Persistent Hyperplastic Primary Vitreous Research Articles

Diagnostic sensitivity and specificity of color Doppler flow imaging for persistent hyperplastic primary vitreous

Objective To observe the diagnostic sensitivity and specificity of color Doppler flow imaging (CDFI) for persistent hyperplastic primary vitreous (PHPV). Methods The clinical data of 71 children (93 eyes) with congenital cataract which suspected of concurrent PHPV were retrospectively analyzed. The children included 45 males (54 eyes) and 26 females (39 eyes), aged from 1 to 24 months, with an average age of (7.6±4.3) months. All eyes were examined by CDFI, and observe whether there was a pathological strip in the vitreous, the site of the connection between the strip echo and the wall of the eye and the signal of blood flow on the strip echo. Within 1 week after a CDFI examination under general anesthesia, 64 children (79 eyes) underwent lens excision combined with vitrectomy and the other 14 eyes of 7 children underwent mydriatic fundus examination by two experienced eye specialists. Combined with clinical features of PHPV, the diagnosis and differential diagnosis were made according to the clouding of the lens, posterior capsule proliferation, vitreous proliferation and retinal detachment position which were found during operation and fundus examination. Compare and analyze the CDFI examination results and the above diagnosis results, calculate the sensitivity and specificity of CDFI for PHPV. Results In surgery and mydriatic fundus examination results of 93 eyes, vitreous abnormal in 85 eyes, no significant changes were found in vitreous of the other 8 eyes. In 85 eyes of abnormal vitreous, 68 eyes were diagnosed as PHPV, 16 eyes were diagnosed as familial exudative vitreoretinopathy (FEVR), and 1 eye was diagnosed as treactional retinal detachment. In 85 eyes of abnormal vitreous which were found by surgery and fundus examination, CDFI confirmed 81 eyes and its diagnostic sensitivity was 95.3%; the other 4 eyes were not found vitreous abnormality, and the missed diagnosis rate was 4.7%. Surgery and mydriatic fundus examination found no vitreous abnormal in 8 eyes, but CDFI explored strip low echo connected with the optic disc or posterior lens capsule in vitreous. In the 68 eyes of PHPV which were diagnosed by surgery or fundus examination, 59 eyes had the same diagnosis of CDFI, the sensitivity of CDFI was 86.8%; PHPV was not diagnosed in 25 eyes by surgery or fundus examination, but only 8 eyes were also not diagnosed by CDFI, and the specificity of CDFI was 32.0%. The remaining 17 eyes were diagnosed as FEVR in 16 eyes and traction retinal detachment in 1 eye after surgery or mydriatic fundus examination, but they were all diagnosed as PHPV in CDFI. The misdiagnosis rate of CDFI was 68.0%. Conclusion For PHPV, the diagnostic sensitivity and specificity of CDFI are 86.8% and 32.0%, respectively. Key words: Persistent hyperplastic primary vitreous/diagnosis; Ultrasonography, doppler, color

Immediate Sequential Bilateral Pediatric Vitreoretinal Surgery: An International Multicenter Study

To determine the feasibility and safety of bilateral simultaneous vitreoretinal surgery in pediatric patients. International, multicenter, interventional, retrospective case series. Patients 17 years of age or younger from 24 centers worldwide who underwent immediate sequential bilateral vitreoretinal surgery (ISBVS)-defined as vitrectomy, scleral buckle, or lensectomy using the vitreous cutter-performed in both eyes sequentially during the same anesthesia session. Clinical history, surgical details and indications, time under anesthesia, and intraoperative and postoperative ophthalmic and systemic adverse events were reviewed. Ocular and systemic adverse events. A total of 344 surgeries from 172 ISBVS procedures in 167 patients were included in the study. The mean age of the cohort was 1.3±2.6 years. Nonexclusive indications for ISBVS were rapidly progressive disease (74.6%), systemic morbidity placing the child at high anesthesia risk (76.0%), and residence remote from surgery location (30.2%). The most common diagnoses were retinopathy of prematurity (ROP; 72.7% [P < 0.01]; stage 3, 4.8%; stage 4A, 44.4%; stage 4B, 22.4%; stage 5, 26.4%), familial exudative vitreoretinopathy (7.0%), abusive head trauma (4.1%), persistent fetal vasculature (3.5%), congenital cataract (1.7%), posterior capsular opacification (1.7%), rhegmatogenous retinal detachment (1.7%), congenital X-linked retinoschisis (1.2%), Norrie disease (2.3%), and viral retinitis (1.2%). Mean surgical time was 143±59 minutes for both eyes. Higher ROP stage correlated with longer surgical time (P= 0.02). There were no reported intraoperative ocular complications. During the immediate postoperative period, 2 eyes from different patients demonstrated unilateral vitreous hemorrhage (0.6%). No cases of endophthalmitis, choroidal hemorrhage, or hypotony occurred. Mean total anesthesia time was 203±87 minutes. There were no cases of anesthesia-related death, malignant hyperthermia, anaphylaxis, or cardiac event. There was 1 case of reintubation (0.6%) and 1 case of prolonged oxygen desaturation (0.6%). Mean follow-up after surgery was 103 weeks, and anatomic success and globe salvage rates were 89.8% and 98.0%, respectively. This study found ISBVS to be a feasible and safe treatment paradigm for pediatric patients with bilateral vitreoretinal pathologic features when repeated general anesthesia is undesirable or impractical.

Congenital cataract surgery without intraocular lens implantation in persistent fetal vasculature syndrome: Long-term clinical and functional results

To evaluate long-term clinical and functional outcomes after congenital cataract surgery in persistent fetal vasculature (PFV). Department of Ophthalmology, Goethe-University, Frankfurt, Germany. Retrospective comparative case series. The records of eyes with congenital cataract associated or not associated with PFV that had cataract surgery without intraocular lens (IOL) implantation within the first 18months of life were reviewed. Long-term visual outcomes and clinical parameters, including aphakic glaucoma, posterior capsule opacification (PCO), vitreous and anterior segment hemorrhage, retinal detachment (RD), and fibrin reaction, were evaluated. Congenital cataract was associated with PFV in 19 eyes (19 children) and not associated in 69 eyes (40 children). Sixteen patients had isolated anterior PFV; 3 eyes were classified as combined anterior and posterior PFV. The mean follow-up was 53.21months. Postoperative visual acuity improvement was recorded in 68.4% of PFV-associated cataract eyes with a corrected visual acuity up to 20/100. Long-term visual outcomes in PFV-associated cataract eyes were significantly worse than in the 11 unilateral cataract eyes without additional PFV (P=.0067). The presence of PFV was strongly associated with a long-term increased risk for postoperative hemorrhage (P=.0001) and RD (P=.009) after primary cataract surgery and secondary IOL implantation. The prevalence of aphakic glaucoma, PCO, and fibrinous reaction was similar between PFV cataract eyes and controls. In most cases of PFV-associated congenital cataract, postoperative visual acuity improvement is possible. However, congenital cataract eyes associated with PFV have a long-term increased risk for postoperative hemorrhage and RD. None of the authors has a financial or proprietary interest in any material or method mentioned.

Apply of RetCam Ⅱ and color Doppler imaging in persistent hyperplastic primary vitreous

To observe the manifestations of RetCam Ⅱ and color Doppler imaging (CDI) in a retrospective case series of persistent hyperplastic primary vitreous (PHPV). Retrospective study. The medical records of 9 eyes/9 patients with PHPV went through RetCamⅡ and CDI from 2009 to 2014. There were 6 young boys and 3 young girl in this study, age from 2 months to 5 years. All the patients were born at full term. 9 eyes had complication (cataract). The manifestations of RetCam Ⅱ: There were pale in optic disc. There were white fibre rod connected with optic disc, then prolonged to vitreous cavity, connected with posterior lens capsule. CDI showed arterial blood stream signal in band-shaped echogenic structure within vitreous cavity, prolonged to lens from the optic disc, or showed funnel-shaped echogenic mass at the posterior surface of lens and anterior of vitreous body, adhered to ciliary body, lens and the optic disc. PHPV is congenital ocular anomalies because of a failure of primary vitreous and the hyaloids vascular system to regress. It manifests as unilateral and boys. We diagnosis PHPV by RetCamⅡ and CDI.

Ocular axial growth in pseudophakic eyes of patients operated for monocular infantile cataract: a comparison of operated and fellow eyes measured at surgery and 5 or more years later

To report the change in axial length (AL) over time and to compare the percentage of AL growth of pseudophakic eyes operated on for monocular cataract to that of the unoperated fellow eyes. The medical records of children operated on by a single surgeon for monocular congenital cataract before 7months of age were retrospectively reviewed. Inclusion criteria were corneal diameter of ≥9mm and availability of AL data for >5years' follow-up after cataract surgery and >1year after IOL implantation (in case of secondary IOL). Cataract with persistent fetal vasculature causing stretching of the ciliary processes, diagnosis of glaucoma or glaucoma suspect, and eyes with aphakia were excluded. Globe AL was measured by immersion ultrasound at surgery and 5 or more years later. A total of 24 children were identified. Average age at cataract surgery was 2.6±2.1months. Age at last follow-up was 8.4±2.8years and duration of follow-up was 8.2±2.8years. 13 eyes received a primary IOL and 11 eyes received a secondary IOL. AL was significantly different between operative and fellow eyes, preoperatively (18.1mm vs 18.7mm, P=0.004), and at the final follow-up (22.2mm vs 23.0mm, P=0.03). Differences in AL growth of operated and fellow eyes were not significant (4.1mm vs 4.4mm, P=0.4). Similarly, percentage of AL growth of operated and fellow eyes was also not significantly different (23% vs 23.6%, P=0.7). Eyes operated for monocular cataract have similar axial growth to that of fellow unoperated eyes, despite having a shorter AL at the time of surgery.

The effect of repeated eye examinations and breeding advice on the prevalence and incidence of cataracts and progressive retinal atrophy in German dachshunds over a 13-year period.

To analyze the change in prevalence and incidence of hereditary eye diseases (HED) in dachshunds due to breeding regulations based on biennial examinations performed by the German panel of veterinary ophthalmologists (DOK) from 1998 to 2011. A total of 12 242 dachshunds examined by the DOK and pedigree data of 318 852 dachshunds provided by the German Dachshund Club (DTK). The prevalence of congenital cataract (CC), distichiasis (DIST), hereditary cataract (HC), persistent pupillary membranes (PPMs), persistent hyperplastic tunica vasculosa lentis / persistent hyperplastic primary vitreous (PHTVL/PHPV), progressive retinal atrophy (PRA), retinal dysplasia (RD), and findings such as fiberglass-like cataract (FGC) and prominent suture lines (PSLs) was analyzed. The significance (P), confidence interval (CI), odds ratio (OR), relative risk (RR) and inbreeding coefficients (F) were calculated and P < 0.05 was considered significant. The incidence was evaluated based on affected dogs within birth cohorts from 1993 to 2006. The prevalent conditions studied were as follows: CC 0.5%, DIST 6.7%, HC 3.9%, PPMs 8.4%, PHTVL/PHPV 0.4%, PRA 1.5%, RD 0.2%, FGC 2.2%, and PSL 1.5%. The incidence of PRA decreased significantly from 6.0% to 0.6% for dogs born from 1993 to 2006, while HC showed a decreasing trend from 8.7% to 3.1%. More males than females were diagnosed with HC and PRA. Dachshunds with HEDs had an F that was not significantly higher than that of healthy dachshunds. The decreasing incidence of PRA and HC in dachshunds supports the use of frequent HED examinations in combination with breeding control.

Severe hemophilia in a girl infant with mosaic Turner syndrome and persistent hyperplastic primary vitreous

A 6-month-old girl was referred by an ophthalmologist because of postoperative bleeding. She was scheduled for operation because of persistent hyperplastic primary vitreous. Workups were done and prolonged partial thromboplastin time with normal platelet count, normal bleeding time, and prothrombin time were detected. There was negative family history of bleeding tendency in both maternal and paternal family, so at the first step, Factor XI assay was requested which was normal. Then, von Willebrand factor and factor VIII were assayed which was 127% and less than 1%, respectively. Severe factor VIII deficiency was not suspected in a girl unless in siblings of a hemophilic patient who gets married with her carrier cousin. Chromosomal study and genetic testing were requested and mosaic Turner syndrome (45 XO) with ring X (p22, 2q13) along with inversion 22 (hemizygote) was detected. Abdominal and pelvic sonography showed absence of both ovaries with presence of infantile uterus. Maternal genetic study was in favor of carrier of hemophilia (heterozygote inversion 22). To the best of our knowledge, this is the first case of association of Turner syndrome with severe hemophilia A and persistent hyperplastic primary vitreous.

Study of the Genesis of Persistent Fetal Vasculature through Clinical Observations of Two Pediatric Patients

PurposePersistent fetal vasculature (PFV) is a rare congenital disease caused by fetal blood vessels remaining in the eyes, with various residues and persistent hyperplasia. A series of observations in 2 typical PFV were conducted to better understand fatal development in normal eyes and to illustrate involved controversies.MethodsCase One was an 11‐month girl who was found to have leukocoria accompanied by black spherical goiter in the right eye approximately 50 days after birth. Case Two was a 3‐year old girl who was found to have leukokoria at birth. IN both cases, image data prior to surgery and series of photographs during the procedures were carefully colliaected and reviewed comparatively with surgical video record. Novel tissue samples obtained from surgeries were observed histopathologically. Comprehensive analysis was carried out with literature review,ResultsMajority of the abnormal signs were concomitant with those that Goldberg described in Jackson Memorial Lecture emphasizing the congenital anomalies caused by different degrees of PFV, which seemingly existed in isolation, but were intrinsically syntrophic. Pigment epithelium layer of iris detoured over stoma through pupil to adhere with the back surface of cornea, which manifested as an iris cyst. Trace of fatal development supplied a hard evidence that corneal endothelium was originated from neuroectodermal cells. Network profile of persistent papillary membrane tended to be formed by anterior tunica vasculosa lentis while the remnants were coated by iris stromal tissues which were believed to be originated from neural crest cells.ConclusionsClose relation between corneal endothelium and pigment epithelium of iris at early stage of fatal development was evidenced by clinical observations in the two pediatric cases. Corneal endothelium and Descemet's membrane were most possibly originated from neuroectodermal and spread with the manner migrated from centre to periphery. Neural crest cells went forward to center from periphery via the staggered gap between developing endothelium and anterior surface of optic cup to form stroma of iris. Mechanism of persistent pupil membrane formation could be a result of mutualism between anterior tunica vasculosa lentis and stroma of iris.

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.