Healthy Corneas Research Articles

Changes in Corneal Higher Order Aberrations Following Cataract Surgery With Different Incision Sites: A Prospective, Randomized Study.

To compare the effect of superior and temporal clear corneal incisions, regardless of the steep axis, on postoperative changes in corneal higher order aberrations (HOAs) in patients with healthy corneas and mild preoperative corneal astigmatism. In this prospective cohort study, the right eyes of study participants were randomly assigned to one of two groups prior to cataract surgery: temporal incision (TI) and superior incision (SI). Preoperatively and 6 weeks after surgery, measurements were taken of corneal HOAs over a 6-mm optical zone. The study included 102 eyes (50 eyes in the TI group and 52 eyes in the SI group) that underwent routine phacoemulsification using a 2.4-mm clear corneal incision. Significant changes in vertical coma (P = .019), horizontal coma (P = .042), and vertical trefoil (P = .001) were observed in the SI group. In the subgroup analysis of the SI group, significant changes in vertical coma (P = .025) and vertical trefoil (P = .047) were observed in the eyes with preoperative with-the-rule corneal astigmatism, and significant changes in horizontal coma (P = .038) were observed in eyes with preoperative against-the-rule corneal astigmatism. The TI group showed no significant difference between the preoperative and postoperative periods. The SI induced vertical and horizontal coma in accordance with the preoperative axis of the steep meridian. These alterations in corneal HOAs may affect the quality of vision after surgery. TI may potentially provide an advantage over SI in terms of corneal HOAs. [J Refract Surg. 2024;40(11):e792-e796.].

Mechanical properties of stromal striae, and their impact on corneal tissue behavior

Cornea is an essential element of our eye. The refractive power of the cornea is closely related to its shape, which depends on the balance between its mechanical properties and the intraocular pressure. However, in keratoconus, the shape of the cornea is altered, and the mechanical properties (i.e., elastic modulus and viscosity) are reduced. These alterations have been associated with the development of striae within the cornea. Recently, such striae have been observed in healthy corneas as well, but with slightly different shapes. Our study investigated the mechanical role of these striae. To this end, we performed an inflation test under Optical Coherence Tomography: tomographic volumes were acquired in the central zone of eleven human corneas during an inflation test. Striae planes were extracted from the segmented images, and principal deformation maps were obtained by Digital Volume Correlation (DVC). We observe that the pattern of the striae does not change with pressure, even far above physiological pressure. Maximum principal strains are co-localized with the striae and are oriented perpendicular to the striae. We also observe that principal deformations on the striae increase with depth in the cornea. Our results show that striae lead to greater deformability in the direction perpendicular to the striae, especially in the posterior part of the cornea where they are the most visible. This supports the idea that the striae are undulations in the cornea collagenous microstructure, which are progressively unfolded under loading. They decrease the global stiffness of the cornea, in particular in the posterior part, and thus may help in accommodating deformations.

Effect of Ritanserin and Duloxetine on the Gene Expression of Primary Aniridia and Healthy Human Limbal Stromal Cells, In Vitro.

In congenital aniridia caused by mutations in paired box 6 (PAX6), PAX6 influences the migration and differentiation of limbal epithelial cells (LECs), thereby playing a pivotal role in aniridia-associated keratopathy. The antidepressants ritanserin and duloxetine affect PAX6 expression in LECs. Limbal stromal cells, which support limbal epithelial stem cells, are crucial in the limbal stem cell niche. This study explores how ritanserin and duloxetine influence gene expression in primary human limbal stromal cells from subjects with congenital aniridia and from healthy subjects, in vitro. Primary human limbal stromal cells from corneas affected by aniridia (AN-LSCs) (n = 8) and from healthy corneas (LSCs) (n = 8) were isolated and cultured in either low-glucose serum-free (LGSF) or normal-glucose serum-containing (NGSC) media. Cells were treated with 4µM ritanserin or duloxetine for 24h. Quantitative PCR (qPCR) and western blot were used to assess the expression of PAX6, FOSL2, TGF-β1, ACTA2A1, LUM, COL1A1, COL5A1, DSG1, FABP5 and ADH7. In AN-LSCs with LGSF-medium, ritanserin increased PAX6 messenger RNA (mRNA) (p = 0.007) and decreased TGF-β1 and FOSL2 mRNA levels (P = 0.005, P = 0.038). In addition, TGF-β1 protein levels decreased with both treatments (P = 0.02, P = 0.007), and FABP5 protein level increased, using ritanserin (P = 0.019). In LSCs with LGSF-medium, ACTA2A1 mRNA levels decreased using ritanserin and duloxetine (P = 0.028; P = 0.031), while FABP5 mRNA levels increased with ritanserin treatment (P = 0.003). Also, duloxetine use reduced α-SMA protein (P = 0.013) and increased FABP5 protein levels (P = 0.029). In LSCs with NGSC-medium, ritanserin elevated LUM, FABP5 and ADH7 mRNA and protein levels (P = 0.025, P = 0.003, P = 0.047, P = 0.024, P = 0.013, P = 0.039). The results of our study confirmed that the antipsychotropic drugs ritanserin and duloxetine alter PAX6 and TGF-β1 gene expression in AN-LSCs cultured in LGSF-medium. These drugs were found to have an impact on retinoic acid signaling pathways and keratocyte characteristic markers both in LSCs and AN-LSCs, using different culture media.

Continuum versus micromechanical modeling of corneal biomechanics

Two alternative numerical models of the human cornea are used to simulate the mechanical response under the action of a physiological intraocular pressure (IOP). The first model is continuum or macromechanical, considering the stromal tissue as a bulk material with stochastic distribution of the spatial variability of reinforcing collagen fibers. The second model is discrete or micromechanical, considering the sole collagen-crosslink stiffening micro-structure. The geometry of the two models is reconstructed from corneal topographer images. Simulations consider the behavior of a healthy cornea and of a keratoconus cornea. For the keratoconus the material properties of a portion of the cornea are reduced to 1/8 of the values used for the healthy tissue. It is found that, for suitable choice of the material parameters for the discrete model, in the healthy case the mechanical responses of the two models are fully comparable. In the keratoconus case, both models capture with comparable accuracy the anterior shape of the conus; in addition, the discrete model is able to describe the tissue thinning typical of the pathology. Despite the inclusion of stochastic material properties, starting from a healthy condition, continuum models of the cornea are not able to predict the thinning of a keratoconus cornea, while the inclusion of the underlying collagen microstructure allows for a proper description of pathologic mechanical behaviors.

A comparative study of central corneal thickness using an ultrasonic pachymeter and a noncontact specular microscope in adult patients coming to the ophthalmology outpatient department in a tertiary care hospital in Western India

Objective: To evaluate and compare the accuracy of measuring central corneal thickness (CCT) using an ultrasonic pachymeter and a noncontact specular microscope and whether they can be used interchangeably in adult patients with healthy cornea. Methodology: A comparative and observational study was carried out in adult patients coming to the ophthalmology outpatient department (OPD) in a tertiary care hospital in Western India. In all patients, CCT is measured using an ultrasonic pachymeter and a noncontact specular microscope to perform a comparative study. Statistical analysis was done using paired t-test. Two-tailed hypothesis was applied. Results: This study included a sample size of 300 eyes of 150 adult patients. We want to test whether CCT values by Ultrasound Pachymeter and Noncontact specular Microscope is significantly different for right eyes and left eyes of the same patients, therefor we applied paired t-test for statistical analysis. T value for the right eye CCT measurement was −0.4 and the value of P was 0.69. T value for the left eye CCT measurement was −0.79 and the value of P was 0.43. P > 0.05 suggested that the results were nonsignificant. Conclusion: Our study suggests that the noncontact specular microscope produces CCT values that do not vary significantly from ultrasonic pachymeter. In subjects with healthy cornea, ultrasound pachymeter and specular microscope can be used interchangeably.

Changes in anterior segment after short-term scleral lens wear in healthy Chinese population

PurposeTo evaluate the impact of short-term scleral lens (SL) wear on anterior chamber (AC) dimension and central corneal thickness (CCT) in healthy Chinese people. MethodsThis is a prospective, daily wear study. Eligible participants were dispensed SLs to correct refractive errors. Anterior segment (AS) parameters were measured by AS optical coherence tomography (AS-OCT) before, during, and after 2 and 4 hours of lens wear. Repeated-measures analysis of variance (ANOVA) was used to analyze the changes in AS parameters over time. ResultsTwelve subjects (10 females and 2 males) with a mean age of 25.3 ± 3.8 years (ranging from 21 to 34 years) were recruited. The AC parameters, including anterior chamber depth (ACD) from the endothelium (endo-ACD), angle opening distance at 500 μm (AOD500), and trabecular-iris space area at 500 μm (TISA500), significantly decreased after wearing SLs for 4 hours (P<0.05). CCT increased by 12 μm (2.29 %) after wearing SLs for 4 hours (P=0.013). ConclusionThis study suggests that SL wear has a significant impact on AS dimensions in patients with healthy corneas in the short term with SL in situ, but tend to recover quickly after SL removal. Further research is needed to determine whether the change in AS dimensions during SL wear affects aqueous humor (AH) outflow and causes changes in intraocular pressure (IOP).

Computational approach for correcting defocus and suppressing speckle noise in line-field optical coherence tomography images.

The trade-off between transverse resolution and depth-of-focus (DOF) typical for optical coherence tomography (OCT) systems based on conventional optics, prevents "single-shot" acquisition of volumetric OCT images with sustained high transverse resolution over the entire imaging depth. Computational approaches for correcting defocus and higher order aberrations in OCT images developed in the past require highly stable phase data, which poses a significant technological challenge. Here, we present an alternative computational approach to sharpening OCT images and reducing speckle noise, based on intensity OCT data. The novel algorithm uses non-local priors to model correlated speckle noise within a maximum a posteriori framework to generate sharp and noise-free images. The performance of the algorithm was tested on images of plant tissue (cucumber) and in-vivo healthy human cornea, acquired with line-field spectral domain OCT (LF-SD-OCT) systems. The novel algorithm effectively suppressed speckle noise and sharpened or recovered morphological features in the OCT images for depths up to 13×DOF (depth-of-focus) relative to the focal plane.

Redefining our vision: an updated guide to the ocular immune system.

Balanced immune responses in the eyes are crucial to preserve vision. The ocular immune system has long been considered distinct, owing to the so-called 'immune privilege' of its component tissues. More recently, intravital imaging and transcriptomic techniques have reshaped scientific understanding of the ocular immune landscape, such as revealing the specialization of immune cell populations in the various tissues of the eye. As knowledge of the phenotypes of corneal and retinal immune cells has evolved, links to both the systemic immune system, and the central and peripheral nervous systems, have been identified. Using intravital imaging, T cells have recently been found to reside in, and actively patrol, the healthy human cornea. Disease-associated retinal microglia with links to retinal degeneration have also been identified. This Review provides an updated guide to the ocular immune system, highlighting current knowledge of the immune cells that are present in steady-state and specific diseased ocular tissues, as well as evidence for their relationship to systemic disease. In addition, we discuss emerging intravital imaging techniques that can be used to visualize immune cell morphology and dynamics in living human eyes and how these could be applied to advance understanding of the human immune system.

Expression of matrix metalloproteinases and their inhibitors in corneal stromal fibroblasts and keratocytes from healthy and keratoconus corneas.

To examine the in-vitro expression of matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) in corneal stromal cells by distinguishing between fibroblasts and keratocytes of healthy and keratoconus (KC) corneas. Stromal cells were isolated from healthy and KC corneas (n = 8). A normal-glucose, serum-containing cell culture medium (NGSC-medium) was used for cultivation of healthy human corneal fibroblasts (HCFs) and KC human corneal fibroblasts (KC-HCFs). In order to obtain a keratocyte phenotype, the initial cultivation with NGSC-medium was changed to a low-glucose, serum-free cell culture medium for healthy (Keratocytes) and KC cells (KC-Keratocytes). Gene and protein expression of MMP-1, -2, -3, -7, -9 and TIMP-1, -2, -3 were measured by quantitative PCR and Enzyme-Linked Immunosorbent Assay (ELISA) from the cell culture supernatant. KC-HCFs demonstrated a lower mRNA gene expression for MMP-2 compared to HCFs. In contrast to their respective fibroblast groups (either HCFs or KC-HCFs), Keratocytes showed a higher mRNA gene expression of TIMP-3, whereas TIMP-1 mRNA gene expression was lower in Keratocytes and KC-Keratocytes. Protein analysis of the cell culture supernatant revealed lower concentrations of MMP-1 in KC-HCFs compared to HCFs. Compared to Keratocytes, TIMP-1 concentrations was lower in the cell culture supernatant of KC-Keratocytes. In HCFs and KC-HCFs, protein levels of MMP-1 and TIMP-1 were higher and MMP-2 was lower compared to Keratocytes and KC-Keratocytes, respectively. This study indicates an imbalance in MMP and TIMP expression between healthy and diseased cells. Furthermore, differences in the expression of MMPs and TIMPs exist between corneal fibroblasts and keratocytes, which could influence the specific proteolytic metabolism in-vivo and contribute to the progression of KC.

The central and peripheral corneal response to short-term hypoxia.

To quantify the magnitude and recovery of central and limbal corneal oedema induced by short-term unilateral eyelid closure without contact lens wear. The left eye of 10 adults with healthy corneas was patched using a folded eye pad for 30 min. High-resolution optical coherence tomography images (which captured the limbal and central corneal regions simultaneously) were obtained before patching, immediately after eye opening and again at 1, 2, 5, 6, 9, 10, 14 and 15 mins after eyelid opening. Oedema was measured from the limbus (scleral spur) to the central cornea (thinnest corneal location) along the horizontal meridian. A greater amount of limbal oedema was noted (mean [SD] 3.84 [1.79] %) compared to the central cornea (2.48 [0.61] %; p = 0.04) after 30 mins of unilateral eyelid closure. Both central and limbal corneal oedema recovered rapidly following eyelid opening, with no significant differences in the rate of corneal recovery between corneal locations (p = 0.90). Short-term unilateral eyelid closure resulted in ~55% more relative oedema in the limbal region compared to the central cornea. Rapid recovery of oedema and corneal overshoot (thinning beyond the baseline corneal thickness) was observed within 1-2 min of eyelid opening for both central and peripheral regions.

Nanotopography by chromatic confocal microscopy of the endothelium in Fuchs endothelial corneal dystrophy, pseudophakic bullous keratopathy and healthy corneas

AimTo investigate the interest of chromatic confocal microscopy (CCM) to characterise guttae in Fuchs endothelial corneal dystrophy (FECD).MethodsDescemet’s membranes (DM) were obtained during endothelial keratoplasty in patients with FECD and...

The landscape of clinical trials in corneal regeneration: A systematic review of tissue engineering approaches in corneal disease.

The limited availability of a healthy donor cornea and the incidence of allograft failure led researchers to seek other corneal substitutes via tissue engineering. Exploring the trend of clinical trials of the cornea with the vision of tissue engineering provides an opportunity to reveal future potential corneal substitutes. The results of this clinical trial are beneficial for future study designs to overcome the limitations of current therapeutic approaches. In this study, registered clinical trials of bio-based approaches were reviewed for corneal regeneration on March 22, 2024. Among the 3955 registered trials for the cornea, 392 trials were included in this study, which categorized in three main bio-based scaffolds, stem cells, and bioactive macromolecules. In addition to the acellular cornea and human amniotic membrane, several bio-based materials have been introduced as corneal substrates such as collagen, fibrin, and agarose. However, some synthetic materials have been introduced in recent studies to improve the desired properties of bio-based scaffolds for corneal substitutes. Nevertheless, new insights into corneal regenerative medicine have recently emerged from cell sheets with autologous and allogeneic cell sources. In addition, the future perspective of corneal regeneration is described through a literature review of recent experimental models.

Can unilateral lattice dystrophy be triggered by cataract surgery in an elderly patient?

ABSTRACT Purpose Aim is to report unilateral lattice corneal dystrophy (LCD) possibly triggered after cataract surgery in an elderly patient and to demonstrate anterior segment optic coherence tomography (AS-OCT) findings. Case Report A 77-year-old male presented with irritation and photophobia in the left eye. His medical history revealed that the patient had undergone cataract surgery on the left eye 5 months ago and his symptoms exaggerated after the surgery. Best corrected visual acuity (BCVA) was 20/32 in OD and 20/63 in OS. Slit lamp examination indicated clear cornea with nuclear sclerosis in the right eye, multiple fine lattice lines at the level of middle stroma in the left eye. The lattice lines extended radially but did not involve the limbus. The overlying epithelium was intact. AS-OCT was consistent with LCD in the left eye with the presence of hyperreflective material at the level of the middle stroma. In contrast, AS-OCT in the right eye showed a normal, healthy cornea. Conclusion LCD is an inherited disease that can rarely present with unilateral involvement. Apart from its unilaterality and lack of limbal-limbal extension, the time of onset of the lattice lines is another distinguishing feature of this case report. Herein, clinical findings appeared at an older age compared to the literature. In addition, the occurrence of findings after phacoemulsification surgery has raised the question that environmental factors may trigger the emergence of unilateral LCD in patients with genetic predisposition. It is not yet known whether unilateral LCD is an asymmetric and asynchronous presentation of bilateral LCD or a different entity triggered by external factors. AS-OCT enables to demonstrate the corneal microstructural changes, and confirm the diagnosis of unilateral LCD by showing that the fellow eye is healthy.

Corneal densitometry in Chinese adults with healthy corneas: associations with sex, age, ocular metrics, and optical characteristics

BackgroundStandardized corneal densitometry (CD) values in large samples of healthy Chinese individuals are scarce. Therefore, we aimed to determine the standard CD values using a Scheimpflug camera in healthy corneas, investigate the correlations of sex, age, and ocular parameters with corneal density, and explore the impact of corneal density on the forward scattering and optical quality of the eye.MethodsThis retrospective observational study involved 990 healthy Chinese individuals, including 494 males and 496 females (mean age: 23.88 ± 6.90 years). The CD values at various depths and radial areas of 0–12 mm were measured using a Scheimpflug camera. Densitometric measurements were expressed in standardized grayscale units (GSU). The optical scatter index (OSI), modulation transfer function cutoff values (MTFcutoff), and Strehl’s ratio (SR) were also determined using an optical quality analysis system.ResultsThe average CD within a 12 mm diameter area was 16.26 ± 1.35 GSU. The highest and lowest optical densities at different depths were observed in the anterior (21.41 ± 2.16 GSU) and posterior (12.00 ± 1.01 GSU) layers, respectively (P < 0.001). Similarly, the maximum and minimum optical densities at different radial areas were observed in the 10–12 mm (14.09 ± 0.93 GSU) and 2–6 mm (25.93 ± 4.77 GSU) circles, respectively (P < 0.001). There was no significant difference in the average CD within a 12 mm diameter area between males and females (P > 0.05). However, upon adjusting for age, central corneal thickness (CCT), corneal curvature, white-to-white (WTW) corneal diameter, and axial length, females exhibited a greater average CD within the 12 mm diameter and in the 6–10 mm and 10–12 mm circles than males. Age-related changes in CD were evident, except in the 2–6 mm circle. CCT, corneal curvature, WTW corneal diameter, and partial depth correlated with CD in the radial area, and CD in different areas correlated with the OSI, MTFcutoff, and SR (P < 0.05).ConclusionsThis study provides the normative CD measurement data of Chinese adults with healthy corneas, emphasizing the significance of sex, age, CCT, corneal curvature, and WTW corneal diameter in CD evaluation. Notably, elevated CD can lead to increased forward scattering within the eye, thereby affecting the optical quality.

Detection of corneal pathology among Indians using WBC count as inflammatory marker.

The multifaceted role of NLR as a biomarker in corneal pathologies, aiming to enhance clinicians' understanding for better patient outcomes is of interest. An extensive ophthalmic assessment was conducted. Patients with corneal pathologies were identified as cases and those with healthy cornea as controls. A complete WBC blood count was performed using Automated Flow Cytometric method and the counts of white blood cells, neutrophils, platelets, and lymphocytes where recorded. NLR, PLR, and MLR were calculated by dividing the Neutrophil/Platelet/Monocyte counts by the lymphocyte counts. The study revealed that the Neutrophil-to-Lymphocyte Ratio (NLR), Monocyte-to-Lymphocyte Ratio (MLR), and Platelet-to-Lymphocyte Ratio (PLR) were significantly higher in the case group compared to the control group. N/L proved the best predictor among inflammatory markers, followed by M/L and P/L, highlighting the intricate immune response in corneal diseases, urging customized assessments in ocular health research.

How does atmospheric pressure cold helium plasma affect the biomechanical behaviour on alkali-lesioned corneas?

BackgroundMelting corneal ulcers are a serious condition that affects a great number of animals and people around the world and it is characterised by a progressive weakening of the tissue leading to possible severe ophthalmic complications, such as visual impairment or blindness. This disease is routinely treated with medical therapy and keratoplasty, and recently also with alternative regenerative therapies, such as cross-linking, amniotic membrane transplant, and laser. Plasma medicine is another recent example of regenerative treatment that showed promising results in reducing the microbial load of corneal tissue together with maintaining its cellular vitality. Since the effect of helium plasma application on corneal mechanical viscoelasticity has not yet been investigated, the aim of this study is first to evaluate it on ex vivo porcine corneas for different exposition times and then to compare the results with previous data on cross-linking treatment.Results94 ex vivo porcine corneas divided into 16 populations (healthy or injured, fresh or cultured and treated or not with plasma or cross-linking) were analysed. For each population, a biomechanical analysis was performed by uniaxial stress-relaxation tests, and a statistical analysis was carried out considering the characteristic mechanical parameters. In terms of equilibrium normalised stress, no statistically significant difference resulted when the healthy corneas were compared with lesioned plasma-treated ones, independently of treatment time, contrary to what was obtained about the cross-linking treated corneas which exhibited more intense relaxation phenomena.ConclusionsIn this study, the influence of the Helium plasma treatment was observed on the viscoelasticity of porcine corneas ex vivo, by restoring in lesioned tissue a degree of relaxation similar to the one of the native tissue, even after only 2 min of application. Therefore, the obtained results suggest that plasma treatment is a promising new regenerative ophthalmic therapy for melting corneal ulcers, laying the groundwork for further studies to correlate the mechanical findings with corneal histology and ultrastructural anatomy after plasma treatment.

3D bioprinting of stromal cells-laden artificial cornea based on visible light-crosslinkable bioinks forming multilength networks

3D bioprinting has the potential for the rapid and precise engineering of hydrogel constructs that can mimic the structural and optical complexity of a healthy cornea. However, the use of existing light-activated bioinks for corneal printing is limited by their poor cytocompatibility, use of cytotoxic photoinitiators (PIs), low photo-crosslinking efficiency, and opaque/colored surface of the printed material. Herein, we report a fast-curable, non-cytotoxic, optically transparent bioprinting system using a new water-soluble benzoyl phosphinate-based PI and photocrosslinkable methacrylated hyaluronic acid (HAMA). Compared with commercially available PIs, the newly developed PI, lithium benzoyl (phenyl) phosphinate (BP), demonstrated increased photoinitiation efficiency under visible light and low cytotoxicity. Using a catalytic amount of BP, the HA-based bioinks quickly formed 3D hydrogel constructs under low-energy visible-light irradiation (405 nm, <1 J cm−2). The mechanical properties and printability of photocurable bioinks were further improved by blending low (10 kDa) and high (100 kDa) molecular weight (MW) HAMA by forming multilength networks. For potential applications as corneal scaffolds, stromal cell-laden dome-shaped constructs were fabricated using MW-blended HAMA/BP bioink and a digital light processing printer. The HA-based photocurable bioinks exhibited good cytocompatibility (80%–95%), fast curing kinetics (<5 s), and excellent optical transparency (>90% in the visible range), potentially making them suitable for corneal tissue engineering.

Chemical, Physical, and Biological Corneal Decellularization Methods: A Review of Literature.

The cornea is one of the most commonly transplanted tissues worldwide. It is used to restore vision when severe visual impairment or blindness occurs in patients with corneal diseases or after trauma. Due to the global shortage of healthy donor corneas, decellularized corneal tissue has significant potential as an alternative to corneal transplantation. It preserves the native and biological ultrastructure of the cornea and, therefore, represents the most promising scaffold. This article discusses different methods of corneal decellularization based on the current literature. We searched PubMed.gov for articles from January 2009 to December 2023 using the following keywords: corneal decellularization, decellularization methods, and corneal transplantation. Although several methods of decellularization of corneal tissue have been reported, a universal standardised protocol of corneal decellularization has not yet been introduced. In general, a combination of decellularization methods has been used for efficient decellularization while preserving the optimal properties of the corneal tissue.

Diabetic Ocular Surface Has Defects in Oxygen Uptake Revealed by Optic Fiber Microsensor.

Diabetes mellitus causes diabetic keratopathy (DK). This and other ocular surface disorders are underdiagnosed and problematic for affected patients as well as recipients of diabetic donor corneas. Thus, it is important to find noninvasive means to facilitate determination of the potentially vision-threatening DK. It has been reported that diabetic corneas uptake significantly less oxygen (O2) than healthy controls. However, an integral assessment of the ocular surface is missing. Using an optic-fiber O2 micro-sensor (optrode) we demonstrated recently that the healthy ocular surface displays a unique spatiotemporal map of O2 consumption. We hypothesize that diabetes impairs the spatiotemporal profile of O2 uptake at the ocular surface. Using streptozotocin (STZ)-induced diabetic mice, we found diminished O2 uptake and loss of the unique pattern across the ocular surface. A diabetic cornea consumes significantly less O2 at the bulbar conjunctiva and limbus, but not the central and peripheral cornea, compared to controls. Further, we show that, contrary to the healthy cornea, the diabetic cornea does not increase the O2 consumption at the limbus in the evening as the normal control. Altogether, our measurements reveal a previously unknown impairment in O2 uptake at the diabetic cornea, making it a potential tool to diagnose ocular surface abnormalities and suggesting a new etiology mechanism.

Inflammation-suppressing cornea-in-a-syringe with anti-viral GF19 peptide promotes regeneration in HSV-1 infected rabbit corneas

Pathophysiologic inflammation, e.g., from HSV-1 viral infection, can cause tissue destruction resulting in ulceration, perforation, and ultimately blindness. We developed an injectable Cornea-in-a-Syringe (CIS) sealant-filler to treat damaged corneas. CIS comprises linear carboxylated polymers of inflammation-suppressing 2-methacryloyloxyethyl phosphorylcholine, regeneration-promoting collagen-like peptide, and adhesive collagen-citrate glue. We also incorporated GF19, a modified anti-viral host defense peptide that blocked HSV-1 activity in vitro when released from silica nanoparticles (SiNP-GF19). CIS alone suppressed inflammation when tested in a surgically perforated and HSV-1-infected rabbit corneal model, allowing tissue and nerve regeneration. However, at six months post-operation, only regenerated neocorneas previously treated with CIS with SiNP-GF19 had structural and functional features approaching those of normal healthy corneas and were HSV-1 virus-free. We showed that composite injectable biomaterials can be designed to allow regeneration by modulating inflammation and blocking viral activity in an infected tissue. Future iterations could be optimized for clinical application.