Ophthalmology. Retina最新文献

Purpose: To report the detailed histopathology of two enucleated eyes from two patients who developed severe visual loss associated with retinal hemorrhages, vessel sheathing and vascular nonperfusion after administration of an initial dose of intravitreal pegcetacoplan, and to propose, with supportive histopathology, the pathogenesis of the clinical syndrome previously termed hemorrhagic occlusive retinal vasculitis (HORV).

Design: Case series.

Subjects: Two enucleated eyes from two patients treated with intravitreal pegcetacoplan.

Methods: Retrospective, multicenter consecutive clinical-pathologic analysis.

Main outcome measures: Histopathologic review and immunophenotypic characterization.

Results: Both patients presented with inflammation and significant vision loss nine days following the initial injection of pegcetacoplan with no subsequent improvement and underwent enucleation for pain control. Histologic examination of the enucleated eyes (patient one at 4 months post-injection and patient two at 40 days) revealed extensive vascular thrombosis, retinal hemorrhages and necrosis, and a dense inflammatory infiltrate in the uvea and variably the optic nerve, episclera, and muscle tendons composed of predominantly of T-cells, macrophages, and eosinophils. Notably, the inflammatory infiltrate was absent from the retina. In addition, one eye demonstrated multiple foci of glomerular-like vascular proliferations in the uveal tract and thrombosis with focal recanalization of vessels in the optic nerve.

Conclusion: Drug-induced, immune-mediated, retinal vasculopathy and choroiditis (DIRVAC) is a rare complication following pegcetacoplan injection. Although some limitations arise in interpretation of histopathologic findings due to compensatory changes in the eyes over time (prior to enucleation), the authors propose that the combined clinical, histopathologic, and immunohistochemical findings suggest a mixed-type, delayed hypersensitivity reaction as mechanism of initial injury.

Purpose: To describe the incidence, complications and management of reverse pupillary block (RPB) after implantation of Carlevale IOL.

Design: Multicenter, retrospective, cross-sectional study.

Participants: Out of a sample of 128 patients that had undergone Carlevale IOL implantation, 19 patients were found to present RPB.

Methods: Nineteen patients with RPB after Carlevale IOL implantation were evaluated and treated with laser peripheral iridotomy (LPI).

Main outcome measures: Demographic data (age, gender), data on preexisting medication, axial length (Zeiss IOLMaster 500 and Zeiss IOLMaster 700), presence of pseudoexfoliation material (PXF), presence of reverse pupillary block (Anterior segment swept-source SS-OCT Anterion, Heidelberg Engineering), presence of macular edema (Irvine Gass syndrome, OCT Spectralis, Heidelberg Engineering), anterior chamber depth (ACD) before and after LPI, best corrected visual acuity (BCVA) before and after LPI and intraocular pressure (IOP) before and after LPI were analyzed.

Results: An incidence of RPB of 14.8% was found. The prevalence of pseudoexfoliation syndrome was 21.1% and 42.1% of patients presented an axial length >24.00 mm. Mean pre-LPI ACD was 4.78 ± 0.465 mm and post-LPI was 4.23 ± 0.404 mm, a statistically significant increase of 0.54 (p=0.000, IC 95% 0.26-0.83) mm of ACD was observed. There were no differences between pre- and post- LPI BCVA. Pre-LPI IOP was 17.10 (range 12-34) mmHg and post-LPI IOP was 14.47 (range 10-21) mmHg, (p= 0.391). Cystic macular oedema (Irvine Gass) was identified in 4 out of 19 patients, reporting an incidence of 21.1% in RPB cases.

Conclusion: Reverse pupillary block is a relatively common complication after Carlevale lens implantation, which may be associated with an increase of macular oedema incidence but does not clearly correlate an increase of intraocular pressure. Our hypothesis is that indentation of the sclera induces a posterior rotation of the peripheral iris, causing RPB. Our results encourage to look over the Carlevale IOL implantation technique to consider a routinely intraoperative surgical peripheral iridotomy to avoid RPB and its further complications.

Objective: This study aimed to demonstrate the clinical equivalence of biosimilar QL1205 and reference ranibizumab, Lucentis®, in patients with neovascular age-related macular degeneration (nAMD).

Design: This was a multi-center, double-blinded, randomized controlled phase 3 trial.

Subjects, participants, and controls: Treatment-naïve patients with active nAMD were randomly assigned to receive QL1205 or reference ranibizumab.

Methods, intervention, or testing: Patients received intravitreal injection of QL1205 or reference ranibizumab at a dose of 0.5 mg in the study eye once every four weeks for 48 weeks.

Main outcome measures: The primary endpoint was change in best-corrected visual acuity (BCVA) by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 8 compared to baseline level. Biosimilarity of QL1205 to reference ranibizumab was assessed with an equivalence range for the difference in BCVA letters between -3.49 and +3.49.

Results: Between June 27, 2019 and June 8, 2021, 616 patients were randomized to the QL1205 group (n=308) and the reference ranibizumab group (n=308). The mean improvement of BCVA was +6.3±9.13 ETDRS letters in the QL1205 group and +7.3±8.82 ETDRS letters in the reference ranibizumab group at week 8. Both the 90% confidence interval (CI) [-2.23, 0.13] and 95% CI [-2.46, 0.36] of the difference between the two treatment groups (P=0.1434) were within the predefined equivalence range. Safety profiles were manageable in both groups.

Conclusions: QL1205 was biosimilar to reference ranibizumab regarding clinical efficacy, ocular and systemic safety, as well as immunogenicity and pharmacokinetics profiles in the treatment of patients with nAMD.

Purpose: To identify the susceptibility loci for myopic macular neovascularization (mMNV) in patients with high myopia.

Design: A genome-wide association study (GWAS) meta-analysis (meta-GWAS).

Participants: We included 2,783 highly myopic individuals, including 608 patients with mMNV and 2,175 control participants without mMNV.

Methods: We performed a meta-analysis of three independent GWASs conducted according to genotyping platform (Illumina Asian Screening Array [ASA] dataset, Illumina Human610 BeadChip [610K] dataset, and whole genome sequencing [WGS] dataset), adjusted for age, sex, axial length and the first to third principal components. We used DeltaSVM to evaluate the binding affinity of transcription factors to DNA sequences around the susceptibility single nucleotide polymorphisms (SNPs). In addition, we evaluated the contribution of previously reported age-related macular degeneration (AMD) susceptibility loci.

Main outcome measures: The association between SNPs and mMNV in patients with high myopia.

Results: The meta-GWAS identified rs56257842 at TEX29 -LINC02337 as a novel susceptibility SNP for mMNV (odds ratio [OR]_meta = 0.62, P_meta = 4.63 × 10^-8, I² = 0.00), which was consistently associated with mMNV in all datasets (OR_ASA = 0.59, P_ASA = 1.71 × 10^-4; OR_610K = 0.63, P_610K = 5.53 × 10^-4; OR_WGS = 0.66, P_WGS = 4.38 × 10^-2). Transcription factor-wide analysis showed that the transcription factors ZNF740 and EGR1 lost their binding affinity to this locus when rs56257842 had the C allele (alternative allele), and the WNT signaling-related transcription factor ZBTB33 gained binding affinity when rs56257842 had the C allele. When we examined the associations of AMD susceptibility loci, rs12720922 at CETP showed a statistically significant association with mMNV (OR_meta = 0.52, P_meta = 1.55 × 10^-5), while rs61871745 near ARMS2 showed a marginal association (OR_meta = 1.25, P_meta =7.79 × 10^-3).

Conclusions: Our study identified a novel locus associated with mMNV in high myopia. Subsequent analyses offered important insights into the molecular biology of mMNV, providing the potential therapeutic targets for mMNV. Furthermore, our findings imply shared genetic susceptibility between mMNV and AMD.