Persistent Hyperplastic Primary Vitreous Research Articles

A case of iridofundal coloboma with persistent fetal vasculature and lens subluxation

Persistent fetal vasculature and fundal coloboma are important congenital vitreoretinal disorders that can severely affect a child's visual acuity. Each disorder has its own set of potential complications. We discuss the case of a visually challenged child who presented with a combination of both these disorders, along with inferior lens subluxation.

Surgical outcomes of congenital and developmental cataracts in Japan.

To retrospectively analyze the surgical outcomes of congenital/developmental cataracts in Japan. A mail questionnaire was sent to facilities engaged in surgical treatment of congenital cataracts. Twenty-nine facilities reported on 809 eyes of 508 patients with congenital/developmental cataracts. Three hundred fifty-nine eyes underwent intraocular lens implantation (pseudophakia group), while 450 eyes were left aphakic (aphakia group). The average age at surgery was significantly higher in the pseudophakia group (70±53months) than in the aphakia group (14±24months) (P<0.0001). A significantly larger proportion of patients with unilateral cataract (52.0%) received IOL implantation than did those with bilateral cataracts (42.6%) (P=0.0224). The prevalence of associated ocular disorders, such as nystagmus, microcornea, nanophthalmos, and persistent fetal vasculature, was significantly higher in the aphakia group than in the pseudophakia group. Postoperatively, glaucoma developed more frequently in the aphakia group (5.8%) than in the pseudophakia group (0.7%) (P=0.0003). Posterior capsule opacification developed more frequently in the pseudophakic eyes even when both posterior capsulotomy and anterior vitrectomy were performed, especially in patients aged 1year or younger. Postoperative visual acuity was significantly better in the pseudophakia group than in the aphakia group, both in the unilateral and in the bilateral cases. Surgeons tended to select IOL implantation, rather than to leave the eye aphakic, in patients who were older at the time of surgery, had fewer coexisting ocular disorders, and suffered from unilateral cataract. Under such circumstances, pseudophakic eyes obtained significantly better postoperative visual acuity than did aphakic eyes.

Mice Homozygous for a Deletion in the Glaucoma Susceptibility Locus INK4 Show Increased Vulnerability of Retinal Ganglion Cells to Elevated Intraocular Pressure

A genomic region located on chromosome 9p21 is associated with primary open-angle glaucoma and normal tension glaucoma in genome-wide association studies. The genomic region contains the gene for a long noncoding RNA called CDKN2B-AS, two genes that code for cyclin-dependent kinase inhibitors 2A and 2B (CDKN2A/p16(INK4A) and CDKN2B/p15(INK4B)) and an additional protein (p14(ARF)). We used a transgenic mouse model in which 70 kb of murine chromosome 4, syntenic to human chromosome 9p21, are deleted to study whether this deletion leads to a discernible phenotype in ocular structures implicated in glaucoma. Homozygous mice of this strain were previously reported to show persistent hyperplastic primary vitreous. Fundus photography and optical coherence tomography confirmed that finding but showed no abnormalities for heterozygous mice. Optokinetic response, eletroretinogram, and histology indicated that the heterozygous and mutant retinas were normal functionally and morphologically, whereas glial cells were activated in the retina and optic nerve head of mutant eyes. In quantitative PCR, CDKN2B expression was reduced by approximately 50% in the heterozygous mice and by 90% in the homozygous mice, which suggested that the CDKN2B knock down had no deleterious consequences for the retina under normal conditions. However, compared with wild-type and heterozygous animals, the homozygous mice are more vulnerable to retinal ganglion cell loss in response to elevated intraocular pressure.

CRYβA3/A1-Crystallin Knockout Develops Nuclear Cataract and Causes Impaired Lysosomal Cargo Clearance and Calpain Activation.

βA3/A1-crystallin is an abundant structural protein of the lens that is very critical for lens function. Many different genetic mutations have been shown to associate with different types of cataracts in humans and in animal models. βA3/A1-crystallin has four Greek key-motifs that organize into two crystallin domains. It shown to bind calcium with moderate affinity and has putative calcium-binding site. Other than in the lens, βA3/A1 is also expressed in retinal astrocytes, retinal pigment epithelial (RPE) cells, and retinal ganglion cells. The function of βA3/A1-crystallin in the retinal cell types is well studied; however, a clear understanding of the function of this protein in the lens has not yet been established. In the current study, we generated the βA3/A1-crystallin knockout (KO) mouse and explored the function of βA3/A1-crystallin in lens development. Our results showed that βA3-KO mice develop congenital nuclear cataract and exhibit persistent fetal vasculature condition. At the cellular level KO lenses show defective lysosomal clearance and accumulation of nuclei, mitochondria, and autophagic cargo in the outer cortical region of the lens. In addition, the calcium level and the expression and activity of calpain-3 were increased in KO lenses. Taken together, these results suggest the lack of βA3-crystallin function in lenses, alters calcium homeostasis which in turn causes lysosomal defects and calpain activation. These defects are responsible for the development of nuclear cataract in KO lenses.

Primary versus secondary IOL implantation following removal of infantile unilateral congenital cataract: outcomes after at least 5 years

To report outcomes after at least 5years' follow-up of consecutive patients at a single center undergoing unilateral congenital cataract surgery during infancy with primary intraocular lens (IOL) implantation at the time of surgery or undergoing secondary IOL implantation later in childhood. The medical records of pseudophakic children who received initial cataract surgery before 7months of age were retrospectively reviewed. Children with acquired cataract, persistent fetal vasculature, congenital glaucoma, or follow-up of <5years were excluded. Mean age at time of cataract surgery was 2.7months in the primary group (n=13) and 1.9months in the secondary group (n=13). Mean age at IOL implantation in the latter group was 4.9±2.2years. Mean age at final follow-up was 10.7±4.2years in the primary group and 8.7±3.0years in the secondary group. Glaucoma surgery was performed in 2 primary group eyes and 1 secondary group eye; it was medically controlled in 2 additional eyes of the latter group. One secondary group eye was diagnosed as glaucoma suspect. Visual axis opacification required surgery in 5 primary group eyes and 2 secondary group eyes before IOL implantation. Unplanned IOL exchange or removal for high myopia was required in 3 primary group eyes and 1 secondary group eye. Strabismus surgery was performed in 3 primary group eyes and 7 secondary group eyes. Median visual acuity at final follow-up was 20/150 in both groups. Refraction at last follow-up was -2.9±3.3 D in the primary and -1.8±2.5 D in the secondary group. Reoperations were common in both groups over long-term follow-up. Close monitoring for glaucoma is also needed in both groups.

P19Arf limits primary vitreous cell proliferation driven by PDGF-B

Arf encodes an important tumor suppressor, p19Arf, which also plays a critical role to control hyperplasia in the primary vitreous during mouse eye development. In the absence of Arf, mice are born blind and display a phenotype closely mimicking severe forms of the human eye disease, persistent hyperplastic primary vitreous (PHPV). In this report, we characterize p19Arf expression in perivascular cells that normally populate the primary vitreous and express the Arf promoter. Using a new ex vivo model, we show that these cells respond to exogenous Tgfβ, despite being isolated at a time when Tgfβ has already turned on the Arf promoter. Treatment of the cells with PDGF-B ligand doubles the population of cells in S-phase and ectopic expression of Arf blunts that effect. We show this effect is mediated through Pdgfrβ as expression of Arf represses expression of Pdgfrβ mRNA and protein to approximately 60%. p53 is not required for Arf-dependent blockade of PDGF-B driven proliferation and repression of Pdgfrβ protein as ectopic expression of Arf is still able to inhibit the 2-fold increase in the S-phase fraction of cells upon treatment with PDGF-B. Finally, induction of mature miR-34a, a microRNA previously identified to be regulated by p19Arf does not depend on p53 while the expression of the primary transcript does require p53. These data corroborate that, as in vivo, p19Arf functions to inhibit PDGF-B driven proliferation ex vivo.

Plasmin Enzyme-Assisted Vitrectomy in Pediatric Patients with Vitreoretinal Diseases

Purpose: To evaluate the efficacy and safety of using plasmin-assisted vitrectomy in pediatric patients with vitreoretinal diseases. Methods: We prospectively recruited children aged 16 years or younger who presented with vitreoretinopathies and underwent plasmin-assisted vitrectomy between 2012 and 2013. The main outcome measure was the induction of posterior vitreous detachment (PVD) using a suction power of 200 mm Hg or less during surgery. Results: Eleven eyes of 11 patients (mean age: 3.7 years; average follow-up duration: 14.1 months) were included. Of these 11 patients, there were 3 (27%) cases of stage 5 retinopathy of prematurity, 2 (18%) cases of persistent fetal vasculature, 2 (18%) cases of rhegmatogenous retinal detachment, 2 (18%) cases of idiopathic epiretinal membrane, 1 (9%) case of traumatic macular pucker, and 1 (9%) case of traumatic vitreous hemorrhage (9%). PVD was achieved in all cases (100%) during surgery using low suction after plasmin treatment (mean: 150 ± 39 mm Hg; range: 100-200). Overall, anatomical success was achieved in 8 eyes (73%). Visual acuity improved in all 5 (100%) patients for whom vision could be measured at 6 months after the operation. Cataracts were found in 4 eyes (36%), and a rise in transient intraocular pressure was observed in 1 eye (9%). Conclusions: Plasmin-assisted vitrectomy offers an effective and less traumatic intervention for a variety of pediatric vitreoretinal diseases.

VARIABLE EXPRESSION OF RETINOPATHY IN A PEDIGREE OF PATIENTS WITH INCONTINENTIA PIGMENTI.

To characterize the varied ocular manifestations of incontinentia pigmenti (IP) in a large pedigree. All available members of the kindred who were affected with IP were examined with ophthalmoscopy, wide-field color photos, and fluorescein angiography. Individual family members demonstrated variable expression of retinopathy characteristic of IP. There was severe retinopathy in two eyes: one associated with concurrent persistent fetal vasculature and another with rhegmatogenous retinal detachment. Another individual with biopsy-confirmed IP demonstrated no retinopathy in either eye. When present, retinopathy manifested asymmetrically between eyes of the same individual. Cutaneous manifestations of IP are irregular and nonuniform due to lyonization of the X chromosome. In this report, we identify asymmetric retinal disease between eyes in the same individual and variable retinal findings within the kindred. These differences may be explained by random inactivation of the X chromosome or other epigenetic modifications.

Combined Persistent Fetal Vasculature: A Classification Based on High-Resolution B-Mode Ultrasound and Color Doppler Imaging

The purpose of this study was to classify combined persistent fetal vasculature (PFV) on the basis of the ultrasonographic and Doppler characteristics. The potential clinical significance for both surgery design and prognosis determination was discussed. A cross-sectional case series. The eyes of 54 children diagnosed with unilateral combined PFV were evaluated using B-mode ultrasound and color Doppler imaging (CDI). Each participant's age at first presentation, diagnosis for referral, gender, family history, and systemic or other ocular anomalies were recorded. Retinal detachment, optic nerve abnormalities, and macular dislocation were also recorded in detail according to the RetCam (Clarity Medical Systems, Pleasanton, CA), ultrasound, and Doppler findings. The PFV eyes were divided into 4 groups on the basis of the ultrasound and CDI findings. Intergroup analysis was performed. Overall and intergroup analyses of the demographic features of the children with PFV were performed. The axial length, depth of the anterior chamber, and lens thickness were compared between the affected eyes and the fellow healthy eyes among the 4 groups. Some 22.2%, 18.5%, 33.3%, and 25.9% of the eyes were grouped into type I ("I" shape), II ("Y" shape), III (inverted "Y" shape), and IV ("X" shape) combined PFV, respectively. The age at first presentation for type I was older than that for the other groups (P= 0.014). The axial length was reduced (P= 0.012) and the anterior chamber more shallow (P= 0.011) than in fellow healthy eyes for type IV eyes, but not for the other 3groups. Ultrasound and CDI are informative screening and diagnostic tools that show characteristic flow patterns in the 4 types of combined PFV. This novel classification system provides new and important information for the diagnosis of PFV and, if validated, may play a role in guiding treatment recommendations in the future.

Susceptibility weighted imaging in a case of lissencephaly: Evidence of persistent fetal vasculature

Lissencephaly, with posterior-anterior gradient, are congenital brain malformations characterized by the presence of a few broad, flat gyri with thickened cortex. It results from the arrest of neuronal migration in early gestation. Magnetic resonance imaging (MRI) findings are characteristic and show thickened dysplastic cortex with a paucity of gyri and sulci. We report a case of lissencephaly with posterior-anterior gradient with unique imaging findings on susceptibility weighted imaging. Susceptibility weighted imaging revealed prominent venous channels traversing the thickened cortex. These channels possibly represent primitive vessels, similar to those seen in early cortical development, and can probably be seen due to the enormously thickened cortex in case of lissencephaly.

Fundus fluorescein angiography of pediatric morning glory syndrome patients

Objective To observe the fundus fluorescein angiography (FFA) manifestations of pediatric morning glory syndrome (MGS) patients. Methods Fourteen eyes diagnosed as MGS of 14 patients were studied. Among the 14 cases, there were 7 male and 7 female patients. At the time of FFA, the mean age of the patients was (38.75±33.91) months old, ranging from 5.5 to 128.0 months. Among the 14 eyes, four (28.57%) were associated with persistent hyperplastic primary vitreous; four (28.57%) were associated with retinal detachment with no retinal breaks, and one (7.14%) was associated with peripapillary subretinal exudation. All patients underwent peripapillary laser photocoagulation under general anesthesia first and then FFA with the third generation of wide-angle digital retinal imaging system. The arm-retinal circulation time (A-RCT), numbers of blood vessels on the edges of optic disc of the MGS eyes and the contralateral healthy eyes, retinal vascular morphology, the peripheral avascular area, neovascularization, retinal detachment and other abnormalities were documented. The horizontal and vertical diameters of the optic disc of the affected eyes and the contralateral healthy eyes were measured. To compare the A-RCT, 16 children with normal FFA were selected as control group. Results The diameters of the vertical and horizontal axis of the affected eyes were as (2.56±0.58) and (2.73±0.60) times of the contralateral healthy eyes respectively. The average A-RCT of the affected eyes and eyes of the control group were (13.25±4.10) and (9.34±2.20) s respectively. The affected eyes had significantly prolonged A-RCT. At early stage, the optic disc and peripapillary areas showed hypo-fluorescence, while the irregular retinochoroidal atrophy area outside of the optic disk manifested as hyper-fluorescence ring. At late stage, optic disc showed hyper-fluorescence. Numbers of blood vessels on the edge of the optic disc of the affected eyes and contralateral healthy eyes were 30.27±4.86 and 15.83±1.95 respectively, the affected eyes had much more vessels than the contralateral healthy eyes. All affected eyes had peripheral retinal non-perfusion areas. Conclusion FFA examination showed prolonged A-RCT and peripheral retinal non-perfusion areas in the affected MGS eyes. Key words: Optic nerve diseases/ diagnosis; Optic disk/abnormalities; Fluorescein angiography

Frizzled-4 Variations Associated with Retinopathy and Intrauterine Growth Retardation: A Potential Marker for Prematurity and Retinopathy

To present the association between mutations affecting the Wnt-signaling receptor protein (FZD4), inherited vitreoretinopathies, and retinopathy of prematurity (ROP). Retrospective analysis of prospective samples at a tertiary referral center. Patients referred to our practice for management of a variety of pediatric vitreoretinopathies were offered participation in an ophthalmic biobank (421 participants with vitreoretinopathies were included in this study). Full-term healthy infants (n = 98) were recruited to the study as controls. Patients with various vitreoretinopathies were prospectively enrolled in an ophthalmic biobank, approved by the Human Investigation Committee at William Beaumont Hospital. Retrospective genetic analysis of the FZD4 gene was performed (Sanger sequencing). Participants with a diagnosis of familial exudative vitreoretinopathy (FEVR), Norrie disease, Coats' disease, bilateral persistent fetal vasculature, and ROP were reviewed for the presence of a FZD4 variant. Data retrieval included status of retinopathy (including staging when possible), gestational age (GA), birth weight (BW) (when available), and family and birth histories. The association of FZD4 variants with the presence of vitreoretinopathy. The sequence variation p.[P33S(;)P168S] is the most prevalent FZD4 variant and is statistically significant for ROP and FEVR (P = 4.6E-04 and P = 2.4E-03, respectively) compared with full-term newborns (P = 1.7E-01). In addition, infants expressing the sequence variation tended to have significantly lower BWs for respective GA (P = 0.04). This suggests that the FZD4 p.[P33S(;)P168S] variant may be a risk factor for retinopathy and restricted intrauterine growth. Testing for FZD4 gene mutations is useful in patients with suspected FEVR and ROP. The relatively high prevalence of the p.[P33S(;)P168S] variant in ROP and intrauterine growth restriction suggests that it also may be a marker for increased risk of developing ROP and preterm birth.

Extended Follow-up of Treated and Untreated Retinopathy in Incontinentia Pigmenti

Extended follow-up of treated and untreated retinopathy in incontinentia pigmenti (IP) has not previously been documented, to our knowledge. To determine which eyes with IP are at risk for retinal detachment. Observational cohort study of patients with IP who were retrospectively identified at a tertiary care academic center between 1976 and 2013. Fifty eyes of 25 female participants meeting clinical criteria for IP were followed up for at least 6 months. The last year of follow-up was between 1987 and 2014. Progression of retinopathy or the development of retinal detachment was assessed with fluorescein angiography, clinical examination, or both. The median duration of follow-up was 9.3 years (range, 0.5-22.8 years). Over this period, 11 eyes (22%; 95% CI, 11%-33%) developed retinal detachment. The odds of retinal detachment were increased if there was retinal neovascularization (odds ratio, 11.61; 95% CI, 1.34-100.56; P = .03) or ischemic optic neuropathy (odds ratio, 5.27; 95% CI, 1.61-17.23; P = .006) on initial examination. A bimodal distribution of retinal detachments was observed, with most tractional detachments (7 eyes) occurring by age 2.5 years (median, 1.5 years; range, 14 days-7.0 years) and most rhegmatogenous detachments (4 eyes) occurring in adults (median age, 31.5 years; range, 14.0-47.0 years). Three eyes of young patients (≤2.5 years) developed tractional detachment, despite prophylactic ablation in 4 eyes; only one eye of older patients (≥14.0 years) developed retinal detachment following prophylactic ablation in 6 eyes. Persistent fetal vasculature appears to occur more commonly in IP (14%; 95% CI, 4%-25%) than in the general population. All eyes with retinopathy due to IP should be monitored throughout adulthood for the development of retinal complications. During infancy and early childhood, ophthalmoscopic examination should be performed frequently so that prompt treatment can be initiated if there is progressive disease. Because of the nonrandomized nature of this study, the indications for prophylactic ablation and its success rate remain uncertain. Patients with less than 6 months of follow-up were excluded from the analysis, which could have biased this study cohort toward patients with more severe or less severe disease.

Visual outcome in early vitrectomy for posterior persistent fetal vasculature associated with traction retinal detachment.

This study investigates the anatomical and visual outcome of vitrectomy for the treatment of unilateral posterior persistent fetal vasculature with associated traction retinal detachment in very young patients. A retrospective case series study from 1998 through 2010 of 11 eyes in 11 patients who underwent pars plana vitrectomy with or without lensectomy for unilateral posterior persistent fetal vasculature with traction retinal detachment affecting the macula. Ten of the 11 patients (91%) received surgical intervention when 13 months old or younger (average age, 4 months). Postoperatively, 6 of 10 eyes (60%) had 20/800 or better vision, 2 of which had 20/60 vision. All 10 patients in this group had their retinas reattached postoperatively with significant reversal of retinal dragging. One of the 11 patients (9%) received surgical intervention for posterior persistent fetal vasculature at 33 months of age. This patient had persistent traction retinal detachment and a postoperative visual acuity of hand motion. Postoperative glaucoma was detected in 4 patients (36%). This study suggests that early intervention in patients with unilateral posterior persistent fetal vasculature with associated macula affecting traction retinal detachment may provide a better visual and anatomical outcome when vitrectomy and retinal reattachment are performed at a very early age.

Clinical characteristics of congenital and developmental cataract undergoing surgical treatment.

To analyze the clinical characteristics of congenital/developmental cataract undergoing surgery. A mail questionnaire was sent to 49 facilities engaged in surgical treatment of congenital cataracts, and data on preoperative clinical features were collected. Twenty nine facilities reported on 864 eyes of 521 patients with congenital/infantile cataract, ranging in age at initial visit from 0 to 18.8 years (2.6 ± 3.3 years, mean ± standard deviation). Among the patients, 65.8 % had bilateral cataracts and 34.2 % were unilaterally affected. Family history was found for 22.4 % of cases, of which 98.1 % were bilateral. Family history was positive for 33.1 % of bilateral and 1.3 % of unilateral cases. The most common main complaint was white pupil for 35.7 % of bilateral cases and 32.7 % for unilateral cases. Concomitant systemic abnormalities were more frequently associated with bilateral cases (31.6 %) than with unilateral cases (16.7 %). Associated ocular diseases, such as strabismus, persistent fetal vasculature, and posterior lenticonus, were more frequently seen among unilateral cases whereas nystagmus was more common among bilateral cases. Among congenital/developmental cataracts, the ratio of bilateral and unilateral cases was approximately 2:1. Almost all patients with a family history of congenital cataract were bilateral. Initial visits to a physician were rather late, 2.6 years from birth; this should be improved.

Lesions Simulating Retinoblastoma at a Tertiary Care Center.

Purpose:To determine the types and frequency of ocular conditions simulating retinoblastoma (pseudo-retinoblastoma) at Farabi Eye Hospital, Tehran, Iran.Methods:We reviewed data of patients who were referred with a diagnosis of retinoblastoma to Farabi Eye Hospital oncology clinic, from January 2009 to July 2013. Examination under general anesthesia was performed for all patients. Other investigations, such as ultrasonography, were performed as required.Results:Of a total of 331 patients (aged 1-60 months), 138 (42%) were found to be suffering from a benign disorder. Among these pseudo-retinoblastoma cases, Coats’ disease was the most prevalent codition (n = 36, 26%); persistent hyperplastic primary vitreous (PHPV) and familial exudative vitreo-retinopathy (FEVR) were the next two common pseudo-retinoblastoma cases in our series.Conclusion:The rate of misdiagnosis upon referral to our center was close to 40%. The most common pseudo-retinoblastomas entities include Coats’ disease, PHPV and FEVR. An accurate diagnosis is essential for management of pseudo-retinoblastoma cases.

Findings of Eye Screening Examinations with Wide-Field Digital Imaging System in Healthy Newborns

Purpose: To present the results of eye screening examinations using RetCam in healthy newborns. Methods: Eye screening examinations were performed using the RetCam wide-field digital imaging system (Clarity Medical System, Pleasanton, CA, USA), as requested by parents, on healthy newborns within a week after birth in an obstetrics and gynecology hospital between June 2012 and September 2014. During the examination, photographs were taken showing red reflex and the fundus. The reading was conducted by a pediatric ophthalmologist. Results: The examinations included a total of 10,023 newborn babies, and abnormalities were discovered in 2,916 patients (29.09%). The most commonly found abnormality was retinal hemorrhage, which was discovered in 2,796 babies (27.89%) and 471 patients showed a large amount of bleeding or macular hemorrhage. In 71 patients (0.7%), ophthalmologic examination was recommended after newborns presented with one of the following conditions: congenital cataracts, retinoblastoma, persistent hyperplastic primary vitreous, vitreous hemorrhaging, persistent pupillary membrane, choroidal nevus or albinism. Due to unclear photographs, 85 eyes of 49 patients (0.48%) could not be read. Conclusions: Ophthalmologic screening using RetCam is a safe, simple and useful technique for discovering ophthalmologic abnormalities. Additionally, when abnormalities are suspected, the role of a pediatric ophthalmologist is increasingly important in helping patients receive appropriate ophthalmologic treatment. Furthermore, retinal hemorrhage, which occurred in the majority of all observed abnormalities, requires further investigation to examine the possibilities of amblyopia in cases with a large amount of bleeding or macula involvement. J Korean Ophthalmol Soc 2015;56(10):1617-1623

Unusual persistent fetal vasculature presentation in a premature baby

Persistent fetal vasculature (PFV) is a congenital developmental disorder manifesting as a fibrovascular remnant of the embryonal hyaloid vascular system within the vitreal space. Retinopathy of prematurity (ROP) presents as varying degrees of non-vascularized retinal tissue with potentially devastating ocular complications. Both pathologies arise from ocular vascular system abnormalities, and various treatment modalities have been attempted in the past. In this report we describe a unique case of a late manifesting PFV that may be associated with the development of ROP, complicated by a visually significant cataract. Citation: Zahavi A, Hilely A, Weinberger D, Snir M, Kella YR (2015) Unusual persistent fetal vasculature presentation in a

Macular structural characteristics in children with congenital and developmental cataracts

To investigate macular structural characteristics in children with congenital or developmental cataracts. Children 5-16 years of age with a history of surgery for congenital or acquired cataract were enrolled. Eligible patients had visual acuity of 20/400 or better and ≥37 weeks gestational age at birth. Patients were divided into two groups: unilateral (n = 22) and bilateral (n = 19). Fourier domain optical coherence tomography (FD-OCT) was used to image the retinal structure. Retinal volume scans centered on the fovea were obtained. Using the instrument's segmentation software, central subfield thickness (CST) and the thickness of the inner and outer retinal layer regions were measured. In the unilateral group, 1 child with persistent fetal vasculature had unidentifiable retinal structure and was excluded. Most unilateral eyes (20/21) had a CST within the normal range. However, the CST, superior, nasal, inferior, and temporal sectors were all significantly thicker in the cataractous eye compared to the noncataractous eye (all P < 0.01 [paired t test]). The interocular difference for CST was not associated with age at surgery or interocular difference for visual acuity. In the bilateral group, although 34 of 38 eyes were within the normal range, the average CST of this group was significantly thicker than the noncataractous eye in the unilateral group. Following cataract extraction during infancy or childhood, most cataractous eyes had normal macular structure. Cataractous eyes of both unilaterally and bilaterally affected children have thicker CST values compared to the noncataractous eye.

Novel mutation in TSPAN12 leads to autosomal recessive inheritance of congenital vitreoretinal disease with intra-familial phenotypic variability.

Developmental malformations of the vitreoretinal vasculature are a heterogeneous group of conditions with various modes of inheritance, and include familial exudative vitreoretinopathy (FEVR), persistent fetal vasculature (PFV), and Norrie disease. We investigated a large consanguineous kindred with multiple affected individuals exhibiting variable phenotypes of abnormal vitreoretinal vasculature, consistent with the three above-mentioned conditions and compatible with autosomal recessive inheritance. Exome sequencing identified a novel c.542G > T (p.C181F) apparently mutation in the TSPAN12 gene that segregated with the ocular disease in the family. The TSPAN12 gene was previously reported to cause dominant and recessive FEVR, but has not yet been associated with other vitreoretinal manifestations. The intra-familial clinical variability caused by a single mutation in the TSPAN12 gene underscores the complicated phenotype-genotype correlation of mutations in this gene, and suggests that there are additional genetic and environmental factors involved in the complex process of ocular vascularization during embryonic development. Our study supports considering PFV, FEVR, and Norrie disease a spectrum of disorders, with clinical and genetic overlap, caused by mutations in distinct genes acting in the Norrin/β-catenin signaling pathway.