INTACS for keratoconus.
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Corneal Stroma↗
Biomedical subjects
Yaron S Rabinowitz
Publications and source records attributed to Yaron S Rabinowitz.
Ectasia after laser in situ keratomileusis.
PURPOSE OF REVIEW: The potential for litigation has resulted in increased interest in ectasia after laser in situ keratomileusis. This article summarizes papers written during this past year on this subject. RECENT FINDINGS: A panel of refractive surgery experts have summarized the current state of knowledge on this subject and provided guidelines to minimize risk. Because ectasia may occur in the absence of risk factors, there may be corneas with biomechanical factors not detectable with present technology which are at risk. Several articles point out the limitations of the Orbscan (Bausch & Lomb, Rochester, New York, USA), in particular its accuracy and reproducibility with regard to data generated from the posterior surface of the cornea. A biomechanical model of the cornea is proposed which suggests that each cornea's response to laser in situ keratomileusis is unique. Several case reports are also reviewed which provide insight into pathogenesis and potential new treatment options; these include reports on histopathology, topographic pseudokeratectasia, ectasia from transient raised intraocular pressure, poor response to laser in situ keratomileusis after incisional surgery, intracorneal rings, collagen cross-linking and conductive keratoplasty to stabilize and sphericize the cornea with ectasia. SUMMARY: Our knowledge about ectasia is still in evolution. Insights into the biomechanics and genetics of the cornea may allow us to further reduce its occurrence.
Biomechanical Phenomena↗
No VSX1 gene mutations associated with keratoconus.
PURPOSE: To determine whether mutations of the VSX1 gene play a pathogenetic role in the development of keratoconus (KTCN). METHODS: DNA extraction, PCR amplification, and direct sequencing of the VSX1 gene were performed in 100 unrelated patients with diagnoses of clinical and topographic features of KTCN. RESULTS: Of the four previously identified presumed pathogenic mutations in the VSX1 gene (Leu17Pro, Asp144Glu, Leu159Met, and Arg166Trp), only Asp144Glu was identified in a single affected patient. Two novel single nucleotide polymorphisms (SNPs), both resulting in synonymous substitutions, were identified: c.53G>T (Ser6Ser) in four affected patients and c.209G>T (Pro58Pro) in two affected patients. Two previously reported SNPs were also identified: c.426C>A (Arg131Ser) in one affected patient and c.581A>G (Ala182Ala) in 51 of the 100 affected patients. CONCLUSIONS: Only one of the presumed pathogenic mutations in the VSX1 gene, Asp144Glu, was identified in a single member of the cohort of affected patients. However, as previously demonstrated, Asp144Glu is a non-disease-causing polymorphism. The absence of pathogenic mutations in the VSX1 gene in a large number of unrelated KTCN patients indicates that other genetic factors are involved in the development of this disorder.
Adolescent↗
Two-stage genome-wide linkage scan in keratoconus sib pair families.
PURPOSE: To identify susceptibility gene loci for keratoconus. METHODS: A genome-wide linkage analysis was performed with data from 67 keratoconus sib pair families with 110 affected sib pairs of white or Hispanic origin. A total of 351 subjects were genotyped for 380 microsatellite markers along the genome at approximately 10-cM density. An additional 58 microsatellite markers at approximately 2-cM density in the identified linkage regions on chromosomes 4, 5, 9, 12, and 14 were also genotyped. Multipoint linkage analysis was performed in all pedigrees by nonparametric methods and maximum likelihood estimates of identity by descent sharing as implemented in GeneHunter (http://linkage.rockefeller.edu/soft/gh/ provided in the public domain by Rockefeller University, New York, NY). RESULTS: The strongest evidence of linkage was observed at the telomere (159 cM) of chromosome 9 (lod = 4.5) in all pedigrees. Other regions suggestive of linkage were identified at 176 cM of chromosome 4 (lod = 2.7), 143 cM of chromosome 5 (lod = 2.0), 7 cM of chromosome 9 (lod = 2.8), 12 cM of chromosome 11 (lod = 2.3), 27 cM of chromosome 12 (lod = 2.3), and 14 cM of chromosome 14 (lod = 2.9). Two significant linkage regions were also observed on chromosomes 17 at 86 cM (lod = 3.9) and 9 at 34 cM (lod = 3.8) in the Hispanic subjects only. After fine mapping these regions (with the exception of chromosomes 11 and 17), most linkage peaks remained similar (lod = 2.2 at 176 cM on chromosome 4; lod = 1.7 at 146 cM on chromosome 5; lod = 3.5 at 160 cM on chromosome 9; lod = 2.5 at 7 cM on chromosome 12; and lod = 2.6 at 19 cM on chromosome 14). CONCLUSIONS: These results indicate that one or more loci may contribute to keratoconus susceptibility.
Asian People↗
INTACS inserts using the femtosecond laser compared to the mechanical spreader in the treatment of keratoconus.
PURPOSE: To determine the efficacy of INTACS insertion using a femtosecond laser in the treatment of keratoconus and to compare it to the technique using a mechanical spreader. METHODS: INTACS were inserted in 10 eyes using the mechanical spreader to create the channels and subsequently on another 20 eyes using the femtosecond laser. Uncorrected (UCVA) and best spectacle-corrected visual acuity (BSCVA), manifest refraction, and corneal topography were measured prior to surgery, at 6 months (femtosecond group), and 1 year (mechanical group). Pre- and postoperative data were analyzed to determine changes in the above parameters. RESULTS: Both groups showed significant reduction in average keratometry (K), spherical equivalent refraction, BSCVA, UCVA, surface regularity index (SRI), and surface asymmetry index (SAI). The laser group performed better in all parameters except change in SRI. Results of the laser versus the mechanical spreader were as follows: reduction in spherical equivalent refraction (3.98 vs 2.96), change in average K (2.91 vs 2.52), improvement in UCVA (4.13 vs 3.63), improvement in BSCVA (3.92 vs 1.63), change in SRI (0.37 vs 0.64), and change in SAI (1.00 vs 0.70). Statistical analysis, however, did not reveal any statistically significant differences between the two groups for any single parameter studied. The biggest improvement in the laser group versus the mechanical group was BSCVA (P=.09). Overall success, defined as contact lens or spectacles tolerance, was 85% in the laser group and 70% in the mechanical group. CONCLUSIONS: Inserting INTACS using the femtosecond laser to create the channels is as effective as using the mechanical spreader.
Adult↗
Gene expression profile studies of human keratoconus cornea for NEIBank: a novel cornea-expressed gene and the absence of transcripts for aquaporin 5.
PURPOSE: To increase the database of genes expressed in human cornea and to gain insights into the molecular basis of keratoconus (KC). METHODS: A cDNA library was constructed from KC corneas harvested at keratoplasty and used for expressed sequence tag (EST) analysis. Data were analyzed using grouping and identification of sequence tags (GRIST). Expression of selected clones was examined by RT-PCR. RESULTS: A total of 7680 clones was sequenced from the 5' end. After bioinformatics analysis, 4090 clusters of clones, each potentially representing individual genes, were identified. Of these, 887 genes were represented by more than one clone. The five most abundant transcripts, represented by >60 clones each, were for keratin-12, TGFBI (BIGH3), decorin, ALDH3, and enolase 1, all known markers for cornea. Many other markers for epithelial, stromal, and endothelial genes were also present. One cluster of six clones came from an apparently novel gene (designated KC6) located on chromosome 18 at p12.3. RT-PCR of RNA from several human tissues detected KC6 transcripts only in cornea. In addition, no clones were observed for the usually prominent corneal epithelial cell marker aquaporin 5 (AQP5), a water channel protein. Semiquantitative RT-PCR confirmed that expression of AQP5 is much lower in KC cornea than in non-KC cornea. CONCLUSIONS: This analysis increases the database of genes expressed in the human cornea and provides insights into KC. KC6 is a novel gene of unknown function that shows cornea-preferred expression, whereas the suppression of transcripts for AQP5 provides the first clear evidence of a molecular defect identified in KC.
Amino Acid Sequence↗
Visual function in an 11 year old with Fraser cryptophthalmos syndrome.
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Abnormalities, Multiple↗
Longitudinal study of the normal eyes in unilateral keratoconus patients.
PURPOSE: To determine the rate at which clinically normal eyes in unilateral keratoconus (KC) patients progress to KC and to identify the risk factors that might predict the development of KC in a longitudinal study. DESIGN: Prospective observational study. PARTICIPANTS: We recruited 778 patients with KC and 252 normal controls in Los Angeles, California. One hundred sixteen of 778 patients (14.9%) were diagnosed with clinically unilateral KC at baseline. METHODS: Both eyes of these unilateral KC patients were examined at baseline, and 85 patients were followed up with clinical evaluation and videokeratography for a period ranging from 6 months to 8 years. MAIN OUTCOME MEASURES: Progression to clinical KC from previously normal fellow eyes. Quantitative and qualitative videokeratography variables, contact lens wear, and demographic variables were analyzed as potential predictive factors for this progression. RESULTS: During the follow-up period, 30 of 85 (35.3%) clinically normal fellow eyes had KC develop, and 25 of these 30 (83.3%) had KC develop within the first 6 years after the initial KC diagnosis. By use of the time period from the patients' first diagnosis of unilateral KC to the end of the follow-up period (range, 6 months-41 years), the median time (estimated from the survival analysis) to the development of KC was 16.7 years (95% confidence interval, 11.34, 28.91). Fellow eyes with higher inferior-superior dioptric asymmetry value (I-S) or KC percentage index (logKISA) values had higher risk for KC developing (I-S, risk ratio [RR] = 1.348, P = 0.022; log(KISA), RR = 4.245, P = 0.003). Asymmetric patterns also showed an increased risk for KC developing (P = 0.03), especially the asymmetric bowtie with skewed radial axes (AB/SRAX) pattern. CONCLUSIONS: Approximately 50% of clinically normal fellow eyes will progress to KC within 16 years. The greatest risk is during the first 6 years of the onset. Quantitative indices (I-S and KISA values) and qualitative patterns (AB/SRAX) might predict this progression.
Adult↗
Quality of life related to visual function in three young adults with mucopolysaccharidoses.
The systemic mucopolysaccharidoses are complex syndromes, which may include corneal clouding as a mechanism leading to decreased vision and hence decreased quality of life. This study presents three young adult patients with mucopolysaccharidoses in order to compare their visual status through retrospective chart review, including patient and guardian interview, history, and examination, including a modified form of the VF-14 questionnaire (visual function with 14 questions). When the visual acuity and VF-14 results of the three patients were compared, the results of the VF-14 correlated with the patients" visual acuity status. The two patients who retained clear corneas or underwent penetrating keratoplasty had a wider range of social and physical activities, and an overall better quality of life than did the patient with decreased vision due to opacified corneas. We conclude that close monitoring of the ocular health of patients with storage syndromes that may compromise visual acuity must be stressed, and intervention to insure good vision is of the utmost importance to maintaining a good quality of life for these patients, especially as new therapies assist these patients to achieve increased longevity with better health.
Adult↗
The genetics of keratoconus.
Isolated keratoconus with no associations is by far the most common keratoconus presentation seen by a practicing clinician. This article explores the genetics of this most common form of keratoconus.
Humans↗
Genomewide linkage scan in a multigeneration Caucasian pedigree identifies a novel locus for keratoconus on chromosome 5q14.3-q21.1.
PURPOSE: Keratoconus is a corneal dystrophy with an incidence of 1 in 2000 and a leading cause for cornea transplantation in Western developed countries. Both clinical observations and segregation analyses suggest a major role for genes in its pathogenesis. It is genetically heterogeneous, most commonly sporadic, but inherited patterns with recessive or dominant modes have also been reported. We studied a four-generation autosomal-dominant pedigree to identify disease loci for keratoconus. METHODS: A two-stage genome-wide scan was applied to 27 family members. First linkage analysis was performed with 343 microsatellite markers along the 22 autosomal chromosomes at approximately 10 cM density. This was followed by fine mapping at approximately 2 cM density, in regions suggestive of linkage. Multipoint linkage analysis was performed using GeneHunter2. RESULTS: Evidence of suggestive linkage from the initial scan was observed at the 82 to 112 cM region of chromosome 5q14.1-q21.3 with a maximum lod score (LOD) of 3.48 (penetrance = 0.5). Fine mapping by testing an additional 11 microsatellite markers at 1 to 3 cM intervals revealed a narrower and higher peak (99-119 cM) with LOD 3.53. By analysis of the recombination of haplotypes, the putative locus of keratoconus was further narrowed to a 6 cM region (8.2 Mbp physical distance) between markers D5S2499 and D5S495. CONCLUSION: These results indicate a promising new locus for keratoconus in this pedigree. Because of the heterogeneous nature of keratoconus, this locus may be specific to familial autosomal-dominant keratoconus. Nevertheless, the identification of this locus may provide new insights into the pathogenesis of keratoconus.
Adult↗