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Refractive errors remain a global health concern, as a large proportion of the world's population is myopic. Current ablative approaches are costly, not without risks, and not all patients are candidates for these procedures. Electromechanical reshaping (EMR) has been explored as a viable cost-effective modality to directly shape tissues, including cartilage. In this study, stromal collagen structure and fibril orientation was examined before and after EMR with second-harmonic generation microscopy (SHG), a nonlinear multiphoton imaging method that has previously been used to study native corneal collagen with high spatial resolution. EMR, using a milled metal contact lens and potentiostat, was performed on the corneas of five extracted rabbit globes. SHG was performed using a confocal microscopy system and all images underwent collagen fibril orientation analysis. The collagen SHG signal in controls is uniform and is similarly seen in samples treated with pulsed potential, while continuous EMR specimens have reduced, nonhomogeneous signal. Collagen fibril orientation in native tissue demonstrates a broad distribution with suggestion of another peak evolving, while with EMR treated eyes a bimodal characteristic becomes readily evident. Pulsed EMR may be a means to correct refractive errors, as when comparing its SHG signal to negative control, preservation of collagen structures with little to no damage is observed. From collagen fiber orientation analysis, it can be inferred that simple DC application alters the structure of collagen. Future studies will involve histological assessment of these layers and multi-modal imaging analysis of dosimetry.

Induced corneal collagen crosslinking and mechanical stiffening via ultraviolet-A photoactivation of riboflavin (UVA CXL) is now a common treatment for corneal ectasia and Keratoconus. Some effects of the procedure such as induced mechanical stiffening, corneal flattening, and cellular toxicity are well-known, but others remain more controversial. Authors report a variety of contradictory effects, and provide evidence based on individual results and observations. A full understanding of the effects of and mechanisms behind this procedure are essential to predicting its outcome. A growing interest in modifications to the standard UVA CXL protocol, such as transepithelial or accelerated UVA CXL, makes analyzing the literature as a whole more urgent. This review presents an analysis of both the agreed-upon and contradictory results reported and the various methods used to obtain them.

AIM: To explore the synthesis of thermo-sensitive poly N-isopropylacry-lamide(PNIPAAm)and the petri dish grafted with PNIPAAm hydrogels by the electron accelerator, as well as the growth conditions and the biological characteristics of rabbit corneal stromal cells on thermo-sensitive PNIPAAm hydrogels, and the cell sheets obtained from the PNIPAAm hydrogels.METHODS: NIPAAm monomer was dissolved in 2-propanol at concentrations of 55% with 0.5% N,N'-Methylenebisacry-lamide(MBA). Solution(70 μL)was added and spread uniformly over 35 mm petri dish. These dishes were immediately subjected to irradiation. After follow-up treatment, rabbit corneal stromal cells were cultured on thermo-sensitive petri dish in vitro.RESULTS: According to the monomer formula and radiation synthesis scheme in this experiment, PNIPAAm can be synthesized on the surface of the petri dish. Rabbit corneal stromal cells grew well in the thermo- sensitive surface and can be separated into sheets.CONCLUSION: The single and multilayer carrier-free cell sheets can be obtained from the use of thermo-sensitive petri dish.

Objective: Unusual or unexpected effect of treatment Background: Acute corneal hydrops, a rare complication of keratoconus, is characterized by sudden onset of corneal stroma edema. It typically manifests as an acute decrease in visual acuity, accompanied by pain and photophobia. Prompt recognition and interventions are critical for effective resolution of hydrops and prevention of corneal vascularization. Herein, we present a case of a patient with keratoconus who developed corneal hydrops, successfully managed using full-thickness compression sutures and intracameral air injection. Case Report: A woman in her early 30s, with a history of keratoconus, presented with symptoms of acute hydrops in her left eye. On presentation, best corrected visual acuity was hand motion. Slit-lamp examination revealed marked corneal edema with multiple stromal clefts. The decision was made to perform full-thickness compression sutures combined with intracameral air injection to expedite edema resolution and prevent neovascularization. Three full-thickness sutures were placed across Descemet membrane breaks, and an air bubble was left, filling 50% of the anterior chamber. At 3-month follow-up, a clear, compact cornea was noted, with no evidence of vascularization. The patient was scheduled for penetrating keratoplasty for visual rehabilitation. Conclusions: The combination of full-thickness compression sutures and intracameral air seems to be an effective and safe method for preventing corneal angiogenesis following hydrops. As corneal scaring is often an inevitable complication of acute corneal hydrops, keratoplasty is necessary for improving visual acuity. Hence, the prevention of corneal vascularization should be the major aim in the management of corneal hydrops to ensure successful keratoplasty. [ABSTRACT FROM AUTHOR]

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During life up to 70% of aniridia subjects develop aniridia-associated keratopathy (AAK). AAK is characterized by limbal stem cell insufficiency, impaired corneal epithelial cell differentiation and abnormal cell adhesion, which leads to centripetal spreading vascularization, conjunctivalization, and thickening of the cornea. Our aim was to examine the subbasal nerve plexus and central corneal stromal microstructure in subjects with congenital aniridia, using in vivo confocal laser scanning microscopy CLSM. 31 eyes of 18 patients (55.6% males, mean age: 25.22 ± 16.35 years) with congenital aniridia and 46 eyes of 29 healthy subjects (41.4% males, mean age 30 ± 14.82 years) were examined using the Rostock Cornea Module of Heidelberg Retina Tomograph-III. At the subbasal nerve plexus, corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), corneal total branch density (CTBD), and corneal nerve fiber width (CNFW) were analyzed using ACCMetrics software. Keratocyte density in the anterior, middle and posterior stroma was assessed manually. The CNFD (2.02 ± 4.08 vs 13.99 ± 6.34/mm2), CNFL (5.78 ± 2.68 vs 10.56 ± 2.82 mm/mm2) and CTBD (15.08 ± 15.62 vs 27.44 ± 15.05/mm2) were significantly lower in congenital aniridia subjects than in controls (p < 0.001 for all). CNFW was significantly higher in aniridia subjects than in controls (0.03 ± 0.004 vs 0.02 ± 0.003 mm/mm2) (p = 0.003). Keratocyte density was significantly lower in all stromal layers of aniridia subjects than in controls (p < 0.001 for all). Stromal alterations included confluent keratocytes, keratocytes with long extensions and hyperreflective dots between keratocytes in aniridia. Decrease in CNFD, CNFL, and CTBD, as well as increase in CNFW well refer to the congenital aniridia-associated neuropathy. The decreased keratocyte density and the stromal alterations may be related to an increased cell death in congenital aniridia, nevertheless, stromal changes in different stages of AAK have to be further analyzed in detail. [ABSTRACT FROM AUTHOR]

The corneal stroma consists of orthogonally stacked collagen-fibril lamellae that determine the shape of the cornea and provide most of the refractive power of the eye. We have applied electromechanical reshaping (EMR), an electrochemical platform for remodeling cartilage and other semirigid tissues, to change the curvature of the cornea as a potential procedure for nonsurgical vision correction. EMR relies on short electrochemical pulses to electrolyze water, with subsequent diffusion of protons into the extracellular matrix of collagenous tissues; protonation of immobilized anions within this matrix disrupts the ionic-bonding network, leaving the tissue transiently responsive to mechanical remodeling. Re-equilibration to physiological pH restores the ionic matrix, resulting in persistent shape change of the tissue. Using ex vivo rabbit eyes, we demonstrate here the controlled change of corneal curvature over a wide range of refractive powers with no loss of optical transparency. Optical coherence tomography (OCT), combined with second-harmonic generation (SHG) and confocal microscopy, establish that EMR enables extremely fine control of corneal contouring while maintaining the underlying macromolecular collagen structure and stromal cellular viability, positioning electrochemical vision therapy as a potentially simple and ultralow-cost modality for correcting routine refractive errors.

Corneal stroma is a significant part of the cornea and plays a significant role in the eye's refractive system. Although corneal transplantation is now the most effective treatment for corneal stromal disease, its advancement has been constrained by a shortage of donors, the need for prolonged immunosuppressive medicine to prevent rejection, and low graft survival rates. An alternate strategy is to use the corneal stroma's natural capacity for regeneration to create the ideal conditions for the collagenous extracellular matrix of the stroma to self-renew. However, it is challenging to replicate the intricate ultrastructure of the corneal stroma in vitro. Regenerative medicine has so been used to address these issues. These approaches refer to numerous disciplines, including stem cell-induced differentiation, tissue engineering and gene editing. This article provides potential directions for the future clinical applications of corneal stromal regeneration and repair while summarizing pertinent techniques, research progress, and issues.

BackgroundImaging features obtained with Fourier-domain optical coherence tomography (FD-OCT) and in vivo confocal microscopy (IVCM) for corneal stromal disorders have been sparsely reported in dogs. This case report is a compilation of imaging features for three cases of different stromal disorders of the canine cornea which have not yet been reported elsewhere.Case presentationLipid deposition in case 1 appeared as needle-shaped hyperreflective lines along the collagen lamellae, which correlated histologically with lipid clefts. In case 2, glycosaminoglycan accumulation by mucopolysaccharidosis type 1 caused diffuse stromal hyperreflectivity and depletion of keratocytes on IVCM and was associated with secondary corneal degeneration presumed to be calcium deposition. In case 3, posterior corneal stromal opacities in the absence of ocular inflammation were identified. Hyperreflective particles were scattered in the middle and posterior corneal stroma on FD-OCT. With IVCM, hyperreflective deposits were identified within keratocytes and the number of enlarged keratocytes containing hyperreflective deposits increased towards the posterior stroma. The bilateral, non-inflammatory nature and unique appearance with IVCM is most consistent with a posterior stromal dystrophy reminiscent of pre-Descemet corneal dystrophy described in humans.ConclusionsIn vivo multimodal corneal imaging facilitated instantaneous microstructural analysis and may be valuable in the differential diagnosis of corneal stromal disorders in veterinary clinical practice. The non-specific nature of imaging findings occurs in some conditions such as mucopolysaccharidosis, thus in vivo corneal imaging should be complemented with other gold standard methods of definitive diagnosis.

PURPOSE: To verify corneal biomechanical changes, poststromal augmentation using myopic small-incision lenticule extraction's (SMILEs) lenticules in advanced keratoconus (KCN) through Corvis ST (Oculus, Wetzlar, Germany). MATERIALS AND METHODS: A clinical trial enrolled 22 advanced KCN patients. We implanted lenticules exceeding 100 μ according to a nomogram and evaluated biomechanical factors through Corvis ST at 3-, 6-, and 24-month postimplantation. We examined parameters during the first applanation (A1), second applanation (A2), highest concavity (HC)/max concavity events, and Vinciguerra screening parameters, as recently established criteria derived from the ideal blend of diverse biomechanical and ocular factors and formulated through the application of logistic regression. Regression analyses explored relationships with age, mean keratometry value, thickness, sphere, cylinder, and best-corrected visual acuity. RESULTS: Patients were well matched for age, intraocular pressure, and central corneal thickness (CCT). The mean spherical equivalent decreased from −13.48 ± 2.86 Diopters (D) to −8.59 ± 2.17 D (P < 0.007), and mean keratometry decreased from 54.68 ± 2.77 D to 51.95 ± 2.21 D (P < 0.006). Significant increases were observed in HC time (HCT), Radius–central curvature radius at the HC state–, peak distance (PD) during HC state, CCT, first applanation time, and stiffness parameter (A1T and SP-A1), whereas HC deformation amplitude, maximum deformation amplitude ratio at 2 mm, Corvis Biomechanical Index (CBI), integrated radius (IR), second applanation deformation amplitude (A2DA), first applanation velocity and deflection amplitude (A1V and A1DeflA) significantly decreased postlenticule implantation. Multivariable regression revealed age positively correlated with SP-A1 (P = 0.003) and negatively with HC delta Arc length (P = 0.007). Mean K positively correlated with CCT (P = 0.05) and negatively with CBI (P = 0.032). Best-corrected visual acuity positively correlated with HCT (P = 0.044), and the cylinder positively correlated with PD (P = 0.05) and CCT (P = 0.05) whereas negatively with IR (P = 0.025). CONCLUSIONS: Stromal augmentation using myopic SMILE lenticules induces significant corneal biomechanical changes in KCN.

PURPOSE: To verify corneal biomechanical changes, poststromal augmentation using myopic small-incision lenticule extraction's (SMILEs) lenticules in advanced keratoconus (KCN) through Corvis ST (Oculus, Wetzlar, Germany). MATERIALS AND METHODS: A clinical trial enrolled 22 advanced KCN patients. We implanted lenticules exceeding 100 µ according to a nomogram and evaluated biomechanical factors through Corvis ST at 3-, 6-, and 24-month postimplantation. We examined parameters during the first applanation (A1), second applanation (A2), highest concavity (HC)/max concavity events, and Vinciguerra screening parameters, as recently established criteria derived from the ideal blend of diverse biomechanical and ocular factors and formulated through the application of logistic regression. Regression analyses explored relationships with age, mean keratometry value, thickness, sphere, cylinder, and best-corrected visual acuity. RESULTS: Patients were well matched for age, intraocular pressure, and central corneal thickness (CCT). The mean spherical equivalent decreased from -13.48 ± 2.86 Diopters (D) to -8.59 ± 2.17 D (P < 0.007), and mean keratometry decreased from 54.68 ± 2.77 D to 51.95 ± 2.21 D (P < 0.006). Significant increases were observed in HC time (HCT), Radius-central curvature radius at the HC state-, peak distance (PD) during HC state, CCT, first applanation time, and stiffness parameter (A1T and SP-A1), whereas HC deformation amplitude, maximum deformation amplitude ratio at 2 mm, Corvis Biomechanical Index (CBI), integrated radius (IR), second applanation deformation amplitude (A2DA), first applanation velocity and deflection amplitude (A1V and A1DeflA) significantly decreased postlenticule implantation. Multivariable regression revealed age positively correlated with SP-A1 (P = 0.003) and negatively with HC delta Arc length (P = 0.007). Mean K positively correlated with CCT (P = 0.05) and negatively with CBI (P = 0.032). Best-corrected visual acuity positively correlated with HCT (P = 0.044), and the cylinder positively correlated with PD (P = 0.05) and CCT (P = 0.05) whereas negatively with IR (P = 0.025). CONCLUSIONS: Stromal augmentation using myopic SMILE lenticules induces significant corneal biomechanical changes in KCN. [ABSTRACT FROM AUTHOR]

Key Clinical Message A corneal stroma circular ring has captured by smartphone adaptor slit lamp camera after smile for 1 week.

The article presents a literature review of the modern concept of anatomical and physiological structure and functioning of the cornea. The strict morphological structure and corneal tissue homeostasis ensure its transparency. Studying the mechanisms that regulate the constancy of the corneal tissue internal environment allows us to get closer to understanding the prospects forregenerative therapy for the corneal stroma pathology. The article discusses in detail the role and functional potential of corneal stromal cells, which are capable of reverse cytologic differentiation, which primarily ensures the maintenance of tissue homeostasis and corneal transparency. The functional activity of corneal cells can change for a number of reasons, which may be exogenous, iatrogenic (trauma, infection, etc.) or endogenous. Endogenous causes include: cell autoregulation pathologies (for example, enzyme defects); defects in transport systems leading to tissue hypoxia; disorders of the neuro-humoral regulation of trophism. The physical reason forthe violation of the corneal transparency is an increase in the light scattering. The article presents five main causes of increased light scattering in the opaque cornea, and also provides an overview of the main substances – components and products of cellular synthesis of corneal stromal cells: cytokines and growth factors (complex of the signal molecule and the SDF1/CXCR4 receptor, insulin-like growth factor 1, tumor necrosis factor alpha, intercellular adhesion molecule 1, erythropoietin, neurotrophic factors, etc.). Thus, corneal opacity can be caused by a single pathogenic mechanism or be the result of a complex effect of several factors. The main processes of tissue homeostasis regulation are aimed at maintaining the unique morphological structure of the cornea.

PurposeCorneal keratocyte-fibroblast-myofibroblast (KFM) transformation plays a critical role in corneal stromal wound healing. However, the impact of engineered nanomaterials (ENMs), found in an increasing number of commercial products, on this process is poorly studied. This study investigates the effects of metal oxide ENMs on KFM transformation in vitro and in vivo.MethodsCell viability of rabbit corneal fibroblasts (RCFs) was tested following treatment with 11 metal oxide ENMs at concentrations of 0.5 to 250 µg/ml for 24 hours. Messenger RNA (mRNA) and protein expression of αSMA, a marker of myofibroblast transformation, were measured using RCFs after exposure to 11 metal oxide ENMs at a concentration that did not affect cell viability, in media containing either 0 or 10 ng/ml of TGF-β1. Additionally, the effect of topical Fe2O3 nanoparticles (NPs) (50 ng/ml) on corneal stromal wound healing following phototherapeutic keratectomy (PTK) was determined.ResultsV2O5, Fe2O3, CuO, and ZnO ENMs were found to significantly reduce cell viability as compared to vehicle control and the other seven metal oxide ENMs tested. V2O5 nanoflakes significantly reduced mRNA and protein αSMA concentrations in the presence of TGF-β1. Fe2O3 NPs significantly increased αSMA mRNA expression in the presence of TGF-β1 but did not alter αSMA protein expression. Topically applied Fe2O3 NPs in an in vivo rabbit corneal stromal wound healing model did not delay healing.ConclusionsFe2O3 NPs promote corneal myofibroblast induction in vitro but do not impair corneal stromal wound healing in vivo.Translational relevanceThese experimental results can apply to human nanomedical research.

Corneal stromal is an important structure to maintain corneal transparency. The corneal stroma can be injured by trauma, infection and surgery. Therefore, corneal stromal wound starts repair with phenotype changes in stromal cell, extracellular matrix remodeling and immune cells migration. The corneal scar was the leading cause of blindness worldwide, which can be caused by corneal stromal fibrosis from increased myofibroblasts and deposited extracellular matrix after sever damage. At present, corneal transplantation is the main treatment for corneal scar, which has limited therapeutic effect because of corneal donor shortage, surgical requirements and the risk of postoperative immune rejection. Recently, great progress has been made in the study of control mechanism of corneal stromal wound healing with various molecules, cells and tissues. This paper reviews the repair mechanism of corneal stromal injury and the regulation mechanism of cause of corneal injury, corneal structure and molecule factors towards corneal stromal injury. It aims at providing new ideas for exploring the mechanism of corneal stromal repair and regeneration, which is supposed to help prevent corneal scar clinically.

Purpose: Compare the safety and efficacy of wavefront guided photorefractive keratotomy (PRK) 6 months after cross linking (CXL) to wavefront guided PRK alone for refractive correction in patients with bilateral asymmetric corneal topography. Methods: Prospective randomized clinical trial with 16 patients (32 eyes). CXL with subsequent PRK after 6 months in one eye, and PRK alone was performed in contralateral eyes. The follow up was 10 years. We analyzed visual outcomes, Scheimpflug topography, and corneal haze evaluation. Results: Eyes in the PRK group showed better results than in the CXL + PRK group. Mean postoperative CDVA was 0.044 logmar (SD, 0.073) in the PRK group and 0.1 logmar (SD, 0.21) in the CXL + PRK group, the mean sphere was + 0.21 (SD, 0.6) D in the PRK group and 0.87 (SD, 2.3) D in the CXL + PRK group, and mean SE was -0.35 (SD, 0.65) D in the PRK group and 0.62 (SD, 2.32) D in the CXL + PRK group. In one patient, a steepening of 2.5 D and a thinning of 17 µm occurred in PRK alone group. Two patients in the CXL + PRK group presented corneal haze. The overall complication rate was 18,75% (haze and ectasia). Conclusion: Non simultaneous CXL and PRK procedures yielded good refractive results, but worse than those obtained with PRK alone. Although one patient in the PRK group developed corneal ectasia, the CXL + PRK group had a higher loss of vision lines, indicating less safety. [ABSTRACT FROM AUTHOR]

This study investigated the interplay between transforming growth factor beta (TGF-β1/T1 and TGF-β3/T3), and sex hormone receptors using our 3D in vitro cornea stroma model. Primary human corneal fibroblasts (HCFs) from healthy donors were plated in transwells at 106 cells/well and cultured for four weeks. HCFs were supplemented with stable vitamin C (VitC) and stimulated with T1 or T3. 3D construct proteins were analyzed for the androgen receptor (AR), progesterone receptor (PR), estrogen receptor alpha (ERα) and beta (ERβ), luteinizing hormone receptor (LHR), follicle-stimulating hormone receptor (FSHR), gonadotropin-releasing hormone receptor (GnRHR), KiSS1-derived peptide receptor (KiSS1R/GPR54), and follicle-stimulating hormone subunit beta (FSH-B). In female constructs, T1 significantly upregulated AR, PR, ERα, FSHR, GnRHR, and KiSS1R. In male constructs, T1 significantly downregulated FSHR and FSH-B and significantly upregulated ERα, ERβ, and GnRHR. T3 caused significant upregulation in expressions PR, ERα, ERβ, LHR, FSHR, and GNRHR in female constructs, and significant downregulation of AR, ERα, and FSHR in male constructs. Semi-quantitative Western blot findings present the interplay between sex hormone receptors and TGF-β isoforms in the corneal stroma, which is influenced by sex as a biological variable (SABV). Additional studies are warranted to fully delineate their interactions and signaling mechanisms. [ABSTRACT FROM AUTHOR]

BackgroundAnterior segment optical coherence tomography (AS OCT) is a helpful tool used to diagnose and manage many corneal conditions, but its use has not been reported in case of peripheral ulcerative keratitis (PUK). The aim of this study is to describe AS OCT findings in cases of PUK.MethodsRetrospective observational case series of six eyes presenting with a PUK and proven systemic vasculitis. Clinical course, slit lamp photographs, and AS OCT findings were the main outcomes.ResultsThe AS OCT findings were found to correlate with the ocular disease's level of activity. In the acute stage, an absence of corneal epithelium, a scrambled appearance of the anterior stroma and a heterogeneous stromal reflectivity were observed. During the reduction of disease level activity, an irregular hyporeflective epithelium, a smoother anterior stroma, and a homogenous hyperreflective stroma were seen. At the healed stage, a filling of the corneal defect by a hyporeflective thick epithelium, the persistence of the hyperreflective underlying stroma, and a demarcation line were observed. The mean total corneal thickness at last follow-up was significantly thicker (509 ± 147 μm) compared with the mean corneal thickness at onset (408 ± 131 μm; P = 0.03).ConclusionsAS OCT provides an assessment of structural changes occurring in PUK, useful for its diagnosis and monitoring.

PurposeGlycosaminoglycans (GAGs) are important components of the corneal stroma, and their spatiotemporal arrangement regulates the organization of collagen fibrils and maintains corneal transparency. This study was undertaken to determine the consequences of hyaluronidase (HAse) injected into the corneal stroma on stromal stiffness and ultrastructure.MethodsEqual volumes of HAse or balanced salt solution (vehicle) were injected intrastromally into the corneas of New Zealand white rabbits. Ophthalmic examination and multimodal imaging techniques, including Fourier-domain optical coherence tomography and in vivo confocal microscopy (IVCM), were performed at multiple time points to evaluate the impact of HAse treatment in vivo. Atomic force microscopy and transmission electron microscopy (TEM) were used to measure corneal stiffness and collagen's interfibrillar spacing, respectively.ResultsCentral corneal thickness progressively decreased after HAse injection, reaching its lowest value at day 7, and then returned to normal by day 42. The HAse did not impact the corneal endothelium but transiently altered keratocyte morphology at days 1 and 7, as measured by IVCM. HAse-injected corneas became stiffer by day 1 postinjection, were stiffest at day 7, and returned to preinjection values by day 90. Changes in stromal stiffness correlated with decreased interfibrillar spacing as measured by TEM.ConclusionsDegradation of GAGs by HAse decreases the corneal thickness and increases stromal stiffness through increased packing of the collagen fibrils in a time-dependent manner.Translational relevanceIntrastromal HAse injection appears relatively safe in the normal cornea, but its impact on corneal biomechanics and structure under pathologic conditions requires further study.

The cornea is the most external layer of the eye and serves two important roles in (1) the refraction of light and (2) protection from the outside environment, both of which are highly dependent on the collagen assembly of the corneal stroma. This study sought to determine the collagen fiber arrangement of the canine corneal stroma and correlate the stromal organization with tissue stiffness in the anterior and posterior cornea. Collagen organization of the canine cornea was visualized through second-harmonic generation (SHG) imaging, and tissue stiffness of the anterior and posterior corneal stroma was determined by atomic force microscopy. Analysis of the canine anterior corneal stroma using SHG imaging documented intertwining of the collagen fibers with a high degree of fiber branching, with a more lamellar and non-branching posterior stroma. The anterior stroma had significantly higher tissue stiffness in both dogs and humans, when compared with the posterior corneal stroma (canine median: 1.3 kPa vs. 0.3 kPa; human median: 14.6 kPa vs. 2.1 kPa, respectively). There was a direct correlation between corneal collagen stromal organization and tissue stiffness in the dog, which was consistent with other mammalian species previously examined and likely reflects the need for maintenance of rigidity and corneal curvature.

The cornea is the outermost transparent and refractive barrier surface of the eye necessary for vision. Development of the cornea involves the coordinated production of extracellular matrix, epithelial differentiation, and endothelial cell expansion to produce a highly transparent tissue. Here we describe the production of multilayered three-dimensional organoids from human-induced pluripotent stem cells. These organoids have the potential for multiple downstream applications which are currently unattainable using traditional in vitro techniques.

Purpose: Compare the safety and efficacy of wavefront-guided photorefractive keratotomy (PRK) 6 months after cross-linking (CXL) to wavefront-guided PRK alone for refractive correction in patients with bilateral asymmetric corneal topography. Methods: Prospective randomized clinical trial with 16 patients (32 eyes). CXL with subsequent PRK after 6 months in one eye, and PRK alone was performed in contralateral eyes. The follow-up was 10 years. We analyzed visual outcomes, Scheimpflug topography, and corneal haze evaluation. Results: Eyes in the PRK group showed better results than in the CXL + PRK group. Mean postoperative CDVA was 0.044 logmar (SD, 0.073) in the PRK group and 0.1 logmar (SD, 0.21) in the CXL + PRK group, the mean sphere was + 0.21 (SD, 0.6) D in the PRK group and 0.87 (SD, 2.3) D in the CXL + PRK group, and mean SE was −0.35 (SD, 0.65) D in the PRK group and 0.62 (SD, 2.32) D in the CXL + PRK group. In one patient, a steepening of 2.5 D and a thinning of 17 μm occurred in PRK alone group. Two patients in the CXL + PRK group presented corneal haze. The overall complication rate was 18,75% (haze and ectasia). Conclusion: Non-simultaneous CXL and PRK procedures yielded good refractive results, but worse than those obtained with PRK alone. Although one patient in the PRK group developed corneal ectasia, the CXL + PRK group had a higher loss of vision lines, indicating less safety.

The cornea is the most external layer of the eye and serves two important roles in (1) the refraction of light and (2) protection from the outside environment, both of which are highly dependent on the collagen assembly of the corneal stroma. This study sought to determine the collagen fiber arrangement of the canine corneal stroma and correlate the stromal organization with tissue stiffness in the anterior and posterior cornea. Collagen organization of the canine cornea was visualized through second-harmonic generation (SHG) imaging, and tissue stiffness of the anterior and posterior corneal stroma was determined by atomic force microscopy. Analysis of the canine anterior corneal stroma using SHG imaging documented intertwining of the collagen fibers with a high degree of fiber branching, with a more lamellar and non-branching posterior stroma. The anterior stroma had significantly higher tissue stiffness in both dogs and humans, when compared with the posterior corneal stroma (canine median: 1.3 kPa vs. 0.3 kPa; human median: 14.6 kPa vs. 2.1 kPa, respectively). There was a direct correlation between corneal collagen stromal organization and tissue stiffness in the dog, which was consistent with other mammalian species previously examined and likely reflects the need for maintenance of rigidity and corneal curvature.

Decellularized corneas offer a promising and sustainable source of replacement grafts, mimicking native tissue and reducing the risk of immune rejection post-transplantation. Despite great success in achieving acellular scaffolds, little consensus exists regarding the quality of the decellularized extracellular matrix. Metrics used to evaluate extracellular matrix performance are study-specific, subjective, and semi-quantitative. Thus, this work focused on developing a computational method to examine the effectiveness of corneal decellularization. We combined conventional semi-quantitative histological assessments and automated scaffold evaluations based on textual image analyses to assess decellularization efficiency. Our study highlights that it is possible to develop contemporary machine learning (ML) models based on random forests and support vector machine algorithms, which can identify regions of interest in acellularized corneal stromal tissue with relatively high accuracy. These results provide a platform for developing machine learning biosensing systems for evaluating subtle morphological changes in decellularized scaffolds, which are crucial for assessing their functionality.

The purpose of this study was to measure collagen fiber crimping (CFC) using nonlinear optical imaging of second harmonic generated (SHG) signals to determine the effects of UVA-riboflavin induced corneal collagen crosslinking (UVA CXL) on collagen structure. Two groups, four rabbits each, were treated in the right eye with standard UVA CXL. In vivo confocal microscopy was performed at 1, 2, and 4 weeks after treatment for the first group and up to three months for the second group to measure epithelial/stromal thickness and corneal haze during recovery. Rabbits were sacrificed at one and three months, respectively, and their corneas fixed under pressure. Regions of crosslinking were identified by the presence of collagen autofluorescence (CAF) and then collagen structure was imaged using SHG microscopy. The degree of CFC was determined by measuring the percentage difference between the length of the collagen fiber and the linear distance traveled. CFC was measured in the central anterior and posterior CXL region, the peripheral non-crosslinked region in the same cornea, and the central cornea of the non-crosslinked contralateral eye. No change in corneal thickness was detected after one month, however the stromal thickness surpassed its original baseline thickness at three months by 25.9 μm. Corneal haze peaked at one month and then began to clear. Increased CAF was detected in all CXL corneas, localized to the anterior stroma and extending to 42.4 ± 3.4% and 47.7 ± 7.6% of the corneal thickness at one and three months. There was a significant (P

Corneal wound healing is a complex process that consists of cellular integration of multiple soluble biochemical cues and cellular responses to biophysical attributes associated with the matrix of the wound space. Upon corneal stromal wounding, the transformation of corneal fibroblasts to myofibroblasts is promoted by transforming growth factor-β (TGFβ). This process is critical for wound healing; however, excessive persistence of myofibroblasts in the wound space has been associated with corneal fibrosis resulting in severe vision loss. The objective of this study was to determine the effect of hepatocyte growth factor (HGF), which can modulate TGFβ signaling, on corneal myofibroblast transformation by analyzing the expression of α-smooth muscle actin (αSMA) as a marker of myofibroblast phenotype particularly as it relates to biomechanical cues. Human corneal fibroblasts were cultured on tissue culture plastic (>1 GPa) or hydrogel substrates mimicking human normal or wounded corneal stiffness (25 and 75 kPa) in media containing TGFβ1 ± HGF. The expression of αSMA was analyzed by quantitative PCR, Western blot and immunocytochemistry. Cellular stiffness, which is correlated with cellular phenotype, was measured by atomic force microscopy (AFM). In primary human corneal fibroblasts, the mRNA expression of αSMA showed a clear dose response to TGFβ1. The expression was significantly suppressed when cells were incubated with 20 ng/ml HGF in the presence of 2 ng/ml of TGFβ1. The protein expression of αSMA induced by 5 ng/ml TGFβ1 was also decreased by 20 ng/ml of HGF. Cells cultured on hydrogels mimicking human normal (25 kPa) and fibrotic (75 kPa) cornea also showed an inhibitory effect of HGF on αSMA expression in the presence or absence of TGFβ1. Cellular stiffness was decreased by HGF in the presence of TGFβ1 as measured by AFM. In this study, we have demonstrated that HGF can suppress the myofibroblast phenotype promoted by TGFβ1 in human corneal stromal cells. These data suggest that HGF holds the potential as a therapeutic agent to improve wound healing outcomes by minimizing corneal fibrosis.

To examine the widely accepted dogma that the eye is an immune-privileged organ that can suppress antigen immunogenicity, we explored systemic immune responses to a model vaccine antigen (tetanus toxoid) delivered to six compartments of the rodent eye (ocular surface, corneal stroma, anterior chamber, subconjunctival space, suprachoroidal space, vitreous body). We discovered that antigens delivered to corneal stroma induced enhanced, rather than suppressed, antigen-specific immune responses, which were 18- to 30-fold greater than conventional intramuscular injection and comparable to intramuscular vaccination with alum adjuvant. Systemic immune responses to antigen delivered to the other ocular compartments were much weaker. The enhanced systemic immune responses after intrastromal injection were related to a sequence of events involving the formation of an antigen "depot" in the avascular stroma, infiltration of antigen-presenting cells, up-regulation of MHC class II and costimulatory molecules CD80/CD86, and induction of lymphangiogenesis in the corneal stroma facilitating sustained presentation of antigen to the lymphatic system. These enhanced immune responses in corneal stroma suggest new approaches to medical interventions for ocular immune diseases and vaccination methods. [Display omitted] • We explored immune responses to vaccine antigens delivered to six compartments of the rodent eye. • Antigens delivered to corneal stroma induced enhanced, rather than suppressed, antigen-specific immune responses. • The mechanism for enhanced immune responses to antigens delivered to corneal stroma was investigated. [ABSTRACT FROM AUTHOR]

Purpose: To quantitatively analyze human corneal stromal dehydration and estimate proper corneal stromal exposure time during corneal refractive surgery. Methods: The central thickness changes over time in 34 pieces of human corneal tissue were measured using a white light interferometer. The corneal stromal tissue was obtained by femtosecond laser small incision lenticule extraction. The thickness-time dehydration fitting curves were drawn, and the determination coefficient R2 was calculated. The differences in the fitting curve equation coefficients were compared between the thin and thick lenticule groups. The optimal stromal exposure time was calculated under various conditions, including different optical zones and allowable refractive errors. Results: A water loss variation model was successfully established. Linear and quadratic fitting curves were drawn, and the determination coefficient R2 values were significantly close to 1. The average values of R2 for quadratic curves and linear phases 1, 2, and 3 were 0.998 ± 0.002, 0.995 ± 0.007, 0.996 ± 0.003, and 0.984 ± 0.035, respectively. The optimal stromal exposure time varied under different optical zones and allowable diopter error conditions. Taking the allowable error of 0.50 D and the optical zone size of 6.5 mm as an example, the optimal time was approximately 24 s. Conclusions: The dehydration rate of the human corneal stroma is nonlinear, and the quadratic stromal thickness–time dehydration fitting curve is more in line with the actual water loss trend. The length of the stroma exposure time may affect the postoperative refractive accuracy after corneal refractive surgery. [ABSTRACT FROM AUTHOR]

Because of corneal transplantation limitations, there is a need for cornea-specific regenerative medicine. The development of such regenerative medicine has been delayed because of the complex and unique structure of the corneal stroma. Few studies have explored the corneal stroma cell distribution and cell types in vivo. This study investigated regional differences in morphological characteristics and distributions of corneal keratocytes and immunocompetent cells in the corneal stroma to clarify their functions and structural characteristics. The porcine eyeballs were subjected to light microscopy, transmission electron microscopy, scanning electron microscopy, and immunofluorescence staining analyses. Corneal cells were primarily located in the limbus, rather than the center of the cornea; the long keratocyte diameter was largest on the epithelial side of the corneal limbus, while the short diameter was largest on the endothelial side of the central cornea. Moreover, there were significantly more corneal cells on the epithelial side than on the endothelial side in both the central and limbus areas. Gap junctions between cells in the corneal stroma were present on the surfaces of cytoplasmic processes. Many cytoplasmic processes were scattered throughout the corneal stroma; they were connected both vertically and horizontally, forming an intercellular network. Additionally, immunocompetent cells on the epithelial side suggested to participate in this network via gap junctions. The morphology of keratocytes and immunocompetent cells on the epithelial side suggests that they play important roles in corneal homeostasis. [ABSTRACT FROM AUTHOR]

This study investigated the interplay between transforming growth factor beta (TGF-β1/T1 and TGF-β3/T3), and sex hormone receptors using our 3D in vitro cornea stroma model. Primary human corneal fibroblasts (HCFs) from healthy donors were plated in transwells at 106 cells/well and cultured for four weeks. HCFs were supplemented with stable vitamin C (VitC) and stimulated with T1 or T3. 3D construct proteins were analyzed for the androgen receptor (AR), progesterone receptor (PR), estrogen receptor alpha (ERα) and beta (ERβ), luteinizing hormone receptor (LHR), follicle-stimulating hormone receptor (FSHR), gonadotropin-releasing hormone receptor (GnRHR), KiSS1-derived peptide receptor (KiSS1R/GPR54), and follicle-stimulating hormone subunit beta (FSH-B). In female constructs, T1 significantly upregulated AR, PR, ERα, FSHR, GnRHR, and KiSS1R. In male constructs, T1 significantly downregulated FSHR and FSH-B and significantly upregulated ERα, ERβ, and GnRHR. T3 caused significant upregulation in expressions PR, ERα, ERβ, LHR, FSHR, and GNRHR in female constructs, and significant downregulation of AR, ERα, and FSHR in male constructs. Semi-quantitative Western blot findings present the interplay between sex hormone receptors and TGF-β isoforms in the corneal stroma, which is influenced by sex as a biological variable (SABV). Additional studies are warranted to fully delineate their interactions and signaling mechanisms.

While tissue form and function is highly dependent upon tissue-specific collagen composition and organization, little is known of the mechanisms controlling the bundling of collagen fibrils into fibers and larger structural designs that lead to the formation of bones, tendons and other tissues. Using the cornea as a model system, our previous 3 dimensional mapping of collagen fiber organization has demonstrated that macrostructural organization of collagen fibers involving interweaving, branching and anastomosing plays a critical role in controlling mechanical stiffness, corneal shape and refractive power. In this work, the cellular and mechanical mechanisms regulating critical events in the assembly of collagen macrostructure are analysed in the developing chicken cornea. We elucidated the temporal events leading to adult corneal structure and determined the effects of intraocular pressure (IOP) on the organization of the collagen macrostructure. Our findings indicate that the complex adult collagen organization begins to appear on embryonic day 10 (E10) after deposition of the primary stroma and full invasion of keratocytes. Importantly, organizational changes in keratocytes appearing at E9 preceded and predicted later changes in collagen organization. Corneal collagen organization remained unaffected when the development of IOP was blocked at E4. These findings support a primary role for keratocytes in controlling stromal organization, mechanical stiffness and corneal shape that are not regulated by the IOP. Our findings also suggest that the avian cornea represents an excellent experimental model for elucidating key regulatory steps and mechanisms controlling the collagen fiber organization that is critical to determining tissue form and function.Statement of significanceThis work by using an ex ovo model system, begins to investigate the potential mechanisms controlling collagen fibril macrostructure. In particular, this work highlights a convergent role for the corneal keratocytes in organizing the complex collagen macrostructure, necessary to support high visual acuity. Our data supports that the intraocular pressure does not influence collagen fibril macrostructure and suggest that the avian cornea represents an excellent experimental model for elucidating key regulatory steps and mechanisms controlling the collagen fiber organization that is critical to determining tissue form and function. Clearly understanding the cellular and molecular mechanisms that underlie collagen fibril macrostructure will be highly beneficial for future tissue engineering and regenerative medicine applications.

Hepatocyte growth factor (HGF) is a glycoprotein produced by mesenchymal cells and operates as a key molecule for tissue generation and renewal. During corneal injury, HGF is primarily secreted by stromal fibroblasts and promotes epithelial wound healing in a paracrine manner. While this mesenchymal-epithelial interaction is well characterized in various organs and the cornea, the role of HGF in corneal stromal and endothelial wound healing is understudied. In addition, HGF has been shown to play an anti-fibrotic role by inhibiting myofibroblast generation and subsequent production of a disorganized extracellular matrix and tissue fibrosis. Therefore, HGF represents a potential therapeutic tool in numerous organs in which myofibroblasts are responsible for tissue scarring. Corneal fibrosis can be a devastating sequela of injury and can result in corneal opacification and retrocorneal membrane formation leading to severe vision loss. In this article, we concisely review the available literature regarding the role of HGF in corneal wound healing. We highlight the influence of HGF on cellular behaviors in each corneal layer. Additionally, we suggest the possibility that HGF may represent a therapeutic tool for interrupting dysregulated corneal repair processes to improve patient outcomes.

Corneal regeneration has become a prominent study area in recent decades. Because the corneal stroma contributes about 90% of the corneal thickness in the corneal structure, corneal stromal regeneration is critical for the treatment of cornea disease. Numerous materials, including deacetylated chitosan, hydrophilic gel, collagen, gelatin methacrylate (GelMA), serine protein, glycerol sebacate, and decellularized extracellular matrix, have been explored for keratocytes regeneration. GelMA is one of the most prominent materials, which is becoming more and more popular because of its outstanding three-dimensional scaffold structure, strong mechanics, good optical transmittance, and biocompatibility. This review discussed recent research on corneal stroma regeneration materials and related GelMA. [ABSTRACT FROM AUTHOR]

Exosomes have been related to various disorders, but their study in relation to ocular pathologies has been limited. In this article, we analyze exosomes produced by corneal stromal cells from healthy individuals and from patients with keratoconus. The proteomic study allowed for the identification of 14 new proteins with altered expression, related to molecules previously associated with the pathology. miRNA analysis detected 16 altered species, including miR-184, responsible for familial severe keratoconus. The prediction of its potential biological targets identified 1121 genes, including some related to this pathology. Exosomes produced by keratoconic cells induced a marked increase in the migration of stromal cells and corneal epithelium, while those produced by healthy cells had no effect on stromal cells. Both types of nanovesicles reduced the proliferation of stromal and corneal cells, but those produced by healthy cells had less effect. Exosomes produced by healthy cells had concentration-dependent effects on the transcription of genes encoding proteoglycans by keratoconus cells, with a relative normalization observed at concentrations of 240 µg/mL. These results show the alteration of stromal exosomes in keratoconus and suggest an influence on the development of the pathology, although the use of healthy exosomes could also have therapeutic potential. [ABSTRACT FROM AUTHOR]

Adipose-derived stem cells are a subtype of mesenchymal stem cell that offers the important advantage of being easily obtained (in an autologous manner) from low invasive procedures, rendering a high number of multipotent stem cells with the potential to differentiate into several cellular lineages, to show immunomodulatory properties, and to promote tissue regeneration by a paracrine action through the secretion of extracellular vesicles containing trophic factors. This secretome is currently being investigated as a potential source for a cell-free based regenerative therapy for human tissues, which would significantly reduce the involved costs, risks and law regulations, allowing for a broader application in real clinical practice. In the current article, we will review the existing preclinical and human clinical evidence regarding the use of such adipose-derived mesenchymal stem cells for the regeneration of the three main layers of the human cornea: the epithelium (derived from the surface ectoderm), the stroma (derived from the neural crest mesenchyme), and the endothelium (derived from the neural crest cells). [ABSTRACT FROM AUTHOR]

The complex anatomy of the cornea and the subsequent keratocyte-fibroblast transition have always made corneal stromal regeneration difficult. Recently, 3D printing has received considerable attention in terms of fabrication of scaffolds with precise dimension and pattern. In the current work, 3D printable polymer hydrogels made of GelMA/agarose are formulated and its rheological properties are evaluated. Despite the variation in agarose content, both the hydrogels exhibited G'>G'' modulus. A prototype for 3D stromal model is created using Solid Works software, mimicking the anatomy of an adult cornea. The fabrication of 3D-printed hydrogels is performed using pneumatic extrusion. The FTIR analysis speculated that the hydrogel is well crosslinked and established strong hydrogen bonding with each other, thus contributing to improved thermal and structural stability. The MTT analysis revealed a higher rate of cell proliferation on the hydrogels. The optical analysis carried out on the 14th day of incubation revealed that the hydrogels exhibit transparency matching with natural corneal stromal tissue. Specific protein marker expression confirmed the keratocyte phenotype and showed that the cells do not undergo terminal differentiation into stromal fibroblasts. The findings of this work point to the potential of GelMA/A hydrogels as a novel biomaterial for corneal stromal tissue engineering., (© 2024 Wiley‐VCH GmbH.)

Key Clinical Message: A corneal stroma circular ring has captured by smartphone adaptor slit lamp camera after smile for 1 week. [ABSTRACT FROM AUTHOR]

A 27-year-old male presented with complaints of irritation and watering in the left eye following injury by a shrub. These symptoms subsided on rubbing the eyes and an eyewash. Slit-lamp bio-microscopy revealed an edematous cornea with vegetative foreign bodies embedded in the stroma, which were confirmed by anterior-segment optical coherence tomography. Antimicrobial therapy and immediate foreign body removal was undertaken. The patient was discharged the next day, with regular follow-ups. Foreign bodies either get embedded on the corneal surface or penetrate into the anterior chamber; it is rare for them to be retained intracorneally. The patient made a full and uneventful recovery following surgery.

PurposeTo determine whether riboflavin-induced collagen crosslinking (CXL) could be precisely achieved in the corneal stroma of ex vivo rabbit eyes using nonlinear optical excitation with a low numerical aperture lens and enlarged focal volume.SettingGavin Herbert Eye Institute, University of California Irvine, Irvine, California, USA.DesignExperimental study.MethodsThe corneal epithelium was removed and the corneas were soaked in 0.5% riboflavin solution. Using a 0.1 numerical aperture objective, a theoretical excitation volume of 150 μm × 3 μm was generated using 1 W of 760 nm femtosecond laser light and raster scanned with 4.4 μm line separation at varying effective speeds over a 4.50 mm × 2.25 mm area. Corneal sections were examined for collagen autofluorescence.ResultsCollagen autofluorescence was enhanced 2.9 times compared with ultraviolet-A (UVA) CXL. Also, increasing speed was linearly associated with decreasing autofluorescence intensity. The slowest speed of 2.69 mm/s showed a mean of 182.97 μm ± 52.35 (SD) long autofluorescent scan lines axially in the central cornea compared with 147.84 ± 4.35 μm for UVA CXL.ConclusionsDecreasing dwell time was linearly associated with decreasing autofluorescence intensity, approaching that of UVA CXL at a speed of 8.9 mm/s. Using an effective speed of 8.9 mm/s, nonlinear optical CXL could be achieved over a 3.0 mm diameter area in fewer than 4 minutes. Further development of nonlinear optical CXL might result in safer, faster, and more effective CXL treatments.Financial disclosureNone of the authors has a financial or proprietary interest in any material or method mentioned.

In this work, both theoretical model and finite element simulation are combined to address the influence of gradiently distributed cross-links on the underlying deformation mechanisms of corneal stroma. Theoretically, a hyperelastic model is developed that involves the strengthening contributions of ultraviolet A (UVA)-induced cross-links, collagen fibers and matrix materials. Thereinto, the influence of collagen cross-linking (CXL) is characterized by a mechanism-based strain energy function, which not only explicitly depends on the density of cross-links (as a function of the corneal thickness and UVA irradiation dose), but also relies on the discrepant distribution of cross-links in the proteoglycan matrix and along the fibers. Moreover, the developed constitutive laws are incorporated into the subroutine UMAT of ABAQUS to simulate the expansion deformation of porcine cornea with/without the treatment by CXL. It is noticed that the simulated results can fit well with the experimental data, and are able to predict the macroscopic intraocular pressure (IOP)-apex displacement relations at different UVA irradiation doses. Corresponding stiffening and strengthening behaviors induced by cross-links, fibers and the matrix are systematically compared at different corneal surfaces along the thickness direction in order to obtain a sophisticated comprehension of the fundamental deformation mechanisms, which may theoretically help design and guide the operation of CXL in clinics.

AIM:To assess the changes of posterior corneal elevation after small incision lenticule extraction(SMILE). METHODS:A retrospective study was conducted on 120 patients(240 eyes)who underwent SMILE surgery with myopia. All patients were examined with the Pentacam of preoperation and 1d, 1wk, 1, 3, 6 and 12mo postoperatively, respectively. We analyze the change of the posterior corneal elevation of the apex, and the change of mean posterior corneal elevation in the circle of 2mm, and 6mm diameter.RESULTS:Comparison among the three groups showed that the differences of apex and 2mm circle at a different time and between the groups were statistically significant(apex: Ftime=30.09, Ptime

The human cornea is thicker in the periphery than the center and it has been suggested that this must be due to greater numbers of lamellae in the peripheral corneal stroma. The purpose of this study was to use high-resolution ultrastructural imaging to determine if the greater thickness of the peripheral cornea is due to the presence of more lamellae or if there is some other anatomical explanation. In this study, full thickness corneas from three human donors were processed for light microscopy (LM) and transmission electron microscopy (TEM). Images were taken in three distinct stromal regions (anterior, middle, and posterior) from the central and peripheral cornea. Stromal thickness was evaluated by LM while TEM was used to evaluate numbers and thicknesses of lamellae, mean collagen fibril diameter, and mean collagen fibril density. Mean stromal thickness was significantly thinner in the central (415 ± 34 µm) compared to the peripheral (536 ± 29 µm) cornea (P = 0.009). Numbers of lamellae were not significantly different between central (246 ± 14) and peripheral (251 ± 14) cornea. Average lamellar thickness was not different across all regions of the cornea, except for the peripheral posterior where the lamellae were approximately 50 % thicker (P < 0.05). Collagen fibril diameters were larger in the peripheral cornea by approximately 30 % when compared to the central cornea, in all regions (P < 0.01). This study shows that it is an increase peripheral posterior lamellar thickness, rather than an increase in the number of lamellae, that accounts for the increase in corneal stromal thickness in the periphery of the human cornea. While collagen fibril diameters are greater throughout the peripheral stroma, the lamellae in the mid and anterior peripheral stroma are not thicker than centrally. [ABSTRACT FROM AUTHOR]