Yakov Goldich

Clinical and corneal biomechanical changes after collagen cross-linking with riboflavin and UV irradiation in patients with progressive keratoconus: results after 2 years of follow-up.

Purpose: To assess the biomechanical and keratometric effects and the safety of treatment of progressive keratoconus with UV–riboflavin collagen cross-linking (CXL). Methods: This is a prospective clinical controlled study. Fourteen eyes of 14 patients with progressive keratoconus were treated with CXL after corneal deepithelization. Patients were assessed preoperatively, at week 1 and at months 1, 3, 6, 9, 12, and 24 after treatment. We measured uncorrected visual acuity (UCVA) and best spectacle–corrected visual acuity (BSCVA) (logarithm of the minimum angle of resolution), refraction, biomicroscopy and fundus examination, intraocular pressure, axial length, endothelial cell density, corneal topography, minimal corneal thickness, macular optical coherence tomography, and corneal biomechanics with the ocular response analyzer. Results: Comparing the preoperative results with 24-month postoperative results, we observed significant improvement in BCVA (0.21 ± 0.1 to 0.14 ± 0.1, P = 0.002) and stability in UCVA (0.62 ± 0.5 and 0.81 ± 0.49, P = 0.475). We observed a significant decrease in steepest-meridian keratometry (diopters) (53.9 ± 5.9 to 51.5 ± 5.4, P = 0.001) and in mean cylinder (diopters) (10.2 ± 4.1 to 8.1 ± 3.4, P = 0.001). Significant elongation of the eyes was observed, from 24.39 ± 1.7 mm to 24.71 ± 1.9 mm (P = 0.007). No significant change was observed in mean simulated keratometry, minimal corneal thickness, endothelial cell density, corneal hysteresis, and corneal resistance factor or foveal thickness. Conclusions: Two years after CXL, the observation of stable UCVA, improved BCVA, and reduced keratometry suggests stabilization in progression of keratoconus. Unchanged corneal thickness, endothelial cell density, and foveal thickness suggest the long-term safety of this procedure. The observed increase in axial length and stability in corneal biomechanical parameters measured with the ocular response analyzer require further study for verification and explanation.

Can we measure corneal biomechanical changes after collagen cross-linking in eyes with keratoconus?--a pilot study.

Purpose: To assess changes in biomechanical properties of human cornea after treatment of keratoconus with UV-A-riboflavin corneal collagen cross-linking (CXL). Design: Single-center, prospective, interventional study. Methods: Ten eyes of 10 patients aged 26.5 ± 5.7 (mean ± SD) years with progressive keratoconus were treated with UV-A-riboflavin CXL and assessed with the Ocular Response Analyzer (ORA) that measured corneal hysteresis (CH), corneal resistance factor (CRF), Goldmann-correlated intraocular pressure (IOPg), and corneal compensated intraocular pressure (IOPcc). Intraocular pressure was also measured by Goldmann applanation tonometry (GAT-IOP). Patients were assessed with ORA preoperatively, at week 1, months 1, 3, and 6 after treatment. Postoperative measurements at each visit were compared with preoperative values. Results: CH and CRF were transiently elevated after cross-linking treatment, with the difference not statistically significant (P > 0.3). IOPcc and IOPg were statistically significantly higher at 1 week and 1 month but not subsequently (P < 0.04). GAT-IOP was statistically significantly higher at 1 week and at 1 and 3 months (P < 0.01). Conclusions: There were no significant differences in corneal biomechanical properties, as measured with the ORA parameters CH and CRF, after CXL in keratoconus. IOPcc, IOPg, and GAT-IOP values were transiently elevated after CXL treatment in our study. Whether this reflects a measurement artifact resulting from corneal changes or true elevation of intraocular pressure is unclear.

Safety of corneal collagen cross-linking with UV-A and riboflavin in progressive keratoconus.

Purpose: To assess the possible damage to ocular tissues during treatment of keratoconus with UV-A-riboflavin corneal collagen cross-linking (CXL). Design: Single center, prospective, interventional study. Methods: Fourteen eyes of 14 patients aged 28.2 ± 5.9 (mean ± SD) years with progressive keratoconus were treated with UV-A-riboflavin CXL. Corneal endothelium was assessed with the endothelial specular microscope. Central retina was assessed with biomicroscopy fundus examination and with optical coherence tomography using macular thickness protocol. Patients were assessed preoperatively, at week 1, month 1, 3, 6, 9, and 12 after treatment. Results: Comparative preoperative and postoperative results showed stable endothelial cell density (2730 cells/mm2, 2793 cells/mm2, and 2640 cells/mm2, preoperatively, at month 6, and at month 12, respectively) and stable foveal thickness (203, 202, and 205 μm, preoperatively, at month 6, and at month 12, respectively). No morphological abnormalities were noted. Conclusions: UV-A-riboflavin CXL seems to be a safe procedure that does not cause damage to the corneal endothelium and central retina.

Accelerated (9-mW/cm2) corneal collagen crosslinking for keratoconus-A 1-year follow-up.

Purpose: The aim of this study was to assess the efficacy of accelerated crosslinking (irradiance of 9 mW/cm2; 10 minutes) in keratoconus-affected eyes through topographical, visual, and refractive end points. Methods: Mild-moderate keratoconus-affected eyes that underwent accelerated corneal collagen crosslinking (CXL) treatment and had 6 and 12 months of follow-up were reviewed retrospectively. Data regarding uncorrected distance visual acuity (UDVA), manifest refraction, corrected distance visual acuity (CDVA), and computerized corneal topography data before surgery and post-CXL treatment were extracted and analyzed. Results: Sixteen eyes of 14 patients were included in the study. The mean patient age was 24.9 ± 5.8 years (range: 17.1–38.3 years). No statistically significant changes were found in the mean CDVA, mean refractive cylinder, or mean manifest refraction spherical equivalent at either time point. There was a gain of 0.13 logarithm of the minimum angle of resolution lines in the mean UDVA (P = 0.012) at 12 months. All corneal parameters including Ksteep, Kflat, average K (Km), corneal astigmatism (Kcyl), and maximal curvature reading at the corneal apex (Kmax) were stable at 6 and 12 months in all patients. No complications were observed during the follow-up period. Conclusions: Accelerated corneal CXL is effective in stabilizing topographic parameters after 12 months of follow-up in mild-moderate keratoconus-affected corneas. Improvement in the UDVA and stabilization of all tested corneal parameters were noted after the treatment. However, a longer follow-up with larger cohorts is necessary to validate these findings.

Variations in corneal biomechanical parameters and central corneal thickness during the menstrual cycle

PURPOSE: To assess variations in the biomechanical properties and central corneal thickness (CCT) throughout the female menstrual cycle. SETTING: Department of Ophthalmology, Assaf Harofeh Medical Center, Zerifin Israel. DESIGN: Case series. METHODS: Young healthy women were prospectively recruited. Every participant was assessed at the beginning of the menstrual cycle, at ovulation, and at the end of the cycle. At every time point, corneal hysteresis (CH) and the corneal resistance factor (CRF) were measured with the Ocular Response Analyzer and the CCT was measured with an ultrasonic pachymeter. RESULTS: Twenty‐two eyes of 22 women (mean age 19.5 years ± 1.5 [SD]) were included. The CH was statistically significantly decreased at ovulation (10.1 mm Hg) compared with the beginning (11.1 mm Hg, P<.001) and the end (11.4 mm Hg, P<.001) of the cycle. The CRF was also significantly decreased at ovulation (9.8 mm Hg) compared with the beginning (10.6 mm Hg, P<.001) and the end (10.5 mm Hg, P<.001) of the cycle. The central cornea was thinnest at the beginning (535 μm) and statistically significantly thicker at ovulation (542 μm, P<.001) and at the end of the menstrual cycle (543 μm, P<.001). CONCLUSIONS: The CCT and biomechanical parameters significantly varied during the menstrual cycle. The CH and CRF were temporarily decreased at ovulation. The cornea was thinnest at the beginning and thicker at ovulation and at the end of the cycle. Such corneal changes may be important to consider during screening of candidates for laser refractive surgery. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Corneal collagen cross-linking for the treatment of progressive keratoconus: 3-year prospective outcome

OBJECTIVE To assess the long-term effects of treatment of progressive keratoconus with ultraviolet A-riboflavin collagen cross-linking (CXL). DESIGN This was a prospective clinical study. PARTICIPANTS Seventeen eyes of 17 patients with progressive keratoconus were treated with CXL. METHODS Patients were examined preoperatively, at week 1, months 1, 3, 6, 9, 12, 24, and 36 after treatment. We assessed uncorrected visual acuity (UCVA) and best spectacle-corrected visual acuity (BSCVA), refraction, biomicroscopy and fundus appearance, intraocular pressure, endothelial cell density (ECD), corneal topography, minimal corneal thickness (MCT), macular optical coherence tomography, axial length, and corneal biomechanics with the ocular response analyzer. RESULTS Comparing the 36-month time point results with pretreatment values, we found that UCVA and BSCVA were unchanged. Steepest meridian keratometry (D) and mean cylinder (D) did not show significant change compared with pretreatment values but showed a slight increase as compared with the 24-month time point (53.9 vs 51.7 vs 52.5, and 10.5 vs 8.1 vs 9.2 before, at 24 months, and at 36 months, respectively). Axial length (mm) showed an elongation trend throughout the follow-up period (24.56 vs 24.61 [p = 0.04] vs 24.71 [p = 0.05], before, at 24 months, and at 36 months, respectively). No significant change was observed in ECD, corneal hysteresis and corneal resistance factor, MCT, or foveal thickness. CONCLUSIONS Three-year results after CXL show stable visual acuity, stable corneal thickness, and stable corneal biomechanical parameters. The decreasing trend in keratometry values that was observed during the first 2 years after CXL was no longer evident. Longer follow-up is needed to decide whether it is a first sign of loss of achieved stability and resumption of keratoconus progression.

Repeatability of the Sirius imaging system and agreement with the Pentacam HR.

PURPOSE To assess measurement repeatability of corneal curvature, minimal corneal thickness, and anterior chamber depth obtained with the Sirius imaging system (Costruzioni Strumenti Oftalmici) and to assess its agreement with the Pentacam HR imaging system (Oculus Optikgeräte GmbH). METHODS Healthy individuals were prospectively recruited. To assess repeatability, eight consecutive measurements were performed in the right eye of healthy individuals with the Sirius. A single measurement was then performed consecutively with both systems. The anterior and posterior corneal radii (antR and posR, respectively), anterior chamber depth, and minimal corneal thickness were evaluated. Repeatability of Sirius was evaluated by calculating coefficients of variation (CoV). Agreement between Sirius and Pentacam was assessed by calculating 95% limits of agreement (LoA) and plotting Bland-Altman graphs. RESULTS Forty-five eyes from individuals (21 men, 24 women) aged 20 to 61 years were evaluated. The mean CoV was 0.37% and 1.32% for antR and posR at 3 mm, respectively, and 0.36% and 1.28% for antR and posR at 7 mm, respectively. For anterior chamber depth and minimal corneal thickness, the CoV was 0.56% and 1.69%, respectively. Calculated 95% LoA were -0.1 to 0.12 mm (mean difference: 0.018 mm) and -0.54 to 0.33 mm (mean difference: 0.1 mm) for antR and posR at 3 mm, respectively. For anterior chamber depth, 95% LoA was -0.23 to 0.09 mm (mean difference: 0.068 mm) and -9.61 to 33.44 μm (mean difference: 11.91 μm) for minimal corneal thickness. CONCLUSIONS The Sirius showed good to excellent repeatability for all measured parameters. Agreement analysis suggests that Sirius and Pentacam should not be used interchangeably.

Goldmann applanation tonometry versus ocular response analyzer for intraocular pressure measurements in keratoconic eyes.

Purpose: To compare intraocular pressure (IOP) measurements obtained with the Goldmann applanation tonometer (GAT) and the ocular response analyzer (ORA) in patients with keratoconus (KC) and analyze their dependence on ocular anatomic parameters. Methods: Patients with KC were recruited prospectively. IOP was measured using GAT and ORA. The ORA provided a Goldmann correlated IOP (IOPg) and a corneal correlated IOP (IOPcc). Assessment of refractive status, visual acuity, axial length, corneal topography, and pachymetry was done. Results: Fifty-nine eyes of 59 patients with KC (39 men, 20 women; mean age: 27.8 ± 6.8 years) were included. The differences in mean IOP values between GAT (10.9 ± 2.0 mm Hg) and IOPg (9.5 ± 2.8 mm Hg) and between GAT and IOPcc (13.3 ± 2.5 mm Hg) were statistically significant (all P < 0.001). Both pressure measurements provided by the ORA showed significant correlation with corneal curvature. No significant effect of corneal thickness on any of the pressures was observed. Conclusions: IOP measurements taken with GAT and ORA in keratoconic eyes were significantly different. Although IOPcc was significantly higher, IOPg was significantly lower than GAT IOP. Unlike GAT measurements, ORA readings seemed to be affected mainly by corneal curvature. As a result of described differences, we suggest these devices should not be used interchangeably but rather in a complementary fashion to assess IOP in keratoconic eyes.

The Effects of Sleep Deprivation on Oculomotor Responses

Purpose: Fatigue due to sleep deprivation is one of the main causes of accidents. An objective and efficient method for determining whether the person is tired could provide a valuable tool in accident prevention. In this study, we evaluated whether oculomotor responses related to pupillary light reflex and saccadic velocity can identify subjects with sleep deprivation and whether these objective values correlate with subjective feeling of sleepiness. Methods: Thirteen normal subjects (5 male, 8 female) participated in a 4-day study. During the first two days following a full night’s (8 hr in bed) sleep, they underwent baseline automated oculomotor testing using the FIT-2500-Fatigue-Analyzer. Following a third full night’s sleep, participants were then sleep-deprived for 28 hr. Ten measurements of automated oculomotor tests were performed during the sleep deprivation period. Visually-guided saccadic velocity (SV), initial pupil diameter (PD), pupillary constriction latency (CL), and amplitude of pupil constriction (CA) were assessed using the FIT-2500-Fatigue-Analyzer. The FIT-index, which expresses the deviation of the ocular parameters from the baseline measurements, was calculated. Correlation of oculomotor parameters with the subjective Stanford Sleepiness Scale (SSS) was performed. Results: We found that oculomotor measures showed a significant increase in CL (298.6 to 308.4 msec, P < 0.05) and calculated FIT index (3.4 to 16.8, P < 0.05) and a significant decrease in SV (64.8 to 59.6 deg/sec) during sleep deprivation. The SSS was found to significantly increase over the sleep deprivation period (2.05 to 5.05, P < 0.05) and was significantly correlated with the FIT-index (r > 0.66, P < 0.02). Conclusion: Evaluation of oculomotor responses, particularly CL and SV together with the FIT-index, might have practical applications for the assessment of an individual’s state of alertness or fatigue. Correlation of the FIT-index to the SSS provides evidence for the potential usefulness of oculomotor function measurements in the detection of subjective sleepiness.

Fellow eye comparison of corneal thickness and curvature in descemet membrane endothelial keratoplasty and descemet stripping automated endothelial keratoplasty.

Purpose: To compare posterior corneal curvature in the fellow eye of the same patients after Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK). Methods: This retrospective, case series comparative study included consecutive patients who underwent DSAEK in one eye and DMEK in the fellow eye. Each eye underwent corneal evaluation with Pentacam HR (Oculus, Wetzlar, Germany). Postoperative corneal curvature, corneal thickness, and visual acuity were assessed. Results: Twenty eyes of 10 patients (5 women and 5 men) aged 72.5 ± 13.5 (range, 42–87) years were included. No significant differences were observed between front flat Ks (43.01 ± 1.6 vs. 43.5 ± 0.9, P = 0.27) and front steep Ks (44.17 ± 1.5 vs. 44.52 ± 0.7, P = 0.39) in DMEK vs. DSAEK eyes, accordingly. Posterior curvature was statistically significantly flatter in DMEK compared with DSAEK eyes; back flat Ks (−6.30 ± 0.2 vs. −6.84 ± 0.6, P = 0.012), back steep Ks (−6.64 ± 0.1 vs. −7.2 ± 0.3, P = 0.03), and back Km (−6.45 ± 0.1 vs. −6.99 ± 0.4, P = 0.005), accordingly. Corneas in DMEK eyes were significantly thinner than in DSAEK eyes (541.0 ± 61 vs. 627.9 ± 70 &mgr;m, P = 0.007). Conclusions: Eyes that underwent DSAEK surgery have thicker corneas with steeper posterior corneal curvature than fellow eyes that underwent DMEK. This difference may explain the hyperopic shift commonly observed after DSAEK and should be considered when choosing an intraocular lens for cataract surgery.