Novel ATF6 homozygous variant in a Chinese patient with achromatopsia.

BACKGROUND: ATF6-associated Achromatopsia (ACHM) is a rare autosomal recessive disorder characterized by reduction of visual acuity, photophobia, nystagmus, and poor color vision. METHODS: Detailed ophthalmological examinations were performed in a Chinese patient with ACHM. Whole exome sequencing and Sanger sequencing were performed to detect the disease-causing gene in the patient. RESULTS: A 6-year-old girl presented photophobia, low vision and reduced color discrimination. Small yellow lesion in the macula of both eyes was observed. FAF demonstrated hypofluorescence in the macular fovea. OCT images revealed interruption of ellipsoid and interdigitation zone in the foveal area and a loss of the foveal pit. ERG showed relatively normal rod responses and unrecordable cone responses. Sequencing result identified a novel splicing variant c.354 + 6T>C in the ATF6 gene (NM_007348.4). CONCLUSIONS: We reported detailed clinical features and genetic analysis of a new Chinese ATF6-associated patient with ACHM.

Advances in swept-source optical coherence tomography and optical coherence tomography angiography.

Background: The fast development of swept-source optical coherence tomography (SS-OCT) and swept-source optical coherence tomography angiography (SS-OCTA) enables both anterior and posterior imaging of the eye. These techniques have evolved from a research tool to an essential clinical imaging modality. Main text: The longer wavelength and faster speed of SS-OCT and SS-OCTA facilitate better visualization of structure and vasculature below pigmented tissue with a larger field of view of the posterior segment and 360-degree visualization of the anterior segment. In the past 10 years, algorithms dealing with OCT and OCTA data also vastly improved the image quality and enabled the automated quantification of OCT- and OCTA-derived metrics. This technology has enriched our current understanding of healthy and diseased eyes. Even though the high cost of the systems currently limited the widespread use of SS-OCT and SS-OCTA at the first beginning, the gap between research and clinic practice got obviously shortened in the past few years. Conclusions: SS-OCT and SS-OCTA will continue to evolve rapidly, contributing to a paradigm shift toward more widespread adoption of new imaging technology in clinical practice.

Hyaluronan-CD44 Interaction Regulates Mouse Retinal Progenitor Cells Migration, Proliferation and Neuronal Differentiation.

Cell-based therapies have shown great potential because of their abilities to replace dying retinal neuron cells and preserve vision. The migration, proliferation and differentiation of retinal progenitor cells(RPCs) plays a vital role in the integration of the RPCs into the retina when transplanted into the host. Our study aimed to explore the effects of Hyaluronan(HA)-CD44 interactions on the regulation of RPCs migration, proliferation and differentiation, and investigate the underlying regulatory mechanisms. We found that CD44 was expressed in RPCs, and the HA-CD44 interaction markedly improved RPCs adhesion and migration. The stimulation of microRNA-21(miR-21) expression by the HA-CD44 interaction was protein kinase C (PKC)/Nanog-dependent in RPCs. Treatment of RPCs with PKC- or Nanog-specific ASODN or miR-21 antagomir effectively blocked HA-mediated RPCs adhesion and migration. Moreover, Rho-Kinase(ROK)/ Grb2-associated binders(Gab-1) associated phosphatidylinositol 3-kinase(PI3K)/AKT signalling activation was required for HA-CD44 interaction mediated RPCs proliferation and neuronal differentiation. Our findings demonstrated new roles for the HA-CD44 interaction in regulating the migration, proliferation and neuronal differentiation of RPCs. HA-CD44 signalling could represent a novel approach to controlling RPC fates, and the findings may be instructive for the application of RPCs for future therapeutic applications.

Rapid flattening of massive hemorrhagic retinal pigment epithelial detachment secondary to polypoidal choroidal vasculopathy after surgery.

Purpose: To report 2 polypoidal choroidal vasculopathy (PCV) patients whose massive hemorrhagic pigment epithelial detachments (PEDs) were flattened within a short period after surgery. Observations: Two PCV patients who presented with submacular hemorrhage and massive hemorrhagic PEDs with sizes of more than 50 disc areas underwent pars plana vitrectomy combined with subretinal injection of tissue plasminogen activator (tPA), intravitreous injection of anti-vascular endothelial growth factor medicine, and perfluoropropane tamponade. The massive hemorrhagic PEDs were flattened within a short period after both surgeries, and both patients experienced improved visual acuity. Conclusions: These findings suggest that subretinal injection of tPA together with perfluoropropane tamponade promotes the rapid clearance of hemorrhage under RPE.

Evaluation of a new Q-switched Nd:YAG laser on premacular hemorrhage.

BACKGROUND: Premacular hemorrhage is among the causes of sudden deterioration of visual acuity. This study aimed to investigate the therapeutic outcomes of a new Q-switched Nd:YAG laser on premacular hemorrhage. METHODS: Retrospective, case series study of 16 eyes from 16 patients diagnosed with premacular hemorrhage, including 3 cases of Valsalva retinopathy, 8 cases of retinal macroaneurysm, 3 cases of diabetic retinopathy, 1 case of trauma-related hemorrhage and 1 case with leukemia. A 1064nm Q-switched Nd:YAG laser was performed to puncture the posterior hyaloid and inner limiting membrane to drain the hemorrhage. RESULTS: The success rate of 16 patients with premacular hemorrhage drainage was 100% in this study. Improved visual acuity was observed in each patient. CONCLUSIONS: In this case series of 16 patients, the new Q-switched Nd:YAG laser was successful in draining premacular hemorrhage with no serious complications.

Investigation of the Role of Carcinoembryonic Antigen-Related Cell Adhesion Molecule-1 in Diabetic Retinopathy.

PURPOSE: Diabetic retinopathy (DR) has become a major cause of blindness with increased prevalence of diabetic mellitus. Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) plays a part in pathological neovascularization. This study aimed to investigate the role of CEACAM1 in the progression of DR. METHODS: Aqueous and vitreous samples were collected from proliferative or non-proliferative DR and the control group. Multiplex fluorescent bead-based immunoassays were used to detect the levels of Cytokines. Expression of CEACAM1, VEGF, VEGF receptor 2 (VEGFR2) and hypoxia-induced factor-1α (HIF-1α) were detected in human retinal microvascular endothelial cells (HRECs). RESULTS: CEACAM1 and VEGF levels were significantly upregulated in PDR group and positively correlated with PDR progression. Expression CEACAM1 and VEGFR2 were increased in HRECs under hypoxic conditions. The HIF-1α/VEGFA/VEGFR2 pathway was blocked by CEACAM1 siRNA in vitro. CONCLUSIONS: CEACAM1 might play a role in the pathology of PDR. CEACAM1 might be a therapeutic target for retinal neovasculariztion.

Cell division cycle 42 reflects disease risk, symptoms, Th1/Th2 disproportion, and its short-term variation indicates symptom amelioration after treatment in allergic rhinitis patients.

BACKGROUND: Cell division cycle 42 (CDC42) modulates the pathogenesis of allergic rhinitis (AR) through regulating immunity, allergic response, and T-helper (Th)1/Th2 imbalance. This study aimed to evaluate the potential of CDC42 to reflect disease risk, symptom scores, and Th1/Th2 axis of AR and the correlation of its vertical change with symptom amelioration after treatment. METHODS: CDC42, Th1 cells, and Th2 cells in the peripheral blood mononuclear cells (PBMCs) and interferon-γ and interleukin-4 in the serum were determined in 200 AR patients. Simultaneously, PBMC CDC42 was detected in 50 non-atopic obstructive snoring patients [as disease controls (DCs)] and 50 healthy controls (HCs). RESULTS: CDC42 was increased in AR patients compared with DCs and HCs (both p < 0.001) but showed no difference between DCs and HCs (p = 0.054). In AR patients, CDC42 was positively linked to rhinorrhea, itching, sneezing, and total nasal symptom scores (TNSS) (all p < 0.05), but not congestion score (p = 0.052). Meanwhile, CDC42 showed positive correlations with Th2 cells (p < 0.001) and interleukin-4 (p = 0.005), a negative correlation with Th1/Th2 axis (p = 0.001), but no correlation with Th1 cells (p = 0.095) or interferon-γ (p = 0.174). Notably, CDC42 at week 4 after treatment (W4) was reduced compared with that at enrollment (W0) (p < 0.001) and positively correlated with TNSS at W4 (p < 0.001); from W0 to W4, CDC42 change also positively correlated with TNSS change (p = 0.004). CONCLUSION: CDC42 is elevated and positively correlates with symptom scores and Th2 cells, whose short-term reduction reflects symptom alleviation in AR patients.

Beneficial Actions of Essential Fatty Acids in Streptozotocin-Induced Type 1 Diabetes Mellitus.

The essential fatty acids (EFA), n3 alpha-linolenic acid (ALA), and n6 linoleic acid (LA) are of benefit in diabetes mellitus, but their mechanisms of action are unknown. We, therefore, examined the effects of EFAs on the metabolism, gut microbiota, and inflammatory and retinal histopathology indices in streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) animals, and we assessed the levels of vitreal lipoxin A4 (LXA4)-derived from LA-in subjects with diabetic retinopathy (DR). STZ-induced T1DM rats received LA or ALA 100 µg/day intraperitoneally on alternate days for 21 days, and their blood glucose; lipid profile; plasma, hepatic, and retinal fatty acid profiles (by gas chromatography); retinal histology; activities of hepatic and retinal desaturases; and inflammatory markers (by qRT-PCR) were evaluated. Gut microbiota composition was assayed by 16S rDNA sequencing technology of the fecal samples, and their short-chain fatty acids and bile acids were assayed by gas chromatography, liquid chromatography coupled with tandem mass spectrometry, respectively. The human vitreal fatty acid profiles of subjects with proliferative DR and LXA4 levels were measured. LA and ALA significantly improved the plasma glucose and lipid levels; increased the abundance of Ruminococcaceae (the ALA-treated group), Alloprevotella, Prevotellaceae_Ga6A1_group, Ruminococcaceae_UCG_010, and Ruminococcus_1 (the LA-treated group) bacteria; enhanced acetate and butyrate levels; and augmented fecal and hepatic concentrations of cholic acid, chenodeoxycholic acid, and tauro ursodeoxycholic acid in ALA- and LA-treated animals. Significant STZ-induced decreases in plasma LA, gamma-linolenic acid, arachidonic acid, and ALA levels reverted to near normal, following LA and ALA treatments. Significant changes in the expression of desaturases; COX-2, 5-LOX, and 12-LOX enzymes; and cytokines in T1DM were reverted to near normal by EFAs. DR subjects also had low retinal LXA4 levels. The results of the present study show that ALA and LA are of significant benefit in reversing metabolism, gut microbiota, and inflammatory and retinal index changes seen in T1DM, suggesting that EFAs are of benefit in diabetes mellitus.

Cytomegalovirus Retinitis and Retinal Detachment following Chimeric Antigen Receptor T Cell Therapy for Relapsed/Refractory Multiple Myeloma.

Cytomegalovirus (CMV) retinitis is a rare end-organ disease of CMV infection and is a marker of severe immunosuppression, especially in human immunodeficiency virus (HIV)-positive patients. In multiple myeloma (MM) patients, CMV retinitis has been reported in the post-transplant setting, with an incidence lower than 0.2%, and in patients receiving lenalidomide. Here, we describe the first case of CMV retinitis in myeloma patients following B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T (BCMA CAR-T) cell therapy. In addition to CMV, the patient developed multiple infections including a mouth ulcer, pneumonia, and fungal enteritis. While the complete remission (CR) status of MM was maintained, he regained a visual acuity of 20/1000 after appropriate ophthalmologic treatment. This single case illustrates the potential of BCMA CAR-T therapy to induce profound humoral immunosuppression, and demonstrates an imperative need for an established standard of monitoring and prophylaxis of post-CAR-T infections.

Genome-Wide Analysis of KNOX Transcription Factors and Expression Pattern of Dwarf-Related KNOX Genes in Pear.

KNOTTED1-like homeobox (KNOX) transcription factors (TFs) belonging to the homeobox TF family play important roles in plant growth, development, and responses to abiotic and biotic stress. However, little information is available on KNOX TF in pear (Pyrus). In this study, 19 PbKNOXs TFs were re-identified in pear (Pyrus bretschneideri Rehd.). Phylogenetic analysis revealed that the TFs were clustered into three groups with 10 conserved motifs, some of which were group- or subgroup-specific, implying that they are important for the functions of the KNOX in these clades. PbKNM1 and PbKNM2 are KNM (encodes a MEINOX domain but not a homeodomain) genes identified in pear for the first time. KNOX genes in Pyrus and Malus were closely related, and a collinear relationship among PbKNOX genes in Pyrus and Malus was observed. Analysis of the expression patterns of PbKNOX genes in different tissues, at various growth stages, and in response to abiotic and biotic stress revealed that PbKNOXs are involved in plant growth and development. Our comparative transcriptional analysis of dwarf mutant varieties revealed that genes belonging to class I are highly expressed compared with genes in other classes. Analysis of the expression of PbKNOX genes in the hybrid offspring of vigorous and dwarf varieties revealed that PbKNOX genes were highly expressed in the vigorous offspring and weakly expressed in the dwarf offspring. These findings provide new insight into the function of KNOX TFs in pear and will aid future studies of dwarf fruit trees.

Visual Loss Caused by Central Retinal Artery Occlusion After Bee Sting: A Case Report.

A bee sting can lead to an extremely rare case of visual loss caused by central retinal artery occlusion (CRAO). In this study, we report a 66-year-old healthy woman who was referred to our Eye Center because of visual loss, which had occurred after bee sting 2 days earlier. The visual acuity was no light perception (NLP). Examination revealed left eyelid edema, conjunctiva congestion, a 6-mm fixed pupil, scattered retinal hemorrhage, and white-appearing ischemic retina with one small area of the normal-appearing retina temporal to the optic disk. Fundus fluorescein angiography revealed CRAO with one cilioretinal artery sparing. Her systemic workup revealed hypersensitivity, hypercoagulable state, myocardial damage, and hepatic damage. After topical and systemic treatments, the visual acuity was still NLP with improved systemic workup. In brief, CRAO may occur after bee sting, and visual acuity should be monitored for early diagnosis.

[Characteristics and Source of VOCs During O3 Pollution Between August to September, Langfang Development Zones].

A total of 99 volatile organic compound(VOC) species were detected the Langfang development zones based on continuous monitoring using a ZF-PKU-1007 between August 25 and September 30, 2018. The concentrations, reactivity, and sources of VOCs were studied under different O3 concentrations using compositional analysis. The results showed that the average VOCs concentration during the research period was(75.17±38.67)×10-9, and was(112.33±30.96)×10-9, (66.25±34.84)×10-9 on pollution days and cleaning days, respectively(VOCs concentrations were 69.6% higher on pollution days). The contribution of VOCs species to the ozone formation potential(OFP) were ranked in the order aldehydes > aromatics > alkenes > alkanes. In the case of L·OH, the main contributions were from aromatics(30.0%) and alkenes(25.8%) on pollution days, while the contribution from aromatic alkenes(29.8%) was a slightly higher than aromatics(28.0%) on cleaning days. By applying the positive matrix factorization(PMF) model, five major VOCs sources were extracted, namely vehicle emissions(34.4%), solvent usage and evaporation(31.7%), the petrochemical industry(15.7%), combustion(11.1%), and plant emissions(7.9%). The contributions of solvent usage and evaporation and plant emission sources on pollution days were 13.1% and 1.2% higher than on cleaning days, respectively, which was likely due to relatively higher temperatures on these days. Therefore, vehicle emissions and solvent usage and evaporation should be priorities in VOCs control strategies for the Langfang development zones between August to September.

Clinical Characteristics and Visual Outcomes in Patients with Intralenticular Foreign Bodies with Self-Sealing Corneal Penetrating Wounds.

PURPOSE: Siderosis bulbi may occur as a result of retained intralenticular foreign bodies (ILFBs) that were missed during examination in patients with self-sealing wounds and without a significant decrease in visual acuity. This study aimed to explore the clinical characteristics and visual outcomes of ILFBs with self-sealing corneal penetrating wounds. METHODS: Fifteen eyes of 15 patients with ILFBs and self-sealing corneal penetrating wounds, seen between October 2014 and September 2019, were retrospectively analyzed. Data regarding the patient demographics, clinical features, surgical procedure, and initial and final best-corrected visual acuity (BCVA) were analyzed. RESULTS: All patients were male with a mean age of 41 years. The foreign bodies passed through the cornea, sometimes through the iris, through the anterior capsule, and finally localized in the lens. All ILFBs were pointed and metallic objects and were successfully removed with phacoemulsification and posterior chamber intraocular lens (IOL) implantation. Anterior capsule violation was found in three eyes, but no posterior capsule rupture was found. The IOL was placed in a capsule bag in all the cases. The BCVA ranged from 20/200 to 20/25 preoperatively and improved to between 20/32 and 20/20 at the last follow-up visit. The IOLs were well-centered. Apart from posterior capsule opacity in four eyes, no other postoperative complications were found. CONCLUSIONS: In patients with a pointed metallic ILFB and self-sealing corneal penetrating wounds (with or without cataracts), early diagnosis and removal of the metallic ILFB combined with lens removal and IOL implantation may avoid late complications and achieve good visual outcomes.

Outcomes and Prognostic Factors of Posttraumatic Endophthalmitis: A Three-Year Retrospective Study.

PURPOSE: To describe the clinical features, management, and outcomes of patients with posttraumatic endophthalmitis (PTE) and to determine risk factors for poor visual prognosis. METHODS: We retrospectively reviewed the medical records of 42 consecutive patients presenting with PTE who were treated at our institution between 2017 and 2019. Each patient's data, including demographic characteristics, ocular injury details, surgical records, patient outcomes, and laboratory results, were collected and analyzed. Multivariate analysis was conducted to determine the factors associated with poor visual outcomes. RESULTS: In our series, male (n = 36, 85.7%) and patients below 60 years of age (20-40 years, 23.8%; 40-60 years, 57.14%) comprised most of the total cohort. On presentation, 39 (92.8%) of the 42 PTE patients presented best-corrected visual acuity (BCVA) worse than counting fingers. Pars plana vitrectomy (PPV) was performed in all the patients. 59.5% (n = 25) of the patients' BCVA improved after surgery and 33.3% (n = 14) achieved BCVA of 20/200 or better. The rate of evisceration was 7.1% (n = 3). Of the 42 specimens, the culture was positive in 10 (23.8%) eyes. By univariate analysis, factors including sex, occupation, systemic disease, source of trauma, lens injury, silicone oil tamponade, usage of intravitreal antibiotics, BCVA at presentation, and culture positive for any organism did not affect the final visual outcome. The features associated with poor BCVA (grouped as < 20/200 and ≥ 20/200) included older age (P=0.035), corneal-sclera wound (versus sclera wound) (P=0.047), retained intraocular foreign bodies (IOFBs) (P=0.006), treatment > 3 days (versus < 1 day) (P=0.033), and more times of surgeries (P=0.033). CONCLUSIONS: PTE is a severe complication of penetrating globe injuries associated with irreversible visual loss. Our results highlighted the importance of conducting early therapeutic PPV and IOFB removal to achieve better visual outcomes.

Optical Coherence Tomography Angiography-Based Quantitative Assessment of Morphologic Changes in Active Myopic Choroidal Neovascularization During Anti-vascular Endothelial Growth Factor Therapy.

Purpose: To establish quantitative profile of the morphologic changes among patients with active myopic choroidal neovascularization (mCNV) before and after anti-vascular endothelial growth factor (VEGF) therapy using optical coherence tomography angiography (OCTA) to assess the therapeutic response. Methods: Patients with active mCNV who received anti-VEGF injections between February 2017 to October 2020 and fit the study criteria were retrospectively reviewed. Quantitative analysis of their OCTA images were carried out to evaluate the morphologic features and vascular changes of mCNV lesions in response to anti-VEGF therapy. For further quantitative profiling, mCNV area, fractal dimension, vessel area, vessel density, vessel diameter, vessel length, vessel junction, junction density, and vessel tortuosity were obtained by means of advanced skeletonization postprocessing analyses. Results: Thirty-one eyes of 29 consecutive patients with OCTA-positive mCNV lesions (mean spherical equivalent: -12.55 ± 3.24 diopters) were included. The 31 cases were divided into two phenotypes at baseline: organized interlacing pattern (83.87%) and disorganized vascular loops pattern (16.13%). The values of mCNV area, fractal dimension, vessel area, vessel length, vessel junction, and junction density decreased remarkably 1 month after the initial anti-VEGF injection (p < 0.001). Although, vessel density, vessel diameter, and vessel tortuosity increased meanwhile, only vessel diameter displayed statistical significance (p = 0.027). Of note, relative ratio analysis showed that vessel junction was the most sensitive biomarker in response to anti-VEGF therapy, reflecting a mean decrease of 50.36%. Sensitivity lowered successively in biomarkers of vessel length, vessel area, junction density, mCNV area, and fractal dimension. In addition, percent change of mCNV area (r = 0.552, p = 0.002), fractal dimension (r = 0.446, p = 0.017), vessel area (r = 0.518, p = 0.005), and vessel length (r = 0.440, p = 0.019) were moderately associated with that of central retinal thickness. Conclusions: The study showed morphological as well as quantitative changes on OCTA responding to anti-VEGF treatment in mCNV patients, among which vessel junctions might be the most predictive biomarker. OCTA-based analysis, providing intuitive images and a large spectrum of quantitative data at the same time, could promote new insights into the therapeutic response assessment in mCNV patients.

Serum vitamin D level in mice with allergic rhinitis is correlated with inflammatory factors.

OBJECTIVE: This study aimed to explore the correlation between serum vitamin D and inflammatory factors in mice with allergic rhinitis. METHODS: Female BALB/c mice in SPF grade were used to construct allergic rhinitis model by systemic injection and repeated nasal antigens. 12 allergic rhinitis mice without other treatment were treated as group A, another 12 allergic rhinitis mice treated with vitamin D3 were selected as group B, and group C included 12 mice that received PBS injection. Nasal symptoms, behavioral scores, serum vitamin D levels, nasal mucosal pathology HE staining, serum inflammatory factors IL-4 and IFN-γ levels were compared between the groups. The relationship between serum vitamin D level and serum inflammatory factor levels were analyzed. RESULTS: The nasal itching, sneezing, nasal secretions, behavioral scores, and total scores of group A and group B were significantly different from those of group C (P < 0.05). It showed obvious nasal mucosal edema, interrupted and lodging cilia, increased goblet cells carrying secretory bodies, and the inflammatory cells infiltrated under the mucosa in group A. They were significantly reduced in group B compared with group A. Total vitamin D levels and vitamin D3 levels exhibited obviously difference among the groups (F = 53.19, P < 0.05). IL-4 and INF-γ levels in group A and group B were markedly higher than those in group C (P < 0.05). IL-4 decreased following serum vitamin D level elevation (Y = -3.3515X+122.04, R2 = 0.9984). CONCLUSION: Vitamin D in young mouse is implicated with allergic rhinitis and attenuated inflammation. Vitamin D level was significantly negatively correlated with IL-4, suggesting that vitamin D was closely related to inflammation.

Microvascular comparison in younger and older patients with retinal vein occlusion analyzed by OCT angiography.

BACKGROUND: To compare changes in retinal microvasculature of young and elderly patients with retinal vein occlusion (RVO) after anti-VEGF treatment. METHODS: RVO patients who underwent anti-VEGF treatment were retrospectively reviewed and categorized into two groups based on age. The OCT angiography images were obtained during each visit. Best corrected visual acuity (BCVA), vessel density (VD) and foveal avascular zone (FAZ) were measured and compared between the two groups. Vision improvements and retinal microvasculature changes were also correlated. RESULTS: Twenty patients with 20 eyes were enrolled in the younger group and 46 patients with 46 eyes were enrolled in the older group. Younger patients demonstrated better BCVA, higher VD and smaller FAZ than older patients at 12 months after the first anti-VEGF treatment. The improvement of VD was observed only in the younger group. A positive correlation between vision improvement and VD increase was noted. CONCLUSIONS: Young patients with RVO can achieve rapid rehabilitation of deep retinal vasculature which lead to a better visual outcome.