Neuroprotective Effects of Novel Treatments on Acute Optic Neuritis-A Meta-Analysis.

Optic neuritis, inflammation of the optic nerve, can cause visual impairment through retinal nerve fiber layer (RNFL) degeneration. Optical coherence tomography could serve as a sensitive noninvasive tool for measuring RNFL thickness and evaluating the neuroprotective effects of treatment. We conducted a meta-analysis to compare RNFL loss between novel add-on treatments and corticosteroid therapy at least 3 months after acute optic neuritis. The outcome measures were mean differences (MDs) in (1) RNFL thickness compared with the baseline in the affected and unaffected eye and (2) LogMAR visual acuity (VA). Seven studies involving five novel agents (memantine, erythropoietin, interferon-beta, phenytoin, and clemastine) were analyzed. When compared with the baseline RNFL thickness of the affected eye, the neuroprotective effects of novel add-on treatments could not be demonstrated. The difference in visual outcomes was also not significant between the two treatment groups. One study revealed that phenytoin has the potential to alleviate RNFL loss when the baseline thickness of the unaffected eye is considered. Larger randomized controlled trials with suitable outcome measures are warranted to evaluate the neuroprotective effects of novel treatments. Further studies should also tailor therapies to specific patient populations and investigate a more targeted treatment for acute optic neuritis.

PREDICTED PROTEIN STRUCTURE VARIATIONS INDICATE THE CLINICAL PRESENTATION OF CYP4V2-RELATED BIETTI CRYSTALLINE DYSTROPHY.

PURPOSE: To investigate the relationship between different CYP4V2 disease-causing variants and disease severity in Bietti crystalline dystrophy (BCD). METHODS: Twenty-one subjects from 19 unrelated families with a clinical diagnosis of BCD were enrolled. A novel severity prediction score for BCD based on the predicted molecular impact of CYP4V2 variants was applied for grouping and subsequent analyses. The more severe variants led to less CYP4V2 protein function preservation and a higher severity prediction score. RESULTS: All subjects harbored two alleles of CYP4V2 disease-causing variants, of which c.802-8_810del17insGC was the most prevalent (14/21, 66.67%) and c.1507G>C was novel. According to the severity score, the subjects were categorized into severe, moderate, and mild groups with different preservation of central vision (mean logMAR visual acuity 0.95 ± 0.82, 0.89 ± 1.22, and 0.56 ± 0.64, respectively). The patients with a lower severity score had slower disease progression. CONCLUSION: This is the first cohort study of BCD in Taiwan, and we established a novel BCD severity index based on the molecular impact of different CYP4V2 variants. More severe impairment of CYP4V2 protein led to a more severe disease course with earlier progression. Our results could be helpful in identifying a therapeutic window for patients with BCD.

Application of deep learning image assessment software VeriSee™ for diabetic retinopathy screening.

PURPOSE: To develop a deep learning image assessment software VeriSee™ and to validate its accuracy in grading the severity of diabetic retinopathy (DR). METHODS: Diabetic patients who underwent single-field, nonmydriatic, 45-degree color retinal fundus photography at National Taiwan University Hospital between July 2007 and June 2017 were retrospectively recruited. A total of 7524 judgeable color fundus images were collected and were graded for the severity of DR by ophthalmologists. Among these pictures, 5649 along with another 31,612 color fundus images from the EyePACS dataset were used for model training of VeriSee™. The other 1875 images were used for validation and were graded for the severity of DR by VeriSee™, ophthalmologists, and internal physicians. Area under the receiver operating characteristic curve (AUC) for VeriSee™, and the sensitivities and specificities for VeriSee™, ophthalmologists, and internal physicians in diagnosing DR were calculated. RESULTS: The AUCs for VeriSee™ in diagnosing any DR, referable DR and proliferative diabetic retinopathy (PDR) were 0.955, 0.955 and 0.984, respectively. VeriSee™ had better sensitivities in diagnosing any DR and PDR (92.2% and 90.9%, respectively) than internal physicians (64.3% and 20.6%, respectively) (P < 0.001 for both). VeriSee™ also had better sensitivities in diagnosing any DR and referable DR (92.2% and 89.2%, respectively) than ophthalmologists (86.9% and 71.1%, respectively) (P < 0.001 for both), while ophthalmologists had better specificities. CONCLUSION: VeriSee™ had good sensitivity and specificity in grading the severity of DR from color fundus images. It may offer clinical assistance to non-ophthalmologists in DR screening with nonmydriatic retinal fundus photography.

Prognostic factors for combined ranibizumab and prompt verteporfin photodynamic therapy for polypoidal choroidal vasculopathy.

PURPOSE: To investigate the prognostic factors for the combined therapy of ranibizumab and prompt verteporfin photodynamic therapy (vPDT) for eyes with polypoidal choroidal vasculopathy (PCV). METHODS: Sixty-two PCV eyes of 62 patients that received the initial treatment of intravitreal ranibizumab followed by vPDT within 1 week plus a 2nd intravitreal ranibizumab 1 month later in one single medical center were retrospectively enrolled. Best-corrected visual acuity (BCVA) and parameters obtained from optical coherence tomography at baseline, 3 months, 6 months and 1  year were measured and compared. Factors associated with polyp regression, recurrent hemorrhage and visual improvement were analyzed. RESULTS: After the loading treatment, complete and partial polyp regression was achieved in 53.6% and 39.3% of cases, respectively at Month 3. The mean logarithm of the minimum angle of resolution of BCVA improved from 0.64 ±â€¯0.38 to 0.55 ±â€¯0.46 (P =  0.008) at Month 12. Recurrent hemorrhage (P =  0.001) and previous anti-vascular endothelial growth factor (VEGF) treatment (P =  0.017) were associated with poorer visual improvement at Month 12. Incomplete polyp regression (P =  0.038) and previous anti-VEGF treatment (P =  0.005) were associated with a higher risk of recurrent hemorrhage. CONCLUSIONS: Recurrent hemorrhage was associated with poor visual improvement after combined ranibizumab and vPDT for PCV. Complete polyp eradication was associated with a lower risk of recurrent hemorrhage. Patients who had previously received anti-VEGF were associated with recurrent hemorrhage and poor visual improvement; more frequent follow-ups and more aggressive subsequent treatments may be needed for these cases.

Optic Disc Parameters of Myopic Children with Atropine Treatment.

PURPOSE: To characterize optic disc parameters, retinal nerve fiber layer thickness (RNFLT), and the intraocular pressure (IOP) of myopic children under continual topical 0.25% atropine treatment. METHODS: From October 1, 2010 to September 31, 2011, 67 eyes of 35 myopic children were recruited. The children were treated with 0.25% atropine nightly for myopia control. Visual acuity, refraction, IOP, axial length (AL, IOL Master), RNFLT, and optic disc parameters (Stratus OCT) were measured at enrollment and every 2 months. All patients had at least 1 year of follow-up. RESULTS: Enrolled children had a mean age of 10.3 ± 2.4 years (5-15 years). Of the 67 studied eyes, the mean spherical equivalent (SE) was -2.60 ± 1.58 diopters (D) (-6.75--0.5 D). Under the treatment of 0.25% atropine, myopia increased by 0.53 ± 0.10D per year (P < 0.0001), and AL elongated by 0.245 ± 0.042 mm per year (P < 0.0001). No significant change was noted in the IOP and optic nerve parameters including peripapillary RNFLT, areas of optic disc, cup and rim, or cup/disc ratio over the follow-up period during atropine treatment (P > 0.05). CONCLUSIONS: 0.25% Atropine treatment for myopia control did not significantly affect the IOP, optic nerve parameters, and RNFLT in children over a mean of 15.2 ± 2.4 months treatment and follow-up. 0.25% Atropine is a relatively safe option for myopia control.

Subtenon Triamcinolone Acetonide Removal for Uncontrolled Ocular Hypertension After Posterior Subtenon Injection of Triamcinolone Acetonide.

PURPOSE: To report the control of intraocular pressure (IOP) after removal of subtenon triamcinolone acetonide (TA) plaques in patients with uncontrolled ocular hypertension after posterior subtenon injection of triamcinolone acetonide (PSTA) and to evaluate the factors associated with rapid IOP normalization after subtenon TA removal. MATERIALS AND METHODS: Data from 8 eyes of 7 patients receiving excision of subtenon TA plaques for uncontrolled ocular hypertension after PSTA in 1 hospital from June 2010 to December 2012 were retrospectively collected. The percentage of IOP lowering on postoperative day 1 and the time to IOP normalization after subtenon TA removal were reported. Pearson correlation analysis was used to analyze the factors for rapid IOP normalization after subtenon TA removal. RESULTS: The IOP lowering on postoperative day 1 ranged from 12% to 75%. All cases achieved IOP normalization within a mean of 2.5±1.9 days (range, 1 to 5 d) after subtenon TA removal. Fewer kinds of antiglaucoma agents used before subtenon TA removal was associated with greater IOP lowering on postoperative day 1 (P=0.01) and more rapid return to normal IOP (P=0.01). Older age and more time from PSTA to ocular hypertension were both correlated with shorter time to achieve IOP normalization after operation (P=0.01 and 0.02, respectively). CONCLUSIONS: In medically uncontrolled ocular hypertension after PSTA, excision of subtenon TA plaques provided IOP normalization as rapidly as 1 to 5 days. Fewer preoperative antiglaucoma agents, older age, and more time from PSTA to ocular hypertension were correlated with more rapid IOP normalization after subtenon TA removal.

Triphenylene-based tris-N-heterocyclic stannylenes.

Two planar tridentate N-heterocyclic stannylenes are synthesized from the corresponding 2,3,6,7,10,11-hexaamino-triphenylene and Sn[N(TMS)2]2. Multinuclear NMR and absorption spectra of these tris-stannylenes are reported. Molecular structure of the N-benzhydryl-substituted tris-stannylene is also realized.

Photodynamic therapy for choroidal hemangioma unresponsive to ranibizumab.

PURPOSE: To report a patient with circumscribed choroidal hemangioma with serous macular detachment successfully treated with photodynamic therapy (PDT) after being unresponsive to treatment with intravitreal ranibizumab. CASE REPORT: A 63-year-old Asian woman was incidentally found to have a circumscribed choroidal hemangioma without symptoms in the left eye during a routine health examination. Blurred vision of the left eye developed 3.5 years later, and a serous macular detachment was observed. Two consecutive intravitreal ranibizumab injections were administered, but the subretinal fluid (SRF) persisted and the vision did not improve. One PDT session was then given, and the SRF resolved completely within 1 month. The best-corrected visual acuity improved from 20/50 before treatment to 20/25 at 4 months after the PDT. The tumor thickness also decreased from 3.84 mm before treatment to 2.86 mm at 14 months after PDT. CONCLUSIONS: Circumscribed choroidal hemangioma with serous macular detachment may not respond to anti-vascular endothelial growth factor agents. Photodynamic therapy may be an effective choice in such cases to remove SRF and improve vision.

Ankrd17, an ubiquitously expressed ankyrin factor, is essential for the vascular integrity during embryogenesis.

Ankyrin repeat domain 17 (Ankrd17) encodes an ubiquitously expressed protein with two clusters of ankyrin repeats. We have used gene targeting strategy to ablate the Ankrd17 gene in mouse. The Ankrd17-deficient mice died between embryonic day (E) 10.5 and E11.5 due to cardiovascular defects. Serious hemorrhages were detected and the vascular smooth muscle cells (vSMCs) surrounding the vessels were drastically reduced in the Ankrd17-deficient embryos, suggesting that the vascular maturation was not completed. Interestingly, vSMC differentiation marker genes were up-regulated in the mutant embryos. Our data have demonstrated the indispensability of Ankrd17 functioning for vascular maturation during early development. The Ankrd17-deficient mice also provide a new animal model for the analysis of the regulatory pathways of the differentiation of vSMC precursor cells.

Epigenetic regulation of the Drosophila chromosome 4 by the histone H3K9 methyltransferase dSETDB1.

The polytene chromosomes of Drosophila melanogaster consist of condensed heterochromatin regions most of which are in the chromocenter, telomeres, and the fourth chromosome. Whereas suppressor of variegation 3-9 [SU(VAR)3-9], a histone methyltransferase, is mainly responsible for lysine 9 of histone H3 (H3K9) methylation of the chromocenter and consequent binding of the heterochromatin-protein HP1, the enzyme for painting of the fourth chromosome by H3K9 methylation has been elusive. We show here that dSETDB1, the Drosophila ortholog of the mammalian SETDB1, is an authentic H3K9 methyltransferase and a pleiotropic regulator of the fly's development. Drosophila mutants hypomorphic or null in dSETDB1 expression lose most of the H3K9 methylation as well as HP1-binding on the fourth chromosome. We also show that binding of painting of fourth (POF), a known fourth chromosome-specific protein, and the dSETDB1-controlled H3K9 methylation of this chromosome are interdependent. Furthermore, POF and dSETDB1 interact with each other in vivo. The deregulation of H3K9 methylation, HP1-binding, and POF-binding resulted in, on the average, a global reduction of gene expression from the fourth chromosome but not the other chromosomes. Deficiency of dSETDB1 also up-regulated the expression of HP1. These results have suggested an interactive network, as controlled in part by dSETDB1, regulating the epigenetic modification and gene expression of Drosophila chromosome 4.