Dual band dual focus optical coherence tomography for imaging the whole eye segment

We developed an improved dual band dual focus spectral domain optical coherence tomography (SD-OCT) for in vivo 2D/3D imaging of the whole eye segment, including the whole anterior segment and retina. The system featured two OCT channels with two different bands centered at 840 nm and 1050 nm, which were designed to image the retina and the anterior segments of the eye, respectively. By combing the two probe light beams for co-axial scanning and separating them for focusing at different segments of the eye with a combination of three dichroic mirrors, we not only minimized the loss of the backscattered light from the sample but also improved the imaging depth, scan range and resolution. The full resolved complex (FRC) method was applied to double the imaging depth for the whole anterior segment imaging, with which an imaging depth of 36.71 mm in air was achieved. We demonstrated that this system was capable of measuring the dynamic changes of ocular dimensions, including the asphericity of the cornea and lens, during accommodation.OCIS codes: (110.4500) Optical coherence tomography, (330.7322) Visual optics, accommodation, (170.3880) Medical and biological imaging, (170.4460) Ophthalmic optics and devices, (170.4470) Ophthalmology, (170.4500) Optical coherence tomography     

Imaging and full-length biometry of the eye during accommodation using spectral domain OCT with an optical switch

An optical switch was implemented in the reference arm of an extended depth SD-OCT system to sequentially acquire OCT images at different depths into the eye ranging from the cornea to the retina. A custom-made accommodation module was coupled with the delivery of the OCT system to provide controlled step stimuli of accommodation and disaccommodation that preserve ocular alignment. The changes in the lens shape were imaged and ocular distances were dynamically measured during accommodation and disaccommodation. The system is capable of dynamic in vivo imaging of the entire anterior segment and eye-length measurement during accommodation in real-time.     

Simultaneous real-time imaging of the ocular anterior segment including the ciliary muscle during accommodation

We demonstrated a novel approach of imaging the anterior segment including the ciliary muscle using combined and synchronized two spectral domain optical coherence tomography devices (SD-OCT). In one SD-OCT, a Complementary Metal-Oxide-Semiconductor Transistor (CMOS) camera and an alternating reference arm was used to image the anterior segment from the cornea to the lens. Another SD-OCT for imaging the ciliary muscle was equipped with a light source with a center wavelength of 1,310 nm and a bandwidth of 75 nm. Repeated measurements were performed under relaxed and 4.00 D accommodative stimulus states in six eyes from 6 subjects. We also imaged dynamic changes in the anterior segment in one eye during accommodation. The biometry of the anterior segment and the ciliary muscle was obtained. The combined system appeared to be capable to simultaneously real-time image the biometry of the anterior segment, including the ciliary muscle, in vivo during accommodation.OCIS codes: (170.4500) Optical coherence tomography, (170.3880) Medical and biological imaging, (170.4580) Optical diagnostics for medicine, (330.4460) Ophthalmic optics and devices, (330.7322) Visual optics, accommodation     

Retinal, anterior segment and full eye imaging using ultrahigh speed swept source OCT with vertical-cavity surface emitting lasers

We demonstrate swept source OCT utilizing vertical-cavity surface emitting laser (VCSEL) technology for in vivo high speed retinal, anterior segment and full eye imaging. The MEMS tunable VCSEL enables long coherence length, adjustable spectral sweep range and adjustable high sweeping rate (50–580 kHz axial scan rate). These features enable integration of multiple ophthalmic applications into one instrument. The operating modes of the device include: ultrahigh speed, high resolution retinal imaging (up to 580 kHz); high speed, long depth range anterior segment imaging (100 kHz) and ultralong range full eye imaging (50 kHz). High speed imaging enables wide-field retinal scanning, while increased light penetration at 1060 nm enables visualization of choroidal vasculature. Comprehensive volumetric data sets of the anterior segment from the cornea to posterior crystalline lens surface are also shown. The adjustable VCSEL sweep range and rate make it possible to achieve an extremely long imaging depth range of ~50 mm, and to demonstrate the first in vivo 3D OCT imaging spanning the entire eye for non-contact measurement of intraocular distances including axial eye length. Swept source OCT with VCSEL technology may be attractive for next generation integrated ophthalmic OCT instruments.OCIS codes: (110.4500) Optical coherence tomography, (120.4640) Optical instruments, (140.3600) Lasers, tunable, (170.4460) Ophthalmic optics and devices, (170.4470) Ophthalmology     

High-resolution 1050 nm spectral domain retinal optical coherence tomography at 120 kHz A-scan rate with 6.1 mm imaging depth

We report a newly developed high speed 1050nm spectral domain optical coherence tomography (SD-OCT) system for imaging posterior segment of human eye. The system is capable of an axial resolution at ~10 µm in air, an imaging depth of 6.1 mm in air, a system sensitivity fall-off at ~6 dB/3mm and an imaging speed of 120,000 A-scans per second. We experimentally demonstrate the system’s capability to perform phase-resolved imaging of dynamic blood flow within retina, indicating high phase stability of the SDOCT system. Finally, we show an example that uses this newly developed system to image posterior segment of human eye with a large view of view (10 × 9 mm²), providing detailed visualization of microstructural features from anterior retina to posterior choroid. The demonstrated system parameters and imaging performances are comparable to those that a typical 1 µm swept source OCT would deliver for retinal imaging.OCIS codes: (170.4460) Ophthalmic optics and devices, (170.3880) Medical and biological imaging, (170.4500) Optical coherence tomography     

Drug-induced toxic reactions in the eye: an overview.

Every drug can produce untoward consequences, even when used according to standard or recommended methods of administration. Adverse drug reactions can involve every organ and system of the body, even the eye, and frequently are mistaken for signs of underlying disease. Reactions in the eye may involve the eyelids, periorbital tissues, lacrimal apparatus, conjunctiva, cornea, lens, iris, ciliary body, intraocular pressure, retina, optic nerve, and ocular movement. In addition, fetal abnormalities can be caused by the use of eye drugs during pregnancy. Topical ophthalmic therapies or the use of ophthalmic dyes may cause systemic reactions. This article reviews drugs used systemically or topically that may cause adverse effects in the eye and related structures. Adverse ocular reactions to medications create an important health problem, and nursing professionals in close contact with patients inside and outside the hospital must assume a role in detecting them early, identifying them, educating the patient about them, and treating them.     

Calculation of crystalline lens power using a modification of the Bennett method

We present a method for measuring lens power from extended depth OCT biometry, corneal topography, and refraction using an improvement on the Bennett method. A reduced eye model was used to derive a formula for lens power in terms of ocular distances, corneal power, and objective spherical equivalent refraction. An error analysis shows that the formula predicts relaxed lens power with a theoretical accuracy of ± 0.5 D for refractive error ranging from −10 D to + 10 D. The formula was used to calculate lens power in 16 eyes of 8 human subjects. Mean lens power was 24.3 D ± 1.7 D.OCIS codes: (170.4500) Optical coherence tomography, (170.4580) Optical diagnostics for medicine, (330.7325) Visual optics, metrology, (330.7326) Visual optics, modeling     

Therapy of neurotrophic keratopathy in trigeminal schwannoma with radiosurgery

BACKGROUND: We present a patient with neurotrophic keratopathy due to a trigeminal nerve neurinoma, who was successfully treated by radiosurgery. PATIENT: A patient was referred to us with recurrent corneal erosions of unknown origin in his left eye. In addition, he suffered from mild hypoesthesia in the distribution of the first branch of the trigeminal nerve. He was started on topical lubricants (hyaluronic acid 0.5%) and antibiotic ointments (gentamycin), but since no corneal healing occurred, a soft contact lens was applied. The patient developed severe corneal neovascularization within four weeks and the contact lens had to be removed. Three months later an MRI scan was performed, which showed an intracranial tumor originating from the first branch of the trigeminal nerve. Neurinoma of the trigeminal nerve was suspected, and this presumed diagnosis was confirmed by fine needle biopsy. The patient underwent radiosurgery seven weeks later. The epithelium closed, the cornea recovered and stayed stable until the last examination 18 months after radiosurgery. CONCLUSION: Radiosurgery is a promising alternative to conventional microsurgery in cases of neurinomas of the trigeminal nerve including neurotrophic keratopathy, to keep or restore vision.     

Periscope for noninvasive two-photon imaging of murine retina in vivo

Two-photon microscopy allows visualization of subcellular structures in the living animal retina. In previously reported experiments it was necessary to apply a contact lens to each subject. Extending this technology to larger animals would require fitting a custom contact lens to each animal and cumbersome placement of the living animal head on microscope stage. Here we demonstrate a new device, periscope, for coupling light energy into mouse eye and capturing emitted fluorescence. Using this periscope we obtained images of the RPE and their subcellular organelles, retinosomes, with larger field of view than previously reported. This periscope provides an interface with a commercial microscope, does not require contact lens and its design could be modified to image retina in larger animals.OCIS codes: (170.0110) Imaging systems, (170.4460) Ophthalmic optics and devices, (170.5755) Retina scanning, (180.4315) Nonlinear microscopy, (330.7327) Visual optics, ophthalmic instrumentation     

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).OCIS codes: (110.4500) Optical coherence tomography, (120.6650) Surface measurements, figure, (110.6880) Three-dimensional image acquisition, (100.2960) Image analysis, (330.7327) Visual optics, ophthalmic instrumentation, (330.7322) Visual optics, accommodation, (330.7323) Visual optics, aging changes     

Contact lenses for continuous corneal temperature monitoring

Temperature variation is a ubiquitous medical sign to monitor ocular conditions including dry eye disease (DED), glaucoma, carotid artery stenosis, diabetic retinopathy, and vascular neuritis. The ability to measure OST in real time is desirable in point-of-care diagnostics. Here, we developed minimally invasive contact lens temperature sensors for continuous monitoring of the corneal temperature. The contact lens sensor consisted of a laser patterned commercial contact lens embedding temperature-sensitive Cholesteric Liquid Crystals (CLCs), which exhibited a fully reversible temperature-dependent color change in the visible spectrum. The contact lens allowed the corneal temperature to be mapped in four key areas, at distances of 0.0, 1.0, 3.0, and 5.0 mm from the pupil''s edge. Liquid crystals exhibited a wavelength shift from 738 ± 4 nm to 474 ± 4 nm upon increasing the temperature from 29.0 °C to 40.0 °C, with a time responsivity of 490 ms and a negligible hysteresis. Readouts were performed using a smartphone, which output RGB triplets associated to temperature values. Contact lens sensors based on CLCs were fitted and tested on an ex vivo porcine eye and readouts were compared with infrared thermal measurements, resulting in an average difference of 0.3 °C.

Temperature variation is a ubiquitous medical sign to monitor ocular conditions including dry eye disease (DED), glaucoma, carotid artery stenosis, diabetic retinopathy, and vascular neuritis.     

Ocular ketone reductase distribution and its role in the metabolism of ocularly applied levobunolol in the pigmented rabbit

The distribution of ketone reductase activity in the anterior segment tissues of the pigmented rabbit eye and its influence on the ocular metabolism of topically applied levobunolol were studied. A reversed phase high-performance liquid chromatography procedure was used to assay for this drug and its metabolite, dihydrolevobunolol. Ocular ketone reductase activity was 3 to 4 times more dependent on NADPH than on NADH. The rank order of activity was corneal epithelium greater than iris-ciliary body greater than conjunctiva greater than lens. No activity was detected in the tears, corneal stroma, sclera or aqueous humor. Ketone reductase activity was entirely cytosolic. The pigmented rabbit was significantly less active than the albino rabbit in ketone reductase. Its activity in the corneal epithelium, iris-ciliary body and lens was most sensitive to inhibition by quercetin, whereas that in the conjunctiva was most sensitive to metyrapone. The ketone reductase in the corneal epithelium contributed more to the metabolism of topically applied levobunolol than its counterpart in the iris-ciliary body and lens. Moreover, the extent of levobunolol metabolism both during and after corneal penetration was dose-dependent. Overall, these findings indicate that ocularly applied drugs containing the ketone functional group are subject to varying degrees of metabolism by NADPH-dependent ketone reductases in the corneal epithelium, iris-ciliary body and lens.     

Keratopathy of multiple myeloma masquerading as corneal crystals of ocular cystinosis

We describe a 49-year-old woman in whom ocular cystinosis was diagnosed on the basis of a routine eye examination 12 years previously. Conjunctival biopsy was reported to support the diagnosis. The patient described photophobia for the past 5 years and reported a 2-fold increase in her serum IgG level for the past 12 years. On ophthalmic examination, corneal crystals were evident in the epithelium and superficial stromal layers, rather than throughout the corneal epithelium and the entire stroma as in ocular cystinosis. The patient's serum protein level was elevated at 8.7 g/dL; protein electrophoresis showed an elevated gamma-globulin peak, and the IgG level was twice that of normal at 2820 mg/dL. Bone marrow biopsy confirmed the diagnosis of multiple myeloma. This case illustrates that multiple myeloma can mimic corneal findings of cystinosis.     

Portable boom-type ultrahigh-resolution OCT with an integrated imaging probe for supine position retinal imaging

To expand the clinical applications and improve the ease of use of ultrahigh-resolution optical coherence tomography (UHR-OCT), we developed a portable boom-type ophthalmic UHR-OCT operating in supine position that can be used for pediatric subjects, bedridden patients and perioperative conditions. By integrating the OCT sample arm probe with real-time iris display and automatic focusing electric lens for easy alignment, coupling the probe on a self-locking multi-directional manipulator to reduce motion artifacts and operator fatigue, and installing the OCT module on a moveable cart for system mobility, our customized portable boom-type UHR-OCT enables non-contact, high-resolution and high-stability retinal examinations to be performed on subjects in supine position. The spectral-domain UHR-OCT operates at a wavelength of 845 nm with 130 nm FWHM (full width at half maximum) bandwidth, achieving an axial resolution of ≈2.3µm in tissue with an A-line acquisition rate up to 128 kHz. A high-definition two-dimensional (2D) raster protocol was used for high-quality cross-sectional imaging while a cube volume three-dimensional (3D) scan was used for three-dimensional imaging and en-face reconstruction, resolving major layer structures of the retina. The feasibility of the system was demonstrated by performing supine position 2D/3D retinal imaging on healthy human subjects, sedated infants, and non-sedated awake neonates.     

In vivo three-dimensional characterization of the adult zebrafish brain using a 1325 nm spectral-domain optical coherence tomography system with the 27 frame/s video rate

In this study, a spectral-domain optical coherence tomography (SD-OCT) system was used for noninvasive imaging of the adult zebrafish brain. Based on a 1325 nm light source and two high-speed galvo mirrors, our SD-OCT system can offer a large field of view of brain morphology with high resolution (12 μm axial and 13 μm lateral) at video rate (27 frame/s). In vivo imaging of both the control and injured brain was performed using adult zebrafish model. The recovered results revealed that olfactory bulb, optic commissure, telencephalon, tectum opticum, cerebellum, medulla, preglomerular complex and posterior tuberculum could be clearly identified in the cross-sectional SD-OCT images of the adult zebrafish brain. The reconstructed results also suggested that SD-OCT can be used for diagnosis and monitoring of traumatic brain injury. In particular, we found the reconstructed volumetric SD-OCT images enable a comprehensive three-dimensional characterization of the control or injured brain in the intact zebrafish.OCIS codes: (170.3880) Medical and biological imaging, (110.4500) Optical coherence tomography, (170.0110) Imaging systems     

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).OCIS codes: (110.4500) Optical coherence tomography, (120.6650) Surface measurements, figure, (120.4640) Optical instruments, (120.4800) Optical standards and testing, (110.6880) Three-dimensional image acquisition, (330.7327) Visual optics, ophthalmic instrumentation     

角膜绷带镜提高翼状胬肉患者术后舒适度的效果观察

目的探讨翼状胬肉患者术后佩戴角膜绷带镜对舒适度的改善情况。方法将100例行翼状胬肉切除联合角膜缘干细胞移植的单眼原发性翼状胬肉患者,按随机数字表分为对照组和观察组各50例,对照组给予常规护理,观察组在常规护理基础上应用角膜绷带镜,对患者术后眼部不适症状进行问卷量表评分,比较眼部疼痛程度,观察角膜创面愈合情况。结果观察组患者的刺激感、烧灼感、眼部刺痛、流泪、睁眼困难等不舒适症状评分均低于对照组,差异具有统计学意义(P0.001);观察组患者术后眼部疼痛程度较轻,差异有统计学意义(P0.05);观察组术后2 d内角膜创面愈合者32例(64%),3 d内愈合者18例(36%),对照组2 d内角膜创面愈合者16例(32%),3 d内愈合者34例(68%),两组比较差异有统计学意义(P0.05),观察组所用时间较短。结论联合角膜绷带镜的综合护理措施可以显著减轻翼状胬肉切除联合自体角膜缘移植术后患者眼部诸多不适症状和疼痛,促进角膜创面愈合。     

Micrometer axial resolution OCT for corneal imaging

An optical coherence tomography (OCT) for high axial resolution corneal imaging is presented. The system uses 375 nm bandwidth (625 to 1000 nm) from a broadband supercontinuum light source. The system was developed in free space to minimize image quality degradation due to dispersion. A custom-designed spectrometer based on a Czerny Turner configuration was implemented to achieve an imaging depth of 1 mm. Experimentally measured axial resolution was 1.1 μm in corneal tissue and had a good agreement with the theoretically calculated resolution from the envelope of the spectral interference fringes. In vivo imaging was carried out and thin corneal layers such as the tear film and the Bowman's layer were quantified in normal, keratoconus, and contact lens wearing eyes, indicating the system's suitability for several ophthalmic applications.     

Optical phase modulation by natural eye movements: application to time-domain FF-OCT image retrieval

Eye movements are commonly seen as an obstacle to high-resolution ophthalmic imaging. In this context we study the natural axial movements of the in vivo human eye and show that they can be used to modulate the optical phase and retrieve tomographic images via time-domain full-field optical coherence tomography (TD-FF-OCT). This approach opens a path to a simplified ophthalmic TD-FF-OCT device, operating without the usual piezo motor-camera synchronization. The device demonstrates in vivo human corneal images under the different image retrieval schemes (2-phase and 4-phase) and different exposure times (3.5 ms, 10 ms, 20 ms). Data on eye movements, acquired with a spectral-domain OCT with axial eye tracking (180 B-scans/s), are used to study the influence of ocular motion on the probability of capturing high-signal tomographic images without phase washout. The optimal combinations of camera acquisition speed and amplitude of piezo modulation are proposed and discussed.     

Potential long-term inhibition of ocular neovascularisation by recombinant adeno-associated virus-mediated secretion gene therapy

Neovascularisation (NV) within the eye often results in visual loss. Vascular endothelial growth factor (VEGF) has been implicated in the development of ocular NV. Previous studies have shown that VEGF antagonists successfully suppressed retinal and choroidal NV in animal models. However, the systemic approach and transient nature of the delivery systems used in these studies hinder therapeutic application. To achieve stable and localised ocular anti-angiogenic therapy, we explored the use of recombinant adeno-associated virus (rAAV)-mediated secretion gene therapy (SGT). In this study, we generated a rAAV vector encoding soluble VEGF receptor 1, sFlt-1 (AAV-CMV.sflt) and determined its ability to inhibit cautery-induced corneal NV and laser-induced choroidal NV. Delivery of AAV-CMV.sflt into the anterior chamber resulted in transgene expression in the iris pigment epithelium and corneal endothelium, which reduced the development of corneal NV in the stroma of cauterised rats by 36% compared with cauterised control groups (P = 0.009). Subretinal delivery of AAV-CMV.sflt near the equator of the eye also suppressed choroidal NV at the laser lesions around the optic nerve by 19% (P = 0.002), indicating that there was diffusion of the secreted anti-angiogenic protein across the retina. Both results suggest that the long-term suppression of ocular NV is possible through the use of stable rAAV-mediated SGT.