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.

Association Between Corneal Changes and Retinal Oximetry in Diabetes Mellitus.

Purpose: Diabetes mellitus (DM) causes different corneal changes that are associated with the severity of diabetic retinopathy. To identify the pathophysiological reasons for this, corneal tomography and optical densitometry (COD) were combined with retinal oximetry. Methods: Patients with DM and healthy subjects were included in this pilot study. Spatially resolved corneal thickness and COD were assessed using the Pentacam HR (Oculus). The pachymetry difference (PACDiff) was calculated as an indicator of an increase in the peripheral corneal thickness. Oxygen saturation (SO2) of the retinal vessels was measured using the Retinal Vessel Analyzer (Imedos Systems UG). Subsequently, the associations between corneal and retinal parameters were analyzed. Results: Data from 30 patients with DM were compared with those from 30 age-matched healthy subjects. In DM, arterial (P = 0.048) and venous (P < 0.001) SO2 levels were increased, and arteriovenous SO2 difference was decreased (P < 0.001). In patients, PACDiff was higher than that in healthy subjects (P < 0.05), indicating a stronger increase in peripheral corneal thickness. The COD was reduced in DM (P = 0.004). The PACDiff of concentric rings with a diameter of 4 mm (r = -0.404; P = 0.033) to 8 mm (r = -0.522; P = 0.004) was inversely correlated with the arteriovenous SO2 difference. Furthermore, PACDiff 4 mm was negatively associated with arterial SO2 (r = -0.389; P = 0.041), and the COD of the peripheral corneal areas correlated positive with arterial SO2 (COD total 10-12 mm: r = 0.408; P = 0.025). Conclusion: These associations might indicate a common pathogenesis of corneal and retinal changes in DM, which could be caused by reduced oxygen supply, mitochondrial dysfunction, oxidative stress, and cytokine effects.

Retinal changes are particularly important for ophthalmologists in the management of diabetes mellitus. These are primarily consequences of diabetic vascular changes that can lead to a lack of oxygen. However, there is also evidence of significant changes in the cornea of patients with diabetes. In the present study, the associations between changes in corneal thickness profile, optical density of the cornea, and oxygen saturation of retinal vessels in diabetes mellitus were demonstrated for the first time. Therefore, this study could contribute to clarifying the possible causes of corneal changes in patients with diabetes.

The retinal venous pressure at different levels of airway pressure measured with a new method.

PURPOSE: This study is to investigate the increase in retinal venous pressure (RVP) induced by a stepwise increase in airway pressure (AirP) using the new IOPstim method, which is designed to artificially increase the intraocular pressure (IOP) and thus to stimulate vascular pulsation. METHODS: Twenty-eight healthy subjects were examined in the left eye. The RVP was measured at baseline and at four different levels of AirP (10, 20, 30, and 40 mmHg) using the new IOPstim method: a half balloon of 8 mm diameter is inflated laterally to the cornea under observation of the central retinal vein. As soon as the vein pulsates at a certain AirP level, the IOP is measured with a commercially available tonometer, which then corresponds to the RVP. RESULTS: Spontaneous venous pulsation was observed in all study participants. The mean RVP values at baseline and at the AirP levels of 10, 20, 30, and 40 mmHg were 17.6 ± 2.8 mmHg; 20.1 ± 3.0 mmHg; 22.1 ± 3.5 mmHg; 24.3 ± 3.7 mmHg, and 26.6 ± 4.2 mmHg, respectively. The mean RVP values of each AirP level were statistically significantly different from each other in pairwise comparison. In a linear mixed model, the effect of AirP on RVP was highly significant (p < 0.001). In the model, a 10-mmHg increase in AirP resulted in a linear increase in RVP of 2.2 mmHg. CONCLUSION: An increase in AirP was accompanied by a linear increase in RVP. The influence of AirP on RVP, and thus on retinal perfusion pressure during the Valsalva maneuver, is less than was assumed based on previous studies in which contact lens dynamometry was used.

Five decades of the use of botulinum toxin in ophthalmology.

Botulinum toxin (BoNT) has been known for over 50 years. It has conquered many areas of medicine and has become indispensable in contemporary medicine. Now, BoNT is used to treat at least 26 conditions in six medical specialties. Although the use of BoNT began in strabology, it became the gold standard for many ophthalmologic pathologies. The present review of the literature focuses on the use of BoNT in ophthalmology and treatment of the following conditions: blepharospasm, facial hemispasm, facial palsy, spastic entropion, strabismus, endocrine orbitopathy, convergence spasm, and facial trauma. We conclude that nearly half a century of experience in utilizing BoNT in ophthalmology ensured a satisfactory level of effectiveness and safety for patients with many pathologies. Areas of future research include the application of BoNT in new selected indications, the development of the route of application without injections, and the development of long-acting BoNT forms for patients who require repeated long-term treatment.

Measurement of the retinal venous pressure with a new instrument in patients with primary open angle glaucoma.

PURPOSE: To compare the results of retinal venous pressure (RVP) measurement performed with contact lens dynamometry (CLD) and with the new IOPstim. METHODS: In this cross-sectional study, we included 36 patients with primary open angle glaucoma with a median age (Q25; Q75) of 74 (64; 77) years (m/f = 18/18), baseline intraocular pressure (IOP): 13.9 (12.2; 15.1) mmHg. Median mean defect: - 5.8 (- 11.9; - 2.6) db. Principle of the IOPstim: an empty balloon with a diameter of 8 mm is positioned on the eye, laterally of the limbus. Under observation of the central retinal vein (CRV), the examiner inflates the balloon. As soon as the CRV starts pulsation, the inflation is stopped and the IOP is measured, equaling the RVP at this moment. In the CLD, the pulsation of the CRV is observed with a contact lens. The RVP is calculated from the attachment force applied when pulsation appears. COURSE OF EXAMINATIONS: Three single measurements of RVP in quick succession with both methods. The sequence of the two methods was randomized. The means of the three RVP measurements were compared. RESULTS: Pressures in mmHg. RVP: IOPstim: 19.4 ± 5.4 (mean ± SD), CLD: 20.3 ± 5.9. Range of three single measurements: IOPstim: 2.9 ± 1.5, CLD: 2.2 ± 1.1. The differences were RVPIOPstim - RVPCLD = - 0.94 ± 1.15, and approximately normally distributed. Bland-Altman analysis: only one data point was 0.5 mmHg higher than the upper line of agreement. The confidence interval of this line was 0.65 mmHg. Concordance correlation coefficient according to Lin (CCC): 0.96. Intraclass correlation coefficient: both methods, 0.94. CONCLUSION: In both methods, the range of the single measurements may be taken as a sign of good reliability, the CCC of 0.96 as a sign of a very good agreement. At the mean, the IOPstim RVP values were 1 mmHg lower than those obtained with the CLD. This difference may be due to the different directions of the prevailing force vectors induced by the instruments. The IOPstim seems applicable in glaucoma diagnostics.

PRESERFLO ™ MicroShunt versus trabeculectomy: 1-year results on efficacy and safety.

PURPOSE: To compare the efficacy and safety of the PRESERFLO™ MicroShunt versus trabeculectomy in patients with primary open-angle glaucoma (POAG) after one year. PATIENTS AND METHODS: Institutional prospective interventional cohort study comparing eyes with POAG, which had received the PRESERFLO™ MicroShunt versus trabeculectomy. The MicroShunt group was matched with the trabeculectomy group for age, known duration of disease, and number and classes of intraocular pressure (IOP) lowering medications to have similar conjunctival conditions. The study is part of the Dresden Glaucoma and Treatment Study, using a uniform study design, with the same inclusion and exclusion criteria, follow-ups and standardized definitions of success and failure for both procedures. PRIMARY OUTCOME MEASURES: mean diurnal IOP (mdIOP, mean of 6 measurements), peak IOP, and IOP fluctuations. SECONDARY OUTCOME MEASURES: success rates, number of IOP lowering medications, visual acuity, visual fields, complications, surgical interventions, and adverse events. RESULTS: Sixty eyes of 60 patients, 30 in each group, were analyzed after 1-year follow-ups. Median [Q25, Q75] mdIOP (mmHg) dropped from 16.2 [13.8-21.5] to 10.5 [8.9-13.5] in the MicroShunt and from 17.6 [15.6-24.0] to 11.1 [9.5-12.3] in the trabeculectomy group, both without glaucoma medications. Reduction of mdIOP (P = .596), peak IOP (P = .702), and IOP fluctuations (P = .528) was not statistically significantly different between groups. The rate of interventions was statistically significantly higher in the trabeculectomy group, especially in the early postoperative period (P = .018). None of the patients experienced severe adverse events. CONCLUSION: Both procedures are equally effective and safe in lowering mdIOP, peak IOP and IOP fluctuations in patients with POAG, one year after surgery. CLINICAL TRIAL REGISTRATION: NCT02959242.

Estimating pulsatile ocular blood volume from intraocular pressure, ocular pulse amplitude, and axial length.

The purpose of this study was to develop a method of estimating pulsatile ocular blood volume (POBV) from measurements taken during an ophthalmic exam, including axial length and using a tonometer capable of measuring intraocular pressure (IOP) and ocular pulse amplitude (OPA). Unpublished OPA data from a previous invasive study was used in the derivation, along with central corneal thickness (CCT) and axial length (AL), as well as IOP from the PASCAL dynamic contour tonometer (DCT) and intracameral (ICM) measurements of IOP for 60 cataract patients. Intracameral mean pressure was set to 15, 20, and 35 mmHg (randomized sequence) in the supine position, using a fluid-filled manometer. IOP and OPA measurements were acquired at each manometric setpoint (DCT and ICM simultaneously). In the current study, ocular rigidity (OR) was estimated using a published significant relationship of OR to the natural log of AL in which OR was invasively measured through fluid injection. Friedenwald's original pressure volume relationship was then used to derive the estimated POBV, delivered to the choroid with each heartbeat as a function of OR, systolic IOP (IOPsys), diastolic IOP (IOPdia), and OPA, according to the derived equation POBV = log (IOPsys/IOPdia) / OR. Linear regression analyses were performed comparing OPA to OR and calculated POBV at each of the three manometric setpoints. POBV was also compared to OPA/IOPdia with all data points combined. Significance threshold was p < 0.05. OR estimated from AL showed a significant positive relationship to OPA for both DCT (p < 0.011) and ICM (p < 0.006) at all three manometric pressure setpoints, with a greater slope for lower IOP. Calculated POBV also showed a significant positive relationship to OPA (p < 0.001) at all three setpoints with greater slope at lower IOP, and a significant negative relationship with IOPdia. In the combined analysis, POBV showed a significant positive relationship to OPA/ IOPdia (p < 0.001) in both ICM and DCT measurements with R2 = 0.9685, and R2 = 0.9589, respectively. POBV provides a straight-forward, clinically applicable method to estimate ocular blood supply noninvasively. Higher IOP in combination with lower OPA results in the lowest values of POBV. The simplified ratio, OPA/ IOPdia, may also provide a useful clinical tool for evaluating changes in ocular blood supply in diseases with a vascular component, such as diabetic retinopathy and normal tension glaucoma. Future studies are warranted.

Evaluation of Biomechanical Changes After Accelerated Cross-Linking in Progressive Keratoconus: A Prospective Follow-Up Study.

PURPOSE: The aim of this study was to analyze the biomechanical effect of accelerated corneal cross-linking (9*10) in progressive keratoconus (KC) in comparison to untreated fellow eyes using Scheimpflug-based tonometry (Corvis ST, CVS). METHODS: Forty-three eyes of 43 patients with KC showed progressive KC and were treated using accelerated corneal cross-linking. Twenty-five untreated fellow eyes were used as the control group. All eyes were examined biomechanically (CVS) and tomographically (Pentacam) at baseline, after 1-month, 6-month, and 12-month follow-up. Statistical analysis was performed using a linear mixed model. A logistic regression was performed to attribute the effects of changes in each parameter to treatment status (treated or untreated). RESULTS: Maximum keratometry values decreased statistically significantly at 12 months by -1.1 D (95 confidence interval: -2.0 to -0.1, P = 0.025) compared with baseline. Thinnest corneal thickness decreased significantly after 1 month ( P < 0.001) and recovered to baseline after 12 months ( P = 0.752). In the corneal cross-linking (CXL) group, biomechanical changes were observed by an increased bIOP, a shorter A2 time, and a lower integrated radius after 1 month (all P < 0.05). No biomechanical and tomographical changes were observed in the control group (all P > 0.05). Logistic regression pointed out that treated eyes can be separated from untreated eyes by differences in bIOP, corneal thickness, A1 velocity, integrated radius, and Kc mean at 1, 6, and 12 months. CONCLUSIONS: The alterations in biomechanical parameters indicated a corneal stiffening effect after CXL treatment, which was mostly detectable 1 month after treatment, although corneal thickness was reduced. The logistic regression model showed an adequate separation between CXL-treated and untreated eyes.

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.

Evaluation of corneal biomechanical properties using the ocular response analyzer and the dynamic Scheimpflug-Analyzer Corvis ST in high pressure and normal pressure open-angle glaucoma patients.

PURPOSE: To characterize differences in corneal biomechanics in high (HPG) and normal pressure (NPG) primary open-angle glaucoma, and its association to disease severity. METHODS: Corneal biomechanical properties were measured using the Ocular Response Analyzer (ORA) and the dynamic Scheimpflug-Analyzer Corvis ST (CST). Disease severity was functionally assessed by automated perimetry (Humphrey field analyzer) and structurally with the Heidelberg Retina Tomograph. To avoid a possible falsification by intraocular pressure, central corneal thickness and age, which strongly influence ORA and CST measurements, group matching was performed. Linear mixed models and generalized estimating equations were used to consider inter-eye correlation. RESULTS: Following group matching, 60 eyes of 38 HPG and 103 eyes of 60 NPG patients were included. ORA measurement revealed a higher CRF in HPG than in NPG (P < 0.001). Additionally, the CST parameter integrated radius (P < 0.001) was significantly different between HPG and NPG. The parameter SSI (P < 0.001) representing corneal stiffness was higher in HPG than in NPG. Furthermore, regression analysis revealed associations between biomechanical parameters and indicators of disease severity. In HPG, SSI correlated to RNFL thickness. In NPG, dependencies between biomechanical readings and rim area, MD, and PSD were shown. CONCLUSION: Significant differences in corneal biomechanical properties were detectable between HPG and NPG patients which might indicate different pathophysiological mechanisms underlying in both entities. Moreover, biomechanical parameters correlated to functional and structural indices of diseases severity. A reduced corneal deformation measured by dynamic methods was associated to advanced glaucomatous damage.

Repeatability of corneal deformation response parameters by dynamic ultra-high-speed Scheimpflug imaging before and after corneal crosslinking.

PURPOSE: To evaluate the repeatability of deformation corneal response (DCR) parameters before and after corneal crosslinking (CXL) compared with their untreated fellow eyes (uFEs). SETTING: University Hospital Carl Gustav Carus, Dresden, Germany; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. DESIGN: Multicenter, interventional reliability analysis. METHODS: 53 eyes of 53 patients with keratoconus who received CXL treatment after the disease progression (CXL group) were included. Patients were measured 3 times using a dynamic Scheimpflug analyzer to determine repeatability before and 1 month after CXL treatment. The uFEs were measured in the same way (uFE group). Reliability of DCR parameters was assessed by a coefficient of repeatability, coefficient of variation, and intraclass correlation coefficient (ICC). RESULTS: The repeatability of DCR parameters did not change after CXL compared with the preoperative values for all investigated DCR parameters ( P > .05). In the uFE group, no statistically significant shift was observed regarding the repeatability ( P > .05). An ICC greater than 0.75 was achieved in both groups for almost all parameters. Concerning the biomechanical stiffening induced by CXL, integrated inverse radius and stress-strain index were found to be statistically significantly decreased and increased ( P < .001), respectively, both indicating stiffening. No changes were observed for the uFE group. CONCLUSIONS: The study demonstrated highly repeatable measurements of the dynamic Scheimpflug analyzer before and after CXL. The improvement of certain DCR parameters after CXL confirmed the capability of the device to detect the stiffening effect.

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.

Effectiveness and safety of VISULAS® green selective laser trabeculoplasty: a prospective, interventional multicenter clinical investigation.

PURPOSE: To evaluate the effectiveness and safety of Selective Laser Trabeculoplasty (SLT) with the SLT mode of the VISULAS® green laser in patients with primary open-angle glaucoma (POAG). METHODS: This prospective, interventional multicenter clinical investigation included patients with POAG who either needed a treatment escalation because the individual intraocular pressure (IOP) target was not met or treatment initiation and had an IOP ≥ 17 mmHg at baseline in the study eye. The study was conducted in five research centers across Germany. Approximately 100 laser applications were delivered to 360° of the trabecular meshwork. Glaucoma medications were not modified during the 3-month follow-up to allow evaluation of the sole effect of VISULAS® green with SLT. Efficacy outcomes were postoperatively absolute and relative IOP changes at 1 and 3 months. Safety outcomes analyzed the rate of intra- and postoperative adverse events. RESULTS: Thirty-four eyes of 34 POAG patients were included. The overall mean number of preoperative glaucoma medications was 2.2 ± 1.4 in 29 treated eyes, 5 eyes were treatment naïve. Mean baseline IOP (mmHg) was 21.0 ± 2.69 and was reduced by - 3.53 ± 3.34 [95% CI - 4.61; - 2.45] and - 3.59 ± 3.41 [95% CI - 4.64; - 2.53] at the 1- and 3-month follow-up, respectively (p < 0.0001), with 48.5% of cases achieving a ≥ 20% IOP reduction at 3 months [95% CI = 30.8%; 66.5%]. The mean relative IOP reduction was - 16.4% and - 16.3% at 1 and 3 months, respectively (p < 0.0001). Potentially device- or procedure-related adverse events were mild to moderate and included 3 postoperative IOP-spikes and 6 reports regarding eye pain and discomfort. All were resolved without sequelae. CONCLUSIONS: SLT performed with the VISULAS® green laser achieved clinically significant additional IOP reductions in medically treated as well as in treatment naïve eyes with POAG and there were no relevant safety issues. The results are comparable to other reported SLT studies.

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.].

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.

Two-Year Follow-up of MicroPulse Transscleral Laser Therapy in Patients with Primary Open-Angle Glaucoma. / 2-Jahres-Ergebnisse nach transskleraler MicroPulse-Lasertherapie bei Patienten mit primärem Offenwinkelglaukom.

PURPOSE: To determine the long-term efficacy and safety of MicroPulse transscleral laser therapy (TLT) over a 24-month period in patients with primary open angle glaucoma. METHODS: This prospective interventional case series evaluated data from 44 medically treated eyes of primary open angle glaucoma (POAG) patients who received MicroPulse TLT to achieve further reduction in IOP. The reduction in 24-hr mean diurnal intraocular pressure (IOP), diurnal IOP fluctuations, and peak IOP were monitored after 3, 12, and 24 months. Postoperative complications, failure rates, and factors influencing IOP reduction were also evaluated. RESULTS: IOP decreased from 16.1 ± 3.4 mmHg preoperatively to 13.0 ± 2.9 mmHg (n = 31; p < 0.001), 12.3 ± 3.0 mmHg (n = 27; p < 0.001), and 13.1 ± 2.6 mmHg (n = 23; p < 0.001) at the 3-month, 12-month and 24-month follow-ups. At 24 months, 23 eyes (52%) had a sufficient IOP reduction to reach the individual target pressure. No severe complications were observed. No parameters could be identified that correlated with successful IOP reduction after treatment. The highest failure rate was observed during the first 3 months and remained stable thereafter. CONCLUSION: For about 50% of POAG eyes receiving the maximum tolerated treatment, MicroPulse TLT proved an effective method of further lowering IOP so as to reach the individual target pressure.

Statistical Evaluation of Correlated Measurement Data in Longitudinal Setting Based on Bilateral Corneal Cross-Linking.

PURPOSE: In ophthalmology, data from both eyes of a person are frequently included in the statistical evaluation. This violates the requirement of data independence for classical statistical tests (e.g. t-Test or analysis of variance (ANOVA)) because it is correlated data. Linear mixed models (LMM) were used as a possibility to include the data of both eyes in the statistical evaluation. METHODS: The LMM is available for a variety of statistical software such as SPSS or R. The application was applied to a retrospective longitudinal analysis of an accelerated corneal cross-linking (ACXL (9*10)) treatment in progressive keratoconus (KC) with a follow-up period of 36 months. Forty eyes of 20 patients were included, whereas sequential bilateral CXL treatment was performed within 12 months. LMM and ANOVA for repeated measurements were used for statistical evaluation of topographical and tomographical data measured by Pentacam (Oculus, Wetzlar, Germany). RESULTS: Both eyes were classified into a worse and better eye concerning corneal topography. Visual acuity, keratometric values and minimal corneal thickness were statistically significant between them at baseline (p < 0.05). A significant correlation between worse and better eye was shown (p < 0.05). Therefore, analyzing the data at each follow-up visit using ANOVA partially led to an overestimation of the statistical effect that could be avoided by using LMM. After 36 months, ACXL has significantly improved BCVA and flattened the cornea. CONCLUSION: The evaluation of data of both eyes without considering their correlation using classical statistical tests leads to an overestimation of the statistical effect, which can be avoided by using the LMM.

Corneal Biomechanics in Glaucoma. / Biomechanische Parameter der Hornhaut als Biomarker beim primären Offenwinkelglaukom und Normaldruckglaukom.

Now that is possible to measure the biomechanical parameters of the cornea in vivo, scientific and clinical interest has increased in changes in these parameters in glaucoma. These parameters may act as biomarkers for early diagnosis, but also serve to emphasize the increased vulnerability to intraocular pressure, reduced blood flow or changing ocular perfusion pressure. Measuring and interpreting these parameters may help in achieving better and individually tailored glaucoma management.