These 62 patients with the Kabuki make-up syndrome (KMS) were collected in a collaborative study among 33 institutions and analyzed clinically, cytogenetically, and epidemiologically to delineate the phenotypic spectrum of KMS and to learn about its cause. Among various manifestations observed, most patients had the following five cardinal manifestations: 1) a peculiar face (100%) characterized by eversion of the lower lateral eyelid; arched eyebrows, with sparse or dispersed lateral one-third; a depressed nasal tip; and prominent ears; 2) skeletal anomalies (92%), including brachydactyly V and a deformed spinal column, with or without sagittal cleft vertebrae; 3) dermatoglyphic abnormalities (93%), including increased digital ulnar loop and hypothenar loop patterns, absence of the digital triradius c and/or d, and presence of fingertip pads; 4) mild to moderate mental retardation (92%); and 5) postnatal growth deficiency (83%). Thus the core of the phenotypic spectrum of KMS is rather narrow and clearly defined. Many other inconsistent anomalies were observed. Important among them were early breast development in infant girls (23%), and congenital heart defects (31%), such as a single ventricle with a common atrium, ventricular septal defect, atrial septal defect, tetralogy of Fallot, coarctation of aorta, patent ductus arteriosus, aneurysm of aorta, transposition of great vessels, and right bundle branch block. Of the 62 KMS patients, 58 were Japanese, an indication that the syndrome is fairly common in Japan. It was estimated that its prevalence in Japanese newborn infants is 1/32,000. All the KMS cases in this study were sporadic, the sex ratio was even, there was no correlation with birth order, the consanguinity rate among the parents was not high, and no incriminated agent was found that was taken by the mothers during early pregnancy. Three of the 62 patients had a Y chromosome abnormality involving a possible common breakpoint (Yp11.2). This could indicate another possibility, i.e., that the KMS gene is on Yp11.2 and that the disease is pseudoautosomal dominant. These findings are compatible with an autosomal dominant disorder in which every patient represents a fresh mutation. The mutation rate was calculated at 15.6 X 10(6).

Diabetic nephropathy and retinopathy (DR) including diabetic macular edema (DMe) are representative microvascular complications of diabetes. We conducted a retrospective multicenter study analyzing records from patients with DR (132 eyes in 70 patients) and end-stage renal diseases (ESRD) who underwent hemodialysis for the first time. We demonstrated that the central retinal thickness (CRT) values were significantly decreased (p < 0.0001), and the best-corrected visual acuity (BCVA) values were improved (p < 0.05) at 1, 3, 6, 9, and 12 months after hemodialysis initiation, in spite of a lack of specific ocular treatments for DME in 93.2% of eyes. We found a significant positive correlation in the rates of cRt changes between right and left eyes. the cRt reductions were greater in eyes with DMe type subretinal detachment than in those with spongelike swelling and cystoid macular edema. the visual outcome gain was associated with the CRT reduction at 12 months in the eyes with good initial BCVA (≧20/50). Hemodialysis induction contributed to functional and anatomical improvements after 1 year, independently of initial laboratory values before the hemodialysis. Diabetes mellitus (DM) is a chronic disease characterized by persistent hyperglycemia requiring continuous care and management. Diabetic retinopathy (DR) and nephropathy (DN) are representative microvascular complications of DM 1. DR and DN are life-threatening because these complications can lead to blindness and end-stage renal diseases (ESRD), respectively 1. In patients with DR, the visual function can be severely damaged by complications of diabetic macular edema (DME) 2. DME results from the hyperpermeability of retinal vessels, and intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents has become a gold standard in DME treatment 3-5. However, many patients with DME show a low response to anti-VEGF treatment, and repeated injections are required to maintain its therapeutic effects 6-8. Dialysis is an effective treatment modality for ESRD. In Japan, the number of patients undergoing dialysis increases yearly, and the prevalence was 2,597 patients per million population in 2016 9. DN was the most common kidney disease (38.8%) requiring dialysis in 2016, followed by chronic glomerulonephritis (28.8%) and nephrosclerosis (9.9%). ESRD and DME are sometimes present in the same patient, and assessing the effect of hemodialysis on DME is clinically important.

Purpose To investigate the relationship between microaneurysm (MA) density and residual oedema after intravitreal injection of an anti‐vascular endothelial growth factor agent for the treatment of diabetic macular oedema (DMO). Methods Patients with DMO were divided into those with residual oedema (RO) and those with no residual oedema (NRO) by the presence and absence of oedema at 1 month after intravitreal injection of either aflibercept or ranibizumab. We then compared MA density, best corrected visual acuity (BCVA), central retinal thickness (CRT) and size of the severely thickened area, as indicated by a white area (WA) on optical coherence tomography. Results We examined 48 eyes in the RO group and 25 eyes in the NRO group (n = 73). In both groups, the CRT and WA size significantly decreased and BCVA improved at 1 month and thereafter. CRT was significantly higher and BCVA was poor in the RO group at 1 and 3 months, while WA size was larger at 1, 3 and 6 months compared with the NRO group (p < 0.05). The number of injections in the RO group (3.62 ± 1.75) was larger than the NRO group (1.89 ± 0.97; p < 0.0001). At 1 and 6 months, the MA density in the area with persistent oedema was significantly higher than in the area with improved oedema (1 month: p = 0.0001, 6 months: p = 0.029). Conclusion High MA density and extensive swelling may be characteristic of RO following treatment for DMO with intravitreal injection of either aflibercept or ranibizumab.

PURPOSE. The purpose of this study was to evaluate whether photocoagulation of the retinal nonperfusion area suppresses ocular vascular endothelial growth factor (VEGF) expression in a rabbit retinal vein occlusion (RVO) model. METHODS.The retinas of pigmented rabbits were made ischemic by a laser on the main branch of retinal veins following intravenous injection of Rose Bengal. The eyes were enucleated before treatment and at 1, 7, and 14 days after laser occlusion. VEGF protein levels in the vitreous humor, sensory retina, and retinal pigment epithelium-choroid were measured with enzyme-linked immunosorbent assay. In situ hybridization of VEGF messenger RNA was performed to detect the location of VEGF expression in the sensory retina.RESULTS. In the vitreous body, the VEGF protein level in the RVO group, but not that in the RVO þ panretinal photocoagulation group, significantly increased on day 14. In the retina, the VEGF protein level in the RVO þ panretinal photocoagulation group was significantly higher than that in the RVO group on day 1, but was significantly lower than that in the RVO group on days 7 and 14. In the in situ hybridization analysis, the RVO group showed a high expression of VEGF in the inner nuclear and ganglion cell layers on days 7 and 14. In contrast, VEGF expression in the RVO þ panretinal photocoagulation group was strongly suppressed in both the inner nuclear and ganglion cell layers on days 7 and 14.CONCLUSIONS. This study is the first using an animal RVO model to demonstrate that laser photocoagulation of the retinal nonperfusion area suppresses VEGF-A expression in the retina.

We report on a sporadic case of heterotaxia with a de novo chromosome structural abnormality. The patient had inversely located heart (dextrocardia), stomach, duodenum, and cecum. In addition, she had cerebral atrophy, hypertelorism with telecanthus, infraorbital skin furrows, ear-lobe grooves, prominent maxilla and teeth, large carp mouth, short fifth fingers with limited flexion, generalized hypotonicity, and severe psychomotor retardation. High-resolution chromosome banding analysis demonstrated an apparently balanced translocation: 46,XX,t(6;18)(q21;q21.3). It is hypothesized that both heterotaxia and the chromosomal abnormality in the patient are causally related and a putative situs determining gene has been disrupted by the chromosome break, i.e., a position effect or a cryptic deletion at around the breakpoints. The translocation in our patient may be a good source for positional cloning of the gene.