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This narrative review explores the pathophysiology of ocular surface inflammation and highlights the therapeutic potential of patch amniotic membrane transplantation (patch-AMT) in ocular surface repair. Disruptions in ocular surface homeostasis caused by trauma, disease, or immune dysregulation trigger an inflammatory cascade that, if unresolved, can impair epithelial healing, lead to fibrosis, corneal haze, and vision loss. Patch-AMT provides a biological intervention with epitheliotropic, anti-inflammatory, anti-fibrotic, anti-angiogenic, and neuroprotective effects that support wound healing, regulate inflammation, and reduce pain. The review examines patch-AMT’s role in acute conditions (chemical burns, Stevens-Johnson Syndrome) and chronic disease (persistent epithelial defects, dry eye disease), focusing on its ability to entrap immune cells, regulate cytokine signaling, and prevent fibrotic remodeling while releasing trophic proteins. Additionally, this review explores how preservation methods, application orientation, and intervention timing influences patch-AMT’s efficacy. Recent advancements in non-surgical application methods have expanded accessibility, enabling earlier intervention and outpatient use. However, variability in clinical protocols emphasize the need for standardized guidelines. The review concludes by highlighting the need for further research to refine treatment timing, optimize repeat application strategies, and evaluate cost-effectiveness. While patch-AMT remains underutilized, growing evidence underscores its potential to improve clinical outcomes, particularly when applied early in disease progression.
Andrew Hopkinson and Francisco C. Figueiredo are contributed equally to this work.
Key Summary Points
Immunoregulatory role of patch-AMT. Patch amniotic membrane transplantation (patch-AMT) provides key immunoregulatory benefits, including reduction of inflammation, promotion of epithelial healing, and prevention of stromal fibrosis in ocular surface conditions
Early intervention advantage. Early application of patch-AMT in acute ocular surface injuries and diseases, such as burns or Stevens-Johnson Syndrome, mitigates inflammation escalation, accelerates recovery, and improves visual outcomes
Advancements in accessibility. Developments in sutureless AMT and outpatient-friendly technologies have expanded access to treatment across a broader spectrum of ocular surface diseases
Influence of Preservation methods and orientation. Preservation method, application orientation, and treatment duration significantly influence therapeutic efficacy
Introduction
Ocular surface homeostasis relies on epithelial integrity, immune regulation, tear film stability, neurovascular function, and normal blinking [1]. Disruptions, whether from trauma, infection, or immune dysregulation, can trigger an inflammatory cascade [2], leading to stromal fibrosis, corneal haze (myofibroblast activation and extracellular matrix deposition), and vision loss (Fig. 1) [3‐7].
Fig. 1
Pathophysiology of corneal inflammation following epithelial damage. This figure outlines the sequential stages of corneal inflammation and repair following epithelial damage, emphasizing key inflammatory and reparative mechanisms. A Color-coded key summarizing the stages of inflammation. B Initial epithelial insult. C Acute inflammation in the first 24 h and pro-inflammatory cytokines release (i) perpetuates tissue damage and inflammation (ii) and triggers innate immunity (iii). PMNs are recruited (iv) and release pro-inflammatory cytokines and proteolytic enzymes that exacerbate epithelial (ii) and stromal damage. An intact BM (vi) prevents inflammatory infiltration into the stroma (vi). D Compromised BM enables the penetration of inflammatory cytokines (i) and cells (ii), leading to keratocyte apoptosis. Infiltrated PMNs release pro-inflammatory cytokines (iii, viii) and free radicals (iv), which in turn impedes healing (v) and drives keratocyte apoptosis (vi) [3, 40, 42]. E TGF-β influx during the first 48 h actives fibrosis (i), myofibroblast activity associated with haze, and scarring (ii, iii). Continued inflammation (iv) impedes epithelial healing (v) [3], promoting further keratocyte apoptosis and PMN infiltration (vi, vii) [7, 42]. Stromal degradation (ix, x) progresses. F PMNs are typically short-lived, undergoing apoptosis within 3–5 days, which defines the acute phase of ocular surface damage [37] but transitions to chronic inflammation from day 7 triggering macrophage recruitment (i), adaptive immune response (ii), and lymphocyte and extended life PMN infiltration (iii, iv) [2]. This exacerbates tissue damage (v, vi, vii). G Healing phase: epithelial closure reduces inflammation by preventing inflammatory cell infiltration (i), and PMN apoptosis occurs (ii), but fibrosis continues (iii, iv). H BM restoration quenches TGF-β influx (i), triggers IL-1-mediated myofibroblast apoptosis (ii) [37, 120], enabling keratocyte renewal and ECM remodeling (iii) [120]. BM Basement membrane, CEC corneal epithelial cell, ECM extracellular matrix, IL interleukin, PMNs polymorphonuclear leukocytes, TGF-β tumor growth factor beta
Amniotic membrane transplantation (AMT) is a biologically active therapy with immunoregulatory, anti-inflammatory [4], anti-fibrotic [6], epitheliotropic [8‐10], anti-angiogenic, and neuroprotective properties [11, 12]. These combined effects, along with its barrier function, allow AMT to modulate inflammation, promote wound healing, and prevent fibrosis [10, 13‐16].
Depending on disease severity and therapeutic objectives, AMT can be applied in different modes [15, 17, 18]. Traditionally, AMT has been used for wound healing and under complex reconstruction conditions [19, 20], but patch-AMT is increasingly recognized for its immunoregulatory role in acute and chronic ocular surface diseases, including chemical burns, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), persistent epithelial defects (PED), dry eye disease (DED) and as an adjunct therapy in the management of infectious keratitis [17, 21‐23].
Despite its well-documented benefits, patch-AMT remains underutilized [24]. This is due to inconsistencies in application techniques, preservation methods, and logistical constraints (Table 1) [2, 17, 24]. However, recent advances in non-surgical sutureless patch-AMT application have improved accessibility and reduced costs, facilitating earlier intervention and outpatient use [19, 20, 25, 26].
Table 1
Summary of clinical papers reporting anti-inflammatory benefit of patch-amniotic membrane transplantation
This table presents clinical evidence evaluating the anti-inflammatory effects of patch-amniotic membrane transplantation (AMT). It also provides a structured overview of AMT applications, linking therapeutic strategies to clinical outcomes for ocular surface repair
aModes of AMT application, namely, patch (P), graft (G), and sandwich (S)
bThe orientation of the amnion—amniotic epithelial cell (AEC) side or stromal side—facing the defect is specified. Dash indicates missing data
cAMT duration. Dash indicates missing data; number in brackets indicate range
dThe type of amniotic membrane used (e.g., cryopreserved [CPAM], self-retained cryopreserved [Prokera], low temperature vacuum-evaporation dehydrated [Omnigen], fresh, or did not say [DNS]) and application settings (surgical [S] vs. non-surgical [C])
fConditions treated are classified as acute, chronic, borderline acute (*), or sub-chronic (**). Dash indicates missing data
gStudy design/type: NCS, prospective, noncomparative, interventional case series; CCS, prospective, comparative, interventional case series; RT, retrospective case series
hN (AMT): Number of treated eyes (and AMT-treated Eyes)
iEvidence of anti-inflammatory benefits supported by: clinical data (D), in vitro inflammatory cell analysis (IM), or observational findings, i.e., clinical observation but no data (O). Ci refers to no data but cited, and dash indicates missing data
This narrative review focuses on the pathophysiology of ocular surface inflammation and the immunoregulatory mechanism of patch-AMT. By synthesizing evidence from preclinical and clinical studies, the review highlights the clinical relevance of patch-AMT application, different preservation methods, application techniques, and the importance of intervention timing in inflammation control.
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This article is a narrative review of previously published studies and does not involve any new studies with human participants or animals performed by the authors. As such, ethical approval was not required.
Pathophysiology of Ocular Surface Inflammation
Disruption to ocular surface homeostasis initiates a multiphase inflammatory cascade that, if unresolved, can impair epithelial healing, induce fibrosis and opacity, and lead to vision loss (Fig. 1) [3‐7].
Acute Inflammation Basement Membrane Breakdown
Epithelial injury or stress triggers pro-inflammatory cytokine (interleukin [IL]-6 [IL-6], tumor necrosis factor-alpha [TNF-α], and IL-1 beta [IL-1β]) release (Fig. 1b) [27‐29], which together with chemokines (monocyte chemoattractant protein 1 [MCP-1] and IL-8), lead to the recruitment of polymorphonuclear neutrophils (PMNs) [27‐29]. PMNs release reactive oxygen species (ROS) and matrix metalloproteinase-9 (MMP-9), a key enzyme in tissue remodeling, which degrades the basement membrane (BM) and extracellular matrix (ECM), delaying epithelial closure and intensifying inflammation [30‐33].
BM breakdown exposes the stroma to inflammatory mediators (Fig. 1d), particularly IL-1α and TNF-α, which drives keratocyte apoptosis and immune cell infiltration [30, 34, 35]. Since keratocytes play an important role in regulating corneal transparency [36, 37], their loss initiates stromal disorganization, ECM remodeling, and progressive fibrosis (Fig. 1e) [36‐38].
Fibrosis and Corneal Haze Formation
Persistent inflammation activates fibroblasts, which transform into myofibroblasts via the key fibrogenic cytokine, transforming growth factor-beta (TGF-β) [37, 39]. Myofibroblasts deposit excessive ECM (collagen I and III), causing corneal haze and scarring (Fig. 1e, f). PMNs exacerbate inflammation through excessive pro-inflammatory cytokine release, oxidative stress, proteolytic activity (e.g., MMP-9), further intensifying keratocyte apoptosis and ECM remodeling [40, 41]. Without effective immune resolution, prolonged myofibroblast activity causes irreversible fibrosis [3, 40, 42].
Chronic Inflammation and Progressive Damage
Failure to resolve acute inflammation leads to chronic macrophage infiltration, lymphocyte activation, and sustained cytokine signaling (Fig. 1F) [37]. Chronic inflammation disrupts epithelial healing and depletes limbal stem cells, causing progressive corneal damage and conjunctivalization.
Chronicity and Neurogenic Inflammation
Corneal nerves regulate immune homeostasis, but inflammation-associated nerve injury triggers immune dysregulation, releasing neuropeptide (substance P, calcitonin gene-related peptide [CGRP]), amplifying inflammation, and contributing to persistent epithelial instability, pain, and stromal fibrosis [43‐45].
Clinical Significance of Poor Immunoregulation
Uncontrolled ocular surface inflammation leads to persistent tissue damage, delayed epithelial healing, scarring, and long-term vision impairment [37, 46, 47]. Poor immunoregulation manifests in PEDs, corneal haze, limbal stem cell deficiency (LSCD), and corneal neovascularization, all of which contribute to ocular surface instability and progressive visual loss.
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Post-Refractive Surgery Corneal Haze and Stromal Fibrosis
Excimer laser-based surface ablation (ELSA), including photorefractive keratectomy (PRK) and laser-assisted subepithelial keratectomy (LASEK), induces controlled epithelial injury involving immune-mediated wound healing [48, 49]. Although epithelial closure typically occurs within 5 days, PMN infiltration and prolonged myofibroblast activity contribute to excessive ECM remodeling, leading to corneal haze [50, 51]. TGF-β signaling remains active until BM regeneration is complete (Fig. 1h) [37, 52], sustaining myofibroblast activation, fibrotic changes, and corneal haze [38, 39, 52, 53]. Early immune modulation is therefore critical to minimizing post-surgical fibrosis and ensuring optimal visual recovery.
Persistent Epithelial Defects and Corneal Scarring
Persistent epithelial defects result from impaired epithelial migration and attachment, often driven by excessive MMP-9 activity and cytokine dysregulation [31‐33]. Failure to re-epithelialize exposes the corneal stroma to chronic inflammation, leading to stromal degradation and permanent corneal opacification [37, 39].
Corneal Melting and Perforation
Excessive proteolytic enzyme activity, particularly from MMPs and neutrophil elastase, can degrade the corneal stroma, causing thinning and perforation [8, 21, 23, 54‐57]. In these cases, urgent intervention with AMT, or keratoplasty is required to preserve globe integrity. Early immunomodulation remains essential to stabilizing the ocular surface and preventing further stromal loss.
Severe Inflammatory Conditions: Chemical Burns and SJS
In chemical burns, substantial cytokine release (IL-1β, TNF-α, IL-6) and oxidative stress induces extensive epithelial destruction, chronic pain, fibrosis, and LSCD [2, 58]. Delayed or inadequate treatment leads to corneal conjunctivalization, scarring, and vascularization, all of which further impair visual outcomes.
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In SJS/TEN, autoimmune-mediated epithelial apoptosis and persistent inflammation lead to severe DED, corneal keratinization, and progressive ocular surface failure [59]. Uncontrolled immune activation exacerbates tissue loss, necessitating early aggressive therapeutic intervention to mitigate irreversible damage [60].
While conventional anti-inflammatory treatments suppress immune activation, they do not actively promote epithelial healing or prevent fibrosis [61]. AMT, by contrast, directly modulates inflammation while supporting corneal repair. In section The Immunoregulatory Benefits of AMT, we explore the immunoregulatory mechanisms and therapeutic potential of AMT in ocular surface disease.
The Immunoregulatory Benefits of AMT
Amniotic membrane is an immune-privileged tissue that plays a pivotal role in fetal development by protecting against maternal immune rejection, exerting direct immunoregulatory effects that counteract inflammation-driven tissue damage [14, 18]. Similarly, patch-AMT functions both as and biological barrier and a bioactive matrix capable of modulating immune response, suppressing pro-inflammatory cytokines and promoting epithelial healing, which are multifaceted mechanisms crucial in limiting corneal fibrosis and preventing long-term visual impairment (Fig. 2) [22, 62‐65].
Fig. 2
The immunoregulatory role of the amnion in wound healing. This figure depicts the mechanisms by which patch-AMT) modulates inflammation and promotes wound healing. A Stages of amnion-mediated repair. B Depiction of how patch-AMT, applied post-injury, traps PMNs and inflammatory cells (i), thereby preventing stromal infiltration and keratocyte apoptosis (ii). The membrane’s bioactive components aid epithelial healing (iii), inhibit proteinase and MMP activity (iv), and promote a favorable microenvironment for natural regeneration (v). C Benefits of patch-AMT, including reduced stromal damage (i), prevention of myofibroblast differentiation (ii), minimized haze, and restoration of stromal homeostasis (iii). Roman numerals align with labeled mechanisms in the figure, providing a detailed visualization of patch-AMT’s multifaceted immunoregulatory effects. This figure emphasizes the importance of AMT in resolving inflammation, accelerating healing, and preserving corneal transparency. AMT Amniotic membrane transplantation, MMP Matrix metalloproteinase, PMNs polymorphonuclear leukocytes
One of the key immunoregulatory actions of patch-AMT is the sequestering of infiltrating inflammatory cells within its stromal matrix; patch-AMT physically entraps PMNs and macrophages, reducing their infiltration into the corneal stroma and limiting TGF-β- and MMP-driven fibrosis (Fig. 2b) [4, 66, 67]. Once trapped, these cells undergo apoptosis or functional modulation, facilitated by bioactive proteins [68‐71], including Fas ligand (FasL), TNF-related apoptosis-inducing ligand (TRAIL), and macrophage inhibitory factor (MIF) [71‐73].
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FasL and MIF are key immunomodulatory proteins involved in maternal–fetal tolerance and immune privilege [63, 71, 74‐76]. Their expression within amniotic membrane enhances its ability to suppress neutrophil and macrophage activation, thereby reducing cytokine-driven inflammation and stromal degradation. By controlling excessive immune cell infiltration, patch-AMT helps to preserve corneal stromal architecture and reduces excessive ECM remodeling, thereby limiting scarring and preventing disease progression.
Cytokine and Fibrosis Modulation
Patch-AMT exerts direct anti-inflammatory and anti-fibrotic effects by suppressing pro-inflammatory cytokines (IL-6 and TNF-α) while enhancing anti-inflammatory mediators such as IL-10 [77, 78]. Additionally, AMT modulates TGF-β signaling to inhibit myofibroblast differentiation, a key step in corneal haze formation and fibrotic scarring [39, 66]. These effects collectively reduce the risk of vision-compromising fibrosis following ocular surface injury.
Antioxidant and Anti-Proteinase Activity
Oxidative stress and excessive protease activity contribute significantly to corneal tissue breakdown and delayed epithelial healing. Patch-AMT absorbs ROS, reducing oxidative damage while simultaneously inhibiting MMP activity to protect the BM and ECM [40, 79‐81] to enable expedited epithelial recovery.
Neuroprotective and Anti-Angiogenic Effects
Patch-AMT supports corneal nerve regeneration by promoting sensory nerve survival, which is crucial for ocular surface healing [11, 12, 64]. Additionally, patch-AMT suppresses vascular endothelial growth factor (VEGF)-driven neovascularization, which is critical in preventing LSCD progression and preserving visual function [64]. These neuroprotective effects further distinguish AMT from conventional anti-inflammatory treatments.
Given the ability of patch-AMT to modulate inflammation, control fibrosis, promote epithelial healing, and support nerve regeneration, this treatment represents a valuable intervention in ocular surface disease. Unlike pharmacologic treatments, which primarily suppress inflammation, AMT actively remodels the healing microenvironment to promote long-term tissue restoration.
In the following sections, we explore preclinical and clinical evidence supporting the immunoregulatory properties of AMT and assess how preservation methods, application orientation, and intervention timing influence its therapeutic efficacy.
Preclinical Evidence Supporting AMT’s Immunoregulatory Role
Extensive preclinical studies have provided mechanistic insights into how AMT influences inflammatory cell dynamics, epithelial healing, stromal preservation, and fibrosis prevention.
Reduction in PMN Infiltration and Stromal Haze
In a rabbit PRK model, Park et al. [40] demonstrated that a 24-h application of cryopreserved patch-AMT significantly reduced PMN infiltration and corneal haze, with effects persisting for up to 12 weeks (p < 0.001). Similar studies have corroborated these findings, showing reduced inflammatory infiltration and enhanced stromal preservation [66, 82, 83]. In an Herpes simplex virus 1 (HSV-1) keratitis model, patch-AMT reduced inflammatory cell infiltration and also significantly reduced epithelial ulceration and stromal necrosis [67].
Entrapment and Apoptosis of Immune Cells
Chemical burn models have shown that patch-AMT actively modulates immune cell behavior by entrapping inflammatory cells and inducing apoptosis [81, 84]. Liu et al. [84] reported a significant reduction in CD147-positive PMNs and CD68+ macrophages following patch-AMT application, with a positive correlation with reduced MMP-9 activity and improved stromal preservation. Similarly, in HSV-1 keratitis models, patch-AMT induced apoptosis in trapped inflammatory cells, dampening the immune response and promoting faster epithelial recovery [68].
Macrophage Polarization and Fibrosis Prevention
AMT Plays an Active Immunoregulatory Role, Influencing Macrophage Behavior
Extracellular matrix heavy-chain hyaluronic acid (HC-HA) enhances the immunomodulatory profile of AMT by binding CD44 onto inflammatory cells, facilitating their entrapment and polarizing macrophages toward M2 pro-repair phenotypes [64, 68, 79, 85, 86]. This transition suppresses pro-inflammatory cytokine secretion (e.g., IL-6 and TNF-α), preventing excessive inflammation and fibrosis and preserving corneal architecture.
Prevention of Fibrosis and Corneal Haze
Woo et al. [83] reported that patch-AMT application post-PRK in rabbits significantly limited myofibroblast differentiation, thereby significantly reducing stromal haze and fibrosis. This highlights the potential of AMT to mitigate long-term fibrotic complications in controlled epithelial injuries.
Enhanced Epithelial Healing
The epitheliotropic properties of patch-AMT to accelerate epithelial closure by providing a protective scaffold that promotes epithelial migration reduces inflammatory cytokine activity, minimizing epithelial apoptosis. Choi et al. [82] observed that patch-AMT application reduced epithelial defect size by 30.5% (p < 0.001) within 3 days in the rabbit PRK model.
Clinical Evidence Supporting the Immunoregulatory Role of AMT
The immunoregulatory properties of patch-AMT have been extensively studied across various clinical indications, with the results demonstrating the ability of this treatment to modulate inflammation, accelerate epithelial healing, and prevent fibrosis
Reduction of Inflammatory Cell Infiltration and Modulation of Immune Responses
Advanced diagnostic tools, such as impression cytology tear biomarker analysis [87] and flow cytometry, have provided objective evidence of the immunoregulatory role of AMT. Ferrari et al. [88] established a correlation between ocular surface inflammatory grading scales (e.g., Efron and McMonnies scale) and quantitative measures of PMN infiltration, enabling the role of AMT in inflammation control to be further understood.
The findings from several clinical studies confirm that patch-AMT entraps and modulates inflammatory cells, preventing excessive immune infiltration into the corneal stroma and reducing proteolytic enzyme activity (Fig. 2). Shimmura et al. [4] evaluated patch-AMT in 12 patients with chronic PED with inflammation, demonstrating adaptive immune cell (CD14+ lymphocyte) entrapment. These authors reported that the results correlated with enhanced epithelial integrity following a 1-week stromal-side-down application. Kheirkhah et al. [89] reported that sequential sutureless applications of patch-AMT, with a mean duration of 3.7 days per application, significantly reduced the accumulation of inflammatory debris in moderate acute chemical burns; these authors also reported a correlation with accelerated epithelial healing in 80% of cases. Histological analysis of recovered patch-AMT confirmed inflammatory cell entrapment correlated to membrane cloudiness, which decreased with each application.
Liu et al. [84] demonstrated that surgically applied cryopreserved patch-AMT (stromal-side-down, 7–9 days) entrapped inflammatory cells. Histopathological analysis of the retrieved AMT confirmed the presence of CD147-positive inflammatory cells, including CD15 + PMNs and CD68 + macrophages. The entrapment was associated with reduced MMP-9 activity and enhanced stromal preservation, reinforcing the role of AMT in immune modulation and proteolytic enzyme suppression. Furthermore, these authors reported that AMT’s immunoregulatory effects were application dependent, noting that moderate disease achieved complete epithelial closure with a single AMT application, whereas severe burns required at least a second application to sustain inflammation control and achieve full healing, likely due to higher inflammatory cell burden [84]. Further studies also adopted repeat applications in severe cases to improve outcomes [25, 89, 90]. The ability to sequester immune cells within the amniotic matrix prevents infiltration into the corneal stroma, therefore mitigating immune-mediated tissue damage and proteolytic enzyme degradation.
Suppression of Fibrotic Pathways and Prevention of Corneal Haze
Post-injury and -surgery inflammation and persistent TGF-β activation drive myofibroblast differentiation and stromal fibrosis, leading to corneal haze. Patch-AMT actively suppresses cytokine activity and TGF-β signaling of fibroblast-to-myofibroblast transformation, preventing ECM deposition, which is a key mechanism underlying haze formation following refractive surgery and ocular surface injury (Table 1).
Lee et al. [91] studied 152 eyes (84 patients) undergoing LASEK and demonstrated that cryopreserved patch-AMT (stromal-side-down) reduced corneal haze scores (0.5 ± 0.2 vs. 2.5 ± 0.3 [controls]) and improved visual outcomes 4 weeks post-procedure. These findings aligned with preclinical results by Woo et al. [83], who demonstrated that patch-AMT not only acts as a physical barrier to inflammatory cells, but also serves as a bioactive reservoir that mitigates myofibroblast activity and promotes epithelial healing. Sharma et al. [92] reported that early patch-AMT application in acute SJS completely prevented corneal haze development (0/25) at 6 months, while corneal haze was still observed in 44% (11/25) of the medical therapy control group.
In non-surgical studies involving self-retained cryopreserved AMT (Prokera® corneal bandages; BioTissue, Miami, FL, USA), Vlasov et al. [93] and Cox et al. [94] observed variability in haze prevention and epithelial healing. These authors attributed this variability to potential mechanical trauma from the application ring-device rather than from the bioactivity of AMT.
Taken together, these findings confirm the immunomodulatory role of AMT in limiting myofibroblast activation and preventing the development of excessive stromal fibrosis.
Preservation of Corneal Integrity in Severe Acute Inflammatory States
Patch-AMT has been employed in high-risk ocular surface disease where excessive inflammation and proteolytic degradation contribute to severe tissue damage. While its efficacy is well-established in moderate injuries, its role in severe acute cases with extensive limbal ischemia (i.e., damage) remains limited, particularly in cases of chemical burns and SJS (Table 1).
In their study, Kheirkhah et al. [89] reported that sutureless patch-AMT in moderate (Grade I–III) acute chemical burns facilitated epithelial defect closure in all (5/5) cases undergoing treatment, with conjunctival defects healing within 8.2 days on average and corneal defects healing within 13.6 days on average. The study highlighted the role of patch-AMT in reducing acute inflammation and preserving limbal stem cells, potentially reducing long-term complications requiring surgical intervention.
Lui et al. [84] investigated early surgical patch-AMT (≤ 7 days) in chemical burns, reporting that moderate burns healed with a single application, while severe burns required a second application to sustain immunoregulatory benefits and better stabilize the ocular surface. However, epithelial healing remained compromised in cases with extensive limbal ischemia and stem cell deficiency. These authors study highlighted that AMT reduced inflammation and promoted epithelial recovery in cases with residual limbal function, whereas in severe burns where limbal stem cell loss prevented epithelial regeneration, its role was to minimize pathology progression [84].
Tabatabaei et al. [23] demonstrated that early surgical patch-AMT, when used adjunctively in bacterial keratitis after initial antimicrobial therapy, improved visual outcomes and reduced corneal scarring compared to antibiotics alone. In this study, AMT was not intended for use in infection control but rather for modulating inflammation, suppressing proteolytic activity, and limiting neovascularization, thereby reducing the risk of perforation. Early application (within 2–5 days of antibiotic initiation) was associated with better structural and functional outcomes [23].
A randomized controlled trial by Sharma et al. [92] demonstrated that ‘early’ (7–14 days) surgically applied cryopreserved patch-AMT in severe SJS cases prevented LSCD, conjunctival congestion (an important indicator of active inflammation), and other ocular surface complications, whereas these remained prevalent in the medical therapy control group.
Promotion of Epithelial Healing and Modulation of Chronic Disease
In chronic inflammatory conditions, persistent low-grade inflammation impairs epithelial regeneration, contributing to ocular surface instability and recurrent ulceration. Patch-AMT has demonstrated significant benefits in reducing epithelial inflammation, stabilizing corneal homeostasis, and restoring regenerative capacity (Table 1).
Shimmura et al. [4] reported that a 1-week patch-AMT application in patients with PED resulted in marked reductions in epithelial inflammation. While existing fibrosis was not reversed, the study demonstrated AMT’s role in stabilizing disease progression.
A recent randomized controlled trial by Travé-Huarte et al. [12] evaluated the efficacy of bilaterally applied dehydrated patch-AMT in refractory moderate-to-severe DED. At 6 months, these authors observed a significant 65% reduction in Ocular Surface Disease Index (OSDI) scores, decreased corneal dendritic cell density, and improved subbasal nerve plexus integrity. These results confirmed the long-term immunoregulatory and neuroprotective effects of AMT.
In chronic ocular surface diseases, repeated patch-AMT applications may help maintain functional efficacy. Unlike surgical AMT, non-surgical, in-clinic patch-AMT enables timely initial application and subsequent reapplications, supporting sustained immunomodulation and improved epithelial healing [95, 96].
Clinical evidence consistently demonstrates that patch-AMT modulates inflammation, prevents fibrosis, and promotes epithelial regeneration in both acute (chemical burns, SJS) and chronic (DED, PED) ocular surface diseases. By entrapping immune cells, regulating fibrosis, and enhancing epithelial healing, patch-AMT provides a biologically-driven approach to chronic ocular surface repair.
Key factors influencing the immunoregulatory efficacy of AMT, including preservation techniques, application orientation, and timing—to optimize clinical outcomes and therapeutic benefits, are discussed in section Key Factors Influencing the Immunoregulatory Benefits of Amnion .
Key Factors Influencing the Immunoregulatory Benefits of Amnion
The ability of patch-AMT to modulate inflammation, promote epithelial healing, and prevent fibrosis is influenced by its preservation method, application orientation, and intervention timing (Table 1).
Preservation Methods: Cryopreserved Versus Dehydrated AMT
Cryopreserved AMT is widely regarded as the benchmark for maintaining native ECM components, such as HC-HA/PTX3 [86]. However, damage caused by freezing and thawing may deplete the levels of soluble bioactive factors, including FasL, TRAIL, thrombospin-1, and TIMP metallopeptidase inhibitor 1 (TIMP-1), along with those of essential growth factors (epidermal growth factor [EGF], hepatocyte growth factor [HGF], TGF-β1, and TNF-α), all of which are crucial for inflammation resolution and epithelial regeneration [65, 77, 97‐100].
Dehydrated amnion offers a number of advantages, including longer shelf-life, ease of use, and room temperature storage, making it more accessible for point-of-care application. However, traditional dehydration methods (heat and freeze-drying) may degrade ECM proteins and biomolecules [101‐103], potentially diminishing therapeutic efficacy. Recent advancements in dehydration technologies have resulted in the improved preservation of immunoregulatory proteins and ECM integrity, enhancing AMT’s therapeutic potential [22, 65].
Application Orientation: Epithelial versus Stromal Side Down
The orientation of the AMT during application affects its interaction with the ocular surface and immune system. The amnion has two distinct surfaces, namely, the epithelial (AEC) and stromal surface, each with unique bioactive properties. Results from preclinical studies suggest that orientation can modulate inflammatory cell entrapment, epithelial healing, and stromal remodeling [40, 81]. However, as highlighted in Table 1, no clinical consensus exists on the optimal orientation, highlighting the need for standardized protocols [17, 21].
AEC-Side-Down (stroma facing up)
This orientation (stroma facing up) maximizes inflammatory cell entrapment and apoptosis, (Fig. 2) [40, 77, 81], but the exposed stromal layer (spongy layer) may adhere to the lid margin, leading to potential problems such as AMT dislocation (personal communication, F. Figueiredo).
Stromal-Side-Down (AEC side Up)
This orientation functions as a physical barrier against inflammatory cell infiltration [40, 81], but may require more frequent re-applications in severe cases, such as chemical burns, to sustain anti-inflammatory effects [84, 89, 104]. Additionally, adherence to the exposed corneal stroma can delay epithelial closure [91, 105], contributing to haze persistence, as suggested by Wang et al. [66] in PRK models.
Further studies are needed to establish optimal orientation protocols for standardized application [84, 89].
Timing of Patch-AMT Intervention
In severe ocular surface disease, graft-AMT (inlay) has historically been reserved for later-stage application, following the resolution of acute inflammation. Maharajan et al. [106] reported that graft-AMT was more effective when applied after inflammation subsided, likely because it functions as a structural substrate supporting epithelial regrowth, which requires a stable microenvironment. However, patch-AMT serves a distinct role, acting earlier in the disease course by modulating inflammation, suppressing proteolytic activity, and preventing further tissue damage. While graft-AMT is best suited for structural repair, patch-AMT is ideally positioned for early intervention to limit inflammatory damage and preserve regenerative potential (Table 1).
In acute ocular injuries, such as chemical burns and SJS, ‘early’ surgical patch-AMT has traditionally been applied within 6–10 days (Table 1) [20, 92, 107‐109]. However, increasing evidence suggests that intervention within < 6 days significantly reduces complications and improves visual outcomes, particularly in moderate burns and infectious keratitis [19, 23, 108, 110].
Despite its efficacy, logistical challenges (e.g., operating room availability, specialized expertise, and AMT supply) often contribute to delayed application [111]. Delayed intervention in acute conditions, such as chemical burns and SJS, increases the risk of LSCD, fibrosis, and scarring, leading to poorer long-term outcomes [107, 108, 112]. In cases of extensive limbal ischemia and conjunctival damage, AMT alone may not be sufficient to prevent LSCD [107, 108], necessitating subsequent interventions, such as limbal stem cell transplantation or tenoplasty. However, earlier patch-AMT application may help suppress ischemic inflammation, prevent further limbal damage, and reduce fibrosis and scarring, thereby preserving epithelial healing potential [84, 86, 89].
Expanding Access to Earlier AMT Intervention: Advantages of Non-Surgical Patch-AMT
While early surgical patch-AMT has shown promise, its role in severe injuries with extensive limbal ischemia remains uncertain. Ghosh et al. [107] reported that when applied within 5–10 days, Dua Grade > IV cases still developed LSCD, highlighting the need for additional interventions in these cases. However, other studies have suggested that earlier intervention within < 6 days can reduce the impact of Grade IV burns [108], supporting patch-AMT as an improved adjunctive therapy for earlier intervention in severe disease.
The development of non-surgical patch-AMT technologies has broadened accessibility by eliminating surgical delays, allowing for earlier treatment in both acute and chronic ocular diseases. Unlike surgical patch-AMT, which is typically a one-time intervention due to surgical costs, non-surgical patch-AMT can be reapplied as needed, sustaining its immunoregulatory and healing benefits [26, 95, 96]. This adaptability is particularly relevant in cases requiring ongoing inflammation control and epithelial regeneration.
Self-retained cryopreserved AMT (e.g., Prokera®; AmnioClip [DGFG, Hannover, Germany]) has been used in the management of epithelial defects and DED [11, 26, 89, 113]. However, its reliance on cold-chain logistics, potential patient discomfort, and variable treatment tolerance have limited widespread adoption [89, 93, 94, 104].
In contrast, sutureless dehydrated patch-AMT (e.g., AmbioDisc [Corza Medical, Westwood, MA, USA], Omnigen) offers greater practicality, allowing for both scheduled and emergency applications [65, 90, 95, 114]. Studies report that non-surgical dehydrated patch-AMT provides comparable, or superior, outcomes to sutureless cryopreserved patch-AMT [25, 90, 95, 96, 115].
A prospective study by Lotfy et al. [25] demonstrated that dehydrated patch-AMT applied within 48 h of acute chemical eye injuries resulted in complete healing within 1 month in all 23 eyes, including severe (Grade IV) cases, with 43% exhibiting severe limbal ischemia. Repeat applications in severe cases improved final outcomes and stability, although mild limbal ischemia (< 1/3 limbus) persisted in 13% (3 eyes). In refractory PED, complete epithelial closure rates of up to 94% have been reported within 25 days [95, 96, 115].
The flexibility of non-surgical patch-AMT, combined with its practicality and cost-effectiveness, makes it a viable option in both routine and urgent care settings where surgical patch-AMT may not be feasible [12]. While repeat applications may benefit moderate-to-severe acute disease, the role of repeat applications in severe limbal-conjunctival damage remains adjunctive rather than definitive. Repeat applications should be carefully tailored to individual cases, with factors such as wound stability, risk of mechanical trauma, and suitability for sutureless procedures taken into consideration. In cases of complete limbal stem cell failure, AMT plays a crucial role in stabilizing the ocular surface, preventing further degradation, and creating an environment conducive to subsequent stem cell transplantation for ocular surface restoration [25, 84, 89].
While early and repeated application of patch-AMT has the potential to improve the management of acute and chronic ocular surface diseases, the optimization of patch-AMT protocols, including preservation methods, application orientation, and timing, is essential for maximizing therapeutic outcomes in ocular trauma and inflammatory disease management.
Health Economic Benefits of Patch-AMT
Ocular surface diseases can impose a significant socioeconomic burden, with vision impairment affecting quality-adjusted life years (QALYs) and productivity at levels comparable to those of major chronic diseases like diabetes and cardiovascular disease [116‐118].
The cost-effectiveness of patch-AMT lies in its ability to be applied early (≤ 6 days post-injury) [19, 23, 119] and non-surgically [89, 93, 94], thereby improving recovery and reducing the need for downstream invasive procedures and long-term vision impairment. Dehydrated, non-surgical patch-AMT further eliminates cold-chain storage and logistical barriers associated with traditional cryopreserved AMT. Its feasibility in outpatient, emergency, and unscheduled care settings facilitates earlier intervention, with potential benefits in accessibility and cost efficiency across different healthcare systems.
Studies have reported high epithelial healing rates following non-surgical patch-AMT, particularly in PED and acute chemical injuries [25, 90, 95, 96, 115]. While initial evidence supports the cost-effectiveness of patch-AMT compared to surgical alternatives, further research is needed to quantify its long-term impact on healthcare costs and resource utilization across different settings.
Limitations and Future Directions for Patch-AMT Applications
Despite the therapeutic potential of patch-AMT, broader clinical adoption of patch-AMT is influenced by logistical, procedural, ethical, and regulatory challenges. Variability in preservation methods and application techniques may impact clinical outcomes [13, 106], although recent advancements, such as dehydrated amniotic membranes, have improved bioactivity consistency and accessibility [22, 65].
Standardizing application protocols and clinician training is critical for ensuring reproducible outcomes and improving the integration of patch-AMT into more routine care [12, 17, 22, 40, 89, 104]. Ethical concerns regarding donor consent, tissue traceability, and regulatory oversight have largely been addressed through strict adherence to international safety standards [22]. To date, no published cases of infection transmission have been reported despite widespread clinical use of AMT.
Future research should focus on refining personalized protocols for patch-AMT; comparing surgical versus non-surgical AMT for preventing LSCD, corneal haze, and long-term complications; optimizing application timing, duration, orientation, and repeat application criteria to maximize therapeutic efficacy; and assessing healthcare cost-effectiveness and standardizing application protocols across healthcare systems.
By addressing these challenges, patch-AMT could become an integral component of ocular surface disease management, expanding its role in both acute and chronic care settings.
Concluding Remarks
Ocular surface inflammation, if unregulated, disrupts corneal integrity, delays epithelial healing, and drives stromal fibrosis, ultimately leading to vision impairment. Conventional anti-inflammatory and wound-healing strategies often focus on symptom control rather than addressing the underlying immune dysregulation. Patch-AMT has emerged as a biologically driven therapeutic option that not only provides a protective scaffold but actively modulates the inflammatory response, prevents fibrosis, and promotes epithelial regeneration.
In this review, we have outlined the multifaceted immunoregulatory mechanisms of patch-AMT, including its ability to sequester inflammatory cells, suppress pro-fibrotic pathways, and restore corneal homeostasis. Evidence from preclinical and clinical studies supports the efficacy of patch-AMT in acute inflammatory conditions such as chemical burns, SJS, and PED, as well as in chronic ocular surface diseases, including DED.
Despite the demonstrated clinical benefits of patch-ATM, broader and earlier adoption of this treatment has been hindered by logistical, procedural, and regulatory challenges, particularly regarding the standardization of preservation methods, application techniques, and treatment protocols. Recent advancements, including non-surgical, sutureless application techniques and room-temperature stable dehydrated AMT, have improved accessibility, allowing for earlier intervention and outpatient-based treatment. However, further research is needed to optimize treatment timing, refine indications for repeat applications, and establish comparative cost-effectiveness against conventional therapies.
Looking ahead, standardizing clinical protocols, ensuring consistent preservation techniques, and conducting comparative trials across different healthcare settings will be key to maximizing the therapeutic benefits of patch-AMT. The ability of patch-AMT to modulate inflammation, promote corneal healing, and prevent fibrosis positions it as a critical adjunctive therapy in both acute and chronic ocular surface disease management.
By addressing these clinical, logistical, and economic considerations, patch-AMT has the potential to become a mainstay therapy in ocular surface disease management, expanding its role beyond complex surgical cases to routine early intervention strategies that improve patient outcomes and preserve vision.
Declarations
Conflict of Interest
Andrew Hopkinson is the chief scientific officer and director of NuVision Biotherapies. Francisco Figueiredo reports no conflicts of interest in this work. The review was constructed independently entirely through academic channels, but NuVision kindly funded the publication fee.
Ethical Approval
This narrative review is based entirely on previously published literature and does not contain any studies with human participants or animals performed by the authors. Ethics compliance is therefore not applicable.
Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
Severe immune-mediated disorders that affect the skin and mucous membranes, including the ocular surface, causing inflammation and scarring
1.
Aragona P, Rolando M. Towards a dynamic customised therapy for ocular surface dysfunctions. Br J Ophthalmol. 2013;97(8):955–60.PubMedCrossRef
2.
Dua HS, Ting DSJ, Al Saadi A, Said DG. Chemical eye injury: pathophysiology, assessment and management. Eye (Lond). 2020;34(11):2001–19.PubMedCrossRef
3.
Wagoner MD, Kenyon KR, Gipson IK, Hanninen LA, Seng WL. Polymorphonuclear neutrophils delay corneal epithelial wound healing in vitro. Invest Ophthalmol Vis Sci. 1984;25(10):1217–20.PubMed
4.
Shimmura S, Shimazaki J, Ohashi Y, Tsubota K. Antiinflammatory effects of amniotic membrane transplantation in ocular surface disorders. Cornea. 2001;20(4):408–13.PubMedCrossRef
5.
Schuerch K, Baeriswyl A, Frueh BE, Tappeiner C. Efficacy of amniotic membrane transplantation for the treatment of corneal ulcers. Cornea. 2020;39(4):479–83.PubMedCrossRef
6.
Tseng SC, Li DQ, Ma X. Suppression of transforming growth factor-beta isoforms, TGF-beta receptor type II, and myofibroblast differentiation in cultured human corneal and limbal fibroblasts by amniotic membrane matrix. J Cell Physiol. 1999;179(3):325–35.PubMedCrossRef
7.
Solomon A, Wajngarten M, Alviano F, et al. Suppression of inflammatory and fibrotic responses in allergic inflammation by the amniotic membrane stromal matrix. Clin Exp Allergy. 2005;35(7):941–8.PubMedCrossRef
8.
Meller D, Pires RT, Mack RJ, et al. Amniotic membrane transplantation for acute chemical or thermal burns. Ophthalmology. 2000;107(5):980–9 (discussion 90).PubMedCrossRef
9.
Guo Q, Hao J, Yang Q, Guan L, Ouyang S, Wang J. A comparison of the effectiveness between amniotic membrane homogenate and transplanted amniotic membrane in healing corneal damage in a rabbit model. Acta Ophthalmol. 2011;89(4):e315–9.PubMedCrossRef
10.
Meller D, Pauklin M, Thomasen H, Westekemper H, Steuhl K-P. Amniotic membrane transplantation in the human eye. Dtsch Arzteblatt Int. 2011;108(14):243–8.
11.
John T, Tighe S, Sheha H, Hamrah P, Salem ZM, Cheng AMS, et al. Corneal nerve regeneration after self-retained cryopreserved amniotic membrane in dry eye disease. J Ophthalmol. 2017;2017:6404918.PubMedPubMedCentralCrossRef
12.
Travé-Huarte S, Wolffsohn JS. Sutureless dehydrated amniotic membrane (Omnigen) application using a specialised bandage contact lens (OmniLenz) for the treatment of dry eye disease: a 6-month randomised control trial. Medicina (Kaunas). 2024;60:985.PubMedCrossRef
13.
Dua HS, Maharajan VS, Hopkinson A. Controversies and limitations of amniotic membrane in ophthalmic surgery. In: Reinhard T, Larkin DFP, editors. Cornea and external eye disease. Berlin: Springer; 2006. p. 21–33.CrossRef
14.
Tseng SCG, Espana EM, Kawakita T, et al. How does amniotic membrane work? Ocul Surf. 2004;2(3):177–87.PubMedCrossRef
15.
Dua HS, Gomes JA, King AJ, Maharajan VS. The amniotic membrane in ophthalmology. Surv Ophthalmol. 2004;49(1):51–77.PubMedCrossRef
16.
Rock T, Bartz-Schmidt KU, Landenberger J, Bramkamp M, Rock D. Amniotic membrane transplantation in reconstructive and regenerative ophthalmology. Ann Transplant. 2018;23:160–5.PubMedPubMedCentralCrossRef
17.
Walkden A. Amniotic membrane transplantation in ophthalmology: an updated perspective. Clin Ophthalmol. 2020;14:2057–72.PubMedPubMedCentralCrossRef
18.
Sangwan VS, Burman S, Tejwani S, Mahesh SP, Murthy R. Amniotic membrane transplantation: a review of current indications in the management of ophthalmic disorders. Indian J Ophthalmol. 2007;55(4):251–60.PubMedCrossRef
19.
Tandon R, Gupta N, Kalaivani M, Sharma N, Titiyal JS, Vajpayee RB. Amniotic membrane transplantation as an adjunct to medical therapy in acute ocular burns. Br J Ophthalmol. 2011;95(2):199–204.PubMedCrossRef
20.
Sharma N, Singh D, Maharana PK, et al. Comparison of amniotic membrane transplantation and umbilical cord serum in acute ocular chemical burns: a randomized controlled trial. Am J Ophthalmol. 2016;168:157–63.PubMedCrossRef
21.
Ting DSJ, Henein C, Said DG, Dua HS. Amniotic membrane transplantation for infectious keratitis: a systematic review and meta-analysis. Sci Rep. 2021;11(1):13007.PubMedPubMedCentralCrossRef
22.
Sanders FWB, Huang J, Alió Del Barrio JL, Hamada S, McAlinden C. Amniotic membrane transplantation: structural and biological properties, tissue preparation, application and clinical indications. Eye (Lond). 2023;38(4):668–79.PubMedCrossRef
23.
Tabatabaei SA, Soleimani M, Behrouz MJ, Torkashvand A, Anvari P, Yaseri M. A randomized clinical trial to evaluate the usefulness of amniotic membrane transplantation in bacterial keratitis healing. Ocul Surf. 2017;15(2):218–26.PubMedCrossRef
24.
Liu J, Li L, Li X. Effectiveness of cryopreserved amniotic membrane transplantation in corneal ulceration: a meta-analysis. Cornea. 2019;38(4):454-62. https://doi.org/10.1097/ICO.0000000000001866.
25.
Lotfy NM, Al Rashidi S, Hagras SM. Clinical outcomes of vacuum-dehydrated amniotic membrane (Omnigen) mounted on contact lens (Omnilenz) in eyes with acute chemical eye injuries. Graefes Arch Clin Exp Ophthalmol. 2023;261(12):3541–7.PubMedPubMedCentralCrossRef
26.
Hofmann N, Salz A-K, Kleinhoff K, et al. AmnioClip-plus as sutureless alternative to amniotic membrane transplantation to improve healing of ocular surface disorders. Transplantology. 2021;2(4):425–32.CrossRef
27.
Netto MV, Mohan RR, Ambrósio R Jr, Hutcheon AEK, Zieske JD, Wilson SE. Wound healing in the cornea: a review of refractive surgery complications and new prospects for therapy. Cornea. 2005;24(5):509–22.PubMedCrossRef
28.
Shimazaki J, Shimmura S, Fujishima H, Tsubota K. Association of preoperative tear function with surgical outcome in severe Stevens-Johnson syndrome. Ophthalmology. 2000;107(8):1518–23.PubMedCrossRef
29.
Yamaguchi T, Calvacanti BM, Cruzat A, et al. Correlation between human tear cytokine levels and cellular corneal changes in patients with bacterial keratitis by in vivo confocal microscopy. Invest Ophthalmol Vis Sci. 2014;55(11):7457–66.PubMedPubMedCentralCrossRef
30.
Li W, He H, Kuo CL, Gao Y, Kawakita T, Tseng SC. Basement membrane dissolution and reassembly by limbal corneal epithelial cells expanded on amniotic membrane. Invest Ophthalmol Vis Sci. 2006;47(6):2381–9.PubMedCrossRef
31.
Fini ME, Cook JR, Mohan R. Proteolytic mechanisms in corneal ulceration and repair. Arch Dermatol Res. 1998;290(Suppl):S12-23.PubMedCrossRef
32.
Fini ME, Parks WC, Rinehart WB, et al. Role of matrix metalloproteinases in failure to re-epithelialize after corneal injury. Am J Pathol. 1996;149(4):1287–302.PubMedPubMedCentral
33.
Utsunomiya T, Ishibazawa A, Yoshioka T, Song YS, Yoshida K. Assessing effects of mechanical stimulation of fluid shear stress on inducing matrix Metalloproteinase-9 in cultured corneal epithelial cells. Exp Eye Res. 2023;234: 109571.PubMedCrossRef
34.
Mulholland B, Tuft SJ, Khaw PT. Matrix metalloproteinase distribution during early corneal wound healing. Eye. 2005;19(5):584–8.PubMedCrossRef
35.
Sun CC, Cheng CY, Chien CS, et al. Role of matrix metalloproteinase-9 in ex vivo expansion of human limbal epithelial cells cultured on human amniotic membrane. Invest Ophthalmol Vis Sci. 2005;46(3):808–15.PubMedCrossRef
36.
Netto MV, Mohan RR, Sinha S, Sharma A, Dupps W, Wilson SE. Stromal haze, myofibroblasts, and surface irregularity after PRK. Exp Eye Res. 2006;82(5):788–97.PubMedCrossRef
37.
Wilson SE, Chaurasia SS, Medeiros FW. Apoptosis in the initiation, modulation and termination of the corneal wound healing response. Exp Eye Res. 2007;85(3):305–11.PubMedPubMedCentralCrossRef
38.
Tomás-Juan J, Murueta-Goyena Larrañaga A, Hanneken L. Corneal regeneration after photorefractive keratectomy: a review. J Optometry. 2015;8(3):149–69.CrossRef
39.
Jester JV, Huang J, Barry-Lane PA, Kao WW, Petroll WM, Cavanagh HD. Transforming growth factor(beta)-mediated corneal myofibroblast differentiation requires actin and fibronectin assembly. Invest Ophthalmol Vis Sci. 1999;40(9):1959–67.PubMed
40.
Park WC, Tseng SC. Modulation of acute inflammation and keratocyte death by suturing, blood, and amniotic membrane in PRK. Invest Ophthalmol Vis Sci. 2000;41(10):2906–14.PubMed
41.
Resan M, Vukosavljevic M, Vojvodic D, Pajic-Eggspuehler B, Pajic B. The acute phase of inflammatory response involved in the wound-healing process after excimer laser treatment. Clin Ophthalmol (Auckland, NZ). 2016;10:993–1000.
42.
Brancato R, Fiore T, Papucci L, et al. Concomitant effect of topical ubiquinone Q10 and vitamin E to prevent keratocyte apoptosis after excimer laser photoablation in rabbits. J Refract Surg. 2002;18(2):135–9.PubMedCrossRef
Lasagni Vitar RM, Rama P, Ferrari G. The two-faced effects of nerves and neuropeptides in corneal diseases. Prog Retin Eye Res. 2022;86: 100974.PubMedCrossRef
45.
Wu M, Hill LJ, Downie LE, Chinnery HR. Neuroimmune crosstalk in the cornea: the role of immune cells in corneal nerve maintenance during homeostasis and inflammation. Prog Retin Eye Res. 2022;91: 101105.PubMedCrossRef
46.
Ohta K, Yamagami S, Taylor AW, Streilein JW. IL-6 antagonizes TGF-β and abolishes immune privilege in eyes with endotoxin-induced uveitis. Invest Ophthalmol Vis Sci. 2000;41(9):2591–9.PubMed
47.
Sheng J, Chen W, Zhu HJ. The immune suppressive function of transforming growth factor-beta (TGF-beta) in human diseases. Growth Factors. 2015;33(2):92–101.PubMedCrossRef
48.
Naderi M, Ghadamgahi S, Jadidi K. Photorefractive keratectomy (PRK) is safe and effective for patients with myopia and thin corneas. Med Hypothesis Discov Innov Ophthalmol. 2016;5(2):58–62.PubMedPubMedCentral
49.
Zhou J, Xu Y, Li M, Knorz MC, Zhou X. Preoperative refraction, age and optical zone as predictors of optical and visual quality after advanced surface ablation in patients with high myopia: a cross-sectional study. BMJ Open. 2018;8(6):e023877.PubMedPubMedCentralCrossRef
50.
Choi H, Ju L, Kim J, Choi S, Lee D. Successful treatment with combined PTK/PRK guided by intraoperative skiascopy of patients with corneal haze after surface ablation. Korean J Ophthalmol. 2015;29(1):74–6.PubMedPubMedCentralCrossRef
51.
Erie JC. Corneal wound healing after photorefractive keratectomy: a 3-year confocal microscopy study. Trans Am Ophthalmol Soc. 2003;101:293–333.PubMedPubMedCentral
52.
Nakamura K, Kurosaka D, Bissen-Miyajima H, Tsubota K. Intact corneal epithelium is essential for the prevention of stromal haze after laser assisted in situ keratomileusis. Br J Ophthalmol. 2001;85(2):209.PubMedPubMedCentralCrossRef
53.
Corbett MC, Prydal JI, Verma S, Oliver KM, Pande M, Marshall J. An in vivo investigation of the structures responsible for corneal haze after photorefractive keratectomy and their effect on visual function. Ophthalmology. 1996;103(9):1366–80.PubMedCrossRef
54.
Austin A, Lietman T, Rose-Nussbaumer J. Update on the management of infectious keratitis. Ophthalmology. 2017;124(11):1678–89.PubMedCrossRef
55.
Bahaa-Eldin Hasan A, Mostafa Mohamed W, Ahmed AMG, Ghada B, Ragy RSN. Amniotic membrane graft to conjunctival flap in treatment of non-viral resistant infectious keratitis: a randomised clinical study. Br J Ophthalmol. 2015;99(1):59.CrossRef
56.
Larkin DFP, Alexander RA, Cree IA. Infiltrating inflammatory cell phenotypes and apoptosis in rejected human corneal allografts. Eye. 1997;11(1):68–74.PubMedCrossRef
57.
Ting DSJ, Ho CS, Deshmukh R, Said DG, Dua HS. Infectious keratitis: an update on epidemiology, causative microorganisms, risk factors, and antimicrobial resistance. Eye. 2021;35(4):1084–101.PubMedPubMedCentralCrossRef
58.
Lorenzana-Blanco N, Santander-García D, Güell JL, Alejandre-Alba N. Acute management of ocular chemical burns: a review. J EuCornea. 2022;11(3).
59.
Tóth G, Lukács A, Schirra F, et al. Ophthalmic aspects of Stevens-Johnson syndrome and toxic epidermal necrolysis: a narrative review. Ophthalmol Ther. 2023;12(4):1795–811.PubMedPubMedCentralCrossRef
60.
Thorel D, Ingen-Housz-Oro S, Royer G, et al. Management of ocular involvement in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: French national audit of practices, literature review, and consensus agreement. Orphanet J Rare Dis. 2020;15(1):259.PubMedPubMedCentralCrossRef
61.
Dua HS, Gomes JA, Singh A. Corneal epithelial wound healing. Br J Ophthalmol. 1994;78(5):401–8.PubMedPubMedCentralCrossRef
62.
Niknejad H, Peirovi H, Jorjani M, Ahmadiani A, Ghanavi J, Seifalian AM. Properties of the amniotic membrane for potential use in tissue engineering. Eur Cell Mater. 2008;15:88–99.PubMedCrossRef
63.
Runic R, Lockwood CJ, LaChapelle L, et al. Apoptosis and Fas expression in human fetal membranes. J Clin Endocrinol Metab. 1998;83(2):660–6.PubMed
64.
Tseng SC. HC-HA/PTX3 purified from amniotic membrane as novel regenerative matrix: insight into relationship between inflammation and regeneration. Invest Ophthalmol Vis Sci. 2016;57(5):ORSFh1-8.PubMedCrossRef
65.
Allen CL, Clare G, Stewart EA, et al. Augmented dried versus cryopreserved amniotic membrane as an ocular surface dressing. PLoS One. 2013;8(10): e78441.PubMedPubMedCentralCrossRef
66.
Wang MX, Gray TB, Park WC, et al. Reduction in corneal haze and apoptosis by amniotic membrane matrix in excimer laser photoablation in rabbits. J Cataract Refract Surg. 2001;27(2):310–9.PubMedCrossRef
67.
Heiligenhaus A, Bauer D, Meller D, Steuhl KP, Tseng SC. Improvement of HSV-1 necrotizing keratitis with amniotic membrane transplantation. Invest Ophthalmol Vis Sci. 2001;42(9):1969–74.PubMed
68.
Bauer D, Wasmuth S, Hennig M, Baehler H, Steuhl K-P, Heiligenhaus A. Amniotic membrane transplantation induces apoptosis in T lymphocytes in murine corneas with experimental herpetic stromal keratitis. Invest Ophthalmol Vis Sci. 2009;50(7):3188–98.PubMedCrossRef
69.
Bauer D, Wasmuth S, Hermans P, et al. On the influence of neutrophils in corneas with necrotizing HSV-1 keratitis following amniotic membrane transplantation. Exp Eye Res. 2007;85(3):335–45.PubMedPubMedCentralCrossRef
70.
Li W, He H, Kawakita T, Espana EM, Tseng SC. Amniotic membrane induces apoptosis of interferon-gamma activated macrophages in vitro. Exp Eye Res. 2006;82(2):282–92.PubMedCrossRef
71.
Li H, Niederkorn JY, Neelam S, et al. Immunosuppressive factors secreted by human amniotic epithelial cells. Invest Ophthalmol Vis Sci. 2005;46(3):900–7.PubMedCrossRef
72.
Rossi D, Pianta S, Magatti M, Sedlmayr P, Parolini O. Characterization of the conditioned medium from amniotic membrane cells: prostaglandins as key effectors of its immunomodulatory activity. PLoS ONE. 2012;7(10): e46956-e.CrossRef
73.
Ueta M, Kweon MN, Sano Y, et al. Immunosuppressive properties of human amniotic membrane for mixed lymphocyte reaction. Clin Exp Immunol. 2002;129(3):464–70.PubMedPubMedCentralCrossRef
74.
Runic R, Lockwood CJ, Ma Y, Dipasquale B, Guller S. Expression of Fas ligand by human cytotrophoblasts: implications in placentation and fetal survival. J Clin Endocrinol Metab. 1996;81(8):3119–22.PubMed
75.
Griffith TS, Brunner T, Fletcher SM, Green DR, Ferguson TA. Fas ligand-induced apoptosis as a mechanism of immune privilege. Science. 1995;270(5239):1189.PubMedCrossRef
76.
Kubo M, Sonoda Y, Muramatsu R, Usui M. Immunogenicity of human amniotic membrane in experimental xenotransplantation. Invest Ophthalmol Vis Sci. 2001;42(7):1539–46.PubMed
77.
Hao Y, Ma DH, Hwang DG, Kim WS, Zhang F. Identification of antiangiogenic and antiinflammatory proteins in human amniotic membrane. Cornea. 2000;19(3):348–52.PubMedCrossRef
78.
He H, Li W, Chen SY, et al. Suppression of activation and induction of apoptosis in RAW264.7 cells by amniotic membrane extract. Invest Ophthalmol Vis Sci. 2008;49(10):4468–75.PubMedCrossRef
79.
He H, Li W, Tseng DY, et al. Biochemical characterization and function of complexes formed by hyaluronan and the heavy chains of inter-alpha-inhibitor (HC*HA) purified from extracts of human amniotic membrane. J Biol Chem. 2009;284(30):20136–46.PubMedPubMedCentralCrossRef
80.
Lockington D, Agarwal P, Young D, Caslake M, Ramaesh K. Antioxidant properties of amniotic membrane: novel observations from a pilot study. Can J Ophthalmol. 2014;49(5):426–30.PubMedCrossRef
81.
Kim JS, Kim JC, Na BK, Jeong JM, Song CY. Amniotic membrane patching promotes healing and inhibits proteinase activity on wound healing following acute corneal alkali burn. Exp Eye Res. 2000;70(3):329–37.PubMedCrossRef
82.
Choi YS, Kim JY, Wee WR, Lee JH. Effect of the application of human amniotic membrane on rabbit corneal wound healing after excimer laser photorefractive keratectomy. Cornea. 1998;17(4):389–95.PubMedCrossRef
83.
Woo HM, Kim MS, Kweon OK, Kim DY, Nam TC, Kim JH. Effects of amniotic membrane on epithelial wound healing and stromal remodelling after excimer laser keratectomy in rabbit cornea. Br J Ophthalmol. 2001;85(3):345–9.PubMedPubMedCentralCrossRef
84.
Liu T, Zhai H, Xu Y, et al. Amniotic membrane traps and induces apoptosis of inflammatory cells in ocular surface chemical burn. Mol Vis. 2012;18:2137–46.PubMedPubMedCentral
85.
Higa K, Shimmura S, Shimazaki J, Tsubota K. Hyaluronic acid-CD44 interaction mediates the adhesion of lymphocytes by amniotic membrane stroma. Cornea. 2005;24(2):206–12.PubMedCrossRef
86.
Ogawa Y, He H, Mukai S, et al. Heavy Chain-Hyaluronan/Pentraxin 3 from amniotic membrane suppresses inflammation and scarring in murine lacrimal gland and conjunctiva of chronic graft-versus-host disease. Sci Rep. 2017;7:42195.PubMedPubMedCentralCrossRef
87.
Figueiredo GS, Hogg J, Okonkwo A, et al. Understanding ocular surface inflammation in tears before and after autologous cultivated limbal epithelial stem cell transplantation. Ophthalmol Ther. 2023;12(2):1097–107.PubMedPubMedCentralCrossRef
88.
Ferrari G, Rabiolo A, Bignami F, et al. Quantifying ocular surface inflammation and correlating it with inflammatory cell infiltration in vivo: a novel method. Invest Ophthalmol Vis Sci. 2015;56(12):7067–75.PubMedCrossRef
89.
Kheirkhah A, Johnson DA, Paranjpe DR, Raju VK, Casas V, Tseng SC. Temporary sutureless amniotic membrane patch for acute alkaline burns. Arch Ophthalmol. 2008;126(8):1059–66.PubMedPubMedCentralCrossRef
90.
Mehta A, Pradhan S, Figueiredo F. Low temperature vacuum-dehydrated amnion membrane (Omnigen)—case series for the treatment of ocular surface burn and related complications at a tertiary eye unit in the UK. Investig Ophthalmol Visual Sci. 2021;62(8):1258.
91.
Lee HK, Kim JK, Kim SS, et al. Effect of amniotic membrane after laser-assisted subepithelial keratectomy on epithelial healing: clinical and refractive outcomes. J Cataract Refract Surg. 2004;30(2):334–40.PubMedCrossRef
92.
Sharma N, Thenarasun SA, Kaur M, et al. Adjuvant role of amniotic membrane transplantation in acute ocular Stevens-Johnson syndrome: a randomized control trial. Ophthalmology. 2016;123(3):484–91.PubMedCrossRef
93.
Vlasov A, Sia RK, Ryan DS, et al. Sutureless cryopreserved amniotic membrane graft and wound healing after photorefractive keratectomy. J Cataract Refract Surg. 2016;42(3):435–43.PubMedCrossRef
94.
Cox AR, Sia RK, Purt B, et al. Assessment of corneal haze after PRK and the effect of sutureless amniotic membrane graft by corneal densitometry. J Refract Surg. 2020;36(5):293–9.PubMedCrossRef
95.
Maqsood S, Elsawah K, Dhillon N, Set al. Management of persistent corneal epithelial defects with human amniotic membrane-derived dry matrix. Clin Ophthalmol. 2021;15:2231–8.PubMedPubMedCentralCrossRef
96.
Maqsood S, Elalfy M. Management of ocular surface inflammation with persistent epithelial defects using a sutureless human amniotic membrane dehydrated matrix: a prospective study utilizing a digital ocular surface assessment tool. Clin Ophthalmol. 2024;18:1467–78.PubMedPubMedCentralCrossRef
97.
Hopkinson A, McIntosh RS, Layfield R, Keyte J, Dua HS, Tighe PJ. Optimised two-dimensional electrophoresis procedures for the protein characterisation of structural tissues. Proteomics. 2005;5(7):1967–79.PubMedCrossRef
98.
Niknejad H, Peirovi H, Ahmadiani A, Ghanavi J, Jorjani M. Differentiation factors that influence neuronal markers expression in vitro from human amniotic epithelial cells. Eur Cell Mater. 2010;19:22–9.PubMedCrossRef
99.
Hopkinson A, McIntosh RS, Tighe PJ, James DK, Dua HS. Amniotic membrane for ocular surface reconstruction: donor variations and the effect of handling on TGF-beta content. Invest Ophthalmol Vis Sci. 2006;47(10):4316–22.PubMedCrossRef
100.
Hopkinson A, McIntosh RS, Shanmuganathan V, Tighe PJ, Dua HS. Proteomic analysis of amniotic membrane prepared for human transplantation: characterization of proteins and clinical implications. J Proteome Res. 2006;5(9):2226–35.PubMedCrossRef
101.
Cooke M, Tan EK, Mandrycky C, He H, O’Connell J, Tseng SC. Comparison of cryopreserved amniotic membrane and umbilical cord tissue with dehydrated amniotic membrane/chorion tissue. J Wound Care. 2014;23(10):465–74 (76).PubMedCrossRef
102.
Connon CJ, Doutch J, Chen B, et al. The variation in transparency of amniotic membrane used in ocular surface regeneration. Br J Ophthalmol. 2010;94(8):1057–61.PubMedCrossRef
103.
Rodríguez-Ares MT, López-Valladares MJ, Touriño R, et al. Effects of lyophilization on human amniotic membrane. Acta Ophthalmol. 2009;87(4):396–403.PubMedCrossRef
104.
Kheirkhah A, Casas V, Raju VK, Tseng SCG. Sutureless amniotic membrane transplantation for partial limbal stem cell deficiency. Am J Ophthalmol. 2008;145(5):787–94.PubMedPubMedCentralCrossRef
105.
Lee H-K, Kim J-K, Kim EK, Kim G-O, Lee I-S. Phototherapeutic keratectomy with amniotic membrane for severe subepithelial fibrosis following excimer laser refractive surgery. J Cataract Refract Surg. 2003;29(7):1430–5.PubMedCrossRef
106.
Maharajan VS, Shanmuganathan V, Currie A, Hopkinson A, Powell-Richards A, Dua HS. Amniotic membrane transplantation for ocular surface reconstruction: indications and outcomes. Clin Exp Ophthalmol. 2007;35(2):140–7.PubMedCrossRef
107.
Ghosh S, Salvador-Culla B, Kotagiri A, et al. Acute chemical eye injury and limbal stem cell deficiency—a prospective study in the United Kingdom. Cornea. 2019;38(1):8-12.
108.
Westekemper H, Figueiredo FC, Siah WF, Wagner N, Steuhl KP, Meller D. Clinical outcomes of amniotic membrane transplantation in the management of acute ocular chemical injury. Br J Ophthalmol. 2017;101(2):103–7.PubMedCrossRef
109.
Di Pascuale MA, Espana EM, Liu DT, et al. Correlation of corneal complications with eyelid cicatricial pathologies in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis syndrome. Ophthalmology. 2005;112(5):904–12.PubMedCrossRef
Fletcher D, Edwards D, Tolchard S, Baker R, Berstock J. Improving theatre turnaround time. BMJ Qual Improv Rep. 2017;6(1): u219831.w8131.PubMedPubMedCentralCrossRef
112.
Arora R, Mehta D, Jain V. Amniotic membrane transplantation in acute chemical burns. Eye (Lond). 2005;19(3):273–8.PubMedCrossRef
113.
McDonald MB, Sheha H, Tighe S, et al. Treatment outcomes in the DRy Eye Amniotic Membrane (DREAM) study. Clin Ophthalmol. 2018;12:677–81.PubMedPubMedCentralCrossRef
114.
Memmi B, Leveziel L, Knoeri J, et al. Freeze-dried versus cryopreserved amniotic membranes in corneal ulcers treated by overlay transplantation: a case-control study. Cornea. 2022;41(3):280–5.PubMedCrossRef
O’Conor R, Smith SG, Curtis LM, Benavente JY, Vicencio DP, Wolf MS. Mild visual impairment and its impact on self-care among older adults. J Aging Health. 2018;30(3):327–41.PubMedCrossRef
117.
Crews JE, Chou CF, Zhang X, Zack MM, Saaddine JB. Health-related quality of life among people aged ≥65 years with self-reported visual impairment: findings from the 2006–2010 behavioral risk factor surveillance system. Ophthalmic Epidemiol. 2014;21(5):287–96.PubMedPubMedCentralCrossRef
118.
Park SJ, Ahn S, Park KH. Burden of visual impairment and chronic diseases. JAMA Ophthalmol. 2016;134(7):778–84.PubMedCrossRef
119.
Shammas MC, Lai EC, Sarkar JS, Yang J, Starr CE, Sippel KC. Management of acute Stevens-Johnson syndrome and toxic epidermal necrolysis utilizing amniotic membrane and topical corticosteroids. Am J Ophthalmol. 2010;149(2):203–13 (e2).PubMedCrossRef
120.
Barbosa FL, Chaurasia SS, Kaur H, de Medeiros FW, Agrawal V, Wilson SE. Stromal interleukin-1 expression in the cornea after haze-associated injury. Exp Eye Res. 2010;91(3):456–61.PubMedPubMedCentralCrossRef
121.
Tamhane A, Vajpayee RB, Biswas NR, et al. Evaluation of amniotic membrane transplantation as an adjunct to medical therapy as compared with medical therapy alone in acute ocular burns. Ophthalmology. 2005;112(11):1963–9.PubMedCrossRef
122.
Prabhasawat P, Tesavibul N, Prakairungthong N, Booranapong W. Efficacy of amniotic membrane patching for acute chemical and thermal ocular burns. J Med Assoc Thai. 2007;90(2):319–26.PubMed
123.
Eslani M, Baradaran-Rafii A, Cheung AY, et al. Amniotic membrane transplantation in acute severe ocular chemical injury: a randomized clinical trial. Am J Ophthalmol. 2019;199:209–15.PubMedCrossRef
124.
Kobayashi A, Yoshita T, Sugiyama K, et al. Amniotic membrane transplantation in acute phase of toxic epidermal necrolysis with severe corneal involvement. Ophthalmology. 2006;113(1):126–32.PubMedCrossRef
125.
Ma KN, Thanos A, Chodosh J, Shah AS, Mantagos IS. A novel technique for amniotic membrane transplantation in patients with acute Stevens-Johnson syndrome. Ocul Surf. 2016;14(1):31–6.PubMedCrossRef
126.
Tseng SCG, Prabhasawat P, Barton K, Gray T, Meller D. Amniotic membrane transplantation with or without limbal allografts for corneal surface reconstruction in patients with limbal stem cell deficiency. Arch Ophthalmol. 1998;116(4):431–41.PubMedCrossRef
127.
Chen HJ, Pires RT, Tseng SC. Amniotic membrane transplantation for severe neurotrophic corneal ulcers. Br J Ophthalmol. 2000;84(8):826–33.PubMedPubMedCentralCrossRef
128.
Honavar SG, Bansal AK, Sangwan VS, Rao GN. Amniotic membrane transplantation for ocular surface reconstruction in Stevens-Johnson syndrome. Ophthalmology. 2000;107(5):975–9.PubMedCrossRef
129.
Dogru M, Yildiz M, Baykara M, Özçetin H, Ertürk H. Corneal sensitivity and ocular surface changes following preserved amniotic membrane transplantation for nonhealing corneal ulcers. Eye. 2003;17(2):139–48.PubMedCrossRef
130.
Kim JS, Kim JC, Hahn TW, Park WC. Amniotic membrane transplantation in infectious corneal ulcer. Cornea. 2001;20(7):720–6.PubMedCrossRef
131.
Chen H-C, Tan H-Y, Hsiao C-H, Huang SC-M, Lin K-K, Ma DH-K. Amniotic membrane transplantation for persistent corneal ulcers and perforations in acute fungal keratitis. Cornea. 2006;25(5):564–72.PubMedCrossRef
132.
Travé-Huarte S, Wolffsohn JS. Bilateral sutureless application of human dehydrated amniotic membrane with a specialised bandage contact lens for moderate-to-severe dry eye disease: a prospective study with 1-month follow-up. Clin Ophthalmol. 2024;18:1329–39.PubMedPubMedCentralCrossRef
133.
Solomon A, Meller D, Prabhasawat P, et al. Amniotic membrane grafts for nontraumatic corneal perforations, descemetoceles, and deep ulcers. Ophthalmology. 2002;109(4):694–703.PubMedCrossRef
Je höher der BMI, umso höher ist das Risiko, bei einer Infektion zu sterben. Das gilt nicht nur für Covid-19, sondern für Infektionen allgemein. Bei einer Grad-III-Adipositas ist die Mortalität während einer Infektion sogar verdreifacht. Darauf deuten Daten aus Finnland und Großbritannien.
Periphere Fazialisparesen sollten nicht vorschnell als idiopathisch klassifiziert werden. Vor allem bei atypischen Manifestationen gilt es, auf dem Quivive zu sein. Der Fall einer 73-Jährigen zeigt, warum.
Bei der Festlegung der Intervalle für Kontrollkoloskopien nach einer Polypektomie sollten nicht ausschließlich polypenbezogene Merkmale berücksichtigt werden. Wie eine internationale Studie zeigt, beeinflussen auch individuelle demografische Faktoren, wie Geschlecht, Body-Mass-Index und Ethnie, das Rezidivrisiko.
In einer Kohortenstudie wurde ein Zusammenhang zwischen oralen Bakterien und Pilzen und dem Auftreten von Pankreaskarzinomen gesehen. Diese Assoziation könnte helfen, Patientinnen und Patienten für gezielte Vorsorgeuntersuchungen ausfindig zu machen.
