Localized versus 360-degree laser photocoagulation with limited pars plana vitrectomy in the management of primary rhegmatogenous retinal detachment.

BACKGROUND: To compare the efficacy of intraoperative localized and 360-degree laser photocoagulation in 23-gauge limited pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). METHODS: This retrospective, comparative, consecutive, interventional study included 155 eyes of 155 patients who underwent primary repair of RRD utilizing 23-gauge PPV with at least six months of follow up. Medical records were retrospectively reviewed, and the corresponding demographic data, preoperative ophthalmic features, surgical management, and postoperative course were recorded. Main outcome measures included single surgery anatomical success, pre- and post-operative visual acuity, and complications. RESULTS: Eighty-three patients (group A) received localized laser photocoagulation in PPV, while the remaining 72 patients (group B) received underwent circumferential 360-degree laser photocoagulation in PPV. Two skilled-surgeons performed all the surgeries, and 23-gauge PPV instrumentation, a wide-angle viewing system, endolaser photocoagulation, and gas tamponade were used in each case. No significant difference was identified in baseline characteristics. The single surgery anatomical success rate was 96.4 % in group A, and 95.8 % in group B, showing no significant difference (p = 1.00). Primary anatomical failure was caused by re-detachment due to break in 2 eyes in each group (no new break 1 eye, new break 1eye in group A, 2 eyes with no new break in group B), and proliferative vitreoretinopathy in 1 eye in each group. Other complications were epiretinal membrane in 7 eyes (3 in group A, 4 in group B), and macular hole in 1 eye in group B. There were no differences in pre- and post-operative best-corrected visual acuity (BCVA) as well as BCVA improvement (p=0.144, p=0.866 and p=0.263, respectively). CONCLUSION: Localized laser photocoagulation showed no difference in anatomic and visual outcome in RRD patients, when compared with 360-degree laser photocoagulation in limited PPV. Routine circumferential 360-degree laser photocoagulation may not be necessary in vitrectomy surgery for primary rhegmatogenous retinal detachment without severe PVR.

Effect of Foveal Pit Restoration in Foveal Avascular Zone after Surgery for Idiopathic Epiretinal Membrane.

PURPOSE: To investigate the relationship between ophthalmic parameters-including optical coherence tomography (OCT) and OCT angiography findings-and foveal pit restoration in eyes that had undergone vitrectomy for idiopathic epiretinal membrane (iERM) removal. METHODS: This study retrospectively analyzed data of patients who underwent pars planar vitrectomy for the removal of epirentinal membrane. Only eyes with iERM above stage 2 with a follow-up over 6 months were included. Baseline data and changes in ophthalmic parameters were analyzed from 3 months before to 12 months after surgery. Additionally, we stratified iERM patients into two groups (foveal pit restoration and no restoration group). Longitudinal comparison analyses between the two groups were done in best-corrected visual acuity (BCVA), central foveal thickness (CFT) and foveal avascular zone (FAZ) areas measurements using swept-source OCT and OCT angiography. RESULTS: Forty-three patients with a mean age of 75 ± 5 years were enrolled. After surgery, BCVA, FAZ, and CFT showed improvements over time (all p < 0.002). Thirty-one patients were designated into the foveal pit restoration (R) group and 12 patients into the no restoration (NR) group. Differences in BCVA and FAZ area in both groups existed up to 6 months. However, BCVA improved and FAZ expanded (R, 0.20 ± 0.05 vs. NR, 0.18 ± 0.04) in both groups showing no statistical difference 12 months postsurgery. The CFT decreased in both groups, but the R group was thinner at every point compared to the NR group (all p < 0.05). CONCLUSIONS: The removal of epirentinal membrane in pars planar vitrectomy significantly improves BCVA, decreases the CFT and expands the FAZ. Foveal pit restoration improves BCVA, CFT, and FAZ area possibly at a faster rate in the early months but long-term improvements could be achieved regardless of the status of foveal pit restoration.

Preclinical Efficacy and Safety of VEGF-Grab, a Novel Anti-VEGF Drug, and Its Comparison to Aflibercept.

Purpose: VEGF-Grab is a novel anti-vascular endothelial growth factor (VEGF) candidate drug with higher affinity to both VEGF and placental growth factor (PlGF) compared to aflibercept. We investigated the preclinical efficacy of VEGF-Grab for ophthalmic therapy and compared it to that of aflibercept. Methods: The in vitro anti-VEGF efficacy of VEGF-Grab was determined using VEGF-induced cell proliferation/migration and tube formation assays. The in vivo antiangiogenic efficacy of intravitreal injection of either VEGF-Grab or aflibercept was evaluated using murine models of ocular angiogenesis: mouse oxygen-induced retinopathy (OIR) and rat laser-induced choroidal neovascularization (CNV). The in vivo retinal toxicity in the mouse eye resulting from the injection of either drug was evaluated with light and electron microscopy. Results: VEGF-Grab showed greater inhibition of VEGF-induced cell proliferation/migration than aflibercept, but it showed comparable inhibition of tube formation in vitro. In the in vivo OIR model, VEGF-Grab showed a comparable suppression of retinal neovascularization compared to aflibercept. Additionally, VEGF-Grab showed an efficacy similar to that of aflibercept in terms of CNV inhibition in the laser-induced CNV model. Histology and transmission electron microscopy showed no significant signs of toxicity in the mouse retina at 7 and 30 days following the intravitreal injection of VEGF-Grab or aflibercept. Conclusions: Compared to aflibercept, VEGF-Grab presented comparable in vivo antiangiogenic efficacy and superior in vitro anti-VEGF activity. The retinal safety profiles were comparable for the two drugs. Considering its known higher binding affinity to VEGF and PlGF compared to aflibercept, VEGF-Grab could be a potential candidate drug for neovascular retinal diseases and an alternative to aflibercept.

Laser and anti-vascular endothelial growth factor treatment for drusenoid pigment epithelial detachment in age-related macular degeneration.

This study aims to report the 12 months results of efficacy and safety of laser photocoagulation and anti-vascular endothelial growth factor (VEGF) injections for drusenoid pigment epithelial detachment (dPED). In this prospective study, patients with treatment naïve bilateral intermediate age-related macular degeneration, featuring dPED, with visual acuity ≤ 83 letters were enrolled. The study group received PASCAL laser (532 nm) along the periphery of the dPED, and the fellow eye served as a control group. To prevent complications of choroidal neovascularization, intravitreal anti-VEGF injections to laser treated eye were performed on a 3-month interval up to 1 year. Primary outcomes-drusen area, PED height-and secondary outcomes-best-corrected visual acuity (BCVA), contrast sensitivity, degree of metamorphopsia, NEI-VFQ 25, and fundus autofluorescence-were analyzed. Among 21 patients, a total of 20 patients satisfied the 12 months follow-up. Drusen area and PED height decreased significantly in the laser group, while no significant change appeared in the control group (74.1% vs. - 3.5%, P < 0.001; 76.6% vs. 0.1%, P < 0.001). Mean BCVA improved 4.6 letters in the laser group (vs. 1.1 letters in the control group, P = 0.019). As for safety, one study eye developed retinal pigment epithelial tear, and one control eye developed retinal angiomatous proliferation. Low energy laser photocoagulation and anti-VEGF injection in eyes with dPED showed some improvement in visual acuity. dPED regressed without developing center involving GA in the study eye, but a longer term follow-up is necessary to reveal the efficacy and safety of these treatments. The 2-year results of this study will be followed to reveal long term efficacy and safety of the treatment for dPED.

Association of Irregular Pigment Epithelial Detachment in Central Serous Chorioretinopathy with Genetic Variants Implicated in Age-related Macular Degeneration.

We evaluated phenotype and genotype correlation of central serous chorioretinopathy (CSC) patients with or without irregular pigment epithelial detachment (PED) on optical coherence tomography (OCT). For CSC, a flat, irregular protrusion of retinal pigment epithelium (RPE) with hyper-reflective sub-RPE fluid on OCT was defined as an irregular PED. Participants were classified into 5 subgroups; (1) total CSC (n = 280) (2) CSC with irregular PED (n = 126) (3) CSC without irregular PED (n = 154) (4) typical choroidal neovascularization (CNV) (n = 203) and (5) polypoidal choroidal vasculopathy (PCV) (n = 135). Ten known major AMD-associated single-nucleotide polymorphisms (SNPs) were analyzed. Age, sex adjusted logistic regression was performed for the association between subgroups. Association analysis between CSC without irregular PED and CNV revealed that significant difference for rs10490924 in ARMS2, rs10737680 in CFH, and marginally significant difference for rs800292 in CFH. Between CSC without irregular PED and PCV, rs10490924, rs10737680, and rs800292 were significantly different. In contrast, CSC with irregular PED and CNV revealed no SNP showing significant difference. Between CSC with irregular PED and PCV, only rs10490924 was significantly different. CSC with irregular PED and CSC without irregular PED revealed significant difference for rs800292, and marginal difference for rs10737680. These findings suggest CSC patients with irregular PED are genetically different from those without irregular PED and may have genetic and pathophysiologic overlap with AMD patients.

POSTTREATMENT POLYP REGRESSION AND RISK OF MASSIVE SUBMACULAR HEMORRHAGE IN EYES WITH POLYPOIDAL CHOROIDAL VASCULOPATHY.

PURPOSE: To study the association between the risk of massive submacular hemorrhage (SMH) and polyp regression after initial treatment of polypoidal choroidal vasculopathy using long-term follow-up data. METHODS: Retrospective study of 223 patients who were diagnosed with polypoidal choroidal vasculopathy and were followed up for up to 11 years. Subjects were categorized into "regression" and "no regression" groups, according to their polyp status after the initial treatment. Kaplan-Meier survival analyses were performed on development of massive SMH. The association between treatment methods and the occurrence of massive SMH was also analyzed. RESULTS: The incidence rates of massive SMH at 3, 6, and 9 years in the "no regression" group were 6.50, 22.59, and 38.03%, respectively, and in the "regression" group were 1.14, 6.47, and 10.92%, respectively (P = 0.005, log-rank test). The hazard ratio of massive SMH was 3.677 for cluster-type polyps and 0.271 for polyp regression after initial treatment. A higher rate of polyp regression was associated with photodynamic therapy (PDT) than anti-VEGF monotherapy (64.4 vs. 33.3%, P < 0.001). Additional anti-VEGF treatments after initial PDT showed lower risk of massive SMH than PDT only. (9.5 vs 38.5%, P = 0.005). CONCLUSION: The long-term risk of massive SMH after initial treatment on polypoidal choroidal vasculopathy is significantly higher in eyes with persistent polyps than those with regressed polyps. Ophthalmologists should pay attention to the risk of massive SMH and the polyp status when treating polypoidal choroidal vasculopathy.

Therapeutic effects of a novel siRNA-based anti-VEGF (siVEGF) nanoball for the treatment of choroidal neovascularization.

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries and is characterized by the development of choroidal neovascularization (CNV). Therapies for AMD have focused on suppressing angiogenic factors, such as vascular endothelial growth factor (VEGF), mainly via conventional anti-VEGF antibody agents. However, additional efforts have been made to develop effective small-interfering RNA (siRNA)-based intracellular therapeutic agents. In this study, we have manufactured a novel siRNA-based anti-VEGF nanoball (siVEGF NB). The siVEGF NB was composed of a siRNA hydrogel with a core of anti-VEGF sequence siRNA coated with branched PEI (bPEI) and hyaluronic acid (HA) in order by applying an electrical force. The novel siVEGF NBs, which were employed in a laser-induced CNV mouse model, were optimized as a retinal and choroidal delivery system through the vitreous humor to the sub-retinal space via CD44 receptor endocytosis on the inner limiting membrane, and showed therapeutic effects via pathways bypassing the TLR3-induced siRNA-class effect. The therapeutic effects of siVEGF NBs lasted for 2 weeks after intravitreal injection showing high targeting efficiency to the sub-retinal space. Thus, the newly developed siVEGF NB may have great potential for the delivery of RNAi-based therapeutics for ocular diseases, including AMD.

Incidence Rate of Massive Submacular Hemorrhage and its Risk Factors in Polypoidal Choroidal Vasculopathy.

PURPOSE: To investigate the incidence rate of massive submacular hemorrhage (SMH) in patients with polypoidal choroidal vasculopathy (PCV) and analyze the associated risk factors. DESIGN: Retrospective cohort study. METHODS: Patients diagnosed with PCV from May 2003 to May 2014 were included. Two hundred forty-five eyes of 245 patients were enrolled. The time between the initial visit to the clinic with subjective visual symptoms and the date of massive SMH was recorded. SMH larger than 4 disc diameters was defined as massive SMH. Age; hypertension; visual acuity (VA); indocyanine green angiography findings, including the greatest linear dimension, largest polyp size, and PCV type (cluster vs non-cluster); and treatment methods were reviewed for risk factor analysis using Kaplan-Meier survival and Cox regression analyses. RESULTS: The incidence rate of massive SMH within 1 year after the initial visit was 2.45%. Massive SMH occurred within 3, 5, and 10 years after the first visit in 6.17%, 11.09%, and 29.85% of patients, respectively. Cox regression analysis revealed that the cluster type of PCV was significantly associated with massive SMH (hazard ratio [HR], 3.418; P = .003). Photodynamic therapy followed by anti-vascular endothelial growth factor injection lowered the risk of massive SMH (HR = .242; P = .047]. Final VA in eyes with massive SMH was significantly lower than that in patients without massive SMH (1.34 ± 0.66 vs 0.63 ± 0.53 logMAR; P < .001). CONCLUSIONS: Patients with PCV who develop massive SMH experience severe vision loss. The incidence rate of massive SMH in PCV increases with time. The cluster type of polyp in PCV is a significant risk factor for massive SMH.

Anti-VEGF PolysiRNA Polyplex for the Treatment of Choroidal Neovascularization.

Choroidal neovascularization (CNV) is a major cause of severe vision loss in patients with age-related macular degeneration (AMD). Present ocular siRNA delivery technology is limited due to poor delivery through the retina to the choroid, where CNV originates. Our goal was to develop an optimized nanosized polyRNAi-based therapeutic delivery system to the subretinal space. We developed it by siRNA multimerization (polysiRNA) followed by coating with branched polyethylenimine and hyaluronic acid, and then evaluated its efficacy in vitro and in vivo. The polysiRNA polyplex showed a narrow size distribution (260.7 ± 43.27 nm) and negative charge (-4.98 ± 0.47 mV) owing to the hyaluronic acid outer layer. In vitro uptake of the polysiRNA polyplex by human ARPE cells was discovered, and the direct inhibition of VEGF mRNA translation was confirmed in B16F10 cells. The intravitreally administered polysiRNA polyplex overcame both the vitreous and retina barriers in vivo and reached the subretinal space efficiently. Intravitreal injection of the polysiRNA polyplex was not toxic to the retina in histopathology. Furthermore, intravitreal injections of the polysiRNA polyplex at both 1 and 7 days after laser photocoagulation inhibited laser-induced choroidal neovascularization, compared to that of the control (p < 0.05). These results suggest that anti-VEGF polysiRNA polyplexes show great potential in delivering multimeric RNAi-based therapeutics to treat retinal or choroidal disorders.

MANAGEMENT OF VITREAL LOSS FROM POSTERIOR CAPSULAR RUPTURE DURING CATARACT OPERATION: Posterior Versus Anterior Vitrectomy.

PURPOSE: To compare the efficacy between 23-gauge sutureless pars planar vitrectomy (PPV) and anterior vitrectomy in the management of vitreous loss associated with posterior capsular rupture during cataract surgery. METHODS: Medical records of 139 eyes which sustained posterior capsular rupture and vitreal prolapse to anterior chamber during cataract surgery were retrospectively reviewed. Thirty-two eyes which underwent 23-gauge sutureless PPV (group PPV) and 107 eyes which underwent anterior vitrectomy (group AntV) were compared in postoperative visual and anatomical outcomes, operation time, and complications. RESULTS: No significant differences were found between the groups in final best-corrected visual acuity of 20/40 or better (AntV vs. PPV = 80.4 vs. 90.6%, P = 0.139). However, the visual recovery rates (20/40 or better) 1 day, 1 week, 1 month postoperatively were significantly higher in group PPV (AntV vs PPV = 22.4 vs. 44%, 32.2 vs 58.6, 51.9 vs. 78.1%). Postoperative intraocular pressure-related complications requiring medication were less evident in group PPV (AntV vs. PPV = 52.3 vs. 6.3%, P < 0.001). Twelve cases (11.2%) of group AntV and 0 cases of group PPV underwent secondary operation during follow-up. Although no postoperative complications occurred in group PPV, complications such as endophthalmitis, retinal detachment, cystoid macular edema, intraocular lens instability were observed in the AntV group (none vs. 14%, P = 0.022). CONCLUSION: Twenty-three-gauge sutureless PPV is a safe and reliable solution for managing vitreous loss during cataract surgery. Therefore, it is expected to be considered primarily in institutes with vitreoretinal surgeons.

Morphologic Characteristics of Choroid in the Major Choroidal Thickening Diseases, Studied by Optical Coherence Tomography.

We investigated morphologic features of choroid in the choroidal thickening diseases, including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV), and Vogt-Koyanagi-Harada disease (VKH), by a novel tomographic classification system of the choroid. This cross-sectional study involved 30 patients with active CSC, 30 patients with active PCV, and 27 patients with active VKH, and 30 normal controls. Utilizing enhanced depth imaging optical coherence tomography, we classified the morphology of the choroid into five categories: 1) Standard (S), 2) Dilated outer layer and Attenuated inner layer (DA), 3) Darkened (D), 4) Marbled (M), and 5) Pauci-Vascular (PV) types. Additional tomographic characteristics of the choroid such as choroidal vascular dilation, convolution, scleral invisibility, and choroidal hyper- or hypo-thickening were identified as well. The distribution of five choroidal tomographic morphology and additional tomographic characteristics in each group were analyzed. The DA type was observed in the CSC group more frequently than in the normal control group (53.3% vs 3.3%, P < 0.001). Additional tomographic characteristics, such as choroidal vascular dilation (76.7%), and choroidal hyper-thickening (36.7%), were more prevalent in the CSC group than in the control group. The PCV group showed higher prevalence of DA type (33.3% vs. 3.3%, P = 0.006) than the control group. The VKH group showed a significantly higher frequency of the D type (63.0%), convolution (40.7%), and scleral invisibility (70.4%) than controls (0% for all three findings). In conclusion, CSC and PCV shared common morphologic characteristics of choroid, including dilated outer vascular layer and focally attenuated innermost layer. Dense hypo-reflectivity and convolution of choroid were the specific tomographic markers for acute VKH. A new tomographic classification system of choroid may provide discrimination ability and insight into major pachychoroidopathies.

Ocular toxocariasis: clinical features, diagnosis, treatment, and prevention.

Despite being one of the most common zoonotic infections worldwide, human toxocariasis has been one of the neglected tropical diseases. Although most human infections are asymptomatic, two main syndromes of human toxocariasis are classically recognized: systemic toxocariasis, which encompasses diseases in major organs; and ocular toxocariasis (OT), disease in the eye or optic nerve, caused by the migration of Toxocara larvae into the eye. OT is usually a unilateral disease, which typically presents as retinal granuloma, a yellowish or whitish inflammatory mass, in the posterior pole or peripheral retina. Granuloma itself or other comorbid conditions such as epiretinal membrane, macular edema, and retinal detachment can lead to permanent retinal damage and visual loss in eyes with OT. OT is diagnosed clinically by identification of clinical signs on ophthalmologic examination. Serological tests, such as enzyme-linked immunosorbent assay (ELISA) for detection of serum antibody against the Toxocara larvae, can confirm the diagnosis. In addition, serum immunoglobulin E and detection of ocular fluid antitoxocara antibody by ELISA may give additional aid to the diagnosis. Standard treatment of OT is corticosteroid in patients with active intraocular inflammation. Although the role of anthelmintic therapy is unclear, favorable outcome has been reported by combined corticosteroid and albendazole therapy in eyes with active inflammation. Prevention, by increasing public awareness and reducing the risk of infection, is also important. Recently, the association between ingestion of uncooked meat or liver and toxocariasis was reported, especially in adult patients. Future research on the potential source of infection, diagnosis, and treatment should be performed.

Thermal imaging comparison of Signature, Infiniti, and Stellaris phacoemulsification systems.

BACKGROUND: To compare the heat production of 3 different phacoemulsification machines under strict laboratory test conditions. More specifically, the thermal behavior was analyzed between the torsional modality of the Infiniti system and longitudinal modalities of the Abbot WhiteStar Signature Phacoemulsification system and Bausch and Lomb Stellaris system. METHODS: Experiments were performed under in-vitro conditions in this study.Three phacoemulsification handpieces (Infiniti, Signature, and Stellaris) were inserted into balanced salt solution-filled silicone test chambers and were imaged side-by-side by using a thermal camera. Incision compression was simulated by suspending 30.66-gram weights from the silicone chambers. The irrigation flow rate was set at 0, 1, 2, 3, 4, and 5 cc/min and the phacoemulsification power on the instrument consoles was set at 40, 60, 80, and 100%. The highest temperatures generated from each handpiece around the point of compression were measured at 0, 10, 30, and 60 seconds. RESULTS: Under the same displayed phacoemulsification power settings, the peak temperatures measured when using the Infiniti were lower than when using the other two machines, and the Signature was cooler than the Stellaris. At 10 seconds, torsional phacoemulsification with Infiniti at 100% power showed data comparable to that of the Signature at 80% and the Stellaris at 60%. At 30 seconds, the temperature from the Infiniti at 100% power was lower than the Signature at 60% and the Stellaris at 40%. CONCLUSIONS: Torsional phacoemulsification with the Infiniti generates less heat than longitudinal phacoemulsification with the Signature and the Stellaris. Lower operating temperatures indicate lower heat generation within the same fluid volume, which may provide additional thermal protection during cataract surgery.

Human papilloma virus in retinoblastoma tissues from Korean patients.

PURPOSE: Recent reports suggest the association of human papilloma virus (HPV) with retinoblastoma. This study was performed to elucidate whether HPV infection is related to retinoblastoma among Koreans. METHODS: A total of 54 cases diagnosed with retinoblastoma were enrolled from Seoul National University Children's Hospital and Seoul Metropolitan Government-Seoul National University Boramae Medical Center. Presence of human papilloma viral DNA was detected by in situ hybridization in formalin-fixed paraffin-embedded retinoblastoma tissues using both probes against high- and low risk HPV types. RESULTS: The mean age at diagnosis was 22.0 months (range, 1.1 to 98.0 months), and the mean age at enucleation was 27.8 months (range, 1.5 to 112.7 months) among the 54 patients with retinoblastoma. HPV was not detected in any of the retinoblastoma samples using either high risk or low risk HPV probes. CONCLUSIONS: Our study, being the first study in the Korean population, proposes that HPV infection may have no causal relationship with retinoblastoma in Koreans.

Regression of iris neovascularization after subconjunctival injection of bevacizumab.

To describe three cases of neovascular glaucoma (NVG) where iris or angle neovascularization regressed remarkably after subconjunctival bevacizumab injections used as the initial treatment before pan retinal photocoagulation (PRP) and/or filtering surgery. Three consecutive NVG patients whose intraocular pressure (IOP) was not controlled with maximal medication were offered an off-label subconjunctival injection of bevacizumab (2.5-3.75 mg/0.1-0.15 mL, Avastin). Bevacizumab was injected into the subconjunctival space close to the corneal limbus in two or three quadrants using a 26-gauge needle. Serial anterior segment photographs were taken before and after the injection. Following subconjunctival injection of bevacizumab, iris or angle neovascularization regressed rapidly within several days. Such regression was accompanied by lowering of IOP in all three cases. The patients underwent subsequent PRP and/or filtering surgery, and the IOP was further stabilized. Our cases demonstrate that subconjunctival bevacizumab injection can be potentially useful as an initial treatment in NVG patients before laser or surgical treatment.

A family of oculofaciocardiodental syndrome (OFCD) with a novel BCOR mutation and genomic rearrangements involving NHS.

Oculofaciocardiodental syndrome (OFCD) is an X-linked dominant disorder associated with male lethality, presenting with congenital cataract, dysmorphic face, dental abnormalities and septal heart defects. Mutations in BCOR (encoding BCL-6-interacting corepressor) cause OFCD. Here, we report on a Korean family with common features of OFCD including bilateral 2nd-3rd toe syndactyly and septal heart defects in three affected females (mother and two daughters). Through the mutation screening and copy number analysis using genomic microarray, we identified a novel heterozygous mutation, c.888delG, in the BCOR gene and two interstitial microduplications at Xp22.2-22.13 and Xp21.3 in all the three affected females. The BCOR mutation may lead to a premature stop codon (p.N297IfsX80). The duplication at Xp22.2-22.13 involved the NHS gene causative for Nance-Horan syndrome, which is an X-linked disorder showing similar clinical features with OFCD in affected males, and in carrier females with milder presentation. Considering the presence of bilateral 2nd-3rd toe syndactyly and septal heart defects, which is unique to OFCD, the mutation in BCOR is likely to be the major determinant for the phenotypes in this family.