Observation of the Curative Effect of the Dexamethasone Vitreous Cavity Implant for the Treatment of Irvine-Gass Syndrome.

Objective: To investigate the clinical efficacy of dexamethasone vitreous cavity implants (Ozurdex) for the treatment of macular edema (Irvine-Gass Syndrome) after cataract surgery. Method: Eight patients (eight eyes) with Irvine-Gass syndrome were enrolled for vitreous injections with Ozurdex. The patients included six men (six eyes) and two women (two eyes) with a mean age of 67.12 ± 11.92 years. Changes in the patients best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure were compared before and after treatment. Result: The mean visual acuity BCVA of the patients was 0.81 ± 0.26 before implantation, which improved to 0.20 ± 0.12, 0.13 ± 0.09, and 0.15 ± 0.13 at 2 weeks, 1 month, and 3 months after implantation, respectively ( P < 0.001). The patient's mean CMT before implantation was 703.00 ± 148.88 µm, and it reduced to 258.87 ± 37.40 µm, 236.25 ± 28.74 µm, and 278.00 ± 76.82 µm at 2 weeks, 1 month, and 3 months after implantation, respectively ( P < 0.001). Conclusion: The dexamethasone vitreous cavity implant (Ozurdex) is a safe and effective treatment, which can effectively improve patient's visual acuity and reduce macular edema associated with cataract surgery.

Macular Morphology in Patients With Diabetic Retinopathy Treated by ILM Peeling: A Propensity Score-Matched Analysis.

BACKGROUND AND OBJECTIVE: To analyze the effects of vitrectomy combined with internal limiting membrane (ILM) peeling in patients with diabetic retinopathy (DR) by propensity score-matched analysis. PATIENTS AND METHODS: Patients with proliferative DR that underwent pars plana vitrectomy were divided into two groups: without or with additional ILM peeling. Propensity score-matched analyses of variables were carried out. Optical coherence tomography (OCT) was conducted at the 6-month follow-up. The primary outcome measures were epiretinal membrane (ERM), intraretinal cystic changes, recurrent macular edema, and blurring of the inner segment/outer segment (IS/OS) margin. RESULTS: There were 41 patients in Group 1 (non-ILM peeling) and 41 patients in Group 2 (ILM peeling). ERM was observed in 11 of 41 eyes (26.8%) in Group 1, and three of 41 eyes (7%) in Group 2 at the 6-month follow-up (P = .019). Intraretinal cystoid changes were observed in 13 eyes of Group 1 and four eyes of Group 2 (P = .014). The median central macular thickness was 250.00 ± 135.09 µm in Group 1 and 235.00 ± 101.55 µm in Group 2 (P = .738). Macular edema was observed in 24 eyes (58.5%) in Group 1 and 19 eyes (46.3%) in Group 2 (P = 0.269). There was no significant difference in foveal dip angle between the groups (P = .820). The IS/OS margin was disrupted in 48.8% and 56.1% of eyes in Groups 1 and 2, respectively, without significant difference. There was also no significant difference in best-corrected visual acuity (BCVA) between two groups before surgery, and there was no significant difference in BCVA between two groups at 6 months after surgery (P = .13). CONCLUSION: The authors' results indicate that vitrectomy combined with ILM peeling can minimize ERM formation and eliminate intraretinal cystoid changes, but the functional recovery is limited. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:420-425.].

Novel Norrie disease gene mutations in Chinese patients with familial exudative vitreoretinopathy.

PURPOSE: This study aims to analyze the Norrie disease gene (NDP) variants in patients with familial exudative vitreoretinopathy (FEVR) and their clinical features. METHODS: Thirty-three Chinese patients (22 familial and 11 simplex) who were diagnosed as FEVR underwent detailed ocular examinations in Beijing Tongren Hospital. Peripheral venous blood was drawn from the patients and their family members for the extraction of genomic DNA. All exons of NDP gene were analyzed by direct sequencing of PCR-amplified DNA fragments. RESULTS: Four novel mutations in NDP gene were identified in four X-linked FEVR families: a C → T transversion, c. 625C → T, in exon 3, resulting in a serine-to-proline change in codon 73 (S73P); a C → G transition, c. 751C → G, in exon 3, resulting in an arginine-to-glycine change in codon 115 (R115G); a T → C transversion of nucleotide 331 at 5'UTR in exon 2 (c.331 T → C); and a C → T transversion of the nucleotide 5 in intron 1 (IVS1 + 5C → T). The mutations were not present in the control group (n = 100). CONCLUSIONS: Our results extend the spectrum of NDP gene mutations. The mutations in the non-coding region of NDP may play a crucial role in the pathogenesis of FEVR.

Risk Factors of Recurrent Retinal Detachment Following Surgical Treatment for Rhegmatogenous Retinal Detachment: A Retrospective Study.

OBJECTIVE: To identify potential risk factors for recurrent retinal detachment after surgical treatment for rhegmatogenous retinal detachment with choroidal detachment (RRD-CD) in a Chinese population. METHODS: A total of 1212 patients with RRD-CD admitted to Beijing Tongren Hospital from 2004 to 2018 were reviewed retrospectively. The rate of recurrent retinal detachment was calculated, and risk factors were analyzed by logistic regression analysis. RESULTS: The average age of the patients was 48.51 years, 760 patients (62.7%) were male, and 630 patients (52.0%) had right eye disease. The recurrence rate in the same eye was 21.3%. The incidence of recurrence retinal detachment was higher in patients who were male, middle age, and with poor preoperative vision, longer axial length, and scleral buckling. Recurrence usually occurred 3 months after surgery. CONCLUSION: Male, middle age, longer axial length, and scleral buckling could be risk factors for recurrent retinal detachment following surgical treatment in patients with RRD-CD.

Early Blockade of TLRs MyD88-Dependent Pathway May Reduce Secondary Spinal Cord Injury in the Rats.

To determine the role of toll-like receptors (TLRs) myeloid differentiation factor 88 (MyD88) dependent pathway in the spinal cord secondary injury, compression injury was made at T8 segment of the spinal cord in adult male Sprague-Dawley rats. Shown by RT-PCR, TLR4 mRNA in the spinal cord was quickly elevated after compression injury. Intramedullary injection of MyD88 inhibitory peptide (MIP) resulted in significant improvement in locomotor function recovery at various time points after surgery. Meanwhile, injury area, p38 phosphorylation, and proinflammation cytokines in the injured spinal cord were significantly reduced in MIP-treated animals, compared with control peptide (CP) group. These data suggest that TLRs MyD88-dependent pathway may play an important role in the development of secondary spinal cord injury, and inhibition of this pathway at early time after primary injury could effectively protect cells from inflammation and apoptosis and therefore improve the functional recovery.

Beneficial effect of the traditional chinese drug shu-xue-tong on recovery of spinal cord injury in the rat.

Shu-Xue-Tong (SXT) is a traditional Chinese drug widely used to ameliorate stagnation of blood flow, such as brain or myocardial infarction. Whether SXT may have therapeutic value for spinal cord injury (SCI), during which ischemia plays an important role in its pathology, remains to be elucidated. We hypothesized that SXT may promote SCI healing by improving spinal cord blood flow (SCBF), and a study was thus designed to explore this possibility. Twenty-five male Sprague-Dawley rats were used. SCI was induced by compression, and SXT was administrated 24 h postinjury for 14 successive days. The effects of SXT were assessed by means of laser-Doppler flowmetry, motor functional analysis (open-field walking and footprint analysis), and histological analysis (hematoxylin-eosin and thionin staining and NeuN immunohistochemistry). SXT significantly promoted SCBF of the contused spinal cord and enhanced the recovery of motor function. Histological analysis indicated that the lesion size was reduced, the pathological changes were ameliorated, and more neurons were preserved. Based on these results we conclude that SXT can effectively improve SCI.

Novel frizzled-4 gene mutations in chinese patients with familial exudative vitreoretinopathy.

OBJECTIVES: To search for mutations in the Frizzled-4 gene (FZD4) in Chinese patients with familial exudative vitreoretinopathy (FEVR) and to delineate the mutation-associated clinical features. METHODS: Forty-eight Chinese patients with FEVR and 100 unrelated control subjects were recruited and had complete ophthalmic examinations performed. The coding regions of FZD4 were screened for mutations by polymerase chain reaction and direct sequencing. Multiple sequence alignment was conducted to evaluate the conservation of residues among different FZD4 homologs and the human Frizzled family. Genotype-phenotype correlations were also analyzed. RESULTS: Twelve putative disease-causing mutations were identified in total, 9 of which were novel: 1 deletion (P14fsX57), 1 nonsense mutation (S491X), and 7 missense mutations (G22E, E180K, T237R, R253C, F328S, A339T, and D470N). Three reported FZD4 mutations were also detected: H69Y, M105V, and W496X. Remarkably, 2 patients who harbored compound heterozygous mutations (H69Y with E180K or W496X) had a more severe ocular phenotype than carriers of a single H69Y mutation. CONCLUSIONS: FZD4 mutations were responsible for FEVR in 15 of 48 Chinese patients (31.3%) in this study, similar to other ethnic groups. This study supports the highly polymorphic nature of FZD4 with a differential mutation profile in the Chinese population. CLINICAL RELEVANCE: The profile of the mutations obtained in FZD4 further illustrates the complexity of FEVR and provides a better understanding of the genotype-phenotype correlations.

Correction of the disease phenotype of myocilin-causing glaucoma by a natural osmolyte.

PURPOSE: To characterize a novel Asp384Asn (D384N) mutant myocilin (MYOC) that causes juvenile-onset open-angle glaucoma (JOAG) and investigate the correction of mutant phenotype by a natural osmolyte, trimethylamine N-oxide (TMAO). METHODS: A Chinese JOAG family was recruited and genomic DNA was extracted from peripheral blood obtained from 44 family members. Coding regions of the MYOC were sequenced. Two hundred individuals (>60 years old) without ocular hypertension or glaucoma were the control subjects. Full-length human wild-type MYOC cDNA was cloned in p3xFLAG-myc-CMV-25 and missense mutation was introduced by site-directed mutagenesis. Transfected human trabecular meshwork cells were treated with small-molecule chemical chaperones. Secreted MYOC was analyzed by combined immunoprecipitation-Western blot analysis. Intracellular myocilin was fractionated into Triton X-100-soluble and insoluble fractions, and analyzed by Western blot analysis. Intracellular aggregate and apoptosis were assayed by immunofluorescence. The effect of TMAO on subcellular myocilin distribution was analyzed by density gradient fractionation, followed by Western blot analysis. RESULTS: A novel c.1150G>A change of MYOC was identified. Screening of optineurin, WDR36, and CYP1B1 showed an absence of disease-causing polymorphisms. Mutated D384N myocilin had reduced solubility and was aggregation-prone and nonsecreted. Treatment of transfected cells with TMAO improved the solubility of the D384N mutant, which was corrected for secretion in a dose-response manner. TMAO reduced the distribution of the D384N mutant in the endoplasmic reticulum (ER), alleviated ER stress, and rescued cells from apoptosis. CONCLUSIONS: The results indicate that TMAO, with chaperoning activity, facilitated the folding and secretion of mutant MYOC. This therapeutic approach assisted by a chemical chaperone can be developed for treating glaucoma.

Multiple gene polymorphisms analysis revealed a different profile of genetic polymorphisms of primary open-angle glaucoma in northern Chinese.

PURPOSE: To evaluate the individual and interactive effects of polymorphisms in the myocilin (MYOC),optineurin (OPTN), WD repeat domain 36 (WDR36), and apolipoprotein E (APOE) genes on primary open-angle glaucoma (POAG) in northern Chinese. METHODS: Northern Chinese study subjects, 176 POAG patients and 200 controls, were recruited for screening of the coding exons and splicing regions of MYOC. Five single nucleotide polymorphisms (SNPs) in OPTN (M98K, R545Q, IVS5+38T>G, IVS8-53T>C, and IVS15+10G>A), one SNP in WDR36 (IVS5+30C>T) as well as the APOE promoter and epsilon2/epsilon3/epsilon4 polymorphisms were also examined. Association analysis was performed by using chi(2) analysis. High-order gene-gene interaction was also analyzed using the multifactor dimensionality reduction (MDR) method. RESULTS: In MYOC, 22 variants were identified. Four of them were novel but found in controls only. The missense mutation, Val53Ala, is likely a glaucoma causing mutation, accounting for 0.6% of cases. No individual polymorphism in OPTN, WDR36, or APOE was associated with POAG. MDR analysis identified a best 6-factor model for POAG: MYOC IVS2+35A>G, OPTN Met98Lys, OPTN IVS5+38T>G, OPTN IVS8-53T>C, WDR36 IVS5+30C>T, and APOE -491A>T. CONCLUSIONS: The association pattern between the genes, MYOC, OPTN, WDR36, and APOE, and POAG in northern Chinese is different from that of southern Chinese. Disease-causing mutations in MYOC accounted for a small proportion of northern Chinese POAG patients. Common polymorphisms in these genes were not associated with POAG individually but might interactively contribute to the disorder, supporting a polygenic etiology.

Evaluation of LOXL1 polymorphisms in primary open-angle glaucoma in southern and northern Chinese.

PURPOSE: The lysyl oxidase-like protein 1 (LOXL1) gene is strongly associated with exfoliation glaucoma, which is very rare in the Chinese population. The implicated LOXL1 polymorphisms have not been associated with primary open-angle glaucoma (POAG). In this study, we investigated three of the LOXL1 polymorphisms in POAG in a southern Chinese population of Hong Kong and northern Chinese from Beijing. METHODS: The Hong Kong group included 293 POAG patients and 250 controls, and the Beijing group included 169 POAG patients and 197 controls. LOXL1 single nucleotide polymorphisms (SNPs), rs1048661, rs3825942, and rs2165241, were genotyped by direct DNA sequencing. Individual association was analyzed using the chi(2) test, and haplotype-based association analysis was performed in WHAP. RESULTS: Each of the candidate SNPs was not statistically associated with POAG in either group (p>0.017, Bonferroni correction). Haplotype-based association analysis had identified a significant omnibus association (Omnibus chi(2)=18.16, p=0.00115) between these SNPs and POAG in the Hong Kong group. A minor haplotype (T-G-T) showed significant statistical association with POAG. It presented in 2.1% of cases and 0.4% of controls, conferring a 5.24 fold of increased risk to the disease (95% CI: 1.17-23.54, P(perm)=0.00108). However, this haplotype was absent in the Beijing group. CONCLUSIONS: Individual LOXL1 SNPs, rs1048661, rs3825942, and rs2165241, were not associated with POAG in the Chinese population. However, a minor haplotype T-G-T was found to be associated with the disorder in the southern Chinese. The low frequencies of the at-risk alleles at rs1048661 and rs2165241 may be one of the factors that led to the low prevalence of exfoliation syndrome in the general populations of the Chinese.

Effect of topical Ginkgo biloba extract on steroid-induced changes in the trabecular meshwork and intraocular pressure.

OBJECTIVE: To study the effects of Ginkgo biloba extract (GBE) on dexamethasone (DEX)-induced ocular hypertension. METHODS: Rabbits aged 7 weeks received topical TobraDEX (Alcon Labs, Hünenberg, Switzerland) and/or 5 microg of GBE four times daily for 14 days. Intraocular pressure (IOP) was recorded every 3 days. After enucleation, trabecular meshwork (TM) cellularity and extracellular matrix deposition were graded. The effect of GBE on apoptosis and expression of myocilin and cell stress-related genes in DEX-treated human TM cells were studied by immunofluorescence, Western blotting, and quantitative polymerase chain reaction. RESULTS: Ginkgo biloba extract suppressed DEX-induced IOP elevation in rabbits. It reduced the DEX-associated accumulation of extracellular materials within the cribriform layers of the TM and achieved better TM cellularity. In cultured human TM cells, GBE substantially attenuated anti-Fas ligand-induced apoptosis and reduced DEX-induced myocilin expression. Ginkgo biloba extract modulated the expression of alphaB-crystallin and heat-shock proteins 70 and 90alpha but not other stress-related genes. Furthermore, changes associated with DEX were found less in GBE-treated or GBE-primed TM cells. CONCLUSION: We showed that GBE, a nontoxic, antiapoptotic, herbal compound significantly suppressed steroid-induced IOP elevation in rabbits and it seems to prevent the adverse effects of DEX on TM cells. CLINICAL RELEVANCE: Ginkgo biloba extract could be a therapeutic agent or dietary supplement to prevent steroid-induced ocular hypertension.

[Photodynamic therapy of pigmented choroidal melanomas in rabbits using hematoporphyrin monomethyl ether].

OBJECTIVE: The purpose is to determine the effectiveness of photodynamic therapy of experimental choroidal melanoma in rabbits using hematoporphyrin monomethyl ether (HMME). METHODS: Pigmented choroidal melanomas were established in 46 New Zealand albino rabbit eyes. The animals were treated with daily injection of cyclosporine A. The tumors were followed up with funduscopic examination and ultrasonography until they were 1.5 to 4.6 mm in height. Then the rabbits were divided randomly into two groups. In the treatment group, 41 rabbits were injected intravenously with hematoporphyrin monomethyl ether (HMME, 10 mg/kg). 3 hours later, the tumors were irradiated at 630 nm through an He-Ne laser at estimated total light doses of 60 approximately 150 J/cm(2). Control animals (5 rabbit eyes) were treated with light only (2 rabbit eyes), photosensitizer only (2 rabbit eyes), or observation only (1 rabbit eyes). Each animal then was followed up for 4 to 5 weeks with indirect ophthalmoscopy, ultrasonography, and fundus photography (16 rabbit eyes among the treatment group were extirpated for pathologic examination 24 hours or 1 week after the treatment). In the end, all the rabbits were sacrificed and the pathologic examinations were performed. RESULTS: With the fluences of >or= 70 J/cm(2), all the tumors regressed evidently. With the fluence of 60 J/cm(2), not all the animals showed complete tumor arrest. In the control group, all the tumors showed continuous growth and filled most of the vitreous cavity in 2 to 3 weeks. CONCLUSION: The photodynamic therapy with homemade photosensitizer HMME may have a role in the treatment of pigmented choroidal melanomas.

[Relationship between ciliary muscle contraction and the pseudo accommodation after the implantation of foldable intraocular lenses].

OBJECTIVE: To investigate the relationship between high frequency component of accommodative microfluctuation (HFC) and the pseudo accommodation after the implantation of foldable intraocular lenses (IOL). METHODS: With ARK-730A accommodation analyzer we checked HFC in 50 cases (50 eyes) of patients who had good pupil reaction to light and the pupil diameter was 2.0 approximately 3.5 mm approximately. Three months after the implantation of foldable IOL, the relationship among ciliary muscle accommodative microfluctuation, IOL movement and pseudo accommodation was analyzed. RESULTS: There was positive correlation between ciliary muscle accommodative microfluctuation and IOL movement (r = 0.702, P < 0.01), between IOL movement and pseudo accommodation (r = 0.861, P < 0.01), and between ciliary muscle accommodative microfluctuation and pseudo accommodation (r = 0.915, P < 0.01). Pseudo accommodation was greater in patients who showed more ciliary muscle accommodative microfluctuation and IOL movement. CONCLUSION: HFC induces IOL movement, and it is one of the most important reasons for pseudo accommodation after foldable IOL implantation.