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Abstract

To describe baseline and longitudinal findings of the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. The CLEK Study is an 8-year, multi-center, natural history study of 1209 patients with keratoconus who were examined annually for 8 years. Its goals are to prospectively characterize changes in vision, corneal curvature, corneal status, and vision-specific quality of life. CLEK Study subjects had a mean age at baseline of 39.3+/-10.9 years. At study entry, 65% of the patients wore rigid contact lenses, and 14% reported a family history of the disease. Subjects exhibited a 7-year decrease in high- (2.03 letters) and low- (4.06 letters) contrast, best-corrected visual acuity, with 19% demonstrating decreases of 10 or more letters in high-contrast, best-corrected acuity and 31% of subjects demonstrating decreases of 10 or more letters in low-contrast, best-corrected acuity in at least one eye. Subjects exhibited an average 8-year increase in corneal curvature of 1.60D in the flat corneal meridian, with 24% demonstrating increases of 3.00D or more. The 8-year incidence of corneal scarring was 20%, with younger age, corneal staining, steeper baseline corneal curvature, contact lens wear, and poorer low-contrast visual acuity predictive of corneal scarring. Data from the National Eye Institute Visual Function Questionnaire suggest that the effect of keratoconus on vision-specific quality of life is disproportionate to its low prevalence and clinical severity. Although we report measures of disease severity and visual function across the CLEK sample, clinicians can begin to envisage the course of keratoconus in individual patients by determining whether factors predictive of disease progression are present in those patients.

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... [15,33,36] The Collaborative Longitudinal Assessment of Keratoconus (CLEK) study showed the most significant functional discomfort in women, not evidenced in the clinical examination. [37] A possible relationship between sex hormones and corneal biomechanical properties at different stages of life was raised after discovering that there are estrogen, progesterone, and androgen receptors on corneal epithelial cells and keratocytes. [38] High estrogen levels during pregnancy impair corneal biomechanics and thickness. ...
... [15,29,46,47] The CLEK study found a positive family history of keratoconus in 13.5% of the patients. [37] The Dundee University Scottish Keratoconus Study [48] reported a keratoconus rate of 5% for Caucasians and 25% for the Asian subgroup. This difference confirms a higher level of positive family history in populations with a higher prevalence of keratoconus. ...
... The CLEK study reported that 48% of keratoconus patients rubbed both eyes vigorously, and 2.2% rubbed only one eye. [37] Asymmetric keratoconus has also been correlated with eye rubbing. The mechanism behind this association includes the trauma on the ocular surface [53] that induces epithelial and stromal cells to secrete matrix metalloproteinases, which together with the release of inflammatory mediators lead to apoptosis of keratocytes and progressive loss of the stromal collagen and corneal thinning. ...
Article
Keratoconus is an ectatic corneal disease that affects both men and women, usually at a young age. Risk factors such as eye rubbing, environmental and genetic factors contribute to its pathogenesis. Keratoconus presents a variable prevalence, being as high as 5% of the population in the Middle East. In this review, an English-language search for keratoconus epidemiology was undertaken using the PubMed database. We present and discuss the findings of the most relevant epidemiological studies on keratoconus and describe its characteristics and risk factors, correlating them with its pathogenesis.
... KC affects both genders [90,127], but most of the recent publications report a male preponderance [36,130]. KC is known to affect all ethnicities [61,90,96,120,123]. ...
... Unfortunately, the oldest and most widely classification for the staging of KC has not been thus fas sufficient. Both the Amsler-Krumeich classification [3,66] and, the classification for the Collaborative Longitudinal Evaluation of Keratoconus Study (CLEK) [120] do not include topographic or tomographic criteria. ...
... In addition, since patients must contend with many more years of potential progression, there is often a greater need for corneal transplantation in these patients. [9][10][11][12] A detailed review of the literature indicates that information regarding the prevalence and incidence of KC in children is sketchy at best and altogether missing for very young children (2-12 years). We have, therefore, for the first time, undertaken this study to gather information on the clinical and presenting features of KC in a large cohort of young children from the pre-teen age group (2-12 years of age) in India. ...
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Purpose: To study the demographics and clinical profile of keratoconus (KC) presenting in pre-teen children in India. Methods: This was a retrospective case series conducted as a single-institutional study at a tertiary eye center in India. A total of 586 eyes from 294 KC patients (aged 12 years or less) without any active comorbid conditions of the eye were included in the study. Slit-lamp biomicroscopy was used to document the clinical signs of KC. Information on age; gender; reason for consultation; family history; history of allergy, atopy, and eye rubbing; manifest refraction; uncorrected and best-corrected distance visual acuity (UCVA and BCVA, respectively); clinical presentation; and contact lens usage were also analyzed, along with data on types of medical and surgical treatments for KC and their outcomes. Results: The mean age of this pediatric KC patient cohort was 9.3 ± 1.8 years, and there was a male (70%) preponderance. Baseline mean UCVA, BCVA, steep keratometry, and flat keratometry were 0.86 ± 0.58 logMAR, 0.44 ± 0.38 logMAR, 54.82 ± 8.4 D, and 48.21 ± 9.5 D, respectively. Progression, necessitating collagen crosslinking (CXL), was noted in 12.7% eyes. Post-CXL, visual and topographic parameters remained stable without any complications till 6 months posttreatment. However, in eyes that did not undergo CXL, significant progression over time (P < 0.001) was observed. A keratoplasty was required in 2.3% eyes. Conclusion: KC was present at an advanced stage in 25% of the pre-teens in our series, and therefore, it is an important diagnostic entity when a refractive error is diagnosed, even in very young children.
... Keratoconus severity was classified by CLEK (collaborative longitudinal evaluation of keratoconus) study criterion based on the steep keratometry reading into mild (<45 D), moderate (45-52 D) and severe (>52 D) stages. 17 Data were analyzed in SPSS.22 software (IBM Inc., Chicago, Illinois, USA). The Kolmogorov-Smirnov test was used to assess the normality of quantitative data distribution. ...
Article
Purpose To compare the corneal cone location on different maps and instruments and their agreements with elevation maps. Methods In 90 left eyes with bilateral keratoconus, the apex of cone location was determined based on the maximum simulated keratometry (Kmax) location on the anterior sagittal curvature map by Pentacam HR, the maximum curvature on the mean curvature map by ATLAS 9000, most elevated point of the island of positive elevation relative to the best fit sphere on the front and back corneal elevation maps by Pentacam HR, and thinnest point on the thickness map by Pentacam HR and Orbscan, and the thinnest points on pachymetry and epithelial thickness maps by RTVue OCT. Results There was a significant difference among the location on different maps along the x- and y- axes (p< 0.001). The lowest agreement with the cone apex on both front and back elevation maps was for the anterior sagittal curvature map and the highest agreement for the Pentacam thickness map. The majority of keratoconus cone apexes were displaced in the inferotemporal direction on the different maps except for the epithelial thickness maps. Conclusions Despite the variability between different devices and methods; the thickness map on the Pentacam HR showed the highest correlation with the front and back elevation maps, while the RTVue epithelial thickness map showed the poorest correlation. Based on this study, epithelial thickness maps and anterior curvature maps should be utilized with caution to determine the location of the cone.
... [1][2][3][8][9][10][11][12][13] In addition, associations between KCN and patient sociodemographic factors such as age, sex, and region of residence have been assessed. 1,[14][15][16] Although comorbid conditions and sociodemographic factors have been reported to have associations with KCN, existing studies are either not recent or have a small 5 sample size. 8,10,11,13 There is also a paucity of data on characteristics and risk factors which influence a patient's likelihood to undergo keratoplasty. ...
Article
Purpose To identify sociodemographic factors and comorbid conditions associated with receiving keratoplasty for keratoconus (KCN) Design Retrospective, cross-sectional study Methods Health records of KCN patients aged <65 years from 2011 to 2018 were obtained from the IBM MarketScan Database. A multivariable model adjusted for potential confounders was used to examine factors associated with the risk of receiving keratoplasty. Results Of 42,086 total KCN patients identified, 1,282 (3.0%) patients had keratoplasty to treat KCN. In the fully adjusted analysis, female sex (OR=0.87 [95% CI=0.78-0.98]) and living in metropolitan areas (OR=0.75 [0.63-0.90]) were associated with lower odds of receiving keratoplasty. Compared to individuals aged 10-19 years, those aged 20-29 (OR=1.77 [1.31-2.41]) and 30-39 (OR=1.61 [1.19-2.17]) were more likely to have keratoplasty, while individuals in the older age groups (50-64) did not show statistically significant associations. Conditions associated with higher odds of receiving keratoplasty were corneal hydrops (OR=4.87 [4.07-5.82]), Leber congenital amaurosis (OR=2.41 [1.02-5.71]), sleep apnea (OR=1.46 [1.25-1.71]), diabetes mellitus (OR=1.32 [1.13-1.54]), and depression (OR=1.22 [1.03-1.44]). Conditions associated with lower odds were prior contact lens usage (OR=0.61 [0.50-0.74]) and a history of glaucoma (OR=0.60 [0.49-0.73]). Conclusions This analysis of a large sample of KCN patients reveals previously unidentified risk factors associated with receiving keratoplasty including Leber congenital amaurosis, depression, and diabetes. Future research should examine if young patients with these conditions may benefit from more frequent follow-up and/or early crosslinking to reduce the need for subsequent keratoplasty.
... Keywords: Artificial intelligence, Corneal biomechanics, Corvis ST, Grading, Keratoconus, Machine learning Background Keratoconus (KC) is a bilateral ectatic disease of the cornea that is characterized by corneal steepening and thinning [1]. As a result, irregular astigmatism may lead to loss of vision. ...
Article
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Background To investigate machine-learning (ML) algorithms to differentiate corneal biomechanical properties between different topographical stages of keratoconus (KC) by dynamic Scheimpflug tonometry (CST, Corvis ST, Oculus, Wetzlar, Germany). In the following, ML models were used to predict the severity in a training and validation dataset. Methods Three hundred and eighteen keratoconic and one hundred sixteen healthy eyes were included in this monocentric and cross-sectional pilot study. Dynamic corneal response (DCR) and corneal thickness related (pachymetric) parameters from CST were chosen by appropriated selection techniques to develop a ML algorithm. The stage of KC was determined by the topographical keratoconus classification system (TKC, Pentacam, Oculus). Patients who were classified as TKC 1, TKC 2 and TKC 3 were assigned to subgroup mild, moderate, and advanced KC. If patients were classified as TKC 1–2, TKC 2–3 or TKC 3–4, they were assigned to subgroups according to the normative range of further corneal indices (index of surface variance, keratoconus index and minimum radius). Patients classified as TKC 4 were not included in this study due to the limited amount of cases. Linear discriminant analysis (LDA) and random forest (RF) algorithms were used to develop the classification models. Data were divided into training (70% of cases) and validation (30% of cases) datasets. Results LDA model predicted healthy, mild, moderate, and advanced KC eyes with a sensitivity (S n )/specificity (S p ) of 82%/97%, 73%/81%, 62%/83% and 68%/95% from a validation dataset, respectively. For the RF model, a S n /S p of 91%/94%, 80%/90%, 63%/87%, 72%/95% could be reached for predicting healthy, mild, moderate, and advanced KC eyes, respectively. The overall accuracy of LDA and RF was 71% and 78%, respectively. The accuracy for KC detection including all subgroups of KC severity was 93% in both models. Conclusion The RF model showed good accuracy in predicting healthy eyes and various stages of KC. The accuracy was superior with respect to the LDA model. The clinical importance of the models is that the standalone dynamic Scheimpflug tonometry is able to predict the severity of KC without having the keratometric data. Trial registration NCT04251143 at Clinicaltrials.gov, registered at 12 March 2018 (Retrospectively registered).
... In the present study, only 1.16% of patients with keratoconus underwent corneal transplantation during the mean follow-up period of 2.97 ± 1.59 years, which is much lower than what has previously been reported. Tuft et al. reported that 21.6% of the 5242 eyes studied underwent corneal transplantation during an average follow-up period of 54 months 10 , and the Collaborative Longitudinal Evaluation of Keratoconus study group reported that the eight-year incidence of corneal transplantation was 15% of the 2418 eyes of participants aged < 40 years 22 . The low rate of corneal transplantation in patients with keratoconus in our study compared to that in previous largescale studies might be attributable to the following reasons: (1) the follow-up period in our study was shorter than that of previous studies; therefore, we might have missed patients who underwent corneal transplantation after the study period and (2) the previous studies reported were published before imaging modalities had been improved; therefore, our study may comprise a large proportion of patients with mild keratoconus since it is now diagnosed more frequently and much earlier than it was in the past. ...
Article
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This nationwide population-based study investigated the incidence rate of and risk factors for the progression to corneal transplantation in patients with keratoconus in South Korea using claims data from the Health Insurance Review and Assessment service. Among the entire South Korean population, 10,612 patients newly diagnosed with keratoconus between January 2010 and June 2015 were identified and included in the study. During the study period, 124 patients (1.17%) underwent corneal transplantation, with an average follow-up period of 2.97 ± 1.59 years. The incidence rate of corneal transplantation in patients with keratoconus was 4.46 cases per 1000 person-years. The rate of corneal transplantation for keratoconus was relatively low in South Korea compared to other countries. Multivariate Cox regression analysis revealed that male sex (HR 2.37; 95% CI 1.61–3.50; P < 0.001), severe atopic dermatitis (HR 2.32; 95% CI 1.02–5.28; P = 0.044), obstructive sleep apnea (HR 9.78; 95% CI 1.36–70.10; P = 0.023), and intellectual disability (HR 4.48; 95% CI 1.33–15.11; P = 0.016) significantly increased the risk of progression to corneal transplantation. In patients with keratoconus, male sex, severe atopic dermatitis, obstructive sleep apnea, and intellectual disability were associated with an increased risk of corneal transplantation.
... K eratoconus (KC) is a chronic, progressive, and degenerative disease characterized by alterations at the corneostructural level such as thinning, protrusion, and increased curvature of the corneal tissue. 1 Generally, KC is an asymmetric condition whose structural changes lead to the appearance of refractive errors, especially irregular astigmatisms, which represent a significant loss of vision and, consequently, a great impact on quality of life. 2 Although KC usually appears in isolation, roughly a quarter of diagnosed patients report a positive family history of this disease, which suggests the influence of heredity in its etiopathogenesis. 3,4 Keratoconus was considered a noninflammatory disease, but recent studies have shown the alteration in the expression of molecules involved in inflammatory processes, as well as in oxidative stress, extracellular matrix proteolysis, and cellular apoptosis, 5-10 evidencing the participation of all of these biological mechanisms in the KC pathophysiology. ...
Article
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Purpose: To elucidate dysregulated proteins in keratoconus (KC) to provide a better understanding of the molecular mechanisms that lead to the development of the disease using sequential window acquisition of all theoretical mass spectra (SWATH-MS) as a protein quantification tool of the tear proteomic profile. Methods: Prospective cross-sectional study that includes 25 keratoconic eyes and 25 healthy eyes. All participants underwent a clinical, tomographic, and aberrometric exam. Tear sample was collected using Schirmer strips and analyzed by liquid chromatography with tandem mass spectrometry. SWATH-MS was used as a quantification tool of the tear proteomic profile. The expression of the quantified proteins was compared between groups, and the biological and molecular functions of the dysregulated proteins as well as their functional relationships were studied by in silico analysis. Results: A total of 203 proteins were quantified in tear samples of patients with KC and control participants, of which 18 showed differential expression between groups (P < 0.05). An increase in the expression of 7 proteins and a decrease in the expression of 11 proteins were observed. Protein-protein interactions and gene ontology analysis showed the involvement of these dysregulated proteins in structural, inflammatory-immune, iron homeostasis, oxidative stress, and extracellular matrix proteolysis processes. Conclusions: Tear protein quantification has revealed the dysregulation of proteins involved in biological processes previously associated with KC. Among them, iron homeostasis should be highlighted as a relevant pathway in the KC pathophysiology, and it should be taken into account in the development of therapeutic targets to cope with tissue damage derived from iron accumulation and toxicity.
... Visual http://annalsofrscb.ro hypertension was additionally substantially more typical in PK (26%) contrasted and DALK (6%). Strikingly, assumed corticosteroid-related height of intraocular pressure has been accounted for in up to 35% of keratoconus eyes after keratoplasty; along these lines, the advantage of momentary steroid inclusion might be critical [26][27][28]. ...
Article
Full-text available
The previous 20 years have seen a blast in our insight into keratoconus, joined by an extreme change of the board choices. A 2-hit speculation proposes a fundamental hereditary inclination combined with outer ecological elements, including eye scouring and atopy. The variable pervasiveness and regular history have been exceptional characterized remembering huge cone movement for middle age. Consequently, current administration should incorporate early conclusion, standard checking, and treatment of natural cofactors. Scenes and contact focal points stay basic to the optical administration of keratoconus. Intrastromal corneal ring portions have been progressively utilized, giving improvement in the corneal shape, rectified visual keenness, and contact focal point wear. Be that as it may, similar to contact focal points, intrastromal corneal ring portions don't treat the hidden sickness measure. In this manner, current methodologies should likewise think about medicines to limit keratoconus movement. Luckily, there is expanding proof that corneal collagen crosslinking will end or slow movement much of the time. Until generally as of late, infiltrating keratoplasty was the favored intercession for cutting edge keratoconus, with long haul achievement in the locale of 90%; be that as it may, the most serious danger of disappointment stays endothelial allograft dismissal. Profound foremost lamellar keratoplasty has arisen in the new thousand years as a favored way to deal with ration the host endothelium and dodge dismissal. In any case, the general prevalence of profound foremost lamellar keratoplasty contrasted and entering keratoplasty, as far as optical and endurance benefits are as yet discussed. This viewpoint gives an outline of our present information on keratoconus and current administration choices. A stage stepping stool way to deal with overseeing keratoconus is plot to furnish the specialist with a contemporary administration worldview.
... Soft CLs and corneal RGP lenses are utilised to treat the mild-to-moderate cases with scleral and hybrid lenses generally being fitted in more advanced stages. 24,25,26,27 Surgical management of KC can include intrastromal corneal segments (INTACS) and corneal cross-linking (CXL), which attempts to strengthen the cornea with bonds between collagen fibres and corneal transplants (keratoplasty). 27,28 Early diagnosis and intervention with CXL have made a positive impact on retarding the disease progression. ...
Article
Full-text available
Background: Keratoconus (KC) is a non-inflammatory, self-limiting corneal ectasia that causes reduced visual acuity and if left undiagnosed and/or untreated may lead to visual impairment. Optometrists remain the first point of contact for affected patients, making appropriate timeous care essential. Aim: To investigate keratoconus management in the public sector in KwaZulu-Natal, South Africa. Setting: Public sector eye care facilities in KwaZulu-Natal, South Africa. Methods: In a quantitative, cross-sectional study, a questionnaire was distributed to optometrists employed by the Department of Health in KwaZulu-Natal (DoH-KZN). Data on practitioner demographic profile and clinical competence, facility attendance statistics, resources available and KC clinical protocols were collected. Results: The response rate was 36 (71%). The optometrists’ mean age was 30.19 ± 4.53 years, and 80% of them had work experience of less than 10 years. The majority of the health facilities (63.9%) reported a monthly attendance of 51–300 patients, and, of these, 72% of the respondents reported seeing only between 1 and 10 keratoconic patients. A lack of equipment and/or fitting of contact lenses being disallowed by the DoH-KZN were cited by the majority (61%) as the reason for routinely referring KC patients to optometrists in private practice. Conclusion: This study highlights a deficiency in the minimum standard of optometric care for KC in the public sector in KZN, primarily because of a lack of equipment and resources. It is recommended that the management of KC at all levels of the public health system be reviewed to improve the quality of service for keratoconic patients.
... The Collaborative Longitudinal Evaluation of Keratoconus was a large prospective study of 2418 KC eyes with a mean age of 39.3 years. At the end of the follow-up, the patient's BCVA lost 2 Snellen letters compared to the baseline, which was quite stable38 . Wittig-Silva et al. conducted a clinical trial on progressive KC in patients 16 to 50 years of age and showed that at 24 months, the mean cylinder was stable (p = 0.15), but there was a significant progression of 1.2 D (p = 0.02) at 36 months 39 . ...
Article
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To present the natural course of keratoconus (KC) and compare pediatric and adult patients. Design A retrospective cohort study. Setting Hospital-based. Patient Population In total, 152 patients (288 eyes) diagnosed with KC at Chang Gung Memorial Hospital, Taiwan, were included. Previously managed patients and those with missing optical data were excluded. Observation Procedures Patients were divided into pediatric (≤ 18 years) and adult (> 18 years) groups. Demographics, clinical data, and optical variables were collected, including corrected distance visual acuity (CDVA), refractive error, and keratometric readings (K). Main Outcome Measure Optical variables at the final follow-up before aggressive treatment. Results In total, 20 pediatric (37 eyes) and 132 adults (251 eyes) patients were eligible for this study. The mean follow-up time was 2.98 years. Male predominance was observed in both groups. Both groups had similar clinical characteristics and optical variables at the initial diagnosis. Pediatric patients progressed significantly more rapidly in refractive errors, including spheres and cylinders, spherical equivalence, steep K, and flat K during the follow-up. However, significant change between the two study groups was only seen in sphere refractive error spherical equivalence. Conclusion Pediatric patients had more rapidly progressive KC than adult patients, so early detection and frequent follow-up for prompt interventions are necessary for these patients.
... [1] The collaborative longitudinal evaluation of KC study was the first optometry-based, multicenter, natural history study of 1209 patients with KC who were examined annually for 8 years in the United States of America. [2] Currently, there are no large-scale ethnic epidemiological similar studies in Asia for KC. We begin our issue with a review article on "KC epidemiology." ...
Article
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This editorial summary of the thematic issue “keratoconus”. The full text is free and can be downloaded from here.
... Less frequently it may initiate earlier in life, following a more aggressive and rapid progression (2)(3)(4). There is some variability in the presentation and evolution of this condition, although changes in ocular refraction provoked by the development of irregular astigmatism and the consequent loss of visual acuity (VA) are characteristic features of KC (5)(6)(7). The macroscopic and microscopic alterations that can be observed depend on the stage of KC and they include central or paracentral stromal thinning, the protrusion of the cornea as a cone, Fleischer rings, Vogt's striae, prominent corneal nerves, Munson's and Rizzuti's signs, sub-epithelial opacity, and stromal scarring (1). ...
Article
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Purpose Keratoconus (KC) is a corneal ectasia characterized by structural changes, resulting in progressive thinning and biomechanical weakening that can lead to worsening visual acuity due to irregular astigmatism. Corneal collagen Crosslinking (CXL) and Intracorneal Ring Segment (ICRS) are widely used treatments in KC disease, but the alterations they cause in biomechanical mediators are still poorly understood. The aim of this study was to analyze the tear proteome profile before and after treatments to identify biomarkers altered by surgery. Materials and methods An observational, prospective, case-control pilot study was conducted, analyzing tear samples from KC patients by nano-liquid chromatography-mass spectrometry (nLC-MS/MS). Data are available via ProteomeXchange with identifier PXD035655. Patients with KC who underwent ICRS surgery ( n = 4), CXL ( n = 4), and healthy subjects (Ctrl, n = 4) were included in this study. Clinical parameters were measured and tear samples were collected before and 18 months after surgery. Proteins with ≥2 expression change and p -value < 0.05 between groups and times were selected to study their role in post-operative corneal changes. Results These analyses led to the identification of 447 tear proteins, some of which were dysregulated in KC patients. In comparisons between the two surgical groups and Ctrls, the biological processes that were altered in KC patients at baseline were those that were dysregulated as a consequence of the disease and not of the surgical intervention. Among the biological processes seen to be altered were: immune responses, cytoskeleton components, protein synthesis and metabolic reactions. When comparing the two treatment groups (ICRS and CXL), the process related to cytoskeleton components was the most altered, probably due to corneal thinning which was more pronounced in patients undergoing CXL. Conclusion The changes observed in tears after 18 months post-operatively could be due to the treatments performed and the pathology. Among the deregulated proteins detected, A-kinase anchor protein 13 (AKAP-13) deserves special attention for its involvement in corneal thinning, and for its strong overexpression in the tears of patients with more active KC and faster disease progression. However, it should be kept in mind that this is a pilot study conducted in a small number of patients.
... Like many former studies, a gradual increase in corneal curvature and a decrease in visual acuity were observed in the CLEK study in patients with keratoconus [15]. Scratching triggers inflammation, the progression in the pediatric age group is higher than in adults due to excessive rubbing [16]. ...
Article
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Wearing Rigid High Gas-Permeable Contact Lens (RGPCL) is a primary method of vision rehabilitation in keratoconus eyes. The aim of the study is to investigate the effects of using RGPCL on the topographical variations at the keratoconus progress. All patients had undergone ophthalmic examination including corneal topography, and their medical history and keratoconus characteristics were documented. Fifty-one eyes of those who wore RGPCL without any problems and 42 eyes of those who did not wear any lenses were evaluated retrospectively. It was accepted that the follow-up period was terminated when patients received any treatment or change lenses. The mean follow-ups were 36.5±12.7 and 38.4±14.6 months in the control and lens-wearing samples, respectively. The changes in topographic indices were compared from the baseline to the final visit. The difference between spectacle-best corrected visual acuity was not significant in both groups from baseline to final visit (p>0.05). In the RGPCL wearing group, apical keratometric power ( Kmax ) increased from mean 51.86±3.70 diopter (D) to 52.54±3.85 D at the sagittal map in the following period, but this difference was not significant (p>0.05). Similarly, in the control group, Kmax increased from mean 52.14±2.51 D to 52.94±3.02 D, and this difference was not significant (p>0.05). Lens-wearing and control group mean keratometry values increased from 47.36±1.7 D and 47.17±1.65 D to 47.94±2.05 D and 47.74±1.76 D, respectively (p>0.05). Pachymetry at the thinnest corneal point decreased significantly in both groups from baseline to final visit (p=0.008, p=0.01). In conclusion, the comfortable usage of RGPCL has no effect on the progression of keratoconus.
... 13 Gender prevalence of keratoconus is still unclear but most of the studies show it is male predominant. 12,14,15 Two studies from North India 16,17 and one from Western India 18 shows it is male predominant. Only one study from Central India shows KC is predominant in female 10 Aetiology of KC is still poorly understood 19 Lots of theories and hypotheses suggested about KC such as genetic, metabolic, immunological, endocrinological, ecological, etc. Ultraviolet ray has negative effect so it more common in hot climate. ...
Article
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Purpose: Keratoconus is an ectatic disorder of cornea and mostly involve teen aged group, still the pathogenesis and aetiology is not clearly defined. We try to establish the progression of the diseases is inversely proportional to the age of onset of the patient. Design: It was an observational study, carried out at a private eye hospital where patient was referred for RGP contact lenses. Methods: This observational study was carried out from Jan’ 2017 to Dec’ 2019 total three year period and 304 patients with Keratoconus were in the initial study and we divided them into two groups. Group: A, ≤25 years old and Group: B, >25 years old but among these 304 patient we included 200 patients in our study those who completed minimum 3 years follow-up and meet the inclusion criteria. Results: After three years ‘K’ value in group: A, <0.0001 in group: B, <0.3655. Sim K’s Astigmatism <0.0001 in group: A. <0.0223 in group: B. Central corneal thickness <0.0001 in group: A and 0.1957 in group: B. ‘K’ value and central corneal thickness (CCT) deteriorate more in group: A, than group: B. It is also found that KC progress more in case of VKC and it is more prominent in dominant hand side. Conclusion: At diagnosis, keratoconus is often more advanced in children than in adults, with faster disease progression. Early detection and close monitoring are therefore crucial in young patients.
Article
Purpose: To investigate the effect of varying the fluid reservoir (FR) thickness of scleral lenses (SL) on corrected distance visual acuity (CDVA), contrast sensitivity (CS) and higher-order aberrations (HOAs) in keratoconic eyes. Methods: Forty eyes with keratoconus were fitted with a diagnostic Boston Sight SL having three different FR thicknesses. CDVA, CS and HOAs were measured before and after 30 min of lens wear. An i-Trace aberrometer and anterior segment optical coherence tomography (AS-OCT) were used to measure HOAs and FR thickness, respectively. Results: Statistically significant improvements in CDVA and CS were seen with different FR thickness lenses (p < 0.01). Baseline CDVA (0.22 ± 0.15) improved to 0.03 ± 0.06, 0.04 ± 0.07 and 0.07 ± 0.08 with low, standard and high FR lenses, respectively. Post-hoc testing showed better CDVA with low (p = 0.006) and standard FR (p = 0.009) lenses compared to high FR lenses. Before lens wear, CS was 1.27 ± 0.27, which improved to 1.67 ± 0.11, 1.73 ± 0.12 and 1.66 ± 0.89 with low, standard and high FR lenses, respectively. Lenses with standard FR showed better CS compared with those having low (p = 0.009) and high FRs (p < 0.001). A statistically significant reduction of higher order-root mean square aberrations (HO-RMS), coma, spherical aberration, secondary astigmatism and trefoil were found with all FR thickness lenses compared to baseline (p < 0.01). No significant difference was noted between lenses (p = 0.01). All three lenses corrected almost equal amount of HOAs. A moderate positive correlation was observed between CDVA and HO-RMS (r = 0.61, p < 0.001) for low FR lenses. Conclusions: BostonSight SCLERALs were found to be very effective in improving vision, CS and reducing HOAs in keratoconus. Lenses with varying FR thickness showed equal effectiveness in visual performance and reducing HOAs. FR thickness should be considered an important factor to provide better vision and CS by minimising HOAs, as well as to maintain the normal physiology of eyes with keratoconus.
Article
Purpose: Although previous studies have assessed the relationship between diabetes and keratoconus, the findings were controversial and warranted further clarifications. The objective of this study was to investigate the association between diabetes and keratoconus by conducting a systematic review and meta-analysis. Methods: A comprehensive literature search was performed to identify eligible studies reporting the association of diabetes with keratoconus from their inception to April 2021 through PubMed, Embase, and Web of Science. The quality of included studies was assessed using the Newcastle-Ottawa scale. Combined odds ratios (ORs) and 95% confidence intervals were calculated using a random-effects model. Results: In all, 8 case-control studies and 3 cohort studies reporting the association between diabetes and keratoconus were included in the meta-analysis. Diabetes was not associated with keratoconus in the overall analysis (combined OR = 0.85, 95% confidence interval: 0.66-1.10). The associations were found to be nonsignificant in subgroup analysis when stratified by study quality, design, source, types, and population. No publication bias was detected from either the Egger test (P = 0.46) or Begg test (P = 0.16). Sensitivity analysis revealed that differences between groups were not statistically significant. Conclusions: This meta-analysis indicates that current literature does not support a significant association between diabetes and keratoconus. Further studies with more definite control for confounders and well-designed cohorts or interventions are warranted.
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Keratoconus (KC) is a multifactorial disease for which genetic, biomechanical, and environmental components are involved. The knowledge of biomechanical component of the cornea, together with the associated inflammatory factor, has aroused great interest in the scientific community regarding the role of eye rubbing in the genesis and/or progression of keratoconus. Eye rubbing is a common physiological response induced by several facts: fatigue, dust or allergen exposure, contact lens wear, stress, inflammation, among others. Studies carried out by our group described in this chapter have shown that the impact of eye rubbing in keratoconus eyes is different from healthy eyes, probably due to their previously altered and lower biomechanics metrics, and therefore should be widely prohibited in keratoconus eyes. The chapter also describes a way of measuring the mechanical trauma induced by eye rubbing in the ocular surface through a snake cell protein, which is a nuclear morphologic alteration of the conjunctival epithelium considered an indicator of mechanical stress on the ocular surface such as eye rubbing; discusses the presence of this alteration in both keratoconus eyes and allergic eye rubbers; and suggests that the eye-rubbing event by itself is not a cause of KC; however, its association as a risk factor is not questioned.KeywordsKeratoconusEye rubbingScheimpflug imagingSnake like protein cells
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This work intends to determine the optimal refractive spectacle and scleral lens corrections for keratoconus patients using the visual Strehl (VSX) visual image quality metric and the SyntEyes models with the synthetic biometry of 20 normal eyes and 20 keratoconic eyes. These included the corneal tomography and intraocular biometry. A series of virtual spherocylindrical spectacle and scleral lens corrections spanning the entire phoropter range were separately applied to each eye, followed by ray tracing to determine the residual wavefront aberrations and identify the correction with the highest possible VSX (named a "focus"). To speed up calculations, a smart scanning algorithm was used, consisting of three consecutive scans over increasingly finer dioptric grids. In the dioptric space, the VSX pattern for normal eyes considered over the correction range for either spectacle or scleral lens corrections resembled an hourglass with one distinct focus and a quick drop in VSX away from that focus. For 18 of the 20 keratoconic eyes, the spectacle-corrected VSX pattern resembled a shell that in 9 of the 20 cases showed two foci separated by a large dioptric distance (13.3 ± 4.9 diopters). In keratoconic eyes, scleral lenses also produced hourglass patterns, but with a VSX lower than in normal eyes. The hourglass pattern in dioptric space shows how, in normal eyes, the refracting process automatically funnels practitioners toward the optimal correction. The shell patterns in keratoconus, however, present far more complexity and, possibly, multiple foci. Depending on the starting point, refracting procedures may lead to a local maximum rather than the optimal correction.
Article
Aims To evaluate the rates of keratoconus progression and associated factors in eyes of children and adolescents. Methods Retrospective, cohort study of individuals ≤18 years old at the time of keratoconus diagnosis and with at least 6 months of follow-up. Corneal tomography was performed using an Orbscan tomographer (Bausch & Lomb, Rochester, New York, USA) to determine whether progression occurred. Tomographic progression of keratoconus was defined as a change in any of the investigated parameters (keratometry values, K MAX , maximum anterior or posterior elevation, central pachymetry, thinnest pachymetry) beyond the limits of repeatability. Results 148 eyes of 106 patients with a mean age of 15.2±2.5 years were studied over a mean follow-up period of 2.9±2.2 years. The overall rate of tomographic progression was 77.0% (114/148 eyes). Eyes that progressed had more advanced disease at presentation with higher anterior curvature (K MAX 55.4±6.3 vs 52.2±5.4 dioptres; p<0.01), posterior elevation (108.2±40.9 vs 86.3±35.6 µm; p<0.01) and lower central pachymetry measurements (442.1±56.7 vs 454.4±47.5 µm; p=0.01). Age at presentation, gender, atopy, documented eye rubbing, ethnicity and duration of follow-up were not significantly associated with progression in the multivariate analyses. There was a higher rate of bilateral progression if at least one eye had severe keratoconus (73.9%) compared with no severe keratoconus in either eye (36.8%; p=0.03). Conclusions A high rate of progression was identified in keratoconic eyes of children and adolescents. More advanced disease at initial presentation may increase the risk of further keratoconus progression.
Article
The aim of this study was to investigate the relationship between keratoconus disease and the antioxidant activities of catalase (CAT), reduced glutathione (GSH) and superoxide dismutase (SOD) and the level of the oxidative stress marker malondialdehyde (MDA) in serum. The study included 50 patients diagnosed with keratoconus and 53 healthy age- and sex-matched control subjects. The keratoconus patients were grouped according to the four keratoconus stages based on the modified Krumeich keratoconus classification system. The CAT, GSH and SOD activities and MDA levels in the serum samples collected from the patient and control groups were compared. The mean serum CAT, GSH, SOD and MDA levels in the keratoconus group were determined to be 0.075 (0.074–0.078)U/L, 0.002 (0.001–0.006) mmol/ml, 1.56 (1.51–1.62)U/L and 1.69 (1.65–1.99) mmol/L, respectively, and those in the control group were determined to be 0.024 (0.013–0.037)U/L, 0.029 (0.018–0.049) mmol/ml, 4.13 (4.01–4.17) U/L and 0.74 (0.65–0.82) mmol/L. The serum GSH levels and SOD activity were significantly lower in the keratoconus group (p < 0.001 for both) than in the control group while the CAT activity and MDA levels were significantly higher (p < 0.001 for both). The low serum GSH levels and SOD activity and the high CAT activity and MDA levels observed in this study suggest the presence of oxidative stress and inadequate antioxidant defence mechanisms in keratoconus patients. The studied parameters may offer auxiliary markers for use in the diagnosis and treatment of the keratoconus disease and in its potential therapeutic targets in the future.
Article
Keratoconus is morphologically associated with increasing deformation, thinning and scarring of the cornea. This functionally leads to refractive changes and visual deterioration. In the early stages there are often no clear clinical signs in the slit-lamp examination; however, confirming the diagnosis as early as possible is important in order to provide patients with an appropriate treatment. For the early diagnosis of keratoconus, various diagnostic devices have been introduced in recent years and decades. These include keratometry with reflection-based or elevation-based systems and optical coherence tomography. High-frequency ultrasound microscopy and corneal biomechanics can also be used to establish the diagnosis of keratoconus by the measurement of other parameters. The necessity and the available possibilities for early diagnosis of keratoconus are presented in more detail in this article.
Article
Purpose: Early diagnosis of keratoconus (KCN) and corneal collagen cross-linking can ensure that best-corrected visual acuity is preserved. We report the sequence of events leading to the diagnosis of KCN, as well as its impact on quality of life. Methods: This survey-based study included patients diagnosed with KCN for the first time at our center. Their corneal tomography was analyzed, and they were provided with a proforma and the NEI-VFQ-25 questionnaire and were asked to answer the given set of questions. Results: The study included 328 eyes of 164 patients. At the time of diagnosis, 112 (68.3%) patients were not aware of a disease called "keratoconus." VKC was present in 56 patients, and 92 patients were not aware of the need to avoid eye rubbing. In total, 101 patients gave a history of sleeping more often on the side with worse KCN. The preferred primary point of contact was an optometrist for 45.1% of patients; 51.2% of patients reported never having visited an ophthalmologist. Sixty-four (39%) patients were advised a screening test to rule out KCN before presenting to our center; 42 (71.8%) of these patients did not get it done. Vision-targeted score showed a significant negative correlation with grade of KCN (r value: -0.471) and positive correlation (r value: 0.534) with LogMAR vision. Conclusion: KCN is a disease of the young and severely affects the quality of life. Improving awareness of the general public, ensuring timely referral by optometrists, and keeping a high index of suspicion is emphasized.
Article
Objectives: To assess the quality-of-life improvement after scleral lens fitting in patients with keratoconus. Methods: We conducted a prospective observational study of all consecutive patients with keratoconus starting scleral lens fitting in 2019, from January 2 to December 27, at the Dijon University Hospital, France. Quality of life was assessed before and after wearing scleral lenses for 3 months through the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ 25) questionnaire. We investigated factors potentially influencing quality of life: final visual acuity, keratoconus stage, and maximum keratometry reading. Results: In total, 41 eyes of 24 patients were successfully fitted with scleral lenses, 92.9% were 18 mm in diameter and 7.1% were 17 mm. The visual acuity improved by -0.4±0.3 logarithm of the minimum angle of resolution (P<0.001) after scleral lens fitting. Visual gain increased with keratometry and keratoconus severity (P<0.001; P<0.01). The NEI-VFQ 25 score increased by 19.5±19.1 points on average (P<0.001). No association was found between the factors under study and improvement in quality of life. Conclusion: Our study confirms the functional improvement in patients with keratoconus fitted with scleral lenses, especially in patients with more advanced disease. Moreover, it suggests a major role of these lenses in improving quality of life, independently of the severity of the disease and the visual gain.
Resumen Introducción El queratocono es la ectasia corneal más frecuente y la segunda causa de queratoplastia en el mundo. Las características clínicas y epidemiológicas del queratocono no han sido apenas estudiadas en España y, hasta la fecha, no se ha hecho ningún trabajo en Asturias. Material y métodos Se realizó un estudio transversal analizando todos los casos de queratocono diagnosticado en las primeras consultas de la sección de Córnea y Superficie de los centros Hospital Universitario Central de Asturias (Oviedo) y Hospital Universitario de Cabueñes (Gijón) entre 2017 y 2020. A todos los pacientes se les recogieron datos demográficos, agudeza visual y se les realizó una topografía corneal. Resultados Se incluyeron un total de 112 pacientes (42,0% mujeres y 58,0% hombres). La edad media era de 36,84 ± 15,59, teniendo un 39,3% una edad superior a 40 años. Un 31,8; 28,0; 15,0 y 25,2% se encontraban en los estadios i, ii, iii y iv, respectivamente, en la escala Amsler-Krumeich. En un 7,5% se implantaron segmentos corneales, en un 4,7% se realizó cross-linking y en un 13,2% se realizó queratoplastia. Conclusión Aproximadamente un 40% de los queratoconos se detectan en estadios avanzados y otro 40% a una edad superior a los 40 años. Un 13% de los mismos requieren queratoplastia, por lo que sigue siendo una indicación frecuente en nuestro medio. Es necesario, por tanto, realizar un diagnóstico precoz para actuar antes de que exista una pérdida visual irreversible.
Article
Strong evidence suggests that corneal crosslinking is a safe procedure capable of stopping or slowing down the progression of keratoconus, avoiding visual loss associated with progression, and delaying or preventing the need for corneal transplantation. The progressive and chronic nature of the disease makes the option for prompt crosslinking upon keratoconus diagnosis in a pediatric patient valid.
Article
Introduction Keratoconus is the most frequent corneal ectasia and second most common cause of keratoplasty worldwide. The clinical and epidemiological characteristics of keratoconus have rarely been studied in Spain, and to date, no study has been done in Asturias. Material and methods A cross-sectional study was conducted to analyze all cases of keratoconus diagnosed in the first consultations of the Cornea and Surface section of the Hospital Universitario Central de Asturias (Oviedo) and Hospital Universitario de Cabueñes (Gijón) between 2017 and 2020. Demographic data, visual acuity and corneal topography were collected. Results A total of 112 patients (42.0% women and 58.0% men) were included. The mean age was 36.84 ± 15.59, with 39.3% being older than 40 years. 31.8%, 28.0%, 15.0%, and 25.2% were in stages I, II, III and IV, Amsler-Krumeich scale, respectively. Corneal segments were implanted in 7.5% of patients, cross-linking was performed in 4.7%, and keratoplasty was performed in 13.2%. Conclusion Approximately 40% of keratoconus cases are detected at advanced stages and another 40% are detected at an age over 40 years. 13% of these patients require keratoplasty, which is why it is frequently performed in our setting. Therefore, early diagnosis before irreversible visual loss is necessary.
Chapter
Corneal ectasia is a group of disorders affecting the shape of the cornea. Keratoconus is the most common primary ectasia. It usually appears in the second decade of the life and affects both genders and all ethnicities. It is bilateral, usually asymmetric, and characterized by central or paracentral stromal thinning and protrusion that leads to a conical shape. Corneal thinning is thought to be related to a combination of increased activity of stromal proteinase enzymes and decreased proteinase inhibitors with subsequent reduced biomechanical stability. Visual loss occurs primarily from irregular astigmatism and myopia, and secondarily from corneal scarring. Ocular signs and symptoms vary depending on disease severity. The disease process results in mild to marked impairment of the quality of vision. Particular risk factors include vigorous eye-rubbing especially related to ocular allergies. Irregular “scissor” reflex in retinoscopy, “oil droplet” reflex, Rizzuti’s sign, Munson’s sign, Vogt’s striae, and Fleischer’s ring are some of the clinical signs of keratoconus. It is usually diagnosed during the first or second decade of life and progresses until the third or fourth decade when stabilization is expected. Corneal topography and tomography are the usual methods for the early detection and monitoring its progression. When progression stops, clinical features can range from mild irregular astigmatism to severe thinning, protrusion, and scarring requiring keratoplasty. Several classifications have been proposed based on morphology, disease evolution, ocular signs, and index-based systems. Keratoconus is one of the main reasons for keratoplasty in the developed world, although this demand is decreasing with the onset of corneal collagen crosslinking.
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Objectives: To determine corneal biomechanical and tomographic factors associated with keratoconus (KC) progression. Materials and methods: This study included 111 eyes of 111 KC patients who were followed-up for at least 1 year. Progression was defined as the presence of progressive change between the first two consecutive baseline visits in any single parameter (A, B, or C) ≥95% confidence interval or two parameters ≥80% confidence interval for the KC population evaluated by the Belin ABCD progression display. The eye with better initial tomographic findings was chosen as the study eye. Analyzed Pentacam parameters were maximum keratometry (Kmax), minimum pachymetry (Kmin), central corneal thickness, thinnest corneal thickness, 90° vertical anterior and posterior coma data in Zernike analysis, and Belin Ambrosio Enhanced Ectasia Display Final D value. Corneal hysteresis (CH) and corneal resistance factor (CRF) were analyzed together with the waveform parameters obtained with Ocular Response Analyzer (ORA). Factors related to KC progression were evaluated using t-tests and logistic regression tests. Statistical significance was accepted as p<0.05. Results: There were 44 (mean age: 27.1±8.5 years, female: 25) and 67 (mean age: 31.1±9.1 years, female: 36) patients in the progressive and non-progressive groups, respectively. Although Pentacam parameters along with CH and CRF were similar between the two groups, ORA waveform parameter derived from the second applanation signal p2area was statistically significantly lower in the progressive group (p=0.02). Each 100-unit decrease in p2area increased the likelihood of keratoconus progression by approximately 30% in the logistic regression analysis (β=0.707, p=0.001, model r2=0.27). Conclusion: Parameters derived from the second applanation signal of ORA may be superior to conventional ORA parameters and corneal tomography in predicting KC progression.
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Purpose: To investigate whether visual experience with habitual blur alters the neural processing of suprathreshold contrast in emmetropic and highly aberrated eyes. Methods: A large stroke adaptive optics system was used to correct ocular aberrations. Contrast constancy was assessed psychophysically in emmetropic and keratoconic eyes using a contrast matching paradigm. Participants adjusted the contrasts of gratings at various spatial frequencies to match the contrast perception of a reference grating at 4 c/deg. Matching was done both with fully corrected and uncorrected ocular aberrations. Optical correction allowed keratoconus patients to perceive high spatial frequencies that they have not experienced for some time. Results: Emmetropic observers exhibited contrast constancy both with their native aberrations and when their aberrations were corrected. Keratoconus patients exhibited contrast constancy with their uncorrected, native optics but they did not exhibit constancy during adaptive optics correction. Instead. they exhibited striking underconstancy: they required more contrast at high spatial frequencies than the contrast of the 4-c/deg stimulus to make them seem to have the same contrast. Conclusions: The presence of contrast constancy in emmetropes and keratoconus patients viewing with their native optics suggests that they have learned to amplify neural signals to offset the effects of habitual optical aberrations. The fact that underconstancy was observed in keratoconus patients when their optics were corrected suggests that they were unable to learn the appropriate neural amplification because they did not have experience with fine spatial detail. These results show that even adults can learn neural amplification to counteract the effects of their own optical aberrations.
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Keratoconus (KC) is a corneal disorder whose etiology shares a close relationship with Lactoferrin (LTF) dysregulation and Toll-like Receptors 2 (TLR2) overexpression. This study shows how these two important biomarkers are clinically and molecularly interrelated, increasing knowledge about KC pathophysiology, and opening the door to future therapies. In this prospective clinical study, serum and tear LTF concentrations were quantified in 90 KC patients and 60 controls. A correlation analysis with multiple blood and tear immunoinflammatory mediators, and KC-associated tomographic parameters, was performed. An in vitro study using HEK-BlueTMhTLR2 cell cultures was also conducted to determine the expression and functionality of TLR2 under the influence of LTF treatment. As a result, a LTF decreased was observed in KC patients compared to controls (p < 0.0001), evidencing the strong correlation with TLR2 overexpression at systemic and ocular surface level, with inflammatory mediator upregulation and with KC severity. In stimulated cell cultures, TLR2 expression was decreased using 2 mg/mL of LTF. The levels of secreted embryonic alkaline phosphatase (SEAP) and interleukin-8 (IL-8) were also reduced in supernatants after LTF treatment. As conclusions, the dysregulation of LTF and TLR2 in the ocular surface of KC patients contributes to KC severity by maintaining a detrimental chronic immune–inflammatory state. The immunomodulatory properties of LTF on TLR2 expression suggest its potential as a therapeutic approach for KC.
Chapter
Keratoconus is a progressive, ectatic disorder of the cornea. With the advances in the diagnosis and treatment of keratoconus, modern staging systems have been recently devised. The improved diagnostic modalities consider various parameters such as the anterior and posterior corneal curvatures and thickness measurements, not only at the apex of the cone but also at the thinnest points. The newer staging systems for keratoconus seem to better reflect the anatomical changes seen in keratoconus.KeywordsKeratoconusAmsler-Krumeich classificationABCD classificationTopography patterns
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This chapter elaborates on different classification systems for keratoconus and their application to clinical practice in terms of staging, assessing progression, and assessing response to treatment with corneal cross-linking.
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Keratoconus is a progressive ectatic disorder of the cornea, characterized by conical steepening and thinning. It typically manifests at puberty and is almost always bilateral, albeit often asymmetric. Although keratoconus has been intensively investigated, its cause remains elusive. It is clear, however, that this multifactorial disease is influenced by a complex interplay of genetic and environmental factors. Although keratoconus is most commonly an isolated ocular pathology, numerous systemic conditions have been linked to its development and progression. The majority of these systemic associations has generally been classified into conditions of atopy or eczema leading to eye rubbing, connective tissue disorders with abnormal collagen elasticity, and abnormal retinal function or low mental status associated with oculodigital stimulation.
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Keratoconus can fundamentally alter the psychosocial profile of an individual, given its adolescent onset and high disease burden. Among the medical community, the concept of a keratoconic personality characterized by anxiety, insecurity, and distrust is widespread. However, review of the literature reveals mixed evidence about the psychiatric traits of keratoconic patients and fails to clarify a personality profile specific to keratoconus. Rather, patients with keratoconus likely experience significant impact on their quality of life during their formative adolescent years, even in the presence of good corrected visual acuity. As a result, patients may develop and display maladaptive coping mechanisms, especially in interfacing with healthcare systems, leaving providers with the impression of a “keratoconic personality.” A dissonance between the patient and provider assessment of disease burden can further interfere with a healthy patient-provider relationship and subsequent care patterns. Keratoconus is also associated with other mental health disorders such as depression. Providers must consider the significant psychological impact of keratoconus when caring for these patients.
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Keratoconus presents a variable prevalence, being as high as almost 5% of the population in the Middle East. In this chapter, we present the most relevant epidemiological studies of keratoconus and discuss their findings and limitations. In the second part, we describe its epidemiological characteristics and risk factors such as eye rubbing, allergy, environment, genetics, and heredity, and correlate them with its pathogenesis.
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Keratoconus is a progressive disease characterized by thinning of the corneal stroma leading to irregular astigmatism and defective vision. It is mostly bilateral. The incidence of the condition is rising with various screening tools available for laser refractive surgery. The prevalence varies in different parts of the world. Various local and systemic conditions are associated with keratoconus. Recently, eye rubbing has been attributed as an aggravating factor.KeywordsKeratoconusEpidemiologyPrevalence
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Keratoconus forms the majority among all corneal ectatic disorders, and various causative factors have been implicated, of which ocular allergic diseases are of major significance. The commonly proposed pathogenesis includes the release of inflammatory mediators due to eye rubbing which may alter the corneal collagen and lead to corneal ectasia. The disease onset is often early in cases with atopy, and routine corneal tomography is able to detect subclinical forms of keratoconus. Corneal ectatic disorder patients associated with eye rubbing remain more prone to develop acute corneal hydrops with subsequent visually significant stromal scarring, thus warranting contact lens usage and early need of keratoplasty for visual rehabilitation. Therefore, control of allergy and eye rubbing is the best measure to prevent corneal ectasia in cases of ocular allergy.KeywordsKeratoconusAllergic eye diseaseVernal keratoconjunctivitisInflammatory mediatorsTopography
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In this chapter, the authors address the importance of rigid gas permeable (RGP) corneal lenses in the treatment of keratoconus. They discuss the recommended exams and their importance in the fitting of this type of lens and describe the fitting methods of conventional design lenses, such as apical clearance, apical bearing, and three-point touch. They also introduce the new generations of RGP lenses, available in the Brazilian market, with their customizable special designs and parameters.KeywordsKeratoconusRigid Gas Permeable Contact LensesMonocurve DesignAspheric DesignMulticurve DesignFitting
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Keratoconus is the main ectatic disease characterized by the progressive thinning of the cornea which develops irregular astigmatism and reduction of visual acuity. The corneal curvature is the main factor used to determine the disease phase and severity. Nowadays, corneal intrastromal rings, cross-linking, and transplant are modalities available for keratoconus. The primary aim of the alternative techniques other than transplantation is to prevent progression and to rehabilitate vision by using glasses and/or contact lens. However, in some cases, one may not get satisfactory refractive results with good visual acuity, and, then, it is up to the ophthalmologist to choose the best transplant technique. In this chapter we will talk about the main indications and contraindications for anterior lamellar corneal transplantation. It’s well known in the literature that intolerance to contact lens, corneal intrastromal rings intolerance (keratometry >58D, corneal thinning in the ring path), and haze post-cross-linking are the main indications for anterior lamellar corneal transplantation. On the other hand, some cases with severe dry eye syndrome, stein cell limbic deficiency, and irregular palpebral edge may be contraindications for the procedure. For a long time, keratoconus in moderate and advanced stages has been treated as penetrating keratoplasty. With the development of new techniques, DALK has become more replicable and popular, with low rates of rejection and better visual outcomes.KeywordsDALKCorneal anterior lamellar keratoplastyAdvanced keratoconusIntracorneal ring segmentsCross-linkingKeratoconusKeratoplastyIndication keratoplastyContraindication keratoplasty
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Keratoconus (KC) takes part in a group of ectatic corneal disease (ECD) that are characterized by progressive thinning and subsequent bulging of the cornea. Different treatments have been proposed, and with so many current options, having the knowledge of the best time to indicate each one becomes necessary. This chapter summarizes this, discussing them within a flowchart.KeywordsKeratoconusKeratoconus flowchartKeratoconus treatmentKeratoconus managementCorneal ectatic
Article
Purpose: To investigate a method to identification of early progression of keratoconus using deep learning neural networks. Methods: Retrospective evaluation of medical records of patients with progressive keratoconus and had more than one followup visits. Images extracted from the single scheimplug analyzer for analysis were captured during the patient visits. The baseline progression of keratoconus is detected by a change in flat or steep K of ≥1.0D which is labeled as keratometric progression (KP) and progression detected by image based deep learning convolutional neural network (CNN) models, is labeled as latent progression (LP). Patient data consisted of model data (385 eyes of 351patients) to train and test the learning models and prediction data (1331 eyes of 828 patients) to determine the LP based on the learning models. Results: The LP prediction model was able to identify progression at a mean of 11.1 months earlier than KP (p < 0.001). LP prediction model was able to identify progression earlier than KP irrespective of age category, gender, the severity of keratoconus, presenting visual acuity, astigmatism, and spherical equivalent (P < 0.001). When compared to the first visit the corrected distance visual acuity was more stable in 71% of the eyes at LP prediction visit compared to 50% at KP visit (p < 0.001). Conclusion: Through this study, we propose a possible solution to address the shortcomings noted in the current approaches of detecting progression relying only on KP. Avoiding bias towards feature selection from tomography images as done in the current study aids in identifying very subtle changes on the images between visits.
Article
Objective: To compare corneal biomechanics and intraocular pressure (IOP) in keratoconus and penetrating keratoplasty eyes before and after nonfenestrated scleral lens wear. Methods: Twenty-three participants were enrolled, and 37 eyes were included in the analysis (11 penetrating keratoplasty and 26 keratoconus). A range of corneal biomechanical parameters and IOP were measured using the CORVIS ST before and after 8 hr of nonfenestrated scleral lens wear (Keracare, Acculens, Denver, CO). Results: Before lens wear, penetrating keratoplasty eyes displayed significantly greater median values for central corneal thickness (97 μm thicker, P=0.02), IOP (3.89 mm Hg higher, P=0.01), and biomechanical parameter A2 length (0.48 mm longer, P=0.003) compared with keratoconic eyes. No significant changes in corneal biomechanical parameters or IOP were observed after scleral lens wear in either group (all P>0.05). Conclusion: Although nonfenestrated scleral contact lenses can induce a subatmospheric pressure after lens settling and compress tissue surrounding the limbus, no significant changes were detected in the corneal biomechanical parameters studied using CORVIS ST after scleral lens wear in eyes with penetrating keratoplasty and keratoconus.
Article
Clinical relevance: Evaluation of corneal higher-order aberrations can be used clinically to diagnose early cases of keratoconus as well as to classify the severity of keratoconus. Background: To investigate the anterior and posterior corneal higher-order aberrations (HOAs) up to the sixth order and their ability to identify early keratoconus (KCN) as well as differentiate different severities of KCN using cross-validation analysis. Methods: This prospective cross-sectional comparative study was performed at a tertiary eye hospital in Tehran, Iran, in 2019. The study sample consisted of 95 eyes of 95 patients with KCN and 53 eyes of 53 normal individuals. The eyes with KCN were classified into three groups based on the Amsler-Krumeich classification system: group 1 (mild KCN), group 2 (moderate KCN), and group 3 (severe KCN). Corneal wavefront analysis was performed using Pentacam HR. Results: Based on the magnitude of AUC, posterior vertical secondary coma (Z5-1) had an excellent discriminant ability (AUC: 0.91) and anterior vertical coma (Z3-1) and anterior vertical secondary coma (Z5-1) had a good discriminant ability (0.8 < AUC < 0.89) for differentiating eyes with mild KCN from normal eyes. The anterior and posterior primary spherical aberrations (Z4°) had an excellent ability (AUC > 0.9), and anterior secondary spherical aberration (Z6°) had a good ability (AUC: 0.83) for differentiating moderate from mild KCN. In the differentiation of severe from moderate KCN, anterior and posterior primary aspherical aberrations (Z4°) had a good AUC value (AUC > 0.8). Conclusion: Coma-like aberrations had a good discriminant ability between normal eyes and eyes with mild KCN. Spherical aberrations showed a good ability for differentiating between different stages of KCN. The cut-off values reported in this study can be used for early detection of KCN as well as classification of KCN severity.
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Purpose: This study was conducted to determine the agreement and test-retest repeatability of two methods for measuring corneal curvature in keratoconus: keratometry and the First Definite Apical Clearance Lens (FDACL). Our interest in the FDACL procedure stems from the important contact lens-fitting information and documentation of disease progression provided by the FDACL trial lenses and observation of fluorescein patterns. Methods: The Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is an observational study that has enrolled 1,209 keratoconus patients to characterize the progression of keratoconus, to determine factors associated with its progression, and to assess its impact on quality of life. Ten percent of the patients were randomly selected at baseline for a retest examination. The baseline examination, which included keratometry and FDACL, was repeated in this sample. The FDACL is the flattest lens in the standardized CLEK trial lens set that vaults the apex of the cone. FDACL provides an estimate of the sagittal height of the cone. Results: The correlation of FDACL with the steep keratometric reading (r = 0.89; p = 0.0001) and the flat keratometric reading (r = 0.83; p = 0.0001) were high. Test-retest repeatability as measured by the intraclass correlation coefficient (ICC) was high: FDACL ICC, 0.97; steep keratometric reading ICC, 0.96; and flat keratometric reading ICC, 0.95. Test-retest repeatability of FDACL remained high in advanced disease. Conclusion: FDACL provides a repeatable new procedure for determining disease severity in keratoconus. (C) Lippincott-Raven Publishers.
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From 1935 through 1982, keratoconus was newly diagnosed in a total of 64 residents (35 males and 29 females) of Olmsted County, Minnesota. There were no significant trends in incidence rates over time; the overall average annual rate was 2.0 per 100,000 population. The age-specific incidence rates were greatest in the younger groups. The incidence rates did not differ significantly by sex. On Dec. 31, 1982, the overall prevalence rate was 54.5 per 100,000 population. At the time of diagnosis, keratoconus was unilateral in 26 patients (41%) and bilateral in 38 patients (59%). Follow-up of the patients showed that survival did not differ significantly from that of the general population. The cumulative probability of survivorship without corneal transplantation for more than 20 years after diagnosis was greater than 80%.
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Keratoconus is typically managed by a variety of rigid contact lens fitting techniques and lens designs. The two most fundamental fitting techniques are apical corneal touch (including divided or three-point touch) and apical clearance. In the course of designing a multi-center study of keratoconus patients, a standardized keratoconus fitting protocol was developed. All contact lens parameter options are uniform except for base curve and secondary curve radii, which are determined by interpretation of fluorescein patterns using the CLEK Study trial lens set and protocol. The initial trial lens's base curve is the average keratometric reading; sequentially steeper lenses are applied until definite apical clearance is observed. We have evaluated the feasibility of this standardized fitting protocol on 30 keratoconus patients. Our results suggest that we have developed a standardized contact lens fitting set and fitting protocol to simplify contact lens management in patients with mild to moderate keratoconus.
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To describe the baseline findings in patients enrolled in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. This is a longitudinal observational study of 1209 patients with keratoconus enrolled at 16 clinical centers. Its main outcome measures are corneal scarring, visual acuity, keratometry, and quality of life. The CLEK Study patients had a mean age of 39.29+/-10.90 years with moderate to severe disease, assessed by a keratometric-based criterion (95.4% of patients had steep keratometric readings of at least 45 D) and relatively good visual acuity (77.9% had best corrected visual acuity of at least 20/40 in both eyes). Sixty-five percent of the patients wore rigid gas-permeable contact lens, and most of those (73%) reported that their lenses were comfortable. Only 13.5% of patients reported a family history of keratoconus. None reported serious systemic diseases that had been previously reported to be associated with keratoconus. Many (53%) reported a history of atopy. Fifty-three percent had corneal scarring in one or both eyes. Baseline findings suggest that keratoconus is not associated with increased risk of connective tissue disease and that most patients in the CLEK Study sample represent mild to moderate keratoconus. Additional follow-up of at least 3 years will provide new information about the progression of keratoconus, identify factors associated with progression, and assess its impact on quality of life.
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The multicenter Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a prospective, observational study of 1,209 keratoconus patients. We report on the correlation of corneal scarring with clinical and patient-reported variables at the baseline visit. Patients completed a questionnaire on their vision, effect of glare, contact lens wear, and work-related issues. Clinical examination included high- and low-contrast visual acuity, refraction, assessment of corneal scarring by the clinician and by photography, and measurement of corneal curvature. The correlation of central corneal scarring with visual acuity and patient-reported variables was analyzed using multiple regression analysis and generalized estimating equations. High- and low-contrast visual acuity with habitual and optimal correction is reduced in scarred eyes. Multiple regression analyses controlling for age, contact lens wear, and disease severity show that central scarring is associated with poorer visual acuity and increased patient-reported symptoms of glare. Restrictions on day-to-day activities do not appear to be associated with corneal scarring above and beyond the effects of keratoconus alone. Corneal scarring in keratoconus is significantly associated with decreased high- and low-contrast visual acuity.
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Keratoconus is described as a bilateral, asymmetric, non-inflammatory corneal ectasia. The purpose of the study was to examine the relation between disease asymmetry and severity in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study cohort. Analyses included 1037 keratoconus patients from the CLEK Study baseline examination visit, none of whom had undergone corneal surgery in either eye. Disease asymmetry was determined by taking the difference between eyes for continuous variables. For categorical variables, asymmetry was categorised by whether the variable was present in neither, one, or both eyes. Disease severity was defined using the first definite apical clearance lens (FDACL) technique (a rigid contact lens to measure corneal curvature) from the worse (steeper) eye. Statistical analyses included Pearson's correlation coefficients (continuous variables) and analysis of variance (categorical variables). There were generally weak correlations between asymmetry and severity for low contrast habitual visual acuity (r = 0.12, p = 0.0003), high contrast habitual visual acuity (r = 0.14, p<0.0001), low contrast best corrected visual acuity (r = 0.21, p<0.0001), and high contrast best corrected visual acuity (r = 0.29, p<0.0001). Asymmetry in refractive error was more moderately correlated with disease severity (r = 0.41, p<0.0001), as was asymmetry in the flat (r = 0.61, p<0.0001) and steep keratometric readings (r = 0.54, p<0.0001). The average FDACL was significantly steeper in patients who had one eye with Vogt's striae, Fleischer's ring, or corneal scarring compared with the average FDACL when neither eye had these findings. Keratoconus patients with more severe disease are also more asymmetric in their disease status.
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The present investigation aimed to identify factors that predict reduced visual acuity in keratoconus from a prospective, longitudinal study. This report from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study used 7 years of follow-up data from 953 CLEK subjects who did not have penetrating keratoplasty in either eye at baseline and who provided enough data to compute the slope of the change over time in high- or low-contrast best-corrected visual acuity (BCVA). Outcome measures included these slopes and whether the number of letters correctly read decreased by 10 letters or more in at least one eye in 7 years. Mean age of the subjects at the first follow-up visit was 40.2 +/- 11.0 years (mean +/- SD). Overall, 44.4% were female, and 71.9% were white. The slope of the change in high- and low-contrast BCVA (-0.29 +/- 1.5 and -0.58 +/- 1.7 letters correct/year, respectively) translated into expected 7-year decreases of 2.03 high- and 4.06 low-contrast letters correct. High- and low-contrast visual acuity decreases of 10 or more letters correct occurred in 19.0% and 30.8% of subjects, respectively. Independent predictors of reduced high- and low-contrast BCVA included better baseline acuity, steeper first definite apical clearance lens (FDACL), and fundus abnormalities. Each diopter of steeper baseline FDACL predicted an increased deterioration of 0.49 high- and 0.63 low-contrast letters correct. CLEK Study subjects with keratoconus exhibited a slow but clear decrease in BCVA during follow-up, with low-contrast acuity deteriorating more rapidly than high-contrast. Better baseline BCVA, steeper FDACL, and fundus abnormalities were predictive of greater acuity loss with time.
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To identify factors associated with rigid contact lens comfort in keratoconus. Baseline data from the 16 Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study clinical sites were analyzed for all patients wearing a rigid contact lens in their more severely keratoconic eye (as determined by steep keratometry). Corneal transplant patients, patients who did not wear a rigid contact lens in either eye, patients who did not wear a rigid lens in their worse eye, and patients with missing contact lens comfort data were excluded from the sample. A total of 751 eyes were included. Variables assessed included measures of disease severity, visual acuity through the patients' habitual rigid contact lenses, contact lens wearing time, the apical fitting relationship of the contact lens, the degree of peripheral clearance, and the presence of corneal scarring and staining. Comfort was measured by asking the patients "In general, how comfortable are your contact lenses?" (1 = very comfortable through 5 = very irritating). Measures of disease severity (steep keratometry and the first definite apical clearance lens) were not associated with lens comfort. There was no difference in self-reported contact lens comfort between patients fitted with apical touch vs. apical clearance. Patients with a peripheral clearance rating of "minimal unacceptable" (more common among patients with milder keratoconus) were approximately half as likely to report good contact lens comfort compared with patients with "average" peripheral clearance (unadjusted odds ratio, 0.39; 95% confidence interval, 0.19 to 0.79). There was no association between contact lens comfort and the other peripheral clearance ratings compared with ratings of average. There does not appear to be an association between decreasing patient-reported rigid lens comfort and increasing disease severity as measured by steep keratometry or first definite apical clearance lens in this sample. The apical fitting relationship (flat vs. steep) does not appear to be associated with patient-reported comfort. Minimal peripheral clearance may contribute to decreased rigid contact lens comfort in keratoconus.
Article
Purpose, The purpose of the test-retest phase of the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study was to determine the repeatability of the various parts of the CLEK Study protocol. This paper presents the test-retest parameters of the refraction protocol. Methods. We examined 138 CLEK Study-eligible patients on two occasions (median, 90 days; range, 22 to 268 days). All patients underwent subjective refraction on two occasions, and contact lens over-refractions were performed either over the patient's habitual rigid contact lenses or over a trial rigid contact lens equal in base curve to the steep keratometric reading in nonrigid contact lens wearers. Results. Mean interoccasion differences a SD were -0.32 +/- 2.91 D and -0.17 +/- 1.39 D for subjective refraction sphere and cylinder power, respectively, and the mean absolute difference for subjective refraction cylinder axis was 18.1 +/- 20.2 degrees. The mean interoccasion difference a SD for high-contrast visual acuity with subjective refraction was 0.38 +/- 10.9 letters correct. Mean interoccasion differences +/- SD were -0.11 +/- 0.81 D and 0.02 +/- 0.67 D for contact lens over-refraction sphere and cylinder power, respectively, and the mean absolute difference for contact lens over-refraction cylinder axis was 11.6 +/- 9.9 degrees. The mean interoccasion difference +/- SD for visual acuity with contact lens over-refraction was 0.50 +/- 5.2 letters correct and 0.71 +/- 6.9 letters correct for high- and low-contrast visual acuity, respectively. Conclusions. The repeatability of subjective refraction in keratoconus patients is good but somewhat lower than that found in nondiseased eyes. Only 36% of our repeat measures of sphere power from subjective refraction fell within 0.50 D of each other, compared with more than 90% in studies of normal eyes.
Article
Purpose. The multicenter Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a prospective, observational study of 1,209 keratoconus patients. We report on the correlation of corneal scarring with clinical and patient-reported variables at the baseline visit. Methods. Patients completed a questionnaire on their vision, effect of glare, contact lens wear, and work-related issues. Clinical examination included high-and low-contrast visual acuity, refraction, assessment of corneal scarring by the clinician and by photography, and measurement of corneal curvature. The correlation of central corneal scarring with visual acuity and patient-reported variables was analyzed using multiple regression analysis and generalized estimating equations. Results. High-and low-contrast visual acuity with habitual and optimal correction is reduced in scarred eyes. Multiple regression analyses controlling for age, contact lens wear, and disease severity show that central scarring is associated with poorer visual acuity and increased patient-reported symptoms of glare. Restrictions on day-to-day activities do not appear to be associated with corneal scarring above and beyond the effects of keratoconus alone. Conclusions. Corneal scarring in keratoconus is significantly associated with decreased high-and low-contrast visual acuity.
Article
Purpose: This study was conducted to determine the agreement and test-retest repeatability of two methods for measuring corneal curvature in keratoconus: keratometry and the First Definite Apical Clearance Lens (FDACL). Our interest in the FDACL procedure stems from the important contact lens-fitting information and documentation of disease progression provided by the FDACL trial lenses and observation of fluorescein patterns. Methods: The Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is an observational study that has enrolled 1,209 keratoconus patients to characterize the progression of keratoconus, to determine factors associated with its progression, and to assess its impact on quality of life. Ten percent of the patients were randomly selected at baseline for a retest examination. The baseline examination, which included keratometry and FDACL, was repeated in this sample. The FDACL is the flattest lens in the standardized CLEK trial lens set that vaults the apex of the cone. FDACL provides an estimate of the sagittal height of the cone. Results: The correlation of FDACL with the steep keratometric reading (r = 0.89; p = 0.0001) and the flat keratometric reading (r = 0.83; p = 0.0001) were high. Test-retest repeatability as measured by the intraclass correlation coefficient (ICC) was high: FDACL ICC, 0.97; steep keratometric reading ICC, 0.96; and flat keratometric reading ICC, 0.95. Test-retest repeatability of FDACL remained high in advanced disease. Conclusion: FDACL provides a repeatable new procedure for determining disease severity in keratoconus.
Article
Three new visual acuity charts facilitate quantitative use of visual acuity test results. The charts have high-contrast lettering on washable white polystyrene. Each line has five Sloan letters; the lines are of equal difficulty, and there is a geometric progression in letter size from line to line. This provides a similar task for each line on the chart with the letter size being the only variable. Charts with different letter sequences are used for testing right and left eyes. A method of scoring visual acuity using these charts has been developed.
Article
colon; Purpose. The purpose of this paper is to determine the repeatability of visual acuity measurement in keratoconus and to describe the impact of measurement repeatability on sample size. Methods. Approximately 10% of a 1209 patient sample in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study were selected randomly for a Repeat CLEK Study Visit. Patients were tested at the 15 CLEK Participating Clinics. The test-retest sample consisted of 134 keratoconus patients who met the entry criteria of the CLEK Study. High and low contrast Bailey-Lovie visual acuity was measured with the patient's habitual visual correction (entrance visual acuity monocularly and binocularly), and with the best correction monocularly (either the patient's rigid contact lens and over-refraction, or with a CLEK Study trial lens and appropriate over-refraction) at two visits separated by a median of 90 days (range 22 to 268 days). Results. The mean absolute differences between the number of letters correct at the two visits ranged from a low of 3.24 +/- 3.1 for entrance high contrast binocular acuity to a high of 5.48 +/- 5.1 for best corrected low contrast monocular acuity. Intraclass correlation coefficients ranged from 0.757 to 0.853. The visual acuity score was somewhat higher at the Repeat Visit than at the Baseline Visit when the examiners were different between visits. Conclusions. Given the variable vision reported by keratoconus patients, visual acuity in this sample was very repeatable. Repeatability was slightly poorer when different examiners tested visual acuity at the Baseline and Repeat Visits. (C) 1998 American Academy of Optometry
Article
Purpose. Although the influence of flat-fitting contact lenses on corneal scarring in keratoconus is frequently debated, the current standard of care with regard to the apical fitting relationship in keratoconus remains undocumented. Methods. Patients were examined at baseline in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study (N=1209). Patients wearing a rigid contact lens in one or both eyes (N=808) had their habitual rigid contact lenses analyzed, and the fluorescein patterns and base curves were compared to the first definite apical clearance lens (FDACL). The FDACL is the flattest lens in the CLEK Study trial lens set that exhibits an apical clearance fluorescein pattern. For patients wearing a rigid contact lens in both eyes, one eye was selected randomly for analysis. Results. Twelve percent of the rigid contact lens-wearing eyes were wearing lenses fitted with apical clearance based upon the clinician's fluorescein pattern interpretation. The remainder (88%) was wearing lenses fitted with apical touch. For mild (steep keratometric reading <45 D) keratoconus corneas, the mean estimate of the base curve to cornea-fitting relationship was 1.18 D flat (SD +/- 1.84 D); moderate (steep keratometric reading: 45 to 52 D) corneas were fitted on average 2.38 D flat (SD +/- 2.56 D); and severe (steep keratometric reading > 52 D) corneas were fitted an average of 4.01 D flat (SD +/- 4.11 D). Conclusions. Despite the potential risk for corneal scarring imposed by flat-fitting rigid contact lenses, most CLEK Study patients wear flat-fitting lenses. Overall, rigid lenses were fitted an average of 2.86 D (SD +/- 3.31 D) flatter than the FDACL. (C) 1999 American Academy of Optometry
Article
This paper evaluates the repeatability of refraction in keratoconus patients and normal myopes, using representations of spherocylindrical power that are theoretically valid. Data consist of test–retest refraction data from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study and similar data from normal myopes. Dioptric powers are transformed to an orthogonal vector representation of dioptric power. The metric of change is the dioptric difference between test and retest. The median difference between test and retest in keratoconus patients is four to six times larger than in normal myopes. Refraction over a rigid contact lens on a keratoconic cornea improves repeatability but remains approximately twice as large as in normal myopes. The methods demonstrated here possess advantages over previous methods and provide a more valid comparison between test and retest and between different subject groups. The repeatability of refraction in keratoconus patients is substantially worse than in normal myopes.
This paper intoduces new principles for the design and use of letter charts for the measurement of visual acuity. It is advocated that the test task should be essentially the same at each size level on the chart. Such standardization of the test task requires the use of letters of equal legibility, the same number of letters on each row, and uniform between-letter and between-row spacing. It is also advocated that, combined with the test task standardization, there should be a logarithmic progression of letter size. Charts incorporating these design features have been made. These charts facilitate the use of nonstandard testing distances which might be used when there is low visual acuity, when examination room layout prevents testing at the standard distance, or when it is necessary to validate visual acuity scores or detect malingering. Adjusting the visual acuity score according to the chosen testing distance is simplified by the use of logarithmic scaling.
Article
Keratoconus and other noninflammatory corneal thinning disorders (keratoglobus, pellucid marginal degeneration and posterior keratoconus) are characterized by progressive corneal thinning, protrusion and scarring; the result is distorted and decreased vision. The etiology and pathogenesis of these disorders are unknown but may be associated with a variety of factors, including contact lens wear, eye rubbing, Down's syndrome, atopic disease, connective tissue disease, tapetoretinal degeneration and inheritance. Recent advances in techniques for biochemical and pathological investigation are now allowing further exploration in these areas. Early diagnosis is aided by the finding of irregular corneal astigmatism with inferior corneal steepening. Treatment ranges from simple spectacle correction to keratoplasty. In this review, the past and present literature on corneal thinning disorders is reviewed and practical approaches to diagnosis and management are outlined.
Article
Seven keratoconus patients were fitted with gas-permeable lenses, one eye with a large apical bearing lens and the other with a small apical clearance lens. Within 12 months, 4 of the 7 eyes wearing the large flat technique developed corneal scarring, while no scarring developed in the eyes fitted with the apical clearance technique.
Article
Three new visual acuity charts facilitate quantitative use of visual acuity test results. The charts have high-contrast lettering on washable white polystyrene. Each line has five Sloan letters; the lines are of equal difficulty and there is a geometric progression in letter size from line to line. This provides a similar task for each line on the chart with the letter size being the only variable. Charts with different letter sequences are used for testing right and left eyes.
Article
A standardized system for photodocumenting corneal scars and for evaluating these photographs does not exist and is essential for clinical research. To address this need, we developed a system for photographing and evaluating corneal scars. In the "Development Phase," we tested several procedures in small samples totaling 40 eyes of 20 keratoconus patients. In the "Test Phase," we used an independent sample of 150 eyes of 82 keratoconus patients. Fifty-nine of these 150 eyes had corneal scars, and 91 of the eyes did not as determined by the clinician. The photography protocol requires four central parallelepiped and two whole cornea oblique photographs after pupil dilation. With the clinician as gold standard, this technique yielded sensitivity of 96% and specificity of 83%. Evaluation of the corneal photographs as to the presence or absence of corneal scarring was performed independently by two masked readers. Agreement between clinicians on the presence of corneal scarring was 0.99 (kappa); agreement between readers for the presence of scarring was 0.80 (kappa). The corneal photography protocol we describe is recommended for use in clinical investigations of cicatricizing corneal disease and appears robust enough to be used in multicenter studies.
Article
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.
Article
The purpose of this paper is to determine the repeatability of visual acuity measurement in keratoconus and to describe the impact of measurement repeatability on sample size. Approximately 10% of a 1209 patient sample in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study were selected randomly for a Repeat CLEK Study Visit. Patients were tested at the 15 CLEK Participating Clinics. The test-retest sample consisted of 1 34 keratoconus patients who met the entry criteria of the CLEK Study. High and low contrast Bailey-Lovie visual acuity was measured with the patient's habitual visual correction (entrance visual acuity monocularly and binocularly), and with the best correction monocularly (either the patient's rigid contact lens and over-refraction, or with a CLEK Study trial lens and appropriate over-refraction) at two visits separated by a median of 90 days (range 22 to 268 days). The mean absolute differences between the number of letters correct at the two visits ranged from a low of 3.24 +/- 3.1 for entrance high contrast binocular acuity to a high of 5.48 +/- 5.1 for best corrected low contrast monocular acuity. Intraclass correlation coefficients ranged from 0.757 to 0.853. The visual acuity score was somewhat higher at the Repeat Visit than at the Baseline Visit when the examiners were different between visits. Given the variable vision reported by keratoconus patients, visual acuity in this sample was very repeatable. Repeatability was slightly poorer when different examiners tested visual acuity at the Baseline and Repeat Visits.
Article
This study was conducted to determine the agreement and test-retest repeatability of two methods for measuring corneal curvature in keratoconus: keratometry and the First Definite Apical Clearance Lens (FDACL). Our interest in the FDACL procedure stems from the important contact lens-fitting information and documentation of disease progression provided by the FDACL trial lenses and observation of fluorescein patterns. The Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is an observational study that has enrolled 1,209 keratoconus patients to characterize the progression of keratoconus, to determine factors associated with its progression, and to assess its impact on quality of life. Ten percent of the patients were randomly selected at baseline for a retest examination. The baseline examination, which included keratometry and FDACL, was repeated in this sample. The FDACL is the flattest lens in the standardized CLEK trial lens set that vaults the apex of the cone. FDACL provides an estimate of the sagittal height of the cone. The correlation of FDACL with the steep keratometric reading (r = 0.89; p = 0.0001) and the flat keratometric reading (r = 0.83; p = 0.0001) were high. Test-retest repeatability as measured by the intraclass correlation coefficient (ICC) was high: FDACL ICC, 0.97; steep keratometric reading ICC, 0.96; and flat keratometric reading ICC, 0.95. Test-retest repeatability of FDACL remained high in advanced disease. FDACL provides a repeatable new procedure for determining disease severity in keratoconus.
Article
The purpose of the test-retest phase of the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study was to determine the repeatability of the various parts of the CLEK Study protocol. This paper presents the test-retest parameters of the refraction protocol. We examined 138 CLEK Study-eligible patients on two occasions (median, 90 days; range, 22 to 268 days). All patients underwent subjective refraction on two occasions, and contact lens over-refractions were performed either over the patient's habitual rigid contact lenses or over a trial rigid contact lens equal in base curve to the steep keratometric reading in nonrigid contact lens wearers. Mean interoccasion differences +/- SD were -0.32 +/- 2.91 D and -0.17 +/- 1.39 D for subjective refraction sphere and cylinder power, respectively, and the mean absolute difference for subjective refraction cylinder axis was 18.1 +/- 20.2 degrees. The mean interoccasion difference +/- SD for high-contrast visual acuity with subjective refraction was 0.38 +/- 10.9 letters correct. Mean interoccasion differences +/- SD were -0.11 +/- 0.81 D and 0.02 +/- 0.67 D for contact lens over-refraction sphere and cylinder power, respectively, and the mean absolute difference for contact lens over-refraction cylinder axis was 11.6 +/- 9.9 degrees. The mean interoccasion difference +/- SD for visual acuity with contact lens over-refraction was 0.50 +/- 5.2 letters correct and 0.71 +/- 6.9 letters correct for high- and low-contrast visual acuity, respectively. The repeatability of subjective refraction in keratoconus patients is good but somewhat lower than that found in nondiseased eyes. Only 36% of our repeat measures of sphere power from subjective refraction fell within 0.50 D of each other, compared with more than 90% in studies of normal eyes.
Article
Although the influence of flat-fitting contact lenses on corneal scarring in keratoconus is frequently debated, the current standard of care with regard to the apical fitting relationship in keratoconus remains undocumented. Patients were examined at baseline in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study (N = 1209). Patients wearing a rigid contact lens in one or both eyes (N = 808) had their habitual rigid contact lenses analyzed, and the fluorescein patterns and base curves were compared to the first definite apical clearance lens (FDACL). The FDACL is the flattest lens in the CLEK Study trial lens set that exhibits an apical clearance fluorescein pattern. For patients wearing a rigid contact lens in both eyes, one eye was selected randomly for analysis. Twelve percent of the rigid contact lens-wearing eyes were wearing lenses fitted with apical clearance based upon the clinician's fluorescein pattern interpretation. The remainder (88%) was wearing lenses fitted with apical touch. For mild (steep keratometric reading <45 D) keratoconus corneas, the mean estimate of the base curve to cornea-fitting relationship was 1.18 D flat (SD +/- 1.84 D); moderate (steep keratometric reading: 45 to 52 D) corneas were fitted on average 2.38 D flat (SD +/- 2.56 D); and severe (steep keratometric reading > 52 D) corneas were fitted an average of 4.01 D flat (SD +/- 4.11 D). Despite the potential risk for corneal scarring imposed by flat-fitting rigid contact lenses, most CLEK Study patients wear flat-fitting lenses. Overall, rigid lenses were fitted an average of 2.86 D (SD +/- 3.31 D) flatter than the FDACL.
Article
The multicenter Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a prospective, observational study of 1,209 keratoconus patients. We report on the factors associated with corneal scarring at baseline. We defined corneal scarring as scars that had been detected both by the clinician examining the patient with the slit-lamp biomicroscope and by masked readers of corneal photographs at the CLEK Photography Reading Center. We investigated associations between corneal scarring and patient variables including gender, ethnicity, a family history of keratoconus, a history of ocular trauma, eye rubbing, contact lens wear, rigid contact lens fitting relationships, and corneal findings (such as curvature, Vogt's striae, Fleischer's ring, and central/apical staining). Multiple logistic regression analysis using generalized estimating equations to adjust for the correlation between eyes was used for analysis. The following factors were found to increase the odds of corneal scarring at baseline in the CLEK Study: corneal staining (odds ratios (OR) = 3.40, 95% confidence interval 2.53-4.59), contact lens wear (OR = 3.51, 95% confidence interval 2.27-5.45), Fleischer's ring (OR = 1.63, 95% confidence interval 1.11-2.40), steeper first definite apical clearance lens base curve radius (per diopter, OR = 1.29, 95% confidence interval 1.25-1.33), and age (per decade, OR = 1.54, 95% confidence interval 1.35-1.75). These baseline data suggest that corneal scarring in keratoconus is associated with corneal staining, contact lens wear, Fleischer's ring, a steeper cornea, and increasing age. The factors that imply added risk for corneal scarring that may be affected by practitioner intervention are staining of the cornea, contact lens wear, and the contact lens fitting relationship.
Article
This paper evaluates the repeatability of refraction in keratoconus patients and normal myopes, using representations of spherocylindrical power that are theoretically valid. Data consist of test-retest refraction data from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study and similar data from normal myopes. Dioptric powers are transformed to an orthogonal vector representation of dioptric power. The metric of change is the dioptric difference between test and retest. The median difference between test and retest in keratoconus patients is four to six times larger than in normal myopes. Refraction over a rigid contact lens on a keratoconic cornea improves repeatability but remains approximately twice as large as in normal myopes. The methods demonstrated here possess advantages over previous methods and provide a more valid comparison between test and retest and between different subject groups. The repeatability of refraction in keratoconus patients is substantially worse than in normal myopes.
Article
To report baseline differences between eyes on key variables in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study cohort compared with a retrospectively assembled group of myopic contact lens wearers without ocular disease. A total of 1,079 keratoconus patients who had not undergone a penetrating keratoplasty in either eye before their baseline visit were enrolled and examined at baseline. Records from 330 contact lens-wearing myopes were reviewed. Corneal curvature (keratometry), visual acuity, refractive error (manifest refraction), and corneal scarring were measured. The mean differences between keratoconic eyes are as follows (better eye-worse eye for each variable, separately). Flat keratometry: -3.59 +/-4.46 D and steep keratometry: -4.35 +/-4.41 D; high-contrast best-corrected visual acuity: 7.30 +/-6.83 letters; low-contrast best-corrected visual acuity: 8.53 +/-7.51 letters; high-contrast entrance visual acuity: 9.03 +/-8.40 letters; low-contrast entrance visual acuity: 9.43 +/-7.88 letters; spherical equivalent refractive error: 3.15 +/-3.84 D; and refractive cylinder power 1.55 +/-1.42 D. Twenty-one percent of the keratoconus patients had corneal scarring in only one eye. There is an association between patient-reported unilateral eye rubbing and greater asymmetry in corneal curvature, and between a history of unilateral eye trauma and greater asymmetry in corneal curvature and refractive error, with the rubbed/traumatized eye being the steeper eye most of the time. Keratoconus is asymmetric in the CLEK Study sample.
Article
Keratoconus is a chronic, noninflammatory disease of the cornea with onset in early adulthood. As these years are important to financial and social health, keratoconus may have more severe impact on quality of life than would be expected given its clinical severity. We examined the vision-related quality of life of patients in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. Cross-sectional study. The National Eye Institute-Visual Function Questionnaire (NEI-VFQ) was administered to 1166 CLEK Study patients at their first annual follow-up examination. Associations between clinical and demographic factors and NEI-VFQ scale scores were evaluated. Binocular entrance visual acuity worse than 20/40 was associated with lower quality of life scores on all scales except General Health and Ocular Pain. A steep keratometric reading (average of both eyes) >52 diopters (D) was associated with lower scores on the Mental Health, Role Difficulty, Driving, Dependency, and Ocular Pain scales. Scores for CLEK patients on all scales were between patients with category 3 and category 4 age-related macular degeneration (AMD) except General Health, which was better than AMD patients, and Ocular Pain, which was worse than AMD patients. Keratoconus is a disease of relatively low prevalence that rarely results in blindness, but because it affects young adults, the magnitude of its public health impact is disproportionate to its prevalence and clinical severity.
Article
The multicenter Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a prospective, observational study of 1209 keratoconus patients. We report methods to define incident corneal scarring and baseline factors predictive of incident corneal scarring in nonsurgical eyes of CLEK Study keratoconus patients through their fifth year of follow-up. Of the 1,209 patients, 878 patients with at least one unscarred cornea at baseline were included in this study. The cumulative 5-year incidence of scarring is defined as the proportion of patients who developed central corneal opacification as detected by a clinician examining the patient with a slit-lamp biomicroscope and by masked readings of corneal photographs at the CLEK Photography Reading Center. Logistic regression analysis was used to test for relationships between baseline factors and incident corneal scarring. Baseline factors analyzed included age, sex, race, atopic disease, contact lens wear, family history of keratoconus, corneal curvature, and central corneal fluorescein staining, among others. The 5-year incidence of corneal scarring was 13.7% (120 of 878) overall, 16.7% (102 of 609) for contact lens-wearing eyes, and 38.0% (46 of 121) for contact lens-wearing eyes with corneal curvature greater than 52 D. Baseline factors predictive of incident scarring included corneal curvature greater than 52 D (odds ratio [OR] = 4.79; 95% confidence interval [CI], 3.08, 7.45; P < 0.001), contact lens wear (OR = 2.50; 95% CI, 1.40, 4.76; P = 0.003), marked corneal staining (OR = 2.38; 95% CI, 1.49, 3.76; P = 0.0002), and age less than 20 years (OR = 6.34; 95% CI, 2.57, 15.00; P < 0.0001). Multivariate analyses of 5-year prospective data from the CLEK Study cohort showed that baseline corneal curvature, contact lens wear, corneal staining, and younger age were predictive of the development of corneal scarring. The 5-year incidence of scarring is 13.7% for the overall sample and 38.0% for those eyes with corneal curvature greater than 52 D that wore contact lenses. Contact lens wear increased the risk of incident scarring more than 2-fold. These findings suggest a causal contribution of contact lens wear to corneal scarring in keratoconus and imply that corneal scarring might be reduced by modifying the contact lens fit.
Article
The purpose of this article is to compare the safety and efficacy of flat- and steep-fitting rigid contact lenses in keratoconus. The Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a 16-center observational study. Cross-sectional results at baseline were generated for 1091 subjects with longitudinal results from the 871 subjects who completed 8 years of follow up. Of the 761 rigid contact lens-wearing patients at baseline, 41% had a scar at baseline compared with 24% of the nonrigid contact lens wearers (odds ratio [OR], 2.15; 95% confidence interval [CI], 1.35-3.43; p = 0.001). Eighty-seven percent were fitted with flat-fitting lenses, whereas 13% were fitted with steep-fitting lenses. Rigid lens fitting method was also associated with incident corneal scarring. A greater proportion of the corneas wearing flat-fitting contact lenses were scarred (43% compared with 26% for the steep-fitted eyes; OR,= 2.19; 95% CI, 1.37-3.51; p = 0.001). After controlling for corneal curvature, the association of rigid contact lens fit and corneal scarring at baseline did not persist (adjusted OR, 1.20; 95% CI, 0.70-2.06; p = 0.52). Thirty-two percent of unscarred eyes at baseline fitted flat had developed an incident corneal scar by the eighth year follow-up visit compared with 14% of eyes fitted steep (OR, 2.93; 95% CI, 1.34-6.42; p = 0.007). The data reported here indicate that, after controlling for disease severity in the form of corneal curvature, keratoconic eyes fitted with a rigid contact lens resulting in an apical touch fluorescein pattern did not have an increased risk of being scarred centrally at baseline. This "natural history" sample cannot determine causal proof that one method of fitting lenses is safer than another. To achieve this, a randomized clinical trial is needed.
Article
This study was designed to identify factors that predict longitudinal increases in corneal curvature as measured by the First Definite Apical Clearance Lens (FDACL) and flatter keratometric reading (Flat K) in keratoconus. The Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a long-te rm evaluation of the natural history of keratoconus involving 1209 patients. This report uses 8 years of follow-up data from 1032 patients who had penetrating keratoplasty in neither eye at baseline and who provided enough data to compute the slope of the change with time in the FDACL or the Flat K. Outcome measures included the aforementioned slopes and whether the FDACL or the Flat K increased by 3.00 or more diopters (D) in at least 1 eye. At CLEK Study entry, patients were aged 38.9 +/- 10.8 years. Overall, 44.3% of them were women, and 69.3% of them were white. The slope of the change in FDACL (0.18 +/- 0.60 D/y) and Flat K (0.20 +/- 0.80 D) during 8 years translates into expected 8-year increases of 1.44 D in FDACL and 1.60 D in Flat K. Increases of > or = 3.00 D in either eye had an 8-year incidence of 24.8% for FDACL and 24.1% for Flat K. Independent predictors of increased FDACL included younger age, poorer baseline high-contrast manifest refraction visual acuity, and non-white race. Younger age and poorer high-contrast manifest refraction visual acuity were independent predictors of a >3.00-D increase for both FDACL and Flat K. CLEK patients exhibited a slow but clear increase in corneal curvature. Younger age and poorer high-contrast manifest refraction visual acuity at baseline predicted the rate of change in corneal curvature.
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Kelly A. McCann, MFA (Administrative Assistant, 2000– 2001), Pamela Qualley, MA (Study Coordinator, 1994–
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