Corneal Degeneration Research Articles

Schwannome orbitaire : aspects cliniques, radiologiques et chirurgicaux

Schwannoma, or peripheral glioma, is a rare tumor of the orbit (1% of orbital tumors). Its diagnosis remains difficult and can be established only by histological analysis. We discuss through this case report the clinical, radiological and surgical features of this tumor. We report the case of a young 38-year-old woman with high myopia and no specific medical history, presenting with a rapidly progressive decrease in visual acuity of the right eye, associated with swelling of the supero-lateral orbit, and eccentric, non-pulsatile, ipsilateral proptosis. Clinical examination of the right eye revealed corrected visual acuity of 20/40, mobile swelling near the lacrimal gland and limitation of elevation and abduction. Slit lamp exam revealed secondary central corneal degeneration. Fundus exam was remarkable for stage I optic nerve head edema. Examination of the left eye was unremarkable. Orbital CT revealed a mass of 21.3mm×14.8mm, hypodense and heterogeneous, attached to the lacrimal gland, displacing the globe downward and inward, enhancing with contrast and without bone erosion. Excision of the tumor and the remaining stump of the gland was performed through a subciliairy skin incision followed by histological analysis confirming the diagnosis of schwannoma. No recurrence was noted after a follow-up of a year and a half. Schwannoma is a rare tumor of the orbit. Its clinical and radiological diagnosis is always difficult. Only histological study allows confirmation of the diagnosis. The absence of recurrence is dependent upon total surgical excision.

Causes of Visual Impairment and Blindness among Elderly Patients Attending Ophthalmology Clinic at King Hussein Medical Center

Objectives: To investigate the causes of visual impairment and blindness among elderly patients attending ophthalmology clinic at King Hussein Medical Center. Methods: A prospective study that was conducted at King Hussein Medical Center of the Royal Medical Services during the period between January 2010 and January 2012. Inclusion criteria were patients older than 60 years of age attending ophthalmology clinic for any complaint with best corrected visual acuity of less than 6/18 in the better eye. Patients were classified into two groups: first group for patients with visual impairment defined by best corrected visual acuity of less than 6/18 and better than 3/60 in the better eye, and second group for blind patients with best corrected visual acuity of less than 3/60 in the better eye. Ophthalmologic examination included best corrected visual acuity, anterior segment examination via slit lamp, intraocular pressure assessment by applanation tonometry and posterior segment examination via +78 lens. Causes of visual impairment and blindness were investigated for all patients. Results: One thousand and two hundred and forty patients were enrolled in the study. Nine hundreds and eighty nine patients (79.8%) had visual impairment and 251 patients (20.2%) were blind. The most common cause of visual impairment was cataract followed by diabetic retinopathy, glaucoma and age related macular degeneration. For patients with blindness, cataract was the commonest cause followed by age related macular degeneration. Other causes included corneal and myopic degenerations, optic nerve disease and retinal and vascular pathologies. Conclusions: The most common causes of visual impairment and blindness in elderly patients attending ophthalmology clinic at King Hussein Medical Center are treatable with good potential of visual recovery.

Architectural and Biochemical Expressions of Mustard Gas Keratopathy: Preclinical Indicators and Pathogenic Mechanisms

A subset of victims of ocular sulfur mustard (SM) exposure develops an irreversible, idiotypic keratitis with associated secondary pathologies, collectively referred to as mustard gas keratopathy (MGK). MGK involves a progressive corneal degeneration resulting in chronic ocular discomfort and impaired vision for which clinical interventions have typically had poor outcomes. Using a rabbit corneal vapor exposure model, we previously demonstrated a clinical progression with acute and chronic sequelae similar to that observed in human casualties. However, a better understanding of the temporal changes that occur during the biphasic SM injury is crucial to mechanistic understanding and therapeutic development. Here we evaluate the histopathologic, biochemical and ultrastructural expressions of pathogenesis of the chronic SM injury over eight weeks. We confirm that MGK onset exhibits a biphasic trajectory involving corneal surface regeneration over the first two weeks, followed by the rapid development and progressive degeneration of corneal structure. Preclinical markers of corneal dysfunction were identified, including destabilization of the basal corneal epithelium, basement membrane zone abnormalities and stromal deformation. Clinical sequelae of MGK appeared abruptly three weeks after exposure, and included profound anterior edema, recurring corneal erosions, basement membrane disorganization, basal cell necrosis and stromal degeneration. Unlike resolved corneas, MGK corneas exhibited frustrated corneal wound repair, with significantly elevated histopathology scores. Increased lacrimation, disruption of the basement membrane and accumulation of pro-inflammatory mediators in the aqueous humor provide several mechanisms for corneal degeneration. These data suggest that the chronic injury is fundamentally distinct from the acute lesion, involving injury mechanisms that operate on different time scales and in different corneal tissues. Corneal edema appears to be the principal pathology of MGK, in part resulting from persistent necrosis of the basal corneal epithelium and deterioration of the basement membrane. The findings also provide a potential explanation as to why administration of anti-inflammatories transiently delays, but does not prevent, the development of MGK sequelae.

Ring-shaped corneoscleral lamellar keratoplasty guided by high-definition optical coherence tomography and Scheimpflug imaging for severe Terrien’s marginal corneal degeneration

To evaluate the clinical efficacy of ring-shaped corneoscleral lamellar keratoplasty under guidance of high-definition optical coherence tomography (HD-OCT) and Scheimpflug imaging for severe Terrien's marginal corneal degeneration. Twenty-five patients (25 eyes) with Terrien's marginal corneal degeneration and ≥ 6 diopters of astigmatism were treated at the Shandong Eye Institute from January 2008 through December 2010. In these patients, the diseased area was > 1 quarter of the cornea, and the thickness at the thinnest corneal area was < 150 μm with residual corneal stroma. Ring-shaped corneoscleral lamellar keratoplasty was performed, and the depth and width of dissection was set according to the HD-OCT and Pentacam examinations. Data of complications, surgical effects, visual acuity, and astigmatism were collected. No intraoperative corneal perforation occurred. No patients had liquid accumulation between the graft and the recipient. At 1 year after surgery, the average best-corrected visual acuity improved to 6/9 from preoperative 6/36, and the average astigmatism reduced to 4.37 (2.04) diopters from preoperative 13.39 (7.52) diopters. There was no recurrence of the disease or corneal graft rejection in the follow-up period. Ring-shaped corneoscleral lamellar keratoplasty guided by HD-OCT and Pentacam imaging appears to be effective in the treatment of severe Terrien's marginal corneal degeneration. Surgical perforation can be significantly reduced.

Review

Keratoconus is an ectatic corneal disorder for which exciting therapeutic and diagnostic technologies are emerging. However, its pathogenesis is still heterogeneous and elusive. We researched overlooked Asian keratoconus data by literature review of databases (PubMed, MEDLINE, Ovid, Google Scholar, Cornea, and Cochrane) using key words "keratoconus, Asia, epidemiology, treatment, risk factors, genes" and names of Asian countries. Articles and their references were analyzed. Studies showed that keratoconus may be more prevalent, have earlier onset, and have greater disease progression in certain Asian and non-Asian ethnicities, particularly Indians, Pakistanis, Middle Easterners, and Polynesians, compared with white populations. Epidemiological risk factors include ethnicity, age (younger than 30 years), gender (male), positive family history, and eye rubbing. Genetic and disease risk factors include atopy, vernal keratoconjunctivitis, Down syndrome, pellucid marginal corneal degeneration, VSX1 (visual system homeobox 1) gene, and Leber congenital amaurosis. Differentiation of heterogeneous keratoconus subsets with detailed genotype-phenotype characterization may advance understanding. Comprehensive multiethnic population studies with valid large-scale data are needed. New effective treatments (deep anterior lamellar keratoplasty, intrastromal corneal ring segments, and corneal collagen cross-linking with riboflavin) are succeeding previous treatments.

Ping-Pong-Transmission von Herpes-simplex-Virus 1 nach Hornhauttransplantation

Primary corneal graft failure (PCGF) after penetrating keratoplasty (PKP) despite good endothelial cell count of the transplant in organ culture rarely occurs in young patients. A herpes simplex virus type I (HSV-1) infection (transmission through the donor or reactivation by the patient) can lead to PCGF. We report on a 43-year-old man with pellucid marginal corneal degeneration and neurodermitis, who was underwent penetrating keratoplasty (PKP) on the left eye after acute corneal hydrops in both eyes. A repeat keratoplasty (re-PKP) had to be performed 15 days after the first PKP due to a primary graft failure. A re-re-PKP with simultaneous amniotic membrane transplantation (as a patch) and partial lateral tarsorrhaphy became necessary 4 months after the re-PKP due to melting on the edge of the graft with persistent epithelial defects. After intensive cooperation between ophthalmologists and pathologists the histopathological findings showed keratocytes which reacted immunohistochemically positive for HSV-1 antigens in the deep corneal stroma of both corneal grafts. The excised own cornea of the patient was histopathologically negative but the DNA-PCR for HSV-1 was weakly positive. After adequate topical and systemic antiviral therapy the third graft has remained clear for 12 months. In cases of PCGF after normal risk corneal transplantation the possibility of HSV infection should always be considered. After confirmation of the diagnosis with the help of the immunohistochemical tests and/or PCR, an adequate treatment with antiviral medication (acyclovir tablets 2 × 400mg for more than 1 year) should be administered to the patient after repeat PKP.

Clinical features of ankylosing spondylitis associated with acute anterior uveitis in Chinese patients.

To characterize the clinical features, diagnosis, treatment and prognosis of uveitis associated with ankylosing spondylitis (AS) in Chinese patients. Two hundred and three patients with uveitis associated with AS followed-up in the Third Military Medical University Daping Hospital between 2005 and 2010 were retrospectively evaluated in this study. Complete ophthalmological examinations were evaluated at baseline and during the follow-up period. The gender, age, follow-up time, mean frequency of uveitis onset, and accompanying eye examination findings, history, demographical parameters were reviewed. All the patients presented complete clinical and radiologic (sacroiliac, lumbar, dorsal and cervical spine, knee, ankle, shoulder, hip, elbow) evaluation. HLA-B27 typing was also searched. There were 203 patients diagnosed with AS associated uveitis. All showed sacroiliac X-ray changes indicative of AS. There were 184 male and 19 female patients. The average age of patients was 35±12 (range 18-50). Mean follow-up period was 2.4 years (1-5 years). Acute anterior uveitis was the most common type of uveitis in both genders. 121 eyes presented unilateral involvement (55.2%), and 92 eyes presented bilateral involvement (45.3%) with onset alternately. 22 eyes occurred hypopyon, 16 eyes were found anterior vitreous cells, 7 eyes were noted reactive macular edema or exudation, 29 eyes presented posterior synechiae of iris, and 14 eyes presented cataract, 9 eyes presented secondary glaucoma, 2 eyes presented bend corneal degeneration and 1 eyes presented atrophy of eyeball. At the final visit, uveitis was well controlled in most patients. AS associated with uveitis in Chinese patients mainly manifests as acute anterior uveitis. A combination of corticosteroids with other mydriasis agents is effective for most AS associated with uveitis patients. In general, the prognosis is good in these cases.

Pathogenesis of Acute and Delayed Corneal Lesions After Ocular Exposure to Sulfur Mustard Vapor

Sulfur mustard (SM) exposure results in dose-dependent morbidities caused by cytotoxicity and vesication. Although lesions resulting from ocular exposure often resolve clinically, an idiopathic delayed mustard gas keratopathy (MGK) can develop after a moderate or severe exposure. Sequelae include persistent keratitis, recurring epithelial lesions, corneal neovascularization, and corneal degeneration, which can lead to impaired vision or loss of sight. The purpose of this effort is to correlate structural changes with injury progression during the development of MGK. New Zealand White rabbit corneas were exposed to SM using a vapor cup delivery system. The transition from acute to delayed injury was characterized by clinical, histological, and ultrastructural metrics over 8 weeks. Exposure dose was correlated to the likelihood of developing MGK but not to its severity. In a 56-animal cohort, a 2.5-minute exposure generated a corneal lesion, with 89% of corneas developing MGK within 5 weeks. A significant decrease in corneal edema at 2 weeks was predictive of the 11% of corneas that underwent asymptomatic recovery. Ultrastructural comparison of asymptomatic and MGK corneas at 8 weeks indicates that MGK is characterized by persistent edema and profound disorganization of the basement membrane zone. Ultrastructural changes associated with the delayed pathophysiology of corneal SM vapor exposure involve severe degeneration of the basement membrane zone and persistent edema. The mechanisms underlying MGK pathogenesis seem to alter injury progression as soon as 2 weeks after exposure. These data suggest that the vapor cup model system is suitable for therapeutic evaluation.

Dependence of Corneal Stem/Progenitor Cells on Ocular Surface Innervation

Neurotrophic keratopathy (NK) is a corneal degeneration associated with corneal nerve dysfunction. It can cause corneal epithelial defects, stromal thinning, and perforation. However, it is not clear if and to which extent epithelial stem cells are affected in NK. The purpose of this study was to identify the relationship between corneolimbal epithelial progenitor/stem cells and sensory nerves using a denervated mouse model of NK. NK was induced in mice by electrocoagulation of the ophthalmic branch of the trigeminal nerve. The absence of corneal nerves was confirmed with β-III tubulin immunostaining and blink reflex test after 7 days. ATP-binding cassette subfamily G member 2 (ABCG2), p63, and hairy enhancer of split 1 (Hes1) were chosen as corneolimbal stem/progenitor cell markers and assessed in denervated mice versus controls by immunofluorescent microscopy and real-time PCR. In addition, corneolimbal stem/progenitor cells were detected as side population cells using flow cytometry, and colony-forming efficiency assay was performed to assess their function. ABCG2, p63, and Hes1 immunostaining were significantly decreased in denervated eyes after 7 days. Similarly, the expression levels of ABCG2, p63, K15, Hes1, and N-cadherin transcripts were also significantly decreased in denervated eyes. Stem/progenitor cells measured as side population from NK mice were decreased by approximately 75% compared with normals. In addition, the authors found a significant (P = 0.038) reduction in colony-forming efficiency of stem/progenitor cells harvested from denervated eyes. Corneolimbal stem/progenitor cells are significantly reduced after depletion of sensory nerves. The data suggest a critical role of innervation in maintaining stem cells and/or the stem cell niche.

Focus on Molecules: Lysyl oxidase

1. StructureLysyl Oxidase (LOX, also called protein-lysine 6-oxidase)(Genbank accession numbers: Nucleotide NM_002317.5, ProteinNP_002308.2, EC 1.4.3.13) is one of the five LOX family members(LOX and LOX Like1-4). The human LOX gene is located onchromosome 5q23.2. LOX is synthesized as a 50 kDa pre-proteincontaining 3 domains; the N-terminal signal peptide sequence(aa1-21), the N-terminal pro-peptide domain (aa 22-162), and theC-terminal catalytic domain (aa 162-417). The signal peptide isremoved by cleavage at the Cys21-Ala22 bond and the pro-peptidedomain is N-glycosylated in the endoplasmic reticulum and Golgiapparatus yielding a pro-enzyme, which is then secreted fromcells as a catalytically inactive protein. The 32 kDa active enzyme(C-terminal domain) is released by proteolytic cleavage of thepro-peptide at Gly162eAsp163 by procollagen C-proteinase (bonemorphogenetic protein 1; BMP-1) (Kagan and Li, 2003)(Fig. 1).2. FunctionLOX belongs to a family of amine oxidases. LOX was initiallyreported to be expressed andsecreted by fibrogenic cells but is nowknown to be expressed in several other cell types. LOX oxidizespeptidyl lysine and hydroxylysine residues in collagen and lysineresidues in elastin to produce peptidyl alpha-aminoadipic-delta-semialdehydes. These aldehyde modifications can spontaneouslycombine with vicinal peptidyl aldehydes or with epsilon-aminogroups of peptidyl lysine to form covalent cross-links that stabilizeand cause collagen and elastin fibers to be insoluble in the extra-cellular matrix (ECM). The significance of LOX was demonstrated inthe LOX knockout mouse, which could not survive at birth, due torupture of the aorta and diaphragm from incomplete elastin cross-linking. LOX is also essential for development of the distal andproximal airways, and the formation of alveoli in the lungs. LOX isalso critical for notochord formation and muscle development. LOXaffects differentiation of osteoblasts by forming cross-links in thesurrounding collagen matrix. These results underline the impor-tance of LOX in the morphogenesis and repair of connective tissuesof the cardiovascular, respiratory, skeletal, and other organ systems(Fongetal.,2009).LOXcanalsoinducecross-linkingbetweenlysinesin histones in the nucleus (Kagan and Li, 2003). LOX has also beenreported as a potent chemotactic agent for monocytes and vascularsmooth muscle cells.3. Disease involvementDuetotherangeofLOXbiologicalfunctions,abnormalitiesofLOXexpression underlie the development of a number of pathologicalprocesses related with an imbalance in ECM synthesis/degradation.LOX is expressed in several ocular tissues, and the followingdiseases of the eye have been linked with LOX:A. Keratoconus: Keratoconus is a corneal degeneration in whichthe extracellular matrix of the cornea loses its integrity, slowlychanging from the normal round shape to a cone shape. Onestudy reported that corneal LOX mRNA expression was signif-icantly lower in keratoconus patients when compared to theirage-matched controls. Another study showed that reducingcopper levels in tears results in keratoconus in an animalmodel. Copper is an essential cofactor for LOX activity.B. Diabetic retinopathy (DR): There are a number of reports oflower expression of LOX co-factors in DR retina samples andlower LOX cross-linking activity in vitreous samples of patientswith DR. However, theeffectofhigh glucose onLOXexpressionand enzymatic activity in cultured human retinal endothelialcells is less clear, with conflicting evidence suggesting eitherincreased or decreased LOX expression. Although discrepant,these studies indicate a potential involvement of LOX in theobserved DR phenotype.

X-Linked Megalocornea Caused by Mutations in CHRDL1 Identifies an Essential Role for Ventroptin in Anterior Segment Development

X-linked megalocornea (MGC1) is an ocular anterior segment disorder characterized by an increased cornea diameter and deep anterior chamber evident at birth and later onset of mosaic corneal degeneration (shagreen), arcus juvenilis, and presenile cataracts. We identified copy-number variation, frameshift, missense, splice-site and nonsense mutations in the Chordin-like 1 gene (CHRDL1) on Xq23 as the cause of the condition in seven MGC1 families. CHRDL1 encodes ventroptin, a bone morphogenic protein antagonist with a proposed role in specification of topographic retinotectal projections. Electrophysiological evaluation revealed mild generalized cone system dysfunction and, in one patient, an interhemispheric asymmetry in visual evoked potentials. We show that CHRDL1 is expressed in the developing human cornea and anterior segment in addition to the retina. We explored the impact of loss of ventroptin function on brain function and morphology in vivo. CHRDL1 is differentially expressed in the human fetal brain, and there is high expression in cerebellum and neocortex. We show that MGC1 patients have a superior cognitive ability despite a striking focal loss of myelination of white matter. Our findings reveal an unexpected requirement for ventroptin during anterior segment development and the consequences of a lack of function in the retina and brain.

Differential response of lens crystallins and corneal crystallins in degenerative corneas

Corneal degenerations, occurring either spontaneously or as a complication to other diseases, cause vision problems by endangering corneal transparency. Our past cornea research projects involving mice revealed that some recruited mice presented corneal problems similar to human corneal degeneration. The present study examines the histology of diseased mice corneas, including ultrastructure. Genome-wide microarray and proteomic methods were utilized to screen for molecular changes in the diseased corneas. It was found that abnormalities affected mainly anterior layers of the corneas. The most often observed histological abnormalities included neoplasm or detachment of the epithelial layer, erosion or breakage of Bowman membranes, blood vessel formation, and bleeding in the stroma. Microarray assay showed that among the 46 up-regulated probes in diseased corneas, 13 were for lens crystallins. However, all corneal crystallins genes remained unchanged. αA-crystallin was among the proteins that showed the greatest increase in diseased corneas, as detected by gel electrophoresis. We propose that lens crystallins, rather than corneal crystallins, are involved in the pathological process of corneal degeneration. Further study along these lines would provide insight into the mechanism of corneal transparency.

Role of optical coherence tomography on corneal surface laser ablation.

This paper focuses on reviewing the roles of optical coherence tomography (OCT) on corneal surface laser ablation procedures. OCT is an optical imaging modality that uses low-coherence interferometry to provide noninvasive cross-sectional imaging of tissue microstructure in vivo. There are two types of OCTs, each with transverse and axial spatial resolutions of a few micrometers: the time-domain and the fourier-domain OCTs. Both have been increasingly used by refractive surgeons and have specific advantages. Which of the current imaging instruments is a better choice depends on the specific application. In laser in situ keratomileusis (LASIK) and in excimer laser phototherapeutic keratectomy (PTK), OCT can be used to assess corneal characteristics and guide treatment decisions. OCT accurately measures central corneal thickness, evaluates the regularity of LASIK flaps, and quantifies flap and residual stromal bed thickness. When evaluating the ablation depth accuracy by subtracting preoperative from postoperative measurements, OCT pachymetry correlates well with laser ablation settings. In addition, OCT can be used to provide precise information on the morphology and depth of corneal pathologic abnormalities, such as corneal degenerations, dystrophies, and opacities, correlating with histopathologic findings.

Phototherapeutic keratectomy

Phototherapeutic keratectomy (PTK) is done regularly for anterior corneal diseases such as corneal dystrophies, corneal degenerations, scars, and band-shaped keratopathy. The various indications include both therapeutic and visual. The aim of this article is to discuss the therapeutic indications for PTK, the specific technique pertaining to a specific etiology, the various other procedures like amniotic membrane graft combined with PTK or PTK being done for recurrences in the grafts, and PTK done before cataract surgery when the anterior corneal pathology coexists with the cataract. Post PTK management such as healing of an epithelial defect, use of steroids in the post PTK period, recurrences of primary disease pathology, and infections, will be discussed. Methods of literature search: A Medline search was carried out for articles in the English language, with the keywords, phototherapeutic keratectomy, band-shaped keratopathy, spheroidal degeneration, scars, bullous keratopathy, and corneal dystrophy. The relevant references are mentioned here.

Atypical Presentation of Salzmann Nodular Degeneration Diagnosed With Ultra-High–Resolution Optical Coherence Tomography

A 59-year-old woman presented with bilateral, peripheral, circular corneal infiltrates. There was a clear zone separating the outer margin of the degeneration from the limbus in both eyes. The inner margins were indistinct. Ultra-high-resolution optical coherence tomography (UHR-OCT) imaging demonstrated subepithelial infiltrations with epithelial thinning and corneal surface elevation. The infiltrate was accompanied by significant stromal scarring, which reached deep layers of the corneal stroma. UHR-OCT findings were consistent with Salzmann nodular degeneration. UHR-OCT can be used as an optical biopsy to diagnose atypical corneal degenerations without tissue sampling.

Altered corneal nerve morphology and epithelial wound healing in experimental lacrimodeficient dry eye

AbstractPurpose To analyze the morphological changes of corneal nerves and its influence on corneal epithelial wound healing in a lacrimodeficient dry eye model in the guinea‐pig.Methods Corneal nerve architecture and the rate of corneal epithelial wound healing were studied in guinea‐pigs to whom the main lacrimal gland was removed 4 weeks before (dry eye) and in control animals. Eyes were fixed, cryoprotected and incubated with neuronal class III Beta‐tubulin antibody. Epithelial migration rate (EMR) and estimated time of healing (ETH) were calculated for 2mm‐diameter epithelial corneal debridations stained with fluorescein, photographed regularly until complete closure and analyzed with image processing software.Results Density (16±6 vs 27±11 nerves/mm2) and length (115±45 vs 186±74 µm) of subbasal nerves decreased significantly in dry eye. Subbasal nerves were less branched and tortuous. Epithelial nerve terminals were also reduced. EMR decreased significantly (63±4 vs 110±1 µm/h) and ETH increased significantly (38.6±1.8 vs 20.1±0.1 h) in dry eye.Conclusion The morphological appearance and the decreased density, length and branches of corneal subbasal nerves are suggestive of corneal nerve degeneration at 4 weeks after lacrimal gland removal. Lacrimodeficient eyes presented also a slowing‐down in corneal epithelial wound healing suggesting an early trophic defect consecutive to nerve damage. (Supported by: SAF2008‐00529, CSD2007‐00023, BFU2008‐04425, BFU2009‐07793 and RETICS RD07/0062/0012 from Ministerio de Ciencia e Innovación, Spain, and the Leonardo da Vinci Lifelong Learning Program.)

Image Reconstruction of the Subbasal Nerve Plexus with In Vivo Confocal Microscopy

To overcome the anterior corneal mosaic (ACM) phenomenon in in vivo confocal laser scanning microscopy (CLSM) and to reconstruct undistorted images of the subbasal nerve plexus (SNP), facilitating morphometric analysis in the presence of ACM ridges. CLSM was performed in five healthy volunteers. An original image processing algorithm based on phase correlation was used to analyze and reduce motion distortions in volume scan image sequences. Three-dimensional tracing of the SNP was performed to reconstruct images containing only the SNP layer, with nerve fibers clearly visible even in ACM areas. Real-time mapping of the SNP revealed the presence of ridges with K-structures underneath them in all cases. The occurrence of K-structures correlated directly with development of ACM observed by slit lamp and resulted in massive deformation at the level of Bowman's membrane, seriously interfering with examination of SNP structures. The average elevation of ACM ridges was 20.6 μm (range, 8.7-34.0 μm). The novel method presented permitted reconstruction of the SNP layer in regions of ACM. The described method allows the precise analysis and elimination of motion artifacts in CLSM volume scans, in conjunction with the capability to reconstruct SNP structures even in the presence of severe ACM. The robustness and automation of the described algorithms require ongoing development, but this will provide a sound basis for extended studies of corneal nerve regeneration or degeneration and for use in clinical practice.

Corneal nerve morphology and sensitivity changes after ultraviolet A/riboflavin treatment

Collagen crosslinking induced by riboflavin and ultraviolet A irradiation (UVAR) has recently been introduced as a clinical treatment to halt or reverse the progression of keratoconus. We investigated changes in corneal sensitivity and nerve morphology as part of a comprehensive safety evaluation of this treatment. Fifty-four New Zealand white rabbits were divided into three experimental groups: UVAR with deepithelialization, UVAR without deepithelialization, and deepithelialization alone. Corneal sensitivity was measured with a Cochet-Bonnet esthesiometer before treatment and 3, 7, 14, 30, 90, and 180 days after treatment. Corneal nerve morphology was evaluated using acetylcholinesterase histochemistry staining. We found that corneal sensitivity in the center of the treated area was significantly reduced 3 days after UVAR with deepithelialization treatment compared with the corneal sensitivity of the control eye but gradually recovered to normal levels at 90 days. Corneal sensitivity after deepithelialization treatment was significantly lower than control corneal sensitivity at 3 days but was significantly higher after 30 days of recovery compared with the corneal sensitivity after UVAR with deepithelialization. Corneal sensitivity after UVAR without deepithelialization treatment had significantly decreased at 7 days compared with control corneal sensitivity but was not significantly different from control values at other measurement times. In parallel with these functional alterations, corneal nerve degeneration was visible in the treatment area by 3 days; by 7 days there was a significant decrease in nerve density. Corneal nerve sprouts were identified from neighboring non-injured nerve fibers 7 days after treatment; by 90 days, excessively regenerating nerves were observed throughout the anterior stroma. The density of corneal nerve fibers appeared normal by 180 days. Ultraviolet A/riboflavin with deepithelialization treatment resulted in corneal nerve fiber damage and subsequent regeneration in the treatment area, simultaneously accompanied by the reduction and recovery of corneal sensitivity.

In Vivo Confocal Microscopy in Terrien Marginal Corneal Degeneration: A Case Report

To report an advanced case of Terrien marginal corneal degeneration (TMD) analyzed by means of confocal microscopy. A 62-year-old woman with TMD underwent a routine ophthalmological examination and was evaluated for the disease by using in vivo laser scanning confocal microscopy with the Heidelberg Retina Tomograph 2 Rostock Cornea Module. The slit-lamp examination of the right eye showed an upper peripheral cornea thinning associated with a deposition of refractile yellow-white materials in the anterior stroma. Superficial radial vessels in the upper peripheral cornea were the only pathological findings of the left eye. Confocal microscopy of the right eye lesion showed deposition of hyperreflective material, and the stroma below presented a honeycomb-like pattern. Inflammatory cell infiltration, abnormal subbasal nerve plexus, epithelial basal membrane defects, irregular Bowman membrane, and the presence of activated keratocytes were observed in the cornea of both eyes. In vivo confocal microscopy can detect subtle corneal changes in an advanced case of TMD, which may be signs of subclinical inflammation.

Corneal transplantation in Hungary (1946-2009)

To identify changing trends in indications for corneal transplantation in Debrecen, Hungary over the past 64 years. Retrospective study, at the Department of Ophthalmology, University of Debrecen, Hungary. Four thousand seven hundred and seventy-eight patients who underwent keratoplasty. The analysis was based on medical charts, surgical descriptions and eye bank records. Keratoplasty indications between January 1946 and December 2009. For an easier overview, the 64-year interval was divided into seven time periods (1946-1955, I; 1956-1965, II; 1966-1975, III; 1976-1985, IV; 1986-1995, V; 1996-2005, VI; 2006-2009, VII). Over the 64 years, clinical indications for keratoplasty were corneal scarring (24.9%), regraft (18.6%), keratoconus (18.6%), pseudophakic/aphakic corneal oedema (12%), stromal corneal dystrophies (6%), non-infectious keratitis (4.7%), chemical injuries (3.3%), corneal degenerations (3%), mechanical trauma (1.7%), infectious keratitis (1.4%), endothelial corneal dystrophies (1.3%) and others (4.5%). During periods I-IV, corneal scarring was the most common indication for corneal transplantation. In period V, corneal ectasia became the leading clinical indication. Regraft was the most frequent indication in period VI. In the most recent years, an emerging tendency in pseudophakic/aphakic corneal oedema as the indication for keratoplasty was observed. In Hungary, the number of grafts has increased greatly in the past 64 years, the transplantation rates are similar to those of industrial countries. Indications for corneal transplantation have changed considerably over the last half decade from corneal scarring to corneal ectasia, regraft and pseudophakic/aphakic corneal oedema.