Thyroid eye disease (TED) is a complex autoimmune orbital disease where clinical assessment tools, such as the Clinical Activity Score, often fail to capture the underlying molecular transitions between active inflammation and permanent fibrosis. As the field moves toward precision medicine, tear film metabolomics has emerged as a powerful, noninvasive source of biomarkers that can decode the orbital microenvironment. This review synthesizes current evidence on the metabolic signatures of TED, highlighting the shift from traditional protein biomarkers to small-molecule metabolites, including lipids, amino acids, and oxidative stress products. The current literature provides evidence that alterations in amino acid metabolism, polyamine synthesis, acylcarnitine profiles, and other markers of oxidative stress indicate disease activity in TED. We explore how liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) have identified key dysregulated pathways-most notably in the ornithine-polyamine axis, with an increased putrescine-to-ornithine ratio correlating best with inflammatory activity. By bridging the gap between systemic thyroid dysfunction and localized ocular manifestations, tear metabolomics offers a promising noninvasive approach for biomarker development, disease stratification, and therapeutic decision-making in thyroid eye disease.

Thyroid eye disease (TED) is the most common extrathyroidal manifestation of Graves' disease, causing proptosis, diplopia, and, in severe cases, vision loss. The 2020 approval of the first insulin-like growth factor 1 receptor (IGF-1R) inhibitor for TED introduced disease-specific pharmacotherapy and prompted accelerated development of additional biological agents across multiple mechanistic classes. This review summarizes the clinical trial evidence for biological agents currently approved or in late-stage development for TED, drawing on peer-reviewed publications, conference presentations, and sponsor disclosures through early 2026. Among the mechanistic classes evaluated, IGF-1R inhibition has accumulated the largest randomized trial evidence base. Multiple IGF-1R-directed agents, delivered by intravenous, subcutaneous, and oral routes, have demonstrated statistically significant reductions in proptosis in placebo-controlled trials, with responder rates that vary by agent, route, and disease activity. Interleukin-6 receptor (IL-6R) antagonism produced discordant Phase 3 primary endpoint outcomes across 2 parallel pivotal trials. Neonatal Fc receptor (FcRn) inhibition and selective interleukin-17A blockade each failed to meet primary endpoints in Phase 2 or Phase 3 studies. B-cell directed therapies and other off-label agents have produced inconsistent results in smaller, generally nonrandomized studies. In parallel, the use of orbital decompression has declined in the era following IGF-1R inhibitor approval, reflecting the changing role of surgery in pathways that initially lead with medical therapy. As comparative trial data emerge and the field moves toward treatment selection based on phenotype, clinicians will be better equipped to individualize biological therapy by disease stage, severity, safety profile, and patient preference.

Secondary acquired lacrimal duct obstructions (SALDO) are a diverse group of disorders which encompasses epiphora due to mechanical causes, trauma, neoplasms, infections and inflammatory causes. The present manuscript describes a few updates based on recent research on the varied types of SALDO, their identification, assessment, treatment and outcomes.

Facial fillers are widely regarded as a safe and effective method for cosmetic enhancement, with common adverse effects including bruising, swelling, and tenderness. Rarely, however, vascular complications can occur, resulting in severe outcomes such as sudden blindness. The classic theory posits that a retrograde column of filler is injected into a vessel and reaches the take-off of the central retinal artery, yet several biomechanical and clinical inconsistencies challenge this mechanism. We propose an alternative theory in which filler emboli enter a vessel and follow anterograde flow to reach the central retinal artery. This model better accounts for the rapid and sometimes simultaneous distribution of emboli observed clinically. Understanding the underlying pathophysiology is essential, as prevention strategies may differ depending on the mechanism.

Congenital levator synkinesis represents a complex spectrum of neurodevelopmental disorders characterized by involuntary coupling of eyelid movement with activation of extraocular or masticatory muscles. This review proposes a clinical classification of levator synkinesis into excitatory, inhibitory, and combined phenomena, based on whether synkinetic input results in eyelid elevation, depression, or a combination of both. The underlying pathophysiology is most consistent with a developmental dysinnervation process, likely involving aberrant neural connectivity "miswiring" or, supranuclear release of latent primitive pathways. Histopathologic evidence further supports a neurogenic etiology rather than primary myopathy. Surgical management, largely derived from experience with Marcus Gunn jaw-winking syndrome remains individualized and debated, ranging from levator-disabling procedures with frontalis suspension to more conservative levator-preserving approaches. Recognition of these entities is essential for accurate diagnosis, differentiation from simple congenital ptosis and acquired mimics, and appropriate surgical planning.

Lacrimal gland (LG) choristomas are ectopically located lacrimal gland tissue that present as mass lesions, and their diagnosis is confirmed by histopathology. The current study reviews cases of lacrimal gland choristoma published between 2016 and 2025 and reports a rare case of bilateral epibulbar lacrimal gland choristoma associated with a limbal dermoid and ocular colobomatous anomalies in a young female. LG choristomas have been reported in the conjunctiva, eyelid, orbit, lacrimal drainage system, and intraocular structures. They can be simple or have associated syndromic presentations such as Goldenhar syndrome, linear nevus sebaceous syndrome, epidermal nevus syndrome, and craniofacial microsomia. Molecular studies in syndromic cases demonstrated postzygotic somatic mutations in HRAS, KRAS, and NRAS, affecting the RAS-MAPK signaling pathway. Histopathology demonstrated mature lacrimal gland acini and ductal structures within fibrofatty stroma. Whole-exome sequencing did not identify pathogenic mutations associated with choristoma syndromes, ectodermal dysgenesis, or neuroectodermal developmental disorders.

Fistulas involving the eyelid, lacrimal system, and orbit represent a diverse group of pathologies characterized by abnormal epithelialized communications between 2 separate epithelial-lined tissue elements. They arise from a wide range of etiologies, including congenital defects, trauma, surgery, infection, inflammation, and neoplasia. Although individually rare, their cumulative clinical burden is significant due to diagnostic delays, recurrent infection, cosmetic deformity, and the potential for functional impairment. This review synthesizes data from the current literature to (1) provide a structured classification based on anatomic location or etiopathogenesis, (2) delineate the mechanisms underlying fistula formation, (3) discuss the clinical presentation, (4) diagnostic evaluation, and (5) management strategies for each subtype, with emphasis placed in the management section on the importance of performing complete excision of the epithelialized tract, and employing appropriate reconstructive techniques to achieve durable closure.

While the microscopic anatomy and histology of the lacrimal drainage system have been well described, the same cannot be said of its neuroanatomy and neurophysiology, which are largely unknown. Earlier studies have delineated several aspects of lacrimal drainage anatomy, including discrepancies between living and cadaveric dimensions, radiologic anatomy, endoscopic anatomy, and ultrastructural features. However, unlike the peripheral nervous system elsewhere in the body, the neural topography and neural mapping of the lacrimal drainage system are poorly understood. The present review aims to elucidate the existing knowledge and point out the existing gaps in the understanding of the neuroanatomy of the lacrimal drainage system and possible future course to bridge those gaps.

Epithelial lacrimal gland tumors are rare but important to diagnose early. The initial surgical decision to do an incisional biopsy versus gross total resection depends largely on the radiologic characteristics of the lacrimal gland mass. Until recently, orbital exenteration was considered the standard surgical approach for malignant epithelial tumors of the lacrimal gland. However, more recently, eye-sparing surgical resection followed by radiation therapy has gained popularity in selected patients. In this manuscript, we will review the typical clinical and radiologic features of pleomorphic adenoma of the lacrimal gland compared with those of lacrimal gland carcinoma, and we will review published data regarding local control and survival for malignant lacrimal gland tumors with eye-sparing surgery and radiation.

Acute invasive fungal rhino-orbital sinusitis (AIFROS) is a fulminant, angioinvasive infection that can rapidly threaten vision, the orbit, and life. Traditional management has often favored radical orbital exenteration once orbital or apical disease is detected, based on the assumption that removal of orbital tissue limits intracranial spread. However, growing clinical and radiologic evidence suggests that disease biology, particularly tissue perfusion and vascular dissemination, may be more important than the anatomic extent of orbital involvement alone. This manuscript presents an imaging-driven, biologically grounded framework for managing AIFROS with an emphasis on orbit preservation whenever feasible. Contrast-enhanced magnetic resonance imaging is proposed as the central tool for assessing tissue viability, distinguishing viable inflamed tissue from localized or diffuse necrosis, and identifying intracranial vascular spread. This stratification supports targeted treatment using systemic antifungals, aggressive sinus debridement, transcutaneous retrobulbar amphotericin B injections, and selective orbital debridement, rather than routine exenteration. Particular attention is given to the orbital apex, where involvement does not necessarily mandate radical surgery. Instead, cavernous sinus disease, internal carotid artery involvement, and cerebral infarction emerge as stronger predictors of mortality. Contemporary evidence increasingly supports orbit-sparing management in selected patients without compromising survival. AIFROS should therefore be approached as a perfusion-driven disease, where treatment is tailored to tissue vitality and vascular behavior rather than surgical radicality alone.