Role of corneal epithelial thickness mapping in the evaluation of keratoconus

PurposeTo investigate the corneal epithelial thickness profiles in patients with a confirmed diagnosis of stable and progressive keratoconus.SettingStudio Italiano di Oftalmologia, Rome, Italy.DesignObservational study.Methods86 patients with either stable (n = 52) or progressive (n = 34) keratoconus and 182 healthy controls were enrolled in the study. Disease progression was confirmed by repeated corneal topographies over 1 year follow-up before inclusion in the study. All subjects had full corneal and epithelial thickness mapping taken by spectral domain optical coherence tomography (SD-OCT). The full corneal mapping was investigated by evaluating the central corneal thickness, the thinnest point, the superonasal-inferotemporal thickness difference and the minimum-median thickness difference. The epithelial mapping was investigated by assessing the 2 mm central thickness, the inferior paracentral (2–5 mm) thickness, and the minimum-maximum thickness difference.ResultsNo significant differences in full corneal mapping were found between stable and progressive keratoconic eyes. Of note, the inferior paracentral region of the corneal epithelium was significantly thinner in progressive (50 ± 3 μm) than stable (53 ± 4 μm) keratoconus (P < 0.001).ConclusionsThe SD-OCT corneal epithelial mapping was valuable for detecting local thickness changes in eyes with keratoconus. Monitoring the corneal epithelial changes across the inferior area in patients with keratoconus could be worthy for assessing disease progression.     

Scleral shape and its correlation with corneal parameters in keratoconus

PurposeTo assess the correlation of the scleral shape and corneal tomographic parameters in keratoconus.MethodsTwenty eyes of 15 keratoconus patients with no previous specialty lens wear or ocular surgery were included in this study. Corneal imaging was obtained with the Pentacam HR and three-dimensional (3D) corneoscleral maps were acquired using the Eye Surface Profiler, ESP. Sagittal height was calculated at the central corneal level (annulus of 0–4 mm radius), peripheral cornea (annulus 4–6 mm radius) and sclera (annulus 6–8 mm radius) using ESP maps and Pentacam HR (exclusively for the central cornea). The flattest and steepest regions of each annulus and the circumferential scleral asymmetry were calculated based on custom-made software. The Pearson correlation coefficient (r) was used to evaluate the correlation between corneal parameters as measured by Pentacam HR and scleral asymmetry.ResultsAnterior corneal parameters, such as flattest and steepest keratometry, were found to be correlated with scleral asymmetry in keratoconus (all r>0.5, p < 0.05). In contrast, anterior astigmatism showed poor correlation with the level of scleral irregularity (r=-0.11; p = 0.32). Other disease-specific parameters pertaining to the posterior corneal curvature and corneal thickness were not correlated with scleral asymmetry. The steepest regions of the central cornea, peripheral cornea, and sclera tended to share a common angle (r = 0.92; p < 0.001 for central cornea compared to sclera).ConclusionAnterior corneal parameters measured by corneal imaging are associated with the level of scleral asymmetry and the orientation of the steepest area of the sclera in eyes with keratoconus.     

Efficacy of corneal tomography parameters and biomechanical characteristic in keratoconus detection

AimTo determine the efficacy of corneal thickness parameters and corneal biomechanical properties (CBPs) in discriminating between normal and keratoconus eyes.MethodAfter performing a comprehensive ophthalmic examination, 50 mild to moderate keratoconus and 50 age and sex matched myopic astigmatism eyes were prospectively included in the study. The corneal topographic maps and CBP were obtained by Pentacam and Ocular response analyser, respectively. Central corneal thickness (CCT), thinnest corneal thickness (TCT), corneal thickness (CT) and percentage thickness increase (PTI) at 1, 3 and 5 mm from the thinnest point and corneal volume (CV) at 3, 5, 7 and 10 centred on thinnest point, corneal hysteresis (CH) and corneal resistance factor (CRF) were recorded. Independent t-test and receiver operating characteristic (ROC) were done with SPSS software (version 15.0, SPSS, Inc.).ResultsCCT, TCT, CT at 1, 3 and 5, CV at 3, 5, 7 and 10 mm, CH and CRF were significantly lower in keratoconus eyes compared to controls (p < 0.001). In addition, PTI at 1, 3 and 5 mm from the thinnest point showed significantly higher values in keratoconus group. ROC analysis demonstrated good predictive accuracy for cut-off point values. However, the centrally located indices had higher predictive accuracy compared to the peripherally located indices.ConclusionAlthough good sensitivity and specificity were found for the mentioned parameters, the centrally located indices had higher predictive accuracy compared to peripherally located indices. It is suggested to use a combination of corneal pachymetry together with CBP for more accurate detection of keratoconus.     

A pilot study on corneal Langerhans cells in keratoconus

Purpose

To report the density and morphology of cells that are analogous to corneal Langerhans cells and their associations in keratoconus.

Randomised controlled trial of corneal vs. scleral rigid gas permeable contact lenses for keratoconus and other ectatic corneal disorders

PurposeTo compare the comfort and visual performance of corneal rigid gas permeable contact lenses (CoL) and scleral rigid gas permeable contact lenses (SL) in participants with corneal ectasia, successfully wearing “habitual” CoL.MethodsIn a randomised controlled trial (RCT) with a 2 × 2 crossover, 34 participants were recruited and randomised into two groups. Group 1 (sequence AB), were fitted in period 1, with new CoL and after a 4-week washout period, in which habitual CoL were worn, were fitted with and crossed-over to SL, period 2. Group 2 (sequence BA), were first fitted with SL in period 1 and after a washout period of 4 weeks, crossed-over to new CoL, period 2. The median lengths in weeks of Periods 1 and 2 were: 17.5 (IQR 12.4) and 14.5 (IQR 6.2) respectively. The outcome measures for visual performance were best corrected visual acuity and the contrast sensitivity function. Vision related quality of life (Qol) was assessed using the National Eye Institute Visual Function Questioannaire-25 and reported subjective perception of vision (SPV) and reported subjective perception of comfort (SPC) scores, recorded on a scale from 1–10. The final outcome measure was the selection of the preferred lens type at the completion of the RCT.ResultsFor the 30 who completed the trial, significantly higher SPC scores were found for SL compared to CoL (p = 0.002). Significantly higher SPC scores for CoL were found in participants who selected CoL as their preferred lens for future use, compared to those who selected SL (p = 0.009). All other outcomes exhibited no significant difference between the experimental lenses. There was no significant difference (p=0.86) in the proportion preferring CoL (53%) and SL (47%).ConclusionSignificantly better comfort was reported for SL compared with CoL. Significantly higher comfort in CoL was found in those who preferred CoL, than those who preferred SL. Successful CoL wearers whose SPC in CoL is <7 are likely to achieve better comfort with SL. On average, successful CoL wearers found SL more comfortable and there are unlikely to be any significant visual or visual Qol advantage or disadvantage in refitting successful CoL wearers with keratoconus and other corneal ectasia disorders, with SL and vice versa.     

A case of concomitant keratoconus and granular corneal dystrophy type II

PurposeWe report a Korean case of concomitant keratoconus and granular corneal dystrophy type II.MethodsCase report.ResultsA 29-year-old man visited our clinic for a routine ocular check-up. Slit-lamp examination revealed a few well-circumscribed, greyish-white, discrete granular opacities in the central corneal stromae of both eyes. Direct sequencing of exon 4 of the BIGH3 gene revealed a heterozygous transversion from G to A in the second-nucleotide position of codon 124. In addition, a Fleischer ring and Vogt's striae were evident in the cornea. The corneal topography was suggestive of keratoconus.ConclusionGranular corneal dystrophy type II can co-exist with keratoconus and should be included in the differential diagnosis.     

Evaluation estrogen,progesteron and androgen receptor expressions in corneal epithelium in keratoconus

PurposeTo evaluate the role of sex steroid hormone receptors in corneal epithelium in etiopathogenesis of keratoconus (KC).MethodsThirty patients with KC who were planned for corneal collagen-crosslinking and 20 patients who were planned for excimer laser for refractive errors included in this study. Corneal epitheliums were curated mechanically during surgeries. Right eyes were evaluated immunohistochemically and left eyes were evaluated by quantitative polymerase chain reaction (qPCR) to investigate estrogenα, estrogenβ, progesterone and androgen receptors.ResultsImmunohistochemically, staining for progesterone and androgen receptors did not significantly differ between KC and control groups (p > 0.05). None of the cases had staining for estrogenα and estrogenβ receptors. qPCR showed that mRNA expressions of estrogenα and androgen receptors were significantly higher in the KC group (p < 0.001).ConclusionA significantly higher rate of estrogenα and androgen receptor expressions in corneal epithelium from patients with KC through qPCR supports a possible relation between KC and sex steroid hormones.     

Longitudinal corneal tomographical changes in eyes of patients with unilateral and bilateral non-progressive keratoconus

AimTo evaluate the tomographic indices changes in keratoconic eyes which were classified as unilateral and bilateral non-progressive keratoconus according to the definition of Global Consensus on keratoconus and ectatic disease.MethodsFifty non-progressive fellow eyes of 50 keratoconus patients who underwent corneal cross-linking treatment for the other progressive eyes (group 1), 50 eyes of 50 keratoconus patients who were followed up as bilateral non-progressive keratoconus (group 2), and 50 eyes of 50 control subjects (group 3) were included in this retrospective study. Topographic, topometric, and Belin–Ambrósio Enhanced Ectasia Display-III indices were recorded at baseline and after six months.ResultsGroups were similar in terms of age and gender. The changes in topographic parameters and topometric indices were similar among the three groups (p > 0.05 for all values). The maximum pachymetric progression index (PPI_max), maximum Ambrósio relational thickness (ART_max), and final D significantly increased at sixth-months in group 1 (p < 0.001, p = 0.004, and p = 0.02 respectively) but did not change in groups 2 and 3 (p > 0.05 for all values). ART_max, PPI_max, and final D value changes indicated a statistically significant difference among the groups using the one-way ANOVA test (p = 0.03, p = 0.007, and p = 0.03 respectively). The Bonferroni posttest revealed that these values increased at a higher rate in group 1 than in group 2 (p = 0.03, p = 0.01, and p = 0.04 respectively) and group 3 (p = 0.04, p = 0.03, and p = 0.04, respectively).ConclusionsFellow eyes of keratoconus patients who have underwent CXL for their progressive eyes may be more prone to progress than the patients who have no progression in both eyes. Screening unilateral non-progressive patients more closely than those with bilateral non-progressive patients and evaluating the changes in final D, ART_max, and PPI_max values may be helpful in the follow up of non-progressive keratoconus.     

Improved contact lens fitting after corneal cross-linking in eyes with progressive keratoconus

ObjectivesThe study aimed to assess the possible effects of corneal cross-linking (CXL) on contact lens (CL) fitting in patients with progressive keratoconus who initially had CL intolerance.MethodsA retrospective review was performed of the medical records of patients who had stopped CL wear due to discomfort prior to CXL and who were fitted with CLs after CXL. All eyes were evaluated pre- and 1, 6, 12, 24 months postoperatively. Data collected included pre- and post-CXL refraction, corneal topographic data, uncorrected visual acuity, and best-corrected visual acuity (BCVA). CL comfort was evaluated using the Likert scale post-CXL.ResultsA total of 20 eyes from 14 patients were included in the study. Preoperative Kmax values significantly decreased by 2.8 D at 6 months and by 4.1 D at 12 months after CXL (p < 0.001 for both). CLs were prescribed on average 12 ± 2.5 months after CXL. The mean duration of successful CL wear was 10.4 ± 2.8 months during the follow-up period. Subjective CL comfort scores were satisfactory post-CXL.ConclusionCXL not only halts the progression of keratoconus but may also improve CL tolerance by providing a more regular shaped cornea in these patients. Ongoing corneal topographic changes in the late postoperative period after CXL may have a positive effect on CL fitting.     

The research progress on the molecular mechanism of corneal cross-linking in keratoconus treatment

Keratoconus (KC) is a corneal anomaly that is manifested in a limited cone-like bulge with corneal thinning. Many molecules in the cornea change during the development of KC, including various components of the extracellular matrix, cytokines, cell connection, and cell adhesion-related proteins. Several treatment options are available, with corneal cross-linking (CXL) being the treatment of choice for early KC. However, postoperative complications have been reported in some CXL patients, mainly caused by corneal epithelial resection. Despite the fact that some novel approaches have helped to reduce some of the initial post-operative issues, their effectiveness seems to be inferior to that of the original CXL. To keep effectiveness while avoiding these negative effects, it is necessary to study the mechanism of CXL in KC treatment at the molecular level. This article provides a review of the molecular mechanism of CXL in the treatment of KC from four aspects: enzyme activity, signal transduction pathway, corneal-related proteins, and other KC-related molecules, further confirming the feasibility of CXL treatment of KC, providing new ideas for improving CXL.     

Assessment of corneal endothelial cell density in patients with keratoconus not using contact lenses

PurposeTo assess the corneal endothelial cell density (ECD) in keratoconus patients with no history of contact lens use.SettingYuzuncu Yil University, School of Medicine and Van Training and Research Hospital, Department of Ophthalmology, Van, Turkey.DesignCross-sectional controlled study.MethodsThe eyes of 65 patients with the diagnosis of keratoconus with no history of contact lens wear and the eyes of 40 healthy controls were prospectively examined using the Heidelberg Retinal Tomography Rostock Cornea Module (HRT3/RCM). The average ECD from the two groups were then compared.ResultsOf the cases with keratoconus, 44 (67.7%) were men and 21 (32.3%) were women. The mean age was 20.9 ± 6.8 (range = 10–41) years. Of the controls, 28 (70%) were men and 12 (30%) were women. The mean age was 23.9 ± 5.8 (range = 14–35) years. Of the 65 eyes with keratoconus, 19 (29.2%) had mild keratoconus, 21 (32.3%) had moderate keratoconus, and 25 (38.5%) had severe keratoconus. The mean ECD was 2731.6 ± 303.2 cells/mm² in cases with keratoconus and 2664.9 ± 319.5 cells/mm² in controls. There was no difference between the densities (unpaired t-test, P = 0.4). No significant relationships were found between the ECD data and central corneal thickness or steepest keratometric.ConclusionsEndothelial cell density was unaltered in keratoconic patients without a history of contact lens use when compared with healthy controls. Change in ECD is independent from the central corneal thickness and the stage of keratoconus.     

Clinical evaluation of meibomian gland dysfunction in patients with keratoconus

PurposeTo investigate the association of keratoconus (KC) with meibomian gland dysfunction (MGD) and to describe the epidemiological characteristics of MGD in this disease.MethodsIn this observational study, 120 KC patients seen in the Department of Ophthalmology of the Complexo Hospitalario Universitario de Santiago de Compostela and 87 controls were analyzed. The Ocular surface disease index (OSDI) questionnaire was administered and several DED tests and an evaluation of the meibomian glands and lid margin were performed. MGD signs and DED tests were compared between the groups. Symptoms were further analyzed in patients and controls with and without MGD.ResultsKC was significantly associated with MGD after adjusting for age and sex [adjusted odds ratio (ORa), 2.40]. The frequency of MGD in KC patients [59 (49.2%) KC patients and 25 (28.7%) controls had MGD] correlated with the severity of KC (r = 0.206) (P = 0.020). Mean OSDI score in KC patients with and without MGD was 31.1 ± 24.1 and 35.2 ± 26.0 (P = 0.326), and 17.2 ± 22.7 and 13.3 ± 14.1 in controls with and without it (P = 0.366). The most common MGD signs coincided in both groups. Staining with fluorescein (P = 0.000) and lissamine green (P = 0.019) was higher in KC patients, but no differences were detected with TBUT (P = 0.116) or the Schirmer test (P = 0.637). Hypersecretory MGD was the most prevalent variant in both groups.ConclusionsMGD and DED are common in KC patients. MGD correlates with the severity of KC and is indistinguishable from MGD in patients without KC. No association was found with symptoms. Patients with KC should be screened for MGD because of its possible clinical implications. Further research is needed to clarify the role of MGD in KC patients.     

Prospective two year study of changes in corneal density following transepithelial pulsed,epithelium-off continuous and epithelium-off pulsed,corneal crosslinking for keratoconus

PurposeTo compare the corneal densitometry changes after transepithelial pulsed (t-ACXL), epithelium-off continuous (c-ACXL) and epithelium-off pulsed (p-ACXL), accelerated corneal crosslinking for patients with progressive keratoconus.MethodsProspective, interventional case series at a university hospital tertiary referral center. Forty eyes received t-ACXL, 40 eyes received c-ACXL, and 40 eyes received p-ACXL. Corneal tomography, densitometry and visual acuity were evaluated preoperatively and at 1, 3, 6, 12 and 24 months postoperatively.ResultsTotal densitometry values of the total layer over the annular diameters 0–12 mm expressed in grayscale units (GSU) showed no significant change after t-ACXL and p-ACXL but increased significantly after c-ACXL at 1 month (16.76 ± 2.38, P value < 0.01) and 3 months (16.12 ± 2.22, P value 0.04), returning to baseline levels at month 6 (14.97 ± 2.13, P value 0.99) and remained stable until final follow-up. At 1 month, the mean change in total densitometry value of the t-ACXL group (-0.53 ± 2.08) was significantly lower than the p-ACXL (0.70 ± 1.96 P value 0.04) and c-ACXL (1.97 ± 2.65 P value < 0.01). There was no statistical difference in the mean change in total densitometry between the three groups from 6 to 24 months. In the c-ACXL group, a higher degree of CXL-induced corneal haze at 1 month was observed in patients with steeper preoperative keratometry readings and in individuals where a greater flattening effect was achieved at 24 months.ConclusionsContinuous epithelium-off accelerated cornea crosslinking appears to induce more corneal haze than pulsed epithelium-off and transepithelial pulsed cornea crosslinking in the early postoperative period. Differences resolve by six-months.     

Impact of corneal collagen cross-linking on vision-related quality of life measured with the keratoconus outcomes research questionnaire (KORQ) in patients with keratoconus

PurposeTo assess the impact of corneal collagen cross-linking on self-reported vision-related quality of life (VR-QoL) in keratoconus patients by means of the Keratoconus Outcomes Research Questionnaire (KORQ), a new disease-specific patient reported outcomes measures (PROMs) tool.MethodsPatients with progressive keratoconus undergoing corneal collagen cross-linking were consecutively enrolled. Patients completed the KORQ before and after the treatment, at 1, 3 and 6 months. Data were collected regarding the visual acuity and the topographic, aberrometric and pachymetric parameters of both eyes. Patients were also asked to quantify their eye rubbing behavior on a Visual Analogue Scale (VAS) from 0 to 10, before and 6 months after treatment.The KORQ scores were associated with the visual acuity, topographic, aberrometric and pachymetric data by means of the Spearman correlation coefficient.ResultsThe Activity Limitation (AL) subscale score was higher after surgery. Preoperatively, negative correlations were observed between the KORQ AL score and Best Corrected Visual Acuity (logMAR), maximum keratometry, flattest keratometry, steepest keratometry, symmetry index front and higher order aberrations (HOA) of the treatment eye. Postoperatively, we observed a shift toward the fellow eye, with stronger correlation of the KORQ scores with the fellow eye parameters. The Symptoms subscale score correlated with the aberrometric parameters of both eyes at various time points. Statistically significant correlations were observed between the change in KORQ scores and the change in aberrometric parameters. A statistically significant reduction in the eye rubbing behavior was detected (p < 0,0001).ConclusionsThese results suggest that the corneal cross-linking treatment is effective both in improving the subjective perception of the disease by the patient and in stabilizing the objective indicators of disease progression. Keratometric, aberrometric and visual acuity values showed a significant impact on self-reported VR-QoL. Corneal cross-linking, by halting the worsening of these parameters, may bear a beneficial effect on VR-QoL.     

Clinical evaluation of different types of contact lenses in keratoconus management

PurposeTo compare the clinical and topographical findings of the keratoconus patients according to the prescribed contact lens type and to investigate the effects of corneal collagen cross-linking (CXL) and cone location on lens selection.MethodsThe records of 301 eyes of 195 keratoconus patients who were prescribed contact lenses were analyzed retrospectively. The eyes were grouped according to the lens type: Soft toric contact lens (STCL), rigid gas-permeable contact lens (RGPCL), hybrid contact lens (HCL) and mini-scleral contact lens (MSCL). The history of having CXL, ophthalmological examination findings, and the topographical findings were compared between the groups. Brown-Forsythe, Chi-square, and post-hoc tests were used to compare the groups. Mann-Whitney U test was used for subgroup analysis. Comparison of the lens-corrected visual acuity (LCVA) and spectacle-corrected visual acuity (SCVA) levels was made with Wilcoxon signed-ranks test.ResultsThere was no significant difference between the groups regarding topographical cone location, CXL history, spherical refraction, and LCVA. The difference between spectacle-corrected visual acuity and LCVA was higher in RGPCL and MSCL groups than STCL group (p=0.01). Keratometry of RGPCL and MSCL groups were higher than STCL and HCL groups (p=0.01, p<0.001). In RGPCL group, eyes with central cones had a higher increase in visual acuity with contact lenses compared to eyes with paracentral cones (p=0.043). STCL and MSCL were mostly prescribed in mild and severe keratoconic eyes, respectively. In RGPCL group, the increase in visual acuity with contact lens was higher in eyes treated with CXL (p= <0.01).ConclusionsWhile STCL and HCL were mostly prescribed in mild keratoconus, RGPCL and MSCL were selected for moderate or advanced disease. If appropriately chosen, all types of contact lenses could result in a good visual acuity level. CXL history did not affect the prescribed lens type. Having central cone location and CXL history in RGPCL group improved visual acuity more efficiently.     

Contact lens care in keratoconus.

PURPOSE: To quantify the complexity involved in fitting contact lenses on the eyes of patients with keratoconus. METHODS: The contact lens care of one randomly selected eye each of 38 keratoconus patients was retrospectively analyzed and compared to that of 38 gender and age matched controls. We evaluated the number of diagnostic contact lenses used to establish the initial contact lens order, number of ordered rigid gas permeable (RGP) contact lenses needed to complete the fit, number of office visits during the initial 4 months of care, best spectacle and RGP contact lenses corrected Log MAR visual acuities, complications encountered, and whether or not the patient was successful in contact lens wear. RESULTS: Keratoconic eyes statistically used more diagnostic lenses, more ordered lenses, and more office visits than did normal eyes. Visual acuities improved from an average of 20/40 with spectacles to an average of 20/20 by use of RGP contact lenses in keratoconic eyes. Visions were corrected to 20/20 with both spectacles and contact lenses in control eyes. Sixty nine percent (69%) of keratoconic eyes and 95% of controls were successful in contact lens wear. CONCLUSIONS: Contact lens care of keratoconic eyes is more challenging than care of normal eyes because of the need for more diagnostic and ordered contact lenses and the use of more professional time. Keratoconic eyes may suffer more complications than normals during contact lens care, but this does not affect the success rates, and such patients benefit from enhanced visual acuity with RGP contact lenses compared to that achieved with spectacles.     

Acute corneal edema decades after penetrating keratoplasty for keratoconus in eyes wearing scleral contact lenses

PurposeTo report three cases of acute corneal edema occurring decades after penetrating keratoplasty (PK) for keratoconus in eyes wearing scleral contact lenses (ScCLs) with previously clear corneal grafts.MethodsRetrospective chart review of three ScCL wearers presenting for sudden onset pain and blurred vision. Data extracted included clinical presentation, year and reason for PK, ocular medications and comorbidities, contact lens wearing history, results of any ancillary testing available including corneal topography, anterior segment optical coherence tomography (OCT), and specular microscopy surrounding the event, treatment and outcomes of intervention. The number of PK eyes fit with ScCLs in the author’s practice was determined to estimate the prevalence of this event.ResultsThe three patients each had a longstanding PK for keratoconus performed between 33–35 years prior to presentation and recurrent ectasia. Each patient presented with an acute, painful eye and reduced vision either 3 days, 4 months or 9 years after refitting into ScCLs. Each eye had well demarcated focal microcystic epithelial and stromal edema within the graft and crossing the wound margin onto the host cornea. Although a definitive break or detachment of Descemet’s membrane was not visualized, the presentations suggest these were episodes of acute hydrops.ConclusionsLongstanding PKs with recurrent ectasia and acute focal edema suggestive of corneal hydrops is demonstrated in this case series of ScCL wearers. Although similar events have occurred as part of the natural history of post-PK corneas for keratoconus, the proximity of ScCL refitting to two of the events suggests some association.     

Accelerated versus standard corneal collagen cross-linking in pediatric keratoconus patients: 24 months follow-up results

Purpose

To compare the 24 month visual, refractive, topographic and aberrometric results of the accelerated and standard corneal collagen cross-linking (CXL) in pediatric keratoconus patients.