Laser in situ keratomileusis for myopia up to -11 diopters with up to -5 diopters of astigmatism with the summit autonomous LADARVision excimer laser system.

OBJECTIVE: To assess the safety and effectiveness of the Summit Autonomous LADARVision active tracking narrow beam excimer laser system for laser in situ keratomileusis (LASIK) correction of myopia and astigmatism. DESIGN: A multicenter, prospective noncomparative case series. PARTICIPANTS: This cohort consisted of 177 eyes corrected for spherical myopia up to -11 diopters (D) and 170 eyes corrected for myopia up to -11 D spherical equivalent with astigmatism up to -5 D. INTERVENTION: Treatments were performed at four sites in the United States using a 6-mm optic zone for spherical myopes and a 5.5-mm optic zone with a 1-mm blend for astigmats. MAIN OUTCOME MEASURES: Visual acuity, subjective refraction, vector analysis, subject satisfaction, intraocular pressure, complications, and adverse reactions. RESULTS: Six-month follow-up was available on 157 spherical eyes and 113 astigmatic eyes. For spherical myopes, uncorrected visual acuity (UCVA) was 20/20 or better in 60.5%, 20/25 or better in 80.3%, and 20/40 or better in 93.9%. The mean spherical equivalent was -0.29 +/- 0.45 D with 75.2% +/- 0.50 D and 94.9% +/- 1.00 D of intended. A loss of two lines of best spectacle-corrected visual acuity (BSCVA) occurred in 0.6%, and no eyes lost greater than two lines of BSCVA. For astigmatic myopes, UCVA was 20/20 or better in 52.0%, 20/25 or better in 74.5%, and 20/40 or better in 94.1%. The mean spherical equivalent was -0.23 +/- 0.49 D with 75.2% +/- 0.50 D and 95.6% +/- 1.00 D of intended. A loss of two lines of BSCVA occurred in 0.9%, and no eyes lost greater than two lines of BSCVA. Vector analysis showed that 99% of the intended cylinder was corrected on average with a mean angle of error of 4.2 degrees. Refractive stability was achieved between 1 and 3 months in 97.5% of spherical eyes and 99.4% of astigmatic eyes and confirmed between 3 and 6 months in 100% of both spherical and astigmatic eyes. CONCLUSIONS: Eyes treated for myopia up to -11 D of spherical equivalent with or without astigmatism up to -5 D show early refractive stability, good UCVA outcomes, no significant loss of BSCVA, accurate correction of astigmatism, and slight undercorrection without a change from the photorefractive keratectomy algorithm and with a single treatment.

Surgical treatment of advanced pellucid marginal degeneration.

PURPOSE: To determine the efficacy of simultaneous peripheral crescentic lamellar keratoplasty (LK) and central penetrating keratoplasty (PK) for advanced pellucid marginal degeneration (PMD). DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Five patients with advanced PMD. METHOD: Simultaneous peripheral crescentic LK and central PK followed by selective suture removal and astigmatic keratotomy in the postoperative period. MAIN OUTCOME MEASURES: These included interval of time required for visual rehabilitation, best spectacle-corrected visual acuity achieved, and amount of corneal astigmatism, as measured by videokeratography. Measuring the change in corneal astigmatism by videokeratography over the subsequent follow-up period after spectacle correction had been prescribed assessed stability of the achieved refraction. RESULTS: Visual acuity results were 20/40 in three eyes, 20/80 in one eye, and 20/400 in one eye. The latter two had decreased acuity from posterior subcapsular cataract formation, which may have been caused by topical steroid use. The time required for visual rehabilitation ranged from 5.13 to 10.93 (mean, 9.92) months, and the amount of corneal astigmatism at the end of this period ranged from 0.3 diopters (D) to 5.3 D. A tendency for an increase in "with the rule astigmatism" after the rehabilitation period was noted. Two patients had elevations of intraocular pressure that responded to reduction in topical steroid dose. CONCLUSIONS: The short-term results with this technique are excellent in that it provides early and stable visual rehabilitation in patients with advanced PMD. Low to moderate levels of postkeratoplasty astigmatism were achieved in all the eyes treated. The usual tendency of an increase in "against the rule astigmatism" that occurs when PK alone is done for PMD was eliminated.

Genetic epidemiological study of keratoconus: evidence for major gene determination.

Keratoconus (KC) is a noninflammatory corneal thinning disorder and the major cause of cornea transplantation in the Western world. Genetic factors have been suggested in the cause of KC. We conducted a family study to investigate genetic contributions to the development of KC by evaluating familial aggregation and testing genetic models with segregation analysis. KC was diagnosed based on clinical criteria. Familial aggregation of KC was evaluated using both clinical status and three videokeratography indices generated by the Topographic Modeling System (TMS-1). The estimated KC prevalence in first-degree relatives was 3.34% (41/1,226, 95% CI: 3. 22-3.46%), which is 15 to 67 times higher than that in the general population (0.23-0.05%). For all three videokeratography indices, CK, IS, and KISA, KC propositi had significantly higher mean values than controls (all P < 0.0001). Clinically unaffected parents also had significantly higher values for these indices than controls (all P < 0.016). The correlation of KISA in sib and parent-offspring pairs (r = 0.30 and 0.22, respectively, both P < 0.0005) was significantly greater than that in marital pairs (r = 0.14), and the latter was not significantly different from zero. We performed segregation analysis on KISA in 95 families ascertained through KC propositi. Hypotheses of both sporadic and environmental models were rejected (P < 0.001); a major gene model was not rejected (P > 0.1). Additionally, the most parsimonious model was autosomal recessive. In conclusion, we observed strong evidence of familial aggregation in KC and its subclinical indices and this aggregation is likely due to a major gene effect.

Corneal transplantation in a patient with mucopolysaccharidosis type VII (Sly disease).

PURPOSE: To illustrate a good visual outcome following penetrating keratoplasty in a patient with Sly disease, a rare mucopolysaccharidosis (MPS) caused by a deficiency of beta-glucuronidase. METHODS: A 15-year-old male with progressive bilateral corneal opacification had a complete medical, genetic, and ophthalmic evaluation followed by a penetrating keratoplasty. RESULTS: The cornea has remained clear for two years following surgery. Histopathology of the corneal button demonstrated vacuoles and granular inclusions consistent with this lysosomal storage disease. CONCLUSION: While research is ongoing in the fields of enzyme replacement and bone marrow transplantation, these treatments may not alleviate or reverse the corneal clouding. This case illustrates that cornea transplantation may be a valuable treatment option for visually rehabilitating such patients.

Keratocyte apoptosis associated with keratoconus.

Keratoconus is an ectatic corneal dystrophy associated with stromal thinning and disruption of Bowman's layer. The purpose of this study was to explore a possible association between keratocyte apoptosis and keratoconus. Keratocyte apoptosis was evaluated in corneas of patients with keratoconus, corneas of patients with stromal dystrophies, and normal donor corneas using the transferase-mediated dUTP-digoxigenin nick and labeling (TUNEL) assay. Keratocyte apoptosis was also studied in keratoconus and normal corneas using transmission electron microscopy. TUNEL-stained keratocytes were detected in 60% of corneas with keratoconus, but only 35% of corneas with stromal dystrophies (P =0.03). The number of TUNEL-positive keratocytes detected in the keratoconus, stromal dystrophy, and normal corneas was 7+/-1 (mean+/-standard error, range 0-20), 2+/-0. 8 (range 0-9), and 0+/-0 (range 0-0) TUNEL-positive cells per section, respectively. The differences between the keratoconus and the stromal dystrophy (P =0.0097) or the normal cornea (P =0.01) groups were statistically significant. The difference between the stromal dystrophy and normal cornea groups was not statistically significant (P =0.45). The stromal dystrophy group was included to account for surgery-associated keratocyte apoptosis. No TUNEL-stained keratocytes were detected in normal corneas. Cell morphologic changes consistent with apoptosis were detected by transmission electron microscopy (TEM) in keratocytes of keratoconus corneas, but not in keratocytes in normal corneas. Chronic keratocyte apoptosis associated with ongoing epithelial injury may link risk factors associated with keratoconus such as chronic eye rubbing, contact lens wear, or atopic eye disease. Similarly, increases that have been detected in several different degradative enzymes in keratoconus corneas could be associated with chronic keratocyte apoptosis and less than perfect control of release of intracellular contents.

KISA% index: a quantitative videokeratography algorithm embodying minimal topographic criteria for diagnosing keratoconus.

PURPOSE: To formulate and test an algorithm using minimal topographic criteria for accurately diagnosing clinical keratoconus. SETTING: Subspecialty cornea practice and Keratoconus Genetic Research Project. METHODS: Both eyes of 86 keratoconic patients who had never worn contact lenses and 195 normal participants were studied with the TMS-1 videokeratoscope to evaluate the KISA% index, an algorithm that topographically quantifies the phenotypic features of keratoconus. The diagnostic efficacy of the KISA% index was compared with that of the modified Rabinowitz/McDonnell (K- and I-S values) and the Maeda/Klyce (KCI% and KPI) indices. The same indices were calculated for an additional 8 eyes with keratoconus-suspect topography and 12 eyes with early keratoconus. RESULTS: The mean KISA% was significantly greater in the keratoconus group (10,382%) than in the normal control group (20.44%) with minimal overlap. At a cutoff point for KISA% of 100, 280 of 281 participants (99.6%) were correctly classified. In contrast, the correct classification rate for the other indices were KCI%, 274 of 281 (97.5%); KPI, 249 of 281 (88.6%); K, 272 of 281 (96.8%); I-S, 269 of 281 (95.7%). Six of the 8 eyes with keratoconus-suspect topography had a KISA% between 60% and 100%, and 11 of the 12 eyes with early keratoconus had a KISA% greater than 100%. CONCLUSIONS: The KISA% index set at 100 was highly sensitive and specific for diagnosing keratoconus; a range of 60% to 100% may be useful for designating suspects. This index is more useful than any of the other currently available tools for classifying patients with keratoconus for computerized segregation analysis and for distinguishing eyes with keratoconus from normal eyes in topographic screening of refractive surgical candidates.

Superficial lamellar keratectomy using an automated microkeratome to excise corneal scarring caused by photorefractive keratectomy.

Corneal haze is a recognized complication of excimer laser photorefractive keratectomy. When severe, it can result in the formation of a dense corneal scar, with a reduction in best corrected visual acuity. In extreme cases, medical treatment and repeated phototherapeutic excimer ablations may fail to restore corneal transparency. In these patients, penetrating keratoplasty (PKP) has been used to restore visual function. We describe a technique for excising a superficial corneal scar using an automated microkeratome. The resultant corneal surface is quite smooth, and good visual acuity may be restored without resorting to PKP.

Method for safer penetrating keratoplasty in patients with low scleral rigidity.

In eyes with low scleral rigidity, penetrating keratoplasty (PKP) is a high-risk procedure because forward movement of the lens-iris diaphragm can result in prolapse of intraocular contents, expulsive choroidal hemorrhage, and damage to the crystalline lens. We developed a method for safer PKP in eyes with low scleral rigidity. In this technique, the host cornea is incompletely excised and remains attached at the 6 and 12 o'clock positions while the cardinal sutures to secure the donor button over the host are placed. Donor endothelium is protected by an intervening layer of viscoelastic material. After the first 3 cardinal sutures are placed, the host button is completely excised and removed and the donor cornea is sutured. This technique prevents the unopposed forward movement of the lens-iris diaphragm and may reduce the risk of expulsive choroidal hemorrhage and spontaneous extrusion or damage to the crystalline lens during PKP in patients with low scleral rigidity.

Fluorescein test for the detection of striae in the corneal flap after laser in situ keratomileusis.

PURPOSE: To report a technique for detecting striae in the corneal flap after laser in situ keratomileusis. METHODS: Fluorescein dye was instilled in the eye, and the patient was asked to blink. The tear film was examined at the slit lamp with the cobalt filter 1 or 2 seconds after blinking. RESULTS: The uneven pattern of pooling in the tear film was a sensitive indicator of the presence of striae in the flap. CONCLUSION: This technique may be useful in detecting minimal striae in the corneal flap in patients with unexplained suboptimal visual acuity after laser in situ keratomileusis.

Accuracy of ultrasonic pachymetry and videokeratography in detecting keratoconus.

PURPOSE: To compare the accuracy of ultrasonic pachymetry measurements and videokeratography-derived indices in distinguishing keratoconus patients from those with normal eyes. SETTING: A subspecialty cornea practice (Los Angeles, California, USA) and the Keratoconus Genetics Research Project. METHODS: Corneal thickness was measured by ultrasonic pachymetry at the center and inferior margins of the pupil of 142 normal and 99 keratoconus patients The corneal surface topography of patients was studied with the Topographic Modeling System (TMS-1). The videokeratographs obtained were analyzed with a computer program that automatically calculates two indices derived from data points in the central and paracentral cornea: central K and I-S values. Linear discriminant analysis was used to determine the correct classification percentages using pachymetry measurements and indices derived from videokeratography as the independent variables. RESULTS: The range of corneal thickness in normal and keratoconic eyes overlapped considerably. In the discriminant analysis, videokeratography indices provided a 97.5% correct classification rate and pachymetry data, an 86.0% rate (P < .01, McNemar's test). CONCLUSION: Keratoconus is more accurately distinguished from the normal population by videokeratography-derived indices than by ultrasonic pachymetry measurements. This may be due to the large variation in corneal thickness in the normal population or the inability of ultrasonic pachymetry to accurately detect the location of corneal thinning in keratoconus by measuring standard points on the cornea. Pachymetry should not be relied on to exclude or diagnose keratoconus because the false-negative and false-positive rates are unacceptably higher than those obtained by videokeratography.

Keratoconus.

Keratoconus is a bilateral noninflammatory corneal ectasia with an incidence of approximately 1 per 2,000 in the general population. It has well-described clinical signs, but early forms of the disease may go undetected unless the anterior corneal topography is studied. Early disease is now best detected with videokeratography. Classic histopathologic features include stromal thinning, iron deposition in the epithelial basement membrane, and breaks in Bowman's layer. Keratoconus is most commonly an isolated disorder, although several reports describe an association with Down syndrome, Leber's congenital amaurosis, and mitral valve prolapse. The differential diagnosis of keratoconus includes keratoglobus, pellucid marginal degeneration and Terrien's marginal degeneration. Contact lenses are the most common treatment modality. When contact lenses fail, corneal transplant is the best and most successful surgical option. Despite intensive clinical and laboratory investigation, the etiology of keratoconus remains unclear. Clinical studies provide strong indications of a major role for genes in its etiology. Videokeratography is playing an increasing role in defining the genetics of keratoconus, since early forms of the disease can be more accurately detected and potentially quantified in a reproducible manner. Laboratory studies suggest a role for degradative enzymes and proteinase inhibitors and a possible role for the interleukin-1 system in its pathogenesis, but these roles need to be more clearly defined. Genes suggested by these studies, as well as collagen genes and their regulatory products, could potentially be used as candidate genes to study patients with familial keratoconus. Such studies may provide the clues needed to enable us to better understand the underlying mechanisms that cause the corneal thinning in this disorder.

Interobserver and intraobserver reliability of a classification scheme for corneal topographic patterns.

AIMS: To determine the interobserver and the intraobserver reliability of a published classification scheme for corneal topography in normal subjects using the absolute scale. METHOD: A prospective observational study was done in which 195 TMS-1 corneal topography maps in the absolute scale were independently classified twice by three classifiers--a cornea fellow, an ophthalmic technician, and an optometrist. From these observations the interobserver reliability for each category and the intraobserver reliability for each observer were determined in terms of the median weighted kappa statistic for each category and for each observer. RESULTS: For interobserver reliability, the median weighted kappa statistic for each category varied from 0.72 to 0.97 and for intraobserver reliability the range was 0.79 to 0.98. CONCLUSION: This classification scheme is extremely robust and even in the hands of less experienced observers with minimal training it can be relied upon to provide consistent results.

Surgical correction of incomplete cryptophthalmos in Fraser syndrome.

PURPOSE: To demonstrate favorable long-term visual outcome after ocular reconstruction in an infant with Fraser syndrome and with complete left cryptophthalmos. METHODS: Reconstruction of incomplete right cryptophthalmos in our patient was accomplished in a stepwise manner, beginning in the third week of life, by dissecting the eyelids from the cornea, reconstructing the conjunctival fornices with buccal mucosa, and repairing the upper lid coloboma in a flap reconstruction using the inferior eyelid margin. RESULTS: At age 3 years, the patient currently has good movement of the right eyelids when blinking, reasonable right tear function, and a visual acuity in the right eye between 20/200 and 20/360 on forced preferential looking. CONCLUSION: In selected cases of incomplete cryptophthalmos, oculoplastic and corneal surgery may result in useful vision and in good eyelid movement when blinking.

Tangential vs sagittal videokeratographs in the "early" detection of keratoconus.

PURPOSE: To illustrate the difference between tangential and sagittal videokeratographs in the "early" (subclinical) detection of keratoconus. METHODS: The clinically normal fellow eye of a patient with unilateral keratoconus was studied with a topographer, which can display both a sagittal and a tangential map on the same page using the same color scale. RESULTS: The tangential map depicted a pattern more consistent with keratoconus and provided a maximum power of 51 diopters compared with the 46 diopters of the sagittal map. CONCLUSIONS: Tangential videokeratographs, derived from instantaneous radius of curvature algorithms, may be more useful than sagittal displays for detecting subtle corneal topographic abnormalities.

Influence of contact lens wear on the corneal topography of keratoconus.

PURPOSE: Corneal videokeratography is frequently used to evaluate keratoconus patients, as it is believed to allow for a more thorough appreciation of the complex curvature changes associated with the anterior corneal surface. The goal of this study was to determine the qualitative and quantitative influence of soft and rigid contact lens wear on the corneal topography of keratoconus. METHODS: 205 keratoconus patients were analyzed by computerized videokeratography for both qualitative corneal topographic patterns and quantitative indices. Fifty-six patients were non-contact lens wearers, 130 wore polymethylmethacrylate (PMMA) or rigid gas permeable (RGP) contact lenses, and 19 wore soft contact lenses. Data from the keratoconus patients were also compared to a control group comprised of normal patients with no history of contact lens wear. RESULTS: All three keratoconus groups had a significantly increased frequency of an asymmetric bowtie/skewed radial axes (AB/SRAX) pattern compared with normals. Differences among the videokeratography patterns for the kertoconus patients included a significant shift from the AB/SRAX videokeratographic pattern to the irregular videokeratographic pattern in the rigid (PMMA or RGP) lens subgroup as well as an increased frequency of the irregular pattern in the soft contact lens group versus the no contact lens group (P < 0.0001). Additional differences between the rigid contact lens and no contact lens keratoconus groups included increased values for the quantitative indices of SAI, SRI, SIM-K, and central K in the rigid contact lens group (P < 0.05). CONCLUSIONS: The increased frequency of qualitative and quantitative corneal irregularity in the rigid contact lens keratoconus group may reflect a mechanical effect of contact lens wear or an advanced disease state in these patients limiting them to rigid lens wear. The advanced disease is evidenced by steeper SIM-K and Central K indices in the rigid contact lens group.

Videokeratography database of normal human corneas.

AIM: To form a database of videokeratography patterns and quantitative indices describing normal human corneas using the absolute scale. METHODS: Both eyes of 195 normal subjects were examined with a TMS-1 videokeratoscope. Videokeratographs were divided into 10 categories based on a classification scheme devised from the absolute scale and analysed with 10 quantitative indices devised to describe phenotypic features of keratoconus videokeratographs. Correlations were sought between videokeratograph patterns and quantitative indices. Additionally, data were analysed for differences in age, sex, and ethnicity. RESULTS: For symmetric videokeratography patterns, analysis in the absolute scale was similar to a previous study done in the normalised scale. In the asymmetric categories, analyses differed markedly. Using the absolute scale and our classification scheme more variation in normal videokeratography patterns could be appreciated. There was good correlation between quantitative indices and videokeratography patterns. Neither videokeratography patterns nor indices differed significantly between sex, ethnic groups, or age using two way analysis of variance. CONCLUSIONS: Pattern analysis of videokeratographs in the absolute scale using, a standard classification scheme, may be more useful in trying to determine whether a cornea is normal or represents subtle early disease than analysis in the normalised scale. Quantitative indices could remove the subjectivity from the decision making process thus facilitating universal reproducibility of videokeratography data interpretation.

Corneal dystrophies and keratoconus.

This year's reports have given us a better understanding of several dystrophies as well as improvements in diagnosis and treatment. Eight corneal dystrophies have now been mapped to specific chromosomes and of these lattice, granular, Avellino, and Reis Bückler's dystrophies map to the same region of chromosome 5q, raising the question whether they are the result of mutations in separate genes or of mutations within alleles of a single gene. Phototherapeutic keratoplasty appears to offer an advantage in the initial treatment of several dystrophies whose symptoms arise from superficial corneal change. Some success has been reported in reducing the degree of hyperopic shift that accompanies deeper ablations. Further support for the genetic basis of keratoconus comes from a study in monozygotic twins and from improvements in quantitative videokeratographic indices, which have also improved our ability to distinguish keratoconus from other topographic abnormalities of the cornea. A new hypothesis for the mechanism of keratoconus proposes that an increased expression of interleukin-1 receptors, acting through a paracrine pathway, may disturb keratocyte activity and turnover, leading to a loss of stromal mass.

Videokeratography of keratoconus in monozygotic twins.

PURPOSE: To determine the corneal topographic appearance in a pair of monozygotic twins and family members of the twins because one of the twins had keratoconus and the other appeared normal by clinical examination. METHODS: Clinical examination and videokeratography (Topographic Modeling System, Tomey) of the patient, his monozygotic twin brother, an older brother, and his parents were performed. The I-S values (difference in the average dioptric powers of symmetrical points between the inferior and superior cornea) were calculated. RESULTS: The patient, a 28-year-old man, had clinical keratoconus confirmed with videokeratography. Clinical examination of family members including a twin brother, an older brother and both parents revealed no corneal abnormalities. Videokeratography of the clinically normal twin brother showed inferior steepening with progression over time. The I-S value of the clinically normal brother was 1.36 (right eye) (greater than 2.00 SD of normal controls), which progressed to 1.69 (right eye), 1.32 (left eye) 5 months later and to 1.87 (right eye), 1.43 diopters (D) (left eye) 14 months later. Minimal asymmetric inferior steepening was noted in an older brother who had an I-S value of 0.81 (right eye), 1.27 (left eye). The mother appeared topographically normal. CONCLUSIONS: This study lends support to the existence of subclinical keratoconus detectable by videokeratography only.

Corneal topography.

As more clinicians utilize videokeratography, an understanding of corneal topography is assuming an increasing role in the practice of ophthalmology. During this past year investigators have critically examined the methods employed in the utility of these devices as well as the accuracy and reproducibility of the algorithms embodied in videokeratoscopes. Clinical studies of patients undergoing incisional surgery and excimer laser photoablation have yielded new information about the effects of surgery on corneal shape. This has resulted in new methods being devised to improve the ultimate refractive outcome of these procedures. Videokeratography screening prior to refractive surgery has received significant attention during this past year with articles focussing on screening for keratoconus, hypotheses about the effects of surgery on undetected keratoconus "suspects," and results of incisional surgery on patients with atypical inferior steepening. Additionally, a new software program devised to screen for keratoconus on an automated basis has been developed. Corneal pachymetric topography, a novel technique of corneal analysis, is described for the first time this year.