Switching to Intravitreal Brolucizumab after Ranibizumab or Aflibercept Using Treat and Extend Regimen for Neovascular Age-Related Macular Degeneration in Japanese Patients: 1-Year Results and Factors Associated with Treatment Responsiveness.

Objective: To purpose of this study was to retrospectively evaluate the 1-year outcomes and factors associated with the treatment responsiveness of switching to intravitreal brolucizumab (IVBR) for neovascular age-related macular degeneration (nAMD) in Japanese patients refractory to ranibizumab or aflibercept using a treat and extend (TAE) regimen. Methods: A total of 48 eyes of 47 nAMD patients were switched to IVBR, and 36 eyes of 35 patients (27 males and 8 females) underwent 1-year treatment after the switch. Results: The rate of dry macula was significantly higher 12 months after the switch to IVBR (p < 0.001), with a significant decrease in the mean central macular thickness (CMT) and the mean central choroidal thickness (CCT) (p < 0.01 and p < 0.01, respectively). The injection interval was significantly extended from 7.0 ± 1.7 weeks to 10.3 ± 2.5 weeks 12 months after the switch (p < 0.001). In the multivariate analysis, a smaller number of prior anti-VEGF injections (p = 0.025; odds ratio: 0.947; 95% confidence interval: 0.903-0.994) and a pre-switching CCT of less than 250 µm (p = 0.023; odds ratio: 0.099; 95% confidence interval: 0.013-0.731) were associated with the good response group. Conclusions: These results suggest that IVBR may suppress disease activity and prolong the injection interval by switching for AMD patients with an insufficient response to treatment with ranibizumab and aflibercept.

One-Year Outcome of Intravitreal Injection of Ranibizumab Biosimilar for Myopic Choroidal Neovascularization in Japanese Patients.

Objectives: To evaluate the one-year outcomes of intravitreal ranibizumab biosimilar (RBZ-BS) injections for myopic choroidal neovascularization (mCNV) in Japanese patients. Methods: Twenty-one patients (mean age 69.0 years; 4 males, 17 females) with high myopia and mCNV were retrospectively reviewed. Twelve were treatment-naïve, and nine had previous anti-VEGF treatments. Efficacy measures included best-corrected visual acuity (BCVA) and central macular thickness (CMT). Results: The treatment-naïve group showed significant BCVA improvement from 0.55 ± 0.34 at baseline to 0.24 ± 0.28 at 12 months. The previously treated group had no significant BCVA changes. CMT significantly decreased in both groups: from 295.3 ± 105.2 µm to 207.3 ± 63.0 µm in the treatment-naïve group, and from 196.1 ± 62.0 µm to 147.2 ± 50.1 µm in the previously treated group. Dry macula rates were high: 83% at 3 months and 83% at 12 months in the treatment-naïve group, and 67% at 3 months and 89% at 12 months in the previously treated group. No adverse events were reported. Conclusions: These findings indicate that RBZ-BS is an effective and safe treatment for mCNV, particularly in treatment-naïve patients. The use of RBZ-BS offers a cost-effective alternative to original ranibizumab, reducing financial burdens while maintaining high therapeutic efficacy. Further studies with larger sample sizes and longer follow-up periods are needed to confirm these results and evaluate long-term outcomes and cost-effectiveness.

The impact of removing the epiretinal membrane and inner limiting membrane for sustained subretinal fluid by macular neovascularization refractory to anti-VEGF therapy.

Purpose: Anti-vascular endothelial growth factor (VEGF) therapy is the most prevalent intervention for exudative lesions secondary to neovascular age-related macular degeneration (nAMD) and other macular neovascularization (MNV). However, in some cases refractory to the latest anti-VEGF agents is associated with epiretinal membrane (ERM) or vitreomacular traction. We applied a vitrectomy to remove those pathologies which may be effective for reducing the exudation. Observations: In this case report, we present 2 cases with sustained subretinal fluid and macular neovascularization secondary to nAMD or dome-shaped macula that poorly responded to anti-VEGF therapy. In both cases, removing thin ERM or vitreomacular traction with an inner limiting membrane peeling promptly resolved the subretinal fluid and no recurrence was observed thereafter. Conclusions and importance: Vitrectomy could be an effective modality for anti-VEGF drug-resistant MNV cases with vitreomacular traction or ERM even in the anti-VEGF era.

Symptoms of Isolated Optic Neuropathy in a Patient with Systemic, Brain, and Meningeal Metastases from Breast Cancer: A Case Report.

Introduction: Ocular metastases from breast cancer, particularly involving the optic nerve, are rare and pose a diagnostic challenge. Typically, optic nerve metastases are believed to originate from nearby choroidal metastases or hematogenous spread through the posterior ciliary arteries. However, there have been some reports of metastases through leptomeningeal dissemination. The aim of this report was to describe a case of multiple brain metastases from breast cancer without subjective symptoms other than central scotoma, which was diagnosed with repeated magnetic resonance imaging (MRI). Case Presentation: A 62-year-old woman who had previously undergone a mastectomy for left breast cancer complained of left ocular pain during eye movement and left visual loss. Initial contrast-enhanced MRI showed no significant abnormalities, and idiopathic optic neuritis was suspected. Despite steroid pulse therapy, her visual function did not improve. After four and a half months, her visual acuity worsened, and repeat contrast-enhanced MRI showed brain metastases involving the optic nerve sheath. Conclusion: Despite the multiple brain metastases, ultimately the patient's only symptom was unilateral visual loss. These findings highlight the usefulness of repeated contrast-enhanced MRI for detecting brain metastases, especially in cases without other apparent neurological symptoms or initial imaging abnormalities.

Comparative Treatment Study on Macular Edema Secondary to Branch Retinal Vein Occlusion by Intravitreal Ranibizumab with and without Selective Retina Therapy.

The purpose of this study was to compare the safety and efficacy of selective retina therapy (SRT) combined with the intravitreal injection of ranibizumab (IVR) in patients with macular edema (ME) secondary to branch retinal vein occlusion (BRVO). This trial was a 12-month single-center, randomized, single-masked prospective study. Eligible patients were randomized (1:1) to IVR and SRT (IVR + SRT group), or IVR and sham SRT (IVR + sham group). After the initial IVR, all participants received ME resolution criteria-driven pro re nata treatment. SRT or sham SRT was always applied one day after IVR. The primary outcome measure of this study was the mean change in central macular thickness (CMT) from baseline, and the secondary outcome measures were the mean change in visual acuity from baseline and the number of IVR treatments at a 52-week follow-up. Thirteen patients were in the IVR + SRT group, and 11 were in the IVR + sham group. Compared to the baseline, mean CMT and BCVA improved significantly after 52 weeks in both groups, with no significant difference between the two groups. The mean number of IVR was 2.85 ± 1.52 in the IVR + SRT group and 4.73 ± 2.33 in the IVR + sham group at the 52-week follow-up, with a significant difference between the two groups (p < 0.05). IVR combined with SRT may significantly decrease the number of IVR treatments while maintaining the visual and anatomical improvement effect of IVR monotherapy.

Practical treatment options for persistent central serous chorioretinopathy and early visual and anatomical outcomes.

PURPOSE: Persistent central serous chorioretinopathy (pCSC) may be treated by laser photocoagulation (PC), selective retina therapy (SRT), or photodynamic therapy (PDT). We conducted retrospective analyses regarding the choice of therapy for pCSC in the best clinical practice and the outcomes of these modalities. STUDY DESIGN: A retrospective interventional study. METHODS: The records of 71 eyes of 68 treatment naïve pCSC cases who underwent PC, SRT, or PDT were reviewed. First, the baseline clinical parameters were evaluated to find significant factors associated with the choice of treatment option. Second, the 3 months' visual and anatomical outcomes of each modality were assessed. RESULTS: The PC, SRT, and PDT groups included 7, 22, and 42 eyes, respectively. The leakage pattern in fluorescein angiography (FA) was significantly associated with the choice of treatment (p<0.005). The dry macula ratio at 3 months post-treatment was 29%, 59%, and 81% in the PC, SRT, and PDT groups, respectively, which significantly differed among the groups (p<0.01). The best-corrected visual acuities tended to be improved after the treatments in all groups. Central choroidal thickness (CCT) was significantly decreased in all groups (p<0.05, p<0.01, and p<0.00001, in PC, SRT, and PDT groups, respectively). Logistic regression analysis for dry macula revealed that SRT (p<0.05), PDT (p<0.05), and the changes in CCT (p<0.01)were the significant association factors. CONCLUSION: The leakage pattern in FA was associated with the choice of treatment option for pCSC. PDT achieved a significantly higher dry macula ratio than PC, 3 months after the treatment.

Fundus white spots associated with graft-versus-host disease in the remission phase of acute myeloid leukemia.

Purpose: To report a case of fundus white spots associated with graft-versus-host disease (GVHD) during the remission phase of acute myelogenous leukemia (AML). Observations: A 60-year-old woman was diagnosed with AML 7 months earlier, and after 3 months of chemotherapy, she underwent bone marrow transplantation 2 months earlier and was in remission. When she first came to our department with the chief complaint of persistent bilateral floaters before she developed AML, she had a skin rash caused by GVHD that had been diagnosed 4 days earlier, and the fundi of both eyes showed multiple white spots in the deep retinal layers. One month later, the GVHD skin rash had resolved with topical steroid treatment, and the fundus white spots had mostly disappeared. Fifteen months after the initial visit, the fundus white spots had completely disappeared, with remaining hypofluorescent dots on fundus autofluorescence. Her best-corrected visual acuity was 1.2 in each eye at the first visit and remained at 1.0 in the right eye and 1.2 in the left eye at the final visit 15 months later. Conclusions and importance: Fundus white spots may occur in the early phase of GVHD, causing focal retinal pigment epithelium atrophy after resolution.

Early anatomical changes and association with photodynamic therapy induced acute exudative maculopathy in patients with macular diseases.

The purpose of this study was to investigate the occurrence rate and predictors of photodynamic therapy (PDT) induced acute exudative maculopathy (PAEM). This retrospective study included 39 eyes of 39 patients (32 males and 7 females), who were treated with initial PDT. PAEM was defined as an increase in central retinal thickness (CRT) of 15% or more measured by OCT on day 3 after PDT compared with baseline. Sixteen of 39 eyes (41%) were classified in the PAEM+ group. CRT and central choroidal thickness (CCT) were significantly increased at 3 days in the PAEM+ group and significantly decreased at 1 month after PDT in the PAEM- group. In a multiple comparison, neovascular age-related macular degeneration (nAMD) had a significantly higher incidence of PAEM compared to polypoidal choroidal vasculopathy (PCV) and central serous chorioretinopathy (CSC). The incidence of PAEM was lower in PCV and CSC, and higher in nAMD. BCVA at 1 month was significantly worse in the PAEM group, which may be related to visual prognosis after PDT. Since both CRT and CCT decrease at 1 month, the detection of PAEM needs to be assessed a few days after PDT.

A case of angioid streaks that produced choroidal neovascularization after the onset of unilateral acute retinopathy in pseudoxanthoma elasticum.

Purpose: To report a case of angioid streaks that showed non-exudative choroidal neovascularization (CNV) after the onset of acute retinopathy in pseudoxanthoma elasticum (PXE). Observations: A 64-year-old woman with PXE visited our department for an ophthalmologic evaluation. Her decimal best-corrected visual acuity (BCVA) was 1.5, with angioid streaks (AS) around the optic disc in either eye at the first visit. Seven years later, her left eye's BCVA suddenly decreased by 0.3, and the fundus showed blurring of the Ellipsoid zone and vitreous cells along with the retinal pigment streaks on the nasal fovea. Diagnosed as acute retinopathy in PXE, twenty-two weeks after the start of oral prednisolone, the Ellipsoid zone became clear and the BCVA improved to 1.2, but CNV gradually developed. After intravitreal injection of bevacizumab, the CNV was decreased. Conclusions and importance: CNV on the AS lesion may occur after acute retinopathy in PXE.

Factors affecting resolution of subretinal fluid after selective retina therapy for central serous chorioretinopathy.

The purpose of this study was to investigate the factors of clinical outcome of selective retina therapy (SRT) for central serous chorioretinopathy (CSC). This retrospective study included 77 eyes of 77 patients, who were treated with SRT for CSC and observed at least 6 months after the treatment. SRT laser (527 nm, 1.7 µs, 100 Hz) was used for treatment. The mean best-corrected visual acuity (logMAR), central macular thickness (CMT) and central choroidal thickness were changed from baseline to at 6-months follow-up with significant difference. The multivariate analyses found that the rate of change (reduction) in CMT was associated with focal leakage type on fluorescein angiography (FA) (p = 0.03, coefficient 15.26, 95% confidence interval 1.72-28.79) and larger baseline CMT (p < 0.01, coefficient - 0.13, 95% confidence interval - 0.13 to - 0.05). Complete resolution of subretinal fluid was associated with nonsmoking history (p = 0.03, odds ratio 0.276, 95% confidence interval 0.086-0.887) and focal leakage type on FA (p < 0.01, odds ratio 0.136, 95% confidence interval 0.042-0.437). These results may be useful for predicting the therapeutic effectiveness of SRT.

Selective retina therapy (SRT) for macular serous retinal detachment associated with tilted disc syndrome.

PURPOSE: Tilted disc syndrome (TDS) may be associated with a macular serous retinal detachment (MSRD). However, ideal therapy for this complication is still unestablished yet to date. The purpose of this study is to investigate the effect of selective retina therapy (SRT) for MSRD associated with TDS. METHODS: This retrospective study included 11 eyes of 10 patients (1 male and 9 females), who were treated with SRT for MSRD associated with TDS, and observed at least 12 months after treatment. The mean age was 56 years old (range 44-66). An SRT laser (527 nm, 1.7 µs, 100 Hz; Medical Laser Center Lübeck, Germany) was used for treatment. The changes of best-corrected visual acuity (BCVA), central macular thickness (CMT), and central choroidal thickness (CCT) were examined. Subfoveal curve height (SFCH) was calculated at baseline. RESULTS: The mean follow-up period was 24.4 months (range 12-48 months). The mean BCVA (logMAR), CMT, and CCT changed from 0.03 ± 0.10, 324 ± 82 µm, and 194 ± 68 µm preoperatively to 0.07 ± 0.17, 274 ± 94 µm, and 188 ± 65 µm at final follow-up, respectively, with significant difference on CMT (BCVA: p = 0.44, CMT: p < 0.05, CCT: p = 0.21). The MSRD disappeared in 6 eyes (55%) and the average number of SRT irradiations until resolution of MSRD was 2.6 times (range 1-5 times). There was no significant association between SFCH and resolution of MSRD (p = 0.19). CONCLUSIONS: SRT may promote absorption of MSRD and maintenance of BCVA for TDS. Randomized and prospective clinical studies are needed to evaluate the effectiveness of SRT for MSRD associated with TDS.

One-Year Results of a Treat-and-Extend Regimen of Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy.

INTRODUCTION: To evaluate 1-year outcomes of intravitreal aflibercept (IVA) using a treat-and-extend (TAE) regimen for polypoidal choroidal vasculopathy (PCV) and identify the factors for patients whose treatment intervals could be extended. METHODS: Fifty-one eyes of treatment-naïve PCV patients treated with IVA using a TAE regimen for at least 1 year were examined retrospectively. All patients received at least three IVA injections every 5 weeks, and the intervals were then extended by 2-week adjustments up to 13 weeks. When retinal exudation recurred, the patient was treated with the same regimen, but with a shortened interval of 5 weeks. The main outcome measures were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) as well as the treatment interval at 1 year. RESULTS: The mean logarithm of the minimum angle of resolution BCVA improved from 0.24 ± 0.32 at baseline to 0.18 ± 0.31 at 12 months (p = 0.048). The mean CRT decreased from 350.3 ± 147.7 µm at baseline to 215.3 ± 75.0 µm at 4 months (p < 0.001), after which it was maintained at this level. At 12 months, the administration interval was 5 weeks in eight eyes (15.7%), 7 weeks in six eyes (11.8%), 9 weeks in two eyes (3.9%), 11 weeks in four eyes (7.8%), and 13 weeks in 31 eyes (60.8%). Female sex, a thinner CRT at 6 months, and absence of polypoidal lesions at 12 months were significant factors related to patients whose treatment intervals could be extended without recurrence to 13 weeks. CONCLUSION: IVA using a TAE regimen improved visual and anatomical outcomes in eyes with PCV at 1 year using a protocol to adjust the injection intervals specifically for each patient so as to obtain no retinal exudation.

Selective retina therapy for subretinal fluid associated with choroidal nevus.

PURPOSE: To report a case of a patient with subretinal fluid (SRF) associated with choroidal nevus (CN), who was treated with selective retina therapy (SRT) and ultimately achieved resolution of the SRF. OBSERVATIONS: A 41-year-old man with SRF associated with CN in his right eye (RE) underwent ophthalmologic evaluation, including optic coherence tomography, fluorescein angiography (FA) and indocyanine green angiography. The best corrected visual acuity (BCVA) converted to the logarithm of the minimum angle of resolution (logMAR) was 0.00 in the RE. SRT (532 nm, 1.7 µs pulse duration, 30 pulses in 100Hz; Medical Laser Center Lübeck) was performed with the laser spots equally distributed across the FA leakage area. Until 20 months SRT was repeated several times because the SRF decreased every time in response to SRT, but was not completely resolved and sometimes increased with time. After performing 6 times of SRT session, leakage on FA stopped at 21 months follow-up and SRF was resolved at 31 months. At 60 months after the first SRT, there were no signs of malignant transformation, no SRF, and the BCVA in the RE was 0.22. CONCLUSIONS AND IMPORTANCE: SRT seems to be a useful treatment and proper clinical studies are necessary to establish the best treatment protocol for SRF associated with CN.