Sebastiano Serrao

Adaptive Optics Technology for High-Resolution Retinal Imaging

Adaptive optics (AO) is a technology used to improve the performance of optical systems by reducing the effects of optical aberrations. The direct visualization of the photoreceptor cells, capillaries and nerve fiber bundles represents the major benefit of adding AO to retinal imaging. Adaptive optics is opening a new frontier for clinical research in ophthalmology, providing new information on the early pathological changes of the retinal microstructures in various retinal diseases. We have reviewed AO technology for retinal imaging, providing information on the core components of an AO retinal camera. The most commonly used wavefront sensing and correcting elements are discussed. Furthermore, we discuss current applications of AO imaging to a population of healthy adults and to the most frequent causes of blindness, including diabetic retinopathy, age-related macular degeneration and glaucoma. We conclude our work with a discussion on future clinical prospects for AO retinal imaging.

Analysis of retinal capillaries in patients with type 1 diabetes and nonproliferative diabetic retinopathy using adaptive optics imaging.

Purpose: To illustrate a noninvasive method to analyze the retinal capillary lumen caliber in patients with Type 1 diabetes. Methods: Adaptive optics imaging of the retinal capillaries were acquired in two parafoveal regions of interest in eyes with nonproliferative diabetic retinopathy and unaffected controls. Measures of the retinal capillary lumen caliber were quantified using an algorithm written in Matlab by an independent observer in a masked manner. Comparison of the adaptive optics images with red-free and color wide fundus retinography images was also assessed. Results: Eight eyes with nonproliferative diabetic retinopathy (eight patients, study group), no macular edema, and preserved visual acuity and eight control eyes (eight healthy volunteers; control group) were analyzed. The repeatability of capillary lumen caliber measurements was 0.22 &mgr;m (3.5%) with the 95% confidence interval between 0.12 and 0.31 &mgr;m in the study group. It was 0.30 &mgr;m (4.1%) with the 95% confidence interval between 0.16 and 0.43 &mgr;m in the control group. The average capillary lumen caliber was significantly narrower in eyes with nonproliferative diabetic retinopathy (6.27 ± 1.63 &mgr;m) than in the control eyes (7.31 ± 1.59 &mgr;m, P = 0.002). Conclusion: The authors demonstrated a noninvasive method to analyze, with micrometric scale of resolution, the lumen of retinal capillaries. The parafoveal capillaries were narrower in patients with Type 1 diabetes and nonproliferative diabetic retinopathy than in healthy subjects, showing the potential capability of adaptive optics imaging to detect pathologic variations of the retinal microvascular structures in vaso-occlusive diseases.

Eccentricity dependent changes of density, spacing and packing arrangement of parafoveal cones

To investigate the distribution of cone density and spacing as well as the preferred packing arrangement of the cone mosaic as a function of retinal eccentricity.

Adaptive optics imaging of parafoveal cones in type 1 diabetes.

Purpose: To evaluate the parafoveal cone density in patients with Type 1 diabetes mellitus (DM1). Methods: Adaptive optics retinal images of the photoreceptor mosaic were acquired from 11 DM1 patients (study group) and 11 age-matched healthy subjects (control group). Cone density was analyzed, along the horizontal and vertical meridian, at 230-µm, 350-µm, and 460-µm eccentricity from the fovea. Central retinal thickness was measured using a Spectralis spectral-domain optical coherence tomography. A multiple regression model was performed to determine the relationships between the explanatory variables (age, glycohemoglobin level, presence of diabetic retinopathy, duration of diabetes, and central retinal thickness) and cone density. Results: Patients had a diagnosis of DM1 in the past 9 years to 21 years. Of these, five patients had a diagnosis of no diabetic retinopathy and six had mild nonproliferative diabetic retinopathy. On average, cone density was 10% lower in the study than in the control group at each retinal eccentricity along the horizontal and vertical meridians (analysis of variance, P < 0.001). The central retinal thickness was thicker in DM1 eyes than in the control eyes (278 ± 20 µm and 260 ± 13 µm; P < 0.05). The model explained 61% (P < 0.01) of the variance of cone density in the population, with the variables representing an abnormal glucose metabolism, that is, a higher glycohemoglobin level, the presence of diabetic retinopathy, and a chronic diabetes, having the highest influence on cone density decline. Conclusion: A subtle decrease of parafoveal cone density was found in DM1 patients in comparison with age-matched control subjects via high-resolution adaptive optics retinal imaging. The cone density decline was moderately associated with a disturbance in the glucose metabolism.

Biomechanical changes in the human cornea after transepithelial corneal crosslinking using iontophoresis

Purpose To evaluate the corneal response to variable intraocular pressure (IOP) in human eye globes after ultraviolet‐A (UVA) transepithelial corneal crosslinking using iontophoresis. Setting Fondazione G.B. Bietti IRCCS, Rome, Italy. Design Experimental study. Methods Four human donor eye globes were treated with transepithelial crosslinking using iontophoresis and rapid UVA corneal irradiation, and 4 globes had standard crosslinking. Inflation experiments were performed on the globes before and after crosslinking. Topographic maps of the anterior and posterior cornea were acquired using Scheimpflug topography. Images were obtained using a mechanical regimen to analyze corneal strain in response to cyclic stress. Corneal shape changes were analyzed as a function of IOP, and corneal stress–strain curves were generated. Results Before crosslinking, instillation of hypotonic riboflavin‐5–phosphate sodium 0.1% solution using iontophoresis increased corneal thickness by 5% and instillation of dextran‐enriched riboflavin 0.1% solution decreased corneal thickness by 13%. Five minutes after treatment, both crosslinking procedures reduced corneal thickness by 2%. Young’s modulus (E) of the anterior cornea increased by a mean of 1.8 times (from 1.6 to 2.9 MPa) and 1.9 times (from 1.3 to 2.5 MPa) after transepithelial crosslinking using iontophoresis and standard crosslinking, respectively. The E value of the posterior cornea also increased after both procedures (mean 1.7 times versus 3.1 times). Conclusions Transepithelial crosslinking using iontophoresis increased the biomechanical strength of human corneal tissue in inflation testing of donor eye globes. The effect on corneal stiffness was almost comparable to that of standard crosslinking. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

Interocular symmetry of parafoveal photoreceptor cone density distribution.

Purpose: To investigate the variation and symmetry of cone density distribution along the nasal and temporal retina of fellow eyes. Methods: An adaptive optics retinal camera (rtx1; Imagine Eyes) was used to obtain images of the parafoveal cone mosaic in 20 healthy subjects. Cone density was estimated at 250, 420, 760, and 1,300 &mgr;m eccentricity from the fovea along the nasal and temporal retina of both eyes in each subject. The coefficient of variation and the intraclass correlation coefficient were used to calculate the variation and absolute agreement of cone density between the same retinal eccentricity locations of fellow eyes, respectively. Results: A considerable variation of cone density between subjects was found at all eccentricities along the nasal and temporal retina (intersubject coefficient of variation ≥ 11%, P < 0.001). The intrasubject variation of cone density was, however, moderate (coefficient of variation ⩽ 13% in 95% of the subjects); a high agreement was, on average, found between the cone density estimates at the same eccentricity along the nasal and temporal retina of fellow eyes (intraclass correlation coefficient ≥ 0.86, P < 0.001). Conclusion: Cone density follows a symmetrical distribution between fellow eyes. A systematic distribution of parafoveal cones between fellow eyes may provide an anatomical basis for the involvement of the photoreceptor layer in the first step of binocular spatial sampling.

Photorefractive Keratectomy With and Without Smoothing: A Bilateral Study

PURPOSE To assess whether a smoother stromal surface and a faster epithelium regeneration after excimer laser photorefractive keratectomy (PRK) may lead to better visual results. METHODS Ten patients had unilateral PRK and contralateral PRK plus smoothing. The operative outcome was checked by means of digital standardized photographs taken at 0, 20, 40, and 60 hours after surgery. Complete clinical examinations were performed before and 1 and 3 months after surgery. RESULTS Between 20 and 40 hours after surgery, the average velocity of radial epithelial migration in eyes in which smoothing was performed was 0.083 +/- 0.008 mm/h. This was faster than that (0.064 +/- 0.007 mm/h [P<.01]) observed in the eyes without smoothing. The corneal regularity index at 1 and 3 months was worse in the PRK alone group compared to the PRK plus smoothing group (P=.1). At 3 months, better visual outcome and less haze were observed in the PRK plus smoothing group. CONCLUSION When using a flying spot laser, PRK plus smoothing improved the visual results and diminished regression and haze at 3 months, but gave rise to a slight hyperopic shift.

Interocular high-order corneal wavefront aberration symmetry

The interocular symmetry of the high-order corneal wavefront aberration (WA) in a population of myopic eyes was analyzed before and after photorefractive keratectomy (PRK). The preoperative and one-year postoperative corneal aberration data (from third to seventh Zernike orders) for 4- and 7-mm pupils from right and left eyes were averaged after correcting for the effects of enantiomorphism to test for mirror symmetry. Also, the mean corneal point-spread function (PSF) for right and left eyes was calculated. Preoperatively, a moderate and high degree of correlation in the high-order corneal WA between eyes was found for 4- and 7-mm pupils, respectively. Myopic PRK did not significantly change the interocular symmetry of corneal high-order aberrations. No discernible differences in the orientation PSF between eyes were observed one year after surgery in comparison with the preoperative state over the two analyzed pupils.

Evaluation of Femtosecond Laser Clear Corneal Incision: An Experimental Study

PURPOSE To evaluate the changes of corneal topography following femtosecond laser and manual clear corneal incision (CCI). METHODS Inflation testing was performed in 14 human eye globes to evaluate the topographic response of the cornea to CCIs. In seven samples (femtosecond laser group), a 2.75-mm three-plane CCI was created using the iFS femtosecond laser (Abbott Medical Optics, Inc., Santa Ana, CA); the remaining seven samples (control group) received a 2.75-mm manual CCI using disposable angled knives. Topographic maps of the anterior and posterior cornea were acquired using a Scheimpflug topographer Pentacam HR (Oculus Optikgeräte GmbH, Wetzlar, Germany). Keratometric data were used to analyze the curvature changes of the cornea. The changes of corneal astigmatism were analyzed by vector analysis. RESULTS After CCI, the mean change of the anterior keratometric power was 0.04 ± 0.39 and 0.05 ± 0.51 diopters (D) (analysis of variance, P > .05) in the femtosecond laser and control groups, respectively. The mean change (P > .05) of the posterior corneal keratometric power was 0.16 ± 0.19 and 0.15 ± 0.18 D, respectively. The average change of the anterior and posterior corneal astigmatism vector magnitude was 0.17 D or less in both groups (P > .05). A slight against-the-rule astigmatic change of the anterior and posterior corneal interfaces was found after both CCI techniques. CONCLUSION The 2.75-mm three-plane CCI created with femtosecond laser showed minimal changes of the anterior and posterior corneal topography, comparable with those of single-plane angled manual incision.

Analysis of intraocular lens surface properties with atomic force microscopy

PURPOSE: To analyze the surface optics of 4 currently available intraocular lenses (IOLs) with atomic force microscopy. SETTING: Licryl Laboratory, University of Calabria, Rende, Italy. METHODS: The surface roughness and topography of poly(methyl methacrylate) (PMMA), silicone, hydrophobic, and hydrophilic acrylic IOLs were evaluated with atomic force microscopy in contact mode. The analysis was performed in a liquid environment using cantilevers with a 0.01 Newtonw/meter nominal elastic constant. Measurements were made over areas of 10 μm2 on different locations of the posterior optic surface of the IOL. RESULTS: Atomic force microscopy permitted high‐resolution imaging of IOL optic surface characteristics. Surface topography showed different features with respect to the lens biomaterial. The root‐mean‐square roughness of the IOL optic surface was significantly different between lenses of various materials (P<.001). The hydrophobic acrylic and silicone IOLs had the lowest mean surface roughness, 3.8 nm ± 0.2 (SD) and 4.0 ± 0.5 nm, respectively, and the 2 PMMA IOLs had the highest mean surface roughness, 6.6 ± 0.3 nm and 7.0 ± 0.6 nm. CONCLUSIONS: Atomic force microscopy was effective and accurate in analyzing IOL optics. The surface topography of IOLs may vary with different manufacturing processes.