesis. Transcriptome profiling revealed that peroxidasin affects the transcription of developmental and eye disease-related genes at early eye development. These findings suggest that peroxidasin is necessary for cell proliferation and differentiation and for basement membrane consolidation during eye development. Our studies provide pathogenic mechanisms of PXDN mutation-induced congenital eye diseases.

Characterization of ex vivo cultured neuronal- and glial- like cells from human idiopathic epiretinal membranes.

BACKGROUND: Characterization of the neuro-glial profile of cells growing out of human idiopathic epiretinal membranes (iERMs) and testing their proliferative and pluripotent properties ex vivo is needed to better understand the pathogenesis of their formation. METHODS: iERMs obtained during uneventful vitrectomies were cultivated ex vivo under adherent conditions and assessed by standard morphological and immunocytochemical methods. The intracellular calcium dynamics of the outgrowing cells was assessed by fluorescent dye Fura-2 in response to acetylcholine (ACh)- or mechano- stimulation. RESULTS: The cells from the iERMs formed sphere-like structures when cultured ex vivo. The diameter of the spheres increased by 5% at day 6 and kept an increasing tendency over a month time. The outgrowing cells from the iERM spheres had mainly glial- and some neuronal- like morphology. ACh- or mechano- stimulation of these cells induced intracellular calcium propagation in both cell types; in the neuronal-like cells resembling action potential from the soma to the dendrites. Immunocytochemistry confirmed presence of glial- and neuronal cell phenotype (GFAP and Nestin-1 positivity, respectively) in the iERMs, as well as presence of pluripotency marker (Sox2). CONCLUSION: iERMs contain cells of neuronal- and glial- like origin which have proliferative and pluripotent potential, show functionality reflected through calcium dynamics upon ACh and mechano- stimulation, and a corresponding molecular phenotype.

New recessive compound heterozygous variants of RP1L1 in RP1L1 maculopathy.

AIM: To identify a maculopathy patient caused by new recessive compound heterozygous variants in RP1L1. METHODS: Comprehensive retinal morphological and functional examinations were evaluated for the patient with RP1L1 maculopathy. Targeted sequence capture array technique was used to screen potential pathologic variants. Polymerase chain reaction and Sanger sequencing were used to confirm the screening results. RESULTS: Fundus examination showed round macular lesions appeared in both eyes. Optical coherence tomography showed that the inner segment/outer segment continuity was disorganized and disruptive in the left eye, but it was uneven and slightly elevated in the right eye. Fundus autofluorescence showed patchy hyper-autofluorescence in the macula. Visual field examination indicates central defects in both eyes. Electroretinogram (ERG) and multifocal ERG showed no obvious abnormalities. Fundus fluorescein angiography in the macula showed obviously irregular hyper-fluorescence in the right eye and slightly hyper-fluorescence in the left eye. We found that the proband carried a missense variant (c.1972C>T) and a deletion variant (c.4717_4718del) of RP1L1, which were originated from the parents and formed compound heterozygous variants. Both variants are likely pathogenic according to the ACMG criteria. Multimodal imaging, ERG and detailed medical history are important diagnostic tools for differentiating between acquired and inherited retinal disorders. CONCLUSION: A maculopathy case with detailed retinal phenotype and new recessive compound heterozygous variants of RP1L1 is identified in a Chinese family, which expands the understanding of phenotype and genotype in RP1L1 maculopathy.

Exploitation of enhanced prime editing for blocking aberrant angiogenesis.

INTRODUCTION: Aberrant angiogenesis plays an important part in the development of a variety of human diseases including proliferative diabetic retinopathy, with which there are still numerous patients remaining a therapeutically challenging condition. Prime editing (PE) is a versatile gene editing approach, which offers a novel opportunity to genetically correct challenging disorders. OBJECTIVES: The goal of this study was to create a dominant-negative (DN) vascular endothelial growth factor receptor (VEGFR) 2 by editing genomic DNA with an advanced PE system to block aberrant retinal angiogenesis in a mouse model of oxygen-induced retinopathy. METHODS: An advanced PE system (referred to as PE6x) was established within two lentiviral vectors, with one carrying an enhanced PE guide RNA and a canonical Cas9 nickase fused with an optimized reversal transcriptase, and the other conveying a nicking guide RNA and a DN-MLH1 to improve PE efficiency. Dual non-integrating lentiviruses (NILVs) produced with the two lentiviral PE6x vectors were then employed to create a mutation of VEGFR2 T17967A by editing the Mus musculus VEGFR2 locus in vitro and in vivo, leading to generation of a premature stop codon (TAG, K796stop) to produce DN-VEGFR2, to interfere with the wild type VEGFR2 which is essential for angiogenesis. RESULTS: NILVs targeting VEGFR2 delivered into cultured murine vascular endothelial cells led to 51.06 % VEGFR2 T17967A in the genome analyzed by next generation sequencing and the production of DN-VEGFR2, which was found to hamper VEGF-induced VEGFR2 phosphorylation, as demonstrated by Western blot analysis. Intravitreally injection of the dual NILVs into postnatal day 12 mice in a model of oxygen-induced retinopathy, led to production of retinal DN-VEGFR2 in postnatal day 17 mice which blocked retinal VEGFR2 expression and activation as well as abnormal retinal angiogenesis without interfering with retinal structure and function, as assessed by electroretinography, optical coherence tomography, fundus fluorescein angiography and histology. CONCLUSION: DN-VEGFR2 resulted from editing genomic VEGFR2 using the PE6x system can be harnessed to treat intraocular pathological angiogenesis.

RDH12-associated retinal degeneration caused by a homozygous pathogenic variant of 146C>T and literature review.

AIM: To describe the clinical, electrophysiological, and genetic features of an unusual case with an RDH12 homozygous pathogenic variant and reviewed the characteristics of the patients reported with the same variant. METHODS: The patient underwent a complete ophthalmologic examination including best-corrected visual acuity, anterior segment and dilated fundus, visual field, spectral-domain optical coherence tomography (OCT) and electroretinogram (ERG). The retinal disease panel genes were sequenced through chip capture high-throughput sequencing and Sanger sequencing was used to confirm the result. Then we reviewed the characteristics of the patients reported with the same variant. RESULTS: A 30-year male presented with severe early retinal degeneration who complained night blindness, decreased visual acuity, vitreous floaters and amaurosis fugax. The best corrected vision was 0.04 OD and 0.12 OS, respectively. The fundus photo and OCT showed bilateral macular atrophy but larger areas of macular atrophy in the left eye. Autofluorescence shows bilateral symmetrical hypo-autofluorescence. ERG revealed that the amplitudes of a- and b-wave were severely decreased. Multifocal ERG showed decreased amplitudes in the local macular area. A homozygous missense variant c.146C>T (chr14:68191267) was found. The clinical characteristics of a total of 13 patients reported with the same pathologic variant varied. CONCLUSION: An unusual patient with a homozygous pathogenic variant in the c.146C>T of RDH12 which causes late-onset and asymmetric retinal degeneration are reported. The clinical manifestations of the patient with multimodal retinal imaging and functional examinations have enriched our understanding of this disease.

Reduced Retinal Vascular Density and Skeleton Length in Amblyopia.

Purpose: This study aimed to investigate the possible relationship between retinal vascular abnormalities and amblyopia by analyzing vascular structures of fundus images. Methods: In this observational study, retinal fundus images were collected from 36 patients with unilateral amblyopia, 33 patients with bilateral amblyopia, and 36 healthy control volunteers. We developed a customized training algorithm based on U-Net to digitalize the vasculature in the fundus images to quantify vascular density (area and fractal dimension), skeleton length, and number of bifurcation points. For statistical comparisons, this study divided participants into two groups. The amblyopic eyes and the fellow eyes of patients with unilateral amblyopia formed the paired group, while bilateral amblyopic patients and healthy controls formed the independent group. Results: In the paired group, the vascular area (P = 0.007), vascular fractal dimension (P = 0.007), and vascular skeleton length (P = 0.002) of the amblyopic eyes were significantly smaller than those of the fellow eyes. In the independent group, significant decreases in the vascular fractal dimension (P = 0.006) and skeleton length (P = 0.048) were observed in bilateral amblyopia compared to control. The vascular area was also significantly correlated with best-corrected visual acuity in amblyopic eyes. Conclusions: This study demonstrated that retinal vascular density and skeleton length in amblyopic eyes were significantly smaller compared to control, indicating an association between the changes in retinal vascular features and the state of amblyopia. Translational Relevance: Our algorithm presents amblyopic retinal vascular changes that are more biologically interpretable for both clinicians and researchers.

Novel small-eye allele in paired box gene 6 (Pax6) is caused by a point mutation in intron 7 and creates a new exon.

PURPOSE: Within a mutagenesis screen, we identified the new mouse mutant Aey80 with small eyes; homozygous mutants were not obtained. The aim of the study was its molecular characterization. METHODS: We analyzed the offspring of paternally N-ethyl-N-nitrosourea (ENU)-treated C3HeB/FeJ mice for dysmorphology parameters, which can be observed with the naked eye. The Aey80 mutant (abnormality of the eye) was further characterized with laser interference biometry, Scheimpflug imaging, and optical coherence tomography. Linkage analysis of the Aey80 mutant was performed using a panel of single nucleotide polymorphisms different among C3HeB/FeJ and C57BL/6J mice. The Aey80 mutation was identified with sequence analysis of the positional candidate gene. RESULTS: We identified a new mutant characterized by an obvious small-eye phenotype; homozygotes are not viable after birth. Embryos at embryonic day 15.5 demonstrate a clear gene-dosage effect: Heterozygotes have small eyes, whereas homozygous mutants do not have eyes. In adult mice, the lenses and the entire eyes of the heterozygous mutants were significantly smaller than those of the wild-types (p<0.01). No other ocular phenotypes were observed; the lenses were fully transparent, and no adhesion to the cornea was observed. The mutation was mapped to chromosome 2; markers between 70.8 MB and 129.5 MB showed significant linkage to the mutation resulting in paired box gene 6 (Pax6) as an excellent candidate gene. We amplified cDNAs from the embryonic eyes and observed an additional band while amplifying the region corresponding to exons 7 and 8. The additional band included an alternative exon of 141 bp, which was associated with a G->A exchange four bases downstream of the end of the alternative exon. The alternative exon in the mutants is predicted to encode 30 novel amino acids and three stop codons. This alternative exon kept the paired domain intact but led to a loss of the homeodomain and the C-terminal proline-serine-threonine (PST) domain. The mutation cosegregated in the mutant line, since all five additional small-eyed mice from this line showed the same mutation. A general polymorphism at the mutated site was excluded with sequence analysis of seven other wild-type mouse strains different from C3HeB/FeJ. CONCLUSIONS: These findings demonstrate a novel allele of the paired box gene 6 (Pax6) that affects lens development in a semidominant manner leading to a classical small-eye phenotype. However, the site of the mutation more than 1 kb downstream of exon 7 and resulting in an alternative exon is quite unusual. It indicates the importance of sequence analysis of cDNA for mutation detection; mutations like this are unlikely to be identified by analyzing genomic sequences only. Moreover, this particular mutation demonstrates how a novel exon can be created by only a single base-pair exchange.

Altered functional connectivity of the primary visual cortex in subjects with amblyopia.

Amblyopia, which usually occurs during early childhood and results in poor or blurred vision, is a disorder of the visual system that is characterized by a deficiency in an otherwise physically normal eye or by a deficiency that is out of proportion with the structural or functional abnormalities of the eye. Our previous study demonstrated alterations in the spontaneous activity patterns of some brain regions in individuals with anisometropic amblyopia compared to subjects with normal vision. To date, it remains unknown whether patients with amblyopia show characteristic alterations in the functional connectivity patterns in the visual areas of the brain, particularly the primary visual area. In the present study, we investigated the differences in the functional connectivity of the primary visual area between individuals with amblyopia and normal-sighted subjects using resting functional magnetic resonance imaging. Our findings demonstrated that the cerebellum and the inferior parietal lobule showed altered functional connectivity with the primary visual area in individuals with amblyopia, and this finding provides further evidence for the disruption of the dorsal visual pathway in amblyopic subjects.

Association between prediabetes/hyperglycemia and retinal diseases: A meta-analysis.

PURPOSE: To explore the effect of prediabetes/hyperglycemia on the incidence of retinopathy. METHODS: PubMed and EMBASE databases were retrieved to screen case-control studies or prospective cohort studies of retinopathy in prediabetic patients from January, 2004 to December, 2019. After quality evaluation by two evaluators according to inclusion and exclusion criteria, RevMan 5.3 software was used for meta-analysis. RESULTS: A total of 18 articles were included. Meta-analysis showed that there have been more incidents of retinal diseases in patients with prediabetes/hyperglycemia [MD (mean difference) = 2.50, 95% CI (1.74 to 3.6)] than those in normal controls (p < 0.05). The incidence of macular diseases [MD = 1.36, 95% CI (1.05 to 1.76)] was significantly higher in prediabetic patients than that of the control group (p < 0.05). No significant differences in DR-like retinopathy were found between both groups [MD = 2.02, 95% CI (0.84 to 4.85)] (p > 0.05). In neonates, hyperglycemia was associated with an increased risk of ROP [MD = 3.6, 95% CI (1.89 to 6.86)] (p < 0.001). CONCLUSIONS: Prediabetes/hyperglycemia is associated with an increased risk of retinal diseases. Retinal diseases screening such as macular diseases among people with prediabetes should be warranted. But no significant differences in DR-like retinopathy were found. However, more further studies are needed to clarify the details between prediabetes/hyperglycemia and different kinds of retinal diseases.

Genome Editing of Pik3cd Impedes Abnormal Retinal Angiogenesis.

Abnormal angiogenesis is associated with myriad human diseases, including proliferative diabetic retinopathy (PDR). Signaling transduction through phosphoinositide 3-kinases (PI3Ks) plays a critical role in angiogenesis. Herein, we showed that p110δ, the catalytic subunit of PI3Kδ, was highly expressed in pathological retinal vascular endothelial cells (ECs) in a mouse model of oxygen-induced retinopathy (OIR) and in fibrovascular membranes from patients with PDR. To explore novel intervention with PI3Kδ expression, we developed a recombinant dual adeno-associated viral (rAAV) system for delivering CRISPR/Cas9 in which Streptococcus pyogenes (Sp) Cas9 expression was driven by an endothelial specific promoter of the intercellular adhesion molecule 2 (pICAM2) to edit genomic Pik3cd, the gene encoding p110δ. We then demonstrated that infection of cultured mouse vascular ECs with the dual rAAV1s of rAAV1-pICAM2-SpCas9 and rAAV1-SpGuide targeting genomic Pik3cd resulted in 80% DNA insertion/deletion in the locus of genomic Pik3cd and 70% depletion of p110δ expression. Furthermore, we showed that in the mouse model of OIR editing retinal Pik3cd with the dual rAAV1s resulted in not only a significant decrease in p110δ expression, and Akt activation, but also a dramatic reduction in pathological retinal angiogenesis. These findings reveal that Pik3cd editing is a novel approach to treating abnormal retinal angiogenesis.

Macular hole Delphi consensus statement (MHOST).

PURPOSE: To derive a Delphi method-based consensus for the surgical management of Full Thickness Macular Hole (FTMH) and Lamellar Macular Hole (LMH). METHODS: 37 expert VR surgeons from 21 mainly European countries participated in Delphi method-based questionnaire for diagnosis and treatment of FTMHs and LMHs. RESULTS: A total of 36 items were rated in round 1 by 37 participants, of which 10 items achieved consensus: intraoperative verification of PVD; clinical superiority of OCT-based FTMH classification; practical ineffectiveness of ocriplasmin; circular 360° ILM peeling for small macular holes; use of regular surgical technique for the size of the hole in concomitant retinal detachment; performing complete vitrectomy; SF6 gas as preferred tamponade; cataract surgery if crystalline lens is mildly/moderately opaque; removal of both ILM and LHEP in LMH surgery. In round 2, 18 items with moderate consensus (45-70% agreement) in round 1 were rated by 35 participants. Final consensus was reached in 35% of questions related to both diagnosis and surgical procedures. CONCLUSIONS: This Delphi study provides valuable information about the consensus/disagreement on different scenarios encountered during FTMH and LMH management as a guide tosurgical decision-making. High rate of disagreement and/or variable approaches still exist for treating such relatively common conditions.

Video game treatment of amblyopia.

Amblyopia is visual impairment characterized by a structurally normal eye showing significantly lower visual acuity than the fellow eye. Traditional treatment of amblyopia includes patching the good eye to force the amblyopic eye to work during normal daily activities; however, this approach is are limited by low compliance. Recently, researchers proposed a new treatment for amblyopia: video game playing. In the current review, we discuss whether video game playing can treat amblyopia, whether video game playing could better treat amblyopia than traditional treatments, and how the video game treats amblyopia and its possible mechanism. Based on results from our literature review and meta-analysis, we suggest there is strong evidence for the effectiveness of video game treatments. Moreover, multiple factors within and outside of video games could influence the treatment effect.

A Novel Role of IL13Rα2 in the Pathogenesis of Proliferative Vitreoretinopathy.

Proliferative vitreoretinopathy (PVR), an inflammatory and fibrotic blinding disease, is still a therapeutic challenge. Retinal pigment epithelial (RPE) cells dislodged in the vitreous play a central role in the PVR pathogenesis. To identify potential novel contributors to the pathogenesis of PVR, we investigated a profile of vitreous-induced changes in ARPE-19 cells by RNA sequencing. Bioinformatics analysis of the sequencing data showed that there were 258 genes up-regulated and 835 genes down-regulated in the ARPE-19 cells treated with human vitreous. Among these genes, there were three genes related to eye disease with more than threefold changes. In particular, quantitative PCR and western blot results showed that interleukin 13 receptor (IL13R)α2 that is over-expressed in a variety of cancers was up-regulated more than three times in the vitreous-treated ARPE-19 cells. Immunofluorescence analysis indicated that interleukin-13 receptor subunit α2 (IL13Rα2) was highly expressed in ARPE-19 cells within epiretinal membranes from patients with PVR. Importantly, blocking IL13Rα2 with its neutralizing antibody significantly inhibited vitreous-induced contraction of ARPE-19 cells, suggesting a novel role of IL13Rα2 in the PVR pathogenesis. These findings will improve our understanding of the molecular mechanisms by which PVR develops and provides potential targets for PVR therapeutics.

Contralateral lateral rectus muscle recession in a patient with unilateral exotropic Duane retraction syndrome type II: A case report.

A fixation preference for the affected eye is uncommon in patients with unilateral Duane retraction syndrome (DRS), and surgery on the fellow eye is rarely advocated. We are presenting a case report of a 9-year-old boy with unilateral DRS type II in the left eye who received lateral rectus muscle recession in his right amblyopic eye. The patient was orthophoric and his face turn was gone 6 months postoperatively. Surgery on the fellow amblyopic eye is a good choice for unilateral DRS where the affected eye dominants the fixation, and the satisfactory outcome suggests that alignment in the primary position can correct the face turn effectively despite the muscle duction deficit in the affected eye and further extend the binocular single visual field.

Postoperative Endophthalmitis Caused by Cutibacterium (Formerly Propionibacterium) Acnes: Case Series and Review.

We report the clinical features, treatment strategies and outcomes in a series of patients with infectious endophthalmitis after cataract surgery caused by Cutibacterium acnes (C. acnes), formerly known as Propionibacterium acnes (P. acnes). This retrospective case series includes six eyes of six patients with chronic postoperative endophthalmitis caused by culture-proven C. acnesfrom December 2010 to July 2019 at a University referral center. All patients underwent prior cataract extraction with intraocular lens (CE/IOL) implantation. The mean time between cataract surgery and the microbiologic diagnosis of endophthalmitis was 7.4 ± 5.2 months (range 1.5-17 months). The average time from obtaining the specimen to culture positivity was 7.7 ± 4.4 days (range 3-15 days). Three eyes (50%) presented with hypopyon and three eyes (50%) presented with prominent keratic precipitates without hypopyon. Presenting visual acuity ranged from 20/25 to 2/200. Initial treatments included intravitreal antibiotics alone (n = 2), pars plana vitrectomy (PPV) with partial capsulectomy and intravitreal antibiotics (n = 3), and pars plana vitrectomy with IOL removal and intravitreal antibiotics (n = 1). Follow-up treatments included IOL removal (n = 2), intravitreal antibiotics (n = 1), and topical antibiotics (n = 1). The best-corrected visual acuity at last follow-up was 20/70 or better in all patients. In a literature review, the clinical features and treatment outcomes for all case series of delayed-onset postoperative endophthalmitis caused by C. acnes(n = 120) are listed. A definitive cure (the absence of recurrent inflammation) was achieved in 100% of patients that underwent IOL removal, in 77% of those that underwent PPV/partial capsulectomy and intravitreal antibiotics, and in 18% of cases treated with intravitreal antibiotics alone. Endophthalmitis after CE/IOL caused by C. acnesis characterized by slowly progressive intraocular inflammation and has a protracted course from surgery to microbiologic diagnosis. Visual outcomes are generally favorable, but IOL explantation may be necessary for definitive cure.

New compound heterozygous CYP4V2 mutations in bietti crystalline corneoretinal dystrophy.

Bietti crystalline corneoretinal dystrophy (BCD) is an autosomal recessive retinal dystrophy which is caused by the mutations of CYP4V2, usually progressing to legal blindness by the 5th or 6th decade of life. Here we identified CYP4V2 compound heterozygous mutations in two female siblings with BCD without subjective symptoms. After 381 pathogenic genes related to retinal diseases were screened by targeted sequence capture array techniques and confirmed by Sanger sequencing, two compound heterozygous mutations in CYP4V2 were found. One was missense mutation c.1198C>T (p.R400C) and the other was frameshift mutation c.802-8_810delinsGC (p.V268_E329del). Optical coherence tomography (OCT) showed that the ellipsoid zone was absent in the macular regions and electroretinogram (ERG) revealed poor cone and rod responses. Compound heterozygous mutations in CYP4V2 are related to the BCD. Our study expands our knowledge of heterogenic phenotypes and genotypes through genetic diagnosis of the BCD patients.

Quantitative Analysis of Retinal Vasculature in Rhegmatogenous Retinal Detachment Based on Ultra-Widefield Fundus Imaging.

PURPOSE: To quantitatively analyze retinal vascular morphological features, such as vascular density, caliber, and tortuosity, in rhegmatogenous retinal detachment (RRD). METHODS: A total of 244 patients with RRD and 400 healthy controls (HC) were included. Retinal fundus images were collected using OPTOS PLC Daytona P200T. Retinal images were divided into RRD and non-RRD regions of interest (ROIs). All visible retinal fundus vessels were then extracted mainly based on edge detection within ROI to form the whole-vascular image. Retinal vasculature parameters, such as vascular density, caliber, and tortuosity, were calculated. RESULTS: For the absolute density, the mean rank (MR) value of normal controls was significantly higher than that in non-RRD (p < 0.001). A consistent tendency of significant vascular density was increased from non-RRD to RRD (p < 0.001). The average and median diameters of normal controls were both significantly larger than RRD (p < 0.001). The average and median diameters were also appeared significantly thinner in non-RRD. Unweighted and width-inversely-weighted vascular tortuosity in RRD and non-RRD comparison exhibited non-significant differences. All types of tortuosity calculated from HC were significantly larger (p < 0.001) in values compared to RRD. All types of tortuosity values of HC were significantly higher than non-RRD. Compared with non-RRD, RRD was significantly larger in area-weighted, length-weighted, and width-weighted vascular tortuosity. CONCLUSIONS: This study showed that RRD affects both the quantity and morphology of retinal vasculature, such as RRD and non-RRD areas. Smaller average and medium vascular diameters and tortuosity values were found in RRD. However, the absolute vascular density, the average and median diameter, and tortuosity values were also reduced in non-RRD although the retina is still attached. This work indicates that RRD may affect the retinal vasculature beyond the detached retina.