Safety of high-intensity corneal collagen crosslinking.

PURPOSE: To evaluate the safety of a new high-intensity corneal collagen crosslinking (CXL) treatment protocol for keratoconus. SETTING: Vardinoyiannion Eye Institute of Crete, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece. DESIGN: Prospective interventional case series. METHODS: Patients with progressive keratoconus had CXL using a new treatment protocol with 9 mW/cm(2) irradiance for duration of 10 minutes. The rate of reepithelialization, endothelial cell density (ECD), corrected distance visual acuity (CDVA), and steep and flat keratometry (K) values were evaluated preoperatively and 3 months postoperatively. RESULTS: Nine patients (10 eyes) were enrolled. No intraoperative or early postoperative complications were observed in any patient. The ECD did not change significantly 3 months postoperatively (P=.169). The CDVA improved from 0.19 logMAR ± 0.20 (SD) preoperatively to 0.10 ± 0.16 logMAR 3 months postoperatively; however, the improvement did not attain significance (P=.141). No eye lost lines of CDVA. The mean steep K readings decreased significantly from 48.04 ± 2.57 diopters (D) preoperatively to 46.51 ± 2.81 D 3 months postoperatively (P=.047); the mean flat K readings did not change significantly postoperatively (P=.285). CONCLUSIONS: Corneal collagen crosslinking at 9 mW/cm(2) irradiance for 10 minutes did not cause significant changes in ECD or intraoperative or early postoperative complications. None patient lost a line of CDVA 3 months after the procedure. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Correlation of the corneal collagen cross-linking demarcation line using confocal microscopy and anterior segment optical coherence tomography in keratoconic patients.

PURPOSE: To evaluate and compare the depth of the corneal stromal demarcation line after corneal collagen cross-linking (CXL) using 2 different methods: confocal microscopy and anterior segment optical coherence tomography (AS OCT). DESIGN: Prospective, comparative, interventional case series. METHODS: Seventeen patients (18 eyes) with progressive keratoconus were enrolled. All patients underwent uneventful CXL treatment according to the Dresden protocol. One month after surgery, corneal stromal demarcation line depth was measured in all patients by 2 independent observers using confocal microscopy and AS OCT. RESULTS: Mean corneal stromal demarcation line depth measured using confocal microscopy by the first observer was 306.22 ± 51.54 µm (range, 245 to 417 µm) and that measured by the second observer was 303.5 ± 46.98 µm (range, 240 to 390 µm). The same measurements using AS OCT were 300.67 ± 41.56 µm (range, 240 to 385 µm) and 295.72 ± 41.01 µm (range, 228 to 380 µm) for the first and second observer, respectively. Pairwise comparisons did not reveal any statistically significant difference between confocal microscopy and AS OCT measurements for both observers (P = .3219 for the first observer and P = .1731 for the second observer). CONCLUSIONS: Both confocal microscopy and AS OCT have similar results in evaluating the depth of the corneal stromal demarcation line after CXL.

Contralateral-eye study of surface refractive treatments: clinical and confocal microscopy evaluation.

PURPOSE: To compare the visual and refractive outcomes and the corneal structural changes in myopic patients after surface refractive treatments (ie, photorefractive keratectomy [PRK] with adjuvant mitomycin-C [MMC] and epithelial laser in situ keratomileusis [epi-LASIK]). SETTING: University of Crete, Heraklion, Crete, Greece. DESIGN: Prospective comparative case series. METHODS: One eye of consecutive myopic patients was randomly assigned to PRK-MMC, and the fellow eye was treated with epi-LASIK. Visual and refractive outcomes and corneal confocal microscopy findings were evaluated. All patients were examined preoperatively and 1, 3, 6, 12, and 24 months postoperatively. RESULTS: Twenty-six eyes (13 patients) were included. The mean follow-up was 2.47 years ± 0.35 (SD) (range 1.64 to 2.93 years). In the PRK-MMC group, the mean preoperative spherical equivalent refraction was -3.84 ± 1.59 diopters (D) (range -1.5 to -8.7 D) and -0.21 ± 0.44 D (range -0.5 to 1.0 D) at the last follow-up and in the epi-LASIK group, -3.91 ± 1.48 D (range -1.5 to -8.5 D) and -0.18 ± 0.36 (range +0.5 to -0.5 D), respectively. Qualitative analysis of the subepithelial nerve plexus, haze development, and keratocyte distribution were similar in the 2 groups. There was no statistically significant difference in endothelial cell density between the groups throughout the follow-up (P>.05). CONCLUSION: Epithelial LASIK and PRK-MMC gave similar visual, refractive, and corneal structural outcomes in patients with myopia for up to 2 years postoperatively. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Effect of corneal collagen cross-linking on corneal innervation, corneal sensitivity, and tear function of patients with keratoconus.

PURPOSE: To evaluate the effect of corneal collagen cross-linking (CXL) on corneal innervation, corneal sensitivity, and tear function in patients with keratoconus. DESIGN: Prospective, interventional case series. PARTICIPANTS: Twenty-four patients with bilateral keratoconus (30 eyes) who presented to the Institute of Vision and Optics, University of Crete, from May 2008 to October 2008. METHODS: Patients underwent CXL. Confocal microscopic analysis of corneal sub-basal nerve plexus (total nerve length per image), corneal sensitivity (assessed with the Cochet-Bonnet esthesiometer), basic tear secretion (assessed with Schirmer's I test with anesthesia), and tear film stability (evaluated by means of tear film break-up time [TFBUT]) were assessed preoperatively and at 1, 3, 6, 9, 12, 18, and 24 months postoperatively. MAIN OUTCOME MEASURES: Comparisons between preoperative and each postoperative value of total nerve length per image, corneal sensitivity, Schirmer's I test results, and TFBUT. RESULTS: Total nerve length per image and corneal sensitivity were significantly decreased until postoperative month 6 (for both parameters: P<0.05 paired-samples t test at 1, 3, and 6 months postoperatively). Total nerve length per image tended to increase up to 2 years postoperatively, when it reached the preoperative level, but differences with the preoperative values after the sixth post-CXL month were insignificant. The results of Schirmer's I test and TFBUT had no statistically significant difference at any time point. CONCLUSIONS: A transient decrease in corneal innervation and corneal sensitivity can be observed up to 6 months after CXL. No significant effect of CXL could be detected on basic tear secretion and tear film stability in our group of patients. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Prospective study of foveal thickness alterations after cataract surgery assessed by optical coherence tomography.

BACKGROUND/AIMS: To evaluate the alterations of mean foveal thickness (MFT) and visual acuity (VA) outcomes after uncomplicated cataract surgery in different groups of patients. METHODS: This study included eyes of consecutive patients who underwent cataract surgery between November 2007 and June 2009. The patients included in the study were divided into 4 groups, as follows: history-free patients, patients with diabetes mellitus without macular involvement at baseline, patients with glaucoma, and patients with epiretinal membrane (ERM). Preoperatively and at 1, 3 and 6 months postoperatively, patients were evaluated for MFT by optical coherence tomography at the central 1-mm macular zone and for logarithm of the minimum angle of resolution best spectacle-corrected VA (BSCVA). RESULTS: A total of 202 eyes were included in the study. MFT values demonstrated a statistically significant increase (p < 0.01) after cataract surgery in all groups at the first and third postoperative month. The history-free (p = 0.09) and glaucoma (p = 0.19) groups did not demonstrate a statistically significant difference in MFT values between the preoperative and 6-month measurements. MFT values 6 months after cataract surgery in the diabetes and ERM groups remained significantly higher (p < 0.01). Despite these findings, VA increased significantly (p < 0.01) in all groups at all postoperative follow-ups. CONCLUSIONS: MFT values increased significantly in all groups at the first and third months after cataract surgery. At 6 months, MFT values returned to preoperative levels in the history-free and glaucoma patients, while they remained significantly higher in the diabetic and ERM patients. Despite these macular alterations, BSCVA improved significantly after cataract surgery in all groups at all postoperative follow-ups.

Detection of macular function changes in early (AREDS 2) and intermediate (AREDS 3) age-related macular degeneration.

BACKGROUND/AIM: To evaluate if retinal sensitivity values obtained with a dedicated (screening) device can be used to functionally identify early and intermediate age-related macular degeneration (ARMD). METHODS: A fully automatic fundus perimeter combined with an image-stabilized scanning laser ophthalmoscope was used in 200 ARMD patients (319 eyes) in 5 study sites. The age-matched control group consisted of 200 normals. Sensitivity point values (S values), mean retinal sensitivity, number of points below 24 dB (K value, cutoff for normal values) and fixation stability were recorded. RESULTS: Of 319 eyes, 164 were classified as early (AREDS 2) and 155 as intermediate (AREDS 3) ARMD. Mean retinal sensitivity was significantly reduced in ARMD patients versus normals (p < 0.001). K values were different between normals and ARMD patients (p < 0.001). Fixation stability did not differ between early and intermediate ARMD patients. CONCLUSIONS: Macular sensitivity is reduced in patients with early and intermediate ARMD when compared to age-matched normals. These changes may be detected with a screening device.

Evaluation of image quality metrics for the prediction of subjective best focus.

PURPOSE: Seven existing and three new image quality metrics were evaluated in terms of their effectiveness in predicting subjective cycloplegic refraction. METHODS: Monochromatic wavefront aberrations (WA) were measured in 70 eyes using a Shack-Hartmann based device (Complete Ophthalmic Analysis System; Wavefront Sciences). Subjective cycloplegic spherocylindrical correction was obtained using a standard manifest refraction procedure. The dioptric amount required to optimize each metric was calculated and compared with the subjective refraction result. Metrics included monochromatic and polychromatic variants, as well as variants taking into consideration the Stiles and Crawford effect (SCE). WA measurements were performed using infrared light and converted to visible before all calculations. RESULTS: The mean difference between subjective cycloplegic and WA-derived spherical refraction ranged from 0.17 to 0.36 diopters (D), while paraxial curvature resulted in a difference of 0.68 D. Monochromatic metrics exhibited smaller mean differences between subjective cycloplegic and objective refraction. Consideration of the SCE reduced the standard deviation (SD) of the difference between subjective and objective refraction. CONCLUSIONS: All metrics exhibited similar performance in terms of accuracy and precision. We hypothesize that errors pertaining to the conversion between infrared and visible wavelengths rather than calculation method may be the limiting factor in determining objective best focus from near infrared WA measurements.

Mitomycin C aqueous humor concentration after photorefractive keratectomy: an experimental study.

PURPOSE: To evaluate mitomycin C (MMC) aqueous humor concentration after photorefractive keratectomy (PRK). METHODS: In this experimental study, twenty-four eyes of 12 male pigmented rabbits were divided into 4 groups and studied at the Institute of Vision and Optics, Department of Medicine, University of Crete, Greece. Eyes in groups 1 and 2 underwent PRK to correct -5 diopters (D) in a 6-mm optical zone, while sponges soaked with 0.02% MMC were applied on the exposed corneal stroma for 60 and 120 seconds, respectively. Similarly, eyes in groups 3 and 4 underwent PRK to correct -10 D in a 6-mm optical zone, while sponges soaked with 0.02% MMC were applied on the exposed corneal stroma for 60 and 120 seconds, respectively. Aqueous humor was extracted from all rabbit eyes 10 minutes after MMC application and high-performance liquid chromatography was performed immediately to detect and quantify MMC levels. RESULTS: The mean aqueous humor concentration of MMC was 0.23+/-0.03 microg/mL, 0.39+/-0.05 microg/mL, 0.28+/-0.04 microg/mL, and 0.52+/-0.16 microg/mL in groups 1, 2, 3, and 4, respectively. The effect of application time and correction on aqueous humor MMC concentration was significant (p<0.0001 and p=0.019), while the exposure time had a greater impact on aqueous humor MMC concentration when compared with the attempted correction. CONCLUSIONS: Both exposure time of MMC on the corneal stroma and the attempted correction was correlated with MMC aqueous humor concentrations.

Higher-order aberrations produce orientation-specific notches in the defocused contrast sensitivity function.

Local minima or notches in the defocused contrast sensitivity function (CSF) have been linked to the aberrations of the eye. We use theoretical modeling of the effects of the aberrations to show these notches can be orientation-selective due to the effects of aberration terms such as coma and trefoil. Notches that changed with orientation were observed in the defocused CSF of four subjects. The measured CSFs were found to match well with theoretical predictions produced using the individual aberrations. Theoretical modeling highlighted orientation-specific differences in notches for both positive and negative blur. The results indicate that orientation is an important variable when testing for the functional effects of higher-order aberrations.

Confocal scanning laser tomography analysis of choroidal neovascularization and correlation with quantitative fluorescein angiography.

PURPOSE: To investigate the agreement between confocal scanning laser tomography and quantitative fluorescein angiography in the analysis of retinal-thickness changes in patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). MATERIALS AND METHODS: The edema index of a cSLT was measured in 18 eyes of 16 patients with CNV secondary to AMD that underwent photodynamic therapy (PDT) with Visudyne. Measurements were taken 1 hour before as well as 1 hour, 1 month, and 3 months after therapy. Moreover, a custom-written algorithm was used to analyze the integrated contrast amplitude (ICA) of fluorescein angiograms acquired before as well as 1 month and 3 months after PDT. Confocal scanning laser analysis of the edema index (EI) before and after PDT and correlation of the results with quantitative fluorescein angiography was performed. RESULTS: A statistical significant increase of the EI was observed 1 hour after PDT. Nonetheless, no other statistical significant change over time was observed either on the EI or the ICA. Significant correlation was observed between the EI and the ICA as well as their changes over time, yet better results were observed when non-parametric correlation was calculated. CONCLUSIONS: The axial intensity profile of the cSLT and the edema index provide important information with respect to the neovascular membranes and correlate well with quantitative fluorescein angiography. The application of cSLT and the EI provide an important tool that could complement the investigation of new treatments of neovascular membranes.

One-year follow-up of corneal confocal microscopy after corneal cross-linking in patients with post laser in situ keratosmileusis ectasia and keratoconus.

PURPOSE: To investigate corneal tissue alterations after corneal collagen cross-linking in patients with post laser in situ keratosmileusis (LASIK) keratectasia and keratoconus. DESIGN: Prospective comparative case series. METHODS: Five patients (5 eyes) with iatrogenic keratectasia after LASIK and 5 patients (5 eyes) with progressive keratoconus were included. All eyes underwent corneal cross-linking and were assessed by corneal in vivo confocal microscopy. Three normal/healthy and 3 post-LASIK without ectasia corneas were also examined as controls. RESULTS: All corneas revealed normal epithelial thickness before and after surgery. Images of both keratoconic and post-LASIK corneal ectasia eyes revealed similar morphologic alterations. The subepithelial nerve plexus was absent immediately after treatment; regeneration of nerves was evident after the third postoperative month. Keratocytes were absent from the anterior 300 mum of the stroma in the first 3 months while the posterior stromal density of keratocytes was increased. Corneal collagen fibers in the anterior stroma were distributed unevenly in a net-like formation. Full-thickness keratocyte repopulation in the anterior and mid-corneal stroma was detected 6 months after treatment. The corneal endothelium did not undergo any significant changes, since the cell density and hexagonality was not found altered during the follow-up period. CONCLUSIONS: Keratocyte nuclei apoptosis in the anterior and intermediate corneal stroma along with collagen alterations were observed during the first 3 postcorneal cross-linking months. Gradual keratocyte repopulation was demonstrated over the following months. Corneal alterations after corneal cross-linking were similar in both keratoconic and post-LASIK corneal ectasia eyes.

Alterations in endothelial cell density after photorefractive keratectomy with adjuvant mitomycin.

PURPOSE: To elucidate the distinct role of the intraoperative use of mitomycin C (MMC) on endothelial cell density after photorefractive keratectomy (PRK) in human eyes. DESIGN: Prospective, double-masked, randomized clinical trial. METHODS: One eye of 15 patients was treated with PRK with intraoperative use of topical 0.02% MMC (15 seconds), whereas the fellow eye was treated with Epipolis laser in situ keratomileusis (Epi-LASIK) in random order. Corneal confocal microscopy was performed in all eyes preoperatively and at one, three, six, and 12 months after the surgery. Moreover, three endothelial images were acquired in each of 15 preoperative-normal eyes to evaluate the repeatability of measuring endothelial cell density. Repeated measures analysis of variance was used to compare the temporal variations of endothelial cell density between the two techniques and the changes of endothelial cell density over time. RESULTS: The coefficient of repeatability of endothelial cell count was 148 cells/mm(2). Preoperative endothelial cell density was not significantly different between the two groups (P = .82). Moreover, the effect of the treatment on the temporal variation of endothelial cell density was insignificant (P = .83), whereas the differences between the preoperative and the postoperative endothelial cell densities reached statistical significance (P .05). CONCLUSIONS: The prophylactic intraoperative application of MMC (up to 15 seconds) after PRK does not seem to affect the endothelial cell density.

The effect of ocular aberrations on steady-state errors of accommodative response.

It is well accepted that the accommodation system is characterized by steady-state errors in focus. The purpose of this study was to correlate these errors with changes in ocular wavefront aberration and corresponding image quality when accommodating. A wavefront analyzing system, the Complete Ophthalmic Analysis System (COAS), was used in conjunction with a Badal optometer to allow continuous recording of the aberration structure of the eye for a range of accommodative demands (up to 8 D). Fifty consecutive recordings from seven subjects were taken. Monocular accommodative response was calculated as (i) the equivalent refraction minimizing wavefront error and (ii) the defocus needed to optimize the modulation transfer function at high spatial frequencies. Previously reported changes in ocular aberrations with accommodation (e.g., the shift of spherical aberration to negative values) were confirmed. Increased accommodation errors for near targets (lags) were evident for all subjects, although their magnitude showed a significant intersubject variability. It is concluded that the one-to-one stimulus/response slope in accommodation function should not always be considered as ideal, because higher order aberrations, especially changes of spherical aberration, may influence the actual accommodative demand. Fluctuations may serve to preserve image quality when errors of accommodation are moderate, by temporarily searching for the best focus.

Intraobserver repeatability of macula measurements by confocal scanning laser tomography.

PURPOSE: To assess the repeatability of macula measurements provided by the Heidelberg Retina Tomograph II (HRT II) in normal subjects, patients with diabetic macular edema (DME), and patients with choroidal neovascularization (CNV). DESIGN: Prospective, observational case. SETTING: Institutional-based study. PATIENT POPULATION: Ten normal eyes, 14 eyes with DME, and 14 eyes with CNV. OBSERVATIONAL PROCEDURE: Three scans within a single day. An additional three scans of each of the 10 normal eyes on a different day. MAIN OUTCOME MEASURES: Bland and Altman analysis for a 0.25 mm, 0.50 mm, and 0.75 mm radius circle. RESULTS: Variability and repeatability of the measurements were not related to circle size for either group of patients. Coefficient of variability values of the normal group and a 0.50-mm radius circle were 17%, 5.7%, and 6.1% for mean surface height, signal width, and edema index, respectively. The corresponding values were 15.6%, 10%, and 10% for the DME group, and 10.5%, 7.4%, and 8.5% for the CNV group. The 95% confidence interval of the difference between single observations across days of the normal group was +/-106 microm, +/-80 microm, and +/-0.10 for mean surface height, signal width, and edema index, respectively. When three scans were combined, the corresponding values were +/-61.5 microm, +/-46.7 microm, and +/-0.06. CONCLUSIONS: The repeatability and variability of measurements of normal subjects, patients with DME, and patients with CNV were determined. Differences between the three groups exist and are important for diagnosing a pathologic condition or measuring the effect of various treatments.

Variability of wavefront aberration measurements in small pupil sizes using a clinical Shack-Hartmann aberrometer.

BACKGROUND: Recently, instruments for the measurement of wavefront aberration in the living human eye have been widely available for clinical applications. Despite the extensive background experience on wavefront sensing for research purposes, the information derived from such instrumentation in a clinical setting should not be considered a priori precise. We report on the variability of such an instrument at two different pupil sizes. METHODS: A clinical aberrometer (COAS Wavefront Scienses, Ltd) based on the Shack-Hartmann principle was employed in this study. Fifty consecutive measurements were performed on each right eye of four subjects. We compared the variance of individual Zernike expansion coefficients as determined by the aberrometer with the variance of coefficients calculated using a mathematical method for scaling the expansion coefficients to reconstruct wavefront aberration for a reduced-size pupil. RESULTS: Wavefront aberration exhibits a marked variance of the order of 0.45 microns near the edge of the pupil whereas the central part appears to be measured more consistently. Dispersion of Zernike expansion coefficients was lower when calculated by the scaling method for a pupil diameter of 3 mm as compared to the one introduced when only the central 3 mm of the Shack - Hartmann image was evaluated. Signal-to-noise ratio was lower for higher order aberrations than for low order coefficients corresponding to the sphero-cylindrical error. For each subject a number of Zernike expansion coefficients was below noise level and should not be considered trustworthy. CONCLUSION: Wavefront aberration data used in clinical care should not be extracted from a single measurement, which represents only a static snapshot of a dynamically changing aberration pattern. This observation must be taken into account in order to prevent ambiguous conclusions in clinical practice and especially in refractive surgery.