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At least 649 records · Page 36

Proton Radiation Therapy for the Treatment of Retinoblastoma

Purpose: To investigate long-term disease and toxicity outcomes for pediatric retinoblastoma patients treated with proton radiation therapy (PRT). Methods and Materials: This is a retrospective analysis of 49 retinoblastoma patients (60 eyes) treated with PRT between 1986 and 2012. Results: The majority (84%) of patients had bilateral disease, and nearly half (45%) had received prior chemotherapy. At a median follow-up of 8 years (range, 1-24 years), no patients died of retinoblastoma or developed metastatic disease. The post-PRT enucleation rate was low (18%), especially in patients with early-stage disease (11% for patients with International Classification for Intraocular Retinoblastoma [ICIR] stage A-B disease vs 23% for patients with ICIR stage C-D disease). Post-PRT ophthalmologic follow-up was available for 61% of the preserved eyes (30 of 49): 14 of 30 eyes (47%) had 20/40 visual acuity or better, 7 of 30 (23%) had moderate visual acuity (20/40-20/600), and 9 of 30 (30%) had little or no useful vision (worse than 20/600). Twelve of 60 treated eyes (20%) experienced a post-PRT event requiring intervention, with cataracts the most common (4 eyes). No patients developed an in-field second malignancy. Conclusions: Long-term follow-up of retinoblastoma patients treated with PRT demonstrates that PRT can achieve high local control rates, even in advanced cases, and many patients retain useful vision in the treated eye. Treatment-related ocular side effects were uncommon, and no radiation-associated malignancies were observed.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Cell transdifferentiation in ocular disease: Potential role for connexin channels

Highlights: • Cell transdifferentiation including EMT and EndMT is a pathological process in a number of ocular diseases. • Gap junction channels and connexin hemichannels play a role in cell transdifferentiation in ocular diseases. • Connexin-blocking therapies demonstrate efficacy in ocular disease models. • Future studies could explore connexin-based therapies for prevention and treatment of pathological transdifferentiation. Cell transdifferentiation is the conversion of a cell type to another without requiring passage through a pluripotent cell state, and encompasses epithelial- and endothelial-mesenchymal transition (EMT and EndMT). EMT and EndMT are well defined processes characterized by a loss of epithelial/endothelial phenotype and gain in mesenchymal spindle shaped morphology, which results in increased cell migration and decreased apoptosis and cellular senescence. Such cells often develop invasive properties. Physiologically, these processes may occur during embryonic development and can resurface, for example, to promote wound healing in later life. However, they can also be a pathological process. In the eye, EMT, EndMT and cell transdifferentiation have all been implicated in development, homeostasis, and multiple diseases affecting different parts of the eye. Connexins, constituents of connexin hemichannels and intercellular gap junctions, have been implicated in many of these processes. In this review, we firstly provide an overview of the molecular mechanisms induced by transdifferentiation (including EMT and EndMT) and its involvement in eye diseases. We then review the literature for the role of connexins in transdifferentiation in the eye and eye diseases. The evidence presented in this review supports the need for more studies into the therapeutic potential for connexin modulators in prevention and treatment of transdifferentiation related eye diseases, but does indicate that connexin channel modulation may be an upstream and unifying approach for regulating these otherwise complex processes.

60 APPLIED LIFE SCIENCES↗

Noninvasive referencing of intraocular tumors for external beam radiation therapy using optical coherence tomography: A proof of concept

Purpose: External beam radiation therapy is currently considered the most common treatment modality for intraocular tumors. Localization of the tumor and efficient compensation of tumor misalignment with respect to the radiation beam are crucial. According to the state of the art procedure, localization of the target volume is indirectly performed by the invasive surgical implantation of radiopaque clips or is limited to positioning the head using stereoscopic radiographies. This work represents a proof-of-concept for direct and noninvasive tumor referencing based on anterior eye topography acquired using optical coherence tomography (OCT). Methods: A prototype of a head-mounted device has been developed for automatic monitoring of tumor position and orientation in the isocentric reference frame for LINAC based treatment of intraocular tumors. Noninvasive tumor referencing is performed with six degrees of freedom based on anterior eye topography acquired using OCT and registration of a statistical eye model. The proposed prototype was tested based on enucleated pig eyes and registration accuracy was measured by comparison of the resulting transformation with tilt and torsion angles manually induced using a custom-made test bench. Results: Validation based on 12 enucleated pig eyes revealed an overall average registration error of 0.26 ± 0.08° in 87 ± 0.7 ms for tilting and 0.52 ± 0.03° in 94 ± 1.4 ms for torsion. Furthermore, dependency of sampling density on mean registration error was quantitatively assessed. Conclusions: The tumor referencing method presented in combination with the statistical eye model introduced in the past has the potential to enable noninvasive treatment and may improve quality, efficacy, and flexibility of external beam radiotherapy of intraocular tumors.

60 APPLIED LIFE SCIENCES↗

Vestibular compensation and orientation during locomotion

Body, head, and eye movements were studied in three dimensions while walking and turning to determine the role of the vestibular system in directing gaze and maintaining spatial orientation. The body, head, and eyes were represented as three-dimensional coordinate frames, and the movement of these frames was related to a trajectory frame that described the motion of the body on a terrestrial plane. The axis-angle of the body, head, and eye rotation were then compared to the axis-angle of the rotation of the gravitoinertial acceleration (GIA). We inferred the role of the vestibular system during locomotion and the contributions of the VCR and VOR by examining the interrelationship between these coordinate frames. Straight walking induced head and eye rotations in a compensatory manner to the linear accelerations, maintaining head pointing and gaze along the direction of forward motion. Turning generated a combination of compensation and orientation responses. The head leads and steers the turn while the eyes compensate to maintain stable horizontal gaze in space. Saccades shift horizontal gaze as the turn is executed. The head pitches, as during straight walking. It also rolls so that the head tends to align with the orientation of the GIA. Head orientation changes anticipate orientation changes of the GIA. Eye orientation follows the changes in GIA orientation so that the net orientation gaze is closer to the orientation of the GIA. The study indicates that the vestibular system utilizes compensatory and orienting mechanisms to stabilize spatial orientation and gaze during walking and turning.

Non-NASA Center↗

Efficacy of a Radiation Absorbing Shield in Reducing Dose to the Interventionalist During Peripheral Endovascular Procedures: A Single Centre Pilot Study

PurposeThis prospective pilot study was undertaken to evaluate the feasibility and effectiveness of using a radiation absorbing shield to reduce operator dose from scatter during lower limb endovascular procedures.Materials and MethodsA commercially available bismuth shield system (RADPAD) was used. Sixty consecutive patients undergoing lower limb angioplasty were included. Thirty procedures were performed without the RADPAD (control group) and thirty with the RADPAD (study group). Two separate methods were used to measure dose to a single operator. Thermoluminescent dosimeter (TLD) badges were used to measure hand, eye, and unshielded body dose. A direct dosimeter with digital readout was also used to measure eye and unshielded body dose. To allow for variation between control and study groups, dose per unit time was calculated.ResultsTLD results demonstrated a significant reduction in median body dose per unit time for the study group compared with controls (p = 0.001), corresponding to a mean dose reduction rate of 65 %. Median eye and hand dose per unit time were also reduced in the study group compared with control group, however, this was not statistically significant (p = 0.081 for eye, p = 0.628 for hand). Direct dosimeter readings also showed statistically significant reduction in median unshielded body dose rate for the study group compared with controls (p = 0.037). Eye dose rate was reduced for the study group but this was not statistically significant (p = 0.142).ConclusionInitial results are encouraging. Use of the shield resulted in a statistically significant reduction in unshielded dose to the operator’s body. Measured dose to the eye and hand of operator were also reduced but did not reach statistical significance in this pilot study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Central Corneal Edema with Scleral-Lens Wear

Purpose: To assess the safety of scleral-lens designs, we model and clinically assess central corneal edema induced by scleral-lens wear for healthy subjects. Materials and Methods: Typically, central corneal swelling during scleral-lens wear is measured using optical coherence tomography (OCT). Transport resistances are modeled for oxygen diffusion through the scleral lens and post-lens tear-film (PoLTF), and into the cornea. Oxygen deficiency in the cornea activates anaerobic metabolic reactions that induce corneal edema. Oxygen permeability, carbon-dioxide permeability, settled-lens PoLTF thickness, and scleral-lens thickness are varied in the calculations to mimic different lens fits. Results: Transport modeling predicts that for open eyes, increasing PoLTF thickness from 50 to 400 µm increases central corneal swelling by approximately 1–1.5% when oxygen transmissibility ( Dk/L ) is greater than 10 hBarrer/cm (i.e., hectoBarrer/cm). Although swelling is larger for oxygen Dk/L < 10 hBarrer/cm, PoLTF thickness has minimal impact in this range. For open eye, oxygen transmissibility of the lens plays a significant role in corneal edema, but is negligible when oxygen Dk/L is > 40 hBarrer/cm. For closed eye, central corneal swelling is greater than 5% for an oxygen Dk/L range of 0–100 hBarrer/cm with typical lens-fitting parameters. For carbon-dioxide transmissibilities increasing from 50 to 250 hBarrer/cm and with a fixed oxygen Dk/L of 25 hBarrer/cm, calculated swelling diminishes by an additional 0.5%. Comparison of model calculations to clinical-swelling data is within the error range of the clinical measurements. Conclusions: Oxygen/metabolite transport calculations for open-eye scleral-lens wear demonstrate that normal PoLTF thicknesses fitted by clinicians (i.e., PoLTF thicknesses < 400 µm) with modern scleral lenses (i.e., oxygen Dk/L > 25 hBarrer/cm) produce corneal swelling of less than 2% in agreement with experiment. Therefore, scleral lenses prescribed today evoke less than physiological hypoxic swelling (i.e., less than 4%) for healthy corneas during open-eye. Closed-eye wear, however, appears clinically unsafe.

60 APPLIED LIFE SCIENCES↗

Thermal safety of ultrasound-enhanced ocular drug delivery: A modeling study

Purpose: Delivery of sufficient amounts of therapeutic drugs into the eye for treatment of various ocular diseases is often a challenging task. Ultrasound was shown to be effective in enhancing ocular drug delivery in the authors’ previous in vitro and in vivo studies. Methods: The study reported here was designed to investigate the safety of ultrasound application and its potential thermal effects in the eye using PZFlex modeling software. The safety limit in this study was set as a temperature increase of no more than 1.5 °C based on regulatory recommendations and previous experimental safety studies. Acoustic and thermal specifications of different human eye tissues were obtained from the published literature. The tissues of particular interest in this modeling safety study were cornea, lens, and the location of optic nerve in the posterior eye. Ultrasound application was modeled at frequencies of 400 kHz–1 MHz, intensities of 0.3–1 W/cm{sup 2}, and exposure duration of 5 min, which were the parameters used in the authors’ previous drug delivery experiments. The baseline eye temperature was 37 °C. Results: The authors’ results showed that the maximal tissue temperatures after 5 min of ultrasound application were 38, 39, 39.5, and 40 °C in the cornea, 39.5, 40, 42, and 43 °C in the center of the lens, and 37.5, 38.5, and 39 °C in the back of the eye (at the optic nerve location) at frequencies of 400, 600, 800 kHz, and 1 MHz, respectively. Conclusions: The ocular temperatures reached at higher frequencies were considered unsafe based on current recommendations. At a frequency of 400 kHz and intensity of 0.8 W/cm{sup 2} (parameters shown in the authors’ previous in vivo studies to be optimal for ocular drug delivery), the temperature increase was small enough to be considered safe inside different ocular tissues. However, the impact of orbital bone and tissue perfusion should be included in future modeling efforts to determine the safety of this method in the whole orbit especially regarding potential adverse optic nerve heating at the location of the bone.

60 APPLIED LIFE SCIENCES↗

Experiment K-7-30: Effects of Spaceflight in the Cosmos Biosatellite 2044 on the Vestibular-Ocular Reflex (VOR) of Rhesus Monkeys

This technical paper discusses the following: (1) The VOR of two rhesus monkeys was studied before and after 14 days of spaceflight to determine effects of microgravity on the VOR. Horizontal, vertical and roll eye movements were recorded in these and six other monkeys implanted with scleral search coils. Animals were rotated about a vertical axis to determine the gain of the horizontal, vertical and roll VOR. They were rotated about axes tilted from the vertical (off-vertical axis rotation, OVAR) to determine steady state gains and effects of gravity on modulations in eye position and eye velocity. They were also tested for tilt dumping of post-rotatory nystagmus. (2) The gain of the horizontal VOR was close to unity when animals were tested 15 and 18 hours after flight. VOR gain values were similar to those registered before flight. If the gain of the horizontal VOR changes in microgravity, it must revert to normal soon after landing. (3) Steady state velocities of nystagmus induced by off-vertical axis rotation (OVAR) were unchanged by adaptation to microgravity, and the phase of the modulations was similar before and after flight. However, modulations in horizontal eye velocity had more variation after landing and were on mean about 50% larger for angles of tilt of the axis of rotation between 50 and 90?/s after flight. This difference was similar in both animals and was significant. (4) A striking finding was that tilt dumping was lost in the one animal tested for this function. This loss persisted for several days after return. This is reminiscent of the loss of response to pitch while rotating in the M-131 experiments of Skylab, and must be studied in detail in future spaceflights. (5) Thus, two major findings emerged from these studies: after spaceflight the modulation of horizontal eye velocity was larger during OVAR, and one animal lost its ability to tilt-dump its nystagmus. Both findings are consistent with the postulate that adaptation to microgravity causes alterations in the way that otolith information is processed in the central nervous system. The experiments lay the groundwork for studying the vertical and roll VOR before and after future space flights, as well as for studying modulations in vertical and roll eye position during OVAR and tilt dumping.

Cohen, B.↗

Pursuit Latency for Chromatic Targets

The temporal dynamics of eye movement response to a change in direction of stimulus motion has been used to compare the processing speeds of different types of stimuli (Mulligan, ARVO '97). In this study, the pursuit response to colored targets was measured to test the hypothesis that the slow response of the chromatic system (as measured using traditional temporal sensitivity measures such as contrast sensitivity) results in increased eye movement latencies. Subjects viewed a small (0.4 deg) Gaussian spot which moved downward at a speed of 6.6 deg/sec. At a variable time during the trajectory, the dot's direction of motion changed by 30 degrees, either to the right or left. Subjects were instructed to pursue the spot. Eye movements were measured using a video ophthalmoscope with an angular resolution of approximately 1 arc min and a temporal sampling rate of 60 Hz. Stimuli were modulated in chrominance for a variety of hue directions, combined with a range of small luminance increments and decrements, to insure that some of the stimuli fell in the subjects' equiluminance planes. The smooth portions of the resulting eye movement traces were fit by convolving the stimulus velocity with an exponential having variable onset latency, time constant and amplitude. Smooth eye movements with few saccades were observed for all stimuli. Pursuit responses to stimuli having a significant luminance component are well-fit by exponentials having latencies and time constants on the order of 100 msec. Increases in pursuit response latency on the order of 100-200 msec are observed in response to certain stimuli, which occur in pairs of complementary hues, corresponding to the intersection of the stimulus section with the subjects' equiluminant plane. Smooth eye movements can be made in response to purely chromatic stimuli, but are slower than responses to stimuli with a luminance component.

Mulligan, Jeffrey B.↗

The Right Track for Vision Correction

More and more people are putting away their eyeglasses and contact lenses as a result of laser vision correction surgery. LASIK, the most widely performed version of this surgical procedure, improves vision by reshaping the cornea, the clear front surface of the eye, using an excimer laser. One excimer laser system, Alcon s LADARVision 4000, utilizes a laser radar (LADAR) eye tracking device that gives it unmatched precision. During LASIK surgery, laser During LASIK surgery, laser pulses must be accurately placed to reshape the cornea. A challenge to this procedure is the patient s constant eye movement. A person s eyes make small, involuntary movements known as saccadic movements about 100 times per second. Since the saccadic movements will not stop during LASIK surgery, most excimer laser systems use an eye tracking device that measures the movements and guides the placement of the laser beam. LADARVision s eye tracking device stems from the LADAR technology originally developed through several Small Business Innovation Research (SBIR) contracts with NASA s Johnson Space Center and the U.S. Department of Defense s Ballistic Missile Defense Office (BMDO). In the 1980s, Johnson awarded Autonomous Technologies Corporation a Phase I SBIR contract to develop technology for autonomous rendezvous and docking of space vehicles to service satellites. During Phase II of the Johnson SBIR contract, Autonomous Technologies developed a prototype range and velocity imaging LADAR to demonstrate technology that could be used for this purpose.

Source record↗

Gravity modulates Listing's plane orientation during both pursuit and saccades

Previous studies have shown that the spatial organization of all eye orientations during visually guided saccadic eye movements (Listing's plane) varies systematically as a function of static and dynamic head orientation in space. Here we tested if a similar organization also applies to the spatial orientation of eye positions during smooth pursuit eye movements. Specifically, we characterized the three-dimensional distribution of eye positions during horizontal and vertical pursuit (0.1 Hz, +/-15 degrees and 0.5 Hz, +/-8 degrees) at different eccentricities and elevations while rhesus monkeys were sitting upright or being statically tilted in different roll and pitch positions. We found that the spatial organization of eye positions during smooth pursuit depends on static orientation in space, similarly as during visually guided saccades and fixations. In support of recent modeling studies, these results are consistent with a role of gravity on defining the parameters of Listing's law.

NASA Discipline Developmental Biology↗

Contribution of the cerebellar flocculus to gaze control during active head movements

The flocculus and ventral paraflocculus are adjacent regions of the cerebellar cortex that are essential for controlling smooth pursuit eye movements and for altering the performance of the vestibulo-ocular reflex (VOR). The question addressed in this study is whether these regions of the cerebellum are more globally involved in controlling gaze, regardless of whether eye or active head movements are used to pursue moving visual targets. Single-unit recordings were obtained from Purkinje (Pk) cells in the floccular region of squirrel monkeys that were trained to fixate and pursue small visual targets. Cell firing rate was recorded during smooth pursuit eye movements, cancellation of the VOR, combined eye-head pursuit, and spontaneous gaze shifts in the absence of targets. Pk cells were found to be much less sensitive to gaze velocity during combined eye-head pursuit than during ocular pursuit. They were not sensitive to gaze or head velocity during gaze saccades. Temporary inactivation of the floccular region by muscimol injection compromised ocular pursuit but had little effect on the ability of monkeys to pursue visual targets with head movements or to cancel the VOR during active head movements. Thus the signals produced by Pk cells in the floccular region are necessary for controlling smooth pursuit eye movements but not for coordinating gaze during active head movements. The results imply that individual functional modules in the cerebellar cortex are less involved in the global organization and coordination of movements than with parametric control of movements produced by a specific part of the body.

NASA Discipline Neuroscience↗

Tilt and Translation Motion Perception during Off Vertical Axis Rotation

The effect of stimulus frequency on tilt and translation motion perception was studied during constant velocity off-vertical axis rotation (OVAR), and compared to the effect of stimulus frequency on eye movements. Fourteen healthy subjects were rotated in darkness about their longitudinal axis 10deg and 20deg off-vertical at 0.125 Hz, and 20deg offvertical at 0.5 Hz. Oculomotor responses were recorded using videography, and perceived motion was evaluated using verbal reports and a joystick with four degrees of freedom (pitch and roll tilt, mediallateral and anteriorposterior translation). During the lower frequency OVAR, subjects reported the perception of progressing along the edge of a cone. During higher frequency OVAR, subjects reported the perception of progressing along the edge of an upright cylinder. The modulation of both tilt recorded from the joystick and ocular torsion significantly increased as the tilt angle increased from 10deg to 20deg at 0.125 Hz, and then decreased at 0.5 Hz. Both tilt perception and torsion slightly lagged head orientation at 0.125 Hz. The phase lag of torsion increased at 0.5 Hz, while the phase of tilt perception did not change as a function of frequency. The amplitude of both translation perception recorded from the joystick and horizontal eye movements was negligible at 0.125 Hz and increased as a function of stimulus frequency. While the phase lead of horizontal eye movements decreased at 0.5 Hz, the phase of translation perception did not vary with stimulus frequency and was similar to the phase of tilt perception during all conditions. During dynamic linear acceleration in the absence of other sensory input (canal, vision) a change in stimulus frequency alone elicits similar changes in the amplitude of both self motion perception and eye movements. However, in contrast to the eye movements, the phase of both perceived tilt and translation motion is not altered by stimulus frequency. We conclude that the neural processing to distinguish tilt and translation linear acceleration stimuli differs between eye movements and motion perception.

Wood, Scott J.↗

Development of a Protocol to Test Proprioceptive Utilization as a Predictor for Sensorimotor Adaptability

Astronauts returning from space flight show significant inter-subject variations in their abilities to readapt to a gravitational environment because of their innate sensory weighting. The ability to predict the manner and degree to which each individual astronaut will be affected would improve the effectiveness of countermeasure training programs designed to enhance sensorimotor adaptability. We hypothesize participant's ability to utilize individual sensory information (vision, proprioception and vestibular) influences adaptation in sensorimotor performance after space flight. The goal of this study is to develop a reliable protocol to test proprioceptive utilization in a functional postural control task. Subjects "stand" in a supine position while strapped to a backpack frame holding a friction-free device using air-bearings that allow the subject to move freely in the frontal plane, similar to when in upright standing. The frame is attached to a pneumatic cylinder, which can provide different levels of a gravity-like force that the subject must balance against to remain "upright". The supine posture with eyes closed ensures reduced vestibular and visual contribution to postural control suggesting somatosensory and/or non-otolith vestibular inputs will provide relevant information for maintaining balance control in this task. This setup is called the gravity bed. Fourteen healthy subjects carried out three trials each with eyes open alternated with eyes closed, "standing" on their dominant leg in the gravity bed environment while loaded with 60 percent of their body weight. Subjects were instructed to: "use your sense of sway about the ankle and pressure changes under the foot to maintain balance." Maximum length of a trial was 45 seconds. A force plate underneath the foot recorded forces and moments during the trial and an inertial measurement unit (IMU) attached on the backpack's frame near the center of mass of the subject recorded upper body postural responses. Series of linear and non-linear analyses were carried out on several force plate and IMU data including stabilogram diffusion analysis on the center of pressure (COP) to find a subset of parameters that were sensitive to detect differences in postural performance between eyes open and closed conditions. Results revealed that seven parameters (root mean square (RMS) of medio-lateral (ML) COP, range of ML COP, RMS of roll moment, range of trunk roll, minimum time-to-boundary (TTB), integrated TTB, and critical mean square planar displacement (delta r (sup 2) (sub c)) were significantly different between eyes open and closed conditions. We will present data to show the efficacy of using performance in single leg stance with eyes closed on the gravity bed to assess individuals' ability to utilize proprioceptive information in a functional postural control task to predict re-adaptation for sensorimotor and functional performance.

Goel, R.↗

Incidence and Progression of Chorioretinal Folds During Long-Duration Spaceflight

Importance: The primary contributing factor for development of chorioretinal folds during spaceflight is unknown. Characterizing fold types that develop and tracking their progression may provide insight into the pathophysiology of spaceflight-associated neuro-ocular syndrome and elucidate the risk of fold progression for future exploration-class missions exceeding 12 months in duration. Objective: To determine the incidence and presentation of chorioretinal folds in long-duration International Space Station crew members and objectively quantify the progression of choroidal folds during spaceflight. Design, Setting, and Participants: In this retrospective cohort study, optical coherence tomography scans of the optic nerve head and macula of crew members completing long-duration spaceflight missions were obtained on Earth prior to spaceflight and during flight. A panel of experts examined the scans for the qualitative presence of chorioretinal folds. Peripapillary total retinal thickness was calculated to identify eyes with optic disc edema, and choroidal folds were quantified based on surface roughness within macular and peripapillary regions of interest. Interventions or Exposures: Spaceflight missions ranging 6 to 12 months. Main Outcomes and Measures: Incidence of peripapillary wrinkles, retinal folds, and choroidal folds; peripapillary total retinal thickness; and Bruch membrane surface roughness. Results: A total of 36 crew members were analyzed (mean [SD] age, 46 [6] years; 7 [19%] female). Chorioretinal folds were observed in 12 of 72 eyes (17%; 6 crew members). In eyes with early signs of disc edema, 10 of 42 (24%) had choroidal folds, 4 of 42 (10%) had inner retinal folds, and 2 of 42 (5%) had peripapillary wrinkles. Choroidal folds were observed in all eyes with retinal folds and peripapillary wrinkles. Macular choroidal folds developed in 7 of 12 eyes (4 of 6 crew members) with folds and progressed with mission duration; these folds extended into the fovea in 6 eyes. Circumpapillary choroidal folds developed predominantly superior, nasal, and inferior to the optic nerve head and increased in prevalence and severity with mission duration. Conclusions and Relevance: Choroidal folds were the most common fold type to develop during spaceflight; this differs from reports in idiopathic intracranial hypertension, suggesting differences in the mechanisms underlying fold formation. Quantitative measures demonstrate the development and progression of choroidal folds during weightlessness, and these metrics may help to assess the efficacy of spaceflight-associated neuro-ocular syndrome countermeasures.

Connor R. Ferguson↗

Outcomes of Proton Therapy for the Treatment of Uveal Metastases

Purpose/Objective(s): Radiation therapy can be used to treat uveal metastases with the goal of local control and improvement of quality of life. Proton therapy can be used to treat uveal tumors efficiently and with expectant minimization of normal tissue injury. Here, we report the use of proton beam therapy for the management of uveal metastases. Methods and Materials: A retrospective chart review was made of all patients with uveal metastases treated at our institution with proton therapy between June 2002 and June 2012. Patient and tumor characteristics, fractionation and dose schemes, local control, and toxicities are reported. Results: Ninety patients were identified. Of those, 13 were excluded because of missing information. We report on 77 patients with 99 affected eyes with available data. Patients were 68% female, and the most common primary tumor was breast carcinoma (49%). The median age at diagnosis of uveal metastasis was 57.9 years. Serous retinal detachment was seen in 38% of treated eyes. The median follow-up time was 7.7 months. The median dose delivered to either eye was 20 Gy(relative biological effectiveness [RBE]) in 2 fractions. Local control was 94%. The median survival after diagnosis of uveal metastases was 12.3 months (95% confidence interval, 7.7-16.8). Death in all cases was secondary to systemic disease. Radiation vasculopathy, measured decreased visual acuity, or both was observed in 50% of evaluable treated eyes. The actuarial rate of radiation vasculopathy, measured decreased visual acuity, or both was 46% at 6 months and 73% at 1 year. The 6 eyes with documented local failure were successfully salvaged with retreatment. Conclusions: Proton therapy is an effective and efficient means of treating uveal metastases. Acutely, the majority of patients experience minor adverse effects. For longer-term survivors, the risk of retinal injury with vision loss increases significantly over the first year.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Temporal Evolution and Dose-Volume Histogram Predictors of Visual Acuity After Proton Beam Radiation Therapy of Uveal Melanoma

Purpose: To perform an in-depth temporal analysis of visual acuity (VA) outcomes after proton beam radiation therapy (PBRT) in a large, uniformly treated cohort of uveal melanoma (UM) patients, to determine trends in VA evolution depending on pretreatment and temporally defined posttreatment VA measurements; and to investigate the relevance of specific patient, tumor and dose-volume parameters to posttreatment vision loss. Methods and Materials: Uveal melanoma patients receiving PBRT were identified from a prospectively maintained database. Included patients (n=645) received 56 GyE in 4 fractions, had pretreatment best corrected VA (BCVA) in the affected eye of count fingers (CF) or better, with posttreatment VA assessment at specified post-PBRT time point(s). Patients were grouped according to the pretreatment BCVA into favorable (≥20/40) or unfavorable (20/50-20/400) and poor (CF) strata. Temporal analysis of BCVA changes was described, and univariate and forward stepwise multivariate logistic regression analyses were performed to identify predictors for VA loss. Results: Median VA follow-up was 53 months (range, 3-213 months). At 60-month follow up, among evaluable treated eyes with favorable pretreatment BCVA, 45% retained BCVA ≥20/40, whereas among evaluable treated eyes with initially unfavorable/poor BCVA, 21% had vision ≥20/100. Among those with a favorable initial BCVA, attaining BCVA of ≥20/40 at any posttreatment time point was associated with subsequent maintenance of excellent BCVA. Multivariate analysis identified volume of the macula receiving 28GyE (P<.0001) and optic nerve (P=.0004) as independent dose-volume histogram predictors of 48-month post-PBRT vision loss among initially favorable treated eyes. Conclusions: Approximately half of PBRT-treated UM eyes with excellent pretreatment BCVA assessed at 5 years after treatment will retain excellent long-term vision. 28GyE macula and optic nerve dose-volume histogram parameters allow for rational treatment planning optimization that may lead to improved visual outcomes. The detailed temporal analysis with intermediate as well as long-term functional prognosis, and the relationship of outcomes with clinical and treatment planning parameters, is critical for informed care of UM patients before and after PBRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Characterization and implementation of OSL dosimeters for use in evaluating the efficacy of organ-based tube current modulation for CT scans of the face and orbits

Purpose: The purpose of this work was to characterize commercially available optically stimulated luminescent (OSL) dosimeters for general clinical applications and apply the results to the development of a method to evaluate the efficacy of a vendor-specific organ-based tube current modulation application for both phantom and clinical computed tomography (CT) scans of the face and orbits. Methods: This study consisted of three components: (1) thorough characterization of the dosimeters for CT scans in phantom, including evaluations of depletion, fading, angular dependence, and conversion from counts to absorbed dose; (2) evaluation of the efficacy of using plastic glasses to position the dosimeters over the eyes in both phantom and clinical studies; and (3) preliminary dosimetry measurements made using organ-based tube current modulation in computed tomography dose index (CTDI) and anthropomorphic phantom studies. Results: (1) Depletion effects were found to have a linear relationship with the output of the OSL dosimeters (R{sup 2} = 0.96). Fading was found to affect dosimeter readings during the first two hours following exposure but had no effect during the remaining 60-h period observed. No significant angular dependence was observed for the exposure conditions used in this study (with p-values ranging from 0.9 to 0.26 for all t-tests). Dosimeter counts varied linearly with absorbed dose when measured in the center and 12 o’clock positions of the CTDI phantoms. These linear models of counts versus absorbed dose had overlapping 95% confidence intervals for the intercepts but not for the slopes. (2) When dosimeters were positioned using safety glasses, there was no adverse effect on image quality, and there was no statistically significant difference between this placement and placement of the dosimeters directly on the eyes of the phantom (p = 0.24). (3) When using organ-based tube current modulation, the dose to the lens of the eye was reduced between 19% and 43%, depending on the scan protocol used and the positioning of the phantom. Furthermore, the amount of dose reduction was significantly affected by the vertical position of the phantom, with the largest reduction in dose seen when the phantom was centered in the gantry. Conclusions: (1) An appropriate correction factor, specific to CT scanning, was developed to account for depletion and fading characteristics of the dosimeters. Additionally, an equation to convert dosimeter counts to absorbed dose was established. (2) The use of plastic safety glasses was validated as an appropriate positioning device when measuring dose to the lens of the eye. (3) The use of organ-based tube current modulation can reduce dose to the lens of the eye during CT scanning. The amount of dose reduction, however, is largely influenced by the positioning of the anatomy in the gantry.

62 RADIOLOGY AND NUCLEAR MEDICINE↗