Comparing the clinical applicability of wavefront phase imaging in keratoconus versus normal eyes.

The aim of this work is to quantitatively assess the wavefront phase of keratoconic eyes measured by the ocular aberrometer t·eyede (based on WaveFront Phase Imaging Sensor), characterized by a lateral resolution of 8.6 µm without requiring any optical element to sample the wavefront information. We evaluated the parameters: root mean square error, Peak-to-Valley, and amplitude of the predominant frequency (Fourier Transform analysis) of a section of the High-Pass filter map in keratoconic and healthy cohorts. Furthermore, we have analyzed keratoconic eyes that presented dark-light bands in this map to assess their period and orientation with the Fourier Transform. There are significant statistical differences (p value < 0.001) between healthy and keratoconic eyes in the three parameters, demonstrating a tendency to increase with the severity of the disease. Otherwise, the quantification of the bands reveals that the width is independent of eye laterality and keratoconic stage as orientation, which tends to be oblique. In conclusion, the quantitative results obtained with t·eyede could help to diagnose and monitor the progression of keratoconus.

Real-Time Wavefront Sensing at High Resolution with an Electrically Tunable Lens.

We have designed, assembled, and evaluated a compact instrument capable of capturing the wavefront phase in real time, across various scenarios. Our approach simplifies the optical setup and configuration, which reduces the conventional capture and computation time when compared to other methods that use two defocused images. We evaluated the feasibility of using an electrically tunable lens in our camera by addressing its issues and optimizing its performance. Additionally, we conducted a comparison study between our approach and a Shack-Hartmann sensor. The camera was tested on multiple targets, such as deformable mirrors, lenses with aberrations, and a liquid lens in movement. Working at the highest resolution of the CMOS sensor with a small effective pixel size enables us to achieve the maximum level of detail in lateral resolution, leading to increased sensitivity to high-spatial-frequency signals.

Ultra-High Resolution Optical Aberrometry in Patients with Keratoconus: A Cross-Sectional Study.

INTRODUCTION: This study performs optical aberration assessment in patients using a novel ultra-high-resolution device. The objective of this study is to analyze optical aberrations, especially the very high order wavefront (more than 10th order of Zernike coefficients), and compare between keratoconus and healthy patients. METHODS: In this cross-sectional study, we analyzed 43 eyes from 25 healthy patients and 43 eyes from 27 patients with keratoconus using corneal tomography and a very high-resolution (8.55 µm) aberrometer prototype (T-eyede) outfitted with a sensor originally developed for use in the field of astrophysics. Corneal aberration values were assessed using an optical model built with Zemax optical software, while ocular aberrations were assessed using T-eyede. In addition, image-processing analysis was performed of the wavefront phase, creating a high-pass filter map. RESULTS: We found lower values for ocular aberrations than corneal aberrations in both groups (p < 0.001). Specifically, we found a reduction in primary astigmatism (0.145 µm) and primary coma (0.017 µm). Also, the keratoconus group showed significantly higher wavefront aberration values compared with controls (p < 0.001). An analysis of the high-pass filter map revealed 2 contrasting results: one smooth or clear, while the other presented a banding pattern. Almost all in the control group (95%) showed the first pattern, while 77% of the keratoconus group showed a banding pattern on the filtered map (chi-squared test, p < 0.001). CONCLUSION: This device provides reliable, precise measurements of ocular aberrations that correlate well with corneal aberrations. Furthermore, the extraordinary high-resolution measurements revealed unprecedented micro changes in the wavefront phase of patients with keratoconus that varied with disease stage. These findings could lead to new screening or follow-up methods.

Wavefront phase measurement of striae in optical glass.

We present a method for evaluating the quality of optical glass using a high-resolution wavefront sensor, the wavefront phase imaging (WFPI) sensor. As shadowgraphy is a widely used method for inspecting striae in optical glass, it does not provide a quantitative metric that represents the potential optical quality of the glass and should be based on the operator's experience. We compare the proposed method in two experiments. First, we compare it with the results obtained by shadowgraphy on a variety of samples. Second, we compare the results of a single-point chromatic confocal profilometer on a calibrated sample. The WFPI shows results comparable to the reference method in both cases but provides more information than shadowgraphy and avoids the human factor in the measurement.

The optics of the human eye at 8.6 µm resolution.

Ocular optics is normally estimated based on up to 2,600 measurement points within the pupil of the eye, which implies a lateral resolution of approximately 175 µm for a 9 mm pupil diameter. This is because information below this resolution is not thought to be relevant or even possible to obtain with current measurement systems. In this work, we characterize the in vivo ocular optics of the human eye with a lateral resolution of 8.6 µm, which implies roughly 1 million measurement points for a pupil diameter of 9 mm. The results suggest that the normal human eye presents a series of hitherto unknown optical patterns with amplitudes between 200 and 300 nm and is made up of a series of in-phase peaks and valleys. If the results are analysed at only high lateral frequencies, the human eye is also found to contain a whole range of new information. This discovery could have a great impact on the way we understand some fundamental mechanisms of human vision and could be of outstanding utility in certain fields of ophthalmology.

Crystalline lens gradient refractive index distribution in the guinea pig.

PURPOSE: The crystalline lens undergoes morphological and functional changes with age and may also play a role in eye emmetropisation. Both the geometry and the gradient index of refraction (GRIN) distribution contribute to the lens optical properties. We studied the lens GRIN in the guinea pig, a common animal model to study myopia. METHODS: Lenses were extracted from guinea pigs (Cavia porcellus) at 18 days of age (n = 4, three monolaterally treated with negative lenses and one untreated) and 39 days of age (n = 4, all untreated). Treated eyes were myopic (-2.07 D on average) and untreated eyes hyperopic (+3.3 D), as revealed using streak retinoscopy in the live and cyclopeged animals. A custom 3D spectral domain optical coherence tomography (OCT) system (λ = 840 nm, Δλ = 50 nm) was used to image the enucleated crystalline lens at two orientations. Custom algorithms were used to estimate the lens shape and GRIN was modelled with four variables that were reconstructed using the OCT data and a minimisation algorithm. Ray tracing was used to calculate the optical power and spherical aberration assuming a homogeneous refractive index or the estimated GRIN. RESULTS: Guinea pig lenses exhibited nearly parabolic GRIN profiles. When comparing the two age groups (18- and 39 day-old) there was a significant increase in the central thickness (from 3.61 to 3.74 mm), and in the refractive index of the surface (from 1.362 to 1.366) and the nucleus (from 1.443 to 1.454). The presence of GRIN shifted the spherical aberration (-4.1 µm on average) of the lens towards negative values. CONCLUSIONS: The guinea pig lens exhibits a GRIN profile with surface and nucleus refractive indices that increase slightly during the first days of life. GRIN plays a major role in the lens optical properties and should be incorporated into computational guinea pig eye models to study emmetropisation, myopia development and ageing.

Morphological changes of human crystalline lens in myopia.

Ocular biometric parameters, including full shape crystalline lens, were assessed in myopes and emmetropes using 3-D optical coherence tomography. The anterior chamber depth, the radius of the curvature of the anterior cornea, anterior lens, and posterior lens, lens thickness, lens equatorial diameter, surface area, equatorial position, volume, and power, were evaluated as functions of refractive errors and axial lengths while controlling for age effects. The crystalline lens appears to change with myopia consistent with lens thinning, equatorial, and capsular stretching while keeping constant volume. Axial elongation appears counteracted by a crystalline lens power reduction, while corneal power remains unaffected.

Perceptual impact of astigmatism induction in presbyopes.

We investigated the effect of induced astigmatism on subjective best focus and on visual acuity in 28 subjects of different ages (pre-presbyopic and presbyopic) and with different refractive profiles (emmetropes and astigmats). Measurements were performed using a custom-developed Adaptive Optics system, which allowed correction of high order aberrations and induction of astigmatism (0.5, 1, 1.5 and 2.0 D; axis: 180°, 45° and 22.5°). Upon induction of astigmatism, best focus shifted towards negative values in pre-presbyopic emmetropic eyes (by -0.14 D for 0.5 D and by -0.33 D for 2.0 D), while it shifted towards positive values in presbyopes, both in emmetropic presbyopes (by +0.04 D for 0.50 D and by +0.16 D for 2.0 D) and in astigmatic presbyopes (by +0.23 D for 0.50 D and by +0.40 D for 2.0 D). Also, visual acuity was most sensitive to astigmatism induction in pre-presbyopic emmetropes and least sensitive in presbyopes, particularly when high order aberrations were corrected: visual acuity ratio with/without astigmatism was: 0.74/0.85/0.98 (for astigmatism induced at 180°) and 0.68/0.73/0.86 at 45°, for pre-presbyopic emmetropes/presbyopic emmetropes/presbyopic astigmats. These findings may be connected to long term exposure to astigmatism in astigmats and corrected presbyopes.

Three-dimensional OCT based guinea pig eye model: relating morphology and optics.

Custom Spectral Optical Coherence Tomography (SOCT) provided with automatic quantification and distortion correction algorithms was used to measure the 3-D morphology in guinea pig eyes (n = 8, 30 days; n = 5, 40 days). Animals were measured awake in vivo under cyclopegia. Measurements showed low intraocular variability (<4% in corneal and anterior lens radii and <8% in the posterior lens radii, <1% interocular distances). The repeatability of the surface elevation was less than 2 µm. Surface astigmatism was the individual dominant term in all surfaces. Higher-order RMS surface elevation was largest in the posterior lens. Individual surface elevation Zernike terms correlated significantly across corneal and anterior lens surfaces. Higher-order-aberrations (except spherical aberration) were comparable with those predicted by OCT-based eye models.

OCT-based full crystalline lens shape change during accommodation in vivo.

The full shape of the accommodating crystalline lens was estimated using custom three-dimensional (3-D) spectral OCT and image processing algorithms. Automatic segmentation and distortion correction were used to construct 3-D models of the lens region visible through the pupil. The lens peripheral region was estimated with a trained and validated parametric model. Nineteen young eyes were measured at 0-6 D accommodative demands in 1.5 D steps. Lens volume, surface area, diameter, and equatorial plane position were automatically quantified. Lens diameter & surface area correlated negatively and equatorial plane position positively with accommodation response. Lens volume remained constant and surface area decreased with accommodation, indicating that the lens material is incompressible and the capsular bag elastic.

Optical Coherence Tomography Based Estimates of Crystalline Lens Volume, Equatorial Diameter, and Plane Position.

PURPOSE: Measurement of crystalline lens geometry in vivo is critical to optimize performance of state-of-the-art cataract surgery. We used custom-developed quantitative anterior segment optical coherence tomography (OCT) and developed dedicated algorithms to estimate lens volume (VOL), equatorial diameter (DIA), and equatorial plane position (EPP). METHODS: The method was validated ex vivo in 27 human donor (19-71 years of age) lenses, which were imaged in three-dimensions by OCT. In vivo conditions were simulated assuming that only the information within a given pupil size (PS) was available. A parametric model was used to estimate the whole lens shape from PS-limited data. The accuracy of the estimated lens VOL, DIA, and EPP was evaluated by comparing estimates from the whole lens data and PS-limited data ex vivo. The method was demonstrated in vivo using 2 young eyes during accommodation and 2 cataract eyes. RESULTS: Crystalline lens VOL was estimated within 96% accuracy (average estimation error across lenses ± standard deviation: 9.30 ± 7.49 mm3). Average estimation errors in EPP were below 40 ± 32 µm, and below 0.26 ± 0.22 mm in DIA. Changes in lens VOL with accommodation were not statistically significant (2-way ANOVA, P = 0.35). In young eyes, DIA decreased and EPP increased statistically significantly with accommodation (P < 0.001) by 0.14 mm and 0.13 mm, respectively, on average across subjects. In cataract eyes, VOL = 205.5 mm3, DIA = 9.57 mm, and EPP = 2.15 mm on average. CONCLUSIONS: Quantitative OCT with dedicated image processing algorithms allows estimation of human crystalline lens volume, diameter, and equatorial lens position, as validated from ex vivo measurements, where entire lens images are available.

OCT-based crystalline lens topography in accommodating eyes.

Custom Spectral Domain Optical Coherence Tomography (SD-OCT) provided with automatic quantification and distortion correction algorithms was used to measure anterior and posterior crystalline lens surface elevation in accommodating eyes and to evaluate relationships between anterior segment surfaces. Nine young eyes were measured at different accommodative demands. Anterior and posterior lens radii of curvature decreased at a rate of 0.78 ± 0.18 and 0.13 ± 0.07 mm/D, anterior chamber depth decreased at 0.04 ± 0.01 mm/D and lens thickness increased at 0.04 ± 0.01 mm/D with accommodation. Three-dimensional surface elevations were estimated by subtracting best fitting spheres. In the relaxed state, the spherical term accounted for most of the surface irregularity in the anterior lens (47%) and astigmatism (70%) in the posterior lens. However, in accommodated lenses astigmatism was the predominant surface irregularity (90%) in the anterior lens. The RMS of high-order irregularities of the posterior lens surface was statistically significantly higher than that of the anterior lens surface (x2.02, p<0.0001). There was significant negative correlation in vertical coma (Z3 (-1)) and oblique trefoil (Z3 (-3)) between lens surfaces. The astigmatic angle showed high degree of alignment between corneal surfaces, moderate between corneal and anterior lens surface (~27 deg), but differed by ~80 deg between the anterior and posterior lens surfaces (including relative anterior/posterior lens astigmatic angle shifts (10-20 deg).

Impact of astigmatism and high-order aberrations on subjective best focus.

We studied the role of native astigmatism and ocular aberrations on best-focus setting and its shift upon induction of astigmatism in 42 subjects (emmetropes, myopes, hyperopes, with-the-rule [WTR] and against-the-rule [ATR] myopic astigmats). Stimuli were presented in a custom-developed adaptive optics simulator, allowing correction for native aberrations and astigmatism induction (+1 D; 6-mm pupil). Best-focus search consisted on randomized-step interleaved staircase method. Each subject searched best focus for four different images, and four different conditions (with/without aberration correction, with/without astigmatism induction). The presence of aberrations induced a significant shift in subjective best focus (0.4 D; p < 0.01), significantly correlated (p = 0.005) with the best-focus shift predicted from optical simulations. The induction of astigmatism produced a statistically significant shift of the best-focus setting in all groups under natural aberrations (p = 0.001), and in emmetropes and in WTR astigmats under corrected aberrations (p < 0.0001). Best-focus shift upon induced astigmatism was significantly different across groups, both for natural aberrations and AO-correction (p < 0.0001). Best focus shifted in opposite directions in WTR and ATR astigmats upon induction of astigmatism, symmetrically with respect to the best-focus shift in nonastigmatic myopes. The shifts are consistent with a bias towards vertical and horizontal retinal blur in WTR and ATR astigmats, respectively, indicating adaptation to native astigmatism.

Full OCT anterior segment biometry: an application in cataract surgery.

In vivo three-dimensional (3-D) anterior segment biometry before and after cataract surgery was analyzed by using custom high-resolution high-speed anterior segment spectral domain Optical Coherence Tomography (OCT). The system was provided with custom algorithms for denoising, segmentation, full distortion correction (fan and optical) and merging of the anterior segment volumes (cornea, iris, and crystalline lens or IOL), to provide fully quantitative data of the anterior segment of the eye. The method was tested on an in vitro artificial eye with known surfaces geometry at different orientations and demonstrated on an aging cataract patient in vivo. Biometric parameters CCT, ACD/ILP, CLT/ILT Tilt and decentration are retrieved with a very high degree of accuracy. IOL was placed 400 µm behind the natural crystalline lens, The IOL was aligned with a similar orientation of the natural lens (2.47 deg superiorly), but slightly lower amounts (0.77 deg superiorly). The IOL was decentered superiorly (0.39 mm) and nasally (0.26 mm).