Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in older adults. Advanced AMD comprises an atrophic ("dry") form characterized by retinal pigment epithelium (RPE) and photoreceptor degeneration and a neovascular ("wet") form driven by choroidal neovascularization (CNV). Beyond genetic predisposition and environmental stressors, chronic dysregulation of innate immunity is increasingly recognized as a convergent mechanism linking drusen/Bruch's membrane alterations to outer retinal cell death and pathological angiogenesis. Retinal myeloid cells-including resident microglia and, in specific disease contexts, recruited monocyte-derived macrophages-can support homeostasis by clearing lipids and cellular debris, yet may also exacerbate inflammation, matrix remodeling, and neovascularization. Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor expressed by microglia and other myeloid cells that regulates phagocytosis, lipid handling, migration, survival, immunometabolism, and inflammatory tone. Recent retinal studies suggest that TREM2-associated programs can restrain lesion expansion in outer retinal degeneration models and modulate CNV severity in experimental neovascularization; however, interpretation remains limited by disease stage, anatomical niche, and the difficulty of cleanly separating microglia from infiltrating macrophages in vivo. Here, we synthesize current evidence on retinal myeloid contributions to dry and neovascular AMD, provide an updated mechanistic framework for TREM2 signaling, and discuss therapeutic strategies and translational challenges for targeting TREM2 in AMD.

Bovine ocular squamous cell carcinoma (BOSCC) is the most common ocular tumour in cattle, with a multifactorial aetiology involving ultraviolet (UV) radiation, genetic factors, pigmentation, and management practices. A detailed epidemiological characterisation of BOSCC in the Azores, Portugal, is provided, with particular emphasis on its spatial distribution and potential risk determinants. Data were obtained through an epidemiological questionnaire completed by field veterinarians between August 2023 and March 2025. A total of 85 BOSCC cases were recorded across 62 farms-45 on Terceira Island and 17 on São Miguel Island. All affected animals were adult Holstein Friesian dairy cows, managed under extensive pasture-based systems. The nictitating membrane was the most frequently affected structure (69.5%), and multiple lesions occurred in 20% of the cases. Farms located at 200-400 m of altitude presented the highest number of cases. Continuous exposure to UV under pasture-based management represents the main environmental risk factor. Although periocular pigmentation may provide partial protection, other environmental and genetic factors can also contribute to tumour development. Artificial insemination is considered a promising preventive tool, enabling genetic selection for protective traits such as periocular pigmentation. This research provides the first regional epidemiological characterization of BOSCC in the Azores, highlighting the interplay among environmental, genetic, and management-related factors in disease occurrence.

Background/Objectives: Pachydrusen are a drusen subtype associated with the pachychoroid disease spectrum; however, their long-term natural history and pathophysiological significance remain unclear. We investigated 5-year morphological and topographic changes in pachydrusen using diagnostic criteria incorporating late-phase indocyanine green angiography (ICGA) hyperfluorescence. Methods: This retrospective observational study included fellow eyes with pachydrusen from patients with unilateral neovascular age-related macular degeneration. Pachydrusen were defined as sub-retinal pigment epithelium (RPE) deposits ≥ 125 µm in size with corresponding hyperfluorescence on late-phase ICGA. Lesion number, size, and spatial distribution (ETDRS grid and quadrant-based classification) were evaluated at baseline and 5 years. The incidence of macular neovascularization (MNV) and its colocalization with pachydrusen were assessed. Results: Among 57 fellow eyes with pachydrusen, incident MNV developed in 8 eyes (14.0%) during follow-up; the mean time to onset was 25.6 ± 16.3 months. No clear colocalization between pachydrusen and incident MNV was observed. Nineteen eyes completed the 5-year follow-up period. Pachydrusen were predominantly located outside the 6000 µm ETDRS grid at baseline (63.4%) and 5 years (66.3%), significantly exceeding the expected proportion based on the area ratio (p < 0.001). The lesions were most frequently observed in the superotemporal quadrant (52.6%). Over 5 years, 19.8% of the lesions increased in size, 67.2% remained stable, and 12.9% regressed; none of the regressed lesions were accompanied by RPE atrophy. Conclusions: Pachydrusen, defined as late-phase ICGA hyperfluorescence, was predominantly distributed outside the ETDRS grid with a superotemporal predilection and could increase or decrease over a 5-year follow-up period. No colocalization with MNV was observed, and no accompanying RPE atrophy after pachydrusen regression was identified, suggesting that late-phase ICGA-hyperfluorescent pachydrusen may represent a pathophysiology distinct from that of soft drusen.

Background/Objectives: Collision tumors between seborrheic keratosis and melanoma represent a well-known diagnostic pitfall, particularly when the benign keratinocytic component constitutes the predominant portion of the lesion. In such cases, melanoma-specific dermoscopic clues may be obscured by typical seborrheic keratosis patterns, leading to potential underestimation. The aim of this scoping review was to map and summarize the dermoscopic interface features reported in melanoma-seborrheic keratosis collision tumors. Secondary aims were to discuss diagnostic pitfalls, explore potential tumor microenvironment considerations, and assess the adjunctive role of Wood's lamp-assisted dermoscopy. Methods: This review was conducted as a scoping review and reported according to the PRISMA-ScR guidelines using PubMed, Scopus, and Web of Science. Studies reporting histologically confirmed melanoma-seborrheic keratosis collision tumors with available dermoscopic documentation were included. Eligible articles consisted of case reports and case series. Dermoscopic features at the interface between seborrheic keratosis and melanoma were qualitatively synthesized. Results: Five studies describing five melanoma-seborrheic keratosis collision tumors met the inclusion criteria. In all cases, the seborrheic keratosis component was dermoscopically recognizable. Asymmetric interface-related hyperpigmentation was consistently observed in collisions involving pigmented melanomas, whereas it was absent in the single reported case of hypopigmented melanoma. Conclusions: Asymmetric interface-related hyperpigmentation within seborrheic keratosis is a recurrent dermoscopic finding in melanoma-seborrheic keratosis collision tumors and could be considered a monitoring clue rather than a melanoma-specific diagnostic criterion. Given the dynamic nature of melanoma growth, longitudinal assessment of the dermoscopic interface may be particularly informative. Adjunctive techniques, including Wood's lamp-assisted dermoscopy, may support interface-focused evaluation in selected equivocal cases.

Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is a rare entity consisting of lesions similar to those of age-related macular degeneration (AMD) and type 1 aneurysmal neovascularization (N1a), but located outside the macular region in the peripheral retina. We present the case of an 89-year-old woman who presented to the emergency department with loss of visual acuity (VA) in both eyes (OU) due to a massive macular subretinal hemorrhage in the right eye (OD) and a vitreous hemorrhage in her left eye (OS), accompanied in both eyes by peripheral hemorrhagic retinal pigment epithelium detachments (HPED). Ophthalmological examination and multimodal imaging led to the diagnosis of PEHCR. This case highlights the importance of the differential diagnosis of PEHCR from other vascular and neoplastic pathologies in order to avoid unnecessary tests and treatments. Early recognition and diagnosis are essential for establishing appropriate management, with intravitreal injections of anti-vascular endotelial groth factors (anti-VEGF) being recommended in cases with loss of VA or threat thereof. This case also contributes to the limited published literature on bilateral PEHCR, reinforcing the need to consider this pathology in elderly patients with peripheral hemorrhagic lesions.

Nevus lipomatosus cutaneous superficialis (NLCS) is a rare benign cutaneous hamartoma characterised by the presence of mature adipose tissue within the dermis. We report the case of a woman in her mid-20s who presented with an uncomfortable progressively enlarging lesion over the gluteal region. Histopathological examination of a skin biopsy demonstrated mature adipocytes interspersed among dermal collagen bundles, confirming the diagnosis. The patient underwent surgical excision for symptomatic relief, with no recurrence at one-year follow-up. This case underscores the importance of clinicopathological correlation in differentiating NLCS from other dermal and subcutaneous nodular lesions.

Oxidative stress-induced retinal pigment epithelium (RPE) damage and ferroptosis are critical in retinal degenerative diseases, particularly in age-related macular degeneration (AMD)─a major cause of irreversible blindness. Current clinical AMD treatment is predominantly dependent on intravitreal anti-VEGF administration targeting only late-stage choroidal neovascularization (CNV), with limitations of incomplete response and adverse effects. Herein, a facile synthesis of Nuci@PAM-BR, which was designed by modification of antioxidant bilirubin to the surface and encapsulation of antiferroptosis nuciferine in the hydrophobic cavity of polyamidoamine dendrimers, was reported, thus achieving iron homeostasis restoration via triple-pool-targeted scavenging properties for eradicating CNV in AMD management. Our results demonstrated that Nuci@PAM-BR could significantly attenuate CNV by targeting the detrimental "triple pool" in damaged RPE cells, exhibiting excellent antioxidant and anti-inflammatory properties that contributed to its excellent antiangiogenic effect, achieving an over 80% reduction in leakage area and an over 85% decline in neovascular lesion. Such triple-pool-targeted nanotherapy offers a promising alternative and holds significant potential for the future clinical treatment of diverse fundus neovascularization diseases, including AMD.

Angioid streaks (AS) are irregular breaks in a calcified Bruch's membrane that appear as pigmented linear lesions radiating from the optic disc. In approximately 50% of cases, AS are associated with systemic diseases such as pseudoxanthoma elasticum, Paget's disease, various hemoglobinopathies, and they may also be idiopathic. Visual impairment in patients with AS is primarily related to the development of choroidal neovascularization along the streaks, followed by retinal pigment epithelium atrophy. Diagnosis of AS is based on clinical examination and modern imaging methods. This literature review summarizes current data on the epidemiology, etiology, and pathogenesis of diseases associated with AS, as well as treatment approaches, including anti-angiogenic therapy, and their potential complications.