Efficacy of selective laser trabeculoplasty on lowering intraocular pressure fluctuations and nocturnal peak intraocular pressure in treated primary open-angle glaucoma patients.

PURPOSE: To investigate the efficacy of adjunctive selective laser trabeculoplasty (SLT) in reducing 24-h intraocular pressure (IOP) fluctuations and nocturnal IOP peaks. METHODS: In this prospective interventional case series, 157 medically treated eyes of 157 patients with primary open-angle glaucoma (POAG) who were assigned SLT to further reduce IOP were consecutively included. Each patient had a complete glaucoma work-up and 24-h IOP monitoring (6 measurements, including one in the supine position) taken before and on average 6 months after SLT. The main outcome measures were the reduction of 24-h IOP fluctuations and nocturnal peak IOP. Secondary outcome measures were success rates, factors influencing the reduction of high 24-h IOP fluctuations and nocturnal peak IOP, complications, and severe adverse events. RESULTS: Medicated mean 24-h IOP (mmHg) was statistically significantly reduced from 15.1 ± 2.6 to 13.8 ± 2.4 (P < 0.001) and IOP fluctuations from 6.5 ± 2.7 to 5.4 ± 2.6 (P < 0.001) 6 months after SLT. Ninety-four eyes (59.9%) initially had high IOP fluctuations (more than 5 mmHg). These were reduced from 8.1 ± 2.3 to 5.6 ± 2.7 at 6 months (P < 0.001). Fifty-two eyes (55.3%) had fluctuations below 5 mmHg post-SLT which was defined as success. Fifty-one patients (32.5%) had nocturnal IOP peaks. In these cases, nocturnal IOP was reduced by 19.2% from 20.1 ± 3.4 to 16.2 ± 3.3 mmHg at 6 months (P = 0.001). CONCLUSIONS: The current study demonstrates that adjunctive SLT not only reduces mean 24-h IOP in treated POAG patients, but also has an additional benefit in reducing IOP fluctuations and nocturnal peak IOP. TRIAL REGISTRATION: Clinical trial registration: NCT02959242.

[Therapeutic Options in Keratoconus]. / Keratokonus: heutige Therapieoptionen.

A recent epidemiology study revealed that prevalence of keratoconus was much higher than previously assumed. Therefore, it is no longer deemed an "orphan disease", as it has a relevant socioeconomic impact on the healthcare system. One of the most important risk factors for developing keratoconus is chronic eye rubbing which, apart from other known risk factors such as atopy or Down's syndrome, is the only modifiable factor. Informing the patient and offering behavior modifying therapies seems to be essential. Further therapeutic options regarding improvement of visual function include the wearing of glasses and the fitting of rigid gas permeable contact lenses and implantation of intrastromal corneal ring segments or phakic intraocular lenses. Corneal crosslinking (CXL) has been proven to be a highly effective and safe procedure in keratoconus cases showing disease progression. Significantly fewer corneal transplants were performed in this indication following the introduction of CXL. Recent studies reevaluated a combination of photorefractive keratectomy, which has been contraindicated until recently for patients with primary corneal ectasia with CXL, reporting a positive visual refractive outcome and stability of keratoconus. Still, penetrating keratoplasty is the gold standard of surgical treatment for end-stage keratoconus, whereas recently lamellar procedures have gained higher importance.

The CellBorderTracker, a novel tool to quantitatively analyze spatiotemporal endothelial junction dynamics at the subcellular level.

Endothelial junctions are dynamic structures organized by multi-protein complexes that control monolayer integrity, homeostasis, inflammation, cell migration and angiogenesis. Newly developed methods for both the genetic manipulation of endothelium and microscopy permit time-lapse recordings of fluorescent proteins over long periods of time. Quantitative data analyses require automated methods. We developed a software package, the CellBorderTracker, allowing quantitative analysis of fluorescent-tagged cell junction protein dynamics in time-lapse sequences. The CellBorderTracker consists of the CellBorderExtractor that segments cells and identifies cell boundaries and mapping tools for data extraction. The tool is illustrated by analyzing fluorescent-tagged VE-cadherin the backbone of adherence junctions in endothelium. VE-cadherin displays high dynamics that is forced by junction-associated intermittent lamellipodia (JAIL) that are actin driven and WASP/ARP2/3 complex controlled. The manual segmentation and the automatic one agree to 90 %, a value that indicates high reliability. Based on segmentations, different maps were generated allowing more detailed data extraction. This includes the quantification of protein distribution pattern, the generation of regions of interest, junction displacements, cell shape changes, migration velocities and the visualization of junction dynamics over many hours. Furthermore, we demonstrate an advanced kymograph, the J-kymograph that steadily follows irregular cell junction dynamics in time-lapse sequences for individual junctions at the subcellular level. By using the CellBorderTracker, we demonstrate that VE-cadherin dynamics is quickly arrested upon thrombin stimulation, a phenomenon that was largely due to transient inhibition of JAIL and display a very heterogeneous subcellular and divers VE-cadherin dynamics during intercellular gap formation and resealing.

Crosslinking with UV-A and riboflavin in progressive keratoconus: From laboratory to clinical practice - Developments over 25 years.

Changes in the biomechanical and biochemical properties of the human cornea play an important role in the pathogenesis of ectatic diseases. A number of conditions in primarily acquired (keratoconus or pellucid marginal degeneration) or secondarily induced (iatrogenic keratectasia after refractive laser surgeries) ectatic disorders lead to decreased biomechanical stability. Corneal collagen cross-linking (CXL) represents a technique to slow or even halt the progression of ectatic pathologies. In this procedure, riboflavin is applied in combination with ultraviolet A radiation. This interaction induces the production of reactive oxygen species, which leads to the formation of additional covalent bonds between collagen molecules and subsequent biomechanical corneal strengthening. This procedure is so far the only method that partially interferes etiopathogenetically in the treatment of ectatic diseases that slows or stops the process of corneal destabilization, otherwise leading to the need for corneal transplantation. Besides, CXL process increases markedly resistance of collagenous matrix against digesting enzymes supporting its use in the treatment of corneal ulcers. Since the discovery of this therapeutic procedure and the first laboratory experiments, which confirmed the validity of this method, and the first clinical studies that proved the effectiveness and safety of the technique, it has been spread and adopted worldwide, even with further modifications. Making use of the Bunsen-Roscoe photochemical law it was possible to shorten the duration of this procedure in accelerated CXL and thus improve the clinical workflow and patient compliance while maintaining the efficacy and safety of the procedure. The indication spectrum of CXL can be further expanded by combining it with other vision-enhancing procedures such as individualized topographically-guided excimer ablation. Complementing both techniques will allow a patient with a biomechanically stable cornea to regularize it and improve visual acuity without the need for tissue transplantation, leading to a long-term improvement in quality of life.

Corneal Crosslinking With Riboflavin and UVA Light in Progressive Keratoconus: Fifteen-Year Results.

PURPOSE: To analyze the 15-year results of corneal crosslinking (CXL) in progressive keratoconus. DESIGN: Retrospective follow-up analysis of interventional study patients. METHODS: This study included keratoconic eyes with progressive disease treated from 2001 to 2006 at the Department of Ophthalmology, Carl Gustav Carus University Hospital, TU Dresden, Germany. CXL was performed by applying riboflavin and ultraviolet A (UVA) light according to a standard protocol. The best-corrected distance visual acuity (BCVA), slitlamp examination, and corneal topography as well as corneal thickness values were recorded preoperatively and 15 years after the treatment. RESULTS: A total of 42 eyes received a complete follow-up of 15 years. The mean age of the patients at baseline was 26.9 (95% CI: 25.0-28.8) years. The maximum keratometry was 61.6 (95% CI: 58.2 - 64.9) diopters (D) preoperatively and 55.1 (95% CI: 51.6-58.4) D postoperatively; the decrease was statistically significant (P < .001). The mean keratometry value changed from 50.3 (95% CI: 48.3-52.4) D to 47.5 (95% CI: 45.3-49.4) D (P < 0.001). Furthermore, the thinnest corneal thickness decreased statistically significantly by 40 (95% CI: 24-56) µm (P < .001). The BCVA improved statistically significantly from 0.4 to 0.2 logMAR after the treatment. Retreatment was needed in 14% of cases. Mild scarring of the superficial stromal corneal layers was observed in 36% of the eyes, and in 67% of them visual acuity was stable or even improved. CONCLUSIONS: The CXL procedure proved to be an effective method in the treatment of keratoconic eyes in the progressive stage of the disease, and achieved long-term stabilization without the occurrence of serious complications or side effects.

Comparison of corneal tomography using a novel swept-source optical coherence tomographer and rotating Scheimpflug system in normal and keratoconus eyes: repeatability and agreement analysis.

BACKGROUND: To determine the repeatability and agreement using corneal tomography of a swept-source optical coherence tomographer (SS-OCT) compared to a rotating Scheimpflug camera (RSC) in normal eyes and keratoconus (KC) eyes. METHODS: This prospective repeatability analysis was performed at the Department of Ophthalmology of University Hospital Carl Gustav Carus, Dresden, Germany. Forty-three normal and 57 KC eyes were enrolled in the study. Three consecutive measurements were performed by the same operator on each device. Corneal parameters of anterior and posterior corneal surface, such as simulated keratometry (SimK), as well as central and thinnest corneal thickness were evaluated. Repeatability and agreement were assessed by using the coefficient of repeatability and Bland-Altman analysis. RESULTS: The repeatability of anterior corneal parameters was comparable between RSC and SS-OCT in normal eyes (repeatability < 0.5 D). Repeatability was increased in mild and moderate KC for all parameters using both devices. In moderate KC, repeatability of Kmax was 1.33 D and 0.78 D for RSC and SS-OCT, respectively. Repeatability of posterior corneal parameters was consistently better for SS-OCT. Significant offsets and wide ranges of limits of agreement were found between the devices for SimK and corneal thickness values. CONCLUSIONS: SS-OCT showed highly repeatable measurements of anterior and posterior corneal parameters in normal and KC eyes. Compared to RSC, the SS-OCT had a better repeatability of anterior corneal parameters in mild and moderate KC as well as posterior corneal parameters in all groups. Both devices should not be used interchangeably in the diagnostic process of patients. Trial registration NCT04251143 at Clinicaltrials.gov, registered on 12 March 2018, https://clinicaltrials.gov/ct2/show/NCT04251143?cond=Keratoconus&cntry=DE&city=Dresden&draw=2&rank=1.

Agreement and repeatability of corneal tomography in healthy eyes using a new swept-source OCT, a rotating Scheimpflug camera, and a dual Scheimpflug-Placido system.

PURPOSE: To investigate the accordance and repeatability of tomographic parameters measured by a new swept-source optical coherence tomographer (SS-OCT, ANTERION), a rotating Scheimpflug camera (RSC, Pentacam), and a dual Scheimpflug-Placido system (DSP, Galilei G6). SETTING: Department of Ophthalmology of University of Hospital Carl Gustav Carus, Dresden, Germany. DESIGN: Prospective reliability analysis. METHODS: Normal tomography was ensured by bilaterally evaluating appropriated parameters using RSC. All subjects received 3 consecutive measurements on each device by the same operator and in the uniform order RSC, SS-OCT, and DSP. Anterior (ACP) and posterior (PCP) corneal parameters such as flat and steep keratometry and corneal thickness were analyzed. Repeatability was assessed by using a coefficient of repeatability (CoR) and a coefficient of variation. Agreement between RSC and SS-OCT and between RSC and DSP were shown by Bland-Altman plots. RESULTS: This study included 30 randomly selected eyes of 30 healthy participants. CoR of ACP did not exceed 0.5 diopters. There were no statistically significant differences in repeatability of ACP obtained from the 3 devices (P > .05). For PCP and corneal thickness, there was statistically significant higher repeatability mostly found for SS-OCT as opposed to RSC and DSP (P < .05). For a wide range of analyzed parameters, there were large limits of agreement (95% LoA) found between the devices. CONCLUSIONS: The SS-OCT showed highly repeatable measurements in healthy subjects regarding anterior, posterior, and corneal thickness parameters. Repeatability of ACP did not differ between the devices. A mostly wide range of 95% LoA prevents interchangeability between the devices.

[Principles of corneal cross-linking : Presentation based on the development of the various treatment protocols]. / Grundlagen des kornealen Crosslinking : Dargestellt anhand der Entwicklung der verschiedenen Behandlungsprotokolle.

BACKGROUND: Corneal cross-linking (CXL) is used to treat corneal ectatic diseases. The aim is to improve the reduced consolidation of the cornea in order to halt further corneal protrusion and therefore subsequent deterioration of the optical imaging proportions. MATERIAL AND METHODS: In this article the principles of corneal cross-linking based on riboflavin and UV light are presented including recent research results. Furthermore, the most important treatment protocols including standard CXL (S-CXL), accelerated CXL (A-CXL), transepithelial CXL (TE-CXL) and the approach of the CXL procedure for thin corneas are explained. RESULTS: The CXL method depends on four major components, the riboflavin solution, oxygen, UV light and the availability of cross-linking sites on the collagen tissue. According to the present state of knowledge, the photochemical process of the CXL method induces covalent bonds between the fibrils and proteoglycans and thus stabilizes the collagen fibers, resulting in corneal consolidation. In addition to the S­CXL, which has proven its effectiveness and safety in a large number of studies, there are other treatment protocols that have been developed based on the Bunsen-Roscoe law of reciprocity. The A­CXL protocol has the advantage of having a shorter irradiation time but it seems to be less effective than the S­CXL protocol concerning the increase in corneal stiffness. The use of TE-CXL has so far not yet gained acceptance in the clinical practice. CONCLUSION: The CXL procedures primarily aim to stabilize the cornea. In the future, in addition to stabilization of the cornea, simultaneous improvement of visual acuity will be the main focus.

Evaluation of Corneal Biomechanical Indices in Distinguishing Between Normal, Very Asymmetric, and Bilateral Keratoconic Eyes.

PURPOSE: To evaluate the ability of biomechanical indices provided by the Ocular Response Analyzer (ORA; Reichert Ophthalmic Instruments) and dynamic Scheimpflug analyzer (Corvis ST; Oculus Optikgeräte GmbH) to distinguish between normal eyes and eyes with very asymmetric ectasia (VAE) and mild and moderate keratoconus. METHODS: This prospective, observational, and monocentric study included normal eyes (defined as keratoconus percentage index < 60, Belin/Ambrósio total deviation value [BAD-D] < 1.6, inferior-superior keratometry [I-S value] < 1.45 and maximum keratometry [Kmax] < 47) and eyes with clinical bilateral keratoconus (mild and moderate) and VAE (defined as unilateral keratoconus, where one eye showed a clinical keratoconus and the fellow eye was topographically normal [VAE-NT] or topographically and tomographically normal [VAE-NTT]). All eyes were measured by the Pentacam (Oculus Optikgeräte GmbH), ORA, and Corvis ST. Receiver operating characteristic curve analysis was performed to test the diagnostic ability. RESULTS: Fifty-eight normal eyes and 238 ectatic eyes were included. The highest area under the curve (AUC) was provided by the Corvis Biomechanical Index (CBI) with an AUC of 0.979, followed by ORA corneal resistance factor (0.865), and corneal hysteresis (0.824) separating normal eyes from all ectatic subgroups. The AUC of the CBI was statistically significantly higher than all other parameters (DeLong test, P < .001). A sensitivity of 100% and 70.9%, respectively, and a specificity of 93.1% was found to distinguish normal eyes from VAE-NT and VAE-NTT using a cut-off value of 0.2. CONCLUSIONS: The assessment of biomechanical properties is an additional important method to evaluate corneal ectasia independent of its stage. The CBI provides further information for ectasia screening in cases where corneal topography and tomography are clinically not suspicious by using a cutoff of 0.2. [J Refract Surg. 2022;38(6):364-372.].

Risk Factors for Progression of Keratoconus and Failure Rate After Corneal Cross-linking.

PURPOSE: To assess the occurrence of risk factors for progression of keratoconus and failure rate after corneal cross-linking (CXL) in patients with progressive keratoconus. METHODS: This retrospective study observed 230 eyes of 173 patients with a minimum follow-up of 36 months after CXL. A total of 185 eyes underwent CXL once (80%) (control) and 45 (20%) underwent this treatment more than once (Re-CXL-group). Subgroup analysis included standard CXL with the Dresden protocol (S-CXL group, n = 120) and accelerated CXL with a reduced radiation time of 10 minutes and a higher radiation power of 9 mW/cm2 (A-CXL group, n = 110). Risk factors of interest were age, maximum keratometry (Kmax), minimum corneal thickness (MCT), sex, and atopy (including allergic bronchial asthma, food allergy, allergic rhinitis, and neurodermatitis). RESULTS: Follow-up for the control group was 76.0 ± 33.2 months. Re-CXL was performed after 46.2 ± 34.1 months overall and after 62.6 ± 41.9 months in the S-CXL subgroup and 29.2 ± 19.2 months in the A-CXL subgroup (P = .02). Kaplan-Meier analysis revealed a cumulative prediction rate of success after CXL of 92.5% (S-CXL) and 86.4% (A-CXL) after 36 months (P = .103). A high preoperative Kmax value (odds ratio = 1.056, P = .003 and odds ratio = 1.067, P = .028) in both subgroups and the presence of neurodermatitis combined with other atopic diseases in the A-CXL group (odds ratio = 11.662, P = .003) were significant risk factors for new progression of keratoconus after CXL. CONCLUSIONS: Risk factors for progression of keratoconus after CXL are both high preoperative Kmax values and the presence of neurodermatitis combined with other atopic diseases. Patients with severe atopy should receive the S-CXL procedure. [J Refract Surg. 2021;37(12):816-823.].

[Scedosporium apiospermum-a rare pathogen of keratomycosis]. / Scedosporium apiospermum ­ Seltener Erreger einer mykotischen Keratitis.

This article presents the case of a 44-year-old contact lens wearer who presented with acute keratitis resistant to antibacterial treatment in the right eye. The anterior segment of the eye showed circular conjunctival hyperemia, a corneal white cell infiltrate with radiating margins and a central corneal erosion. Microbiological investigation of a corneal scraping revealed growth of Scedosporium apiospermum. Intensive antimycotic treatment and several corneal collagen crosslinking procedures were performed; however, because of rapidly evolving necrotizing ulcerative keratitis, a keratoplasty à chaud was carried out.

Hair cortisol concentration in patients with active central serous chorioretinopathy is elevated - a pilot study.

PURPOSE: To investigate hair cortisol concentration (HCC), a biochemical correlate of long-term cortisol output patterns, and its relationship to active central serous chorioretinopathy (CSC). METHODS: Twenty-six participants were included in this observational pilot study (11 patients with active CSC and 15 healthy controls). Hair cortisol concentrations (HCCs) were determined from 3 cm hair strands collected near the scalp from patients and controls as an index of cumulative cortisol secretion over the 3-month period prior to hair sampling. RESULTS: Patients with CSC exhibited higher HCCs (mean value: 20.14, 95% CI: 14.89-27.16 pg/mg) than healthy controls (mean value: 11.06, 95% CI: 8.63-14.22 pg/mg, p = 0.008). Group differences were not affected by relevant covariates (BMI, smoking status, sex). CONCLUSION: Patients with active CSC have increased HCC, supporting the fact that cortisol is a major player in CSC pathogenesis.

Rapid progressive visual decline and visual field defects in two patients with the Heidenhain variant of Creutzfeld-Jakob disease.

BACKGROUND: Heidenhain variant of Creutzfeldt-Jakob (HvCJD) is a rare disease, patients presenting with loss of visual acuity and a decline in visual fields. CASE PRESENTATION: Two patients with rapid loss of visual acuity and declining visual fields presented with homonymic hemianopsia over several weeks. Cranial MRI showed neither stroke nor other morphological changes explaining the severe visual field defects. Neurological examination revealed no pathologies. However, lumbar puncture showed an increase in total protein in cerebrospinal fluid (CSF). Visual field testing revealed further deterioration during follow-up. Several weeks later, patients' behaviour changed markedly, exhibiting aggression, declining memory function and physical degeneration. The suspected diagnosis was the Heidenhain variant of Creutzfeld-Jakob disease (HvCJD). CSF analysis showed evidence of PrPSc and 14-3-3 protein. Both patients died within 8 weeks of the CJD diagnosis. CONCLUSIONS: Loss of visual acuity and a decline in visual fields without corresponding MRI findings and marked changes in behaviour should lead to a diagnosis of HvCJD. Corresponding diagnostic tests should be performed for confirmation. The prognosis for survival is poor and should be immediately communicated to affected patients and their relatives.

Posterior amorphous corneal dystrophy in a patient with 12q21.33 deletion.

Posterior amorphous corneal dystrophy (PACD) (OMIM 612868) is a rare autosomal dominant disorder characterized by partial or complete posterior lamellar corneal opacification, decreased corneal thickness and flattening of the corneal curvature. PACD is associated with heterozygous deletions in chromosome band 12q21.33 harboring DCN, KERA, LUM, and EPYC which encode small leucine-rich proteoglycans. We report on a 7-year-old male patient with PACD who had an interstitial deletion of 1.3 Mb in 12q21.33. His mother carried a balanced insertional translocation involving this 12q21.33 segment which was inserted into the proximal part of the long arm of one chromosome 13. The patient corroborates previous observations that PACD is a contiguous gene syndrome caused by combined haploinsufficiency of DCN, KERA, LUM, and EPYC and provides the first example of a balanced chromosome rearrangement involving 12q21.33 in an unaffected parent.

Increased Hair Cortisol Concentrations in Patients With Progressive Keratoconus.

PURPOSE: To investigate hair cortisol concentration (HCC), a biochemical correlate of chronic psychological stress, and its relationship to the progression of keratoconus. METHODS: Eighty-six participants were included in this prospective observational study (32 patients with progressive keratoconus, 32 patients with stable keratoconus, and 22 healthy controls). Hair cortisol concentrations were determined from 3-cm hair strands collected near the scalp from patients and controls as an index of cumulative cortisol secretion during the 3-month period prior to hair sampling. In addition, self-reported chronic stress was assessed using the Trier Inventory for the Assessment of Chronic Stress screening scale. RESULTS: Patients with progressive keratoconus exhibited higher hair cortisol concentrations (mean value: 29.11 pg/mg; 95% confidence interval [CI]: 22.13 to 38.28) than patients with stable keratoconus (mean value: 15.88 pg/mg; 95% CI: 12.25 to 20.65; P = .007) and healthy controls (mean value: 16.98 pg/mg; 95% CI: 12.30 to 23.44; P = .049). There were no significant differences in hair cortisol concentrations between healthy controls and patients with stable keratoconus (P = .991). Group differences were not affected by relevant covariates (body mass index, age, or sex). CONCLUSIONS: This study shows that increased hair cortisol concentration seems to be associated with the progression of keratoconus. There are a variety of causes of increased hair cortisol concentration. [J Refract Surg. 2017;33(6):383-388.].

Characterization of Ocular Biomechanics in Pellucid Marginal Degeneration.

PURPOSE: This study sought to investigate the diagnostic capacity of corneal biomechanical response parameters in a group of patients with pellucid marginal degeneration (PMD) using the Ocular Response Analyzer (ORA) and Corvis ST devices. METHODS: In this prospective clinical study, we used the Corvis ST and ORA devices to investigate the ocular biomechanics of patients with PMD. Eighty-one eyes were included, and 2 study groups were formed: the PMD group (the study group, n = 29) and the control group (n = 52). We focused on 13 biomechanical parameters. Statistical analysis was performed using SPSS. Biomechanical parameters for the 2 groups were compared using analysis of covariance. RESULTS: The ORA results demonstrated that the Keratoconus Match Index was significantly lower in the PMD group than in the control group (0.031 ± 0.37 vs. 0.79 ± 0.33; P = 0.001). The 2 groups did not significantly differ with respect to intraocular pressure- and central corneal thickness-adjusted values for corneal hysteresis or corneal resistance factor. Regarding the Corvis parameters, differences between the control and PMD groups were detected for CorWmax amp (control 1.01 ± 0.01, PMD 1.06 ± 0.01; P = 0.020) and CorA2 t (control 21.78 ± 0.03, PMD 21.66 ± 0.04; P = 0.0003). CONCLUSIONS: We identified 2 Corvis parameters that could be used to characterize PMD and differentiate PMD corneas from normal corneas. These parameters support the hypothesis that there is significantly less deformation of the central cornea in PMD corneas than in healthy corneas. However, because useful "first-line" diagnostic devices for diagnosing PMD (such as Pentacam and the ORA) exist, the Corvis ST serves as an additional diagnostic tool that can also be used for long-term monitoring after diagnosis confirmation.