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.

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.

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 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.

The Impact of Repetitive and Prolonged Eye Rubbing on Corneal Biomechanics.

PURPOSE: To evaluate the effect of simulated repetitive eye rubbing on the corneal biomechanics of porcine eyes using an ex vivo model system. METHODS: The average rubbing force that patients with keratoconus apply to their eyelids was previously determined. Fresh porcine eyes with eyelids were either exposed to 10,500 rub cycles from a custom-built eye rubbing machine that rubbed with a similar force to knuckle human eye rubbing (n = 33) or no rubbing at all (control; n = 37). A total of 10,500 rubs are equivalent to 1 year of rubbing six times daily, five movements per rub. The corneal biomechanical properties of these eyes were then tested by measuring the elastic modulus of 5-mm strips. RESULTS: The elastic modulus at the range of 1% and 5% of strain was 1.219 ± 0.284 and 1.218 ± 0.304 N/mm2 in the eye rubbing group and the no-rub control group, respectively. Corneal stiffness was similar in both groups (P = .984). CONCLUSIONS: The threshold to induce biomechanical changes (purely by eye rubbing) must be higher than 10,500 rubbing movements, suggesting that occasional eye rubbing may not affect corneal biomechanics in normal eyes, and likely only triggers keratoconus progression in predisposed corneas. Further in vivo studies assessing the impact eye rubbing has on inflammatory activity and the biomechanical properties of weakened corneas is warranted. [J Refract Surg. 2022;38(9):610-616.].

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.

Effect of upper eyelid blepharoplasty on corneal biomechanical, topographic and tomographic parameters 4 weeks after surgery.

PURPOSE: To investigate the effect of "skin-only" upper eyelid blepharoplasty on corneal biomechanics and central as well as peripheral topographic/tomographic parameters before and 4 weeks after surgery. METHODS: In a prospective study, the corneal hysteresis (CH) and corneal resistance factor (CRF) were evaluated before and after blepharoplasty. Corneal topographic (maximum simulated keratometry value, inferior-superior value, index of surface variance, index of vertical asymmetry, index of height asymmetry, index of height decentration) and tomographic parameters (corneal thickness, corneal astigmatism and mean 5-mm- and 7-mm-zone keratometry value) were measured by the Pentacam HR. Statistical analysis was performed using a linear mixed model considering correlated data of both eyes. RESULTS: This study included 42 eyes of 35 patients (mean age: 64.5 years, range 52-82 years). Four weeks after surgery CH and CRF increased (9.4 ± 2.3 to 10.2 ± 2.2 mmHg and 9.7 ± 2.1 to 10.5 ± 2.2 mmHg) but did not reach statistical significance (P = 0.100 and P = 0.072). A significant increase in central maximum simulated keratometry value (Kmax) from 45.0 ± 2.3 to 45.4 ± 2.2 diopters (D) was observed (P = 0.004). Inferior-superior value (I-S) and index of surface variance (ISV) showed significant changes from 0.32 ± 0.98 to 0.10 ± 0.98 D (P = 0.02) and from 19.98 ± 9.84 to 22.93 ± 11.23 (P = 0.009), respectively. These alterations did not affect the subjective spherical equivalent (-0.09 ± 4.71 to -0.04 ± 4.51 D; P = 0.437) and the best-corrected distance visual acuity of patients (0.11 ± 0.14 to 0.15 ± 0.15 logMAR; P = 0.142). Age, gender and corneal thickness were not correlated with pre and postoperative differences of CH, CRF, corneal compensated IOP, Kmax, corneal astigmatism or I-S. CONCLUSION: The trend of increasing CH and CRF values might indicate a rise of corneal damping capacity. Despite statistically significant differences of Kmax, I-S and ISV, all other tomographical and topographical parameters did not change 4 weeks after surgery. The corneal steepening with a mean change of 0.4 diopters and the decrease of I-S with a mean of 0.22 diopters do not seem to have a clinically relevant effect for blepharoplasty patients in daily practice.

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.].

Comparison of waveform-derived corneal stiffness and stress-strain extensometry-derived corneal stiffness using different cross-linking irradiances: an experimental study with air-puff applanation of ex vivo porcine eyes.

PURPOSE: To assess corneal stiffening of standard (S-CXL) and accelerated (A-CXL) cross-linking protocols by dynamic corneal response parameters and corneal bending stiffness (Kc[mean/linear]) derived from Corvis (CVS) Scheimpflug-based tonometry. These investigations were validated by corneal tensile stiffness (K[ts]), derived from stress-strain extensometry in ex vivo porcine eyes. METHODS: Seventy-two fresh-enucleated and de-epithelized porcine eyes were soaked in 0.1% riboflavin solution including 10% dextran for 10 min. The eyes were separated into four groups: controls (n = 18), S-CXL (intensity in mW/cm2*time in min; 3*30) (n = 18), A-CXL (9*10) (n = 18), and A-CXL (18*5) (n = 18), respectively. CXL was performed using CCL Vario. CVS measurements were performed on all eyes. Subsequently, corneal strips were extracted by a double-bladed scalpel and used for stress-strain measurements. K[ts] was calculated from a force-displacement curve. Mean corneal stiffness (Kc[mean]) and constant corneal stiffness (Kc[linear]) were calculated from raw CVS data. RESULTS: In CVS, biomechanical effects of cross-linking were shown to have a significantly decreased deflection amplitude as well as integrated radius, an increased IOP, and SP A1 (P < 0.05). Kc[mean]/Kc[linear] were significantly increased after CXL (P < 0.05). In the range from 2 to 6% strain, K[ts] was significantly higher in S-CXL (3*30) compared to A-CXL (9*10), A-CXL (18*5), and controls (P < 0.05). At 8% to 10% strain, all protocols induced a higher stiffness than controls (P < 0.05). CONCLUSION: Several CVS parameters and Kc[mean] as well as Kc[linear] verify corneal stiffening effect after CXL on porcine eyes. S-CXL seems to have a higher tendency of stiffening than A-CXL protocols have, which was demonstrated by Scheimpflug-based tonometry and stress-strain extensometry.

Is the Corneal Thickness Profile Altered in Diabetes Mellitus?

Purpose: To investigate the influence of chronic hyperglycemia in diabetes mellitus (DM) on spatial corneal thickness distribution and to analyze the influence of disease-specific factors. Methods: DM patients and healthy subjects were matched according to age and intraocular pressure (IOP). In diabetics, disease duration, DM type, and HbA1c value were assessed. Spatially resolved corneal thickness was measured by Pentacam HR. Thinnest corneal thickness (TCT) and peripheral pachymetry of concentric circles around TCT were determined. The Dynamic Scheimpflug Analyzer Corvis ST (CST) was used to measure the parameter pachy slope, which is an indicator of the change of corneal thickness from the apex to the periphery. Results: 59 DM patients and 57 healthy subjects were included. Age (P = .486) and IOP (P = .154) were not different between the groups. In DM, pachy slope was significantly higher than in healthy subjects (41.1 ± 9.87 vs. 35.18 ± 10.64 µm, P = .004). Also, the differences between TCT and the average of peripheral corneal thickness of concentric circles with a diameter of 2 mm (10.3 ± 1.7 vs. 9.3 ± 3.8 µm, P < .001) to 6 mm (82.2 ± 12.4 vs. 76.8 ± 12.6 µm, P = .011) were increased in patients. Changes in thickness profile were associated with HbA1c value and presence of diabetic retinopathy or maculopathy. Conclusion: In DM, a stronger peripheral corneal thickness increase was detectable. This change was shown using the novel CST parameter pachy slope and confirmed by Pentacam readings. These alterations might affect IOP and biomechanical measurements, and influence refractive procedures.

Corneal Densitometry in Diabetes Mellitus.

PURPOSE: Chronic hyperglycemia induces morphological and functional changes of the cornea. Corneal clarity is essential for visual function, and the measurement of corneal optical density (COD) might provide further information on diabetes mellitus (DM)-induced alterations. METHODS: COD of patients with DM and age-matched healthy subjects was measured using the Pentacam HR. Furthermore, central and thinnest corneal thickness and peripheral pachymetry of concentric circles around thinnest corneal thickness were investigated. In DM, information on disease duration, type, presence of diabetic retinopathy and maculopathy, and HbA1c value was recorded. RESULTS: In this study, 76 patients with DM and 65 healthy subjects were included. In patients with DM, the COD values of nearly all corneal layers and zones were reduced in comparison with healthy subjects (P < 0.05). Furthermore, the COD measurements were inversely correlated with the HbA1c value (total COD central layer: r = -0.424, P = 0.044) and stage of diabetic retinopathy (total COD: r = -0.271, P = 0.019). Diabetic patients with maculopathy revealed lower total COD values than patients without maculopathy (16.5 ± 5.6 vs. 21 ± 7.6, P = 0.031), and COD was lower in DM type 1 than in type 2 (16.1 ± 5.1 vs. 20.8 vs. 7.5, P = 0.035). In both groups, the COD values increased with age (patients with DM: r = 0.336, P = 0.003; healthy subjects: r = 0.679, P < 0.001) and decreased with peripheral corneal thickness increase. CONCLUSIONS: In patients with DM, COD was significantly reduced in comparison with healthy subjects. These changes were associated to disease-specific factors and measurements of peripheral corneal thickness profiles.

Factors Influencing Corneal Biomechanics in Diabetes Mellitus.

PURPOSE: Diabetes mellitus (DM) induces changes in corneal biomechanical properties. The influence of disease-specific factors was evaluated, and a novel DM index was created. METHODS: Eighty-one patients with DM and 75 healthy subjects were matched according to age, intraocular pressure, and central corneal thickness. Information on the disease was collected, and measurements with the Ocular Response Analyzer and the Corvis ST were taken. Results were compared between the groups, and the influence of disease-specific factors was evaluated. From dynamic corneal response parameters, a DM index was calculated. RESULTS: In DM, corneal hysteresis was higher than in healthy subjects (10.5 ± 1.9 vs. 9.7 ± 1.9 mm Hg, P = 0.008). In addition, dynamic corneal response parameters showed significant differences. Among others, highest concavity (HC) (17.212 ± 0.444 vs. 16.632 ± 0.794 ms, P < 0.001) and A2 time (21.85 ± 0.459 vs. 21.674 ± 0.447 ms, P = 0.017) as well as A1 (0.108 ± 0.008 vs. 0.104 ± 0.011 mm, P = 0.019) and A2 deflection amplitudes (0.127 ± 0.014 vs. 0.119 ± 0.014 mm, P < 0.001) were increased in DM. In DM type 1, HC deformation amplitude (1.14 ± 0.19 vs. 1.095 ± 0.114 mm, P = 0.035) was higher than in type 2. The time of deflection amplitude max correlated with the severity of retinopathy (R = 0.254, P= 0.023). In case of diabetic maculopathy, A1 velocity (0.155 ± 0.018 vs. 0.144 ± 0.019 ms, P = 0.043) and A2 time (22.052 ± 0.395 vs. 21.79 ± 0.46 ms, P = 0.04) were increased. Deformation amplitude max (R = 0.297, P = 0.024), HC time (R = 0.26, P = 0.049), HC deformation amplitude (R = 0.297, P = 0.024), and A2 deformation amplitude (R = 0.276, P = 0.036) were associated to disease duration. The DM index revealed a sensitivity of 0.773 and a specificity of 0.808 (area under the curve of receiver operating characteristic = 0.833). CONCLUSIONS: In DM, changes in corneal biomechanics were correlated with disease-specific factors. The DM index achieved reliable sensitivity and specificity values.

Intraocular pressure measurements in diabetes mellitus.

PURPOSE: To investigate the impact of diabetes mellitus-induced changes on intraocular pressure measurements using Goldmann applanation tonometry, Ocular Response Analyzer, and Corvis ST. METHODS: Measurements were done using Goldmann applanation tonometry, Ocular Response Analyzer, and Corvis ST in 69 diabetic patients. Biomechanical-corrected intraocular pressure values by Ocular Response Analyzer (IOPcc) and Corvis ST (bIOP) were used. In addition, biometry and tomography were performed and information on diabetes mellitus specific factors was collected. Results were compared to an age-matched group of 68 healthy subjects. RESULTS: In diabetes mellitus, Goldmann applanation tonometry intraocular pressure (P = 0.193) and central corneal thickness (P = 0.184) were slightly increased. Also, IOPcc (P = 0.075) and bIOP (P = 0.542) showed no significant group difference. In both groups, IOPcc was higher than Goldmann applanation tonometry intraocular pressure (P = 0.002, P < 0.001), while bIOP was nearly equal to Goldmann applanation tonometry intraocular pressure (P = 0.795, P = 0.323). Central corneal thickness showed a tendency to higher values in poorly controlled than in controlled diabetes mellitus (P = 0.059). Goldmann applanation tonometry intraocular pressure correlated to central corneal thickness, while IOPcc and bIOP were independent from central corneal thickness in both groups. All intraocular pressure values showed significant associations to corneal biomechanical parameters. Only in diabetes mellitus, bIOP was correlated to Pachy slope (P = 0.023). CONCLUSION: In diabetes mellitus, Goldmann applanation tonometry intraocular pressure was slightly, but not significantly, increased, which might be caused by a higher central corneal thickness and changes in corneal biomechanical properties. However, intraocular pressure values measured by Ocular Response Analyzer and Corvis ST were not significantly different between diabetes mellitus patients and healthy subjects. The bIOP showed a higher agreement with Goldmann applanation tonometry than IOPcc and was independent from central corneal thickness.

Intraocular Pressure Measurement Using Ocular Response Analyzer, Dynamic Contour Tonometer, and Scheimpflug Analyzer Corvis ST.

PURPOSE: To compare intraocular pressure (IOP) measurements with Goldmann applanation tonometry (GAT), ocular response analyzer (ORA), dynamic contour tonometer (DCT), and Corvis ST (CST) in healthy subjects. METHODS: In a prospective, observational study, IOP measurements with GAT (GAT-IOPc), ORA (IOPcc), DCT (DCT-IOP), and CST (bIOP) were performed and analyzed in 94 healthy subjects. RESULTS: Mean age of the participants was 45.6 ± 17.2 years (range 18 to 81 years). Mean GAT-IOPc was 12.9 ± 2.4 mmHg, mean DCT-IOP was 16.1 ± 2.6 mmHg, and mean IOPcc was 15.6 ± 3.3 mmHg. DCT-IOP and IOPcc were significantly higher than GAT-IOPc (P < 0.001). Mean bIOP was 13.5 ± 2.4 mmHg that was slightly higher but not significantly different from GAT-IOPc (P=0.146). Correlation analysis of IOP values and central corneal thickness (CCT) revealed a negative correlation between GAT-IOPc and CCT (r = -0.347; P=0.001). However, IOPcc, DCT-IOP, and bIOP showed no significant correlation to CCT. Only bIOP revealed a weak but significant age dependency (r = 0.321, P=0.002). CONCLUSION: All tonometry devices showed a good agreement of biomechanical corrected IOP values with GAT-IOPc. As no influence of CCT on IOPcc, DCT-IOP, and bIOP was detectable, the used correction algorithms appear to be appropriate in these tonometers in the clinical setting. The highest agreement was found between GAT-IOPc and bIOP. However, bIOP weakly correlated with participants' age. Further studies are needed to elucidate the role of bIOP for IOP measurement.

A new biomechanical glaucoma factor to discriminate normal eyes from normal pressure glaucoma eyes.

BACKGROUND: To test the ability of the newly calculated Dresden biomechanical glaucoma factor (DBGF) based on dynamic corneal response (DCR) deformation and corneal thickness parameters, to discriminate between healthy and normal pressure glaucoma (NPG) eyes. METHODS: Seventy healthy and 70 NPG patients of Caucasian origin were recruited for this multicentre cross-sectional pilot study, which included both eyes for analysis. Logistic regression analysis with generalized estimating equation (GEE) models to account for correlations between eyes and a threefold cross-validation were performed to determine the optimal combination of Corvis ST parameters in order to separate normal from NPG eyes. RESULTS: The DBGF was calculated using 5 Corvis ST parameters, which showed the best discrimination power: deformation amplitude ratio progression, highest concavity time, pachymetry slope, the biomechanically corrected intraocular pressure and pachymetry. In a threefold cross-validation, the receiver operating characteristic (ROC) curve confirmed an area under the curve (AUC) of 0.814 with a sensitivity of 76% and a specificity of 77% using a logit cut-off value of a DBGF = 0.5. CONCLUSION: The DBGF shows to be sensitive and specific to discriminate healthy from NPG eyes. Since diagnosis of NPG is often challenging, the DBGF may help with the differential diagnosis of NPG in daily clinical practice. Therefore, it might be considered as a new possible screening method for NPG.

Assessment of corneal biomechanical parameters in healthy and keratoconic eyes using dynamic bidirectional applanation device and dynamic Scheimpflug analyzer.

PURPOSE: To investigate corneal biomechanical parameters in healthy and keratoconic eyes using the Ocular Response Analyzer dynamic bidirectional applanation device (ORA) and the Corvis ST dynamic Scheimpflug analyzer (CST). SETTING: Department of Ophthalmology, Carl Gustav Carus University Hospital Dresden, Germany. DESIGN: Prospective, monocentric, case-control study. METHODS: Corneal biomechanical parameters were obtained in 60 eyes of 60 healthy participants (Group I) and 60 eyes of 60 keratoconus patients (Group II) with different grades of severity using the ORA and the CST. Participants were matched by age (Group I: 38.3 years ± 12.8 [SD], Group II: 37.3 ± 11.2 years) and intraocular pressure (Group I: 13.7 ± 1.7 mm Hg, Group II: 13.6 ± 1.5 mm Hg). RESULTS: For the ORA, the receiver operating characteristic curve analysis showed an area under the curve (AUC) of 0.950 for the keratoconus score, a sensitivity of 87% and a specificity of 93%. The AUC for the corneal resistant factor and corneal hysteresis was 0.930 and 0.868 with a sensitivity of 87% and a specificity of 87%, and sensitivity of 80% and a specificity of 80%, respectively. For the CST, the corneal biomechanical index showed the highest AUC (0.977) with a sensitivity of 97% and a specificity of 98%. The AUC of integrated radius (0.974; 90% sensitivity, 93% specificity) was followed by maximum inverse radius (0.962; 92% sensitivity, 93% specificity). Most parameters were able to discriminate healthy eyes from different keratoconus stages and early stages of keratoconus from moderate stages. CONCLUSION: Both devices allowed for good differentiation between healthy eyes and keratoconic eyes and between different severity grades of keratoconus. Several parameters of ORA and CST revealed high sensitivity and specificity values for keratoconus detection.

Comparison of Central Corneal Thickness Measurements Using Optical and Ultrasound Pachymetry in Glaucoma Patients and Elderly and Young Controls.

PRéCIS:: Optical and ultrasound pachymetry cannot be used interchangeably in young, healthy adults. In elderly, healthy and glaucoma patients the speed of ultrasound in the cornea increases because of changing corneal biomechanical characteristics in age and disease and the different devices could be used interchangeably. PURPOSE: The purpose of this study was to compare central corneal thickness (CCT) using optical and ultrasound pachymetry in patients with open-angle glaucoma and young as well as elderly, healthy controls. Further to investigate whether the devices could be used interchangeably. METHODS: In total, 69 eyes of 41 glaucoma patients, 51 eyes of 32 elderly and 50 eyes of 25 young controls were consecutively included in this cross-sectional observational study. Optical CCT measurements were obtained using the noncontact Specular Microscope CEM-530 (NCSM). Ultrasound pachymetry (USP) was measured using the Pachy Meter SP 3000. RESULTS: In young subjects (27.2±4.8 y), the mean CCT taken with NCSM and USP was 562.1±33.6 µm and 565.8±35.8 µm, respectively. This was significantly different (USP>NCSM, P=0.019). In elderly subjects (70.6±10.7 y) CCT measured with NCSM (562.5±27.8 µm) compared to USP (564.9±27.1 µm) was not statistically significantly different (P= 0.121). In glaucoma patients (65.0±11.1 y), USP measured thinner CCT values compared to NCSM, without significant differences between the devices (NCSM 525.3±32.3 µm; USP 522.9±33.15 µm; P=0.067). CCT was significantly thinner in comparison to both healthy groups (P< 0.001). CONCLUSIONS: In young subjects, ultrasound pachymetry measurements are higher than they are with optical pachymetry. This difference is no longer observed in elderly subjects and is even reversed in glaucoma patients. A higher speed of ultrasound in the cornea due to changing corneal biomechanical properties in the elderly and glaucoma patients could explain this. The devices could be used interchangeably in older and glaucoma patients, but not in young individuals.