Neovascularization of the macula, a common complication of many chorioretinal diseases such as neovascular age-related macular degeneration, polypoidal choroidal vasculopathy, and pathologic myopia, results from increased synthesis of vascular endothelial growth factor (VEGF) by the retinal pigment epithelium and/or Müller cells because of localized ischemia and inflammation. The Consensus on Neovascular AMD Nomenclature (CONAN) study group acknowledged that these vessels may originate from either the choriocapillaris or the retinal microvasculature, prompting them to propose the term 'macular neovascularization' (MNV) to include intraretinal, subretinal, and sub-pigment epithelial neovascularization localized to the macula. MNV frequently appears as a grey-green macular lesion with overlying intraretinal thickening and/or subretinal exudation, causing metamorphopsia, reduced central vision, relative central scotoma, decreased reading speed, and problems with color recognition. Multimodal imaging with optical coherence tomography (OCT), OCT angiography, dye-based angiographies, fundus autofluorescence, and multiwavelength photography help establish the diagnosis and aid in selecting an appropriate treatment. The standard of care for MNV is usually intravitreal anti-vascular endothelial growth factor injections, though thermal laser photocoagulation, verteporfin photodynamic therapy, and vitreoretinal surgery are occasionally used. We discuss the etiology and clinical features of MNV, the role of multimodal imaging in establishing the diagnosis, and the available therapeutic options.

The choroid is a thin layer of highly vascular uveal tissue enclosed externally by sclera and internally by neurosensory retinal tissue. The choroid is a "middle layer" ocular tissue with anatomically challenging surgical access. The primary functional role of the choroid is to provide rapid, oxygenated, and nutrient-rich blood flow to both the highly metabolic retinal pigment epithelium and outer retina (i.e. photoreceptors) while simultaneously removing waste products. Historically, incisional choroidal surgery (ICS) has involved tumor biopsy or excision, removal of choroidal neovascular complex or autologous choroidal translocations; however, ICS also holds unique potential for novel and innovative approaches to address macular pathology. Using large-animal surgical studies, researchers have explored ICS with the objective of finding safer and more effective techniques to reduce surgical risks such as bleeding, tissue contraction, and scar tissue formation. We explore the relevant anatomy and embryology, existing surgical techniques, discuss the implications for retinal drug delivery, define ICS guiding principles, and offer a rationale for implementation of ICS into a vitreoretinal surgical practice. We also identify other future challenges and anticipate future innovations that will advance ICS.

The relationship between retinal morphology, as assessed by optical coherence tomography (OCT), and retinal function in microperimetry (MP) has not been well studied, despite its increasing importance as an essential functional endpoint for clinical trials and emerging therapies in retinal diseases. Normative databases of healthy ageing eyes are largely missing from literature.

Healthy subjects above 50 years were examined using two MP devices, MP-3 (NIDEK) and MAIA (iCare). An identical grid, encompassing 45 stimuli was used for retinal sensitivity (RS) assessment. Deep-learning-based algorithms performed automated segmentation of ellipsoid zone (EZ), outer nuclear layer (ONL), ganglion cell layer (GCL) and retinal nerve fibre layer (RNFL) from OCT volumes (Spectralis, Heidelberg). Pointwise co-registration between each MP stimulus and corresponding location on OCT was performed via registration algorithm. Effect of age, eccentricity and layer thickness on RS was assessed by mixed effect models.

Three thousand six hundred stimuli from twenty eyes of twenty patients were included. Mean patient age was 68.9 ± 10.9 years. Mean RS for the first exam was 28.65 ± 2.49 dB and 25.5 ± 2.81 dB for MP-3 and MAIA, respectively. Increased EZ thickness, ONL thickness and GCL thickness were significantly correlated with increased RS (all p < 0.001). Univariate models showed lower RS with advanced age and higher eccentricity (both p < 0.05).

This work provides reference values for healthy age-related EZ and ONL-thicknesses without impairment of visual function and evidence for RS decrease with eccentricity and increasing age. This information is crucial for interpretation of future clinical trials in disease.

To monitor intraocular mediator dynamics in treatment-naïve neovascular age-related macular degeneration (nAMD) patients treated with anti-VEGF intravitreal injections (IVIs) to identify individual mediator patterns correlating with treatment response.

Interventional, monocentric, prospective, clinical study.

Treatment-naïve nAMD patients.

Aqueous humor samples (100-200 μL) were collected by clear cornea paracentesis at baseline (before the first anti-VEGF IVI) and before the second and third anti-VEGF IVIs. The levels of 13 intraocular mediators were measured (VEGF-A, VEGF-C, PlGF, IL-1β, IL-6, IL-10, IL-18, CXCL1, CXCL5, CXCL7, CXCL8, MIP-1α and TNFα) using multiplex arrays.

The primary endpoint was the changes in intraocular inflammatory mediator levels between baseline and month 3. Secondary endpoints were the changes in best-corrected visual acuity (BCVA) and Central Retinal Thickness (CRT) between baseline and month 4.

Fifteen eyes were included in the study. BCVA remained stable throughout the study (p = 0.07). CRT, foveal thickness, and the presence of intraretinal and subretinal fluid significantly decreased after anti-VEGF IVIs (p < 0.0001, p < 0.0001, p < 0.001 and p < 0.001, respectively). After anti-VEGF IVIs, VEGF-A levels significantly decreased (p < 0.0001). No significant differences in all other mediator levels were observed. Three patients had baseline VEGF-A levels ≤50 pg/mL: they showed higher baseline IL-6 levels (p = 0.05), and elevated IL-6 (p = 0.03), PlGF (p = 0.02), VEGF-C (p = 0.005), IL-8 (p = 0.04), and TNFα (p = 0.013) levels after the first IVI. Good clinical responders had significantly higher baseline VEGF-A levels (p = 0.007). Patients who required a fourth IVI within 8 weeks of the loading dose had higher baseline TNFα levels (p = 0.05); higher MIP-1α levels after the first IVI (p = 0.045); and elevated TNFα (p = 0.026) and IL-8 (p = 0.029) levels after the second IVI.

The aqueous humor levels of the studied mediators remained stable after anti-VEGF IVIs, except for a significant decrease in VEGF-A levels in all patients. Patients with low baseline intraocular VEGF-A levels (i.e., ≤50 pg/mL) showed an intraocular inflammatory profile with elevated IL-6, PlGF, VEGF-C, IL-8 and TNFα levels. Treatment response correlated with high baseline VEGF-A levels. An interval > 8 weeks between the third and fourth anti-VEGF IVIs was associated with a pro-angiogenic/pro-inflammatory environment.

This study investigates the role of bone morphogenetic protein-4 (BMP4) in age-related macular degeneration (AMD), with a focus on its effects on subretinal fibrosis and choroidal neovascularization (CNV). Using a mouse model of laser-induced CNV, we found that BMP4 expression was significantly elevated in CNV lesions. BMP4 was shown to promote fibroblast proliferation and their differentiation into myofibroblasts, as indicated by increased expression of α-smooth muscle actin (α-SMA). Additionally, BMP4 promoted the transition of endothelial progenitor cells (EPCs) into endothelial cells (ECs), a process that was modulated by mitochondrial function. Intravitreal administration of Noggin, a BMP4 inhibitor, significantly reduced CNV lesion volume and decreased the expression of CD31 and α-SMA, suggesting a decrease in neovascularization and fibrosis. These findings underscore BMP4's critical role in AMD pathogenesis by driving both angiogenesis and fibrosis. Targeting BMP4 with Noggin presents a promising therapeutic approach for AMD, addressing both neovascularization and fibrosis in a single intervention, and highlights BMP4 as a potential novel target for AMD therapy.

To identify demographic and baseline OCT characteristics that are predictive of VA outcomes after the first and post-loading injections in patients treated with 2 mg aflibercept.

This study evaluated VA outcomes in 1999 eyes of 1862 patients with nAMD initiated on aflibercept therapy. Demographic and OCT (Spectralis, Heidelberg Engineering) features associated with good VA outcome defined as VA ≥ 68 ETDRS letters (Snellen ≥  6/12) and poor VA outcome of <54 ETDRS letters (Snellen < 6/18) or a loss of ≥5 ETDRS letters after first and post-loading injections were analysed using logistic regression via generalised estimating equations.

The mean age was 79.3 (SD 7.8) years, 1126 (60.5%) were females, and predominantly white ethnic background (1772 [95.2%]). The mean presenting VA was 58.0 (SD 14.5) ETDRS letters. After the loading phase, 930/1994 (46.6%) eyes achieved VA ≥ 68 ETDRS letters, and 457 (22.9%) attained VA < 54 ETDRS letters. Increasing age, non-white ethnicity, and baseline VA < 54 letter score is associated with VA < 54 letters. The OCT parameters associated with reduced odds of VA ≥ 68 ETDRS letters and increased odds of VA < 54 ETDRS letters after first and post-loading phase included fovea-involving intraretinal fluid, all types of macular neovascularisation (MNV) versus type 1 MNV, fovea-involving MNV (vs. non-foveal MNV), subfoveal MNV complex, increased central subfield thickness, foveal presence of subretinal hyper-reflective material, atrophy, fibrosis, ungradable or ellipsoid zone and/or external limiting membrane loss.

This study could provide individual-level visual prognosis about their post-loading VA based on demography, VA and OCT characteristics at presentation.

To analyze visual and anatomical outcomes in patients switched to brolucizumab and previously treated with other intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents for exudative neovascular age-related macular degeneration (nAMD). These outcomes were was assessed in the real-world setting of a tertiary center with a follow-up period of 2 years.

This retrospective longitudinal study included 29 eyes of 24 patients with exudative nAMD previously treated with at least three injections of another intravitreal anti-VEGF molecule. The eyes were then treated with brolucizumab for at least 24 months following the switch. A pro re nata ("as needed") therapeutic regimen was followed in our clinic between January 2021 and June 2024, during which time clinical and anatomical parameters were evaluated, and possible adverse events were recorded.

After 24 months of treatment with brolucizumab, patients showed a significant reduction in central macular thickness (P = 0.001) and choroidal thickness (P < 0.001). Visual acuity remained stable during the follow-up period. "Poor responders" had longer disease duration and had received more injections before the switch than "good responders." Adverse events included one subretinal hemorrhage and one intraocular inflammation across 302 injections.

Treatment with brolucizumab is effective in patients previously treated with other therapeutic molecules. The best outcomes were achieved in patients who switched therapy to brolucizumab early in their disease. Treatment with brolucizumab in this population demonstrated an acceptable risk profile, with only one intraocular inflammatory event out of 302 intravitreal injections.

This study examines the long-term effectiveness of anti-VEGF therapy in managing neovascular age-related macular degeneration (nAMD). Despite the well-established short-term improvements of anti-VEGF therapy, there is limited data on its continued efficacy over extended periods. This meta-analysis synthesises real-world data to evaluate anti-VEGF therapy's long-term outcomes systematically.

We conducted a comprehensive literature review across PubMed, EMBASE and Cochrane databases, focusing on studies that reported outcomes of anti-VEGF treatment for nAMD over a decade. The analysis included pooling baseline patient characteristics, study designs, sample sizes and changes in visual acuity (VA) over 10 years.

Our search produced 12 observational studies encompassing 7509 eyes, with 1274 completing 10-years of follow-up. The most substantial improvement in VA was observed in the first year following the initiation of anti-VEGF therapy. On average, there was a decline of 8.11 letters in VA after 10 years from baseline (95% CI -10.83 to -5.39, p < 0.01). In some cases, VA reverted to baseline levels after 10 years; in others, it declined significantly below baseline. Meta-regression showed that mean VA change was greater in those with a lower baseline VA and those treated with a higher number of injections over 10-years(p < 0.01).

Our findings suggest that the mean visual acuity of eyes treated for nAMD deteriorates progressively over the long-term from two years after starting treatment. Regular injections appear crucial for preserving maximum vision. While our analysis did not identify an increased incidence of serious ocular adverse events, the long-term impact of anti-VEGF therapy on geographic atrophy remains unclear and warrants further investigation.

The increasing prevalence of age-related macular degeneration (AMD), a disease that can result in the loss of central vision, is an emerging problem worldwide due to aging societies. Growing patient numbers create a challenge for the healthcare system. Understanding the mechanisms of AMD pathogenesis will aid in early, personalized, and efficient intervention, helping to mitigate this issue. Current diagnostic methods rely on optical coherence tomography and angiography imaging, which identify existing damages, but do not provide information on the mechanisms behind them. In the present work, we demonstrate a difference in the serum RNA profile between neovascular AMD (nAMD) patients and controls. Moreover, the RNA profile of nAMD patients corresponded with anatomical changes in the retinal fluid compartments as well as atrophic changes of the retina. We followed two independent ways to control false positive leads, and when these approaches were combined, thioredoxin-related transmembrane protein 4 (TMX4) was observed to be differentially expressed by both approaches. This finding opens a new pathway in AMD studies, which are limited due to restricted access to live human target material and the limited value of animal models of human AMD.

To check whether prolonged fundus autofluorescence (FAF) lifetimes in age-related macular degeneration (AMD) could be an artefact resulting from lens fluorescence.

Fluorescence lifetime imaging ophthalmoscopy (FLIO) was performed in pseudophakic intermediate AMD as well as healthy controls. The median values of FAF lifetimes in the centre, the inner and the outer ring of the ETDRS grid, obtained as amplitude-weighted mean of the lifetimes from a three-exponential fit of the fluorescence decay over time in two spectral channels, as well as peak emission wavelengths (PEW) were compared between patients and controls. The age dependence of FAF lifetime was checked per group. In the patient cohort, FAF lifetimes of individuals with and without subretinal drusenoid deposits (SDD) were compared.

Forty-four AMD patients (mean age 80.0 ± 6.0 years) and 26 controls (mean age 73.0 ± 10.2 years) were included. The FAF lifetimes of a subgroup of patients (N = 25, mean age 76.3 ± 5.6 years), age-matched to the controls, were significantly longer than those of the controls (all grid areas and spectral channels p < 0.001). FAF lifetimes increased with age in the controls (p = 0.006-0.03), but not in the patients. Patients with SDD had longer FAF lifetimes than those without (p = 0.003-0.068). PEW neither showed significant group differences nor age dependence.

Although long fluorescence lifetimes of the lens can affect FAF lifetime measurements, prolonged FAF lifetimes in AMD are specific to the disease and not a lens artefact as shown in pseudophakic eyes. The effect of AMD on the lifetimes outweighs that of age. Patients with SDD, who have a higher risk of AMD progression, also show longer FAF lifetimes.

To assess choriocapillaris flow deficit percentage (CCFD%) across stages of dry age-related macular degeneration (AMD) using swept-source optical coherence tomography angiography (SS-OCTA).

This cross-sectional, observational study included 270 eyes (182 patients), classified as early (70 eyes), intermediate (121 eyes) and geographic atrophy (GA, 79 eyes).Participants underwent a complete examination including macular 6×6 mm SS-OCTA scans (PLEX Elite 9000). Scans were reviewed and analysed for subretinal drusenoid deposits (SDDs), retinal pigment epithelium (RPE) atrophy size, incomplete RPE and outer retinal atrophy (iRORA) and drusen volume (3 mm). CCFD% was calculated after compensation and binarisation using Phansalkar's method (r=4-15 pixels) in various early treatment for diabetic retinopathy study sectors. Linear mixed-effects models adjusted for age evaluated associations with AMD stages and other imaging biomarkers.

CCFD% progressively increased with advancing dry AMD stages. Intermediate AMD eyes showed higher CCFD% than early AMD ones across all regions (p<0.001). GA eyes exhibited significantly higher CCFD% compared with early (p<0.001) and intermediate AMD eyes (p<0.001).SDDs were significantly associated with higher CCFD% in early (p<0.01) and intermediate AMD (p<0.05) for almost all regions examined, but not in GA (p>0.05). iRORA presence in iAMD and larger RPE atrophy in GA correlated with increased CCFD% (p<0.001).

This study provides a comprehensive reference database for CCFD% across the stages of dry AMD using SS-OCTA. CCFD% increased with AMD severity, iRORA, SDDs, particularly in early and intermediate stages, and RPE atrophy size. Our findings support CCFD% as a valuable biomarker for clinical and research applications, warranting longitudinal studies to validate its prognostic value.

To study the outcome of the first dose versus three monthly doses of 2 mg aflibercept in the initiation phase of neovascular age-related macular degeneration (nAMD) to inform future clinical trial design on novel durable agents. These agents may take time to act and so initial dosing with aflibercept 2 mg is required for immediate effect.

Visual acuity (VA) outcomes and associations with baseline VA and OCT characteristics were analysed using logistic regression via generalised estimating equations. In addition, VA outcomes based on different combinations of eligibility criteria were assessed.

A total of 1999 eyes of 1862 patients were analysed. The mean age was 79.3 (SD 7.8) years. The mean presenting VA was 58.0 (SD 14.5) ETDRS letter score. A statistical difference in VA was found after first injection (visit 2, 61.6, SD 14.3 ETDRS letter score) and after three monthly injections (visit 4, 62.7, SD 14.9 ETDRS letter score) (P < 0.001). Lower baseline VA and OCT features suggestive of structural changes in the fovea are associated with lower VA after both first and post- initiating doses. Eyes with baseline VA > / = 54 letters alone had similar VA outcomes to eyes with both VA > / = 54 letters and central subfield thickness (CST) of <500 microns.

Mean VA outcomes after three monthly anti-VEGF injections are significantly better than after the first initiating dose. However, baseline OCT characteristics associated with VA in these two timepoints are not clinically different.

We previously reported 1-year outcomes of a treat-and-extend (TAE) regimen with intravitreal faricimab (IVF) for treatment-naïve neovascular age-related macular degeneration (nAMD). Herein, we evaluated the second-year results of this TAE regimen with IVF in eyes completing the first-year treatment.

Retrospective, interventional case series.

We retrospectively studied 30 eyes with treatment-naïve nAMD that had completed the initial year of treatment, assessing best-corrected visual acuity (BCVA), foveal thickness (FT), central choroidal thickness (CCT), total number of injections over 2 years, and intended injection interval at the last visit.

Twenty-five eyes completed the 2-year IVF treatment. There was no significant difference between pre-treatment and 2 years post-treatment BCVA. FT and CCT both showed significant reductions, maintained during the 2-year study period. The total number of injections was 10.1 ± 1.2 over the 2 years. The intended injection interval at the last visit was 13.0 ± 3.4 weeks. Of 5 eyes not completing 2 years of IVF treatment, 4 were switched to other anti-vascular endothelial growth factor (VEGF) agents due to persistent fluids despite IVF at 8-week intervals. In the remaining eye, IVF treatment was discontinued due to suspected faricimab-related intraocular inflammation.

The TAE regimen with IVF for treatment-naïve nAMD was effective during a 2-year period for improving exudative changes and maintaining visual acuity. Although IVF was found to be a relatively safe treatment for nAMD, there were cases requiring a switch to other anti-VEGF agents due to inadequate fluid control effect.

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.

Type 1 macular neovascularization (MNV) is the most common type of MNV located in the sub-retinal pigment epithelium (RPE). Although type 1 MNV harbors significant clinical variabilities, the underlying pathomechanism has not been fully elucidated yet. The present study evaluated the characteristics of the choroidal feeding artery in 51 eyes with type 1 MNV using a multimodal imaging composite. In most cases (88.2%), a clear, visible connection between the MNV and choroidal artery was not confirmed. A seamless connection between the MNV and the underlying choroidal feeding artery was found in six of 51 eyes (11.8%). Patients with this aberrant choroidal feeding artery showed large pigment epithelial detachments (PED; P < 0.001) and sub-RPE deposits (P < 0.001) more frequently. Patients with aberrant choroidal feeding arteries achieved a dry macula of a similar percentage (P = 0.680) with more frequent anti-vascular endothelial growth factor injections (P = 0.005) and a switch to brolucizumab (P = 0.042) during a similar follow-up period (P = 0.305). Type 1 MNV with aberrant choroidal feeding arteries showed distinct characteristics from unimpeded blood flow (Large PED and sub-RPE deposits), suggesting that the aberrant choroidal arteries serve not only as a source of blood flow but also contribute to the development of MNV by arteriogenesis.

Objective: A bibliometric analysis was performed in the domain of ranibizumab and age-related macular degeneration (AMD) to delineate current trends in international research dynamics and to provide a visual representation of research hotspots and challenges associated with ophthalmic drugs over the past 15 years. This study also evaluates the sustainability of ranibizumab therapy through reduced injection burden, cost-effectiveness compared to alternative treatments, and long-term outcomes that minimize healthcare resource utilization. Method: In this cross-sectional study, bibliometrics analyzed data retrieved and extracted from the Web of Science Core Collection (WOSCC) database to analyze the evolution and thematic trends in the delivery of studies from January 1, 2008, to September 2, 2023, for ranibizumab and AMD studies. A total of 2691 articles on the field were assessed for specific characteristics such as the year of publication, journal, author, institution, country/region, citation, and keywords. Co-authorship analysis, co-occurrence analysis, co-citation analysis, and network visualization were constructed using VOSviewer. Some important subtopics identified by bibliometric characterization were further discussed and reviewed. Results: From 2008 to 2023, the cumulative number of articles published globally increased from 1 to 2,691, with the highest number of articles published in 2020 (255 papers). RETINA THE JOURNAL OF RETINAL AND VITREOUS DISEASES published the most manuscripts (285 papers) and was cited (6496 citations), followed by OPHTHALMOLOGY (193 papers) and GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY (163 papers). OPHTHALMOLOGY was the most cited (20,865 citations), with the United States (786 papers, 38,014 citations), Univ Sydney (98 papers, 5245 citations), and Kim, Jong Woo (56 papers, 550 citations) being the most productive and influential institutions, countries, and authors, respectively. Five clusters were formed by summarizing the top 100 keywords, which marked the emerging frontier of ranibizumab and AMD-related research. Further discussion of the five clusters of research is to assist the researcher in determining the scope of the research topic and planning the direction of the research. Conclusion: Over the past two decades, there has been a notable increase in the number of publications and citations pertaining to ranibizumab and AMD across various countries, institutions, and authors. This study elucidates current trends, global collaboration patterns, foundational knowledge, research hotspots, and developmental trajectories within the realm of ranibizumab-related AMD research. Key advancements in AMD treatment with ranibizumab over the last 15 years have centered on less frequent injection schedules, extended drug efficacy, and enhanced safety profiles.

This trial evaluated the noninferiority of a relaxed compared to a strict treat-and-extend treatment strategy in patients with neovascular Age-related macular degeneration (AMD).

Multicenter, randomized, controlled, phase IV, non-inferiority clinical trial. Patients with treatment-naïve nAMD were randomized 1:1 to a relaxed or strict treat-and-extend treatment regimen. Aflibercept 2 mg/0.05 mL was used. In the relaxed regimen, up to 100 μm subfoveal subretinal fluid was tolerated, vs. no tolerance of any fluid in the strict regimen. The primary outcome was the change in best corrected visual acuity (BCVA; ETDRS letters) from baseline to the end of the study at week 104 and its difference between the two treatment arms, with a 5-letter non-inferiority margin.

We randomized 150 patients. The full analysis showed non-inferiority of the relaxed treatment, with a mean difference of -0.12 letters (95%-CI: -3.45 to infinity, H0; mean. diff. ≤ 5 letters: p = 0.008), and a visual acuity gain of 7.3 (4.82; 9.78) vs. 7.01 (3.67; 10.36) letters in the strict vs. relaxed regimen, respectively. Many patients deviated from the protocol due to Covid-19. Per-protocol analysis showed a mean difference of -1.78 letters (95%-CI: -6.61 to infinity, H0; mean. diff. ≤ 5 letters: p = 0.136). Fewer injections were needed in the relaxed regimen, with a mean difference of -2.34 (95%-CI: -4.11 to -0.56, p = 0.01).

Tolerating up to 100 μm subfoveal subretinal fluid achieves good visual outcomes in our 24-month follow-up period, in patients treated with aflibercept for nAMD, with significantly fewer injections needed.

This study aimed to investigate the peripheral retinal and choroidal thicknesses in eyes with reticular pseudodrusen (RPD).

Imaging data of ultrawide-field swept-source optical coherence tomography taken from 40 patients with age-related macular degeneration (AMD) were analyzed. Thirty-nine eyes of 20 patients had RPD (RPD group) and 39 eyes of 20 patients had no RPD (control group). Eyes with RPD were divided into localized/intermediate and diffuse types according to the fundus distribution. The retinal and choroidal thicknesses were measured at the fovea and six peripheral points in each eye, and the results were statistically analyzed.

The mean ages were 78.0 ± 6.1 years in the RPD group and 74.4 ± 7.2 years in the control group. The RPD group showed a thinner retina only at the nasal point (p = 0.002) than the control group. The choroid was significantly thinner in the RPD group than in the control group at most peripheral points, except for the far temporal and far inferior points. Diffuse and localized/intermediate types of RPD eyes showed no significant difference in choroidal thickness, except at the nasal point, which was thinner in the diffuse type (p = 0.049).

In eyes with RPD, most peripheral retinal thicknesses were not different from those of eyes with AMD without RPD; however, most peripheral choroidal thicknesses were thinner regardless of the fundus distribution status of the RPD. Nasal choroidal thickness may be associated with RPD severity.

En face optical coherence tomography (OCT) is a practical and informative imaging modality to noninvasively visualize distinct retinal and choroidal layers by providing coronal images using boundary-specific segmentation. Ongoing research with this method is generating breakthroughs in the illustration of new perspectives of retinal disease. The clinical value of en face OCT as an advanced retinal imaging tool is growing steadily and it has unveiled many new insights into the pathoanatomy of retinal disorders. Moreover, this modality can capture various en face OCT biomarkers that correspond to different cell or tissue subtypes, which were previously only identified through histological or electron microscopy methods, underscoring the significance of this technique in providing valuable pathoanatomical information. In this comprehensive review, we will systematically summarize the en face OCT findings across a broad spectrum of retinal diseases, including disorders of the vitreoretinal interface and retinal vascular system (e.g. paracentral acute middle maculopathy or PAMM and diabetic retinopathy), in addition to the en face OCT features of other conditions such as age-related macular degeneration, pachychoroid disease spectrum, myopic degeneration, uveitis and inflammatory disorders, inherited retinal dystrophies, and drug toxicity. We will discuss and highlight the unique clinical and pathoanatomical findings uncovered with en face OCT of each these diseases mentioned above.

Faricimab, a bispecific antibody targeting VEGF-A and angiopoietin-2, has shown promise in treating neovascular age-related macular degeneration (nAMD). This study evaluates 1-year outcomes of faricimab in treatment-experienced nAMD patients.

This single-centre retrospective cohort study included patients previously treated for nAMD who switched to faricimab between November 2022 and March 2024. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and treatment intervals were assessed at baseline, 6, and 12 months.

One hundred eighty-four patients (215 eyes) were included. Patients had received a median of 18 (interquartile range [IQR] 10-28.5) anti-VEGF injections per eye over an average of 5.02 ± 11.82 years before switch. An average of 8.63 ± 2.2 faricimab injections were administered per eye over an average follow-up of 12.19 ± 2.70 months. Median BCVA decreased from 70 ETDRS letters (IQR 55-76) at baseline to 62 (IQR 47-76) at 12 months (p = 0.0038). Median CMT improved from 259.5 μm (IQR 223-299.75) at baseline to 232 μm (202.0-272.5) at 12 months (p < 0.0001). At the last follow-up, 40.2% of eyes were dry on OCT. The median dosing interval doubled from 4 weeks (IQR 4-4) to 8 weeks (IQR 6-10) with faricimab (p < 0.0001). 47.4% and 16.3% of eyes achieved treatment intervals of ≥8-12 weeks and ≥12 weeks, respectively. Three events of uveitis were noted following the loading phase.

This real-world study demonstrates that faricimab maintains vision and achieves significant anatomical improvements in treatment-experienced nAMD patients. The extended treatment intervals could significantly reduce the burden on patients and healthcare resources.

Artificial intelligence (AI)-driven biomarker segmentation offers an objective approach to assessing neovascular age-related macular degeneration (nAMD). In addition, faricimab, a bispecific VEGF and Ang-2 inhibitor, presents new potential in disease management. This study applies an AI-based segmentation algorithm to quantify key optical coherence tomography (OCT) biomarkers and assess the short-term efficacy of intravitreal faricimab in treatment-naïve patients.

This retrospective analysis includes 40 eyes from 38 treatment-naïve patients with nAMD treated with faricimab at LMU University Hospital Munich between January 2023 and September 2024. Patients received 4-monthly intravitreal injections. Biomarkers of disease activity, including central retinal thickness (CRT), intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM) and fibrovascular pigment epithelium detachment (fvPED), were quantified using a deep learning-based semantic segmentation algorithm. Best-corrected visual acuity (BCVA) and OCT imaging data were analyzed at baseline (mo0) and after 1 (mo1), 2 (mo2) and 3 months (mo3).

AI-driven analysis revealed significant reductions in key biomarkers. CRT decreased from 433.6 (IQR: 306.6) µm at mo0 to 241.5 (IQR: 130.8) µm at mo3 (p < 0.0001). IRF and SRF volumes were reduced by > 99% from mo0 to mo3 (both p < 0.0001). BCVA improved from 0.60 (IQR: 0.30) logMAR at mo0 to 0.40 (IQR: 0.33) logMAR at mo3 (p < 0.0001). Correlation analysis identified IRF and SHRM reductions as the strongest predictors of visual improvement.

This study demonstrates the potential of AI-assisted biomarker analysis for precise disease monitoring in nAMD. Faricimab significantly reduced disease activity biomarkers and improved visual acuity in treatment-naïve patients, reinforcing its efficacy in early disease control. Future studies should explore long-term outcomes and further integrate AI-driven biomarker evaluation in clinical practice.

To investigate the relationship between high temperature requirement A (HTRA1) and the local complement system, we measured HTRA1 and complement activation products in the aqueous humor of patients with neovascular age-related macular degeneration (nAMD).

Surveys (cross-sectional studies).

One hundred twenty-one eyes of 121 patients with nAMD and 55 control eyes were enrolled. HTRA1, complement activation products (C3a and C4a), and proinflammatory cytokines (vascular endothelial growth factor [VEGF] and monocyte chemoattractant protein-1) were measured. Genotyping of ARMS2 A69S, in linkage disequilibrium with the HTRA1 gene, was performed in all patients and controls.

The respective GG, GT, and TT genotypes for ARMS2 A69S were distributed as follows: 23 (19.0%), 54 (44.6%), and 44 (36.4%) in nAMD patients, and 26 (47.3%), 22 (40.0%), and 7 (12.7%) in controls, (p < 0.001). HTRA1 concentrations in the aqueous humor were higher in nAMD (994 pg/ml; interquartile range, 743-1450) than controls (794 pg/ml; 490-1325). The difference in the HTRA1 concentrations in the aqueous humor between each genotype of ARMS2 A69S was not significant (GG genotype: 857 pg/ml; 508-1115, GT genotype: 957 pg/ml; 758-1474, TT genotype: 1,141 pg/ml; 757-1663, p = 0.1417). VEGF and C3a concentrations in the eyes with the risk allele (T allele) were significantly higher than those with the non-risk allele (p = 0.0400 and p = 0.0197, respectively). HTRA1 concentration was correlated with only the VEGF concentration (ρ = 0.3651, p < 0.0001).

Concentrations of HTRA1 in the aqueous humor were not increased in patients with the ARMS2 risk allele and did not correlate with C3a and C4a concentrations. HTRA1 concentrations in aqueous humor do not reflect local complement activation in nAMD.

Age-related macular degeneration (AMD) is a leading cause of visual impairment and irreversible blindness worldwide. High-resolution imaging techniques have been pivotal in characterizing the morphological alterations in the retina and in identifying structural biomarkers with prognostic significance. In clinical practice, visual function is primarily assessed through visual acuity testing, which, however, does not completely reflect the functional deficits experienced by patients. Microperimetry provides a more comprehensive evaluation of macular function, enabling a direct correlation with retinal structure. We examine the current literature on the correlation between morphological biomarkers - identified via optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence - and retinal sensitivity, as assessed by microperimetry. By encompassing all stages of AMD, we explore the association between retinal sensitivity and a broad spectrum of structural parameters, including distinct drusen phenotypes, hyperreflective foci, the integrity and thickness of various retinal layers, the junctional zone of geographic atrophy, exudative features of neovascular AMD, choriocapillaris flow deficits, and diverse patterns of autofluorescence, among numerous other relevant structural markers. By offering a deeper understanding of the structure-function correlations in disease progression, we provide critical up-to-date insights into the underlying mechanisms of AMD. Moreover, as novel therapeutic strategies continue to emerge, these correlations may serve as more robust endpoints for future clinical trials.

The purpose of this study was to evaluate the angiographic predictors of response to the anti-vascular endothelial growth factor-C/-D agent, sozinibercept.

Prespecified and post hoc subgroup analyses of a phase 2b, randomized, double-masked, sham-controlled trial of 240 participants with treatment-naïve neovascular age-related macular degeneration, comparing monthly intravitreal sozinibercept 0.5 mg or 2 mg, plus ranibizumab 0.5 mg, versus monthly ranibizumab monotherapy.

Visual acuity benefits at week 24 were greatest in participants with occult lesions receiving 2 mg sozinibercept combination therapy (+15.65 [n = 53] letters versus +9.62 [n = 51] with ranibizumab monotherapy; least squares mean difference +6.03; P = 0.0009). A composite analysis of occult and minimally classic lesions excluding retinal angiomatous proliferation (n = 175/240) also favored sozinibercept over control (+16.08 versus +10.34 letters; +5.74; P = 0.0002). Structural outcomes mirrored sozinibercept visual acuity benefits, with less leakage and smaller lesions on multimodal imaging.

Angiographic lesion characteristics were found to predict the response to sozinibercept combination therapy. [Ophthalmic Surg Lasers Imaging Retina 2025;56:287-296.].

To identify optical coherence tomography-based imaging biomarkers that can localize focal leakage points without fluorescein angiography in central serous chorioretinopathy (CSC).

This retrospective case-control study analyzed 119 consecutive patients (123 eyes) with CSC between April 2018 and February 2024, comprising 66 eyes with focal-leakage type and 57 eyes with diffuse-leakage type. We assessed leakage sites using optical coherence tomography, and the proportions of optical coherence tomography findings were compared between focal-leakage and diffuse-leakage types.

Hyporeflective lucency signs were observed in 27 eyes (40.9%) with focal-type CSC, while no such signs were detected in diffuse-type CSC cases (0.0%; P < 0.001). In focal-type CSC, these signs were exclusively localized to leakage points, with no occurrence in other areas within serous retinal detachment. Microrips of retinal pigment epithelium and subretinal hyperreflective material were identified in 23 (34.8%) and 47 eyes (71.2%) with focal-type CSC, respectively, and also in eyes with diffuse-type CSC (5.3% and 19.3%, respectively; P < 0.001 for both comparisons).

Only the hyporeflective lucency sign is present exclusively in focal leakage points of fluorescein angiography. Our findings suggested that the hyporeflective lucency sign may serve as a potential therapeutic target in CSC.

Given how the diagnosis and management of many ocular and, most specifically, retinal diseases heavily rely on various imaging modalities, the introduction of artificial intelligence (AI) into this field has been a logical, inevitable, and successful development in recent decades. The field of retinal diseases has practically become a showcase for the use of AI in medicine. In this article, after providing a short overview of the most relevant retinal diseases and their socioeconomic impact, we highlight various aspects of how AI can be applied in research, diagnosis, and disease management and how this is expected to alter patient flows, affecting also health care professionals beyond ophthalmologists.

Age-related macular degeneration (AMD) is an eye disease that can lead to legal blindness and vision loss. In its advanced stages, it is classified into dry and neovascular AMD. In neovascular AMD, the formation of new blood vessels disrupts the structure of the retina and induces an inflammatory response. Treatment for neovascular AMD involves antibodies and fusion proteins targeting vascular endothelial growth factor A (VEGFA) and its receptors to inhibit neovascularization and slow vision loss. However, a fraction of patients with neovascular AMD do not respond to therapy. Many of these patients exhibit a subretinal fibrotic scar. Thus, retinal fibrosis may contribute to resistance against anti-VEGFA therapy and the cause of irreversible vision loss in neovascular AMD patients. Retinal pigment epithelium cells, choroidal fibroblasts, and retinal glial cells are crucial in the development of the fibrotic scar as they can undergo a mesenchymal transition mediated by transforming growth factor beta and other molecules, leading to their transdifferentiation into myofibroblasts, which are key players in subretinal fibrosis. Autophagy, a process that removes cellular debris and contributes to the pathogenesis of AMD, regardless of its type, may be stimulated by epithelial-mesenchymal transition and later inhibited. The mesenchymal transition of retinal cells and the dysfunction of the extracellular matrix-the two main aspects of fibrotic scar formation-are associated with impaired autophagy. Nonetheless, the causal relationship between autophagy and subretinal fibrosis remains unknown. This narrative/perspective review presents information on neovascular AMD, subretinal fibrosis, and autophagy, arguing that impaired autophagy may be significant for fibrosis-related resistance to anti-VEGFA therapy in neovascular AMD.

Vascular endothelial growth factor (VEGF) is a key mediator of exudative age-related macular degeneration (eAMD), yet non-invasive biomarkers for disease monitoring remain limited. This study evaluates VEGF levels in human tear fluid as a potential biomarker for eAMD and investigates the molecular dynamics of VEGF in a laser-induced choroidal neovascularization (lCNV) mouse model. Tear VEGF levels were quantified using proximity qPCR immunoassays in eAMD patients (n = 29) and healthy controls (n = 21) and correlated with optical coherence tomography (OCT) findings. Molecular analyses, including immunohistochemistry, gene expression profiling, and phosphorylation assays, were conducted on choroid-retinal pigment epithelium (RPE) and lacrimal gland (LG) tissues from lCNV mice (n = 25). Tear VEGF levels were significantly elevated in eAMD patients, correlating with disease severity. Females exhibited higher VEGF levels, a pattern not replicated in the mouse model. In lCNV mice, VEGF overexpression originated from the choroid-RPE, driven by hypoxic and inflammatory signaling, with no significant LG contribution. Increased VEGF, IL-6, and vimentin expression, along with NF-κB and STAT3 activation, were observed. These findings suggest that tear VEGF is a promising non-invasive biomarker for eAMD, warranting further validation for clinical application in disease monitoring and treatment optimization.

Understanding the clinical characteristics and underlying mechanisms of simultaneous geographic atrophy (GA) and choroidal neovascularization (CNV)/macular neovascularization (MNV) is necessary for the long-term management of late age-related macular degeneration (AMD) in clinical practice.

The authors reviewed the literature on the incidence, risk factors, and clinical characteristics of simultaneous GA and CNV/MNV and developed consensus recommendations for the diagnosis, assessment, and management of simultaneous GA and CNV/MNV in clinical practice.

The incidence rate of CNV/MNV in eyes with GA is reported as 7.4% per patient-year or 13.8% in 4.1 years, while that of macular atrophy (MA) subsequent to CNV/MNV is reported as 24.4% to 37% in 24 months. Recent studies using optical coherence tomography angiography (OCT-A) revealed the presence of subclinical CNV/MNV in 11% to 16% of eyes with GA. Fundus autofluorescence is used to detect MA; optical coherence tomography (OCT) and OCT-A are useful for detecting MA, especially around the fovea, with OCT-A offering high sensitivity and specificity in the detection of both MA and CNV/MNV. GA and CNV/MNV share the genetic risk factors of HTRA1, complement factor H, complement factors 3 and 2, and ARMS2, and clinical risk factors of large drusen, cuticular drusen, intraretinal hyperreflective foci, and subretinal drusenoid deposits, suggesting that simultaneous GA and CNV/MNV represents a continuum of AMD. Anti-vascular endothelial growth factor therapy for CNV/MNV is reported to have no impact on the speed or magnitude of MA development or enlargement. An association has been observed between CNV subtype and MA progression, with the latter being slower in the presence of type 1 CNV/MNV.

These findings suggest there is a high probability of coexistence of GA and CNV/MNV and that they should not be considered separately. Future clinical studies should assess the two conditions simultaneously using OCT and OCT-A.

What is known Owing to differences in their clinical characteristics, geographic atrophy (GA) and choroidal neovascularization (CNV)/macular neovascularization (MNV) have historically been regarded as two separate entities; however, several cases of coexistent GA and CNV/MNV have been reported recently in the published literature. What is new The findings of this review confirm that GA and CNV/MNV share common genetic risk factors and clinical characteristics, and suggest that these two entities are part of a continuum of late-stage age-related macular degeneration (AMD). The potential for GA and CNV/MNV to coexist should be considered in any discussion of the long-term management of late AMD; moreover, clinicians should assess for CNV/MNV in patients with GA, and for GA in those with CNV/MNV, using multimodal imaging.

Background: Anti-Vascular Endothelial Growth Factor (VEGF) therapy is an effective therapy for improving and stabilizing the vision of patients with neovascular age-related macular degeneration (nAMD). However, the treatment requirements, particularly the number of intraocular injections, can vary significantly among patients. This study aimed to analyze the vascular characteristics of macular neovascularizations (MNVs) to identify potential biomarkers that could predict the required injection frequency throughout the disease course. Methods: In all patients, the initial diagnosis of nAMD was confirmed using optic coherence tomography (OCT), fluorescein angiography, and OCT angiography (OCTA). MNVs detected using OCTA were subjected to quantitative vascular analysis of their area, total vascular length (sumL), fractal dimension (FD), and flow density. These results were then correlated with the number of intravitreal anti-VEGF treatments administered during the first 3 years of treatment. Additionally, the relationship between the parameters and visual acuity progression was analyzed. Results: A total of 68 treatment-naïve eyes were included in the study, comprising 31 eyes with type 1 MNV, 19 eyes with type 2 MNV, and 18 eyes with type 3 MNV. The average MNV area at baseline was 1.11 mm2 ± 1.18 mm2, the mean total vascular length was 12.95 mm ± 14.24 mm, the mean fractal dimension was 1.26 ± 0.14, and the mean flow density was 41.19 ± 5.87. On average, patients in our cohort received 19.8 ± 8.5 intravitreal injections (IVIs). A significant correlation was found between the number of administered IVIs in the first 3 treatment years and the MNV area (p < 0.005), sumL (p < 0.005), and FD (p < 0.05), while no correlation was found with flow density. Additionally, there was no significant association between MNV type and treatment requirements, nor between MNV vascular architecture and visual acuity progression. Conclusions: The results suggest that the specific vascular structure of untreated MNV may serve as a predictor of long-term treatment demand. With the emergence of new drug classes and advancements in imaging techniques, these parameters could offer valuable insights for forecasting treatment requirements.

Artificial intelligence (AI)-driven biomarker segmentation offers an objective and reproducible approach for quantifying key anatomical features in neovascular age-related macular degeneration (nAMD) using optical coherence tomography (OCT). Currently, Faricimab, a novel bispecific inhibitor of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2), offers new potential in the management of nAMD, particularly in treatment-resistant cases. This study utilizes an advanced deep learning-based segmentation algorithm to analyze OCT biomarkers and evaluate the efficacy and durability of Faricimab over nine months in patients with therapy-refractory nAMD.

This retrospective real-world study analyzed patients with treatment-resistant nAMD who switched to Faricimab following inadequate responses to ranibizumab or aflibercept. Automated segmentation of key OCT biomarkers - including fibrovascular pigment epithelium detachment (fvPED), intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), choroidal volume, and central retinal thickness (CRT) - was conducted using a deep learning algorithm based on a convolutional neural network.

A total of 46 eyes from 41 patients completed the nine-month follow-up. Significant reductions in SRF, fvPED, and choroidal volume were observed from baseline (mo0) to three months (mo3) and sustained at nine months (mo9). CRT decreased significantly from 342.7 (interquartile range (iqr): 117.1) µm at mo0 to 296.6 (iqr: 84.3) µm at mo3 and 310.2 (iqr: 93.6) µm at mo9. The deep learning model provided precise quantification of biomarkers, enabling reliable tracking of disease progression. The median injection interval extended from 35 (iqr: 15) days at mo0 to 56 (iqr: 20) days at mo9, representing a 60% increase. Visual acuity remained stable throughout the study. Correlation analysis revealed that higher baseline CRT and fvPED volumes were associated with greater best-corrected visual acuity (BCVA) improvements and longer treatment intervals.

This study highlights the potential of AI-driven biomarker segmentation as a precise and scalable tool for monitoring disease progression in treatment-resistant nAMD. By enabling objective and reproducible analysis of OCT biomarkers, deep learning algorithms provide critical insights into treatment response. Faricimab demonstrated significant and sustained anatomical improvements, allowing for extended treatment intervals while maintaining disease stability. Future research should focus on refining AI models to improve predictive accuracy and assessing long-term outcomes to further optimize disease management.

Ethics approval was obtained from the Institutional Review Board of LMU Munich (study ID: 20-0382). This study was conducted in accordance with the Declaration of Helsinki.

Prior research has demonstrated the therapeutic potential of peroxisome proliferator-activated receptor α (PPARα) agonist fenofibrate on diabetic retinopathy. In the present study, a novel non-fibrate PPARα agonist, A190, was designed with higher potency and selectivity than fenofibrate in PPARα agonism. A190 was encapsulated in biodegradable microparticles (A190-MP) to ensure sustained drug release, with detection in the retina up to 6 months following a single intravitreal injection. A190-MP alleviated retinal dysfunction as shown by electroretinography in Vldlr-/- (wet-AMD model) and Abca4-/-/Rdh8-/- (dry-AMD model) mice. A190-MP also attenuated the decreases in cone photoreceptor density and outer nuclear layer thickness as demonstrated by optical coherence tomography and histology. Moreover, A190-MP reduced vascular leakage and neovascularization in Vldlr-/- mice, suggesting an anti-inflammatory and anti-angiogenic effect. A190-MP upregulated expression of PPARα, PGC1α, and TOMM20 in the retina of Vldlr-/- and Abca4-/-/Rdh8-/- mice. A190-MP also improved retinal mitochondrial function as shown by Seahorse analysis using retinal biopsy. In vitro, A190 attenuated oxidative stress and preserved cell viability in a photoreceptor-derived cell line exposed to 4-HNE and improved mitochondrial function, via a PPARα-dependent mechanism. These findings revealed sustained therapeutic effects of A190-MP in wet and dry AMD models, through improving mitochondrial function by activating PPARα.

Investigation of the morphological changes by optical coherence tomography angiography (OCT-A) and the development of visual acuity in secondary macular neovascularization (sMNV) in central serous chorioretinopathy (CCS) during anti-vascular endothelial growth factor (VEGF) treatment.

Retrospective study of all treatment-naïve eyes with respect to anti-VEGF treatment, in which sMNV in CCS was detected by fluorescein angiography (FA) and OCT‑A and which were treated at the University Eye Hospital Würzburg between July 2021 and the end of December 2022. All patients were treated according to a pro re nata injection regimen (PRN regimen) and followed up for 1 year.

In the study 20 eyes from 16 patients with sMNV in CCS were included. Using FA the sMNV could be confirmed in 35% of cases and using OCT‑A in 100% of cases. Morphologically, the sMNV was clearly demarcated by OCT‑A as "sea-fan"-like in 10 eyes and filamentous in 10 eyes. The decrease in area of the sMNV from 0.94 ± 1.2 mm2 at baseline to 0.72 ± 0.82 mm2 at 12 months was not statistically significant (p = 0.12). During the observational period an average of 8.7 ± 1.6 intravitreal injections (IVOM) were administered (5-12 IVOM, median 9 IVOM).

Both FA and OCT‑A were used to detect sMNV in CCS, with OCT‑A providing more reliable detection of sMNV than FA. With OCT‑A two different types of sMNV could be detected: 1) the "sea-fan" type and 2) the filamentous MNV type. Within the first year of treatment sMNV in CCS requires a comparable number of IVOMs as the treatment of neovascular age-related macular degeneration.

Background/Objectives: Periodontitis is a chronic inflammatory disease that leads to systemic low-grade inflammation. Systemic low-grade inflammation has been found in patients with age-related macular degeneration (AMD). In this systematic review and meta-analysis, we evaluated the association between periodontitis and AMD. Methods: We searched 11 scientific literature databases on 16th December 2024 for studies of a diagnosis of periodontitis and prevalent or incident AMD. Eligible studies underwent a qualitative review and meta-analysis of the association. Study selection, data extraction, and risk of bias within studies were made in duplicate by two authors and conferred with a senior author. Results: Seven studies eligible for review included in total 149,217 individuals. Across the seven studies, different study designs, diagnoses and definitions of periodontitis, and diagnosis and definitions of AMD were employed. Our meta-analysis showed an association between periodontitis and AMD with an odds ratio of 1.42 (95% CI: 1.12 to 1.78; p = 0.003). Conclusions: Periodontitis is significantly associated with AMD. Unlike genetic predisposition and high age, which are important risk factors of AMD that cannot be modified, periodontitis is a risk factor that can be treated and potentially eliminated, thus allowing for a personalized approach for risk elimination in AMD. Attention should be given to the dental health of patients at risk of AMD.

This retrospective, real-life cohort was analyzed to detect the frequency of different HRM evolution patterns and their correlation with MNV types, morphological and functional changes in exudative nAMD under long-term anti-VEGF therapy. We evaluated optical coherence tomography (OCT) volume scans in 143 eyes of 94 nAMD patients (start of anti-VEGF therapy 2009-2018, therapy until the last visit) and recorded the VA at all visits. HRM evolution patterns were differentiated: pattern 1 = no HRM, pattern 2 = subretinal HRM resolved during follow-up, pattern 3 = persistent subretinal HRM with new HRM-boundary remodeling [BR], pattern 4 = persistent subretinal HRM without HRM-BR. Pattern 1 was observed in 58 eyes (40.6%), 33 eyes (23.1%) showed pattern 2, 39 eyes (27.3%) pattern 3 and 13 eyes (9.1%) pattern 4. HRM pattern correlated with type 1-3 MNV (p = 0.02), especially pattern 1 with type 1 MNV and pattern 3 with type 2 MNV. Over time, a change of MNV types could be observed only from type 2 into type 1 MNV (p = 0.0001). Some eyes with HRM pattern 3 changed during follow-up into pattern 4, which was often associated with the presence of macular atrophy (p = 0.0001) and demonstrated a reduced mean VA compared to pattern 1-3 at baseline (p = 0.0001), year 1 (p = 0.0001) and final visit (p = 0.02).In this study, we characterized different HRM evolution patterns in a real-world dataset and demonstrated their associations with MNV transformation during long term anti-VEGF therapy. The HRM patterns may provide prognostic value with morphological and functional implications.

To analyze our outcome for patients with neovascular age-related macular degeneration (nAMD) treated with aflibercept in a treat-and-extend regimen pursuing an exit strategy (with best possible adherence to the "Bern" exit criteria) over 6 years in a real-world setting. The primary objective of the study was to investigate the proportion of patients who were able to achieve and maintain treatment exit.

This is a retrospective chart review study of treatment-naïve patients diagnosed with nAMD receiving intravitreal aflibercept injections performed at our department with at least 2 years of follow-up visits. The primary outcome was the percentage of patients able to achieve and maintain the treatment exit regarding intravitreal anti-VEGF injections. Further outcome measures were best-corrected visual acuity (BCVA), incidence of recurrence after treatment cessation, duration of therapy, and number and intervals of injections.

There were 31 eyes of 25 patients included in this retrospective study. The observation period was from September 1, 2017 to August 31, 2023. Of all included patient eyes, 22.6% (n = 7) reached exit criteria. Of all the "exit" patients, 28.6% (n = 2) suffered from disease relapse and therapy was restarted at a mean (± SD) of 41.5 ± 12.5 weeks (range: 29 to 54 weeks). Regarding the eyes that met treatment exit, 5 of 31 (16.1%) had no disease recurrence in the observed study period. The median BCVA (Snellen decimal; ± interquartile range: IQR) changed from 0.63 (0.27) at baseline to 0.63 (0.4) in the first year, 0.63 (0.3) in the second year, 0.63 (0.46) in the third year, 0.63 (0.3) in the fourth year, 0.63 (0.4) in the fifth year, and 0.4 (0.04) in the sixth year. The median number of injections (± IQR) per eye in the first year of treatment was 8 (2), in the second year 5 (2), in the third year 5 (2.5), in the fourth year 5 (1), in the fifth year 3 (0.8), and in the sixth year 3 (0). Extension of the treatment interval after the loading phase in weeks was achieved up to a median (± IQR) of 5.8 (4) in the first year, 8.4 (6) in the second year, 8 (5.7) in the third year, 9.4 (5.6) in the fourth year, 7 (6.9) in the fifth year, and 8.4 (3.1) in the sixth year of observation.

Our study indicates a lower rate of patients reaching exit criteria with a treat-and-extend regimen compared to clinical study settings, and a similar recurrence rate of nAMD after treatment cessation. Nonadherence to a strict treat-and-extend protocol might influence the result.

Type 3 macular neovascularization (MNV) is a unique form of neovascular age-related macular degeneration (AMD) that presents distinct pathogenetic features, clinical manifestations, and prognostic considerations when compared to types 1 and 2 MNV. Insights gained from clinicopathological correlations, bridging in vivo examination techniques with ex vivo histological analysis, have significantly enhanced our comprehension of this MNV phenotype, shaped current management strategies and influenced future directions for therapeutics. The particularities of type 3 MNV, which may largely stem from its origin from the retinal vasculature, are critically important for predicting the disease course. Our current understanding suggests that type 3 MNV occurs in response to retinal pigment epithelium (RPE) disruption and photoreceptor loss when neovessels originating from the deep capillary plexus are accompanied by activated Müller glia as they infiltrate sub-retinal pigment epithelium basal laminar deposits. Dysregulation of angiogenic and angiostatic factors are thought to play a key role in its pathogenesis. The prognosis for type 3 MNV is likely bilateral involvement and progression towards macular atrophy. It may be imperative for practitioners to distinguish type 3 MNV from other mimicking pathologies such as intraretinal microvascular anomalies, which are also part of the type 3 disease spectrum. For instance, deep retinal age-related microvascular anomalies (DRAMA) may present with similar features on multimodal imaging yet may necessitate distinct management protocols. Distinguishing between these conditions may be vital for implementing tailored treatment regimens and improving patient outcomes in the diverse landscape of AMD phenotypes in the future.

To investigate the clinical course and prognostic factors of age-related macular degeneration without macular neovascularization (MNV) in patients presenting with pigment epithelial detachment (PED) and the associated subretinal fluid (SRF).

Morphological characteristics of spectral-domain optical coherence tomography images were analyzed to determine anatomic outcomes. Factors associated with the progression to late AMD, defined as complete retinal pigment epithelium and outer retinal atrophy (cRORA) or MNV, were investigated.

Fifty eyes of 41 patients were included in this study. The most common SRF location was the angle of the PED (56%), and there was a significant decrease in SRF thickness and PED height and width over the follow-up period. Eleven (22%) eyes developed cRORA, and seven (14%) eyes developed MNV during a mean period of 52.1 months. Multivariate analysis revealed that hyperreflective foci and MNV in the fellow eye were associated with the development of cRORA, and higher PED height was a significant factor associated with the development of MNV.

In patients with AMD, SRF can be accompanied by PED in the absence of MNV. Notably, patients with this characteristic entity can progress to late AMD, including cRORA and MNV, in a significant proportion of cases.

Optical coherence tomography angiography (OCTA) holds promise in enhancing the care of various retinal vascular diseases, including neovascular age-related macular degeneration (nAMD). Given nAMD's vascular nature and the distinct vasculature of macular neovascularization (MNV), detailed analysis is expected to gain significance. Research in artificial intelligence (AI) indicates that en-face OCTA views may offer superior predictive capabilities than spectral domain optical coherence tomography (SD-OCT) images, highlighting the necessity to identify key vascular parameters. Analyzing vasculature could facilitate distinguishing MNV subtypes and refining diagnosis. Future studies correlating OCTA parameters with clinical data might prompt a revised classification system. However, the combined utilization of qualitative and quantitative OCTA biomarkers to enhance the accuracy of diagnosing disease activity remains underdeveloped. Discrepancies persist regarding the optimal biomarker for indicating an active lesion, warranting comprehensive prospective studies for validation. AI holds potential in extracting valuable insights from the vast datasets within OCTA, enabling researchers and clinicians to fully exploit its OCTA imaging capabilities. Nevertheless, challenges pertaining to data quantity and quality pose significant obstacles to AI advancement in this field. As OCTA gains traction in clinical practice and data volume increases, AI-driven analysis is expected to further augment diagnostic capabilities.