Forme Fruste Keratoconus Research Articles

Search for genetic markers for precise diagnostics of keratoconus

Keratoconus is a chronic disorder of the cornea, characterized by its progressive thinning, stretching, and conical protrusion. Diagnostics of subclinical keratoconus, as well as its early stages (forme fruste), is a complex problem. The presence of these forms of keratoconus in a patient is one of the reasons for the development of keratectasia after laser refractive surgery. Currently, the role of genetic factors in keratoconus development has been proven. This indicates the possibility of diagnostics of subclinical and forme fruste keratoconus using genetic markers. Knowledge about the patient's genetic susceptibility to keratoconus would allow correcting the tactics of treatment of refractive anomalies and avoiding serious side effects. The studies of causal mutations indicate the genetic heterogeneity of keratoconus, which complicates the development of a diagnostic panel. Selection of candidate variants from the currently known ones based on clear criteria may be one of the approaches for diagnostic markers search. In this review, we have analyzed articles on keratoconus markers in order to form a list of candidate variants for genotyping in the Russian population. The selection criteria took into account the complexes of symptoms in which a marker was found, populations in which a particular marker was investigated, the presence and results of replication studies. The analysis included markers in VSX1, SOD1, ZEB1, LOX, CAST, DOCK9, TGFBI, HGF, MAP3K19, KCND3, COL4A3, COL4A4, COL5A1, FNDC3B, FOXO1, BANP-ZNF469, MPDZ-NF1B, WNT10A genes. Based on the results of the analysis, the following candidate variants were selected for genotyping in the Russian population of patients with keratoconus: rs1536482 and rs7044529 in the COL5A1 gene, rs5745752 and rs2286194 in the HGF gene, rs4954218 in the MAP3K19 gene, rs4839200 near the KCND3 gene, rs2721051 near the FOXO1 gene, rs1324183 between the MPDZ and the NF1B genes, and rs121908120 in the WNT10A gene.

Comparison of topographic indices and corneal higher order aberrations in eyes with an extreme asymmetry of keratoconus with control eyes

Purpose: To compare topographic indices and anterior corneal higher order aberrations (HOAs) of forme fruste keratoconus (KC) (fellow eyes) with clinical KC and control eyes. Setting: Tertiary Eye Hospital, India. Materials and Methods: This study retrospectively reviewed 298 patients with KC. Patients were evaluated with placido-based topographer. KC was diagnosed according to Rabinowitz and McDonnell criteria and clinical sign. Twenty-one patients with clinical KC in one eye (Group A), fellow eye (Group B) with normal topography with no clinical sign, and 21 control eyes (Group C) were included in the study. Topographic indices (keratometry, inferior superior ratio, irregularity, shape factor, and eccentricity) and HOAs (trefoil, coma, spherical aberration, total root mean square [RMS], HOAs RMS of third to seventh order for 6 mm diameter) were obtained. Group B was compared with Groups A and C. Results: The prevalence of an extreme asymmetry of KC in our study population is 7.04% with mean age of 21.98 ± 7.39 years. All topographic indices were higher in Group A compared to Group B (P

Involvement of anterior and posterior corneal surface area imbalance in the pathological change of keratoconus

Keratoconus (KC) is an ectatic disorder with a high prevalence rate. However, the exact cause of the disease and possible underlying mechanisms of development remain unclear. In this present study, we aimed to investigate the anterior and the posterior corneal surface area in normal, forme fruste keratoconus (FFKC), and keratoconic eyes (as a reference group) using anterior segment optical coherence tomography (AS-OCT) in order to assess the pathological change of KC. The surface areas of the anterior or posterior cornea, and the anterior-posterior (As/Ps) ratio of corneal surface area, were measured at the central 5.0 mm-, 6.0 mm-, and 7.0 mm-diameter areas via AS-OCT, and a comparison between the normal eyes and FFKC eyes was then performed using the Mann-Whitney U test. The posterior surface area at the central 5.0 mm areas in the FFKC eyes (20.430 mm2) and KC eyes (20.917 mm2) seemed to become larger than that of normal eyes (20.389 mm2) (normal vs FFKC; P = 0.06). Moreover, the As/Ps of the corneal surface area in the FFKC eyes (0.986) and the KC eyes (0.976) was significantly smaller than that of the normal eyes (0.988) (normal vs FFKC; P < 0.01). Anterior and posterior corneal surface area imbalance may reflect keratoconic eyes at the early stage of the disease.

Topographic Asymmetry Indices: Correlation between Inferior Minus Superior Value and Index of Height Decentration.

Purpose To investigate the correlation between decentration index (index of height decentration, IHD) automatically calculated by the Pentacam HR software and the manually calculated inferior minus superior (I‐S) value. Setting Al Watany Eye Hospital, Cairo, Egypt. Methods In a retrospective study, history taking, clinical examination, and rotating Scheimpflug camera scanning (by Oculyzer II equivalent to Pentacam HR) were done to 128 eyes: 82 normal, 24 forme fruste keratoconus FFKC (apparently normal cornea with evident keratoconus in the fellow eye), and 22 keratoconus (KC). All cases of corneal scars or previous corneal surgeries were excluded. The (I‐S) value was calculated manually from 10 points astride the horizontal meridian. The IHD is calculated automatically by the device software 1.17r119. Results The mean (±SD) of (I‐S) value in normal, FFKC, and KC eyes were 0.30 ± 0.93, 0.11 ± 2.03, and 4.62 ± 3.89, respectively, and those of IHD were 0.008 ± 0.004, 0.011 ± 0.005, 0.066 ± 0.067, respectively. The two indices were highly correlated (p < 0.0001) with a correlation coefficient (r2 = 0.874). Deduced regression formulae linking the two indices were calculated. Conclusions The two topographic decentration indices are highly correlated. Deduced formulae were proposed linking them.

Corneal crosslinking without epithelial removal

To evaluate the effect of riboflavin-ultraviolet (UV)-A corneal crosslinking (CXL) without epithelial removal on ectatic corneal disease. Woolfson Eye Institute, Atlanta, Georgia, USA. Prospective observational study. Patients were treated with a new riboflavin formulation without epithelial removal, then exposed to UV light (365nm) at 4mW/cm2 with on-off cycling for 30minutes. Uncorrected (UDVA) and corrected (CDVA) distance visual acuities, maximum corneal curvature (maximum keratometry [Kmax]), total higher-order aberrations (HOAs), and coma were measured at 3, 6, 12, and 24months postoperatively. Progression was defined as an increase of more than 1 diopter (D) in Kmax and loss of more than 1 line of CDVA. Five hundred twelve eyes of 308 patients with keratoconus or forme fruste keratoconus and 80 eyes of 55 patients with ectasia after laser insitu keratomileusis (LASIK) were treated with the new riboflavin formulation without epithelial removal; 229 patients received bilateral treatments, 95 of which were simultaneous. The mean UDVA and CDVA improved by 1 to 1.5 Snellen lines at 1 and 2years postoperatively (P<.0001). Mean Kmax decreased by 0.48 D at 2years postoperatively (P=.0002). Mean total HOAs and coma decreased by 36% (P<.0001) and 37% (P=.0002), respectively, at 2years postoperatively. Kmax decreased more than 1 D in three times as many eyes as it increased more than 1 D (P<.0001). No eyes progressed, and there was no loss of effect between 1 and 2years postoperatively. No vision-threatening events were observed. Pain typically resolved within 24hours, and visual acuity returned to preoperative levels in 1 to 2days. Epithelium-on CXL using this new protocol halted the progression of keratoconus and ectasia after LASIK. It was safer and provided more rapid visual recovery than CXL with epithelial removal, allowing routine bilateral, simultaneous treatment.

The importance of corneal biomechanics in assessing first degree family members of keratoconus patients

Aim: to determine the values of biomechanical parameters (corneal hysteresis - CH, corneal resistance factor - CRF and keratoconus match index - KMI) in patients with keratoconus and their first degree family members. The purpose of the present study was to investigate the importance of assessing corneal biomechanics in subjects at risk of developing the primary ectasia. Materials and methods: 48 participants divided into three groups were analyzed in an observational study after a complete ophthalmological exam with the primary focus on Ocular Response Analyzer. Results: The mean values of CH, CRF, and KMI in the group of relatives were lower compared with the controls but higher when compared with keratoconus patients. We noted significant differences of CH and CRF between all three groups, while in the case of KMI, only the keratoconus group presented statistically significant differences compared with the relatives, respectively with the healthy subjects. Conclusions: the decreased values of CH and CRF may raise the question whether corneal biomechanics could be an adjuvant tool in the screening of a first-degree family member of a keratoconus patient in the attempt of the early detection of a possible forme fruste keratoconus.

Comparative analysis of safety and efficacy of photorefractive keratectomy versus photorefractive keratectomy combined with crosslinking.

PurposeTo assess the safety, efficacy, and refractive predictability of half-fluence accelerated corneal collagen crosslinking (CXL) applied concurrently with photorefractive keratectomy (PRK), and compare the results to standard PRK.SettingRefractive Services, The Eye Foundation, Coimbatore, India.DesignInterventional comparative case series.MethodsPatients seeking refractive correction for myopia or myopic astigmatism were included in the study. Photorefractive keratectomy with concurrent half-fluence crosslinking (PRK Xtra) was performed in eyes with borderline suspicious tomography (not amounting to forme fruste keratoconus) or low pachymetry between 450 and 474 µm with an otherwise unremarkable corneal tomography. Eyes with normal corneal tomography and thickness between 475 and 500 µm underwent standard PRK. The minimum follow-up period was 1 year.ResultsIn total, 109 eyes underwent PRK Xtra (Group A) and 118 eyes underwent PRK alone (Group B). The preoperative MRSE was −3.64 D and −3.38 D in Groups A and B, respectively (P=0.28). Group A had a significantly higher number of eyes with thinner corneas (P<0.01) and corneal tomographic abnormalities (P=0.02). At 1 year follow-up, 96.3% of eyes in group A as against 99.1% of eyes in group B achieved a best corrected distance visual acuity (CDVA) of 20/20 or better. No iatrogenic ectasia or hyperopic shift secondary to progressive flattening was noted in the PRK Xtra group. No significant difference in incidence of haze was noted.ConclusionPRK Xtra showed comparable safety, efficacy, and stability to PRK in eyes with thinner pachymetry and tomographic abnormalities. Combining crosslinking with PRK in suspicious tomographies augurs for safe and predictable outcomes.

Objective and subjective diagnostic parameters in the fellow eye of unilateral keratoconus

BackgroundKeratoconus (KC) is usually a bilateral corneal ectatic disease. For significant asymmetric presentation (so called unilateral KC), the fellow eye has the mildest and earliest form of the disease, which is typically called forme fruste keratoconus. The aim of this study was to evaluate the sensitivity and specificity of parameters derived from a Scheimpflug imaging system (Pentacam) as well as the changes in the quality of mesopic vision in the apparently normal fellow eye (forme fruste) to detect the earliest and most sensitive parameters.MethodsPatients with clinical keratoconus in one eye and forme fruste keratoconus in the fellow eye were compared to subjects with normal eyes. The patients were examined using a rotating Scheimpflug imaging system (Pentacam).The following parameters were evaluated: keratometry, minimum corneal thickness, pachymetry progression index (PPI), Ambrósio relational thickness (ART), posterior elevation, back difference elevation (BDE) and multimetric D index(D index). Receiver operating characteristic (ROC) curves were analyzed by evaluating the area under the curve (AUC) to detect the sensitivity and specificity of each parameter. Mesopic vision evaluations were performed by contrast sensitivity and glare tests for each group.ResultsA total of 48 patients with clinical keratoconus in one eye and forme fruste keratoconus in the fellow eye and 72normal subjects were evaluated. In the clinical keratoconus eyes, the mean K, back difference elevation (BDE), pachymetric progression index maximum(PPI max), and multimetric D were significantly higher compared to the normal subjects, whereas the corneal pachymetry and Ambrósio relational thickness maximum (ART max) were significantly lower. In the forme fruste eyes, the ROC analysis showed that the AUC values of the mean K, thinnest pachymetry, ARTmax, BDE, D index, and PPI max were 0.82, 0.61, 0.88, 0. 67, and 0.64, respectively. The contrast sensitivity and glare tests were significantly affected in the forme fruste cases.ConclusionIn forme fruste keratoconus eyes, the ART max is considered a highly sensitive objective parameter. Contrast sensitivity and glare is an important subjective test, which is affected in forme fruste patients.

Comparison of Corneal Dynamic and Tomographic Analysis in Normal, Forme Fruste Keratoconic, and Keratoconic Eyes.

To investigate and compare the diagnostic ability of corneal tomography and dynamic corneal response to differentiate between normal eyes and those with forme fruste keratoconus and keratoconus. Corneal tomography was performed using Pentacam (Pentacam HR; Oculus Optikgeräte, Wetzlar, Germany). Corneal deformation response was captured via Corvis ST (Optikgeräte) using a beta version of Corvis software. Classification analysis between normal eyes and eyes with forme fruste keratoconus and between normal and keratoconic eyes was evaluated using receiver operating characteristic curves. The area under the ROC curve (AUC) and partial AUC (pAUC) for each classifying parameter were compared. Twenty-one patients with forme fruste keratoconus in one eye and clinically evident keratoconus in the fellow eye and 38 normal individuals were recruited. Overall, 21 eyes with forme fruste keratoconus and 18 eyes with keratoconus were compared with 73 normal eyes. The mean age of the participants was comparable between groups. Comparative analysis between Pentacam and Corvis ST parameters showed significantly lower AUC and pAUC for Corvis ST parameters in differentiating keratoconic from normal eyes (P ≥ .049). However, comparable AUC and pAUC was observed between the Corvis Biomechanical Index (AUC = 0.785; pAUC = 0.079) and D value of the Belin/Ambrósio Enhanced Ectasia Display (AUC = 0.757; pAUC = 0.068) (P ≥ .477) for detection of forme fruste keratoconus with sensitivities of 63.2% and 52.6%, given a common specificity of 80.3%. The current study showed the feasibility of use of non-tomographical parameters obtained from the Corvis ST for differentiating normal eyes and those with forme fruste keratoconus and keratoconus. The diagnostic ability of the Corvis ST was comparable to that of the Pentacam for differentiating normal eyes and eyes with forme fruste keratoconus. [J Refract Surg. 2017;33(9):632-638.].

Topographic typology in a consecutive series of refractive surgery candidates.

The term 'keratoconus (KC) suspect' is used as a blanket term to refer to any deviation of virgin cornea shape toward KC features. We intend to subclassify such topographies in meaningful and informative designations. Pentacam corneal topographies of 199 consecutive refractive surgery candidates (398 eyes) are examined. Features of steepness, inferior-superior asymmetry, focal steepening, thinning, and bounded anterior or posterior elevations are observed in the quad map. Scissoring on retinoscopy, loss of best spectacle-corrected visual acuity, and iron ring deposition were looked for. Through iterative observation and refinement of classification criteria-partly taken from the literature-all eyes were designated a specific topographic diagnosis, i.e., circumventing the usage of the expression KC 'suspect'. Topographies of 308, 48, 21, 13, 6, 1, and 1 (collectively 398 eyes) were designated: normal, 'atypical normal,' forme fruste KC, posterior KC, subclinical/mild KC, superior KC, and pseudo-KC, respectively. Current imaging modalities of the cornea and our accumulated experience in refractive science allow assignment of distinctive designations for abnormal corneal shapes along the topography spectrum. We devised and used the expressions: normal, atypical normal, forme fruste (arrested-incomplete) KC, posterior KC, subclinical (active latent) KC, superior KC, and pseudo-keratoconus. Identification of 1.5% (mild) KC highlights the importance of screening for ultraviolet cross-linkage candidacy in refractive surgery referrals.

Risk profiles of ectasia after keratorefractive surgery.

To identify and evaluate the risk factors of iatrogenic ectasia after refractive surgery. We reviewed recently published papers that identified various risk factors associated with ectasia after LASIK, photorefractive keratectomy, small incision lenticule extraction, and other refractive surgical procedures. We also attempted to evaluate the relative contributions of these factors to the development of ectasia following refractive surgery. Forme fruste keratoconus, genetic predisposition to keratoconus, low residual stromal bed thickness (through high myopia, thin preoperative cornea, or thick LASIK flap), and irregular corneal topography have been identified as risk factors for keratectasia development after refractive surgical procedures. A newly proposed metric, percentage tissue altered, has been reported to be a robust indicator for post LASIK ectasia risk calculation. Several cases of keratectasia have also been reported 6 to 12 months following minimally invasive small incision lenticule extraction procedure. Other risk factors associated with iatrogenic ectasia include eye rubbing, young age, and pregnancy. Ectasia after refractive surgery is a relatively rare complication which can lead to sight-threatening complications if not detected and treated in time. It is important to continue our quest to improve our methods of identifying absolute and relative risk factors of ectasia and their cut-off values following various keratorefractive surgical procedures.

Ocular, corneal, and internal aberrations in eyes with keratoconus, forme fruste keratoconus, and healthy eyes.

The purpose of this study is to evaluate ocular, corneal, and internal aberration parameters in eyes with keratoconus (KC), forme fruste keratoconus (FFKC), and normal eyes. In a prospective study, one eye of 110 patients with KC, 60 FFKC patients, and 150 healthy participants was evaluated using OPD-Scan II. Ocular, corneal, and internal higher-order aberrations were measured through a sixth-order Zernike polynomial decomposition. Receiver operating characteristic analysis was performed to evaluate the diagnostic ability of the aberration parameters in discriminating KC and FFKC from normal eyes. The root mean square of the all ocular aberration measurements was significantly higher in the KC and FFKC patients than that of normal participants (p<0.05). All of the corneal aberration measurements were significantly higher in KC patients than those of normal patients (p<0.05); however, only corneal total higher-order aberration (HOA), vertical and total coma, and higher-order astigmatism were significantly higher in the FFKC patients than normal participants (p<0.05). The results also showed that internal aberration lower-order astigmatism, total trefoil, and total higher-order spherical aberration were significantly different between KC and normal groups (p<0.05). In comparison, internal total HOA, lower and higher-order astigmatism, total trefoil, and vertical coma were significantly different between FFKC and normal groups (p<0.05). Ocular vertical and total coma had the highest ability in discriminating keratoconic from normal eyes. Ocular total higher aberration and total coma had the highest diagnostic ability in discriminating FFKC from normal eyes. The diagnostic ability of internal aberration, on the other hand, was moderate to poor in discriminating KC and FFKC from normal eyes. Ocular aberration especially vertical and total coma and total HOA were found to be suitable parameters to discriminate KC and FFKC from normal patients. These two parameters could be used as discriminating factors in evaluating the patient for refractive surgery in an attempt to avoid iatrogenic ectasia.

Keratoconus must be diagnosed in advance. Case report and discussion of the diagnostic approach

Performing cataract surgery on a patient with keratoconus is not uncommon. Cataract surgery for such patients does require some additional testing and consideration for the best visual outcomes. Choosing the appropriate lens and lens power can be more challenging. Most patients with keratoconus have high negative spherical aberration and implantation of multifocal intraocular lenses (IOLs) will result in loss of contrast sensitivity associated with these lenses which will be magnified by the corneal irregularity. Also, decentration of IOL relative to the apex of the cone will induce coma and decrease the quality of vision. Our goal was to describe the result after implantation of multifocal intraocular lens in a patient with forme fruste keratoconus and to show that the preoperative selection of an appropriate IOL in such patient is the key for better visual function.

Distinguishing between contact lens warpage and ectasia: Usefulness of optical coherence tomography epithelial thickness mapping

To distinguish between corneal ectasia and contact lens-related warpage by characteristic patterns on corneal topography and optical coherence tomography (OCT) epithelial thickness maps. Casey Eye Institute, Portland, Oregon, USA. Prospective and retrospective case series. Axial and mean power maps were obtained on corneal topography systems. Epithelial thickness maps were generated using RTVue OCT. A sector divider was applied to all maps. The locations of the minimum epithelial thickness, maximum epithelial thickness, maximum axial power, and maximum mean power were determined based on sector averages. Agreement was defined as the extremums occurring in the same or adjacent sectors. Twenty-one eyes with keratoconus, 6 eyes with forme fruste keratoconus (better eye of asymmetric keratoconus), and 15 eyes with contact lens-related warpage were identified. The keratoconus and forme fruste keratoconus eyes had coincident topographic steepening with epithelial thinning. The locations of minimum epithelial thickness and maximum axial power agreed in 90% of the keratoconic eyes, while the minimum epithelial thickness and maximum mean power agreed in 95% of them. Conversely, the warpage eyes had coincident topographic steepening with epithelial thickening and normal pachymetry maps. The locations of maximum epithelial thickness and maximum axial power agreed in 93% of the warpage eyes, while the maximum epithelial thickness and maximum mean power agreed in all warpage eyes. Results show that epithelial thickness maps and corneal topographic maps are powerful synergistic tools in evaluating eyes with abnormal topography and can help differentiate between keratoconus and nonectatic conditions.

Application of high resolution OCT to evaluate irregularity of Bowman's layer in asymmetric keratoconus.

Irregularity of the Bowman's layer (BL) in keratoconus (KC, sample size (n) = 28) and forme fruste keratoconus (FFKC, n=18) eyes was evaluated. Subjects underwent high resolution OCT imaging (Bioptigen Inc., USA) and corneal tomography (Pentacam v1.20r41, OCULUS Optikgeräte GmbH, Germany). Anterior edge of the BL was segmented. A Bowman's roughness index (BRI) was defined as the sum of the enclosed areas between segmented edge and a smooth 3rd order polynomial fit to the edge. BRI was compared with corneal aberrations, Keratoconus percentage index (KISA), Cone location magnitude index (CLMI) and Belin-Ambrosio enhanced ectasia display overall deviation index (BAD-D). Area under the curve (AUC) was determined with logistic regression (LR). Mean BRI (×10-3 ) was 2.12 mm2 , 1.81 mm2 and 1.7 mm2 in normal (n=26), FFKC and KC eyes, respectively (p<0.001). BAD-D (0.79) and BRI (0.74) had the best AUC for FFKC. By combining BAD-D and BRI, the AUC improved to 0.85 (p=0.01). For KC eyes, KISA (0.94), CLMI (0.88), BAD-D (0.96) and aberrations had comparable AUC (p>0.05). However, LR with BRI and other indices didn't improve the AUC in KC eyes (p>0.05). BRI was significantly reduced in FFKC and KC eyes. It improved the detection of FFKC but not KC eyes.

Differentiating Keratoconus and Corneal Warpage by Analyzing Focal Change Patterns in Corneal Topography, Pachymetry, and Epithelial Thickness Maps.

PurposeTo differentiate between keratoconus and contact lens-related corneal warpage by combining focal change patterns in anterior corneal topography, pachymetry, and epithelial thickness maps.MethodsPachymetry and epithelial thickness maps of normal, keratoconus, and warpage, and forme fruste keratoconus (FFK) eyes were obtained from a Fourier-domain optical coherence tomography (OCT). Epithelial pattern standard deviation (PSD) was calculated and combined with two novel indices, the Warpage Index and the Anterior Ectasia Index, to differentiate between normal, keratoconus, and warpage eyes. The values of the three parameters were compared between groups.ResultsThe study included 22 normal, 31 keratoconic, 11 warpage, and 8 FFK eyes. The epithelial PSD was normal (< 0.041) for 100% normal eyes and abnormal (> 0.041) for 100% of keratoconic eyes, 81.8% of warpage eyes, and 87.5% of FFK eyes. The Anterior Ectasia Index of normal eyes (1.66 ± 0.74) was significantly lower than that for the keratoconus eyes (17.5 ± 7.17), the warpage eyes (2.98 ± 1.69), and the FFK eyes (6.95 ± 5.86). The Warpage Index was positive in all warpage eyes and negative for all keratoconic and FFK eyes except three wearing rigid gas-permeable contact lens.ConclusionsThe epithelial PSD can distinguish normal from keratoconus or warpage, but does not distinguish between these two conditions. The Anterior Ectasia Index is abnormal in keratoconus but not warpage. The Warpage Index is positive for warpage and negative for keratoconus, except in cases where keratoconus and warpage coexist. Together, the three parameters are strong tripartite discriminators of normal, keratoconus, and warpage.

Quantitative Evaluation of the Natural Progression of Keratoconus Using Three-Dimensional Optical Coherence Tomography

We quantified the chronologic progression of keratoconus using anterior segment optical coherence tomography (AS-OCT). A total of 217 eyes from 113 patients with keratoconus, keratoconus suspect, or forme fruste keratoconus were evaluated by corneal tomography using swept-source OCT. Age-dependent changes in the radius of the posterior best-fit sphere (Rpost), minimum corneal thickness (Tmin), and distance from the thinnest point to the corneal vertex (Dmin) were examined over follow-up periods of up to 5.79 years and were analyzed using generalized estimating equation (GEE) nonlinear regression model. Annual changes in Rpost (mean, -0.017 mm) and Tmin (-2.69 μm) were significantly higher in younger patients (P < 0.01, GEE nonlinear regression) and in patients with higher maximal K value (Kmax; P < 0.01, GEE nonlinear regression), whereas no changes were observed in Dmin. Even in patients 30 years or older, 14% of eyes revealed remarkable progression in Rpost. In eyes with acute hydrops, annual changes in Rpost (-0.22 mm) and Tmin (-33.8 μm) before acute corneal hydrops were more than 10 times faster than those in other eyes (P < 0.001, GEE nonlinear regression). Chronologic measurements of corneal tomography in keratoconus demonstrated that the progression of steepening at posterior corneal surface was found not only in patients under 30 years but also in older patients, particularly in advanced keratoconus. The rate of progression can be measured by mapping of corneal curvature and thickness using OCT, and the risk of progression was greater in younger patients with steeper Kmax.

Astigmatic Vector Analysis of Posterior Corneal Surface: A Comparison Among Healthy, Forme Fruste, and Overt Keratoconic Corneas

To determine novel diagnostic parameters for keratoconus, and to assess the correlation between anterior and posterior corneal surfaces based on vectorial astigmatism analyses. Retrospective case-control study. Six hundred and ninety-eight eyes of 698 patients were enrolled in the study. Healthy corneas, or controls (C, n= 264), were compared to keratoconic corneas, further categorized as forme fruste (FFKc, n= 212) and overt keratoconus (Kc, n= 222). Corneal measurements were obtained from a Scheimpflug-based tomographer. Vectorial analyses were conducted in accordance with the method proposed by Thibos. Posterior corneal astigmatic power vector (APV) >0.23 diopter (D) yielded a test for overt Kc with sensitivity and specificity rates of, respectively, 81% and 77%, indicating a positive likelihood ratio (LR+) of 3.5 and a negative likelihood ratio (LR-) of 0.25. Posterior corneal overall blur vector (Blur) >6.45 D yielded a test slightly less sensitive and specific, with rates of 75% and 72%, respectively, associated to LR+ of 2.7 and LR- of 0.35. The highest (Spearman ρ) correlation coefficients between anterior and posterior corneal astigmatisms were associated with Blur, being 0.93 for Kc, 0.87 for C, and 0.81 for FFKc. The astigmatism vectors along the 45-degree (J45) and 0-dregree meridians (J0) and APV most often presented higher coefficient values for Kc and FFKc than for C (P= .01). Posterior corneal vectors APV and Blur constitute objective supplemental parameters for the diagnosis of Kc. Anterior and posterior corneal surfaces correlate in all groups, although it was not possible to accurately predict posterior astigmatism from anteriorastigmatism.

Corneal Deformation Response with Dynamic Ultra-high-speed Scheimpflug Imaging for Detecting Ectatic Corneas

ABSTRACT Purpose To test the ability of metrics derived from corneal response to noncontact tonometry (NCT) to distinguish between normal and ectatic cases. Materials and methods The prototype of CorVis ST (Oculus, Wetzlar, Germany) was used for assessing corneal biomechanical response using ultra-high-speed 8 mm horizontal Scheimpflug photography, taking 4,330 frames per second during NCT. Patients were stratified based on clinical data, including rotating Scheimpflug corneal tomography (Oculus Pentacam HR). Biomechanical data from one eye randomly selected of 177 patients with normal corneas (N) and from 79 patients with bilateral keratoconus (KC) were investigated. Group forme fruste keratoconus (FFKC) was composed of 20 eyes with normal topographic patterns from cases with ectasia detected in the fellow eye. Group keratoconus suspect (KCS) had 16 eyes from 16 patients with topographic patterns suspicious of KC but documented stability over 3 years and normal tomographic findings. A combination of deformation parameters using linear regression analysis (Prototype Factor 1, pF1) was created by the BrAIn (Brazilian Artificial Intelligence on Corneal Tomography and Biomechanics) study group in order to provide the best possible separation of KC and normals. Results Statistical significant differences were found for N × KC for several parameters, including first and second applanation times, deformation amplitude, and maximal concavity radius (Mann–Whitney, p &lt; 0.001). However, the areas under the receiver operating characteristic curves (AUC) were lower than 0.90. The pF1 had AUC of 0.945 (IC 0.909–0.97; sensitivity = 87.3% and specificity = 89.3%). The pF1 had statistically significant differences between the ectatic (KC and FFKC) and nonectatic groups (N and KCS) (p &lt; 0.05, Kruskall–Wallis Test with post hoc Dunn's test). Conclusion Corneal deformation response analysis by ultra- high-speed 8 mm horizontal Scheimpflug photography provides relevant data for distinguishing ectatic and nonectatic corneas but cannot be used independently to detect KC. This data may be integrated with corneal tomography data for enhancing sensitivity and specificity for screening ectasia. How to cite this article Salomão MQ, Correia FF, Ramos I, Luz A, Ambrósio R Jr. Corneal Deformation Response with Dynamic Ultra-high-speed Scheimpflug Imaging for Detecting Ectatic Corneas. Int J Kerat Ect Cor Dis 2016;5(1):1-5.

Subclinical Keratoconus Detection in Identical Twins

ABSTRACT Purpose To report clinical keratoconus in only one eye of two identical female twins, along with subclinical disease in the fellow eyes, elaborating on the two-hit hypothesis of ectasia development, which relates to the combination of genetics and the impact of environment. Methods Case report and literature review. Results Two identical 48-year-old female twins were presented for clinical evaluation. Mild keratoconus was detected in the right eye of twin 1, characterized by classic slit-lamp findings (exacerbated corneal nerves and incomplete Fleisher's ring) and front surface curvature abnormalities, including asymmetry of the inferior–superior curvature at 6 mm (I–S value) of 2.78 D and a grade 1 Topographic Keratoconus Classification pattern. Topographic Keratoconus Classification was possible in the fellow eye of twin 1 (I–S value = 1.22 D) and negative in both eyes of twin 2 (I–S value = −0.46 OD and −0.13 OS). Ambrósio's Relational Thickness for the maximal progression meridian was 209 and 354 in twin 1 and 360 and 392 in twin 2 in the right and left eyes respectively. The final deviation value of the Belin–Ambrósio Enhanced Ectasia Display was 4.54 and 1.47 in twin 1 and 1.7 and 1.35 in twin 2. Conclusion Corneal tomography data provide a better representation of corneal genotype in detecting mild, subclinical, or forme fruste keratoconus in the fellow eyes with normal topography of these twins. These cases present high risk or susceptibility for ectasia progression if environmental factors are associated (second hit). How to cite this article Guerra G, de Oliveira VB, Ferreira I, Ramos I, Belin MW, Ambrósio R Jr. Subclinical Keratoconus Detection in Identical Twins. Int J Kerat Ect Cor Dis 2016;5(1):35-39.