Efficacy of Brolucizumab in Polyp Regression of Treatment-Naïve Polypoidal Choroidal Vasculopathy and Its Effect on One-Year Treatment Outcome.

Purpose: To evaluate the efficacy of intravitreal brolucizumab in polyp regression of treatment-naïve polypoidal choroidal vasculopathy (PCV) patients and its effect on one-year treatment outcome. Methods: Medical records of 31 treatment-naïve PCV patients, who received three monthly intravitreal brolucizumab injections followed by as-needed injections for at least a year, were retrospectively reviewed. Visual and anatomical outcomes were evaluated at 3-month, 6-month, and 12-month. Complete polyp regression rate and percentage change of vascular lesion and polyp area were evaluated after three monthly injections of brolucizumab. The effect of complete polyp regression and the impact of vascular lesion and polyp reduction rate on one-year treatment outcome were also evaluated. Additionally, the incidence of brolucizumab-related intraocular inflammation (IOI) and its clinical course were examined. Results: In terms of visual outcome, best-corrected visual acuity(BCVA) significantly improved after 12 month follow-up (p<0.001). In terms of anatomical outcome, central macular thickness(CMT) and central choroidal thickness(CCT) significantly decreased after 12 month follow-up (p<0.001). Complete polyp regression was observed in 74.2% (23/31) after three monthly injections. Group with complete polyp regression had a higher rate of achieving dry macula at 3-month(p=0.026) and fewer number of injections(p<0.001) compared to the group without complete polyp regression. Higher polyp reduction rate was significantly associated with higher CMT change from baseline at 3-month (p=0.048) while higher vascular lesion reduction rate was significantly associated with higher CMT change from baseline at 12-month(p=0.031) and fewer number of injections(p=0.012). Brolucizumab related IOI occurred in one eye (1/31, 3.2%). Conclusion: Intravitreal brolucizumab injection effectively improved visual and anatomical outcomes and achieved significant polyp regression in treatment-naïve PCV patients. Complete polyp regression and the reduction rate of vascular lesion size and polyp size after loading injection significantly influence the treatment outcome of PCV patients. However, careful monitoring and preoperative warning is warranted due to occurrence of brolucizumab-related IOI.

Subset of retinoblastoma tumours is associated with BRCA1/2 mutations.

BACKGROUND: We investigated the potential association between pathogenic BRCA1/2 variants and retinoblastoma pathogenicity. METHODS: In this single-centre, retrospective case series, we performed hereditary cancer panel tests using blood samples for patients with retinoblastoma diagnosed between March 2017 and October 2021. Bioinformatics prediction tools were then used to conduct in silico pathogenicity assessments for patients with BRCA1/2 family variants, in addition to the American College of Medical Genetics and Genomics (ACMG) variant classification. One patient with a germline BRCA1 variant was analysed with whole-genome sequencing (WGS), mutational signature analysis and methylation analysis for RB1 and BRCA using the patient's tumour and blood samples. RESULTS: Of 30 retinoblastoma patients who underwent panel sequencing, six (20%) were found to carry germline variants in the BRCA1/2 or BRIP1 genes. Among these six patients, two had pathogenic or likely pathogenic variants as per the ACMG variant classification. Additionally, three patients showed potential pathogenic BRCA1/2 family variants through further analysis with alternative bioinformatics prediction tools. In the WGS analysis of a tumour from a patient with a germline likely pathogenic BRCA1 variant in one allele, we observed the loss of one RB1 allele due to a large deletion. No somatic non-synonymous mutations or frameshift indels were detected in the RB1 locus of the remaining allele. This sample also showed BRCA1 gene promoter hypermethylation in the tumour, indicating additional epigenetic silencing. CONCLUSION: This study demonstrated that some retinoblastoma patients harboured germline BRCA1/2 family variants, which may be associated with the development of retinoblastoma along with RB1 mutations.

PROGRESSION OF MYOPIC MACULOPATHY IN PATIENTS WITH MYOPIC TRACTION MACULOPATHY AFTER VITRECTOMY.

PURPOSE: To compare the progression of myopic maculopathy with or without vitrectomy in patients with myopic traction maculopathy (MTM). METHODS: Seventy-seven eyes with MTM were classified into either the observation group (n = 38) or the vitrectomy group (n = 39). Progression of myopic maculopathy was assessed with fundus photography using infrared images. Progression within stage was evaluated as an increase in the area of atrophic lesions on infrared images using ImageJ software. The rate of progression was compared using the paired t -test. RESULTS: The mean follow-up period was 60.0 ± 47.5 months. The initial mean stage of myopic maculopathy for the observation group was 1.86 ± 0.86, and it progressed to 2.00 ± 0.83 ( P = 0.023) at the last visit. For the vitrectomy group, the stage progressed from 1.82 ± 0.96 to 2.05 ± 1.09 ( P = 0.011). Four eyes (10.5%) in the observation group showed progression at 87.3 months, and seven eyes (17.9%) in the vitrectomy group showed progression at 31.3 months. CONCLUSION: Surgery in patients with MTM may accelerate the progression of myopic maculopathy. Therefore, care should be taken when considering surgery for patients with MTM.

Incidence and risk factors of progressive nasal inner nuclear layer thickening after surgical peeling of epiretinal membrane.

To assess incidence and risk factors of postoperative progressive nasal inner nuclear layer (INL) thickening after epiretinal membrane (ERM) surgery. Progressive nasal INL thickening was defined as 1.5-fold increase in thickness of nasal INL after ERM surgery compared to preoperative examination. Kaplan-Meier survival analysis was done to compare the cumulative risk ratio between groups stratified by presence of progressive nasal INL thickening. Logistic regression was performed to identify possible risk factors. Progressive nasal INL thickening occurred in 13.0% of ERM removal patients. Patients without progressive nasal INL thickening showed better visual acuity recovery compared to patients with nasal INL thickening (p = 0.029). Presence of cystoid space in inner retinal layer before surgery (odds ratio [OR] = 0.143, 95% confidence interval [CI] 0.028-0.736; p = 0.020), older age (OR = 0.896, 95% CI 0.817-0.982, p = 0.020), and thicker preoperative central macular thickness (OR = 0.994, 95% CI 0.988-1.000, p = 0.039) were correlated inversely with thickening of nasal INL. Correlation between nasal INL thickness and postoperative visual outcome was significant. Absence of cystoid space before ERM surgery, younger age, and thinner central macular thickness were risk factors for progressive postoperative nasal INL thickening. Progressive nasal INL thickening may serve as a new biomarker for worsened visual symptom after ERM surgery.