Treatment Of Corneal Diseases Research Articles

Unveiling challenging corneal infections: a comprehensive etiological diagnosis through metagenomic next-generation sequencing (mNGS) of corneal tissue samples.

The objective of this study was to assess the clinical diagnostic value of metagenomic next-generation sequencing (mNGS) in cases of challenging corneal infections using corneal tissue samples. This retrospective study involved 42 patients with corneal infections, where conventional diagnostic techniques failed to identify the causative pathogen. Corneal tissue specimens underwent mNGS, followed by microbial culture for validation. Sensitivity-guided antimicrobial therapy was administered upon identification of the pathogen. The diagnostic and therapeutic efficacy of mNGS was analyzed to evaluate its clinical utility. A total of 42 patients were included in this study, with mNGS detection results obtained for 38 cases (90.48%). Among them, 30 cases (71.43%) were clinically significant, eight cases (19.05%) had low clinical relevance, and four cases (9.52%) showed no detection. Following corresponding antimicrobial treatment, 30 patients exhibited significant improvement, resulting in a treatment effectiveness of 71.43%. The prognosis of mNGS-positive patients was superior to that of mNGS-negative patients, with statistically significant differences observed (P < 0.001). Corneal tissue mNGS facilitated the rapid identification of causative agents in challenging corneal infections with unclear clinical diagnoses. It could be seamlessly integrated with traditional diagnostic methods to guide the diagnosis and treatment of corneal diseases.

Methylation in cornea and corneal diseases: a systematic review.

Corneal diseases are among the primary causes of blindness and vision loss worldwide. However, the pathogenesis of corneal diseases remains elusive, and diagnostic and therapeutic tools are limited. Thus, identifying new targets for the diagnosis and treatment of corneal diseases has gained great interest. Methylation, a type of epigenetic modification, modulates various cellular processes at both nucleic acid and protein levels. Growing evidence shows that methylation is a key regulator in the pathogenesis of corneal diseases, including inflammation, fibrosis, and neovascularization, making it an attractive potential therapeutic target. In this review, we discuss the major alterations of methylation and demethylation at the DNA, RNA, and protein levels in corneal diseases and how these dynamics contribute to the pathogenesis of corneal diseases. Also, we provide insights into identifying potential biomarkers of methylation that may improve the diagnosis and treatment of corneal diseases.

Emphasizing precision minimally invasive corneal surgery

In recent years, precision minimally invasive surgery has emerged as a significant developmental direction within the field of ophthalmology, bringing about revolutionary changes in the treatment of corneal diseases. Employing cutting-edge techniques and surgical methods, corneal surgeries have achieved greater precision and safety. In cases such as immune-mediated corneal diseases, it remains crucial to underscore the enhancement of vision through minimally invasive surgical approaches, thereby avoiding potential irreversible complications that surgery might induce. This article aims to assist readers in comprehending the profound impact of precision minimally invasive surgery on the treatment of corneal diseases, and calls upon medical professionals and researchers to continually explore and refine the realm of precision minimally invasive corneal surgery, fostering its further advancement.

Culture and characterization of canine and feline corneal epithelial organoids: A new tool for the study and treatment of corneal diseases

In this study, we isolated and cultured canine and feline 3D corneal organoids. Samples derived from corneal limbal epithelium from one canine and one feline patient were obtained by enucleation after euthanasia. Stem cell isolation and organoid culture were performed by culturing organoids in Matrigel. Organoids were subsequently embedded in paraffin for further characterization. The expression of key corneal epithelial and stromal cell markers in canine and feline organoids was evaluated at the mRNA level by RNA-ISH and at the protein level by immunofluorescence (IF) and immunohistochemistry (IHC), while histochemical analysis was performed on both tissues and organoids using periodic-acid Schiff (PAS), Sirius Red, Gomori's Trichrome, and Colloidal Iron stains. IF showed consistent expression of AQP1 within canine and feline organoids and tissues. P63 was present in canine tissues, canine organoids, and feline tissues, but not in feline organoids. Results from IHC staining further confirmed the primarily epithelial origin of the organoids. Canine and feline 3D corneal organoids can successfully be cultured and maintained and express epithelial and stem cell progenitor markers typical of the cornea. This novel in vitro model can be used in veterinary ophthalmology disease modeling, corneal drug testing, and regenerative medicine.

Awareness and attitude towards eye donation among rural population

Voluntary eye donation especially among rural areas is less and is associated with lot of myths and gaps in the knowledge.Aim of the study was to assess the awareness and attitude towards eye donation among rural population. : Cross-sectional observational study conducted from November 2019 to February 2020, in OPD and eye camps. After written informed consent, self-designed questionnaire in the regional language with dichotomous closed ended questions was given.: Of 400 people, 47(11.75%) knew only front of the eye can be donated.301 (75.25%) were aware that eye can be donated only after death. 253 (63.25%) mentioned that there is no age limit for eye donation. 298 (74.5%) knew diabetics could donate eyes. Majority of them had no idea about eye donation in infectious diseases such as HIV, HbsAg and were unaware as to who can give consent (111-27.75%), and place of retrieval of the eye 93(23.25%). 92(23%) answered eye should be donated within 6 hours after death. 29 (7.25%) answered that donated eyes can be used in the treatment of corneal disease. 164 (41%) were willing to donate eyes out of which nobility was the major reason for 104 (64%). 236 (59%) were not willing for donation due to fear of disfigurement.: In our results we observed that awareness for eye donation is less among people of community and majority of them were unwilling to donate eyes. Hence, extensive awareness programs can change the attitude towards eye donation and motivate people to donate eyes. Community awareness is the major chain link for the success of eye donation for corneal transplantation.

The first-in-human implantation of the CorNeat keratoprosthesis.

To describe the first clinical implantation of the CorNeat™ keratoprosthesis, which utilizes a polymeric scaffold for biointegration within ocular tissue. The CorNeat keratoprosthesis was implanted in the right eye of a patient with bilateral corneal opacification and neovascularization secondary to multiple failed grafts. The following surgical technique was used: 360 degree peritomy; epithelial scraping and corneal marking; pre-placement of three corneo-scleral sutures through the implant; central trephination using a 7 mm trephine and host cornea removal; keratoprosthesis placement and sutures tightening while fitting the corneal edge into the posterior groove of the CorNeat keratoprosthesis; and repositioning of the conjunctiva over the implant skirt and fixation with sutures and Fibrin sealant. Twelve months postoperatively visual acuity improved to 1/16 from hand movement. The keratoprosthesis was properly positioned. Tactile intraocular pressure was assessed as normal. Regional, mostly nasal, conjunctival retraction of 4-5 mm over the nano-fibre skirt was seen throughout follow-up. The anterior chamber was quiet and well-formed. No other postoperative complications were observed. This initial case may imply a potential breakthrough in the treatment of corneal disease not amenable to standard corneal transplant. Long follow-up and additional implantations are desired to prove the long-term safety and efficacy of this device.

Tissue engineered scaffolds for corneal endothelial regeneration: a material's perspective.

Currently, the treatment of corneal diseases caused by damage to the corneal endothelium requires a donor cornea. Because of their limited availability (1 donor cornea for 70 patients in need), researchers are investigating alternative approaches that are independent of donor tissue. One of them includes the development of a tissue engineered scaffold onto which corneal endothelial cells are seeded. In order to function as a suitable substrate, some of its essential properties including thickness, permeability, transparency and mechanical strength should meet certain demands. Additionally, the membrane should be biocompatible and allow the formation of a functional endothelium on the surface. Many materials have already been investigated in this regard including natural, semi-synthetic and synthetic polymers. In the current review, we present an overview of their characteristics and provide a critical view on the methods exploited for material characterization. Next, also the suitability of scaffolds to serve their purpose is discussed along with an overview of natural tissues (e.g. amniotic membrane and lens capsule) previously investigated for this application. Eventually, we propose a consistent approach to be exploited ideally for membrane characterization in future research. This will allow a scientifically sound comparison of materials and membranes investigated by different research groups, hence benefitting research towards the creation of a suitable/optimal tissue engineered endothelial graft.

Optical Coherence Tomography for Diagnosis and Treatment of Corneal Diseases

Optical coherence tomography (OCT) is a modern non-contact real-time imaging of anterior and posterior eye’s segments. Based on the principle of low-coherence interferometry, it provides the analysis of tissue structures. In this review, we discuss technical aspects of two different OCT platforms: Time-Domain OCT (TD-OCT), and Spectral-Domain (SD-OCT) with the use of Fourier transformation — Fourier-Domain (FD-OCT). Over the last several years, the development of OCT has increased the resolution of images by different ways of optical filtering. The usage of tunable swept laser instead of superluminescent diode in modern Swept-Source OCT (SS-OCT) provides the sufficient quality of image. Anterior segment OCT can detect the pathological changes in different ocular structures and may be a key tool for monitoring of their progression. In pterygium OCT shows the true extent of fibrovascular granulation tissue in stromal layers, whereas in keratitis it provides imaging of corneal infiltration. Frequently, OCT-pachymetry can be advantageous in the detection of subclinical keratectasias. In patients with bullous keratopathy OCT can help to distinguish corneal edema and fibrosis. The new era of OCT is characterized by application of this method in keratorefractive surgery. Microscope-mounted (portable) and microscopeintegrated OCT systems have been developed. During LASIK surgery intraoperative OCT (iOCT) helps to assess flap interface, measure flap and residual bed thickness. It is a useful tool to reveal the structural changes during corneal collagen crosslinking. At the beginning of keratoplasty, iOCT helps to determine the corneal thickness, extent and depth of opacity, Descemet membrane perforation. iOCT guides decision-making regarding keratoplasty modification, depth and diameter of trephination. Furthermore, a real-time visualization of ocular structures during keratoplasty decreases the frequency of intra- and postsurgical complications.

Use of Plasma Rich in Growth Factors and ReGeneraTing Agent Matrix for the Treatment of Corneal Diseases.

This study aimed to investigate the use of Plasma Rich in Growth Factors (PRGF) associated with tissue ReGeneraTing Agent (RGTA) drops for the treatment of noninfectious corneal ulcers. RGTA treatment was applied (one drop every two days); however, if ulcer closure was not achieved, PRGF eye drops treatment was added (four times/day). The time taken to reach the ulcer closure, the Best Corrected Visual Acuity (BCVA), intraocular pressure (IOP), Visual Analog Scale (VAS, in terms of frequency and severity of symptoms), and Ocular Surface Disease Index (OSDI) were evaluated. Seventy-four patients (79 eyes) were included, and the mean age was 56.8 ± 17.3 years. The neurotrophic corneal ulcer was the most frequent disorder (n = 27, 34.2%), mainly for herpes virus (n = 15, 19.0%). The time of PRGF eye drops treatment associated with the RGTA matrix was 4.2 ± 2.2 (1.5–9.0) months, and the follow-up period was 44.9 ± 31.5 months. The ulcer closure was achieved in 76 eyes (96.2%). BCVA, VAS and OSDI improved from the baseline (p < 0.001), and IOP remained unchanged (p = 0.665). RGTA and PRGF in noninfectious ulcers were effective and could be a therapeutic alternative for this type of corneal disease.

In vivo human corneal natural frequency quantification using dynamic optical coherence elastography: Repeatability and reproducibility

Reliable and quantitative assessment of corneal biomechanics is important for the detection and treatment of corneal disease. The present study evaluates the repeatability and reproducibility of a novel optical coherence tomography (OCT)-based elastography (OCE) method for in vivo quantification of corneal natural frequency in 20 normal human eyes. Sub-micron corneal oscillations were induced by repeated low-force (13 Pa) microliter air pulses at the corneal apex and were observed by common-path phase-sensitive OCT imaging adjacent to a measurement region of 1–6.25 mm2. Corneal natural frequencies were quantified using a single degree of freedom model based on the corneal oscillations. Corneal natural frequencies ranged from 234 to 277 Hz (coefficient of variation: 3.2%; n = 286 for a 2.5 × 2.5 mm2 area; time: 28.6 s). The same natural frequencies can be acquired using a smaller sampling size (n = 9 for 1 mm2) and a shorter time (0.9 s). Spatial distribution and local changes in natural frequencies can be distinguished using denser sampling (e.g., 26 × 41 points for 2.5 × 5 mm2). This novel optical method demonstrates highly repeatable and reliable in vivo measurements of human corneal natural frequencies. While further studies are required to fully characterize anatomical and structural dependencies, this method may be complementary to the current OCE methods used to estimate Young’s modulus from strain- or shear-wave-based measurements for the quantitative determination of corneal biomechanics.

Letter to the editor: PROKERA® slim corneal bandage now approved in Taiwan for treatment of corneal diseases.

Letter to the editor: PROKERA® slim corneal bandage now approved in Taiwan for treatment of corneal diseases.

Application of Anterior Segment Optical Coherence Tomography in Refractive Surgery

With the development of modern medical technology, the accuracy and safety of refractive surgery in ophthalmology have been constantly improved. Many new examination methods have been applied in research and clinical practice, and anterior segment optical coherence tomography (AS-OCT) is a new non-contact non-invasive optical image diagnosis technology, which can be used to measure the biological structure of anterior segment. AS-OCT is widely used in the clinical diagnosis and treatment of corneal diseases, cataracts, glaucoma and other specialties due to its advantages of fast scanning speed, deep layer, high penetration rate and high resolution. In addition, AS-OCT can also obtain: corneal thickness, corneal epithelial thickness map, corneal topographic map, anterior chamber depth (ACD), white to white (WTW), crystal arch height (LV), Angle width of the anterior chamber, etc., so it is especially suitable for the pre-operative screening, design of operation scheme and safety evaluation after the operation of auxiliary ophthalmic refractive surgery (including corneal refractive surgery and intraocular refractive surgery). At present, corneal refractive surgery mainly includes excimer laser in-situ keratomileusis (LASIK), femtosecond laser-assisted LASIK (FS-LASIK), femtosecond laser stromal lens removal for small incision (SMILE), and transepithelial laser keratoplasty (T-PRK), and ICL implantation is the main method of intraocular refractive surgery. This article will review the clinical application of AS-OCT in corneal refractive surgery and intraocular refractive surgery, and provide reference for clinical practice.

Quantification of collagen structural changes during chick corneal development.

As the most abundant structural mammalian protein, collagen has been implicated in the pathogenesis of numerous diseases such as osteogenesis imperfecta, and cancer. In the case of cornea, abnormal cornea development can lead to conditions such as agenesis, megalocornea, microcornea, and cornea plana. Therefore, understanding the mechanisms of collagen assembly during development may contribute to the prevention or treatment of corneal diseases. In this study, we applied fast Fourier transform second harmonic generation microscopy to quantify parameters of corneal structures during chick development. Our results show that both the rotational pitch and overall rotational angle of corneal stroma modulate between E9 and E19. In addition, we found that corneal structures between left and right corneas are highly correlated during development.

In vivo evaluation of corneal biomechanical properties by optical coherence elastography at different cross-linking irradiances.

.Corneal collagen cross-linking (CXL) strengthens the biomechanical properties of damaged corneas. Quantifying the changes of stiffness due to different CXL protocols is difficult, especially in vivo. A noninvasive elastic wave-based optical coherence elastography system was developed to construct in vivo corneal elasticity maps by excitation of air puff. Biomechanical differences were compared for rabbit corneas given three different CXL protocols while keeping the total energy delivered constant. The Young’s modulus was weaker in corneas treated with higher irradiance levels over shorter durations, and a slight increase of Young’s modulus was present in all groups one week after the recovery process. Due to the noninvasive nature and minimal force to generate corneal elastic waves, this technique has the potential for early detection and treatment of corneal diseases in clinic.

Role of Stem Cells in Treatment of Acanthamoebic Corneal Ulcer

Regeneration of lost human tissue is well known, the research on regenerative medicine has gained scientific advancements. The growing understanding of biological concepts in the regeneration of ocular tissues as well as experiments on stem cells result in shift in the treatment of corneal diseases. Stem cells have been successfully isolated from variety of human tissues including mesenchymal tissues. Initial evidence from several studies has documented the likely breakthrough that stem cells offer for various life-threatening diseases that have so far defeated modern medical care. So, this research aimed to study the role of stem cells in treatment of Acanthamoebic corneal ulcer. Test experiment included Acanthamoeba-infected female albino rats started local treatment by chlorhexidine 0.02% after 2 weeks post infection and mesenchymal stem cells (MSCs) injected. Female rats were subdivided into 4 groups. Group (Gp) I: 15 rats infected and injected with MSCs intravenously at 2 weeks post-infection. Gp II: 15 rats infected and intravenously injected with MSCs at 3 weeks post-infection. Gp III: 15 rats infected and injected locally subconjunctival at 2 weeks post-infection. Gp IV: 15 rats infected and locally subconjunctival injected at 3 weeks post-infection with MSCs. Control groups were composed of age- and weight-matched control female rats, subdivided into: Gp V, Gp VI, Gp VII, and Gp VIII. Gp V was composed of 10 Acanthamoeba-infected and non-injected (non- treated negative control) rats. Each 10 of them was sacrificed on dates corresponding to sacrifice dates of each test groups (at one-week post treatment). Gp VI is composed of 10 rats infected and intravenously injected by PBS (vehicle). Each were sacrificed on dates corresponding to sacrifice dates of Gp I and II (at one-week post treatment). Gp VII: 10 rats infected and locally subconjunctival injected by PBS (vehicle). Each 10 was sacrificed on dates corresponding to sacrifice dates of Gp III and IV (at one-week post treatment). Gp VIII: 10 Acanthamoeba-infected and locally treated by chlorhexidine 0.02% positive control rats which are infected and not injected with MSCs. Each 10 of them was sacrificed on dates like sacrifice dates of each test group (at one-week post treatment). Rates were sacrificed on the planned dates, then corneal specimens and blood samples were collected. There were significant decrease in the level of vascular endothelial growth factor (VEGF) in group I, III and highly significant decrease in the level of nitric oxide (NO) in group I, II, III in comparison to positive control group VIII .There were 20% engraftments with MSC in group I. Treatment of Acanthamoeba corneal ulcer with chlorhexidine 0.02% and MSCs accelerated regeneration of the corneal epithelium and restored the antioxidant protective mechanism.

Imaging Corneal Biomechanical Responses to Ocular Pulse Using High-Frequency Ultrasound.

Imaging corneal biomechanical changes or abnormalities is important for better clinical diagnosis and treatment of corneal diseases. We propose a novel ultrasound-based method, called ocular pulse elastography (OPE), to image corneal deformation during the naturally occurring ocular pulse. Experiments on animal and human donor eyes, as well as synthetic radiofrequency (RF) data, were used to evaluate the efficacy of the OPE method. Using very high-frequency ultrasound (center frequency = 55 MHz), correlation-based speckle tracking yielded an accuracy of less than 10% error for axial tissue displacements of or above. Satisfactory speckle tracking was achieved for out-of-plane displacements up to . Using synthetic RF data with or without a pre-defined uniform strain, the OPE method detected strains down to 0.0001 axially and 0.00025 laterally with an error less than 10%. Experiments in human donor eyes showed excellent repeatability with an intraclass correlation of 0.98. The measurement outcome from OPE was also shown to be highly correlated with that of standard inflation. These results suggest the feasibility of OPE as a potential clinical tool for evaluating corneal biomechanics in vivo.

Advances in the treatment of corneal diseases with cataracts

Corneal lesion with cataract is a problem that corneal disease doctors often encounter.Triple procedure does not need a second operation, which can avoid corneal grafts damage and restore visual acuity quickly, thus it becomes the primary surgical method of corneal lesions with cataracts.But due to the unstable cornea curvature and irregular cornea topography after corneal transplantation, it is difficult to predict the refractive status after triple procedure.Conversely, we can accurately measure the degree of intraocular lens to reduce the refractive error after operation if we perform cataract extraction and intraocular lens implantation after corneal suture was completely removed.Accordingly, there are also many ophthalmic surgeons tend to operate penetrating keratoplasty firstly and cataract surgery laterly.The two kinds of operations have their own advantages on operation safety and postoperative effect, so the choice of operation has been controversial.In recent years, with improvement of ophthalmology microsurgery technology and development of surgical instruments, we have a new understanding on the surgical treatment strategy of the disease.Therefore, recent advances of surgical therapy for the disease are reviewed in this paper. Key words: Corneal diseases; Cataract; Astigmatism; Therapeutics

Design and implementation of optical system for Placido-disc topography

Corneal topography provides powerful support in the diagnosis and treatment of corneal disease by displaying the corneal surface topography in data or image format. To realize the precise detection of corneal surface topography, an optical system for the corneal topography that is based on a Placido disc is designed, which includes a ring distribution on a Placido disc, an imaging system and a collimating illumination system. First, a mathematical model that is based on the corneal topography working principles is established with MATLAB to determine the distribution of white-and-black rings on the Placido disc, in which the ellipsoid facial rings-target of the Placido disc is utilized. Second, the imaging lens structure is designed and optimized by Zemax software. Last, the collimating illumination lens structure is designed by paraxial ray trace equations. The quality of the corneal topography, which is based on our designed optical system, is evaluated. The high-contrast image of uniformly distributed white-and-black rings is observed through the CCD camera. Our optical system for the corneal topography has high precision, with a measuring region of the cornea with a diameter of approximately 10 mm. Therefore, the creation of this optical system offers guidance for designing and improving the optical system of Placido-disc topography.

Feasibility of bacterial cellulose membrane as biological scaffold for construction of tissue engineering corneal epithelium

Background Corneal transplantation is a primary method for the treatment of serious corneal diseases, but its application is limited because of the shortage of corneal donor. The study on tissue engineering corneal epithelium provides a new approach to corneal transplantation, and the biological scaffold materials for tissue engineering corneal epithelium is an issue of increasing concern. Bacterial cellulose membrane has been used in medical field, but its application in tissue engineering corneal epithelium deserves more researching. Objective This study was to evaluate the biocompatibility of bacterial cellulose membrane as a biological scaffold of tissue engineering corneal epithelium. Methods Corneal epithelium was isolated from 1 month-old New Zealand White rabbit. Corneal epithelial cells were cultured using explant method and identified by detecting the CK-3 expression using immunofluorescence technique. The second generation cells were inoculated on bacterial cellulose membrane and culture plate, respectively, and the growth status of the cells were examined and compared under the optical microscope. The cell activity/toxicity test was performed by LIVE/DEAD cell staining kit at the third day after inoculation to evaluate the survival rate. The ultrastructure of the cell surface was examined under the scanning electron microscope. The study was performed in accordance with the ARVO Statement. Results Rabbit corneal epithelial cells grew well 1 week after primarily cultured with a cobblestone-like appearance and positive response for CK3 antibody. The cells on the bacterial cellulose membrane presented a round shape and regular arrangement and showed the green fluorescence for LIVE/DEAD test, with the survival rate 100%. Abundant leafy protrusion, microvilli and intercellular junction were seen under the scanning electron microscope. In addition, mitosis phase of cells and many filopodia between the cells and bacterial cellulose membrane were also exhibited. Conclusions Rabbit corneal epithelial cells can grow well in bacterial cellulose membrane. Bacterial cellulose membrane has good biocompatibility, indicating that bacterial cellulose membrane can be used as new biological material for tissue engineering corneal epithelium. Key words: [Key words] Epithelium, corneal/cytology; Tissue engineering; Tissue scaffolds/microbiology; Biocompatible materials; Cells, cultured; Rabbits; Bacterial cellulose

Early Complications After Penetrating Keratoplasty

Although endothelial keratoplasty has gained increasing popularity over the last decade in the US, penetrating keratoplasty (PK) continues to have a role in the treatment of corneal diseases. This is especially true in developing nations where endothelial keratoplasty has not been popularized, and where isolated endothelial disease is much less common. In these situations, PK is still indicated. As with any surgical procedure, PK carries with it complications that can threaten the success of the procedure, including wound-related issues, ocular surface disease, infections, and suture-related complications. This article will review the various aspects of early complications after PK occurring within the first 2 months of surgery, along with management techniques. A review of the current literature was performed via a Medline search using the keywords “penetrating keratoplasty,” “complications,” “cornea,” and “transplant.” All articles containing descriptions of early postoperative complications after PK were reviewed, and the more commonly encountered complications are discussed in this article.