British Journal of Ophthalmology最新文献

Background/aim: With the popularity of endothelial keratoplasty (EK) procedures, Descemet membrane (DM) EK and pre-Descemet EK, considerable work has been done on understanding the posterior corneal anatomy. Most of the information available relates to the central cornea. We evaluated the peripheral cornea to explore the immunohistological and anatomical relationship between the pre-Descemet layer (PDL), DM and trabecular meshwork (TM).

Methods: Six donor human sclerocorneal discs were studied. PDL, DM and TM were examined by light microscopy, transmission electron microscopy (TEM) and immunohistology. The DM was peeled from the centre to the limit of its peripheral attachment, to reach the transition zone (TZ) between TM and peripheral cornea. Ten-micron sections were stained with antibodies against collagens 1, 2, 3, 4, 5, 6, 12, elastin, myocilin, wnt-1, aquaporin, tenascin C, laminin and integrin alpha 3.

Results: Collagens 2, 3, 4, laminin and myocilin were predominantly seen in the TZ between TM and peripheral cornea. Wnt-1, integrin alpha 3 and tenascin C were highly concentrated in TM. Collagen 1 was present predominantly in the corneal stroma. On TEM; DM was thinner with a denser banded structure spread throughout its thickness in the periphery compared with the central cornea where it presents as the distinct anterior banded layer.

Conclusion: The TZ between DM, PDL and TM shows a unique histological structure at the periphery. The collagen and elastin fibres of the TM are continuous with the PDL. The structures are firmly attached to each other. These findings provide structural information that is relevant to the preparation of DMEK donor tissue.

Background: Pigmentation could be a relevant prognostic factor in uveal melanoma (UM) development. Microphthalmia-associated transcription factor (MITF) regulates melanin synthesis by activating tyrosinase-related protein 2 (TYRP2) and silver protein (SILV) that induce the melanogenesis pathway. Although their oncogenic potential has been observed in various malignancies but has not been investigated in UM Asian population. Our aim is to study the ultrastructure of melanosomes and the prognostic significance of pigmentation markers such as TYRP2, MITF and SILV in UM.

Methods: Transmission electron microscopy was performed to compare the ultrastructure of melanosomes in the normal choroid and UM cases. Immunoexpression of TYRP2, SILV and MITF was analysed in 82 UM samples. The mRNA expression level of all genes was measured in 70 UM cases. A statistical correlation was performed to determine the prognostic significance of all markers.

Results: Premelanosomes and mature melanosomes undergoing dedifferentiation were observed in high-pigmented UM cases as compared with low-pigmented UM cases. Seventy per cent of UM cases showed high SILV expression while TYRP2 and MITF expression was present in 58% and 56% of cases, respectively. At the mRNA level, upregulation of TYRP2, SILV and MITF markers was seen in around 50% of UM cases, which was statistically significant with high pigmentation. Reduced metastatic-free survival was statistically significant with the MITF protein expression.

Conclusion: Our results demonstrated that ultrastructural changes in melanosomes and high expression of TYRP2, MITF and SILV could dysregulate the melanogenesis pathway and might be responsible for the aggressive behaviour of UM.

Aims: To investigate the long-term natural history of ellipsoid zone (EZ) width in USH2A-retinopathy.

Methods: EZ width measurements from optical coherence tomography were retrospectively obtained from 110 eyes of 55 participants with molecularly confirmed biallelic USH2A-retinopathy. We used a hierarchical Bayesian method to construct and compare different mathematical models describing the long-term decline of EZ width.

Results: Compared with linear and quadratic models, exponential decline best represented the long-term loss of EZ width based on the deviance information criterion score. Log-transformed EZ width declined linearly over 30 years of inferred disease duration (median: 0.063 (IQR: 0.040-0.086) log (µm)/year). Compared with the raw EZ width decline rate, the log-transformed EZ width decline rate required 48% fewer patients to achieve an identically powered 1-year trial (38 vs 73 participants). Log EZ width decline rate was uncoupled from baseline EZ width (Spearman ρ=-0.18, p=0.06) and age (ρ=-0.10, p=0.31). Eyes with Usher syndrome exhibited earlier median onset ages of macular EZ width loss (18.8 (IQR: 13.1-24.7) vs 28.1 (IQR: 18.5-35.8) years, p<0.001) but comparable log EZ width decline rates (0.060 (IQR: 0.035-0.100) vs 0.065 (IQR: 0.050-0.079) log (µm)/year; p=0.42).

Conclusions: EZ width follows an exponential decline in USH2A-retinopathy. Compared with raw EZ width decline rate, log-transformed EZ width decline rate may be a superior endpoint for clinical trials. Syndromic eyes exhibit an earlier onset of macular EZ width loss but progress at comparable rates to non-syndromic eyes.

Background: It has been reported that the gut microbiome is involved in the pathogenesis of uveitis, but the specific pathogenic microbes and metabolites in different types of uveitis are still unclear.

Methods: Microbiome and metabolites were detected using 16S ribosomal DNA and LC‒MS/MS (liquid chromatography tandem mass spectrometry) in 45 individuals, including 16 patients with Vogt Koyanagi Harada (VKH), 11 patients with acute anterior uveitis (AAU) and 18 healthy controls.

Result: The diversity of intestinal microbes among the VKH, AAU and control groups was not significantly different. Thirteen specific microbes and 38 metabolites were detected in the VKH group, and 7 metabolites (vanillin, erythro-isoleucine, pyrimidine, 1-aminocyclopropanecarboxylic acid, beta-tocopherol, (-)-gallocatechin and N1-methyl-4-pyridone-3-carboxamide) significantly changed only in patients with VKH, which mainly acted on nicotinamide and nicotinamide metabolism and biotin metabolism (p<0.05). Compared with the VKH group, the AAU group had milder intestinal changes. Only 11 specific microbes and 29 metabolites changed in the AAU group, while these metabolites were not specific (p<0.05). These metabolites mainly acted on arachidonic acid metabolism. In addition, three microbes and two metabolites had the same changes in the VKH and AAU groups (p<0.05). Multiple correlations were found between gut microbes and metabolites in the VKH and AAU groups. Six microbes (Pediococcus, Pseudomonas, Rhodococcus, Photobacterium, Gardnerella and Lawsonia) and two metabolites (pyrimidine and gallocatechin) as biomarkers could effectively distinguish patients with VKH from patients with AAU and healthy individuals, with AUC (area under the curve) values greater than 82%. Four microbes (Lentilactobacillus, Lachnospiraceae_UCG-010, Cetobacterium, Liquorilactobacillus) could distinguish patients with AAU from patients with VKH and healthy controls with AUC>76%.

Conclusion: Significant differences in intestinal microbes and metabolites suggest their different roles in the pathogenesis of uveitis entities. Changes in the metabolism of certain B vitamins may be involved in the pathogenesis of VKH.