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PubMed1982

Immunoglobulin patterns in keratoconus with particular reference to total and specific IgE levels.

A selection of sufferers from keratoconus and random controls were assessed in order to substantiate claims that there existed a significant incidence of patients with both keratoconus and a raised serum level of immunoglobulin E. The results appeared to confirm a high incidence of raised total serum IgE levels in patients with keratoconus and also indicated that the additional measurement of serum specific IgE was more sensitive than total IgE. In fact 59% of the patients with keratoconus in our study were identified as having significantly raised level of specific immunoglobulin E, and 52% were identifiable by measuring total immunoglobulin E. This compares favourably with a previous incidence in a keratoconus population of 47% with raised total immunoglobulin E. Our study avoids clinical estimation of known associated systemic manifestations of atopic disease, thereby reaffirming the correlation between raised serum levels of IgE and keratoconus as objectively as possible. This identification pattern may be useful in reviewing high-risk groups and aid in the earlier detection of the condition.

Female↗
PubMed2006

Dynamic contour tonometry and goldman applanation tonometry in eyes with keratoconus.

PURPOSE: The dynamic contour tonometer is a nonapplanation contact tonometer designed to be largely independent of the structural properties of the cornea. Theoretically, it may measure intraocular pressure most accurately in abnormally thinner corneas. This study compares intraocular pressure measurements by dynamic contour tonometry with Goldman applanation tonometry in eyes with normal corneas and eyes with advanced keratoconus. METHODS: A comparative case series. Subjects underwent intraocular pressure measurements by dynamic contour tonometry, Goldman applanation tonometry, ultrasonic pachymetry, and slit scanning topography. EXCLUSION CRITERIA: any ocular pathology other than keratoconus, previous corneal or refractive surgery, stromal scarring due to acute hydrops, or any other corneal opacities. RESULTS: Ten patients with keratoconus were included in Group A, and 12 normal patients composed Group B according to the pre-established criteria. The mean Goldman tonometry measurement in group A was 10.3 +/- 1.8 mm Hg and group B was 14.3 +/- 0.75 mm Hg. (P = 0.024). In group A, the mean measurement with the dynamic contour tonometer was 14.6 +/- 2.09 mm Hg, and in group B, it was 17.4 +/- 3.1 mm Hg (P = 0.026). The difference between both methods of measurement in group A was statistically significant (P < 0.0002). CONCLUSION: Intraocular pressure readings with dynamic contour tonometry in the keratoconus group were significantly higher than Goldman measurements and lower when compared to the control group. As there are no published manometric studies in eyes with keratoconus, these lower intra-ocular readings with the dynamic contour tonometry could be related to the discrepancy between the radius of corneal curvature and its tip, the significant thinning of the cornea, or other corneal biomechanical abnormalities related to advanced keratoconus.

Adult↗
PubMed1992

Altered lectin binding sites in keratoconus corneas.

We investigated the glycoconjugates in frozen sections of keratoconus corneas, using a panel of 12 biotin- or fluorescein isothiocyanate-labeled lectins. No differences between the lectin binding sites of the epithelium, endothelium and Descemet's membrane of normal and keratoconus corneas could be observed. However, in contrast to normal corneas, intense staining with peanut agglutinin (PNA) could be detected at breaks in Bowman's layer, in scar tissue and in the adjacent stroma. Furthermore, in the majority of cases binding sites for Phaseolus vulgaris erythroagglutinin (PHA-E) and increased staining with Ricinus communis agglutinin I (RCA-I) and Lens culinaris agglutinin (LCA) could also be detected in ruptures in Bowman's layer and in scar tissue. These data suggest that the scarred regions of the anterior stroma in keratoconus corneas may contain oligosaccharides with terminal D-galactose (beta 1-3)-D-N-acetylgalactosamine disaccharides (recognized by PNA), increased amounts of glycoconjugates with terminal beta-galactose residues (recognized by RCA-I), increased amounts of glycoconjugates with glucose/mannose residues (recognized by LCA), and finally, biantennary complex-type glycopeptides containing two outer galactose residues and a residue of N-acetylglucosamine (recognized by PHA-E). Since corneal scars due to causes other than keratoconus revealed lectin binding sites (particularly for PNA and to a lesser extent also for PHA-E, LCA and RCA-I) similar to those seen in scar tissue of keratoconus corneas, we conclude that it is mainly scar formation that may be responsible for the altered lectin binding sites in keratoconus.

Adolescent↗
PubMed2006

Corneal and epithelial thickness in keratoconus: a comparison of ultrasonic pachymetry, Orbscan II, and optical coherence tomography.

PURPOSE: To compare corneal thickness measurements in individuals with keratoconus using optical coherence tomography (OCT), Orbscan II, and ultrasonic pachymetry and to measure epithelial and stromal thickness in these individuals using OCT. METHODS: Twenty individuals with keratoconus and 20 controls (without keratoconus) were enrolled. The Orbscan II was used to locate the steepest area of the cornea, which was taken to represent the cone apex. Each instrument was used to obtain four total corneal thickness measurements-from the cone apex, corneal center, mid-nasal, and mid-temporal cornea. Optical coherence tomography scans were analyzed to provide epithelial and stromal thickness readings. RESULTS: In individuals with keratoconus, mean central corneal thickness (CCT) measured by ultrasonic pachymetry, Orbscan, and OCT was 494.2 +/- 50.0 microm, 438.6 +/- 47.7 microm, and 433.5 +/- 39.7 microm, respectively. The central keratoconic cornea was 57.7 microm thinner than the normal cornea (post-hoc P<.001). The cone apex was thinner than the central cornea (P<.001). Keratoconic epithelium was 48.2 +/- 5.5 microm centrally and 42.1 +/- 4.5 microm at the apex. Central keratoconic epithelium was 4.7 microm thinner and central keratoconic stroma was 57.8 microm thinner than the normal cornea (P<.001, respectively). Comparing instruments, Orbscan and OCT correlated in CCT measurement (r=0.890) and apical thickness (r=0.846). All instruments produced similar readings for mid-nasal and mid-temporal corneal thickness in participants with keratoconus (P>.05). CONCLUSIONS: Ultrasonic pachymetry produced the highest corneal thickness readings in the center and apex, compared to Orbscan II and OCT. Centrally, the total cornea, epithelium, and stroma were thinner in individuals with keratoconus than in normal individuals.

Adolescent↗
PubMed2000

Everett Kinsey lecture. The elusive causes of keratoconus: a working hypothesis.

PURPOSE: Keratoconus is a diseasethat has been recognized clinically for many years. However, it is only more recently that a better understanding has been achieved in the area of keratoconus pathogenesis. The purpose of this paper is to summarize the completed research, review ongoing studies, and present a hypothesis for keratoconus pathology. METHODS: We used immunochemistry and molecular techniques to characterize keratoconus corneas. RESULTS AND CONCLUSIONS: Our hypothesis attempts to incorporate many of the recognized biochemical and molecular abnormalities found in the keratoconus corneas. Our hypothesis states: 1) there is abnormal processing of the free radicals and superoxides within the keratoconus corneas; 2) there is a build-up of destructive aldehydes or peroxynitrites within the corneas; 3) the cells that are damaged irreversibly undergo the process of apoptosis; and 4) the cells that are damaged reversibly undergo wound healing or repair. As part of the wound healing process, various degradative enzymes and wound healing factors are upregulated, which leads to focal areas of corneal thinning and fibrosis. Future studies will be directed to testthis working hypothesis and determine if these theories are valid.

Apoptosis↗
PubMed2002

A locus for autosomal dominant keratoconus: linkage to 16q22.3-q23.1 in Finnish families.

PURPOSE: The estimated world-wide prevalence of keratoconus is 50 to 230 per 100,000 in the general population. Sporadic keratoconus is the leading cause of corneal transplantation surgery in Western countries. Positive family history has been reported in 6% to 8% of patients. The purpose of this study was to map the disease locus in 20 Finnish families with autosomal dominant keratoconus, each family having two or more affected members and with no other associated genetic disease. METHODS: DNA was extracted from blood samples, collected from 42 affected and 34 unaffected family members. Genomic DNA from patients and their parents, was typed for alleles of 292 polymorphic markers. A genome-wide screening was performed to localize the disease gene. Fluorescent markers were amplified by polymerase chain reaction and separated on an automated sequencer. Allele sizes were assigned to each family member, after which LOD scores were calculated. RESULTS: The disease locus was mapped to chromosome 16q, between the markers D16S2624 and D16S3090, with a maximum parametric multipoint LOD score of 4.10 and corresponding nonparametric score of 3.27 (NPL, P = 0.00006). Evidence from 20 families provided support for the linkage, consistent with a single locus for familial autosomal dominant keratoconus without heterogeneity. CONCLUSIONS: This study is the first genome-wide linkage study to map the keratoconus gene. The results suggest that the causative gene in keratoconus is located within the 16q22.3-q23.1 chromosomal region.

Adolescent↗
PubMed2002

Expression of betaig-h3 in keratoconus and normal cornea.

OBJECTIVES: To observe the expression of betaig-h3 in normal cornea and keratoconus and to elucidate the role of extracellular matrix in keratoconus. METHODS: In situ hybridization was used to detect the expression of betaig-h3 in the cornea. The cDNA library was screened with human betaig-h3 cDNA probe to locate betaig-h3 mRNA in cells. RESULTS: Expression of betaig-h3 was found mainly in the stroma of the normal cornea and keratoconus, but decrease depending on the degree of keratopathy. In some serious cases, no expression signal was detected. The strongest expression was seen at the border of the normal region and keratoconus. CONCLUSIONS: betaig-h3, the structural component of the extracellular matrix, can affect cell adhensiveness in the development of corneal fibrous interstitial organization. During the development of keratoconus, decreasing levels of betaig-h3 cause the diminution of corneal steadiness, which is related to formation of keratoconus.

Cornea↗
PubMedDate not supplied

[Pathogenetic basis for treatment of primary keratoconus by a combined method of excimer laser surgery (combination of photorefraction and phototherapeutic keratectomy)].

Bearing in mind that the pathological process in keratoconus starts with anterior corneal layers and is gradually progressing into inner corneal parts we put a question whether a pathological process can be stopped by affecting the anterior layers of the cornea. This paper presents the results of 5-year experience excimer laser surgery, a combination of photorefractive and phototherapeutic keratectomy (PRK + PTK) in the treatment of the initial keratoconus. The diagnosis of early keratoconus was based upon computed tomographic data, pachymetry in 5 points, and biomicroscopy of the cornea. The "firework" symptom a stromal ramification area that corresponds to the future apex of the keratoconus is described. PRK was performed with an ablation zone of 6 mm, and the transitional zone of 7 mm. The ablation zone in PhTk was dislocated towards the most ectasia--conical apex, topography and the apex site were predetermined of computed tomography. The PTK was performed with ablation zone of 8.00 mm and transitional zone of 9 mm. The described method allowed the authors to increase average uncorrected acuity of vision from 0.07 +/- 0.003 to 0.76 +/- 0.03. At the same time the acuity of vision was 1.0 in 69.2% of the eyes to enhance the mean corrected acuity of vision from 0.70 +/- 0.03 to 0.83 +/- 0.04. 2 by gradually progressing significantly to decline the degree of ametropia. The spherical component of refraction--myopia--decreased from 5.32 +/- 0.62 to 1.55 +/- 0.3 D. The cylindrical component of refraction myopic astigmatism reduced from 3.25 +/- 0.53 to 1.75 +/- 0.25 D. 3 to stop the progression of keratoconus in 91.3% of cases at a follow-up of 40.8 +/- 1.5 months (3 years 4 months) and at the maximal follow-up of 5.5 years. Thus, PRK + PTK with pathogenetically based, effective method in the treatment of the patients with initial keratoconus.

Humans↗
PubMed1992

Axial length in keratoconus.

Axial length is a major determinant of ocular refractive power that has not been well established for keratoconus eyes. The purpose of this study was to establish the mean and range of axial length among both keratoconus eyes with no previous surgery and postkeratoplasty keratoconus eyes, and to determine if there is a significant reduction of axial length following variations in surgical techniques in penetrating keratoplasty. The axial length of 157 keratoconus eyes with no previous surgery was measured using applanation ultrasonography. The mean axial length measurement was 24.39 (+/- 1.13 mm), with a range of 21.82-28.69 mm. The axial length of 66 postkeratoplasty keratoconus eyes was similarly measured. The mean axial length measurement was 24.10 (+/- 1.22 mm), with a range of 21.83-26.87 mm. These values are not significantly different from the axial length mean and range found among emmetropic eyes. A significant shortening of the axial length (F = 5.2, p = 0.04) was obtained in the postoperative penetrating keratoplasty eye if the donor trephine was 0.3 mm smaller in diameter than the recipient trephine. The axial length of individual keratoconus eyes is a major factor in determining postoperative refractive error. It therefore becomes important when considering variations in surgical procedures to reduce postoperative myopia.

Analysis of Variance↗
PubMed1994

Alpha 2-macroglobulin levels in normal human and keratoconus corneas.

PURPOSE: To compare the levels of alpha 2-macroglobulin, one of the major proteinase inhibitors, in corneas with keratoconus to those in normal human corneas and corneas with other diseases. METHODS: An immunoperoxidase technique was used to visualize the presence of alpha 2-macroglobulin in the corneas. Western blot analysis was performed, and the levels of this inhibitor in extracts of keratoconus and normal human corneas were subsequently analyzed by a dot blot assay. RESULTS: alpha 2-Macroglobulin was demonstrated immunohistochemically in the epithelium, stroma, and endothelium of all corneal sections. Compared with normal human control specimens, the staining intensity in the epithelium of keratoconus corneas was markedly reduced. The majority of scarred and other diseased corneas exhibited normal staining intensity for alpha 2-macroglobulin. Dot blot assays showed that the alpha 2-macroglobulin levels in the epithelial and stromal extracts of keratoconus corneas were lower than those found in normal human control counterparts. CONCLUSION: Keratoconus corneas contained a reduced level of alpha 2-macroglobulin. This result lends further support to the hypothesis that degradation processes may be aberrant in keratoconus.

Adolescent↗
PubMed1996

Keratoconus in two pairs of identical twins.

We studied two sets of identical twins with keratoconus. The first 21-year-old pair had bilateral fully developed keratoconus and the second 35-year-old pair presented with early bilateral keratoconus detected by videokeratography. To our knowledge, these are the seventh and eighth sets of identical twins with keratoconus reported in the literature. They support the evidence of heredity as a factor in the etiology of keratoconus. Videokeratography proved to be a valuable adjunct for the detection of early keratoconus in a cornea with normal slit-lamp microscopy and photokeratoscopy results. Radial keratotomy in one eye produced an unstable refraction.

Adult↗
PubMed1976

[Keratoconus and contact lenses (author's transl)].

This work is a survey of 82 cases of keratoconus which have been followed up for 1 to 12 years. Among them only 66 were fitted with contact lenses. The contra-indications for them are: 1. a better visual acuity with spectacles than with contact lenses, 2. advanced cases (4th degree of Amsler) whose fitting is impossible, 3. unilateral keratoconus, 4. associated diseases such as trachomatous pannus, allergic kerato-conjunctivitis. Hard corneal lenses are now in use in most of the cases. Scleral lenses are much less used than they were 10 years ago, owing probably to the great improvement of the corneal lenses during this time. These hard corneal lenses have a short Ro (4 to 7 mm), an overall diameter between 8 and 11 mm, and an optic diameter of 5 mm. They are fitted under fluorescein control. The mobility must be good too. One case was fitted with soft lenses. The visual acuity is good and so is the tolerance: 80% of the patients wear their lenses 10 hours a day or more. Contact lenses do not affect the progression of keratoconus thus finally a keratoplasty must be performed in many cases. After the operation a contact lens is very often necessary, but its daily wearing time must be divided by two, to avoid corneal neo-vascularisation. Soft corneal lenses may be used in some cases of keratoconus. They are indicated when the hard lenses are no longer tolerated and before a keratoplasty. The base curves of these soft lenses are not related to the radii of the conic cornea. In most of the cases they are between 7.50 and 8.60 mm. The diameter is large: 14 or 15 mm. The lenses must not move too much: 1 mm up or down when the patient blinks. The edge of the lens must not depress the bulbar conjunctiva and there must be no air bubble under the lens. In many cases a cylindrical spectacle lens is necessary to obtain a good visual acuity. Some authors prefer to fit a hard corneal lens over the soft one: this is the "piggy back" method. Sometimes keratoconus has appeared in patients already fitted during several years to correct a myopic astigmatism. It is not clear whether these keratoconus have been produced or not be the contact lenses.

Adolescent↗
PubMed2002

Lysosomal hydrolase staining of conjunctival impression cytology specimens in keratoconus.

PURPOSE: This study sought to assess the feasibility of impression cytology for the determination of conjunctival intracellular lysosomal hydrolase (acid esterase) levels in patients with keratoconus. METHODS: Twenty-two patients with keratoconus currently enrolled in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study and 22 age-and sex-similar controls underwent impression cytology. Samples were collected from each subject and control pair on the same day. The cells of the respective specimens were fixed immediately and were stained for acid esterase with use of identical batches of fixatives and stains. After staining, the specimens were cleared in xylene for mounting in synthetic resin on glass slides. The acid esterase staining intensity of each specimen was quantified as the percentage of light transmitted with use of an image analysis system (Zeiss). Multiple cells from each specimen were analyzed for each sample collected. RESULTS: Mixed model analysis was used to account for the subject-control pairings and for the multiple cells from each sample. With this method, the mean light transmission for normal controls (mean = 63.0; standard error [SE] = 3.0) was highly statistically significantly different from that for the keratoconus subjects (mean = 52.4; SE = 3.0) (two-tailed p= 0.0032). CONCLUSIONS: This study establishes the feasibility of adapting an acid esterase staining technique to conjunctival cells collected via impression cytology. Higher levels of lysosomal enzyme staining in patients with keratoconus have been previously reported by other investigators using full-thickness conjunctival specimens. We also demonstrate the value of using objective microspectrophotometry in measuring lysosomal enzyme staining with impression cytology specimens.

Acetylesterase↗
PubMed1988

Glycoconjugate abnormalities in cultured keratoconus stromal cells.

We examined the plasma membrane glycoconjugates of cultured corneal stromal cells derived from patients with keratoconus and healthy subjects. Using radiolabeled lectins as probes, we found that a majority of our keratoconus strains contained more binding sites for concanavalin A, Ricinus communis agglutinin I, and soybean agglutinin than did the controls. The number of binding sites in cultured keratoconus cells for radioactive peanut agglutinin, wheat germ agglutinin, and Griffonia simplicifolia agglutinin I, however, was similar to that found in normal controls. Using a second method with biotin-labeled lectins as probes, we confirmed that increased amounts of glycoconjugates would bind to concanavalin A and R communis agglutinin I in stromal cells of patients with keratoconus compared with those of the control subjects. This study suggests that plasma membranes of cells derived from some patients with keratoconus may contain elevated amounts of glycoconjugates with glucose and/or mannose, terminal galactose, and N-acetylgalactosamine residues.

Adolescent↗
PubMed1990

Computer-assisted corneal topography in family members of patients with keratoconus.

In about 6% of patients with keratoconus, there is a history of familial disease. High keratometric astigmatism and mildly irregular mires observed by placidois disc have been suggested to represent variable forms of expression of a gene in family members of patients with keratoconus. We used a computer-assisted digital videophotokeratoscope to map the corneas of 28 family members of 5 patients with keratoconus. Abnormalities observed in family members included central steepening, greater steepening of the cornea inferior to the apex, and substantial asymmetry in the central dioptric power between the two eyes of the same individual. These findings were similar to, but less severe than, those found in patients with keratoconus and may represent the variable expression of a gene contributing to the development of keratoconus. Pedigree analysis in these families suggests an autosomal dominant mode of inheritance.

Adolescent↗
PubMed1992

Computer-assisted corneal topography in parents of patients with keratoconus.

Recently developed computer-assisted devices allow detection of early topographic abnormalities of the cornea, including mild or abortive forms of keratoconus. To address the possibility that keratoconus is an inherited condition, we examined both parents of 12 randomly selected patients with keratoconus whom we were following up. Of the 12 sets of parents, at least one parent in each of seven sets had abnormal corneal characteristics. Using previously determined quantitative criteria (eg, central corneal steepening, greater steepening inferiorly than superiorly, and asymmetry between the two eyes) to distinguish normal from keratoconic corneas we found evidence of keratoconus in at least one of the 14 parents. The remaining five patients had parents with normal corneal characteristics. These data support the hypothesis that keratoconus is sometimes an inherited condition, exhibiting, at least in some families, autosomal dominant inheritance with incomplete penetrance.

Adult↗
PubMed1997

Expression of transcription factors in keratoconus, a cornea-thinning disease.

Transcription factors are known to regulate gene transcription through the recognition and binding of specific DNA sequences in the promoter or enhancer regions of many genes. Keratoconus is a cornea-thinning disease in which upregulated expression of degradative enzymes and downregulated expression of protease inhibitors have been demonstrated. In view of the alteration in gene expression for multiple proteins, five common transcription factors, AP1, AP2, CREB, Sp1, and NF-kappa B were examined for their possible roles in keratoconus. Immunostaining experiments and Western blotting showed that Sp1 exhibited enhanced expression in keratoconus corneas. Increased binding of Sp1 consensus sequence oligonucleotides with nuclear extracts from the epithelium of keratoconus corneas was also seen by gel mobility shift assays. This is believed to be a first demonstration connecting Sp1 alteration to a human disease. The elevated Sp1 expression may contribute to the enzyme and inhibitor abnormalities found in keratoconus corneas.

Adolescent↗
PubMed2002

Early diagnosis of keratoconus with Orbscan-II anterior system.

Orbscan-II anterior system was used for early diagnosis of keratoconus. 48 Eyes of 24 patients with suspicious keratoconus were examined by Orbscan-II anterior system from Dec. 1999 to Dec. 2000 and followed up. The values of Diff and anterior chamber depth (ACD) were recorded. Results indicated that values of Diff and ACD were increased in 4 eyes of 2 patients with keratoconus trend during follow-up. Taking advantage of Orbscan-II anterior system to observe the values of Diff and ACD can early diagnose the sub-clinical keratoconus. The values of Diff and ACD can sensitively report the progression of keratoconus.

Adolescent↗