Algorithm and software for field distortion correction in a commercial SD-OCT for corneal curvature assessment.

Accurate assessment of corneal curvatures using frequency domain optical coherence tomography (OCT) with galvanometer scanners remains challenging due to the well-known scan field distortion. This paper presents an algorithm and software for correcting the distortion using only two simple measurements in which a readily available standard sphere is positioned in different depths in front of the OCT scanner. This offers a highly accessible and easily reproducible method for the field distortion correction (FDC). The correction was validated by measuring different spherical phantoms and conducting corneal curvature measurements of ex vivo porcine corneas using a commercial spectral-domain OCT system and a clinically approved swept-source OCT as a reference instrument. Thus, the error in radius measurements of spherical phantoms was reduced by >90% and astigmatism by >80% using FDC. In explanted porcine eyes, the error in astigmatism measurements with the Telesto was reduced by 75% for power and 70% for angle. The best fitting sphere radius was determined up to a deviation of 0.4% from the Anterion. This paper describes a correction algorithm for OCT immanent distortion that is applicable to any scanning OCT setup and enables precise corneal curvature measurements. The MATLAB software for the FDC is publicly available on GitHub.

Algorithms for optoacoustically controlled selective retina therapy (SRT).

OBJECTIVES: Selective Retina Therapy (SRT) uses microbubble formation (MBF) to target retinal pigment epithelium (RPE) cells selectively while sparing the neural retina and the choroid. Intra- and inter-individual variations of RPE pigmentation makes frequent radiant exposure adaption necessary. Since selective RPE cell disintegration is ophthalmoscopically non-visible, MBF detection techniques are useful to control adequate radiant exposures. It was the purpose of this study to evaluate optoacoustically based MBF detection algorithms. METHODS: Fifteen patients suffering from central serous chorioretinopathy and diabetic macula edema were treated with a SRT laser using a wavelength of 527 nm, a pulse duration of 1.7 µs and a pulse energy ramp (15 pulses, 100 Hz repetition rate). An ultrasonic transducer for MBF detection was embedded in a contact lens. RPE damage was verified with fluorescence angiography. RESULTS: An algorithm to detect MBF as an indicator for RPE cell damage was evaluated. Overall, 4646 irradiations were used for algorithm optimization and testing. The tested algorithms were superior to a baseline model. A sensitivity/specificity pair of 0.96/1 was achieved. The few false algorithmic decisions were caused by unevaluable signals. CONCLUSIONS: The algorithm can be used for guidance or automatization of microbubble related treatments like SRT or selective laser trabeculoplasty (SLT).

Advances in Imaging of Subbasal Corneal Nerves With Micro-Optical Coherence Tomography.

Purpose: To investigate the most peripheral corneal nerve plexus using high-resolution micro-optical coherence tomography (µOCT) imaging and to assess µOCT's clinical potential as a screening tool for corneal and systemic diseases. Methods: An experimental high-resolution (1.5 × 1.5 × 1 µm) µOCT setup was applied for three-dimensional imaging of the subbasal nerve plexus in nonhuman primates (NHPs) and swine within 3 hours postmortem. Morphologic features of subbasal nerves in µOCT were compared to ß3 tubulin-stained fluorescence confocal microscopy (FCM). Parameters such as nerve density, nerve distribution, and imaging repeatability were evaluated, using semiautomatic image analysis in form of a custom corneal surface segmentation algorithm and NeuronJ. Results: Swine and NHP corneas showed the species-specific nerve morphology in both imaging modalities. Most fibers showed a linear course, forming a highly parallel pattern, converging in a vortex with overall nerve densities varying between 9.51 and 24.24 mm/mm2. The repeatability of nerve density quantification of the µOCT scans as approximately 88% in multiple image recordings of the same cornea. Conclusions: Compared to the current gold standard of FCM, µOCT's larger field of view of currently 1 × 1 mm increases the conclusiveness of density measurements, which, coupled with µOCT's feature of not requiring direct contact, shows promise for future clinical application. The nerve density quantification may be relevant for screening for systemic disease (e.g., peripheral neuropathy). Translational Relevance: Technological advances in OCT technology may enable a quick assessment of corneal nerve density, which could be valuable evaluating ophthalmic and systemic peripheral innervation.

Investigations on Retinal Pigment Epithelial Damage at Laser Irradiation in the Lower Microsecond Time Regime.

Purpose: New lasers with a continuous wave power exceeding 15 W are currently investigated for retinal therapies, promising highly localized effects at and close to the Retinal Pigment Epithelium (RPE). The goal of this work is to evaluate mechanisms and thresholds for RPE cell damage by means of pulse durations up to 50 µs. Methods: A diode laser with a wavelength of 514 nm, a power of 15 W, and adjustable pulse durations between 2 µs and 50 µs was used. Porcine RPE-choroidal explants (ex vivo) and chinchilla bastard rabbits (in vivo) were irradiated to determine threshold radiant exposures for RPE damage \({\bar H_{Cell}}\) by calcein vitality staining and fluorescence angiography, respectively. Thresholds for microbubble formation (MBF) \({\bar H_{MBF}}\) were evaluated by time-resolved optoacoustics. Exemplary histologies support the findings. Results: \({\bar H_{{{MBF}}}}\) is significantly higher than \({\bar H_{Cell}}\) at pulse durations ≥ 5 µs (P < 0.05) ex vivo, while at 2 µs, no statistically significant difference was found. The ratios between \({\bar H_{{{MBF}}}}\) and \({\bar H_{Cell}}\) increase with pulse duration from 1.07 to 1.48 ex vivo and 1.1 to 1.6 in vivo, for 5.2 and 50 µs. Conclusions: Cellular damage with and without MBF related disintegration are both present and very likely to play a role for pulse durations ≥ 5 µs. With the lower µs pulses, selective RPE disruption might be possible, while higher values allow achieving spatially limited thermal effects without MBF. However, both modi require a very accurate real-time dosing control in order to avoid extended retinal disintegration in this power range.

Micro-optical coherence tomography for high-resolution morphologic imaging of cellular and nerval corneal micro-structures.

We demonstrate the highest resolution (1.5×1.5×1 µm) micrometer optical coherence tomography (µOCT) imaging of the morphologic micro-structure of excised swine and non-human primate corneas. Besides epithelial, stromal, and endothelial cell morphology, this report focuses on investigating the most peripheral corneal nerve fibers, the nerve fibers of the subbasal plexus (SBP). Alterations of SBP nerve density and composition are reportedly linked to major neurologic disorders, such as diabetic neuropathy, potentially indicating earliest onsets of denervation. Here, the fine, hyperreflective, epithelial nerve structures located just above Bowman's membrane, are i) visualized using our µOCT prototype, ii) validated by comparison to fluorescence confocal microscopy (including selective immunohistochemical staining), and iii) segmented using state-of-the-art image processing. Here, we also introduce polarization sensitive (PS) µOCT imaging, demonstrating, to the best of our knowledge, the highest resolution corneal PS-OCT scans reported to date.

Stromal Nerve Imaging and Tracking Using Micro-Optical Coherence Tomography.

Purpose: To image, track and map the nerve fiber distribution in excised rabbit corneas over the entire stromal thickness using micro-optical coherence tomography (µOCT) to develop a screening tool for early peripheral neuropathy. Methods: Excised rabbit corneas were consecutively imaged by a custom-designed µOCT prototype and a commercial laser scanning fluorescence confocal microscope. The µOCT images with a field of view of approximately 1 × 1 mm were recorded with axial and transverse resolutions of approximately 1 µm and approximately 4 µm, respectively. In the volumetric µOCT image data, network maps of hyper-reflective, branched structures traversing different stromal compartments were segmented using semiautomatic image processing algorithms. Furthermore, the same corneas received ßIII-tubulin antibody immunostaining before digital confocal microscopy, and a comparison between µOCT image data and immunohistochemistry analysis was performed to validate the nerval origin of the tracked network structures. Results: Semiautomatic tracing of the nerves with a high range of different thicknesses was possible through the whole corneal volumes, creating a skeleton of the traced nerves. There was a good conformity between the hyper-reflective structures in the µOCT data and the stained nerval structures in the immunohistochemistry data. Conclusions: This article demonstrates nerval imaging and tracking as well as a spatial correlation between µOCT and a fluorescence corneal nerve standard for larger nerves throughout the full thickness of the cornea ex vivo. Translational Relevance: Owing to its advantageous properties, µOCT may become useful as a noncontact method for assessing nerval structures in humans to screen for early peripheral neuropathy.

Corneal Stromal Filler Injection as a Novel Approach to Correct Presbyopia-An Ex Vivo Pilot Study.

Purpose: To evaluate the ex vivo feasibility of corneal stromal filler injection to create bifocality to correct presbyopia by flattening the central posterior corneal surface and thus increase refractive power. Methods: Femtosecond laser-assisted corneal stromal pockets of varying diameters close to the posterior corneal curvature were cut into rabbit eyes ex vivo. Subsequently, hyaluronic acid was injected to flatten the central posterior curvature. Refractive parameters were determined using perioperatively acquired three-dimensional optical coherence tomography (OCT) scans. Using micrometer-resolution OCT, corneal endothelial cell morphology and density were evaluated. Results: Following filler injection into the corneal stromal pockets, a fair volume-dependent increase of central refractive power up to 4 diopters (dpt) was observed. Unremarkable refractive changes of the peripheral posterior (3 mm, 0.20 ± 0.11 dpt; 2 mm, 0.11 ± 0.10 dpt) and the anterior corneal curvature (3 mm, 0.20 ± 0.34 dpt; 2 mm, 0.33 ± 0.31 dpt) occurred. Only negligible changes in astigmatism were observed. Different sizes of optical zones could be established. Furthermore, no alterations of corneal endothelial morphology or endothelial cell density (2831 ± 356 cells/mm2 vs. 2734 ± 292 cells/mm2; P = 0.552) due to the adjacent laser treatment were observed. Conclusions: The ex vivo investigations proved the principle of injecting a filler material into femtosecond laser-created corneal stromal pockets close to the posterior corneal curvature as an efficacious, individually adjustable, and novel approach to correct presbyopia without ablating corneal tissue. Translational Relevance: Due to the aging population worldwide, presbyopia is an increasing problem; thus, our study may encourage further exploration to extend the treatment spectrum of clinically used femtosecond laser systems to correct presbyopia.

Refractive Changes After Corneal Stromal Filler Injection for the Correction of Hyperopia.

PURPOSE: To evaluate a new non-ablative and adjustable procedure for laser ablative refractive corneal surgery in hyperopia using the injection of a biocompatible liquid filler material into a stromal pocket. METHODS: A total of 120 stromal pockets were created using a clinical femtosecond laser system in 96 rabbit corneoscleral discs and 24 whole globes. Pockets were cut at a depth of 120 or 250 µm below the epithelial surface. Hyaluronic acid was injected manually into the pocket. To determine the refractive changes, three-dimensional optical coherence tomography images and a specifically developed picture recognition Matlab (The Mathworks) routine were used. RESULTS: After injection, a steepening of the anterior and flattening of the posterior corneal surface was observed, which led to hyperopic correction. The two main factors determining the amount of correction were the pocket depth and the injected volume. After the pocket was homogeneously filled, an initial refractive increase was observed, followed by a linear relation between the injected volume and the refraction increase. CONCLUSIONS: This possible clinical protocol for controlled refraction correction of hyperopia suggests a potential readjustable clinical application. [J Refract Surg. 2020;36(6):406-414.].

First Assessment of a Carbon Monoxide Laser and a Thulium Fiber Laser for Fractional Ablation of Skin.

BACKGROUND AND OBJECTIVES: A recent generation of 5,500 nm wavelength carbon monoxide (CO) lasers could serve as a novel tool for applications in medicine and surgery. At this wavelength, the optical penetration depth is about three times higher than that of the 10,600 nm wavelength carbon dioxide (CO2 ) laser. As the amount of ablation and coagulation is strongly influenced by the wavelength, we anticipated that CO lasers would provide extended coagulation zones, which could be beneficial for several medical applications, such as tissue tightening effects after laser skin resurfacing. Until now, the 1,940 nm wavelength thulium fiber (Tm:fiber) laser is primarily known as a non-ablative laser with an optical penetration depth that is eight times higher than that of the CO2 laser. The advantage of lasers with shorter wavelengths is the ability to create smaller spot sizes, which has a determining influence on the ablation outcome. In this study, the ablation and coagulation characteristics of a novel CO laser and a high power Tm:fiber laser were investigated to evaluate their potential application for fractional ablation of the skin. STUDY DESIGN/MATERIALS AND METHODS: Laser-tissue exposures were performed using a novel CO laser, a modified, pulse-width-modulated CO2 laser, and a Tm:fiber laser. We used discarded ex vivo human skin obtained from abdominoplasty as tissue samples. Similar exposure parameters, such as spot size (108-120 µm), pulse duration (2 milliseconds), and pulse energy (~10-200 mJ) were adjusted for the different laser systems with comparable temporal pulse structures. Laser effects were quantified by histology. RESULTS: At radiant exposures 10-fold higher than the ablation threshold, the CO laser ablation depth was almost two times deeper than that of the CO2 laser. At 40-fold of the ablation threshold, the CO laser ablation was 47% deeper. The ablation craters produced by the CO laser exhibited about two times larger coagulation zones when compared with the CO2 laser. In contrast, the Tm:fiber laser exhibited superficial ablation craters with massive thermal damage. CONCLUSIONS: The tissue ablation using the Tm:fiber laser was very superficial in contrast to the CO laser and the CO2 laser. However, higher etch depths should be obtainable when the radiant exposure is increased by using higher pulse energies and/or smaller spot sizes. At radiant exposures normalized to the ablation threshold, the CO laser was capable of generating deeper ablation craters with extended coagulation zones compared with the CO2 laser, which is possibly desirable depending on the clinical goal. The effect of deep ablation combined with additional thermal damage on dermal remodeling needs to be further confirmed with in vivo studies. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Selective Equatorial Sclera Crosslinking in the Orbit Using a Metal-Coated Polymer Waveguide.

Purpose: Photochemical crosslinking of the sclera is an emerging technique that may prevent excessive eye elongation in pathologic myopia by stiffening the scleral tissue. To overcome the challenge of uniform light delivery in an anatomically restricted space, we previously introduced the use of flexible polymer waveguides. We presently demonstrate advanced waveguides that are optimized to deliver light selectively to equatorial sclera in the intact orbit. Methods: Our waveguides consist of a polydimethylsiloxane cladding and a polyurethane core, coupled to an optical fiber. A reflective silver coating deposited on the top and side surfaces of the waveguide prevents light leakage to nontarget, periorbital tissue. Postmortem rabbits were used to test the feasibility of in situ equatorial sclera crosslinking. Tensometry measurements were performed on ex vivo rabbit eyes to confirm a biomechanical stiffening effect. Results: Metal-coated waveguides enabled efficient light delivery to the entire circumference of the equatorial sclera with minimal light leakage to the periorbital tissues. Blue light was delivered to the intact orbit with a coefficient of variation in intensity of 22%, resulting in a 45 ± 11% bleaching of riboflavin fluorescence. A 2-fold increase in the Young's modulus at 5% strain (increase of 92% P < 0.05, at 25 J/cm2) was achieved for ex vivo crosslinked eyes. Conclusions: Flexible polymer waveguides with reflective, biocompatible surfaces are useful for sclera crosslinking to achieve targeted light delivery. We anticipate that our demonstrated procedure will be applicable to sclera crosslinking in live animal models and, potentially, humans in vivo.

Optimization-based vessel segmentation pipeline for robust quantification of capillary networks in skin with optical coherence tomography angiography.

Optical coherence tomography angiography (OCTA) provides in-vivo images of microvascular perfusion in high resolution. For its application to basic and clinical research, an automatic and robust quantification of the capillary architecture is mandatory. Only this makes it possible to reliably analyze large amounts of image data, to establish biomarkers, and to monitor disease developments. However, due to its optical properties, OCTA images of skin often suffer from a poor signal-to-noise ratio and contain imaging artifacts. Previous work on automatic vessel segmentation in OCTA mostly focuses on retinal and cerebral vasculature. Its applicability to skin and, furthermore, its robustness against imaging artifacts had not been systematically evaluated. We propose a segmentation method that improves the quality of vascular quantification in OCTA images even if corrupted by imaging artifacts. Both the combination of image processing methods and the choice of their parameters are systematically optimized to match the manual labeling of an expert for OCTA images of skin. The efficacy of this optimization-based vessel segmentation is further demonstrated on sample images as well as by a reduced error of derived quantitative vascular network characteristics.

Correction of hyperopia by intrastromal cutting and liquid filler injection.

Correction of hyperopia requires an increase of the refractive power by steepening of the corneal surface. Present refractive surgical techniques based on corneal ablation (LASIK) or intrastromal lenticule extraction (SMILE) are problematic due to epithelial regrowth. Recently, it was shown that correction of low hyperopia can be achieved by implanting intracorneal inlays or allogeneic lenticules. We demonstrate a steepening of the anterior corneal surface after injection of a transparent, liquid filler material into a laser-dissected intrastromal pocket. We performed the study on ex-vivo porcine eyes. The increase of the refractive power was evaluated by optical coherence tomography (OCT). For a circular pocket, injection of 1 µl filler material increased the refractive power by +4.5 diopters. An astigmatism correction is possible when ellipsoidal intrastromal pockets are created. Injection of 2 µl filler material into an ellipsoidal pocket increased the refractive power by +10.9 dpt on the short and +5.1 dpt on the long axis. OCT will enable to monitor the refractive change during filler injection and is thus a promising technique for real-time dosimetry.

Selective retina therapy: toward an optically controlled automatic dosing.

Selective retina therapy (SRT) targets the retinal pigment epithelium (RPE) with pulsed laser irradiation by inducing microbubble formation (MBF) at the intracellular melanin granula, which leads to selective cell disruption. The following wound healing process rejuvenates the chorio-retinal junction. Pulse energy thresholds for selective RPE effects vary intra- and interindividually. We present the evaluation of an algorithm that processes backscattered treatment light to detect MBF as an indicator of RPE cell damage since these RPE lesions are invisible during treatment. Eleven patients with central serous chorioretinopathy and four with diabetic macula edema were treated with a SRT system, which uses a wavelength of 527 nm, a repetition rate of 100 Hz, and a pulse duration of 1.7 µs. Fifteen laser pulses with stepwise increasing pulse energy were applied per treatment spot. Overall, 4626 pulses were used for algorithm parameter optimization and testing. Sensitivity and specificity were the metrics maximized through an automatic optimization process. Data were verified by fluorescein angiography. A sensitivity of 1 and a specificity of 0.93 were achieved. The method introduced in this paper can be used for guidance or automatization of microbubble-related treatments like SRT or selective laser trabeculoplasty.

Simple approach for aberration-corrected OCT imaging of the human retina.

Aberration-corrected imaging of human photoreceptor cells, whether hardware or software based, presently requires a complex and expensive setup. Here we use a simple and inexpensive off-axis full-field time-domain optical coherence tomography (OCT) approach to acquire volumetric data of an in vivo human retina. Full volumetric data are recorded in 1.3 s. After computationally correcting for aberrations, single photoreceptor cells were visualized. In addition, the numerical correction of ametropia is demonstrated. Our implementation of full-field optical coherence tomography combines a low technical complexity with the possibility for computational image correction.

Enhanced quantification of metabolic activity for individual adipocytes by label-free FLIM.

Fluorescence lifetime imaging microscopy (FLIM) of intrinsic fluorophores such as nicotinamide adenine dinucleotide (NADH) allows for label-free quantification of metabolic activity of individual cells over time and in response to various stimuli, which is not feasible using traditional methods due to their destructive nature and lack of spatial information. This study uses FLIM to measure pharmacologically induced metabolic changes that occur during the browning of white fat. Adipocyte browning increases energy expenditure, making it a desirable prospect for treating obesity and related disorders. Expanding from the traditional two-lifetime model of NADH to a four-lifetime model using exponential fitting and phasor analysis of the fluorescence decay results in superior metabolic assessment compared to traditional FLIM analysis. The four lifetime components can also be mapped to specific cellular compartments to create a novel optical ratio that quantitatively reflects changes in mitochondrial and cytosolic NADH concentrations and binding states. This widely applicable approach constitutes a powerful tool for studies where monitoring cellular metabolism is of key interest.

Assessment of skin lesions produced by focused, tunable, mid-infrared chalcogenide laser radiation.

BACKGROUND: Traditionally, fractional laser treatments are performed with focused laser sources operating at a fixed wavelength. Using a tunable laser in the mid-infrared wavelength range, wavelength-dependent absorption properties on the ablation process and thermal damage formation were assessed with the goal to obtain customizable tissue ablations to provide guidance in finding optimized laser exposure parameters for clinical applications. METHODS: Laser tissue experiments were carried out on full thickness ex vivo human abdominal skin using a mid-infrared tunable chromium-doped zinc selenide/sulfide chalcogenide laser. The laser has two independent channels: a continuous wave (CW) output channel which covers a spectrum ranging from 2.4 µm to 3.0 µm with up to 9.2 W output power, and a pulsed output channel which ranges from 2.35 µm to 2.95 µm. The maximum pulse energy of the pulsed channel goes up to 2.8 mJ at 100 Hz to 1,000 Hz repetition rate with wavelength-dependent pulse durations of 4-7 ns. RESULTS: Total ablation depth, ablation efficiency, and coagulation zone thickness were highly correlated to wavelength, pulse width, and pulse energy. Using the same total radiant exposure at 2.85 µm wavelength resulted in 10-times smaller coagulation zones and 5-times deeper ablation craters for one hundred 6 ns pulses compared to one 100 ms pulse. For a fixed pulse duration of 6 ns and a total radiant exposure of 2.25 kJ/cm2 the ablation depth increased with longer wavelengths. CONCLUSION: The tunable laser system provides a useful research tool to investigate specific laser parameters such as wavelength on lesion shape, ablation depth and thermal tissue damage. It also allows for customization of the characteristics of laser lesions and therefore facilitates the selection of suitable laser parameters for optimized fractional laser treatments. Lasers Surg. Med. 50:961-972, 2018.© 2018 Wiley Periodicals, Inc.

Interface Bonding With Corneal Crosslinking (CXL) After LASIK Ex Vivo.

Purpose: Interface bonding with corneal crosslinking (CXL) after LASIK using two different photosensitizers was studied ex vivo. Methods: A LASIK flap was created in enucleated rabbit eyes using a femtosecond laser. After the dissection, CXL was performed to seal the interface. In one group interface CXL was performed using rose bengal and green light, whereas in a second group riboflavin and UV-A light was used. In both groups irradiance, radiant exposure, dye concentration, and imbibition time was varied. In a control group, LASIK only was performed. After the procedures, the maximal shear-force required to separate the flap from the stroma was measured. Additionally, corneal transmission spectra were recorded. Results: Optimized parameters for rose bengal/green-light bonding lead to a 2.1-fold increase in shear-force compared with untreated control eyes (P < 0.01). The optimal parameter combination was: irradiance of 180 mW/cm2 for 14 minutes (total radiant exposure 150 J/cm2), rose bengal concentration 0.1%, and an imbibition time of 2 minutes. Optimized riboflavin/UV-A light parameters were 0.5% for 2 minutes with a radiant exposure of 8.1 J/cm2 obtained by an irradiance of 30 mW/cm2 for 4.5 minutes. These optimized parameters lead to a 2-fold increase compared with untreated control eyes (P < 0.01). Optical transmission experiments suggest safety for more posterior structures. Conclusions: Based on ex-vivo results, interface bonding after LASIK using crosslinking with either rose bengal or riboflavin increases the adhesion between flap and stromal bed. In vivo trials are needed to evaluate the temporal evolution of the effect.

Power-controlled temperature guided retinal laser therapy.

Laser photocoagulation has been a treatment method for retinal diseases for decades. Recently, studies have demonstrated therapeutic benefits for subvisible effects. A treatment mode based on an automatic feedback algorithm to reliably generate subvisible and visible irradiations within a constant irradiation time is introduced. The method uses a site-individual adaptation of the laser power by monitoring the retinal temperature rise during the treatment using optoacoustics. This provides feedback to adjust the therapy laser power during the irradiation. The technique was demonstrated on rabbits in vivo using a 532-nm continuous wave Nd:YAG laser. The temperature measurement was performed with 523-nm Q-switched Nd:YLF laser pulses with 75-ns pulse duration at 1-kHz repetition rate. The beam diameter on the fundus was 200 µm for both lasers, respectively. The aim temperatures ranged from 50°C to 75°C in 11 eyes of 7 rabbits. The results showed ophthalmoscopically invisible effects below 55°C with therapy laser powers over a wide range. The standard deviation for the measured temperatures ranged from 2.1°C for an aim temperature of 50°C to 4.7°C for 75°C. The ED50 temperature value for ophthalmoscopically visible lesions in rabbits was determined as 65.3°C. The introduced method can be used for retinal irradiations with adjustable temperature elevations.

Biomedical optics centers: forty years of multidisciplinary clinical translation for improving human health.

Despite widespread government and public interest, there are significant barriers to translating basic science discoveries into clinical practice. Biophotonics and biomedical optics technologies can be used to overcome many of these hurdles, due, in part, to offering new portable, bedside, and accessible devices. The current JBO special issue highlights promising activities and examples of translational biophotonics from leading laboratories around the world. We identify common essential features of successful clinical translation by examining the origins and activities of three major international academic affiliated centers with beginnings traceable to the mid-late 1970s: The Wellman Center for Photomedicine (Mass General Hospital, USA), the Beckman Laser Institute and Medical Clinic (University of California, Irvine, USA), and the Medical Laser Center Lübeck at the University of Lübeck, Germany. Major factors driving the success of these programs include visionary founders and leadership, multidisciplinary research and training activities in light-based therapies and diagnostics, diverse funding portfolios, and a thriving entrepreneurial culture that tolerates risk. We provide a brief review of how these three programs emerged and highlight critical phases and lessons learned. Based on these observations, we identify pathways for encouraging the growth and formation of similar programs in order to more rapidly and effectively expand the impact of biophotonics and biomedical optics on human health.

In-vivo retinal imaging with off-axis full-field time-domain optical coherence tomography.

With a simple setup, mainly composed of a low coherence light source and a camera, full-field optical coherence tomography (FF-OCT) allows volumetric tissue imaging. However, fringe washout constrains its use in retinal imaging. Here, we present a novel motion-insensitive approach to FF-OCT, which introduces path-length differences between the reference and the sample light in neighboring pixels using an off-axis reference beam. The temporal carrier frequency in scanned time-domain OCT is replaced by a spatial carrier frequency. Volumetric in-vivo FF-OCT measurements of the human retina were acquired in only 1.3 s, comparable to the acquisition times of current clinically used OCT devices.