Patient experience and repeatability of measurements made with the Pentacam HR in patients with keratoconus.

BACKGROUND: To investigate whether the repeatability of measurements with the Pentacam HR in patients with keratoconus is improved by patients gaining more experience of the measurement situation. Such an improvement could enhance the accuracy with which progressive keratoconus can be detected. METHODS: Four replicate measurements were performed on Day 0 and on Day 3. Parameters commonly used in the diagnosis of progressive keratoconus were included in the analysis, namely the flattest central keratometry value (K1), the steepest central keratometry value (K2), the maximum keratometry value (Kmax), and the parameters A, B and C from the Belin ABCD Progression Display. In addition, quality parameters used by the Pentacam HR to assess the quality of the measurements were included, namely the analysed area (front + back), 3D (front + back), XY, Z, and eye movements. RESULTS: Neither the diagnostic parameters nor the quality parameters showed any statistically significant improvement on Day 3 compared to Day 0. The quality parameter "eye movements" deteriorated significantly with increasing Kmax. CONCLUSION: Gaining experience of the measurement situation did not increase the accuracy of the measurements. Further investigations should be performed to determine whether the increasing number of eye movements with increasing disease severity has a negative effect on the repeatability of the measurements.

Peripheral blood immune cell profiling of acute corneal transplant rejection.

Acute rejection (AR) of corneal transplants (CT) has a profound effect on subsequent graft survival but detailed immunological studies in human CT recipients are lacking. In this multi-site, cross-sectional study, clinical details and blood samples were collected from adults with clinically diagnosed AR of full-thickness (FT)-CT (n = 35) and posterior lamellar (PL)-CT (n = 21) along with Stable CT recipients (n = 177) and adults with non-transplanted corneal disease (n = 40). For those with AR, additional samples were collected 3 months later. Immune cell analysis was performed by whole-genome microarrays (whole blood) and high-dimensional multi-color flow cytometry (peripheral blood mononuclear cells). For both, no activation signature was identified within the B cell and T cell repertoire at the time of AR diagnosis. Nonetheless, in FT- but not PL-CT recipients, AR was associated with differences in B cell maturity and regulatory CD4+ T cell frequency compared to stable allografts. These data suggest that circulating B cell and T cell subpopulations may provide insights into the regulation of anti-donor immune response in human CT recipients with differing AR risk. Our results suggest that, in contrast to solid organ transplants, genetic or cellular assays of peripheral blood are unlikely to be clinically exploitable for prediction or diagnosis of AR.

Revealing the presence of tear extracellular vesicles in Keratoconus.

Extracellular vesicles (EVs) are lipid-bound vesicles that originate from the endosomal system or budded off from the plasma membrane. EVs are involved in cell-cell communication via transporting DNA, RNA, and proteins from one cell to another. Tear EVs (tEVs) have been reported in dry eye, SjÓ§gren's Syndrome, and primary open-angle glaucoma. In this study, we sought to investigate the presence of tEVs in relation to keratoconus (KC). Tears were passively collected from the lateral meniscus from 10 healthy (5 males and 5 females) and 9 KC (4 males and 5 females) subjects. Tear samples were processed and analyzed using the ExoView™ R100. Statistical analysis was performed using a Mann-Whitney U non-parametric Student's t-test. All tEVs, in both Healthy and KC subjects, showed a CD9+ dominant tEV cohort independent of sex. A significant decrease in CD63+/CD9+ and CD63+/CD81+/CD9+ was found in the male KC tEVs (p < 0.05), but not in females compared to their healthy counterparts. Neither Healthy nor KC tEVs showed differences in the total number of tEVs, however significant differences were identified between the sexes (p < 0.05), with males having a higher number of tEVs. tEVs diameters ranged from 50 to 200 nm, in both Healthy and KC cohorts, with the majority in the 50-80 nm range suggesting exosome-dominant cohorts. To our knowledge, this is the first time, to date, that tEVs have been isolated and characterized in KCs. While further studies are warranted, the tEVs differences between KC and Healthy subjects suggest a potential role for tEVs in KC pathogenesis.

Pigmentation Is Associated with Stemness Hierarchy of Progenitor Cells Within Cultured Limbal Epithelial Cells.

Ex vivo cultured human limbal epithelial stem/progenitor cells (hLESCs) are the main source for regenerative therapy of limbal stem cell deficiency (LSCD), which is worldwide one of the major causes of corneal blindness. Despite many stemness-associated markers have been identified within the limbal niche, the phenotype of the earliest hLESCs has not been hitherto identified. We sought to confirm or refute the use of tumor protein p63 (p63) and ATP binding cassette subfamily B member 5 (ABCB5) as surrogate markers for hLESCs early within the limbal differentiation hierarchy. Based on a robust fluorescence-activated cell sorting and subsequent RNA isolation protocol, a comprehensive transcriptomic profile was obtained from four subpopulations of cultured hLESCs. The subpopulations were defined by co-expression of two putative stem/progenitor markers, the p63 and ABCB5, and the corneal differentiation marker cytokeratin 3. A comparative transcriptomic analysis yielded novel data that indicated association between pigmentation and differentiation, with the p63 positive populations being the most pigmented and immature of the progenitors. In contrast, ABCB5, either alone or in co-expression patterns, identified more committed progenitor cells with less pigmentation. In conclusion, p63 is superior to ABCB5 as a marker for stemness. Stem Cells 2018;36:1411-1420.

Prolactin-Induced Protein is a novel biomarker for Keratoconus.

PURPOSE: The purpose of the study was to investigate the role of Prolactin-Induced Protein (PIP) as a predictive biomarker for Keratoconus (KC). PARTICIPANTS: This study included one hundred and forty-seven patients with KC (105 male, 42 female), and sixty healthy controls (27 male, 33 female). METHODS: Tears, plasma and saliva samples were collected from all participants. In both KC and healthy groups all collected samples were divided into four age subgroups (15-24y), (25-34y), (35-44y) and (45y and up). Samples were analyzed using western blot (WB) and enzyme-linked immunosorbent assay (ELISA). Areas under the receiver operating characteristic curves (AUROCs) were used to evaluate diagnostic accuracy for distinguishing between KC and healthy eyes. MAIN OUTCOME MEASURES: Difference in PIP protein levels between patients with KC and healthy controls. RESULTS: Results showed significant downregulation of PIP expression in all three biological fluids on KC patients when compared to healthy controls, independent of age, sex and severity. Since PIP is a hormonal-regulated protein, we also investigated the expression of major sex hormones. We detected significant upregulation in salivary and plasma Dehydroepiandrosterone sulfate (DHEA-S) levels and significant downregulation of estrone and estriol levels, in KC patients compared to healthy controls, independent of sex, age, and KC severity stage. ROC was used to determine the overall predictive accuracy of this protein in KC. Data showed an area under the curve (AUC) for PIP in tears of 0.937 (95%CI: 0.902-0.971), in plasma of 0.928 (95%CI: 0.890-0.968) and in saliva of 0.929 (95%CI: 0.890-0.968). CONCLUSIONS: Conclusively, our results show that PIP levels are reduced in all three human biological fluids tested, and may independently or in combination with current imaging techniques aid in screening and diagnosis of KC. Our data revealed that PIP levels can potentially differentiate between disease and healthy cases, and PIP levels are stable in relation to KC severity, sex and age. Moreover, alterations in sex hormone levels in correlation with reduced PIP levels in KC provide an intriguing insight in the underlying KC pathophysiology and highlights the role of PIP as a KC biomarker.

Corneal injury: Clinical and molecular aspects.

Currently, over 10 million people worldwide are affected by corneal blindness. Corneal trauma and disease can cause irreversible distortions to the normal structure and physiology of the cornea often leading to corneal transplantation. However, donors are in short supply and risk of rejection is an ever-present concern. Although significant progress has been made in recent years, the wound healing cascade remains complex and not fully understood. Tissue engineering and regenerative medicine are currently at the apex of investigation in the pursuit of novel corneal therapeutics. This review uniquely integrates the clinical and cellular aspects of both corneal trauma and disease and provides a comprehensive view of the most recent findings and potential therapeutics aimed at restoring corneal homeostasis.

Maintaining RNA Integrity for Transcriptomic Profiling of Ex Vivo Cultured Limbal Epithelial Stem Cells after Fluorescence-Activated Cell Sorting (FACS).

BACKGROUND: Transcriptomic profiling of ex vivo cultured human limbal epithelial stem cells (hLESCs) will foster better understanding of corneal physiology and novel treatment paradigms to limbal stem cell deficiency (LSCD). However, currently such profiling studies are hampered due to difficulties with producing sufficient amounts of intact mRNA for deep RNA sequencing (RNA-seq) from subpopulations sorted on the basis of co-expression of membrane and intracellular antigens by fluorescence-activated cell sorting (FACS). METHODS: To address this problem, we systematically analyzed the critical steps, and found that ethanol fixation together with optimized downstream procedures provided a pipeline that yielded high quality total RNA in amounts to readily support the RNA-seq procedure, while still preserving good discrimination between the individual hLESC immunophenotypes. RESULTS: The average RNA integrity number (RIN) was 7.7 ± 0.4, and the average yield was 4.6 ± 1.7 pg of RNA per cell. The sequencing analysis of the isolated RNA produced high quality data with more than 70% of read pairs mapping uniformly to the reference genome and 80% of bases with a Phred score of at least 30. CONCLUSION: In this study, we developed a reliable FACS-based procedure using ethanol as a fixative that would support accurate isolation of limbal epithelial progenitor subpopulations along with RNA yield and quality sufficient to enable deep transcriptomic profiling.

LASIK surgery of granular corneal dystrophy type 2 patients leads to accumulation and differential proteolytic processing of transforming growth factor beta-induced protein (TGFBIp).

More than 60 mutations in transforming growth factor beta-induced protein (TGFBIp) have been reported in humans causing a variety of phenotypic protein aggregates in the cornea, commonly termed corneal dystrophies. One mutation, generating an arginine to histidine amino acid substitution at position 124 in mature TGFBIp leads to granular corneal dystrophy type 2 (GCD2). Homozygous GCD2 cases develop massive protein accumulation early in life whereas heterozygous GCD2 cases become affected much later and generally with a much less severe outcome. However, if heterozygous GCD2 patients undergo laser-assisted in situ keratomileusis (LASIK) surgery protein accumulation is accelerated and they develop massive protein accumulations a few years after surgery. Here, we present the protein profile of aggregate-containing corneal tissue from GCD2 patients with a history of LASIK surgery using LC-MS/MS. Label-free quantification of corneal extracellular matrix proteins showed accumulation of TGFBIp. This was supported by 2DE and immunoblotting against TGFBIp that revealed the accumulation of full-length TGFBIp. In addition, a high molecular weight TGFBIp complex was more apparent in GCD2 patients after LASIK surgery, which may be important for the disease progression. Lastly, 2DE also revealed differential processing between GCD2 patients with a history of LASIK surgery when compared to healthy individuals.

Toric Intraocular Lenses in the Correction of Astigmatism During Cataract Surgery: A Systematic Review and Meta-analysis.

TOPIC: We performed a systematic review and meta-analysis to evaluate the benefit and harms associated with implantation of toric intraocular lenses (IOLs) during cataract surgery. Outcomes were postoperative uncorrected distance visual acuity (UCDVA) and distance spectacle independence. Harms were evaluated as surgical complications and residual astigmatism. CLINICAL RELEVANCE: Postoperative astigmatism is an important cause of suboptimal UCDVA and need for distance spectacles. Toric IOLs may correct for preexisting corneal astigmatism at the time of surgery. METHODS: We performed a systematic literature search in the Embase, PubMed, and CENTRAL databases within the Cochrane Library. We included randomized clinical trials (RCTs) if they compared toric with non-toric IOL implantation (± relaxing incision) in patients with regular corneal astigmatism and age-related cataracts. We assessed the risk of bias using the Cochrane Risk of Bias tool. We assessed the quality of evidence across studies using the GRADE profiler software (available at: www.gradeworkinggroup.org). RESULTS: We included 13 RCTs with 707 eyes randomized to toric IOLs and 706 eyes randomized to non-toric IOLs; 225 eyes had a relaxing incision. We found high-quality evidence that UCDVA was better in the toric IOL group (logarithm of the minimum angle of resolution [logMAR] mean difference, -0.07; 95% confidence interval [CI], -0.10 to -0.04) and provided greater spectacle independence (risk ratio [RR], 0.51; 95% CI, 0.36-0.71) and moderate quality evidence that toric IOL implantation was not associated with an increased risk of complications (RR, 1.73; 95% CI, 0.60-5.04). Residual astigmatism was lower in the toric IOL group than in the non-toric IOL plus relaxing incision group (mean difference, 0.37 diopter [D]; 95% CI, -0.55 to -0.19). CONCLUSIONS: We found that toric IOLs provided better UCDVA, greater spectacle independence, and lower amounts of residual astigmatism than non-toric IOLs even when relaxing incisions were used.

Comparison of corneal shape changes and aberrations induced By FS-LASIK and SMILE for myopia.

PURPOSE: To compare corneal curvatures, corneal power calculations, and higher-order aberrations (HOAs) of femtosecond laser-assisted LASIK (FS-LASIK) with small incision lenticule extraction (SMILE) following surgery for moderate to high myopia. METHODS: A retrospective study of 736 eyes of 368 patients treated with SMILE and 148 eyes of 74 patients treated with FS-LASIK. Preoperative mean spherical equivalent was -7.3 ± 1.5 diopters in the SMILE group and -7.6 ± 1.3 diopters in the FS-LASIK group. Corneal curvatures, corneal power calculations performed by ray tracing, and HOAs measured with Scheimpflug technology before and 3 months after surgery were analyzed. RESULTS: Corneal curvatures changed significantly in the anterior corneal surface, but not in the posterior corneal surface, in both groups; after SMILE, the sagittal curvature was constant for the central 4-mm diameter, in contrast to FS-LASIK where the curvature showed a gradual steepening with increasing diameter. Corneal power calculations were different across the cornea depending on the measurement diameter between the two groups postoperatively. Measured over a 5-mm zone on the total cornea, FS-LASIK induced 0.11 µm more coma (P < .001) and 0.13 µm higher spherical aberration (P < .001) as compared to SMILE; similar results in other HOAs were seen for the anterior corneal surface. Negligible differences in HOAs were induced on the posterior corneal surface. CONCLUSIONS: SMILE and FS-LASIK produced distinct changes in anterior corneal shape evident in different postoperative corneal curvatures and power measurements between the two groups. Postoperative HOAs were much lower after SMILE as compared to FS-LASIK.

Venting incisions in DSAEK: implications for astigmatism, aberrations, visual acuity, and graft detachment.

PURPOSE: To evaluate the impact of venting incisions on the best corrected visual acuity (BCVA), astigmatism, aberrations, and risk of graft detachment in Descemet stripping automated keratoplasty (DSAEK). METHODS: This was a retrospective, comparative, consecutive case series of DSAEK procedures performed with (n = 266) and without (n = 110) venting incisions. Patients were treated with DSAEK for Fuchs' endothelial dystrophy at Aarhus University Hospital between 2011 and 2013. Data included preoperative keratometry and postoperative BCVA, subjective astigmatism, and Pentacam® HR tomography with corneal front surface (CFS) aberrations at 1 to 2 years of follow-up. Numbers of triple procedures (concurrent cataract surgery) and post-operative graft detachments were also noted. The venting and non-venting groups were compared by the data-means. Unpaired t-tests and Mann-Whitney tests were used for normally and non-normally distributed data, respectively. Differences in graft detachments were analyzed with Fisher's exact and Chi square test. RESULTS: There was no significant difference in any parameter, except the numbers of triple procedures. BCVA (logMAR) was 0.25 ± 0.18 in the venting group and 0.25 ± 0.19 in the non-venting group (p = 0.92), subjective astigmatism was -1.53 ± 0.99 diopters and -1.33 ± 0.78 diopters (p = 0.15), respectively. CFS astigmatism and higher order aberrations were statistically uniform. The relative risk (RR) of graft detachment was also uniform between the venting versus non-venting group (RR 0.72, p = 0.40), and between triple versus non-triple procedures (RR 0.71, p = 0.43). The preoperative corneal curvature had no impact on the risk of graft detachment (p = 0.74). CONCLUSION: Venting incisions in DSAEK do not significantly alter BCVA, astigmatism, CFS aberrations or reduce the risk of graft detachment in triple or non-triple procedures.

Assessing the corneal power change after refractive surgery using Scheimpflug imaging.

PURPOSE: To investigate whether the Pentacam HR could accurately predict the surgically induced refractive change in patients operated with small-incision lenticule extraction (SMILE) for myopia or femto-second laser in situ keratomileusis (FS-LASIK) for myopia or hyperopic astigmatism. METHODS: Data from three groups consisting of (1) 410 myopic eyes of 410 patients operated with SMILE, (2) 111 myopic eyes of 111 patients operated with FS-LASIK, and (3) 40 eyes of 40 patients with hyperopic astigmatism operated with FS-LASIK were retrospectively analysed. The change in manifest refraction due to surgery was compared with the objectively measured change in corneal power by the Pentacam HR in three different ways: Sagittal Power (calculated as for placido topographers), True Net Power (calculated by a Gaussian optics formula), and Total Corneal Refractive Power (calculated by ray tracing). Multiple linear regression analysis was performed to investigate which parameters influenced the Pentacam HR's prediction of the change in subjective refraction due to surgery. RESULTS: The Total Corneal Refractive Power Apex, Zone calculation in a diameter of 4.0 mm effectively predicted the surgically induced refractive change for all three patient groups. The spherical equivalent was predicted with an error of 0.08 ± 0.41 D for the SMILE eyes, 0.05 ± 0.61 D for the myopic eyes operated with FS-LASIK, and -0.15 ± 0.49 D for the hyperopic astigmatic eyes treated with FS-LASIK. Regression showed that preoperative refractive error had a significant impact on the prediction error of the Pentacam HR. CONCLUSIONS: Ray tracing calculations based on Scheimpflug imaging accurately assessed the change in manifest refraction due to corneal laser surgery.

Proteomics of Fuchs' endothelial corneal dystrophy support that the extracellular matrix of Descemet's membrane is disordered.

Fuchs' endothelial corneal dystrophy (FECD) is a major corneal disorder affecting the innermost part of the cornea, leading to visual impairment. As the morphological changes in FECD are mainly observed in the extracellular matrix of the Descemet's membrane/endothelial layer, we determined the protein profiles of diseased and control tissues using two relative quantitation MS methods. The first quantitation method, based on the areas of the extracted ion chromatograms, quantified the 51 and 48 most abundant proteins of the Descemet's membrane/endothelial layer in patient and control tissues, respectively, of which 10 were significantly regulated. The results indicated that the level of type VIII collagen was unaltered even though the protein previously has been shown to be implicated in familial early-onset forms of the disease. Using the second relative quantitation method, iTRAQ, we identified 22 differentially regulated proteins, many of which are extracellular proteins known to be involved in proper assembly of the basement membrane in other tissues. In total, 26 differentially regulated proteins were identified, of which 6 proteins were regulated in both methods. These results support that the morphological changes observed in FECD are caused in part by an aberrant assembly of the extracellular matrix within the Descemet's membrane/endothelial layer.

Technical brief: Optimized pipeline for isolation of high-quality RNA from corneal cell subpopulations.

PURPOSE: Attempts to determine the transcriptional profile of discrete subsets of limbal epithelial cells in situ using laser capture microdissection (LCM) face two major challenges. First, the transcriptional profile of cells within a tissue may rapidly change as the tissue is excised and exposed to cold ischemia. Second, there is a risk of degradation of the RNA as the cellular compartment is separated from the remaining tissue. An optimized protocol for LCM of corneal epithelium is presented to address these issues. METHODS: Experiments using porcine eye globes were carried out to determine both optimal procedures and settings for tissue harvest, transport, storage, histology, LCM, and RNA isolation. The optimized protocol was validated using human corneal epithelium. RESULTS: To facilitate preservation of the gene expression profile, we have developed a mechanical tool for dissection of cornea that, in combination with flash freezing, enables tissue to be stored within 5 min of enucleation of the eye. Furthermore, we describe how RNA from limbal crypt cells may be obtained using a procedure involving cryosectioning, histological staining, and LCM. CONCLUSION: In this paper, we describe an optimized method for isolating high-quality RNA from cellular subpopulations confined to the limbal crypts of the cornea. The procedure yields RNA in amounts and quality suitable for downstream gene expression analyses, such as microarrays or next generation sequencing.

Safety and complications of more than 1500 small-incision lenticule extraction procedures.

PURPOSE: To evaluate the safety and complications of small-incision lenticule extraction (SMILE). DESIGN: Clinical control cohort study. PARTICIPANTS: A total of 922 healthy patients (1800 eyes) who were treated for myopia or myopic astigmatism between January 2011 and March 2013 at the Department of Ophthalmology, Aarhus, Denmark. METHODS: Patients received a full preoperative examination and were treated with SMILE in both eyes and followed for 3 months (1574 eyes). Patients with complications, including loss of corrected distance visual acuity (CDVA) or dissatisfaction, were offered a late reexamination. MAIN OUTCOME MEASURES: Surgical complications and CDVA. RESULTS: Mean preoperative spherical equivalent refraction was -7.25±1.84 diopters (D). Average postoperative refraction was -0.28±0.52 D, and mean error of treatment was -0.15±0.50 D. By 3 months, 86% (1346 eyes) had unchanged or improved CDVA. A loss of 2 or more lines was observed in 1.5% of eyes; however, at a late follow-up visit (average, 18 months), CDVA was within 1 line of the preoperative level in all eyes. Perioperative complications included epithelial abrasions (6%), small tears at the incision (1.8%), and difficult lenticule extraction (1.9%). The cap was perforated in 4 eyes, and a major tear occurred in 1 eye; however, none of these patients had late visual symptoms. In 0.8% (14 eyes), suction was lost during surgery. Re-treatment was successful in 13 eyes, whereas 1 eye had ghost images and was re-treated with topography-guided photorefractive keratectomy (PRK). Postoperative complications included trace haze (8%), epithelial dryness on day 1 (5%), interface inflammation secondary to central abrasion (0.3%), and minor interface infiltrates (0.3%); these complications had an impact on CDVA at 3 months in only 1 case. Irregular corneal topography occurred in 1.0% of eyes, resulting in reduced 3-month CDVA (12 eyes) or ghost images (6 eyes). Topography-guided PRK was performed in 4 eyes, with improvement in 3 cases. Satisfaction was high, with only 2 patients dissatisfied at their latest visit because of blurred vision or residual astigmatism. CONCLUSIONS: Overall, SMILE had acceptable safety. Although 1.5% of eyes had reduced CDVA by 3 months, visual acuity was restored in the long term. Likewise, patient satisfaction was high.

Post-cataract prevention of inflammation and macular edema by steroid and nonsteroidal anti-inflammatory eye drops: a systematic review.

PURPOSE: Favorable outcome after cataract surgery depends on proper control of the inflammatory response induced by cataract surgery. Pseudophakic cystoid macular edema is an important cause of visual decline after uncomplicated cataract surgery. DESIGN: We compared the efficacy of topical steroids with topical nonsteroidal anti-inflammatory drugs (NSAIDs) in controlling inflammation and preventing pseudophakic cystoid macular edema (PCME) after uncomplicated cataract surgery. PARTICIPANTS: Patients undergoing uncomplicated surgery for age-related cataract. METHODS: We performed a systematic literature search in Medline, CINAHL, Cochrane, and EMBASE databases to identify randomized trials published from 1996 onward comparing topical steroids with topical NSAIDs in controlling inflammation and preventing PCME in patients undergoing phacoemulsification with posterior chamber intraocular lens implantation for age-related cataract. MAIN OUTCOME MEASURES: Postoperative inflammation and pseudophakic cystoid macular edema. RESULTS: Fifteen randomized trials were identified. Postoperative inflammation was less in patients randomized to NSAIDs. The prevalence of PCME was significantly higher in the steroid group than in the NSAID group: 3.8% versus 25.3% of patients, risk ratio 5.35 (95% confidence interval, 2.94-9.76). There was no statistically significant difference in the number of adverse events in the 2 treatment groups. CONCLUSIONS: We found low to moderate quality of evidence that topical NSAIDs are more effective in controlling postoperative inflammation after cataract surgery. We found high-quality evidence that topical NSAIDs are more effective than topical steroids in preventing PCME. The use of topical NSAIDs was not associated with an increased events. We recommend using topical NSAIDs to prevent inflammation and PCME after routine cataract surgery.

Correction of myopic astigmatism with small incision lenticule extraction.

PURPOSE: To evaluate the outcome after small incision refractive lenticule extraction (SMILE) in patients with myopic astigmatism. METHODS: Seven hundred seventy-five eyes from 403 patients with myopia treated with SMILE for a cylinder of 0.75 diopters (D) or more were identified from patient records. Six hundred sixty-nine eyes were defined as receiving low (< 2.5 D) and 106 eyes as receiving high (⩾ 2.5 D) astigmatic correction. Patients were examined before and 3 months after surgery. SMILE was performed with a Visumax femtosecond laser (Carl Zeiss Meditec, Jena, Germany). Preoperative and postoperative refractions were converted to polar values. Induced torsion and achieved corrections of sphere and cylinder were determined. RESULTS: In low astigmatism, the mean preoperative spherical equivalent (SE) was -7.57 ±1.67 D and the cylinder was -1.22 ± 0.49 D. Three months after surgery, SE was -0.19 ± 0.48 D from target, astigmatism was 0.17 ± 0.42 D undercorrected, and a small but significant torsion of the cylinder axis corresponding to 0.05 ± 0.37 D was found. The astigmatic undercorrection measured 13% per diopter of attempted correction. In high astigmatism, preoperative SE was -5.91 ± 2.56 D and cylinder was -3.22 ± 0.67 D. After surgery, the average astigmatic undercorrection was 0.59 ± 0.65 D, equivalent to 16% per diopter of attempted correction. No undercorrection in SE occurred and no torsion was found. CONCLUSIONS: SMILE in myopic astigmatism offers predictable correction of SE, but a small, significant undercorrection of the astigmatic error. The undercorrection increases with the attempted treatment. Only very little rotation of the cylinder axis was found.

Topography-guided photorefractive keratectomy for irregular astigmatism after small incision lenticule extraction.

PURPOSE: To report the outcome of topography-guided photorefractive keratectomy (PRK) after complicated small incision lenticule extraction (SMILE). METHODS: Retrospective case series of 5 eyes with irregular topography and ghost images after complicated SMILE. All eyes received transepithelial topography-guided PRK. Two eyes were treated with 0.02% mitomycin C. Patients were examined after a minimum of 3 months with evaluation of uncorrected (UDVA) and corrected (CDVA) distance visual acuity, Pentacam tomography (Oculus Optikgeräte, Wetzlar, Germany), and whole-eye aberrometry. RESULTS: In 3 eyes, subjective symptoms were diminished and UDVA, CDVA, topography, and corneal wavefront aberrations were improved. The remaining 2 eyes developed significant haze with worsened topography and wavefront aberrations. One eye experienced a two-line reduction in CDVA. Eyes with haze development had not been treated with mitomycin C. CONCLUSIONS: Transepithelial topography-guided PRK may reduce visual symptoms after complicated SMILE if postoperative haze can be controlled. To reduce the risk of haze development, application of mitomycin C may be considered.

Dynamic Scheimpflug-based assessment of keratoconus and the effects of corneal cross-linking.

PURPOSE: To evaluate the ability of the Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) to distinguish between normal and keratoconic corneas and detect the possible stiffening effect of corneal cross-linking (CXL) in vivo. METHOD: A retrospective study including 86 eyes of 86 participants (27 patients with untreated keratoconus, 27 patients with CXL-treated keratoconus, and 32 normal patients). The prospective study included 9 keratoconic eyes measured 24 days before and 97 days after CXL. RESULTS: The following parameters from the Corvis ST showed a significant difference between keratoconic and normal eyes: intraocular pressure, corneal thickness, first applanation time, highest concavity (HC) radius, HC deformation amplitude, and HC deflection amplitude (analysis of variance, P < .0001). Receiver operating characteristic curve analysis showed the highest area under the curve for HC deflection amplitude (0.942, P < .0001). Prediction intervals for individual measurements within the two groups overlapped considerably. No significant difference was found between the untreated and CXL-treated keratoconus groups (analysis of variance, P > .05). Measurements performed before and after CXL in the same patients showed significant difference in HC deformation amplitude (P = .018), HC time (P = .018), and second applanation time (P = .027). CONCLUSIONS: Although the corneal deformation characteristics differed between groups of keratoconic and normal eyes, this study showed that the standard parameters of the Corvis ST cannot readily be used for diagnosis of keratoconus in the individual patient or to document the effect of CXL in vivo.

Central corneal sublayer pachymetry and biomechanical properties after refractive femtosecond lenticule extraction.

PURPOSE: To compare central corneal sublayer pachymetry and biomechanical properties after femtosecond lenticule extraction (FLEX) and small-incision lenticule extraction (SMILE). METHODS: A prospective, randomized, single-masked clinical trial of 35 patients treated for moderate to high myopia with FLEX in one eye and SMILE in the other. Anterior segment optical coherence tomography imaging (Heidelberg Spectralis; Heidelberg Engineering GmbH, Heidelberg, Germany) was used to measure central corneal thickness (CCT) and epithelial, flap/cap, and residual stromal bed thickness centrally. The Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, NY) was used to assess corneal hysteresis (CH) and corneal resistance factor (CRF). Patients were examined before and 6 months after surgery. RESULTS: Mean decrease in CCT was 105 µm in FLEX-treated eyes and 106 µm in SMILE-treated eyes (P = .70), which is equivalent to approximately 14 µm/diopters corrected. Mean central epithelial thickness increased 7 ± 6 µm in FLEX-treated eyes and 6 ± 5 µm in SMILE-treated eyes (P = .64). Achieved mean flap/cap thickness was 4 ± 6 µm from the expected thickness in FLEX-treated eyes and 4 ± 9 µm in SMILE-treated eyes (P = .37). CH was reduced 2.7 ± 1.3 mm Hg in FLEX-treated eyes and 3.3 ± 1.2 mm Hg in SMILE-treated eyes (P = .08). CRF was reduced 4.5 ± 1.2 mm Hg in FLEX-treated eyes and 4.6 ± 1.2 mm Hg in SMILE-treated eyes (P = .71). CH and CRF were highly correlated with CCT, but not patient age. CONCLUSIONS: In this paired-eye study, the flap-based FLEX and cap-based SMILE resulted in almost identical changes in central corneal sublayer pachymetry and biomechanical properties for moderate to high myopia 6 months after treatment.