The novel HLA-B*27:267 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.

HLA-B*27:267 differs from HLA-B*27:04:01 by one nucleotide in exon 2.

Srgap2 suppression ameliorates retinal ganglion cell degeneration in mice.

Slit-Robo GTPase-activating protein 2 (SRGAP2) plays important roles in axon guidance, neuronal migration, synapse formation, and nerve regeneration. However, the role of SRGAP2 in neuroretinal degenerative disease remains unclear. In this study, we found that SRGAP2 protein was first expressed in the retina of normal mice at the embryonic stage and was mainly located in the mature retinal ganglion cell layer and the inner nuclear layer. SRGAP2 protein in the retina and optic nerve increased after optic nerve crush. Then, we established a heterozygous knockout (Srgap2+/-) mouse model of optic nerve crush and found that Srgap2 suppression increased retinal ganglion cell survival, lowered intraocular pressure, inhibited glial cell activation, and partially restored retinal function. In vitro experiments showed that Srgap2 suppression activated the mammalian target of rapamycin signaling pathway. RNA sequencing results showed that the expression of small heat shock protein genes (Cryaa, Cryba4, and Crygs) related to optic nerve injury were upregulated in the retina of Srgap2+/- mice. These results suggest that Srgap2 suppression reduced the robust activation of glial cells, activated the mammalian target of rapamycin signaling pathway related to nerve protein, increased the expression of small heat shock protein genes, inhibited the degeneration of retinal ganglion cells, and partially restored optic nerve function.

An effective treatment and suspicious adverse reaction to Ibrutinib in a patient diagnosed with splenic B-cell lymphoma/leukaemia with prominent nucleoli: A first case report.

RATIONALE: Splenic B-cell lymphoma/leukemia with prominent nucleoli (SBLPN) is a new classification, which is so rare that it lacks clinical data. PATIENT CONCERNS: An increased proportion of prolymphocytes (84%) in the bone marrow smear. Whole exon sequence analysis revealed a TP53 mutation. DIAGNOSES: Combining the clinical features with laboratory test results led to a diagnosis of SBLPN which was made according to the 5th edition of the WHO classification of hematolymphoid tumors, although the patient was diagnosed with B-PLL when guided by the 4th edition of the WHO classification. INTERVENTIONS: The use of Ibrutinib as an effective treatment. OUTCOMES: The patient was in complete remission after 5 months of Ibrutinib and then died of sudden aortic dissection. LESSONS: Ibrutinib was an effective regimen for SBLPN. Aortic dissection might be considered as a suspicious adverse reaction to Ibrutinib.

KeratoScreen: Early Keratoconus Classification With Zernike Polynomial Using Deep Learning.

PURPOSE: We aimed to investigate the usefulness of Zernike coefficients (ZCs) for distinguishing subclinical keratoconus (KC) from normal corneas and to evaluate the goodness of detection of the entire corneal topography and tomography characteristics with ZCs as a screening feature input set of artificial neural networks. METHODS: This retrospective study was conducted at the Affiliated Eye Hospital of Wenzhou Medical University, China. A total of 208 patients (1040 corneal topography images) were evaluated. Data were collected between 2012 and 2018 using the Pentacam system and analyzed from February 2019 to December 2021. An artificial neural network (KeratoScreen) was trained using a data set of ZCs generated from corneal topography and tomography. Each image was previously assigned to 3 groups: normal (70 eyes; average age, 28.7 ± 2.6 years), subclinical KC (48 eyes; average age, 24.6 ± 5.7 years), and KC (90 eyes; average age, 25.9 ± 5.4 years). The data set was randomly split into 70% for training and 30% for testing. We evaluated the precision of screening symptoms and examined the discriminative capability of several combinations of the input set and nodes. RESULTS: The best results were achieved using ZCs generated from corneal thickness as an input parameter, determining the 3 categories of clinical classification for each subject. The sensitivity and precision rates were 93.9% and 96.1% in subclinical KC cases and 97.6% and 95.1% in KC cases, respectively. CONCLUSIONS: Deep learning algorithms based on ZCs could be used to screen for early KC and for other corneal ectasia during preoperative screening for corneal refractive surgery.

Characteristics of macular microvasculature before and after idiopathic macular hole surgery.

AIM: To evaluate the macular microvasculature before and after surgery for idiopathic macular hole (MH) and the association of preoperative vascular parameters with postoperative recovery of visual acuity and configuration. METHODS: Twenty eyes from 20 patients with idiopathic MH were enrolled. Optical coherence tomography angiography (OCTA) images were obtained before, 2wk, 1, and 3mo after vitrectomy with internal limiting membrane peeling. Preoperative foveal avascular zone (FAZ) area and perimeter and regional vessel density (VD) in both layers were compared according to the 3-month best-corrected visual acuity (BCVA). RESULTS: The BCVA improved from 0.98±0.59 (logMAR, Snellen 20/200) preoperatively to 0.30±0.25 (Snellen 20/40) at 3mo postoperatively. The preoperative deep VD was smaller and the FAZ perimeter was larger in the 3-month BCVA<20/32 group (all P<0.05). A significant reduction was observed in FAZ parameters and all VDs 2wk postoperatively. Except for deep perifoveal VD, all VDs recovered only to their preoperative values. The postoperative FAZ parameters were lower during follow-up. Decreases in preoperative deep VDs were correlated with worse postoperative BCVA (Pearson's r=-0.667 and -0.619, respectively). A larger FAZ perimeter (Spearman's r=-0.524) and a lower deep perifoveal VD preoperatively (Pearson's r=0.486) were associated with lower healing stage. CONCLUSION: The status of the deep vasculature may be an indicator of visual acuity in patients with a closed MH. Except for the deep perifoveal region, VD recovers only to preoperative levels.

Foveal pit morphological changes in asymptomatic carriers of the G11778A mutation with Leber's hereditary optic neuropathy.

AIM: To investigate the foveal pit morphology changes in unaffected carriers and affected Leber's hereditary optic neuropathy (LHON) patients with the G11778A mutation from one family. METHODS: This study was a prospective cross-sectional study. Both eyes from 16 family members (age from 9 to 47y) with the G11778A mutation were analyzed and compared with 1 eye from 20 normal control subjects. Eleven family members with the G11778A mutation but without optic neuropathy were classified as unaffected carriers (n=22 eyes). Five family members (n=10 eyes) expressed the LHON phenotype and were classified as affected patients. Retinal images of all the subjects were taken by optical coherence tomography (OCT), and an automatic algorithm was used to segment the retina to eight layers. Horizontal and vertical OCT images centered on the fovea were used to measure intra-retinal layer thicknesses and foveal morphometry. RESULTS: Thicker foveal thickness, thinner foveal pit depth, and flatter foveal slopes were observed in unaffected carriers and affected LHON patients (all P<0.001). Further, the slopes of all four sectors in the LHON were flatter than those in the unaffected carriers (all P<0.001). Compared with the control group, affected LHON patients had a thinner retinal nerve fiber layer (RNFL), ganglion cell layer and inner plexiform layer (GCL+IPL), and total retina (all P<0.01). The retinal nerve fiber layer (RNFL) of affected patients was 38.0% thinner than that of controls while the GCL+IPL was 40.1% thinner. CONCLUSION: The foveal pit morphology shows changes in both unaffected carriers and affects patients. RNFL and GCL+IPL are thinner in affected LHON patients but not in unaffected carriers.

Short term effect of choroid thickness in the horizontal meridian detected by spectral domain optical coherence tomography in myopic children after orthokeratology.

AIM: To investigate choroidal thickness changes in the horizontal meridian after orthokeratology. METHODS: This is a prospective cross-sectional observed study. Subjects (n=30; 11.3±1.7y) with low-to-moderate myopia (-1.0 to -6.0 diopters), wore orthokeratology (Ortho-K) lenses for 3mo. Before and after Ortho-K, OCT scans were made through the fovea in the horizontal meridian. Choroid thickness around the fovea was acquired by custom software. The analyzed regions along the horizontal meridian were divided into 7 equal zones. Ocular parameters were measured by Lenstar LS 900 non-contact biometry. RESULTS: Only the right eye ocular parameters were analyzed in this study. Before Ortho-K, choroidal thickness along the horizontal meridian was 273.7±31.8 µm in the temporal zone, 253.1±38.6 µm in the macula zone, and 194.8±52.2 µm in the nasal zone. After Ortho-K, the choroid was thicker in each horizontal zone (P<0.05). The increased thickness was greatest in the temporal zone (13.5±22.5 µm) and least in the nasal zone (8.4±14.2 µm). The axial length (AL) increased 0.02 mm (P>0.05). The choroid thickness change in each horizontal zone was negatively correlated with AL (r, -0.3 to -0.4; P<0.05) except one of the nasal zones. CONCLUSION: In myopic children, the thickness of the choroid is greatest in the temporal zone and thinnest in the nasal zone. After nightly Ortho-K for 3mo, the thickness increase along the horizontal meridian. The choroid thickness changes are negatively correlated with the change of AL.

Prognostic impact of elevation of vascular endothelial growth factor family expression in patients with non-small cell lung cancer: an updated meta-analysis.

BACKGROUND: The vascular endothelial growth factor family has been implicated in tumorigenesis and metastasis. The prognostic value of each vascular endothelial growth factor family member, particular VEGF/ VEGFR co-expression, in patients with non-small lung cancer remains controversial. MATERIALS AND METHODS: Relevant literature was identified by searching PubMed, EMBASE and Web of Science. Studies evaluating expression of VEGFs and/or VEGFRs by immunohistochemistry or ELISA in lung cancer tissue were eligible for inclusion. Hazard ratios (HRs) and 95% confidence intervals (CIs) from individual study were pooled by using a fixed- or random-effect model, heterogeneity and publication bias analyses were also performed. RESULTS: 74 studies covering 7,631 patients were included in the meta-analysis. Regarding pro-angiogenesis factors, the expression of VEGFA (HR=1.633, 95%CI: 1.490-1.791) and VEGFR1 (HR=1.924, 95%CI: 1.220-3.034) was associated separately with poor survival. Especially, VEGFA over-expression was an independent prognostic factor in adenocarcinoma (ADC) (HR=1.775, 95%CI: 1.384-2.275) and SCC (HR=2.919, 95%CI: 2.060-4.137). Co-expression of VEGFA/VEGFR2 (HR=2.011, 95%CI: 1.405-2.876) was also significantly associated with worse survival. For lymphangiogenesis factors, the expression of VEGFC (HR=1.611, 95%CI: 1.407-1.844) predicted a poor prognosis. Co-expression of VEGFC/VEGFR3 (HR=2.436, 95%CI: 1.468-4.043) emerged as a preferable prognostic marker. CONCLUSIONS: The expression of VEGFA (particularly in SCC and early stage NSCLC), VEGFC, VEGFR1 indicates separately an unfavorable prognosis in patients with NSCLC. Co-expression VEGFA/ VEGFR2 is comparable with VEGFC/VEGFR3, both featuring sufficient discrimination value as preferable as prognostic biologic markers.