Intraocular Pressure Reduction Effect of 0.005% Latanoprost Eye Drops in a Hyaluronic Acid-Chitosan Nanoparticle Drug Delivery System in Albino Rabbits.

Purpose: The purpose of this study was to evaluate the intraocular pressure (IOP) reduction efficiency of hyaluronic acid-chitosan-latanoprost link nanoparticle (HA-CS-latanoprost link NP) formulated eye drops. Methods: The IOP reduction study was performed in 24 normotensive albino rabbits. The test animals were randomized and grouped accordingly to treatment namely, HA-CS-latanoprost link NP, plain latanoprost, and the commercially available Xalatan eye drop, all were formulated with 0.005% latanoprost. The 9 days of the experiment were divided into baseline period (days 1-2), treatment period (days 3-6), and recovery period (days 7-9). A wireless noncontact tonometer was used to measure IOP at a time interval of 2 hours for 12 hours per day with 5 readings each. Results: The highest mean daily IOP reduction during the treatment period was 24% for plain latanoprost, 23% for Xalatan, and 29% for HA-CS-latanoprost link NP. The maximum reduction in IOP for plain latanoprost and Xalatan all occurred at the sixth hour with the peak effects of 4.85 mm Hg (37%) and 4.8 mm Hg (36%), respectively. Although HA-CS-latanoprost link NP had peak effects of 5.75 mm Hg (43%) at the sixth hour and 5.22 mm Hg (39%) at the eighth hour. Daily mean IOP measurements of each treatment group showed that HA-CS-latanoprost link NP has a greater IOP reduction effect compared with the other two treatments (P < 0.001). Conclusions: The results showed that the formulation of latanoprost with CS and HA is more effective in reducing the IOP than by drug alone. Translational Relevance: The results provide evidence from animal experiment that HA-CS-latanoprost link NP formulation could improve and sustain drug concentration in the anterior segment of the eye. The improved reduction in IOP with that HA-CS-latanoprost link NP formulation can serve as a basis that latanoprost eye drops can be formulated with decreased concentration of benzalkonium HCl, an irritant preservative and penetration enhancer.

Accuracy of Total Corneal Astigmatism Measurements With a Scheimpflug Imager and a Color Light-Emitting Diode Corneal Topographer.

PURPOSE: To determine the accuracy of total corneal astigmatism measurements with a Scheimpflug imager and a color light-emitting diode corneal topographer, and to compare the accuracy of total corneal astigmatism measurements with the accuracy of measurements that are based only on the anterior corneal surface. DESIGN: Prospective validity assessment. METHODS: This study was conducted at the Rotterdam Ophthalmic Institute, Rotterdam, Netherlands. The study population consisted of 91 eyes of 91 patients with monofocal, non-toric intraocular lenses (IOLs). Refractive astigmatism was measured with the ARK-530A autorefractor (Nidek, Gamagori, Japan). Anterior and total corneal astigmatism were measured with the Pentacam HR (Oculus, Wetzlar, Germany) and the Cassini (i-Optics, The Hague, Netherlands). Under the assumption that refractive astigmatism must equal total corneal astigmatism in these patients, accuracy of the corneal astigmatism measurements was defined as the vectorial difference with the refractive astigmatism, with lower vector differences denoting higher accuracy. RESULTS: The median refractive astigmatic magnitude was 0.84 diopter (D). The mean difference vector lengths were 0.61 D, 0.58 D, 0.49 D, and 0.45 D for Pentacam anterior, Cassini anterior, Pentacam total, and Cassini total corneal astigmatism, respectively. The mean difference vector length decreased by 0.12 and 0.13 D for Pentacam and Cassini, respectively, if the total instead of anterior corneal astigmatism was measured. These decreases were statistically significant (P < .001). CONCLUSIONS: With Pentacam as well as with Cassini, the accuracy of total corneal astigmatism measurements was higher than that of anterior corneal astigmatism measurements. Measuring total instead of anterior corneal astigmatism may therefore decrease the residual astigmatism in toric IOL implantation.

Value of posterior keratometry in the assessment of surgically induced astigmatic change in cataract surgery.

PURPOSE: To investigate the value of posterior keratometry in the assessment of surgically induced astigmatic change (AC) in cataract surgery, with particular emphasis on the influence of test-retest variability. METHODS: Seventy-seven eyes of 77 cataract patients scheduled for routine cataract surgery were enrolled. All patients received a 2.2-mm self-sealing scleral incision (n = 24), single-plane clear corneal incision (SPCCI; n = 29) or biplanar clear corneal incision (BPCCI; n = 24). Measurements of anterior and posterior corneal astigmatism were performed with a rotating Scheimpflug camera (Pentacam HR) preoperatively and postoperatively. Two repeated readings were taken preoperatively to assess the role of the test-retest effect. Astigmatic change (AC) was analysed according to the polar value method. RESULTS: On the anterior corneal surface, SPCCIs and BPCCIs caused a statistically significant mean flattening of the incisional meridian of 0.37 and 0.27 dioptres (D), respectively. Scleral incisions on average did not cause AC, although steepening, flattening or torque beyond the test-retest effect was observed in individual cases. On the posterior surface, mean power changes in the incisional meridian were below 0.1 D for all incisions, and these changes were of the same order of magnitude as the test-retest effect. CONCLUSION: Surgically induced AC of the posterior corneal surface after cataract surgery is of negligible clinical relevance. Moreover, it is of the same order of magnitude as the test-retest variability of the measurement device and therefore cannot (yet) be reliably assessed.

Long-term changes in intraocular lens position and corneal curvature after cataract surgery and their effect on refraction.

PURPOSE: To evaluate the role of intraocular lens (IOL) position shift and changes in corneal curvature on long-term refractive shift after cataract surgery. SETTING: Rotterdam Ophthalmic Institute, Rotterdam, the Netherlands. DESIGN: Prospective cohort study. METHODS: Patients who had routine cataract surgery with implantation of a hydrophobic acrylic 1-piece IOL (Acrysof SA60AT) in the capsular bag were enrolled. Measurements were performed preoperatively and 1 month, 3 months, and 1 year postoperatively. Refraction was measured with the ARK-530A autorefractor. The IOL position and corneal curvature were measured with the Lenstar LS-900 biometer. The refractive effect of changes in IOL position and corneal curvature was calculated with a Gaussian optics-based thin-lens formula and correlated with the measured refractive shift. RESULTS: The study group comprised 59 eyes of 59 patients. The median measured absolute refractive change was 0.25 diopter (D). The IOL position showed a statistically significant mean posterior shift of 0.033 mm ± 0.060 (SD) between 1 month and 1 year postoperatively (P < .01), of which the median calculated absolute refractive effect was 0.05 D. This did not correlate with the measured refractive shift (Pearson r = 0.10, P = .46). Natural fluctuations in corneal curvature caused a median calculated absolute refractive effect of 0.17 D, which correlated well with the measured refractive shift (Pearson r = .55, P < .001). CONCLUSIONS: Long-term changes in refraction after cataract surgery resulted from natural fluctuations in corneal curvature rather than from IOL position shift. These fluctuations limit the accuracy with which the refractive outcome can be planned. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Evaluation of keratometry with a novel Color-LED corneal topographer.

PURPOSE: To assess the performance of a novel keratometer based on reflections of colored light-emitting diodes (LEDs) and compare it with devices based on Placido rings, monochromatic LEDs, and Scheimpflug images. METHODS: Sixty-three eyes of 63 patients with virgin corneas underwent keratometry with color-LED corneal topography (Cassini; i-Optics, The Hague, The Netherlands) and with devices based on Placido ring reflections (Keratron; Optikon, Rome, Italy), monochromatic LED reflections (Lenstar; Haag-Streit, Koeniz, Switzerland), and Scheimpflug imaging (Pentacam; Oculus Optikgeräte, Wetzlar, Germany). Three repeated measurements were performed with each device. Comparability and repeatability of corneal power and cylinder measurements were assessed. The Bonferroni-corrected α-threshold for statistical significance was 0.016. RESULTS: Corneal power measurements with the Cassini topographer were not statistically significantly different from those with the Pentacam (P = .64). They were statistically significantly lower than those with the Keratron and Lenstar (P < .01), but the differences were of negligible clinical relevance. Cylinder measurements with the Cassini topographer were not statistically significantly different from those with any other device (P = .46). Repeatability of Cassini corneal power measurements was not statistically significantly different from that of the Keratron (P = .02), but was statistically significantly lower than that of the Lenstar and Pentacam (P < .001). Repeatability of Cassini cylinder measurements was statistically significantly higher than that of the Pentacam and Keratron (P < .001), but was not statistically significantly different from that of the Lenstar (P > .05). CONCLUSIONS: Corneal power and cylinder measurements with color-LED corneal topography yielded values that were comparable to those of other commonly used devices. Repeatability of corneal power measurements was lower compared to some devices, but repeatability of cylinder measurements was relatively high. This may be of particular interest when using toric intraocular lenses.

Phase-stabilized optical frequency domain imaging at 1-µm for the measurement of blood flow in the human choroid.

In optical frequency domain imaging (OFDI) the measurement of interference fringes is not exactly reproducible due to small instabilities in the swept-source laser, the interferometer and the data-acquisition hardware. The resulting variation in wavenumber sampling makes phase-resolved detection and the removal of fixed-pattern noise challenging in OFDI. In this paper this problem is solved by a new post-processing method in which interference fringes are resampled to the exact same wavenumber space using a simultaneously recorded calibration signal. This method is implemented in a high-speed (100 kHz) high-resolution (6.5 µm) OFDI system at 1-µm and is used for the removal of fixed-pattern noise artifacts and for phase-resolved blood flow measurements in the human choroid. The system performed close to the shot-noise limit (<1dB) with a sensitivity of 99.1 dB for a 1.7 mW sample arm power. Suppression of fixed-pattern noise artifacts is shown up to 39.0 dB which effectively removes all artifacts from the OFDI-images. The clinical potential of the system is shown by the detection of choroidal blood flow in a healthy volunteer and the detection of tissue reperfusion in a patient after a retinal pigment epithelium and choroid transplantation.

Wide-range calibration of corneal backscatter analysis by in vivo confocal microscopy.

PURPOSE: To report intra- and interinstrument calibration methods for corneal backscatter analysis by in vivo confocal microscopy. METHODS: Applicability of two reference standards was evaluated for corneal backscatter calibration. Repeated measurements of four concentrations of AMCO Clear (GFS Chemicals, Inc., Powell, OH) suspension and three transparencies (26%, 49%, and 65%) of polymethylmethacrylate (PMMA) slabs were performed to assess image intensity acquisition in a wide backscatter range. Intra- and intersession repeatability and lot-to-lot variation were determined for both standards. The effect of light intensity (LI) variation on image intensity acquisition was evaluated by examination of PMMA slabs with nonreference (60% and 80%) and reference (72%) LIs. Both reference standards were implemented in the protocol. Intrainstrument calibration was verified by measuring three normal corneas with 60%, 72%, and 80% LIs. Interinstrument calibration was tested by measuring PMMA slabs on a second, similar confocal microscope. RESULTS: AMCO Clear was used to express image intensity in absolute scatter units (SU), whereas the 49% transparent PMMA slab showed best repeatability, without image saturation, to adjust for LI variation. Intrainstrument calibration for LI variation reduced mean differences from -38.3% to 1.7% (60% LI) and from 33.9% to -0.6% (80% LI). The mean difference between similar microscopes decreased from 18.4% to 1.2%, after calibration of the second microscope. CONCLUSIONS: Large interinstrument differences necessitate calibration of corneal backscatter measurements. With AMCO Clear suspension and PMMA slabs, standardization was achieved in a wide backscatter range corresponding to normal and opaque corneas. These methods can easily be applied in ophthalmic practice.

Forward ray tracing for image projection prediction and surface reconstruction in the evaluation of corneal topography systems.

A forward ray tracing (FRT) model is presented to determine the exact image projection in a general corneal topography system. Consequently, the skew ray error in Placido-based topography is demonstrated. A quantitative analysis comparing FRT-based algorithms and Placido-based algorithms in reconstructing the front surface of the cornea shows that arc step algorithms are more sensitive to noise (imprecise). Furthermore, they are less accurate in determining corneal aberrations particularly the quadrafoil aberration. On the other hand, FRT-based algorithms are more accurate and more precise showing that point to point corneal topography is superior compared to its Placido-based counterpart.

Performance in specular reflection and slit-imaging corneal topography.

PURPOSE: Assessment of the relative performance in measuring corneal shape and corneal aberrations for two specular reflection topographers: Keratron Placido Ring Topographer, VU Topographer, and two slit-lamp imaging instruments: Orbscan II and Topcon SL-45 Scheimpflug. METHODS: Corneal height maps of the anterior corneal surface were obtained from a group of 34 subjects with all four instruments; posterior corneal surface height maps were only obtained with the two slit-lamp imaging instruments. Corneal surface shapes are calculated in terms of radius of curvature and asphericity fitting an aspheric model. Wave aberrations for the anterior corneal surface and the total cornea are determined up to and including sixth order Zernike convention by means of ray tracing. RESULTS: Clinical relevant differences were observed for radius of curvature of the anterior corneal surface, where the slit-imaging instruments measure higher values (mean difference = 0.05 mm, p < 0.05) and anterior corneal astigmatism for which the Orbscan II measures higher values than the VU Topographer [mean difference = 0.174 microm (0.134 Equivalent Diopters), p < 0.01]. Small significant differences were observed for asphericity and spherical aberration of the anterior corneal surface; however, these are not clinically relevant. Clinically relevant differences were also observed for posterior radius (difference = 0.135 mm p < 0.001), total corneal astigmatism (difference = 0.207 microm (0.159 Equivalent Diopters), p = 0.001), and central corneal thickness (CCT) (difference = -18.6 microm, p < 0.001). The differences found for total corneal coma and trefoil were not clinical relevant. Furthermore, the precision of the specular reflection topographers is superior to that of the slit-lamp instruments by at least a factor of two. CONCLUSIONS: For traditional spectacle and contact lens applications, the corneal topographers are interchangeable except for measuring anterior radius of curvature. However, for more modern techniques as customized corneal refractive surgery, the subtle differences (e.g., total corneal astigmatism and CCT) between the instruments are clinically relevant.

Pseudo forward ray-tracing: a new method for surface validation in cornea topography.

PURPOSE: A pseudo forward ray-tracing (PFRT) algorithm is developed to evaluate surface reconstruction in corneal topography. The method can be applied to topographers where one-to-one correspondence between mire and image points can be established. METHODS: The PFRT algorithm was applied on a corneal topographer designed and constructed at the VU University Medical Center, Amsterdam, The Netherlands. Performance of the algorithm was evaluated using artificial test surfaces and two sample eyes. The residual output of the PFRT algorithm is displayed as pixel displacements of actual feature points on the corneal image. Displacement of 1 pixel indicates submicrometer corneal height accuracy. RESULTS: PFRT residual increases with complexity of the measured surface. Using Zernike radial order 6, the mean residual for the artificial surfaces is subpixel. The mean residual for the regular cornea and the irregular cornea is 1.16 and 2.94 respectively. To some extent, increasing the Zernike radial order improves the accuracy. The improvement from order 6 to 20 is factor 2.3 for the irregular cornea. Using the residuals to further improve the accuracy brought local changes as high as 0.28 D in some areas of the reconstructed corneal power map. CONCLUSION: PFRT can be used to evaluate how close a reconstructed corneal surface is to the actual one. The residue information obtained from this algorithm can be displayed simultaneously with the corneal image. This provides accurate information about the corneal shape that is useful for application in laser refractive surgery.

The contribution of the posterior surface to the coma aberration of the human cornea.

Scheimpflug imaging was used to measure in six meridians the shape of the anterior and posterior cornea of the right eye of 114 subjects, ranging in age from 18 to 65 years. Subsequently, a three-dimensional model of the shape of the whole cornea was reconstructed, from which the coma aberration of the anterior and whole cornea could be calculated. This made it possible to investigate the compensatory role of the posterior surface to the coma aberration of the anterior corneal surface with age. Results show that, on average, the posterior surface compensates approximately 3.5% of the coma of the anterior surface. The compensation tends to be larger for young subjects (6%) than for older subjects (0%). This small effect of the posterior cornea on the coma aberration makes it clear that for the coma aberration of the whole eye, only the anterior corneal surface and the crystalline lens play a role. Consequently, for the design of an intraocular lens that is able to correct for coma aberration, it would be sufficient to only take the anterior corneal surface into account.

Topographer reconstruction of the nonrotation-symmetric anterior corneal surface features.

PURPOSE: The purpose of this study is to demonstrate the performance of a topographer (the VU topographer, prototype development, VU University Medical Center, Amsterdam, The Netherlands) that uses a color-coded stimulus pattern to reconstruct both the rotation-symmetric and nonrotation-symmetric shape features of the anterior corneal surface. METHODS: Spherical surfaces, toric surfaces, the Rand surface (surface with peripheral corrugations), and sample eyes were measured. A ring topographer (Keratron, Optikon 2000, Rome, Italy) and the Haag-Streit ophthalmometer (Haag Streit, Bern, Switzerland) were used for comparison. RESULTS: All three instruments produced similar values for the radii of curvature of spherical surfaces with a tolerance of 0.02 mm. The Keratron gave underestimated values for the astigmatic power of toric surfaces (>0.25 D for toric surfaces with astigmatism >9 D). Because it eliminates skew ray error, only the VU topographer was able to reconstruct the correct shape of the Rand surface in contrast with ring topographers. The effect of skew ray error was also observed in the surface reconstruction of a radially keratotomized (RK) eye. There was height difference of 2.75 +/- 1.25 microm between the output of the VU topographer and the output of the Keratron. CONCLUSION: The VU topographer is just as accurate in reconstructing the rotation-symmetric features of the anterior corneal surface as the ring topographers but is superior in recovering the nonrotation-symmetric shape features.

Spherical aberration of the anterior and posterior surfaces of the human cornea.

A ray-tracing procedure was applied to corrected Scheimpflug photography measurements to determine the spherical aberration of the anterior and posterior surfaces of the cornea. It was found that the total spherical aberration of the cornea increases slightly with age. The spherical aberration of the posterior corneal surface is negative at a young age and becomes positive at an older age. To make an accurate description of the spherical aberration for the whole eye, the posterior surface must also be measured.

Corneal surface reconstruction algorithm that uses Zernike polynomial representation.

We developed an algorithm that directly determines Zernike coefficients for the corneal anterior surface derived from the reflection image of a stimulus with pseudorandom encoding. This algorithm does not need to include calculation of corneal height maps. The numerical performance of the algorithm is good. It has the potential of determining corneal shape with submicrometer accuracy in obtaining Zernike coefficients. When applied to real eye measurements the accuracy of the procedure will be limited by the topographer that is used.