Purpose
This study aimed to compare functional and morphologic changes in the loading phase between patients with treatment-naïve macular neovascularization (MNV) due to neovascular age–related ...macular degeneration (nAMD) treated with either intravitreal brolucizumab (IVBr) or intravitreal faricimab (IVF) injections in a clinical setting.
Methods
We retrospectively studied 92 consecutive eyes of 90 patients with neovascular nAMD who were scheduled to receive IVBr (42 eyes of 41 patients) or IVF (50 eyes of 49 patients) injections between October 2021 and December 2022. All patients received three consecutive monthly injections of 6.0 mg/0.05 mL brolucizumab or 6.0 mg/0.05 mL faricimab. The best-corrected visual acuity (BCVA), central foveal thickness (CFT), and central choroidal thickness (CCT) at baseline and 1, 2, and 4 months after the initial treatment were measured and compared between the groups.
Results
Thirty-seven eyes in IVBr group and forty-seven eyes in IVF group who finished treatments in the loading phase were assessed at the follow-up examination. The BCVA, CFT, and CCT changed significantly after loading phase in both groups (
P
< 0.05 for both comparisons). The IVBr group had more rapid improvement of the BCVA (
P
= 0.037) at 1 month than the IVF group, but there was no difference at 4 months (
P
= 0.367). The CFT and CCT decreases tended to be greater in the IVBr group than in the IVF group throughout the follow-up period. Of the five eyes excluded from the IVBr group, one eye (2.4%) each had intraocular inflammation (IOI) and was a non-responder, and two eyes (4.8%) had retinal pigment epithelial tears after treatment. Of the three eyes excluded from the IVF group, two eyes (4.0%) did not respond to the treatment.
Conclusions
Both IVBr and IVF injections were well-tolerated and improved the VA in treatment-naïve patients with MNV due to nAMD after a loading phase, although IVBr caused a trend toward faster visual improvements in the BCVA. The IVBr group also had greater reductions of the CFT and CCT than the IVF group. However, the potential for adverse events and no response to treatment with each drug are considerations.
To evaluate the 1-year visual outcomes and anatomic responses of Japanese patients who received intravitreal brolucizumab (IVBr) injections for polypoidal choroidal vasculopathy (PCV). This was a ...retrospective study of 17 treatment-naïve eyes with PCV that were treated with IVBr. We evaluated the best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT) and number of injections for 1 year. The eradication of polypoidal lesions was also evaluated using by indocyanine green angiography during the 1-year follow-up. Non-infectious intraocular inflammation developed in two (11.8%) eyes; 15 eyes were assessed at the 1-year follow-up examination. The mean BCVA improved significantly from 0.28 at baseline to 0.13 (P < 0.05) at 1 year. The CMT and CCT decreased significantly after 1 year. The mean number of injections was 6.4 ± 0.13. The rate of complete resolution of polypoidal lesions at 1 year was 93.3%. A dry macula was achieved in 13 eyes (86.6%) after the loading phase and in 11 eyes (73.3%) at 1 year. The IVBr injections appeared to be effective for improving both functional and anatomic outcomes in Japanese patients with PCV, with a high regression rate of polypoidal lesions.
Ionizing radiation can damage DNA and, therefore, is a risk factor for cancer. Eker rats, which carry a heterozygous germline mutation in the tumor‐suppressor gene tuberous sclerosis complex 2 ...(Tsc2), are susceptible to radiation‐induced renal carcinogenesis. However, the molecular mechanisms involved in Tsc2 inactivation are unclear. We subjected Fischer 344 × Eker (Long Evans Tsc2+/−) F1 hybrid rats to gamma‐irradiation (2 Gy) at gestational day 19 (GD19) or postnatal day 5 (PND5) and investigated the patterns of genomic alterations in the Tsc2 allele of renal tumors that developed at 1 year after irradiation (N = 24 tumors for GD19, N = 10 for PND5), in comparison with spontaneously developed tumors (N = 8 tumors). Gamma‐irradiation significantly increased the multiplicity of renal tumors. The frequency of LOH at the chromosome 10q12 region, including the Tsc2 locus, was 38%, 29% and 60% in renal carcinomas developed from the nonirradiated, GD19 and PND5 groups, respectively. Array comparative genomic hybridization analysis revealed that the LOH patterns on chromosome 10 in renal carcinomas were classified into chromosomal missegregation, mitotic recombination and chromosomal deletion types. LOH of the interstitial chromosomal deletion type was observed only in radiation‐associated carcinomas. Sequence analysis for the wild‐type Tsc2 allele in the LOH‐negative carcinomas identified deletions (nonirradiated: 26%; GD19: 21%) and base‐substitution mutations (GD19: 4%). Reduced expression of Tsc2 was also observed in the majority of the LOH‐negative carcinomas. Our results suggest that interstitial chromosomal deletion is a characteristic mutagenic event caused by ionizing radiation, and it may contribute to the assessment of radiation‐induced cancer risk.
In this study, we used the Tsc2 heterozygous mutant Eker rat model to investigate the effects of radiation on the development of renal tumors and genomic alterations in those tumors. We found that in renal cancers of Eker rats, the tumor‐suppressor gene Tsc2 was inactivated by multiple mechanisms, including LOH with mitotic recombination or chromosomal deletion, point mutation, deletion and reduced Tsc2 expression. Importantly, our results suggest that interstitial chromosomal deletion is a characteristic mutagenic event caused by ionizing radiation, and it may be a useful indicator for more precise assessment of ionizing radiation‐induced cancer risk.
The purpose of this study was to evaluate the 1-year visual outcomes of patients treated with intravitreal aflibercept (IVA) or brolucizumab (IVBr) for submacular hemorrhage (SMH) secondary to ...neovascular age-related macular degeneration (AMD). We retrospectively studied 62 treatment-naïve eyes with SMHs exceeding one disc area (DA) secondary to AMD treated with IVA or IVBr. All patients received three monthly intravitreal injections in the loading phase followed by as-needed injections or fixed dosing. If a vitreous hemorrhage (VH) developed during the follow-up period, injections were discontinued and vitrectomy was performed. We evaluated the changes in the best-corrected visual acuity (BCVA) and factors that affected the BCVA improvement and VH development. A VH during treatment developed in five eyes (8.1%) (VH + group), and the mean BCVA worsened from 0.45 to 0.92. The BCVA improved significantly (P = 0.040) in the remaining 57 eyes (VH - group) from 0.42 to 0.36. The development of VHs was associated with significantly (P < 0.001) less VA improvement. Furthermore, large DAs and younger age at baseline were associated significantly (P = 0.010 and 0.046, respectively) with the development of VHs. Both IVA and IVBr appeared to improve functional outcomes in patients with SMH secondary to AMD when VHs did not develop. However, a VH developed in 8.1% of eyes after treatment. Although anti-vascular endothelial growth factor treatments were well-tolerated, for cases with large SMH at baseline, it should be considered that VH may occur during the monotherapy treatment process using IVA or IVBr, and that achieving good visual outcomes may be difficult in some cases.
Abstract
The purpose of this study was to report the incidence of elevated intraocular pressure (IOP) after intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) in Japanese ...patients with age-related macular degeneration (AMD). A retrospective study of chart review of patients who underwent ≥ 10 intravitreal anti-VEGF injections between April 2009 and December 2019 was conducted. Elevated IOP was defined as IOP ≥ 25 mmHg at one visit. Cases with elevated IOP resulting from IVI were identified. Furthermore, the association between elevated IOP and some parameters, as the risk factors that influence elevated IOP, was investigated. A total of 402 eyes of 370 patients were included in this study. Twenty-eight eyes of 26 patients (7.0%) were identified as cases with elevated IOP after IVI. The mean time of elevation after baseline was 50.6 ± 26.5 months. History of glaucoma (
p
= 0.021; odds ratio, 5.85), treatment modality (
p
= 0.019; odds ratio, 6.32), and total number of injections (
p
= 0.003; odds ratio, 1.03) were significantly associated with elevated IOP. A late complication of elevated IOP is associated with IVI in patients with AMD. Particularly, history of glaucoma and treat and extend regimen with frequent injections were found to be risk factors of elevated IOP.
Purpose
To evaluate the outcomes of a 6-month follow-up after switching to brolucizumab from aflibercept to treat neovascular age-related macular degeneration (AMD) in Japanese patients.
Study design
...Retrospective observational study.
Methods
We studied 45 consecutive eyes of 42 patients diagnosed with neovascular AMD, who were switched to intravitreal brolucizumab injection (IVBr) after receiving intravitreal aflibercept injection (IVA) using a treat-and-extend (TAE) regimen. Patients who had brolucizumab-associated intraocular inflammation (IOI) were excluded from the study. The mean changes in the logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), central foveal thickness (CFT), central choroidal thickness (CCT), and treatment intervals were evaluated at 6 months after the switch to IVBr.
Results
One eye of 1 patient was excluded because of IOI after the switch; 44 eyes of 41 patients were enrolled in this study. The mean logMAR BCVA was maintained throughout the follow-up period when compared with the baseline value (
P
> .05 at 6 months). However, the mean CFT and CCT at 6 months had decreased significantly (
P
< .05 and
P
< .001, respectively). The mean treatment interval was extended from 5.75 to 8.12 weeks.
Conclusion
Switching to brolucizumab from aflibercept using a TAE regimen might be effective for maintaining functional outcomes and extending intervals in Japanese patients with AMD.
This retrospective study aimed to investigate the progression of central retinal vein occlusion (CVO) prior to treatment initiation and its impact on prognosis. Of the 54 studied eyes with acute CVO, ...the average logMAR visual acuity (VA) at the initial visit was 0.65 ± 0.49 with an average time to treatment of 14.9 ± 14.5 days. VA at the initial treatment was identified as a stronger predictor of VA at the final visit compared to VA at the first visit or other factors. Patients who received treatment more than 28 days after the initial visit experienced a significant decline in VA compared to those treated within 28 days (0.21 ± 0.35 vs. 0.04 ± 0.13, p = 0.006). Additionally, patients who were treated between 15 and 28 days showed a greater decrease in VA compared to those treated within 14 days (0.12 ± 0.46 vs. 0.018 ± 0.02, p = 0.026). These findings from the current retrospective analysis suggesting that there is a possibility of VA decline at the initial treatment associating with worse prognosis even when treatment is administered within a month should be further investigated in the prospective study. Also, it may be crucial to consider frequent monitoring of acute CVO patients for initiating treatment at the optimal timing.
This study aims to evaluate the couch modeling accuracy of two types of TomoTherapy devices, namely Radixact and Hi-Art. First, we performed chamber measurement using A1SL and Cheese phantom for ...beams from the posterior direction to evaluate the couch modeling accuracy of the both tomotherapy units. Next, the couch model was corrected to achieve optimal dose delivery. Subsequently, patient dose verification for ten TomoDirect plans with only the posterior beams and ten TomoHelical plans was performed using Delta4. The gamma passing rate (γ-index) with 3 mm/3% and 2 mm/2% of Radixact (before and after couch correction modeling (CCM)) and Hi-Art (before and after CCM) were evaluated and statistically compared. Dose differences between the measurement and calculation in Radixact ranged from − 3.3% to 0%, whereas the dose differences in Hi-Art ranged from − 2.2% to 0.9%. Considerable differences were observed in the
γ
-index of TomoDirect plans between Radixact before and after CCM (P < 0.05) for both gamma criteria; however, these were not considerably different between Hi-Art before and after CCM. Moreover, no considerable differences were noted in the
γ
-index of TomoHelical plans in both units. After optimizing the couch model, the γ-index for TomoDirect plans significantly improved for the patient dose verification of Radixact with Delta4. In addition, the γ-index for TomoDirect and TomoHelical plans for Hi-Art were improved after CCM despite no statistically significant differences. These findings can serve as a reference data when considering the effects of couch modeling on irradiation during TomoTherapy in clinical practice.
The aim of this study is to establish the treatment couch model of TomoTherapy in a RayStation treatment-planning system. Point-dose measurements using a cylindrical solid phantom and ionizing ...chamber were performed to determine the optimal mass densities of the couch components by minimizing the discrepancy between the measured and calculated attenuations. To validate the efficacy of the determined mass densities, patient-specific delivery quality assurance (DQA) of the TomoDirect plans for eight palliative spine radiotherapy (PSR), five postmastectomy radiotherapy (PMRT), and TomoHelical plans for ten treatment sites were performed using an ionizing chamber, EBT3 film, and Delta4 diode detector with the default couch model (DCM) and corrected couch model (CCM). The dose differences and global gamma statistics at 3 mm/3% and at 2 mm/2% were evaluated and statistically compared between the DQA plans of DCM and CCM. When applying the default and optimal couch models for treatment planning, the mean dose differences between the measured and calculated attenuations were − 4.8% and − 0.1%, respectively. In all DQA for PSR cases using the CCM, the dose difference and gamma statistics were statistically improved compared to those using the DCM (
P
< 0.05). However, there was no significant difference in the dose differences and gamma statistics between the PMRT and TomoHelical cases, except for the film DQA for PMRT. The results demonstrated that the couch model in RayStation should be commissioned for TomoTherapy treatment planning when a greater dose contribution is expected from the posterior direction.
To analyze the long-term visual outcomes of pachychoroid spectrum diseases (PSD). Retrospective study. We reviewed the medical charts of consecutive patients with PSD, including focal choroidal ...excavation (FCE), pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), and pachychoroid neovasculopathy (PNV). The patients initially visited the Tokyo University Hospital from January 2008 to March 2021. Survival analyses were performed, in which loss of vision was defined as visual acuity (VA) of 0.2 logarithm of minimal angle of resolution (logMAR) or worse, 0.5 logMAR or worse, or VA worsening by 0.3 logMAR or greater. Moreover, we further investigated factors associated with visual prognosis, particularly in the CSC group. A total of 741 eyes of 638 patients were included in this analysis. The CSC or PNV group showed significantly worse visual prognosis than the FCE&PPE group for VA to 0.2 logMAR or worse (P = 0.0117 or 0.0001, respectively) and for VA worsening by 0.3 logMAR or greater (P = 0.0283 or 0.0037, respectively). In the CSC group, unlike age, sex, or treatment history, the accumulative duration of subfoveal fluid existence ≥ 12 months (continuous or intermittent) was significantly associated with visual prognosis (P < 0.0001). Among PSD, CSC and PNV were associated with a higher risk of vision loss in the long term than FCE and PPE. The duration of subretinal fluid existence was identified as a significant factor affecting long-term visual outcomes in CSC.
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