Search Results (24)

Objectives: This paper aims to explore optical coherence tomography (OCT)-based choroidal vascular changes in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents, faricimab and ranibizumab, in a pilot study. Methods: This retrospective pilot cohort study enrolled 28 treatment-naïve nAMD patients who received three consecutive intravitreal anti-VEGF injections at Nara Medical University Hospital. In total, 17 patients (61%) were Type 1 MNV and 11 patients (39%) were Type 2 MNV. Patients were divided into a faricimab group (13 eyes) and a ranibizumab group (15 eyes). The type of macular neovascularization (MNV) and the presence of polyps were recorded. The central choroidal thickness (CCT) and the ratio of luminal area to choroidal area (L/C ratio), derived from binarized OCT images, were measured at baseline after the first and third injections. Results: Type 1 MNV was observed in 61% of eyes, with polyps confirmed in 53%. There was no significant difference in best corrected visual acuity (BCVA) for both faricimab and ranibizumab during treatment (p = 0.12, 0.94, respectively). After the third injection, a dry macula was achieved in 62% of the faricimab group and 60% of the ranibizumab group. In the ranibizumab group, CCT significantly decreased after the first injection, while no significant change was observed in the faricimab group. Conversely, the L/C ratio significantly decreased in the faricimab group after the third injection (p = 0.010). Among faricimab-treated eyes, those with type 1 MNV showed a significantly greater reduction in the L/C ratio compared to type 2 MNV (p = 0.017). Conclusions: This pilot study suggests that faricimab may exert combined anti-VEGF and Ang-2 effects predominantly on type 1 MNV, potentially leading to vascular constriction. These exploratory findings warrant confirmation in larger studies. Full article

Objectives: This study aimed to evaluate the 6-month real-world outcomes of switching to faricimab in patients with aflibercept-resistant neovascular age-related macular degeneration (nAMD). Methods: A retrospective review was conducted on the eyes of 60 patients with aflibercept-resistant nAMD that were switched to faricimab. Best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, including central subfield thickness (CST), subfoveal choroidal thickness (SFCT), and both the maximum height and width of pigment epithelial detachment (PED), at baseline and 1, 3, and 6 months after switching were evaluated. The type of PED and retinal fluid were also analyzed. Results: The results showed that BCVA remained stable at month 6 (p = 0.150), while CST significantly decreased (p = 0.020), and SFCT remained unchanged (p = 0.072). The maximum PED height significantly decreased (p = 0.030), while the maximum PED width did not change (p = 0.07). The mean injection interval significantly increased from 6.8 ± 2.4 weeks before switching to 11.2 ± 1.7 weeks after switching (p = 0.068). Furthermore, the dry macula rate was 43.3% at month 6. Conclusions: Switching to faricimab in aflibercept-resistant nAMD patients showed stable visual outcomes, significant anatomical improvements, and reduced treatment burden over 6 months in real-world clinical settings. Full article

Background/Objectives: To investigate the impact of pachychoroid on the clinical features of neovascular age-related macular degeneration (nAMD) in Japan using the deep learning-based Hokkaido University pachychoroid index (HUPI), which has a high discriminative ability for pachychoroid. Methods: This retrospective observational study examined 124 eyes of 111 treatment-naïve nAMD patients, including 44 eyes with type 1 macular neovascularization (MNV), 26 eyes with type 2 MNV, and 54 eyes with polypoidal choroidal vasculopathy (PCV). HUPI was calculated for each eye from EDI-OCT choroidal images using our modified LeNet that had learned the image patterns of pachychoroid. Differences in HUPI between nAMD types and inter-relationships between nAMD parameters, including HUPI, were evaluated. Results: The mean HUPI was 0.53 ± 0.30 for type 1 MNV, 0.33 ± 0.23 for type 2 MNV, and 0.61 ± 0.3 for PCV, with significant differences between any two of the three groups (p < 0.05, for each). Round-robin multiple regression analysis for nAMD parameters showed the close associations of the HUPI with choroidal vascular hyperpermeability (CVH) and subretinal fluid (SRF) (p = 0.017 and p < 0.001 for each) and the clear division of nAMD parameters into the following two groups: one including intraretinal fluid and type 1 and type 2 MNV and the other including SRF, CVH, polypoidal lesions, and HUPI. Conclusions: HUPI revealed that eyes with type 1 MNV and PCV had more pachychoroid-like features than eyes with type 2 MNV. HUPI was tightly associated with CVH and SRF but not MNV per se in nAMD parameters, reinforcing the pathoetiological concept of differentiating pachychoroid from typical nAMD. Full article

Background/Objectives: The aim was to investigate the short-term outcomes of three consecutive monthly aflibercept 8 mg administrations for treatment-naïve eyes with exudative age-related macular degeneration (AMD). Methods: Twenty-one eyes with exudative AMD were included (type 1 macular neovascularization: eleven eyes; type 2 macular neovascularization, four eyes; and polypoidal choroidal vasculopathy (PCV), six eyes). All eyes received three consecutive monthly administrations of aflibercept 8 mg (114.3 mg/mL) at an injection volume of 0.07 mL. Indocyanine green angiography (ICGA) was performed on eyes with PCV at baseline and at the 3-month visit. Results: The best-corrected visual acuity significantly (BCVA) improved from 0.31 ± 0.38 (baseline) to 0.25 ± 0.38 at the 3-month visits (p = 0.035). Dry macula achieved 62% and 100% at the 1-month and 3-month visits, respectively. Central retinal thickness and subfoveal choroidal thickness significantly decreased by 55.7% and 19.8%, from 341 ± 112 (baseline) to 190 ± 64 (3-month visits) and from 192 ± 50 (baseline) to 154 ± 51 (3-month visits), respectively (both p < 0.001). Complete regression of polypoidal lesions was seen in five (83.3%) eyes out of six on ICGA at the 3-month visit. No systemic adverse events were noted, and one eye developed a retinal pigment epithelial tear one month after the first injection. Conclusions: Three consecutive monthly administrations of aflibercept (8 mg) were safe and effective for resolving exudation and polyp regression, with significant BCVA improvement in treatment-naïve eyes with exudative AMD. Full article

Background/Objectives: In a recent study, we investigated anti-VEGF treatment strategies for three subtypes of neovascular age-related macular degeneration (nAMD)—typical AMD (tAMD), polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP)—among a large cohort of Japanese patients. To further explore these findings, we conducted a post hoc analysis of this cohort to identify factors associated with the discontinuation of anti-VEGF therapy for nAMD in a real-world clinical setting. Methods: We collected medical records of patients newly diagnosed with nAMD who initiated intravitreal anti-VEGF antibody injection therapy. Patients were divided into two groups: those who continued anti-VEGF therapy for one year and those who discontinued treatment. Baseline best-corrected visual acuity, optical coherence tomography (OCT) findings, injection regimen, and the type of anti-VEGF antibody drug used were analyzed using univariate and multivariate analyses. Results: A total of 667 treatment-naïve nAMD patients initiated anti-VEGF agents and followed the therapy for 1 year. The one-year dropout rate in this study was 13%. Logistic regression analysis revealed that poor initial visual acuity and a PRN treatment regimen were significantly associated with higher odds of dropout. Age, gender, systemic factors, and the choice of intravitreal injection did not show any significant differences. Conclusions: Poor initial visual acuity and PRN treatment regimens may increase the risk of treatment dropout and should be carefully monitored. Full article

Intraocularly, fatty acid-binding protein 4 (FABP4) and 5 (FABP5) mainly originate from human ocular choroidal fibroblasts (HOCF), and human nonpigmented ciliary epithelium (HNPCE) cells have been suggested to be pivotally involved in intraocular pathophysiology. To elucidate the unidentified regulatory mechanisms of the gene expression and protein secretion of FABPs, the effects of glucose levels, fatty acids (FAs), and peroxisome proliferator-activated receptor (PPAR) modulators were studied. To elucidate the additional biological role of FABPs, laser choroidal neovascularization (CNV) in Fabp4^−/− and Fabp4/5^−/− mice was analyzed by fluorescein angiography. By changing glucose levels, the secretion and expression of FABP4 in HOCF were significantly upregulated, whereas the secretion and expression of FABP5 in HNPCE decreased. The administration of various FAs, particularly docosahexaenoic acid (DHA), markedly increased the expression and secretion of both FABPs. PPAR modulators also influenced the secretion and expression of FABPs. In vivo, wild-type retina exhibited evident CNV with high fluorescein intensity, while Fabp4^−/− retina showed reduced CNV formation and Fabp4/5^−/− retina displayed evident CNV along with vitreous leakage. These findings suggest that (1) the production and secretion of intraocular FABP4 and FABP5 are distinctly regulated by glucose levels, FAs, and PPARs; and (2) intraocular FABP4 and FABP5 are critical for inducing retinal neovascularization and maintaining the blood-aqueous barrier. Full article

Background/Objectives: Anti-vascular endothelial growth factor (VEGF) therapy is the first-line treatment for neovascular age-related macular degeneration (nvAMD). While proactive and adequate treatment generally leads to better visual outcomes, various factors, including the disease type, ocular findings, lifestyle, and systemic status, affect the visual prognosis in clinical settings. This study aimed to identify the factors that affect the visual prognosis in patients with nvAMD treated with anti-VEGF therapy. Methods: We conducted a multicenter retrospective cohort study at eight tertiary referral centers in Japan, where we reviewed the medical records of patients newly diagnosed with nvAMD between January 2014 and December 2019. These patients had started treatment with either ranibizumab (0.5 mg) or aflibercept (2.0 mg) and were followed for at least 1 year. We evaluated the impact of the disease type, systemic factors, and initial fundus findings on the best-corrected visual acuity (BCVA) at 1 year. Results: This study included 182 patients (129 men, 53 women), with a mean age of 75.0 ± 8.6 years. The disease types were categorized as typical AMD (53%), polypoidal choroidal vasculopathy (PCV) (43%), and retinal angiomatous proliferation (RAP) (4%). Univariate analysis identified age, the baseline logarithm of the minimum angle of resolution BCVA, intraretinal fluid (IRF), pigment epithelial detachment (PED), and subretinal hyperreflective material (SHRM). Multivariate analysis identified the following significant risk factors associated with vision worsening: age, smoking history, diabetes, and the presence of IRF and PED. Conclusions: The presence of IRF, PED, and SHRM at the start of treatment and a history of smoking and diabetes may be associated with a poor visual prognosis in patients with nvAMD. Full article

Background: Subretinal hyper-reflective material (SHRM) sometimes causes vision loss in spite of anti-vascular endothelial growth factor (VEGF) therapy in eyes with neovascular age-related macular degeneration (nvAMD). We evaluated the impacts of combination therapy with intravitreal ranibizumab (IVR) and tissue plasminogen activator (tPA) in eyes with nvAMD accompanying SHRM. Methods: In total, 25 eyes of 25 patients (16 men and 9 women, 76.7 years old), who underwent IVR/tPA for nvAMD with SHRM and were followed up for at least 12 months, were retrospectively reviewed. In total, 15 eyes were treatment-naïve and 10 eyes had previous treatment for nvAMD. Results: In total, 16 eyes had type 2 macular neovascularization (MNV), 5 eyes type 1 MNV with fibrovascular pigment epithelial detachment and 4 eyes polypoidal choroidal vasculopathy. At month 12, SHRM regressed or reduced in 18 eyes (72%) and the best-corrected visual acuity (BCVA) improved in 6 eyes (24%) and was unchanged in 14 eyes (56%), while the mean BCVA was just stabilized. The mean central retinal thickness, macular volume and SHRM thickness significantly improved from 408 µm to 287 µm, from 11.9 mm³ to 9.6 mm³, from 369 µm to 165 µm, respectively (p < 0.01). Conclusions: The combination therapy with IVR/tPA for nvAMD with SHRM may help preserve vision by prompt regression of SHRM. Full article

We investigated the factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The primary endpoint was a more than two-week extension of the treatment interval after 6 months. In addition, factors related to the success or failure of extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes from 43 patients. Extended dosing intervals of >2 weeks were identified in 14 eyes (32.6%). A short dosing interval before switching, absence of polypoidal lesions, and thin central choroidal thickness before switching were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend existing dosing intervals. Full article

Background: Macular neovascularization (MNV) has been evaluated by optical coherence tomography (OCT) imaging using various approaches. However, few studies have examined their differences. This study analyzed type 1 MNV with a combination of two approaches: scale bar and binarization. Methods: We enrolled 84 patients with untreated type 1 MNV. We measured choroidal parameters using a scale bar and defined the ratios of superficial choroidal thickness to choroidal vessel diameter (SV ratios). We also used binarization and calculated the ratios of the luminal to the choroidal area (LC ratios) in two directions (horizontal and vertical). Results: Fifty-one patients (61%) were classified as having polyps. SV ratios in the group with polyps were significantly lower than in the group without (p < 0.001). The receiver operating characteristic (ROC) curve showed that the SV ratio was predictive of polyps (AUC 0.733, 95% CI: 0.621–0.844). In patients without polyps, horizontal LC ratios were significantly higher in a subgroup with subretinal fluid than in those without (p = 0.047). The ROC curve showed that the LC ratio was predictive of subretinal fluid (AUC 0.722, 95% CI: 0.517–0.926). Conclusion: The SV ratio reflects the MNV disease type, whereas the LC ratio reflects MNV disease activity. Establishing cut-off values for each ratio may be useful for MNV diagnosis. Full article

Background: Optical coherence tomography angiography (OCTA) is a noninvasive imaging modality used to analyze the retinochoroidal vasculature and detect vascular flow. The resulting images can be segmented to view each vascular plexus individually. While fluorescein angiography is still the gold standard for the diagnosis of posterior uveitis, it has limitations, and can be replaced by OCTA in some cases. Methods: This case series describes five patients with posterior noninfectious uveitis and their description by OCTA. Results: Cases included lupus retinopathy (n = 1) for which OCTA showed ischemic maculopathy as areas of flow deficit at the superficial and deep capillary plexus; choroidal granulomas (n = 1) with a non-detectable flow signal in the choroid; active punctate inner choroiditis and multifocal choroiditis (n = 1) with OCTA that showed active inflammatory chorioretinal lesions as non-detectable flow signals in choriocapillaris and choroid; dense type 2 inflammatory secondary neovascularization (n = 1) associated with active choroiditis; and acute posterior multifocal placoid pigment epitheliopathy (APMPPE) (n = 1) without flow abnormalities at the superficial and deep retinal plexuses but non-detectable flow at the levels of the choriocapillaris and choroid. Conclusions: Ophthalmologists can use OCTA to identify inflammatory changes in retinal and choroidal vasculature, aiding in the diagnosis, management, and monitoring of posterior uveitis. Full article

Background: The aim of this study was to investigate optical coherence tomography (OCT) and OCT angiography (OCTA) parameters in patients with neovascular age-related macular degeneration (nAMD) and macular neovascularization (MNV) type 1, type 2, and type 3. Methods: In this retrospective study, 105 treatment-naïve eyes of 105 patients (60 men and 45 women) with a definite diagnosis of active nAMD and MNV of different types and 105 frequency-matched age and gender healthy subjects were evaluated (61 men and 44 women). All subjects underwent a full ophthalmic examination and multimodal imaging assessment, including spectral domain (SD) OCT and OCTA. The main outcome measures were choroidal vascularity index (CVI), subfoveal choroidal thickness (SFCT), central macular thickness (CMT), and outer retina to choriocapillaris (ORCC) MNV flow area (ORCCFA). Results: Significant differences were found in terms of CVI, CMT, and ORCCFA between MNV 1 and the two other groups. CVI was significantly different between MNV 1 and healthy control patients (p < 0.001) and between MNV 1 and MNV 2 (p < 0.001). ORCCFA and CMT were significantly different between MNV1 and MNV2 (p < 0.005). The difference in subfoveal CT between the three groups was not statistically significant (p = 0.458). A significant negative correlation was found between CVI and ORCCFA. Furthermore, CVI showed a positive correlation with subfoveal CT. Full article

Purpose: To evaluate the classification system of branching neovascular network (BNN) morphology in polypoidal choroidal vasculopathy (PCV) patients based on swept-source optical coherence tomography (SS-OCT) and swept-source optical coherence tomography angiography (SS-OCTA), and analyze the morphological features in each group as potential prognostic features. Methods: A total of 32 PCV eyes were included in this retrospective study. SS-OCT and SS-OCTA images of 6 mm × 6 mm centered on the foveal of each eye were analyzed. PCV cases were classified into three types (“trunk”, “glomeruli”, and “stick” type) based on the morphological features of BNN. OCT and OCTA features were compared among the three groups. The correlation of OCT/OCTA features with visual acuity at 12 months after anti-VEGF treatment was also analyzed. Results: Type 1 group had the largest BNN area and the largest numbers of polypoidal lesions. Type 2 group has the largest pigment epithelial detachment (PED) area, PED volume, subretinal fluid (SRF) area, and SRF volume. Type 3 group had better baseline BCVA, the smallest BNN area, the smallest PED size, and the smallest SRF size. Type 1 was also featured by a clear break on Bruch’s membrane which corresponded to the origin of neovascular tissue. BCVA at 12 months was not significantly different among groups. Baseline BCVA and baseline central macular thickness were correlated with the final BCVA. Conclusions: The current classification system based on BNN morphology on SS-OCTA was highly applicable and revealed distinct characteristics in each group. The BNN type was not correlated with BCVA at 12 months after treatment. Full article

Age-related macular degeneration (AMD) is a major cause of blindness. Recent studies have reported impaired glycolysis in AMD patients with a high lactate/pyruvate ratio. Elevated homocysteine (Hcy) (Hyperhomocysteinemia, HHcy) was observed in several clinical studies, reporting an association between HHcy and AMD. We established the effect of HHcy on barrier function, retinal pigment epithelium (RPE) structure, and induced choroidal neovascularization (CNV) in mice. We hypothesize that HHcy contributes to AMD by inducing a metabolic switch in the mitochondria, in which cells predominantly produce energy by the high rate of glycolysis, or “Warburg”, effect. Increased glycolysis results in an increased production of lactate, cellular acidity, activation of angiogenesis, RPE barrier dysfunction, and CNV. Evaluation of cellular energy production under HHcy was assessed by seahorse analysis, immunofluorescence, and western blot experiments. The seahorse analysis evaluated the extracellular acidification rate (ECAR) as indicative of glycolysis. HHcy showed a significant increase in ECAR both in vivo using (Cystathionine β-synthase) cbs^+/− and cbs^−/− mice retinas and in vitro (Hcy-treated ARPE-19) compared to wild-type mice and RPE cells. Moreover, HHcy up-regulated glycolytic enzyme (Glucose transporter-1 (GlUT-1), lactate dehydrogenase (LDH), and hexokinase 1 (HK1)) in Hcy-treated ARPE-19 and primary RPE cells isolated from cbs^+/+, cbs^+/−, and cbs^−/− mice retinas. Inhibition of GLUT-1 or blocking of N-methyl-D-aspartate receptors (NMDAR) reduced glycolysis in Hcy-treated RPE and improved albumin leakage and CNV induction in Hcy-injected mice eyes. The current study suggests that HHcy causes a metabolic switch in the RPE cells from mitochondrial respiration to glycolysis during AMD and confirms the involvement of NMDAR in this process. Therefore, targeting Glycolysis or NMDAR could be a novel therapeutic target for AMD. Full article

The purpose of the study is to explore the morphofunctional fluctuations in eyes treated for neovascular AMD (nAMD) when treatment is switched from aflibercept or ranibizumab to brolucizumab. A total of 31 eyes of 31 patients with nAMD with type 1 macular neovascularization (MNV) were included. All patients were imaged using spectral domain optical coherence tomography (SD-OCT). The OCT acquisition was performed at the following visits: (i) “T1 visit” corresponding to the last follow-up examination in which an intravitreal injection of aflibercept or ranibizumab was performed before switching to brolucizumab because of the lack of improvement and (ii) “T2 visit” corresponding to the examination performed 1 month after T1, the latter visit corresponding to the day when a switch to brolucizumab injection was performed, (iii) and 1 month after the latter injection “(T3)”. The main outcome measures were: (1) central macular thickness (CMT), (2) choroidal vascularity index (CVI), (3) subfoveal choroidal thickness (CT), and best-corrected visual acuity (BCVA). Functional outcome showed significant differences at each time. Mean ± SD BCVA was 0.43 ± 0.12 LogMAR at T1 and 0.56  ±  0.16 LogMAR at T2 (p = 0.038). A significant improvement in BCVA was displayed at T3 (0.34  ±  0.21 LogMAR) as compared with T2 (p  = 0.019). CMT analysis showed fluctuations three times. In detail, T2 displayed a thicker CMT in comparison with T1, although not statistically significant (p = 0.12). Contrariwise, T3 showed a thinner CMT in comparison with T2 (p = 0.002). Analyzing CVI among the three different times, the luminal choroidal area (LCA) and total choroidal area (TCA) showed significantly different values before and after switching to brolucizumab. T2 showed a significant reduction in both vessel lumen and total area compared with T1 (p = 0.032 and p  =  0.046, respectively). Moreover, T3 showed a greater value of both LCA and TCA in comparison with T2 (p = 0.008 and p  =  0.01, respectively). CT did not show significant differences at each time (p > 0.05). Our results reported early experiences on morphofunctional fluctuations in patients with nAMD who switched to brolucizumab. The anatomical impact of brolucizumab administration appears to result in choroidal vascular enlargement, accompanied by the resolution of subretinal fluid (SRF) and intraretinal fluid (IRF). Full article