Assessment of Health Disparities and Barriers to Accessing Keratoconus and Crosslinking at a Tertiary Referral Center.

PURPOSE: The aim of this study was to determine the barriers to accessing the crosslinking service in Auckland, New Zealand. METHODS: This was a prospective 1-year study of patients at Auckland District Health Board. Studied parameters included age, sex, body mass index, ethnicity, New Zealand Deprivation (NZDep; an area-based measure of socioeconomic status, 1 = low deprivation-10 = high deprivation) score of residence, disease severity (maximum keratometry and thinnest corneal thickness), attendance, distance travelled, car ownership, employment status, and visual outcomes. Statistical analysis was performed using independent t tests, Pearson correlation, independent samples ANOVA, MANCOVA, and binomial logistic regression. RESULTS: Four hundred fifty-four patients with keratoconus were analyzed and had a mean age of 24.1 ± 0.8 years, mean body mass index of 33.0 ± 9.7 kg/m 2 , and 43% were female. Pacific Peoples consisted 40.2% of the population; Maori 27.2%; Europeans 21.2%; Asian 9.9%; and Middle Eastern, Latin American, and African (MELAA) 1.3%. The mean distance travelled was 12.5 ± 9.5 km, NZDep score was 6.8 ± 2.6, and attendance was 69.0 ± 42.5%. The lowest attendance was observed in Pacific Peoples (58.9%) and the highest was in Asians (90%) ( P = 0.019). The mean worst-eye visual acuity at attendance was 0.75 ± 0.47 logMAR (6/35). Unemployment was associated with worse best-eye visual acuity at FSA ( P = 0.01) and follow-up ( P < 0.05). Maori and Pacific Peoples had the highest NZDep ( P < 0.001), were younger at presentation ( P = 0.019), had higher disease severity ( P < 0.001), and worse visual acuity ( P < 0.001). CONCLUSIONS: Poor attendance was seen in this cohort. Pacific Peoples and Maori presented younger with worse disease severity and visual acuity but also had the highest nonattendance. These results suggest that deprivation, factors associated with ethnicity, and unemployment are potential barriers to attendance.

A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.

Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.

Early Diagnosis of Keratoconus in Chinese Myopic Eyes by Combining Corvis ST with Pentacam.

Purpose: This study was designed to evaluate and compare the sensitivity and specificity of the Belin/Ambrósio Deviation (BADD), Corneal Biomechanical Index (CBI) and Tomographic and Biomechanical Index (TBI) for the diagnosis of keratoconus in Chinese myopic eyes prior to undergoing corneal refractive surgery.Methods: A total of 125 patients (185 eyes) planned to undergo corneal refractive surgery were selected from the Refractive Center of Beijing Tongren Hospital between December 2017 and December 2018. They were divided into four groups: the normal group, bilateral keratoconus (BK) group, unilateral keratoconus (UK) group, and the forme fruste keratoconus (FFK) group. After determining the BADD, CBI, and TBI for each eye using the Corvis ST combined with Pentacam, the sensitivity and specificity of these three indices in diagnosing keratoconus were analyzed through receiver operating characteristic (ROC) curves.Results: The TBI exhibited the highest diagnostic efficiency in normal vs. UK (area under the ROC curve [AUROC]: 0.992), normal vs. UK+BK (AUROC: 0.988), normal vs. UK+BK* (*stand randomly selecting one eye of each patient in BK group) (AUROC: 0.982), normal vs. UK+BK+FFK (AUROC: 0.965), and normal vs. UK+BK*+FFK (AUROC: 0.953). The CBI demonstrated the highest diagnostic efficiency in normal vs. FFK (AUROC: 0.897). Finally, the BADD showed the highest diagnostic efficiency in normal vs. BK (AUROC: 0.998) and normal vs. BK* (AUROC: 0.996).Conclusion: The BADD, CBI, and TBI performed well in diagnosing keratoconus in Chinese myopic eyes. The CBI showed the highest diagnostic efficiency compared with normal for FFK. In addition, the TBI offered the greatest accuracy in detecting keratoconus and FFK eyes vs. the other parameters.

Detection of Subclinical Corneal Ectasia Using Corneal Tomographic and Biomechanical Assessments in a Japanese Population.

PURPOSE: To test the detection of subclinical corneal ectasia using integrated Scheimpflug tomography and biomechanical assessment in a Japanese population. METHODS: This prospective, case-control study included 23 patients with very asymmetric ectasia (VAE) and 70 normal controls. Patients with VAE had defined clinical ectasia in one eye and a fellow eye with normal topography (VAE-NT). Objective topography for confirming normal topography in VAE-NT cases included having 0% similarity and 0% severity derived from Placido-disk based topography. Scheimpflug-based corneal tomography and corneal biomechanical assessment were performed. The Belin/Ambrósio Enhanced Ectasia Deviation index (BAD-D), Corvis Biomechanical Index (CBI), and Tomographic Biomechanical Index (TBI) were compared and their discriminating ability for detecting ectasia was assessed. RESULTS: For differentiating normal and VAE-NT eyes, the areas under the receiver operating curve for the BAD-D, CBI, and TBI were 0.668, 0.660, and 0.751, respectively. The TBI cut-off of 0.259 provided 52.17% sensitivity and 88.57% specificity. Fourteen VAE-NT cases (60.9%) were abnormal in at least one of the criteria of the BAD-D > 1.60 (39.1%), CBI > 0.5 (26.1%), or TBI > 0.29 (43.5%). Conversely, nine VAE-NT cases (39.1%) exhibited normal values for the BAD-D, CBI, and TBI. CONCLUSIONS: In the current study, 40% of VAE-NT eyes were classified as normal by the BAD-D, CBI, and TBI. Although some of these cases may truly represent unilateral ectasia, further advances are needed to enhance ectasia detection and characterize the susceptibility for ectasia progression. [J Refract Surg. 2019;35(6):383-390.].

A nationwide population-based study of social demographic factors, associated diseases and mortality of keratoconus patients in Denmark from 1977 to 2015.

PURPOSE: To study sociodemographic factors, associated diseases and survival of Danish keratoconus patients. METHODS: All patients diagnosed with keratoconus 1977-2015 (n = 2679) were matched to 10 persons who had not been diagnosed with keratoconus (n = 26 790). Conditional logistic regression assessed whether sociodemographic factors and specific systemic diseases were associated with the odds of keratoconus. Mortality was assessed with time-to-event analysis. RESULTS: After adjustment, non-Europeans had more than threefold higher odds of keratoconus compared to Europeans (OR, 3.34; 96% CI 2.94-3.80). Single persons had 27% higher odds (OR, 1.27; 95% CI 1.13-1.43), and divorced persons had 18% lower odds (OR 0.82; 95% CI 0.68-0.97) of keratoconus compared with persons in a relationship. Persons living in cities with <500 and 500-4999 inhabitants had 40% (OR, 0.60; 95% CI 0.51-0.71) and 30% (OR, 0.70; 95% CI 0.61-0.81) lower odds of keratoconus, respectively, compared with those living in the capital (>1 000 000 inhabitants). Persons receiving government substitution had 68% higher odds of keratoconus (OR, 1.68; 95% CI 1.30-2.17) compared to self-employed. Keratoconus patients had more than twofold higher odds of asthma (OR, 2.21; 95% CI 1.91-2.55), more than threefold higher odds of allergic rhinitis (OR, 3.44; 95% CI 2.75-4.30), more than sevenfold higher odds of atopic dermatitis (OR, 7.97; 95% CI, 6.21-10.21) and 69% higher odds of depression (OR, 1.69; 95% CI 1.18-2.43). Mortality rates were similar among keratoconus patients and controls (HR, 1.02; 95% CI 0.90-1.16). CONCLUSION: Danish keratoconus patients differ from controls on several sociodemographic factors and have higher risk of allergic rhinitis, asthma, atopic dermatitis and depression. They do not have excess mortality compared to controls.

Rare, potentially pathogenic variants in 21 keratoconus candidate genes are not enriched in cases in a large Australian cohort of European descent.

Many genes have been suggested as candidate genes for keratoconus based on their function, their proximity to associated polymorphisms or due to the identification of putative causative variants within the gene. However, very few of these genes have been assessed for rare variation in keratoconus more broadly. In contrast, VSX1 and SOD1 have been widely assessed, however, the vast majority of studies have been small and the findings conflicting. In a cohort of Australians of European descent, consisting of 385 keratoconus cases and 396 controls, we screened 21 keratoconus candidate genes: BANP, CAST, COL4A3, COL4A4, COL5A1, FOXO1, FNDC3B, HGF, IL1A, IL1B, ILRN, IMMP2L, MPDZ, NFIB, RAB3GAP1, RAD51, RXRA, SLC4A11, SOD1, TF and VSX1. The candidate genes were sequenced in these individuals by either whole exome sequencing or targeted gene sequencing. Variants were filtered to identify rare (minor allele frequency <1%), potentially pathogenic variants. A total of 164 such variants were identified across the two groups with no variants fulfilling these criteria in cases in IL1RN, BANP, IL1B, RAD51 or SOD1. The frequency of variants was compared between cases and controls using chi-square or Fishers' Exact tests for each gene with at least one rare potentially pathogenic variant identified in the case cohort. The number of rare potentially pathogenic variants per gene ranged from three (RXRA) to 102 (MPDZ), however for all genes, there was no difference in the frequency between the cases and controls. We conclude that rare potentially pathogenic variation in the 21 candidate genes assessed do not play a major role in keratoconus susceptibility and pathogenesis.

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.

Rare, Potentially Pathogenic Variants in ZNF469 Are Not Enriched in Keratoconus in a Large Australian Cohort of European Descent.

Purpose: The Zinc Finger Protein 469 (ZNF469) gene has been proposed as a candidate gene for keratoconus due to the association of an upstream polymorphism (rs9938149) with the disease in two independent studies, and the role of the gene in the autosomal recessive disease Brittle Cornea Syndrome. Coding variants in ZNF469 have been assessed for association with keratoconus in several small studies, with conflicting results. We assessed rare, potentially pathogenic variants in ZNF469 for enrichment in keratoconus patients in a cohort larger than all previous studies combined. Methods: ZNF469 was sequenced in 385 Australian keratoconus patients of European descent, 346 population controls, and 230 ethnically matched screened controls by either whole exome sequencing or targeted gene sequencing. The frequency of rare and very rare potentially pathogenic variants was compared between cases and controls using χ2 or Fisher's exact tests and further explored using a gene based test (Sequence Kernel Association Test [SKAT]), weighting on the rarity of variants. Results: A total of 49 rare, including 33 very rare, potentially pathogenic variants were identified across all groups. No enrichment of rare or very rare potentially pathogenic variants in ZNF469 was observed in our cases compared to the control groups following analysis using χ2 or Fisher's exact tests. This finding was further supported by the SKAT results, which found no significant difference in the frequency of variants predicted to be damaging between cases and either control group (P = 0.06). Conclusions: Rare variants in ZNF469 do not contribute to keratoconus susceptibility and do not account for the association at rs9938149.

The Association Between Sociodemographic Factors, Common Systemic Diseases, and Keratoconus: An Analysis of a Nationwide Heath Care Claims Database.

PURPOSE: The purpose of this study was to determine whether an association exists between common systemic diseases, sociodemographic factors, and keratoconus (KCN) among a large, diverse group of insured individuals in the United States. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: Sixteen thousand fifty-three patients with KCN were matched 1:1 with persons without KCN. METHODS: Persons with KCN were identified using billing codes and matched by age, gender, and overall health with a control group with no record of KCN. Multivariable logistic regression assessed whether sociodemographic factors and certain systemic diseases affected the odds of KCN. MAIN OUTCOME MEASURES: Odds ratios (ORs) with 95% confidence intervals (CIs) of receiving a KCN diagnosis. RESULTS: After adjustment for confounders, black persons had 57% higher odds (adjusted OR, 1.57; 95% CI, 1.38-1.79; P < 0.001) and Latino persons had 43% higher odds (adjusted OR, 1.43; 95% CI, 1.26-1.62; P < 0.001) of being diagnosed with KCN compared with whites. Asians had 39% reduced odds (adjusted OR, 0.61; 95% CI, 0.50-0.75; P < 0.001) of being diagnosed with KCN compared with whites. Patients with uncomplicated diabetes mellitus (DM) had 20% lower odds of KCN (adjusted OR, 0.80; 95% CI, 0.71-0.90; P = 0.002), and patients with DM complicated by end-organ damage had 52% lower odds of having KCN (adjusted OR, 0.48; 95% CI, 0.40-0.58; P < 0.001) compared with those without DM. Persons with collagen vascular disease had 35% lower odds of KCN (adjusted OR, 0.65; 95% CI, 0.47-0.91; P = 0.01). Other conditions found to have increased odds of KCN included sleep apnea (adjusted OR, 1.13; 95% CI, 1.00-1.27; P = 0.05), asthma (adjusted OR, 1.31; 95% CI, 1.17-1.47; P < 0.001), and Down syndrome (adjusted OR, 6.22; 95% CI, 2.08-18.66; P < 0.001). There was no association between KCN and allergic rhinitis, mitral valve disorder, aortic aneurysm, or depression (P > 0.1 for all comparisons). CONCLUSIONS: Clinicians caring for persons with KCN should inquire about breathing or sleeping and, when appropriate, refer patients for evaluation for sleep apnea or asthma. Patients with DM have lower risk of KCN, potentially because of corneal glycosylation.

Validation of an Objective Scoring System for Forme Fruste Keratoconus Detection and Post-LASIK Ectasia Risk Assessment in Asian Eyes.

PURPOSE: To investigate the efficacy of the SCORE Analyzer (Bausch+Lomb TechnoLas, Germany) in detecting forme fruste keratoconus (FFKC) in Asian eyes and validate its usefulness as a risk assessment system for post-laser in situ keratomileusis (LASIK) keratectasia. METHODS: We retrospectively evaluated corneal topographies with the Orbscan IIz system and independently tested them with the SCORE Analyzer through masked investigators. Eyes were classified into 2 groups: (1) The FFKC group included clinically and topographically normal eyes with definite keratoconus in the contralateral eye. (2) The control group included normal preoperative topographies of patients with LASIK performed at least 4 years before with no resultant keratectasia. The main outcome measures were accuracy indicators: sensitivity, specificity, positive, and negative predictive values. Parameters in the calculation of the SCORE including irregularity at 3 mm, thinnest pachymetry, the difference between central and thinnest pachymetry (CP - TP), vertical decentration of the thinnest point, maximum posterior elevation, and anterior elevation of the thinnest point were compared in both groups. RESULTS: We analyzed 128 Orbscans of 128 Asian patients. There were 24 FFKC eyes and 104 control eyes. SCORE was negative in 7 eyes (false negative) in the FFKC group and was positive in 2 eyes in the control group (false positive). The sensitivity was 70.8%, specificity 98.1%, positive predictive value 89.5%, and negative predictive value 93.6%. Irregularity at 3 mm, thinnest pachymetry, CP - TP, thinnest point decentration, maximum posterior elevation, and anterior elevation of the thinnest point were significantly different in both groups. CONCLUSIONS: The SCORE Analyzer algorithm, developed and validated in eyes of white subjects, was found to be valid and consistent in Asian eyes, showing good sensitivity and specificity in FFKC detection, and to be useful in objectively identifying cases at risk of post-LASIK keratectasia.

Polymorphism of the LIG3 gene in keratoconus and Fuchs endothelial corneal dystrophy.

The product of the LIG3 gene encodes DNA ligase III, which is involved in the repair of oxidatively damaged DNA in the base excision repair pathway. We hypothesized that polymorphism in this gene may change susceptibility to oxidative stress and predispose individuals to the development of keratoconus (KC) and Fuchs endothelial corneal dystrophy (FECD). Therefore, we investigated the association between genotypes and haplotypes of the g.29661G>A polymorphism (rs1003918) and the g.29059C>T polymorphism (rs1052536) of the LIG3 gene and the occurrence of KC and FECD in patients with FECD (258 individuals) or KC (283) and ethnically matched controls (300). The A/A genotype and the A allele of the g.29661G>A polymorphism were associated with increased occurrence of KC, while the G allele of this polymorphism was positively correlated with a decreased occurrence of this disease. The T/C genotype of the g.29059C>T polymorphism was associated with decreased FECD occurrence. In addition, the AT haplotype was associated with increased occurrence of KC and FECD, while the GT haplotype was associated with decreased occurrence of these diseases. The g.29661G>A and g.29059C>T polymorphisms may play a role in the KC and FECD pathogenesis and can be considered as markers in these diseases.

Association of mitochondrial haplogroups H and R with keratoconus in Saudi Arabian patients.

PURPOSE: Keratoconic corneas exhibit more mitochondrial DNA (mtDNA) damage than do normal corneas and thus mtDNA may represent a potential candidate for genetic susceptibility studies in keratoconus. To test this hypothesis we determined mitochondrial haplogroups in Saudi patients with keratoconus and healthy controls of same ethnicity. METHODS: Mitochondrial haplogrouping was performed by polymerase chain reaction-based automated Sanger sequencing in 114 patients with keratoconus and 552 healthy controls. RESULTS: Mitochondrial haplogroups H and R were significantly overrepresented in patients with keratoconus (28.9% vs. 8.5%, P < 0.0001 and 17.5% vs. 3.1%, P < 0.0001, respectively) as compared to healthy controls. CONCLUSIONS: Our data suggest that individuals with mitochondrial haplogroups H and R are at increased risk to develop keratoconus. In addition, the results provide further evidence for a plausible role of mtDNA in keratoconus etiology.

Modulatory effect of different riboflavin compositions on the central corneal thickness of African keratoconus corneas during collagen crosslinking.

PURPOSE: A pilot investigation to transfer the established corneal collagen crosslinking (CXL) procedure in European eyes into clinically affected African eyes and to optimize the treatment by adapting the riboflavin composition. MATERIALS AND METHODS: CXL was performed in 15 eyes (11 patients) with advanced stages of keratoconus in the Eye Clinic of Bafoussam in the West Region of Cameroon. The following six riboflavin compositions with different portions of active swelling additives were applied: Solution 1 (0.5% methylhydroxypropylcellulose [MHPC]), solution 2 (1.0% MHPC), solution 3 (1.7% MHPC), solution 4 (5% dextran), solution 5 (10% dextran) and solution 6 (no active swelling ingredient). The central corneal thickness (CCT) was measured by ultrasound pachymetry before and after de-epithelialization and at least every 10 min during CXL. RESULTS: THE APPLICATION OF THE RIBOFLAVIN SOLUTIONS RESULTED IN THE FOLLOWING MEAN FINAL CCT VALUES: 172 ± 15% using solution 1 (60 min/n = 5); 183 ± 8% using solution 2 (60 min/n = 5); 170% using solution 3 (60 min/n = 1); 80% using solution 4 (45 min/n = 1); 99% using solution 5 (45 min/n = 1) and 150 ± 13% using solution 6 (50 min/n = 2). CONCLUSIONS: The combination of riboflavin compositions with swelling and stabilizing effects on the corneal stroma seems necessary in African eyes with advanced keratoconus. Further studies are required to confirm these primary results.

Ethnic variation in central corneal refractive power and steep cornea in Asians.

PURPOSE: To describe ethnic differences in the distribution of central corneal refractive power and steep cornea in a multiethnic Asian population. METHODS: A total of 2968 Chinese, 2957 Indian and 2928 Malay participants aged over 40 years were included in this study. Each subject underwent standardized systematic and ocular examinations, interviewer-administered questionnaires, and blood investigations for risk factor assessment. Central corneal refractive power was measured using an autorefractor. Steep cornea was defined as central corneal refractive power exceeding 48 diopters (D) measured by keratometry. RESULTS: Mean keratometry readings were 43.9 ± 1.5 D in Malays, 44.2 ± 1.5 D in Indians and 43.9 ± 1.5 D in Chinese. The prevalence of steep cornea was 0.6% (95% confidence interval, CI, 0.3-0.9%) in Malays, 1.0% (95% CI 0.7-1.4%) in Indians and 0.5% (95% CI 0.3-0.8%) in Chinese. In multivariate analysis, increasing central corneal refractive power was associated with Indian race, shorter body height, non-smokers, absence of pterygium, shorter axial length, thinner corneas and greater anterior chamber depth, while the presence of steep cornea was significantly associated with Indian race, shorter axial length and thinner corneas. CONCLUSIONS: Indian participants had the steepest corneas among the three major ethnic groups in Singapore. Central corneal refractive power was related to several ocular parameters including anterior chamber depth, axial length and central corneal thickness. These data have important clinical implications for understanding the risk of keratoconus.

Topographic progression of keratoconus in the Korean population.

PURPOSE: To develop a criterion for determining the topographic progression of keratoconus and to analyze the prognostic factors of progression. METHODS: Medical records of 211 eyes of 128 patients who had been followed up for more than 2 years on three or more occasions were retrospectively reviewed. Topographic parameters, including simulated K, corneal astigmatism, irregular astigmatism at 3 and 5 mm, thinnest-point pachymetry, anterior and posterior elevation, and inferior minus superior index, were used to determine topographic progression. Topographic progression was determined by the greatest kappa value associated with progression to corneal graft surgery. Eyes were separated into progressed and non-progressed groups on the basis of topographic progression. The association of clinical factors with topographic progression, including demographic factors, contact lens use, corneal erosion, and atopic history at the time of diagnosis, was assessed by logistic regression. RESULTS: When topographic progression was defined as five or more progressed topographic parameters, the greatest kappa value (0.354) was obtained. Ninety-four of the 211 keratoconic eyes (44.5%) were identified as topographically progressed. Age at diagnosis was significantly different between the progressed and non-progressed groups (22.2 vs. 24.7 years, p = 0.014). Logistic regression revealed that younger age at diagnosis was a risk factor for topographic progression (odds ratio, 0.948; 95% confidence interval, 0.907 to 0.991; p = 0.010). CONCLUSIONS: We developed a criterion for evaluating topographic progression of keratoconus using diverse topographic indices. Younger age at diagnosis was associated with topographic progression of keratoconus.

Corneal thickness and volume in subclinical and clinical keratoconus.

To evaluate corneal thickness and volume in subclinical and clinical keratoconus in Asian population with the aim of discriminating between normal and ectatic cornea. Eyes were placed into one of the following three groups: normal, subclinical, and mild-moderate keratoconus. Pentacam Scheimpflug imaging (Oculus Inc., Wetzlar, Germany) was performed for each participant to record thinnest corneal thickness, central corneal thickness, corneal volume (CV), peripheral corneal thickness (PCT) and percentage thickness increase (PTI) at 2, 4, 6, and 8 mm. The data were exported to SPSS for statistical analysis. Subjects comprised 52 normal, 15 subclinical keratoconus, and 32 mild-moderate clinical keratoconus eyes. Our results indicated that corneal thickness (CT) distribution, PTI, and CV in normal eyes were significantly different compared with subclinical and clinical keratoconus (P < .05). Overall, subclinical group exhibited lower CT distribution and volume, and higher PTI in comparison with normal eyes. However, they showed higher CT distribution and volume, and lower PTI compared with keratoconus group. In addition, there was a smaller change in PCT and PTI from the thinnest point of the cornea to the periphery. The results of the present study indicate that CT parameters and CV were significantly different in normal versus subclinical group and in normal versus keratoconus group. These findings could help clinicians to better discriminate between normal and ectatic cornea.

Topographic Progression of Keratoconus in the Korean Population

PURPOSE: To develop a criterion for determining the topographic progression of keratoconus and to analyze the prognostic factors of progression. METHODS: Medical records of 211 eyes of 128 patients who had been followed up for more than 2 years on three or more occasions were retrospectively reviewed. Topographic parameters, including simulated K, corneal astigmatism, irregular astigmatism at 3 and 5 mm, thinnest-point pachymetry, anterior and posterior elevation, and inferior minus superior index, were used to determine topographic progression. Topographic progression was determined by the greatest kappa value associated with progression to corneal graft surgery. Eyes were separated into progressed and non-progressed groups on the basis of topographic progression. The association of clinical factors with topographic progression, including demographic factors, contact lens use, corneal erosion, and atopic history at the time of diagnosis, was assessed by logistic regression. RESULTS: When topographic progression was defined as five or more progressed topographic parameters, the greatest kappa value (0.354) was obtained. Ninety-four of the 211 keratoconic eyes (44.5%) were identified as topographically progressed. Age at diagnosis was significantly different between the progressed and non-progressed groups (22.2 vs. 24.7 years, p = 0.014). Logistic regression revealed that younger age at diagnosis was a risk factor for topographic progression (odds ratio, 0.948; 95% confidence interval, 0.907 to 0.991; p = 0.010). CONCLUSIONS: We developed a criterion for evaluating topographic progression of keratoconus using diverse topographic indices. Younger age at diagnosis was associated with topographic progression of keratoconus.

Paraoxonase 1 status in keratoconus: a preliminary study of activity and polymorphism / Estatus de la paraoxonasa 1 en el queratocono: estudio preliminar de actividad y polimorfismo

OBJECTIVE: To determine the activity of paraoxonase 1 (PON1) in keratoconus in a Malaysian population in comparison with non-keratoconic subjects. METHODS: Clinical eye examinations were performed on patients with keratoconus and non-keratoconic subjects after questionnaires were completed. Blood samples were collected and subjected to spectrophotometry analysis of paraoxonase and diazoxonase activities for the determination of the status of PON1 of every individual. RESULTS: Of the 11 keratoconic patients and 55 non-keratoconic control samples collected, eight patients of Indian ethnicity were keratoconic (73%), whereas 33 non-Indians were non-keratoconic (60%; p = 0.047). Paraoxonase activity was lower in Indians compared to the non-Indians ie Malays and Chinese (p = 0.008). Keratoconic subjects had a lower paraoxonase activity compared to non-keratoconics (p = 0.038). CONCLUSIONS: The reduced paraoxonase activity in keratoconic patients suggests that the keratoconic corneas were more susceptible to oxidative stress. Reduced paraoxonase activity and keratoconus status appears to be associated with ethnicity.

OBJETIVO: Determinar la actividad de paraoxonasa 1 (Pon 1) en el queratocono en una población malaya, en comparación con sujetos no queratocónicos. MÉTODOS: Se realizaron exámenes clínicos oculares a pacientes con queratocono y a sujetos no queratocónicos luego que los mismos respondieran a los cuestionarios. Se recogieron muestras de sangre, que fueron entonces sometidas a análisis espectrofotométrico en relación con las actividades de la paraoxonasa y la diazoxonasa para la determinación del estatus de la paraoxonasa 1 de cada individuo. RESULTADOS: De los 11 pacientes queratocónicos y las 55 muestras de control no queratocónicas recogidas, 8 pacientes de etnicidad india fueron queratocónicos (73%), mientras que 33 no indios fueron no queratocónicos (60%; p = 0.047). La actividad de la paraoxonasa fue más baja en los indios en comparación con los no indios, es decir, los malayos y los chinos (p = 0.008). Los sujetos queratocónicos tenían una actividad de la paraoxonasa más baja, comparada con los no queratocónicos (p = 0.038). CONCLUSIONES: La actividad de la paraoxonasa reducida en los pacientes queratocónicos sugiere que las córneas queratocónicas son más susceptibles al estrés oxidativo. La actividad de la paraoxonasa reducida y el estatus del queratocono parecen estar asociados con la etnicidad.

Comparison of corneal thickness and curvature in myopic and keratoconic eyes of patients from French Caribbean Isles and continental France.

PURPOSE: To evaluate the corneal thickness and curvature of myopic and patients with keratoconus from two countries. METHODS: This cross-sectional study was conducted at Cabinet Opale, Fort de France, French West Indies and University Hospital of Bordeaux, France. Corneal thickness and curvature were assessed in 170 keratoconic eyes of 89 residents of the French Caribbean Islands (FCI) and 159 keratoconic eyes of 91 residents of the Aquitaine region of southwest France. A group of age-matched keratoconus-free patients who had been referred for refractive surgery owing to myopia (173 FCI [173 eyes; 87 individuals] and Aquitaine [181 eyes; 93 individuals]) were also assessed. RESULTS: The mean age at keratoconus diagnosis was significantly higher among FCI than Aquitaine residents (p = 0.009). The mean keratometric (Km) reading was statistically higher for keratoconic FCI than Aquitaine patients, at 48.06 versus 46.21 diopters (p = 0.001). This difference was more pronounced among patients aged >40 years than those ≤40 years (p = 0.009). Patients with keratoconus showed no significant difference in mean central corneal thickness and thinnest corneal point values, irrespective of region. Myopic individuals from the FCI, however, had significantly lower mean central corneal thickness and thinnest corneal point measurements than Aquitaine myopics, irrespective of age group (p ≤ 0.0008). CONCLUSION: The corneas of patients with keratoconus of African-Caribbean and Caucasian origins are of similar thickness. Myopic African-Caribbean patients referred for refractive surgery tend to present with thinner corneas than Caucasians.

Review: keratoconus in Asia.

Keratoconus is an ectatic corneal disorder for which exciting therapeutic and diagnostic technologies are emerging. However, its pathogenesis is still heterogeneous and elusive. We researched overlooked Asian keratoconus data by literature review of databases (PubMed, MEDLINE, Ovid, Google Scholar, Cornea, and Cochrane) using key words "keratoconus, Asia, epidemiology, treatment, risk factors, genes" and names of Asian countries. Articles and their references were analyzed. Studies showed that keratoconus may be more prevalent, have earlier onset, and have greater disease progression in certain Asian and non-Asian ethnicities, particularly Indians, Pakistanis, Middle Easterners, and Polynesians, compared with white populations. Epidemiological risk factors include ethnicity, age (younger than 30 years), gender (male), positive family history, and eye rubbing. Genetic and disease risk factors include atopy, vernal keratoconjunctivitis, Down syndrome, pellucid marginal corneal degeneration, VSX1 (visual system homeobox 1) gene, and Leber congenital amaurosis. Differentiation of heterogeneous keratoconus subsets with detailed genotype-phenotype characterization may advance understanding. Comprehensive multiethnic population studies with valid large-scale data are needed. New effective treatments (deep anterior lamellar keratoplasty, intrastromal corneal ring segments, and corneal collagen cross-linking with riboflavin) are succeeding previous treatments.