Phosphoprotein network analysis of corneal epithelium of keratoconus patients.

Keratoconus (KC) is non-inflammatory, bilateral progressive corneal ectasia, and a disease of established biomechanical instability. The etiology of KC is believed to be multifactorial. Although previous studies gained insight into the understanding of the disease, little is known thus far on global protein phosphorylation changes in keratoconus. We performed phosphoproteome analysis of corneal epithelium from control (N = 5) and KC patients. Tandem mass tag (TMT) multiplexing technology along with immobilized metal affinity chromatography (IMAC) were used for the phosphopeptides enrichment and quantitation. Enriched peptides were analyzed on Orbitrap Fusion Tribrid mass spectrometer. This leads to the identification of 2939 unique phosphopeptides derived from 1270 proteins. We observed significant differential phosphorylation of 591 phosphopeptides corresponding to 375 proteins. Our results provide first phosphoproteomic signature of the keratoconus disease and identified dysregulated signaling pathways that can be targeted for therapy in future studies.

Probing the effect of matrix stiffness in endocytic signalling pathway of corneal epithelium.

Matrix stiffness regulates the physiology of the cells and plays an important role in maintaining its homeostasis. It has been reported to regulate cell division, proliferation, migration, extracellular uptake and various other physiological processes. The alteration in matrix stiffness has also been well reported in various disease pathologies. However, in ocular system, Keratoconus (KC) is an ideal model to study the effect of matrix stiffness on endocytosis since the progression of the disease is controlled by increasing the stromal elasticity. Our study using corneal epithelial and retinal pigment epithelial cell lines showed that ocular cells do respond to matrix stiffness by altering their morphology and endocytic uptake of FITC-Dextran 20 kDa. Further, by using KC epithelium as a clinical model, we hypothesize that change in stromal elasticity may also affect the endocytosis of KC epithelium. Our results clearly showed alteration in the expression of actin binding proteins such as Phosphorylated Cofilin, Profilin, Focal adhesion kinase, and Vinculin. Apart from cytoskeletal rearrangement proteins, we also observed endocytic proteins such as Clathrin, Caveolin1 and Rab 11 to be affected by matrix stiffness. Our study thus establishes connecting role between endocytosis and matrix stiffness which could be used to understand the pathophysiology of keratoconus that it is influenced by both mechanical and biochemical factors.

Spectrum of Binocular Vision Anomalies in Keratoconus Subjects.

Keratoconus (KC) is typically a bilateral asymmetric corneal condition associated with anisometropia. A detailed evaluation of binocular vision function is therefore a critical component of ocular examination in these patients for early detection and treatment of binocular vision anomalies. PURPOSE: The purposes of this study were to measure the various parameters of binocular vision (BV) in patients with KC and to identify the factors that possibly influence them. METHODS: This was a prospective, observational study of BV in patients with KC and with best-corrected visual acuity ≤0.4 logMAR in each eye. Age-matched, nonstrabismic normal patients served as controls. Binocular vision examination included motor assessment, accommodation parameters, and fusional vergence. RESULTS: Binocular vision parameters of 84 KC patients were compared with those of 71 normal controls. The KC group showed statistically significant differences between fellow eyes in refractive cylinder (0.44 ± 2.1 D, P = .03), best-corrected visual acuity (0.06 ± 0.09 logMAR, P = .001), and maximum keratometry (6.64 ± 8.2D, P = .005). The control group showed no significant difference in any refractive or keratometric parameter between fellow eyes. Sixty-six (78.6%) of 84 KC patients had various combinations of BV anomalies: 48.8% had impaired stereopsis, 44% had abnormal fusional vergence, and 39.3% had accommodative infacility. Among individual parameters, all except accommodative amplitudes and negative distance fusional vergence showed statistically significant impairment compared with controls (P < .001). Median (interquartile range) stereoacuity was 70 (50 to 550) arc sec in the KC group and 40 (30 to 50) arc sec in control (P < .0001). There was a statistically significant but weak correlation between stereoacuity and positive fusional vergence for near (P = .008; Spearman coefficient, -0.28) and weak but significant negative correlation between phoria status and negative fusional vergence for near (P = .03; Spearman coefficient, -0.24). CONCLUSIONS: A large proportion of KC patients have BV anomalies. Assessment of BV function should be included in the clinical examination of all KC patients.

Topographic, Tomographic, and Aberrometric Characteristics of Post-LASIK Ectasia.

PURPOSE: To report the refractive, topographic, tomographic, and aberrometric characteristics of post-LASIK ectasia; to compare these characteristics with normal post-LASIK controls; and to propose a comprehensive system to grade the severity of post-LASIK ectasia. METHODS: The refraction, corrected distance visual acuity (CDVA), magnitude, and location of the steepest and thinnest point on the cornea, the highest anterior and posterior surface elevation, the radius of best fit sphere, corneal asphericity, and corneal aberrations were measured in 50 eyes of 29 patients with post-LASIK ectasia. These were compared with corresponding parameters in 50 eyes that did not develop ectasia for more than 1 year after LASIK. A logistic regression analysis was used to create a scoring system to grade the severity. RESULTS: Eyes with post-LASIK ectasia had significantly higher myopia with astigmatism and a lower CDVA than control eyes. Mean topographic toricity was 3.4 ± 1.9D, mean keratometry at the steepest point was 55.32 ± 6.63D, mean highest posterior elevation was 69.72 ± 3 µm, and mean coma was -2.06 ± 1.2 µm. All these parameters were significantly higher than corresponding values in the control group (p < 0.001 in all). Spherical aberration was more negative and the change in asphericity indicated significantly greater prolate shape of the cornea in eyes with post-LASIK ectasia compared to controls. Five parameters, namely, CDVA, spherical equivalent, highest posterior corneal elevation, spherical aberration, and corneal asphericity, were identified as significant predictors of post-LASIK ectasia and used to create a scoring system. CONCLUSION: Post-LASIK ectasia is characterized by significant changes in refraction, topography, tomography, and aberrometry. The proposed scoring system may be useful in diagnosing, grading, and monitoring post-LASIK ectasia.

Study on polymethylmethacrylate ring in protecting limbal stem cells during collagen cross-linking.

OBJECTIVE: The UV rays used in the collagen cross-linking (CXL) procedure seem to cause potential damage to the limbal stem cells. This study was designed to evaluate the ability of polymethylmethacrylate (PMMA) hemiannulus as an alternative to protect corneal limbal stem cells during CXL. METHODS: Ten freshly enucleated human cadaveric eyeballs were subjected to the corneal CXL procedure. The cadaveric eye ball was divided into 2 sectors: A and B. Sector A was left unprotected, while sector B was covered by a PMMA shield. Limbal biopsies from both sectors before and after the procedure were analyzed. Each limbal tissue was placed on human amniotic membrane (HAM) to check the cultivability and was subjected to marker studies using reverse transcriptase PCR. RESULTS: Before CXL, biopsies from both sectors showed growth on HAM. After CXL, biopsies from sector A showed no growth on HAM while 2 out of the 10 from sector B covered with the PMMA ring did show growth on HAM. The putative stem-cell marker ABCG2 was negative in all the samples from sector A after CXL and was positive in 2 out of the 10 samples from sector B. CONCLUSION: Covering the limbal region with PMMA offers partial protection of the limbus from the UV rays during the CXL procedure.

Keratoconus: A Biomechanical Perspective.

PURPOSE: The relevance of corneal biomechanics and the importance of including it in the clinical assessment of corneal ectasias are being increasingly recognized. The connection between corneal ultrastructure, biomechanical properties, and optical function is exemplified by a condition like keratoconus. Biomechanical instability is seen as the underlying basis for the secondary morphological changes in the cornea. Asymmetric biomechanical weakening is believed to drive progressive corneal steepening and thinning. Biomechanical strengthening is the principle of collagen crosslinking that has been shown to effectively arrest progression of the keratoconus. Corneal biomechanics has therefore ignited the interest of researchers and clinicians alike and has given us new insights into the cause and course of the disease. This article is an overview of the extensive work published, predominantly in the last two decades, on the biomechanical aspect of keratoconus. METHODS: Published articles on corneal biomechanics in the specific context of keratoconus were reviewed, based on an electronic search using PubMed, Elsevier, and Science Direct. The search terms used included "Corneal Biomechanics," "Mechanical properties of the cornea," "Corneal ultrastructure," "Corneal Collagen," and "Keratoconus". Articles pertaining to refractive surgery, keratoplasty, collagen crosslinking, or intrastromal rings were excluded. RESULTS: The electronic search revealed more than 500 articles, from which 80 were chosen for this article. CONCLUSIONS: The structural and organizational pattern of the corneal stroma determines its mechanical properties and are responsible for the maintenance of the normal shape and function of the cornea. Changes in the ultrastructure are responsible for the biomechanical instability that leads to corneal ectasia. As non-invasive methods for evaluating corneal biomechanics in vivo evolve, our ability to diagnose subclinical keratoconus will improve, allowing identification of patients at risk to develop ectasia and to allow early treatment to arrest progression of the disease.

New simulation software to predict postoperative corneal stiffness before laser vision correction.

PURPOSE: To develop a new virtual surgery simulation platform to predict postoperative corneal stiffness (Kc mean ) after laser vision correction (LVC) surgery. SETTING: Narayana Nethralaya Eye Hospital and Sankara Nethralaya, India; Humanitas Clinical and Research Center, Italy. DESIGN: Retrospective observational case series. METHODS: 529 eyes from 529 patients from 3 eye centers and 10 post-small-incision lenticule extraction (SMILE) ectasia eyes were included. The software (called AcuSimX) derived the anisotropic, fibril, and extracellular matrix biomechanical properties (using finite element calculation) of the cornea using the preoperative Corvis-ST, Pentacam measurement, and inverse finite element method assuming published healthy collagen fibril orientations. Then, the software-computed postoperative Kc mean was adjusted with an artificial intelligence (AI) model (Orange AI) for measurement uncertainties. A decision tree was developed to classify ectasia from normal eyes using the software-computed and preoperative parameters. RESULTS: In the training cohort (n = 371 eyes from 371 patients), the mean absolute error and intraclass correlation coefficient were 6.24 N/m and 0.84 (95% CI, 0.80-0.87), respectively. Similarly, in the test cohort (n = 158 eyes from 158 patients), these were 6.47 N/m and 0.84 (0.78-0.89), respectively. In the 10 ectasia eyes, the measured in vivo (74.01 [70.01-78.01]) and software-computed (74.1 [69.03-79.17]) Kc mean were not statistically different ( P = .96). Although no statistically significant differences in these values were observed between the stable and ectasia groups ( P ≥ .14), the decision tree classification had an area under the receiver operating characteristic curve of 1.0. CONCLUSIONS: The new software provided an easy-to-use virtual surgery simulation platform for post-LVC corneal stiffness prediction by clinicians and was assessed in post-SMILE ectasia eyes. Further assessments with ectasia after surgeries are required.

Optimized Artificial Intelligence for Enhanced Ectasia Detection Using Scheimpflug-Based Corneal Tomography and Biomechanical Data.

PURPOSE: To optimize artificial intelligence (AI) algorithms to integrate Scheimpflug-based corneal tomography and biomechanics to enhance ectasia detection. DESIGN: Multicenter cross-sectional case-control retrospective study. METHODS: A total of 3886 unoperated eyes from 3412 patients had Pentacam and Corvis ST (Oculus Optikgeräte GmbH) examinations. The database included 1 eye randomly selected from 1680 normal patients (N) and from 1181 "bilateral" keratoconus (KC) patients, along with 551 normal topography eyes from patients with very asymmetric ectasia (VAE-NT), and their 474 unoperated ectatic (VAE-E) eyes. The current TBIv1 (tomographic-biomechanical index) was tested, and an optimized AI algorithm was developed for augmenting accuracy. RESULTS: The area under the receiver operating characteristic curve (AUC) of the TBIv1 for discriminating clinical ectasia (KC and VAE-E) was 0.999 (98.5% sensitivity; 98.6% specificity [cutoff: 0.5]), and for VAE-NT, 0.899 (76% sensitivity; 89.1% specificity [cutoff: 0.29]). A novel random forest algorithm (TBIv2), developed with 18 features in 156 trees using 10-fold cross-validation, had a significantly higher AUC (0.945; DeLong, P < .0001) for detecting VAE-NT (84.4% sensitivity and 90.1% specificity; cutoff: 0.43; DeLong, P < .0001) and a similar AUC for clinical ectasia (0.999; DeLong, P = .818; 98.7% sensitivity; 99.2% specificity [cutoff: 0.8]). Considering all cases, the TBIv2 had a higher AUC (0.985) than TBIv1 (0.974; DeLong, P < .0001). CONCLUSIONS: AI optimization to integrate Scheimpflug-based corneal tomography and biomechanical assessments augments accuracy for ectasia detection, characterizing ectasia susceptibility in the diverse VAE-NT group. Some patients with VAE may have true unilateral ectasia. Machine learning considering additional data, including epithelial thickness or other parameters from multimodal refractive imaging, will continuously enhance accuracy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Cornea Classic: Spoerl et al, 2007, the "Holy Grail of CXL".

ABSTRACT: Corneal collagen cross-linking has established itself as the only known treatment with a proven ability to arrest the progression of keratoconus. The efficacy and safety of the procedure have been entirely due to meticulous preparation by the innovators of this technique, before clinical application was confidently advocated. The article by Spoerl et al, entitled "Safety of UVA riboflavin crosslinking of the cornea," one of the most frequently cited articles in the journal " Cornea ," explains the logic behind the formulation of the "Dresdon protocol" that remains the gold standard in the treatment of keratoconus by collagen cross-linking.

In Vivo Biomechanical Changes Associated With Keratoconus Progression.

PURPOSE: To assess the biomechanical deterioration arising from keratoconus progression in-vivo. METHODS: The preoperative examinations of 32 progressive KC cases that were submitted to corneal cross-linking were evaluated. The examinations included the corneal tomography using the Pentacam HR and biomechanical parameters assessed by the Corvis ST (Oculus, Wetzlar, Germany). The results were recorded at two time points, the latter of which was at the last visit before the CXL procedure. Keratoconus progression was characterised by a significant change in the ABCD system. RESULTS: At the last follow-up visit (41.4 ± 40.9 months) all morphological parameters of the ABCD grading system showed significant deterioration (p < 0.001). The comparative analyses revealed a significant reduction in corneal stiffness expressed by a significant reduction in the stress-strain index (SSI: -0.10 ± 0.06, p < 0.001), the Stiffness parameter A1 (SP-A1: -6.1 ± 12.0 mmHg/mm, p = 0.011), by a significant increase in the integrated Inverse Radius (IIR: 0.95 ± 1.04 mm-1, p < 0.001) and in the deflection amplitude (DA) ratio (0.23 ± 0.58, p = 0.034). A barely significant increase in the DA also pointed towards corneal stiffness reduction. (0.04 ± 0.13 mm, p = 0.056). The SSI and the IIR were the indices with the smallest overlaps between the two examinations. CONCLUSIONS: It has been demonstrated in-vivo that corneal biomechanical deterioration occurs with keratoconus progression. The larger changes observed in the SSI and the IIR when compared to the remaining biomechanical parameters suggests that these parameters could be suitable to assess the corneal stiffness reduction in keratoconus natural progression.

In vivo Assessment of Localised Corneal Biomechanical Deterioration With Keratoconus Progression.

Purpose: To evaluate the regional corneal biomechanical deterioration with keratoconus (KC) progression as measured by the Stress-Strain Index (SSI) maps. Methods: The preoperative examinations of 29 progressive KC cases that were submitted to corneal cross-linking (CXL) were evaluated. The examinations included the tomography and the SSI measured by the Pentacam HR and the Corvis ST (Oculus, Wetzlar, Germany), respectively. The results were recorded twice, the latter of which was at the last visit before the CXL procedure. The patient-specific SSI maps were built, using data at each examination, based on finite element modelling and employing inverse analysis to represent the regional variation of biomechanical stiffness across the cornea. Results: All cases presented significant shape progression (above the 95% CI of repeatability) in anterior and posterior curvatures and minimum thickness. The overall corneal stiffness as measured by the SSI within the central 8 mm-diameter area underwent slight but significant reductions from the first to the last examination (-0.02 ± 0.02, range: -0.09 to 0, p < 0.001). In all 29 cases, the reduction in stiffness was localised and concentred in the area inside the keratoconus cone. The SSI values inside the cone were significantly lower in the last examination (by 0.15 ± 0.09, range: -0.42 to -0.01, p < 0.001), while the SSI outside the cone presented minimal, non-significant variations (0 ± 0.01, range: -0.04 to 0.01, p = 0.999). Conclusion: It has been observed through the SSI maps that the regional deterioration in stiffness was concerted inside the area of pathology, while only mild non-significant alterations were observed outside the area of pathology.

Implications of Diagnostic Drops on Scheimpflug Tomography: The Proper Order for Clinical Testing.

PURPOSE: The purpose of this article was to study the impact of instillation of 1% fluorescein and mydriatics on measurements made by Scheimpflug imaging. METHODS: This was a cross-sectional study of patients who had measurements of corneal shape (maximum keratometry and best fit sphere of anterior and posterior corneal surfaces), pachymetry (at the pupil center, corneal apex, and thinnest location), and anterior chamber parameters (depth, volume, and angle of anterior chamber and corneal volume) using the Pentacam HR before and after the instillation of fluorescein and mydriatics. Group A had baseline measurements that were repeated 1.5 hours after the instillation of 1% fluorescein and 0.8% tropicamide+ 5% phenylephrine eye drops. Group B had baseline measurements that were repeated 10 minutes after the instillation of 1% fluorescein, and group C had baseline measurements that were repeated 1.5 hours after the instillation of mydriatics. RESULTS: Overall, 131 eyes of 131 patients were studied: 87 in group A, 28 in group B, and 16 in group C. Significant differences and wide variations were noted in corneal pachymetry and anterior chamber parameters in all 3 groups. The highest magnitude and range of difference was observed in pachymetry at the pupil center (17 ± 53.5 µm) and in anterior chamber volume (26.7 ± 69.8 mm 3 ). Corneal shape measurements of anterior and posterior corneal surfaces were not significantly affected by either fluorescein or mydriatics. Pupillary dilation also affected the ability of the Pentacam to accurately trace the pupil margin in 19.5% of cases. CONCLUSIONS: For consistent and accurate measurements, it is important that Scheimpflug imaging be performed before other tests which may need the instillation of fluorescein or mydriatics.

Evaluation of corneal biomechanical behavior in vivo for healthy and keratoconic eyes using the stress-strain index.

PURPOSE: To evaluate the characteristics of corneal material properties in healthy individuals and keratoconic patients using the stress-strain index (SSI). SETTING: Vincieye Clinic in Milan, Italy, and Instituto de Olhos Renato Ambrósio in Rio de Janeiro, Brazil. DESIGN: Retrospective observational cross-sectional study. METHODS: Records of 1221 patients were divided into 3 groups: healthy corneas (n = 728), bilateral keratoconus (KC, n = 388), and very asymmetric ectasia (VAE, n = 105) when patients presented with clinical ectasia in 1 eye and normal topography (VAE-NT) in the fellow eye. All patients were examined with Pentacam HR and Corvis ST. Severity of KC cases was stratified according to the Pentacam topographic KC classification. The SSI distribution across the different groups and its correlation with age, biomechanically corrected intraocular pressure (bIOP), and central corneal thickness (CCT) were assessed. RESULTS: A statistically significant difference between healthy individuals and each of the keratoconic groups ( P < .001) was observed, and a progressive reduction in the SSI was observed across the groups. A significant correlation was observed between the SSI and age in all groups ( P < .010) but KC severe subgroup ( P = .361). No correlation between the SSI and bIOP and CCT was observed in all KC subgroups and VAE-NT groups ( P > .050). Among healthy eyes, there was only a mild correlation between the SSI and bIOP ( R = 0.12, P = .002) and CCT ( R = 0.13, P = .001). CONCLUSIONS: This study estimates the in vivo corneal material properties in healthy individuals and patients with KC using a new method. The SSI showed a progressive deterioration within the advance in disease stages while being relatively independent of bIOP and CCT but positively correlated with age.

Clinical, Morphological, and Optical Correlates of Visual Function in Patients With Fuchs Endothelial Corneal Dystrophy.

PURPOSE: The purpose of this article was to study the clinical, optical, and morphological correlates of visual function in patients with Fuchs endothelial corneal dystrophy (FECD). METHODS: The case records were analyzed for patients diagnosed with FECD between September 2019 and March 2020. The best-corrected visual acuity (BCVA) was recorded as decimal visual acuity and converted to the logarithm of the minimum angle of resolution units. Contrast sensitivity was measured with the Pelli-Robson contrast sensitivity test. Corneal alterations, including central corneal thickness, depression of the posterior cornea, and corneal densitometry values, were evaluated using Scheimpflug images. Corneal epithelial thickness was measured by spectral-domain optical coherence tomography. RESULTS: A total of 107 eyes of 61 patients (18 male and 43 female) with FECD were retrospectively investigated. The Spearman rank correlation coefficient showed moderate correlation between BCVA and contrast sensitivity (ρ = -0.66, P < 0.001), with some patients maintaining relatively good BCVA but having reduced contrast sensitivity. Logistic regression analysis demonstrated that age, central corneal thickness, depression of the posterior cornea, and epithelial thickening were negatively associated with contrast sensitivity but not with BCVA. CONCLUSIONS: Contrast sensitivity is a useful tool for assessing visual dysfunction and should be incorporated into the assessment protocol of patients with FECD. Alterations in the cornea, including central corneal thickness, depression of the posterior cornea, and epithelial thickening, might be objective parameters that can help the clinician in grading the severity of the disease and tracking its progression.

Reliability of Aqueous Flare Measurements During Uveitis by a Spot Fluorometer.

Purpose: To evaluate the reliability of intensity of light scatter (ILS) for diagnosing mild-to-moderate uveitis, which is difficult to score by the subjective standardized uveitis nomenclature (SUN) grading. Methods: ILS (in millivolts) was measured in healthy subjects and uveitis patients by a custom-made Spot fluorometer. The reliability was assessed by noise analysis of the instrument using turbid samples and intra- and interobserver variabilities. Results: ILS increased with the severity of inflammation: healthy (0.1498 ± 0.0564) and SUN0 (0.1590 ± 0.0564) < SUN1+ (0.2050 ± 0.0887) < SUN2+ (0.4283 ± 0.1895). The increase in ILS was more significant between healthy and SUN1+ (P < 0.0001) compared to the difference between SUN0 and SUN1+ (P = 0.0006). The instrument noise was small (σ = 0.002). Intraobserver measurements revealed no variability (P > 0.98) between measurements and predicted repeatability coefficients of 0.0754, 0.0522, and 0.0532 in healthy, SUN0, and SUN1+, respectively. Interobserver measurements also showed no variability (P > 0.88) and predicted intraclass correlation coefficient > 0.63 in healthy and uveitis subjects. Conclusions: The fluorometer enables precise measurement of ILS with negligible instrument noise, and the measurements are unaffected by intra- and interobserver variabilities. However, the difference in mean ILS between SUN0 and SUN1+ is greater than the instrument noise and comparable to intra- and interobserver variabilities. Thus, ILS measurements are likely impacted by blinking, eye movements, and focusing jitter. The impact of these factors must be reduced before using the fluorometer to distinguish mild-to-moderate uveitis.

Twelve-Months Follow-Up Postmarket Study of a Hydrophobic Intraocular Lens Using a Preloaded Automated Injector in an Indian Population.

Purpose: To assess real-world clinical outcomes and safety of the Clareon® intraocular lens (IOL) and AutonoMe® automated preloaded delivery system in an Indian population. Patients and methods: This was a prospective, single-arm, multicenter, 12-month clinical study in patients aged ≥20 years with unilateral or bilateral cataracts. Surgery was performed by phacoemulsification followed by implantation of the Clareon monofocal IOL (CNA0T0). Monocular best-corrected distance visual acuity (BCDVA) and uncorrected distance visual acuity (UCDVA) were assessed at 1 week and 1, 6, and 12 months after implantation. Posterior capsular opacification (PCO), surface haze, and glistenings were evaluated at all visits. Surgeons' satisfaction with automated injector system was also evaluated using a questionnaire. Safety was assessed by monitoring adverse events (AEs). Results: A total of 151 eyes received the CNA0T0 IOL. Mean ± SD monocular BCDVA improved from 0.53±0.44 logMAR preoperatively to 0.00±0.08 logMAR at week 1 and -0.03±0.08 logMAR at 12 months after implantation. At 12 months, 137/137 (100%) of eyes achieved BCDVA of 0.3 logMAR or better. Mean ± SD monocular UCDVA was 0.78±0.40 logMAR preoperatively, 0.11±0.15 logMAR at week 1, and 0.08±0.13 logMAR at 12 months after implantation. At 12 months, 132/137 (96%) eyes achieved UCDVA of 0.3 logMAR or better. Serious intraoperative AEs were posterior capsule rupture (n=1) and ciliary zonular dehiscence (n=1). Surgeons reported that the automated preloaded device was more intuitive compared with other push- or screw-style preloaded injector systems. None of the eyes in this study presented surface haze; all were graded as 0 glistenings at all visits. No clinically significant PCO or neodymium-doped yttrium aluminum garnet (Nd:YAG) capsulotomies were reported. Conclusion: The hydrophobic IOL preloaded in an automated injector system provided good visual and refractive outcomes, as well as no surface haze and grade 0 glistenings. None of the patients required Nd:YAG capsulotomy.

Pediatric Descemet Membrane Endothelial Keratoplasty.

PURPOSE: To report the technique and outcome of Descemet membrane endothelial keratoplasty (DMEK) in pediatric patients older than 6 years of age. DESIGN: Institutional interventional retrospective case series. METHODS: This study included 5 eyes of patients less than 15 years of age with endothelial dysfunction who underwent DMEK. Three eyes had Descemet stripping done of the same size as the donor graft. Two eyes underwent non-Descemet stripping endothelial keratoplasty. Attachment of DMEK scroll and improvement in corneal clarity, vision, pachymetry, and intraoperative or postoperative complication was noted. We defined primary graft failure as nonclearing corneal edema despite a well-attached lenticule on anterior segment optical coherence tomography. RESULTS: A total of 5 eyes of 5 children (all male) with a mean (± standard deviation) age of 9.2 ± 3.42 years underwent DMEK. The mean preoperative visual acuity of 1.93 ± 0.25 logMAR units improved postoperatively to 0.98 ± 0.29 (95% confidence interval, P = .03). Anatomic success (well-attached scroll with a more transparent cornea with a decrease in pachymetry) was seen in 4 of 5 eyes (80%). One eye had a primary donor failure. Two out of the 5 eyes (40%) required rebubbling. The mean pachymetry in eyes with successful procedure reduced from 1094.5 ± 101.5 µm to 619.25 ± 150.3 µm (P = .03). CONCLUSIONS: Although DMEK in pediatric eyes is challenging, the early results are encouraging, and it is a viable option in pediatric patients with endothelial failure.

Extreme corneal flattening following collagen crosslinking for progressive keratoconus.

PURPOSE: To study the clinical, tomographic and densitometric features of eyes that showed >5 D of corneal flattening following collagen crosslinking (CXL) for progressive keratoconus and to identify preoperative predictive factors for such a response. METHODS: This was a retrospective case control study of 548 eyes with progressive keratoconus which had undergone epithelium-off CXL (Dresden protocol) with a follow-up of 1 to 10 years. Eyes that showed ⩾5 D corneal flattening in maximum keratometry (Kmax) following CXL (group A) were compared with one eye of the remaining patients in the same cohort (group B). Changes in refraction and visual acuity, Kmax and thinnest pachymetry were compared between both groups. Univariate and multivariate regression analysis identified preoperative risk factors for unusual corneal flattening. RESULTS: Forty three eyes in group A were compared with 502 eyes in group B. At the time of maximum flattening, group A showed more flattening (-7.6 ± 3.2 D) and thinning (-53.7 ± 45.2 µ) than group B (-1.69 ± 2.9 D and -26.6 ± 36.7 µ, respectively). Multivariate analysis based on parameters suggested by a univariate regression analysis identified pre-op Kmax to be the most significant predictor of intense corneal flattening. A subgroup analysis of K-matched eyes revealed that the duration of time following CXL was a significant risk factor for extreme corneal flattening following CXL. CONCLUSION: An intense corneal flattening >5 D in Kmax was documented in 7.85% of a cohort of keratoconus patients who underwent CXL. High preoperative Kmax and the duration of time following CXL were significant predictors of this response which was accompanied by significant corneal thinning.

Analysis of Immune Cells on Donor Corneal Endothelium After Corneal Transplantation Using the HRT-Rostock Cornea Module.

PURPOSE: The aim of this study was to investigate the immune cells on corneal endothelium of the graft in patients who underwent penetrating keratoplasty (PK), Descemet-stripping endothelial keratoplasty (DSEK), and Descemet membrane endothelial keratoplasty (DMEK). METHODS: A total of 43 eyes of 43 patients who underwent PK (17 eyes), DSEK (13 eyes), and DMEK (13 eyes) and who did not show any sign of graft rejection were recruited for the study. Patients who underwent cataract surgery (26 eyes) served as controls. Immune cells on the corneal endothelium were examined with laser in vivo confocal microscopy. The associations between the corneal endothelial cell density, type of keratoplasty, aqueous flare, repeated keratoplasty, and time after surgery versus the density of immune cells were investigated. RESULTS: In vivo confocal microscopy visualized similar numbers of immune cells on the corneal endothelium in the PK, DSEK, and DMEK groups, whereas no immune cells were observed in any of the control patients. The numbers of immune cells tended to be higher in regraft eyes in the PK group (P = 0.00221) and in the DSEK group (P = 0.168) than those in the primary graft eyes. No significant association was found between the density of immune cells and corneal endothelial cell density in the PK, DSEK, and DMEK groups. CONCLUSIONS: Immune cells were observed to a similar extent in the eyes of PK, DSEK, and DMEK subjects even in the absence of any clinical sign of immune rejection. A further prospective longitudinal study will evaluate the effect of immune cells on long-term graft survival and the risk for graft rejection.