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PubMed2006

Quantitative analysis of corneal microstructure in keratoconus utilising in vivo confocal microscopy.

PURPOSE: To establish and quantify the in vivo confocal microscopic features of moderate to advanced keratoconus. METHODS: Nineteen keratoconus subjects were catergorised using Orbscan-derived corneal apex power and pachymetry as exhibiting moderate (n=7) and advanced (n=12) keratoconus. Control subjects included 23 noncontact lens wearers (Group A) and 15 contact lens wearers (Group B). All subjects underwent Confoscan slit scanning in vivo confocal microscopy. RESULTS: Compared with Group A (4912+/-434 cells/mm(2)), basal epithelial density was significantly lower in both moderate (4592+/-414 cells/mm(2), P<0.05) and advanced keratoconus (4530+/-596 cells/mm(2), P=0.01). In comparison to Group A (761+/-118 cells/mm(2)), anterior stroma keratocyte density was significantly greater in both moderate keratoconus (883+/-111 cells/mm(2), P=0.001) and advanced keratoconus (952+/-122 cells/mm(2), P<0.001). Compared to Group A (504+/-80 cells/mm(2)) posterior stroma keratocyte density was also significantly greater in advanced keratoconus (599+/-97 cells/mm(2), P<0.001) and posterior stromal keratocyte density appeared to increase with increasing severity of keratoconus (P<0.05). However, comparing control Groups A and B, contact lens wear per se, was associated with significantly reduced (P=0.000) keratocyte density in the anterior stroma (609+/-66 cells/mm(2)) and demonstrated a trend (P=0.056) in the posterior stroma (470+/-63 cells/mm(2)). Keratoconic corneas (429+/-72 microm) were significantly thinner than control Groups A (508+/-77 mm) and B (495+/-80 microm). The presence of keratoconus did not affect the endothelial cell density (P=0.54). CONCLUSION: In vivo confocal microscopy can provide insight into the microstructural changes that occur in keratoconus.

Adult↗
PubMed1995

[Autosomal dominant keratoconus as the chief ocular symptom in Lobstein osteogenesis imperfecta tarda].

BACKGROUND: Osteogenesis imperfecta is an autosomal inherited generalized disease of the soft tissue which can be divided into a congenital form (Vrolik) and a late-onset form named Lobstein. As the typical ocular symptom we find blue sclera whereas corneal changes as keratoconus are rarely documented. We report a family of 6 patients, all 5 examined being affected by keratoconus. PATIENTS AND METHODS: After a 14-year-period of wearing hard contact lenses due to a keratoconus a 26-year-old female patient developed a painful therapy-resistant keratitis (Acanthamoeba) which afforded a keratoplasty. A history of osteogenesis imperfecta tarda was known since childhood. Five further members in three generations of the family were certainly affected by osteogenesis imperfecta. We examined five patients with a computer-assisted corneal topography analysis system. RESULTS: Referring to localization and configuration of the keratoconus all of the five patients had a similar degree of affection. Only our patient revealed blue sclera. There was no correlation between the corneal curvature and the degree of affection of the bone. Both the keratoconus and the bone affections had shown no more progression after adolescence. CONCLUSION: With the use of computer-assisted corneal topography analysis we were able to show a keratoconus associated with osteogenesis imperfecta. The typical blue sclera was not found that often in this family. The shape of the keratoconus was similar in localization and configuration. Contrary to the normal progression of keratoconus in this family there was no more progression of refractive changes after adolescence. Association of keratoconus with osteogenesis imperfecta should be considered. Likewise in osteogenesis imperfecta the ophthalmologist should consider keratoconus beside blue sclera.

Acanthamoeba Keratitis↗
PubMedDate not supplied

A quantitative corneal topography index for detection of keratoconus.

BACKGROUND: Detection of keratoconus has become a critical issue in patients who are potential candidates for refractive surgical procedures. In eyes with early stages of keratoconus, slit-lamp corneal changes are either absent or too subtle for detection, and keratometry may be normal. Videokeratography systems have greater sensitivity for detection of such cases, but interpretation of the topographic map is sometimes difficult, especially when pathologies with similar topographic patterns are suspected. We introduce an index using corneal topography for detection of keratoconus. METHODS: From March 1994 to December 1995, a total of 513 unoperated eyes, with no pathology other than keratoconus, from 283 consecutive patients were categorized into three groups based on slit-lamp examination and corneal topographic findings. Those with clinically obvious keratoconus were placed in the first group (53 eyes [10.3%]), those with keratoconus suspect comprised the second group (17 eyes [3.3%]), and the third group was that of normal eyes (443 eyes [86.4%]). In all videokeratographs of these eyes, the highest rate of corneal power changes (in diopters per millimeter) away from the apex (the point of maximum power) to the periphery was measured along its semimeridian. This index, called the "highest rate of steepening (HRS)", was statistically analyzed in the three groups. RESULTS: The mean +/- SD of highest rate of steepening was 3.60 +/- 1.70 D/mm (range 1.59 to 7.53 D/mm) in the clinically obvious keratoconus group, 1.59 +/- 0.21 D/mm (range 1.35 to 1.98 D/mm) in the keratoconus suspect group, and 0.72 +/- 0.31 D/mm (range 0.18 to 1.63 D/mm) in normal eyes. There was a highly statistically significant difference in the means of highest rate of steepening in the three groups (p < 0.0001). A small overlap in the highest rate of steepening ranges was shown among the three groups. Considering the first and second groups as cases of keratoconus, and 1.40 D/mm as the optimum cut-off value for highest rate of steepening, a sensitivity of 95.7% (67 out of 70 cases were detected), a specificity of 96.4% (16 false-positive cases), and an accuracy of 96.3% was obtained. CONCLUSION: The highest rate of steepening may be a useful measure for keratoconus screening with videokeratography. Validation is needed to evaluate its accuracy.

Adult↗
PubMedDate not supplied

Validation of the estimation of corneal aberrations from videokeratography in keratoconus.

PURPOSE: To validate the estimation of corneal aberrations from videokeratography against a laser ray tracing technique that measured total eye aberrations, in eyes without keratoconus (ie, cornea-dominated wave aberrations). METHODS: We measured total and corneal wave aberrations of three eyes diagnosed with keratoconus by slit-lamp microscopy and corneal topography: two eyes from one patient with early keratoconus and one eye with more advanced keratoconus. Total aberrations were measured with laser ray tracing. Corneal aberrations were obtained from corneal elevation data measured with a corneal videokeratoscope using custom software that performs virtual ray tracing on the measured front corneal surface. RESULTS: The keratoconus eyes showed a dramatic increase in aberrations (both corneal and total) particularly coma-like terms, which were 3.74 times higher on average than normal. Anterior corneal surface aberrations and total aberrations Were similar in keratoconus. This similarity was greater for the early keratoconus patient, suggesting a possible implication of the posterior corneal surface in advanced keratoconus. CONCLUSIONS: The similarity found between corneal and total aberration patterns in keratoconus provided a cross-validation of both types of measurements (corneal topography and aberrometry). Both techniques were useful in diagnosing and quantifying optical degradation imposed by keratoconus.

Adult↗
PubMed2005

[Study on enhanced leukocyte antigen-related tyrosine phosphatase in keratoconus].

OBJECTIVE: To study the enhanced expression of leukocyte antigen-related tyrosine phosphatase (LAR) in human keratoconus cornea. METHODS: Corneal buttons of patients received keratoplasty in Eye Center of Beijing Tongren from December 2001 to March 2002 were collected. Total RNA was isolated from the buttons from keratoconus (15 eyes), normal cornea (7 eyes), bullous keratopathy (6 eyes), non-neovascular cornea scar (3 eyes) and corneal dystrophy (2 eyes). Polymerase chain reaction (RT-PCR) was performed in this group. The results were displayed by agarose gels electrophoresis. In another group of patients, the corneal buttons of patients received keratoplasty in Eye Center of Beijing Tongren from July 2002 to December 2002 were collected. Total protein was extracted from the buttons of keratoconus (6 eyes), normal cornea (3 eyes), bullous keratopathy (3 eyes), non-neovascular cornea scar (3 eyes) and corneal dystrophy (2 eyes). Western blot was performed in this group. The results were displayed by enhanced chemical illumination. Bands of LAR RNA and LAR protein from these two tests were analyzed quantitatively. RESULTS: In RT-PCR study using the same amount of total RNA, high signal of LAR RNA was detected in RNA from the keratoconus, whereas low or no signal was detected in normal cornea and other diseases. Sequence analysis of the product of amplified LAR fragment from keratoconus showed deletion of exon 13. In Western blot study using the same amount of total protein, high signal of LAR was detected in keratoconus by the LAR antibodies, while low or no signal was detected in normal cornea and other diseases. CONCLUSIONS: LAR mRNA and protein are enhanced in keratoconus, whereas there are low or no expression in normal cornea, bullous keratopathy, non-neovascular cornea scar and corneal dystrophy. Elevated LAR in keratoconus indicates that LAR plays an essential role in the occurrence of keratoconus. Deletion of exon 13 in keratoconus may play a potential role in the abnormal LAR function.

Humans↗
PubMed1997

Cathepsin G, acid phosphatase, and alpha 1-proteinase inhibitor messenger RNA levels in keratoconus corneas.

PURPOSE: Keratoconus is characterized by thinning and scarring of the central region of the cornea. The authors have shown, in corneas obtained from patients with keratoconus, that lysosomal enzyme activities are elevated, whereas levels of protease inhibitors such as alpha 1-proteinase inhibitor (alpha 1-PI) are reduced. This study was undertaken to examine further the gene expression of cathepsin G, acid phosphatase, and alpha 1-PI in keratoconus corneas. METHODS: Corneal buttons were collected from patients with keratoconus, normal subjects, and patients with other corneal diseases. In situ hybridization was performed on paraffin sections using a tritium-labeled probe for cathepsin G or alpha 1-PI. Competitive polymerase chain reaction (PCR) was used to determine the messenger RNA (mRNA) levels for lysosomal acid phosphatase and alpha 1-PI in epithelial and stromal cells of keratoconus corneas. RESULTS: Silver grains, indicative of positive in situ hybridization products, were observed in all three cell types of normal corneas for both DNA probes. Compared with normal and other diseased controls, the labeling was enhanced for cathepsin G but was diminished for alpha 1-PI in the epithelium of keratoconus corneas. Competitive PCR showed that the mRNA level for acid phosphatase was higher and that the mRNA level for alpha 1-PI was lower in keratoconus corneas. CONCLUSIONS: These results indicate that the mRNA level for degradative enzymes in increased and that for alpha 1-PI it is reduced in keratoconus corneas. This study provides the first evidence that the altered expression of multiple enzymes and inhibitors in keratoconus occurs at the gene level. Furthermore, it implicates a possible role of coordinated transcriptional regulation of gene expressions in keratoconus.

Acid Phosphatase↗
PubMed2000

Is keratoconus a true ectasia? An evaluation of corneal surface area.

BACKGROUND: Keratoconus has long been considered to be an ectasia produced by stromal stretching. Although stretching should result in increased corneal surface area, previous observations of topography during progression of keratoconus have suggested that surface area may actually be conserved. A novel objective surface area measurement based on corneal topography was tested and applied to data from actual corneas under various conditions for comparative analysis. SETTING: The LSU Eye Center clinic videokeratography archives. METHODS: TMS-1 videokeratography files (Tomey Corp, Cambridge, Mass) were obtained from 6 groups of corneas: normal (n = 29), keratoconus from mild to severe states (n = 51), topographically judged keratoconus-suspect conditions (n = 10), postoperative photorefractive keratectomy for myopia (n = 39), with-the-rule corneal astigmatism (n = 17), and keratoglobus (n = 1). Additionally, 3 different spherical test surfaces were analyzed to verify the accuracy of the process. Only maps with no missing data out to ring 29 were used. The cumulative surface area from center to periphery was determined by calculating and summing the area of individual patches along consecutive annular rings. Mean surface area with respect to mean chord radius was plotted for each corneal condition, and curve fitting was used to extend each result to a 5. 85-mm limbus. Means, SEs, and 95% confidence intervals were calculated at intervals for statistical comparisons among all groups. Computer-generated surfaces helped to evaluate the relationship between shape and surface area. RESULTS: When videokeratographic test targets were used, surface area error was less than 2%, which was deemed acceptable. Normal corneas had a mean +/- SE surface area of 120.3 +/- 2.2 mm(2), whereas all keratoconus corneas combined had a mean +/- SE surface area of 116.2 +/- 3.4 mm(2). The difference was not significant at any chord radius (analysis of variance, P<. 05). The keratoglobus cornea was found to have a surface area of 129. 9 mm(2), which was 7.98% greater than normal. An individual with progressive keratoconus exhibited no appreciable trend toward increasing surface area during a 76-month period. The corneas in the other groups resembled normal corneas in their total surface area. CONCLUSIONS: With the exception of the single case of keratoglobus, corneal surface area tended to be conserved near a value of 120 mm(2) for all groups in the study, including corneas with keratoconus. Surface area is remarkably insensitive to curvature change near the vertex. Flattening seen in the periphery of corneas with keratoconus suggests that biomechanical coupling compensates for any increase in curvature occurring in the region of the cone itself. Thus, it seems that keratoconus is not a true ectasia as is keratoglobus, but rather a specialized type of warpage, at least in mild to moderate forms of the disease. Arch Ophthalmol. 2000;118:1179-1186

Algorithms↗
PubMed2005

An evaluation of corneal nerve morphology and function in moderate keratoconus.

PURPOSE: To investigate corneal nerve morphology and corneal sensitivity in keratoconus. METHODS: The central cornea of 13 subjects with keratoconus and 13 age-matched control subjects was assessed using in vivo confocal microscopy and corneal aesthesiometry. RESULTS: Significant differences in corneal nerve fibre density were found between the subjects with keratoconus and the control subjects (keratoconus versus control; 1018.3+/-489.6 microm versus 1820.7+/-789.5 microm; p = 0.006). The mean diameter of nerve fibres in the stroma was found to be greater in subjects with keratoconus compared to control subjects (keratoconus versus control; 10.2+/-4.6 microm versus 5.5+/-1.9 microm; p = 0.007). The orientation of corneal nerve fibres in the subjects with keratoconus appeared to be altered from the predominantly vertical orientation seen in the control subjects. Corneal touch threshold was found to be similar in the two groups, although the subjects with keratoconus using contact lens correction had reduced corneal sensitivity compared to the contact lens-wearing control subjects (keratoconus with contact lenses versus controls with contact lenses; 1.18+/-0.19 g/mm2 versus 0.98+/-0.05 g/mm2; p = 0.03). CONCLUSION: This study reveals significant reductions in nerve density in the keratoconic cornea. The thickened stromal nerve fibres observed in the keratoconic corneas may explain why prominent corneal nerves are often seen using slit lamp biomicroscopy in keratoconic patients.

Adult↗
PubMed2006

Extended long-term outcomes of penetrating keratoplasty for keratoconus.

OBJECTIVE: To report graft survival results for initial penetrating keratoplasty (PK) performed more than 20 years ago for keratoconus. Secondary outcome measures included recurrent keratoconus, best spectacle-corrected visual acuity (BSCVA), and rates of glaucoma. DESIGN: Retrospective, consecutive, noncomparative case series. PARTICIPANTS: All patients with clinical and histopathological keratoconus who underwent initial PK at the University of Iowa Hospitals and Clinics from 1970 to 1983. Patients with pellucid marginal degeneration were excluded. METHODS: At baseline, age, preoperative BSCVA, keratometric astigmatism, and host/donor graft sizes for each eye were recorded. Visual acuity and intraocular pressure were followed until the eyes reached 1 of 4 end points: graft failure, recurrent keratoconus, loss to follow-up, or death. Kaplan-Meier survival analysis was performed to estimate the long-term probability of graft failure and recurrent keratoconus. RESULTS: Among the 112 eyes of 84 patients who met entry criteria, there was a mean age at transplant of 33.7 years and preoperative BSCVA of 20/193. With a mean follow-up of 13.8 years (range, 0.5-30.4), 7 eyes (6.3%) experienced graft failure. Recurrent keratoconus was confirmed clinically or histologically in 6 eyes (5.4%), with a mean time to recurrence of 17.9 years (range, 11-27). Kaplan-Meier analysis estimated a graft survival rate of 85.4% and a rate of recurrent keratoconus of 11.7% at 25 years after initial transplantation. Six eyes (5.4%) developed open-angle glaucoma, and 2 eyes required trabeculectomy. At the last follow-up visit, 82 eyes (73.2%) had BSCVA of 20/40 or better. CONCLUSION: Penetrating keratoplasty offers good long-term visual rehabilitation for keratoconus. Relative to other indications for PK, there is a low rate of graft failure. Late recurrence of disease occurs with increasing frequency over time. Given the younger age at which keratoconus patients undergo corneal transplantation, these long-term findings should be incorporated into preoperative counseling.

Adolescent↗
PubMed1999

[Keratoconus screening with wave-front parameters based on topography height data].

BACKGROUND: The image-forming properties of a keratoconus eye are degraded even in the early stage of this disease. The purpose of this study was to develop keratoconus detection scheme based on topography height data independent of the currently used system which avoids the disadvantages of detection algorithms currently used in clinical practice. PATIENTS AND METHODS: Eighty-eight patients with keratoconus (46 with mild and 42 with severe clinical signs) and a control group of 40 normal subjects were included in this study. A decomposition of corneal topography height data into orthogonal Zernike polynomials was performed using the commercially available corneal topographer TMS-1. Expansion coefficients of the different groups were compared to evaluate significant differences. Elevated terms were used to detect the disease. The statistical significance of this detection scheme was compared to those given by the keratoconus detection software of the TMS-1. From the elevated Zernike terms a neural network was constructed and optimized for dividing keratoconus patients and normal controls. RESULTS: Some low-order Zernike coefficients with a radial order n < 8 were found to be elevated in patients with keratoconus and were used to define a new detection algorithm. This index performed at least as well (sensitivity in mild/severe keratoconus 93.4%/100% with a specificity of 100%) as keratoconus detection schemes based on the Klyce-Maeda and the Rabinowitz-Klyce indices as well as the I-S value and the Surface Asymmetry Index SAI in our study population. CONCLUSIONS: Zernike decomposition of corneal topography height data allows a definition of an exact and robust algorithm for detection of keratoconus. It avoids the drawbacks of refractive power based definitions and is independent on the individual topographer design.

Adolescent↗
PubMed1994

Increased gelatinolytic activity in keratoconus keratocyte cultures. A correlation to an altered matrix metalloproteinase-2/tissue inhibitor of metalloproteinase ratio.

Keratoconus is a noninflammatory corneal disorder characterized by gradual stromal thinning and astigmatism. Altered degradation of corneal extracellular matrix is a suggested etiology for this disorder. In the present study we established keratocyte cultures from normal and keratoconus corneas and investigated the roles that matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP, TIMP-2) may play. After chemical modification (reduction and alkylation) to remove the inhibitor and activation of enzyme with p-aminophenylmercuric acetate (APMA), keratoconus-conditioned media displayed a significant increase (p < 0.05) in the total potential gelatinolytic activity when compared with normal culture media treated in a similar manner. Basal levels of gelatinolytic activity in keratoconus culture media (no reduction, alkylation, or APMA treatment), determined by two different assay methods, tended to be about twice that of normal cell cultures. By zymography, both keratoconus and normal cultures showed identical enzyme patterns, which represented MMP-2 (72 kDa) in its proform and, depending on the treatment of the media, varying amounts of activated MMP-2 (65 kDa). This suggests that the increased gelatinolytic activity in keratoconus was not correlated with an increased appearance of either the 65-kDa-activated form of MMP-2 or a new MMP species. In addition, no differences in the amount of MMP-2 were detected that could account for the increased activities in keratoconus cultures. However, a relative decline in the detectable TIMP levels in keratoconus cultures resulted in an apparent three-fold increase in the ratio of MMP-2/TIMP. Northern blots showed no significant changes in mRNA levels for MMP-1, MMP-2, MMP-3, TIMP, or TIMP-2. These data suggest that a possible alteration in the interaction between MMP-2 and TIMP may play a role in the increased gelatinolytic activity seen in keratoconus tissues.

Adolescent↗
PubMed1998

Evaluation of mild, moderate, and advanced keratoconus using ultrasound pachometry and the EyeSys videokeratoscope.

BACKGROUND: The absolute accuracy of videokeratoscope (VKS) mapping of keratoconus is still in question, with contact lens-induced corneal warpage and chalazion having been shown to resemble this condition closely. Corneal thinning is investigated as a further aid to the diagnosis and description of keratoconus. METHODS: The diagnosis of keratoconus in 41 individuals was verified by measuring the corneal thickness difference (I-S difference) between two disparate corneal locations, one inferior to (I) and one superior to (S) the corneal apex, using a Humphrey model 870 Ultrasound pachometer. Corresponding measures of I-S radii were made using radius values obtained from the EyeSys VKS. RESULTS: A comparison between I-S pachometry and I-S radius demonstrated a marginally increased sensitivity for the latter measurement. Using 95% confidence levels from normative pachometric data, classification of severity of keratoconus is proposed as follows: (1) keratoconus suspect/early keratoconus: I-S pachometry 75 to 100 microns; (2) moderate keratoconus: 100 to 125 microns; and (3) advanced keratoconus: > 125 microns. CONCLUSION: I-S pachometry can be used as a descriptor of keratoconus.

Cornea↗
PubMed2006

Collagenolytic proteinases in keratoconus.

PURPOSE: To study the proteolytic phenomena contributing to the pathogenesis of keratoconus, corneal enzymes with potential to cleave fibrillar collagen were studied. METHODS: Immunohistochemical labeling was undertaken of conventional and novel mammalian collagenases (MMP-1, -2, -8, -13, and -14) of the matrix metalloproteinase (MMP) family and other collagenolytic proteinases of the serine (human trypsin-2) and cysteine (cathepsin K) endoproteinase families. The results were analyzed using a semiquantitative scoring system. RESULTS: Labeling of MMP-8 was moderate in healthy controls, but weak in keratoconus. Moderate MMP-2 and weak MMP-14 expressions were similar in controls and keratoconus. MMP-1 was slightly overexpressed in keratoconus. In contrast, MMP-13 was weak in controls compared to moderate in keratoconus and human trypsin-2 and cathepsin K were moderate in controls and strong in keratoconus. CONCLUSIONS: The collagenolytic milieu of human cornea is more complex than expected. Mesenchymal isoform of MMP-8 (ie, collagenase-2) participates in normal tissue remodeling, which may be impaired in keratoconus. MMP-2 (gelatinase A with interstitial collagenase activity) and MMP-14 (membrane-type MMP type I with collagenolytic potential) seem to be constitutively expressed and probably play a role in normal corneal remodeling. The most prominent changes in keratoconic cornea were observed in collagenase MMP-13 (ie, collagenase-3), and particularly, in cathepsin K and human trypsin-2, which were strongly expressed in keratoconus suggesting a role in intra- and extracellular pathological collagen destruction, respectively. This may contribute to stromal thinning characteristic for keratoconus.

Cathepsin K↗
PubMed2005

Histopathological and immunohistochemical studies of lenticules after epikeratoplasty for keratoconus.

AIMS: To examine histopathological and immunohistochemical changes in lenticules and host of corneal buttons from patients who previously underwent epikeratoplasty for keratoconus. METHODS: 12 penetrating keratoplasty specimens from patients with keratoconus who had previously undergone epikeratoplasty, eight keratoconus, and seven normal corneas were examined. Immunostaining for Sp1, alpha1-proteinase inhibitor (alpha1-PI), and alpha2-macroglobulin (alpha2M) were performed. RESULTS: In nine of the 12 lenticules, the keratoconus-like disruptions were found in Bowman's layer. Peripheral and posterior keratocyte repopulation of the lenticules was observed in all cases. Keratocyte repopulation in the anterior and mid-stromal regions of the lenticules appeared related to the time since epikeratoplasty. Sp1 nuclear staining of the basal and wing epithelial cells was more intense in lenticules and keratoconus corneas than in normal corneas. Lenticular, host, and keratoconus keratocytes showed positive Sp1 staining, whereas staining was absent in normal corneas. Compared to normal corneas, alpha1-PI and alpha2M immunostaining was lower in the lenticules, host, and keratoconus specimens. CONCLUSIONS: The epithelial cells and keratocytes repopulated in the lenticules retain keratoconus-like biochemical abnormalities such as upregulation of Sp1 and downregulation of alpha1-PI and alpha2M. The authors speculate that both keratocytes and the corneal epithelium may participate in the development of keratoconus.

Adolescent↗
PubMed2001

Keratocan expression is increased in the stroma of keratoconus corneas.

BACKGROUND: Keratoconus is a noninflammatory disease characterized by thinning and scarring of the central portion of the cornea. The etiology is unclear. In this study, we sought to identify mRNAs that are differentially expressed in the stroma of keratoconus corneas in comparison to those of corneas from normal individuals and patients with other corneal diseases. MATERIALS AND METHODS: Total RNA was isolated from the stromal layer of normal human, keratoconus, and pseudophakic bullous keratopathy corneas. cDNA was synthesized and PCR-select subtractive hybridization experiments were performed. The differentially expressed genes noted were verified by dot blot analysis, cloned, and sequenced. Immunohistochemical staining, in situ hybridization, and/or reverse transcription polymerase chain reaction were used to assess expression of the identified genes at protein and/or mRNA levels in normal, keratoconus, and other diseased corneas. RESULTS: A number of genes were found to be up-regulated in keratoconus specimens. These included heat shock protein 90, decorin, fibronectin, ferritin heavy chain, and keratocan. Among them, keratocan mRNA transcript and protein were demonstrated to be expressed at a higher level specifically in the keratoconus stroma. CONCLUSIONS: Keratocan expression in the stoma was increased in keratoconus corneas. This up-regulation appears to be keratoconus specific. Keratocan is one of the three keratan sulfate proteoglycans in the cornea speculated to be important for structure of the stromal matrix and maintenance of corneal transparency. The overexpressed keratocan may conceivably alter the fibrillogenesis in the stroma, leading to structural defects and contributing to the development of keratoconus.

Adolescent↗
PubMedDate not supplied

Automated keratoconus detection using height data of anterior and posterior corneal surfaces.

PURPOSE: To develop a keratoconus detection algorithm using the corneal topographic data of the anterior and posterior corneal surfaces. METHODS: Topographic measurements of the cornea were made with a slit-scanning corneal topographer. We examined 120 subjects (165 eyes); keratoconus patients and keratoconus suspect patients comprised the keratoconus group, and post-photorefractive keratectomy patients, with-the-rule astigmatism patients, and controls without disease comprised the nonkeratoconus group. Two variables of the anterior corneal surface, two variables of the posterior corneal surface, and one corneal thickness variable were obtained by applying the Fourier harmonic decomposition formula. By performing a logistic regression analysis with a training set to differentiate the keratoconus group from the nonkeratoconus group, the Fourier-incorporated keratoconus detection Index (FKI) was created. The validity of the FKI was determined by using independent validation sets. RESULTS: The FKI distinguished the keratoconus group from the nonkeratoconus group with 96.9% sensitivity and 95.4% specificity in the validation set. CONCLUSIONS: A newly developed automated keratoconus classifier can be used to screen keratoconic patients. The index is based on information obtained by Fourier analysis from not only the anterior corneal surface but also from the posterior corneal surface and corneal thickness.

Adult↗
PubMed2005

Characteristics of keratoconus and pellucid marginal degeneration in mean curvature maps.

PURPOSE: To characterize keratoconus and pellucid marginal degeneration (PMD) on mean curvature maps. DESIGN: Observational case series. METHODS: A retrospective analysis of clinical records of 19 keratoconus eyes and eight PMD eyes. Keratometric mean curvature maps were computed from a placido-disk-based corneal topography system. The peak location and amplitude of distortions were quantified by fitting two-dimensional Gaussian functions. Computer simulations of keratoconic corneal topography were used to help interpret the results. RESULTS: Keratoconus and PMD eyes had a characteristic localized increase in convexity (cone) on mean curvature maps. Computer simulations showed that the peak on the mean curvature map accurately represented the peak of the cone-like distortion. However, the peak location and appearance of the same conic distortion on axial and tangential maps were greatly influenced by coexisting astigmatism. The Gaussian function provided an excellent model of keratoconus on mean curvature maps, with a mean cross-correlation of 0.80. According to Gaussian fitting, the vertical cone peak locations were -1.10 +/- 0.43 mm (mean +/- SD) in keratoconus eyes and -1.94 +/- 0.53 mm in PMD eyes (P < .01). The locations of peaks on axial and tangential maps differed considerably from those on mean curvature maps. Advanced keratoconus tended to have higher cones (amplitude 13.31 +/- 6.87 diopters) than early keratoconus (amplitude 10.65 +/- 1.56 diopters). CONCLUSIONS: Gaussian fitting of mean curvature maps accurately quantifies the peak location and amplitude of the cone in keratoconus and PMD eyes. This new topographic analysis might be useful in the diagnosis and tracking of corneal ectatic diseases.

Computer Simulation↗
PubMed2000

Changes in anterior and posterior corneal curvatures in keratoconus.

OBJECTIVE: To quantitatively evaluate the changes in anterior and posterior corneal curvatures of eyes with keratoconus. DESIGN: Case-control retrospective and observational study. PARTICIPANTS: Thirty-one patients who were clinically diagnosed to have unilateral or bilateral keratoconus and 18 normal subjects. INTERVENTION: The anterior and posterior topographies were obtained using scanning-slit videokeratography and assessed by Fourier series harmonic analysis. MAIN OUTCOME MEASURES: Quantitative descriptors of the topography data, spherical power, regular astigmatism, and irregular astigmatism (asymmetry and higher order irregularity) components were compared between the anterior and posterior surfaces and among groups of clinically diagnosed keratoconus (33 eyes), keratoconus suspect (13 eyes), and normal subjects (36 eyes). RESULTS: Spherical power (P = 0.0003, Mann-Whitney U test with Bonferroni's correction of P values), regular astigmatism (P = 0.0166), and asymmetry (P = 0.0031) of the anterior surface were significantly greater in the keratoconus eyes than in the normal controls. For the posterior surface, spherical power (P<0.0001), regular astigmatism (P = 0.0143), asymmetry (P< 0.0001), and higher order irregularity (P = 0.0032) of the keratoconus group were significantly greater than those of the control group. The keratoconus suspect eyes, when compared with the normal controls, showed a significantly greater amount of spherical power (P = 0. 0166) and asymmetry (P<0.0001) in the anterior surface and spherical power (P <0.0001), regular astigmatism (P = 0.0244), asymmetry (P<0.0001), and higher order irregularity (P = 0.0276) in the posterior surface. All refractive components demonstrated statistically significant correlations between the anterior and posterior surfaces (P<0.0001, Spearman's rank correlation). CONCLUSIONS: Not only the anterior but also the posterior corneal curvature is affected in keratoconus. These changes are observed from the early stage of this disorder.

Adolescent↗