Search

Objective: To demonstrate optical coherence tomography for high-resolution, noninvasive imaging of the human retina. Optical coherence tomography is a new imaging technique analogous to ultrasound B scan that can provide cross-sectional images of the retina with micrometer-scale resolution. Design: Survey optical coherence tomographic examination of the retina, including the macula and optic nerve head in normal human subjects. Setting: Research laboratory. Participants: Convenience sample of normal human subjects. Main Outcome Measures: Correlation of optical coherence retinal tomographs with known normal retinal anatomy. Results: Optical coherence tomographs can discriminate the cross-sectional morphologic features of the fovea and optic disc, the layered structure of the retina, and normal anatomic variations in retinal and retinal nerve fiber layer thicknesses with 10-??m depth resolution. Conclusion: Optical coherence tomography is a potentially useful technique for high depth resolution, cross-sectional examination of the fundus.

Objective: To demonstrate a new diagnostic technique, optical coherence tomography, for highresolution cross-sectional imaging of structures in the anterior segment of the human eye in vivo. Optical coherence tomography is a new, noninvasive, noncontact optical imaging modality that has spatial resolution superior to that of conventional clinical ultrasonography ( 90 dB). Design: Survey of intraocular structure and dimension measurements. Setting: Laboratory. Patients: Convenience sample. Main Outcome Measures: Correlation with range of accepted normal intraocular structure profiles and dimensions. Results: Direct in vivo measurements with micrometer-scale resolution were performed of corneal thickness and surface profile (including visualization of the corneal epithelium), anterior chamber depth and angle, and iris thickness and surface profile. Dense nuclear cataracts were successfully imaged through their full thickness in a cold cataract model in calf eyes in vitro. Conclusions: Optical coherence tomography has potential as a diagnostic tool for applications in noncontact biometry, anterior chamber angle assessment, identification and monitoring of intraocular masses and tumors, and elucidation of abnormalities of the cornea, iris, and crystalline lens.

Objective: Excimer photorefractive keratectomy is a promising method to reduce myopia. We evaluated the effectiveness, predictability, stability, and safety of photorefractive keratectomy performed by two surgeons at a single site with a 1-year follow-up. Methods: An excimer laser (Summit Excimed UV200, Summit Technology, Waltham, Mass) was used to treat 47 eyes. Preoperative uncorrected visual acuity averaged 20/277 and ranged from 20/60 to 20/500. Spherical equivalent averaged −3.9 diopters and ranged from −1.5 to −6.1 D. Results: One year postoperatively, best corrected visual acuity averaged 20/13 and ranged from 20/10 to 20/20. No patients lost any of best corrected visual acuity. The uncorrected visual acuity at 1 year averaged 20/20 and ranged from 20/10 to 20/200. Ninety-four percent of eyes had an uncorrected visual acuity of 20/40 or better; 83%, 20/25 or better; and 74%, 20/20 or better. An initial hyperopic overcorrection is followed by gradual regression to emmetropia during a 12-month period. Refractive spherical equivalent averaged 0.44 D and ranged from −3 to +2.6 D at 1 year. The proportion of eyes within I D of emmetropia was 80% at 1 year. The most significant shifts in refraction occurred between the first and second months, but small shifts occurred up to 12 months. Subgrouping the results according to age revealed a significantly greater effect with larger residual hyperopia in those older than 40 years. Patient satisfaction with the procedure was high. Conclusion: During a 1-year period, excimer photorefractive keratectomy appears to be an effective, predictable, stable, and safe method to reduce myopia. Age may play a role in the effectiveness of the procedure, with greater hyperopia resulting in those older than 40 years.

Background: In more than 50% of eyes with idiopathic, full-thickness macular holes, vitrectomy results in clinical closure of the hole and improvement in visual acuity. Other than cataract formation, late complications of the procedure have not been reported. Methods: Over a 4-year period, 167 eyes underwent successful vitreous surgery for idiopathic macular holes documented by clinical closure of the hole and an improvement in visual acuity of at least two Snellen lines. The authors retrospectively studied eight of these eyes. All initially had successful surgery; however, they subsequently had spontaneous late re-opening of the macular hole with acute diminution in vision. Results: Late re-opening developed in these eyes between 2 and 22 months after initial surgery. The mean time for re-opening was 12.5 months. Three of eight eyes underwent a second vitrectomy, which was successful in improving visual acuity in two eyes. Another patient manifested the growth of an epiretinal membrane that apparently sealed the re-opened macular hole and improved vision. Conclusion: Late re-opening can complicate initially successful macular hole surgery and may occur in at least 4.8% (8 of 167) of initially successful operations. Re-opening has been documented as late as 22 months after initial surgery. Repeat vitrectomy with gas injection may result in reclosure of the hole and improvement in vision.

We used benzoporphyrin derivative-monoacid (BPD-MA), a new photosensitizing agent, in photodynamic therapy (PDT) to occlude choroidal vessels in the rabbit. Using BPD-MA, seven dutch-belted rabbit eyes were photodynamically treated to achieve acute choroidal vessel closure. Fundoscopy, fluorescein angiography (FA), and histology were performed 1 hour, 1 day, 3 days, 7 days, 14 days, 21 days, and 28 days after PDT. On FA, PDT-treated spots remained nonperfused until day 3 when gradual reperfusion from the periphery began to appear. By day 28 the area of PDT appeared completely reperfused. Histology of lesions showed acute damage to choroidal vascular endothelial cells and retinal pigment epithelial (RPE) cells. Over subsequent days, recovery of RPE cells and regeneration of large choroidal vascular endothelial cells occurred. In addition, retinal degeneration occurred gradually over the 28 days of follow-up. Since current argon laser therapy of retinal neovascularization causes immediate retinal damage, the ability to occlude choroidal vessels without inducing acute thermal damage holds promise for treating clinical pathologic conditions that feature abnormal neovascularization, such as age-related macular degeneration and diabetic retinopathy.

Dye-enhanced diode laser photocoagulation, using the dye indocyanine green (ICG), has shown some potential in the treatment of choroidal neovascularizations (CNV). A diode laser system was developed and optimized to emit at the absorption maximum of ICG. In a clinical study at two retinal centers, more than 70 patients, the majority of which had age-related macular degeneration, were treated. Eighteen cases with ill-defined subfoveal CNV were followed an average of 11 months after laser treatment. The results show success in resolving the CNV with an average long-term preservation of visual function equal to or superior to data provided by the Macular Photocoagulation Study for confluent burns of low intensity applied to the CNV. Details of the technique and discussion of the controversies inherent in such a treatment strategy will be presented.© (1994) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

Endoscopic laser dacryocystorhinostomy (DCR) enables an obstructed lacrimal sac to be opened through an intranasal approach, avoiding the need for a skin incision. The holmium:yttrium aluminum garnet (holmium:YAG) laser is well-suited for this procedure because of its properties of fiberoptic delivery, effective bone cutting, and precise soft-tissue coagulation. Efficient bone ablation is particularly important for primary DCR which requires removal of relatively thick bone along the lateral nasal wall to expose the lacrimal sac. Forty-six endoscopic laser DCRs were performed on 40 patients. There were no intraoperative or postoperative complications. The surgery successfully relieved lacrimal obstruction in 85% of patients. Endoscopic instrumentation allowed for the rapid identification and correction of intranasal causes of DCR failure, including ethmoid sinus disease and middle turbinate hypertrophy. Endoscopic laser DCR appears to be a safe and effective procedure which should be considered as an alternative to external DCR for the surgical treatment of nasolacrimal duct obstruction.

Chloro-aluminum sulfonated phthalocyanine (CASPc) is a photo-chemically active dye employed in photodynamic therapy (PDT). CASPc is a potent generator of singlet oxygen when irradiated with 675 nm light and is also capable of fluorescence, allowing visualization of the dye in tissues. We devised an angiography system using CASPc fluorescence to determine its localization in experimental choroidal neovascularization in monkeys and then investigated the ability of CASPc to produce photochemical closure of neovascularization upon irradiation with 675nm laser light. Fluorescent imaging indicated that CASPc localized angiographically in areas of neovascularization for at least 24 hours. Irradiation with 675 nm laser light 5-30 minutes after CASPc injection produced complete closure of choroidal neovascularization with minimal damage to overlying retina. We conclude that CASPc localizes in neovascular choroidal vessels and that CASPc photodynamic therapy can produce closure of these choroidal vessels.

Er-YAG (2.9 microns, 200 microseconds pulsewidth) and Ho-YAG (2.12 microns, 250 microseconds pulsewidth) lasers were used to irradiate bovine crystalline lenses. Mass ablated increased with increasing fluence for both lasers and was greater for the Er-YAG than the Ho-YAG laser at all fluences. The mass loss vs. fluence curve was nonlinear for the Er-YAG and linear for the Ho-YAG laser. Ablation threshold was lower for the Er-YAG. Grossly, the Er-YAG laser produced less charring and expressed fewer, smaller tissue pieces than the Ho-YAG. Scanning electron microscopy indicated that the Er-YAG produced smoother walled craters. The Ho-YAG laser produced more dessicated and disrupted craters. The Er-YAG radiation, delivered by fiberoptic probes, may provide a method of performing minimally invasive cataract surgery.

The ultimate goal of the study is to provide an imaging tool to detect the earliest signs of glaucoma before clinically visible damage occurs to the retinal nerve fiber layer (RNFL). Studies have shown that the optical reflectance of the damaged RNFL at short wavelength (560 nm) is reduced much more than that at long wavelength, which provides spectral contrast for imaging the earliest damage to the RNFL. To image the spectral contrast we built a dual-band spectral-domain optical coherence tomography (SD-OCT) centered at 808 nm (NIR) and 415 nm (VIS). The light at the two bands was provided by the fundamental and frequency-doubled outputs of a broadband Ti:Sapphire laser. The depth resolution of the NIR and VIS OCT systems are 4.7 µm and 12.2 µm in the air, respectively. The system was applied to imaging the rat retina in vivo. Significantly different appearances between the OCT cross sectional images at the two bands were observed. The ratio of the light reflected from the RNFL over that reflected from the entire retina at the two bands were quantitatively compared. The experimental results showed that the dual-band OCT system is feasible for imaging the spectral contrasts of the RNFL.

Techniques for non-invasive biomedical imaging include nuclear magnetic resonance, ultrasound, positron emission tomography, x-ray computed to- mography, and optical transillumination. Each of these methods has dif- ferent advantages and limitations and has found particular applications in medicine. Optical imaging of tissue offers the potential of a non-invasive diagnostic with non-ionizing radiation and the possibility of using spectro- scopic properties to distinguish tissue type and probe metabolic function.

We present a new technique for coherent optical imaging of ocular structure based on optical coherence tomography (OCT). OCT is a noncontact, noninvasive, tomographic imaging technique with superior spatial resolution to ultrasound (< 20 micrometers ) and high sensitivity (100 dB dynamic range). We have used OCT to perform direct imaging of ocular structure in the anterior and posterior segments of human eyes in vitro and in vivo. In the anterior segment, we have measured corneal thickness and profile, anterior chamber depth and angle, and iris thickness and profile. These and other possible measurements have potential applications in diagnosis of pathologies of the cornea, angle, and iris, as well as in noncontact biometry for applications in cataract and corneal refractive surgeries. In the posterior segment, we have obtained high-resolution images of retinal structure in human subjects in vivo. These images demonstrate higher resolution than available with any other existing technique, and include characterization of optic disk morphology and topology. These measurements have potential applications in early diagnosis and assessment of glaucoma and other retinal diseases.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

We investigated the feasibility of simultaneously imaging two distinctive molecular contrasts provided by the absorbed photons in biological tissues with a single light source. The molecular contrasts are based on two physical effects induced by the absorbed photons: photoacoustics (PA) and autofluorescence (AF). In an integrated multimodal imaging system, the PA and AF signals were detected by a high-sensitivity ultrasonic transducer and an avalanche photodetector, respectively. The system was tested by imaging ocular tissue samples, including the retinal pigment epithelium and the ciliary body. The acquired images provided information on the spatial distributions of melanin and lipofuscin in these samples.

We have developed an adaptive optics photoacoustic microscope (AO-PAM) for high-resolution imaging of biological tissues, especially the retina. To demonstrate the feasibility of AO-PAM we first designed the AO system to correct the wavefront errors of the illuminating light of PAM. The aberrations of the optical system delivering the illuminating light to the sample in PAM was corrected with a close-loop AO system consisting of a 141-element MEMS-based deformable mirror (DM) and a Shack-Hartmann (SH) wavefront sensor operating at 15 Hz. The photoacoustic signal induced by the illuminating laser beam was detected by a custom-built needle ultrasonic transducer. When the wavefront errors were corrected by the AO system, the lateral resolution of PAM was measured to be better than 2.5 µm using a low NA objective lens. We tested the system on imaging ex vivo ocular samples, e.g., the ciliary body and retinal pigment epithelium (RPE) of a pig eye. The AO-PAM images showed significant quality improvement. For the first time we were able to resolve single RPE cells with PAM.

Since the photoacoustic effect relies only on the absorbed optical energy, the back-reflected photons from samples in optical-resolution photoacoustic microscopy are usually discarded. By employing a 2 x 2 single-mode fiber optical coupler in a laser-scanning optical-resolution photoacoustic microscope for delivering the illuminating laser light and collecting the back reflected photons, a fiber-optic confocal microscope is integrated with the photoacoustic microscope. Thus, simultaneous multimodal imaging can be achieved with a single light source and images from the two modalities are intrinsically registered. Such capabilities are demonstrated in imaging both phantoms and small animals in vivo.

Optical coherence tomography (OCT) has traditionally been used in the outpatient environment as an important diagnostic tool for retinal clinical decision making. Recent advances in OCT technology have made intraoperative use of OCT feasible. [Ophthalmic Surg Lasers Imaging 2010;41:6.]

The authors performed digital indocyanine-green angiography in 37 patients with chorioretinal disorders. Eighteen patients had choroidal neovascutarization, 7 patients had atrophic age-related maculopathy, and 12 patients had uncommon choroidal and retinal disorders. A Topcon indocyanine-green camera was integrated with a digital (1024-line resolution) angiography system. Compared with conventional video or photographic indocyanine-green angiography, this technique offers enhanced image resolution, the possibility of direct qualitative comparison with fluorescein angiography, image archiving, hard-copy generation, and tracing capabilities to plan laser treatment strategies and monitor the adequacy of laser therapy after surgery.

We have developed a laser-scanning optical-resolution photoacoustic microscopy that can potentially be easily integrated with several existing optical microscopic modalities. During data acquisition, the ultrasonic transducer is kept stationary and only the laser light is raster-scanned by an x-y galvanometer scanner. In this configuration, the field-ofview is limited by the beam diameter of the ultrasonic detector, which is related to the active element size, numerical aperture, and the center frequency of the ultrasonic transducer. The spatial resolution is determined by the size of the optical focus. A lateral resolution of 7.8 μm and a circular field-of-view with a diameter of 6 mm were achieved in an optically clear medium. Using a laser system working at a pulse repetition rate of 1024 Hz, the data acquisition time for an image consisting of 256×256 pixels was less than two minutes. In vivo imaging of microvasculature in mouse ears were also achieved.

We have successfully imaged the retinal tumor in a mouse model using an ultra-high resolution spectral-domain optical coherence tomography (SD-OCT) designed for small animal retinal imaging. For segmentation of the tumor boundaries and calculation of the tumor volume, we developed a novel segmentation algorithm. The algorithm is based on parametric deformable models (active contours) and is driven by machine learning-based region classification, namely a Conditional Random Field. With this algorithm we are able to obtain the tumor boundaries automatically, while the user can specify additional constraints (points on the boundary) to correct the segmentation result, if needed. The system and algorithm were successfully applied to studies on retinal tumor progression and monitoring treatment effects quantitatively in a mouse model of retinoblastoma.

• We investigated the effects of semiconductor diode laser contact transscleral cyclophotocoagulation in human cadaver eyes by gross examination, light microscopy, and scanning electron microscopy to determine optimum clinical treatment parameters. Irradiation was performed using a continuous-wave semiconductor diode laser with a fiber-optic probe. At 1.0 to 1.25 mm posterior to the limbus, spots were centered on the pars plicata by gross examination. Exposures of less than 2 J produced no visible damage. A 2- to 3-J exposure produced mild whitening of the ciliary processes, while 4- to 5-J exposures created more intense whitening of the pars plicata. Energies higher than 5 J frequently produced explosive tissue damage. Light microscopy of tissue treated with 1.8 to 6 J at 1.0 to 1.25 mm posterior to the limbus revealed coagulation necrosis of the nonpigmented and pigmented epithelium, with evidence of thermal coagulation of the ciliary stroma and stromal vasculature. Coagulation necrosis was more intense with longer exposure times. We found the optimum parameters for contact transscleral diode laser cyclophotocoagulation in cadaver eyes to be 3 to 4.5 J of energy delivered with the anterior edge of the probe 1.0 to 1.25 mm posterior to the limbus.

The authors successfully performed clinical transpupillary retinal photocoagulation in 30 eyes of 26 patients with retinal vascular disease using a gall ium-aluminum-arsenide (GaAIAs) diode laser emitting at 805 nm. Retinal photocoagulation was performed at treatment powers of 300 to 1300 mW and exposure durations of 0.2 to 0.5 seconds with a 200-µm diameter treatment spot. Patients treated with both diode and argon green lasers required 4.5 ± 1.8 times greater mean laser energy with diode compared with argon to create ophthalmoscopically similar lesions. Parallel experimental retinal photocoagulation in Chinchilla rabbits required 3.1 ± 0.9 times more power to create ophthalmoscopically similar lesions with the diode laser than with the argon laser. Intraoperative subretinal hemorrhage occurred rarely in patients with an incidence of 4 (0.044%) of 9021 treatment spots. Patients complained of moderate-tomarked pain in 10 (43%) of 23 treatments initiated under topical anesthesia. A transpupillary diode laser may be used clinically to perform therapeutic retinal photocoagulation.

Acute and long-term effects of contact transscleral semiconductor diode laser cyclophotocoagulation were studied in rabbits. Immediately following cyclophotocoagulation, light microscopy revealed coagulation necrosis of the ciliary pigmented and nonpigmented epithelia and stroma; destruction increased in relation to power. There was architectural disruption with higher energy levels. The findings with diode and continuous-wave contact neodymium-YAG lasers were similar. In rabbits treated and followed up for 6 weeks there was a decrease in intraocular pressure during the observation period (P less than .05, paired Student's t test). The gross and light microscopic examination revealed focal atrophy and fibrosis of the ciliary processes, with pigment-laden macrophages on the ciliary processes and in the outflow pathways. Higher energy levels caused lens capsule damage and vitritis. The diode laser produced ciliary destruction similar to the continuous-wave contact neodymium-YAG laser in rabbits, with significant intraocular pressure lowering during the 6-week follow-up.

The use of high peak power laser pulses in the short and ultrashort time domains has opened a variety of novel laser-tissue interactions with potential for application in clinical medicine. Photodisruption (optical breakdown) of nominally transparent tissues within the eye, excimer laser tissue ablation, and femtosecond laser tissue ablation are three examples of such tissue effects. Laser tissue interactions in these time domains will be reviewed and selected techniques for investigation of the time scale and damage mechanisms of these interactions will be presented.

We examined the creation of peripheral iridectomies using the semiconductor diode laser in rabbits

To evaluate an optical coherence tomography (OCT)-guided, variable-dosing regimen with intravitreal ranibizumab for the treatment of patients with neovascular age-related macular degeneration (AMD).Open-label, prospective, single-center, nonrandomized, investigator-sponsored clinical study.In this two-year study, neovascular AMD patients with subfoveal choroidal neovascularization (CNV) (n = 40) and a central retinal thickness of at least 300 microm as measured by OCT were enrolled to receive three consecutive monthly intravitreal injections of ranibizumab (0.5 mg). Thereafter, retreatment with ranibizumab was performed if one of the following changes was observed between visits: a loss of five letters in conjunction with fluid in the macula as detected by OCT, an increase in OCT central retinal thickness of at least 100 microm, new-onset classic CNV, new macular hemorrhage, or persistent macular fluid detected by OCT at least one month after the previous injection of ranibizumab.At month 12, the mean visual acuity improved by 9.3 letters (P.001) and the mean OCT central retinal thickness decreased by 178 microm (P.001). Visual acuity improved 15 or more letters in 35% of patients. These visual acuity and OCT outcomes were achieved with an average of 5.6 injections over 12 months. After a fluid-free macula was achieved, the mean injection-free interval was 4.5 months before another reinjection was necessary.This OCT-guided, variable-dosing regimen with ranibizumab resulted in visual acuity outcomes similar to the Phase III clinical studies, but required fewer intravitreal injections. OCT appears useful for determining when retreatment with ranibizumab is necessary.

Purpose To demonstrate the application of high-resolution spectral-domain optical coherence tomography (SD-OCT) for three-dimensional (3D) retinal imaging of small animals and quantitative retinal information extraction using 3D segmentation of the OCT images. Methods A high-resolution SD-OCT system was built for in vivo imaging of rodent retina. OCT fundus images similar to those acquired with a scanning laser ophthalmoscope (SLO) were constructed from the measured OCT data, which provided precise spatial registration of the OCT cross-sectional images on the fundus. A 3D segmentation algorithm was developed for calculation of the retinal thickness map. OCT images were compared by histologic examination. Results High-quality OCT images of the retinas of mice (B6/SJLF2 for normal retina, rhodopsin-deficient Rho(-/-) for photoreceptor degeneration, and LH(BETA)T(AG) for retinoblastoma) and rat (Wistar) were acquired. The OCT images compared well with histology. Not only was a 3D image of the tumor in a retinoblastoma mouse model successfully imaged in vivo but the tumor volume was extracted from the 3D image. Retinal thickness maps were calculated that enabled successful quantitative comparison of the retinal thickness distribution between the normal (202.3 +/- 9.3 microm) and the degenerative (102.7 +/- 12.6 microm) mouse retina. Conclusions High-resolution spectral-domain OCT provides unprecedented high-quality 2D and 3D in vivo visualization of retinal structures of mouse and rat models of retinal diseases. With the capability of 3D quantitative information extraction and precise spatial registration, the OCT system made possible longitudinal study of ocular diseases that has been impossible to conduct.

Optical Doppler tomography (ODT) is a branch of optical coherence tomography (OCT) that can measure the speed of a blood flow by measuring the Doppler shift impinged on the probing sample light by the moving blood cells. However, the measured speed of blood flow is a function of the Doppler angle, which needs to be determined in order to calculate the absolute velocity of the blood flow inside a vessel. We developed a technique that can extract the Doppler angle from the 3D data measured with spectral-domain OCT, which needs to extract the lateral and depth coordinates of a vessel in each measured ODT and OCT image. The lateral coordinates and the diameter of a blood vessel were first extracted in each OCT structural image by using the technique of blood vessel shadowgram, a technique first developed by us for enhancing the retinal blood vessel contrast in the en face view of the 3D OCT. The depth coordinate of a vessel was then determined by using a circular averaging filter moving in the depth direction along the axis passing through the vessel center in the ODT image. The Doppler angle was then calculated from the extracted coordinates of the blood vessel. The technique was applied in blood flow measurements in retinal blood vessels, which has potential impact on the study and diagnosis of blinding diseases like glaucoma.

The development of improved segmentation algorithms for more consistently accurate detection of retinal boundaries is a potentially useful solution to the limitations of existing optical coherence tomography (OCT) software. We modeled artifacts related to operator errors that may normally occur during OCT imaging and evaluated their influence on segmentation results using a novel segmentation algorithm. These artifacts included: defocusing, depolarization, decentration, and a combination of defocusing and depolarization. Mean relative reflectance and average thickness of the automatically extracted intraretinal layers was then measured. Our results show that defocusing and depolarization errors together have the greatest altering effect on all measurements and on segmentation accuracy. A marked decrease in mean relative reflectance and average thickness was observed due to depolarization artifact in all intraretinal layers, while defocus resulted in a less-marked decrease. Decentration resulted in a marked but not significant change in average thickness. Our study demonstrates that care must be taken for good-quality imaging when measurements of intraretinal layers using the novel algorithm are planned in future studies. An awareness of these pitfalls and their possible solutions is crucial for obtaining a better quantitative analysis of clinically relevant features of retinal pathology.

Purpose To evaluate the safety, efficacy, and durability of bevacizumab for the treatment of subfoveal choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (AMD). Design Open-label, single-center, uncontrolled clinical study. Participants Age-related macular degeneration patients with subfoveal CNV (n = 18) and best-corrected visual acuity (VA) letter scores of 70 to 20 (approximate Snellen equivalent, 20/40–20/400). Methods Patients were treated at baseline with an intravenous infusion of bevacizumab (5 mg/kg) followed by 1 or 2 additional doses given at 2-week intervals. Safety assessments were performed at all visits. Ophthalmologic evaluations included protocol VA measurements, ocular examinations, and optical coherence tomography (OCT) imaging at each visit. Retreatment with bevacizumab was performed if there was evidence of recurrent CNV. Main Outcome Measures Assessments of safety and changes from baseline in VA scores and OCT measurements were performed through 24 weeks. Results No serious ocular or systemic adverse events were identified through 24 weeks. The only adverse event identified was a mild elevation of mean systolic and diastolic blood pressure measurements (+11 mmHg, P = 0.004; +8 mmHg, P P P Conclusions Systemic bevacizumab therapy for neovascular AMD was well tolerated and effective for all 18 patients through 24 weeks. By 6 months, most patients did not require any additional treatment beyond the initial 2 or 3 infusions. Despite these impressive results, it is unlikely that systemic bevacizumab will be studied in a large clinical trial because of the potential risks associated with systemic anti-VEGF therapy and the perception that intravitreal therapy is safer.

We previously developed a technique to acquire a SLO (scanning laser ophthalmoscope) like fundus intensity image from the raw spectra measured with spectral-domain optical coherence tomography (OCT), the same spectra used to generate a 3D OCT data set. This technique offers simultaneous fundus and OCT images and, therefore, solves the problem of registering a cross sectional OCT image to fundus features. However, the registration of high density OCT images is still an unsolved problem because no useful fundus image can be generated from the high density scans. High density OCT images can significantly improve the image quality and enhance the visualization of retinal structure, especially the structure of small lesions. We have developed a feature-based algorithm, which can register a high density OCT image on the fundus image generated from normal density scans. The algorithm was successfully tested for both normal and diseased eyes.

Purpose To evaluate the short-term safety of systemic bevacizumab (Avastin, Genentech, Inc., South San Francisco, CA) and its effects on visual acuity (VA) and subfoveal choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (AMD). Design Open-label, single-center, uncontrolled clinical study. Participants Age-related macular degeneration patients with subfoveal CNV (N = 9) and best-corrected VA letter scores of 70 to 20 (approximate Snellen equivalent, 20/40–20/400). Methods Patients were treated at baseline with an infusion of bevacizumab (5 mg/kg), followed by 1 or 2 additional doses given at 2-week intervals. Safety assessments were performed at all visits. Ophthalmologic evaluations included protocol VA measurements and ocular examinations, along with optical coherence tomography (OCT) imaging, fluorescein angiography, and indocyanine green angiography. Main outcome measurements Safety assessments were performed, along with assessments of changes from baseline in VA scores, OCT measurements, and angiographic lesion characteristics. Results There were no serious ocular or systemic adverse events identified. By 6 weeks, the only adverse event identified was a mild elevation of systolic blood pressure (BP) (+12 mmHg; P = 0.035), and this elevation was controlled by either changing or initiating antihypertensive medication. By 12 weeks, the elevation of systolic BP was no longer significant ( P = 0.51). In the study eyes, significant increases in VA were evident within 1 week of treatment, and by 12 weeks, the median and mean VA letter scores increased by 8 letters ( P = 0.011) and 12 letters ( P = 0.008), respectively. The median and mean central retinal thickness measurements decreased by 157 μm ( P = 0.008) and 177 μm ( P = 0.001), respectively. In the fellow eyes at 12 weeks, the median and mean VA letter scores increased by 27 letters ( P = 0.018) and 16 letters ( P = 0.012), and the median and mean central retinal thickness measurements decreased by 59 μm ( P = 0.028) and 92 μm ( P = 0.06). In all study eyes, angiography revealed a marked reduction or an absence of leakage from CNV. Conclusion Overall, bevacizumab therapy was well tolerated, with an improvement in VA, OCT, and angiographic outcomes. Although these preliminary results are promising, a randomized controlled clinical trial is necessary before concluding that systemic bevacizumab therapy is safe and effective for patients with neovascular AMD.

To determine the rate of anatomical closure of idiopathic macular holes undergoing vitreous surgery with respect to preoperative horizontal diameter as determined by optical coherence tomography (OCT) and to correlate postoperative visual acuity, duration of symptoms, and late reopening with initial idiopathic macular hole diameter by OCT.Forty eyes of 40 patients with an idiopathic macular hole were examined with OCT before and after vitreous surgery. All eyes were treated with pars plana vitrectomy, peeling of posterior cortical vitreous, and dilute perfluoropropane or sulfur hexafluoride gas. Face-down positioning was maintained for 7 to 14 days.Twenty-two (92%) of 24 eyes with a preoperative idiopathic macular hole diameter smaller than 400 microm measured by OCT attained anatomical closure following surgery. Anatomical closure was observed in 9 (56%) of 16 eyes with a macular hole diameter of 400 microm or larger measured by OCT (P =.02). The median postoperative visual acuity improvement was 4 Snellen lines in the 31 eyes achieving anatomical closure and no change in the 9 eyes not achieving anatomical closure (P.001). Late macular hole reopening at longer than 6 months occurred in 3 (10%) of 31 eyes with an initially closed macular hole. This event was observed only in macular holes 400 microm or larger measured by OCT. The preoperative macular hole diameter (P =.02) and duration of symptoms (P =.02) were factors predictive of anatomical closure of the macular hole postoperatively.The postoperative closure of idiopathic macular holes following vitreous surgery was related to the preoperative macular hole diameter determined by OCT, with lesions smaller than 400 microm demonstrating higher success rates. A trend toward greater visual acuity improvement was demonstrated for idiopathic macular holes smaller than 400 microm. Late reopening was only seen in macular holes that were 400 microm or larger measured by OCT. Preoperative analysis and measurement of idiopathic macular holes with OCT may help delineate postoperative expectations for successful anatomical closure of the macular hole, visual acuity, and long-term closure.

Objective: To evaluate optical coherence tomography, a new technique for high-resolution cross-sectional imaging of the retina, for quantitative assessment of retinal thickness in patients with macular edema. Design: Survey examination with optical coherence tomography of patients with macular edema. Setting: Referral eye center. Patients: Forty-nine patients with the clinical diagnosis of diabetes or diabetic retinopathy and 25 patients with macular edema secondary to retinal vein occlusion, uveitis, epiretinal membrane formation, or cataract extraction. Main Outcome Measures: Correlation of optical coherence tomograms with slit-lamp biomicroscopy, fluorescein angiography, and visual acuity. Results: Optical coherence tomograms of cystoid macular edema closely corresponded to known histopathologic characteristics. Quantitative measurement of retinal thickness is possible because of the well-defined boundaries in optical reflectivity at the inner and outer margins of the neurosensory retina. Serial optical coherence tomographic examinations allowed tracking of both the longitudinal progression of macular thickening and the resolution of macular edema after laser photocoagulation. In patients with diabetic retinopathy, measurements of central macular thickness with optical coherence tomography correlated with visual acuity, and optical coherence tomography was more sensitive than slit-lamp biomicroscopy to small changes in retinal thickness. Conclusions: Optical coherence tomography appears useful for objectively monitoring retinal thickness with high resolution in patients with macular edema. It may eventually prove to be a sensitive diagnostic test for the early detection of macular thickening in patients with diabetic retinopathy.

Purpose: Quantitative assessment of nerve fiber layer (NFL) thickness in normal and glaucomatous eyes, and correlation with conventional measurements of the optic nerve structure and function. Methods: We studied 59 eyes of 33 subjects by conventional ophthalmologic physical examination, Humphrey 24-2 visual fields, stereoscopic optic nerve head photography, and optical coherence tomography. Results: Nerve fiber layer thickness as measured by optical coherence tomography demonstrated a high degree of correlation with functional status of the optic nerve, as measured by visual field examination ( P =.0001). Neither cupping of the optic nerve nor neuroretinal rim area were as strongly associated with visual field loss as was NFL thickness ( P =.17 and P =.21,respectively). Cupping correlated with NFL thickness only when the cup was small (cup-to-diameter ratio, 0.1 to 0.3) or large (cup-to-diameter ratio, 0.8 to 1.0) ( P =.006); there was no correlation between cupping and NFL thickness otherwise. Nerve fiber layer, especially in the inferior quadrant, was significantly thinner in glaucomatous eyes than in normal eyes ( P =.04). Finally, we found a decrease in NFL thickness with aging, even when controlling for factors associated with the diagnosis of glaucoma ( P =.03). Conclusions: Nerve fiber layer thickness can be measured using optical coherence tomography. These measurements provide good structural and functional correlation with known parameters.

Background: Although adverse reactions to indocyanine green (ICG) are known to occur, the dye has been used for more than 30 years in tests of cardiac and hepatic function, with a high level of safety. Improved digital video technology has renewed interest in the use of intravenous ICG in ophthalmic imaging. This report describes the authors' experience regarding the safety of ICG for digital angiography and their recommendations for its use in the ophthalmic setting. Methods: Digital ICG videoangiography was performed in 1226 consecutive patients, and 1923 ICG videoangiography tests were performed. A registry of adverse reactions to ICG was established. Criteria were used to define mild, moderate, and severe adverse reactions, and these data were recorded for every ICG study performed. Results: There were three (0.15%) mild adverse reactions, four (0.2%) moderate reactions, and one (0.05%) severe adverse reaction. There were no deaths. Conclusions: This study documents the safety of intravenous ICG for use in ophthalmic videoangiography.