BACKGROUND: Neovascular age-related macular degeneration (nAMD) is a common cause of visual impairment and blindness in the elderly with globally increasing prevalence. Vascular endothelial growth factor inhibitor (anti-VEGF) treatment has improved visual prognosis of nAMD, but continuous treatment may cause anxiety and stress, although increase in visual acuity (VA) may also have positive effects on patients\' quality of life. The health care burden due to frequent treatment and monitoring is apparent, but the effect of anti-VEGF treatment on patients\' quality of life is not fully understood. We evaluated the overall impact of nAMD and its treatment on newly diagnosed patients\' health-related quality of life (HRQoL) in real-world setting.
METHODS: The present prospective cohort study included newly diagnosed nAMD patients treated with anti-VEGF injections at Oulu University Hospital during 2019-2020. Data included parameters from comprehensive ophthalmic examination and fundus imaging, age at diagnosis, sex, comorbidities, visual acuity, and frequency of anti-VEGF injections. HRQoL was assessed by 15D questionnaire at diagnosis, 6 months, and 12 months.
RESULTS: 95 nAMD patients were included. They were 78 ± 8 years old, 56 (59%) were female, and 74 (78%) had more than one comorbidity. The patients received 8 ± 3 anti-VEGF-injections. Visual acuity (VA) improved from 56 ± 18 to 61 ± 24 Early treatment diabetic retinopathy study (ETDRS) letters in 12 months. VA improved > 5 ETDRS letters in 45 (47%), remained stable in 30 (32%) and decreased > 5 letters in 17 (18%) eyes. The mean total 15D score reflecting overall HRQoL decreased from 0.850 ± 0.104 to 0.834 ± 0.103 in 12 months. Decreased HRQoL was associated with baseline best-corrected VA (BCVA) ≥ 70 ETDRS letters (p = 0.023) and more than one comorbidity (p = 0.034). HRQoL regarding visual function increased from 0.765 ± 0.194 to 0.789 ± 0.184 during the 12-month follow-up.
CONCLUSIONS: In real world setting, HRQoL regarding visual function improved in anti-VEGF-treated nAMD patients during the first 12 months after the diagnosis and treatment initiation. Good baseline VA or several comorbidities were associated with decreased overall HRQoL during the follow-up. Despite the effectiveness of anti-VEGF treatment on visual function, several other aspects affecting elderly patients\' everyday life should be considered when nAMD treatment is implemented.

OBJECTIVE: To investigate aqueous humor cytokine levels in neovascular age-related macular degeneration (nAMD) patients with subretinal fibrosis and to explore the relationship between cytokine levels and disease severity.
METHODS: The aqueous humor samples were collected from 16 eyes with subretinal fibrosis due to nAMD (SRFi group), 33 eyes with nAMD without subretinal fibrosis (nAMD group) and 28 eyes with cataract patients (control group). Clinical samples were analyzed for 5 cytokines,including vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), basic fibroblast growth factor (bFGF), transforming growth factor-α (TGF-α), platelet-derived growth factor-BB (PDGF-BB).
RESULTS: Aqueous humor cytokines VEGF and bFGF were significantly higher in nAMD patients than controls (all P < 0.05), and VEGF, bFGF and TGF-α levels were significantly higher in SRFi patients than controls (all P < 0.05). No significant differences in 4 cytokine levels were observed between nAMD and SRFi patients in aqueous humor. We also identified a positive correlation between the aqueous humor levels of IL-6 and VEGF in the SRFi group, while bFGF and TGF-α in the nAMD group. Moreover, VEGF levels were strongly related to BCVA, and bFGF levels were positively related to the maximum thickness of subretinal hyperreflective material (SHRM) in fibrosis due to nAMD.
CONCLUSIONS: VEGF and bFGF levels in aqueous humor were elevated in macular neovascularization with and without subretinal fibrosis. TGF-α levels exclusively differed in neovascular AMD with fibrosis. Cytokines are distributed differently and play a synergistic role in different stages (angiogenesis and fibrogenesis) of nAMD. The bFGF levels could predict the negative prognosis in fibrosis due to nAMD.

Neovascular age-related macular degeneration (nARMD) is an important cause of visual impairment and blindness in the elderly, with choroidal neovascularization in the macula as the main pathological feature. The onset of nARMD is closely related to factors including age, oxidative stress, and lipid metabolism. Vascular endothelial growth factor (VEGF) is an important factor contributing to nARMD as well as choroidal neovascularization and retinal leakage formation. At present, anti-VEGF therapy is the only treatment that improves vision and halts disease progression in most patients, making anti-VEGF drugs a landmark development for nARMD treatment. Although intravitreal injection of anti-VEGF drugs has become the first-line treatment for nARMD, this treatment has many shortcomings including repeated injections, poor or no response in some patients, and complications such as retinal fibrosis. As a result, several new anti-VEGF drugs are being developed. This review provides a discussion of these new anti-VEGF drugs for the treatment of nARMD.

UNASSIGNED: Intravitreal injection of anti-VEGF agents is the first-line treatment for patients with neovascular-age related macular degeneration (nAMD). One unique serious adverse event that may be associated with these agents is intraocular inflammation (IOI). The main purpose of this analysis was to evaluate the potential presence of texture-based radiomics features characterizing heterogeneity within the vitreous compartment of spectral domain optical coherence tomography (SD-OCT) images that may precede or develop in association with IOI and might serve as OCT biomarkers for IOI.
UNASSIGNED: This is a post-hoc analysis of a subset of cases (N = 67) involving IOI, endophthalmitis, and/or retinal vascular occlusion in the phase 3 HAWK trial. These were investigator determined diagnoses that were also confirmed by the safety review committee. Intraocular inflammation was any signs of inflammation within the eye, endophthalmitis was inflammation associated with presumed infection, and retinal vascular occlusions consisted of intraocular inflammation with concurrent vascular occlusions/vasculitis. Out of 67 eyes, 34 belonged to the Safety group with an IOI event and 33 were propensity-matched Controls. A total of 481 texture-based radiomics features were extracted from the vitreous compartment of the SD-OCT scans at pre-IOI time point (i.e., much earlier than the actual event). Most discriminating five features, selected by the Wilcoxon Rank Sum feature selection were evaluated using Random Forest (RF) classifier on the training set ( S t r , N = 47) to differentiate between the two patient groups. Classifier performance was subsequently validated on the independent test set ( S t , N = 20). Additionally, the classifier performance in discriminating the Control and Safety group was also validated on S t at the IOI event timepoint.
UNASSIGNED: The RF classifier yielded area under the Receiver Operating Characteristics curve (AUC) of 0.76 and 0.81 on S t using texture-based radiomics features at pre-IOI and event time-point, respectively.
UNASSIGNED: In this analysis, the presence of a pre-IOI safety signal was detected in the form of textural heterogeneity within the vitreous compartment even prior to the actual event being identified by the investigator. This finding may help the clinicians to assess for underlying posterior inflammation.

Introduction Age-related macular degeneration, a chronic and progressive disease, is one of the leading causes of vision loss globally among the elderly population. Multiple hypotheses have been proposed regarding its pathogenesis, including the presence of lipid metabolism alteration. Dysfunctional lipid handling within retinal pigment epithelial cells has been implicated in the accumulation of lipofuscin and subsequent induction of oxidative stress and inflammation, all contributing to retinal degeneration. The present study aims to comparatively analyze the serum lipid fraction distributions in patients with neovascular age-related macular degeneration (AMD) and controls. Materials and methods A retrospective study was carried out between January 2021 and December 2023 on 91 naïve patients with neovascular AMD and 90 controls admitted for routine cataract surgery. All subjects underwent a comprehensive ophthalmological exam, including ophthalmoscopy and optical coherence tomography (OCT) with central macular thickness (CMT) measurement. A complete blood count with differential and lipid fractions values was analyzed. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) were comparatively analyzed between the control group and the test group. Results The groups were comparable in terms of age (73.84 ±7.52 years for the neovascular AMD group vs 72.1±10.92 years in controls; p=0.8) and gender distribution (p=0.243). The mean NLR and PLR values were slightly higher in the AMD group but not statistically significant (p=0.51, p>0.99, respectively). Comparative analysis of lipid profile fractions showed significantly higher HDL-C values in the exudative AMD group compared to normal subjects (61.27±19.4 mg/dL vs 50.99±7.86 mg/dL, p=0.006). Also, the proportion of subjects with HDL-C>60 mg/dL was higher in the exudative AMD group (p=0.014). There were no significant differences in total cholesterol (189.77±53.39 mg/dL vs 190.43±37.84 mg/dL, p=0.681), LDL-C, and TG. Logistic regression analysis showed that serum HDL-C and HDL-C values >60 mg/dL are significantly associated factors with neovascular AMD. However, there is no statistical correlation between the values of these biochemical parameters and visual acuity or CMT in the neovascular AMD patient group. Conclusions There were no correlations between NLR and PLR with neovascular AMD in the study group. Higher HDL-C values exceeding 60 mg/dL were associated with neovascular age-related macular degeneration and could represent a possible therapeutic target in neovascular AMD.

This study aimed to develop a quantitative analysis program of blood flow velocity by vessel diameter in neovascular age-related macular degeneration (nAMD) subjects using high-speed swept-source optical coherence tomography angiography. This retrospective, observational, cross-sectional study included 10 eyes of healthy volunteers and 4 eyes of patients with representative nAMD. Novel scan patterns and variable interscan time analysis were utilized to measure the flow parameter, a surrogate marker of blood flow velocity, by vessel diameter within different depths. Detected vessels at superficial and deep as well as outer retinal regions were categorized into three vessel diameters (major vessels (> 40 μm), medium vessels (20-40 μm), and capillaries (< 20 μm)). The flow parameter increased with enlarged vessel diameter in all participants at superficial and deep layer. All nAMD subjects, except for type 3 macular neovascularization (MNV), contained a structure dominated by medium vessels at outer retinal region. The mean flow parameter at outer retinal region was type 1 MNV (1.46 ms-1), type 1 + 2 MNV (0.98 ms-1), and polypoidal choroidal vasculopathy, including branching vascular networks (1.46 ms-1). This program provides the possibility to extract the blood flow information at different depths by vessel diameter types, which is considered to be useful tool for evaluating nAMD pathology and activity.

Background: To evaluate functional and anatomical outcomesof cataract surgery in neovascular age-related macular neovascularization (nAMD) eyes receiving anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections in modified pro re nata (PRN) regimen. Materials and Methods: Sixty eyes of 60 nAMD patients, including 41 women (68.3%) and 19 men (31.7%) in an average age of 77.35 ± 6.41 years, under treatment with intravitreal aflibercept injections in modified PRN regimen with no signs of macular neovascularization (MNV) activity during two consecutive visits were included in this prospective, observational study. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), as well as the number of anti-VEGF injections were monitored six months before and after phacoemulsification with intraocular lens (IOL) implantation. Further, the change of the abovementioned parameters was assessed during the six-month follow-up period for CRT and the number of injections, while the BCVA was monitored for 54 months. Results: BCVA measured on the first day after surgery (0.17 ± 0.19 logMAR) as well as in the six-month post-surgery (0.13 ± 0.16 logMAR) significantly improved compared to preop values (0.42 ± 0.20 logMAR). BCVA remains stable during the observational period. We found that both differences were statistically significant (p < 0.01). The mean CRT and the mean number of injections did not differ between the six-month pre- and post-surgical periods. Conclusions: We showed the beneficial effect of phacoemulsification in nAMD patients treated with anti-VEGF agents on visual outcomes in the short and long term. Cataract surgery in nAMD eyes treated with anti-VEGF injections does not increase the frequency of anti-VEGF injections and does not cause deterioration of the macular status.

UNASSIGNED: The study aims to investigate the protective effect of Mingjing granule (MG) in a fibrovascular membrane rat model of neovascular age-related macular degeneration (nAMD) and explore the underlying mechanism.
UNASSIGNED: The nAMD fibrovascular membrane model was established by two-stage laser photocoagulation. BN rats were randomly divided into four groups: the model group was gavaged with distilled water, the anti-VEGF group was given an intravitreous injection of ranibizumab, the MG + anti-VEGF group was gavaged with MG combined with an intravitreous injection of ranibizumab, and the normal group not modeled only fed conventionally. Lesions were evaluated by color fundus photograph, optical coherence tomography, fundus fluorescein angiography, and retinal pigment epithelial-choroid-sclera flat mount. The changes in the retinal structure were observed by histopathology. The expression of inflammatory cell markers F4/80, Iba-1, and glial fibrillary acidic protein (GFAP); the fibrosis-related factors collagen-1, fibronectin, α-smooth muscle actin (α-SMA), and transforming growth factor-beta (TGF-β); and the complement system-related factors C3a and C3aR in the retina were detected by immunofluorescence or qRT-PCR.
UNASSIGNED: The current study revealed that MG + anti-VEGF administration more significantly reduced the thickness of fibrovascular lesions, suppressed vascular leakage (exudation area and mean density value), inhibited the area of fibrovascular lesions, and restrained the formation of the fibrovascular membrane than the anti-VEGF agent alone in the two-stage laser-induced rat model. The fluorescence intensities of F4/80, Iba-1, collagen-1, fibronectin, TGF-β, and C3aR showed more significant inhibition in MG + anti-VEGF-treated rats than the anti-VEGF agent alone. The mRNA expression levels of F4/80, Iba-1, GFAP, collagen-1, fibronectin, α-SMA, TGF-β, and C3a showed lower levels in rats treated with MG + anti-VEGF than the anti-VEGF agent alone.
UNASSIGNED: Combining MG with anti-VEGF treatment inhibits the growth of the fibrovascular membrane more effectively than using anti-VEGF treatment alone. The mechanism underlying this effect may involve limiting inflammatory cell aggregation, controlling complement system activation, and decreasing the expression of the fibrotic protein.

UNASSIGNED: To describe the early experiences of patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) whose treatment was switched to faricimab from other anti-vascular endothelial growth factor (VEGF) agents.
UNASSIGNED: This is a prospective cohort of eyes with nAMD and PCV that were previously treated with anti-VEGF agents other than faricimab. We evaluated visual acuity (VA), central subfield thickness (CST), macular volume (MV), pigment epithelial detachment (PED) height, and choroidal thickness (CT) after one administration of faricimab. Where present, fluid was further evaluated according to intraretinal fluid (IRF), subretinal fluid (SRF), or within PED.
UNASSIGNED: Seventy-one eyes from 71 patients were included (45.07% PCV and 54.93% typical nAMD). The mean [standard deviation (± SD)] VA, CST, and MV improved from 0.50 logMAR (± 0.27 logMAR) to 0.46 logMAR (± 0.27 logMAR) (p = 0.20), 383.35 µm (± 111.24 µm) to 322.46 µm (± 103.89 µm (p < 0.01), and 9.40 mm3 (± 1.52 mm3) to 8.75 mm3 (± 1.17 mm3) (p < 0.01) from switch to post switch visit, respectively. The CT reduced from 167 µm (± 151 µm) to 149 µm (± 113 µm) (p < 0.01). There was also a significant reduction in the maximum PED height between visits [302.66 µm (± 217.97 µm)] and the post switch visit [236.66 µm (± 189.05 µm); p < 0.01]. This difference was greater in PEDs that were predominantly serous in nature. In the eyes with typical nAMD (n = 39), improvements were significant for CST, MV, CT, and PED. In the eyes with PCV (n = 32), only reductions in CT were statistically significant, while VA, CST, MV, and PED only showed numerically smaller improvements. One patient developed mild vitritis without vasculitis, which resolved with topical steroids with no sequelae.
UNASSIGNED: In our case series of Asian nAMD patients, switching to faricimab was associated with a stable VA and meaningful anatomical improvements, particularly with typical nAMD subtypes.

Background: The aim of this study is to report short-term outcomes after the shortening of the treatment interval to 4 weeks with a treat-and-extend (TAE) regimen (Si4w) of aflibercept in patients with refractory neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included 34 patients given aflibercept with a TAE regimen of a minimum of a 4-week interval when they had a limited response to bimonthly aflibercept. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) were compared before and after Si4w. The resolution of subretinal and intraretinal fluid before and after Si4w was also examined. The risk factors associated with persistent fluid were analyzed. Results: The average treatment duration until initiation of Si4w was 57.82 ± 28.59 months, with an average of 23.64 ± 12.40 injections administered. The BCVA was not significantly improved after Si4w. The CMT decreased significantly from 427.91 ± 125.74 μm to 336.38 ± 121.67 μm at the third visit (p < 0.001). Eighteen eyes (52.9%) showed complete resolution, and twenty-three eyes (67.6%) experienced complete resolution at least once during the three visits. The duration of fluid before Si4w was significantly associated with complete resolution (p = 0.011). Conclusions: Si4w of aflibercept showed satisfactory anatomical outcomes with complete resolution of fluid in patients with a limited response to bimonthly aflibercept injections, and should be considered as a useful treatment option.