- •Corneal Disease
- •Preface
- •Contents
- •Contributors
- •Core Messages
- •Organisms
- •Detection
- •Acid Fast Smears
- •Culture Media
- •Molecular Tests
- •Nucleic Acid Hybridization Probes
- •Line Probes
- •DNA Sequencing
- •FISH (Fluorescent In Situ Hybridization) Assay
- •DNA Microarray
- •Pulse Field Gel Electrophoresis (PFGE)
- •Management
- •Clinical Diagnosis
- •Medical Therapy
- •Surgical Intervention
- •Penetrating Keratoplasty
- •Corneal Cross-Linking
- •Summary for the Clinician
- •References
- •Core Messages
- •Introduction
- •Epidemiology
- •Visual Morbidity
- •Documentation
- •Causative Factors
- •Causative Bacteria
- •Investigation of Keratitis
- •Laboratory Diagnosis: Susceptibility Testing
- •Susceptibility and Resistance of Bacterial Isolates
- •Treatment: Antimicrobials
- •Current Antimicrobials in Use
- •The Fluoroquinolones
- •Aminoglycosides
- •Cephalosporins
- •Other Antimicrobials Used
- •Development of Existing and New Classes of Drugs
- •Tigecycline
- •Linezolid
- •Meropenem
- •Combination Therapy
- •Drug Delivery to the Cornea
- •Novel Methods of Drug Delivery to the Cornea
- •Conclusion
- •References
- •3: Heredity of Keratoconus
- •Introduction
- •Is Keratoconus a Heritable or Genetic Disease?
- •Mutational Screening of Candidate Genes in Keratoconus
- •Visual System Homeobox Gene 1 (VSX1)
- •Superoxide Dismutase 1 (SOD1)
- •Interleukin 1 (IL1) Superfamily
- •Collagen Genes
- •Genetic Mapping in Keratoconus
- •Genetics of Keratoconus – Mendelian or Complex?
- •References
- •4: Advance in Corneal Imaging
- •Introduction
- •In Vivo Confocal Microscopy (IVCM)
- •Principles of Confocal Microscopy
- •The Normal Cornea
- •Clinical Applications
- •Infectious Keratitis
- •Corneal Dystrophies
- •Refractive Surgery
- •Corneal Surgery
- •Other Clinical Applications
- •Limitations of IVCM
- •Anterior Segment Ocular Coherence Tomography (OCT)
- •Clinical Applications
- •Corneal Thickness Assessment
- •Refractive Surgery
- •Corneal Grafts
- •Limitations
- •Conclusion
- •References
- •Core Messages
- •Introduction
- •“Angiogenic Privilege of the Cornea” or “How Does the Normal Corneal Maintain Its Avascularity?”
- •General Mechanisms
- •Corneal Hemangiogenesis After Low-Risk Keratoplasty
- •Corneal Hemangiogenesis After High-Risk Keratoplasty
- •Corneal Lymphangiogenesis: Essential for Corneal Graft Rejection
- •Corneal Lymphangiogenesis in Dry Eye
- •Imaging of Corneal Lymphatic Vessels
- •Novel Anti(lymph)Angiogenic Treatment Options at the Cornea
- •Current Treatment Options for Immature Corneal (Blood and Lymphatic) Vessels
- •Steroids
- •Anti-VEGFs (Bevazicumab, Ranibuzumab, Pegaptanib, VEGF Trap)
- •Anti-IRS 1-Strategies (Antisense Oligonucleotides Against IRS 1)
- •Treatment Options for Mature Corneal Vessels
- •Unmet Needs and Future Directions
- •References
- •Core Messages
- •Introduction
- •Retrieval of Donor Tissue
- •Technical Aspects
- •Microbiological Aspects
- •Tissue Evaluation Aspects
- •Corneal Storage
- •Moist Chamber Storage of the Donor Eye
- •Technical Aspects
- •Storage Period
- •Microbiological Safety
- •Tissue Evaluation
- •Hypothermic Storage of the Corneoscleral Button
- •Technical Aspects
- •Storage Period
- •Microbiological Safety
- •Tissue Evaluation
- •Organ Culture (Normothermic Storage) of the Corneoscleral Button
- •Technical Aspects
- •Storage Period
- •Microbiological Safety
- •Tissue Evaluation
- •Other Aspects
- •Pre-cutting of Corneal Tissue for Endothelial Keratoplasty (EK)
- •Microkeratome Cutting
- •Femtosecond Laser Cutting
- •Stripping of Descemet’s Membrane with Endothelium
- •Donor Considerations for EK
- •References
- •7: Infant Keratoplasty
- •Core Messages
- •Introduction
- •Indications for Surgery
- •Visual Outcome
- •Patient Selection
- •Patient Assessment
- •Ancillary Testing
- •Donor Tissue
- •Intraoperative Considerations
- •Concurrent Surgical Procedures
- •Postoperative Considerations
- •Suture Management
- •Optical Correction and Amblyopia Therapy
- •Postoperative Complications
- •Glaucoma
- •Graft Rejection
- •Graft Failure
- •Alternatives to Penetrating Keratoplasty
- •Conclusion
- •References
- •Index
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Fig. 4.6 Spectral domain anterior segment ocular coherence tomography (SD-OCT) images of a normal cornea (a) and in a case of Avellino corneal dystrophy (b)
It was only in 2001 that a high-speed OCT (8 images per second) became available using a wavelength of 1,310 nm allowing optimum visualization of the anterior segment. This wavelength gives better penetration through light-retaining tissues such as the sclera or limbus, making it possible to analyze the iridocorneal angle. Since then, new spectral-domain OCTs have been commercially available for the analysis of the anterior segment and the cornea in particular. As a new imaging technique providing the means of obtaining cross sections of the anterior segment in vivo, anterior segment OCT (AS-OCT) has already found many applications.
Clinical Applications
Corneal Thickness Assessment
Naturally, biometric assessment of the anterior segment has drawn great beneÞt from this reproducible and totally noninvasive technique. New AS-OCT devices are able to measure the whole corneal thickness as well as the thickness of each corneal layer from the epithelium to the endothelium, allowing to determine the exact depth of corneal deposits susceptible to beneÞt from phototherapeutic keratectomy (Fig. 4.6). AS-OCT-measured corneal pachymetry is reliable, reproducible, and
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Fig. 4.7 Anterior segment ocular coherence tomography (AS-OCT, Visante OCT¨) images. Evaluation of an Intralase¨ ßap after LASIK (a). Epithelial ingrowth after LASIK (b), the epithelial ingrowth appears as hyper-reßective deposits within the ßap with an increased ßap thickness
closely correlated with ultrasound pachymetry, especially using Stratus or Fourierdomain OCTs [18, 19]. Three-dimensional mapping of the epithelial thickness may also be greatly improved, even though these new data have still to be validated.
Refractive Surgery
Corneal refractive surgery, including surface ablation, laser in situ keratomileusis, femtosecond laser-assisted ßaps (Fig. 4.7a, b) and intracorneal rings (Fig. 4.8), induces deep changes in corneal morphology and optical properties along with cell structure remodeling. Great improvements in corneal imaging allow today microscopic in vivo follow-up of mechanisms involved in corneal wound healing, becoming helpful tools for optimizing our therapeutic decision as well as our surgical procedure.
Preoperatively, high-resolution AS-OCTs, that is, Stratus and Fourier-domain OCTs allow precise measurement of corneal thickness, intracorneal scar localization and volume, or previous LASIK interface depth using qualitative imaging but also quantitative A-mode. Moreover, corneal hydration as well as corneal refractive index can nowadays be assessed thanks to new interferometry-based imaging
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Fig. 4.8 Spectral domain anterior segment ocular coherence tomography (SD-OCT, Spectralis¨) image of corneal rings for keratoconus
procedures [20]. After corneal refractive photoablation, wound healing can be followed in vivo with three-dimensional mapping of epithelial or entire corneal thickness using high-resolution AS-OCT [21]. LASIK ßaps can be precisely imaged from the center to the edges, and light diffraction at the interface can be measured in order to investigate its inßuence on contrast perception. Indeed, femtosecond LASER-assisted LASIK has been demonstrated to perform more precise and homogenous ßap cutting thanks to AS-OCT imaging [22]. Moreover, measuring changes in corneal curvature and refractive index allows today a better understanding of the relation between corneal ablation and refractive changes, becoming an essential tool before secondary corneal/intraocular surgery.
Complicated evolution of corneal remodeling and/or refraction pattern after corneal surgery can be analyzed using high-resolution AS-OCT to better identify causal mechanisms, from slight epithelial remodeling to true ectasia. Flap interface deposits or micro-folds can be easily characterized combining AS-OCT and confocal microscopy in order to better deÞne the therapeutic strategy. Indeed, AS-OCT is able to show undiagnosed micro-folds which might be responsible for postoperative visual impairments [23]. Secondary structural pathologies including basal membrane dystrophy and SalzmannÕs-like nodular degeneration can be complementarily diagnosed using high-resolution AS-OCT.
Additionally, in the Þeld of phakic implants, the work by G. Baikoff has clearly demonstrated the advantages of AS-OCT for preoperative assessment of the exact dimensions of the anterior chamber prior to implantation, and for the analysis and follow-up of relationships between the cornea, the phakic IOL, and the lens after implantation (Fig. 4.9a, b) [24].
Corneal Grafts
Imaging of the ocular anterior structures is one of the key points in the analysis and follow-up of corneal grafts. AS-OCT provides today useful qualitative and quantitative data, especially by imaging corneal architecture in new procedures for corneal graft such as deep anterior lamellar keratoplasty and endothelial graft. Moreover, AS-OCT contributes to the diagnosis of postoperative complications by investigating the graft neighboring and imaging the other anterior structures, offering special usefulness when pathological corneal changes make standard clinical examination difÞcult.
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Fig. 4.9 Anterior segment ocular coherence tomography (AS-OCT, Visante OCT¨) image of a phakic intraocular lens (a) with quantitative measures (b)
After penetrating keratoplasty, AS-OCT allows to analyze the entire graft position as well as its macroscopic features such as thickness and curvature (Fig. 4.10a). Since laser-assisted penetrating keratoplasty was developed, AS-OCT has become a useful tool to assess the interface between the graft and the cornea, contributing to the improvement of surgical techniques. Moreover, long-term complications such as descemet membrane rupture or secondary glaucoma can be better diagnosed using AS-OCT even when important edema exists. In new graft procedures, AS-OCT helps to analyze preoperatively the corneal disease along with the anterior segment dimensions in order to better deÞne the right procedure.
Postoperative management of new developments in endothelial grafts, that is, Descemet stripping automated endothelial keratoplasty (DSAEK) has been dramatically improved thanks to AS-OCT (Fig. 4.10b) by following the corneal thickness related to endothelial function [25] as well as by diagnosing early and late complications including Descemet detachment or late pupillary blockade due to iris-graft synechiae. Other unexpected complications such as epithelial ingrowth in the interface can be imaged using AS-OCT.
Last, AS-OCT can substitute for clinical examination after amniotic membrane graft by following in vivo the corneal wound healing above the graft as well as the amniotic membrane integration into the superÞcial cornea.
